Journal: JAMA Cardiol

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Abstract

Association of Obesity With Adverse Long-term Outcomes in Hypertrophic Cardiomyopathy.

Fumagalli C, Maurizi N, Day SM, Ashley EA, ... Olivotto I,
Importance
Patients with hypertrophic cardiomyopathy (HCM) are prone to body weight increase and obesity. Whether this predisposes these individuals to long-term adverse outcomes is still unresolved.
Objective
To describe the association of body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) with long-term outcomes in patients with HCM in terms of overall disease progression, heart failure symptoms, and arrhythmias.
Design, setting, and participants
In this cohort study, retrospective data were analyzed from the ongoing prospective Sarcomeric Human Cardiomyopathy Registry, an international database created by 8 high-volume HCM centers that includes more than 6000 patients who have been observed longitudinally for decades. Records from database inception up to the first quarter of 2018 were analyzed. Patients were divided into 3 groups according to BMI class (normal weight group, <25; preobesity group, 25-30; and obesity group, >30). Patients with 1 or more follow-up visits were included in the analysis. Data were analyzed from April to October 2018.
Exposures
Association of baseline BMI with outcome was assessed.
Main outcome and measures
Outcome was measured against overall and cardiovascular mortality, a heart failure outcome (ejection fraction less than 35%, New York Heart Association class III/IV symptoms, cardiac transplant, or assist device implantation), a ventricular arrhythmic outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator therapy), and an overall composite outcome (first occurrence of any component of the ventricular arrhythmic or heart failure composite end point, all-cause mortality, atrial fibrillation, or stroke).
Results
Of the 3282 included patients, 2019 (61.5%) were male, and the mean (SD) age at diagnosis was 47 (15) years. These patients were observed for a median (interquartile range) of 6.8 (3.3-13.3) years. There were 962 patients in the normal weight group (29.3%), 1280 patients in the preobesity group (39.0%), and 1040 patients in the obesity group (31.7%). Patients with obesity were more symptomatic (New York Heart Association class of III/IV: normal weight, 87 [9.0%]; preobesity, 138 [10.8%]; obesity, 215 [20.7%]; P < .001) and more often had obstructive physiology (normal weight, 201 [20.9%]; preobesity, 327 [25.5%]; obesity, 337 [32.4%]; P < .001). At follow-up, obesity was independently associated with the HCM-related overall composite outcome (preobesity vs normal weight: hazard ratio [HR], 1.102; 95% CI, 0.920-1.322; P = .29; obesity vs normal weight: HR, 1.634; 95% CI, 1.332-1.919; P < .001) and the heart failure composite outcome (preobesity vs normal weight: HR, 1.192; 95% CI, 0.930-1.1530; P = .20; obesity vs normal weight: HR, 1.885; 95% CI, 1.485-2.393; P < .001) irrespective of age, sex, left atrium diameter, obstruction, and genetic status. Obesity increased the likelihood of atrial fibrillation but not of life-threatening ventricular arrhythmias.
Conclusions and relevance
Obesity is highly prevalent among patients with HCM and is associated with increased likelihood of obstructive physiology and adverse outcomes. Strategies aimed at preventing obesity and weight increase may play an important role in management and prevention of disease-related complications.



JAMA Cardiol: 05 Nov 2019:1-8; epub ahead of print
Fumagalli C, Maurizi N, Day SM, Ashley EA, ... Olivotto I,
JAMA Cardiol: 05 Nov 2019:1-8; epub ahead of print | PMID: 31693057
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Abstract

Association of Sex With Outcomes in Patients Undergoing Percutaneous Coronary Intervention: A Subgroup Analysis of the GLOBAL LEADERS Randomized Clinical Trial.

Chichareon P, Modolo R, Kerkmeijer L, Tomaniak M, ... Mehran R, Serruys PW
Importance
Women experience worse ischemic and bleeding outcomes after percutaneous coronary intervention (PCI).
Objectives
To assess the association of sex with patient outcomes at 2 years after contemporary PCI and with the efficacy and safety of 2 antiplatelet strategies.
Design, setting, and analysis
This study is a prespecified subgroup analysis of the investigator-initiated, prospective, randomized GLOBAL LEADERS study evaluating 2 strategies of antiplatelet therapy after PCI in an unselected population including 130 secondary/tertiary care hospitals in different countries. The main study enrolled 15 991 unselected patients undergoing PCI between July 2013 and November 2015. Patients had an outpatient clinic visit at 30 days and 3, 6, 12, 18, and 24 months after the index procedure. Data were analyzed between January 1, 2019, and March 31, 2019.
Interventions
Eligible patients were randomized to either the experimental or reference antiplatelet strategy. Experimental strategy consisted of 1 month of dual antiplatelet therapy (DAPT) followed by 23 months of ticagrelor monotherapy, while the reference strategy comprised of 12 months of DAPT followed by 12 months of aspirin monotherapy.
Main outcomes and measures
The primary efficacy end point was the composite of all-cause mortality and new Q-wave myocardial infarction at 2 years. The secondary safety end point was Bleeding Academic Research Consortium type 3 or 5 bleeding.
Results
Of the 15 968 patients included in this study, 3714 (23.3%) were women. The risk of the primary end point at 2 years was similar between women and men (adjusted hazard ratio [HR], 1.00; 95% CI, 0.83-1.20). Compared with men, women had higher risk of Bleeding Academic Research Consortium type 3 or 5 bleeding (adjusted HR, 1.32; 95% CI, 1.04-1.67) and hemorrhagic stroke at 2 years (adjusted HR, 4.76; 95% CI, 1.92-11.81). At 2 years, there was no between-sex difference in the efficacy and safety of the 2 antiplatelet strategies. At 1 year, compared with DAPT, ticagrelor monotherapy was associated with a lower risk of bleeding in men (HR, 0.72; 95% CI, 0.53-0.98) but not in women (HR, 1.23; 95% CI, 0.80-1.89; P for interaction = .045).
Conclusions and relevance
Compared with men, women experienced a higher risk of bleeding and hemorrhagic stroke after PCI. The effect of 2 antiplatelet strategies on death and Q-wave myocardial infarction following PCI did not differ between the sexes at 2 years.
Trial registration
ClinicalTrials.gov identifier: NCT01813435.



JAMA Cardiol: 05 Nov 2019:1-10; epub ahead of print
Chichareon P, Modolo R, Kerkmeijer L, Tomaniak M, ... Mehran R, Serruys PW
JAMA Cardiol: 05 Nov 2019:1-10; epub ahead of print | PMID: 31693078
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Abstract

Occurence of First and Recurrent Major Adverse Cardiovascular Events With Liraglutide Treatment Among Patients With Type 2 Diabetes and High Risk of Cardiovascular Events: A Post Hoc Analysis of a Randomized Clinical Trial.

Verma S, Bain SC, Buse JB, Idorn T, ... Ørsted DD, Nauck MA
Importance
After the occurrence of nonfatal cardiovascular events, recurrent events are highly likely. Most cardiovascular outcomes trials analyze first events only; extending analyses to first and recurrent (total) events can provide clinically meaningful information.
Objective
To investigate whether liraglutide is associated with reduced first and recurrent total major adverse cardiovascular events (MACE) compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events.
Design, setting, and participants
This post hoc analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) randomized, double-blind, clinical trial included data from patients with type 2 diabetes who had established or were at high risk for cardiovascular disease at 410 sites in 32 countries from August 2010, to December 2015. Data analysis was performed from August 15, 2016, to July 5, 2019.
Interventions
Patients were randomized 1:1 to receive liraglutide (up to 1.8 mg per day) or placebo, both with standard care, for 3.5 to 5.0 years.
Main outcomes and measures
Assessed outcomes were MACE (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), expanded MACE (primary MACE plus coronary revascularization and hospitalization for heart failure or unstable angina pectoris), and the individual end points.
Results
The 9340 LEADER trial participants (6003 [64.3%] male; mean [SD] age, 64.3 [7.2] years) experienced 1605 total MACE (1302 first and 303 recurrent events; median follow-up, 3.8 years [range, 0-5.2 years]). Patients who experienced any MACE were older (1 MACE: mean [SD] age, 65.6 [8.0] years; >1 MACE: 65.7 [7.9] years) and had diabetes for longer duration (1 MACE: mean [SD] duration, 13.4 [8.3] years; >1 MACE: 14.4 [8.7] years) compared with patients without MACE (mean [SD] age, 64.1 [7.1] years; mean [SD] duration, 12.7 [7.9] years). Fewer first and recurrent MACE occurred in the liraglutide group (n = 4668; 608 first and 127 recurrent events) than in the placebo group (n = 4672; 694 first and 176 recurrent events). Liraglutide was associated with a 15.7% relative risk reduction in total MACE (hazard ratio [HR], 0.84; 95% CI, 0.76-0.93) and a 13.4% reduction in total expanded MACE (HR, 0.87; 95% CI, 0.81-0.93) compared with placebo. For most individual cardiovascular end points, liraglutide was associated with lower risk vs placebo.
Conclusions and relevance
These results suggest that liraglutide treatment is associated with reduced total MACE compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events. This analysis supports the findings of an absolute benefit of liraglutide treatment with respect to the overall burden of cardiovascular events in this high-risk patient population.
Trial registration
ClinicalTrials.gov identifier: NCT01179048.



JAMA Cardiol: 12 Nov 2019; epub ahead of print
Verma S, Bain SC, Buse JB, Idorn T, ... Ørsted DD, Nauck MA
JAMA Cardiol: 12 Nov 2019; epub ahead of print | PMID: 31721979
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Abstract

Association of a P2Y12 Inhibitor Copayment Reduction Intervention With Persistence and Adherence With Other Secondary Prevention Medications: A Post Hoc Analysis of the ARTEMIS Cluster-Randomized Clinical Trial.

Fanaroff AC, Peterson ED, Kaltenbach LA, Cannon CP, ... Fonarow GC, Wang TY
Importance
The Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study (ARTEMIS) cluster-randomized trial found that copayment reduction for P2Y12 inhibitors improved 1-year patient persistence in taking that medication.
Objective
To assess whether providing copayment reduction for P2Y12 inhibitors increases patient persistence in taking other secondary prevention cardiovascular medications.
Design, setting, and participants
This post hoc analysis of the ARTEMIS trial includes data from 287 hospitals that enrolled patients between June 2015 and September 2016. Patients hospitalized with acute myocardial infarction were included. Data analysis occurred from May 2018 through August 2019.
Interventions
Hospitals randomized to the intervention provided patients vouchers that waived copayments for P2Y12 inhibitors fills for 1 year. Hospitals randomized to usual care did not provide study vouchers.
Main outcomes and measures
Persistence in taking β-blocker, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medications at 1 year, defined as the absence of a gap in medication supply of 30 or more days by pharmacy fill data in the intervention-arm (intent-to-treat) population.
Results
A total of 131 hospitals (with 5109 patients) were randomized to the intervention, and 156 hospitals (with 3264 patients) randomized to the control group. Patients discharged from intervention hospitals had higher persistence in taking statins (2247 [46.1%] vs 1300 [41.9%]; adjusted odds ratio, 1.11 [95% CI, 1.00-1.24]), and β-blockers (2235 [47.6%] vs 1277 [42.5%]; odds ratio, 1.23 [95% CI, 1.10-1.38]), although the association was smaller than that seen for P2Y12 inhibitors (odds ratio, 1.47 [95% CI, 1.29-1.66]). Persistence in taking angiotensin-converting enzyme inhibitors or angiotensin II-receptor blockers were also numerically higher among patients in the intervention arm than in the usual-care arm, but this was not significant after risk adjustment (1520 [43.9%] vs 847 [40.5%]; adjusted odds ratio, 1.10 [95% CI, 0.97-1.24]). Patients in the intervention arm reported greater financial burden associated with medication cost than the patients in the usual-care arm at baseline, but these differences were no longer significant at 1 year.
Conclusions and relevance
Reducing patient copayments for 1 medication class increased persistence not only to that therapy class but may also have modestly increased persistence to other post-myocardial infarction secondary prevention medications. These findings have important implications for the clinical utility and cost-effectiveness of medication cost-assistance programs.
Trial registration
ClinicalTrials.gov Identifier: NCT02406677.



JAMA Cardiol: 12 Nov 2019; epub ahead of print
Fanaroff AC, Peterson ED, Kaltenbach LA, Cannon CP, ... Fonarow GC, Wang TY
JAMA Cardiol: 12 Nov 2019; epub ahead of print | PMID: 31721978
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Abstract

Association Between Aging of the US Population and Heart Disease Mortality From 2011 to 2017.

Sidney S, Go AS, Jaffe MG, Solomon MD, Ambrosy AP, Rana JS
Importance
A deceleration in the rate of decrease of heart disease (HD) mortality between 2011 and 2014 has been reported. In the context of the rapid increase in the population of adults aged 65 years and older, extending the examination of HD mortality through 2017 has potentially important implications for public health and medical care.
Objective
To examine changes in the age-adjusted mortality rate and the number of deaths within subcategories of HD from 2011 to 2017 in conjunction with the change in the size of the US population during the same period.
Design, setting, and participants
In this quality improvement study, the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) data set was used to identify national changes in the US population aged 65 years and older and in the age-adjusted mortality rates and number of deaths that were listed with an underlying cause of HD, coronary heart disease (CHD), heart failure, and other HDs from January 1, 2011, to December 31, 2017.
Main outcomes and measures
Changes from 2011 to 2017 in the US population and in age-adjusted mortality rates and number of deaths that were listed with an underlying cause of HD, CHD, heart failure (both as an underlying and a contributing cause), and other HDs overall, by sex and race/ethnicity.
Results
The total size of this population of US adults aged 65 years and older increased 22.9% from 41.4 million to 50.9 million between January 1, 2011, and December 31, 2017, while the population of adults younger than 65 years increased by only 1.7%. During this period, the age-adjusted mortality rate decreased 5.0% for HD and 14.9% for CHD while increasing 20.7% for heart failure and 8.4% for other HDs. The number of deaths increased 8.5% for HD, 38.0% for heart failure, and 23.4% for other HDs while decreasing 2.5% for CHD. A total of 80% of HD deaths occurred in the group of adults aged 65 years and older.
Conclusions and relevance
The substantial increase in the growth rate of the group of adults aged 65 years and older who have the highest risk of HD was associated with an increase in the number of HD deaths in this group despite a slowly declining HD mortality rate in the general population. With the number of adults aged 65 years and older projected to increase an additional 44% from 2017 to 2030, innovative and effective approaches to prevent and treat HD, particularly the substantially increasing rates of heart failure, are needed.



JAMA Cardiol: 29 Oct 2019; epub ahead of print
Sidney S, Go AS, Jaffe MG, Solomon MD, Ambrosy AP, Rana JS
JAMA Cardiol: 29 Oct 2019; epub ahead of print | PMID: 31663094
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Abstract

Weight Gain, Hypertension, and the Emergence of a Maladaptive Cardiovascular Phenotype Among US Football Players.

Kim JH, Hollowed C, Liu C, Al-Badri A, ... Quyyumi AA, Baggish AL
Importance
Former US football athletes are at increased risk of cardiovascular (CV) morbidity and mortality compared with the general population and other professional athletes. However, responsible maladaptive CV phenotypes have not been fully characterized.
Objective
To address the emergence and progression of multiple independent factors associated with CV risk across serial years of collegiate US football participation.
Design, setting, and participants
Collegiate US football athletes from 2 National Collegiate Athletic Association Division I programs were recruited as freshmen between June 2014 and June 2017 and analyzed at multiple points throughout 3 complete years of collegiate US football participation (until January 2019). Excluded athletes were those who did not complete any season of US football training because of injury, illness, or leaving the team. Factors associated with CV risk assessed clinically, by transthoracic echocardiography, and by vascular applanation tonometry were recorded.
Exposures
The exposure of interest was seasonal US football exposure, including training, competition, and the training environment.
Main outcomes and measures
Primary outcome measures were left ventricular mass index and geometry (cardiac structure), early diastolic myocardial relaxation velocity (E\'; diastolic function), and pulse-wave velocity (arterial stiffness).
Results
Of 186 individuals recruited as freshmen, 126 athletes were included in analyzed data. Collegiate US football athletes (62 white individuals [49%]; 63 black individuals [50%]; 77 nonlinemen [61%]; 49 linemen [39%]; 126 male individuals [100%]) weighed a mean (SD) of 101.1 (21.0) kg, with a mean systolic blood pressure of 129.1 (11.6) mm Hg at baseline of the freshman season. Adjusting for race, height, and player position, there were significant increases in weight (mean [SE] Δ, 4.74 [0.6] kg; P < .001), systolic blood pressure (mean [SE] Δ, 11.6 [1.6] mm Hg; P < .001), and pulse-wave velocity (mean [SE] Δ, 0.24 [0.09] m/s; P = .007), and significant declines in E\' (mean [SE] Δ, -1.7 [0.3] cm/s; P < .001) across 3 years of US football participation. Weight gain was associated with both arterial stiffening (increased pulse-wave velocity, β = 0.01 [SE, 0.004]; P = .003) and the development of concentric left ventricular hypertrophy (odds ratio, 1.09 [95% CI, 1.05-1.14]; P < .001); increased systolic blood pressure was also associated with arterial stiffening (β = 0.01 [SE, 0.003]; P = .007) and the development of concentric left ventricular hypertrophy (odds ratio, 1.04 [95% CI, 1.01-1.07]; P = .02).
Conclusions and relevance
Collegiate US football athletes who gain weight and develop increased systolic blood pressure levels are at risk for the development of a pathologic CV phenotype characterized by concentric left ventricular hypertrophy, arterial stiffening, and reduced left ventricular diastolic function. Future work aimed at optimizing CV health in this population, who are young but uniquely at risk, is warranted.



JAMA Cardiol: 15 Oct 2019; epub ahead of print
Kim JH, Hollowed C, Liu C, Al-Badri A, ... Quyyumi AA, Baggish AL
JAMA Cardiol: 15 Oct 2019; epub ahead of print | PMID: 31617867
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Abstract

Association of Mild Echocardiographic Pulmonary Hypertension With Mortality and Right Ventricular Function.

Huston JH, Maron BA, French J, Huang S, ... Hemnes AR, Brittain EL
Importance
Current guidelines recommend evaluation for echocardiographically estimated right ventricular systolic pressure (RVSP) greater than 40 mm Hg; however, this threshold does not capture all patients at risk.
Objectives
To determine if mild echocardiographic pulmonary hypertension (ePH) is associated with reduced right ventricular (RV) function and increased risk of mortality.
Design, setting, and participants
In this cohort study, electronic health record data of patients who were referred for echocardiography at Vanderbilt University Medical Center, Nashville, Tennessee, from March 1997 to February 2014 and had recorded estimates of RVSP values were studied. Data were analyzed from February 2017 to May 2019.
Exposures
Mild ePH was defined as an RVSP value of 33 to 39 mm Hg. Right ventricular function was assessed using tricuspid annular plane systolic excursion (TAPSE), and RV-pulmonary arterial coupling was measured using the ratio of TAPSE to RVSP.
Main outcomes and measures
Associations of mild ePH with mortality adjusted for relevant covariates were examined using Cox proportional hazard models with restricted cubic splines.
Results
Of the 47 784 included patients, 26 758 of 47 771 (56.0%) were female and 6040 of 44 763 (13.5%) were black, and the mean (SD) age was 59 (18) years. Patients with mild ePH had worse RV function compared with those with no ePH (mean [SD] TAPSE, 2.0 [0.6] cm vs 2.2 [0.5] cm; P < .001) and nearly double the prevalence of RV dysfunction (32.6% [92 of 282] vs 16.7% [170 of 1015]; P < .001). Compared with patients with RVSP less than 33 mm Hg, those with mild ePH also had reduced RV-pulmonary arterial coupling (mean [SD] ratio of TAPSE to RVSP, 0.55 [0.18] mm/mm Hg vs 0.93 [0.39] mm/mm Hg; P < .001). An increase in adjusted mortality began at an RVSP value of 27 mm Hg (hazard ratio, 1.32; 95% CI, 1.02-1.70). Female sex was associated with increased mortality risk at any given RVSP value.
Conclusions and relevance
Mild ePH was associated with RV dysfunction and worse RV-pulmonary arterial coupling in a clinical population seeking care. Future studies are needed to identify patients with mild ePH who are susceptible to adverse outcomes.



JAMA Cardiol: 17 Sep 2019; epub ahead of print
Huston JH, Maron BA, French J, Huang S, ... Hemnes AR, Brittain EL
JAMA Cardiol: 17 Sep 2019; epub ahead of print | PMID: 31532457
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Abstract

Population-Attributable Risk for Cardiovascular Disease Associated With Hypertension in Black Adults.

Clark D, Colantonio LD, Min YI, Hall ME, ... Correa A, Muntner P
Importance
The prevalence of hypertension and the risk for hypertension-related cardiovascular disease (CVD) are high among black adults. The population-attributable risk (PAR) accounts for both prevalence and excess risk of disease associated with a risk factor.
Objective
To examine the PAR for CVD associated with hypertension among black adults.
Design, setting, and participants
This prospective cohort study used data on 12 497 black participants older than 21 years without CVD at baseline who were enrolled in the Jackson Heart Study (JHS) from September 26, 2000, through March 31, 2004, and cardiovascular events were adjudicated through December 31, 2015. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants were enrolled from July 1, 2003, through September 12, 2007, and cardiovascular events were adjudicated through March 31, 2016. Data analysis was performed from March 26, 2018, through July 10, 2019.
Exposures
Normal blood pressure and hypertension were defined using the 2017 American College of Cardiology/American Heart Association blood pressure guideline thresholds.
Main outcomes and measures
The PAR for CVD associated with hypertension, calculated using multivariable-adjusted hazard ratios (HRs) for CVD, coronary heart disease, heart failure, and stroke associated with hypertension vs normal blood pressure. Prevalence of hypertension among non-Hispanic black US adults 21 years and older without CVD was calculated using data from the National Health and Nutrition Examination Survey, 2011-2014.
Results
Of 12 497 participants, 1935 had normal blood pressure (638 [33.0%] male; mean [SD] age, 53.5 [12.4] years), 929 had elevated blood pressure (382 [41.1%] male; mean [SD] age, 58.6 [11.8] years), and 9633 had hypertension (3492 [36.3%] male; mean [SD] age, 62.0 [10.3] years). For a maximum 14.3 years of follow-up, 1235 JHS and REGARDS study participants (9.9%) experienced a CVD event. The multivariable-adjusted HR associated with hypertension was 1.91 (95% CI, 1.48-2.46) for CVD, 2.41 (95% CI,1.59-3.66) for coronary heart disease, 1.52 (95% CI, 1.01-2.30) for heart failure, and 2.20 (95% CI, 1.44-3.36) for stroke. The prevalence of hypertension was 53.2% among non-Hispanic black individuals. The PAR associated with hypertension was 32.5% (95% CI, 20.5%-43.6%) for CVD, 42.7% (95% CI, 24.0%-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6%-40.8%) for heart failure, and 38.9% (95% CI, 19.4%-55.6%) for stroke. The PAR was higher among those younger than 60 years (54.6% [95% CI, 37.2%-68.7%]) compared with those 60 years or older (32.0% [95% CI, 11.9%-48.1%]). No differences were present in subgroup analyses.
Conclusions and relevance
These findings suggest that a substantial proportion of CVD cases among black individuals are associated with hypertension. Interventions to maintain normal blood pressure throughout the life course may reduce the incidence of CVD in this population.



JAMA Cardiol: 22 Oct 2019:1-9; epub ahead of print
Clark D, Colantonio LD, Min YI, Hall ME, ... Correa A, Muntner P
JAMA Cardiol: 22 Oct 2019:1-9; epub ahead of print | PMID: 31642869
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Abstract

Association of Circulating Metabolites With Risk of Coronary Heart Disease in a European Population: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

Cavus E, Karakas M, Ojeda FM, Kontto J, ... Zeller T,
Importance
Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment.
Objective
To evaluate the association between circulating metabolites and incident CHD in a large European cohort.
Design, setting, and participants
This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-Sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom).
Main outcomes and measures
Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices.
Results
In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics.
Conclusions and relevance
Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.



JAMA Cardiol: 29 Oct 2019:1-10; epub ahead of print
Cavus E, Karakas M, Ojeda FM, Kontto J, ... Zeller T,
JAMA Cardiol: 29 Oct 2019:1-10; epub ahead of print | PMID: 31664431
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Abstract

Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection.

Chai JC, Deik AA, Hua S, Wang T, ... Clish CB, Qi Q
Importance
Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood.
Objective
To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV.
Design, setting, and participants
Prospective analysis in the Women\'s Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019.
Exposures
Two hundred eleven plasma lipid species.
Main outcomes and measures
Poisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging.
Results
Of the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque.
Conclusions and relevance
This study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.



JAMA Cardiol: 22 Oct 2019; epub ahead of print
Chai JC, Deik AA, Hua S, Wang T, ... Clish CB, Qi Q
JAMA Cardiol: 22 Oct 2019; epub ahead of print | PMID: 31642867
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Impact:
Abstract

Prediction of Pulmonary to Systemic Flow Ratio in Patients With Congenital Heart Disease Using Deep Learning-Based Analysis of Chest Radiographs.

Toba S, Mitani Y, Yodoya N, Ohashi H, ... Shimpo H, Takao M
Importance
Chest radiography is a useful noninvasive modality to evaluate pulmonary blood flow status in patients with congenital heart disease. However, the predictive value of chest radiography is limited by the subjective and qualitive nature of the interpretation. Recently, deep learning has been used to analyze various images, but it has not been applied to analyzing chest radiographs in such patients.
Objective
To develop and validate a quantitative method to predict the pulmonary to systemic flow ratio from chest radiographs using deep learning.
Design, setting, and participants
This retrospective observational study included 1031 cardiac catheterizations performed for 657 patients from January 1, 2005, to April 30, 2019, at a tertiary center. Catheterizations without the Fick-derived pulmonary to systemic flow ratio or chest radiography performed within 1 month before catheterization were excluded. Seventy-eight patients (100 catheterizations) were randomly assigned for evaluation. A deep learning model that predicts the pulmonary to systemic flow ratio from chest radiographs was developed using the method of transfer learning.
Main outcomes and measures
Whether the model can predict the pulmonary to systemic flow ratio from chest radiographs was evaluated using the intraclass correlation coefficient and Bland-Altman analysis. The diagnostic concordance rate was compared with 3 certified pediatric cardiologists. The diagnostic performance for a high pulmonary to systemic flow ratio of 2.0 or more was evaluated using cross tabulation and a receiver operating characteristic curve.
Results
The study included 1031 catheterizations in 657 patients (522 males [51%]; median age, 3.4 years [interquartile range, 1.2-8.6 years]), in whom the mean (SD) Fick-derived pulmonary to systemic flow ratio was 1.43 (0.95). Diagnosis included congenital heart disease in 1008 catheterizations (98%). The intraclass correlation coefficient for the Fick-derived and deep learning-derived pulmonary to systemic flow ratio was 0.68, the log-transformed bias was 0.02, and the log-transformed precision was 0.12. The diagnostic concordance rate of the deep learning model was significantly higher than that of the experts (correctly classified 64 of 100 vs 49 of 100 chest radiographs; P = .02 [McNemar test]). For detecting a high pulmonary to systemic flow ratio, the sensitivity of the deep learning model was 0.47, the specificity was 0.95, and the area under the receiver operating curve was 0.88.
Conclusions and relevance
The present investigation demonstrated that deep learning-based analysis of chest radiographs predicted the pulmonary to systemic flow ratio in patients with congenital heart disease. These findings suggest that the deep learning-based approach may confer an objective and quantitative evaluation of chest radiographs in the congenital heart disease clinic.



JAMA Cardiol: 21 Jan 2020; epub ahead of print
Toba S, Mitani Y, Yodoya N, Ohashi H, ... Shimpo H, Takao M
JAMA Cardiol: 21 Jan 2020; epub ahead of print | PMID: 31968049
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Impact:
Abstract

Apolipoprotein B Particles and Cardiovascular Disease: A Narrative Review.

Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, ... Catapano A, Ference BA
Importance
The conventional model of atherosclerosis presumes that the mass of cholesterol within very low-density lipoprotein particles, low-density lipoprotein particles, chylomicron, and lipoprotein (a) particles in plasma is the principal determinant of the mass of cholesterol that will be deposited within the arterial wall and will drive atherogenesis. However, each of these particles contains one molecule of apolipoprotein B (apoB) and there is now substantial evidence that apoB more accurately measures the atherogenic risk owing to the apoB lipoproteins than does low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol.
Observations
Cholesterol can only enter the arterial wall within apoB particles. However, the mass of cholesterol per apoB particle is variable. Therefore, the mass of cholesterol that will be deposited within the arterial wall is determined by the number of apoB particles that are trapped within the arterial wall. The number of apoB particles that enter the arterial wall is determined primarily by the number of apoB particles within the arterial lumen. However, once within the arterial wall, smaller cholesterol-depleted apoB particles have a greater tendency to be trapped than larger cholesterol-enriched apoB particles because they bind more avidly to the glycosaminoglycans within the subintimal space of the arterial wall. Thus, a cholesterol-enriched particle would deposit more cholesterol than a cholesterol-depleted apoB particle whereas more, smaller apoB particles that enter the arterial wall will be trapped than larger apoB particles. The net result is, with the exceptions of the abnormal chylomicron remnants in type III hyperlipoproteinemia and lipoprotein (a), all apoB particles are equally atherogenic.
Conclusions and relevance
Apolipoprotein B unifies, amplifies, and simplifies the information from the conventional lipid markers as to the atherogenic risk attributable to the apoB lipoproteins.



JAMA Cardiol: 22 Oct 2019; epub ahead of print
Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, ... Catapano A, Ference BA
JAMA Cardiol: 22 Oct 2019; epub ahead of print | PMID: 31642874
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Impact:
Abstract

Association of Cardiovascular Disease With Premature Mortality in the United States.

Chen Y, Freedman ND, Albert PS, Huxley RR, ... Powell-Wiley TM, Berrington de González A
Importance
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the United States. Despite substantial declines in CVD mortality rates during past decades, progress against cardiovascular deaths in midlife has stagnated, with rates increased in some US racial/ethnic groups.
Objective
To examine the trends in premature (ages 25-64 years) mortality from CVD from 2000 to 2015 by demographics and county-level factors, including education, rurality, and the prevalence of smoking, obesity, and diabetes.
Design, setting, and participants
This descriptive study used US national mortality data from the Surveillance, Epidemiology, and End Results data set and included all CVD deaths among individuals ages 25 to 64 years from January 2000 to December 2015. The data analysis began in February 2018.
Exposures
Age, sex, race/ethnicity, and county-level factors.
Main outcomes and measures
Age-standardized mortality rates and average annual percent change (AAPC) in rates by age, sex, race/ethnicity, and county-level factors (in quintiles) and relative risks of CVD mortality across quintiles of each county-level factor.
Results
In 2000 to 2015, 2.3 million CVD deaths occurred among individuals age 25 to 64 years in the United States. There were significant declines in CVD mortality for black, Latinx, and Asian and Pacific Islander individuals (AAPC: range, -1.7 to -3.2%), although black people continued to have the highest CVD mortality rates. Mortality rates were second highest for American Indian/Alaskan Native individuals and increased significantly among those aged 25 to 49 years (AAPC: women, 2.1%; men, 1.3%). For white individuals, mortality rates plateaued among women age 25 to 49 years (AAPC, 0.05%). Declines in mortality rates were observed for most major CVD subtypes except for ischemic heart disease, which was stable in white women and increased in American Indian/Alaska Native women, hypertensive heart disease, for which significant increases in rates were observed in most racial/ethnic groups, and endocarditis, for which rates increased in white individuals and American Indian/Alaska Native men. Counties with the highest prevalence of diabetes (quintile 5 vs quintile 1: relative risk range 1.6-1.8 for white individuals and 1.4-1.6 for black individuals) had the most risk of CVD mortality.
Conclusions and relevance
There have been substantial declines in premature CVD mortality in much of the US population. However, increases in CVD mortality before age 50 years among American Indian/Alaska Native individuals, flattening rates in white people, and overall increases in deaths from hypertensive disease suggest that targeted public health interventions are needed to prevent these premature deaths.



JAMA Cardiol: 15 Oct 2019; epub ahead of print
Chen Y, Freedman ND, Albert PS, Huxley RR, ... Powell-Wiley TM, Berrington de González A
JAMA Cardiol: 15 Oct 2019; epub ahead of print | PMID: 31617863
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Impact:
Abstract

Effect of Face-to-Face vs Virtual Reality Training on Cardiopulmonary Resuscitation Quality: A Randomized Clinical Trial.

Nas J, Thannhauser J, Vart P, van Geuns RJ, ... Bonnes JL, Brouwer MA
Importance
Bystander cardiopulmonary resuscitation (CPR) is crucial for survival after cardiac arrest but not performed in most cases. New, low-cost, and easily accessible training methods, such as virtual reality (VR), may reach broader target populations, but data on achieved CPR skills are lacking.
Objective
To compare CPR quality between VR and face-to-face CPR training.
Design, setting, and participants
Randomized noninferiority trial with a prospective randomized open blinded end point design. Participants were adult attendees from the science section of the Lowlands Music Festival (August 16 to 18, 2019) in the Netherlands. Analysis began September 2019.
Interventions
Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training or VR training using a smartphone app endorsed by the Resuscitation Council (United Kingdom).
Main outcomes and measures
During a standardized CPR scenario following the training, we assessed the primary outcome CPR quality, measured as chest compression depth and rate using CPR manikins. Overall CPR performance was assessed by examiners, blinded for study groups, using a European Resuscitation Council-endorsed checklist (maximum score, 13). Additional secondary outcomes were chest compression fraction, proportions of participants with mean depth (50 mm-60 mm) or rate (100 min-1-120 min-1) within guideline ranges, and proportions compressions with full release.
Results
A total of 381 participants were randomized: 216 women (57%); median (interquartile range [IQR]) age, 26 (22-31) years. The VR app (n = 190 [49.9%]) was inferior to face-to-face training (n = 191 [50.1%]) for chest compression depth (mean [SD], VR: 49 [10] mm vs face to face: 57 [5] mm; mean [95% CI] difference, -8 [-9 to -6] mm), and noninferior for chest compression rate (mean [SD]: VR: 114 [12] min-1 vs face to face: 109 [12] min-1; mean [95% CI] difference, 6 [3 to 8] min-1). The VR group had lower overall CPR performance scores (median [IQR], 10 [8-12] vs 12 [12-13]; P < .001). Chest compression fraction (median [IQR], 61% [52%-66%] vs 67% [62%-71%]; P < .001) and proportions of participants fulfilling depth (51% [n = 89] vs 75% [n = 133], P < .001) and rate (50% [n = 87] vs 63% [n = 111], P = .01) requirements were also lower in the VR group. The proportion of compressions with full release was higher in the VR group (median [IQR], 98% [59%-100%] vs 88% [55%-99%]; P = .002).
Conclusions and relevance
In this randomized noninferiority trial, VR training resulted in comparable chest compression rate but inferior compression depth compared with face-to-face training. Given the potential of VR training to reach a larger target population, further development is needed to achieve the compression depth and overall CPR skills acquired by face-to-face training.
Trial registration
ClinicalTrials.gov identifier: NCT04013633.



JAMA Cardiol: 16 Nov 2019; epub ahead of print
Nas J, Thannhauser J, Vart P, van Geuns RJ, ... Bonnes JL, Brouwer MA
JAMA Cardiol: 16 Nov 2019; epub ahead of print | PMID: 31734702
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Impact:
Abstract

Sex Differences in Cardiometabolic Traits and Determinants of Exercise Capacity in Heart Failure With Preserved Ejection Fraction.

Lau ES, Cunningham T, Hardin KM, Liu E, ... Lewis GD, Ho JE
Importance
Sex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited.
Objective
To examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF.
Design, setting, and participants
This cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019.
Main outcomes and measures
Resting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing.
Results
Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-0.90, SE=0.22; P < .001)).
Conclusions and relevance
Despite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further.



JAMA Cardiol: 29 Oct 2019; epub ahead of print
Lau ES, Cunningham T, Hardin KM, Liu E, ... Lewis GD, Ho JE
JAMA Cardiol: 29 Oct 2019; epub ahead of print | PMID: 31664435
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Abstract

Association of Cardiac Rehabilitation With Decreased Hospitalization and Mortality Risk After Cardiac Valve Surgery.

Patel DK, Duncan MS, Shah AS, Lindman BR, ... Freiberg MS, Bachmann JM
Importance
National guidelines recommend cardiac rehabilitation (CR) after cardiac valve surgery, and CR is covered by Medicare for this indication. However, few data exist regarding current CR enrollment after valve surgery.
Objective
To characterize CR enrollment after cardiac valve surgery and its association with outcomes, including hospitalizations and mortality.
Design, setting, and participants
This cohort study of patients undergoing valve surgery was conducted in calendar year 2014, with follow-up through 2015. The study included all fee-for-service Medicare beneficiaries undergoing open cardiac valve surgery in 2014. Patients identified by inpatient diagnosis codes for open aortic, mitral, tricuspid, and pulmonary valve surgery were included. Data analysis occurred from January 2018 to March 2019.
Exposures
Logistic regression was used to evaluate sociodemographic and clinical factors associated with CR enrollment.
Main outcomes and measures
We used Andersen-Gill models to evaluate the association of CR enrollment with 1-year hospitalization risk and Cox regression models to evaluate the association of CR enrollment with 1-year mortality risk.
Results
A total of 41 369 Medicare beneficiaries (median [interquartile range] age, 73 [68-79] years; 16 935 [40.9%] female) underwent open valve surgery in the United States in 2014. Fewer than half of patients (17 855 [43.2%]) who had valve surgery enrolled in CR programs. Several racial/ethnic groups had lower odds of enrolling in CR programs after valve surgery compared with white patients, including Asian patients (odds ratio [OR], 0.36 [95% CI, 0.28-0.47]), black patients (OR, 0.60 [95% CI, 0.54-0.67]), and Hispanic patients (OR, 0.36 [95% CI, 0.28-0.46]). Patients undergoing concomitant coronary artery bypass grafting had higher odds of CR enrollment (OR, 1.26 [95% CI, 1.20-1.31]) than those without the concomitant coronary artery bypass graft procedure, as did patients in the Midwest census region (OR, 2.40 [95% CI, 2.28-2.54]) compared with those in the South (reference). Cardiac rehabilitation enrollment was associated with fewer hospitalizations within 1 year of discharge (hazard ratio, 0.66 [95% CI, 0.63-0.69] after multivariable adjustment). Enrollment was also associated with a 4.2% absolute decrease in 1-year mortality risk (hazard ratio, 0.39 [95% CI, 0.35-0.44] after multivariable adjustment).
Conclusions and relevance
Fewer than half of Medicare beneficiaries undergoing cardiac valve surgery enroll in CR programs, and there are marked racial/ethnic disparities among those that do. Cardiac rehabilitation is associated with decreased 1-year cumulative hospitalization and mortality risk after valve surgery. These results invite further study on barriers to CR enrollment in this population.



JAMA Cardiol: 22 Oct 2019; epub ahead of print
Patel DK, Duncan MS, Shah AS, Lindman BR, ... Freiberg MS, Bachmann JM
JAMA Cardiol: 22 Oct 2019; epub ahead of print | PMID: 31642866
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Impact:
Abstract

Asymptomatic Degenerative Mitral Regurgitation: A Review.

Flint N, Raschpichler M, Rader F, Shmueli H, Siegel RJ
Importance
Most patients with severe degenerative mitral regurgitation (DMR) are likely to require surgery, but years can pass until there is a clear indication for it. The timing of mitral valve surgery for asymptomatic patients with severe DMR is controversial, and current guidelines are limited because they are based on nonrandomized studies and expert opinion.
Observations
In this narrative review, a decrease in left ventricular ejection fraction and an increase in left ventricular end-systolic diameter are adverse signs in the context of mitral regurgitation. Consequently, serial echocardiography is essential. However, measurements may be imprecise, and the evidence regarding the association with outcome in asymptomatic patients is inconsistent. Mitral valve repair is the preferred surgical approach; however, repair rate, durability, and outcomes vary between centers, rendering decision-making in an asymptomatic patient with DMR even more challenging. The use of natriuretic peptides, stress testing, cardiac magnetic resonance imaging, and myocardial strain imaging can aid in risk stratification and optimization of the timing of mitral valve surgery in an asymptomatic patient.
Conclusions and relevance
Management of asymptomatic patients with DMR requires a comprehensive approach that goes beyond the guidelines. Close follow-up and the use of multiple modalities are recommended. Knowledge of surgical options, experience, and outcomes is important when an intervention is considered.



JAMA Cardiol: 28 Jan 2020; epub ahead of print
Flint N, Raschpichler M, Rader F, Shmueli H, Siegel RJ
JAMA Cardiol: 28 Jan 2020; epub ahead of print | PMID: 31995124
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Impact:
Abstract

Association of Race With Disease Expression and Clinical Outcomes Among Patients With Hypertrophic Cardiomyopathy.

Eberly LA, Day SM, Ashley EA, Jacoby DL, ... Ho CY, Lakdawala NK
Importance
Racial differences are recognized in multiple cardiovascular parameters, including left ventricular hypertrophy and heart failure, which are 2 major manifestations of hypertrophic cardiomyopathy. The association of race with disease expression and outcomes among patients with hypertrophic cardiomyopathy is not well characterized.
Objective
To assess the association between race, disease expression, care provision, and clinical outcomes among patients with hypertrophic cardiomyopathy.
Design, setting, and participants
This retrospective cohort study included data on black and white patients with hypertrophic cardiomyopathy from the US-based sites of the Sarcomeric Human Cardiomyopathy Registry from 1989 through 2018.
Exposures
Self-identified race.
Main outcomes and measures
Baseline characteristics; genetic architecture; adverse outcomes, including cardiac arrest, cardiac transplantation or left ventricular assist device implantation, implantable cardioverter-defibrillator therapy, all-cause mortality, atrial fibrillation, stroke, and New York Heart Association (NYHA) functional class III or IV heart failure; and septal reduction therapies. The overall composite outcome consists of the first occurrence of any component of the ventricular arrhythmic composite end point, cardiac transplantation, left ventricular assist device implantation, NYHA class III or IV heart failure, atrial fibrillation, stroke, or all-cause mortality.
Results
Of 2467 patients with hypertrophic cardiomyopathy at the time of analysis, 205 (8.3%) were black (130 male [63.4%]; mean [SD] age, 40.0 [18.6] years) and 2262 (91.7%) were white (1351 male [59.7%]; mean [SD] age, 45.5 [20.5] years). Compared with white patients, black patients were younger at the time of diagnosis (mean [SD], 36.5 [18.2] vs 41.9 [20.2] years; P < .001), had higher prevalence of NYHA class III or IV heart failure at presentation (36 of 205 [22.6%] vs 174 of 2262 [15.8%]; P = .001), had lower rates of genetic testing (111 [54.1%] vs 1404 [62.1%]; P = .03), and were less likely to have sarcomeric mutations identified by genetic testing (29 [26.1%] vs 569 [40.5%]; P = .006). Implantation of implantable cardioverter-defibrillators did not vary by race; however, invasive septal reduction was less common among black patients (30 [14.6%] vs 521 [23.0%]; P = .007). Black patients had less incident atrial fibrillation (35 [17.1%] vs 608 [26.9%]; P < .001). Black race was associated with increased development of NYHA class III or IV heart failure (hazard ratio, 1.45; 95% CI, 1.08-1.94) which persisted on multivariable Cox proportional hazards regression (hazard ratio, 1.97; 95% CI, 1.34-2.88). There were no differences in the associations of race with stroke, ventricular arrhythmias, all-cause mortality, or the overall composite outcome.
Conclusions and relevance
The findings suggest that black patients with hypertrophic cardiomyopathy are diagnosed at a younger age, are less likely to carry a sarcomere mutation, have a higher burden of functionally limited heart failure, and experience inequities in care with lower use of invasive septal reduction therapy and genetic testing compared with white patients. Further study is needed to assess whether higher rates of heart failure may be associated with underlying ancestry-based disease pathways, clinical management, or structural inequities.



JAMA Cardiol: 03 Dec 2019; epub ahead of print
Eberly LA, Day SM, Ashley EA, Jacoby DL, ... Ho CY, Lakdawala NK
JAMA Cardiol: 03 Dec 2019; epub ahead of print | PMID: 31799990
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Impact:
Abstract

Patient Perceptions and Familiarity With Medical Therapy for Heart Failure.

Samsky MD, Lin L, Greene SJ, Lippmann SJ, ... Fonarow GC, O\'Brien EC
Importance
There are major gaps in use of guideline-directed medical therapy (GDMT) for patients with heart failure (HF). Patient-reported data outlining patient goals and preferences associated with GDMT are not available.
Objective
To survey patients with chronic HF to better understand their experiences and perceptions of living with HF, including their familiarity and concerns with important GDMT therapies.
Design, setting, and participants
Study participants were recruited from the GfK KnowledgePanel, a probability-sampled online panel representative of the US adult population. English-speaking adults who met the following criteria were eligible if they were (1) previously told by a physician that they had HF; (2) currently taking medications for HF; and (3) had no history of left ventricular assist device or cardiac transplant. Data were collected between October and November 2018. Analysis began in December 2018.
Main outcomes and measures
The survey included 4 primary domains: (1) relative importance of disease-related goals, (2) challenges associated with living with HF, (3) decision-making process associated with HF medication use, and (4) awareness and concerns about available HF medications.
Results
Of 30 707 KnowledgePanel members who received the initial survey, 15 091 (49.1%) completed the screening questions, 440 were eligible and began the survey, and 429 completed the survey. The median (interquartile range) age was 68 (60-75) years and most were white (320 [74.6%]), male (304 [70.9%]), and had at least a high school education (409 [95.3%]). Most survey responders reported familiarity with β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. Overall, 107 (24.9%) reported familiarity with angiotensin receptor-neprilysin inhibitors or mineralocorticoid receptor antagonists. Overall, 136 patients (42.5%) reported have safety concerns regarding angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 133 (38.5%) regarding β-blockers, 35 (37.9%) regarding mineralocorticoid receptor antagonists, 38 (36.5%) regarding angiotensin receptor-neprilysin inhibitors, and 123 (37.2%) regarding diuretics. Between 27.7% (n = 26) and 38.5% (n = 136) reported concerns regarding the effectiveness of β-blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, or diuretics, while 41% (n = 132) were concerned with the effectiveness of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers.
Conclusions and relevance
In this survey study, many patients were not familiar with GDMT for HF, with familiarity lowest for angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists. Among patients not familiar with these therapies, significant proportions questioned their effectiveness and/or safety. Enhanced patient education and shared decision-making support may be effective strategies to improve the uptake of GDMT for HF in US clinical practice.



JAMA Cardiol: 16 Nov 2019; epub ahead of print
Samsky MD, Lin L, Greene SJ, Lippmann SJ, ... Fonarow GC, O'Brien EC
JAMA Cardiol: 16 Nov 2019; epub ahead of print | PMID: 31734700
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Impact:
Abstract

Adjunctive Antithrombotic Therapy for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement.

Saito Y, Nazif T, Baumbach A, Tchétché D, ... Prendergast B, Lansky A
Importance
Transcatheter aortic valve replacement (TAVR) is an established alternative to surgery for patients with severe symptomatic aortic stenosis. Adjunctive antithrombotic therapy used to mitigate thrombotic risks in patients undergoing TAVR must be balanced against bleeding complications, since both are associated with increased mortality.
Observation
Stroke risk associated with TAVR is lower than that associated with surgical aortic valve replacement in recent trials including patients at intermediate or low risk, but it is constant beginning at the time of implant and accrues over time based on patient risk factors. Patients with aortic stenosis undergoing TAVR also have a sizable risk of life-threatening or major bleeding. Although dual antiplatelet therapy for 3 to 6 months after TAVR is the guideline-recommended regimen, this practice is not well supported by current evidence. In patients with no indication for oral anticoagulation, current registry-based evidence suggests that single antiplatelet therapy may be safer than dual antiplatelet therapy. Similarly, oral anticoagulation monotherapy appears superior to anticoagulation plus antiplatelet therapy in those where oral anticoagulant use is indicated. To date, no risk prediction models have been established to guide antithrombotic therapy.
Conclusions and relevance
Despite the growing volume of TAVR procedures to treat patients with severe aortic stenosis, evidence for adjunctive antithrombotic therapy remains rather scarce. Ongoing clinical trials will provide better understanding to guide antithrombotic therapy.



JAMA Cardiol: 12 Nov 2019; epub ahead of print
Saito Y, Nazif T, Baumbach A, Tchétché D, ... Prendergast B, Lansky A
JAMA Cardiol: 12 Nov 2019; epub ahead of print | PMID: 31721980
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Impact:
Abstract

Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure.

Ajijola OA, Chatterjee NA, Gonzales MJ, Gornbein J, ... Singh JP, Herring N
Importance
Chronic heart failure (CHF) is associated with increased sympathetic drive and may increase expression of the cotransmitter neuropeptide Y (NPY) within sympathetic neurons.
Objective
To determine whether myocardial NPY levels are associated with outcomes in patients with stable CHF.
Design, setting, and participants
Prospective observational cohort study conducted at a single-center, tertiary care hospital. Stable patients with heart failure undergoing elective cardiac resynchronization therapy device implantation between 2013 and 2015.
Main outcomes and measures
Chronic heart failure hospitalization, death, orthotopic heart transplantation, and ventricular assist device placement.
Results
Coronary sinus (CS) blood samples were obtained during cardiac resynchronization therapy (CRT) device implantation in 105 patients (mean [SD] age 68 [12] years; 82 men [78%]; mean [SD] left ventricular ejection fraction [LVEF] 26% [7%]). Clinical, laboratory, and outcome data were collected prospectively. Stellate ganglia (SG) were collected from patients with CHF and control organ donors for molecular analysis. Mean (SD) CS NPY levels were 85.1 (31) pg/mL. On bivariate analyses, CS NPY levels were associated with estimated glomerular filtration rate (eGFR; rs = -0.36, P < .001); N-terminal-pro hormone brain natriuretic peptide (rs = 0.33; P = .004), and LV diastolic dimension (rs = -0.35; P < .001), but not age, LVEF, functional status, or CRT response. Adjusting for GFR, age, and LVEF, the hazard ratio for event-free (death, cardiac transplant, or left ventricular assist device) survival for CS NPY ≥ 130 pg/mL was 9.5 (95% CI, 2.92-30.5; P < .001). Immunohistochemistry demonstrated significantly reduced NPY protein (mean [SD], 13.7 [7.6] in the cardiomyopathy group vs 31.4 [3.7] in the control group; P < .001) in SG neurons from patients with CHF while quantitative polymerase chain reaction demonstrated similar mRNA levels compared with control individuals, suggesting increased release from SG neurons in patients with CHF.
Conclusions and relevance
The CS levels of NPY may be associated with outcomes in patients with stable CHF undergoing CRT irrespective of CRT response. Increased neuronal traffic and release may be the mechanism for elevated CS NPY levels in patients with CHF. Further studies are warranted to confirm these findings.
Trial registration
ClinicalTrials.gov identifier: NCT01949246.



JAMA Cardiol: 25 Dec 2019; epub ahead of print
Ajijola OA, Chatterjee NA, Gonzales MJ, Gornbein J, ... Singh JP, Herring N
JAMA Cardiol: 25 Dec 2019; epub ahead of print | PMID: 31876927
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Impact:
Abstract

Association of Low-Density Lipoprotein Cholesterol With Risk of Aortic Valve Stenosis in Familial Hypercholesterolemia.

Mundal LJ, Hovland A, Igland J, Veierød MB, ... Leren TP, Retterstøl K
Importance
Aortic valve stenosis (AS) is the most common valve disease. Elevated levels of low-density lipoprotein (LDL) cholesterol are a risk factor; however, lipid-lowering treatment seems not to prevent progression of AS. The importance of LDL cholesterol in the development of AS thus remains unclear. People with familial hypercholesterolemia (FH) have elevated LDL cholesterol levels from birth and until lipid-lowering treatment starts. Thus, FH may serve as a model disease to study the importance of LDL cholesterol for the development of AS.
Objective
To compare the incidence of AS per year in all genetically proven patients with FH in Norway with the incidence of these diseases in the total Norwegian population of about 5 million people.
Design, setting, and participants
This is a registry-based prospective cohort study of all Norwegian patients with FH with regard to first-time AS between 2001 and 2009. All genotyped patients with FH in Norway were compared with the total Norwegian populations through linkage with the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry regarding occurrence of first-time AS. Data were analyzed between January 1, 2018, and December 31, 2018.
Main outcomes and measures
Standardized incidence ratios.
Results
In total, 53 cases of AS occurred among 3161 persons (1473 men [46.6%]) with FH during 18 300 person-years of follow-up. Mean age at inclusion and at time of AS were 39.9 years (range, 8-91 years) and 65 years (range, 44-88 years), respectively. Total standardized incidence ratios were 7.9 (95% CI, 6.1-10.4) for men and women combined, 8.5 (95% CI, 5.8-12.4) in women, and 7.4 (95% CI, 5.0-10.9) in men, respectively, indicating marked increased risk of AS compared with the general Norwegian population.
Conclusions and relevance
In this prospective registry study, we demonstrate a marked increase in risk of AS in persons with FH.



JAMA Cardiol: 15 Oct 2019; epub ahead of print
Mundal LJ, Hovland A, Igland J, Veierød MB, ... Leren TP, Retterstøl K
JAMA Cardiol: 15 Oct 2019; epub ahead of print | PMID: 31617858
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Impact:
Abstract

Identification of a Novel Homozygous Multi-Exon Duplication in RYR2 Among Children With Exertion-Related Unexplained Sudden Deaths in the Amish Community.

Tester DJ, Bombei HM, Fitzgerald KK, Giudicessi JR, ... Temple J, Ackerman MJ
Importance
The exome molecular autopsy may elucidate a pathogenic substrate for sudden unexplained death.
Objective
To investigate the underlying cause of multiple sudden deaths in young individuals and sudden cardiac arrests that occurred in 2 large Amish families.
Design, setting, and participants
Two large extended Amish families with multiple sudden deaths in young individuals and sudden cardiac arrests were included in the study. A recessive inheritance pattern was suggested based on an extended family history of sudden deaths in young individuals and sudden cardiac arrests, despite unaffected parents. A family with exercise-associated sudden deaths in young individuals occurring in 4 siblings was referred for postmortem genetic testing using an exome molecular autopsy. Copy number variant (CNV) analysis was performed on exome data using PatternCNV. Chromosomal microarray validated the CNV identified. The nucleotide break points of the CNV were determined by mate-pair sequencing. Samples were collected for this study between November 2004 and June 2019.
Main outcomes and measures
The identification of an underlying genetic cause for sudden deaths in young individuals and sudden cardiac arrests consistent with the recessive inheritance pattern observed in the families.
Results
A homozygous duplication, involving approximately 26 000 base pairs of intergenic sequence, RYR2\'s 5\'UTR/promoter region, and exons 1 through 4 of RYR2, was identified in all 4 siblings of a family. Multiple distantly related relatives experiencing exertion-related sudden cardiac arrest also had the identical RYR2 homozygous duplication. A second, unrelated family with multiple exertion-related sudden deaths and sudden cardiac arrests in young individuals, with the same homozygous duplication, was identified. Several living, homozygous duplication-positive symptomatic patients from both families had nondiagnostic cardiologic testing, with only occasional ventricular ectopy occurring during exercise stress tests.
Conclusions and relevance
In this analysis, we identified a novel, highly penetrant, homozygous multiexon duplication in RYR2 among Amish youths with exertion-related sudden death and sudden cardiac arrest but without an overt phenotype that is distinct from RYR2-mediated catecholaminergic polymorphic ventricular tachycardia. Considering that no cardiac tests reliably identify at-risk individuals and given the high rate of consanguinity in Amish families, identification of unaffected heterozygous carriers may provide potentially lifesaving premarital counseling and reproductive planning.



JAMA Cardiol: 07 Jan 2020; epub ahead of print
Tester DJ, Bombei HM, Fitzgerald KK, Giudicessi JR, ... Temple J, Ackerman MJ
JAMA Cardiol: 07 Jan 2020; epub ahead of print | PMID: 31913406
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Abstract

Association of Rare PTGIS Variants With Susceptibility and Pulmonary Vascular Response in Patients With Idiopathic Pulmonary Arterial Hypertension.

Wang XJ, Xu XQ, Sun K, Liu KQ, ... Zhang X, Jing ZC
Importance
Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. The genetic basis of IPAH needs further investigation.
Objective
To identify novel IPAH susceptibility genes other than BMPR2.
Design, setting, and participants
This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018.
Exposures
PTGIS rare variants.
Main outcomes and measures
Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing. Functional assessments were conducted to analyze the effects of identified genetic variants on transcript splicing, enzymatic activity, and endothelial cell phenotypes.
Results
Among 230 patients with IPAH (164 female [71.3%]; mean [SD] age, 34 [18] years), an enrichment of rare variants in a gene encoding prostacyclin synthase (PTGIS) was identified in the discovery cohort. The association of PTGIS rare variants with IPAH was confirmed in the replication cohort. In the combined data set, PTGIS rare variants were found in 14 of 230 cases (6.1%) and 8 of 968 controls (0.8%) (odds ratio, 7.8; 95% CI, 3.2-18.8; P = 5 × 10-6, logistic regression). Compared with patients without PTGIS variants, inhaled iloprost induced a more significant decrease of pulmonary vascular resistance (difference in the least square mean, -21.7%; 95% CI, -31.4% to -12.0%; P < .001, linear regression model) and an increase of cardiac index (difference in the least square mean, 18.3%; 95% CI, 8.8%-27.8%; P < .001, linear regression model) in patients with PTGIS variants. The minigene assay indicated that the c.521 + 1G>A variant resulted in aberrant messenger RNA transcripts. The functional studies showed that the 2 missense rare variants (R252Q and A447T) resulted in a decrease in prostacyclin production and increased cell death of pulmonary microvascular endothelial cells.
Conclusions and relevance
This study identified 3 rare loss-of-function variants in the PTGIS gene from 2 independent cohorts with IPAH. The genetic variants of PTGIS predispose pulmonary vascular responses to the iloprost stimulation. These findings suggest that PTGIS variants may be involved in the pathogenesis of IPAH.



JAMA Cardiol: 31 Mar 2020; epub ahead of print
Wang XJ, Xu XQ, Sun K, Liu KQ, ... Zhang X, Jing ZC
JAMA Cardiol: 31 Mar 2020; epub ahead of print | PMID: 32236489
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Impact:
Abstract

Sex Differences in Blood Pressure Trajectories Over the Life Course.

Ji H, Kim A, Ebinger JE, Niiranen TJ, ... Bairey Merz CN, Cheng S
Importance
If we assume that women and men exhibit variations of the same fundamental vascular physiology, then conventional analyses of subclinical measures would suggest that women catch up to men by midlife in the extent of potentially important vascular disease. Alternatively, under the assumption that vascular physiology may fundamentally differ between women and men, a sex-specific analysis of existing data could offer new insights and augment our understanding of sex differences in cardiovascular diseases.
Objective
To evaluate whether longitudinal patterns of blood pressure (BP) elevation differ between women and men during the life course when considering baseline BP levels as the reference.
Design setting, and participants
We conducted sex-specific analyses of longitudinal BP measures (144 599 observations) collected for a period of 43 years (1971 to 2014) in 4 community-based US cohort studies. The combined total included 32 833 participants (54% female) spanning ages 5 to 98 years. Data were analyzed between May 4, 2019, and August 5, 2019.
Exposures
Age and serially assessed longitudinal BP measures: systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure (PP).
Main outcomes and measures
Sex-specific change in each primary BP measure compared with baseline BP levels, derived from multilevel longitudinal models fitted over the age span, and new-onset cardiovascular disease events.
Results
Of the 32 833 participants, 17 733 were women (54%). Women compared with men exhibited a steeper increase in BP that began as early as in the third decade and continued through the life course (likelihood ratio test χ2 = 531 for systolic BP; χ2 = 123 for diastolic BP; χ2 = 325 for MAP; and χ2 = 572 for PP; P for all <.001). After adjustment for multiple cardiovascular disease risk factors, these between-sex differences in all BP trajectories persisted (likelihood ratio test χ2 = 314 for systolic BP; χ2 = 31 for diastolic BP; χ2 = 129 for MAP; and χ2 = 485 for PP; P for all <.001).
Conclusions and relevance
In contrast with the notion that important vascular disease processes in women lag behind men by 10 to 20 years, sex-specific analyses indicate that BP measures actually progress more rapidly in women than in men, beginning early in life. This early-onset sexual dimorphism may set the stage for later-life cardiovascular diseases that tend to present differently, not simply later, in women compared with men.



JAMA Cardiol: 14 Jan 2020; epub ahead of print
Ji H, Kim A, Ebinger JE, Niiranen TJ, ... Bairey Merz CN, Cheng S
JAMA Cardiol: 14 Jan 2020; epub ahead of print | PMID: 31940010
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Impact:
Abstract

Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease.

Trinder M, Francis GA, Brunham LR
Importance
Monogenic familial hypercholesterolemia (FH) is associated with lifelong elevations in low-density lipoprotein cholesterol (LDL-C) levels and increased risk of atherosclerotic cardiovascular disease (CVD). However, many individuals with hypercholesterolemia have a polygenic rather than a monogenic cause for their condition. It is unclear if a genetic variant for hypercholesterolemia alters the risk of CVD.
Objectives
To assess whether a genetic variant for hypercholesterolemia alters the risk of atherosclerotic CVD and to evaluate how this risk compares with that of nongenetic hypercholesterolemia.
Design, setting, and participants
In this genetic-association, case-control, cohort study, individuals aged 40 to 69 years were recruited by the UK Biobank from across the United Kingdom between March 13, 2006, and October 1, 2010, and followed up until March 31, 2017. Genotyping array and exome sequencing data from the UK Biobank cohort were used to identify individuals with monogenic (LDLR, APOB, and PCSK9) or polygenic hypercholesterolemia (LDL-C polygenic score >95th percentile based on 223 single-nucleotide variants in the entire cohort). The data were analyzed from July 1, 2019, to December 30, 2019.
Main outcomes and measures
The study investigated the association of genotype with the risk of coronary and carotid revascularization, myocardial infarction, ischemic stroke, and all-cause mortality among the overall study population and among participants with monogenic FH (n = 277), polygenic hypercholesterolemia (n = 2379), or hypercholesterolemia with undetermined cause (n = 2232) at comparable levels of LDL-C measured at study enrollment.
Results
For the 48 741 individuals with genotyping array and exome sequencing data, the mean (SD) age was 56.6 (8.0) years, and 54.5% were female (n = 26 541 of 48 741). A monogenic FH variant for hypercholesterolemia was found in 277 individuals (0.57%, 1 in 176 individuals). Participants with monogenic FH were significantly more likely than those without monogenic FH to experience an atherosclerotic CVD event at 55 years or younger (17 of 277 [6.1%] vs 988 of 48 464 [2.0%]; P < .001). Compared with the general population, both monogenic and polygenic hypercholesterolemia were associated with an increased risk of CVD events. Moreover, among individuals with comparable levels of LDL-C, both monogenic (hazard ratio, 1.93; 95% CI, 1.34-2.77; P < .001) and polygenic hypercholesterolemia (hazard ratio, 1.26; 95% CI, 1.03-1.55; P = .03) were significantly associated with an increased risk of CVD events compared with the risk of such events in individuals with hypercholesterolemia without an identified genetic cause.
Conclusions and relevance
The findings of this study suggest that among individuals with hypercholesterolemia, genetic determinants of LDL-C levels may impose additional risk of CVD. Thus, understanding the possible genetic cause of hypercholesterolemia may provide important prognostic information to treat patients.



JAMA Cardiol: 11 Feb 2020; epub ahead of print
Trinder M, Francis GA, Brunham LR
JAMA Cardiol: 11 Feb 2020; epub ahead of print | PMID: 32049305
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Impact:
Abstract

Cardiovascular Functional Reserve Before and After Kidney Transplant.

Lim K, Ting SMS, Hamborg T, McGregor G, ... Zehnder D, Hiemstra TF
Importance
Restitution of kidney function by transplant confers a survival benefit in patients with end-stage renal disease. Investigations of mechanisms involved in improved cardiovascular survival have relied heavily on static measures from echocardiography or cardiac magnetic resonance imaging and have provided conflicting results to date.
Objectives
To evaluate cardiovascular functional reserve in patients with end-stage renal disease before and after kidney transplant and to assess functional and morphologic alterations of structural-functional dynamics in this population.
Design, setting, and participants
This prospective, nonrandomized, single-center, 3-arm, controlled cohort study, the Cardiopulmonary Exercise Testing in Renal Failure and After Kidney Transplantation (CAPER) study, included patients with stage 5 chronic kidney disease (CKD) who underwent kidney transplant (KTR group), patients with stage 5 CKD who were wait-listed and had not undergone transplant (NTWC group), and patients with hypertension only (HTC group) seen at a single center from April 1, 2010, to January 1, 2013. Patients were followed up longitudinally for up to 1 year after kidney transplant. Clinical data collection was completed February 2014. Data analysis was performed from June 1, 2014, to March 5, 2015. Further analysis on baseline and prospective data was performed from June 1, 2017, to July 31, 2019.
Main outcomes and measures
Cardiovascular functional reserve was objectively quantified using state-of-the-art cardiopulmonary exercise testing in parallel with transthoracic echocardiography.
Results
Of the 253 study participants (mean [SD] age, 48.5 [12.7] years; 141 [55.7%] male), 81 were in the KTR group, 85 in the NTWC group, and 87 in the HTC group. At baseline, mean (SD) maximum oxygen consumption (V̇O2max) was significantly lower in the CKD groups (KTR, 20.7 [5.8] mL · min-1 · kg-1; NTWC, 18.9 [4.7] mL · min-1 · kg-1) compared with the HTC group (24.9 [7.1] mL · min-1 · kg-1) (P < .001). Mean (SD) cardiac left ventricular mass index was higher in patients with CKD (KTR group, 104.9 [36.1] g/m2; NTWC group, 113.8 [37.7] g/m2) compared with the HTC group (87.8 [16.9] g/m2), (P < .001). Mean (SD) left ventricular ejection fraction was significantly lower in the patients with CKD (KTR group, 60.1% [8.6%]; NTWC group, 61.4% [8.9%]) compared with the HTC group (66.1% [5.9%]) (P < .001). Kidney transplant was associated with a significant improvement in V̇O2max in the KTR group at 12 months (22.5 [6.3] mL · min-1 · kg-1; P < .001), but the value did not reach the V̇O2max in the HTC group (26.0 [7.1] mL · min-1 · kg-1) at 12 months. V̇O2max decreased in the NTWC group at 12 months compared with baseline (17.7 [4.1] mL · min-1 · kg-1, P < .001). Compared with the KTR group (63.2% [6.8%], P = .02) or the NTWC group (59.3% [7.6%], P = .003) at baseline, transplant was significantly associated with improved left ventricular ejection fraction at 12 months but not with left ventricular mass index.
Conclusions and relevance
The findings suggest that kidney transplant is associated with improved cardiovascular functional reserve after 1 year. In addition, cardiopulmonary exercise testing was sensitive enough to detect a decline in cardiovascular functional reserve in wait-listed patients with CKD. Improved V̇O2max may in part be independent from structural alterations of the heart and depend more on ultrastructural changes after reversal of uremia.



JAMA Cardiol: 04 Feb 2020; epub ahead of print
Lim K, Ting SMS, Hamborg T, McGregor G, ... Zehnder D, Hiemstra TF
JAMA Cardiol: 04 Feb 2020; epub ahead of print | PMID: 32022839
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Impact:
Abstract

Prognostic Models Derived in PARADIGM-HF and Validated in ATMOSPHERE and the Swedish Heart Failure Registry to Predict Mortality and Morbidity in Chronic Heart Failure.

Simpson J, Jhund PS, Lund LH, Padmanabhan S, ... Zile MR, McMurray JJV
Importance
Accurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made.
Objective
To develop and validate a prognostic model for patients with HF.
Design, setting, and participants
Multivariable analyses were performed in a stepwise fashion. Harrell C statistic was used to assess the discriminative ability. The derivation cohort was Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) participants. The models were validated using the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure Trial (ATMOSPHERE) study and in the Swedish Heart Failure Registry (SwedeHF). A total of 8399 participants enrolled in PARADIGM-HF. Data were analyzed between June 2016 and June 2018.
Main outcomes and measures
Cardiovascular death, all-cause mortality, and the composite of cardiovascular death or HF hospitalization at both 1 and 2 years.
Results
Complete baseline clinical data were available for 8011 patients in PARADIGM-HF. The mean (SD) age of participants was 64 (11.4) years, 78.2% were men (n = 6567 of 8011), and 70.6% were New York Heart Association class II (n = 5919 of 8011). During a mean follow-up of 27 months, 1546 patients died, and 2031 had a cardiovascular death or HF hospitalization. The common variables were: male sex, race/ethnicity (black or Asian), region (Central Europe or Latin America), HF duration of more than 5 years, New York Heart Association class III/ IV, left ventricular ejection fraction, diabetes mellitus, β-blocker use at baseline, and allocation to sacubitril/valsartan. Ranked by χ2, N-terminal pro brain natriuretic peptide was the single most powerful independent predictor of each outcome. The C statistic at 1 and 2 years was 0.74 (95% CI, 0.71-0.76) and 0.71 (95% CI, 0.70-0.73) for the primary composite end point, 0.73 (95% CI, 0.71-0.75) and 0.71 (95% CI, 0.69-0.73) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.67-0.74) for all-cause death, respectively. When validated in ATMOSPHERE, the C statistic at 1 and 2 years was 0.71 (95% CI, 0.69-0.72) and 0.70 (95% CI, 0.68-0.71) for the primary composite end point, 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.69-0.72) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.68-0.72) for all-cause death, respectively. An online calculator was created to allow calculation of an individual\'s risk (http://www.predict-hf.com).
Conclusions and relevance
Predictive models performed well and were developed and externally validated in large cohorts of geographically representative patients, comprehensively characterized with clinical and laboratory data including natriuretic peptides, who were receiving contemporary evidence-based treatment.



JAMA Cardiol: 28 Jan 2020; epub ahead of print
Simpson J, Jhund PS, Lund LH, Padmanabhan S, ... Zile MR, McMurray JJV
JAMA Cardiol: 28 Jan 2020; epub ahead of print | PMID: 31995119
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Impact:
Abstract

Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial.

Goldstein DJ, Naka Y, Horstmanshof D, Ravichandran AK, ... Farrar DJ, Mehra MR
Importance
Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant.
Objective
To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT).
Design, setting, and participants
This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT).
Main outcomes and measures
The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life.
Results
Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55 [12] years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63 [12] years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rank P = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rank P < .001). For patients in both BTT/BTC and DT groups, there were not significantly different reductions in rates of pump thrombosis, stroke, and gastrointestinal bleeding with HM3 use relative to HMII use. Improvements in quality of life and functional capacity for either pump were not significantly different regardless of preimplant strategy.
Conclusions and relevance
In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure.
Trial registration
ClinicalTrials.gov identifier: NCT02224755.



JAMA Cardiol: 14 Jan 2020; epub ahead of print
Goldstein DJ, Naka Y, Horstmanshof D, Ravichandran AK, ... Farrar DJ, Mehra MR
JAMA Cardiol: 14 Jan 2020; epub ahead of print | PMID: 31939996
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Impact:
Abstract

Association Between Preterm Birth and Arrested Cardiac Growth in Adolescents and Young Adults.

Goss KN, Haraldsdottir K, Beshish AG, Barton GP, ... Wieben O, Eldridge MW
Importance
Premature birth is associated with substantially higher lifetime risk for cardiovascular disease, including arrhythmia, ischemic disease, and heart failure, although the underlying mechanisms are poorly understood.
Objective
To characterize cardiac structure and function in adolescents and young adults born preterm using cardiac magnetic resonance imaging (MRI).
Design, setting, and participants
This cross-sectional cohort study at an academic medical center included adolescents and young adults born moderately to extremely premature (20 in the adolescent cohort born from 2003 to 2004 and 38 in the young adult cohort born in the 1980s and 1990s) and 52 age-matched participants who were born at term and underwent cardiac MRI. The dates of analysis were February 2016 to October 2019.
Exposures
Premature birth (gestational age ≤32 weeks) or birth weight less than 1500 g.
Main outcomes and measures
Main study outcomes included MRI measures of biventricular volume, mass, and strain.
Results
Of 40 adolescents (24 [60%] girls), the mean (SD) age of participants in the term and preterm groups was 13.3 (0.7) years and 13.0 (0.7) years, respectively. Of 70 adults (43 [61%] women), the mean (SD) age of participants in the term and preterm groups was 25.4 (2.9) years and 26.5 (3.5) years, respectively. Participants from both age cohorts who were born prematurely had statistically significantly smaller biventricular cardiac chamber size compared with participants in the term group: the mean (SD) left ventricular end-diastolic volume index was 72 (7) vs 80 (9) and 80 (10) vs 92 (15) mL/m2 for adolescents and adults in the preterm group compared with age-matched participants in the term group, respectively (P < .001), and the mean (SD) left ventricular end-systolic volume index was 30 (4) vs 34 (6) and 32 (7) vs 38 (8) mL/m2, respectively (P < .001). Stroke volume index was also reduced in adolescent vs adult participants in the preterm group vs age-matched participants in the term group, with a mean (SD) of 42 (7) vs 46 (7) and 48 (7) vs 54 (9) mL/m2, respectively (P < .001), although biventricular ejection fractions were preserved. Biventricular mass was statistically significantly lower in adolescents and adults born preterm: the mean (SD) left ventricular mass index was 39.6 (5.9) vs 44.4 (7.5) and 40.7 (7.3) vs 49.8 (14.0), respectively (P < .001). Cardiac strain analyses demonstrated a hypercontractile heart, primarily in the right ventricle, in adults born prematurely.
Conclusions and relevance
In this cross-sectional study, adolescents and young adults born prematurely had statistically significantly smaller biventricular cardiac chamber size and decreased cardiac mass. Although function was preserved in both age groups, these morphologic differences may be associated with elevated lifetime cardiovascular disease risk after premature birth.



JAMA Cardiol: 19 May 2020; epub ahead of print
Goss KN, Haraldsdottir K, Beshish AG, Barton GP, ... Wieben O, Eldridge MW
JAMA Cardiol: 19 May 2020; epub ahead of print | PMID: 32432648
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Impact:
Abstract

Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19).

Inciardi RM, Lupi L, Zaccone G, Italia L, ... Lombardi CM, Metra M
Importance
Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Objective
To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms.
Design, setting, and participant
This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course.
Exposure
Cardiac involvement with COVID-19.
Main outcomes and measures
Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging.
Results
An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization.
Conclusions and relevance
This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.



JAMA Cardiol: 26 Mar 2020; epub ahead of print
Inciardi RM, Lupi L, Zaccone G, Italia L, ... Lombardi CM, Metra M
JAMA Cardiol: 26 Mar 2020; epub ahead of print | PMID: 32219357
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Abstract

Diastolic Heart Failure in Patients With the Fontan Circulation: A Review.

Budts W, Ravekes WJ, Danford DA, Kutty S

The Fontan circulation, accomplished by direct surgical connection of the vena cavae to the pulmonary arteries, can be an effective palliation for patients with a single ventricle. However, failure of the Fontan circulation can result from mechanical obstruction, cardiac arrhythmias, increasing pulmonary vascular resistance, or deteriorating ventricular performance. Although systolic ventricular failure can usually be identified by a combination of clinical signs, symptoms, and imaging findings, diastolic ventricular dysfunction is likely an underrecognized cause of Fontan failure. Methods for detection of impaired diastolic function in a single ventricle are evolving, and established techniques appropriate in the biventricular heart lack validation in single ventricle. Association of biomarkers, cardiac magnetic resonance, and echocardiographic findings with invasively acquired pressure-volume loop data in humans may offer a way forward to accurate, noninvasive diagnosis. Today, therapy for severe diastolic ventricular dysfunction in the Fontan circulation is often disappointing and may require consideration of a ventricular assist device or even cardiac transplant. Progress toward improved outcomes of the Fontan palliation likely depends on successful innovation in primary prevention strategies and the development of more effective pharmacotherapy.



JAMA Cardiol: 04 Feb 2020; epub ahead of print
Budts W, Ravekes WJ, Danford DA, Kutty S
JAMA Cardiol: 04 Feb 2020; epub ahead of print | PMID: 32022823
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Impact:
Abstract

Global Differences in Characteristics, Precipitants, and Initial Management of Patients Presenting With Acute Heart Failure.

Filippatos G, Angermann CE, Cleland JGF, Lam CSP, ... Obergfell A, Collins SP
Importance
Acute heart failure (AHF) precipitates millions of hospital admissions worldwide, but previous registries have been country or region specific.
Objective
To conduct a prospective contemporaneous comparison of AHF presentations, etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions through the International Registry to Assess Medical Practice with Longitudinal Observation for Treatment of Heart Failure (REPORT-HF).
Design, setting, and participants
A total of 18 553 adults were enrolled during a hospitalization for AHF. Patients were recruited from the acute setting in Western Europe (WE), Eastern Europe (EE), Eastern Mediterranean and Africa (EMA), Southeast Asia (SEA), Western Pacific (WP), North America (NA), and Central and South America (CSA). Patients with AHF were approached for consent and excluded only if there was recent participation in a clinical trial. Patients were enrolled from July 23, 2014, to March 24, 2017. Statistical analysis was conducted from April 18 to June 29, 2018; revised analyses occurred between August 6 and 29, 2019.
Main outcomes and measures
Heart failure etiologic factors and precipitants, treatments, and in-hospital outcomes among global regions.
Results
A total of 18 553 patients were enrolled at 358 sites in 44 countries. The median age was 67.0 years (interquartile range [IQR], 57-77), 11 372 were men (61.3%), 9656 were white (52.0%), 5738 were Asian (30.9%), and 867 were black (4.7%). A history of HF was present in more than 50% of the patients and 40% were known to have a prior left-ventricular ejection fraction lower than 40%. Ischemia was a common AHF precipitant in SEA (596 of 2329 [25.6%]), WP (572 of 3354 [17.1%]), and EMA (364 of 2241 [16.2%]), whereas nonadherence to diet and medications was most common in NA (306 of 1592 [19.2%]). Median time to the first intravenous therapy was 3.0 (IQR, 1.4-5.6) hours in NA; no other region had a median time above 1.2 hours (P < .001). This treatment delay remained after adjusting for severity of illness (P < .001). Intravenous loop diuretics were the most common medication administered in the first 6 hours of AHF management across all regions (65.4%-89.9%). Despite similar initial blood pressure across all regions, inotropic agents were used approximately 3 times more often in SEA, WP, and EE (11.3%-13.5%) compared with NA and WE (3.1%-4.3%) (P < .001). Older age (odds ratio [OR], 1.0; 95% CI, 1.00-1.02), HF etiology (ischemia: OR, 1.65; 95% CI, 1.11-2.44; valvular: OR, 2.10; 95% CI, 1.36-3.25), creatinine level greater than 2.75 mg/dL (OR, 1.85; 95% CI, 0.71-2.40), and chest radiograph signs of congestion (OR, 2.03; 95% CI, 1.39-2.97) were all associated with increased in-hospital mortality. Similarly, younger age (OR, -0.04; 95% CI, -0.05 to -0.02), HF etiology (ischemia: OR, 0.77; 95% CI, 0.26-1.29; valvular: OR, 2.01; 95% CI, 1.38-2.65), creatinine level greater than 2.75 mg/dL (OR, 1.16; 95% CI, 0.31-2.00), and chest radiograph signs of congestion (OR, 1.02; 95% CI, 0.57-1.47) were all associated with increased in-hospital LOS.
Conclusions and relevance
Data from REPORT-HF suggest that patients are similar across regions in many respects, but important differences in timing and type of treatment exist, identifying region-specific gaps in medical management that may be associated with patient outcomes.



JAMA Cardiol: 07 Jan 2020; epub ahead of print
Filippatos G, Angermann CE, Cleland JGF, Lam CSP, ... Obergfell A, Collins SP
JAMA Cardiol: 07 Jan 2020; epub ahead of print | PMID: 31913404
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Abstract

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

, Wilemon KA, Patel J, Aguilar-Salinas C, ... Gaziano TA, Gidding SS
Importance
Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH.
Observations
In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created.
Conclusions and relevance
By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.



JAMA Cardiol: 01 Jan 2020; epub ahead of print
, Wilemon KA, Patel J, Aguilar-Salinas C, ... Gaziano TA, Gidding SS
JAMA Cardiol: 01 Jan 2020; epub ahead of print | PMID: 31895433
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Impact:
Abstract

Association Between Change in Circulating Progenitor Cells During Exercise Stress and Risk of Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

Moazzami K, Lima BB, Hammadah M, Ramadan R, ... Vaccarino V, Quyyumi AA
Importance
Stem and progenitor cells mobilize from the bone marrow in response to myocardial ischemia. However, the association between the change in circulating progenitor cell (CPC) counts and disease prognosis among patients with ischemia is unknown.
Objective
To investigate the association between the change in CPC counts during stress testing and the risk of adverse cardiovascular events in patients with stable coronary artery disease (CAD).
Design, setting, and participants
This prospective cohort study included a population-based sample of 454 patients with stable CAD who were recruited between June 1, 2011, and August 15, 2014, at Emory University-affiliated hospitals and followed up for 3 years. Data were analyzed from September 15, 2018, to October 15, 2018.
Exposures
Myocardial perfusion imaging with technetium Tc 99m sestamibi at rest and 30 to 60 minutes after conventional stress testing.
Main outcomes and measures
Circulating progenitor cells were enumerated with flow cytometry as CD34-expressing mononuclear cells (CD45med/CD34+), with additional quantification of subsets coexpressing the chemokine (C-X-C motif) receptor 4 (CD34+/CXCR4+). Changes in CPC counts were calculated as poststress minus resting CPC counts. Cox proportional hazards regression models were used to identify factors associated with the combined end point of cardiovascular death and myocardial infarction after adjusting for clinical covariates, including age, sex, race, smoking history, body mass index, and history of heart failure, hypertension, dyslipidemia, and diabetes.
Results
Of the 454 patients (mean [SD] age, 63 [9] years; 76% men) with stable CAD enrolled in the study, 142 (31.3%) had stress-induced ischemia and 312 (68.7%) did not, as measured by single-photon emission computed tomography. During stress testing, patients with stress-induced ischemia had a mean decrease of 20.2% (interquartile range [IQR], -45.3 to 5.5; P < .001) in their CD34+/CXCR4+ counts, and patients without stress-induced ischemia had a mean increase of 3.2% (IQR, -20.6 to 35.1; P < .001) in their CD34+/CXCR4+ counts. Twenty-four patients (5.2%) experienced adverse events. After adjustment, baseline CPC counts were associated with worse adverse outcomes, but this association was not present after stress-induced ischemia was included in the model. However, the change in CPC counts during exercise remained significantly associated with adverse events (hazard ratio, 2.59; 95% CI, 1.15-5.32, per 50% CD34+/CXCR4+ count decrease), even after adjustment for clinical variables and the presence of ischemia. The discrimination of risk factors associated with incident adverse events improved (increase in C statistic from 0.72 to 0.77; P = .003) with the addition of the change in CD34+/CXCR4+ counts to a model that included clinical characteristics, baseline CPC count, and ischemia.
Conclusions and relevance
In this study of patients with CAD, a decrease in CPC counts during exercise is associated with a worse disease prognosis compared with the presence of stress-induced myocardial ischemia. Further studies are needed to evaluate whether strategies to improve CPC responses during exercise stress will be associated with improvements in the prognosis of patients with CAD.



JAMA Cardiol: 03 Dec 2019; epub ahead of print
Moazzami K, Lima BB, Hammadah M, Ramadan R, ... Vaccarino V, Quyyumi AA
JAMA Cardiol: 03 Dec 2019; epub ahead of print | PMID: 31799987
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Impact:
Abstract

The Learning Curve for Shared Decision-making in Symptomatic Aortic Stenosis.

Coylewright M, O\'Neill E, Sherman A, Gerling M, ... Elwyn G, Durand MA
Importance
Shared decision-making (SDM) is widely advocated for patients with valvular heart disease yet is not integrated into the heart team model for patients with symptomatic aortic stenosis. Decision aids (DAs) have been shown to improve patient-centered outcomes and may facilitate SDM.
Objective
To determine whether the repeated use of a DA by heart teams is associated with greater SDM, along with improved patient-centered outcomes and clinician attitudes about DAs.
Design, setting, and participants
This mixed-methods study included a nonrandomized pre-post intervention and clinician interviews. It was conducted between April 30, 2015, and December 7, 2017, with quantitative analysis performed between January 12, 2017, and May 26, 2017, within 2 academic medical centers in northern New England among 35 patients with symptomatic aortic stenosis who were at high to prohibitive risk for surgery. The qualitative analysis was performed between August 6, 2018, and May 7, 2019. The Severe Aortic Stenosis Decision Aid was delivered by 6 clinicians, with patients choosing between transcatheter aortic valve replacement and medical management.
Main outcomes and measures
Clinician SDM performance was measured using the Observer OPTION5 scale with dual-independent coding of audiotaped clinic visits. Previsit and postvisit surveys measured the patient\'s knowledge, satisfaction, and decisional conflict. Audiotaped clinician interviews were coded, and qualitative thematic analysis was performed.
Results
Six male clinicians and 35 patients (19 of 34 women [55.9%; 1 survey was missing]; mean [SD] age, 85.8 [7.8] years) participated in the study. Shared decision-making increased stepwise with repeated use of the DA (mean [SD] Observer OPTION5 scores: usual care, 17.9 [7.6]; first use of a DA, 60.5 [30.9]; fifth use of a DA, 79.0 [8.4]; P < .001 for comparison between usual care and fifth use of DA). Multiple uses of the DA were associated with increased patient knowledge (mean difference, 18.0%; 95% CI, 1.2%-34.8%; P = .04) and satisfaction (mean difference, 6.7%; 95% CI, 2.5%-10.8%; P = .01) but not decisional conflict (mean [SD]: usual care, 96.0% [9.4%]; first use of DA, 93.8% [12.5%]; fifth use of DA, 95.0% [11.2%]; P = .60). Qualitative analysis of clinicians\' interviews revealed that clinicians perceived that they used an SDM approach without DAs and that the DA was not well understood by elderly patients. There was infrequent values clarification or discussion of stroke risk.
Conclusion and relevance
In a mixed-methods pilot study, use of a DA for severe aortic stenosis by heart team clinicians was associated with improved SDM and patient-centered outcomes. However, in qualitative interviews, heart team clinicians did not perceive a significant benefit of the DA, and therefore sustained implementation is unlikely. This pilot study of SDM clarifies new research directions for heart teams.



JAMA Cardiol: 28 Jan 2020; epub ahead of print
Coylewright M, O'Neill E, Sherman A, Gerling M, ... Elwyn G, Durand MA
JAMA Cardiol: 28 Jan 2020; epub ahead of print | PMID: 31995126
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Impact:
Abstract

Association of Longitudinal Trajectory of Albuminuria in Young Adulthood With Myocardial Structure and Function in Later Life: Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Patel RB, Colangelo LA, Reis JP, Lima JAC, Shah SJ, Lloyd-Jones DM
Importance
Albuminuria, as measured by single urine albumin-to-creatinine ratio (UACR) levels, is associated with cardiac remodeling and adverse clinical outcomes. The longitudinal patterns of change in UACR through young adulthood and their associations with myocardial structure and function later in life remain unclear.
Objective
To describe the trajectory of albuminuria as measured by UACR across a 20-year span and evaluate the association of albuminuria trajectory with echocardiographic indices of structure and function in middle age.
Design, setting, and participants
In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of black and white participants aged 18 to 30 years at baseline (March 1985 to June 1986) were evaluated over 30 years. Participants underwent evaluations at 4 urban US sites. Data were collected from March 1985 to May 2016, and data were analyzed from September 2018 to April 2019.
Exposures
Trajectories of UACR from the year 10 examination to the year 30 examination as determined by latent class modeling.
Main outcomes and measures
Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 30 examination.
Results
Of the 2647 included participants, 1441 (54.4%) were white, 1206 (45.6%) were black, and the mean (SD) age was 35.2 (3.6) years. A total of 5 trajectory groups of UACR were identified, including 1718 participants (64.9%) in the low-stable group, 682 (25.8%) in the moderate-stable group, 116 (4.4%) in the high-stable group, 88 (3.3%) in the moderate-increasing group, and 43 (1.6%) in the high-increasing group. Apart from the high-increasing cohort, the remaining 4 groups had median baseline UACR levels less than 30 mg/g. Male sex, current smoking, diabetes, and elevated blood pressure were more common in the moderate-increasing and high-increasing UACR groups. After adjustment for clinical variables and baseline UACR levels, there were significant differences in left ventricular (LV) mass by trajectory group (mean [SE] LV mass: high-increasing, 98.4 [3.4] g/m2; moderate-increasing, 91.7 [2.2] g/m2; high-stable, 86.0 [2.1] g/m2; moderate-stable, 82.3 [0.8] g/m2; low-stable, 78.6 [0.5] g/m2; P < .001). Significant differences by trajectory group were also noted in LV longitudinal strain, e\' tissue velocities, and estimated LV filling pressures, even after adjustment for clinical variables and baseline UACR level. The association of trajectory group with indices of myocardial structure and function remained significant after adjustment for clinical variables and cumulative UACR from the year 10 to year 25 examinations.
Conclusions and relevance
There are distinct patterns of change in albuminuria among young adults over a 20-year span, and these trajectory groups cannot be identified by baseline UACR level alone. Dynamic changes in albuminuria are independently associated with adverse alterations to cardiac structure, LV systolic function, and LV diastolic function.



JAMA Cardiol: 16 Nov 2019; epub ahead of print
Patel RB, Colangelo LA, Reis JP, Lima JAC, Shah SJ, Lloyd-Jones DM
JAMA Cardiol: 16 Nov 2019; epub ahead of print | PMID: 31734692
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Impact:
Abstract

Statin Use in Primary Prevention of Atherosclerotic Cardiovascular Disease According to 5 Major Guidelines for Sensitivity, Specificity, and Number Needed to Treat.

Mortensen MB, Nordestgaard BG
Importance
Five major guidelines on statin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD) have been published since 2014: the National Institute for Health and Care Excellence (NICE; 2014), US Preventive Services Task Force (USPSTF; 2016), Canadian Cardiovascular Society (CCS; 2016), European Society of Cardiology/European Atherosclerosis Society (ESC/EAS; 2016), and American College of Cardiology/American Heart Association (ACC/AHA; 2018).
Objective
To compare the sensitivity, specificity, and estimated number needed to treat (NNT10) to prevent 1 ASCVD event in 10 years according to statin criteria from the 5 guidelines.
Design, setting, and participants
Population-based contemporary cohort study. Analyses were performed in the Copenhagen General Population Study, with a mean follow-up time of 10.9 years. We included 45 750 individuals aged 40 to 75 years. The participants were enrolled between 2003 and 2009 and were all free of ASCVD at baseline. Data were analyzed between January 1, 2019, and August 4, 2019.
Exposures
Statin treatment according to guideline criteria. We assumed a 25% relative reduction of ASCVD events per 38 mg/dL (to convert to millimoles per liter, multiply by 0.0259) reduction in low-density lipoprotein cholesterol.
Main outcomes and measures
Sensitivity and specificity for ASCVD events and the NNT10 to prevent 1 ASCVD event according to guideline criteria.
Results
Median age at baseline examination was 56 years, and 43% of participants were men (n = 19 870 of 45 750). During follow-up, we observed 4156 ASCVD events. Overall, 44% of individuals in Copenhagen General Population Study were statin eligible with CCS (n = 19 953 of 45 750), 42% with ACC/AHA (n = 19 400 of 45 750), 40% with NICE (n = 19 400 of 45 750), 31% with USPSTF (n = 13 966 of 45 750), and 15% with ESC/EAS (n = 6870 of 45 750). Sensitivity and specificity for ASCVD events were 68% (n = 2815 of 4156) and 59% (n = 24 456 of 41 594) for CCS, 70% (n = 2889 of 4156) and 60% (n = 25 083 of 41 594) for ACC/AHA, 68% (n = 2815 of 4156) and 63% (n = 26 213 of 41 594) for NICE, 57% (n = 2377 of 4156) and 72% (n = 30 005 of 41 594) for USPSTF, and 24% (n = 1001 of 4156) and 86% (n = 35 725 of 41 594) for ESC/EAS. The NNT10 to prevent 1 ASCVD using moderate-intensity and high-intensity statin therapy, respectively, was 32 and 21 for CCS criteria, 30 and 20 for ACC/AHA criteria, 30 and 20 for NICE criteria, 27 and 18 for USPSTF criteria, and 29 and 20 for ESC/EAS criteria.
Conclusions and relevance
With similar NNT10 to prevent 1 event, the CCS, ACC/AHA, and NICE guidelines correctly assign statin therapy to many more of the individuals who later develop ASCVD compared with the USPSTF and ESC/EAS guidelines. Our results therefore suggest that the CCS, ACC/AHA, or NICE guidelines may be preferred for primary prevention.



JAMA Cardiol: 01 Oct 2019; epub ahead of print
Mortensen MB, Nordestgaard BG
JAMA Cardiol: 01 Oct 2019; epub ahead of print | PMID: 31577339
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Impact:
Abstract

Association of Sex With Severity of Coronary Artery Disease, Ischemia, and Symptom Burden in Patients With Moderate or Severe Ischemia: Secondary Analysis of the ISCHEMIA Randomized Clinical Trial.

Reynolds HR, Shaw LJ, Min JK, Spertus JA, ... Hochman JS,
Importance
While many features of stable ischemic heart disease vary by sex, differences in ischemia, coronary anatomy, and symptoms by sex have not been investigated among patients with moderate or severe ischemia. The enrolled ISCHEMIA trial cohort that underwent coronary computed tomographic angiography (CCTA) was required to have obstructive coronary artery disease (CAD) for randomization.
Objective
To describe sex differences in stress testing, CCTA findings, and symptoms in ISCHEMIA trial participants.
Design, setting, and participants
This secondary analysis of the multicenter ISCHEMIA randomized clinical trial analyzed baseline characteristics of patients with stable ischemic heart disease. Individuals were enrolled from July 2012 to January 2018 based on local reading of moderate or severe ischemia on a stress test, after which blinded CCTA was performed in most. Core laboratories reviewed stress tests and CCTAs. Participants with no obstructive CAD or with left main CAD of 50% or greater were excluded. Those who met eligibility criteria including CCTA (if performed) were randomized to a routine invasive or a conservative management strategy (N = 5179). Angina was assessed using the Seattle Angina Questionnaire. Analysis began October 1, 2018.
Interventions
CCTA and angina assessment.
Main outcomes and measures
Sex differences in stress test, CCTA findings, and symptom severity.
Results
Of 8518 patients enrolled, 6256 (77%) were men. Women were more likely to have no obstructive CAD (<50% stenosis in all vessels on CCTA) (353 of 1022 [34.4%] vs 378 of 3353 [11.3%]). Of individuals who were randomized, women had more angina at baseline than men (median [interquartile range] Seattle Angina Questionnaire Angina Frequency score: 80 [70-100] vs 90 [70-100]). Women had less severe ischemia on stress imaging (383 of 919 [41.7%] vs 1361 of 2972 [45.9%] with severe ischemia; 386 of 919 [42.0%] vs 1215 of 2972 [40.9%] with moderate ischemia; and 150 of 919 [16.4%] vs 394 of 2972 [13.3%] with mild or no ischemia). Ischemia was similar by sex on exercise tolerance testing. Women had less extensive CAD on CCTA (205 of 568 women [36%] vs 1142 of 2418 men [47%] with 3-vessel disease; 184 of 568 women [32%] vs 754 of 2418 men [31%] with 2-vessel disease; and 178 of 568 women [31%] vs 519 of 2418 men [22%] with 1-vessel disease). Female sex was independently associated with greater angina frequency (odds ratio, 1.41; 95% CI, 1.13-1.76).
Conclusions and relevance
Women in the ISCHEMIA trial had more frequent angina, independent of less extensive CAD, and less severe ischemia than men. These findings reflect inherent sex differences in the complex relationships between angina, atherosclerosis, and ischemia that may have implications for testing and treatment of patients with suspected stable ischemic heart disease.
Trial registration
ClinicalTrials.gov Identifier: NCT01471522.



JAMA Cardiol: 29 Mar 2020; epub ahead of print
Reynolds HR, Shaw LJ, Min JK, Spertus JA, ... Hochman JS,
JAMA Cardiol: 29 Mar 2020; epub ahead of print | PMID: 32227128
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Impact:
Abstract

Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices.

McCullough M, Caraballo C, Ravindra NG, Miller PE, ... Ahmad T, Desai NR
Importance
Left ventricular assist devices (LVADs) improve outcomes in patients with advanced heart failure, but little is known about the role of neurohormonal blockade (NHB) in treating these patients.
Objective
To analyze the association between NHB blockade and outcomes in patients with LVADs.
Design, setting, and participants
This retrospective cohort analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) included patients from more than 170 centers across the United States and Canada with continuous flow LVADs from 2008 to 2016 who were alive with the device in place at 6 months after implant. The data were analyzed between February and November 2019.
Exposures
Patients were stratified based on exposure to NHB and represented all permutations of the following drug classes: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, and mineralocorticoid antagonists.
Main outcomes and measures
The outcomes of interest were survival at 4 years and quality of life at 2 years based on Kansas City Cardiomyopathy Questionnaire scores and a 6-minute walk test.
Results
A total of 12 144 patients in INTERMACS met inclusion criteria, of whom 2526 (20.8% ) were women, 8088 (66.6%) were white, 3024 (24.9%) were African American, and 753 (6.2%) were Hispanic; the mean (SD) age was 56.8 (12.9) years. Of these, 10 419 (85.8%) were receiving NHB. Those receiving any NHB medication at 6 months had a better survival rate at 4 years compared with patients not receiving NHB (56.0%; 95% CI, 54.5%-57.5% vs 43.9%; 95% CI, 40.5%-47.7%). After sensitivity analyses with an adjusted model, this trend persisted with patients receiving triple therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, β-blocker, and mineralocorticoid antagonist having the lowest hazard of death compared with patients in the other groups (hazard ratio, 0.34; 95% CI, 0.28-0.41). Compared with patients not receiving NHB, use of NHB was associated with a higher Kansas City Cardiomyopathy Questionnaire score (66.6; bootstrapped 95% CI, 65.8-67.3 vs 63.0; bootstrapped 95% CI, 60.1-65.8; P = .02) and a 6-minute walk test (1103 ft; bootstrapped 95% CI, 1084-1123 ft vs 987 ft; bootstrapped 95% CI, 913-1060 ft; P < .001).
Conclusions and relevance
Among patients with LVADs who tolerated NHB therapy, continued treatment was associated with improved survival and quality of life. The optimal heart failure regimen for patients after LVAD implant may be the initiation and continuation of guideline-directed medical therapy.



JAMA Cardiol: 17 Nov 2019; epub ahead of print
McCullough M, Caraballo C, Ravindra NG, Miller PE, ... Ahmad T, Desai NR
JAMA Cardiol: 17 Nov 2019; epub ahead of print | PMID: 31738366
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Impact:
Abstract

Association of Hospital Inpatient Percutaneous Coronary Intervention Volume With Clinical Outcomes After Transcatheter Aortic Valve Replacement and Transcatheter Mitral Valve Repair.

Butala NM, Bucholz EM, Kolte D, Elmariah S
Importance
The US Centers for Medicare and Medicaid Services recently released an updated national coverage determination proposal for transcatheter aortic valve replacement (TAVR) that maintains a focus on hospital TAVR volume and percutaneous coronary intervention (PCI) volume, and the national coverage determination for transcatheter mitral valve repair (TMVr) also has PCI volume requirements. However, the associations between hospital PCI volume and TAVR and TMVr outcomes are unknown.
Objective
To investigate whether hospital inpatient PCI volume is associated with rates of risk-adjusted in-hospital mortality and 30-day hospital readmission after TAVR and TMVr.
Design, setting, and participants
This population-based cross-sectional study of the 2016 Nationwide Readmissions Database included procedures completed in hospitals with a minimum of 5 TAVR or 5 TMVr procedures between January 1, 2016, and November 30, 2016.
Exposures
Hospitals were divided into quartiles based on annual inpatient PCI volumes.
Main outcomes and measures
Primary outcomes were in-hospital mortality and 30-day readmission rates. The associations between hospital inpatient PCI quartile and outcomes were evaluated using Kruskal-Wallis tests. Risk adjustment for in-hospital mortality rates was done through inclusion of variables based on the Elixhauser comorbidity classification, and risk adjustment for 30-day readmission rates was done in accordance with the Hospital-Wide Readmission Measure methodology used by the Centers for Medicare and Medicaid Services for public reporting.
Results
There were 283 hospitals that performed at least 5 TAVRs, with a median inpatient PCI volume of 386 (interquartile range, 299-571) procedures, and 125 hospitals that performed at least 5 TMVr procedures, with a median inpatient PCI volume of 451 (interquartile range, 326-651) procedures. There was no association between hospital inpatient PCI volume and median TAVR risk-standardized in-hospital mortality (median [IQR] rates: bottom quartile, 1.82% [1.77%-1.90%]; second quartile, 1.81% [1.76%-1.86%]; third quartile, 1.81% [1.75%-1.90%]; top quartile, 1.82% [1.76%-1.91%]; P = .75) or the 30-day readmission (median [IQR] rates: bottom quartile, 13.6% [13.2%-14.3%]; second quartile, 13.3% [12.7%-14.0%]; third quartile, 13.5% [12.7%-14.3%]; top quartile, 13.8% [12.8%-14.3%]; P = .10) rates. Similarly, there was no association between hospital inpatient PCI volume and median TMVr risk-standardized in-hospital mortality rates (median [IQR] rates: bottom quartile, 1.84% [1.47%-2.53%]; second quartile, 1.65% [1.21%-3.02%]; third quartile, 1.80% [1.52%-3.58%]; top quartile, 1.76% [1.33%-4.20%]; P = .71) or 30-day readmission rates (median [IQR] rates: bottom quartile, 13.4% [13.1%-13.6%]; second quartile, 13.1% [12.9%-13.5%]; third quartile, 13.1% [12.9%-13.5%]; top quartile, 13.3% [12.8%-13.6%]; P = .30).
Conclusions and relevance
In this study, there was no association between inpatient PCI volume and TAVR or TMVr outcomes. Further evidence is needed to support inclusion of PCI volume minimums in national coverage determination requirements for hospital TAVR and TMVr programs.



JAMA Cardiol: 11 Feb 2020; epub ahead of print
Butala NM, Bucholz EM, Kolte D, Elmariah S
JAMA Cardiol: 11 Feb 2020; epub ahead of print | PMID: 32049303
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Impact:
Abstract

Performance in Federal Value-Based Programs of Hospitals Recognized by the American Heart Association and American College of Cardiology for High-Quality Heart Failure and Acute Myocardial Infarction Care.

Wadhera RK, Vaduganathan M, Jiang GY, Song Y, ... Yeh RW, Fonarow GC
Importance
The US Centers for Medicare & Medicaid Services have implemented national value-based programs that incentivize hospitals to deliver better cardiovascular care. However, it is unclear how hospitals recognized for high-quality cardiovascular care by American Heart Association (AHA) and American College of Cardiology (ACC) national quality improvement initiatives (termed award hospitals) have performed under value-based programs.
Objective
To determine if hospitals that received awards for high-quality cardiovascular care from the AHA/ACC were less likely to be penalized under the Hospital Readmissions Reduction Program (HRRP) and the Hospital Value-Based Purchasing Program (VBP) compared with other hospitals.
Design, setting, and participants
This national cross-sectional study included data from short-term acute care hospitals in the United States that were participating in the HRRP or VBP in fiscal year 2018.
Exposures
Recognition awards for high-quality care from the AHA\'s Get With The Guidelines-Heart Failure and ACC\'s Chest Pain-MI (myocardial infarction) Registry national quality improvement initiatives.
Main outcomes and measures
Proportion of hospitals that received a financial penalty or financial reward under the HRRP or VBP, median payment adjustments, and hospital-level 30-day mortality rates.
Results
This study included 3175 hospitals participating in the HRRP and 2781 hospitals participating in the VBP in fiscal year 2018. Under the HRRP, a higher proportion of award hospitals received financial penalties compared with other hospitals (419 [85.5%] vs 2112 [78.7%]; P < .001), although payment reductions were similar (median, 0.39% [interquartile range (IQR), 0.08%-0.84%] vs 0.33% [IQR, 0.03%-0.89%]; P = .17). Under the VBP, a higher proportion of award hospitals received penalties compared with other hospitals (250 [51.7%] vs 950 [41.4%]; P < .001), and fewer award hospitals received financial rewards (234 [48.4%] vs 1347 [58.6%]; P < .001). Median payment reductions were higher for award hospitals than other hospitals (0.01% [IQR, 0.00%-0.38%] vs 0.0% [IQR, 0.00%-0.28%]; P < .001), and median payment increases were lower (0.0% [IQR, 0.00%-0.34%] vs 0.13% [IQR, 0.00%-0.60%]; P < .001). Thirty-day mortality at award hospitals was similar (acute myocardial infarction, 13.2% vs 13.2%; P = .76) or slightly lower (heart failure, 11.3% vs 11.7%; P = .001) compared with other hospitals.
Conclusions and relevance
Hospitals that received awards for high-quality cardiovascular care from the AHA/ACC were more likely to be penalized and less likely to be financially rewarded by federal value-based programs. These findings highlight the potential need to standardize measurement of cardiovascular care quality.



JAMA Cardiol: 18 Feb 2020; epub ahead of print
Wadhera RK, Vaduganathan M, Jiang GY, Song Y, ... Yeh RW, Fonarow GC
JAMA Cardiol: 18 Feb 2020; epub ahead of print | PMID: 32074242
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Impact:
Abstract

Longitudinal Associations Between Income Changes and Incident Cardiovascular Disease: The Atherosclerosis Risk in Communities Study.

Wang SY, Tan ASL, Claggett B, Chandra A, ... Solomon SD, Kawachi I
Importance
Higher income is associated with lower incident cardiovascular disease (CVD). However, there is limited research on the association between changes in income and incident CVD.
Objective
To examine the association between change in household income and subsequent risk of CVD.
Design, setting, and participants
The Atherosclerosis Risk In Communities (ARIC) study is an ongoing, prospective cohort of 15 792 community-dwelling men and women, of mostly black or white race, from 4 centers in the United States (Jackson, Mississippi; Washington County, Maryland; suburbs of Minneapolis, Minnesota; and Forsyth County, North Carolina), beginning in 1987. For our analysis, participants were followed up until December 31, 2016.
Exposures
Participants were categorized based on whether their household income dropped by more than 50% (income drop), remained unchanged/changed less than 50% (income unchanged), or increased by more than 50% (income rise) over a mean (SD) period of approximately 6 (0.3) years between ARIC visit 1 (1987-1989) and visit 3 (1993-1995).
Main outcomes and measures
Our primary outcome was incidence of CVD after ARIC visit 3, including myocardial infarction (MI), fatal coronary heart disease, heart failure (HF), or stroke during a mean (SD) of 17 (7) years. Analyses were adjusted for sociodemographic variables, health behaviors, and CVD biomarkers.
Results
Of the 8989 included participants (mean [SD] age at enrollment was 53 [6] years, 1820 participants were black [20%], and 3835 participants were men [43%]), 900 participants (10%) experienced an income drop, 6284 participants (70%) had incomes that remained relatively unchanged, and 1805 participants (20%) experienced an income rise. After full adjustment, those with an income drop experienced significantly higher risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 1.17; 95% CI, 1.03-1.32). Those with an income rise experienced significantly lower risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 0.86; 95% CI, 0.77-0.96).
Conclusions and relevance
Income drop over 6 years was associated with higher risk of subsequent incident CVD over 17 years, while income rise over 6 years was associated with lower risk of subsequent incident CVD over 17 years. Health professionals should have greater awareness of the influence of income change on the health of their patients.



JAMA Cardiol: 08 Oct 2019; epub ahead of print
Wang SY, Tan ASL, Claggett B, Chandra A, ... Solomon SD, Kawachi I
JAMA Cardiol: 08 Oct 2019; epub ahead of print | PMID: 31596441
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Impact:
Abstract

Effectiveness of Implanted Cardiac Rhythm Recorders With Electrocardiographic Monitoring for Detecting Arrhythmias in Pregnant Women With Symptomatic Arrhythmia and/or Structural Heart Disease: A Randomized Clinical Trial.

Sliwa K, Azibani F, Johnson MR, Viljoen C, ... Ntsekhe M, Chin A
Importance
Arrhythmias are an important cause of maternal morbidity and mortality but remain difficult to diagnose.
Objective
To compare implantable loop recorder (ILR) plus 24-hour Holter electrocardiographic (ECG) monitoring with standard 24-hour Holter ECG monitoring alone in terms of acceptability, ability to identify significant arrythmias, and effect on management and pregnancy outcome in women who were symptomatic or at high risk of arrythmia because of underlying structural heart disease.
Design, setting, and participants
This single-center, prospective randomized clinical trial recruited 40 consecutive patients from the Cardiac Disease and Maternity Clinic at Groote Schuur Hospital in Cape Town, South Africa. Pregnant patients with symptoms of arrhythmia and/or structural heart disease at risk of arrhythmia were included.
Intervention
Patients were randomized to standard care (SC; 24-hour Holter ECG monitoring [n = 20]) or standard care plus ILR (SC-ILR; 24-hour Holter ECG monitoring plus ILR [n = 20]). Only 17 consented to ILR insertion, and the 3 who declined ILR were allocated to the SC group.
Main outcomes and measures
Arrhythmias considered included atrial fibrillation, atrial flutter, premature ventricular complexes, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation.
Results
Among the 40 women in this trial, the mean (SD) age was 28.4 (5.5) years. Holter monitoring detected arrhythmias in 3 of 23 patients (13%) in the SC group and 4 of 17 patients (24%) in the SC-ILR group compared with 9 of 17 patients (53%) patients who had arrhythmias detected by ILR. Seven patients (4 with supraventricular tachycardia, 1 with premature ventricular complexes, and 2 with paroxysmal atrial fibrillation recorded by ILR) did not have arrhythmias detected by 24-hour Holter monitoring. Three of these 7 patients (43%) had a change in management as a result of their ILR recordings. There were no maternal deaths. However, the SC group had a significantly lower mean (SD) gestational stage at delivery (35 [5] weeks vs 38 [2], P = .04).
Conclusions and relevance
The ILR was better than 24-hour Holter monitoring in detecting arrhythmias, which led to a change in management for a significant proportion of patients. Our findings suggest that ILR may be beneficial for pregnant women at risk of arrhythmia.
Trial registration
ClinicalTrials.gov Identifier: NCT02249195.



JAMA Cardiol: 18 Feb 2020; epub ahead of print
Sliwa K, Azibani F, Johnson MR, Viljoen C, ... Ntsekhe M, Chin A
JAMA Cardiol: 18 Feb 2020; epub ahead of print | PMID: 32074256
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Impact:
Abstract

Association of High-Density Calcified 1K Plaque With Risk of Acute Coronary Syndrome.

van Rosendael AR, Narula J, Lin FY, van den Hoogen IJ, ... Min JK, Shaw LJ
Importance
Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known.
Objective
To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS.
Design, setting, and participants
This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019.
Exposures
Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque).
Main outcomes and measures
Association between calcium density and future ACS risk.
Results
A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases.
Conclusions and relevance
Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.



JAMA Cardiol: 21 Jan 2020; epub ahead of print
van Rosendael AR, Narula J, Lin FY, van den Hoogen IJ, ... Min JK, Shaw LJ
JAMA Cardiol: 21 Jan 2020; epub ahead of print | PMID: 31968065
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Impact:
Abstract

Association of Blood Pressure Patterns in Young Adulthood With Cardiovascular Disease and Mortality in Middle Age.

Yano Y, Reis JP, Lewis CE, Sidney S, ... Muntner P, Lloyd-Jones DM
Importance
Determining blood pressure (BP) patterns in young adulthood that are associated with cardiovascular disease (CVD) events in later life may help to identify young adults who have an increased risk for CVD.
Objective
To determine whether the long-term variability of BP across clinical visits and the rate of change in BP from young adulthood to midlife are associated with CVD and all-cause mortality by middle age, independently of mean BP during young adulthood and a single BP in midlife.
Design, setting, and participants
This prospective cohort study included a community-based sample of 3394 African American and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, enrolled from March 1985 through June 1986. Patterns of systolic BP (SBP) were evaluated with measurements at year 0 (baseline) and 2, 5, 7, and 10 years after baseline. Visit-to-visit SBP variability was estimated as BP variability independent of the mean (VIM). Data were collected from March 1985 through August 2015 and analyzed from June through October 2019.
Main outcomes and measures
Cardiovascular disease and all-cause mortality experienced through August 2015 were adjudicated. The associations of each SBP pattern with CVD events and all-cause mortality were determined using Cox proportional hazards regression models.
Results
At year 10, the mean (SD) age of the 3394 participants was 35.1 (3.6) years; 1557 (45.9%) were African American; 1892 (55.7%) were women; and 103 (3.0%) were taking antihypertensive medication. During a median follow-up of 20.0 (interquartile range, 19.4-20.2) years, 162 CVD events and 181 deaths occurred. When all BP pattern measurements were entered into the same model including a single SBP measurement at the year 10 examination, the hazard ratios for CVD events for each 1-SD increase in SBP measures were 1.25 (95% CI, 0.90-1.74) for mean SBP, 1.23 (95% CI, 1.07-1.43) for VIM SBP, and 0.99 (95% CI, 0.81-1.26) for annual change of SBP. The VIM for SBP was the only BP pattern associated with all-cause mortality (hazard ratio, 1.24; 95% CI, 1.09-1.41).
Conclusions and relevance
The results of this study suggest that the assessment of visit-to-visit SBP variability may help identify young adults at increased risk for CVD and all-cause mortality later in life.



JAMA Cardiol: 21 Jan 2020; epub ahead of print
Yano Y, Reis JP, Lewis CE, Sidney S, ... Muntner P, Lloyd-Jones DM
JAMA Cardiol: 21 Jan 2020; epub ahead of print | PMID: 31968050
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Impact:
Abstract

Time-Varying Outcomes With the Absorb Bioresorbable Vascular Scaffold During 5-Year Follow-up: A Systematic Meta-analysis and Individual Patient Data Pooled Study.

Stone GW, Kimura T, Gao R, Kereiakes DJ, ... Ali ZA, Serruys PW
Importance
Bioresorbable scaffolds were designed to provide clinical benefits after their complete bioresorption. Prior studies demonstrated early risks with the Absorb polymeric bioresorbable vascular scaffold (BVS). Whether this risk profile changes over time during the course of its bioresorption is unknown.
Objective
To examine outcomes of the first-generation BVS before and after 3 years, the point of its complete bioresorption in animals.
Data sources
We searched MEDLINE and the Cochrane database, conference proceedings, and public websites for relevant studies.
Study selection
Eligible studies were randomized clinical trials of BVS vs metallic drug-eluting stents in patients with coronary artery disease with at least 5-year follow-up. Four trials of BVS vs everolimus-eluting stents (EES) with 3384 patients met criteria.
Data extraction and synthesis
Individual patient data from the 4 trials were pooled, and summary-level meta-analysis was performed.
Main outcomes and measures
The major effectiveness and safety measures were target lesion failure (TLF; cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization) and device thrombosis. Outcomes were examined through 5-year follow-up and between 0 to 3 and 3 to 5 years.
Results
Mean age for the 3384 patients was 62.8 years; 2452 patients were men (72.5%), and diabetes was present in 1020 patients (30.2%). Through 5-year follow-up, treatment with BVS compared with EES was associated with higher rates of TLF (14.9% vs 11.6%; HR, 1.26; 95% CI, 1.03-1.54; P = .03) and device thrombosis (2.5% vs 0.8%; HR, 2.87; 95% CI, 1.46-5.65; P = .002). Target lesion failure occurred in 11.6% of BVS-treated patients vs 7.9% of EES-treated patients between 0 to 3 years (HR, 1.42; 95% CI, 1.12-1.80), and 4.3% of BVS-treated patients vs 4.5% of EES-treated patients between 3 to 5 years (HR, 0.92; 95% CI, 0.64-1.31) (P for interaction = .046). Device thrombosis occurred in 2.4% of BVS-treated patients vs 0.6% of EES-treated patients between 0 to 3 years (HR, 3.86; 95% CI, 1.75-8.50) and 0.1% of BVS-treated patients vs 0.3% of EES-treated patients between 3 to 5 years (HR, 0.44; 95% CI, 0.07-2.70) (P for interaction = .03). These results were consistent by spline analysis and after multiple imputation and multivariable analysis.
Conclusions and relevance
The period of excess risk for the first-generation Absorb BVS ends at 3 years. These data provide mechanistic insights into the timing of adverse events after BVS and identify the hurdles to be overcome for bioresorbable technology to be accepted as a valid alternative for patients with coronary artery disease.
Trial registration
ClinicalTrials.gov identifiers: NCT01751906, NCT01844284, NCT01923740, and NCT01425281.



JAMA Cardiol: 26 Sep 2019; epub ahead of print
Stone GW, Kimura T, Gao R, Kereiakes DJ, ... Ali ZA, Serruys PW
JAMA Cardiol: 26 Sep 2019; epub ahead of print | PMID: 31561250
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Impact:
Abstract

Effect of 1 or 2 Doses of Inclisiran on Low-Density Lipoprotein Cholesterol Levels: One-Year Follow-up of the ORION-1 Randomized Clinical Trial.

Ray KK, Stoekenbroek RM, Kallend D, Nishikido T, ... Wijngaard PLJ, Kastelein JJP
Importance
Sustained reductions in low-density lipoprotein cholesterol (LDL-C) with lipid-lowering therapies that require frequent dosing are reliant on patient adherence, and poor adherence is associated with worse clinical outcomes.
Objective
To determine whether inclisiran, a small interfering RNA, reduces mean LDL-C exposure with an infrequent dosing regimen.
Design, setting, and participants
Prespecified analysis of a randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial. Participants were followed up monthly for LDL-C levels and proprotein convertase subtilisin-kexin type 9 (PCSK9) measurements as well as safety until their LDL-C levels had returned to within 20% of their change from baseline (maximum 360 days). The study included patients with elevated LDL-C despite maximally tolerated statin therapy. Data were analyzed between January 11, 2016, and June 7, 2017.
Interventions
One dose (200, 300, or 500 mg on day 1) or 2 doses (100, 200, or 300 mg on days 1 and 90) of inclisiran sodium or placebo.
Main outcomes and measures
Duration of time to return to within 20% of change from baseline for LDL-C levels and time-averaged LDL-C reductions over 1 year.
Results
At baseline, among the 501 participants, 65% were men (n = 326 of 501), mean age was 63 years, 6% had familial hypercholesterolemia (n = 28 of 501), and 69% had established ASCVD (n = 347 of 501). Baseline LDL-C was 128 mg/dL among 501 randomized participants. The percentage of participants who were followed up to day 360 because their LDL-C levels had not returned to within 20% of their change from baseline ranged from 48.3% to 65.0% for those receiving a single dose and between 55.9% and 83.1% of those receiving 2 doses, with similar effects observed for PCSK9. Time-averaged reduction in LDL-C levels over 1 year after a single dose ranged from 29.5% to 38.7% (P < .001 between groups) and from 29.9% to 46.4% (P < .001 between groups) for those who received 2 doses. The 2-dose 300-mg regimen produced the highest proportion of responders at day 360 and the greatest mean reduction in LDL-C over 1 year. Incidence of adverse events was similar through to 1 year.
Conclusions and relevance
Treatment with inclisiran resulted in durable reductions in LDL-C over 1 year. Inclisiran may offer a novel approach to LDL-C reduction with the convenience of infrequent dosing.
Trial registration
ClinicalTrials.gov identifier: NCT02597127.



JAMA Cardiol: 24 Sep 2019; epub ahead of print
Ray KK, Stoekenbroek RM, Kallend D, Nishikido T, ... Wijngaard PLJ, Kastelein JJP
JAMA Cardiol: 24 Sep 2019; epub ahead of print | PMID: 31553410
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Impact:
Abstract

Patient and Hospital Characteristics of Mitral Valve Surgery in the United States.

Vemulapalli S, Grau-Sepulveda M, Habib R, Thourani V, Bavaria J, Badhwar V
Importance
Volume metrics may have relevance in the evaluation of valve center expertise. However, a paucity of data exists regarding the quantity, volume, and geographic location of mitral valve (MV) surgical centers in the United States and the proportion of underserved populations they treat.
Objectives
To evaluate the hospital, patient, and procedural characteristics of mitral valve repair or replacement (MVRR) in the United States as a function of hospital procedure volume.
Design, setting, and participants
This cross-sectional, multicenter observational study was conducted from July 2014 to June 2018. Patients in the Society of Thoracic Surgeons Adult Cardiac Surgery Database undergoing any surgical procedure involving MVRR in the United States were included.
Main outcomes and measures
Volume distribution of MVRR by hospital and hospital referral region.
Results
There were 165 405 MVRRs performed in 1082 centers during the study period, of which 86 488 (52.3%) were MV repairs. There were 575 centers (53.1%) that performed 25 or more MVRRs per year. The geographic distribution of centers performing 25 or more MVRRs per year differed from those performing fewer than 25 MVRRs per year. Of 304 designated hospital referral regions, 235 (77.3%) had at least 1 center performing 25 or more MVRRs per year, representing accessibility to 1 or more such centers for 296.4 million of 320.1 million US residents (92.6% of the US population; Midwest, 60.0 million of 68.0 million [88.4%]; South, 112.6 million of 122.6 million [91.9%]; West, 68.6 million of 72.9 million [94.1%]; and Northeast, 54.9 million of 56.6 million [97.1%]). Of 304 hospital referral regions, 168 (55.3%) had at least 1 center performing 40 or more MVRRs per year, representing accessibility to 1 or more such centers for 259.8 million of 317.90 million (81.7%) of the US population (Midwest, 50.5 million of 67.9 million [74.5%]; South, 94.5 million of 121.1 million [78.1%]; West, 64.0 million of 72.8 million [88.0%]; Northeast, 50.1 million of 56.3 million [90.2%]). More black and Hispanic patients received operations in centers performing 25 or more MVRRs per year (22 984) vs those performing fewer than 25 MVRRs per year (3227), yet the proportion was higher in lower-volume centers (22 984 of 148 385 [15.5%] vs 3227 of 17 020 [19.0%]; P < .001). In centers performing 25 or more MVRRs per year vs fewer than 25 MVRRs per year, there was a lower percentage of Medicare and Medicaid patients (47 920 of 148 385 [32.3%] vs 6183 of 17 020 [.3%]; P < .001) and patients from rural zip codes (21 208 of 148 385 [14.3%] vs 3146 of 17 020 [18.5%]; P < .001).
Conclusions and relevance
Fifty-three percent of all centers performed 25 or more MVRRs per year, and 92.6% of the US population lived in an hospital referral region with at least 1 such center. Disparities in race/ethnicity, rurality, and insurance status exist among patients being treated at centers with different volumes. These data indicate that efforts to centralize care based on volume metrics will need to balance access vs quality.



JAMA Cardiol: 01 Oct 2019; epub ahead of print
Vemulapalli S, Grau-Sepulveda M, Habib R, Thourani V, Bavaria J, Badhwar V
JAMA Cardiol: 01 Oct 2019; epub ahead of print | PMID: 31577335
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Impact:
Abstract

Optimal Antithrombotic Regimens for Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: An Updated Network Meta-analysis.

Lopes RD, Hong H, Harskamp RE, Bhatt DL, ... Gibson CM, Alexander JH
Importance
Antithrombotic treatment in patients with atrial fibrillation (AF) and percutaneous coronary intervention (PCI) presents a balancing act with regard to bleeding and ischemic risks.
Objectives
To evaluate the safety and efficacy of 4 antithrombotic regimens by conducting an up-to-date network meta-analysis and to identify the optimal treatment for patients with AF undergoing PCI.
Data sources
Online computerized database (MEDLINE).
Study selection
Five randomized studies were included (N = 11 542; WOEST, PIONEER AF-PCI, RE-DUAL PCI, AUGUSTUS, ENTRUST-AF PCI).
Data extraction and synthesis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used in this network meta-analysis, in which bayesian random-effects models were applied. The data were analyzed from September 9 to 29, 2019.
Main outcomes and measures
The primary safety outcome was thrombolysis in myocardial infarction (TIMI) major bleeding and the primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE).
Results
The total number of participants included in the study was 11 532. The mean age of the participants ranged from 70 to 72 years, 69% to 83% were male, 20% to 26% were female, and the participants were predominantly white (>90%). Compared with vitamin K antagonists (VKA) plus dual antiplatelet therapy (DAPT) (reference), the odds ratios (ORs) (95% credible intervals) for TIMI major bleeding were 0.57 (0.31-1.00) for VKA plus P2Y12 inhibitor, 0.69 (0.40-1.16) for non-VKA oral anticoagulant (NOAC) plus DAPT, and 0.52 (0.35-0.79) for NOAC plus P2Y12 inhibitor. For MACE, using VKA plus DAPT as reference, the ORs (95% credible intervals) were 0.97 (0.64-1.42) for VKA plus P2Y12 inhibitor, 0.95 (0.64-1.39) for NOAC plus DAPT, and 1.03 (0.77-1.38) for NOAC plus P2Y12 inhibitor.
Conclusions and relevance
The findings of this study suggest that an antithrombotic regimen of VKA plus DAPT should generally be avoided, because regimens in which aspirin is discontinued may lead to lower bleeding risk and no difference in antithrombotic effectiveness. The use of a NOAC plus a P2Y12 inhibitor without aspirin may be the most favorable treatment option and the preferred antithrombotic regimen for most patients with AF undergoing PCI.



JAMA Cardiol: 25 Feb 2020; epub ahead of print
Lopes RD, Hong H, Harskamp RE, Bhatt DL, ... Gibson CM, Alexander JH
JAMA Cardiol: 25 Feb 2020; epub ahead of print | PMID: 32101251
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Impact:
Abstract

Long-term Thromboembolic Risk in Patients With Postoperative Atrial Fibrillation After Left-Sided Heart Valve Surgery.

Butt JH, Olesen JB, Gundlund A, Kümler T, ... Køber L, Fosbøl EL
Importance
New-onset postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery. However, data on the long-term risk of thromboembolism in patients who develop POAF after heart valve surgery are conflicting. In addition, data on stroke prophylaxis in this setting are lacking.
Objective
To assess the long-term risk of thromboembolism in patients developing new-onset POAF after isolated left-sided heart valve surgery relative to patients with nonsurgical, nonvalvular atrial fibrillation (NVAF).
Design, setting, and participants
This observational cohort study was conducted from January 1, 2000, through December 31, 2015, using Danish nationwide registries and the Eastern Danish Heart Surgery Database. Patients who developed POAF after isolated left-sided heart valve surgery (bioprosthetic aortic or mitral valve replacement and/or aortic or mitral valve repair) from 2000 through 2015 were included. These patients were matched with patients with nonsurgical NVAF in a 1:3 ratio by age, sex, heart failure, hypertension, diabetes, a history of thromboembolism, ischemic heart disease, and year of diagnosis. Data analyses took place from January to March 2019.
Main outcomes and measures
Rates of thromboembolism.
Results
Of the 1587 patients who underwent isolated left-sided heart valve surgery, 741 patients (46.7%) developed POAF during admission. Of the 712 patients with POAF who were eligible for matching, 675 patients were matched with 2025 patients with NVAF and made up the study population. In the matched study population, the median age was 71 (interquartile range, 65-77) years, and 1600 (59.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 420 patients with POAF (62.9%) and in 1030 patients with NVAF (51.4%). The crude incidence rates of thromboembolism were 21.9 (95% CI, 17.4-27.6) and 17.7 (95% CI, 15.2-20.6) events per 1000 person-years for patients with POAF and patients with NVAF, respectively. In the adjusted analysis, the long-term risk of thromboembolism was similar in patients with POAF and NVAF (hazard ratio, 1.22 [95% CI, 0.88-1.68]). Oral anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in patients with POAF (hazard ratio, 0.45 [95% CI, 0.22-0.90]) as well as patients with NVAF (hazard ratio, 0.63 [95% CI, 0.45-0.87]) compared with no anticoagulation therapy.
Conclusions and relevance
New-onset POAF after isolated left-sided heart valve surgery was associated with a similar long-term risk of thromboembolism as NVAF. These data warrant studies addressing the role of anticoagulation therapy in POAF after left-sided heart valve surgery.



JAMA Cardiol: 08 Oct 2019; epub ahead of print
Butt JH, Olesen JB, Gundlund A, Kümler T, ... Køber L, Fosbøl EL
JAMA Cardiol: 08 Oct 2019; epub ahead of print | PMID: 31596426
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Impact:
Abstract

Long-term Outcomes in Patients With Severely Reduced Left Ventricular Ejection Fraction Undergoing Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting.

Sun LY, Gaudino M, Chen RJ, Bader Eddeen A, Ruel M
Importance
Data are lacking on the outcomes of patients with severely reduced left ventricular ejection fraction (LVEF) who undergo revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).
Objective
To compare the long-term outcomes in patients undergoing revascularization by PCI or CABG.
Design, setting, and participants
This retrospective cohort study performed in Ontario, Canada, from October 1, 2008, and December 31, 2016, included data from Ontario residents between 40 and 84 years of age with LVEFs less than 35% and left anterior descending (LAD), left main, or multivessel coronary artery disease (with or without LAD involvement) who underwent PCI or CABG. Exclusion criteria were concomitant procedures, previous CABG, metastatic cancer, dialysis, CABG and PCI on the same day, and emergency revascularization within 24 hours of a myocardial infarction (MI). Data analysis was performed from June 2, 2018, to December 28, 2018.
Exposures
Revascularization by PCI or CABG.
Main outcomes and measures
The primary outcome was all-cause mortality. Secondary outcomes were death from cardiovascular disease, major adverse cardiovascular events (MACE; defined as stroke, subsequent revascularization, and hospitalization for MI or heart failure), and each of the individual MACE.
Results
A total of 12 113 patients (mean [SD] age, 64.8 (11.0) years for the PCI group and 65.6 [9.7] years for the CABG group; 5084 (72.5%) male for the PCI group and 4229 (82.9%) male for the PCI group) were propensity score matched on 30 baseline characteristics: 2397 patients undergoing PCI and 2397 patients undergoing CABG. The median follow-up was 5.2 years (interquartile range, 5.0-5.3). Patients who received PCI had significantly higher rates of mortality (hazard ratio [HR], 1.6; 95% CI, 1.3-1.7), death from cardiovascular disease (HR 1.4, 95% CI, 1.1-1.6), MACE (HR, 2.0; 95% CI, 1.9-2.2), subsequent revascularization (HR, 3.7; 95% CI, 3.2-4.3), and hospitalization for MI (HR, 3.2; 95% CI, 2.6-3.8) and heart failure (HR, 1.5; 95% CI, 1.3-1.6) compared with matched patients who underwent CABG.
Conclusions and relevance
In this study, higher rates of mortality and MACE were seen in patients who received PCI compared with those who underwent CABG. The findings may provide insight to physicians who are involved in decision-making for these patients.



JAMA Cardiol: 07 Apr 2020; epub ahead of print
Sun LY, Gaudino M, Chen RJ, Bader Eddeen A, Ruel M
JAMA Cardiol: 07 Apr 2020; epub ahead of print | PMID: 32267465
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Impact:
Abstract

Association Between Current and Future Annual Hospital Percutaneous Coronary Intervention Mortality Rates.

Sandhu AT, Kohsaka S, Bhattacharya J, Fearon WF, Harrington RA, Heidenreich PA
Importance
Multiple states publicly report a hospital\'s risk-adjusted mortality rate for percutaneous coronary intervention (PCI) as a quality measure. However, whether reported annual PCI mortality is associated with a hospital\'s future performance is unclear.
Objective
To evaluate the association between reported risk-adjusted hospital PCI-related mortality and a hospital\'s future PCI-related mortality.
Design, setting, and participants
This study used data from the New York Percutaneous Intervention Reporting System from January 1, 1998, to December 31, 2016, to assess hospitals that perform PCI.
Exposures
Public-reported, risk-adjusted, 30-day mortality after PCI.
Main outcomes and measures
The primary analysis evaluated the association between a hospital\'s reported risk-adjusted PCI-related mortality and future PCI-related mortality. The correlation between a hospital\'s observed to expected (O/E) PCI-related mortality rates each year and future O/E mortality ratios was assessed. Multivariable linear regression was used to examine the association between index year O/E mortality and O/E mortality in subsequent years while adjusting for PCI volume and patient severity.
Results
This study included 67 New York hospitals and 960 hospital-years. Hospitals with low PCI-related mortality (O/E mortality ratio, ≤1) and high mortality (O/E mortality ratio, >1) had inverse associations between their O/E mortality ratio in the index year and the subsequent change in the ratio (hospitals with low mortality, r = -0.45; hospitals with high mortality, r = -0.60). Little of the variation in risk-adjusted mortality was explained by prior performance. An increase in the O/E mortality ratio from 1.0 to 2.0 in the index year was associated with a higher O/E mortality ratio of only 0.15 (95% CI, 0.02-0.27) in the following year.
Conclusions and relevance
At hospitals with high or low PCI-related mortality rates, the rates largely regressed to the mean the following year. A hospital\'s risk-adjusted mortality rate was poorly associated with its future mortality. The annual hospital PCI-related mortality may not be a reliable factor associated with hospital quality to consider in a practice change or when helping patients select high-quality hospitals.



JAMA Cardiol: 17 Sep 2019:1-8; epub ahead of print
Sandhu AT, Kohsaka S, Bhattacharya J, Fearon WF, Harrington RA, Heidenreich PA
JAMA Cardiol: 17 Sep 2019:1-8; epub ahead of print | PMID: 31532454
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Impact:
Abstract

Benefit and Risks of Aspirin in Addition to Ticagrelor in Acute Coronary Syndromes: A Post Hoc Analysis of the Randomized GLOBAL LEADERS Trial.

Tomaniak M, Chichareon P, Onuma Y, Deliargyris EN, ... Serruys PW,
Importance
The role of aspirin as part of antiplatelet regimens in acute coronary syndromes (ACS) needs to be clarified in the context of newer potent P2Y12 antagonists.
Objective
To evaluate the benefit and risks of aspirin in addition to ticagrelor among patients with ACS beyond 1 month after percutaneous coronary intervention (PCI).
Design, setting, and participants
This is a nonprespecified, post hoc analysis of GLOBAL LEADERS, a randomized, open-label superiority trial comparing 2 antiplatelet treatment strategies after PCI. The trial included 130 secondary/tertiary care hospitals in different countries, with 15 991 unselected patients with stable coronary artery disease or ACS undergoing PCI. Patients had outpatient visits at 1, 3, 6, 12, 18, and 24 months after index procedure.
Interventions
The experimental group received aspirin plus ticagrelor for 1 month followed by 23-month ticagrelor monotherapy; the reference group received aspirin plus either clopidogrel (stable coronary artery disease) or ticagrelor (ACS) for 12 months, followed by 12-month aspirin monotherapy. In this analysis, we examined the clinical outcomes occurring between 31 days and 365 days after randomization, specifically in patients with ACS who, within this time frame, were assigned to receive either ticagrelor alone or ticagrelor and aspirin.
Main outcomes and measures
The primary outcome was the composite of all-cause death or new Q-wave myocardial infarction.
Results
Of 15 968 participants, there were 7487 patients with ACS enrolled; 3750 patients were assigned to the experimental group and 3737 patients to the reference group. Between 31 and 365 days after randomization, the primary outcome occurred in 55 patients (1.5%) in the experimental group and in 75 patients (2.0%) in the reference group (hazard ratio [HR], 0.73; 95% CI, 0.51-1.03; P = .07); investigator-reported Bleeding Academic Research Consortium-defined bleeding type 3 or 5 occurred in 28 patients (0.8%) in the experimental group and in 54 patients (1.5%) in the reference arm (HR, 0.52; 95% CI, 0.33-0.81; P = .004).
Conclusions and relevance
Between 1 month and 12 months after PCI in ACS, aspirin was associated with increased bleeding risk and appeared not to add to the benefit of ticagrelor on ischemic events. These findings should be interpreted as exploratory and hypothesis generating; however, they pave the way for further trials evaluating aspirin-free antiplatelet strategies after PCI.
Trial registration
ClinicalTrials.gov identifier: NCT01813435.



JAMA Cardiol: 25 Sep 2019; epub ahead of print
Tomaniak M, Chichareon P, Onuma Y, Deliargyris EN, ... Serruys PW,
JAMA Cardiol: 25 Sep 2019; epub ahead of print | PMID: 31557763
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Impact:
Abstract

Current Demographic Status of Cardiologists in the United States.

Mehta LS, Fisher K, Rzeszut AK, Lipner R, ... Oetgen WJ, Douglas PS
Importance
Increasing cardiology workforce diversity will expand the talent of the applicant pool and may reduce health care disparities.
Objective
To assess US cardiology physician workforce demographics by sex and race/ethnicity in the context of the US population and the available pipelines of trainees.
Design, setting, and participants
This cross-sectional study used data from the Association of American Medical Colleges, the American Medical Association, and the American Board of Internal Medicine to stratify medical students, resident physicians, fellows, and cardiologists by sex and race/ethnicity. Additionally, proportional changes from 2006 through 2016 were assessed for adult and pediatric cardiology. Data analysis took place from August 2018 to January 2019.
Main outcomes and measures
Percentage of cardiologists and trainees by sex and race/ethnicity in 2016, as well as changes in proportions between 2006 and 2016.
Results
Despite a high percentage of female internal medicine resident physicians (10 765 of 25 252 [42.6%]), female physicians were underrepresented in adult general cardiology fellowships (584 of 2720 [21.5%]) and procedural subspecialty fellowships (interventional cardiology, 30 of 305 [9.8%]; electrophysiology, 24 of 175 [13.7%]). The percentage of female adult cardiologists slightly increased from 2006 through 2016 (from 8.9% to 12.6%; slope, 0.36; P < .001) but remained low. Female physicians made up a disproportionately higher number of pediatric residency positions (6439 of 8832 [72.9%]). Trends showed an increase in female pediatric cardiology fellows (from 40.4% to 50.5%; slope, 1.25; P < .001), which resulted in an increase in the percentage of female pediatric cardiologists (from 27.1% to 34.0%; slope, 0.64; P < .001). The percentages of members of underrepresented minority groups in adult and pediatric cardiology fellowships (from 11.1% to 12.4%; slope, 0.15; P = .01; and from 7.7% to 9.9%; slope, 0.29; P = .009; respectively) were low and increased only slightly over time. Additionally, members of underrepresented minorities made up less than 8% of practicing adult and pediatric cardiologists. Although Asian individuals are 5.2% of the US general population, they are not considered underrepresented because they are 22.1% of US medical school graduates (n = 4202 of 18 999), 38.1% of internal medicine resident physicians (n = 9618 of 25 252), 40.4% of adult cardiology fellows (n = 1098 of 2720), 19.9% of adult cardiologists (n = 5973 of 30 016), 22.6% of pediatric resident physicians (n = 1998 of 8832), 28.0% of pediatric cardiology fellows (n = 122 of 436), and 20.1% of pediatric cardiologists (n = 574 of 2860).
Conclusions and relevance
Female physicians remain underrepresented in adult cardiology, despite a robust pipeline of female medical students and internal medicine resident physicians. Women in pediatric cardiology are underrepresented but increasing in number. Members of several racial/ethnic minority groups remain underrepresented in adult and pediatric cardiology, and the percentages of trainees and medical students from these groups were also low. Different strategies are needed to address the continuing lack of diversity in cardiology for underrepresented minority individuals and women.



JAMA Cardiol: 10 Sep 2019; epub ahead of print
Mehta LS, Fisher K, Rzeszut AK, Lipner R, ... Oetgen WJ, Douglas PS
JAMA Cardiol: 10 Sep 2019; epub ahead of print | PMID: 31509160
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Impact:
Abstract

Association of Frailty With 30-Day Outcomes for Acute Myocardial Infarction, Heart Failure, and Pneumonia Among Elderly Adults.

Kundi H, Wadhera RK, Strom JB, Valsdottir LR, ... Kazi DS, Yeh RW
Importance
The addition of a claims-based frailty metric to traditional comorbidity-based risk-adjustment models for acute myocardial infarction (AMI), heart failure (HF), and pneumonia improves the prediction of 30-day mortality and readmission. This may have important implications for hospitals that tend to care for frail populations and participate in Centers for Medicare & Medicaid Services value-based payment programs, which use these risk-adjusted metrics to determine reimbursement.
Objective
To determine whether the addition of frailty measures to traditional comorbidity-based risk-adjustment models improved prediction of outcomes for patients with AMI, HF, and pneumonia.
Design, setting, and participants
A nationwide cohort study included Medicare fee-for-service beneficiaries 65 years and older in the United States between January 1 and December 1, 2016. Analysis began August 2018.
Main outcomes and measures
Rates of mortality within 30 days of admission and 30 days of discharge, as well as 30-day readmission rates by frailty group. We evaluated the incremental effect of adding the Hospital Frailty Risk Score (HFRS) to current comorbidity-based risk-adjustment models for 30-day outcomes across all conditions.
Results
For 785 127 participants, there were 166 200 hospitalizations [21.2%] for AMI, 348 619 [44.4%] for HF, and 270 308 [34.4%] for pneumonia. The mean (SD) age at the time of hospitalization was 79.2 (8.9) years; 656 315 (83.6%) were white and 402 639 (51.3%) were women. The mean (SD) HFRS was 7.3 (7.4) for patients with AMI, 10.8 (8.3) for patients with HF, and 8.2 (5.7) for patients with pneumonia. Among patients hospitalized for AMI, an HFRS more than 15 (compared with an HFRS <5) was associated with a higher risk of 30-day postadmission mortality (adjusted odds ratio [aOR], 3.6; 95% CI, 3.4-3.8), 30-day postdischarge mortality (aOR, 4.0; 95% CI, 3.7-4.3), and 30-day readmission (aOR, 3.0; 95% CI, 2.9-3.1) after multivariable adjustment for age, sex, race, and comorbidities. Similar patterns were observed for patients hospitalized with HF (30-day postadmission mortality: aOR, 3.5; 95% CI, 3.4-3.7; 30-day postdischarge mortality: aOR, 3.5; 95% CI, 3.3-3.6; and 30-day readmission: aOR, 2.9; 95% CI, 2.8-3.0) and among patients with pneumonia (30-day postadmission mortality: aOR, 2.5; 95% CI, 2.3-2.6; 30-day postdischarge mortality: aOR, 3.0; 95% CI, 2.9-3.2; and 30-day readmission: aOR, 2.8; 95% CI, 2.7-2.9). The addition of HFRS to traditional comorbidity-based risk-prediction models improved discrimination to predict outcomes for all 3 conditions.
Conclusions and relevance
Among Medicare fee-for-service beneficiaries, frailty as measured by the HFRS was associated with mortality and readmissions among patients hospitalized for AMI, HF, or pneumonia. The addition of HFRS to traditional comorbidity-based risk-prediction models improved the prediction of outcomes for all 3 conditions.



JAMA Cardiol: 24 Sep 2019; epub ahead of print
Kundi H, Wadhera RK, Strom JB, Valsdottir LR, ... Kazi DS, Yeh RW
JAMA Cardiol: 24 Sep 2019; epub ahead of print | PMID: 31553402
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Impact:
Abstract

Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades.

Sepehrvand N, Alemayehu W, Das D, Gupta AK, ... Kashour Z, Ezekowitz JA
Importance
Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied.
Objective
To investigate how pragmatic or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time.
Data source
Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology.
Study selection
All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included.
Data extraction and synthesis
Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine.
Main outcomes and measures
The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis.
Results
Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point.
Conclusions and relevance
The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.



JAMA Cardiol: 31 Aug 2019; epub ahead of print
Sepehrvand N, Alemayehu W, Das D, Gupta AK, ... Kashour Z, Ezekowitz JA
JAMA Cardiol: 31 Aug 2019; epub ahead of print | PMID: 31473763
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Impact:
Abstract

Effectiveness of Interventions Aimed at Increasing Statin-Prescribing Rates in Primary Cardiovascular Disease Prevention: A Systematic Review of Randomized Clinical Trials.

Sparrow RT, Khan AM, Ferreira-Legere LE, Ko DT, ... Tu JV, Udell JA
Importance
Statins are a cornerstone medication in cardiovascular disease prevention, but their use in clinical practice remains suboptimal, with less than half of people who are indicated for statins actually taking the medication.
Objective
To perform a systematic review and synthesis of the literature on patient-oriented and physician-oriented interventions aimed at increasing statin-prescribing rates in adults without a history of cardiovascular disease.
Evidence review
PubMed, Embase, and the Cochrane Library were searched for randomized clinical trials published between January 2000 and May 2019. Data abstraction was performed using the Cochrane Public Health Review Group\'s data collection template, and a narrative synthesis of study results was conducted. The risk of bias in each study was qualitatively assessed, and a funnel plot was created to further evaluate the risk of publication bias.
Findings
Among 7948 citations and 128 full-text articles reviewed, 20 studies (of 109 807 patients) were included in the review. Eight trials reported a statistically significant increases in statin-prescribing rates. Among the effective trials, absolute effect sizes ranged from 4.2% (95% CI, 2.2%-6.4%) to 23% (95% CI, 7.3%-38.9%) and odds ratios from 1.29 (95% CI, 1.01-1.66) to 11.8 (95% CI, 8.8-15.9). Patient-education initiatives were the most commonly effective intervention, with 4 of 7 trials indicating increases in statin-prescribing rates. Two trials combined electronic decision-support tools with audit-and-feedback systems, both of which were effective overall. Physician-education programs without dynamic input regarding patient risk or updated treatment recommendations were generally found to be less effective.
Conclusions and relevance
While heterogeneous in their interventions and outcomes, a number of interventions have demonstrated increases in statin-prescribing rates, with patient-education initiatives demonstrating more promising results than those focused on physician education alone. As opposed to more education about generic recommendations, tailored patient-focused and physician-focused interventions were more effective when they provided personalized cardiovascular risk information, dynamic decision-support tools, or audit-and-feedback reports in a multicomponent program. There are a number of modestly successful approaches to implement increases in rates of statin prescribing, a proven yet underused cardiovascular disease prevention class of therapy.



JAMA Cardiol: 27 Aug 2019; epub ahead of print
Sparrow RT, Khan AM, Ferreira-Legere LE, Ko DT, ... Tu JV, Udell JA
JAMA Cardiol: 27 Aug 2019; epub ahead of print | PMID: 31461127
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Impact:
Abstract

Association of Daytime and Nighttime Blood Pressure With Cardiovascular Disease Events Among African American Individuals.

Yano Y, Tanner RM, Sakhuja S, Jaeger BC, ... Muntner P, Shimbo D
Importance
Little is known regarding health outcomes associated with higher blood pressure (BP) levels measured outside the clinic among African American individuals.
Objective
To examine whether daytime and nighttime BP levels measured outside the clinic among African American individuals are associated with cardiovascular disease (CVD) and all-cause mortality independent of BP levels measured inside the clinic.
Design, setting, and participants
This prospective cohort study analyzed data from 1034 African American participants in the Jackson Heart Study who completed ambulatory BP monitoring at baseline (September 26, 2000, to March 31, 2004). Mean daytime and nighttime BPs were calculated based on measurements taken while participants were awake and asleep, respectively. Data were analyzed from July 1, 2017, to April 30, 2019.
Main outcomes and measures
Cardiovascular disease events, including coronary heart disease and stroke, experienced through December 31, 2014, and all-cause mortality experienced through December 31, 2016, were adjudicated. The associations of daytime BP and nighttime BP, separately, with CVD events and all-cause mortality were determined using Cox proportional hazards regression models.
Results
A total of 1034 participants (mean [SD] age, 58.9 [10.9] years; 337 [32.6%] male; and 583 [56.4%] taking antihypertensive medication) were included in the study. The mean daytime systolic BP (SBP)/diastolic BP (DBP) was 129.4/77.6 mm Hg, and the mean nighttime SBP/DBP was 121.3/68.4 mm Hg. During follow-up (median [interquartile range], 12.5 [11.1-13.6] years for CVD and 14.8 [13.7-15.6] years for all-cause mortality), 113 CVD events and 194 deaths occurred. After multivariable adjustment, including in-clinic SBP and DBP, the hazard ratios (HRs) for CVD events for each SD higher level were 1.53 (95% CI, 1.24-1.88) for daytime SBP (per 13.5 mm Hg), 1.48 (95% CI, 1.22-1.80) for nighttime SBP (per 15.5 mm Hg), 1.25 (95% CI, 1.02-1.51) for daytime DBP (per 9.3 mm Hg), and 1.30 (95% CI, 1.06-1.59) for nighttime DBP (per 9.5 mm Hg). Nighttime SBP was associated with all-cause mortality (HR per 1-SD higher level, 1.24; 95% CI, 1.06-1.45), but no association was present for daytime SBP (HR, 1.13; 95% CI, 0.97-1.33) and daytime (HR, 0.95; 95% CI, 0.81-1.10) and nighttime (HR, 1.06; 95% CI, 0.90-1.24) DBP.
Conclusions and relevance
Among African American individuals, higher daytime and nighttime SBPs were associated with an increased risk for CVD events and all-cause mortality independent of BP levels measured in the clinic. Measurement of daytime and nighttime BP using ambulatory monitoring during a 24-hour period may help identify African American individuals who have an increased cardiovascular disease risk.



JAMA Cardiol: 13 Aug 2019; epub ahead of print
Yano Y, Tanner RM, Sakhuja S, Jaeger BC, ... Muntner P, Shimbo D
JAMA Cardiol: 13 Aug 2019; epub ahead of print | PMID: 31411629
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Impact:
Abstract

Dual-Energy Computed Tomography Detection of Cardiovascular Monosodium Urate Deposits in Patients With Gout.

Klauser AS, Halpern EJ, Strobl S, Gruber J, ... Stofferin H, Jaschke W
Importance
The prevalence of gout has increased in recent decades. Several clinical studies have demonstrated an association between gout and coronary heart disease, but direct cardiovascular imaging of monosodium urate (MSU) deposits by using dual-energy computed tomography (DECT) has not been reported to date.
Objective
To compare coronary calcium score and cardiovascular MSU deposits detected by DECT in patients with gout and controls.
Design, setting, and participants
This prospective Health Insurance Portability and Accountability Act-compliant study included patients with gout and controls who presented to a rheumatologic clinic from January 1, 2017, to November 1, 2018. All consecutive patients underwent DECT to assess coronary calcium score and MSU deposits in aorta and coronary arteries. In addition, cadavers were assessed by DECT for cardiovascular MSU deposits and verified by polarizing microscope. Analysis began in January 2017.
Main outcomes and measures
Detection rate of cardiovascular MSU deposits using DECT in patients with gout and control group patients without a previous history of gout or inflammatory rheumatic diseases.
Results
A total of 59 patients with gout (mean [SD] age, 59 [5.7] years; range, 47-89 years), 47 controls (mean [SD] age, 70 [10.4] years; range, 44-86 years), and 6 cadavers (mean [SD] age at death, 76 [17] years; range, 56-95 years) were analyzed. The frequency of cardiovascular MSU deposits was higher among patients with gout (51 [86.4%]) compared with controls (7 [14.9%]) (χ2 = 17.68, P < .001), as well as coronary MSU deposits among patients with gout (19 [32.2%]) vs controls (2 [4.3%]) (χ2 = 8.97, P = .003). Coronary calcium score was significantly higher among patients with gout (900 Agatston units [AU]; 95% CI, 589-1211) compared with controls (263 AU; 95% CI, 76-451; P = .001) and also significantly higher among 58 individuals with cardiovascular MSU deposits (950 AU; 95% CI, 639-1261) compared with 48 individuals without MSU deposits (217 AU; 95% CI, 37-397; P < .001). Among 6 cadavers, 3 showed cardiovascular MSU deposits, which were verified by polarizing light microscope.
Conclusion and relevance
Dual-energy computed tomography demonstrates cardiovascular MSU deposits, as confirmed by polarized light microscopy. Cardiovascular MSU deposits were detected by DECT significantly more often in patients with gout compared with controls and were associated with higher coronary calcium score. This new modality may be of importance in gout population being at risk from cardiovascular disease.



JAMA Cardiol: 10 Sep 2019; epub ahead of print
Klauser AS, Halpern EJ, Strobl S, Gruber J, ... Stofferin H, Jaschke W
JAMA Cardiol: 10 Sep 2019; epub ahead of print | PMID: 31509156
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Impact:
Abstract

Association of Pulmonary Hypertension With Clinical Outcomes of Transcatheter Mitral Valve Repair.

Al-Bawardy R, Vemulapalli S, Thourani VH, Mack M, ... Jassar AS, Elmariah S
Importance
Pulmonary hypertension (pHTN) is associated with increased risk of mortality after mitral valve surgery for mitral regurgitation. However, its association with clinical outcomes in patients undergoing transcatheter mitral valve repair (TMVr) with a commercially available system (MitraClip) is unknown.
Objective
To assess the association of pHTN with readmissions for heart failure and 1-year all-cause mortality after TMVr.
Design, setting, and participants
This retrospective cohort study analyzed 4071 patients who underwent TMVr with the MitraClip system from November 4, 2013, through March 31, 2017, across 232 US sites in the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy registry. Patients were stratified into the following 4 groups based on invasive mean pulmonary arterial pressure (mPAP): 1103 with no pHTN (mPAP, <25 mm Hg [group 1]); 1399 with mild pHTN (mPAP, 25-34 mm Hg [group 2]); 1011 with moderate pHTN (mPAP, 35-44 mm Hg [group 3]); and 558 with severe pHTN (mPAP, ≥45 mm Hg [group 4]). Data were analyzed from November 4, 2013, through March 31, 2017.
Interventions
Patients were stratified into groups before TMVr, and clinical outcomes were assessed at 1 year after intervention.
Main outcomes and measures
Primary end point was a composite of 1-year mortality and readmissions for heart failure. Secondary end points were 30-day and 1-year mortality and readmissions for heart failure. Linkage to Centers for Medicare & Medicaid Services administrative claims was performed to assess 1-year outcomes in 2381 patients.
Results
Among the 4071 patients included in the analysis, the median age was 81 years (interquartile range, 73-86 years); 1885 (46.3%) were women and 2186 (53.7%) were men. The composite rate of 1-year mortality and readmissions for heart failure was 33.6% (95% CI, 31.6%-35.7%), which was higher in those with pHTN (27.8% [95% CI, 24.2%-31.5%] in group 1, 32.4% [95% CI, 29.0%-35.8%] in group 2, 36.0% [95% CI, 31.8%-40.2%] in group 3, and 45.2% [95% CI, 39.1%-51.0%] in group 4; P < .001). Similarly, 1-year mortality (16.3% [95% CI, 13.4%-19.5%] in group 1, 19.8% [95% CI, 17.0%-22.8%] in group 2, 22.4% [95% CI, 18.8%-26.1%] in group 3, and 27.8% [95% CI, 22.6%-33.3%] in group 4; P < .001) increased across pHTN groups. The association of pHTN with mortality persisted despite multivariable adjustment (hazard ratio per 5-mm Hg mPAP increase, 1.05; 95% CI, 1.01-1.09; P = .02).
Conclusions and relevance
These findings suggest that pHTN is associated with increased mortality and readmission for heart failure in patients undergoing TMVr using the MitraClip system for severe mitral regurgitation. Further efforts are needed to determine whether earlier intervention before pHTN develops will improve clinical outcomes.



JAMA Cardiol: 19 Nov 2019; epub ahead of print
Al-Bawardy R, Vemulapalli S, Thourani VH, Mack M, ... Jassar AS, Elmariah S
JAMA Cardiol: 19 Nov 2019; epub ahead of print | PMID: 31746963
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Impact:
Abstract

Safety and Efficacy of Femoral Access vs Radial Access in ST-Segment Elevation Myocardial Infarction: The SAFARI-STEMI Randomized Clinical Trial.

Le May M, Wells G, So D, Chong AY, ... Quraishi A, Labinaz M
Importance
Among patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), a survival benefit associated with radial access compared with femoral access remains controversial.
Objective
To assess whether there is a survival benefit when radial access is used instead of femoral access among patients with STEMI referred for primary PCI.
Design, setting, and participants
This multicenter, open-label, randomized clinical trial was conducted at 5 PCI centers in Canada. In total, 2292 patients with STEMI referred for primary PCI were enrolled between July 2011 and December 2018, with a 30-day follow-up. The primary analyses were conducted based on the intention-to-treat population.
Interventions
Patients were randomized to radial access (n = 1136) or to femoral access (n = 1156) for PCI.
Main outcomes and measures
Initially, the primary outcome was bleeding, but this outcome was modified to 30-day all-cause mortality following the recommendation of the granting agency. Secondary outcomes included recurrent myocardial infarction, stroke, and Thrombolysis in Myocardial Infarction-defined major or minor bleeding.
Results
Among the 2292 patients enrolled, the mean (SD) age of the patients randomized to radial access was 61.6 (12.3) years and to femoral access was 62.0 (12.1) years, with 883 male patients in the radial access and 901 male patients in the femoral access group. The trial was stopped early following a futility analysis. Primary PCI was performed in 1082 of 1136 patients (95.2%) in the radial access group and 1109 of 1156 patients (95.9%) in the femoral access group. Bivalirudin was administered to 1001 patients (88.1%) in the radial access group and to 1068 patients (92.4%) in the femoral access group, whereas glycoprotein IIb/IIIa inhibitors were administered in only 69 patients (6.1%) in the radial access group and 68 patients (5.9%) in the femoral access group. A vascular closure device was used in 789 patients (68.3%) in the femoral group. The primary outcome, 30-day all-cause mortality, occurred in 17 patients (1.5%) assigned to radial access and in 15 patients (1.3%) assigned to femoral access (relative risk [RR], 1.15; 95% CI, 0.58-2.30; P = .69). There were no significant differences between patients assigned to radial and femoral access in the rates of reinfarction (1.8% vs 1.6%; RR, 1.07; 95% CI, 0.57-2.00; P = .83), stroke (1.0% vs 0.4%; RR, 2.24; 95% CI, 0.78-6.42; P = .12), and bleeding (1.4% vs 2.0%; RR, 0.71; 95% CI, 0.38-1.33; P = .28).
Conclusions and relevance
No significant differences were found for survival or other clinical end points at 30 days after the use of radial access vs femoral access in patients with STEMI referred for primary PCI. However, small absolute differences in end points cannot be definitively refuted given the premature termination of the trial.
Trial registration
ClinicalTrials.gov identifier: NCT01398254.



JAMA Cardiol: 01 Jan 2020; epub ahead of print
Le May M, Wells G, So D, Chong AY, ... Quraishi A, Labinaz M
JAMA Cardiol: 01 Jan 2020; epub ahead of print | PMID: 31895439
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Impact:
Abstract

Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).

Norrish G, Ding T, Field E, Ziólkowska L, ... Omar RZ, Kaski JP
Importance
Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk.
Objective
To develop and validate an SCD risk prediction model that provides individualized risk estimates.
Design, setting, and participants
A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017.
Exposures
The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping.
Main outcomes and measures
A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise).
Results
Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model\'s ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95%, CI 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years.
Conclusions and relevance
This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model\'s predictions in diverse patient populations.



JAMA Cardiol: 13 Aug 2019; epub ahead of print
Norrish G, Ding T, Field E, Ziólkowska L, ... Omar RZ, Kaski JP
JAMA Cardiol: 13 Aug 2019; epub ahead of print | PMID: 31411652
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Impact:
Abstract

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19).

Guo T, Fan Y, Chen M, Wu X, ... Wang X, Lu Z
Importance
Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce.
Objective
To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.
Design, setting, and participants
This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020.
Main outcomes and measures
Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.
Result
Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001). Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16). During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (41 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels. The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 25.6% (43 of 168).
Conclusions and relevance
Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.



JAMA Cardiol: 26 Mar 2020; epub ahead of print
Guo T, Fan Y, Chen M, Wu X, ... Wang X, Lu Z
JAMA Cardiol: 26 Mar 2020; epub ahead of print | PMID: 32219356
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Impact:
Abstract

Association of Multifaceted Mobile Technology-Enabled Primary Care Intervention With Cardiovascular Disease Risk Management in Rural Indonesia.

Patel A, Praveen D, Maharani A, Oceandy D, ... Sujarwoto S, Tampubolon G
Importance
Cardiovascular diseases (CVDs) are the leading cause of disease burden in Indonesia. Implementation of effective interventions for CVD prevention is limited.
Objective
To evaluate whether a mobile technology-supported primary health care intervention, compared with usual care, would improve the use of preventive drug treatment among people in rural Indonesia with a high risk of CVD.
Design, setting, and participants
A quasi-experimental study involving 6579 high-risk individuals in 4 intervention and 4 control villages in Malang district, Indonesia, was conducted between August 16, 2016, and March 31, 2018. Median duration of follow-up was 12.2 months. Residents 40 years or older were invited to participate. Those with high estimated 10-year risk of CVD risk (previously diagnosed CVD, systolic blood pressure [BP] >160 mm Hg or diastolic BP >100 mm Hg, 10-year estimated CVD risk of 30% or more, or 10-year estimated CVD risk of 20%-29% and a systolic BP >140 mm Hg) were followed up.
Interventions
A multifaceted mobile technology-supported intervention facilitating community-based CVD risk screening with referral, tailored clinical decision support for drug prescription, and patient follow-up.
Main outcomes and measures
The primary outcome was the proportion of individuals taking appropriate preventive CVD medications, defined as at least 1 BP-lowering drug and a statin for all high-risk individuals, and an antiplatelet drug for those with prior diagnosed CVD. Secondary outcomes included mean change in BP from baseline.
Results
Among 22 635 adults, 3494 of 11 647 in the intervention villages (30.0%; 2166 women and 1328 men; mean [SD] age, 58.3 [10.9] years) and 3085 of 10 988 in the control villages (28.1%; 1838 women and 1247 men; mean [SD] age, 59.0 [11.5] years) had high estimated risk of CVD. Of these, follow-up was completed in 2632 individuals (75.3%) from intervention villages and 2429 individuals (78.7%) from control villages. At follow-up, 409 high-risk individuals in intervention villages (15.5%) were taking appropriate preventive CVD medications, compared with 25 (1.0%) in control villages (adjusted risk difference, 14.1%; 95% CI, 12.7%-15.6%). This difference was driven by higher use of BP-lowering medication in those in the intervention villages (1495 [56.8%] vs 382 [15.7%]; adjusted risk difference, 39.4%; 95% CI, 37.0%-41.7%). The adjusted mean difference in change in systolic BP from baseline was -8.3 mm Hg (95% CI, -10.1 to -6.6 mm Hg).
Conclusions and relevance
This study found that a multifaceted mobile technology-supported primary health care intervention was associated with greater use of preventive CVD medication and lower BP levels among high-risk individuals in a rural Indonesian population.



JAMA Cardiol: 27 Aug 2019; epub ahead of print
Patel A, Praveen D, Maharani A, Oceandy D, ... Sujarwoto S, Tampubolon G
JAMA Cardiol: 27 Aug 2019; epub ahead of print | PMID: 31461123
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Impact:
Abstract

Association of Transient Endothelial Dysfunction Induced by Mental Stress With Major Adverse Cardiovascular Events in Men and Women With Coronary Artery Disease.

Lima BB, Hammadah M, Kim JH, Uphoff I, ... Quyyumi AA, Vaccarino V
Importance
Acute mental stress can result in transient endothelial dysfunction, but the prognostic relevance of this phenomenon is unknown.
Objective
To determine the association between mental stress-induced impairment in endothelium-dependent relaxation as assessed by brachial artery flow-mediated vasodilation and adverse cardiovascular outcomes among individuals with stable coronary artery disease.
Design, setting, and participants
This cohort study was conducted at a university-affiliated hospital network between June 2011 and August 2014. A cohort of individuals with stable coronary artery disease were included. Data analysis took place from November 2018 to May 2019.
Exposures
Study participants were subjected to a laboratory mental stress task (public speaking).
Main outcomes and measures
Flow-mediated vasodilation was measured before and 30 minutes after a public-speaking mental stress task. We examined the association of the rest (prestress), poststress, and δ flow-mediated vasodilation (poststress minus prestress levels) with an adjudicated composite end point of adverse events, including cardiovascular death, myocardial infarction, unstable angina leading to revascularization, and heart failure hospitalization, after adjusting for sociodemographic factors, medical history, and depression.
Results
A total of 569 patients were included (mean [SD] age, 62.6 [9.3] years; 420 men [73.8%]). Flow-mediated vasodilation decreased from a mean (SD) of 4.8% (3.7%) before mental stress to 3.9% (3.6%) after mental stress (a 23% reduction; P < .001), and 360 participants (63.3%) developed transient endothelial dysfunction (a decrease in flow-mediated vasodilation). During a median (interquartile range) follow-up period of 3.0 (2.9-3.1) years, 74 patients experienced a major adverse cardiovascular event. The presence of transient endothelial dysfunction with mental stress was associated with a 78% increase (subdistribution hazard ratio [sHR], 1.78 [95% CI, 1.15-2.76]) in the incidence of major adverse cardiovascular event. Both the δ flow-mediated vasodilation (sHR, 1.15 [95% CI, 1.03-1.27] for each 1% decline) and poststress flow-mediated vasodilation (sHR, 1.14 [95% CI, 1.04-1.24] for each 1% decline) were associated with major adverse cardiovascular event. Risk discrimination statistics demonstrated a significant model improvement after addition of either poststress flow-mediated vasodilation (change in the area under the curve, 0.05 [95% CI, 0.01-0.09]) or prestress plus δ flow-mediated vasodilation (change in the area under the curve, 0.04 [95% CI, 0.00-0.08]) compared with conventional risk factors.
Conclusions and relevance
In this study, transient endothelial dysfunction with mental stress was associated with adverse cardiovascular outcomes in patients with coronary artery disease. Endothelial responses to stress represent a possible mechanism through which psychological stress may affect outcomes in patients with coronary artery disease.



JAMA Cardiol: 10 Sep 2019; epub ahead of print
Lima BB, Hammadah M, Kim JH, Uphoff I, ... Quyyumi AA, Vaccarino V
JAMA Cardiol: 10 Sep 2019; epub ahead of print | PMID: 31509180
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Impact:
Abstract

Association Between Visit-to-Visit Blood Pressure Variability in Early Adulthood and Myocardial Structure and Function in Later Life.

Nwabuo CC, Yano Y, Moreira HT, Appiah D, ... Lloyd-Jones DM, Lima JAC
Importance
Long-term blood pressure (BP) variability has emerged as a reproducible measure that is associated with heart failure independent of systemic BP. Visit-to-visit BP variability may be associated with the risk of heart failure early in the life course and thus may be reflected in subclinical alterations in cardiac structure and function.
Objective
To evaluate the association between visit-to-visit BP variability in early adulthood and myocardial structure and function in middle age.
Design, setting, and participants
This cohort study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based cohort study of 5115 participants aged 18 to 30 years at baseline (year 0; March 25, 1985, to June 7, 1986) and followed up over a 30-year interval. A total of 2400 CARDIA study participants underwent evaluation at 4 field sites (Birmingham, Alabama; Oakland, California; Chicago, Illinois; and Minneapolis, Minnesota). Blood pressure was measured at 8 visits over a 25-year interval and participants received echocardiograms at year 25 (June 1, 2010, to August 31, 2011). Data analysis was conducted from June 7, 1986, to August 31, 2011.
Exposures
Visit-to-visit systolic and diastolic BP variability measures included SD, average real variability, and variability independent of the mean.
Main outcomes and measures
Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 25 examination.
Results
Of the 2400 participants, 1024 were men (42.7%) and 976 were African American (40.7%); mean (SD) age at the year 25 examination was 50.4 (3.6) years. Per 1-SD increment, greater visit-to-visit systolic BP variability independent of the mean was associated with higher left-ventricular (LV) mass index (β [SE], 2.66 [0.4] g/m2, P < .001), worse diastolic function (early peak diastolic mitral annular velocity [é]) (β [SE], -0.40 [0.1] cm/s, P < .001), higher LV filling pressures (mitral inflow velocity to early diastolic mitral annular velocity [E/é]) β [SE], 0.37 [0.1] cm/s, P < .001), and worse global longitudinal strain (β [SE], 0.17 [0.1], P = .002). Similarly, greater visit-to-visit diastolic BP variability was associated with higher LV mass index (β [SE], 3.21 [0.5] g/m2, P < .001), worse diastolic function (é: β [SE], -0.24 [0.1] cm/s [P < .001]; E/é: β [SE], 0.23 [0.1] cm/s [P < .001]), and worse global longitudinal strain (β [SE], 0.13 [0.1], P = .02). The findings remained consistent when other BP variability measures were used (SD and average real variability).
Conclusions and relevance
In this cohort study using data from the CARDIA study, greater visit-to-visit systolic and diastolic BP variability have been associated with adverse alterations in cardiac structure as well as systolic and diastolic function independent of mean BP levels.



JAMA Cardiol: 14 Apr 2020; epub ahead of print
Nwabuo CC, Yano Y, Moreira HT, Appiah D, ... Lloyd-Jones DM, Lima JAC
JAMA Cardiol: 14 Apr 2020; epub ahead of print | PMID: 32293640
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Impact:
Abstract

The Clinical Challenge of Clonal Hematopoiesis, a Newly Recognized Cardiovascular Risk Factor.

Sidlow R, Lin AE, Gupta D, Bolton KL, ... Ebert BL, Libby P
Importance
Despite current standards of cardiovascular care, a considerable residual burden of risk remains in both primary and secondary prevention. Clonal hematopoiesis of indeterminate potential (CHIP) has recently emerged as a common, potent, age-associated, independent risk factor for myocardial infarction, stroke, heart failure events, and survival following percutaneous aortic valve intervention. The presence of CHIP results from the acquisition of somatic mutations in a small number of leukemia driver genes found in bone marrow stem cells, leading to the expansion of leukocytes clones in peripheral blood. The association between CHIP and cardiovascular disease likely involves activation of the inflammasome pathway. More common DNA sequencing identifies individuals with CHIP who then seek advice regarding management of their cardiovascular risk.
Observations
Using clinical vignettes based on real encounters, we highlight some of the diverse presentations of CHIP, ranging from incidental identification to that detected during cancer care, that have brought patients to the attention of cardiovascular practitioners. We illustrate how we have applied a consensus-based approach to the evaluation and management of cardiovascular risk in specific patients with CHIP. Since we currently lack evidence to guide the management of these individuals, we must rely on expert opinion while awaiting data to furnish a firmer foundation for our recommendations.
Conclusions and relevance
These vignettes illustrate that the management of CHIP should involve an individualized plan based on features such as comorbidities, life expectancy, and other traditional cardiovascular risk factors. Because individuals with CHIP will increasingly seek advice from cardiovascular specialists regarding management, these examples provide a template for approaches based on a multidisciplinary perspective. The current need for reliance on expert opinion illustrates a great need for further investigation into the management of this newly recognized contributor to residual cardiovascular risk, both in patients who are apparently well and those with established cardiovascular or malignant disease.



JAMA Cardiol: 26 May 2020; epub ahead of print
Sidlow R, Lin AE, Gupta D, Bolton KL, ... Ebert BL, Libby P
JAMA Cardiol: 26 May 2020; epub ahead of print | PMID: 32459358
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Impact:
Abstract

Association of FADS1/2 Locus Variants and Polyunsaturated Fatty Acids With Aortic Stenosis.

Chen HY, Cairns BJ, Small AM, Burr HA, ... Engert JC, Thanassoulis G
Importance
Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets.
Objective
To identify novel genetic loci and pathways associated with AS.
Design, setting, and participants
This genome-wide association study used a case-control design to evaluate 44 703 participants (3469 cases of AS) of self-reported European ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort (from January 1, 1996, to December 31, 2015). Replication was performed in 7 other cohorts totaling 256 926 participants (5926 cases of AS), with additional analyses performed in 6942 participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Follow-up biomarker analyses with aortic valve calcium (AVC) were also performed. Data were analyzed from May 1, 2017, to December 5, 2019.
Exposures
Genetic variants (615 643 variants) and polyunsaturated fatty acids (ω-6 and ω-3) measured in blood samples.
Main outcomes and measures
Aortic stenosis and aortic valve replacement defined by electronic health records, surgical records, or echocardiography and the presence of AVC measured by computed tomography.
Results
The mean (SD) age of the 44 703 GERA participants was 69.7 (8.4) years, and 22 019 (49.3%) were men. The rs174547 variant at the FADS1/2 locus was associated with AS (odds ratio [OR] per C allele, 0.88; 95% CI, 0.83-0.93; P = 3.0 × 10-6), with genome-wide significance after meta-analysis with 7 replication cohorts totaling 312 118 individuals (9395 cases of AS) (OR, 0.91; 95% CI, 0.88-0.94; P = 2.5 × 10-8). A consistent association with AVC was also observed (OR, 0.91; 95% CI, 0.83-0.99; P = .03). A higher ratio of arachidonic acid to linoleic acid was associated with AVC (OR per SD of the natural logarithm, 1.19; 95% CI, 1.09-1.30; P = 6.6 × 10-5). In mendelian randomization, increased FADS1 liver expression and arachidonic acid were associated with AS (OR per unit of normalized expression, 1.31 [95% CI, 1.17-1.48; P = 7.4 × 10-6]; OR per 5-percentage point increase in arachidonic acid for AVC, 1.23 [95% CI, 1.01-1.49; P = .04]; OR per 5-percentage point increase in arachidonic acid for AS, 1.08 [95% CI, 1.04-1.13; P = 4.1 × 10-4]).
Conclusions and relevance
Variation at the FADS1/2 locus was associated with AS and AVC. Findings from biomarker measurements and mendelian randomization appear to link ω-6 fatty acid biosynthesis to AS, which may represent a therapeutic target.



JAMA Cardiol: 17 Mar 2020; epub ahead of print
Chen HY, Cairns BJ, Small AM, Burr HA, ... Engert JC, Thanassoulis G
JAMA Cardiol: 17 Mar 2020; epub ahead of print | PMID: 32186652
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Impact:
Abstract

Periprocedural Risk and Survival Associated With Implantable Cardioverter-Defibrillator Placement in Older Patients With Advanced Heart Failure.

Fudim M, Ali-Ahmed F, Parzynski CS, Ambrosy AP, ... Hernandez AF, Al-Khatib SM
Importance
Little is known about the utilization rates and outcomes of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRT-D) placement among patients with advanced heart failure (HF).
Objective
To examine utilization rates, patient characteristics, and outcomes of ICD and CRT-D placements among patients with advanced HF.
Design, setting, and participants
This cohort study was a post hoc analysis of 81 492 Medicare fee-for-service beneficiaries enrolled in the National Cardiovascular Data Registry ICD Registry between January 2010 and December 2014. Inclusion criteria were patients who had received an HF diagnosis, had a left ventricular ejection fraction of 35% or lower, and showed evidence of advanced HF, which was defined as New York Heart Association (NYHA) class IV symptoms, inotrope use within the last 60 days, left ventricular assist device in situ, or orthotopic heart transplant listing. The comparator group included patients with NYHA class II and no HF hospitalization within the last 12 months, no left ventricular assist device, no orthotopic heart transplant listing, and no current or recent inotrope use. All eligible patients underwent first-time ICD or CRT-D placement for primary prevention of sudden cardiac death. Data were analyzed from January 2010 to December 2014.
Main outcomes and measures
All-cause mortality and periprocedural complications.
Results
Of 81 492 Medicare patients, 3343 had advanced HF (4.1%) and 19 424 were in the comparator group (23.8%). Among the advanced HF population, the mean (SD) age of patients was 74 (9) years, and patients were predominantly white individuals (81.5%) and men (71.1%). The all-cause mortality rate at 30 days was 3.1% (95% CI, 2.6%-3.8%) in the advanced HF group vs 0.5% (0.4%-0.6%) in the comparator group (P < .001). In the advanced HF population, the aggregate in-hospital periprocedural complication rate was 3.74% (95% CI, 3.12%-4.44%) vs 1.10% (95% CI, 0.95%-1.25%) in the comparator group (P < .001). Most adverse events in this group were in-hospital fatality (1.82%; 95% CI, 1.40%-2.34%) and resuscitated cardiac arrest (1.05%; 95% CI, 0.73%-1.45%). Patients with NYHA class IV (hazard ratio, 1.40; 95% CI, 1.02-1.93; P = .04), ischemic heart disease (hazard ratio, 1.24; 95% CI, 1.04-1.48; P = .02), or diabetes (hazard ratio, 1.17; 95% CI, 1.04-1.33; P = .01) had a higher risk of death.
Conclusions and relevance
Among patients undergoing ICD or CRT-D placement for primary prevention of sudden cardiac death, only a small proportion had advanced HF. These patients experienced clinically important periprocedural complication rates associated with in-hospital death and cardiac arrest relative to patients with nonadvanced HF.



JAMA Cardiol: 24 Mar 2020; epub ahead of print
Fudim M, Ali-Ahmed F, Parzynski CS, Ambrosy AP, ... Hernandez AF, Al-Khatib SM
JAMA Cardiol: 24 Mar 2020; epub ahead of print | PMID: 32211811
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Impact:
Abstract

Strategies of Wait-listing for Heart Transplant vs Durable Mechanical Circulatory Support Alone for Patients With Advanced Heart Failure.

Lala A, Rowland JC, Ferket BS, Gelijns AC, ... Pagani FD, Mancini DM
Importance
Given the shortage of donor hearts and improvement in outcomes with left ventricular assist device (LVAD) therapy, a relevant but, to date, unanswered question is whether select patients with advanced heart failure should receive LVAD destination therapy as an alternative to heart transplant.
Objective
To determine whether a strategy of LVAD destination therapy is associated with similar survival benefit as wait-listing for heart transplant with or without LVAD therapy among patients with advanced heart failure.
Design, setting, and participants
This retrospective propensity-matched cohort analysis used data on heart transplants from the United Network for Organ Sharing registry and LVAD implants from the Interagency Registry for Mechanically Assisted Circulatory Support from January 1, 2010, to December 31, 2014. The matched LVAD destination therapy cohort included 3411 patients. Data analysis for this study was conducted from December 22, 2017, to May 24, 2019.
Main outcomes and measures
Survival at 5 years was analyzed using Cox proportional hazards models.
Results
In total, 8281 patients had albumin level, creatinine level, and BMI data recorded and were included in the analysis. Despite propensity score matching, the 3411 patients receiving LVAD destination therapy still tended to be slightly older than the 3411 patients wait-listed for heart transplant (64.0 years [interquartile range, 55.0-70.0 years] vs 60.0 [interquartile range, 54.0-65.0 years]; P < .001), but there was no significant difference in sex (2701 men [79.2%] vs 2648 men [77.6%]; P = .13). After propensity score matching for age, sex, body mass index, renal function, and albumin level, 3411 patients were wait-listed for heart transplant. This included 1607 patients with bridge to transplant LVAD therapy and 1804 patients without LVAD. The strategy of wait-listing for heart transplant was associated with better 5-year survival than LVAD destination therapy (risk ratio, 0.42; 95% CI, 0.38-0.46) after matching and adjusting for key clinical factors. This survival advantage was associated with heart transplant (adjusted risk ratio for time-dependent transplant status, 0.27; 95% CI, 0.24-0.32).
Conclusions and relevance
The present analysis suggests that heart transplant with or without bridge to transplant LVAD therapy was associated with superior 5-year survival compared with LVAD destination therapy among patients matched on several relevant clinical factors. Continued improvement in LVAD technology, along with prospective comparative research, appears to be needed to amend this strategy.



JAMA Cardiol: 14 Apr 2020; epub ahead of print
Lala A, Rowland JC, Ferket BS, Gelijns AC, ... Pagani FD, Mancini DM
JAMA Cardiol: 14 Apr 2020; epub ahead of print | PMID: 32293643
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Impact:
Abstract

Potential Effects of Coronaviruses on the Cardiovascular System: A Review.

Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O
Importance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system.
Observations
Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality.
Conclusions and relevance
Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.



JAMA Cardiol: 26 Mar 2020; epub ahead of print
Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O
JAMA Cardiol: 26 Mar 2020; epub ahead of print | PMID: 32219363
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Impact:
Abstract

Polygenic Risk, Fitness, and Obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Murthy VL, Xia R, Baldridge AS, Carnethon MR, ... Fornage M, Shah RV
Importance
Obesity is a major determinant of disease burden worldwide. Polygenic risk scores (PRSs) have been posited as key predictors of obesity. How a PRS can be translated to the clinical encounter (especially in the context of fitness, activity, and parental history of overweight) remains unclear.
Objective
To quantify the relative importance of a PRS, fitness, activity, parental history of overweight, and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) in young adulthood on BMI trends over 25 years.
Design, setting, and participants
This population-based prospective cohort study at 4 US centers included white individuals and black individuals with assessments of polygenic risk of obesity, fitness, activity, and BMI in young adulthood (in their 20s) and up to 25 years of follow-up. Data collected between March 1985 and August 2011 were analyzed from April 25, 2019, to September 29, 2019.
Main outcomes and measures
Body mass index at the initial visit and 25 years later.
Results
This study evaluated an obesity PRS from a recently reported study of 1608 white individuals (848 women [52.7%]) and 909 black individuals (548 women [60.3%]) across the United States. At baseline (year 0), mean (SD) overall BMI was 24.2 (4.5), which increased to 29.6 (6.9) at year 25. Among white individuals, the PRS (combined with age, sex, self-reported parental history of overweight, and principal components of ancestry) explained 11.9% (at year 0) and 13.6% (at year 25) of variation in BMI. Although the addition of fitness increased the explanatory capability of the model (24.0% variance at baseline and up to 18.1% variance in BMI at year 25), baseline BMI in young adulthood was the strongest factor, explaining 52.3% of BMI in midlife in combination with age, sex, and self-reported parental history of overweight. Accordingly, models that included baseline BMI (especially BMI surveillance over time) were better in predicting BMI at year 25 compared with the PRS. In fully adjusted models, the effect sizes for fitness and the PRS on BMI were comparable in opposing directions. The added explanatory capacity of the PRS among black individuals was lower than among white individuals. Among white individuals, addition of baseline BMI and surveillance of BMI over time was associated with improved precision of predicted BMI at year 25 (mean error in predicted BMI 0 kg/m2 [95% CI, -11.4 to 11.4] to 0 kg/m2 [95% CI, -8.5 to 8.5] for baseline BMI and mean error 0 kg/m2 [95% CI, -5.3 to 5.3] for BMI surveillance).
Conclusions and relevance
Cardiorespiratory fitness in young adulthood and a PRS are modestly associated with midlife BMI, although future BMI is associated with BMI in young adulthood. Fitness has a comparable association with future BMI as does the PRS. Caution should be exercised in the widespread use of polygenic risk for obesity prevention in adults, and close clinical surveillance and fitness may have prime roles in limiting the adverse consequences of elevated BMI on health.



JAMA Cardiol: 07 Jan 2020; epub ahead of print
Murthy VL, Xia R, Baldridge AS, Carnethon MR, ... Fornage M, Shah RV
JAMA Cardiol: 07 Jan 2020; epub ahead of print | PMID: 31913407
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Impact:
Abstract

Temporal Trends and Patterns in Mortality After Incident Heart Failure: A Longitudinal Analysis of 86 000 Individuals.

Conrad N, Judge A, Canoy D, Tran J, ... McMurray JJV, Rahimi K
Importance
Despite considerable improvements in heart failure care, mortality rates among patients in high-income countries have changed little since the early 2000s. Understanding the reasons underlying these trends may provide valuable clues for developing more targeted therapies and public health strategies.
Objective
To investigate mortality rates following a new diagnosis of heart failure and examine changes over time and by cause of death and important patient features.
Design, setting, and participants
This population-based retrospective cohort study analyzed anonymized electronic health records of individuals who received a new diagnosis of heart failure between January 2002 and December 2013 who were followed up until December 2014 from the Clinical Practice Research Datalink, which links information from primary care, secondary care, and the national death registry from a subset of the UK population. The data were analyzed from January 2018 to February 2019.
Main outcomes and measures
All-cause and cause-specific mortality rates at 1 year following diagnosis. Poisson regression models were used to calculate rate ratios (RRs) and 95% confidence intervals comparing 2013 with 2002, adjusting for age, sex, region, socioeconomic status, and 17 major comorbidities.
Results
Of 86 833 participants, 42 581 (49%) were women, 51 215 (88%) were white, and the mean (SD) age was 76.6 (12.6) years. While all-cause mortality rates declined only modestly over time (RR comparing 2013 with 2002, 0.94; 95% CI, 0.88-1.00), underlying patterns presented explicit trends. A decline in cardiovascular mortality (RR, 0.73; 95% CI, 0.67-0.80) was offset by an increase in noncardiovascular deaths (RR, 1.22; 95% CI, 1.11-1.33). Subgroup analyses further showed that overall mortality rates declined among patients younger than 80 years (RR, 0.79; 95% CI, 0.71-0.88) but not among those older than 80 years (RR, 0.97; 95% CI, 0.90-1.06). After cardiovascular causes (898 [43%]), the major causes of death in 2013 were neoplasms (311 [15%]), respiratory conditions (243 [12%]), and infections (13%), the latter 2 explaining most of the observed increase in noncardiovascular mortality.
Conclusions and relevance
Among patients with a new heart failure diagnosis, considerable progress has been achieved in reducing mortality in young and middle-aged patients and cardiovascular mortality across all age groups. Improvements to overall mortality are hindered by high and increasing rates of noncardiovascular events. These findings challenge current research priorities and management strategies and call for a greater emphasis on associated comorbidities. Specifically, infection prevention presents as a major opportunity to improve prognosis.



JAMA Cardiol: 02 Sep 2019; epub ahead of print
Conrad N, Judge A, Canoy D, Tran J, ... McMurray JJV, Rahimi K
JAMA Cardiol: 02 Sep 2019; epub ahead of print | PMID: 31479100
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Impact:
Abstract

Cost-effectiveness of Low-density Lipoprotein Cholesterol Level-Guided Statin Treatment in Patients With Borderline Cardiovascular Risk.

Kohli-Lynch CN, Bellows BK, Thanassoulis G, Zhang Y, ... Sniderman AD, Moran AE
Importance
American College of Cardiology/American Heart Association cholesterol guidelines prioritize primary prevention statin therapy based on 10-year absolute risk (AR10) of atherosclerotic cardiovascular disease (ASCVD). However, given the same AR10, patients with higher levels of low-density lipoprotein cholesterol (LDL-C) experience greater absolute risk reduction from statin therapy.
Objectives
To estimate the cost-effectiveness of expanding preventive statin treatment eligibility from standard care to patients at borderline risk (AR10, 5.0%-7.4%) for ASCVD and with high levels of LDL-C and to estimate cost-effectiveness of statin treatment across ranges of age, sex, AR10, and LDL-C levels.
Design, setting, and participants
This study evaluated 100 simulated cohorts, each including 1 million ASCVD-free survey respondents (50% men and 50% women) aged 40 years at baseline. Cohorts were created by probabilistic sampling of the 1999-2014 US National Health and Nutrition Examination Surveys from the perspective of the US health care sector. The CVD Policy Model microsimulation version projected lifetime health and cost outcomes. Probability of first-ever coronary heart disease or stroke event was estimated by analysis of 6 pooled US cohort studies and recalibrated to match contemporary event rates. Other model variables were derived from national surveys, meta-analyses, and published literature. Data were analyzed from May 15, 2018, through June 10, 2019.
Exposures
Four statin treatment strategies were compared: (1) treat all patients with AR10 of at least 7.5%, diabetes, or LDL-C of at least 190 mg/dL (standard care); (2) add treatment for borderline risk and LDL-C levels of 160 to 189 mg/dL; (3) add treatment for borderline risk and LDL-C levels of 130 to 159 mg/dL; and (4) add treatment for remainder of patients with AR10 of at least 5.0%. Statin treatment was also compared with no statin treatment in age, sex, AR10, and LDL-C strata.
Main outcomes and measures
Lifetime quality-adjusted life-years (QALYs) and costs (2019 US dollars) were projected and discounted 3.0% annually. The primary outcome was the incremental cost-effectiveness ratio.
Results
In these 100 simulated cohorts, each with 1 million patients aged 40 years at baseline (50% women and 50% men), adding preventive statins to individuals with borderline AR10 and LDL-C levels of 160 to 189 mg/dL would be cost-saving; further treating borderline AR10 and LDL-C levels of 130 to 159 mg/dL would also be cost-saving; and treating all individuals with AR10 of at least 5.0% would be highly cost-effective ($33 558/QALY) and would prevent the most ASCVD events. Within age, AR10, and sex categories, individuals with higher baseline LDL-C levels gained more QALYs from statin therapy. Cost-effectiveness increased with LDL-C level and AR10.
Conclusions and relevance
In this study, lifetime statin treatment of patients in a hypothetical cohort with borderline ASCVD risk and LDL-C levels of 160 to 189 mg/dL was found to be cost-saving. Results suggest that treating all patients at borderline risk regardless of LDL-C level would likely be highly cost-effective.



JAMA Cardiol: 27 Aug 2019; epub ahead of print
Kohli-Lynch CN, Bellows BK, Thanassoulis G, Zhang Y, ... Sniderman AD, Moran AE
JAMA Cardiol: 27 Aug 2019; epub ahead of print | PMID: 31461121
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Impact:
Abstract

Association Between Circulating Troponin Concentrations, Left Ventricular Systolic and Diastolic Functions, and Incident Heart Failure in Older Adults.

Myhre PL, Claggett B, Ballantyne CM, Selvin E, ... Skali H, Shah AM
Importance
Cardiac troponin is associated with incident heart failure and greater left ventricular (LV) mass. Its association with LV systolic and diastolic functions is unclear.
Objectives
To define the association of high-sensitivity cardiac troponin T (hs-cTnT) with LV systolic and diastolic functions in the general population, and to evaluate the extent to which that association accounts for the correlation between hs-cTnT concentration and incident heart failure overall, heart failure with preserved LV ejection fraction (LVEF; HFpEF), and heart failure with LVEF less than 50%.
Design, setting, and participants
This analysis of the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing epidemiologic cohort study in US communities, included participants without cardiovascular disease (n = 4111). Available hs-cTnT measurements for participants who attended ARIC Study visits 2 (1990 to 1992), 4 (1996 to 1998), and 5 (2011 to 2013) were assessed cross-sectionally against echocardiographic measurements taken at visit 5 and against incident health failure after visit 5. Changes in hs-cTnT concentrations from visits 2 and 4 were also examined. Data analyses were performed from August 2017 to July 2018.
Main outcomes and measures
Cardiac structure and function by echocardiography at visit 5, and incident heart failure during a median 4½ years follow-up after visit 5.
Results
Of the 6538 eligible participants, 4111 (62.9%) without cardiovascular disease were included. Among these participants, 2586 (62.9%) were female, and the mean (SD) age was 75 (5) years. Median (interquartile range) hs-cTnT concentration at visit 5 was 9 (7-14) ng/L and was detectable in 3946 participants (96.0%). After adjustment for demographic and clinical covariates, higher hs-cTnT levels were associated with greater LV mass index (adjusted mean [SE] for group 1: 33.8 [0.5] vs group 5: 40.1 [0.4]; P for trend < .001) and with worse diastolic function, including lower tissue Doppler imaging e\' (6.00 [0.07] vs 5.54 [0.06]; P for trend < .001), higher E/e\' ratio (11.4 [0.2] vs 12.9 [0.1]; P for trend < .001), and greater left atrial volume index (23.4 [0.4] vs 26.4 [0.3]; P for trend < .001), independent of LV mass index; hs-cTnT level was not associated with measures of LV systolic function. Accounting for diastolic function attenuated the association of hs-cTnT concentration with incident HFpEF by 41% and the association with combined heart failure with midrange and reduced ejection fraction combined (LVEF <50) by 17%. Elevated hs-cTnT concentration and diastolic dysfunction were additive risk factors for incident heart failure. For any value of late-life hs-cTnT levels, longer duration of detectable hs-cTnT from midlife to late life was associated with greater LV mass in late life but not with worse LV systolic or diastolic function.
Conclusions and relevance
This study shows that higher hs-cTnT concentrations were associated with worse diastolic function, irrespective of LV mass, but not with systolic function; these findings suggest that high levels of hs-cTnT may serve as an early marker of subclinical alterations in diastolic function that may lead to a predisposition to heart failure.



JAMA Cardiol: 03 Sep 2019; epub ahead of print
Myhre PL, Claggett B, Ballantyne CM, Selvin E, ... Skali H, Shah AM
JAMA Cardiol: 03 Sep 2019; epub ahead of print | PMID: 31483438
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Impact:
Abstract

Assessment of the German and Italian Stress Cardiomyopathy Score for Risk Stratification for In-hospital Complications in Patients With Takotsubo Syndrome.

Santoro F, Núñez Gil IJ, Stiermaier T, El-Battrawy I, ... Eitel I, Brunetti ND
Importance
Takotsubo syndrome (TTS) is an acute, reversible heart failure syndrome featured by significant rates of in-hospital complications. There is a lack of data for risk stratification during hospitalization.
Objective
To derive a simple clinical score for risk prediction of in-hospital complications among patients with TTS.
Design, setting, and participants
In this prognostic study, 1007 consecutive patients were enrolled in the German and Italian Stress Cardiomyopathy (GEIST) registry from July 1, 2007, through December 31, 2017, and identified as the derivation cohort; 946 patients were enrolled in the Spanish Registry for Takotsubo Cardiomyopathy (RETAKO) as the external score validation. An admission risk score was developed using a stepwise multivariable regression analysis from 2 registries. Data analysis was performed from March 1, 2018, through July 31, 2018.
Main outcomes and measures
In-hospital complications were defined as death, pulmonary edema, need for invasive ventilation, and cardiogenic shock. Four variables were identified as independent predictors of in-hospital complications and were used for the score: male sex, history of neurologic disorder, right ventricular involvement, and left ventricular ejection fraction (LVEF).
Results
Of the 1007 patients enrolled in the GEIST registry, 107 (10.6%) were male, with mean (SD) age of 69.8 (11.4) years. Overall rate of in-hospital complications was 23.3% (235 of 1007) (death, 4.0%; pulmonary edema, 5.8%; invasive ventilation, 6.4%; and cardiogenic shock, 9.1%). The GEIST prognosis score was derived by providing 20 points each for male sex and history of neurologic disorders and 30 points for right ventricular involvement and then subtracting the value in percent of LVEF (decimal values between 0.15 and 0.70). Score accuracy on area under the receiver operating characteristic curve analysis was 0.71, with a negative predictive power of 87% with scores less than 20. External validation in the RETAKO population (124 [13.1%] male; mean [SD] age, 69.5 [14.9] years) revealed an area under the curve of 0.73 (P = .46 vs GEIST derivation cohort). Stratification into 3 risk groups (<20, 20-40, and >40 points) classified 316 patients (40.9%) as having low risk; 342 (44.3%) as having intermediate risk, and 114 (14.8%) as having high risk of complications. The observed in-hospital complication rates were 12.7% for low-risk patients, 23.4% for intermediate-risk patients, and 58.8% for high-risk patients (P < .001 for trend). After 2.6 years of follow-up, patients with in-hospital complications had significantly higher rates of mortality than those without complications (40% vs 10%, P = .01).
Conclusions and relevance
The GEIST prognostic score may be useful in early risk stratification for TTS. High-risk patients with TTS may require an intensive care unit stay, and low-risk patients with TTS could be discharged within a few days. In-hospital complications in patients with TTS may be associated with increased risk of long-term mortality.



JAMA Cardiol: 06 Aug 2019; epub ahead of print
Santoro F, Núñez Gil IJ, Stiermaier T, El-Battrawy I, ... Eitel I, Brunetti ND
JAMA Cardiol: 06 Aug 2019; epub ahead of print | PMID: 31389988
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Impact:
Abstract

Optimal Combination of Compression Rate and Depth During Cardiopulmonary Resuscitation for Functionally Favorable Survival.

Duval S, Pepe PE, Aufderheide TP, Goodloe JM, ... Sugiyama A, Yannopoulos D
Importance
Previous studies of basic cardiopulmonary resuscitation (CPR) indicate that both chest compression rate (CCR) and chest compression depth (CCD) each are associated with survival probability after out-of-hospital cardiac arrest. However, an optimal CCR-CCD combination has yet to be identified, particularly with respect to age, sex, presenting cardiac rhythm, and CPR adjunct use.
Objectives
To identify an ideal CCR-CCD combination associated with the highest probability of functionally favorable survival and to assess whether this combination varies with respect to age, sex, presenting cardiac rhythm, or CPR adjunct use.
Design, setting, and participants
This cohort study used data collected between June 2007 and November 2009 from a National Institutes of Health (NIH) clinical trials network registry of out-of-hospital and in-hospital emergency care provided by 9-1-1 system agencies participating in the network across the United States and Canada (n = 150). The study sample included 3643 patients who had out-of-hospital cardiac arrest and for whom CCR and CCD had been simultaneously recorded during an NIH clinical trial of a CPR adjunct. Subgroup analyses included evaluations according to age, sex, presenting cardiac rhythm, and application of a CPR adjunct. Data analysis was performed from September to November 2018.
Interventions
Standard out-of-hospital cardiac arrest interventions compliant with the concurrent American Heart Association guidelines as well as use of the CPR adjunct device in half of the patients.
Main outcomes and measures
The optimal combination of CCR-CCD associated with functionally favorable survival (modified Rankin scale ≤3) overall and by age, sex, presenting cardiac rhythm, and CPR adjunct use.
Results
Of 3643 patients, 2346 (64.4%) were men; the mean (SD) age was 67.5 (15.7) years. The identified optimal CCR-CCD for all patients was 107 compressions per minute and a depth of 4.7 cm. When CPR was performed within 20% of this value, survival probability was significantly higher (6.0% vs 4.3% outside that range; odds ratio, 1.44; 95% CI, 1.07-1.94; P = .02). The optimal CCR-CCD combination remained similar regardless of age, sex, presenting cardiac rhythm, or CPR adjunct use. The identified optimal CCR-CCD was associated with significantly higher probabilities of survival when the CPR device was used compared with standard CPR (odds ratio, 1.90; 95% CI, 1.06-3.38; P = .03), and the device\'s effectiveness was dependent on being near the target CCR-CCD combination.
Conclusions and relevance
The findings suggest that the combination of 107 compressions per minute and a depth of 4.7 cm is associated with significantly improved outcomes for out-of-hospital cardiac arrest. The results merit further investigation and prospective validation.



JAMA Cardiol: 13 Aug 2019; epub ahead of print
Duval S, Pepe PE, Aufderheide TP, Goodloe JM, ... Sugiyama A, Yannopoulos D
JAMA Cardiol: 13 Aug 2019; epub ahead of print | PMID: 31411632
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Impact:
Abstract

Agreement and Accuracy of Medication Persistence Identified by Patient Self-report vs Pharmacy Fill: A Secondary Analysis of the Cluster Randomized ARTEMIS Trial.

Fanaroff AC, Peterson ED, Kaltenbach LA, Cannon CP, ... Fonarow GC, Wang TY
Importance
Pharmacy fill data are increasingly accessible to clinicians and researchers to evaluate longitudinal medication persistence beyond patient self-report.
Objective
To assess the agreement and accuracy of patient-reported and pharmacy fill-based medication persistence.
Design, setting, and participants
This post hoc analysis of the cluster randomized clinical trial ARTEMIS (Affordability and Real-world Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) enrolled patients at 287 US hospitals (131 randomized to intervention and 156 to usual care) from June 5, 2015, to September 30, 2016, with 1-year follow-up and blinded adjudication of major adverse cardiovascular events. In total, 8373 patients with myocardial infarction and measurement of P2Y12 inhibitor persistence by both patient self-report and pharmacy data were included. Serum P2Y12 inhibitor drug levels were measured for 944 randomly selected patients. Data were analyzed from May 2018 to November 2019.
Interventions
Patients treated at intervention-arm hospitals received study vouchers to offset copayments at each P2Y12 inhibitor fill for 1 year after myocardial infarction.
Main outcomes and measures
Nonpersistence was defined as a gap of 30 days or more in P2Y12 inhibitor use (patient report) or supply (pharmacy fill) and as serum P2Y12 inhibitor levels below the lower limit of quantification (drug level). Among patients in the intervention arm, a \"criterion standard\" definition of nonpersistence was a gap of 30 days or more in P2Y12 inhibitor use by both voucher use and pharmacy fill. Major adverse cardiovascular events were defined as adjudicated death, recurrent myocardial infarction, or stroke.
Results
Of 8373 patients included in this analysis, the median age was 62 years (interquartile range, 54-70 years), 5664 were men (67.7%), and 990 (11.8%) self-reported as nonwhite race/ethnicity. One-year estimates of medication nonpersistence rates were higher using pharmacy fills (4042 patients [48.3%]) compared with patient self-report (1277 patients [15.3%]). Overall, 4185 patients (50.0%) were persistent by both pharmacy fill data and patient report, 1131 patients (13.5%) were nonpersistent by both, and 3057 patients (36.5%) were discordant. By application of the criterion standard definition, the 1-year nonpersistence rate was 1184 of 3703 patients (32.0%); 892 of 3318 patients (26.9%) in the intervention arm who self-reported persistence were found to be nonpersistent, and 303 of 1487 patients (20.4%) classified as nonpersistent by pharmacy fill data were actually persistent. Agreement between serum P2Y12 inhibitor drug levels and either patient-reported (κ = 0.11-0.23) or fill-based (κ = 0.00-0.19) persistence was poor. Patients who were nonpersistent by both pharmacy fill data and self-report had the highest 1-year major adverse cardiac event rate (18.3%; 95% CI, 16.0%-20.6%) compared with that for discordant patients (9.7%; 8.7%-10.8%) or concordantly persistent patients (8.2%; 95% CI, 7.4%-9.0%).
Conclusions and relevance
Patient report overestimated medication persistence rates, and pharmacy fill data underestimated medication persistence rates. Patients who are nonpersistent by both methods have the worst clinical outcomes and should be prioritized for interventions that improve medication-taking behavior.
Trial registration
ClinicalTrials.gov Identifier: NCT02406677.



JAMA Cardiol: 03 Mar 2020; epub ahead of print
Fanaroff AC, Peterson ED, Kaltenbach LA, Cannon CP, ... Fonarow GC, Wang TY
JAMA Cardiol: 03 Mar 2020; epub ahead of print | PMID: 32129795
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Impact:
Abstract

Association of Silent Myocardial Infarction and Sudden Cardiac Death.

Vähätalo JH, Huikuri HV, Holmström LTA, Kenttä TV, ... Myerburg RJ, Junttila MJ
Importance
Myocardial infarction in the absence of major or unrecognized symptoms are characterized as silent (SMI). The prevalence of SMI among individuals who experience sudden cardiac death (SCD), with or without concomitant electrocardiographic (ECG) changes, has not previously been described in detail from large studies to our knowledge.
Objective
To determine the prevalence of SMI in individuals who experience SCD without a prior diagnosis of coronary artery disease (CAD) and to detect ECG abnormalities associated with SMI-associated SCD.
Design, setting, and participants
This case-control study compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in a consecutive cohort of individuals in the Finnish Genetic Study of Arrhythmic Events (Fingesture) study population who were verified to have had SCD. The Fingesture study consists of individuals who had autopsy-verified SCD in Northern Finland between 1998 and 2017. Individuals who had SCD with CAD and evidence of SMI were regarded as having had cases; those who had SCD with CAD without SMI were considered control participants. Analyses of ECG tests were carried out by investigators blinded to the SMI data. Data analysis was completed from October 2018 through November 2018.
Main outcomes and measures
Silent MI was defined as a scar detected by macroscopic and microscopic evaluation of myocardium without previously diagnosed CAD. Clinical history was obtained from medical records, previously recorded ECGs, and a standardized questionnaire provided to the next of kin. The hypothesis tested was that SMI would be prevalent in the population who had had SCD with CAD, and it might be detected or suspected from findings on ECGs prior to death in many individuals.
Results
A total of 5869 individuals were included (2459 males [78.8%]; mean [SD] age, 64.9 [12.4] years). The cause of SCD was CAD in 4392 individuals (74.8%), among whom 3122 had no history of previously diagnosed CAD. Two individuals were excluded owing to incomplete autopsy information. An ECG recorded prior to SCD was available in 438 individuals. Silent MI was detected in 1322 individuals (42.4%) who experienced SCD without a clinical history of CAD. The participants with SMI were older than participants without MI scarring (mean [SD] age, 66.9 [11.1] years; 65.5 [11.6] years; P < .001) and were more often men (1102 of 1322 [83.4%] vs 1357 of 1798 [75.5%]; P < .001). Heart weight was higher in participants with SMI (mean [SD] weight, 483 [109] g vs 438 [106] g; P < .001). In participants with SMI, SCD occurred more often during physical activity (241 of 1322 [18.2%] vs 223 of 1798 [12.4%]; P < .001). A prior ECG was abnormal in 125 of the 187 individuals (66.8%) who had SCD after SMI compared with 139 of 251 (55.4%) of those who had SCD without SMI (P = .02).
Conclusions and relevance
Many individuals who experienced SCD associated with CAD had a previously undetected MI at autopsy. Previous SMI was associated with myocardial hypertrophy and SCD during physical activity. Premortem ECGs in a subset with available data were abnormal in 67% of the individuals who had had a SCD after an SMI.



JAMA Cardiol: 09 Jul 2019; epub ahead of print
Vähätalo JH, Huikuri HV, Holmström LTA, Kenttä TV, ... Myerburg RJ, Junttila MJ
JAMA Cardiol: 09 Jul 2019; epub ahead of print | PMID: 31290935
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Impact:
Abstract

New Directions in Right Ventricular Assessment Using 3-Dimensional Echocardiography.

Addetia K, Muraru D, Badano LP, Lang RM
Importance
Before the introduction of 3-dimensional echocardiography, estimations of right ventricular (RV) size and function by echocardiography were limited to regional approximations of global function. This review describes the novel application of 3-dimensional echocardiography in the assessment of RV size and function, in juxtaposition with what is currently available using 2-dimensional echocardiography.
Observations
Two-dimensional echocardiographic evaluation of RV size and function includes measures of systolic basal longitudinal excursion (tricuspid annular plane systolic excursion and peak systolic velocity), fractional area change, and free-wall strain, all of which are measured from a single tomographic imaging plane: the RV-focused view. Given this limitation, clinical situations in which more accurate assessment of the RV or close patient follow-up were required were resolved with the use of cardiovascular magnetic resonance, computed tomography, and other modalities to obtain global measures of size and function (ie, volume and ejection fraction). With 3-dimensional echocardiography, both volume and ejection fraction assessments of the RV are possible with an accuracy and reproducibility close to that of cardiovascular magnetic resonance imaging. Further, 3-dimensional RV data sets can be cropped, sliced, and rotated to assess device leads, tricuspid valve leaflets, and RV wall-motion abnormalities. The 3-dimensional RV data set opens the horizon to endless possibilities for further exploration of novel parameters, including 3-dimensional RV shape and 3-dimensional RV deformation analysis.
Conclusions and relevance
The use of 3-dimensional echocardiography overcomes many of the limitations associated with conventional 2-dimensional echocardiography and has the potential to provide the detailed information required for the complex clinical decision-making that requires accurate, quantitative information about the RV.



JAMA Cardiol: 23 Jul 2019; epub ahead of print
Addetia K, Muraru D, Badano LP, Lang RM
JAMA Cardiol: 23 Jul 2019; epub ahead of print | PMID: 31339508
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Impact:
Abstract

Effect of Simvastatin-Ezetimibe Compared With Simvastatin Monotherapy After Acute Coronary Syndrome Among Patients 75 Years or Older: A Secondary Analysis of a Randomized Clinical Trial.

Bach RG, Cannon CP, Giugliano RP, White JA, ... Braunwald E, Blazing MA
Importance
Limited evidence is available regarding the benefit and hazard of higher-intensity treatment to lower lipid levels among patients 75 years or older. As a result, guideline recommendations differ for this age group compared with younger patients.
Objective
To determine the effect on outcomes and risks of combination ezetimibe and simvastatin compared with simvastatin monotherapy to lower lipid levels among patients 75 years or older with stabilized acute coronary syndrome (ACS).
Design, setting, participants
In this prespecified secondary analysis of the global, multicenter, prospective clinical randomized Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), outcomes and risks were compared by age among patients 50 years or older after a hospitalization for ACS. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed May 29, 2015, through March 13, 2018, using Kaplan-Meier curves and Cox proportional hazards models.
Interventions
Double-blind randomized assignment to combined simvastatin and ezetimibe or simvastatin and placebo with follow-up for a median of 6 years (interquartile range, 4.3-7.1 years).
Main outcomes and measures
The primary composite end point consisted of death due to cardiovascular disease, myocardial infarction (MI), stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days. Individual adverse ischemic and safety end points and lipid variables were also analyzed.
Results
Of 18 144 patients enrolled (13 728 men [75.7%]; mean [SD] age, 64.1 [9.8] years), 5173 (28.5%) were 65 to 74 years old, and 2798 (15.4%) were 75 years or older at randomization. Treatment with simvastatin-ezetimibe resulted in lower rates of the primary end point than simvastatin-placebo, including 0.9% for patients younger than 65 years (HR, 0.97; 95% CI, 0.90-1.05) and 0.8% for patients 65 to 74 years of age (hazard ratio [HR], 0.96; 95% CI, 0.87-1.06), with the greatest absolute risk reduction of 8.7% for patients 75 years or older (HR, 0.80; 95% CI, 0.70-0.90) (P = .02 for interaction). The rate of adverse events did not increase with simvastatin-ezetimibe vs simvastatin-placebo among younger or older patients.
Conclusions and relevance
In IMPROVE-IT, patients hospitalized for ACS derived benefit from higher-intensity therapy to lower lipid levels with simvastatin-ezetimibe compared with simvastatin monotherapy, with the greatest absolute risk reduction among patients 75 years or older. Addition of ezetimibe to simvastatin was not associated with any significant increase in safety issues among older patients. These results may have implications for guideline recommendations regarding lowering of lipid levels in the elderly.
Trial registration
ClinicalTrials.gov identifier: NCT00202878.



JAMA Cardiol: 16 Jul 2019; epub ahead of print
Bach RG, Cannon CP, Giugliano RP, White JA, ... Braunwald E, Blazing MA
JAMA Cardiol: 16 Jul 2019; epub ahead of print | PMID: 31314050
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Impact:
Abstract

Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis.

Oikonomou EK, Kokkinidis DG, Kampaktsis PN, Amir EA, ... Gupta D, Thavendiranathan P
Importance
Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy-related cardiac dysfunction (CTRCD) has not been performed, to our knowledge.
Objective
To explore the prognostic value of GLS for the prediction of CTRCD.
Data sources
Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018.
Study selection
Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD.
Data extraction and synthesis
Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.
Main outcomes and measures
The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms.
Results
Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from -21.0% to -13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27; 95% CI, 7.73-19.47; area under the HSROC, 0.86; 95% CI, 0.83-0.89). For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82; 95% CI, 5.84-42.85; area under the HSROC, 0.86; 95% CI, 0.83-0.89). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity.
Conclusions and relevance
In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.



JAMA Cardiol: 20 Aug 2019; epub ahead of print
Oikonomou EK, Kokkinidis DG, Kampaktsis PN, Amir EA, ... Gupta D, Thavendiranathan P
JAMA Cardiol: 20 Aug 2019; epub ahead of print | PMID: 31433450
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Impact:
Abstract

Eligibility and Preventive Potential for New Evidence-Based Cardiovascular Drugs in Secondary Prevention.

Mortensen MB, Blaha MJ, Nordestgaard BG
Importance
Recently, 12 randomized clinical trials (RCTs) have demonstrated the efficacy of novel therapies for mainly secondary prevention of atherosclerotic cardiovascular disease. However, given the potential overlapping eligibility of the RCTs, along with the cost of the new therapies, there are uncertainty and questions about implementing these RCT findings in real-world clinical practice.
Objective
To determine the eligibility and preventive potential for these new preventive therapies in a contemporary population.
Design, setting, and participants
This population-based contemporary cohort study included 6292 patients with known ischemic heart disease (IHD) and 2277 with a previous myocardial infarction (MI) enrolled between November 2003 and February 2015. Analyses were performed in the Copenhagen General Population Study with a mean (SD) of 7.7 (3.5) years of follow-up. The data were analyzed between January and October 2019.
Main outcomes and measures
We determined the drug eligibility and evidence-based potential for preventing major cardiovascular events of the 12 cardiovascular drugs tested in the following recent RCTs: IMPROVE-IT, PEGASUS, EMPA-REG, LEADER, SUSTAIN-6, FOURIER, CANVAS, REVEAL, CANTOS, COMPASS, ODYSSEY-OUTCOMES, and REDUCE-IT. The analyses were performed in patients with known IHD or with a previous MI at baseline.
Results
Of 6292 participants, 3861 (61%) were men and the mean (interquartile range) age was 69 (62-76) years. In patients with IHD or MI at baseline, eligibility for 1 or more new medications was 80% (n = 5036) and 99% (n = 2273), respectively, by meeting RCT enrollment criteria. Dividing the new therapies into 4 drug classes (lipid-modifying, antithrombotic, anti-inflammatory, and antidiabetic drugs), 2594 and 1834 patients with IHD or MI (41% and 81%, respectively) were eligible for 2 or more drug classes simultaneously. The 5-year estimated percentage of major cardiovascular events that could be prevented for each new therapy was 1% to 20% in patients with IHD or MI at baseline.
Conclusions and relevance
Most patients with known IHD or previous MI are eligible for additional new secondary prevention therapies. This raises questions for the cardiovascular community and health care authorities about access to these potentially expensive therapies, including strategies for prioritizing their use.



JAMA Cardiol: 01 Jan 2020; epub ahead of print
Mortensen MB, Blaha MJ, Nordestgaard BG
JAMA Cardiol: 01 Jan 2020; epub ahead of print | PMID: 31895459
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Impact:
Abstract

Association of the Duration of Ideal Cardiovascular Health Through Adulthood With Cardiometabolic Outcomes and Mortality in the Framingham Offspring Study.

Corlin L, Short MI, Vasan RS, Xanthakis V
Importance
The American Heart Association ideal cardiovascular health (CVH) score is associated with the risk of cardiovascular disease (CVD) and mortality. However, it is unclear whether the number of years spent in ideal CVH is associated with morbidity or with mortality.
Objective
To evaluate whether living longer with a higher CVH score in midlife is associated with lower risk of hypertension, diabetes, chronic kidney disease, CVD and its subtypes (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease), or all-cause mortality in later life.
Design, setting, and participants
This prospective cohort study used data from 1445 participants from 1991 to 2015 who participated in the community-based Framingham Heart Study Offspring investigation conducted in Massachusetts. The CVH scores of participants were assessed at examination cycles 5, 6, and 7 (1991-1995; 1995-1998; and 1998-2001, respectively). Individuals were excluded from analyses of the association between duration of CVH score and outcomes if they had the outcome of interest at the seventh examination. The median follow-up was approximately 16 years. Data were analyzed from April 2018 to October 2019. The CVH score categories were poor for scores 0 to 7, intermediate for scores 8 to 11, and ideal for scores 12 to 14. A composite score was derived based on smoking status, diet, physical activity, resting blood pressure levels, body mass index, fasting blood glucose levels, and total serum cholesterol levels.
Main outcomes and measures
Number of events and number at risk for each main outcome, including incident hypertension, diabetes, chronic kidney disease, CVD, and all-cause mortality, after the seventh examination.
Results
Of 1445 eligible participants, the mean (SD) age was 60 (9) years, and 751 (52%) were women. Number of events/number at risk for each main outcome after the seventh examination were 348/795 for incident hypertension, 104/1304 for diabetes, 198/918 for chronic kidney disease, 210/1285 for CVD, and 300/1445 for all-cause mortality. At the seventh examination, participants mostly had poor (568 [39%]) or intermediate (782 [54%]) CVH scores. For each antecedent (before examination cycle 7) 5-year duration that participants had intermediate or ideal CVH, they were less likely to develop adverse outcomes (hazards ratios of 0.67 [95% CI, 0.56-0.80] for incident hypertension, 0.73 [95% CI, 0.57-0.93] for diabetes, 0.75 [95% CI, 0.63-0.89] for chronic kidney disease, 0.73 [95% CI, 0.63-0.85] for CVD, and 0.86 [95% CI, 0.76-0.97] for all-cause mortality) relative to living the same amount of time in poor CVH (referent group). No effect modification was observed by age or by sex.
Conclusions and relevance
These results suggest that more time spent in better CVH in midlife may have salutary cardiometabolic benefits and may be associated with lower mortality later in life.



JAMA Cardiol: 10 Mar 2020; epub ahead of print
Corlin L, Short MI, Vasan RS, Xanthakis V
JAMA Cardiol: 10 Mar 2020; epub ahead of print | PMID: 32159731
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Impact:
Abstract

Hybrid Positron Emission Tomography/Magnetic Resonance Imaging in Arrhythmic Mitral Valve Prolapse.

Miller MA, Adams DH, Pandis D, Robson PM, ... Fayad ZA, Trivieri MG
Importance
Myocardial replacement fibrosis has been reported to occur in one-third of patients with mitral valve prolapse (MVP) and significant mitral regurgitation (MR). However, it remains unknown whether there are detectable changes in myocardial metabolism suggestive of inflammation or ischemia that accompany the development of fibrosis.
Objectives
To characterize the burden and distribution of fluorine 18-labeled (18F) fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) in patients with degenerative MVP and ventricular ectopy.
Design, setting, and participants
Prospective observational study of 20 patients with MVP and significant primary degenerative MR who were referred for mitral valve repair and underwent hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Ventricular arrhythmias were categorized as either complex (n = 12) or minor (n = 8). Coregistered hybrid 18F FDG-PET and MRI LGE images were assessed and categorized. Recruitment occurred in the new patient clinic of a mitral valve repair reference center. This study was conducted from January 11, 2018, to June 26, 2019.
Exposures
Simultaneous cardiac 18F FDG-PET and MRI with LGE imaging on a hybrid PET/MRI system and ambulatory rhythm monitoring.
Main outcomes and measures
Patients were categorized by the presence and pattern of FDG uptake and LGE, the severity of ventricular arrhythmias, and the indication for mitral valve surgery.
Results
In the cohort of 20 patients, the median age was 59.5 years (interquartile range, 52.5-63.2 years). Focal, or focal-on-diffuse uptake, of 18F-FDG (PET positive) was detected in 17 of 20 patients (85%). The FDG uptake coexisted with areas of LGE (PET/MRI positive) in 14 patients (70%). Of the 5 asymptomatic patients with normal ventricular indices and absence of any surgical indications, all were PET/MRI positive.
Conclusions and relevance
In this pilot study, we demonstrate a novel association between degenerative MVP and FDG uptake, a surrogate for myocardial inflammation and/or ischemia. Such evidence of myocardial injury, even in asymptomatic patients, suggests an ongoing subclinical disease process. These findings warrant further investigation into whether imaging for myocardial inflammation, ischemia, and scar has a role in arrhythmic risk stratification and whether it provides incremental prognostic value in patients with chronic severe mitral regurgitation undergoing active surveillance.



JAMA Cardiol: 26 May 2020; epub ahead of print
Miller MA, Adams DH, Pandis D, Robson PM, ... Fayad ZA, Trivieri MG
JAMA Cardiol: 26 May 2020; epub ahead of print | PMID: 32459321
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Impact:
Abstract

Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index.

Elnabawi YA, Oikonomou EK, Dey AK, Mancio J, ... Antoniades C, Mehta NN
Importance
Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries.
Objective
To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA).
Design, setting, and participants
This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline.
Exposures
Biologic therapy for psoriasis.
Main outcomes and measures
Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status.
Results
Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti-tumor necrosis factor α, anti-interleukin [IL] 12/23, or anti-IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI -71.22 HU [interquartile range (IQR), -75.85 to -68.11 HU] at baseline vs -76.09 HU [IQR, -80.08 to -70.37 HU] at 1 year; P < .001) concurrent with skin disease improvement (median PASI, 7.7 [IQR, 3.2-12.5] at baseline vs 3.2 [IQR, 1.8-5.7] at 1 year; P < .001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, -71.98 [IQR, -77.36 to -65.64] at baseline vs -72.66 [IQR, -78.21 to -67.44] at 1 year; P = .39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents, including anti-tumor necrosis factor α (median FAI, -71.25 [IQR, -75.86 to -66.89] at baseline vs -75.49 [IQR, -79.12 to -68.58] at 1 year; P < .001) and anti-IL-12/23 or anti-IL-17 therapy (median FAI, -71.18 [IQR, -75.85 to -68.80] at baseline vs -76.92 [IQR, -81.16 to -71.67] at 1 year; P < .001).
Conclusions and relevance
In this study, biologic therapy for moderate to severe psoriasis was associated with reduced coronary inflammation assessed by perivascular FAI. This finding suggests that perivascular FAI measured by CCTA may be used to track response to interventions for coronary artery disease.



JAMA Cardiol: 30 Jul 2019; epub ahead of print
Elnabawi YA, Oikonomou EK, Dey AK, Mancio J, ... Antoniades C, Mehta NN
JAMA Cardiol: 30 Jul 2019; epub ahead of print | PMID: 31365032
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Impact:
Abstract

Myocardial Injury in the Era of High-Sensitivity Cardiac Troponin Assays: A Practical Approach for Clinicians.

McCarthy CP, Raber I, Chapman AR, Sandoval Y, ... Mills NL, Januzzi JL
Importance
Traditionally, elevated troponin concentrations were synonymous with myocardial infarction. But with improvements in troponin assays, elevated concentrations without overt myocardial ischemia are now more common; this is referred to as myocardial injury. Physicians may be falsely reassured by the absence of myocardial ischemia; however, recent evidence suggests that myocardial injury is associated with even more detrimental outcomes. Accordingly, this article reviews the definition, epidemiology, differential diagnosis, diagnostic evaluation, and management of myocardial injury.
Observations
Current epidemiological evidence suggests that myocardial injury without overt ischemia represents about 60% of cases of abnormal troponin concentrations when obtained for clinical indications, and 1 in 8 patients presenting to the hospital will have evidence of myocardial injury. Myocardial injury is a concerning prognosis; the 5-year mortality rate is approximately 70%, with a major adverse cardiovascular event rate of 30% in the same period. The differential diagnosis is broad and can be divided into acute and chronic precipitants. The initial workup involves an assessment for myocardial ischemia. If infarction is ruled out, further evaluation includes a detailed history, physical examination, laboratory testing, a 12-lead electrocardiogram, and (if there is no known history of structural or valvular heart disease) an echocardiogram. Unfortunately, no consensus exists on routine management of patients with myocardial injury. Identifying and treating the underlying precipitant is the most practical approach.
Conclusion and relevance
Myocardial injury is the most common cause of abnormal troponin results, and its incidence will likely increase with an aging population, increasing prevalence of cardiovascular comorbidities, and greater sensitivity of troponin assays. Myocardial injury represents a challenge to clinicians; however, given its serious prognosis, it warrants a thorough evaluation of its underlying precipitant. Future strategies to prevent and/or manage myocardial injury are needed.



JAMA Cardiol: 06 Aug 2019; epub ahead of print
McCarthy CP, Raber I, Chapman AR, Sandoval Y, ... Mills NL, Januzzi JL
JAMA Cardiol: 06 Aug 2019; epub ahead of print | PMID: 31389986
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Impact:
Abstract

Association of Region and Hospital and Patient Characteristics With Use of High-Intensity Statins After Myocardial Infarction Among Medicare Beneficiaries.

Bittner V, Colantonio LD, Dai Y, Woodward M, ... Jaeger BC, Levitan EB
Importance
High-intensity statin use after myocardial infarction (MI) varies by patient characteristics, but little is known about differences in use by hospital or region.
Objective
To explore the relative strength of associations of region and hospital and patient characteristics with high-intensity statin use after MI.
Design, setting, and participants
This retrospective cohort analysis used Medicare administrative claims and enrollment data to evaluate fee-for-service Medicare beneficiaries 66 years or older who were hospitalized for MI from January 1, 2011, through June 30, 2015, with a statin prescription claim within 30 days of discharge. Data were analyzed from January 4, 2017, through May 12, 2019.
Exposures
Beneficiary characteristics were abstracted from Medicare data. Hospital characteristics were obtained from the 2014 American Hospital Association Survey and Hospital Compare quality metrics. Nine regions were defined according to the US Census.
Main outcomes and measures
Intensity of the first statin claim after discharge characterized as high (atorvastatin calcium, 40-80 mg, or rosuvastatin calcium, 20-40 mg/d) vs low to moderate (all other statin types and doses). Trends in high-intensity statins were examined from 2011 through 2015. Associations of region and beneficiary and hospital characteristics with high-intensity statin use from January 1, 2014, to June 15, 2015, were examined using Poisson distribution mixed models.
Results
Among the 139 643 fee-for-service beneficiaries included (69 968 men [50.1%] and 69 675 women [49.9%]; mean [SD] age, 76.7 [7.5] years), high-intensity statin use overall increased from 23.4% in 2011 to 55.6% in 2015, but treatment gaps persisted across regions. In models considering region and beneficiary and hospital characteristics, region was the strongest correlate of high-intensity statin use, with 66% higher use in New England than in the West South Central region (risk ratio [RR], 1.66; 95% CI, 1.47-1.87). Hospital size of at least 500 beds (RR, 1.15; 95% CI, 1.07-1.23), medical school affiliation (RR, 1.11; 95% CI, 1.05-1.17), male sex (RR, 1.10; 95% CI, 1.07-1.13), and patient receipt of a stent (RR, 1.35; 95% CI, 1.31-1.39) were associated with greater high-intensity statin use. For-profit hospital ownership, patient age older than 75 years, prior coronary disease, and other comorbidities were associated with lower use.
Conclusions and relevance
This study\'s findings suggest that geographic region is the strongest correlate of high-intensity statin use after MI, leading to large treatment disparities.



JAMA Cardiol: 23 Jul 2019; epub ahead of print
Bittner V, Colantonio LD, Dai Y, Woodward M, ... Jaeger BC, Levitan EB
JAMA Cardiol: 23 Jul 2019; epub ahead of print | PMID: 31339519
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Impact:
Abstract

Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction.

van der Hoeven NW, Janssens GN, de Waard GA, Everaars H, ... van Leeuwen MAH, van Royen N
Importance
Percutaneous coronary intervention (PCI) of nonculprit vessels among patients with ST-segment elevation myocardial infarction (STEMI) is associated with improved clinical outcome compared with culprit vessel-only PCI. Fractional flow reserve (FFR) and coronary flow reserve are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio was introduced as a nonhyperemic alternative to FFR. Whether these indices can be used in the acute setting of STEMI continues to be investigated.
Objective
To assess the value of hemodynamic indices in nonculprit vessels of patients with STEMI from the index event to 1-month follow-up.
Design, setting, and participants
This substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) randomized clinical trial enrolled 98 patients with STEMI who had an angiographic intermediate stenosis in at least 1 nonculprit vessel. Patient enrollment was between May 1, 2015, and September 19, 2017. After successful primary PCI, nonculprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed from 2 to 7 days and 1 month after primary PCI.
Main outcomes and measures
The value of nonculprit instantaneous wave-free ratio, FFR, coronary flow reserve, hyperemic index of microcirculatory resistance, and resting microcirculatory resistance from the index event to 1-month follow-up.
Results
Of 73 patients with STEMI included in the final analysis, 59 (80.8%) were male, with a mean (SD) age of 60.8 (9.9) years. Instantaneous wave-free ratio (SD) did not change significantly (0.93 [0.07] vs 0.94 [0.06]; P = .12) and there was no change in resting distal pressure/aortic pressure (mean [SD], 0.94 [0.06] vs 0.95 [0.06]; P = .25) from the acute moment to 1-month follow-up. The FFR decreased (mean [SD], 0.88 [0.07] vs 0.86 [0.09]; P = .001) whereas coronary flow reserve increased (mean [SD], 2.9 [1.4] vs 4.1 [2.2]; P < .001). Hyperemic index of microcirculatory resistance decreased and resting microcirculatory resistance increased from the acute moment to follow-up. The decrease in distal pressure from rest to hyperemia was smaller at the acute moment vs follow-up (mean [SD], 10.6 [11.2] mm Hg vs 14.1 [14.2] mm Hg; P = .05). This blunted acute hyperemic response correlated with final infarct size (ρ, -0.29; P = .02). The resistive reserve ratio was lower at the acute moment vs follow-up (mean [SD], 3.4 [1.7] vs 5.0 [2.7]; P < .001).
Conclusions and relevance
In the acute setting of STEMI, nonculprit coronary flow reserve was reduced and FFR was augmented, whereas instantaneous wave-free ratio was not altered. These results may be explained by an increased hyperemic microvascular resistance and a blunted adenosine responsiveness at the acute moment that was associated with infarct size.



JAMA Cardiol: 02 Jul 2019; epub ahead of print
van der Hoeven NW, Janssens GN, de Waard GA, Everaars H, ... van Leeuwen MAH, van Royen N
JAMA Cardiol: 02 Jul 2019; epub ahead of print | PMID: 31268466
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Impact:

This program is still in alpha version.