Journal: JAMA Cardiol

Sorted by: date / impact
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 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

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

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

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

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

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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Impact:
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 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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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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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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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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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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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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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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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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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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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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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

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

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

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 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

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

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

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

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

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

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

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

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

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

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

Association of Medicaid Expansion With Cardiovascular Mortality.

Khatana SAM, Bhatla A, Nathan AS, Giri J, ... Yeh RW, Groeneveld PW
Importance
Medicaid expansion under the Patient Protection and Affordable Care Act led to one of the largest gains in health insurance coverage for nonelderly adults in the United States. However, its association with cardiovascular mortality is unclear.
Objective
To investigate the association of Medicaid expansion with cardiovascular mortality rates in middle-aged adults.
Design, setting, and participants
This study used a longitudinal, observational design, using a difference-in-differences approach with county-level data from counties in 48 states (excluding Massachusetts and Wisconsin) and Washington, DC, from 2010 to 2016. Adults aged 45 to 64 years were included. Data were analyzed from November 2018 to January 2019.
Exposures
Residence in a Medicaid expansion state.
Main outcomes and measures
Difference-in-differences of annual, age-adjusted cardiovascular mortality rates from before Medicaid expansion to after expansion.
Results
As of 2016, 29 states and Washington, DC, had expanded Medicaid eligibility, while 19 states had not. Compared with counties in Medicaid nonexpansion states, counties in expansion states had a greater decrease in the percentage of uninsured residents at all income levels (mean [SD], 7.3% [3.2%] vs 5.6% [2.7%]; P < .001) and in low income strata (19.8% [5.5%] vs 13.5% [3.9%]; P < .001) between 2010 and 2016. Counties in expansion states had a smaller change in cardiovascular mortality rates after expansion (146.5 [95% CI, 132.4-160.7] to 146.4 [95% CI, 131.9-161.0] deaths per 100 000 residents per year) than counties in nonexpansion states did (176.3 [95% CI, 154.2-198.5] to 180.9 [95% CI, 158.0-203.8] deaths per 100 000 residents per year). After accounting for demographic, clinical, and economic differences, counties in expansion states had 4.3 (95% CI, 1.8-6.9) fewer deaths per 100 000 residents per year from cardiovascular causes after Medicaid expansion than if they had followed the same trends as counties in nonexpansion states.
Conclusions and relevance
Counties in states that expanded Medicaid had a significantly smaller increase in cardiovascular mortality rates among middle-aged adults after expansion compared with counties in states that did not expand Medicaid. These findings suggest that recent Medicaid expansion was associated with lower cardiovascular mortality in middle-aged adults and may be of consideration as further expansion of Medicaid is debated.



JAMA Cardiol: 30 Jun 2019; 4:671-679
Khatana SAM, Bhatla A, Nathan AS, Giri J, ... Yeh RW, Groeneveld PW
JAMA Cardiol: 30 Jun 2019; 4:671-679 | PMID: 31166575
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Impact:
Abstract

Genetic Variation in LPA, Calcific Aortic Valve Stenosis in Patients Undergoing Cardiac Surgery, and Familial Risk of Aortic Valve Microcalcification.

Perrot N, Thériault S, Dina C, Chen HY, ... Bossé Y, Arsenault BJ
Importance
Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown.
Objective
To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification.
Design, setting, and participants
This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018.
Exposures
Case-control studies.
Main outcomes and measures
Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography.
Results
This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (<60 mg/dL). In the QUEBEC-CAVS study, each SD increase of the genetic risk score was associated with a higher risk of CAVS (odds ratio [OR], 1.35 [95% CI, 1.10-1.66]; P = .003). Each SD increase of the genetic risk score was associated with a higher risk of CAVS in patients with CAD (OR, 1.30 [95% CI, 1.20-1.42]; P < .001) and without CAD (OR, 1.33 [95% CI, 1.14-1.55]; P < .001). The percentage of individuals with a tissue to background ratio of 1.25 or more or CAVS was higher in first-degree relatives of patients with CAVS and high Lp(a) (16 of 33 [49%]) than control participants (3 of 23 [13%]; P = .006).
Conclusions and relevance
In this study, a genetically elevated Lp(a) level was associated with CAVS independently of the presence of CAD. These findings support further research on the potential usefulness of Lp(a) cascade screening in CAVS.



JAMA Cardiol: 30 Jun 2019; 4:620-627
Perrot N, Thériault S, Dina C, Chen HY, ... Bossé Y, Arsenault BJ
JAMA Cardiol: 30 Jun 2019; 4:620-627 | PMID: 31141105
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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:
Abstract

Association Between Physiological Stenosis Severity and Angina-Limited Exercise Time in Patients With Stable Coronary Artery Disease.

Cook CM, Ahmad Y, Howard JP, Shun-Shin MJ, ... Francis DP, Davies JE
Importance
Physiological stenosis assessment is recommended to guide percutaneous coronary intervention (PCI) in patients with stable angina.
Objective
To determine the association between all commonly used indices of physiological stenosis severity and angina-limited exercise time in patients with stable angina.
Design, setting, and participants
This cohort study included data (without follow-up) collected over 1 year from 2 cardiac hospitals. Selected patients with stable angina and physiologically severe single-vessel coronary artery disease presenting for clinically driven elective PCI were included.
Exposures
Fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), hyperemic stenosis resistance (HSR), and coronary flow reserve (CFR) were measured invasively. Immediately after this, patients maximally exercised on a catheter-table-mounted supine ergometer until they developed rate-limiting angina. Subsequent PCI was performed in most patients, followed by repeat maximal supine exercise testing.
Main outcomes and measures
Associations between FFR, iFR, HSR, CFR, and angina-limited exercise time were assessed using linear regression and Pearson correlation coefficients. Additionally, the associations between the post-PCI increment in exercise time and baseline FFR, iFR, HSR, and CFR were assessed.
Results
Twenty-three patients (21 [91.3%] of whom were male; mean [SD] age, 60.6 [8.1] years) completed the pre-PCI component of the study protocol. Mean (SD) stenosis diameter was 74.6% (10.4%). Median (interquartile range [IQR]) values were 0.54 (0.44-0.72) for FFR, 0.53 (0.38-0.83) for iFR, 1.67 (0.84-3.16) for HSR, and 1.35 (1.11-1.63) for CFR. Mean (SD) angina-limited exercise time was 144 (77) seconds. Anatomical stenosis characteristics were not significantly associated with angina-limited exercise time. Conversely, FFR (R2 = 0.27; P = .01), iFR (R2 = 0.46; P < .001), HSR (R2 = 0.39; P < .01), and CFR (R2 = 0.16; P < .05) were all associated with angina-limited exercise time. Twenty-one patients (19 [90.5%] of whom were male; mean [SD] age, 60.1 [8.2] years) competed the full protocol of PCI, post-PCI physiological assessment, and post-PCI maximal exercise. After PCI, the median (IQR) FFR rose to 0.91 (0.85-0.96), median (IQR) iFR to 0.98 (0.94-0.99), and median (IQR) CFR to 2.73 (2.50-3.12), while the median (IQR) HSR fell to 0.16 (0.06-0.37) (P < .001 for all). The post-PCI increment in exercise time was most significantly associated with baseline iFR (R2 = 0.26; P = .02).
Conclusions and relevance
In a selected group of patients with severe, single-vessel stable angina, FFR, iFR, HSR, and CFR were all modestly correlated with angina-limited exercise time to varying degrees. Notwithstanding the limited sample size, no clear association was demonstrated between anatomical stenosis severity and angina-limited exercise time.



JAMA Cardiol: 31 May 2019; 4:569-574
Cook CM, Ahmad Y, Howard JP, Shun-Shin MJ, ... Francis DP, Davies JE
JAMA Cardiol: 31 May 2019; 4:569-574 | PMID: 31042268
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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

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

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

P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes.

Povsic TJ, Ohman EM, Roe MT, White J, ... Mundl H, Gibson CM
Importance
Physician behavior in response to knowledge of a patient\'s CYP2C19 clopidogrel metabolizer status is unknown.
Objective
To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial.
Design, setting, and participants
The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019.
Interventions
Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization.
Main outcomes and measures
Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected.
Results
Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated.
Conclusions and relevance
Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach.
Clinical trial registration
ClinicalTrials.gov identifier: NCT02293395.



JAMA Cardiol: 30 Jun 2019; 4:680-684
Povsic TJ, Ohman EM, Roe MT, White J, ... Mundl H, Gibson CM
JAMA Cardiol: 30 Jun 2019; 4:680-684 | PMID: 31141104
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Impact:
Abstract

Updated Cost-effectiveness Analysis of Evolocumab in Patients With Very High-risk Atherosclerotic Cardiovascular Disease.

Fonarow GC, van Hout B, Villa G, Arellano J, Lindgren P
Importance
In October 2018, evolocumab was made available at a reduced annual list price of $5850 in the United States. This 60% reduction was aimed at improving patient access by lowering patient copays. Shortly thereafter, the 2018 American College of Cardiology/American Heart Association cholesterol management guideline was released. An updated cost-effectiveness analysis of evolocumab in the United States may be therefore of interest to payers and prescribers.
Objective
To present an updated cost-effectiveness analysis of evolocumab added to standard background therapy compared with standard background therapy alone in patients with very high-risk atherosclerotic cardiovascular disease, reflecting the 2018 ACC/AHA guideline definition and using the new evolocumab list price.
Design, setting, and participants
This study used the Markov model originally used in a previous study by Fonarow et al in 2017. A US societal perspective was considered, and a range of baseline cardiovascular event rates were modeled to reflect varying risk profiles in clinical practice within patients with very high-risk atherosclerotic cardiovascular disease.
Exposures
Addition of evolocumab to standard background therapy, including maximally tolerated statin therapy (ie, the maximum intensity of statin therapy a patient can safely receive), with or without ezetimibe.
Main outcomes and measures
Major cardiovascular events (myocardial infarction, ischemic stroke, and cardiovascular death), costs, quality-adjusted life-years, and incremental cost-effectiveness ratios.
Results
Evolocumab was associated with both increased costs and improved outcomes when added to standard background therapy. Incremental costs ranged from $22 228 to $3411, depending on the varying level of risk within the defined population. Incremental quality-adjusted life years ranged from 0.39 to 0.44. Incremental cost-effectiveness ratios ranged from $56 655 to $7667 per quality-adjusted life-year gained. For a range of baseline cardiovascular event rates in patients with very high-risk atherosclerotic cardiovascular disease, incremental cost-effectiveness ratios were below the generally accepted willingness-to-pay thresholds. Moreover, the ratios were below the threshold of $50 000 per quality-adjusted life-years gained for any baseline rate of 6.9 or more events per 100 patient-years.
Conclusions and relevance
At its current list price, the addition of evolocumab to standard background therapy meets accepted cost-effectiveness thresholds across a range of baseline cardiovascular event rates in patients with very high-risk atherosclerotic cardiovascular disease as defined by the 2018 ACC/AHA guideline.



JAMA Cardiol: 30 Jun 2019; 4:691-695
Fonarow GC, van Hout B, Villa G, Arellano J, Lindgren P
JAMA Cardiol: 30 Jun 2019; 4:691-695 | PMID: 31166576
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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

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

Comparison of Outcomes After Transcatheter vs Surgical Aortic Valve Replacement Among Patients at Intermediate Operative Risk With a History of Coronary Artery Bypass Graft Surgery: A Post Hoc Analysis of the SURTAVI Randomized Clinical Trial.

Reardon MJ, Heijmen RH, Van Mieghem NM, Williams MR, ... Li S, Popma JJ
Importance
Surgical aortic valve replacement (SAVR) has increased risk for patients with aortic stenosis (AS) and a history of coronary artery bypass graft (CABG) surgery. Transcatheter aortic valve replacement (TAVR) may be an alternative.
Objective
To compare TAVR with SAVR outcomes in patients at intermediate operative risk with prior CABG surgery.
Design, setting, and participants
In this post hoc analysis of the Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) noninferiority randomized clinical trial, patients with severe, symptomatic AS at intermediate operative risk were enrolled from 87 centers across the United States, Europe, and Canada from June 2012 to June 2016 and followed-up with up to July 2017. Those with a history of CABG surgery were considered for analysis. Data were analyzed from September to December 2017.
Interventions
A total of 1746 patients were enrolled and randomized 1:1 to self-expanding TAVR or SAVR. An implant was attempted in 1660 patients, of whom 273 had prior CABG surgery, including 136 who underwent attempted TAVR and 137 who underwent attempted SAVR.
Main outcomes and measures
The primary outcome was all-cause mortality or disabling stroke at 1-year follow-up. Efficacy outcomes included quality of life, measured using the Kansas City Cardiomyopathy Questionnaire at 30 days, 6 months, and 1 year, and distance walked in 6 minutes, measured using the 6-minute walk test at 30 days and 1 year.
Results
Of the 136 patients in the TAVR cohort, 111 (81.6%) were male, and the mean (SD) age was 76.9 (6.5) years; of the 137 in the SAVR cohort, 117 (85.4%) were male, and the mean (SD) age was 76.6 (6.5) years. The mean (SD) Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.0% (1.6%) in the TAVR cohort and 5.2% (1.7%) in the SAVR cohort. All-cause mortality or disabling stroke at 1-year follow-up was 8.9% (95% CI, 5.2-15.2) in the TAVR cohort and 6.7% (95% CI, 3.5-12.8) in the SAVR cohort (log-rank P = .53). Compared with patients receiving SAVR, the mean (SD) Kansas City Cardiomyopathy Questionnaire summary score was significantly better among patients receiving TAVR at 30 days (81.4 [19.2] vs 69.7 [22.6]; P < .001); treatments were similar at 1 year (85.7 [14.6] vs 82.8 [18.4]; P = .19). Compared with patients in the SAVR cohort, those in the TAVR cohort showed greater mean (SD) improvement in distance walked at 1 year (48.3 [120.6] m vs 16.8 [88.7] m; P = .04).
Conclusions and relevance
Both TAVR and SAVR were safe for intermediate-risk patients with AS and prior CABG surgery. The transcatheter approach facilitated faster improvement in quality of life and better exercise capacity at 1-year follow-up.
Trial registration
ClinicalTrials.gov identifier: NCT01586910.



JAMA Cardiol: 18 Jun 2019; epub ahead of print
Reardon MJ, Heijmen RH, Van Mieghem NM, Williams MR, ... Li S, Popma JJ
JAMA Cardiol: 18 Jun 2019; epub ahead of print | PMID: 31215985
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Impact:
Abstract

Use of Cardiac Resynchronization Therapy Defibrillator in US Hospitals.

Sandhu A, Bao H, Minges KE, Varosy PD, ... Masoudi F, Bradley SM
Importance
Cardiac resynchronization therapy (CRT) provides significant reduction in morbidity and mortality in select patients with left ventricular systolic dysfunction and specific parameters of electrocardiographic evidence of dyssynchrony. Relative to the 2012 American College of Cardiology/American Heart Association/Heart Rhythm Society guideline update for patient selection, little is known about the contemporary use of CRT in the United States.
Objective
To describe the use of CRT defibrillator (CRT-D) in the period around guideline revision.
Design, setting, and participants
All patients undergoing new CRT-D implantations in the National Cardiovascular Data Registry for implantable cardioverter-defibrillators from January 1, 2012, to December 31, 2015, at 1710 participating hospitals were identified for this population-based study. Rates of CRT-D implantation that were concordant and discordant with the 2012 American College of Cardiology/American Heart Association/Heart Rhythm Society update of the 2008 guidelines for device-based therapy were determined. Analysis began in January 2012.
Main outcomes and measures
Increase in guideline-concordant CRT-D implantation.
Results
Among 135 253 patients undergoing initial CRT-D implantation, 88 923 were included in the study cohort, of which 73 859 implants (83.1%) were guideline concordant. The proportion of guideline-concordant devices increased from 81.2% (16 710 of 20 481) in 2012 to 84.2% (20 515 of 24 356) in 2015 (P for trend < .001). Significant clustering was noted with 33% (565 of 1710) of hospitals accounting for greater than 70% (10 545 of 15 065) of guideline-discordant CRT-D implants. Conduction abnormalities, in particular, underlying right bundle branch block (3597 [23.9%] vs 7425 [10.1%]; P < .001) and nonspecific intraventricular conduction delay (3341 [22.2%] vs 4769 [6.5%]; P < .001) were more common in those who received guideline-discordant devices.
Conclusions and relevance
Rates of guideline-concordant CRT-D implantation increased during the study. The major fraction of guideline-discordant implants were clustered at a minority of hospitals. Conduction abnormalities, particularly non-left bundle branch block and nonspecific intraventricular conduction delay, correlated with guideline-discordant implants indicating continued opportunity for dissemination and understanding of guideline updates.



JAMA Cardiol: 18 Jun 2019; epub ahead of print
Sandhu A, Bao H, Minges KE, Varosy PD, ... Masoudi F, Bradley SM
JAMA Cardiol: 18 Jun 2019; epub ahead of print | PMID: 31215970
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Impact:
Abstract

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation: A Report From the GARFIELD-AF Registry.

Corbalan R, Bassand JP, Illingworth L, Ambrosio G, ... Kakkar AK,
Importance
Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes.
Objective
To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]).
Design, setting, and participants
The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks\' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018.
Exposures
One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed.
Main outcomes and measures
Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals.
Results
The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of β blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9).
Conclusions and relevance
Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM.
Trial registration
ClinicalTrials.gov Identifier: NCT01090362.



JAMA Cardiol: 31 May 2019; 4:526-548
Corbalan R, Bassand JP, Illingworth L, Ambrosio G, ... Kakkar AK,
JAMA Cardiol: 31 May 2019; 4:526-548 | PMID: 31066873
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Impact:
Abstract

Misclassification of Myocardial Injury as Myocardial Infarction: Implications for Assessing Outcomes in Value-Based Programs.

McCarthy C, Murphy S, Cohen JA, Rehman S, ... Januzzi JL, Wasfy JH
Importance
Similar to other patients with acute myocardial infarction, patients with type 2 myocardial infarction (T2MI) are included in several value-based programs, including the Hospital Readmissions Reduction Program and the Hospital Value-Based Purchasing Program. To our knowledge, whether nonischemic myocardial injury is being misclassified as T2MI is unknown and may have implications for these programs.
Objective
To determine whether patients with nonischemic myocardial injury are being miscoded as having T2MI and if this has implications for 30-day readmission and mortality rates.
Design, settings, and participants
Using the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code, we identified patients who were coded as having T2MI between October 2017 and May 2018 at Massachusetts General Hospital. Strict adjudication using the fourth universal definition of MI was then applied.
Main outcome and measures
Clinical adjudication of T2MI and 30-day readmission and mortality rates as a function of T2MI or nonischemic myocardial injury.
Results
Of 633 patients, 369 (58.3%) were men and 514 (81.2%) were white. After strict adjudication, 359 (56.7%) had T2MI, 265 (41.9%) had myocardial injury, 6 (0.9%) had type 1 MI, and 3 (0.5%) had unstable angina. Patients with T2MI had a higher prevalence of cardiovascular comorbidities than those with myocardial injury. Patients with T2MI and myocardial injury had high in-hospital mortality rates (10.6% and 8.7%, respectively; P = .50). Of those discharged alive (563 [88.9%]), 30-day readmission rates (22.7% vs 21.1%; P = .68) and mortality rates (4.4% vs 7.4%; P = .14) were comparable among patients with T2MI and myocardial injury.
Conclusions and relevance
A substantial percentage of patients coded as having T2MI actually have myocardial injury. Both conditions have high 30-day readmission and mortality rates. Including patients with high-risk myocardial injury may have substantial implications for value-based programs.



JAMA Cardiol: 30 Apr 2019; 4:460-464
McCarthy C, Murphy S, Cohen JA, Rehman S, ... Januzzi JL, Wasfy JH
JAMA Cardiol: 30 Apr 2019; 4:460-464 | PMID: 30879022
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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

Association of Rivaroxaban With Thromboembolic Events in Patients With Heart Failure, Coronary Disease, and Sinus Rhythm: A Post Hoc Analysis of the COMMANDER HF Trial.

Greenberg B, Neaton JD, Anker SD, Byra WM, ... Vanden Boom CM, Zannad F
Importance
Whether anticoagulation benefits patients with heart failure (HF) in sinus rhythm is uncertain. The COMMANDER HF randomized clinical trial evaluated the effects of adding low-dose rivaroxaban to antiplatelet therapy in patients with recent worsening of chronic HF with reduced ejection fraction, coronary artery disease (CAD), and sinus rhythm. Although the primary end point of all-cause mortality, myocardial infarction, or stroke did not differ between rivaroxaban and placebo, there were numerical advantages favoring rivaroxaban for myocardial infarction and stroke.
Objective
To examine whether low-dose rivaroxaban was associated with reduced thromboembolic events in patients enrolled in the COMMANDER HF trial.
Design, setting, and participants
Post hoc analysis of the COMMANDER HF multicenter, randomized, double-blind, placebo-controlled trial in patients with CAD and worsening HF. The trial randomized 5022 patients postdischarge from a hospital or outpatient clinic after treatment for worsening HF between September 2013 and October 2017. Patients were required to be receiving standard care for HF and CAD and were excluded for a medical condition requiring anticoagulation or a bleeding history. Patients were randomized in a 1:1 ratio. Analysis was conducted from June 2018 and January 2019.
Intervention
Patients were randomly assigned to receive 2.5 mg of rivaroxaban given orally twice daily or placebo in addition to their standard therapy.
Main outcomes and measures
For this post hoc analysis, a thromboembolic composite was defined as either (1) myocardial infarction, ischemic stroke, sudden/unwitnessed death, symptomatic pulmonary embolism, or symptomatic deep venous thrombosis or (2) all of the previous components except sudden/unwitnessed deaths because not all of these are caused by thromboembolic events.
Results
Of 5022 patients, 3872 (77.1%) were men, and the overall mean (SD) age was 66.4 (10.2) years. Over a median (interquartile range) follow-up of 19.6 (11.7-30.8) months, fewer patients assigned to rivaroxaban compared with placebo had a thromboembolic event including sudden/unwitnessed deaths: 328 (13.1%) vs 390 (15.5%) (hazard ratio, 0.83; 95% CI, 0.72-0.96; P = .01). When sudden/unwitnessed deaths were excluded, the results analyzing thromboembolic events were similar: 153 (6.1%) vs 190 patients (7.6%) with an event (hazard ratio, 0.80; 95% CI, 0.64-0.98; P = .04).
Conclusions and relevance
In this study, thromboembolic events occurred frequently in patients with HF, CAD, and sinus rhythm. Rivaroxaban may reduce the risk of thromboembolic events in this population, but these events are not the major cause of morbidity and mortality in patients with recent worsening of HF for which rivaroxaban had no effect. While consistent with other studies, these results require confirmation in prospective randomized clinical trials.
Trial registration
ClinicalTrials.gov identifier: NCT01877915.



JAMA Cardiol: 31 May 2019; 4:515-523
Greenberg B, Neaton JD, Anker SD, Byra WM, ... Vanden Boom CM, Zannad F
JAMA Cardiol: 31 May 2019; 4:515-523 | PMID: 31017637
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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

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

Comparison of Major Adverse Cardiac Events Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients With or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

, Lee JM, Choi KH, Koo BK, ... Escaned J, Davies JE
Importance
Invasive physiologic indices such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are used in clinical practice. Nevertheless, comparative prognostic outcomes of iFR-guided and FFR-guided treatment in patients with type 2 diabetes have not yet been fully investigated.
Objective
To compare 1-year clinical outcomes of iFR-guided or FFR-guided treatment in patients with and without diabetes in the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) trial.
Design, setting, and participants
The DEFINE-FLAIR trial is a multicenter, international, randomized, double-blinded trial that randomly assigned 2492 patients in a 1:1 ratio to undergo either iFR-guided or FFR-guided coronary revascularization. Patients were eligible for trial inclusion if they had intermediate coronary artery disease (40%-70% diameter stenosis) in at least 1 native coronary artery. Data were analyzed between January 2014 and December 2015.
Interventions
According to the study protocol, iFR of 0.89 or less and FFR of 0.80 or less were used as criteria for revascularization. When iFR or FFR was higher than the prespecified threshold, revascularization was deferred.
Main outcomes and measures
The primary end point was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. The incidence of MACE was compared according to the presence of diabetes in iFR-guided and FFR-guided groups.
Results
Among the total trial population (2492 patients), 758 patients (30.4%) had diabetes. Mean age of the patients was 66 years, 76% were men (1868 of 2465), and 80% of patients presented with stable angina (1983 of 2465). In the nondiabetes population (68.5%; 1707 patients), iFR guidance was associated with a significantly higher rate of deferral of revascularization than the FFR-guided group (56.5% [n = 477 of 844] vs 46.6% [n = 402 of 863]; P < .001). However, it was not different between the 2 groups in the diabetes population (42.1% [n = 161 of 382] vs 47.1% [n = 177 of 376]; P = .15). At 1 year, the diabetes population showed a significantly higher rate of MACE than the nondiabetes population (8.6% vs 5.6%; adjusted hazard ratio [HR], 1.88; 95% CI, 1.28-2.64; P < .001). However, there was no significant difference in MACE rates between iFR-guided and FFR-guided groups in both the diabetes (10.0% vs 7.2%; adjusted HR, 1.33; 95% CI, 0.78-2.25; P = .30) and nondiabetes population (4.7% vs 6.4%; HR, 0.83; 95% CI, 0.51-1.35; P = .45) (interaction P = .25).
Conclusions and relevance
The diabetes population showed significantly higher risk of MACE than the nondiabetes population, even with the iFR-guided or FFR-guided treatment. The iFR-guided and FFR-guided treatment showed comparable risk of MACE and provided equal safety in selecting revascularization target among patients with diabetes.
Trial registration
ClinicalTrials.gov identifier: NCT02053038.



JAMA Cardiol: 16 Jul 2019; epub ahead of print
, Lee JM, Choi KH, Koo BK, ... Escaned J, Davies JE
JAMA Cardiol: 16 Jul 2019; epub ahead of print | PMID: 31314045
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Impact:
Abstract

Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study.

Nazarzadeh M, Pinho-Gomes AC, Smith Byrne K, Canoy D, ... Otto CM, Rahimi K
Importance
Modifiable risk factors for valvular heart disease remain largely unknown, which limits prevention and treatment.
Objective
To assess the association between systolic blood pressure (BP) and major valvular heart disease.
Design, setting, and participants
A UK Biobank population-based cohort of 502 602 men and women aged 40 to 96 years at baseline was evaluated through mendelian randomization using individual participant data. Inclusion criteria were valid genetic data and BP measurements. The participants were recruited between 2006 and 2010; data analysis was performed from June 2018 to January 2019.
Exposures
Systolic BP was measured during clinical assessment and instruments for the genetic effect of high BP were identified from variants that were independently (linkage disequilibrium threshold of r2<0.1) associated with systolic BP with minor allele frequency greater than 0.01. A total of 130 single-nucleotide polymorphisms that have been shown to be associated with systolic BP in a genome-wide association meta-analysis involving 1 million participants of European ancestry were selected.
Main outcomes and measures
Incident aortic stenosis, aortic regurgitation, and mitral regurgitation, individually and combined. Cases were largely based on hospital records linked to the UK Biobank with International Classification of Diseases and Health Related Problems, Tenth Revision codes.
Results
Of the 502 602 individuals screened, 329 237 participants (177 741 [53.99%] women; mean [SD] age, 56.93 [7.99] years) had valid genetic data and BP measurements; of this cohort, 3570 individuals (1.08%) had a diagnosis of valvular heart disease (aortic stenosis, 1491 [0.45%]; aortic regurgitation, 634 [0.19%]; and mitral regurgitation, 1736 [0.53%]). Each genetically associated 20-mm Hg increment in systolic BP was associated with an increased risk of aortic stenosis (odds ratio [OR], 3.26; 95% CI, 1.50-7.10), aortic regurgitation (OR, 2.59; 95% CI, 0.75-8.92), and mitral regurgitation (OR, 2.19; 95% CI, 1.07-4.47), with no evidence for heterogeneity by type of valvular heart disease (P = .90). Sensitivity analyses confirmed the robustness of the association.
Conclusions and relevance
Lifetime exposure to elevated systolic BP appears to be associated with an increased risk of major valvular heart disease.



JAMA Cardiol: 09 Jul 2019; epub ahead of print
Nazarzadeh M, Pinho-Gomes AC, Smith Byrne K, Canoy D, ... Otto CM, Rahimi K
JAMA Cardiol: 09 Jul 2019; epub ahead of print | PMID: 31290937
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Impact:
Abstract

Association Between Warfarin Control Metrics and Atrial Fibrillation Outcomes in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation.

Pokorney SD, Holmes DN, Thomas L, Fonarow GC, ... Peterson ED,
Importance
Bleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range.
Objective
To evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events.
Design, setting, and participants
In this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019.
Exposures
Multiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range.
Main outcomes and measures
Association of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models.
Results
A total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk.
Conclusions and relevance
Three metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.



JAMA Cardiol: 02 Jul 2019; epub ahead of print
Pokorney SD, Holmes DN, Thomas L, Fonarow GC, ... Peterson ED,
JAMA Cardiol: 02 Jul 2019; epub ahead of print | PMID: 31268487
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Impact:
Abstract

Palliative Inotrope Therapy: A Narrative Review.

Chuzi S, Allen LA, Dunlay SM, Warraich HJ
Importance
The number of patients living with end-stage heart failure is steadily growing, and ambulatory intravenous inotropic support is increasingly offered as a palliative therapy. However, the optimal ways to initiate, manage, and discuss the risks and benefits of palliative inotropes in the current era of heart failure care are unclear.
Observations
The initiation of palliative inotropes requires an understanding of clinical, psychosocial, and economic factors, as well as the changing risk-to-benefit calculus. While earlier studies suggested that outpatient inotrope therapy provided symptomatic benefit at the expense of reduced survival, recent data suggest that the survival of patients receiving chronic inotropes may be improving over time, perhaps owing to the use of implantable cardioverter defibrillators, concurrent guideline-directed medical therapy, or lower doses of inotropes. The use of heart failure therapies, such as β-blockade, among patients receiving palliative inotropes is controversial but may be appropriate in select situations.
Conclusions and relevance
The role of palliative inotropes is changing in tandem with advances in chronic heart failure care. However, there remains a profound lack of data and guidance on the effect of palliative inotropes on quality of life and mortality and little consensus on how this therapy can be optimally used in contemporary practice. This review provides a framework for the prescription and management of palliative inotropes, including a discussion of potential risks and benefits and a roadmap for how to initiate, maintain, and wean them.



JAMA Cardiol: 02 Jul 2019; epub ahead of print
Chuzi S, Allen LA, Dunlay SM, Warraich HJ
JAMA Cardiol: 02 Jul 2019; epub ahead of print | PMID: 31268467
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Impact:
Abstract

Differences in Clinical Profile and Outcomes of Low Iron Storage vs Defective Iron Utilization in Patients With Heart Failure: Results From the DEFINE-HF and BIOSTAT-CHF Studies.

Grote Beverborg N, van der Wal HH, Klip IT, Anker SD, ... Voors AA, van der Meer P
Importance
Iron deficiency is present in half of patients with heart failure (HF) and is associated with increased morbidity and an impaired prognosis. Iron deficiency due to low iron storage (LIS) and defective iron utilization (DIU) are not entirely the same clinical problem, although they generally receive the same treatment.
Objective
To define and describe similarities and differences between LIS and DIU in patients with HF.
Design, setting, and participants
This analysis included data from 2 prospective observational studies: the Definition of Iron Deficiency in Chronic Heart Failure (DEFINE-HF) study, a single-center study conducted from 2013 to 2015 including 42 patients with a reduced left ventricular ejection fraction of 45% or less scheduled for coronary artery bypass graft surgery, and the A Systems Biology Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study, a multinational study conducted from 2010 to 2014 including 2357 patients with worsening HF from 69 centers in 11 countries. The median (interquartile range) follow-up time was 1.8 (1.3-2.3) years. Data were analyzed from January 2018 to January 2019.
Main outcomes and measures
The DEFINE-HF cohort was set up to derive a definition for different etiologies of iron deficiency using bone marrow iron staining as the criterion standard. This definition was applied to the BIOSTAT-CHF cohort to assess its association with clinical profile, biomarkers, and the primary composite end point of all-cause mortality or HF hospitalizations.
Results
Among the 42 patients in the DEFINE-HF study, 10 (24%) were women, and the mean (SD) age was 68.0 (9.5) years. Low iron storage was defined as a bone marrow-validated combination of transferrin saturation less than 20% and a serum ferritin concentration of 128 ng/mL or less; DIU was defined as transferrin saturation less than 20% and a serum ferritin concentration greater than 128 ng/mL. These criteria were applied to 2356 patients with worsening HF in the BIOSTAT-CHF study; 1074 (45.6%) were women, and the mean (SD) age was 68.9 (12.0) years. A total of 1453 patients with worsening HF (61.6%) had iron deficiency, of whom 960 (66.1%) had LIS and 493 (33.9%) had DIU. Low iron storage was characterized by a higher proportion of anemia and a poorer quality of life, while DIU was characterized by higher levels of various inflammatory markers. Both LIS and DIU were associated with an impaired 6-minute walking test. Low iron storage was independently associated with the composite end point of all-cause mortality or HF hospitalizations (hazard ratio, 1.47; 95% CI, 1.26-1.71; P < .001), while DIU was not (hazard ratio, 1.05; 95% CI, 0.87-1.26; P = .64).
Conclusions and relevance
In this study, both LIS and DIU were prevalent in patients with HF and had a distinct clinical profile. Only LIS was independently associated with increased rates of morality and HF hospitalizations, while DIU was not.



JAMA Cardiol: 30 Jun 2019; 4:696-701
Grote Beverborg N, van der Wal HH, Klip IT, Anker SD, ... Voors AA, van der Meer P
JAMA Cardiol: 30 Jun 2019; 4:696-701 | PMID: 31188392
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Impact:
Abstract

Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy.

Maron MS, Rowin EJ, Wessler BS, Mooney PJ, ... Link MS, Maron BJ
Importance
Strategies for reliable selection of high-risk patients with hypertrophic cardiomyopathy (HCM) for prevention of sudden cardiac death (SCD) with implantable cardioverter/defibrillators (ICDs) are incompletely resolved.
Objective
To assess the reliability of SCD prediction methods leading to prophylactic ICD recommendations to reduce the number of SCDs occurring in patients with HCM.
Design, setting, and participants
In this observational longitudinal study, 2094 predominantly adult patients with HCM consecutively evaluated over 17 years in a large HCM clinical center were studied. All patients underwent prospective ICD decision making relying on individual major risk markers derived from the HCM literature and an enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines-based risk factor algorithm with complete clinical outcome follow-up. Data were collected from June 2017 to February 2018, and data were analyzed from February to July 2018.
Main outcomes and measures
Arrhythmic SCD or appropriate ICD intervention for ventricular tachycardia or ventricular fibrillation.
Results
Of the 2094 study patients, 1313 (62.7%) were male, and the mean (SD) age was 51 (17) years. Of 527 patients with primary prevention ICDs implanted based on 1 or more major risk markers, 82 (15.6%) experienced device therapy-terminated ventricular tachycardia or ventricular fibrillation episodes, which exceeded the 5 HCM-related SCDs occurring among 1567 patients without ICDs (0.3%), including 2 who declined device therapy, by 49-fold (95% CI, 20-119; P = .001). Cumulative 5-year probability of an appropriate ICD intervention was 10.5% (95% CI, 8.0-13.5). The enhanced ACC/AHA clinical risk factor strategy was highly sensitive for predicting SCD events (range, 87%-95%) but less specific for identifying patients without SCD events (78%). The C statistic calculated for enhanced ACC/AHA guidelines was 0.81 (95% CI, 0.77-0.85), demonstrating good discrimination between patients who did or did not experience an SCD event. Compared with enhanced ACC/AHA risk factors, the European Society of Cardiology risk score retrospectively applied to the study patients was much less sensitive than the ACC/AHA criteria (34% [95% CI, 22-44] vs 95% [95% CI, 89-99]), consistent with recognizing fewer high-risk patients.
Conclusions and relevance
A systematic enhanced ACC/AHA guideline and practice-based risk factor strategy prospectively predicted SCD events in nearly all at-risk patients with HCM, resulting in prophylactically implanted ICDs that prevented many catastrophic arrhythmic events in this at-risk population.



JAMA Cardiol: 30 Jun 2019; 4:644-657
Maron MS, Rowin EJ, Wessler BS, Mooney PJ, ... Link MS, Maron BJ
JAMA Cardiol: 30 Jun 2019; 4:644-657 | PMID: 31116360
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Impact:
Abstract

Demographics, Care Patterns, and Outcomes of Patients Admitted to Cardiac Intensive Care Units: The Critical Care Cardiology Trials Network Prospective North American Multicenter Registry of Cardiac Critical Illness.

Bohula EA, Katz JN, van Diepen S, Alviar CL, ... Morrow DA,
Importance
Single-center and claims-based studies have described substantial changes in the landscape of care in the cardiac intensive care unit (CICU). Professional societies have recommended research to guide evidence-based CICU redesigns.
Objective
To characterize patients admitted to contemporary, advanced CICUs.
Design, setting, and participants
This study established the Critical Care Cardiology Trials Network (CCCTN), an investigator-initiated multicenter network of 16 advanced, tertiary CICUs in the United States and Canada. For 2 months in each CICU, data for consecutive admissions were submitted to the central data coordinating center (TIMI Study Group). The data were collected and analyzed between September 2017 and 2018.
Main outcomes and measures
Demographics, diagnoses, management, and outcomes.
Results
Of 3049 participants, 1132 (37.1%) were women, 797 (31.4%) were individuals of color, and the median age was 65 years (25th and 75th percentiles, 55-75 years). Between September 2017 and September 2018, 3310 admissions were included, among which 2557 (77.3%) were for primary cardiac problems, 337 (10.2%) for postprocedural care, 253 (7.7%) for mixed general and cardiac problems, and 163 (4.9%) for overflow from general medical ICUs. When restricted to the initial 2 months of medical CICU admissions for each site, the primary analysis population included 3049 admissions with a high burden of noncardiovascular comorbidities. The top 2 CICU admission diagnoses were acute coronary syndrome (969 [31.8%]) and heart failure (567 [18.6%]); however, the proportion of acute coronary syndrome was highly variable across centers (15%-57%). The primary indications for CICU care included respiratory insufficiency (814 [26.7%]), shock (643 [21.1%]), unstable arrhythmia (521 [17.1%]), and cardiac arrest (265 [8.7%]). Advanced CICU therapies or monitoring were required for 1776 patients (58.2%), including intravenous vasoactive medications (1105 [36.2%]), invasive hemodynamic monitoring (938 [30.8%]), and mechanical ventilation (652 [21.4%]). The overall CICU mortality rate was 8.3% (95% CI, 7.3%-9.3%). The CICU indications that were associated with the highest mortality rates were cardiac arrest (101 [38.1%]), cardiogenic shock (140 [30.6%]), and the need for renal replacement therapy (51 [34.5%]). Notably, patients admitted solely for postprocedural observation or frequent monitoring had a mortality rate of 0.2% to 0.4%.
Conclusions and relevance
In a contemporary network of tertiary care CICUs, respiratory failure and shock predominated indications for admission and carried a poor prognosis. While patterns of practice varied considerably between centers, a substantial, low-risk population was identified. Multicenter collaborative networks, such as the CCCTN, could be used to help redesign cardiac critical care and to test new therapeutic strategies.



JAMA Cardiol: 23 Jul 2019; epub ahead of print
Bohula EA, Katz JN, van Diepen S, Alviar CL, ... Morrow DA,
JAMA Cardiol: 23 Jul 2019; epub ahead of print | PMID: 31339509
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Impact:
Abstract

Effect of the PCSK9 Inhibitor Evolocumab on Total Cardiovascular Events in Patients With Cardiovascular Disease: A Prespecified Analysis From the FOURIER Trial.

Murphy SA, Pedersen TR, Gaciong ZA, Ceska R, ... Sever PS, Sabatine MS
Importance
The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and first cardiovascular events in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, but patients remain at high risk of recurrent cardiovascular events.
Objective
To evaluate the effect of evolocumab on total cardiovascular events, given the importance of total number of cardiovascular events to patients, clinicians, and health economists.
Design, setting, and participants
Secondary analysis of a randomized, double-blind clinical trial. The FOURIER trial compared evolocumab or matching placebo and followed up patients for a median of 2.2 years. The study included 27 564 patients with stable atherosclerotic disease receiving statin therapy. Data were analyzed between May 2017 and February 2019.
Main outcomes and measures
The primary end point (PEP) was time to first cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; the key secondary end point was time to first cardiovascular death, myocardial infarction, or stroke. In a prespecified analysis, total cardiovascular events were evaluated between treatment arms.
Results
The mean age of patients was 63 years, 69% of patients were taking high-intensity statin therapy, and the median LDL-C at baseline was 92 mg/dL (to convert to millimoles per liter, multiply by 0.0259). There were 2907 first PEP events and 4906 total PEP events during the trial. Evolocumab reduced total PEP events by 18% (incidence rate ratio [RR], 0.82; 95% CI, 0.75-0.90; P < .001) including both first events (hazard ratio, 0.85; 95% CI, 0.79-0.92; P < .001) and subsequent events (RR, 0.74; 95% CI, 0.65-0.85). There were 2192 total primary events in the evolocumab group and 2714 total events in the placebo group. For every 1000 patients treated for 3 years, evolocumab prevented 22 first PEP events and 52 total PEP events. Reductions in total events were driven by fewer total myocardial infarctions (RR, 0.74; 95% CI, 0.65-0.84; P < .001), strokes (RR, 0.77; 95% CI, 0.64-0.93; P = .007), and coronary revascularizations (RR, 0.78; 95% CI, 0.71-0.87; P < .001).
Conclusions and relevance
The addition of the PCSK9 inhibitor evolocumab to statin therapy improved clinical outcomes, with significant reductions in total PEP events, driven by decreases in myocardial infarction, stroke, and coronary revascularization. More than double the number of events were prevented with evolocumab vs placebo as compared with the analysis of only first events. These data provide further support for the benefit of continuing aggressive lipid-lowering therapy to prevent recurrent cardiovascular events.
Trial registration
ClinicalTrials.gov identifier: NCT01764633.



JAMA Cardiol: 30 Jun 2019; 4:613-619
Murphy SA, Pedersen TR, Gaciong ZA, Ceska R, ... Sever PS, Sabatine MS
JAMA Cardiol: 30 Jun 2019; 4:613-619 | PMID: 31116355
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Impact:
Abstract

Identifying Familial Hypercholesterolemia Using a Blood Donor Screening Program With More Than 1 Million Volunteer Donors.

Jackson CL, Keeton JZ, Eason SJ, Ahmad ZA, ... Sayers MH, Khera A
Importance
Familial hypercholesterolemia is an autosomal-dominant disorder that often causes premature coronary artery disease. Unfortunately, familial hypercholesterolemia remains largely undiagnosed.
Objective
To estimate the prevalence of familial hypercholesterolemia in a population of blood donors.
Design
This analysis of deidentified data from blood donors 16 years and older who donated to Carter BloodCare, one of the largest independent blood programs in the United States, between January 2002 and December 2016. Carter BloodCare, which serves a population of about 8 million in Texas, routinely measures total nonfasting serum cholesterol levels as part of a donor health screening program. Data analysis occurred from October 2017 to March 2019.
Exposure
Blood donation.
Main outcomes and measures
Familial hypercholesterolemia was defined using the Make Early Diagnosis to Prevent Early Death general population criteria, with total nonfasting serum cholesterol thresholds of 270, 290, 340, and 360 mg/dL for donors younger than 20 years, 20 to 29 years, 30 to 39 years, and 40 years or older, respectively (to convert cholesterol values to mmol/L, multiply by 0.0259). For repeated donors, the maximum observed total cholesterol level was used for analyses.
Results
The study included 1 178 102 individual donors with a total of 3 038 420 blood donations. Of all individual donors (median total cholesterol level, 183 [interquartile range (IQR), 157-212] mg/dL; median age, 32 [IQR, 19-47] years; 619 583 [52.6%] women), a total of 3473 individuals (or 1 in every 339) met criteria for familial hypercholesterolemia. This group had a median (IQR) total cholesterol of 332 (297-377) mg/dL. Estimated prevalence was higher at younger ages (<30 years: 1:257) compared with older ages (≥30 years: 1:469; P < .001) and in men (1:327) compared with women (1:351; P = .03). Among 2219 repeated donors who met familial hypercholesterolemia criteria at least once, 3116 of 10 833 total donations (28.8%) met FH criteria.
Conclusions and relevance
The prevalence of familial hypercholesterolemia using the Make Early Diagnosis to Prevent Early Death criteria in a large cohort of blood donors was similar to the estimated prevalence of this disorder in the general population. The blood donor screening program could be a novel strategy to detect and notify individuals with potential familial hypercholesterolemia, particularly younger individuals in whom early detection and treatment is especially helpful, as well as guide cascade screening.



JAMA Cardiol: 30 Jun 2019; 4:685-689
Jackson CL, Keeton JZ, Eason SJ, Ahmad ZA, ... Sayers MH, Khera A
JAMA Cardiol: 30 Jun 2019; 4:685-689 | PMID: 31116347
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Impact:
Abstract

Outcomes in Patients Treated With Thin-Strut, Very Thin-Strut, or Ultrathin-Strut Drug-Eluting Stents in Small Coronary Vessels: A Prespecified Analysis of the Randomized BIO-RESORT Trial.

Buiten RA, Ploumen EH, Zocca P, Doggen CJM, ... Linssen GCM, von Birgelen C
Importance
Stenting small-vessel lesions has an increased adverse cardiovascular event risk. Very thin-strut or ultrathin-strut drug-eluting stents might reduce this risk, but data are scarce.
Objective
To assess the outcome of all-comer patients with small coronary vessel lesions treated with 3 dissimilar types of drug-eluting stents.
Design
This is a prespecified substudy of the Comparison of Biodegradable Polymer and Durable Polymer Drug-eluting Stents in an All Comers Population (BIO-RESORT) trial, an investigator-initiated, randomized, patient-blinded comparative clinical drug-eluting stent trial. Patients treated with ultrathin-strut sirolimus-eluting stents, very thin-strut everolimus-eluting stents, or previous-generation thin-strut zotarolimus-eluting stents were enrolled from December 2012 to August 2015. This multicenter trial was conducted in 4 Dutch centers for cardiac intervention. Of all 3514 all-comer BIO-RESORT participants, 1506 patients with treatment in at least 1 small-vessel lesion (reference vessel <2.5 mm) were included. Data were analyzed between September 2018 and February 2019.
Main outcomes and measures
Target lesion failure at 3-year follow-up, a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization, analyzed by Kaplan-Meier methods.
Results
In 1452 of 1506 participants (96.4%) (1057 men [70.2%]; 449 women [29.8%]; mean [SD] age, 64.3 [10.4] years), follow-up was available. Target lesion failure occurred in 36 of 525 patients (7.0%) treated with sirolimus-eluting stents, 46 of 496 (9.5%) with everolimus-eluting stents, and 48 of 485 (10.0%) with zotarolimus-eluting stents (sirolimus-eluting vs zotarolimus-eluting hazard ratio [HR], 0.68; 95% CI, 0.44-1.05; P = .08; everolimus-eluting vs zotarolimus-eluting HR, 0.93; 95% CI, 0.62-1.39; P = .72). There was a difference in target lesion revascularizations between sirolimus-eluting and zotarolimus-eluting stents (2.1% vs 5.3%; HR, 0.40; 95% CI, 0.20-0.81; P = .009) that emerged after the first year of follow-up (1.0% vs 3.7%; P = .006); multivariate analysis showed that sirolimus-eluting stent implantation was independently associated with a lower target lesion revascularization rate at 3-year follow-up (adjusted HR, 0.42; 95% CI, 0.20-0.85; P = .02). In the everolimus-eluting stents, the revascularization rate was 4.0% (vs zotarolimus-eluting, HR, 0.74; 95% CI, 0.41-1.34; P = .31). There was no significant between-stent difference in cardiac death, target vessel myocardial infarction, or stent thrombosis.
Conclusions and relevance
Patients stented in small coronary vessels experienced fewer repeated revascularizations if treated with ultrathin-strut sirolimus-eluting stents vs previous generation thin strut zotarolimus-eluting stents. Further research is required to evaluate the potential effect of particularly thin stent struts.
Trial registration
ClinicalTrials.gov identifier: NCT01674803.



JAMA Cardiol: 30 Jun 2019; 4:659-669
Buiten RA, Ploumen EH, Zocca P, Doggen CJM, ... Linssen GCM, von Birgelen C
JAMA Cardiol: 30 Jun 2019; 4:659-669 | PMID: 31111862
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Impact:
Abstract

Update on Clinical Trials of Losartan With and Without β-Blockers to Block Aneurysm Growth in Patients With Marfan Syndrome: A Review.

Hofmann Bowman MA, Eagle KA, Milewicz DM
Importance
Thoracic aortic aneurysms leading to acute aortic dissections are a major cause of morbidity and mortality despite significant advances in surgical treatment, which remains the main intervention to prevent type A dissections. In the past 2 decades progress has been made toward a better understanding of molecular mechanisms that lead to aneurysm formation and dissections of the thoracic aorta. This focused review emphasizes the results of clinical trials using β-blocker, losartan potassium, and irbesartan in patients with Marfan syndrome and comments briefly on mechanisms of aortic remodeling, including fibrosis and transforming growth factor β signaling.
Observation
The major risk factors for the disease are increased hemodynamic forces, typically owing to poorly controlled hypertension, and heritable genetic variants. The altered genes predisposing to thoracic aortic disease have been shown or are predicted to decrease vascular smooth muscle cell contraction, decrease transforming growth factor β signaling, or alter the extracellular matrix. Preclinical models of Marfan syndrome showed promising results for losartan as a potential therapy to attenuate aortic dilation in mice. However, several clinical trials did not conclusively confirm that losartan attenuated aortic aneurysm expansion better than β-blockers. Most importantly, clinical trials assessing whether losartan therapy not only reduces aortic growth but also improves adverse aortic outcomes, including dissection, need for surgery, and death, have not been conducted. The largest trial to date to our knowledge, the Pediatric Heart Network trial, sponsored by the National Heart, Lung, and Blood Institute, showed a nonsignificant increase in adverse aortic outcomes, with almost a doubling of adverse events in patients randomized to losartan treatment compared with β-blockers, suggesting that this study was underpowered to assess adverse aortic outcomes. On the other hand, the evidence for β-blocker therapy to reduce morbidity and mortality in Marfan syndrome is limited to a single small, prospective randomized and nonblinded clinical trial.
Conclusions and relevance
Taken together, these data emphasize the need for clinical trials adequately powered to assess both aortic aneurysm growth and adverse aortic outcomes to identify effective medical therapies for Marfan syndrome and other aortopathies.



JAMA Cardiol: 30 Jun 2019; 4:702-707
Hofmann Bowman MA, Eagle KA, Milewicz DM
JAMA Cardiol: 30 Jun 2019; 4:702-707 | PMID: 31066871
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Impact:
Abstract

Safety and Efficacy of Antithrombotic Strategies in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis of Randomized Controlled Trials.

Lopes RD, Hong H, Harskamp RE, Bhatt DL, ... Gibson CM, Alexander JH
Importance
The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice.
Objective
To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population.
Data sources
PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens.
Study selection
Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS).
Data extraction and synthesis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019.
Main outcomes and measures
The primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE.
Results
The overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT.
Conclusions and relevance
A regimen of NOACs plus P2Y12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.



JAMA Cardiol: 18 Jun 2019; epub ahead of print
Lopes RD, Hong H, Harskamp RE, Bhatt DL, ... Gibson CM, Alexander JH
JAMA Cardiol: 18 Jun 2019; epub ahead of print | PMID: 31215979
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Impact:
Abstract

Visit-to-Visit Blood Pressure Variability, Coronary Atheroma Progression, and Clinical Outcomes.

Clark D, Nicholls SJ, St John J, Elshazly MB, ... Nissen SE, Puri R
Importance
Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events, but mechanisms and therapeutic implications underlying this association are not well understood.
Objective
To examine the association of intraindividual BPV, coronary atheroma progression, and clinical outcomes using serial intravascular ultrasonography.
Design, setting, and participants
Post hoc patient-level analysis of 7 randomized clinical trials conducted from 2004 to 2016 involving 3912 patients in multicenter, international, clinic-based primary and tertiary care centers. Adult patients with coronary artery disease who underwent serial intravascular ultrasonography in the setting of a range of medical therapies were included. Data were analyzed between November 2017 and March 2019.
Exposures
Visit-to-visit BPV measured using intraindividual standard deviation over 3, 6, 12, 18, and 24 months.
Main outcomes and measures
Percent atheroma volume (PAV) progression and major adverse cardiovascular events (defined as death, myocardial infarction, stroke, urgent revascularization for acute coronary syndrome, and hospitalization for unstable angina).
Results
Of 3912 patients, the mean (SD) age was 58 (9) years, 1093 (28%) were women, and 3633 (93%) were white . Continuous change in PAV was significantly associated with systolic BPV (β, .049; 95% CI, 0.021-0.078; P = .001), diastolic BPV (β, .031; 95% CI, 0.002-0.059; P = .03), and pulse pressure variability (β, .036; 95% CI, 0.006-0.067; P = .02), without a signal for differential effect greater than or less than a mean BP of 140/90 mm Hg. The PAV progression as a binary outcome was significantly associated with systolic BPV (odds ratio, 1.09; 95% CI, 1.01-1.17; P = .02) but not diastolic BPV (odds ratio, 1.04; 95% CI, 0.97-1.11; P = .30) or pulse pressure variability (odds ratio, 1.03; 95% CI, 0.96-1.10; P = .47). Survival curves revealed a significant stepwise association between cumulative major adverse cardiovascular events and increasing quartiles of systolic BPV (Kaplan-Meier estimates for quartiles 1-4: 6.1% vs 8.5% vs 10.1% vs 12.0%, respectively; log-rank P <.001). These distinct stepwise associations were not seen with diastolic BPV or pulse pressure variability.
Conclusions and relevance
Greater BPV, particularly systolic BPV, is significantly associated with coronary atheroma progression and adverse clinical outcomes. These data suggest maintaining stable blood pressure levels may be important to further improve outcomes in patients with coronary disease.



JAMA Cardiol: 30 Apr 2019; 4:437-443
Clark D, Nicholls SJ, St John J, Elshazly MB, ... Nissen SE, Puri R
JAMA Cardiol: 30 Apr 2019; 4:437-443 | PMID: 30969323
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Impact:
Abstract

Association of Ambulatory Hemodynamic Monitoring of Heart Failure With Clinical Outcomes in a Concurrent Matched Cohort Analysis.

Abraham J, Bharmi R, Jonsson O, Oliveira GH, ... Desai AS, Benza RL
Importance
In a randomized clinical trial, heart failure (HF) hospitalizations were lower in patients managed with guidance from an implantable pulmonary artery pressure sensor compared with usual care. It remains unclear if ambulatory monitoring could also improve long-term clinical outcomes in real-world practice.
Objective
To determine the association between ambulatory hemodynamic monitoring and rates of HF hospitalization at 12 months in clinical practice.
Design, setting, and participants
This matched cohort study of Medicare beneficiaries used claims data collected between June 1, 2014, and March 31, 2016. Medicare patients who received implants of a pulmonary artery pressure sensor were identified from the 100% Medicare claims database. Each patient who received an implant was matched to a control patient by demographic features, history of HF hospitalization, and number of all-cause hospitalizations. Propensity scoring based on comorbidities (arrhythmia, hypertension, diabetes, pulmonary disease, and renal disease) was used for additional matching. Data analysis was completed from July 2017 through January 2019.
Exposures
Implantable pulmonary artery pressure monitoring system.
Main outcomes and measures
The rates of HF hospitalization were compared using the Andersen-Gill method. Days lost owing to events were compared using a nonparametric bootstrap method.
Results
The study cohort consisted of 1087 patients who received an implantable pulmonary artery pressure sensors and 1087 matched control patients. The treatment and control cohorts were well matched by age (mean [SD], 72.7 [10.2] years vs 72.9 [10.1] years) and sex (381 of 1087 female patients [35.1%] in each group), medical history, comorbidities, and timing of preimplant HF hospitalization. At 12 months postimplant, 616 HF hospitalizations occurred in the treatment cohort compared with 784 HF hospitalizations in the control cohort. The rate of HF hospitalization was lower in the treatment cohort at 12 months postimplant (hazard ratio [HR], 0.76 [95% CI, 0.65-0.89]; P < .001). The percentage of days lost to HF hospitalizations or death were lower in the treatment group (HR, 0.73 [95% CI, 0.64-0.84]; P < .001) and the percentage of days lost owing to all-cause hospitalization or death were also lower (HR, 0.77 [95% CI, 0.68-0.88]; P < .001).
Conclusions and relevance
Patients with HF who were implanted with a pulmonary artery pressure sensor had lower rates of HF hospitalization than matched controls and spent more time alive out of hospital. Ambulatory hemodynamic monitoring may improve outcomes in patients with chronic HF.



JAMA Cardiol: 31 May 2019; 4:556-563
Abraham J, Bharmi R, Jonsson O, Oliveira GH, ... Desai AS, Benza RL
JAMA Cardiol: 31 May 2019; 4:556-563 | PMID: 31090869
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Impact:
Abstract

Trends in Readmissions and Length of Stay for Patients Hospitalized With Heart Failure in Canada and the United States.

Samsky MD, Ambrosy AP, Youngson E, Liang L, ... Peterson ED, McAlister FA
Importance
Over the past decade, reducing 30-day readmission rates has been emphasized in the United States (including via the implementation of the Hospital Readmissions Reduction Program) but not Canada.
Objective
To examine changes that occurred from April 1, 2005, to December 31, 2015, in the United States and Canada for hospitalization length of stay and 30-day readmission rates of patients with heart failure.
Design, setting, and participants
This cohort study included patients admitted with a primary diagnosis of heart failure to Canadian and US hospitals between April 1, 2005, and December 31, 2015, using International Classification of Diseases, Ninth Revision code 428.xx and Tenth Revision code I50. The study examined secular trends in length of stay and readmissions in both countries and tested for changes after implementation of the Hospital Readmissions Reduction Program using segmented regression models and the association between length of stay and readmissions using patient-level and hospital-level multivariable logistic regression models. Data analysis was completed from February 2018 to August 2018.
Main outcomes and measures
Thirty-day readmissions.
Results
Between 2005 and 2015, mean length of stay declined marginally in Canadian hospitals (from a mean [SD] of 7.5 [5.7] to 7.3 [5.6] days; P < .001) but remained stable in US hospitals (mean [SD], 4.9 [3.7] days to 4.9 [3.5] days). Thirty-day readmission rates declined similarly in Canada (from 4088 of 20 758 patients [19.7%] to 3823 of 21 733 patients [17.6%] for all-cause readmissions; P < .001; and from 1743 of 20 758 patients [8.4%] to 1490 of 21 733 patients [6.9%] for heart failure-specific readmissions; P < .001) and the United States (from 21.2% to 18.5% for all-cause readmissions; from 7.6% to 5.7% for heart failure-specific readmissions; both P < .001). There were small but statistically significant positive correlations between length of stay and 30-day readmissions in both Canada (odds ratio, 1.01 [95% CI, 1.01-1.01]) and the United States (odds ratio, 1.01 [95% CI, 1.01-1.01]). Interrupted time-series analysis comparing readmission rates before and after the Hospital Readmissions Reduction Program implementation revealed no significant difference in either country for all-cause readmission rates before and after October 2012. There was also no change in the slope of the temporal trends; in Canada, all-cause readmissions were decreasing 1.1% per year before implementation and 1.3% after implementation (P = .84 for slope change) compared with 1.6% per year in the United States before implementation and 1.8% per year after October 2012 (P = .60 for slope change).
Conclusions and relevance
Both Canada and the United States exhibited similar temporal declines in 30-day all-cause readmissions over the past decade. These findings suggest that the Hospital Readmissions Reduction Program did not appear to be associated with this secular trend or length of stay for heart failure in the United States.



JAMA Cardiol: 30 Apr 2019; 4:444-453
Samsky MD, Ambrosy AP, Youngson E, Liang L, ... Peterson ED, McAlister FA
JAMA Cardiol: 30 Apr 2019; 4:444-453 | PMID: 30969316
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Impact:
Abstract

Development and Validation of a Deep-Learning Model to Screen for Hyperkalemia From the Electrocardiogram.

Galloway CD, Valys AV, Shreibati JB, Treiman DL, ... Dillon JJ, Friedman PA
Importance
For patients with chronic kidney disease (CKD), hyperkalemia is common, associated with fatal arrhythmias, and often asymptomatic, while guideline-directed monitoring of serum potassium is underused. A deep-learning model that enables noninvasive hyperkalemia screening from the electrocardiogram (ECG) may improve detection of this life-threatening condition.
Objective
To evaluate the performance of a deep-learning model in detection of hyperkalemia from the ECG in patients with CKD.
Design, setting, and participants
A deep convolutional neural network (DNN) was trained using 1 576 581 ECGs from 449 380 patients seen at Mayo Clinic, Rochester, Minnesota, from 1994 to 2017. The DNN was trained using 2 (leads I and II) or 4 (leads I, II, V3, and V5) ECG leads to detect serum potassium levels of 5.5 mEq/L or less (to convert to millimoles per liter, multiply by 1) and was validated using retrospective data from the Mayo Clinic in Minnesota, Florida, and Arizona. The validation included 61 965 patients with stage 3 or greater CKD. Each patient had a serum potassium count drawn within 4 hours after their ECG was recorded. Data were analyzed between April 12, 2018, and June 25, 2018.
Exposures
Use of a deep-learning model.
Main outcomes and measures
Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity, with serum potassium level as the reference standard. The model was evaluated at 2 operating points, 1 for equal specificity and sensitivity and another for high (90%) sensitivity.
Results
Of the total 1 638 546 ECGs, 908 000 (55%) were from men. The prevalence of hyperkalemia in the 3 validation data sets ranged from 2.6% (n = 1282 of 50 099; Minnesota) to 4.8% (n = 287 of 6011; Florida). Using ECG leads I and II, the AUC of the deep-learning model was 0.883 (95% CI, 0.873-0.893) for Minnesota, 0.860 (95% CI, 0.837-0.883) for Florida, and 0.853 (95% CI, 0.830-0.877) for Arizona. Using a 90% sensitivity operating point, the sensitivity was 90.2% (95% CI, 88.4%-91.7%) and specificity was 63.2% (95% CI, 62.7%-63.6%) for Minnesota; the sensitivity was 91.3% (95% CI, 87.4%-94.3%) and specificity was 54.7% (95% CI, 53.4%-56.0%) for Florida; and the sensitivity was 88.9% (95% CI, 84.5%-92.4%) and specificity was 55.0% (95% CI, 53.7%-56.3%) for Arizona.
Conclusions and relevance
In this study, using only 2 ECG leads, a deep-learning model detected hyperkalemia in patients with renal disease with an AUC of 0.853 to 0.883. The application of artificial intelligence to the ECG may enable screening for hyperkalemia. Prospective studies are warranted.



JAMA Cardiol: 30 Apr 2019; 4:428-436
Galloway CD, Valys AV, Shreibati JB, Treiman DL, ... Dillon JJ, Friedman PA
JAMA Cardiol: 30 Apr 2019; 4:428-436 | PMID: 30942845
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Impact:
Abstract

Four Cases of Cholesterol Management Informed by the 2018 American Heart Association/American College of Cardiology Multisociety Guideline on the Management of Blood Cholesterol.

Chuzi S, Pfenniger A, Lloyd-Jones DM, Blumenthal RS, ... Grundy SM, Stone NJ

These 4 hypothetical cases highlight some of the new features in the 2018 American Heart Association/American College of Cardiology multisociety cholesterol management guidelines. Topics include management issues in a secondary prevention patient judged to be at very high risk of another event, a patient with familial hypercholesterolemia with a low-density lipoprotein cholesterol level of 190 mg/dL or greater (to convert to millimoles per liter, multiply by 0.0259), a primary prevention patient with intermediate (7.5%-19.9%) 10-year atherosclerotic cardiovascular risk, and a patient who has statin-associated adverse effects. A multiple-choice format is used to engage clinicians in selecting the best choice based on guidance from the new 2018 cholesterol management guidelines.



JAMA Cardiol: 30 Apr 2019; 4:473-477
Chuzi S, Pfenniger A, Lloyd-Jones DM, Blumenthal RS, ... Grundy SM, Stone NJ
JAMA Cardiol: 30 Apr 2019; 4:473-477 | PMID: 30969319
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Impact:
Abstract

Effect of a Multifaceted Quality Improvement Intervention on the Prescription of Evidence-Based Treatment in Patients at High Cardiovascular Risk in Brazil: The BRIDGE Cardiovascular Prevention Cluster Randomized Clinical Trial.

Machline-Carrion MJ, Soares RM, Damiani LP, Campos VB, ... Berwanger O,
Importance
Studies have found that patients at high cardiovascular risk often fail to receive evidence-based therapies in community practice.
Objective
To evaluate whether a multifaceted quality improvement intervention can improve the prescription of evidence-based therapies.
Design, setting, and participants
In this 2-arm cluster randomized clinical trial, patients with established atherothrombotic disease from 40 public and private outpatient clinics (clusters) in Brazil were studied. Patients were recruited from August 2016 to August 2017, with follow-up to August 2018. Data were analyzed in September 2018.
Interventions
Case management, audit and feedback reports, and distribution of educational materials (to health care professionals and patients) vs routine practice.
Main outcomes and measures
The primary end point was prescription of evidence-based therapies (ie, statins, antiplatelet therapy, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) using the all-or-none approach at 12 months after the intervention period in patients without contraindications.
Results
Of the 1619 included patients, 1029 (63.6%) were male, 1327 (82.0%) had coronary artery disease (843 [52.1%] with prior acute myocardial infarction), 355 (21.9%) had prior ischemic stroke or transient ischemic attack, and 197 (12.2%) had peripheral vascular disease, and the mean (SD) age was 65.6 (10.5) years. Among randomized clusters, 30 (75%) were cardiology sites, 6 (15%) were primary care units, and 26 (65%) were teaching institutions. Among eligible patients, those in intervention clusters were more likely to receive a prescription of evidence-based therapies than those in control clusters (73.5% [515 of 701] vs 58.7% [493 of 840]; odds ratio, 2.30; 95% CI, 1.14-4.65). There were no differences between the intervention and control groups with regards to risk factor control (ie, hyperlipidemia, hypertension, or diabetes). Rates of education for smoking cessation were higher among current smokers in the intervention group than in the control group (51.9% [364 of 701] vs 18.2% [153 of 840]; odds ratio, 11.24; 95% CI, 2.20-57.43). The rate of cardiovascular mortality, acute myocardial infarction, and stroke was 2.6% for patients from intervention clusters and 3.4% for those in the control group (hazard ratio, 0.76; 95% CI, 0.43-1.34).
Conclusions and relevance
Among Brazilian patients at high cardiovascular risk, a quality improvement intervention resulted in improved prescription of evidence-based therapies.
Trial registration
ClinicalTrials.gov identifier: NCT02851732.



JAMA Cardiol: 30 Apr 2019; 4:408-417
Machline-Carrion MJ, Soares RM, Damiani LP, Campos VB, ... Berwanger O,
JAMA Cardiol: 30 Apr 2019; 4:408-417 | PMID: 30942842
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Impact:
Abstract

Risk of Cardiovascular Disease and Mortality in Young Adults With End-stage Renal Disease: An Analysis of the US Renal Data System.

Modi ZJ, Lu Y, Ji N, Kapke A, ... Saran R, Gipson DS
Importance
Cardiovascular disease (CVD) is a leading cause of death among patients with end-stage renal disease (ESRD). Young adult (ages 22-29 years) have risks for ESRD-associated CVD that may vary from other ages.
Objective
To test the hypothesis that young adult-onset ESRD is associated with higher cardiovascular (CV) hospitalizations and mortality with different characteristics than childhood-onset disease.
Design, setting, and participants
This population-based cohort study used the US Renal Data System to categorize patients who initiated ESRD care between 2003 and 2013 by age at ESRD onset (1-11, 12-21, and 22-29 years). Cardiovascular hospitalizations were identified via International Classification of Diseases, Ninth Revision discharge codes and CV mortality from the Centers for Medicare & Medicaid ESRD Death Notification Form. Patients were censored at death from non-CVD events, loss to follow-up, recovery, or survival to December 31, 2014. Adjusted proportional hazard models (95% CI) were fit to determine risk of CV hospitalization and mortality by age group. Data analysis occurred from May 2016 and December 2017.
Exposures
Onset of ESRD.
Main outcomes and measures
Cardiovascular mortality and hospitalization.
Results
A total of 33 156 patients aged 1 to 29 years were included in the study population. Young adults (aged 22-29 years) had a 1-year CV hospitalization rate of 138 (95% CI, 121-159) per 1000 patient-years. Young adults had a higher risk for CV hospitalization than children (aged 1-11 years; hazard ratio [HR], 0.41 [95% CI, 0.26-0.64]) and adolescents (aged 12-21 years; HR, 0.86 [95% CI, 0.77-0.97]). Of 4038 deaths in young adults, 1577 (39.1%) were owing to CVD. Five-year cumulative incidence of mortality in this group (7.3%) was higher than in younger patients (adolescents, 4.0%; children, 1.7%). Adjusted HRs for CV mortality were higher for young adults with all causes of ESRD than children (cystic, hereditary, and congenital conditions: HR, 0.22 [95% CI, 0.11-0.46]; P < .001; glomerulonephritis: HR, 0.21 [95% CI, 0.10-0.44]; P < .001; other conditions: HR, 0.33 [95% CI, 0.23-0.49]; P < .001). Adolescents had a lower risk for CV mortality than young adults for all causes of ESRD except glomerulonephritis (cystic, hereditary, and congenital conditions: HR, 0.45 [95% CI, 0.27-0.74]; glomerulonephritis: HR, 0.99 [95% CI, 0.76-1.11]; other: HR, 0.47 [95% CI, 0.40-0.57]). Higher risks for CV hospitalization and mortality were associated with lack of preemptive transplant compared with hemodialysis (hospital: HR, 14.24 [95% CI, 5.92-34.28]; mortality: HR, 13.64 [95% CI, 8.79-21.14]) and peritoneal dialysis [hospital: HR, 8.47 [95% CI, 3.50-20.53]; mortality: HR, 7.86 [95% CI, 4.96-12.45]). Nephrology care before ESRD was associated with lower risk for CV mortality (HR, 0.77 [95% CI, 0.70-0.85]).
Conclusions and relevance
Cardiovascular disease accounted for nearly 40% of deaths in young adults with incident ESRD in this cohort. Identified risk factors may inform development of age-appropriate ESRD strategies to improve the CV health of this population.



JAMA Cardiol: 31 Mar 2019; 4:353-362
Modi ZJ, Lu Y, Ji N, Kapke A, ... Saran R, Gipson DS
JAMA Cardiol: 31 Mar 2019; 4:353-362 | PMID: 30892557
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Impact:
Abstract

Association of Dimethylguanidino Valeric Acid With Partial Resistance to Metabolic Health Benefits of Regular Exercise.

Robbins JM, Herzig M, Morningstar J, Sarzynski MA, ... Rankinen T, Gerszten RE
Importance
Metabolic responses to exercise training are variable. Metabolite profiling may aid in the clinical assessment of an individual\'s responsiveness to exercise interventions.
Objective
To investigate the association between a novel circulating biomarker of hepatic fat, dimethylguanidino valeric acid (DMGV), and metabolic health traits before and after 20 weeks of endurance exercise training.
Design, setting, and participants
This study involved cross-sectional and longitudinal analyses of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a 20-week, single-arm endurance exercise clinical trial performed in multiple centers between 1993 and 1997. White participants with sedentary lifestyles who were free of cardiometabolic disease were included. Metabolomic tests were performed using a liquid chromatography, tandem mass spectrometry method on plasma samples collected before and after exercise training in the HERITAGE study. Metabolomics and data analysis were performed from August 2017 to May 2018.
Exposures
Plasma DMGV levels.
Main outcome and measures
The association between DMGV levels and measures of body composition, plasma lipids, insulin, and glucose homeostasis before and after exercise training.
Results
Among the 439 participants included in analyses from HERITAGE, the mean (SD) age was 36 (15) years, 228 (51.9%) were female, and the median (interquartile range) body mass index was 25 (22-28). Baseline levels of DMGV were positively associated with body fat percentage, abdominal visceral fat, very low-density lipoprotein cholesterol, and triglycerides, and inversely associated with insulin sensitivity, low-density lipoprotein cholesterol, high-density lipoprotein size, and high-density lipoprotein cholesterol (range of β coefficients, 0.17-0.46 [SEs, 0.026-0.050]; all P < .001, after adjusting for age and sex). After adjusting for age, sex, and baseline traits, baseline DMGV levels were positively associated with changes in small high-density lipoprotein particles (β, 0.14 [95% CI, 0.05-0.23]) and inversely associated with changes in medium and total high-density lipoprotein particles (β, -0.15 [95% CI, -0.24 to -0.05] and -0.19 [95% CI, -0.28 to -0.10], respectively), apolipoprotein A1 (β, -0.14 [95% CI, -0.23 to -0.05]), and insulin sensitivity (β, -0.13; P = 3.0 × 10-3) after exercise training.
Conclusions and relevance
Dimethylguanidino valeric acid is an early marker of cardiometabolic dysfunction that is associated with attenuated improvements in lipid traits and insulin sensitivity after exercise training. Levels of DMGV may identify individuals who require additional therapies beyond guideline-directed exercise to improve their metabolic health.



JAMA Cardiol: 30 Jun 2019; 4:636-643
Robbins JM, Herzig M, Morningstar J, Sarzynski MA, ... Rankinen T, Gerszten RE
JAMA Cardiol: 30 Jun 2019; 4:636-643 | PMID: 31166569
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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

Estimation of the Required Lipoprotein(a)-Lowering Therapeutic Effect Size for Reduction in Coronary Heart Disease Outcomes: A Mendelian Randomization Analysis.

Lamina C, Kronenberg F
Importance
Genetic and epidemiologic data suggest that lipoprotein(a) (Lp[a]) is one of the strongest genetically determined risk factors for coronary heart disease (CHD). Specific therapies to lower Lp(a) are on the horizon, but the required reduction of Lp(a) to translate into clinically relevant lowering of CHD outcomes is a matter of debate.
Objective
To estimate the required Lp(a)-lowering effect size that may be associated with a reduction of CHD outcomes compared with the effect size of low-density lipoprotein cholesterol (LDL-C)-lowering therapies.
Design, setting, and participants
Genetic epidemiologic study using a mendelian randomization analysis to estimate the required Lp(a)-lowering effect size for a clinically meaningful effect on outcomes. We used the effect estimates for Lp(a) from a genome-wide association study (GWAS) and meta-analysis on Lp(a) published in 2017 of 5 different primarily population-based studies of European ancestry. All Lp(a) measurements were performed in 1 laboratory. Genetic estimates for 27 single-nucleotide polymorphisms on Lp(a) concentrations were used. Odds ratios for these 27 single-nucleotide polymorphisms associated with CHD risk were retrieved from a subsample of the CHD Exome+ consortium.
Exposures
Genetic LPA score, plasma Lp(a) concentrations, and observations of statin therapies on CHD outcomes.
Main outcomes and measures
Coronary heart disease.
Results
The study included 13 781 individuals from the Lp(a)-GWAS-Consortium from 5 primarily population-based studies and 20 793 CHD cases and 27 540 controls from a subsample of the CHD Exome+ consortium. Four of the studies were similar in age distribution (means between 51 and 59 years), and 1 cohort was younger; mean age, 32 years. The frequency of women was similar between 51% and 55%. We estimated that the required reduction in Lp(a) effect size would be 65.7 mg/dL (95% CI, 46.3-88.3) to reach the same potential effect on clinical outcomes that can be reached by lowering LDL-C by 38.67 mg/dL (to convert to millimoles per liter, multiply by 0.0259).
Conclusions and relevance
This mendelian randomization analysis estimated a required Lp(a)-lowering effect size of 65.7 mg/dL to reach the same effect as a 38.67-mg/dL lowering of LDL-C. However, this estimate is determined by the observed effect estimates of single-nucleotide polymorphisms on Lp(a) concentrations and is therefore influenced by the standardization of the Lp(a) assay used. As a consequence, calculations of the required Lp(a)-lowering potential of a drug to be clinically effective might have been overestimated in the past.



JAMA Cardiol: 31 May 2019; 4:575-579
Lamina C, Kronenberg F
JAMA Cardiol: 31 May 2019; 4:575-579 | PMID: 31017618
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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

Ideal Cardiovascular Health Metrics and Major Cardiovascular Events in Patients With Prediabetes and Diabetes.

Wang T, Lu J, Su Q, Chen Y, ... Wang W,
Importance
Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear.
Objective
To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation.
Design, setting, and participants
The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016.
Exposures
Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations.
Main outcomes and measures
The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure.
Results
Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHM and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58, 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes.
Conclusions and relevance
Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.



JAMA Cardiol: 30 Jul 2019; epub ahead of print
Wang T, Lu J, Su Q, Chen Y, ... Wang W,
JAMA Cardiol: 30 Jul 2019; epub ahead of print | PMID: 31365039
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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

Effect of Aerobic and Resistance Exercise on Cardiac Adipose Tissues: Secondary Analyses From a Randomized Clinical Trial.

Christensen RH, Wedell-Neergaard AS, Lehrskov LL, Legaard GE, ... Pedersen BK, Ellingsgaard H
Importance
Epicardial and pericardial adipose tissues are emerging as important risk factors for cardiovascular disease, and there is a growing interest in discovering strategies to reduce the accumulation of fat in these depots.
Objective
To investigate whether a 12-week endurance or resistance training intervention regulates epicardial and pericardial adipose tissue mass.
Design, setting, and participants
Secondary analysis of a randomized, assessor-blinded clinical trial initiated on August 2016 and completed April 2018. This single-center, community-based study included 50 physically inactive participants with abdominal obesity.
Interventions
Participants were randomized to a supervised high-intensity interval endurance training (3 times a week for 45 minutes), resistance training (3 times a week for 45 minutes), or no exercise (control group).
Main outcomes and measures
Change in epicardial and pericardial adipose tissue mass assessed by magnetic resonance imaging, based on a prespecified secondary analysis plan including 3 of 5 parallel groups.
Results
Of 50 participants (mean [SD] age, 41 [14] years, 10 men [26%]; mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 32 [5]), 39 [78%] completed the study. Endurance training and resistance training reduced epicardial adipose tissue mass by 32% (95% CI, 10%-53%) and 24% (95% CI, 1%-46%), respectively, compared with the no exercise control group (56% [95% CI, 24%-88%]; P = .001 and 48% [95% CI, 15%-81%]; P < .001, respectively). While there was a nonsignificant reduction in pericardial adipose tissue mass after endurance training (11% [95% CI, -5% to 27%]; P = .17), resistance training significantly reduced pericardial adipose tissue mass by 31% (95% CI, 16%-47%; P < .001) when compared with the no exercise control group. Compared with the no exercise control group, there was an increase in left ventricular mass by endurance (20 g [95% CI, 11%-30%]; P < .001) and resistance training (18 g [95% CI, 8%-28%]; P < .001). Other cardiometabolic outcomes remained unchanged after the 12-week trial period.
Conclusions and relevance
In individuals with abdominal obesity, both endurance and resistance training reduced epicardial adipose tissue mass, while only resistance training reduced pericardial adipose tissue mass. These data highlight the potential preventive importance of different exercise modalities as means to reduce cardiac fat in individuals with abdominal obesity.
Trial registration
ClinicalTrials.gov identifier: NCT02901496.



JAMA Cardiol: 02 Jul 2019; epub ahead of print
Christensen RH, Wedell-Neergaard AS, Lehrskov LL, Legaard GE, ... Pedersen BK, Ellingsgaard H
JAMA Cardiol: 02 Jul 2019; epub ahead of print | PMID: 31268469
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Impact:
Abstract

Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis.

Barbarawi M, Kheiri B, Zayed Y, Barbarawi O, ... Alkotob ML, Manson JE
Importance
Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding.
Objective
We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality.
Data sources
Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database\'s inception to December 15, 2018.
Study selection
Inclusion criteria were randomized clinical trials that reported the effect of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded.
Data extraction and synthesis
Data were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs.
Main outcomes and measures
Major adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points.
Results
Twenty-one randomized clinical trials were included (including 83 291 patients, of whom 41 669 received vitamin D and 41 622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61 943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23). Results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration.
Conclusions and relevance
In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose.



JAMA Cardiol: 18 Jun 2019; epub ahead of print
Barbarawi M, Kheiri B, Zayed Y, Barbarawi O, ... Alkotob ML, Manson JE
JAMA Cardiol: 18 Jun 2019; epub ahead of print | PMID: 31215980
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Impact:
Abstract

Anatomic Relationship of the Complex Tricuspid Valve, Right Ventricle, and Pulmonary Vasculature: A Review.

Hahn RT, Waxman AB, Denti P, Delhaas T
Importance
Severe functional or secondary tricuspid regurgitation (TR) is associated with poor long-term outcomes in natural history studies as well as specific disease states. An understanding of the physiologic causes of the TR is lacking precluding a systematic approach to treatment.
Observations
The complex anatomic relationship between the tricuspid valve apparatus and structure of the right side of the heart lends insight into the functional changes seen with secondary TR. The association of these changes with changes in pulmonary vascular hemodynamics can lead to a cascade of events that result in disease progression.
Conclusions and relevance
Appreciating the role of pulmonary vascular hemodynamics on right ventricular and tricuspid valve morphology and function improves our understanding of the pathophysiology of secondary TR. The limitations of current therapeutic approaches for secondary TR have stimulated interest in improving outcomes with this morbid disease. Changes in timing or approach to intervention require a more comprehensive understanding of the pathophysiology.



JAMA Cardiol: 30 Apr 2019; 4:478-487
Hahn RT, Waxman AB, Denti P, Delhaas T
JAMA Cardiol: 30 Apr 2019; 4:478-487 | PMID: 30994879
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Abstract

Association of Coronary Anatomical Complexity With Clinical Outcomes After Percutaneous or Surgical Revascularization in the Veterans Affairs Clinical Assessment Reporting and Tracking Program.

Valle JA, Glorioso TJ, Bricker R, Barón AE, ... Stone GW, Waldo SW
Importance
Anatomical scoring systems for coronary artery disease, such as the SYNTAX (Synergy Between Percutaneous Coronary Intervention [PCI] With Taxus and Cardiac Surgery) score, are well established tools for understanding patient risk. However, they are cumbersome to compute manually for large data sets, limiting their use across broad and varied cohorts.
Objective
To adapt an anatomical scoring system for use with registry data, allowing facile and automatic calculation of scores and association with clinical outcomes among patients undergoing percutaneous or surgical revascularization.
Design, setting, and participants
This cross-sectional observational cohort study involved procedures performed in all cardiac catheterization laboratories in the largest integrated health care system in the United States, the Veterans Affairs (VA) Healthcare System. Patients undergoing coronary angiography in the VA Healthcare System followed by percutaneous or surgical revascularization within 90 days were observed and data were analyzed from January 1, 2010, through September 30, 2017.
Main outcomes and measures
An anatomical scoring system for coronary artery disease complexity before revascularization was simplified and adapted to data from the VA Clinical Assessment, Reporting, and Tracking Program. The adjusted association between quantified anatomical complexity and major adverse cardiovascular and cerebrovascular events (MACCEs), including death, myocardial infarction, stroke, and repeat revascularization, was assessed for patients undergoing percutaneous or surgical revascularization.
Results
A total of 50 226 patients (49 359 men [98.3%]; mean [SD] age, 66 [9] years) underwent revascularization during the study period, with 34 322 undergoing PCI and 15 904 undergoing coronary artery bypass grafting (CABG). After adjustment, the highest tertile of anatomical complexity was associated with increased hazard of MACCEs (adjusted hazard ratio [HR], 2.12; 95% CI, 2.01-2.23). In contrast, the highest tertile of anatomical complexity among patients undergoing CABG was not independently associated with overall MACCEs (adjusted HR, 1.04; 95% CI, 0.92-1.17), and only repeat revascularization was associated with increasing complexity (adjusted HR, 1.34; 95% CI, 1.06-1.70) in this subgroup.
Conclusions and relevance
These findings suggest that an automatically computed score assessing anatomical complexity can be used to assess longitudinal risk for patients undergoing revascularization. This simplified scoring system appears to be an alternative tool for understanding longitudinal risk across large data sets.



JAMA Cardiol: 25 Jun 2019; epub ahead of print
Valle JA, Glorioso TJ, Bricker R, Barón AE, ... Stone GW, Waldo SW
JAMA Cardiol: 25 Jun 2019; epub ahead of print | PMID: 31241721
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Abstract

Uptake of Drug-Eluting Bioresorbable Vascular Scaffolds in Clinical Practice: An NCDR Registry to Practice Project.

Chau KH, Kennedy KF, Messenger JC, Garratt KN, ... Yeh RW, Kirtane AJ
Importance
Physicians have been criticized for having an overly enthusiastic response to new device approvals, especially for novel technologies. However, to our knowledge, the rates of new product adoption and patterns of new device usage in clinical practice have not been well described.
Objective
To characterize the patterns of uptake of bioresorbable vascular scaffolds (BVS) within the United States following device approval and to describe changes in response to subsequent releases of data and US Food and Drug Administration (FDA) warnings.
Design, setting, and participants
This analysis of the uptake of BVS between January 2016 and June 2017 used CathPCI Registry data; all percutaneous coronary intervention (PCI) procedures with an implant of either a BVS or conventional stent were included. Data analysis was performed in October 2017.
Exposures
Implant of BVS.
Main outcomes and measures
The primary outcome was monthly use of BVS in the United States. In addition, the characteristics of patients who received BVS and of hospitals that used BVS were assessed and comparisons of patient characteristics between BVS recipients and patients who were treated contemporaneously with metallic stents were made.
Results
Of 682 951 procedures, 471 064 (69.0%) were done in men, 587 301 (86.0%) were among white people, and the mean (SD) age of those undergoing procedures with BVS vs conventional stents was 62.6 (11.4) years vs 65.7 (11.9) years. Of these, 4265 procedures (0.6%) used BVS overall (after FDA approval of BVS). Procedures with implants of BVS occurred among patients with fewer comorbidities and lower-acuity presentations compared with procedures with implants of conventional stents. The patient characteristics for BVS use were not dissimilar to the inclusion criteria of the ABSORB III FDA approval trial, with notable differences based on trial eligibility (eg, excluding patients with myocardial infarctions). The maximum monthly use of BVS was 1.25% of all PCI procedures that occurred 90 days after FDA approval, but with site-to-site variability. Declines in use were observed coincident with the scientific presentation of adverse event data as well as FDA warnings.
Conclusions and relevance
Most US physicians and hospitals were selective in their use of BVS, primarily using them in patients similar to those in the device\'s FDA approval trial. In addition, declines in use were evident in the subsequent month following the release of data that reported negative outcomes. These results illustrate an example of an appropriate physician response to adverse data updates and FDA warnings.



JAMA Cardiol: 31 May 2019; 4:564-568
Chau KH, Kennedy KF, Messenger JC, Garratt KN, ... Yeh RW, Kirtane AJ
JAMA Cardiol: 31 May 2019; 4:564-568 | PMID: 31066860
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Abstract

Lifetime Risks for Hypertension by Contemporary Guidelines in African American and White Men and Women.

Chen V, Ning H, Allen N, Kershaw K, ... Lloyd-Jones DM, Wilkins JT
Importance
Patterns of hypertension risk development over the adult lifespan and lifetime risks for hypertension under the American Heart Association and American College of Cardiology (AHA/ACC) 2017 thresholds for hypertension (≥130/80 mm Hg) are unknown.
Objective
To quantify and compare lifetime risks for hypertension in white and African American men and women under the AHA/ACC 2017 and the Seventh Joint National Commission (JNC7) hypertension thresholds.
Design, setting, and participants
We used individual-level pooled data from 3 contemporary cohorts in the Cardiovascular Lifetime Risk Pooling Project: the Framingham Offspring Study, the Coronary Artery Risk Development in Young Adults study, and Atherosclerosis Risk in Communities study. These community-based cohorts included white and African American men and women with blood pressure assessment at multiple cohort examinations.
Main outcomes and measures
Cumulative lifetime risk for hypertension from ages 20 through 85 years, adjusted for competing risk of death and baseline hypertension prevalence. Incident hypertension under the AHA/ACC threshold was defined by a single-occasion blood pressure measurement of 130/80 mm Hg or more or self-reported use of antihypertensive medications. Incident hypertension under the JNC7 threshold was defined by a single-occasion blood pressure measurement of 140/90 mm Hg or more or the use of antihypertensive medications.
Results
A total of 13 160 participants contributed 227 600 person-years of follow-up; the data set included individual-level data on 6313 participants at baseline (median age, 25 years), plus person-year data from participants in the Atherosclerosis Risk in Communities and Framingham Offspring studies who enrolled at older ages. Baseline prevalence of hypertension under the AHA/ACC 2017 threshold in participants entering the data set between 20 and 30 years of age was 30.7% in white men (n = 549 of 1790), 23.1% in African American men (n = 245 of 1063), 10.2% in white women (n = 210 of 2070), and 12.3% in African American women (n = 171 of 1390). White men had lifetime risk of hypertension of 83.8% (95% CI, 82.5%-85.0%); African American men, 86.1% (95% CI, 84.1%-88.1%); white women, 69.3% (95% CI, 67.8%-70.7%); and African American women, 85.7% (95% CI, 84.0%-87.5%). These were greater than corresponding lifetime risks under the JNC7 threshold for hypertension (white men, 60.5% [95% CI, 58.9%-62.1%]; African American men, 74.7% [95% CI, 71.9%-77.5%]; white women, 53.9% [95% CI, 52.5%-55.4%]; and African American women, 77.3% [95% CI, 75.0%-79.5%]).
Conclusions and relevance
Under the AHA/ACC 2017 blood pressure threshold for hypertension, lifetime risks for hypertension exceeded 75% for African American men and women and white men. Furthermore, prevalence of blood pressure of 130/80 mm Hg or more is very high in young adulthood, suggesting that efforts to prevent development of hypertension should be focused early in the life course.



JAMA Cardiol: 30 Apr 2019; 4:455-459
Chen V, Ning H, Allen N, Kershaw K, ... Lloyd-Jones DM, Wilkins JT
JAMA Cardiol: 30 Apr 2019; 4:455-459 | PMID: 30916719
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Impact:
Abstract

Association of Influenza-like Illness Activity With Hospitalizations for Heart Failure: The Atherosclerosis Risk in Communities Study.

Kytömaa S, Hegde S, Claggett B, Udell JA, ... Solomon SD, Vardeny O
Importance
Influenza is associated with an increased risk of cardiovascular events, but to our knowledge, few studies have explored the temporal association between influenza activity and hospitalizations, especially those caused by heart failure (HF).
Objective
To explore the temporal association between influenza activity and hospitalizations due to HF and myocardial infarction (MI). We hypothesized that increased influenza activity would be associated with an increase in hospitalizations for HF and MI among adults in the community.
Design, setting, and participants
As part of the community surveillance component of the Atherosclerosis Risk in Communities (ARIC) study, a population-based study with hospitalizations sampled from 4 US communities, data were collected from 451 588 adults aged 35 to 84 years residing in the ARIC communities from annual cross-sectional stratified random samples of hospitalizations during October 2010 to September 2014.
Exposures
Monthly influenza activity, defined as the percentage of patient visits to sentinel clinicians for influenza-like illness by state, as reported by the Centers for Disease Control and Prevention Surveillance Network.
Main outcomes and measures
The monthly frequency of MI hospitalizations (n = 3541) and HF hospitalizations (n = 4321), collected through community surveillance and adjudicated as part of the ARIC Study.
Results
Between October 2010 and September 2014, 2042 (47.3%) and 1599 (45.1%) of the sampled patients who were hospitalized for HF and MI, respectively, were women and 2391 (53.3%) and 2013 (57.4%) were white, respectively. A 5% monthly absolute increase in influenza activity was associated with a 24% increase in HF hospitalization rates, standardized to the total population in each community, within the same month after adjusting for region, season, race/ethnicity, sex, age, and number of MI/HF hospitalizations from the month before (incidence rate ratio, 1.24; 95% CI, 1.11-1.38; P < .001), while overall influenza activity was not significantly associated with MI hospitalizations (incidence rate ratio, 1.02; 95% CI, 0.90-1.17; P = .72). Influenza activity in the months before hospitalization was not associated with either outcome. Our model suggests that in a month with high influenza activity, approximately 19% of HF hospitalizations (95% CI, 10%-28%) could be attributable to influenza.
Conclusions and relevance
Influenza activity was temporally associated with an increase in HF hospitalizations across 4 influenza seasons. These data suggest that influenza may contribute to the risk of HF hospitalization in the general population.



JAMA Cardiol: 31 Mar 2019; 4:363-369
Kytömaa S, Hegde S, Claggett B, Udell JA, ... Solomon SD, Vardeny O
JAMA Cardiol: 31 Mar 2019; 4:363-369 | PMID: 30916717
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Abstract

Association of Time Between Left Ventricular and Aortic Systolic Pressure Peaks With Severity of Aortic Stenosis and Calcification of Aortic Valve.

Sato K, Kumar A, Jobanputra Y, Betancor J, ... Svensson LG, Kapadia SR
Importance
Diagnosis of low-gradient severe aortic stenosis (AS) is challenging. We hypothesized that the time between left ventricular (LV) and aortic systolic pressure peaks (TLV-Ao) is associated with aortic stenosis (AS) severity and may have additive value in diagnosing severe AS, especially in patients with low-gradient AS.
Objective
To investigate the diagnostic utility of measuring catheter-based TLV-Ao in patients with severe AS.
Design, setting, and participants
We studied 123 patients with severe AS at the Cleveland Clinic Foundation, a tertiary referral center, who underwent transcatheter aortic valve replacement (TAVR) via femoral access and had pre-TAVR cardiac computed tomography assessment and hemodynamic measurements recorded during a TAVR procedure. All patients received hemodynamic evaluation, echocardiographic assessment, and quantification of aortic valve calcification (AVC) by multidetector computed tomography. Hemodynamic data were collected via left heart catheterization done just before TAVR, and TLV-Ao was calculated offline. Data were analyzed between October 5, 2015, and July 20, 2016.
Main outcomes and measures
The association between TLV-Ao and AVC or other conventional imaging parameters was analyzed.
Results
Of the included patients, the mean (SD) age was 81 (9) years, and 65 (54%) were men (54%). Among 123 patients, 48 patients (39%) had low-gradient AS (<40 mm Hg) and mean (SD) TLV-Ao was 69 (39) milliseconds. In multivariable logistic regression analyses, higher TLV-Ao (odds ratio [OR], 1.02; 95% CI, 1.01-1.04; P = .002) and higher peak aortic valve (AV) velocity (OR, 1.01; 95% CI, 1.00-1.02; P = .008) were independently associated with severe AVC (AVC >1000 AU). Adding TLV-Ao to the peak AV velocity and AV area showed significant incremental value to be associated with AVC, with a net reclassification improvement of 0.61 (95% CI, 0.23-0.99; P = .002) and integrated discriminatory improvement of 0.09 (95% CI, 0.03-0.16; P = .003). In a subgroup of patients with low-grade AS, higher TLV-Ao was the only parameter associated with severe AVC (OR, 1.02; 95% CI, 1.001-1.04; P = .03).
Conclusions and relevance
Prolonged TLV-Ao was associated with severe AVC. This catheter-based hemodynamic index may be an additional surrogate to differentiate low-gradient true severe AS. Larger, prospective studies investigating the role of TLV-Ao as a marker of clinical outcomes in patients undergoing TAVR are required.



JAMA Cardiol: 31 May 2019; 4:549-555
Sato K, Kumar A, Jobanputra Y, Betancor J, ... Svensson LG, Kapadia SR
JAMA Cardiol: 31 May 2019; 4:549-555 | PMID: 31042265
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Abstract

The Diagnostic and Prognostic Value of Echocardiographic Strain.

Singh A, Voss WB, Lentz RW, Thomas JD, Akhter N
Importance
Myocardial deformation or strain by speckle-tracking echocardiography (STE) has become an established echocardiographic modality for the diagnostic and prognostic evaluation of cardiac dysfunction. Current literature supports the incremental value of strain in diagnosis, risk stratification, and prognostication of a multitude of cardiac disease states.
Observations
Strain has been studied across the clinical spectrum from common to obscure pathologic conditions. This review presents the current literature evaluating characteristic strain patterns across this clinical spectrum, discusses prognostic implications, and provides a case series of classic strain polar maps, which are also known as bull\'s-eye plots.
Conclusions and relevance
Characteristic bull\'s-eye patterns can be used to guide patient evaluation and management.



JAMA Cardiol: 31 May 2019; 4:580-588
Singh A, Voss WB, Lentz RW, Thomas JD, Akhter N
JAMA Cardiol: 31 May 2019; 4:580-588 | PMID: 31042262
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Impact:
Abstract

Effect of a Quality of Care Improvement Initiative in Patients With Acute Coronary Syndrome in Resource-Constrained Hospitals in China: A Randomized Clinical Trial.

Wu Y, Li S, Patel A, Li X, ... Gao R,
Importance
Prior observational studies suggest that quality of care improvement (QCI) initiatives can improve the clinical outcomes of acute coronary syndrome (ACS). To our knowledge, this has never been demonstrated in a well-powered randomized clinical trial.
Objective
To determine whether a clinical pathway-based, multifaceted QCI intervention could improve clinical outcomes among patients with ACS in resource-constrained hospitals in China.
Design, setting, participants
This large, stepped-wedge cluster randomized clinical trial was conducted in nonpercutaneous coronary intervention hospitals across China and included all patients older than 18 years and with a final diagnosis of ACS who were recruited consecutively between October 2011 and December 2014. We excluded patients who died before or within 10 minutes of hospital arrival. We recruited 5768 and 0 eligible patients for the control and intervention groups, respectively, in step 1, 4326 and 1365 in step 2, 3278 and 3059 in step 3, 1419 and 4468 in step 4, and 0 and 5645 in step 5.
Interventions
The intervention included establishing a QCI team, training clinical staff, implementing ACS clinical pathways, sequential site performance assessment and feedback, online technical support, and patient education. The usual care was the control that was compared.
Main outcomes and measures
The primary outcome was the incidence of in-hospital major adverse cardiovascular events (MACE), comprising all-cause mortality, reinfarction/myocardial infarction, and nonfatal stroke. Secondary outcomes included 16 key performance indicators (KPIs) and the composite score developed from these KPIs.
Results
Of 29 346 patients (17 639 men [61%]; mean [SD] age for control, 64.1 [11.6] years; mean [SD] age for intervention, 63.9 [11.7] years) who were recruited from 101 hospitals, 14 809 (50.5%) were in the control period and 14 537 (49.5%) were in the intervention period. There was no significant difference in the incidence of in-hospital MACE between the intervention and control periods after adjusting for cluster and time effects (3.9% vs 4.4%; odds ratio, 0.93; 95% CI, 0.75-1.15; P = .52). The intervention showed a significant improvement in the composite KPI score (mean [SD], 0.69 [0.22] vs 0.61 [0.23]; P < .01) and in 7 individual KPIs, including the early use of antiplatelet therapy and the use of appropriate secondary prevention medicines at discharge. No unexpected adverse events were reported.
Conclusions and relevance
Among resource-constrained Chinese hospitals, introducing a multifaceted QCI intervention had no significant effect on in-hospital MACE, although it improved a few of the care process indicators of evidence-based ACS management.
Trial registration
ClinicalTrials.gov identifier: NCT01398228.



JAMA Cardiol: 30 Apr 2019; 4:418-427
Wu Y, Li S, Patel A, Li X, ... Gao R,
JAMA Cardiol: 30 Apr 2019; 4:418-427 | PMID: 30994898
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Impact:

This program is still in alpha version.