Journal: JAMA Cardiol

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Abstract

Association of Echocardiographic Left Ventricular End-Systolic Volume and Volume-Derived Ejection Fraction With Outcome in Asymptomatic Chronic Aortic Regurgitation.

Yang LT, Anand V, Zambito EI, Pellikka PA, ... Enriquez-Sarano M, Michelena HI
Importance
Volumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown.
Objective
To assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR.
Design, setting, and participants
This cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019).
Exposures
Clinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF.
Main outcome and measures
Associations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF.
Results
Of 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival.
Conclusions and relevance
In this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.



JAMA Cardiol: 03 Nov 2020; epub ahead of print
Yang LT, Anand V, Zambito EI, Pellikka PA, ... Enriquez-Sarano M, Michelena HI
JAMA Cardiol: 03 Nov 2020; epub ahead of print | PMID: 33146680
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Abstract

Evaluation of Risk-Adjusted Home Time After Hospitalization for Heart Failure as a Potential Hospital Performance Metric.

Pandey A, Keshvani N, Vaughan-Sarrazin MS, Gao Y, ... Yancy C, Girotra S
Importance
Thirty-day home time, defined as time spent alive and out of a hospital or facility, is a novel, patient-centered performance metric that incorporates readmission and mortality.
Objectives
To characterize risk-adjusted 30-day home time in patients discharged with heart failure (HF) as a hospital-level quality metric and evaluate its association with the 30-day risk-standardized readmission rate (RSRR), 30-day risk-standardized mortality rate (RSMR), and 1-year RSMR.
Design, setting, and participants
This hospital-level cohort study retrospectively analyzed 100% of Medicare claims data from 2 968 341 patients from 3134 facilities from January 1, 2012, to November 30, 2017.
Exposures
Home time, defined as time spent alive and out of a short-term hospital, skilled nursing facility, or intermediate/long-term facility 30 days after discharge.
Main outcomes and measures
For each hospital, a risk-adjusted 30-day home time for HF was calculated similar to the Centers for Medicare & Medicaid Services risk-adjustment models for 30-day RSRR and RSMR. Hospitals were categorized into quartiles (lowest to highest risk-adjusted home time). The correlations between hospital rates of risk-adjusted 30-day home time and 30-day RSRR, 30-day RSMR, and 1-year RSMR were estimated using the Pearson correlation coefficient. Distribution of days lost from a perfect 30-day home time were calculated. Reclassification of hospital performance using 30-day home time vs 30-day RSRR was also evaluated.
Results
Overall, 2 968 341 patients (mean [SD] age, 81.0 [8.3] years; 53.6% female) from 3134 hospitals were included in this study. The median hospital risk-adjusted 30-day home time for patients with HF was 21.77 days (range, 8.22-28.41 days). Hospitals in the highest quartile of risk-adjusted 30-day home time (best-performing hospitals) were larger (mean [SD] number of beds, 285 [275]), with a higher volume of patients with HF (median, 797 patients; interquartile range, 395-1484) and were more likely academic hospitals (59.9%) with availability of cardiac surgery (51.1%) and cardiac rehabilitation (68.8%). A total of 72% of home time lost was attributable to stays in an intermediate- or long-term care facility (mean [SD], 2.65 [6.44] days) or skilled nursing facility (mean [SD], 3.96 [9.04] days), 13% was attributable to short-term readmissions (mean [SD], 1.25 [3.25] days), and 15% was attributable to death (mean [SD], 1.37 [6.04] days). Among 30-day outcomes, the 30-day RSRR and 30-day RSMR decreased in a graded fashion across increasing 30-day home time categories (correlation coefficients: 30-day RSRR and 30-day home time, -0.23, P < .001; 30-day RSMR and 30-day home time, -0.31, P < .001). Similar patterns of association were also noted for 1-year RSMR and 30-day home time (correlation coefficient, -0.35, P < .001). Thirty-day home time meaningfully reclassified hospital performance in 30% of the hospitals compared with 30-day RSRR and in 25% of hospitals compared with 30-day RSMR.
Conclusions and relevance
In this study, 30-day home time among patients discharged after a hospitalization for HF was objectively assessed as a hospital-level quality metric using Medicare claims data and was associated with readmission and mortality outcomes and with reclassification of hospital performance compared with 30-day RSRR and 30-day RSMR.



JAMA Cardiol: 27 Oct 2020; epub ahead of print
Pandey A, Keshvani N, Vaughan-Sarrazin MS, Gao Y, ... Yancy C, Girotra S
JAMA Cardiol: 27 Oct 2020; epub ahead of print | PMID: 33112393
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Abstract

Clinical Application of High-Sensitivity Troponin Testing in the Atherosclerotic Cardiovascular Disease Framework of the Current Cholesterol Guidelines.

Marston NA, Bonaca MP, Jarolim P, Goodrich EL, ... Sabatine MS, Morrow DA
Importance
The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol management guidelines identified 2 distinct groups of patients with atherosclerotic cardiovascular disease (ASCVD) prompting different treatment recommendations.
Objective
To investigate whether the addition of high-sensitivity troponin (hsTn) testing to guideline-derived ASCVD risk can improve risk classification and downstream treatment recommendations.
Design, setting, and participants
A prospective cohort biomarker substudy was performed that included 8635 patients enrolled in the Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54 (PEGASUS-TIMI 54) trial. Patients were assigned to risk groups of either very high-risk ASCVD or lower-risk ASCVD based on their cardiovascular history and comorbidities, in line with the 2018 AHA/ACC cholesterol management guidelines criteria. Patients were also classified on the basis of hsTnI level (ARCHITECT assay; Abbott) using cut points of 2 ng/L (limit of detection) and 6 ng/L (risk threshold), followed by joint classification on the basis of clinical features and hsTnI level. The setting was a nested prospective cohort study in a completed multinational trial. Participants were all patients who had a myocardial infarction 1 to 3 years before enrollment, were at least 50 years of age, and had at least 1 high-risk feature. The study dates were October 2010 to December 2014. The dates of analysis were June 2019 to January 2020.
Main outcomes and measures
The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke.
Results
Among 8635 patients enrolled in the PEGASUS-TIMI 54 trial, the median age was 65 years (interquartile range, 58-71 years), and 6614 (76.6%) were men; 8340 (96.6%) were White individuals and 176 (2.0%) were Black individuals. Patients meeting clinical criteria for the very high-risk ASCVD group had a primary end point 3-year event rate of 8.8% compared with 5.0% in the lower-risk ASCVD group (hazard ratio, 2.01; 95% CI, 1.58-2.57; P < .001). When patients in the very high-risk ASCVD group were further risk stratified by hsTnI level, 614 of 6789 patients (9.0%) with an undetectable hsTnI level had a 3-year event rate of 2.7% (<1% per year), which was less than the overall rate in the lower-risk ASCVD group. Analogously, in the lower-risk ASCVD group, 417 of 1846 patients (22.6%) with an hsTnI level exceeding 6 ng/L had an event rate of 9.1%, comparable to the overall rate in the very high-risk ASCVD group. The addition of hsTnI to guideline-derived ASCVD risk led to a net reclassification index at event rate of 0.15 (95% CI, 0.10-0.21). Overall, use of hsTnI reclassified 1031 of 8635 patients (11.9%) (1 in 11 with very high-risk ASCVD and 1 in 4 with lower-risk ASCVD).
Conclusions and relevance
The findings of this cohort substudy suggest that a strategy incorporating hsTn into a guideline-derived ASCVD risk algorithm provides enhanced risk stratification and reclassifies 11.9% of patients into a more appropriate risk group. This application of hsTn testing might be used to optimize the care of patients with ASCVD.



JAMA Cardiol: 31 Oct 2020; 5:1255-1262
Marston NA, Bonaca MP, Jarolim P, Goodrich EL, ... Sabatine MS, Morrow DA
JAMA Cardiol: 31 Oct 2020; 5:1255-1262 | PMID: 32756916
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Abstract

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

Wang N, Salam A, Webster R, de Silva A, ... Rodgers A,
Importance
Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia.
Objective
To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care.
Design, setting, and participants
A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019.
Interventions
Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care.
Main outcomes and measures
Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression.
Results
Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared with the usual care group at baseline (predicted mean [SD] increase in regimen potency: triple pill, 15 [6] mm Hg; usual care, 10 [5] mm Hg; P < .001), whereas there were no significant differences at the week 6 or at week 12 visit. Clinic systolic BP level was the only consistent predictor of treatment intensification during follow-up. During follow-up, there were 23 vs 54 unique treatment regimens per 100 treated patients in the triple pill vs usual care groups, respectively (P < .001).
Conclusions and relevance
Triple pill FDC therapy was associated with greater rates of therapeutic inertia compared with usual care. Despite this, triple pill FDC therapy substantially simplified prescribing patterns and improved 6-month BP control rates compared with usual care. Further improvements in hypertension control could be achieved by addressing therapeutic inertia among the minority of patients who do not achieve BP control after initial FDC therapy.
Trial registration
ANZCTR Identifier: ACTRN12612001120864.



JAMA Cardiol: 31 Oct 2020; 5:1219-1226
Wang N, Salam A, Webster R, de Silva A, ... Rodgers A,
JAMA Cardiol: 31 Oct 2020; 5:1219-1226 | PMID: 32717045
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Abstract

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19).

Puntmann VO, Carerj ML, Wieters I, Fahim M, ... Vehreschild M, Nagel E
Importance
Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.
Objective
To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.
Design, setting, and participants
In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.
Exposure
Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.
Main outcomes and measures
Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).
Results
Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = -0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.
Conclusions and relevance
In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.



JAMA Cardiol: 31 Oct 2020; 5:1265-1273
Puntmann VO, Carerj ML, Wieters I, Fahim M, ... Vehreschild M, Nagel E
JAMA Cardiol: 31 Oct 2020; 5:1265-1273 | PMID: 32730619
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Abstract

One-Year Outcomes of Mitral Valve-in-Valve Using the SAPIEN 3 Transcatheter Heart Valve.

Whisenant B, Kapadia SR, Eleid MF, Kodali SK, ... Makkar RR, Guerrero M
Importance
Bioprosthetic mitral valves are implanted with increasing frequency but inevitably degenerate, leading to heart failure. Reoperation is associated with high morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) using balloon-expandable transcatheter valves has emerged as an alternative for high-surgical risk patients.
Objective
To assess contemporary outcomes of SAPIEN 3 (Edwards Lifesciences) MViV replacement.
Design, setting, and participants
In this registry-based prospective cohort study of SAPIEN 3 MViV, patients entered in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from June 2015 to July 2019 were analyzed. US Centers for Medicare and Medicaid linkage ensured comprehensive collection of death and stroke data.
Exposures
Mitral valve-in-valve for degenerated bioprosthetic mitral valves.
Main outcomes and measures
The primary efficacy end point was 1-year mortality. The primary safety end point was procedural technical success as defined by the Mitral Valve Academic Research Consortium criteria. Secondary end points included 30-day mortality, New York Heart Association-defined heart failure, and mitral valve performance.
Results
A total of 1529 patients (mean [SD] age, 73.3 [11.84] years; 904 women [59.1%]) underwent transseptal or transapical MViV implant at 295 hospitals between June 2015 and July 2019. The mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 11.1% (8.7%). Procedural technical success was achieved for 1480 of 1529 patients (96.8%). All-cause mortality was 5.4% at 30 days and 16.7% at 1 year. Transseptal access was associated with lower 1-year all-cause mortality than transapical access (15.8% vs 21.7%; P = .03). Transcatheter MViV led to early, sustained, and clinically meaningful improvements in heart failure (class III/IV New York Heart Association heart failure of 87.1% at baseline vs 9.7% at 1 year). The mean (SD) mitral valve gradient at 1 year was 7 (2.89) mm Hg.
Conclusions and relevance
Transcatheter MViV using the SAPIEN 3 transcatheter heart valve is associated with high technical success, low 30-day and 1-year mortality, significant improvement of heart failure symptoms, and sustained valve performance. Transseptal MViV should be considered an option for most patients with failed surgical bioprosthetic valves and favorable anatomy.



JAMA Cardiol: 31 Oct 2020; 5:1245-1252
Whisenant B, Kapadia SR, Eleid MF, Kodali SK, ... Makkar RR, Guerrero M
JAMA Cardiol: 31 Oct 2020; 5:1245-1252 | PMID: 32745164
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Abstract

Influence of Clinical Trials of Acute Coronary Syndrome Beyond the Primary Hypothesis: A Systematic Review.

Luoma LM, Westerhout CM, Granger CB, Armstrong PW
Importance
Conducting a clinical trial involves significant risks, time, and resources. The return on investment for these trials, measured by advancing health care and contributions to the scientific literature, is often uncertain.
Objective
To assess the long-term effects of major clinical trials of acute coronary syndromes contemporary to the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) trial, which did not achieve its primary objective.
Evidence review
The Cochrane Central Register of Controlled Trials database was screened for clinical trials of acute coronary syndromes (including unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) with more than 1000 participants and primary results published between January 1, 2005, and December 31, 2009, in Circulation, European Heart Journal, JAMA, Journal of the American College of Cardiology, The Lancet, and The New England Journal of Medicine. For identified trials, bibliographic information, citations, trial name, registration, inclusion diagnosis, intervention type, sample size, primary outcome result, sponsor information, and academic involvement were extracted. To identify secondary analyses, bibliographic information for citing articles, their citations, and their abstracts were extracted. Clinical practice guideline bibliographies for citations of trial publications were reviewed, and the class and level of evidence of resulting recommendations were extracted.
Findings
Of 784 records screened, 30 were primary publications of 25 clinical trials. Through December 31, 2018, these trials were cited a median of 497 times (interquartile range [IQR], 424-931 citations). Trials that did not achieve their primary objective had fewer primary citations (the number of times that each published journal article with the primary [main] results of a trial was cited) (median, 443 [IQR, 396-468] vs 868 [IQR, 645-1774] citations, P = .006). The frequency of secondary analyses peaked within 5 years of the primary trial at 643. Trials that did not achieve the primary objective had fewer secondary analyses (median, 15 [IQR, 5-31] vs 18 [IQR, 10-43] analyses, P = .44) that were not cited significantly less often (median, 484 [IQR, 191-1299] vs 1124 [IQR, 410-4283] citations, P = .16). All trials were cited by at least 1 clinical practice guideline.
Conclusions and relevance
This review found that trials that achieved the primary objective were frequently cited. Secondary research activity did not differ by primary result, and the primary trials and secondary analyses contributed to clinical practice recommendations. These data show the long-term importance of clinical trials regardless of primary outcome result.



JAMA Cardiol: 31 Oct 2020; 5:1286-1297
Luoma LM, Westerhout CM, Granger CB, Armstrong PW
JAMA Cardiol: 31 Oct 2020; 5:1286-1297 | PMID: 32745162
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Abstract

Cost-effectiveness of Sacubitril-Valsartan in Hospitalized Patients Who Have Heart Failure With Reduced Ejection Fraction.

Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD
Importance
Sacubitril-valsartan use reduces mortality and hospitalizations compared with enalapril among patients with chronic heart failure with reduced ejection fraction (HFrEF); however, the cost-effectiveness of these treatments when initiated during hospitalization for HF is unknown.
Objective
To estimate the cost-effectiveness of inpatient initiation of sacubitril-valsartan vs enalapril compared with no initiation or posthospitalization initiation of sacubitril-valsartan among stabilized patients with HFrEF.
Design, setting, and participants
This economic evaluation included data on US patients with HFrEF who were eligible for sacubitril-valsartan treatment from December 8, 2009, to May 15, 2018.
Main outcomes and measures
A 5-state Markov model with all-cause mortality, HF, and non-HF hospitalization probabilities was used. Quality of life was estimated using Euro-QoL EQ-5D scores. Hospitalization, long-term care, and medication costs for sacubitril-valsartan and enalapril were modeled with a discount rate of 3%. The base-case analysis included a lifetime horizon from a health care and societal perspective.
Results
Modeled patients were a mean (SD) age of 63.8 (11.5) years. Inpatient treatment with sacubitril-valsartan ($5628 per year) was associated with 62 fewer HF-related admissions per 1000 patients compared with outpatient initiation or 116 fewer HF-related admissions compared with continuation of enalapril treatment. From a health care system perspective, initiation of sacubitril-valsartan during hospitalization saved $452 per year compared with continuing enalapril and $811 per year compared with initiation at 2 months after hospitalization and was associated with an incremental cost-effectiveness ratio of $21 532 per quality-adjusted life-year compared with continued enalapril treatment over a lifetime. From a societal perspective, inpatient initiation was estimated to save $460 per year per patient compared with no initiation of sacubitril-valsartan and $813 per year per patient compared with initiation after hospitalization. In a budget analysis, inpatient initiation of sacubitril-valsartan was estimated to save up to $449 per person for 1 year or $2550 per person over 5 years compared with continuation of enalapril.
Conclusions and relevance
The findings suggest that, for patients with HFrEF, initiation of sacubitril-valsartan during hospitalization may be associated with reduced hospitalizations, increased quality-adjusted life expectancy, and cost savings compared with no initiation or initiation after hospitalization.



JAMA Cardiol: 31 Oct 2020; 5:1236-1244
Gaziano TA, Fonarow GC, Velazquez EJ, Morrow DA, Braunwald E, Solomon SD
JAMA Cardiol: 31 Oct 2020; 5:1236-1244 | PMID: 32785628
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Abstract

Survival on the Heart Transplant Waiting List.

Bakhtiyar SS, Godfrey EL, Ahmed S, Lamba H, ... Goss J, Rana A
Importance
With continuing improvements in medical devices and more than a decade since the 2006 United Network for Organ Sharing (UNOS) allocation policy, it is pertinent to assess survival among patients on the heart transplantation waiting list, especially given the recently approved 2018 UNOS allocation policy.
Objectives
To assess survival outcomes among patients on the heart transplant waiting list during the past 3 decades and to examine the association of ventricular assist devices (VADs) and the 2006 UNOS allocation policy with survival.
Design, setting, and participants
A retrospective cross-sectional used the UNOS database to perform an analysis of 95 323 candidates wait-listed for heart transplantation between January 1, 1987, and December 29, 2017. Candidates for all types of combined transplants were excluded (n = 2087). Patients were followed up from the time of listing to death, transplantation, or removal from the list due to clinical improvement. Competing-risk, Kaplan-Meier, and multivariable Cox proportional hazards regression analyses were used.
Main outcomes and measures
The analysis involved an unadjusted and adjusted survival analysis in which the primary outcome was death on the waiting list. Because of changing waiting list preferences and policies during the study period, the intrinsic risk of death for wait-listed candidates was assessed by individually analyzing, comparing, and adjusting for several candidate risk factors.
Results
In total, 95 323 candidates (72 915 men [76.5%]; mean [SD] age, 51.9 [12.0] years) were studied. In the setting of changes in listing preferences, 1-year survival on the waiting list increased from 34.1% in 1987-1990 to 67.8% in 2011-2017 (difference in proportions, 0.34%; 95% CI, 0.32%-0.36%; P < .001). The 1-year waiting list survival for candidates with VADs increased from 10.2% in 1996-2000 to 70.0% in 2011-2017 (difference in proportions, 0.60%; 95% CI, 0.58%-0.62%; P < .001). Similarly, in the setting of changing mechanical circulatory support indications, the 1-year waiting list survival for patients without VADs increased from 53.9% in 1996-2000 to 66.5% in 2011-2017 (difference in proportions, 0.13%; 95% CI, 0.12%-0.14%; P < .001). In the decade prior to the 2006 UNOS allocation policy, the 1-year waiting list survival was 51.1%, while in the decade after it was 63.9% (difference in proportions, 0.13%; 95% CI, 0.12%-0.14%; P < .001). In adjusted analysis, each time period after 1987-1990 had a marked decrease in waiting list mortality.
Conclusions and relevance
This study found temporally associated increases in heart transplant waiting list survival for all patient groups (with or without VADs, UNOS status 1 and status 2 candidates, and candidates with poor functional status).



JAMA Cardiol: 31 Oct 2020; 5:1227-1235
Bakhtiyar SS, Godfrey EL, Ahmed S, Lamba H, ... Goss J, Rana A
JAMA Cardiol: 31 Oct 2020; 5:1227-1235 | PMID: 32785619
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Abstract

Considerations for Optimal Device Selection in Transcatheter Aortic Valve Replacement: A Review.

Claessen BE, Tang GHL, Kini AS, Sharma SK
Importance
Aortic valve stenosis (AS) is the most common manifestation of acquired valvular heart disease in developed countries. Several large-scale randomized clinical trials investigating the entire spectrum of patients with severe symptomatic AS from low to prohibitive risk have established transcatheter aortic valve replacement (TAVR) as a safe and effective alternative to surgical aortic valve replacement.
Observations
There are currently only 3 types of TAVR devices commercially available in the US, but several other valve types are undergoing clinical trials in the US. Because of fundamental differences in engineering features, each TAVR device type has specific strengths and limitations. This review aims to provide an overview of design features and clinical outcomes of various TAVR devices that are either commercially available or undergoing clinical investigation.
Conclusions and relevance
Given the lack of large-scale head-to-head comparisons of various TAVR devices and the rapid development of new device iterations, there is insufficient evidence to claim superiority of one device type over another. Nonetheless, as each TAVR device has unique design characteristics, certain patient-related and anatomy-related factors may slightly favor one or several particular designs.



JAMA Cardiol: 08 Sep 2020; epub ahead of print
Claessen BE, Tang GHL, Kini AS, Sharma SK
JAMA Cardiol: 08 Sep 2020; epub ahead of print | PMID: 32902569
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Abstract

Association of Troponin Levels With Mortality in Italian Patients Hospitalized With Coronavirus Disease 2019: Results of a Multicenter Study.

Lombardi CM, Carubelli V, Iorio A, Inciardi RM, ... Metra M, Senni M
Importance
Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates.
Objective
To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19.
Design, setting, and participants
This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values.
Main outcomes and measures
Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values.
Results
A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P < .001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P < .001), heart failure (24 [7.2%]; 63 [22.8%]; P < .001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P < .001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P < .001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P = .01 via multivariable Cox regression analysis), and this was independent from concomitant cardiac disease. Elevated troponin levels were also associated with a higher risk of in-hospital complications: heart failure (44 patients [19.2%] vs 7 patients [2.9%]; P < .001), sepsis (31 [11.7%] vs 21 [6.4%]; P = .03), acute kidney failure (41 [20.8%] vs 13 [6.2%]; P < .001), multiorgan failure (21 [10.9%] vs 6 [2.9%]; P = .003), pulmonary embolism (27 [9.9%] vs 17 [5.2%]; P = .04), delirium (13 [6.8%] vs 3 [1.5%]; P = .02), and major bleeding (16 [7.0%] vs 4 [1.6%]; P = .008).
Conclusions and relevance
In this multicenter, cross-sectional study of Italian patients with COVID-19, elevated troponin was an independent variable associated with in-hospital mortality and a greater risk of cardiovascular and noncardiovascular complications during a hospitalization for COVID-19.



JAMA Cardiol: 31 Oct 2020; 5:1274-1280
Lombardi CM, Carubelli V, Iorio A, Inciardi RM, ... Metra M, Senni M
JAMA Cardiol: 31 Oct 2020; 5:1274-1280 | PMID: 32845276
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Impact:
Abstract

Sociodemographic Disparities in Influenza Vaccination Among Adults With Atherosclerotic Cardiovascular Disease in the United States.

Grandhi GR, Mszar R, Vahidy F, Valero-Elizondo J, ... Omer SB, Nasir K
Importance
Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death and disability in the US and worldwide. Influenza vaccination has shown to decrease overall morbidity, mortality, severity of infection, and hospital readmissions among these individuals. However, national estimates of influenza vaccination among individuals with ASCVD in the US are not well studied.
Objective
To evaluate the prevalence of and sociodemographic disparities in influenza vaccination among a nationally representative sample of individuals with ASCVD.
Design, setting, and participants
Pooled Medical Expenditure Panel Survey data from 2008 to 2016 were used and included adults 40 years or older with ASCVD. Participants\' ASCVD status was ascertained via self-report and/or International Classification of Diseases, Ninth Revision diagnosis of coronary heart disease, peripheral artery disease, and/or cerebrovascular disease. Analysis began April 2020.
Main outcomes and measures
Prevalence and characteristics of adults with ASCVD who lacked influenza vaccination during the past year. Covariates including age, sex, race/ethnicity, family income, insurance status, education level, and usual source of care were assessed.
Results
Of 131 881 adults, 19 793 (15.7%) had ASCVD, corresponding to 22.8 million US adults annually. A total of 7028 adults with ASCVD (32.7%), representing 7.4 million adults, lacked influenza vaccination. The highest odds of lacking vaccination were observed among individuals aged 40 to 64 years (odds ratio [OR], 2.32; 95% CI, 2.06-2.62), without a usual source of care (OR, 2.00; 95% CI, 1.71-2.33), without insurance (OR, 2.05; 95% CI, 1.63-2.58), with a lower education level (OR, 1. 25; 95% CI, 1.12-1.40), with a lower income level (OR, 1.14; 95% CI, 1.01-1.27), and of non-Hispanic Black race/ethnicity (OR, 1.24, 95% CI, 1.10-1.41). A stepwise increase was found in the prevalence and odds of lacking influenza vaccination among individuals with increase in high-risk characteristics. Overall, 1171 individuals (59.7%; 95% CI, 55.8%-63.5%) with 4 or more high-risk characteristics and ASCVD (representing 732 524 US adults annually) reported lack of influenza vaccination (OR, 6.06; 95% CI, 4.88-7.53).
Conclusion and relevance
Despite current recommendations, a large proportion of US adults with established ASCVD lack influenza vaccination, with several sociodemographic subgroups having greater risk. Focused public health initiatives are needed to increase access to influenza vaccinations for high-risk and underserved populations.



JAMA Cardiol: 08 Sep 2020; epub ahead of print
Grandhi GR, Mszar R, Vahidy F, Valero-Elizondo J, ... Omer SB, Nasir K
JAMA Cardiol: 08 Sep 2020; epub ahead of print | PMID: 32902562
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Impact:
Abstract

Trends in Utilization and Cost of Low-Density Lipoprotein Cholesterol-Lowering Therapies Among Medicare Beneficiaries: An Analysis From the Medicare Part D Database.

Sumarsono A, Lalani HS, Vaduganathan M, Navar AM, ... Das SR, Pandey A
Importance
Low-density lipoprotein cholesterol (LDL-C)-lowering therapies are a cornerstone of prevention in atherosclerotic cardiovascular disease. With the introduction of generic formulations and the release of new therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, contemporary Medicare utilization of these therapies remains unknown.
Objective
To determine trends in utilization and spending on brand-name and generic LDL-C-lowering therapies and to estimate potential savings if all Medicare beneficiaries were switched to available therapeutically equivalent generic formulations.
Design, setting, and participants
This cross-sectional study analyzed prescription drug utilization and cost trend data from the Medicare Part D Prescription Drug Event data set from 2014 to 2018 for LDL-C-lowering therapies. A total of 11 LDL-C-lowering drugs with 25 formulations, including 16 brand-name and 9 generic formulations, were included. Data were collected and analyzed from October 2019 to June 2020.
Main outcomes and measures
Number of Medicare Part D beneficiaries, annual spending, and spending per beneficiary for all formulations.
Results
The total number of Medicare Part D beneficiaries ranged from 37 720 840 in 2014 to 44 249 461 in 2018. The number of Medicare beneficiaries taking LDL-C-lowering therapies increased by 23% (from 20.5 million in 2014 to 25.2 million in 2018), while the associated Medicare expenditure decreased by 46% (from $6.3 billion in 2014 to $3.3 billion in 2018). Lower expenditure was driven by greater uptake of generic statin and ezetimibe and a concurrent rapid decline in the use of their brand-name formulations. Medicare spent $9.6 billion on brand-name statins and ezetimibe and could have saved $2.1 billion and $0.4 billion, respectively, if brand-name formulations were switched to equivalent generic versions when available. The number of beneficiaries using PCSK9 inhibitors since their introduction in 2015 has been modest, although use has increased by 144% (from 25 569 in 2016 to 62 476 in 2018) and total spending has increased by 199% (from $164 million in 2016 to $491 million in 2018).
Conclusions and relevance
Between 2014 and 2018, LDL-C-lowering therapies were used by 4.8 million more Medicare beneficiaries annually, with an associated $3.0 billion decline in Medicare spending. This cost reduction was driven by the rapid transition from brand-name formulations to lower-cost generic formulations of statins and ezetimibe. Use of PCSK9 inhibitions, although low, increased over time and could have broad implications on future Medicare spending.



JAMA Cardiol: 08 Sep 2020; epub ahead of print
Sumarsono A, Lalani HS, Vaduganathan M, Navar AM, ... Das SR, Pandey A
JAMA Cardiol: 08 Sep 2020; epub ahead of print | PMID: 32902560
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Impact:
Abstract

Association of Adverse Pregnancy Outcomes With Risk of Atherosclerotic Cardiovascular Disease in Postmenopausal Women.

Søndergaard MM, Hlatky MA, Stefanick ML, Vittinghoff E, ... Manson JE, Parikh NI
Importance
Atherosclerotic cardiovascular disease (ASCVD) may have unique risk factors in women. Most women have a history of pregnancy; common adverse pregnancy outcomes (APOs) appear to be associated with ASCVD, but prior studies have limitations.
Objective
To assess whether APOs are associated with increased ASCVD risk independently of traditional risk factors.
Design, setting, and participants
The APO history among participants in the Women\'s Health Initiative, a large multiethnic cohort of postmenopausal women, was assessed. The associations of 5 self-reported APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight [ie, birth weight less than 2.49 kg], high birth weight [ie, birth weight greater than 4.08 kg], and preterm delivery by 3 weeks or more) with ASCVD were analyzed, adjusting for traditional ASCVD risk factors. Data were collected and analyzed in 2017.
Exposures
APOs (gestational diabetes, hypertensive disorders of pregnancy, low birth weight, high birth weight, and preterm delivery).
Main outcomes and measures
Adjudicated ASCVD.
Results
A total of 48 113 Women\'s Health Initiative participants responded to the survey; the median (interquartile range) age at time of enrollment was 60.0 (55.0-64.0) years. A total of 13 482 participants (28.8%) reported 1 or more APOs. Atherosclerotic cardiovascular disease was more frequent in women who reported an APO compared with those without APOs (1028 of 13 482 [7.6%] vs 1758 of 30 522 [5.8%]). Each APO, analyzed separately, was significantly associated with ASCVD, and gestational diabetes, hypertensive disorders of pregnancy, low birth weight, and preterm delivery remained significant after adjustment for traditional ASCVD risk factors. When all APOs were analyzed together, hypertensive disorders of pregnancy (odds ratio, 1.27; 95% CI, 1.15-1.40) and low birth weight (odds ratio, 1.12; 95% CI, 1.00-1.26) remained independently associated with ASCVD. All findings were materially unchanged by additional adjustment for parity, body mass index, and socioeconomic factors.
Conclusions and relevance
In this large multiethnic cohort of women, hypertensive disorders of pregnancy and low birth weight were independently associated with ASCVD after adjustment for risk factors and other APOs.



JAMA Cardiol: 15 Sep 2020; epub ahead of print
Søndergaard MM, Hlatky MA, Stefanick ML, Vittinghoff E, ... Manson JE, Parikh NI
JAMA Cardiol: 15 Sep 2020; epub ahead of print | PMID: 32936228
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Impact:
Abstract

Long-term Results of Differentiated Anatomic Reconstruction of Bicuspid Aortic Valves.

Schneider U, Hofmann C, Schöpe J, Niewald AK, ... Karliova I, Schäfers HJ
Importance
Bicuspid aortic valve (BAV) repair has been used in limited cohorts, but its long-term results in a large population are unknown.
Objectives
To analyze the long-term stability of BAV repair for survival and the factors associated with repair failure and to evaluate whether a differentiated anatomic repair approach may improve repair stability.
Design, setting, and participants
In this case series, 1024 patients underwent BAV repair for aortic regurgitation or aneurysm between October 1995 and June 2018, with a mean (SD) follow-up time of 56 (49) months and maximum follow-up of 271 months. Systematic modifications in technique based on anatomic principles were introduced in 2009 and applied for the last 727 patients. Data were acquired prospectively and analyzed retrospectively.
Exposures
Repair of BAV with or without concomitant aortic replacement, as well as postoperative clinical and echocardiographic follow-up.
Main outcomes and measures
Survival and incidence of reoperation or recurrent aortic regurgitation, as well as factors associated with valve repair failure.
Results
Among the 1024 patients in the study (920 male [89.8%]; mean [SD] age, 47 [13] years [range, 15-86 years]), the survival rate at 15 years was 82.1%. The cumulative incidence of reoperation was 30.7% (95% CI, 22.7%-38.7%) at 15 years. Cusp calcification (subdistribution hazard ratio, 1.78; 95% CI, 1.14-2.77; P = .01), asymmetric commissural orientation (subdistribution hazard ratio, 1.95; 95% CI, 1.02-3.72; P = .04), and use of a pericardial patch for cusp repair (subdistribution hazard ratio, 5.25; 95% CI, 3.52-7.82; P < .001) were associated with time to reoperation. At 10 years, the incidence of reoperation was significantly reduced among patients who received the anatomic repair concept compared with those who had undergone surgery in the earlier period (8.8% vs 24.6%; P < .001).
Conclusions and relevance
This study suggests that survival after BAV repair is excellent and that a large proportion of BAV repairs will remain stable. Repair stability can be markedly improved by an anatomic repair concept. Cusp calcification and the need for cusp repair using a patch remain the factors most strongly associated with valve failure. In those instances, valve replacement should be preferred.



JAMA Cardiol: 15 Sep 2020; epub ahead of print
Schneider U, Hofmann C, Schöpe J, Niewald AK, ... Karliova I, Schäfers HJ
JAMA Cardiol: 15 Sep 2020; epub ahead of print | PMID: 32936224
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Impact:
Abstract

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data From 12 Studies.

Mishra SR, Chung HF, Waller M, Dobson AJ, ... Weiderpass E, Mishra GD
Importance
Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD.
Objective
To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause.
Design, setting, and participants
Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019.
Exposures
Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older.
Main outcomes and measures
First nonfatal CVD event, including coronary heart disease and stroke events.
Results
A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years.
Conclusions and relevance
Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.



JAMA Cardiol: 15 Sep 2020; epub ahead of print
Mishra SR, Chung HF, Waller M, Dobson AJ, ... Weiderpass E, Mishra GD
JAMA Cardiol: 15 Sep 2020; epub ahead of print | PMID: 32936210
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Impact:
Abstract

Remote Optimization of Guideline-Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction.

Desai AS, Maclean T, Blood AJ, Bosque-Hamilton J, ... Scirica B, MacRae CA
Importance
Optimal treatment of heart failure with reduced ejection fraction (HFrEF) is scripted by treatment guidelines, but many eligible patients do not receive guideline-directed medical therapy (GDMT) in clinical practice.
Objective
To determine whether a remote, algorithm-driven, navigator-administered medication optimization program could enhance implementation of GDMT in HFrEF.
Design, setting, and participants
In this case-control study, a population-based sample of patients with HFrEF was offered participation in a quality improvement program directed at GDMT optimization. Treating clinicians in a tertiary academic medical center who were caring for patients with heart failure and an ejection fraction of 40% or less (identified through an electronic health record-based search) were approached for permission to adjust medical therapy according to a sequential titration algorithm modeled on the current American College of Cardiology/American Heart Association heart failure guidelines. Navigators contacted participants by telephone to direct medication adjustment and conduct longitudinal surveillance of laboratory tests, blood pressure, and symptoms under supervision of a pharmacist, nurse practitioner, and heart failure cardiologist. Patients and clinicians declining to participate served as a control group.
Exposures
Navigator-led remote optimization of GDMT compared with usual care.
Main outcomes and measures
Proportion of patients receiving GDMT in the intervention and control groups at 3 months.
Results
Of 1028 eligible patients (mean [SD] values: age, 68 [14] years; ejection fraction, 32% [8%]; and systolic blood pressure, 122 [18] mm Hg; 305 women (30.0%); 892 individuals [86.8%] in New York Heart Association class I and II), 197 (19.2%) participated in the medication optimization program, and 831 (80.8%) continued with usual care as directed by their treating clinicians (585 [56.9%] general cardiologists; 443 [43.1%] heart failure specialists). At 3 months, patients participating in the remote intervention experienced significant increases from baseline in use of renin-angiotensin system antagonists (138 [70.1%] to 170 [86.3%]; P < .001) and β-blockers (152 [77.2%] to 181 [91.9%]; P < .001) but not mineralocorticoid receptor antagonists (51 [25.9%] to 60 [30.5%]; P = .14). Doses for each category of GDMT also increased from baseline in the intervention group. Among the usual-care group, there were no changes from baseline in the proportion of patients receiving GDMT or the dose of GDMT in any category.
Conclusions and relevance
Remote titration of GDMT by navigators using encoded algorithms may represent an efficient, population-level strategy for rapidly closing the gap between guidelines and clinical practice in patients with HFrEF.



JAMA Cardiol: 15 Sep 2020; epub ahead of print
Desai AS, Maclean T, Blood AJ, Bosque-Hamilton J, ... Scirica B, MacRae CA
JAMA Cardiol: 15 Sep 2020; epub ahead of print | PMID: 32936209
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Impact:
Abstract

Physiologic and Clinical Features of the Paralympic Athlete\'s Heart.

Pelliccia A, Quattrini FM, Cavarretta E, Squeo MR, ... Spataro A, Bernardi M
Importance
Paralympic medicine is a newly adopted term to describe the varied health care issues associated with athletes in the Paralympics. Scarce scientific data, however, are currently available describing the cardiac remodeling in Paralympic athletes.
Objective
To investigate the physiological and clinical characteristics of the Paralympic athlete\'s heart and derive the normative values.
Design, setting, and participants
This is a single-center study on a relatively large cohort of Paralympic athletes, conducted at the Italian Institute of Sport Medicine and Science. Paralympic athletes free of cardiac or systemic pathologic conditions other than their cause of disability were selected for participation in the Paralympic Games from January 2000 to June 2014. Athletes were arbitrarily classified for disability in 2 groups: those with spinal cord injuries (SCI) and those with non-SCI (NSCI). Data analysis occurred from March 2019 to June 2020.
Main outcomes and measures
The primary outcome was the difference in cardiac remodeling in Paralympic athletes according to disability type and sports discipline type. Athletes underwent cardiac evaluation, including 12-lead and exercise electrocardiograms, echocardiography, and cardiopulmonary exercise testing.
Results
Among 252 consecutive Paralympic athletes (median [interquartile range (IQR)] age, 34 [29-41] years; 188 men [74.6%]), 110 had SCI and 142 had NSCI. Those with SCI showed a higher prevalence of abnormal electrocardiogram findings than those with NSCI (13 of 110 [11.8%] vs 6 of 142 [4.2%]; P = .003), smaller left ventricular end-diastolic dimension (median [IQR], 48 [46-52] vs 51 [48-54] mm; P = .001) and left ventricular mass index (median [IQR], 80.6 [69-94] vs 91.3 [80-108] g/m2; P = .001), and lower peak oxygen uptake (VO2) (median [IQR], 27.1 [2-34] vs 38.5 [30-47] mL/min/kg; P = .001) in comparison with those with NSCI. Regarding sport discipline, endurance athletes had a larger left ventricular cavity (median [IQR], 52 [47-54] vs 49 [47-53] mm; P = .006) and higher peak VO2 (median [IQR], 46 [39-55] vs 30 [25-35] mL/min/kg; P = .001) than athletes in nonendurance sports.
Conclusions and relevance
Cardiac remodeling in Paralympic athletes differed by disability and sport discipline. Having NSCI lesions and engaging in endurance sports were associated with the largest left ventricular cavity and left ventricular mass and highest VO2 peak. Having SCI lesions and engaging in nonendurance disciplines, on the contrary, were associated with the smallest left ventricular cavity and mass and lowest VO2 peak.



JAMA Cardiol: 22 Sep 2020; epub ahead of print
Pelliccia A, Quattrini FM, Cavarretta E, Squeo MR, ... Spataro A, Bernardi M
JAMA Cardiol: 22 Sep 2020; epub ahead of print | PMID: 32965484
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Impact:
Abstract

Effect of Clopidogrel and Aspirin vs Aspirin Alone on Migraine Headaches After Transcatheter Atrial Septal Defect Closure: One-Year Results of the CANOA Randomized Clinical Trial.

Wintzer-Wehekind J, Horlick E, Ibrahim R, Cheema AN, ... Houde C, Rodés-Cabau J
Importance
Adding clopidogrel to aspirin for 3 months after transcatheter atrial septal defect (ASD) closure results in a lower incidence of new-onset migraine attacks. However, the outcomes at 6- to 12-month follow-up (after clopidogrel cessation at 3 months) remain largely unknown.
Objective
To assess the incidence of migraine attacks at 6- and 12-month follow-up after transcatheter ASD closure.
Design, setting, and participants
This prespecified analysis of a randomized, double-blind clinical trial included patients with no prior history of migraine undergoing ASD closure from 6 university hospitals in Canada from December 2008 to November 2014. Patients were followed up at 3, 6, and 12 months, and a migraine headache questionnaire was administered at each time. Analysis began June 2019.
Interventions
Patients were randomized (1:1) to receive dual antiplatelet therapy (aspirin plus clopidogrel; n = 84) vs single antiplatelet therapy (aspirin plus placebo; n = 87) for 3 months following transcatheter ASD closure. After 3 months, only single antiplatelet therapy (aspirin) was pursued.
Main outcomes and measures
Incidence and severity of migraine attacks at 6- and 12-month follow-up.
Results
The mean (SD) age of the study population was 38 (12) years, with 106 women (62%). A total of 27 patients (15.8%) had new-onset migraine attacks within the 3 months following ASD closure (8 of 84 [9.5%] vs 19 of 87 [21.8%] in the initial clopidogrel and placebo groups, respectively; P = .03). After cessation of clopidogrel and aspirin monotherapy, the percentage of patients with migraine attacks decreased over time, with 8 (4.7%) and 4 patients (2.3%) continuing to have migraine attacks at 6 and 12 months, respectively (vs 3 months: P < .001). The severity of migraine attacks progressively decreased over time; no moderate or severe attacks occurred at 6 and 12 months (vs 3 months: P < .001). There were no differences between groups in the rate of migraine attacks at 6 months (initial clopidogrel group: 2 of 84 [2.4%]; initial placebo group: 6 of 87 [6.9%]; P = .28) and 12 months (initial clopidogrel group: 3 of 84 [3.6%]; initial placebo group: 1 of 87 [1.1%]; P = .36) after ASD closure. Only 2 patients (1.2%; 1 patient per group) presented with new-onset migraine attacks after 3 months.
Conclusions and relevance
New-onset migraine attacks after ASD closure improved or resolved spontaneously within 6 to 12 months in most patients. No significant rebound effect was observed after clopidogrel cessation at 3 months. These results demonstrate a low rate of migraine events beyond 3 months following transcatheter ASD closure and support the early discontinuation of clopidogrel therapy if administered.
Trial registration
ClinicalTrials.gov Identifier: NCT00799045.



JAMA Cardiol: 22 Sep 2020; epub ahead of print
Wintzer-Wehekind J, Horlick E, Ibrahim R, Cheema AN, ... Houde C, Rodés-Cabau J
JAMA Cardiol: 22 Sep 2020; epub ahead of print | PMID: 32965476
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Impact:
Abstract

Outcomes of Percutaneous Trans-Right Atrial Access to the Left Ventricle for Catheter Ablation of Ventricular Tachycardia in Patients With Mechanical Aortic and Mitral Valves.

Santangeli P, Hyman MC, Muser D, Callans DJ, Shivkumar K, Marchlinski FE
Importance
In patients with mechanical valves in the aortic and mitral positions, percutaneous access to the left ventricle (LV) via a transfemoral approach for catheter ablation of ventricular tachycardia (VT) has been considered infeasible.
Objective
To describe the outcomes of a novel percutaneous trans-right atrial (RA) access to the LV via a femoral venous approach for catheter ablation of VT in patients with mechanical aortic and mitral valves.
Design, setting, and participants
This observational study included consecutive patients with mechanical valves in the aortic and mitral positions and recurrent monomorphic drug-refractory VT associated with an LV substrate. Percutaneous LV access was performed from a transfemoral venous route with the aid of a deflectable sheath and a radiofrequency wire by creating an iatrogenic Gerbode defect with direct puncture of the inferior and medial aspect of the RA, adjacent to the inferior-septal process of the LV (ISP-LV), under intracardiac echography guidance. Once the wire crossed to the LV, balloon dilatation of the ventriculotomy site (with a noncompliant balloon; diameter, 8 to 10 mm) was performed to facilitate passage of the sheath within the LV.
Exposures
Percutaneous trans-RA access to the LV via puncture of the ISP-LV to perform catheter ablation of VT in patients with mechanical aortic and mitral valves.
Main outcomes and measures
Feasibility and safety of a trans-RA access to the LV for catheter ablation of VT.
Results
A total of 4 patients (mean [SD] age, 60 [7] years; mean [SD] LV ejection fraction, 31% [9%]) with recurrent VT associated with an LV substrate (ischemic cardiomyopathy, 3 patients; nonischemic cardiomyopathy, 1 patient) and mechanical valves in the aortic and mitral position underwent trans-RA access through the ISP-LV for catheter ablation of VT. The time to obtain LV access ranged from 60 minutes (first case) to 22 minutes (last case) (mean [SD], 36 [15] minutes). No complications associated with the access occurred. In particular, in the 3 patients with preserved atrioventricular conduction at baseline, no new conduction abnormalities were observed after the access. Complete VT noninducibility at programmed ventricular stimulation was achieved in 3 cases, and no patient had VT recurrence at a median follow-up of 14 months (range, 6-21 months).
Conclusions and relevance
A percutaneous trans-RA access to the LV via a femoral venous approach for catheter ablation of VT in patients with mechanical aortic and mitral valves is feasible and appears safe. This novel technique may allow for catheter ablation of VT in a population of patients in whom conventional LV access via retrograde aortic or atrial transseptal routes is not possible.



JAMA Cardiol: 29 Sep 2020; epub ahead of print
Santangeli P, Hyman MC, Muser D, Callans DJ, Shivkumar K, Marchlinski FE
JAMA Cardiol: 29 Sep 2020; epub ahead of print | PMID: 32997112
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Impact:
Abstract

Frequency and Outcomes of Preoperative Stress Testing in Total Hip and Knee Arthroplasty from 2004 to 2017.

Rubin DS, Hughey R, Gerlach RM, Ham SA, Ward RP, Nagele P
Importance
Cardiac stress testing is often performed prior to noncardiac surgery, although trends in use of preoperative stress testing and the effect of testing on cardiovascular outcomes are currently unknown.
Objective
To describe temporal trends and outcomes of preoperative cardiac stress testing from 2004 to 2017.
Design, setting, and participants
Cross-sectional study of patients undergoing elective total hip or total knee arthroplasty from 2004 to 2017. Trend analysis was conducted using Joinpoint and generalized estimating equation regression. The study searched IBM MarketScan Research Databases inpatient and outpatient health care claims for private insurers including supplemental Medicare coverage and included patients with a claim indicating an elective total hip or total knee arthroplasty from January 1, 2004, to December 31, 2017.
Exposures
Elective total hip or knee arthroplasty.
Main outcomes and measures
Trend in yearly frequency of preoperative cardiac stress testing.
Results
The study cohort consisted of 801 396 elective total hip (27.9%; n = 246 168 of 801 396) and total knee (72.1%; 555 228 of 801 396) arthroplasty procedures, with a median age of 62 years (interquartile range, 57-70 years) and 58.1% women (n = 465 545 of 801 396). The overall rate of stress testing during the study period was 10.4% (n = 83 307 of 801 396). The rate of stress tests increased 0.65% (95% CI, 0.09-1.21; P = .03) annually from quarter (Q) 1 of 2004 until Q2 of 2006. A joinpoint was identified at Q3 of 2006 (95% CI, 2005 Q4 to 2007 Q4) when preoperative stress test use decreased by -0.71% (95% CI, -0.79% to 0.63%; P < .001) annually. A second joinpoint was identified at the Q4 of 2013 (95% CI, 2011 Q3 to 2015 Q3), when the decline in stress testing rates slowed to -0.40% (95% CI, -0.57% to -0.24%; P < .001) annually. The overall rate of myocardial infarction and cardiac arrest was 0.24% (n = 1677 of 686 067). Rates of myocardial infraction and cardiac arrest were not different in patients with at least 1 Revised Cardiac Risk Index condition who received a preoperative stress test and those who did not (0.60%; n = 221 of 36 554 vs 0.57%; n = 694 of 122 466; P = .51).
Conclusions and relevance
The frequency of preoperative stress testing declined annually from 2006 through 2017. Among patients with at least 1 Revised Cardiac Risk Index condition, no difference was observed in cardiovascular outcomes between patients who did and did not undergo preoperative testing.



JAMA Cardiol: 29 Sep 2020; epub ahead of print
Rubin DS, Hughey R, Gerlach RM, Ham SA, Ward RP, Nagele P
JAMA Cardiol: 29 Sep 2020; epub ahead of print | PMID: 32997100
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Abstract

Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease: A Subanalysis of the COMPASS Randomized Clinical Trial.

Kaplovitch E, Eikelboom JW, Dyal L, Aboyans V, ... Yusuf S, Anand SS
Importance
Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban and aspirin.
Objective
To quantify the risk of major vascular events and investigate the response to treatment with low-dose rivaroxaban and aspirin among patients with symptomatic LE-PAD based on clinical presentation and comorbidities.
Design, setting, and participants
This is a subanalysis of a previously reported subgroup of patients with symptomatic LE-PAD who were enrolled in a large, double-blind, placebo-controlled randomized clinical trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]) in 602 centers in 33 countries from March 2013 to January 2020. Data analysis was completed from May 2016 to June 2020.
Interventions
A combination of low-dose rivaroxaban and aspirin compared with aspirin alone.
Main outcomes and measures
Thirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding.
Results
The COMPASS trial enrolled 4129 patients with symptomatic LE-PAD (mean [SD] age, 66.8 [8.8] years; 2932 men [71.0%]). The 30-month Kaplan-Meier incidence risk of MACE or MALE, including major amputation, was 22.6% in those with prior amputation (this outcome was observed in 54 patients), 17.6% (n = 15) in those with Fontaine III or IV symptoms, and 11.8% (n = 142) in those with previous peripheral artery revascularization, classifying these features as high-risk limb presentations. The 30-month incidence risk of MACE or MALE, including major amputation, was 14.1% (n = 118) in those with kidney dysfunction, 13.5% (n = 67) in those with heart failure, 13.4% (n = 199) in those with diabetes, and 12.8% (n = 222) in those with polyvascular disease, classifying these features as high-risk comorbidities. Among patients with either high-risk limb presentations or high-risk comorbidities, treatment with rivaroxaban and aspirin compared with aspirin alone was associated with an estimated 4.2% (95% CI, 1.9%-6.2%) absolute risk reduction for MACE or MALE, including major amputation, at 30 months. Although the estimated absolute risk increase of major bleeding was higher with rivaroxaban and aspirin in combination than aspirin alone (2.0% [95% CI, 0.5%-3.9%]) for patients with either high-risk limb presentation or high-risk comorbidity, the estimated absolute risk increase of fatal or critical organ bleeding was low in this high-risk group (0.4% [95% CI, 0.2%-1.8%]), such that the net clinical benefit was estimated to be 3.2% (95% CI, 0.6%-5.3%).
Conclusions and relevance
Patients with LE-PAD with high-risk limb presentations or high-risk comorbidities had a high incidence of major vascular events. For these patients, treatment with rivaroxaban and aspirin in combination compared with aspirin alone led to a large absolute reduction in vascular risk.



JAMA Cardiol: 29 Sep 2020; epub ahead of print
Kaplovitch E, Eikelboom JW, Dyal L, Aboyans V, ... Yusuf S, Anand SS
JAMA Cardiol: 29 Sep 2020; epub ahead of print | PMID: 32997098
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Abstract

Five-Year Health Status After Self-expanding Transcatheter or Surgical Aortic Valve Replacement in High-risk Patients With Severe Aortic Stenosis.

Arnold SV, Chinnakondepalli KM, Magnuson EA, Reardon MJ, ... Cohen DJ,
Importance
In the CoreValve High-Risk Trial, patients with severe symptomatic aortic stenosis had similar clinical outcomes with transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR) over 5 years of follow-up, with mortality rates of more than 50% in both groups.
Objective
To describe the long-term health status of surviving patients randomized to self-expanding TAVR vs SAVR.
Design, setting, and participants
This randomized clinical trial included patients at high surgical risk with severe aortic stenosis who completed a baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) and were randomized to either self-expanding TAVR or SAVR from 45 US clinical sites. Patients were enrolled from February 2011 to September 2012. Analysis began May 2018 and ended June 2020.
Main outcomes and measures
Change in KCCQ and the 12-Item Short-Form Health Survey over 5 years, as assessed by repeated-measures analysis of covariance. Because there were significant interactions between access site and treatment for 1-month health status outcomes, all analyses were stratified by access site (iliofemoral or noniliofemoral).
Results
Of 713 patients, 377 (53%) were men, and the mean (SD) age was 83 (7) years. Prior to treatment, the mean (SD) KCCQ overall summary score (range, 0-100; higher score indicated better health status) was 47 (23), indicating substantial health status impairment. Among surviving patients, the KCCQ overall summary score increased significantly in both groups with greater early benefit with iliofemoral TAVR than SAVR (1-month difference, 16.8 points; 95% CI, 12.4-21.2). However, this early treatment difference between TAVR and SAVR was no longer apparent by 6 months, and there was no significant difference in health status between groups thereafter. At 5 years, 44% (134 of 305) of patients who underwent iliofemoral TAVR and 39% (105 of 266) who underwent SAVR were alive in this high-risk elderly cohort. Among surviving patients for whom health status data were available, 61% (48 of 79) in the TAVR group and 65% (46 of 71) in the SAVR group had KCCQ overall summary score more than 60 (P = .61). In the noniliofemoral cohort, there were no significant health status differences at any time between TAVR and SAVR. Results were similar for individual KCCQ domains and the Short-Form Health Survey.
Conclusions and relevance
In high-risk patients with severe symptomatic aortic stenosis, there was an early health status benefit with self-expanding iliofemoral TAVR vs SAVR but no difference between groups in long-term health status. Although mortality at 5 years was high in this population, the majority of surviving patients continued to report reasonable health status.
Trial registration
ClinicalTrials.gov Identifier: NCT01240902.



JAMA Cardiol: 29 Sep 2020; epub ahead of print
Arnold SV, Chinnakondepalli KM, Magnuson EA, Reardon MJ, ... Cohen DJ,
JAMA Cardiol: 29 Sep 2020; epub ahead of print | PMID: 32997095
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Abstract

Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease.

Trinder M, Uddin MM, Finneran P, Aragam KG, Natarajan P
Importance
Lipoprotein(a) is a highly heritable biomarker independently associated with atherosclerotic cardiovascular disease (ASCVD). It is unclear whether measured lipoprotein(a) or genetic factors associated with lipoprotein(a) can provide comparable or additional prognostic information for primary prevention.
Objective
To determine whether a genetic risk score (GRS) comprising 43 variants at the LPA gene, which encodes apolipoprotein(a), has clinical utility in assessing ASCVD risk compared with and in addition to lipoprotein(a) measurement.
Design, setting, and participants
The UK Biobank is a prospective observational study of approximately 500 000 volunteers aged 40 to 69 years who were recruited from 22 sites across the United Kingdom between 2006 and 2010. Using externally derived weights, an LPA GRS was calculated for 374 099 unrelated individuals with array-derived genotypes and lipoprotein(a) measures. Data were analyzed from April 2020 to March 2020.
Exposures
Measured lipoprotein(a) and LPA GRS.
Main outcomes and measures
We estimated the associations between measured lipoprotein(a) and LPA GRS with the incidence of ASCVD (peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality) using Cox proportional hazards models. To determine the utility of using measured lipoprotein(a) and LPA GRS as risk enhancers for ASCVD, we assessed the potential improvement in ASCVD risk discrimination by QRISK3 and Pooled Cohort Equations among individuals with borderline to intermediate risk (n = 113 703 and 144 350, respectively).
Results
The mean age of the overall study population was 57.6 years, and 204 355 individuals were female (54.6%). During a median follow-up of 11.1 years (interquartile range, 1.4 years), 15 444 individuals developed an incident ASCVD event (5.1%). The LPA GRS explained approximately 60% of the variation in measured lipoprotein(a) for White/European individuals. Independently, both lipoprotein(a) and LPA GRS were associated with incident, composite ASCVD (hazard ratio per 120 nmol/L increase, 1.26; 95% CI, 1.23-1.28 vs hazard ratio, 1.29; 95% CI, 1.26-1.33; P < .001). The association between LPA GRS and ASCVD was substantially attenuated after adjusting for measured lipoprotein(a). Adding measured lipoprotein(a) or LPA GRS to QRISK3 provided modest improvements to the risk discrimination of incident ASCVD events (area under the receiver operating curve, 0.640; 95% CI, 0.633-0.647 vs 0.642; 95% CI, 0.635-0.649 for both; P = .005 and P = .01, respectively).
Conclusions and relevance
When indicated, cardiovascular risk assessment with lipoprotein(a) at middle-age may include direct measurement or an LPA GRS.



JAMA Cardiol: 05 Oct 2020; epub ahead of print
Trinder M, Uddin MM, Finneran P, Aragam KG, Natarajan P
JAMA Cardiol: 05 Oct 2020; epub ahead of print | PMID: 33021622
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Abstract

Effect of Passive Choice and Active Choice Interventions in the Electronic Health Record to Cardiologists on Statin Prescribing: A Cluster Randomized Clinical Trial.

Adusumalli S, Westover JE, Jacoby DS, Small DS, ... Asch DA, Patel MS
Importance
Statin therapy is underused for many patients who could benefit.
Objective
To evaluate the effect of passive choice and active choice interventions in the electronic health record (EHR) to promote guideline-directed statin therapy.
Design, setting, and participants
Three-arm randomized clinical trial with a 6-month preintervention period and 6-month intervention. Randomization conducted at the cardiologist level at 16 cardiology practices in Pennsylvania and New Jersey. The study included 82 cardiologists and 11 693 patients. Data were analyzed between May 8, 2019, and January 9, 2020.
Interventions
In passive choice, cardiologists had to manually access an alert embedded in the EHR to select options to initiate or increase statin therapy. In active choice, an interruptive EHR alert prompted the cardiologist to accept or decline guideline-directed statin therapy. Cardiologists in the control group were informed of the trial but received no other interventions.
Main outcomes and measures
Primary outcome was statin therapy at optimal dose based on clinical guidelines. Secondary outcome was statin therapy at any dose.
Results
The sample comprised 11 693 patients with a mean (SD) age of 63.8 (9.1) years; 58% were male (n = 6749 of 11 693), 66% were White (n = 7683 of 11 693), and 24% were Black (n = 2824 of 11 693). The mean (SD) 10-year atherosclerotic cardiovascular disease (ASCVD) risk score was 15.4 (10.0); 68% had an ASVCD clinical diagnosis. Baseline statin prescribing rates at the optimal dose were 40.3% in the control arm, 39.1% in the passive choice arm, and 41.2% in the active choice arm. In adjusted analyses, the change in statin prescribing rates at optimal dose over time was not significantly different from control for passive choice (adjusted difference in percentage points, 0.2; 95% CI, -2.9 to 2.8; P = .86) or active choice (adjusted difference in percentage points, 2.4; 95% CI, -0.6 to 5.0; P = .08). In adjusted analyses of the subset of patients with clinical ASCVD, the active choice intervention resulted in a significant increase in statin prescribing at optimal dose relative to control (adjusted difference in percentage points, 3.8; 95% CI, 1.0-6.4; P = .008). No other subset analyses were significant. There were no significant changes in statin prescribing at any dose for either intervention.
Conclusions and relevance
The passive choice and active choice interventions did not change statin prescribing. In the subgroup of patients with clinical ASCVD, the active choice intervention led to a small increase in statin prescribing at the optimal dose, which could inform the design or targeting of future interventions.
Trial registration
ClinicalTrials.gov Identifier: NCT03271931.



JAMA Cardiol: 06 Oct 2020; epub ahead of print
Adusumalli S, Westover JE, Jacoby DS, Small DS, ... Asch DA, Patel MS
JAMA Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33031534
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Impact:
Abstract

Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: A Meta-analysis.

McGuire DK, Shih WJ, Cosentino F, Charbonnel B, ... Masiukiewicz U, Cannon CP
Importance
Sodium-glucose cotransporter 2 (SGLT2) inhibitors favorably affect cardiovascular (CV) and kidney outcomes; however, the consistency of outcomes across the class remains uncertain.
Objective
To perform meta-analyses that assess the CV and kidney outcomes of all 4 available SGLT2 inhibitors in patients with type 2 diabetes.
Data sources
A systematic literature search was conducted in PubMed from January 1, 2015, to January 31, 2020.
Study selection
One hundred forty-five records were initially identified; 137 were excluded because of study design or topic of interest. As a result, a total of 6 randomized, placebo-controlled CV and kidney outcomes trials of SGLT2 inhibitors in patients with type 2 diabetes were identified, with contributory data from 9 publications. All analyses were conducted on the total patient population of these trials.
Data extraction and synthesis
Standardized data search and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. Data were analyzed using a fixed-effect model.
Main outcomes and measures
Outcomes included time to the first event of (1) the composite of major adverse CV events of myocardial infarction, stroke, or CV death, and each component, (2) the composite of hospitalization for heart failure (HHF) or CV death (HHF/CV death) and each component, and (3) kidney composite outcomes. For outcomes in the overall trial populations and in selected subgroups, hazard ratios (HRs) and 95% CIs were pooled and meta-analyzed across trials.
Results
Data from 6 trials comprised 46 969 unique patients with type 2 diabetes, including 31 116 (66.2%) with atherosclerotic CV disease. The mean (SD) age of all trial participants was 63.7 (7.9) years; 30 939 (65.9%) were men, and 36 849 (78.5%) were White. The median number of participants per trial was 8246 (range, 4401-17 160). Overall, SGLT2 inhibitors were associated with a reduced risk of major adverse CV events (HR, 0.90; 95% CI, 0.85-0.95; Q statistic, P = .27), HHF/CV death (HR, 0.78; 95% CI, 0.73-0.84; Q statistic, P = .09), and kidney outcomes (HR, 0.62; 95% CI, 0.56-0.70; Q statistic, P = .09), with no significant heterogeneity of associations with outcome. Associated risk reduction for HHF was consistent across the trials (HR, 0.68; 95% CI, 0.61-0.76; I2 = 0.0%), whereas significant heterogeneity of associations with outcome was observed for CV death (HR, 0.85; 95% CI, 0.78-0.93; Q statistic, P = .02; I2 = 64.3%). The presence or absence of atherosclerotic CV disease did not modify the association with outcomes for major adverse CV events (HR, 0.89; 95% CI, 0.84-0.95 and HR, 0.94; 95% CI, 0.83-1.07, respectively; P = .63 for interaction), with similar absence of associations with outcome modification by prevalent atherosclerotic CV disease for HHF/CV death (P = .62 for interaction), HHF (P = .26 for interaction), or kidney outcomes (P = .73 for interaction).
Conclusions and relevance
In this meta-analysis, SGLT2 inhibitors were associated with a reduced risk of major adverse CV events; in addition, results suggest significant heterogeneity in associations with CV death. The largest benefit across the class was for an associated reduction in risk for HHF and kidney outcomes, with benefits for HHF risk being the most consistent observation across the trials.



JAMA Cardiol: 06 Oct 2020; epub ahead of print
McGuire DK, Shih WJ, Cosentino F, Charbonnel B, ... Masiukiewicz U, Cannon CP
JAMA Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33031522
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Abstract

Transcatheter Aortic Valve Replacement in Low-risk Patients With Bicuspid Aortic Valve Stenosis.

Forrest JK, Ramlawi B, Deeb GM, Zahr F, ... Popma JJ, Reardon MJ
Importance
The outcomes of transcatheter aortic valve replacement (TAVR) in low-risk patients with bicuspid aortic valve stenosis have not been studied in a large scale, multicentered, prospective fashion.
Objective
To evaluate the procedural safety, efficacy, and 30-day outcomes of TAVR in patients with bicuspid aortic stenosis at low surgical risk.
Design, setting, and participants
The Low Risk Bicuspid Study is a prospective, single-arm trial study with inclusion/exclusion criteria developed from the Evolut Low Risk Randomized Trial. Follow-up is planned for 10 years. Patients underwent TAVR at 25 centers in the United States who were also participating in the Evolut Low Risk Randomized Trial from December 2018 to October 2019. Eligible patients had severe bicuspid aortic valve stenosis and met American Heart Association/American College of Cardiology guideline indications for aortic valve replacement.
Interventions
Patients underwent attempted implant of an Evolut or Evolut PRO transcatheter aortic valve, with valve size based on annular measurements.
Main outcomes and measures
The prespecified primary end point was the incidence of all-cause mortality or disabling stroke at 30 days. The prespecified primary efficacy end point was device success defined as the absence of procedural mortality, the correct position of 1 bioprosthetic heart valve in the proper anatomical location, and the absence of more than mild aortic regurgitation postprocedure.
Results
A total of 150 patients underwent an attempted implant. Baseline characteristics include mean age of 70.3 (5.5) years, 48.0% female (n = 72), and a mean Society of Thoracic Surgeons score of 1.4 (0.6%). Most patients (136; 90.7%) had Sievers type I valve morphology. The incidence of all-cause mortality or disabling stroke was 1.3% (95% CI, 0.3%-5.3%) at 30 days. The device success rate was 95.3% (95% CI, 90.5%-98.1%). At 30 days, the mean (SD) AV gradient was 7.6 (3.7) mm Hg and effective orifice area was 2.3 (0.7) cm2. A new permanent pacemaker was implanted in 22 patients (15.1%). No patients had greater than mild paravalvular leak.
Conclusions and relevance
Transcatheter aortic valve replacement in low-surgical risk patients with bicuspid aortic valve stenosis achieved favorable 30-day results, with low rates of death and stroke and high device success rate.
Trial registration
ClinicalTrials.gov Identifier: NCT03635424.



JAMA Cardiol: 06 Oct 2020; epub ahead of print
Forrest JK, Ramlawi B, Deeb GM, Zahr F, ... Popma JJ, Reardon MJ
JAMA Cardiol: 06 Oct 2020; epub ahead of print | PMID: 33031491
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Abstract

Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection.

Braverman AC, Mittauer E, Harris KM, Evangelista A, ... Isselbacher E, Eagle K
Importance
Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs.
Objective
To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection.
Design, setting, and participants
A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018.
Main outcomes and measures
Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery.
Results
A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization.
Conclusions and relevance
Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.



JAMA Cardiol: 13 Oct 2020; epub ahead of print
Braverman AC, Mittauer E, Harris KM, Evangelista A, ... Isselbacher E, Eagle K
JAMA Cardiol: 13 Oct 2020; epub ahead of print | PMID: 33052376
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Impact:
Abstract

Misclassification of Hospital Performance Under the Hospital Readmissions Reduction Program: Implications for Value-Based Programs.

Shen C, Wadhera RK, Yeh RW
Importance
The Centers for Medicare and Medicaid Services (CMS) use point estimates of 30-day risk-standardized readmission rates (RSRRs) to compare hospitals under the Hospital Readmissions Reduction Program (HRRP). An important characteristic of this measure is that it is a point estimate with a margin of error, which may affect the CMS\'s ability to accurately evaluate and distinguish hospital performance in the program.
Objective
To determine the number and percentage of hospitals with a penalty status misclassified under the HRRP.
Design, setting, and participants
This cross-sectional study used the bayesian deconvolution method to estimate the rate of penalty status misclassification for hospitals participating in the HRRP in fiscal year 2019, using data from the CMS Hospital Compare website that were collected between July 1, 2014, and June 30, 2017. Beneficiaries of Medicare fee-for-service coverage who were 65 years or older and hospitalized with acute myocardial infarction, heart failure, or pneumonia in hospitals with 25 or more discharges per condition were included in the data set. Data analysis occurred from November 2019 to July 2020.
Exposures
None.
Main outcomes and measures
The rate of penalty status misclassification for acute myocardial infarction, heart failure, or pneumonia under the HRRP.
Results
The study included 1633, 2626, and 2705 hospitals for acute myocardial infarction, heart failure, and pneumonia, respectively, that participated in the HRRP in fiscal year 2019. The percentages of hospitals that should have been penalized, but were not, were 20.9% (95% CI, 16.0%-25.8%) for acute myocardial infarction, 13.5% (95% CI, 9.8%-17.2%) for heart failure, and 13.2% (95% CI, 10.3%-16.1%) for pneumonia. In contrast, the percentages of hospitals that were incorrectly penalized by the HRRP were 10.1% (95% CI, 5.8%-14.4%) for acute myocardial infarction, 10.9% (95% CI, 7.2%-14.6%) for heart failure, and 12.3% (95% CI, 9.9%-14.6%) for pneumonia.
Conclusions and relevance
The margin of error associated with the 30-day RSRRs resulted in the misclassification of condition-specific penalty status for up to 31% of hospitals. These findings suggest that the hospital-level 30-day RSRR measure may not reliably distinguish hospital performance in the HRRP. This has important implications for CMS value-based programs that use risk-standardized outcomes to evaluate and compare hospital performance.



JAMA Cardiol: 13 Oct 2020; epub ahead of print
Shen C, Wadhera RK, Yeh RW
JAMA Cardiol: 13 Oct 2020; epub ahead of print | PMID: 33052371
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Impact:
Abstract

Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease.

Morton SU, Shimamura A, Newburger PE, Opotowsky AR, ... Seidman JG, Seidman CE
Importance
Patients with congenital heart disease (CHD), the most common birth defect, have increased risks for cancer. Identification of the variables that contribute to cancer risk is essential for recognizing patients with CHD who warrant longitudinal surveillance and early interventions.
Objective
To compare the frequency of damaging variants in cancer risk genes among patients with CHD and control participants and identify associated clinical variables in patients with CHD who have cancer risk variants.
Design, setting, and participants
This multicenter case-control study included participants with CHD who had previously been recruited to the Pediatric Cardiac Genomics Consortium based on presence of structural cardiac anomaly without genetic diagnosis at the time of enrollment. Permission to use published sequencing data from unaffected adult participants was obtained from 2 parent studies. Data were collected for this study from December 2010 to April 2019.
Exposures
Presence of rare (allele frequency, <1 × 10-5) loss-of-function (LoF) variants in cancer risk genes.
Main outcomes and measures
Frequency of LoF variants in cancer risk genes (defined in the Catalogue of Somatic Mutations in Cancer-Cancer Gene Consensus database), were statistically assessed by binomial tests in patients with CHD and control participants.
Results
A total of 4443 individuals with CHD (mean [range] age, 13.0 [0-84] years; 2225 of 3771 with reported sex [59.0%] male) and 9808 control participants (mean [range] age, 52.1 [1-92] years; 4967 of 9808 [50.6%] male) were included. The frequency of LoF variants in regulatory cancer risk genes was significantly higher in patients with CHD than control participants (143 of 4443 [3.2%] vs 166 of 9808 [1.7%]; odds ratio [OR], 1.93 [95% CI, 1.54-2.42]; P = 1.38 × 10-12), and among CHD genes previously associated with cancer risk (58 of 4443 [1.3%] vs 18 of 9808 [0.18%]; OR, 7.2 [95% CI, 4.2-12.2]; P < 2.2 × 10-16). The LoF variants were also nominally increased in 14 constrained cancer risk genes with high expression in the developing heart. Seven of these genes (ARHGEF12, CTNNB1, LPP, MLLT4, PTEN, TCF12, and TFRC) harbored LoF variants in multiple patients with unexplained CHD. The highest rates for LoF variants in cancer risk genes occurred in patients with CHD and extracardiac anomalies (248 of 1482 individuals [16.7%]; control: 1099 of 9808 individuals [11.2%]; OR, 1.59 [95% CI, 1.37-1.85]; P = 1.3 × 10-10) and/or neurodevelopmental delay (209 of 1393 individuals [15.0%]; control: 1099 of 9808 individuals [11.2%]; OR, 1.40 [95% CI, 1.19-1.64]; P = 9.6 × 10-6).
Conclusions and relevance
Genotypes of CHD may account for increased cancer risks. In this cohort, damaging variants were prominent in the 216 genes that predominantly encode regulatory proteins. Consistent with their fundamental developmental functions, patients with CHD and damaging variants in these genes often had extracardiac manifestations. These data may also implicate cancer risk genes that are repeatedly varied in patients with unexplained CHD as CHD genes.



JAMA Cardiol: 20 Oct 2020; epub ahead of print
Morton SU, Shimamura A, Newburger PE, Opotowsky AR, ... Seidman JG, Seidman CE
JAMA Cardiol: 20 Oct 2020; epub ahead of print | PMID: 33084842
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Impact:
Abstract

Coronavirus Disease 2019 and the Athletic Heart: Emerging Perspectives on Pathology, Risks, and Return to Play.

Kim JH, Levine BD, Phelan D, Emery MS, ... Thompson PD, Baggish AL
Importance
Cardiac injury with attendant negative prognostic implications is common among patients hospitalized with coronavirus disease 2019 (COVID-19) infection. Whether cardiac injury, including myocarditis, also occurs with asymptomatic or mild-severity COVID-19 infection is uncertain. There is an ongoing concern about COVID-19-associated cardiac pathology among athletes because myocarditis is an important cause of sudden cardiac death during exercise.
Observations
Prior to relaxation of stay-at-home orders in the US, the American College of Cardiology\'s Sports and Exercise Cardiology Section endorsed empirical consensus recommendations advising a conservative return-to-play approach, including cardiac risk stratification, for athletes in competitive sports who have recovered from COVID-19. Emerging observational data coupled with widely publicized reports of athletes in competitive sports with reported COVID-19-associated cardiac pathology suggest that myocardial injury may occur in cases of COVID-19 that are asymptomatic and of mild severity. In the absence of definitive data, there is ongoing uncertainty about the optimal approach to cardiovascular risk stratification of athletes in competitive sports following COVID-19 infection.
Conclusions and relevance
This report was designed to address the most common questions regarding COVID-19 and cardiac pathology in athletes in competitive sports, including the extension of return-to-play considerations to discrete populations of athletes not addressed in prior recommendations. Multicenter registry data documenting cardiovascular outcomes among athletes in competitive sports who have recovered from COVID-19 are currently being collected to determine the prevalence, severity, and clinical relevance of COVID-19-associated cardiac pathology and efficacy of targeted cardiovascular risk stratification. While we await these critical data, early experiences in the clinical oversight of athletes following COVID-19 infection provide an opportunity to address key areas of uncertainty relevant to cardiology and sports medicine practitioners.



JAMA Cardiol: 25 Oct 2020; epub ahead of print
Kim JH, Levine BD, Phelan D, Emery MS, ... Thompson PD, Baggish AL
JAMA Cardiol: 25 Oct 2020; epub ahead of print | PMID: 33104154
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Impact:
Abstract

Evolving Trends in Adult Heart Transplant With the 2018 Heart Allocation Policy Change.

Kilic A, Mathier MA, Hickey GW, Sultan I, ... Mulukutla SR, Keebler ME
Importance
The US heart allocation policy was changed on October 18, 2018. The association of this change with recipient and donor selection and outcomes remains to be elucidated.
Objective
To evaluate changes in patient characteristics, wait list outcomes, and posttransplant outcomes after the recent allocation policy change in heart transplant.
Design, setting, and participants
In this cohort study, all 15 631 adults undergoing heart transplants, excluding multiorgan transplants, in the US as identified by the United Network for Organ Sharing multicenter, national registry were reviewed. Patients were stratified according to prepolicy change (October 1, 2015, to October 1, 2018) and postpolicy change (October 18, 2018 or after). Follow-up data were available through March 31, 2020.
Exposures
Heart transplants after the policy change.
Main outcomes and measures
Competing risk regression for wait list outcomes was performed. Posttransplant survival was compared using the Kaplan-Meier method, and risk adjustment was performed using multivariable Cox proportional hazards regression analysis.
Results
In this cohort study, of the 15 631 patients undergoing transplant, 10 671 (mean [SD] age, 53.1 [12.7] years; 7823 [73.3%] male) were wait listed before and 4960 (mean [SD] age, 52.7 [13.0] years; 3610 [72.8%] male) were wait listed after the policy change. Competing risk regression demonstrated reduced likelihood of mortality or deterioration (subhazard ratio [SHR], 0.60; 95% CI, 0.52-0.69; P < .001), increased likelihood of transplant (SHR, 1.38; 95% CI, 1.32-1.45; P < .001), and reduced likelihood of recovery (SHR, 0.54; 95% CI, 0.40-0.73; P < .001) for wait listed patients after the policy change. A total of 6078 patients underwent transplant before and 2801 after the policy change. Notable changes after the policy change included higher frequency of bridging with temporary mechanical circulatory support and lower frequency of bridging with durable left ventricular assist devices. Posttransplant survival was reduced after the policy change (1-year: 92.1% vs 87.5%; log-rank P < .001), a finding that persisted after risk adjustment (HR, 1.29; 95% CI, 1.07-1.55; P = .008).
Conclusions and relevance
Substantial changes have occurred in adult heart transplant in the US after the policy change in October 2018. Wait list outcomes have improved, although posttransplant survival has decreased. These data confirm findings from earlier preliminary analyses and demonstrate that these trends have persisted to 1-year follow-up, underscoring the importance of continued reevaluation of the new heart allocation policy.



JAMA Cardiol: 27 Oct 2020; epub ahead of print
Kilic A, Mathier MA, Hickey GW, Sultan I, ... Mulukutla SR, Keebler ME
JAMA Cardiol: 27 Oct 2020; epub ahead of print | PMID: 33112391
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Impact:
Abstract

Value of Coronary Artery Calcium Scanning in Association With the Net Benefit of Aspirin in Primary Prevention of Atherosclerotic Cardiovascular Disease.

Ajufo E, Ayers CR, Vigen R, Joshi PH, ... de Lemos JA, Khera A
Importance
Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear.
Objective
To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds.
Design, setting, and participants
Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020.
Exposures
Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher.
Main outcomes and measures
Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis-derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds.
Results
A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P < .001; HR, 5.3; 95% CI, 3.6-7.9; P < .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (<5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk.
Conclusions and relevance
Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.



JAMA Cardiol: 27 Oct 2020; epub ahead of print
Ajufo E, Ayers CR, Vigen R, Joshi PH, ... de Lemos JA, Khera A
JAMA Cardiol: 27 Oct 2020; epub ahead of print | PMID: 33112372
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Impact:
Abstract

Effectiveness of Home-Based Mobile Guided Cardiac Rehabilitation as Alternative Strategy for Nonparticipation in Clinic-Based Cardiac Rehabilitation Among Elderly Patients in Europe: A Randomized Clinical Trial.

Snoek JA, Prescott EI, van der Velde AE, Eijsvogels TMH, ... Van\'t Hof AWJ, de Kluiver EP
Importance
Although nonparticipation in cardiac rehabilitation is known to increase cardiovascular mortality and hospital readmissions, more than half of patients with coronary artery disease in Europe are not participating in cardiac rehabilitation.
Objective
To assess whether a 6-month guided mobile cardiac rehabilitation (MCR) program is an effective therapy for elderly patients who decline participation in cardiac rehabilitation.
Design, setting, and participants
Patients were enrolled in this parallel multicenter randomized clinical trial from November 11, 2015, to January 3, 2018, and follow-up was completed on January 17, 2019, in a secondary care system with 6 cardiac institutions across 5 European countries. Researchers assessing primary outcome were masked for group assignment. A total of 4236 patients were identified with a recent diagnosis of acute coronary syndrome, coronary revascularization, or surgical or percutaneous treatment for valvular disease, or documented coronary artery disease, of whom 996 declined to start cardiac rehabilitation. Subsequently, 179 patients who met the inclusion and exclusion criteria consented to participate in the European Study on Effectiveness and Sustainability of Current Cardiac Rehabilitation Programmes in the Elderly trial. Data were analyzed from January 21 to October 11, 2019.
Interventions
Six months of home-based cardiac rehabilitation with telemonitoring and coaching based on motivational interviewing was used to stimulate patients to reach exercise goals. Control patients did not receive any form of cardiac rehabilitation throughout the study period.
Main outcomes and measures
The primary outcome parameter was peak oxygen uptake (Vo2peak) after 6 months.
Results
Among 179 patients randomized (145 male [81%]; median age, 72 [range, 65-87] years), 159 (89%) were eligible for primary end point analysis. Follow-up at 1 year was completed for 151 patients (84%). Peak oxygen uptake improved in the MCR group (n = 89) at 6 and 12 months (1.6 [95% CI, 0.9-2.4] mL/kg-1/min-1 and 1.2 [95% CI, 0.4-2.0] mL/kg-1/min-1, respectively), whereas there was no improvement in the control group (n = 90) (+0.2 [95% CI, -0.4 to 0.8] mL/kg-1/min-1 and +0.1 [95% CI, -0.5 to 0.7] mL/kg-1/min-1, respectively). Changes in Vo2peak were greater in the MCR vs control groups at 6 months (+1.2 [95% CI, 0.2 to 2.1] mL/kg-1/min-1) and 12 months (+0.9 [95% CI, 0.05 to 1.8] mL/kg-1/min-1). The incidence of adverse events was low and did not differ between the MCR and control groups.
Conclusions and relevance
These results suggest that a 6-month home-based MCR program for patients 65 years or older with coronary artery disease or a valvular intervention was safe and beneficial in improving Vo2peak when compared with no cardiac rehabilitation.
Trial registration
trialregister.nl Identifier: NL5168.



JAMA Cardiol: 27 Oct 2020; epub ahead of print
Snoek JA, Prescott EI, van der Velde AE, Eijsvogels TMH, ... Van't Hof AWJ, de Kluiver EP
JAMA Cardiol: 27 Oct 2020; epub ahead of print | PMID: 33112363
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Impact:
Abstract

Estimated Prevalence of Masked Asleep Hypertension in US Adults.

Li S, Schwartz JE, Shimbo D, Muntner P, ... Bellows BK, Zhang Y
Importance
High blood pressure (BP) during sleep (asleep blood pressure) is associated with an increased risk of cardiovascular disease, but a national prevalence estimate of masked asleep hypertension (high BP while sleeping but without high BP measured in the clinic [clinic BP]) for the United States is lacking.
Objectives
To estimate the prevalence of masked asleep hypertension among US adults by using BP thresholds from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) and the 2017 American College of Cardiology-American Heart Association (ACC-AHA) BP guidelines.
Design, setting, and participants
This cohort analysis pooled data from 3000 participants in 4 US population-based studies that conducted 24-hour ambulatory BP monitoring (ABPM) and 17 969 participants in the 2011-2016 National Health and Nutrition Examination Survey (NHANES) without ABPM. Masked asleep hypertension status in NHANES was imputed using a 2-stage multiple imputation process. Data were collected from 2000 to 2016 and analyzed from March 4, 2019, to June 29, 2020.
Main outcomes and measures
High clinic BP was defined as clinic systolic BP (SBP)/diastolic BP (DBP) of at least 140/90 mm Hg using JNC7 and at least 130/80 mm Hg using 2017 ACC-AHA guidelines. High asleep BP was defined as mean asleep SBP/DBP of at least 120/70 mm Hg for JNC7 and at least 110/65 mm Hg for the 2017 ACC-AHA guidelines. Masked asleep hypertension was defined as high asleep BP without high clinic BP.
Results
For the 3000 pooled cohort participants, the mean (SD) age was 52.0 (12.0) years, and 62.6% were women. For the 17 969 NHANES participants, the mean (SD) age was 46.7 (17.5) years, and 51.8% (weighted) were women. The estimated prevalence of masked asleep hypertension among US adults was 18.8% (95% CI, 16.7%-20.8%; 44.4 million US adults) using the JNC7 guideline and 22.7% (95% CI, 20.6%-24.8%; 53.7 million US adults) using the 2017 ACC-AHA guideline criteria. The prevalence of masked asleep hypertension was higher among older adults (aged ≥65 years, 24.4% [95% CI, 20.7%-28.0%]), men (27.0% [95% CI, 24.1%-29.9%]), non-Hispanic Black individuals (28.7% [95% CI, 25.4%-32.0%]), those who were taking antihypertensives (24.4% [95% CI, 21.1%-27.8%]), those who had masked daytime hypertension (44.7% [95% CI, 40.1%-49.3%]), and those with diabetes (27.6% [95% CI, 23.5%-31.8%]), obesity (24.3% [95% CI, 21.8%-26.9%]), or chronic kidney disease (21.5% [95% CI, 17.3%-25.6%]) using the 2017 ACC-AHA guideline. An estimated 11.9% of US adults (28.2 million) had isolated masked asleep hypertension (masked asleep hypertension but without high awake BP) using JNC7 guideline criteria, as did an estimated 13.3% (31.5 million) using 2017 ACC-AHA guideline criteria.
Conclusions and relevance
These findings suggest that the prevalence of masked asleep hypertension is high among US adults. Data are needed on the cardiovascular risk reduction benefits of treating asleep hypertension.



JAMA Cardiol: 27 Oct 2020; epub ahead of print
Li S, Schwartz JE, Shimbo D, Muntner P, ... Bellows BK, Zhang Y
JAMA Cardiol: 27 Oct 2020; epub ahead of print | PMID: 33112362
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Impact:
Abstract

Association of Circulating Monocyte Chemoattractant Protein-1 Levels With Cardiovascular Mortality: A Meta-analysis of Population-Based Studies.

Georgakis MK, de Lemos JA, Ayers C, Wang B, ... Benjamin EJ, Dichgans M
Importance
Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored.
Objective
To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population.
Data sources and selection
Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points.
Data extraction and synthesis
Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses.
Main outcomes and measures
Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes).
Results
The meta-analysis included 7 cohort studies involving 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P = .01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P = .02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P < .001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein.
Conclusions and relevance
Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease.



JAMA Cardiol: 03 Nov 2020; epub ahead of print
Georgakis MK, de Lemos JA, Ayers C, Wang B, ... Benjamin EJ, Dichgans M
JAMA Cardiol: 03 Nov 2020; epub ahead of print | PMID: 33146689
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Impact:
Abstract

Temporal Changes and Institutional Variation in Use of Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease in the United States: An NCDR Research to Practice Project.

Secemsky EA, Butala N, Raja A, Khera R, ... Bhatt D, Yeh RW
Importance
After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI).
Objective
To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice.
Design, setting, and participants
This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a PCI to a nonculprit lesion within 45 days of the index procedure.
Exposures
Multivessel PCI, defined as placement of coronary stents in 2 or more major epicardial vessels or the staged placement of 1 or more coronary stents in a major epicardial vessel distinct from the index culprit vessel, within 45 days of the index PCI.
Main outcomes and measures
Outcomes included the proportional use of MV PCI among STEMI admissions with MV disease, and the timing of MV PCI (an index procedure, a staged procedure during index hospitalization, or a postdischarge procedure within 45 days).
Results
Among 359 879 admissions with STEMI and MV disease, MV PCI was performed in 38.5% (n = 138 380; mean [SD] age of patients, 62.3 [12.3] years; 102 266 men [73.9%]) within 45 days. Of those receiving MV PCIs, 30.8% (n = 42 629) had a procedure performed during the index procedure, 31.6% (n = 43 696) as a staged procedure during the index hospitalization, and 37.6% (n = 52 055) within 45 days of discharge. Complete revascularization of all diseased arteries was performed in 76.2% (n = 105 389). From the third quarter of 2009 to the second quarter of 2013, MV PCI use declined by 10%, from 42.7% (3230 of 7572 cases) to a nadir of 32.7% (3386 of 10 342 cases), followed by an increase to 44.0% (5062 of 11 497 cases) by the fourth quarter of 2017. During this time, there was a 13.6% decline in use of postdischarge staged MV PCI (from 23.4% of STEMI cases [1772 of 7572 cases] in the third quarter of 2009 to 9.9% [1094 of 11 171 cases] in the fourth quarter of 2014) and an 12.5% increase in MV PCI performed during the index admission (from 19.3% [1458 of 7572 cases] in the third quarter of 2009 to 31.8% [3557 of 11 171 cases] in the first quarter of 2018). Multivessel PCI use varied substantially across institutions, with a median use of 37.9% (interquartile range, 30.0%-46.5%).
Conclusions and relevance
In this large, nationwide analysis, MV PCI use for patients with STEMI has been increasing through early 2018 but was used in the minority of patients and with wide variability across US institutions. The adoption of new trial results into guidelines and practice may further promote the growth of MV PCI.



JAMA Cardiol: 03 Nov 2020; epub ahead of print
Secemsky EA, Butala N, Raja A, Khera R, ... Bhatt D, Yeh RW
JAMA Cardiol: 03 Nov 2020; epub ahead of print | PMID: 33146666
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Impact:
Abstract

Association of Subclinical Heart Maladaptation With the Pooled Cohort Equations to Prevent Heart Failure Risk Score for Incident Heart Failure.

Cauwenberghs N, Haddad F, Kuznetsova T
Importance
The Pooled Cohort Equations to Prevent Heart Failure (PCP-HF) estimate the 10-year risk for symptomatic heart failure (HF) from routine clinical data. The PCP-HF score should detect asymptomatic individuals with cardiac maladaptation preceding HF symptoms for it to be a useful HF prediction tool in primary prevention.
Objective
To assess the concordance between PCP-HF risk scoring and the presence of subclinical cardiac maladaptation in the community.
Design, setting, and participants
This cross-sectional analysis included participants enrolled in the Flemish Study on Environment, Genes and Health Outcomes who underwent a clinical examination including echocardiography between May 2005 and January 2015. Participants younger than 30 years, older than 79 years, had prevalent cardiovascular disease, and/or had suboptimal echocardiographic imaging quality were excluded. Analysis began February 2020 and ended April 2020.
Exposures
Ten-year HF risk as calculated from routine clinical data using the PCP-HF. Based on tertile limits, participants were categorized as having low (≤0.4%), intermediate (0.4%-2.4%), and high (≥2.4%) 10-year HF risk score.
Main outcomes and measures
Echocardiographic profiles of subclinical heart remodeling and dysfunction.
Results
A total of 1020 individuals were analyzed (mean [SD] age, 52.8 [11.4] years; 541 female [53.0%]). The prevalence of left ventricular (LV) remodeling and dysfunction was significantly higher from low to intermediate and high 10-year HF risk score. A doubling in 10-year HF risk score was associated with higher odds for LV concentric remodeling (odds ratio [OR], 1.48; 95% CI, 1.36-1.61; P < .001), LV hypertrophy (OR, 1.66; 95% CI, 1.51-1.83; P < .001), abnormal LV longitudinal strain (OR, 1.12; 95% CI, 1.05-1.19; P < .001), and LV diastolic dysfunction (OR, 2.28; 95% CI, 1.94-2.69; P < .001). Moreover, the PCP-HF score detected echocardiographic abnormalities with an accuracy of 74% (LV concentric remodeling), 78% (LV hypertrophy), 59% (abnormal LV longitudinal strain), and 87% (LV diastolic dysfunction). The likelihood of LV concentric remodeling, hypertrophy, and diastolic dysfunction were 3.1, 3.8, and 9.4 times higher in participants with high 10-year HF risk score than the average population risk, respectively (P < .001). Of all PCP-HF score components, age, body mass index, and systolic blood pressure were key correlates of echocardiographic abnormalities in multivariable-adjusted analysis.
Conclusions and relevance
PCP-HF risk scoring adequately detected individuals with subclinical heart maladaptation that precedes HF symptoms by years. Thus, it may be a valuable HF prediction tool in primary prevention.



JAMA Cardiol: 10 Nov 2020; epub ahead of print
Cauwenberghs N, Haddad F, Kuznetsova T
JAMA Cardiol: 10 Nov 2020; epub ahead of print | PMID: 33175083
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Impact:
Abstract

Outcomes for Out-of-Hospital Cardiac Arrest in the United States During the Coronavirus Disease 2019 Pandemic.

Chan PS, Girotra S, Tang Y, Al-Araji R, Nallamothu BK, McNally B
Importance
Recent reports from communities severely affected by the coronavirus disease 2019 (COVID-19) pandemic found lower rates of sustained return of spontaneous circulation (ROSC) for out-of-hospital cardiac arrest (OHCA). Whether the pandemic has affected OHCA outcomes more broadly is unknown.
Objective
To assess the association between the COVID-19 pandemic and OHCA outcomes, including in areas with low and moderate COVID-19 disease burden.
Design, setting, and participants
This study used a large US registry of OHCAs to compare outcomes during the pandemic period of March 16 through April 30, 2020, with those from March 16 through April 30, 2019. Cases were geocoded to US counties, and the COVID-19 mortality rate in each county was categorized as very low (0-25 per million residents), low (26-100 per million residents), moderate (101-250 per million residents), high (251-500 per million residents), or very high (>500 per million residents). As additional controls, the study compared OHCA outcomes during the prepandemic period (January through February) and peripandemic period (March 1 through 15).
Exposure
The COVID-19 pandemic.
Main outcomes and measures
Sustained ROSC (≥20 minutes), survival to discharge, and OHCA incidence.
Results
A total of 19 303 OHCAs occurred from March 16 through April 30 in both years, with 9863 cases in 2020 (mean [SD] age, 62.6 [19.3] years; 6040 men [61.3%]) and 9440 in 2019 (mean [SD] age, 62.2 [19.2] years; 5922 men [62.7%]). During the pandemic, rates of sustained ROSC were lower than in 2019 (23.0% vs 29.8%; adjusted rate ratio, 0.82 [95% CI, 0.78-0.87]; P < .001). Sustained ROSC rates were lower by between 21% (286 of 1429 [20.0%] in 2020 vs 305 of 1130 [27.0%] in 2019; adjusted RR, 0.79 [95% CI, 0.65-0.97]) and 33% (149 of 863 [17.3%] in 2020 vs 192 of 667 [28.8%] in 2019; adjusted RR, 0.67 [95% CI, 0.56-0.80]) in communities with high or very high COVID-19 mortality, respectively; however, rates of sustained ROSC were also lower by 11% (583 of 2317 [25.2%] in 2020 vs 740 of 2549 [29.0%] in 2019; adjusted RR, 0.89 [95% CI, 0.81-0.98]) to 15% (889 of 3495 [25.4%] in 2020 vs 1109 of 3532 [31.4%] in 2019; adjusted RR, 0.85 [95% CI, 0.78-0.93]) in communities with very low and low COVID-19 mortality. Among emergency medical services agencies with complete data on hospital survival (7085 total patients), survival to discharge was lower during the pandemic compared with 2019 (6.6% vs 9.8%; adjusted RR, 0.83 [95% CI, 0.69-1.00]; P = .048), primarily in communities with moderate to very high COVID-19 mortality (interaction P = .049). Incidence of OHCA was higher than in 2019, but the increase was largely observed in communities with high COVID-19 mortality (adjusted mean difference, 38.6 [95% CI, 37.1-40.1] per million residents) and very high COVID-19 mortality (adjusted mean difference, 28.7 [95% CI, 26.7-30.6] per million residents). In contrast, there was no difference in rates of sustained ROSC or survival to discharge during the prepandemic and peripandemic periods in 2020 vs 2019.
Conclusions and relevance
Early during the pandemic, rates of sustained ROSC for OHCA were lower throughout the US, even in communities with low COVID-19 mortality rates. Overall survival was lower, primarily in communities with moderate or high COVID-19 mortality.



JAMA Cardiol: 13 Nov 2020; epub ahead of print
Chan PS, Girotra S, Tang Y, Al-Araji R, Nallamothu BK, McNally B
JAMA Cardiol: 13 Nov 2020; epub ahead of print | PMID: 33188678
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Impact:
Abstract

Association of Baseline Low-Density Lipoprotein Cholesterol and Percentage Low-Density Lipoprotein Cholesterol Reduction With Statins, Ezetimibe, and PCSK9 Inhibition.

Marcusa DP, Giugliano RP, Park JG, de Lemos JA, Cannon CP, Sabatine MS
Importance
Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels.
Objective
To evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor.
Design, setting, and participants
This secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor-Thrombolysis in Myocardial Infarction 21 [A to Z-TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020.
Interventions
In A to Z-TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo.
Main outcomes and measures
The percentage LDL-C reduction at either 1 month (A to Z-TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model.
Results
A total of 3187 patients from A to Z-TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P < .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P < .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007).
Conclusions and relevance
The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C-lowering therapy even for patients with lower LDL-C levels.



JAMA Cardiol: 12 Nov 2020; epub ahead of print
Marcusa DP, Giugliano RP, Park JG, de Lemos JA, Cannon CP, Sabatine MS
JAMA Cardiol: 12 Nov 2020; epub ahead of print | PMID: 33185670
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Impact:
Abstract

Applicability of US Food and Drug Administration Labeling for Dapagliflozin to Patients With Heart Failure With Reduced Ejection Fraction in US Clinical Practice: The Get With the Guidelines-Heart Failure (GWTG-HF) Registry.

Vaduganathan M, Greene SJ, Zhang S, Grau-Sepulveda M, ... Yancy CW, Fonarow GC
Importance
In May 2020, dapagliflozin was approved by the US Food and Drug Administration (FDA) as the first sodium-glucose cotransporter 2 inhibitor for heart failure with reduced ejection fraction (HFrEF), based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial. Limited data are available characterizing the generalizability of dapagliflozin to US clinical practice.
Objective
To evaluate candidacy for initiation of dapagliflozin based on the FDA label among contemporary patients with HFrEF in the US.
Design, setting, and participants
This cohort study included 154 714 patients with HFrEF (left ventricular ejection fraction ≤40%) hospitalized at 406 sites in the Get With the Guidelines-Heart Failure (GWTG-HF) registry admitted between January 1, 2014, and September 30, 2019. Patients who left against medical advice, transferred to an acute care facility or to hospice, or had missing data were excluded. The FDA label (which excluded patients with an estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2, those undergoing dialysis, and those with type 1 diabetes) was applied to the GWTG-HF registry sample. Data analyses were conducted from April 1 to June 30, 2020.
Main outcomes and measures
The proportion of patients hospitalized with HFrEF who would be candidates for dapagliflozin under the FDA label.
Results
Among 154 714 patients hospitalized with HFrEF, 125 497 (81.1%; 83 481 men [66.5%]; mean [SD] age, 68 [15] years) would be candidates for dapagliflozin according to the FDA label. Across 355 sites with patients with 10 or more hospitalizations, the median proportion of candidates for dapagliflozin according to the FDA label was 81.1% (interquartile range, 77.8%-84.6%) at each site. This proportion was similar across all study years (interquartile range, 80.4%-81.7%) and was higher among those without type 2 diabetes than with type 2 diabetes (85.5% vs 75.6%). Among GWTG-HF participants, the most frequent reason for not meeting the FDA label criteria was eGFR less than 30 mL/min/1.73 m2 at discharge (18.5%). Among 75 654 patients with available paired admission and discharge data, 14.2% had an eGFR less than 30 mL/min/1.73 m2 at both time points, while 3.8% developed an eGFR less than 30 mL/min/1.73 m2 by discharge. Although there were more older adults, women, and Black patients in the GWTG-HF registry than in the DAPA-HF trial, most clinical characteristics were qualitatively similar between the 2 groups. Compared with the DAPA-HF trial cohort, there was lower use of evidence-based HF therapies among patients in GWTG-HF.
Conclusions and relevance
These data from a large, contemporary US registry of patients hospitalized with heart failure suggest that 4 of 5 patients with HFrEF (with or without type 2 diabetes) would be candidates for initiation of dapagliflozin, supporting its broad generalizability to US clinical practice.



JAMA Cardiol: 12 Nov 2020; epub ahead of print
Vaduganathan M, Greene SJ, Zhang S, Grau-Sepulveda M, ... Yancy CW, Fonarow GC
JAMA Cardiol: 12 Nov 2020; epub ahead of print | PMID: 33185662
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Impact:
Abstract

Association of Early-Life Trauma and Risk of Adverse Cardiovascular Outcomes in Young and Middle-aged Individuals With a History of Myocardial Infarction.

Almuwaqqat Z, Wittbrodt M, Young A, Lima BB, ... Quyyumi AA, Vaccarino V
Importance
Compared with older patients, young adults with a history of myocardial infarction (MI) tend to have a higher burden of psychosocial adversity. Exposure to early-life stressors may contribute to the risk of adverse outcomes in this patient population, potentially through inflammatory pathways.
Objective
To investigate the association of early-life trauma with adverse events and examine whether inflammation plays a role.
Design, setting, and participants
This cohort study included patients aged 18 to 60 years with a verified history of MI in the past 8 months from a university-affiliated hospital network. Baseline data were collected from June 2011 to March 2016, and follow-up data were obtained through July 2019. Analysis began September 2019.
Exposures
Early-life trauma was assessed using the Early Trauma Inventory-Self Report short form (ETI-SR-SF), both as a continuous and as a binary variable at the threshold of a score of 7 or higher. Inflammatory biomarkers, interleukin 6, and C-reactive protein were obtained at baseline.
Main outcomes and measures
A composite end point of recurrent MI, stroke, heart failure hospitalization, and cardiovascular death over a median 3-year follow-up.
Results
Of 300 patients, the mean (SD) age was 51 (7) years, 198 (66%) were African American, and 150 (50%) were women. Compared with participants with MI with an ETI-SR-SF score less than 7, those with a score of 7 or higher had higher levels of interleukin 6 and C-reactive protein at baseline. Compared with participants with an ETI-SR-SF score less than 7, those with a score of 7 or higher were at a greater risk for adverse outcomes, with a hazards ratio of 2.3 (95% CI, 1.3-3.9). Results remained consistent in multivariable analysis. Further adjustment for C-reactive protein rendered the results no longer statistically significant. Early-life trauma displayed a dose-dependent response when analyzed as a continuous variable and by quartiles.
Conclusions and relevance
Early-life trauma is an independent risk factor for adverse outcomes in young and middle-aged individuals with a history of MI. Neurobiological mechanisms leading to lifetime activation of systemic inflammatory cascades may be implicated.



JAMA Cardiol: 12 Nov 2020; epub ahead of print
Almuwaqqat Z, Wittbrodt M, Young A, Lima BB, ... Quyyumi AA, Vaccarino V
JAMA Cardiol: 12 Nov 2020; epub ahead of print | PMID: 33185652
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Impact:
Abstract

Association of Genetic West African Ancestry, Blood Pressure Response to Therapy, and Cardiovascular Risk Among Self-Reported Black Individuals in the Systolic Blood Pressure Reduction Intervention Trial (SPRINT).

Rao S, Segar MW, Bress AP, Arora P, ... de Lemos JA, Pandey A
Importance
Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined.
Objective
To determine the association between the proportion of West African ancestry with the response to antihypertensive medication, BP control, kidney function, and risk of adverse cardiovascular (CV) events among self-identified Black individuals in the Systolic Blood Pressure Intervention Trial (SPRINT).
Design, setting, and participants
This post hoc analysis of the SPRINT trial incorporated data from a multicenter study of self-identified Black participants with available West African ancestry proportion, estimated using 106 biallelic autosomal ancestry informative genetic markers. Recruitment started on October 20, 2010, and ended on August 20, 2015. Data were analyzed from May 2020 to September 2020.
Main outcomes and measures
Trajectories of BP and kidney function parameters on follow-up of the trial were assessed across tertiles of the proportion of West African ancestry using linear mixed-effect modeling after adjustment for potential confounders. Multivariable adjusted Cox models evaluated the association of West African ancestry with the risk of composite CV events (nonfatal myocardial infarction, CV death, and heart failure event).
Results
Among 2466 participants in the current analysis (1122 women [45.5%]; median West African ancestry, 81% [interquartile range, 73%-87%]), there were 120 composite CV events (4.9%) over a mean (SD) of 3.2 (0.9) years of follow-up. At baseline, mean (SD) high-density lipoprotein cholesterol levels were higher (tertile 3: 56.5 [15.0] mg/dL vs tertile 1: 54.2 [14.9] mg/dL; P = .006), smoking prevalence (never smoking: tertile 3: 367 [47.9%] vs tertile 1: 372 [42.2%]; P = .009) and mean (SD) Framingham Risk scores (tertile 3: 16.7 [9.7] vs tertile 1: 18.1 [10.2]; P = .01) were lower, and baseline BP was not different across increasing tertiles of West African ancestry. On follow-up, there was no evidence of differences in longitudinal trajectories of BP, kidney function parameters, or left ventricular mass (Cornell voltage by electrocardiogram) across tertiles of West African ancestry in either intensive or standard treatment arms. In adjusted Cox models, higher West African ancestry was associated with a lower risk of a composite CV event after adjustment for potential confounders (adjusted hazard ratio per 5% higher West African ancestry, 0.92 [95% CI, 0.85-0.99]).
Conclusions and relevance
Among self-reported Black individuals enrolled in SPRINT, the trajectories of BP, kidney function, and left ventricular mass over time were not different across tertiles of the proportion of West African ancestry. A higher proportion of West African ancestry was associated with a modestly lower risk for CV events. These findings suggest that extrinsic and structural societal factors, more than genetic ancestry, may be the major drivers of the well-established racial disparity in cardiovascular health associated with hypertension.



JAMA Cardiol: 12 Nov 2020; epub ahead of print
Rao S, Segar MW, Bress AP, Arora P, ... de Lemos JA, Pandey A
JAMA Cardiol: 12 Nov 2020; epub ahead of print | PMID: 33185651
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Impact:
Abstract

Clinical Outcomes and Response to Vericiguat According to Index Heart Failure Event: Insights From the VICTORIA Trial.

Lam CSP, Giczewska A, Sliwa K, Edelmann F, ... Armstrong PW,
Importance
The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.
Objective
To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial.
Design, setting, and participants
Analysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.
Intervention
Vericiguat titrated to 10 mg daily vs placebo.
Main outcomes and measures
The primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH.
Results
Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.
Conclusions and relevance
Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.
Trial registration
ClinicalTrials.gov Identifier: NCT02861534.



JAMA Cardiol: 12 Nov 2020; epub ahead of print
Lam CSP, Giczewska A, Sliwa K, Edelmann F, ... Armstrong PW,
JAMA Cardiol: 12 Nov 2020; epub ahead of print | PMID: 33185650
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Impact:
Abstract

Association of Visit-to-Visit Variability in Kidney Function and Serum Electrolyte Indexes With Risk of Adverse Clinical Outcomes Among Patients With Heart Failure With Preserved Ejection Fraction.

Segar MW, Patel RB, Patel KV, Fudim M, ... Tang WHW, Pandey A
Importance
Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear.
Objective
To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF.
Design, setting, and participants
This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020.
Main outcomes and measures
Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models.
Results
Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44).
Conclusions and relevance
In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.



JAMA Cardiol: 17 Nov 2020; epub ahead of print
Segar MW, Patel RB, Patel KV, Fudim M, ... Tang WHW, Pandey A
JAMA Cardiol: 17 Nov 2020; epub ahead of print | PMID: 33206129
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Impact:
Abstract

Effect of a Self-care Intervention on 90-Day Outcomes in Patients With Acute Heart Failure Discharged From the Emergency Department: A Randomized Clinical Trial.

Collins SP, Liu D, Jenkins CA, Storrow AB, ... Walsh C, Butler J
Importance
Up to 20% of patients who present to the emergency department (ED) with acute heart failure (AHF) are discharged without hospitalization. Compared with rates in hospitalized patients, readmission and mortality are worse for ED patients.
Objective
To assess the impact of a self-care intervention on 90-day outcomes in patients with AHF who are discharged from the ED.
Design, setting, and participants
Get With the Guidelines in Emergency Department Patients With Heart Failure was an unblinded, parallel-group, multicenter randomized trial. Patients were randomized 1:1 to usual care vs a tailored self-care intervention. Patients with AHF discharged after ED-based management at 15 geographically diverse EDs were included. The trial was conducted from October 28, 2015, to September 5, 2019.
Interventions
Home visit within 7 days of discharge and twice-monthly telephone-based self-care coaching for 3 months.
Main outcomes and measures
The primary outcome was a global rank of cardiovascular death, HF-related events (unscheduled clinic visit due to HF, ED revisit, or hospitalization), and changes in the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) summary score (SS) at 90 days. Key secondary outcomes included the global rank outcome at 30 days and changes in the KCCQ-12 SS score at 30 and 90 days. Intention-to-treat analysis was performed for the primary, secondary, and safety outcomes. Per-protocol analysis was conducted including patients who completed a home visit and had scheduled outpatient follow-up in the intervention arm.
Results
Owing to slow enrollment, 479 of a planned 700 patients were randomized: 235 to the intervention arm and 244 to the usual care arm. The median age was 63.0 years (interquartile range, 54.7-70.2), 302 patients (63%) were African American, 305 patients (64%) were men, and 178 patients (37%) had a previous ejection fraction greater than 50%. There was no significant difference in the primary outcome between patients in the intervention vs usual care arm (hazard ratio [HR], 0.89; 95% CI, 0.73-1.10; P = .28). At day 30, patients in the intervention arm had significantly better global rank (HR, 0.80; 95% CI, 0.64-0.99; P = .04) and a 5.5-point higher KCCQ-12 SS (95% CI, 1.3-9.7; P = .01), while at day 90, the KCCQ-12 SS was 2.7 points higher (95% CI, -1.9 to 7.2; P = .25).
Conclusions and relevance
The self-care intervention did not improve the primary global rank outcome at 90 days in this trial. However, benefit was observed in the global rank and KCCQ-12 SS at 30 days, suggesting that an early benefit of a tailored self-care program initiated at an ED visit for AHF was not sustained through 90 days.
Trial registration
ClinicalTrials.gov Identifier: NCT02519283.



JAMA Cardiol: 17 Nov 2020; epub ahead of print
Collins SP, Liu D, Jenkins CA, Storrow AB, ... Walsh C, Butler J
JAMA Cardiol: 17 Nov 2020; epub ahead of print | PMID: 33206126
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Impact:
Abstract

Associations Between Carotid Artery Plaque Burden, Plaque Characteristics, and Cardiovascular Events: The ARIC Carotid Magnetic Resonance Imaging Study.

Brunner G, Virani SS, Sun W, Liu L, ... Ballantyne CM, Wasserman BA
Importance
It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden.
Objective
To assess associations of CA MRI plaque characteristics with incident CVD events.
Design, setting, and participants
The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020.
Exposures
Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed.
Main outcomes and measures
Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics.
Results
Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated.
Conclusions and relevance
The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.



JAMA Cardiol: 17 Nov 2020; epub ahead of print
Brunner G, Virani SS, Sun W, Liu L, ... Ballantyne CM, Wasserman BA
JAMA Cardiol: 17 Nov 2020; epub ahead of print | PMID: 33206125
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Impact:
Abstract

Association of Low Plasma Transthyretin Concentration With Risk of Heart Failure in the General Population.

Greve AM, Christoffersen M, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A
Importance
Several lines of evidence support low plasma transthyretin concentration as an in vivo biomarker of transthyretin tetramer instability, a prerequisite for the development of both wild-type transthyretin cardiac amyloidosis (ATTRwt) and hereditary transthyretin cardiac amyloidosis (ATTRm). Both ATTRm and ATTRwt cardiac amyloidosis may manifest as heart failure (HF). However, whether low plasma transthyretin concentration confers increased risk of incident HF in the general population is unknown.
Objective
To evaluate whether low plasma transthyretin concentration is associated with incident HF in the general population.
Design, setting, and participants
This study included data from 2 similar prospective cohort studies of the Danish general population, the Copenhagen General Population Study (CGPS; n = 9582) and the Copenhagen City Heart Study (CCHS; n = 7385). Using these data, first, whether low concentration of plasma transthyretin was associated with increased risk of incident HF was tested. Second, whether genetic variants in TTR associated with increasing tetramer instability were associated with lower transthyretin concentration and with higher risk of HF was tested. Data were collected from November 2003 to March 2017 in the CGPS and from November 1991 to June 1994 in the CCHS; participants from both studies were observed for survival time end points until March 2017. Data were analyzed from March to June 2019.
Exposures
Transthyretin concentration at or below the 5th percentile, between the 5th and 95th percentile (reference), and greater than the 95th percentile; genetic variants in TTR.
Main outcome and measure
Incident HF identified using the Danish National Patient Registry.
Results
Of 9582 individuals in the CGPS, 5077 (53.0%) were women, and the median (interquartile range [IQR]) age was 56 (47-65) years. Of 7385 individuals in the CCHS, 4452 (60.3%) were women, and the median (IQR) age was 59 (46-70) years. During a median (IQR) follow-up of 12.6 (12.3-12.9) years and 21.7 (11.6-23.8) years, 441 individuals (4.6%) in the CGPS and 1122 individuals (15.2%) in the CCHS, respectively, developed HF. Baseline plasma transthyretin concentrations at or below the 5th percentile were associated with incident HF (CGPS: hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; CCHS: HR, 1.4; 95% CI, 1.1-1.7). Risk of HF was highest in men with low transthyretin levels. Compared with p.T139M, a transthyretin-stabilizing variant, TTR genotype was associated with stepwise lower transthyretin concentrations for wild-type TTR (-16.5%), p.G26S (-18.1%), and heterozygotes for other variants (p.V142I, p.H110N, and p.D119N; -30.8%) (P for trend <.001). The corresponding HRs for incident HF were 1.14 (95% CI, 0.57-2.28), 1.29 (95% CI, 0.64-2.61), and 2.04 (95% CI, 0.54-7.67), respectively (P for trend = .04).
Conclusions and relevance
In this study, lower plasma and genetically determined transthyretin concentrations were associated with a higher risk of incident HF, suggesting a potential mechanistic association between low transthyretin concentration as a marker of tetramer instability and incident HF in the general population.



JAMA Cardiol: 24 Nov 2020; epub ahead of print
Greve AM, Christoffersen M, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A
JAMA Cardiol: 24 Nov 2020; epub ahead of print | PMID: 33237279
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Impact:
Abstract

Cardiac Structure and Function in Elite Female and Male Soccer Players.

Churchill TW, Petek BJ, Wasfy MM, Guseh JS, ... Chiampas G, Baggish AL
Importance
Population-specific normative data are essential for the evaluation of competitive athletes. At present, there are limited data defining normal electrocardiographic (ECG) and echocardiographic values among elite US soccer players.
Objective
To describe ECG and echocardiographic findings in healthy elite US soccer players.
Design, setting, and participants
This cross-sectional study analyzed Fédération Internationale de Football Association-mandated screening sessions performed at US Soccer National Team training locations from January 2015 to December 2019. US women\'s and men\'s national team soccer players undergoing mandated cardiovascular screening were included.
Main outcomes and measures
Normal training-related and abnormal ECG findings were reported using the International Recommendations for Electrocardiographic Interpretation in Athletes. Echocardiographic measurements of structural and functional parameters relevant to cardiovascular remodeling were assessed relative to American Society of Echocardiography guideline-defined normal ranges.
Results
A total of 238 athletes (122 [51%] female; mean [SD] age, 20 [4] years; age range, 15-40 years) were included. Male athletes demonstrated a higher prevalence of normal training-related ECG findings, while female athletes were more likely to have abnormal ECG patterns (14 [11%] vs 0 in male cohort), largely accounted for by abnormal T-wave inversions. Echocardiography revealed no pathologic findings meeting criteria for sport restriction, but athletes frequently exceeded normal ranges for structural cardiac parameters responsive to exercise-induced remodeling including body surface area-indexed left ventricular (LV) mass (58 of 113 female athletes [51%] and 67 of 114 male athletes [59%]), indexed LV volume (89 of 115 female athletes [77%] and 76 of 111 male athletes [68%]), and LV wall thickness (37 of 122 female athletes [30%] and 47 of 116 male athletes [41%]). Age-stratified analysis revealed age-dependent increases in LV wall thickness, mass, and volumes among female athletes and LV wall thickness and mass among male athletes.
Conclusions and relevance
These data represent the first set of comprehensive normative values for elite US soccer players and one of the largest sport-specific echocardiographic remodeling studies in female athletes. Abnormal ECG findings were more common in female athletes, while both female and male athletes frequently exceeded clinical normality cut points for remodeling-associated echocardiographic parameters.



JAMA Cardiol: 01 Dec 2020; epub ahead of print
Churchill TW, Petek BJ, Wasfy MM, Guseh JS, ... Chiampas G, Baggish AL
JAMA Cardiol: 01 Dec 2020; epub ahead of print | PMID: 33263734
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Impact:
Abstract

Associations of Adiposity, Circulating Protein Biomarkers, and Risk of Major Vascular Diseases.

Pang Y, Kartsonaki C, Lv J, Fairhurst-Hunter Z, ... Li L, Chen Z
Importance
Obesity is associated with a higher risk of cardiovascular disease (CVD), but little is known about the role that circulating protein biomarkers play in this association.
Objective
To examine the observational and genetic associations of adiposity with circulating protein biomarkers and the observational associations of proteins with incident CVD.
Design, setting, and participants
This subcohort study included 628 participants from the prospective China Kadoorie Biobank who did not have a history of cancer at baseline. The Olink platform measured 92 protein markers in baseline plasma samples. Data were collected from June 2004 to January 2016 and analyzed from January 2019 to June 2020.
Exposures
Measured body mass index (BMI) obtained during the baseline survey and genetically instrumented BMI derived using 571 externally weighted single-nucleotide variants.
Main outcomes and measures
Cross-sectional associations of adiposity with biomarkers were examined using linear regression. Associations of biomarkers with CVD risk were assessed using Cox regression among those without prior cancer or CVD at baseline. Mendelian randomization was conducted to derive genetically estimated associations of BMI with biomarkers.
Findings
In observational analyses of 628 individuals (mean [SD] age, 52.2 [10.5] years; 385 women [61.3%]), BMI (mean [SD], 23.9 [3.6]) was positively associated with 27 proteins (per 1-SD higher BMI; eg, interleukin-6: 0.21 [95% CI, 0.12-0.29] SD; interleukin-18: 0.13 [95% CI, 0.05-0.21] SD; monocyte chemoattractant protein-1: 0.12 [95% CI, 0.04-0.20] SD; hepatocyte growth factor: 0.31 [95% CI, 0.24-0.39] SD), and inversely with 3 proteins (Fas ligand: -0.11 [95% CI, -0.19 to -0.03] SD; TNF-related weak inducer of apoptosis, -0.14 [95% CI, -0.23 to -0.06] SD; and carbonic anhydrase 9: (-0.14 [95% CI, -0.22 to -0.05] SD), with similar associations identified for other adiposity traits (eg, waist circumference [r = 0.96]). In mendelian randomization, the associations of genetically elevated BMI with specific proteins were directionally consistent with the observational associations. In meta-analyses of genetically elevated BMI with 8 proteins, combining present estimates with previous studies, the most robust associations were shown for interleukin-6 (per 1-SD higher BMI; 0.21 [95% CI, 0.13-0.29] SD), interleukin-18 (0.16 [95% CI, 0.06-0.26] SD), monocyte chemoattractant protein-1 (0.21 [95% CI, 0.11-0.30] SD), monocyte chemotactic protein-3 (0.12 [95% CI, 0.03-0.21] SD), TNF-related apoptosis-inducing ligand (0.23 [95% CI, 0.13-0.32] SD), and hepatocyte growth factor (0.14 [95% CI, 0.06-0.22] SD). Of the 30 BMI-associated biomarkers, 10 (including interleukin-6, interleukin-18, and hepatocyte growth factor) were nominally associated with incident CVD.
Conclusions and relevance
Mendelian randomization shows adiposity to be associated with a range of protein biomarkers, with some biomarkers also showing association with CVD risk. Future studies are warranted to validate these findings and assess whether proteins may be mediators between adiposity and CVD.



JAMA Cardiol: 01 Dec 2020; epub ahead of print
Pang Y, Kartsonaki C, Lv J, Fairhurst-Hunter Z, ... Li L, Chen Z
JAMA Cardiol: 01 Dec 2020; epub ahead of print | PMID: 33263724
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Impact:
Abstract

Association of Adverse Childhood Experiences With Cardiovascular Disease Later in Life: A Review.

Godoy LC, Frankfurter C, Cooper M, Lay C, Maunder R, Farkouh ME
Importance
Adverse childhood experiences (ACEs) are potentially harmful events that occur during childhood, spanning neglect, physical or sexual abuse, parental separation, or death, among others. At least 50% of the US adult population has experienced 1 or more ACEs before the age of 18 years, but in clinical practice, ACEs remain underrecognized. Adults who have experienced ACEs are at increased risk of developing health risk behaviors and, ultimately, cardiovascular disease (CVD). This review summarizes the evidence regarding the association of ACEs with CVD and the accompanying diagnostic and therapeutic approaches in the adult population.
Observations
ACEs are commonly classified into 3 domains: abuse (psychological, physical, or sexual), household dysfunction (eg, substance use by household members, mental illness, parental separation), and neglect. These experiences elicit chronic activation of the stress response system, leading to autonomic, neuroendocrine, and inflammatory dysfunction. The subsequent development of traditional risk factors, such as diabetes, hypertension, smoking, and obesity, results in the onset of CVD and premature mortality. Adults with 4 or more ACEs compared with those with none have a more than 2-fold higher risk of developing CVD and an almost 2-fold higher risk of premature mortality.
Conclusions and relevance
Identifying methods of mitigating the health consequences of ACEs may lead to better cardiovascular outcomes. Inquiry into ACE exposure during clinical encounters and subsequent referral to psychological services when appropriate may be helpful, but strategies aimed at CVD prevention via management of ACEs in adults continue to lack adequate evidence.



JAMA Cardiol: 01 Dec 2020; epub ahead of print
Godoy LC, Frankfurter C, Cooper M, Lay C, Maunder R, Farkouh ME
JAMA Cardiol: 01 Dec 2020; epub ahead of print | PMID: 33263716
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This program is still in alpha version.