Journal: JAMA Cardiol

Sorted by: date / impact
Abstract

Comparison of Days Alive Out of Hospital With Initial Invasive vs Conservative Management: A Prespecified Analysis of the ISCHEMIA Trial.

White HD, O\'Brien SM, Alexander KP, Boden WE, ... Hochman JS, Maron DJ
Importance
Traditional time-to-event analyses rate events occurring early as more important than later events, even if later events are more severe, eg, death. Days alive out of hospital (DAOH) adds a patient-focused perspective beyond trial end points.
Objective
To compare DAOH between invasive management and conservative management, including invasive protocol-assigned stays, in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) randomized clinical trial.
Design, setting, and participants
In this prespecified analysis of the ISCHEMIA trial, DAOH was compared between 5179 patients with stable coronary disease and moderate or severe ischemia randomized to invasive management or conservative management. Participants were recruited from 320 sites in 37 countries. Stays included overnight stays in hospital or extended care facility (skilled nursing facility, rehabilitation, or nursing home). DAOH was separately analyzed excluding invasive protocol-assigned procedures. Data were collected from July 2012 to June 2019, and data were analyzed from July 2020 to April 2021.
Interventions
Invasive management with angiography and revascularization if feasible or conservative management, with both groups receiving optimal medical therapy.
Main outcomes and measures
The hypothesis was formulated before data lock in July 2020. The primary end point was mean DAOH per patient between randomization and 4 years. Initial stays for invasive protocol-assigned procedures were prespecified to be excluded.
Results
Of 5179 included patients, 1168 (22.6%) were female, and the median (interquartile range) age was 64 (58-70) years. The average DAOH was higher in the conservative management group compared with the invasive management group at 1 month (30.8 vs 28.4 days; P < .001), 1 year (362.2 vs 355.9 days; P < .001), and 2 years (718.4 vs 712.1 days; P = .001). At 4 years, the 2 groups\' DAOH were not significantly different (1415.0 vs 1412.2 days; P = .65). In the invasive management group, 2434 of 4002 stays (60.8%) were for protocol-assigned procedures. There were no clear differences at any time point in DAOH when protocol-assigned procedures were excluded from the invasive management group. There were more hospital and extended care stays in the invasive management vs conservative management group during follow-up (4002 vs 1897; P < .001). Excluding protocol-assigned procedures, there were fewer stays in the invasive vs conservative group (1568 vs 1897; P = .001). Cardiovascular stays following the initial assigned procedures were lower in the invasive management group (685 of 4002 [17.1%] vs 1095 of 1897 [57.8%]; P < .001) due to decreased spontaneous myocardial infarction stays (65 [1.6%] vs 123 [6.5%]; P < .001) and unstable angina stays (119 [3.0%] vs 216 [11.4%]; P < .001).

Conclusions:
and relevance
DAOH was higher for patients in the conservative management group in the first 2 years but not different at 4 years. DAOH was decreased early in the invasive management group due to protocol-assigned procedures. Hospital stays for myocardial infarction and unstable angina during follow-up were lower in the invasive management group. DAOH provides a patient-focused metric that can be used by clinicians and patients in shared decision-making for management of stable coronary artery disease.
Trial registration
ClinicalTrials.gov Identifier: NCT01471522.



JAMA Cardiol: 02 May 2021; epub ahead of print
White HD, O'Brien SM, Alexander KP, Boden WE, ... Hochman JS, Maron DJ
JAMA Cardiol: 02 May 2021; epub ahead of print | PMID: 33938917
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Impact:
Abstract

Assessment of Catheter Ablation or Antiarrhythmic Drugs for First-line Therapy of Atrial Fibrillation: A Meta-analysis of Randomized Clinical Trials.

Turagam MK, Musikantow D, Whang W, Koruth JS, ... Dukkipati SR, Reddy VY
Importance
Early rhythm control of atrial fibrillation (AF) with either antiarrhythmic drugs (AADs) or catheter ablation has been reported to improve cardiovascular outcomes compared with usual care; however, the optimal therapeutic modality to achieve early rhythm control is unclear.
Objective
To assess the safety and efficacy of AF ablation as first-line therapy when compared with AADs in patients with paroxysmal AF.
Data sources
PubMed/MEDLINE, Scopus, Google Scholar, and various major scientific conference sessions from January 1, 2000, through November 23, 2020.
Study selection
Randomized clinical trials (RCTs) published in English that had at least 12 months of follow-up and compared clinical outcomes of ablation vs AADs as first-line therapy in adults with AF. The quality of individual studies was assessed using the Cochrane risk of bias tool. Six RCTs met inclusion criteria, including 1212 patients.
Data extraction and synthesis
Two investigators independently extracted data. Reporting was performed in compliance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. Analysis was performed using a random-effects model with the Mantel-Haenszel method, and results are presented as 95% CIs.
Main outcomes and measures
Main outcomes were safety and efficacy of AF ablation as first-line therapy when compared with AADs. Trials were evaluated as having low risk of selection and attrition biases, high risk of performance bias, and with unclear risk for detection biases due to unblinding and open-label designs.
Results
A total of 6 RCTs involving 1212 patients with AF were included (609 were randomized to AF ablation and 603 to drug therapy; mean [SD] age, 56 [11] years). Compared with AADs, catheter ablation use was associated with reductions in recurrent atrial arrhythmia (32.3% vs 53%; risk ratio [RR], 0.62; 95% CI, 0.51-0.74; P < .001; I2 = 40%), with a number needed to treat with ablation to prevent 1 arrhythmia of 5. Use of ablation was also associated with reduced symptomatic atrial arrhythmia (11.8% vs 26.4%; RR, 0.44; 95% CI, 0.27-0.72; P = .001; I2 = 54%) and hospitalization (5.6% vs 18.7%; RR, 0.32; 95% CI, 0.19-0.53; P < .001) with no significant difference in serious adverse events between the groups (4.2% vs 2.8%; RR, 1.52; 95% CI, 0.81-2.85; P = .19).

Conclusions:
and relevance
In this meta-analysis of randomized clinical trials including first-line therapy of patients with paroxysmal AF, catheter ablation compared with antiarrhythmic drugs was associated with reductions in recurrence of atrial arrhythmias and hospitalizations, with no difference in major adverse events.



JAMA Cardiol: 27 Apr 2021; epub ahead of print
Turagam MK, Musikantow D, Whang W, Koruth JS, ... Dukkipati SR, Reddy VY
JAMA Cardiol: 27 Apr 2021; epub ahead of print | PMID: 33909022
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Impact:
Abstract

Performance of the American Heart Association/American College of Cardiology Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Self-reported Physical Activity Levels.

Pandey A, Mehta A, Paluch A, Ning H, ... Lloyd-Jones DM, Wilkins JT
Importance
The American Heart Association/American College of Cardiology pooled cohort equations (PCEs) are used for predicting 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Pooled cohort equation risk prediction capabilities across self-reported leisure-time physical activity (LTPA) levels and the change in model performance with addition of LTPA to the PCE are unclear.
Objective
To evaluate PCE risk prediction performance across self-reported LTPA levels and the change in model performance by adding LTPA to the existing PCE model.
Design, setting, and participants
Individual-level pooling of data from 3 longitudinal cohort studies-Atherosclerosis Risk in Communities, Multi-Ethnic Study of Atherosclerosis, and Cardiovascular Health Study-was performed. A total of 18 824 participants were stratified into 4 groups based on self-reported LTPA levels: inactive (0 metabolic equivalent of task [MET]-min/wk), less than guideline-recommended (<500 MET-min/wk), guideline-recommended (500-1000 MET-min/week), and greater than guideline-recommended (>1000 MET-min/wk). Pooled cohort equation risk discrimination was studied using the C statistic and reclassification capabilities were studied using the Greenwood Nam-D\'Agostino χ2 goodness-of-fit test. Change in risk discrimination and reclassification on adding LTPA to PCEs was evaluated using change in C statistic, integrated discrimination index, and categorical net reclassification index.
Main outcomes and measures
Adjudicated ASCVD events during 10-year follow-up.
Results
Among 18 824 participants studied, 10 302 were women (54.7%); mean (SD) age was 57.6 (8.2) years. A total of 5868 participants (31.2%) were inactive, 3849 (20.4%) had less than guideline-recommended LTPA, 3372 (17.9%) had guideline-recommended LTPA, and 5735 (30.5%) had greater than guideline-recommended LTPA level. Higher LTPA levels were associated with a lower risk of ASCVD after adjustment for risk factors (hazard ratio [HR] per 1-SD higher LTPA, 0.91; 95% CI, 0.86-0.96). Across LTPA groups, PCE risk discrimination (C statistic, 0.76-0.78) and risk calibration (all χ2 P > .10) was similar. Addition of LTPA to the PCE model resulted in no significant change in the C statistic (0.0005; 95% CI, -0.0004 to 0.0015; P = .28) and categorical net reclassification index (-0.003; 95% CI, -0.010 to 0.010; P = .95), but a minimal improvement in the integrated discrimination index (0.0008; 95% CI, 0.0002-0.0013; P = .005) was observed. Similar results were noted when cohort-specific coefficients were used for creating the baseline model.

Conclusions:
and relevance
Higher self-reported LTPA levels appear to be associated with lower ASCVD risk and increasing LTPA promotes cardiovascular wellness. These findings suggest the American Heart Association/American College of Cardiology PCEs are accurate at estimating the probability of 10-year ASCVD risk regardless of LTPA level. The addition of self-reported LTPA to PCEs does not appear to be associated with improvement in risk prediction model performance.



JAMA Cardiol: 27 Apr 2021; epub ahead of print
Pandey A, Mehta A, Paluch A, Ning H, ... Lloyd-Jones DM, Wilkins JT
JAMA Cardiol: 27 Apr 2021; epub ahead of print | PMID: 33909016
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Impact:
Abstract

Cardiovascular Biomarkers in the Early Discrimination of Type 2 Myocardial Infarction.

Nestelberger T, Boeddinghaus J, Lopez-Ayala P, Kaier TE, ... Mueller C, APACE Investigators
Importance
Rapid and accurate noninvasive discrimination of type 2 myocardial infarction (T2MI), which is because of a supply-demand mismatch, from type 1 myocardial infarction (T1MI), which arises via plaque rupture, is essential, because treatment differs substantially. Unfortunately, this is a major unmet clinical need, because even high-sensitivity cardiac troponin (hs-cTn) measurement provides only modest accuracy.
Objective
To test the hypothesis that novel cardiovascular biomarkers quantifying different pathophysiological pathways involved in T2MI and/or T1MI may aid physicians in the rapid discrimination of T2MI vs T1MI.
Design, setting, and participants
This international, multicenter prospective diagnostic study was conducted in 12 emergency departments in 5 countries (Switzerland, Spain, Italy, Poland, and the Czech Republic) with patients presenting with acute chest discomfort to the emergency departments. The study quantified the discrimination of hs-cTn T, hs-cTn I, and 17 novel cardiovascular biomarkers measured in subsets of consecutively enrolled patients against a reference standard (final diagnosis), centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of MI, using all information, including cardiac imaging and serial measurements of hs-cTnT or hs-cTnI.
Results
Among 5887 patients, 1106 (18.8%) had an adjudicated final diagnosis of MI; of these, 860 patients (77.8%) had T1MI, and 246 patients (22.2%) had T2MI. Patients with T2MI vs those with T1MI had lower concentrations of biomarkers quantifying cardiomyocyte injury hs-cTnT (median [interquartile range (IQR)], 30 (17-55) ng/L vs 58 (28-150) ng/L), hs-cTnI (median [IQR], 23 [10-83] ng/L vs 115 [28-576] ng/L; P < .001), and cardiac myosin-binding protein C (at presentation: median [IQR], 76 [38-189] ng/L vs 257 [75-876] ng/L; P < .001) but higher concentrations of biomarkers quantifying endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress (median [IQR] values: C-terminal proendothelin 1, 97 [75-134] pmol/L vs 68 [55-91] pmol/L; midregional proadrenomedullin, 0.97 [0.67-1.51] pmol/L vs 0.72 [0.53-0.99] pmol/L; midregional pro-A-type natriuretic peptide, 378 [207-491] pmol/L vs 152 [90-247] pmol/L; and growth differentiation factor 15, 2.26 [1.44-4.35] vs 1.56 [1.02-2.19] ng/L; all P < .001). Discrimination for these biomarkers, as quantified by the area under the receiver operating characteristics curve, was modest (hs-cTnT, 0.67 [95% CI, 0.64-0.71]; hs-cTn I, 0.71 [95% CI, 0.67-0.74]; cardiac myosin-binding protein C, 0.67 [95% CI, 0.61-0.73]; C-terminal proendothelin 1, 0.73 [95% CI, 0.63-0.83]; midregional proadrenomedullin, 0.66 [95% CI, 0.60-0.73]; midregional pro-A-type natriuretic peptide, 0.77 [95% CI, 0.68-0.87]; and growth differentiation factor 15, 0.68 [95% CI, 0.58-0.79]).

Conclusions:
and relevance
In this study, biomarkers quantifying myocardial injury, endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress provided modest discrimination in early, noninvasive diagnosis of T2MI.



JAMA Cardiol: 20 Apr 2021; epub ahead of print
Nestelberger T, Boeddinghaus J, Lopez-Ayala P, Kaier TE, ... Mueller C, APACE Investigators
JAMA Cardiol: 20 Apr 2021; epub ahead of print | PMID: 33881449
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Impact:
Abstract

Sex-Related Disparities in Cardiovascular Health Care Among Patients With Premature Atherosclerotic Cardiovascular Disease.

Lee MT, Mahtta D, Ramsey DJ, Liu J, ... Petersen LA, Virani SS
Importance
There is a paucity of data regarding secondary prevention care disparities in women with premature and extremely premature atherosclerotic cardiovascular disease (ASCVD), defined as an ASCVD event at 55 years or younger and 40 years or younger, respectively.
Objective
To evaluate sex-based differences in antiplatelet agents, any statin, high-intensity statin (HIS) therapy, and statin adherence in patients with premature and extremely premature ASCVD.
Design, setting, and participants
This was a cross-sectional, multicenter, nationwide VA health care system-based study with patients enrolled in the Veterans With Premature Atherosclerosis (VITAL) registry. The study assessed patients who had at least 1 primary care visit in the Veterans Affairs (VA) health care system from October 1, 2014, to September 30, 2015. Participants included 147 600 veteran patients with premature ASCVD, encompassing ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD).
Exposures
Women vs men with premature and extremely premature ASCVD.
Main outcomes and measures
Antiplatelet use, any statin use, HIS use, and statin adherence (proportion of days covered [PDC] ≥0.8).
Results
We identified 10 413 women and 137 187 men with premature ASCVD (age ≤55 years) and 1340 women and 8145 men with extremely premature (age ≤40 years) ASCVD. Among patients with premature and extremely premature ASCVD, women represented 7.1% and 14.1% of those groups, respectively. When compared with men, women with premature ASCVD had a higher proportion of African American patients (36.1% vs 23.8%) and lower proportions of Asian patients (0.5% vs 0.7%) and White patients (56.1% vs. 68.1%). In the extremely premature ASCVD group, women had a comparatively higher proportion of African American patients (36.8% vs 23.2%) and lower proportion of White patients (55.0% vs 67.8%) and Asian patients (1.3% vs 1.5%) than men. Among patients with premature IHD, women received less antiplatelet (adjusted odds ratio [AOR], 0.47, 95% CI, 0.45-0.50), any statin (AOR, 0.62; 95% CI, 0.59-0.66), and HIS (AOR, 0.63; 95% CI, 0.59-0.66) therapy and were less statin adherent (mean [SD] PDC, 0.68 [0.34] vs 0.73 [0.31]; β coefficient: -0.02; 95% CI, -0.03 to -0.01) compared with men. Similarly, women with premature ICVD and premature PAD received comparatively less antiplatelet agents, any statin, and HIS. Among patients with extremely premature ASCVD, women also received less antiplatelet therapy (AOR, 0.61; 95% CI, 0.53-0.70), any statin therapy (AOR,0.51; 95% CI, 0.44-0.58), and HIS therapy (AOR, 0.45; 95% CI, 0.37-0.54) than men. There were no sex-associated differences in statin adherence among patients with premature ICVD, premature PAD, or extremely premature ASCVD.

Conclusions:
and relevance
This cross-sectional study revealed that women veterans with premature ASCVD and extremely premature ASCVD receive less optimal secondary prevention cardiovascular care in comparison with men. Women with premature ASCVD, particularly those with IHD, were also less statin adherent. Multidisciplinary and patient-centered interventions are needed to improve these disparities in women.



JAMA Cardiol: 20 Apr 2021; epub ahead of print
Lee MT, Mahtta D, Ramsey DJ, Liu J, ... Petersen LA, Virani SS
JAMA Cardiol: 20 Apr 2021; epub ahead of print | PMID: 33881448
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Impact:
Abstract

Calcium/Calmodulin-Dependent Protein Kinase II Delta Inhibition and Ventricular Remodeling After Myocardial Infarction: A Randomized Clinical Trial.

Boyle AJ, Schultz C, Selvanayagam JB, Moir S, ... Collins N, McLachlan G
Importance
After anterior ST-segment elevation myocardial infarction (STEMI), left ventricular (LV) remodeling results in heart failure and death. Calcium/calmodulin-dependent protein kinase II delta (CaMKIId) is a key molecular mediator of adverse LV remodeling.
Objective
To determine whether NP202, an orally active inhibitor of CaMKIId, prevents LV remodeling in patients after anterior STEMI with early residual LV dysfunction.
Design, setting, and participants
A randomized, double-blind, placebo-controlled multicenter clinical trial of NP202 vs placebo in patients after primary percutaneous coronary intervention (PCI) for anterior STEMI was performed from November 19, 2015, to August 1, 2018. The study was performed at 32 sites across the US, Australia, and New Zealand. Patients presenting with anterior STEMI who underwent PCI within 12 hours of symptom onset and left ventricular ejection fraction (LVEF) less than 45% on screening echocardiogram 48 hours after primary PCI were included in the study. Baseline cardiovascular magnetic resonance (CMR) imaging was performed within 5 days of the STEMI and before administration of the study drug. Follow-up CMR was performed after 3 months. Data were analyzed from November 19, 2015, to August 1, 2018.
Interventions
Patients were randomly assigned to NP202, 1000 mg, daily for 3 months vs corresponding placebo.
Main outcomes and measures
The primary end point was change in LV end-systolic volume index (LVESVi) on CMR. Secondary end points were change in LV end-diastolic volume index, change in LVEF, change in infarct size, and change in diastolic function. Safety and tolerability were also assessed.
Results
A total of 147 patients (mean [SD] age, 58 [11] years; 129 men [88%]; 130 White patients [88%]) who experienced anterior STEMI treated with primary PCI were randomized to receive NP202 (73 [49.7%]) or placebo (74 [50.3%]). Baseline LVEF was similar between groups. At baseline, patients randomized to NP202 had greater LVESVi (48.2 mL/m2) than that in the placebo group (41.3 mL/m2; P = .03). However, the groups were otherwise well matched. For the primary end point of change in LVESVi from baseline to 3 months, there was no significant difference between the placebo (median [interquartile range] change, -0.60 [-9.28 to 5.99] mL/m2) and NP202 groups (-3.53 [-9.24 to 4.81] mL/m2) (P = .78). There was also no difference in the secondary efficacy end points assessed by CMR. NP202 was well tolerated and demonstrated an acceptable safety profile. Major adverse cardiac and cerebrovascular event rates were similar between groups. Two deaths occurred in each group during the follow-up period.

Conclusions:
and relevance
Three months of treatment with NP202 after primary PCI for anterior STEMI with residual LV dysfunction did not improve LV remodeling. The drug was safe and well tolerated.
Trial registration
ClinicalTrials.gov Identifier: NCT02557217.



JAMA Cardiol: 13 Apr 2021; epub ahead of print
Boyle AJ, Schultz C, Selvanayagam JB, Moir S, ... Collins N, McLachlan G
JAMA Cardiol: 13 Apr 2021; epub ahead of print | PMID: 33851966
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Impact:
Abstract

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Zelniker TA, Raz I, Mosenzon O, Dwyer JP, ... Sabatine MS, Wiviott SD
Importance
Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown.
Objective
To assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).
Design, setting, and participants
This secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (<60 vs ≥60 mL/min/1.73 m2), urinary albumin to creatinine ratio (UACR; <30 vs ≥30 mg/g), and of chronic kidney disease (CKD) markers using these subgroups (0, 1, or 2). The study was conducted from May 2013 to September 2018.
Interventions
Dapagliflozin vs placebo.
Main outcomes and measures
The dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF.
Results
At baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher.

Conclusions:
and relevance
The effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria.
Trial registration
ClinicalTrials.gov Identifier: NCT01730534.



JAMA Cardiol: 13 Apr 2021; epub ahead of print
Zelniker TA, Raz I, Mosenzon O, Dwyer JP, ... Sabatine MS, Wiviott SD
JAMA Cardiol: 13 Apr 2021; epub ahead of print | PMID: 33851953
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Impact:
Abstract

Association of Dual Eligibility for Medicare and Medicaid With Heart Failure Quality and Outcomes Among Get With The Guidelines-Heart Failure Hospitals.

Bahiru E, Ziaeian B, Moucheraud C, Agarwal A, ... Yancy CW, Fonarow GC
Importance
The Centers for Medicare & Medicaid Services uses a new peer group-based payment system to compare hospital performance as part of its Hospital Readmissions Reduction Program, which classifies hospitals into quintiles based on their share of dual-eligible beneficiaries for Medicare and Medicaid. However, little is known about the association of a hospital\'s share of dual-eligible beneficiaries with the quality of care and outcomes for patients with heart failure (HF).
Objective
To evaluate the association between a hospital\'s proportion of patients with dual eligibility for Medicare and Medicaid and HF quality of care and outcomes.
Design, setting, and participants
This retrospective cohort study evaluated 436 196 patients hospitalized for HF using the Get With The Guidelines-Heart Failure registry from January 1, 2010, to December 31, 2017. The analysis included patients 65 years or older with available data on dual-eligibility status. Hospitals were divided into quintiles based on their share of dual-eligible patients. Quality and outcomes were analyzed using unadjusted and adjusted multivariable logistic regression models. Data analysis was performed from April 1, 2020, to January 1, 2021.
Main outcomes and measures
The primary outcome was 30-day all-cause readmission. The secondary outcomes included in-hospital mortality, 30-day HF readmissions, 30-day all-cause mortality, and HF process of care measures.
Results
A total of 436 196 hospitalized HF patients 65 years or older from 535 hospital sites were identified, with 258 995 hospitalized patients (median age, 81 years; interquartile range, 74-87 years) at 455 sites meeting the study criteria and included in the primary analysis. A total of 258 995 HF hospitalizations from 455 sites were included in the primary analysis of the study. Hospitals in the highest dual-eligibility quintile (quintile 5) tended to care for patients who were younger, were more likely to be female, belonged to racial minority groups, or were located in rural areas compared with quintile 1 sites. After multivariable adjustment, hospitals with the highest quintile of dual eligibility were associated with lower rates of key process measures, including evidence-based β-blocker prescription, measure of left ventricular function, and anticoagulation for atrial fibrillation or atrial flutter. Differences in clinical outcomes were seen with higher 30-day all-cause (adjusted odds ratio, 1.24; 95% CI, 1.14-1.35) and HF (adjusted odds ratio, 1.14; 95% CI, 1.03-1.27) readmissions in higher dual-eligible quintile 5 sites compared with quintile 1 sites. Risk-adjusted in-hospital and 30-day mortality did not significantly differ in quintile 1 vs quintile 5 hospitals.

Conclusions:
and relevance
In this cohort study, hospitals with a higher share of dual-eligible patients provided care with lower rates of some of the key HF quality of care process measures and with higher 30-day all-cause or HF readmissions compared with lower dual-eligibility quintile hospitals.



JAMA Cardiol: 06 Apr 2021; epub ahead of print
Bahiru E, Ziaeian B, Moucheraud C, Agarwal A, ... Yancy CW, Fonarow GC
JAMA Cardiol: 06 Apr 2021; epub ahead of print | PMID: 33825802
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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: 31 Mar 2021; 6:457-462
Morton SU, Shimamura A, Newburger PE, Opotowsky AR, ... Seidman JG, Seidman CE
JAMA Cardiol: 31 Mar 2021; 6:457-462 | PMID: 33084842
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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: 31 Mar 2021; 6:463-468
Snoek JA, Prescott EI, van der Velde AE, Eijsvogels TMH, ... Van't Hof AWJ, de Kluiver EP
JAMA Cardiol: 31 Mar 2021; 6:463-468 | PMID: 33112363
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Impact:
Abstract

Assessing the Role of Rare Genetic Variation in Patients With Heart Failure.

Povysil G, Chazara O, Carss KJ, Deevi SVV, ... Haefliger C, Goldstein DB
Importance
Sequencing studies have identified causal genetic variants for distinct subtypes of heart failure (HF) such as hypertrophic or dilated cardiomyopathy. However, the role of rare, high-impact variants in HF, for which ischemic heart disease is the leading cause, has not been systematically investigated.
Objective
To assess the contribution of rare variants to all-cause HF with and without reduced left ventricular ejection fraction.
Design, setting, and participants
This was a retrospective analysis of clinical trials and a prospective epidemiological resource (UK Biobank). Whole-exome sequencing of patients with HF was conducted from the Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) and Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) clinical trials. Data were collected from March 1999 to May 2003 for the CHARM studies and September 2003 to July 2007 for the CORONA study. Using a gene-based collapsing approach, the proportion of patients with HF and controls carrying rare and presumed deleterious variants was compared. The burden of pathogenic variants in known cardiomyopathy genes was also investigated to assess the diagnostic yield. Exome sequencing data were generated between January 2018 and October 2018, and analysis began October 2018 and ended April 2020.
Main outcomes and measures
Odds ratios and P values for genes enriched for rare and presumed deleterious variants in either patients with HF or controls and diagnostic yield of pathogenic variants in known cardiomyopathy genes.
Results
This study included 5942 patients with HF and 13 156 controls. The mean (SD) age was 68.9 (9.9) years and 4213 (70.9%) were male. A significant enrichment of protein-truncating variants in the TTN gene (P = 3.35 × 10-13; odds ratio, 2.54; 95% CI, 1.96-3.31) that was further increased after restriction to variants in exons constitutively expressed in the heart (odds ratio, 4.52; 95% CI, 3.10-6.68). Validation using UK Biobank data showed a similar enrichment (odds ratio, 4.97; 95% CI, 3.94-6.19 after restriction). In the clinical trials, 201 of 5916 patients with HF (3.4%) had a pathogenic or likely pathogenic cardiomyopathy variant implicating 21 different genes. Notably, 121 of 201 individuals (60.2%) had ischemic heart disease as the clinically identified etiology for the HF. Individuals with HF and preserved ejection fraction had only a slightly lower yield than individuals with midrange or reduced ejection fraction (20 of 767 [2.6%] vs 15 of 392 [3.8%] vs 166 of 4757 [3.5%]).

Conclusions:
and relevance
An increased burden of diagnostic mendelian cardiomyopathy variants in a broad group of patients with HF of mostly ischemic etiology compared with controls was observed. This work provides further evidence that mendelian genetic conditions may represent an important subset of complex late-onset diseases such as HF, irrespective of the clinical presentation.



JAMA Cardiol: 31 Mar 2021; 6:379-386
Povysil G, Chazara O, Carss KJ, Deevi SVV, ... Haefliger C, Goldstein DB
JAMA Cardiol: 31 Mar 2021; 6:379-386 | PMID: 33326012
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Impact:
Abstract

Assessing the Risks of Bleeding vs Thrombotic Events in Patients at High Bleeding Risk After Coronary Stent Implantation: The ARC-High Bleeding Risk Trade-off Model.

Urban P, Gregson J, Owen R, Mehran R, ... Morice MC, Pocock S
Importance
Patients who are candidates for percutaneous coronary intervention (PCI) and are at high bleeding risk constitute a therapeutic challenge because they often also face an increased risk of thrombotic complications.
Objectives
To develop and validate models to predict the risks of major bleeding (Bleeding Academic Research Consortium [BARC] types 3 to 5 bleeding) and myocardial infarction (MI) and/or stent thrombosis (ST) for individual patients at high bleeding risk and provide assistance in defining procedural strategy and antithrombotic regimens.
Design, setting, and participants
This prognostic study used individual patient data from 6 studies conducted from July 1, 2009, to September 5, 2017, for 6641 patients at more than 200 centers in Europe, the US, and Asia who underwent PCI and were identified as being at high bleeding risk using the Academic Research Consortium criteria. In 1 year of follow-up (excluding periprocedural events), individual patient risks of MI and/or ST and major bleeding were evaluated using 33 baseline variables. To validate these models, a subgroup of 1458 patients at high bleeding risk from the ONYX ONE trial were analyzed. Statistical analysis was performed from February 1, 2019, to April 30, 2020.
Exposures
All patients underwent PCI with bare metal, drug-coated, or drug-eluting stent implants.
Main outcomes and measures
Forward, stepwise multivariable proportional hazards models were used to identify highly significant predictors of MI and/or ST and BARC types 3 to 5 bleeding.
Results
A total of 6641 patients (4384 men [66.0%]; median age, 77.9 years [interquartile range, 70.0-82.6 years]) were included in this study. Over 365 days, nonperiprocedural MI and/or ST occurred in 350 patients (5.3%), and BARC types 3 to 5 bleeding occurred in 381 patients (5.7%). Eight independent baseline predictors of risk of MI and/or ST and 8 predictors for risk of BARC types 3 to 5 bleeding were identified. Four of these predictors were in both risk models. Both risk models showed moderate discrimination: C statistic = 0.69 for predicting MI and/or ST and 0.68 for predicting BARC types 3 to 5 bleeding. Applying these same models to the validation cohort gave a similar strength of discrimination (C statistic = 0.74 for both MI and/or ST and BARC types 3-5 bleeding). Patients with MI and/or ST had a mortality hazard ratio of 6.1 (95% CI, 4.8-7.7), and those with BARC types 3 to 5 bleeding had a mortality hazard ratio of 3.7 (95% CI, 2.9-4.8) compared with patients free of both events. Taking these data into account, the risk scores facilitate investigation of the individual patient trade-off between these 2 risks: 2931 patients (44.1%) at high bleeding risk in the 6 studies had a greater risk of MI and/or ST than of BARC 3 to 5 bleeding, 1555 patients (23.4%) had a greater risk of BARC 3 to 5 bleeding than of MI and/or ST, and 2155 (32.4%) had a comparable risk of both events.

Conclusions:
and relevance
In a large cohort of patients at high bleeding risk undergoing PCI, 2 prognostic models have been developed to identify individual patients\' risk of major coronary thrombotic and bleeding events. In future clinical practice, using an application on a smartphone to evaluate the trade-off between these 2 quantifiable risks for each patient may help clinicians choose the most appropriate revascularization strategy and tailor the duration and intensity of antithrombotic regimens.



JAMA Cardiol: 31 Mar 2021; 6:410-419
Urban P, Gregson J, Owen R, Mehran R, ... Morice MC, Pocock S
JAMA Cardiol: 31 Mar 2021; 6:410-419 | PMID: 33404627
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Impact:
Abstract

Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren: A Cluster Randomized Clinical Trial.

Karki P, Uranw S, Bastola S, Mahato R, ... Jüni P, Pilgrim T
Importance
Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions.
Objective
To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease.
Design, setting, and participants
This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019.
Interventions
In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening.
Main outcomes and measures
Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention.
Results
A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008).

Conclusions:
and relevance
School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions.
Trial registration
ClinicalTrials.gov Identifier: NCT01550068.



JAMA Cardiol: 31 Mar 2021; 6:420-426
Karki P, Uranw S, Bastola S, Mahato R, ... Jüni P, Pilgrim T
JAMA Cardiol: 31 Mar 2021; 6:420-426 | PMID: 33471029
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Impact:
Abstract

Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women.

Dugani SB, Moorthy MV, Li C, Demler OV, ... Glynn RJ, Mora S
Importance
Risk profiles for premature coronary heart disease (CHD) are unclear.
Objective
To examine baseline risk profiles for incident CHD in women by age at onset.
Design, setting, and participants
A prospective cohort of US female health professionals participating in the Women\'s Health Study was conducted; median follow-up was 21.4 years. Participants included 28 024 women aged 45 years or older without known cardiovascular disease. Baseline profiles were obtained from April 30, 1993, to January 24, 1996, and analyses were conducted from October 1, 2017, to October 1, 2020.
Exposures
More than 50 clinical, lipid, inflammatory, and metabolic risk factors and biomarkers.
Main outcomes and measures
Four age groups were examined (<55, 55 to <65, 65 to <75, and ≥75 years) for CHD onset, and adjusted hazard ratios (aHRs) were calculated using stratified Cox proportional hazard regression models with age as the time scale and adjusting for clinical factors. Women contributed to different age groups over time.
Results
Of the clinical factors in the women, diabetes had the highest aHR for CHD onset at any age, ranging from 10.71 (95% CI, 5.57-20.60) at CHD onset in those younger than 55 years to 3.47 (95% CI, 2.47-4.87) at CHD onset in those 75 years or older. Risks that were also noted for CHD onset in participants younger than 55 years included metabolic syndrome (aHR, 6.09; 95% CI, 3.60-10.29), hypertension (aHR, 4.58; 95% CI, 2.76-7.60), obesity (aHR, 4.33; 95% CI, 2.31-8.11), and smoking (aHR, 3.92; 95% CI, 2.32-6.63). Myocardial infarction in a parent before age 60 years was associated with 1.5- to 2-fold risk of CHD in participants up to age 75 years. From approximately 50 biomarkers, lipoprotein insulin resistance had the highest standardized aHR: 6.40 (95% CI, 3.14-13.06) for CHD onset in women younger than 55 years, attenuating with age. In comparison, weaker but significant associations with CHD in women younger than 55 years were noted (per SD increment) for low-density lipoprotein cholesterol (aHR, 1.38; 95% CI, 1.10-1.74), non-high-density lipoprotein cholesterol (aHR, 1.67; 95% CI, 1.36-2.04), apolipoprotein B (aHR, 1.89; 95% CI, 1.52-2.35), triglycerides (aHR, 2.14; 95% CI, 1.72-2.67), and inflammatory biomarkers (1.2- to 1.8-fold)-all attenuating with age. Some biomarkers had similar CHD age associations (eg, physical inactivity, lipoprotein[a], total high-density lipoprotein particles), while a few had no association with CHD onset at any age. Most risk factors and biomarkers had associations that attenuated with increasing age at onset.

Conclusions:
and relevance
In this cohort study, diabetes and insulin resistance, in addition to hypertension, obesity, and smoking, appeared to be the strongest risk factors for premature onset of CHD. Most risk factors had attenuated relative rates at older ages.



JAMA Cardiol: 31 Mar 2021; 6:437-447
Dugani SB, Moorthy MV, Li C, Demler OV, ... Glynn RJ, Mora S
JAMA Cardiol: 31 Mar 2021; 6:437-447 | PMID: 33471027
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Impact:
Abstract

Association of Global Longitudinal Strain With Clinical Status and Mortality in Patients With Chronic Heart Failure.

Tröbs SO, Prochaska JH, Schwuchow-Thonke S, Schulz A, ... Münzel T, Wild PS
Importance
Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited.
Objective
To assess the factors associated with GLS and its prognostic value in patients with chronic HF.
Design, setting, and participants
The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participants with stages A to D HF according to American Heart Association (AHA) criteria were examined at a dedicated study center. Echocardiography was performed with GLS measurement by independent reviewers. Data were analyzed from September 2, 2019, to January 15, 2020.
Main outcomes and measures
All-cause and cardiac mortality were recorded by structured follow-up and validated via death certificates.
Results
In the study sample, data on GLS were available on 2440 individuals, of whom 2186 (mean [SD] age, 65.0 [10.5] years; 1418 [64.9%] men) were classified as having AHA HF stages A to D. Mean (SD) GLS worsened across AHA stages from stage A (n = 434; -19.44 [3.15%]) to stage B (n = 629; -18.01 [3.46%]) to stages C/D (n = 1123; -15.52 [4.64%]). Age (β = -0.27; 95% CI, -0.47 to -0.067; per decade, P = .009), female sex (β = -1.2; 95% CI, -1.6 to -0.77; per decade, P < .001), obesity (β = 0.64; 95% CI, 0.25-1.0; P = .001), atrial fibrillation (β = 1.2; 95% CI, 0.69-1.6; P < .001), myocardial infarction (β = 1.5; 95% CI, 1.00-2.1; P < .001), and estimated glomerular filtration rate (β = -0.53; 95% CI, -0.73 to -0.32; per SD, P < .001) were independently associated with GLS in multivariable regression analysis. Global longitudinal strain was associated with the severity of HF as reflected by N-terminal prohormone B-type natriuretic protein (NT-proBNP) levels after additionally adjusting for cardiac structure and function (P < .001). During follow-up, GLS was associated with all-cause mortality (hazard ratio [HR] per SD, 1.55; 95% CI, 1.19-2.01; P < .001) and cardiac death (HR per SD, 2.32; 95% CI, 1.57-3.42; P < .001) independent of image quality, observer variability, clinical profile, HF medications, NYHA class, and cardiac structure and function. After further adjustment for the NT-proBNP level, GLS remained associated with cardiac death (HR per SD, 1.60; 95% CI, 1.07-2.41; P = .02) but not all-cause mortality (HR per SD, 1.26; 95% CI, 0.95-1.66; P = .11).

Conclusions:
and relevance
In patients with chronic HF, GLS was associated with clinical and cardiac status, reflected neurohormonal activation, and was associated with cardiac mortality independent of clinical and cardiac status. These findings suggest that GLS may serve as a useful tool to improve risk stratification in patients with HF.



JAMA Cardiol: 31 Mar 2021; 6:448-456
Tröbs SO, Prochaska JH, Schwuchow-Thonke S, Schulz A, ... Münzel T, Wild PS
JAMA Cardiol: 31 Mar 2021; 6:448-456 | PMID: 33533883
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Impact:
Abstract

Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial.

Lindenfeld J, Abraham WT, Grayburn PA, Kar S, ... Stone GW, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Investigators
Importance
Transcatheter mitral valve repair (TMVr) plus maximally tolerated guideline-directed medical therapy (GDMT) reduced heart failure (HF) hospitalizations (HFHs) and all-cause mortality (ACM) in symptomatic patients with HF and secondary mitral regurgitation (SMR) compared with GDMT alone in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial but not in a similar trial, Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR), possibly because the degree of SMR relative to the left ventricular end-diastolic volume index (LVEDVi) was substantially lower.
Objective
To explore contributions of the degree of SMR using the effective regurgitation orifice area (EROA), regurgitant volume (RV), and LVEDVi to the benefit of TMVr in the COAPT trial.
Design, setting, and participants
This post hoc secondary analysis of the COAPT randomized clinical trial performed December 27, 2012, to June 23, 2017, evaluated a subgroup of COAPT patients (group 1) with characteristics consistent with patients enrolled in MITRA-FR (n = 56) (HF with grade 3+ to 4+ SMR, left ventricular ejection fraction of 20%-50%, and New York Heart Association function class II-IV) compared with remaining (group 2) COAPT patients (n = 492) using the end point of ACM or HFH at 24 months, components of the primary end point, and quality of life (QOL) (per the Kansas City Cardiomyopathy Questionnaire overall summary score) and 6-minute walk distance (6MWD). The same end points were evaluated in 6 subgroups of COAPT by combinations of EROA and LVEDVi and of RV relative to LVEDVi.
Interventions
Interventions were TMVr plus GDMT vs GDMT alone.
Results
A total of 548 participants (mean [SD] age, 71.9 [11.2] years; 351 [64%] male) were included. In group 1, no significant difference was found in the composite rate of ACM or HFH between TMVr plus GDMT vs GDMT alone at 24 months (27.8% vs 33.1%, P = .83) compared with a significant difference at 24 months (31.5% vs 50.2%, P < .001) in group 2. However, patients randomized to receive TMVr vs those treated with GDMT alone had significantly greater improvement in QOL at 12 months (mean [SD] Kansas City Cardiomyopathy Questionnaire summary scores: group 1: 18.36 [5.38] vs 0.43 [4.00] points; P = .01; group 2: 16.54 [1.57] vs 5.78 [1.82] points; P < .001). Group 1 TMVr-randomized patients vs those treated with GDMT alone also had significantly greater improvement in 6MWD at 12 months (mean [SD] paired improvement: 39.0 [28.6] vs -48.0 [18.6] m; P = .02). Group 2 TMVr-randomized patients vs those treated with GDMT alone tended to have greater improvement in 6MWD at 12 months, but the difference did not reach statistical significance (mean [SD] paired improvement: 35.0 [7.7] vs 16.0 [9.1] m; P = .11).

Conclusions:
and relevance
A small subgroup of COAPT-resembling patients enrolled in MITRA-FR did not achieve improvement in ACM or HFH at 24 months but had a significant benefit on patient-centered outcomes (eg, QOL and 6MWD). Further subgroup analyses with 24-month follow-up suggest that the benefit of TMVr is not fully supported by the proportionate-disproportionate hypothesis.
Trial registration
ClinicalTrials.gov Identifier: NCT01626079.



JAMA Cardiol: 31 Mar 2021; 6:427-436
Lindenfeld J, Abraham WT, Grayburn PA, Kar S, ... Stone GW, Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Investigators
JAMA Cardiol: 31 Mar 2021; 6:427-436 | PMID: 33533873
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Impact:
Abstract

Efficacy and Safety of Revacept, a Novel Lesion-Directed Competitive Antagonist to Platelet Glycoprotein VI, in Patients Undergoing Elective Percutaneous Coronary Intervention for Stable Ischemic Heart Disease: The Randomized, Double-blind, Placebo-Controlled ISAR-PLASTER Phase 2 Trial.

Mayer K, Hein-Rothweiler R, Schüpke S, Janisch M, ... Kastrati A, Massberg S
Importance
The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant.
Objective
To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI.
Design, setting, and participants
A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI).
Interventions
Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy.
Main outcomes and measures
The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days.
Results
Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5\'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36).

Conclusions:
and relevance
Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms.
Trial registration
ClinicalTrials.gov Identifier: NCT03312855.



JAMA Cardiol: 30 Mar 2021; epub ahead of print
Mayer K, Hein-Rothweiler R, Schüpke S, Janisch M, ... Kastrati A, Massberg S
JAMA Cardiol: 30 Mar 2021; epub ahead of print | PMID: 33787834
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Impact:
Abstract

Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction: A Prespecified Analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial.

Butt JH, Docherty KF, Petrie MC, Schou M, ... McMurray JJV, Køber L
Importance
Women may respond differently to certain treatments for heart failure (HF) with reduced ejection fraction (HFrEF) than men.
Objective
To investigate the efficacy and safety of dapagliflozin compared with placebo in men and women with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
Design, setting, and participants
Prespecified subgroup analysis of a phase 3 randomized clinical trial conducted at 410 sites in 20 countries. Patients with New York Heart Association functional class II through IV with an ejection fraction of 40% or less and elevated N-terminal pro-B-type natriuretic peptide were eligible. Data were analyzed between June 2020 and January 2021.
Interventions
Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy.
Main outcomes and measures
The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.
Results
A total of 4744 patients were randomized in DAPA-HF, of whom 1109 were women (23.4%). Compared with placebo, dapagliflozin reduced the risk of worsening HF events or cardiovascular death to a similar extent in both men and women (hazard ratios, 0.73 [95% CI, 0.63-0.85] and 0.79 [95% CI, 0.59-1.06], respectively; P for interaction = .67). Consistent benefits were observed for the components of the primary outcome and all-cause mortality. Compared with placebo, dapagliflozin increased the proportion of patients with a meaningful improvement in symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score of ≥5 points; men, 59% vs 50%; women, 57% vs 54%; P for interaction = .14) and decreased the proportion with worsening symptoms (Kansas City Cardiomyopathy Questionnaire total symptom score decrease of ≥5 points; men, 25% vs 34%; women, 27% vs 31%; P for interaction = .15), irrespective of sex. Results were consistent for the Kansas City Cardiomyopathy Questionnaire clinical summary score and overall summary score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either men or women.

Conclusions:
and relevance
Dapagliflozin reduced the risk of worsening HF, cardiovascular death, and all-cause death and improved symptoms, physical function, and health-related quality of life similarly in men and women with heart failure and reduced ejection fraction. In addition, dapagliflozin was safe and well-tolerated irrespective of sex.
Trial registration
ClinicalTrials.gov Identifier: NCT03036124.



JAMA Cardiol: 30 Mar 2021; epub ahead of print
Butt JH, Docherty KF, Petrie MC, Schou M, ... McMurray JJV, Køber L
JAMA Cardiol: 30 Mar 2021; epub ahead of print | PMID: 33787831
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Impact:
Abstract

Screening for Atrial Fibrillation in the Older Population: A Randomized Clinical Trial.

Gladstone DJ, Wachter R, Schmalstieg-Bahr K, Quinn FR, ... Healey JS, SCREEN-AF Investigators and Coordinators
Importance
Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention.
Objective
To evaluate 2 home-based AF screening interventions.
Design, setting, and participants
This multicenter randomized clinical trial recruited individuals from primary care practices aged 75 years or older with hypertension and without known AF. From April 5, 2015, to March 26, 2019, 856 participants were enrolled from 48 practices.
Interventions
The control group received standard care (routine clinical follow-up plus a pulse check and heart auscultation at baseline and 6 months). The screening group received a 2-week continuous electrocardiographic (cECG) patch monitor to wear at baseline and at 3 months, in addition to standard care. The screening group also received automated home blood pressure (BP) machines with oscillometric AF screening capability to use twice-daily during the cECG monitoring periods.
Main outcomes and measures
With intention-to-screen analysis, the primary outcome was AF detected by cECG monitoring or clinically within 6 months. Secondary outcomes included anticoagulant use, device adherence, and AF detection by BP monitors.
Results
Of the 856 participants, 487 were women (56.9%); mean (SD) age was 80.0 (4.0) years. Median cECG wear time was 27.4 of 28 days (interquartile range [IQR], 18.4-28.0 days). In the primary analysis, AF was detected in 23 of 434 participants (5.3%) in the screening group vs 2 of 422 (0.5%) in the control group (relative risk, 11.2; 95% CI, 2.7-47.1; P = .001; absolute difference, 4.8%; 95% CI, 2.6%-7.0%; P < .001; number needed to screen, 21). Of those with cECG-detected AF, median total time spent in AF was 6.3 hours (IQR, 4.2-14.0 hours; range 1.3 hours-28 days), and median duration of the longest AF episode was 5.7 hours (IQR, 2.9-12.9 hours). Anticoagulation was initiated in 15 of 20 patients (75.0%) with cECG-detected AF. By 6 months, anticoagulant therapy had been prescribed for 18 of 434 participants (4.1%) in the screening group vs 4 of 422 (0.9%) in the control group (relative risk, 4.4; 95% CI, 1.5-12.8; P = .007; absolute difference, 3.2%; 95% CI, 1.1%-5.3%; P = .003). Twice-daily AF screening using the home BP monitor had a sensitivity of 35.0% (95% CI, 15.4%-59.2%), specificity of 81.0% (95% CI, 76.7%-84.8%), positive predictive value of 8.9% (95% CI, 4.9%-15.5%), and negative predictive value of 95.9% (95% CI, 94.5%-97.0%). Adverse skin reactions requiring premature discontinuation of cECG monitoring occurred in 5 of 434 participants (1.2%).

Conclusions:
and relevance
In this randomized clinical trial, among older community-dwelling individuals with hypertension, AF screening with a wearable cECG monitor was well tolerated, increased AF detection 10-fold, and prompted initiation of anticoagulant therapy in most cases. Compared with continuous ECG, intermittent oscillometric screening with a BP monitor was an inferior strategy for detecting paroxysmal AF. Large trials with hard clinical outcomes are now needed to evaluate the potential benefits and harms of AF screening.
Trial registration
ClinicalTrials.gov Identifier: NCT02392754.



JAMA Cardiol: 23 Mar 2021; epub ahead of print
Gladstone DJ, Wachter R, Schmalstieg-Bahr K, Quinn FR, ... Healey JS, SCREEN-AF Investigators and Coordinators
JAMA Cardiol: 23 Mar 2021; epub ahead of print | PMID: 33625468
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Impact:
Abstract

Comparison of New York Heart Association Class and Patient-Reported Outcomes for Heart Failure With Reduced Ejection Fraction.

Greene SJ, Butler J, Spertus JA, Hellkamp AS, ... Hernandez AF, Fonarow GC
Importance
It is unclear how New York Heart Association (NYHA) functional class compares with patient-reported outcomes among patients with heart failure (HF) in contemporary US clinical practice.
Objective
To characterize longitudinal changes and concordance between NYHA class and the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS), and their associations with clinical outcomes.
Design, setting, and participants
This cohort study included 2872 US outpatients with chronic HF with reduced ejection fraction across 145 practices enrolled in the CHAMP-HF registry between December 2015 and October 2017. All patients had complete NYHA class and KCCQ-OS data at baseline and 12 months. Longitudinal changes and correlations between the 2 measure were examined. Multivariable models landmarked at 12 months evaluated associations between improvement in NYHA and KCCQ-OS from baseline to 12 months with clinical outcomes occurring from months 12 through 24. Statistical analyses were performed from March to August 2020.
Exposure
Change in health status, as defined by 12-month change in NYHA class or KCCQ-OS.
Main outcomes and measures
All-cause mortality, HF hospitalization, and mortality or HF hospitalization.
Results
In total, 2872 patients were included in this analysis (median [interquartile range] age, 68 [59-75] years; 872 [30.4%] were women; and 2156 [75.1%] were of White race). At baseline, 312 patients (10.9%) were NYHA class I, 1710 patients (59.5%) were class II, 804 patients (28.0%) were class III, and 46 patients (1.6%) were class IV. For KCCQ-OS, 1131 patients (39.4%) scored 75 to 100 (best health status), 967 patients (33.7%) scored 50 to 74, 612 patients (21.3%) scored 25 to 49, and 162 patients (5.6%) scored 0 to 24 (worst health status). At 12 months, 1002 patients (34.9%) had a change in NYHA class (599 [20.9%] with improvement; 403 [14.0%] with worsening) and 2158 patients (75.1%) had a change of 5 or more points in KCCQ-OS (1388 [48.3%] with improvement; 770 [26.8%] with worsening). The most common trajectory for NYHA class was no change (1870 [65.1%]), and the most common trajectory for KCCQ-OS was an improvement of at least 10 points (1047 [36.5%]). After adjustment, improvement in NYHA class was not associated with subsequent clinical outcomes, whereas an improvement of 5 or more points in KCCQ-OS was independently associated with decreased mortality (hazard ratio, 0.59; 95% CI, 0.44-0.80; P < .001) and mortality or HF hospitalization (hazard ratio, 0.73; 95% CI, 0.59-0.89; P = .002).

Conclusions:
and relevance
Findings of this cohort study suggest that, in contemporary US clinical practice, compared with NYHA class, KCCQ-OS is more sensitive to clinically meaningful changes in health status over time. Changes in KCCQ-OS may have more prognostic value than changes in NYHA class.



JAMA Cardiol: 23 Mar 2021; epub ahead of print
Greene SJ, Butler J, Spertus JA, Hellkamp AS, ... Hernandez AF, Fonarow GC
JAMA Cardiol: 23 Mar 2021; epub ahead of print | PMID: 33760037
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Impact:
Abstract

Utility of a Deep-Learning Algorithm to Guide Novices to Acquire Echocardiograms for Limited Diagnostic Use.

Narang A, Bae R, Hong H, Thomas Y, ... Weissman NJ, Thomas JD
Importance
Artificial intelligence (AI) has been applied to analysis of medical imaging in recent years, but AI to guide the acquisition of ultrasonography images is a novel area of investigation. A novel deep-learning (DL) algorithm, trained on more than 5 million examples of the outcome of ultrasonographic probe movement on image quality, can provide real-time prescriptive guidance for novice operators to obtain limited diagnostic transthoracic echocardiographic images.
Objective
To test whether novice users could obtain 10-view transthoracic echocardiographic studies of diagnostic quality using this DL-based software.
Design, setting, and participants
This prospective, multicenter diagnostic study was conducted in 2 academic hospitals. A cohort of 8 nurses who had not previously conducted echocardiograms was recruited and trained with AI. Each nurse scanned 30 patients aged at least 18 years who were scheduled to undergo a clinically indicated echocardiogram at Northwestern Memorial Hospital or Minneapolis Heart Institute between March and May 2019. These scans were compared with those of sonographers using the same echocardiographic hardware but without AI guidance.
Interventions
Each patient underwent paired limited echocardiograms: one from a nurse without prior echocardiography experience using the DL algorithm and the other from a sonographer without the DL algorithm. Five level 3-trained echocardiographers independently and blindly evaluated each acquisition.
Main outcomes and measures
Four primary end points were sequentially assessed: qualitative judgement about left ventricular size and function, right ventricular size, and the presence of a pericardial effusion. Secondary end points included 6 other clinical parameters and comparison of scans by nurses vs sonographers.
Results
A total of 240 patients (mean [SD] age, 61 [16] years old; 139 men [57.9%]; 79 [32.9%] with body mass indexes >30) completed the study. Eight nurses each scanned 30 patients using the DL algorithm, producing studies judged to be of diagnostic quality for left ventricular size, function, and pericardial effusion in 237 of 240 cases (98.8%) and right ventricular size in 222 of 240 cases (92.5%). For the secondary end points, nurse and sonographer scans were not significantly different for most parameters.

Conclusions:
and relevance
This DL algorithm allows novices without experience in ultrasonography to obtain diagnostic transthoracic echocardiographic studies for evaluation of left ventricular size and function, right ventricular size, and presence of a nontrivial pericardial effusion, expanding the reach of echocardiography to clinical settings in which immediate interrogation of anatomy and cardiac function is needed and settings with limited resources.



JAMA Cardiol: 17 Mar 2021; epub ahead of print
Narang A, Bae R, Hong H, Thomas Y, ... Weissman NJ, Thomas JD
JAMA Cardiol: 17 Mar 2021; epub ahead of print | PMID: 33599681
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Impact:
Abstract

Magnetic Resonance Imaging in Patients With Cardiac Implantable Electronic Devices With Abandoned Leads.

Schaller RD, Brunker T, Riley MP, Marchlinski FE, Nazarian S, Litt H
Importance
Magnetic resonance imaging (MRI) is the modality of choice for many conditions. Conditional devices and novel protocols for imaging patients with legacy cardiac implantable electronic devices (CIEDs) have increased access to MRI in patients with devices. However, the presence of abandoned leads remains an absolute contraindication.
Objective
To assess if the performance of an MRI in the presence of an abandoned CIED lead is safe and whether there are deleterious effects on concomitant active CIED leads.
Design, setting, and participants
This cohort study included consecutive CIED recipients undergoing 1.5-T MRI with at least 1 abandoned lead between January 2013 and June 2020. MRI scans were performed at the Hospital of the University of Pennsylvania. No patients were excluded.
Exposures
CIEDs were reprogrammed based on patient-specific pacing needs. Electrocardiography telemetry and pulse oximetry were monitored continuously, and live contact with the patient throughout the scan via visual and voice contact was performed if possible. After completion of the MRI, CIED evaluation was repeated and programming returned to baseline or to a clinically appropriate setting.
Main outcomes and measures
Variation in pre- and post-MRI capture threshold of 50% or more, ventricular sensing 40% or more, and lead impedance 30% or more, as well as clinical sequelae such as pain and sustained tachyarrhythmia were considered significant. Long-term follow-up lead-related data were analyzed if available.
Results
A total of 139 consecutive patients (110 men [79%]) with a mean (SD) age of 65.6 (13.4) years underwent 200 MRIs of various anatomic regions including the thorax. Repeat examinations were common with a maximum of 16 examinations for 1 patient. There was a total of 243 abandoned leads with a mean (SD) of 1.22 (0.45) per patient. The mean (SD) number of active leads was 2.04 (0.78) and 64 patients (46%) were pacemaker dependent. A transmit-receive radiofrequency coil was used in 41 patients (20.5%), all undergoing MRI of the brain. There were no abnormal vital signs or sustained tachyarrhythmias. No changes in battery voltage, power-on reset events, or changes of pacing rate were noted. CIED parameter changes including decreased right atrial sensing in 4 patients and decreased left ventricular R-wave amplitude in 1 patient were transiently noted. One patient with an abandoned subcutaneous array experienced sternal heating that subsided on premature cessation of the study.

Conclusions:
and relevance
The risk of MRI in patients with abandoned CIED leads was low in this large observational study, including patients who underwent examination of the thorax. The growing aggregate of data questions the absolute contraindication for MRI in patients with abandoned CIED leads.



JAMA Cardiol: 16 Mar 2021; epub ahead of print
Schaller RD, Brunker T, Riley MP, Marchlinski FE, Nazarian S, Litt H
JAMA Cardiol: 16 Mar 2021; epub ahead of print | PMID: 33595595
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Impact:
Abstract

Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction.

Berg DD, Jhund PS, Docherty KF, Murphy SA, ... McMurray JJV, Sabatine MS
Importance
Dapagliflozin has been shown to reduce the risk of cardiovascular death or worsening heart failure (HF) in patients with chronic HF and reduced ejection fraction (HFrEF). However, clinical inertia often underlies deferred initiation of effective therapies.
Objective
To examine timing of onset of clinical benefit with dapagliflozin and magnitude as a function of proximity to prior HF hospitalization.
Design, setting, and participants
This is a secondary analysis of a completed multinational trial. The Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure trial was a double-blind, placebo-controlled randomized clinical trial of dapagliflozin in patients with chronic HFrEF (n = 4744). From February 2017 to August 2018, the study enrolled patients in New York Heart Association classes II through IV and with left ventricular ejection fraction of 40% or less; the median (range) follow-up time was 18.2 (0-27.8) months. Hazard ratios (HRs) were calculated for the primary efficacy outcome with dapagliflozin vs placebo by time following randomization. Efficacy and safety of dapagliflozin were assessed according to the timing of the most recent HF hospitalization prior to trial enrollment.
Exposures
None.
Main outcomes and measures
Composite of cardiovascular death or worsening HF.
Results
A total of 4744 patients were included (1109 women [23.4%]; mean [SD] age, 66.3 [10.9] years). The reduction in the primary outcome with dapagliflozin was rapidly apparent, with a sustained statistically significant benefit by 28 days after randomization (HR at 28 days, 0.51 [95% CI, 0.28-0.94]; P = .03). A total of 2251 patients (47.4%) had been previously hospitalized for HF, and 1301 (27.4%) had been hospitalized within 12 months prior to enrollment. Among patients treated with placebo, there was a stepwise gradient of risk for the primary outcome according to timing of most recent HF hospitalization, with 2-year Kaplan-Meier rates of 21.1%, 25.3%, and 33.8% (adjusted P = .003) for patients with a prior HF hospitalization never, more than 12 months ago, and 12 or fewer months ago, respectively. Across these subgroups, dapagliflozin reduced the relative risk of the primary outcome by 16% (HR, 0.84 [95% CI, 0.69-1.01]), 27% (HR, 0.73 [95% CI, 0.54-0.99]), and 36% (HR, 0.64 [95% CI, 0.51-0.80]), respectively (P = .07 for trend). Accordingly, patients with a more recent HF hospitalization tended to experience greater absolute risk reductions with dapagliflozin at 2 years: 2.1% (95% CI, -1.9% to 6.1%), 4.1% (95% CI, -3.6% to 11.7%), and 9.9% (95% CI, 3.3%-16.5%), respectively (P = .05 for trend).

Conclusions:
and relevance
In this study, treatment with dapagliflozin was associated with rapid reduction in the risk of cardiovascular death or worsening HF, with a sustained statistically significant benefit emerging very early after randomization. Patients with a more recent HF hospitalization were at particularly high risk and experienced greater relative and absolute risk reductions with dapagliflozin.
Trial registration
ClinicalTrials.gov Identifier NCT03036124.



JAMA Cardiol: 16 Mar 2021; epub ahead of print
Berg DD, Jhund PS, Docherty KF, Murphy SA, ... McMurray JJV, Sabatine MS
JAMA Cardiol: 16 Mar 2021; epub ahead of print | PMID: 33595593
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Impact:
Abstract

Association of Posttraumatic Stress Disorder and Incident Ischemic Heart Disease in Women Veterans.

Ebrahimi R, Lynch KE, Beckham JC, Dennis PA, ... Shroyer ALW, Sumner JA
Importance
Posttraumatic stress disorder (PTSD) is associated with greater risk of ischemic heart disease (IHD) in predominantly male populations or limited community samples. Women veterans represent a growing, yet understudied, population with high levels of trauma exposure and unique cardiovascular risks, but research on PTSD and IHD in this group is lacking.
Objective
To determine whether PTSD is associated with incident IHD in women veterans.
Design, setting, and participants
In this retrospective, longitudinal cohort study of the national Veterans Health Administration (VHA) electronic medical records, the a priori hypothesis that PTSD would be associated with greater risk of IHD onset was tested. Women veterans 18 years or older with and without PTSD who were patients in the VHA from January 1, 2000, to December 31, 2017, were assessed for study eligibility. Exclusion criteria consisted of no VHA clinical encounters after the index visit, IHD diagnosis at or before the index visit, and IHD diagnosis within 90 days of the index visit. Propensity score matching on age at index visit, number of prior visits, and presence of traditional and female-specific cardiovascular risk factors and mental and physical health conditions was conducted to identify women veterans ever diagnosed with PTSD, who were matched in a 1:2 ratio to those never diagnosed with PTSD. Data were analyzed from October 1, 2018, to October 30, 2020.
Exposures
PTSD, defined by International Classification of Diseases, Ninth Revision (ICD-9), or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), diagnosis codes from inpatient or outpatient encounters.
Main outcomes and measures
Incident IHD, defined as new-onset coronary artery disease, angina, or myocardial infarction, based on ICD-9 and ICD-10 diagnosis codes from inpatient or outpatient encounters, and/or coronary interventions based on Current Procedural Terminology codes.
Results
A total of 398 769 women veterans, 132 923 with PTSD and 265 846 never diagnosed with PTSD, were included in the analysis. Baseline mean (SD) age was 40.1 (12.2) years. During median follow-up of 4.9 (interquartile range, 2.1-9.2) years, 4381 women with PTSD (3.3%) and 5559 control individuals (2.1%) developed incident IHD. In a Cox proportional hazards model, PTSD was significantly associated with greater risk of developing IHD (hazard ratio [HR], 1.44; 95% CI, 1.38-1.50). Secondary stratified analyses indicated that younger age identified women veterans with PTSD who were at greater risk of incident IHD. Effect sizes were largest for those younger than 40 years at baseline (HR, 1.72; 95% CI, 1.55-1.93) and decreased monotonically with increasing age (HR for ≥60 years, 1.24; 95% CI, 1.12-1.38).

Conclusions:
and relevance
This cohort study found that PTSD was associated with increased risk of IHD in women veterans and may have implications for IHD risk assessment in vulnerable individuals.



JAMA Cardiol: 16 Mar 2021; epub ahead of print
Ebrahimi R, Lynch KE, Beckham JC, Dennis PA, ... Shroyer ALW, Sumner JA
JAMA Cardiol: 16 Mar 2021; epub ahead of print | PMID: 33729463
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Impact:
Abstract

Metabolic Cost of Exercise Initiation in Patients With Heart Failure With Preserved Ejection Fraction vs Community-Dwelling Adults.

Shah RV, Schoenike MW, Armengol de la Hoz MÁ, Cunningham TF, ... Vasan RS, Lewis GD
Importance
Heart failure with preserved ejection fraction (HFpEF) is a joint metabolic and cardiovascular disorder with significant noncardiac contributions.
Objective
To define and quantify the metabolic cost of initiating exercise in individuals with and without HFpEF and its functional consequences.
Design, setting, and participants
This prospective cohort study included individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS). Analysis began April 2016 and ended November 2020.
Exposures
Internal work (IW), a measure of work equivalents required to initiate movement.
Main outcomes and measures
Using breath-by-breath oxygen uptake (V̇o2) measurements and V̇o2-work rate associations, cost of initiating exercise (IW) in patients with HFpEF (MGH-ExS) and in community-dwelling individuals (FHS) was quantified. Linear regression was used to estimate associations between IW and clinical/hemodynamic measures.
Results
Of 3231 patients, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. In the MGH-ExS cohort, 86 (47%) were women, the median (interquartile range) age was 63 (53-72) years, and the median (interquartile range) peak V̇o2 level was 13.33 (11.77-15.62) mL/kg/min. In the FHS cohort, 1620 (53%) were women, the median (interquartile range) age was 54 (48-60) years, and the median (interquartile range) peak V̇o2 level was 22.2 (17.85-27.35) mL/kg/min. IW was higher in patients with HFpEF and accounted for 27% (interquartile range, 21%-39%) of the total work (IW + measured external workload on the cycle), compared with 15% (interquartile range, 12%-20%) of that in FHS participants. Body mass index accounted for greatest explained variance in patients with HFpEF from MGH-ExS and FHS participants (22% and 18%, respectively), while resting cardiac output and biventricular filling pressures were not significantly associated with variance in IW in patients with HFpEF. A higher IW in patients with HFpEF was associated with a greater increase in left- and right-sided cardiac filing pressure during unloaded exercise, despite similar resting hemodynamic measures across IW.

Conclusions:
and relevance
This study found that internal work, a new body mass index-related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is associated with steep, early increases in cardiac filling pressures. These findings highlight the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.



JAMA Cardiol: 16 Mar 2021; epub ahead of print
Shah RV, Schoenike MW, Armengol de la Hoz MÁ, Cunningham TF, ... Vasan RS, Lewis GD
JAMA Cardiol: 16 Mar 2021; epub ahead of print | PMID: 33729454
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Impact:
Abstract

Association of Left Ventricular Systolic Function With Incident Heart Failure in Late Life.

Reimer Jensen AM, Zierath R, Claggett B, Skali H, ... Biering-Sørensen T, Shah AM
Importance
Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life.
Objective
To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life.
Design, setting, and participants
This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020.
Exposures
Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography.
Main outcomes and measures
Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e\', E/e\', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors.
Results
Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS.

Conclusions:
and relevance
These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.



JAMA Cardiol: 16 Mar 2021; epub ahead of print
Reimer Jensen AM, Zierath R, Claggett B, Skali H, ... Biering-Sørensen T, Shah AM
JAMA Cardiol: 16 Mar 2021; epub ahead of print | PMID: 33729428
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Impact:
Abstract

Interpretation of the Seattle Angina Questionnaire as an Outcome Measure in Clinical Trials and Clinical Care: A Review.

Thomas M, Jones PG, Arnold SV, Spertus JA
Importance
Patient-reported outcomes are increasingly used as end points in clinical trials, assessments in clinical care, and tools for population health, with an increasing role in quality assessment. For patients with coronary artery disease, the Seattle Angina Questionnaire (SAQ) has emerged as the most commonly used measure of disease-specific health status to quantify patients\' symptoms of angina and the extent to which their angina affects their functioning and quality of life. This review explains how to interpret the SAQ and describes the construction and face validity of the SAQ, focusing on aligning scores and changes in scores with clinical constructs.
Observations
The SAQ asks questions similar to those an experienced clinician would ask of a patient with stable ischemic heart disease. Therefore, SAQ scores can be aligned with clinical constructs (eg, scores on the SAQ angina frequency scale of 0-30 points indicate daily angina, 31-60 points indicate weekly angina, 61-99 points indicate monthly angina, and 100 points indicate no angina), and changes in scores can be described by aligning them with changes in question responses. After clinical thresholds are defined, it is important for clinical trials to not simply report mean differences between treatment arms but to also report the distributions of patients who have had clinically important benefits so that a number needed to treat can be generated.

Conclusions:
and relevance
The widespread use of the SAQ is a consequence of its well-established validity, reproducibility, prognostic importance, and sensitivity to clinical change. Nevertheless, interpreting the SAQ can be challenging because of lack of familiarity with the clinical importance of its domains, either cross-sectionally or longitudinally. This review provides an overview of the interpretability of the SAQ as a foundation for its use as an end point in clinical trials, a tool to support more patient-centered care, and a means of facilitating population health strategies to provide a better foundation for the integration of patient experiences with clinical care.



JAMA Cardiol: 09 Mar 2021; epub ahead of print
Thomas M, Jones PG, Arnold SV, Spertus JA
JAMA Cardiol: 09 Mar 2021; epub ahead of print | PMID: 33566062
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Impact:
Abstract

Use of Artificial Intelligence and Deep Neural Networks in Evaluation of Patients With Electrocardiographically Concealed Long QT Syndrome From the Surface 12-Lead Electrocardiogram.

Bos JM, Attia ZI, Albert DE, Noseworthy PA, Friedman PA, Ackerman MJ
Importance
Long QT syndrome (LQTS) is characterized by prolongation of the QT interval and is associated with an increased risk of sudden cardiac death. However, although QT interval prolongation is the hallmark feature of LQTS, approximately 40% of patients with genetically confirmed LQTS have a normal corrected QT (QTc) at rest. Distinguishing patients with LQTS from those with a normal QTc is important to correctly diagnose disease, implement simple LQTS preventive measures, and initiate prophylactic therapy if necessary.
Objective
To determine whether artificial intelligence (AI) using deep neural networks is better than the QTc alone in distinguishing patients with concealed LQTS from those with a normal QTc using a 12-lead electrocardiogram (ECG).
Design, setting, and participants
A diagnostic case-control study was performed using all available 12-lead ECGs from 2059 patients presenting to a specialized genetic heart rhythm clinic. Patients were included if they had a definitive clinical and/or genetic diagnosis of type 1, 2, or 3 LQTS (LQT1, 2, or 3) or were seen because of an initial suspicion for LQTS but were discharged without this diagnosis. A multilayer convolutional neural network was used to classify patients based on a 10-second, 12-lead ECG, AI-enhanced ECG (AI-ECG). The convolutional neural network was trained using 60% of the patients, validated in 10% of the patients, and tested on the remaining patients (30%). The study was conducted from January 1, 1999, to December 31, 2018.
Main outcomes and measures
The goal of the study was to test the ability of the convolutional neural network to distinguish patients with LQTS from those who were evaluated for LQTS but discharged without this diagnosis, especially among patients with genetically confirmed LQTS but a normal QTc value at rest (referred to as genotype positive/phenotype negative LQTS, normal QT interval LQTS, or concealed LQTS).
Results
Of the 2059 patients included, 1180 were men (57%); mean (SD) age at first ECG was 21.6 (15.6) years. All 12-lead ECGs from 967 patients with LQTS and 1092 who were evaluated for LQTS but discharged without this diagnosis were included for AI-ECG analysis. Based on the ECG-derived QTc alone, patients were classified with an area under the curve (AUC) value of 0.824 (95% CI, 0.79-0.858); using AI-ECG, the AUC was 0.900 (95% CI, 0.876-0.925). Furthermore, in the subset of patients who had a normal resting QTc (<450 milliseconds), the QTc alone distinguished those with LQTS from those without LQTS with an AUC of 0.741 (95% CI, 0.689-0.794), whereas the AI-ECG increased this discrimination to an AUC of 0.863 (95% CI, 0.824-0.903). In addition, the AI-ECG was able to distinguish the 3 main genotypic subgroups (LQT1, LQT2, and LQT3) with an AUC of 0.921 (95% CI, 0.890-0.951) for LQT1 compared with LQT2 and 3, 0.944 (95% CI, 0.918-0.970) for LQT2 compared with LQT1 and 3, and 0.863 (95% CI, 0.792-0.934) for LQT3 compared with LQT1 and 2.

Conclusions:
and relevance
In this study, the AI-ECG was found to distinguish patients with electrocardiographically concealed LQTS from those discharged without a diagnosis of LQTS and provide a nearly 80% accurate pregenetic test anticipation of LQTS genotype status. This model may aid in the detection of LQTS in patients presenting to an arrhythmia clinic and, with validation, may be the stepping stone to similar tools to be developed for use in the general population.



JAMA Cardiol: 09 Mar 2021; epub ahead of print
Bos JM, Attia ZI, Albert DE, Noseworthy PA, Friedman PA, Ackerman MJ
JAMA Cardiol: 09 Mar 2021; epub ahead of print | PMID: 33566059
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Impact:
Abstract

National Trends in Heart Failure Hospitalizations and Readmissions From 2010 to 2017.

Agarwal MA, Fonarow GC, Ziaeian B
Importance
Previous studies have described the secular trends of overall heart failure (HF) hospitalizations, but the literature describing the national trends of unique index hospitalizations and readmission visits for the primary management of HF is lacking.
Objectives
To examine contemporary overall and sex-specific trends of unique primary HF (grouped by number of visits for the same patient in a given year) and 30-day readmission visits in a large national US administrative database from 2010 to 2017.
Design, setting, and participants
This cohort study used data from all adult hospitalizations in the Nationwide Readmission Database from January 1, 2010, to December 31, 2017, with a primary diagnosis of HF. Data analyses were conducted from March to November 2020.
Exposures
Admission for a primary diagnosis of HF at discharge.
Main outcomes and measures
Unique and overall hospitalizations with a primary diagnosis of HF and postdischarge readmissions. Unique primary HF hospitalizations were grouped by number of visits for the same patient in a given year.
Results
There were 8 273 270 primary HF hospitalizations with a single primary HF admission present in 5 092 626 unique patients, and 1 269 109 had 2 or more HF hospitalizations. The mean age was 72.1 (95% CI, 72.0-72.3) years, and 48.9% (95% CI, 48.7-49.0) were women. The primary HF hospitalization rates per 1000 US adults declined from 4.4 in 2010 to 4.1 in 2013 and then increased from 4.2 in 2014 to 4.9 in 2017. The rates per 1000 US adults for postdischarge HF readmissions (1.0 in 2010 to 0.9 in 2014 to 1.1 in 2017) and all-cause 30-day readmissions (0.8 in 2010 to 0.7 in 2014 to 0.9 in 2017) had similar trends.

Conclusions:
and relevance
In this analysis of a nationally representative administrative data set, for primary HF admissions, crude rates of overall and unique patient hospitalizations declined from 2010 to 2014 followed by an increase from 2014 to 2017. Additionally, readmission visits after index HF hospitalizations followed a similar trend. Future studies are needed to verify these findings to improve policies for HF management.



JAMA Cardiol: 09 Mar 2021; epub ahead of print
Agarwal MA, Fonarow GC, Ziaeian B
JAMA Cardiol: 09 Mar 2021; epub ahead of print | PMID: 33566058
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Impact:
Abstract

Use of Machine Learning Models to Predict Death After Acute Myocardial Infarction.

Khera R, Haimovich J, Hurley NC, McNamara R, ... Mortazavi BJ, Krumholz HM
Importance
Accurate prediction of adverse outcomes after acute myocardial infarction (AMI) can guide the triage of care services and shared decision-making, and novel methods hold promise for using existing data to generate additional insights.
Objective
To evaluate whether contemporary machine learning methods can facilitate risk prediction by including a larger number of variables and identifying complex relationships between predictors and outcomes.
Design, setting, and participants
This cohort study used the American College of Cardiology Chest Pain-MI Registry to identify all AMI hospitalizations between January 1, 2011, and December 31, 2016. Data analysis was performed from February 1, 2018, to October 22, 2020.
Main outcomes and measures
Three machine learning models were developed and validated to predict in-hospital mortality based on patient comorbidities, medical history, presentation characteristics, and initial laboratory values. Models were developed based on extreme gradient descent boosting (XGBoost, an interpretable model), a neural network, and a meta-classifier model. Their accuracy was compared against the current standard developed using a logistic regression model in a validation sample.
Results
A total of 755 402 patients (mean [SD] age, 65 [13] years; 495 202 [65.5%] male) were identified during the study period. In independent validation, 2 machine learning models, gradient descent boosting and meta-classifier (combination including inputs from gradient descent boosting and a neural network), marginally improved discrimination compared with logistic regression (C statistic, 0.90 for best performing machine learning model vs 0.89 for logistic regression). Nearly perfect calibration in independent validation data was found in the XGBoost (slope of predicted to observed events, 1.01; 95% CI, 0.99-1.04) and the meta-classifier model (slope of predicted-to-observed events, 1.01; 95% CI, 0.99-1.02), with more precise classification across the risk spectrum. The XGBoost model reclassified 32 393 of 121 839 individuals (27%) and the meta-classifier model reclassified 30 836 of 121 839 individuals (25%) deemed at moderate to high risk for death in logistic regression as low risk, which were more consistent with the observed event rates.

Conclusions:
and relevance
In this cohort study using a large national registry, none of the tested machine learning models were associated with substantive improvement in the discrimination of in-hospital mortality after AMI, limiting their clinical utility. However, compared with logistic regression, XGBoost and meta-classifier models, but not the neural network, offered improved resolution of risk for high-risk individuals.



JAMA Cardiol: 09 Mar 2021; epub ahead of print
Khera R, Haimovich J, Hurley NC, McNamara R, ... Mortazavi BJ, Krumholz HM
JAMA Cardiol: 09 Mar 2021; epub ahead of print | PMID: 33688915
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Impact:
Abstract

Prevalence of Inflammatory Heart Disease Among Professional Athletes With Prior COVID-19 Infection Who Received Systematic Return-to-Play Cardiac Screening.

Martinez MW, Tucker AM, Bloom OJ, Green G, ... Putukian M, Engel DJ
Importance
The major North American professional sports leagues were among the first to return to full-scale sport activity during the coronavirus disease 2019 (COVID-19) pandemic. Given the unknown incidence of adverse cardiac sequelae after COVID-19 infection in athletes, these leagues implemented a conservative return-to-play (RTP) cardiac testing program aligned with American College of Cardiology recommendations for all athletes testing positive for COVID-19.
Objective
To assess the prevalence of detectable inflammatory heart disease in professional athletes with prior COVID-19 infection, using current RTP screening recommendations.
Design, setting, and participants
This cross-sectional study reviewed RTP cardiac testing performed between May and October 2020 on professional athletes who had tested positive for COVID-19. The professional sports leagues (Major League Soccer, Major League Baseball, National Hockey League, National Football League, and the men\'s and women\'s National Basketball Association) implemented mandatory cardiac screening requirements for all players who had tested positive for COVID-19 prior to resumption of team-organized sports activities.
Exposures
Troponin testing, electrocardiography (ECG), and resting echocardiography were performed after a positive COVID-19 test result. Interleague, deidentified cardiac data were pooled for collective analysis. Those with abnormal screening test results were referred for additional testing, including cardiac magnetic resonance imaging and/or stress echocardiography.
Main outcomes and measures
The prevalence of abnormal RTP test results potentially representing COVID-19-associated cardiac injury, and results and outcomes of additional testing generated by the initial screening process.
Results
The study included 789 professional athletes (mean [SD] age, 25 [3] years; 777 men [98.5%]). A total of 460 athletes (58.3%) had prior symptomatic COVID-19 illness, and 329 (41.7%) were asymptomatic or paucisymptomatic (minimally symptomatic). Testing was performed a mean (SD) of 19 (17) days (range, 3-156 days) after a positive test result. Abnormal screening results were identified in 30 athletes (3.8%; troponin, 6 athletes [0.8%]; ECG, 10 athletes [1.3%]; echocardiography, 20 athletes [2.5%]), necessitating additional testing; 5 athletes (0.6%) ultimately had cardiac magnetic resonance imaging findings suggesting inflammatory heart disease (myocarditis, 3; pericarditis, 2) that resulted in restriction from play. No adverse cardiac events occurred in athletes who underwent cardiac screening and resumed professional sport participation.

Conclusions:
and relevance
This study provides large-scale data assessing the prevalence of relevant COVID-19-associated cardiac pathology with implementation of current RTP screening recommendations. While long-term follow-up is ongoing, few cases of inflammatory heart disease have been detected, and a safe return to professional sports activity has thus far been achieved.



JAMA Cardiol: 03 Mar 2021; epub ahead of print
Martinez MW, Tucker AM, Bloom OJ, Green G, ... Putukian M, Engel DJ
JAMA Cardiol: 03 Mar 2021; epub ahead of print | PMID: 33662103
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Impact:
Abstract

Derivation and Validation of a 4-Level Clinical Pretest Probability Score for Suspected Pulmonary Embolism to Safely Decrease Imaging Testing.

Roy PM, Friou E, Germeau B, Douillet D, ... Moumneh T, Penaloza A
Importance
In patients with suspected pulmonary embolism (PE), overuse of diagnostic imaging is an important point of concern.
Objective
To derive and validate a 4-level pretest probability rule (4-Level Pulmonary Embolism Clinical Probability Score [4PEPS]) that makes it possible to rule out PE solely on clinical criteria and optimized D-dimer measurement to safely decrease imaging testing for suspected PE.
Design, setting, and participants
This study included consecutive outpatients suspected of having PE from US and European emergency departments. Individual data from 3 merged management studies (n = 11 114; overall prevalence of PE, 11%) were used for the derivation cohort and internal validation cohort. The external validation cohorts were taken from 2 independent studies, the first with a high PE prevalence (n = 1548; prevalence, 21.5%) and the second with a moderate PE prevalence (n = 1669; prevalence, 11.7%). A prior definition of pretest probability target values to achieve a posttest probability less than 2% was used on the basis of the negative likelihood ratios of D-dimer. Data were collected from January 2003 to April 2016, and data were analyzed from June 2018 to August 2019.
Main outcomes and measures
The rate of PE diagnosed during the initial workup or during follow-up and the rate of imaging testing.
Results
Of the 5588 patients in the derivation cohort, 3441 (61.8%) were female, and the mean (SD) age was 52 (18.5) years. The 4PEPS comprises 13 clinical variables scored from -2 to 5. It results in the following strategy: (1) very low probability of PE if 4PEPS is less than 0: PE ruled out without testing; (2) low probability of PE if 4PEPS is 0 to 5: PE ruled out if D-dimer level is less than 1.0 μg/mL; (3) moderate probability of PE if 4PEPS is 6 to 12: PE ruled out if D-dimer level is less than the age-adjusted cutoff value; (4) high probability of PE if 4PEPS is greater than 12: PE ruled out by imaging without preceding D-dimer test. In the first and the second external validation cohorts, the area under the receiver operator characteristic curves were 0.79 (95% CI, 0.76 to 0.82) and 0.78 (95% CI, 0.74 to 0.81), respectively. The false-negative testing rates if the 4PEPS strategy had been applied were 0.71% (95% CI, 0.37 to 1.23) and 0.89% (95% CI, 0.53 to 1.49), respectively. The absolute reductions in imaging testing were -22% (95% CI, -26 to -19) and -19% (95% CI, -22 to -16) in the first and second external validation cohorts, respectively. The 4PEPS strategy compared favorably with all recent strategies in terms of imaging testing.

Conclusions:
and relevance
The 4PEPS strategy may lead to a substantial and safe reduction in imaging testing for patients with suspected PE. It should now be tested in a formal outcome study.



JAMA Cardiol: 02 Mar 2021; epub ahead of print
Roy PM, Friou E, Germeau B, Douillet D, ... Moumneh T, Penaloza A
JAMA Cardiol: 02 Mar 2021; epub ahead of print | PMID: 33656522
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Impact:
Abstract

Long-term Clinical and Echocardiographic Outcomes in Young and Middle-aged Adults Undergoing the Ross Procedure.

Romeo JLR, Papageorgiou G, da Costa FFD, Sievers HH, ... Takkenberg JJM, Mokhles MM
Importance
There is no ideal valve substitute for young adults requiring aortic valve replacement. Multicenter data supporting use of the Ross procedure with respect to long-term postoperative valve-related mortality and reintervention, as well as function of the autograft and pulmonary homograft, are needed.
Objective
To determine the long-term clinical and echocardiographic outcomes in young and middle-aged patients undergoing the Ross procedure.
Design, setting, and participants
A retrospective multicenter international cohort study with a median follow-up period of 9.2 years was conducted in 5 experienced centers regularly performing the Ross procedure. Consecutive patients aged 18 to 65 years were included by each center between 1991 and 2018.
Main outcomes and measures
Survival and autograft-related and homograft-related reintervention. Serial echocardiographic measurements of valve function were analyzed using mixed-effects modeling.
Results
During the study period, 1431 patients (74.3% men; n = 1063) were operated on at a median age of 48.5 years (mean [SD], 47.7 [9.5]; range, 18.1-65; interquartile range, 42.7-54.0). Implantation techniques were root inclusion in 355 (24.9%), root replacement in 485 (34.0%), and subcoronary implantation in 587 (41.1%). Right ventricular outflow tract reconstruction was performed with homografts in 98.6% (n = 1189) and bioprostheses in 1.4% (n = 17). Ten patients (0.7%) died before discharge. Median follow-up was 9.2 years (13 015 total patient-years). Survival after 10 and 15 years was 95.1% (95% CI, 93.8%-96.5%) and 88.5% (95% CI, 85.9%-91.1%), respectively. Freedom from autograft and homograft reintervention after 15 years was 92.0% and 97.2%, respectively. Late events were autograft endocarditis in 14 patients (0.11% per patient-year), homograft endocarditis in 11 patients (0.08% per patient-year), and stroke in 37 patients (0.3% per patient-year).

Conclusions:
and relevance
Given its excellent short-term and long-term outcome in young and middle-aged adults in this study, the Ross procedure should be considered in young and middle-aged adults who require aortic valve replacement. Patients should be referred to an experienced center with a program dedicated to the Ross procedure.



JAMA Cardiol: 02 Mar 2021; epub ahead of print
Romeo JLR, Papageorgiou G, da Costa FFD, Sievers HH, ... Takkenberg JJM, Mokhles MM
JAMA Cardiol: 02 Mar 2021; epub ahead of print | PMID: 33656518
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Impact:
Abstract

Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy: Secondary Analysis From the FOURIER Randomized Clinical Trial.

Deedwania P, Murphy SA, Scheen A, Badariene J, ... Sabatine MS, Giugliano RP
Importance
The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Patients with metabolic syndrome (MetS) are at increased cardiovascular risk.
Objective
To investigate outcomes with evolocumab in patients with and without MetS.
Design, setting, and participants
The FOURIER trial randomized patients worldwide with stable atherosclerotic cardiovascular disease receiving statin to evolocumab vs placebo with follow-up for a median of 2.2 years. Data were collected February 2013 to November 2016. For this prespecified analysis, patients with the requisite data were stratified based on the National Cholesterol Education Program Adult Treatment Panel III MetS criteria; in secondary analyses, patients were further substratified by diabetes at baseline. Analysis was intention to treat. Analysis began March 2018 and ended April 2020.
Interventions
Patients were randomized to evolocumab or placebo.
Main outcomes and measures
The primary end point was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point was cardiovascular death, myocardial infarction, or stroke.
Results
Of 27 342 patients (mean [SD] age, 63 [9] years; 20 623 men [75.4%]) included in this analysis, 16 361 (59.8%) with baseline MetS were, when compared with patients without MetS, at higher risk of cardiovascular events (adjusted hazard ratio [95% CI], 1.31 [1.18-1.46]; P < .001 for the primary and 1.38 [1.20-1.57]; P < .001 for the key secondary end point). Evolocumab reduced low-density lipoprotein cholesterol similarly in patients with MetS (median [interquartile range], 92 [79-109] mg/dL vs 30 [19-48] mg/dL; P < .001) and without MetS (median [interquartile range], 92 [81-108] mg/dL vs 29 [18-44] mg/dl; P < .001). For the primary end point, the hazard ratios (95% CI) with evolocumab vs placebo were 0.83 (0.76-0.91) and 0.89 (0.79-1.01) in patients with and without MetS (P for interaction = .39). For the key secondary end point, the corresponding hazard ratios (95% CIs) were 0.76 (0.68-0.86) and 0.86 (0.74-1.01) (P for interaction = .23), respectively. Evolocumab did not increase the risk of new-onset diabetes or other major safety outcomes including worsening glycemic control, compared with placebo in patients with MetS.

Conclusions:
and relevance
Patients with atherosclerotic cardiovascular disease and MetS have substantial residual risk of cardiovascular events despite statin therapy. Evolocumab significantly reduced low-density lipoprotein cholesterol and cardiovascular risk in patients with MetS without increasing new-onset diabetes, worsening glycemic control, or other major safety events. These data suggest the addition of evolocumab to statin therapy in patients with atherosclerotic cardiovascular disease and MetS is safe and efficacious to reduce residual cardiovascular risk.
Trial registration
ClinicalTrials.gov Identifier: NCT01764633.



JAMA Cardiol: 28 Feb 2021; 6:139-147
Deedwania P, Murphy SA, Scheen A, Badariene J, ... Sabatine MS, Giugliano RP
JAMA Cardiol: 28 Feb 2021; 6:139-147 | PMID: 32785614
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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: 28 Feb 2021; 6:209-213
Wintzer-Wehekind J, Horlick E, Ibrahim R, Cheema AN, ... Houde C, Rodés-Cabau J
JAMA Cardiol: 28 Feb 2021; 6:209-213 | PMID: 32965476
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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: 28 Feb 2021; 6:148-158
McGuire DK, Shih WJ, Cosentino F, Charbonnel B, ... Masiukiewicz U, Cannon CP
JAMA Cardiol: 28 Feb 2021; 6:148-158 | PMID: 33031522
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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: 28 Feb 2021; 6:332-335
Shen C, Wadhera RK, Yeh RW
JAMA Cardiol: 28 Feb 2021; 6:332-335 | PMID: 33052371
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Impact:
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: 28 Feb 2021; 6:169-176
Pandey A, Keshvani N, Vaughan-Sarrazin MS, Gao Y, ... Yancy C, Girotra S
JAMA Cardiol: 28 Feb 2021; 6:169-176 | PMID: 33112393
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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: 28 Feb 2021; 6:159-167
Kilic A, Mathier MA, Hickey GW, Sultan I, ... Mulukutla SR, Keebler ME
JAMA Cardiol: 28 Feb 2021; 6:159-167 | 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: 28 Feb 2021; 6:179-187
Ajufo E, Ayers CR, Vigen R, Joshi PH, ... de Lemos JA, Khera A
JAMA Cardiol: 28 Feb 2021; 6:179-187 | PMID: 33112372
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Impact:
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: 28 Feb 2021; 6:189-198
Yang LT, Anand V, Zambito EI, Pellikka PA, ... Enriquez-Sarano M, Michelena HI
JAMA Cardiol: 28 Feb 2021; 6:189-198 | PMID: 33146680
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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: 28 Feb 2021; 6:214-218
Cauwenberghs N, Haddad F, Kuznetsova T
JAMA Cardiol: 28 Feb 2021; 6:214-218 | PMID: 33175083
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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: 28 Feb 2021; 6:258-266
Greve AM, Christoffersen M, Frikke-Schmidt R, Nordestgaard BG, Tybjærg-Hansen A
JAMA Cardiol: 28 Feb 2021; 6:258-266 | PMID: 33237279
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Impact:
Abstract

Objective Risk Assessment vs Standard Care for Acute Coronary Syndromes: A Randomized Clinical Trial.

Chew DP, Hyun K, Morton E, Horsfall M, ... Fox K, Brieger D
Importance
Although international guidelines recommend use of the Global Registries of Acute Coronary Events (GRACE) risk score (GRS) to guide acute coronary syndrome (ACS) treatment decisions, the prospective utility of the GRS in improving care and outcomes is unproven.
Objective
To assess the effect of routine GRS implementation on guideline-indicated treatments and clinical outcomes of hospitalized patients with ACS.
Design, setting, and participants
Prospective cluster (hospital-level) randomized open-label blinded end point (PROBE) clinical trial using a multicenter ACS registry of acute care cardiology services. Fixed sampling of the first 10 patients within calendar month, with either ST-segment elevation or non-ST-segment elevation ACS. The study enrolled patients from June 2014 to March 2018, and data were analyzed between February 2020 and April 2020.
Interventions
Implementation of routine risk stratification using the GRS and guideline recommendations.
Main outcomes and measures
The primary outcome was a performance score based on receipt of early invasive treatment, discharge prescription of 4 of 5 guideline-recommended pharmacotherapies, and cardiac rehabilitation referral. Clinical outcomes included a composite of all-cause death and/or myocardial infarction (MI) within 1 year.
Results
This study enrolled 2318 patients from 24 hospitals and was stopped prematurely owing to futility. Of the patients enrolled, median age was 65 years (interquartile range, 56-74 years), 29.5% were women (n = 684), and 62.9% were considered high risk (n = 1433). Provision of all 3 measures among high-risk patients did not differ between the randomized arms (GRS: 424 of 717 [59.9%] vs control: 376 of 681 [55.2%]; odds ratio [OR], 1.04; 95% CI, 0.63-1.71; P = .88). The provision of early invasive treatment was increased compared with the control arm (GRS: 1042 of 1135 [91.8%] vs control: 989 of 1183 [83.6%]; OR, 2.26; 95% CI, 1.30-3.96; P = .004). Prescription of 4 of 5 guideline-recommended pharmacotherapies (GRS: 864 of 1135 [76.7%] vs control: 893 of 1183 [77.5%]; OR, 0.97; 95% CI, 0.68-1.38) and cardiac rehabilitation (GRS: 855 of 1135 [75.1%] vs control: 861 of 1183 [72.8%]; OR, 0.68; 95% CI, 0.32-1.44) were not different. By 12 months, GRS intervention was not associated with a significant reduction in death or MI compared with the control group (GRS: 96 of 1044 [9.2%] vs control: 146 of 1087 [13.4%]; OR, 0.66; 95% CI, 0.38-1.14).

Conclusions:
and relevance
Routine GRS implementation in cardiology services with high levels of clinical care was associated with an increase in early invasive treatment but not other aspects of care. Low event rates and premature study discontinuation indicates the need for further, larger scale randomized studies.
Trial registration
anzctr.org.au Identifier: ACTRN12614000550606.



JAMA Cardiol: 28 Feb 2021; 6:304-313
Chew DP, Hyun K, Morton E, Horsfall M, ... Fox K, Brieger D
JAMA Cardiol: 28 Feb 2021; 6:304-313 | PMID: 33295965
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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: 28 Feb 2021; 6:316-325
Churchill TW, Petek BJ, Wasfy MM, Guseh JS, ... Chiampas G, Baggish AL
JAMA Cardiol: 28 Feb 2021; 6:316-325 | 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: 28 Feb 2021; 6:276-286
Pang Y, Kartsonaki C, Lv J, Fairhurst-Hunter Z, ... Li L, Chen Z
JAMA Cardiol: 28 Feb 2021; 6:276-286 | 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: 28 Feb 2021; 6:228-235
Godoy LC, Frankfurter C, Cooper M, Lay C, Maunder R, Farkouh ME
JAMA Cardiol: 28 Feb 2021; 6:228-235 | PMID: 33263716
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Impact:
Abstract

Mechanical Complications of Acute Myocardial Infarction: A Review.

Gong FF, Vaitenas I, Malaisrie SC, Maganti K
Importance
Mechanical complications of acute myocardial infarction include left ventricular free-wall rupture, ventricular septal rupture, papillary muscle rupture, pseudoaneurysm, and true aneurysm. With the introduction of early reperfusion therapies, these complications now occur in fewer than 0.1% of patients following an acute myocardial infarction. However, mortality rates have not decreased in parallel, and mechanical complications remain an important determinant of outcomes after myocardial infarction. Early diagnosis and management are crucial to improving outcomes and require an understanding of the clinical findings that should raise suspicion of mechanical complications and the evolving surgical and percutaneous treatment options.
Observations
Mechanical complications most commonly occur within the first week after myocardial infarction. Cardiogenic shock or acute pulmonary edema are frequent presentations. Echocardiography is usually the first test used to identify the type, location, and hemodynamic consequences of the mechanical complication. Hemodynamic stabilization often requires a combination of medical therapy and mechanical circulatory support. Surgery is the definitive treatment, but the optimal timing remains unclear. Percutaneous therapies are emerging as an alternative treatment option for patients at prohibitive surgical risk.

Conclusions:
and relevance
Mechanical complications present with acute and dramatic hemodynamic deterioration requiring rapid stabilization. Heart team involvement is required to determine appropriate management strategies for patients with mechanical complications after acute myocardial infarction.



JAMA Cardiol: 28 Feb 2021; 6:341-349
Gong FF, Vaitenas I, Malaisrie SC, Maganti K
JAMA Cardiol: 28 Feb 2021; 6:341-349 | PMID: 33295949
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Impact:

This program is still in alpha version.