Journal: JAMA Cardiol

Sorted by: date / impact
Abstract

Association Between High-Density Lipoprotein Cholesterol Levels and Adverse Cardiovascular Outcomes in High-risk Populations.

Liu C, Dhindsa D, Almuwaqqat Z, Ko YA, ... Sun YV, Quyyumi AA
Importance
Previous studies have shown lower cardiovascular risk with higher high-density lipoprotein cholesterol (HDL-C) levels. However, recent data in the general population have shown increased risk of adverse outcomes at very high HDL-C concentrations.
Objective
To study the association between very high HDL-C levels (>80 mg/dL) and mortality in patients with coronary artery disease (CAD) and to investigate the association of known HDL-C genotypes with high HDL-C level outcomes.
Design, setting, and participants
This prospective, multicenter, cohort study, conducted from 2006 to present in the UK and from 2003 to present in Atlanta, Georgia, recruited patients with CAD from the UK Biobank (UKB) and the Emory Cardiovascular Biobank (EmCAB), respectively. Patients without confirmed CAD were excluded from the study. Data analyses were conducted from May 10, 2020, to April 28, 2021.
Exposure
High HDL-C levels (>80 mg/dL).
Main outcomes and measures
The primary outcome was all-cause death. The secondary outcome was cardiovascular death.
Results
A total of 14 478 participants (mean [SD] age, 62.1 [5.8] years; 11 034 men [76.2%]) from the UKB and 5467 participants (mean [SD] age, 63.8 [12.3] years; 3632 men [66.4%]) from the EmCAB were included in the study. Over a median follow-up of 8.9 (IQR, 8.0-9.7) years in the UKB and 6.7 (IQR, 4.0-10.8) years in the EmCAB, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P < .001) and cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P = .02) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UKB after adjustment for confounding factors. These results were replicated in the EmCAB. These associations persisted after adjustment for the HDL-C genetic risk score within the UKB. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UKB (HR, 2.63; 95% CI, 1.75-3.95; P < .001 vs HR, 1.39; 95% CI, 0.82-2.35; P = .23).

Conclusions:
and relevance
Results of this cohort study suggest that very high HDL-C levels are paradoxically associated with higher mortality risk in individuals with CAD. This association was independent of the common polymorphisms associated with high HDL-C levels.



JAMA Cardiol: 18 May 2022; epub ahead of print
Liu C, Dhindsa D, Almuwaqqat Z, Ko YA, ... Sun YV, Quyyumi AA
JAMA Cardiol: 18 May 2022; epub ahead of print | PMID: 35583863
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lipoprotein(a) and its Significance in Cardiovascular Disease: A Review.

Duarte Lau F, Giugliano RP
Importance
Lipoprotein(a) (Lp[a]) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). This novel marker of cardiovascular disease acts through induction of vascular inflammation, atherogenesis, calcification, and thrombosis. While an absolute risk threshold remains to be universally accepted, an estimated 20% to 25% of the global population have Lp(a) levels of 50 mg/dL or higher, a level noted by the European Atherosclerosis Society to confer increased cardiovascular risk.
Observations
Compelling evidence from pathophysiological, observational, and genetic studies suggest a potentially causal association between high Lp(a) levels, atherosclerotic cardiovascular disease, and calcific aortic valve stenosis. Additional evidence has demonstrated that elevated Lp(a) levels are associated with a residual cardiovascular risk despite traditional risk factor optimization, including LDL cholesterol reduction. These findings have led to the formulation of the Lp(a) hypothesis, namely that Lp(a) lowering leads to cardiovascular risk reduction, intensifying the search for Lp(a)-reducing therapies. The ineffectiveness of lifestyle modification, statins, and ezetimibe to lower Lp(a); the modest Lp(a) reduction with proprotein convertase subtilisin/kexin type 9 inhibitors; the adverse effect profile and unclear cardiovascular benefit of pharmacotherapies such as niacin and mipomersen; and the impracticality of regular lipoprotein apheresis represent major challenges to currently available therapies. Nevertheless, emerging nucleic acid-based therapies, such as the antisense oligonucleotide pelacarsen and the small interfering RNA olpasiran, are generating interest because of their potent Lp(a)-lowering effects. Assessment of new-onset diabetes in patients achieving very low Lp(a) levels will be important in future trials.

Conclusions:
and relevance
Epidemiologic and genetic studies suggest a potentially causal association between elevated Lp(a) levels, atherosclerotic cardiovascular disease, and aortic valve stenosis. Emerging nucleic acid-based therapies have potent Lp(a)-lowering effects and appear safe; phase 3 trials will establish whether they improve cardiovascular outcomes.



JAMA Cardiol: 18 May 2022; epub ahead of print
Duarte Lau F, Giugliano RP
JAMA Cardiol: 18 May 2022; epub ahead of print | PMID: 35583875
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Rare and Common Genetic Variation Underlying the Risk of Hypertrophic Cardiomyopathy in a National Biobank.

Biddinger KJ, Jurgens SJ, Maamari D, Gaziano L, ... Ellinor PT, Aragam KG
Importance
Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death in young people. Although rare genetic variants are well-established contributors to HCM risk, common genetic variants have recently been implicated in disease pathogenesis.
Objective
To assess the contributions of rare and common genetic variation to risk of HCM in the general population.
Design, setting, and participants
This cohort study of the UK Biobank (data from 2006-2010) and the Mass General Brigham Biobank (2010-2019) assessed the relative and joint contributions of rare genetic variants and a common variant (polygenic) score to risk of HCM. Both rare and common variant predictors were then evaluated in the context of relevant clinical risk factors. Data analysis was conducted from May 2021 to February 2022.
Exposures
Pathogenic rare variants, common-variant (polygenic) score, and clinical risk factors.
Main outcomes and measures
Risk of HCM.
Results
The primary study population comprised 184 511 individuals from the UK Biobank. Mean (SD) age was 56 (8) years, 83 690 (45%) of participants were men, and 204 (0.1%) participants had HCM. Of 51 genes included in clinical genetic testing panels for HCM, pathogenic or likely pathogenic variants in 14 core genes (designated by the American College of Medical Genetics and Genomics [ACMG]) were associated with 55-fold higher odds (95% CI, 35-83) of HCM, while those in the remaining 37 non-ACMG genes were not significantly associated with HCM (OR, 1.8; 95% CI, 0.6-4.0). ClinVar pathogenic or likely pathogenic mutations in MYBPC3 (OR, 72; 95% CI, 39-124) and MYH7 (OR, 61; 95% CI, 26-121) were strongly associated with HCM, as were loss-of-function variants in ALPK3 (OR, 13; 95% CI, 4.4-28). A polygenic score was strongly associated with HCM (OR per SD increase in score, 1.6; 95% CI, 1.4-1.8), with concordant results in the Mass General Brigham Biobank. Genetic factors enhanced clinical risk prediction for HCM: addition of rare variant carrier status and the polygenic score to clinical risk factors (obesity, hypertension, atrial fibrillation, and coronary artery disease) improved the area under the receiver operator characteristic curve from 0.71 (95% CI, 0.65-0.77) to 0.82 (95% CI, 0.77-0.87).

Conclusions:
and relevance
Both rare and common genetic variants contribute substantially to HCM susceptibility in the general population and improve HCM risk prediction beyond that achieved with clinical factors.



JAMA Cardiol: 18 May 2022; epub ahead of print
Biddinger KJ, Jurgens SJ, Maamari D, Gaziano L, ... Ellinor PT, Aragam KG
JAMA Cardiol: 18 May 2022; epub ahead of print | PMID: 35583889
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mortality Among Patients With Early-Onset Atrial Fibrillation and Rare Variants in Cardiomyopathy and Arrhythmia Genes.

Yoneda ZT, Anderson KC, Ye F, Quintana JA, ... Roden DM, Shoemaker MB
Importance
Patients with early-onset atrial fibrillation (AF) are enriched for rare variants in cardiomyopathy and arrhythmia genes. The clinical significance of these rare variants in patients with early-onset AF is unknown.
Objective
To assess the association between rare variants in cardiomyopathy and arrhythmia genes detected in patients with early-onset AF and time to death.
Design, setting, and participants
This prospective cohort study included participants with AF diagnosed before 66 years of age who underwent whole-genome sequencing through the National Heart, Lung and Blood Institute\'s Trans-Omics for Precision Medicine program. Participants were enrolled from November 23, 1999, to June 2, 2015. Data were analyzed from February 26 to September 19, 2021.
Exposures
Rare variants identified in a panel of 145 genes that are included in cardiomyopathy and arrhythmia panels used by commercial clinical genetic testing laboratories.
Main outcomes and measures
The primary study outcome was time to death and was adjudicated from medical records and the National Death Index. Multivariable Cox proportional hazards regression was used to evaluate the association of disease-associated variants with risk of death after adjustment for age at AF diagnosis, sex, race, body mass index, left ventricular ejection fraction, and an interaction term of age at AF diagnosis and disease-associated variant status.
Results
Among 1293 participants (934 [72%] male; median age at enrollment, 56.0 years; IQR, 48.0-61.0 years), disease-associated (pathogenic or likely pathogenic) rare variants were found in 131 (10%). During a median follow-up of 9.9 years (IQR, 6.9-13.2 years), 219 participants (17%) died. In univariable analysis, disease-associated variants were associated with an increased risk of mortality (hazard ratio, [HR], 1.5; 95% CI, 1.0-2.1; P = .05); the association remained significant in multivariable modeling when adjusted for age at AF diagnosis, sex, race, body mass index, left ventricular ejection fraction, and an interaction term between disease-associated variant status and age at AF diagnosis. The interaction demonstrated that disease-associated variants were associated with a significantly higher risk of mortality compared with no disease-associated variant when AF was diagnosed at a younger age (P = .008 for interaction). Higher body mass index (per IQR: HR, 1.4; 95% CI, 1.2-1.6; P < .001) and lower left ventricular ejection fraction (per IQR: HR, 0.8; 95% CI, 0.7-0.8; P < .001) were associated with higher mortality risk. There were 73 cardiomyopathy-related deaths, 40 sudden deaths, and 10 stroke-related deaths. Mortality among patients with the most prevalent genes with disease-associated variants was 26% (10 of 38 patients) for TTN, 33% (6 of 18) for MYH7, 22% (2 of 9) for LMNA, 0% (0 of 10) for MYH6, and 0% (0 of 8) for KCNQ1.

Conclusions:
and relevance
The findings suggest that rare variants in cardiomyopathy and arrhythmia genes may be associated with increased risk of mortality among patients with early-onset AF, especially those diagnosed at a younger age. Genetic testing may provide important prognostic information for patients with early-onset AF.



JAMA Cardiol: 11 May 2022; epub ahead of print
Yoneda ZT, Anderson KC, Ye F, Quintana JA, ... Roden DM, Shoemaker MB
JAMA Cardiol: 11 May 2022; epub ahead of print | PMID: 35544069
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality.

Patel AP, Dron JS, Wang M, Pirruccello JP, ... Aragam KG, Khera AV
Importance
Pathogenic variants associated with inherited cardiomyopathy are recognized as important and clinically actionable when identified, leading some clinicians to recommend population-wide genomic screening.
Objective
To determine the prevalence and clinical importance of pathogenic variants associated with inherited cardiomyopathy within the context of contemporary clinical care.
Design, setting, and participants
This was a genetic association study of participants in Atherosclerosis in Risk Communities (ARIC), recruited from 1987 to 1989, with median follow-up of 27 years, and the UK Biobank, recruited from 2006 to 2010, with median follow-up of 10 years. ARIC participants were recruited from 4 sites across the US. UK Biobank participants were recruited from 22 sites across the UK. Participants in the US were of African and European ancestry; those in the UK were of African, East Asian, South Asian, and European ancestry. Statistical analyses were performed between August 1, 2021, and February 9, 2022.
Exposures
Rare genetic variants predisposing to inherited cardiomyopathy.
Main outcomes and measures
Pathogenicity of observed DNA sequence variants in sequenced exomes of 13 genes (ACTC1, FLNC, GLA, LMNA, MYBPC3, MYH7, MYL2, MYL3, PRKAG2, TNNI3, TNNT2, TPM1, and TTN) associated with inherited cardiomyopathies were classified by a blinded clinical geneticist per American College of Medical Genetics recommendations. Incidence of all-cause mortality, heart failure, and atrial fibrillation were determined. Cardiac magnetic resonance imaging, echocardiography, and electrocardiogram measures were assessed in a subset of participants.
Results
A total of 9667 ARIC participants (mean [SD] age, 54.0 [5.7] years; 4232 women [43.8%]; 2658 African [27.5%] and 7009 European [72.5%] ancestry) and 49 744 UK Biobank participants (mean [SD] age, 57.1 [8.0] years; 27 142 women [54.5%]; 1006 African [2.0%], 173 East Asian [0.3%], 939 South Asian [1.9%], and 46 449 European [93.4%] European ancestry) were included in the study. Of those, 59 participants (0.61%) in ARIC and 364 participants (0.73%) in UK Biobank harbored an actionable pathogenic or likely pathogenic variant associated with dilated or hypertrophic cardiomyopathy. Carriers of these variants were not reliably identifiable by imaging. However, the presence of these variants was associated with increased risk of heart failure (hazard ratio [HR], 1.7; 95% CI, 1.1-2.8), atrial fibrillation (HR, 2.9; 95% CI, 1.9-4.5), and all-cause mortality (HR, 1.5; 95% CI, 1.1-2.2) in ARIC. Similar risk patterns were observed in the UK Biobank.

Conclusions:
and relevance
Results of this genetic association study suggest that approximately 0.7% of study participants harbored a pathogenic variant associated with inherited cardiomyopathy. These variant carriers would be challenging to identify within clinical practice without genetic testing but are at increased risk for cardiovascular disease and all-cause mortality.



JAMA Cardiol: 11 May 2022; epub ahead of print
Patel AP, Dron JS, Wang M, Pirruccello JP, ... Aragam KG, Khera AV
JAMA Cardiol: 11 May 2022; epub ahead of print | PMID: 35544052
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Trends in 10-Year Outcomes Among Medicare Beneficiaries Who Survived an Acute Myocardial Infarction.

Wang Y, Leifheit EC, Krumholz HM
Importance
Short-term outcomes after acute myocardial infarction (AMI) have improved, but little is known about longer-term outcomes.
Objective
To evaluate trends in 10-year all-cause mortality and hospitalization for recurrent AMI by demographic subgroups and examine the association between recurrence and mortality.
Design, setting, and participants
Medicare fee-for-service beneficiaries who survived after AMI from 1995 to 2019. Subgroups were defined by age, sex, race, dual Medicare-Medicaid-eligible status, and residence in health priority areas (geographic areas with persistently high adjusted mortality and hospitalization rates). Data were analyzed from October 2020 to February 2022.
Exposure
Medicare fee-for-service beneficiaries who survived an AMI.
Main outcomes and measures
Ten-year all-cause mortality and hospitalization for recurrent AMI, beginning 30 days from the index AMI admission.
Results
Of an included 3 982 266 AMI survivors, 1 952 450 (49.0%) were female, and the mean (SD) age was 78.0 (7.4) years. Ten-year mortality and recurrent AMI rates were 72.7% (95% CI, 72.6-72.7) and 27.1% (95% CI, 27.0-27.2), respectively. Adjusted annual reductions were 1.5% (95% CI, 1.4-1.5) for mortality and 2.7% (95% CI, 2.6-2.7) for recurrence. In subgroup analyses balancing patient characteristics, hazard ratios (HRs) for mortality and recurrence were 1.13 (95% CI, 1.12-1.13) and 1.07 (95% CI, 1.06-1.07), respectively, for men vs women; 1.05 (95% CI, 1.05-1.06) and 1.08 (95% CI, 1.07-1.09) for Black vs White patients; 0.96 (95% CI, 0.95-0.96) and 1.00 (95% CI, 1.00-1.01) for other race (including American Indian and Alaska Native, Asian, Hispanic, other race or ethnicity, and unreported) vs White patients; 1.24 (95% CI, 1.24-1.24) and 1.21 (95% CI, 1.20-1.21) for dual Medicare-Medicaid-eligible vs non-dual Medicare-Medicaid-eligible patients; and 1.06 (95% CI, 1.06-1.07) and 1.00 (95% CI, 1.00-1.01) for patients in health priority areas vs other areas. For patients hospitalized in 2007 to 2009, the last 3 years for which full 10-year follow-up data were available, 10-year mortality risk was 13.9% lower than for those hospitalized in 1995 to 1997 (adjusted HR, 0.86; 95% CI, 0.85-0.87) and 10-year recurrence risk was 22.5% lower (adjusted HR, 0.77; 95% CI, 0.76-0.78). Mortality within 10 years after the initial AMI was higher for patients with a recurrent AMI (80.6%; 95% CI, 80.5-80.7) vs those without recurrence (72.4%; 95% CI, 72.3-72.5).

Conclusions:
and relevance
In this study, 10-year mortality and hospitalization for recurrence rates improved over the last decades for patients who survived the acute period of AMI. There were marked differences in outcomes and temporal trends across demographic subgroups, emphasizing the urgent need for prioritization of efforts to reduce inequities in long-term outcomes.



JAMA Cardiol: 04 May 2022; epub ahead of print
Wang Y, Leifheit EC, Krumholz HM
JAMA Cardiol: 04 May 2022; epub ahead of print | PMID: 35507330
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Long-term Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-analysis.

Amacher SA, Bohren C, Blatter R, Becker C, ... Marsch S, Hunziker S
Importance
Data on long-term survival beyond 12 months after out-of-hospital cardiac arrest (OHCA) of a presumed cardiac cause are scarce.
Objective
To investigate the long-term survival of adult patients after surviving the initial hospital stay for an OHCA.
Data sources
A systematic search of the EMBASE and MEDLINE databases was performed from database inception to March 25, 2021.
Study selection
Clinical studies reporting long-term survival after OHCA were selected based on predefined inclusion and exclusion criteria according to a preregistered study protocol.
Data extraction and synthesis
Patient data were reconstructed from Kaplan-Meier curves using an iterative algorithm and then pooled to generate survival curves. As a separate analysis, an aggregate data meta-analysis was performed.
Main outcomes and measures
The primary outcome was long-term survival (>12 months) after OHCA for patients surviving to hospital discharge or 30 days after OHCA.
Results
The search identified 15 347 reports, of which 21 studies (11 800 patients) were included in the Kaplan-Meier-based meta-analysis and 33 studies (16 933 patients) in an aggregate data meta-analysis. In the Kaplan-Meier-based analysis, the median survival time for patients surviving to hospital discharge was 5.0 years (IQR, 2.3-7.9 years). The estimated survival rates were 82.8% (95% CI, 81.9%-83.7%) at 3 years, 77.0% (95% CI, 75.9%-78.0%) at 5 years, 63.9% (95% CI, 62.3%-65.4%) at 10 years, and 57.5% (95% CI, 54.8%-60.1%) at 15 years. Compared with patients with a nonshockable initial rhythm, patients with a shockable rhythm had a lower risk of long-term mortality (hazard ratio, 0.30; 95% CI, 0.23-0.39; P < .001). Different analyses, including an aggregate data meta-analysis, confirmed these results.

Conclusions:
and relevance
In this comprehensive systematic review and meta-analysis, long-term survival after 10 years in patients surviving the initial hospital stay after OHCA was between 62% and 64%. Additional research is needed to understand and improve the long-term survival in this vulnerable patient population.



JAMA Cardiol: 04 May 2022; epub ahead of print
Amacher SA, Bohren C, Blatter R, Becker C, ... Marsch S, Hunziker S
JAMA Cardiol: 04 May 2022; epub ahead of print | PMID: 35507352
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex and Race Differences in N-Terminal Pro-B-type Natriuretic Peptide Concentration and Absolute Risk of Heart Failure in the Community.

Myhre PL, Claggett B, Yu B, Skali H, ... Ballantyne CM, Shah AM
Importance
Sex- and race-based differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are poorly understood. Clinical decisions are often informed by absolute-as opposed to relative-risk, but absolute risk of incident heart failure (HF) associated with NT-proBNP concentration across these important demographic categories is unclear.
Objective
To determine whether physiologic determinants of NT-proBNP concentrations account for sex and race differences, and to more uniformly predict HF risk using NT-proBNP in these demographic subgroups.
Design, setting, and participants
In the longitudinal Atherosclerosis Risk in Communities epidemiologic prospective community-based cohort study, the association of NT-proBNP concentration with relative and absolute risk of HF by sex- and race-based categories was assessed at study visit 2 (1990-1992) and study visit 5 (2011-2013) using Cox and Poisson regression. These data were analyzed from June 2018 to October 2021. The contribution of clinical, anthropometric, echocardiographic, and laboratory parameters to sex- and race-based differences in NT-proBNP concentration was assessed at visit 5 using linear regression. Participants included were free of HF in midlife (visit 2; a total of 12 750 participants) and late life (visit 5; a total of 5191 participants).
Exposures
NT-proBNP concentration.
Main outcomes and measures
Incident HF or death.
Results
Among the 5191 HF-free participants at visit 5, the mean (SD) age was 76.0 (5.2) years, 2104 (41%) were male, 1043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. In both midlife and late life, NT-proBNP concentration was lowest in Black men (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and highest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit, 5, 154 [82-268] pg/mL). Sex and race differences in NT-proBNP concentration persisted after accounting for age, income, education, area deprivation index, cardiovascular diseases, left ventricular structure (LV), LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate. Substantial differences in the absolute risk of incident HF or death existed across the sex- and race-based categories at any NT-proBNP concentration (eg, 7-fold [rate ratio, 6.7; 95% CI, 4.6-9.9] and 3-fold [rate ratio, 2.7; 95% CI, 1.7-4.1] difference at visit 2 and visit 5, respectively, at guideline-recommended thresholds) with higher risk consistently observed among Black men and lower risk in White women. Results were replicated in a cohort of participants from the Cardiovascular Health Study.

Conclusions:
and relevance
In this study, sex- and race-based differences in NT-proBNP persisted after accounting for known physiologic determinants. Absolute risk associated with a given value of NT-proBNP varied substantially by sex and race. Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across important demographic subgroups.



JAMA Cardiol: 27 Apr 2022; epub ahead of print
Myhre PL, Claggett B, Yu B, Skali H, ... Ballantyne CM, Shah AM
JAMA Cardiol: 27 Apr 2022; epub ahead of print | PMID: 35476049
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of COVID-19 Vaccination With Risk of COVID-19 Infection, Hospitalization, and Death in Heart Transplant Recipients.

Peters LL, Raymer DS, Pal JD, Ambardekar AV
Importance
Orthotopic heart transplant (OHT) recipients are at increased risk for morbidity and mortality after SARS-CoV-2 infection. Although antibody response to COVID-19 vaccination is lower in solid organ transplant recipients, there has been no study assessing the safety and effectiveness of COVID-19 vaccination in OHT recipients.
Objective
To assess the safety and effectiveness of COVID-19 vaccination and associations with SARS-CoV-2 infection and clinical outcomes in a large population of adult OHT recipients.
Design, setting, and participants
This case-control study examined data from a US heart transplant program at a single center for all adult recipients of OHT who were followed up from January 15, 2021, through January 31, 2022.
Main outcomes and measures
The primary outcome was number of SARS-CoV-2 infections and related hospitalizations, intensive care unit (ICU) admissions, and deaths between vaccinated vs unvaccinated adult recipients of OHT.
Results
A total of 436 patients who received OHT were included in the study, of which 106 patients were infected with COVID-19. The mean (SD) age was 54 (17) years; 303 (69.5%) were men and 133 (30.5%) were women. There were 366 patients in the vaccinated cohort with 72 COVID-19 infections (19.7%), 15 hospitalizations (4.1%), 4 ICU admissions (1.1%), and 3 deaths (0.8%). There were 70 patients in the unvaccinated cohort with 34 COVID-19 infections (48.6%), 10 hospitalizations (14.3%), 3 ICU admissions (4.3%), and 3 deaths (4.3%). COVID-19 vaccination was associated with a lower risk of COVID-19 infection (risk ratio [RR], 0.41; 95% CI, 0.30-0.56), hospitalization (RR, 0.29; 95% CI, 0.14-0.61), and death (RR, 0.19; 95% CI, 0.05-0.82). Among the 366 vaccinated OHT recipients, there was no echocardiographic evidence of graft dysfunction, clinically significant rejection, or allosensitization at 6 months after they received the COVID-19 vaccine.

Conclusions:
and relevance
Patients with OHT who are infected with SARS-CoV-2 are at greater risk of severe infection and death compared with immunocompetent individuals. COVID-19 vaccination was associated with fewer COVID-19 infections, hospitalizations, and deaths, with no heart transplant-specific adverse events. COVID-19 vaccination for all OHT recipients is of paramount importance.



JAMA Cardiol: 27 Apr 2022; epub ahead of print
Peters LL, Raymer DS, Pal JD, Ambardekar AV
JAMA Cardiol: 27 Apr 2022; epub ahead of print | PMID: 35475896
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents.

Karlstad Ø, Hovi P, Husby A, Härkänen T, ... Hviid A, Ljung R
Importance
Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged.
Objective
To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age.
Design, setting, and participants
Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden.
Exposures
The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2.
Main outcomes and measures
Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals.
Results
Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar.

Conclusions:
and relevance
Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.



JAMA Cardiol: 20 Apr 2022; epub ahead of print
Karlstad Ø, Hovi P, Husby A, Härkänen T, ... Hviid A, Ljung R
JAMA Cardiol: 20 Apr 2022; epub ahead of print | PMID: 35442390
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effectiveness of a Text-Based Gamification Intervention to Improve Physical Activity Among Postpartum Individuals With Hypertensive Disorders of Pregnancy: A Randomized Clinical Trial.

Lewey J, Murphy S, Zhang D, Putt ME, ... Patel MS, Levine LD
Importance
Hypertensive disorders of pregnancy are associated with increased risk of cardiovascular disease, yet few interventions have targeted this population to decrease long-term risk.
Objective
To determine whether a digital health intervention improves physical activity in postpartum individuals with hypertensive disorders of pregnancy.
Design, setting, and participants
This 12-week randomized clinical trial enrolled postpartum individuals who delivered at the University of Pennsylvania and had a hypertensive disorder of pregnancy between October 2019 and June 2020. Analysis was intention to treat.
Interventions
All participants received a wearable activity tracker, established a baseline step count, selected a step goal greater than baseline, and were randomly assigned to control or intervention. Participants in the control arm received daily feedback on goal attainment. Participants in the intervention arm were placed on virtual teams and enrolled in a game with points and levels for daily step goal achievement and informed by principles of behavioral economics.
Main outcomes and measures
The primary outcome was change in mean daily step count from baseline to 12-week follow-up. Secondary outcome was proportion of participant-days that step goal was achieved.
Results
A total of 127 participants were randomized (64 in the control group and 63 in the intervention group) and were enrolled a mean of 7.9 weeks post partum. Participants had a mean (SD) age of 32.3 (5.6) years, 70 (55.1%) were Black, and 52 (41.9%) had Medicaid insurance. The mean (SD) baseline step count was similar in the control and intervention arms (6042 [2270] vs 6175 [1920] steps, respectively). After adjustment for baseline steps and calendar month, participants in the intervention arm had a significantly greater increase in mean daily step steps from baseline compared with the control arm (647 steps; 95% CI, 169-1124 steps; P = .009). Compared with the control arm, participants in the intervention arm achieved their steps goals on a greater proportion of participant-days during the intervention period (0.47 vs 0.38; adjusted difference 0.11; 95% CI, 0.04-0.19; P = .003).

Conclusions:
and relevance
In this study, a digital health intervention using remote monitoring, gamification, and social incentives among postpartum individuals at elevated cardiovascular risk significantly increased physical activity throughout 12 weeks.
Trial registration
ClinicalTrials.gov Identifier: NCT03311230.



JAMA Cardiol: 20 Apr 2022; epub ahead of print
Lewey J, Murphy S, Zhang D, Putt ME, ... Patel MS, Levine LD
JAMA Cardiol: 20 Apr 2022; epub ahead of print | PMID: 35442393
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure: A Secondary Analysis of the TRIUMPH Randomized Clinical Trial.

Gnanenthiran SR, Wang N, Di Tanna GL, Salam A, ... Rodgers A, TRIUMPH Study Group
Importance
Cumulative exposure to high blood pressure (BP) is an adverse prognostic marker. Assessments of BP control over time, such as time at target, have been developed but assessments of the effects of BP-lowering interventions on such measures are lacking.
Objective
To evaluate whether low-dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care.
Design, setting, and participants
The Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) trial was a open-label randomized clinical trial of low-dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017. Adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg or in patients with diabetes or chronic kidney disease, systolic BP >130 mm Hg and/or diastolic BP >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy were included. Patients were excluded if they were currently taking 2 or more blood pressure-lowering drugs or had severe or uncontrolled blood pressure, accelerated hypertension or physician-determined need for slower titration of treatment, a contraindication to the triple combination pill therapy, an unstable medical condition, or clinically significant laboratory values deemed by researchers to be unsuitable for the study. All 700 individuals in the original trial were included in the secondary analysis. This post hoc analysis was conducted from December 2020 to December 2021.
Intervention
Once-daily fixed-dose triple combination pill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg) therapy vs usual care.
Main outcomes and measures
Between-group differences in time at target were compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP.
Results
There were a total of 700 randomized patients (mean [SD] age, 56 [11] years; 403 [57.6%] women). Patients allocated to the triple pill group (n = 349) had higher time at target compared with those in the usual care group (n = 351) over 24 weeks\' follow-up (64% vs 43%; risk difference, 21%; 95% CI, 16-26; P < .001). Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001). The association of the triple pill with an increase in time at target was seen early, with most patients achieving more than 50% time at target by 12 weeks. Those receiving the triple pill achieved a consistently higher time at target at all follow-up periods compared with those receiving usual care (mean [SD]: 0-6 weeks, 36.3% [30.9%] vs 21.7% [28.9%]; P < .001; 6-12 weeks, 5.2% [31.9%] vs 33.7% [33.0%]; P < .001; 12-24 weeks, 66.0% [31.1%] vs 43.5% [34.3%]; P < .001).

Conclusions:
and relevance
To our knowledge, this analysis provides the first estimate of time at target as an outcome assessing longitudinal BP control in a randomized clinical trial. Among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill was associated with substantially higher time at target compared with usual care.



JAMA Cardiol: 13 Apr 2022; epub ahead of print
Gnanenthiran SR, Wang N, Di Tanna GL, Salam A, ... Rodgers A, TRIUMPH Study Group
JAMA Cardiol: 13 Apr 2022; epub ahead of print | PMID: 35416909
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of 15-mg Edoxaban on Clinical Outcomes in 3 Age Strata in Older Patients With Atrial Fibrillation: A Prespecified Subanalysis of the ELDERCARE-AF Randomized Clinical Trial.

Kuroda M, Tamiya E, Nose T, Ogimoto A, ... Lip GYH, Okumura K
Importance
Long-term use of oral anticoagulants (OACs) is necessary for stroke prevention in patients with atrial fibrillation (AF). The effectiveness and safety of OACs in extremely older patients (ie, aged 80 years or older) with AF and at high risk of bleeding needs to be elucidated.
Objective
To examine the effects of very low-dose edoxaban (15 mg) vs placebo across 3 age strata (80-84 years, 85-89 years, and ≥90 years) among patients with AF who were a part of the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial.
Design, setting, and participants
This prespecified subanalysis of a phase 3, randomized, double-blind, placebo-controlled trial was conducted from August 5, 2016, to December 27, 2019. Patients with AF aged 80 years or older who were not considered candidates for standard-dose OACs were included in the study; reasons these patients could not take standard-dose OACs included low creatinine clearance (<30 mL per minute), low body weight (≤45 kg), history of bleeding from critical organs, continuous use of nonsteroidal anti-inflammatory drugs, or concomitant use of antiplatelet drugs. Eligible patients were recruited randomly from 164 hospitals in Japan and were randomly assigned 1:1 to edoxaban or placebo.
Interventions
Edoxaban (15 mg once daily) or placebo.
Main outcomes and measures
The primary efficacy end point was the composite of stroke or systemic embolism. The primary safety end point was International Society on Thrombosis and Hemostasis-defined major bleeding.
Results
A total of 984 patients (mean [SD] age: age group 80-84 years, 82.2 [1.4] years; age group 85-89 years, 86.8 [1.4] years; age group ≥90 years, 92.3 [2.1] years; 565 women [57.4%]) were included in this study. In the placebo group, estimated (SE) event rates for stroke or systemic embolism increased with age and were 3.9% (1.2%) per patient-year in the group aged 80 to 84 years (n = 181), 7.3% (1.7%) per patient-year in the group aged 85 to 89 years (n = 184), and 10.1% (2.5%) per patient-year in the group aged 90 years or older (n = 127). A 15-mg dose of edoxaban consistently decreased the event rates for stroke or systemic embolism with no interaction with age (80-84 years, hazard ratio [HR], 0.41; 95% CI, 0.13-1.31; P = .13; 85-89 years, HR, 0.42; 95% CI, 0.17-0.99; P = .05; ≥90 years, HR, 0.23; 95% CI, 0.08-0.68; P = .008; interaction P = .65). Major bleeding and major or clinically relevant nonmajor bleeding events were numerically higher with edoxaban, but the differences did not reach statistical significance, and there was no interaction with age. There was no difference in the event rate for all-cause death between the edoxaban and placebo groups in all age strata.

Conclusions:
and relevance
Results of this subanalysis of the ELDERCARE-AF randomized clinical trial revealed that among Japanese patients aged 80 years or older with AF who were not considered candidates for standard OACs, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism consistently across all 3 age strata, including those aged 90 years or older, albeit with a higher but nonstatistically significant incidence of bleeding.
Trial registration
ClinicalTrials.gov Identifier: NCT02801669.



JAMA Cardiol: 13 Apr 2022; epub ahead of print
Kuroda M, Tamiya E, Nose T, Ogimoto A, ... Lip GYH, Okumura K
JAMA Cardiol: 13 Apr 2022; epub ahead of print | PMID: 35416910
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

TET2-Driven Clonal Hematopoiesis and Response to Canakinumab: An Exploratory Analysis of the CANTOS Randomized Clinical Trial.

Svensson EC, Madar A, Campbell CD, He Y, ... Beste MT, Basson CT
Importance
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of atherosclerotic cardiovascular disease, and mouse experiments suggest that CHIP related to Tet2 loss of function in myeloid cells accelerates atherosclerosis via augmented interleukin (IL) 1β signaling.
Objective
To assess whether individuals with CHIP have greater cardiovascular event reduction in response to IL-1β neutralization in the Canankinumab Anti-inflammatory Thrombosis Outcomes Trial (CANTOS).
Design, setting, and participants
This randomized clinical trial took place from April 2011 to June 2017 at more than 1000 clinical sites in 39 countries. Targeted deep sequencing of genes previously associated with CHIP in a subset of trial participants using genomic DNA prepared from baseline peripheral blood samples were analyzed. All participants had prior myocardial infarction and elevated high-sensitivity C-reactive protein level above 0.20 mg/dL. Analysis took place between June 2017 and December 2021.
Interventions
Canakinumab, an anti-IL-1β antibody, given at doses of 50, 150, and 300 mg once every 3 months.
Main outcomes and measures
Major adverse cardiovascular events (MACE).
Results
A total of 338 patients (8.6%) were identified in this subset with evidence for clonal hematopoiesis. As expected, the incidence of CHIP increased with age; the mean (SD) age of patients with CHIP was 66.3 (9.2) years and 61.5 (9.6) years in patients without CHIP. Unlike other populations that were not preselected for elevated C-reactive protein, in the CANTOS population variants in TET2 were more common than DNMT3A (119 variants in 103 patients vs 86 variants in 85 patients). Placebo-treated patients with CHIP showed a nonsignificant increase in the rate of MACE compared with patients without CHIP using a Cox proportional hazard model (hazard ratio, 1.32 [95% CI, 0.86-2.04]; P = .21). Exploratory analyses of placebo-treated patients with a somatic variant in either TET2 or DNMT3A (n = 58) showed an equivocal risk for MACE (hazard ratio, 1.65 [95% CI, 0.97-2.80]; P = .06). Patients with CHIP due to somatic variants in TET2 also had reduced risk for MACE while taking canakinumab (hazard ratio, 0.38 [95% CI, 0.15-0.96]) with equivocal difference compared with others (P for interaction = .14).

Conclusions:
and relevance
These results are consistent with observations of increased risk for cardiovascular events in patients with CHIP and raise the possibility that those with TET2 variants may respond better to canakinumab than those without CHIP. Future studies are required to further substantiate this hypothesis.
Trial registration
ClinicalTrials.gov Identifier: NCT01327846.



JAMA Cardiol: 06 Apr 2022; epub ahead of print
Svensson EC, Madar A, Campbell CD, He Y, ... Beste MT, Basson CT
JAMA Cardiol: 06 Apr 2022; epub ahead of print | PMID: 35385050
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Thornton GD, Musa TA, Rigolli M, Loudon M, ... Singh A, Treibel TA
Importance
Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived.
Objective
To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement.
Design, setting, and participants
This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021.
Exposures
SAVR or TAVR.
Main outcomes and measures
All-cause and cardiovascular (CV) mortality after aortic valve intervention.
Results
Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume).

Conclusions:
and relevance
In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.



JAMA Cardiol: 06 Apr 2022; epub ahead of print
Thornton GD, Musa TA, Rigolli M, Loudon M, ... Singh A, Treibel TA
JAMA Cardiol: 06 Apr 2022; epub ahead of print | PMID: 35385057
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Assessment of Artificial Intelligence in Echocardiography Diagnostics in Differentiating Takotsubo Syndrome From Myocardial Infarction.

Laumer F, Di Vece D, Cammann VL, Würdinger M, ... Buhmann JM, Templin C
Importance
Machine learning algorithms enable the automatic classification of cardiovascular diseases based on raw cardiac ultrasound imaging data. However, the utility of machine learning in distinguishing between takotsubo syndrome (TTS) and acute myocardial infarction (AMI) has not been studied.
Objectives
To assess the utility of machine learning systems for automatic discrimination of TTS and AMI.
Design, settings, and participants
This cohort study included clinical data and transthoracic echocardiogram results of patients with AMI from the Zurich Acute Coronary Syndrome Registry and patients with TTS obtained from 7 cardiovascular centers in the International Takotsubo Registry. Data from the validation cohort were obtained from April 2011 to February 2017. Data from the training cohort were obtained from March 2017 to May 2019. Data were analyzed from September 2019 to June 2021.
Exposure
Transthoracic echocardiograms of 224 patients with TTS and 224 patients with AMI were analyzed.
Main outcomes and measures
Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the machine learning system evaluated on an independent data set and 4 practicing cardiologists for comparison. Echocardiography videos of 228 patients were used in the development and training of a deep learning model. The performance of the automated echocardiogram video analysis method was evaluated on an independent data set consisting of 220 patients. Data were matched according to age, sex, and ST-segment elevation/non-ST-segment elevation (1 patient with AMI for each patient with TTS). Predictions were compared with echocardiographic-based interpretations from 4 practicing cardiologists in terms of sensitivity, specificity, and AUC calculated from confidence scores concerning their binary diagnosis.
Results
In this cohort study, apical 2-chamber and 4-chamber echocardiographic views of 110 patients with TTS (mean [SD] age, 68.4 [12.1] years; 103 [90.4%] were female) and 110 patients with AMI (mean [SD] age, 69.1 [12.2] years; 103 [90.4%] were female) from an independent data set were evaluated. This approach achieved a mean (SD) AUC of 0.79 (0.01) with an overall accuracy of 74.8 (0.7%). In comparison, cardiologists achieved a mean (SD) AUC of 0.71 (0.03) and accuracy of 64.4 (3.5%) on the same data set. In a subanalysis based on 61 patients with apical TTS and 56 patients with AMI due to occlusion of the left anterior descending coronary artery, the model achieved a mean (SD) AUC score of 0.84 (0.01) and an accuracy of 78.6 (1.6%), outperforming the 4 practicing cardiologists (mean [SD] AUC, 0.72 [0.02]) and accuracy of 66.9 (2.8%).

Conclusions:
and relevance
In this cohort study, a real-time system for fully automated interpretation of echocardiogram videos was established and trained to differentiate TTS from AMI. While this system was more accurate than cardiologists in echocardiography-based disease classification, further studies are warranted for clinical application.



JAMA Cardiol: 30 Mar 2022; epub ahead of print
Laumer F, Di Vece D, Cammann VL, Würdinger M, ... Buhmann JM, Templin C
JAMA Cardiol: 30 Mar 2022; epub ahead of print | PMID: 35353118
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia Treated With β-Blockers.

Mazzanti A, Kukavica D, Trancuccio A, Memmi M, ... Monserrat L, Priori SG
Importance
Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) may experience life-threatening arrhythmic events (LTAEs) despite β-blocker treatment. Further complicating management, the role of implantable cardioverter defibrillator (ICD) in CPVT is debated.
Objective
To investigate the long-term outcomes of patients with RYR2 CPVT treated with β-blockers only and the cost to benefit ratio of ICD.
Design, settings, and participants
This prospective cohort study conducted from January 1988 to October 2020 with a mean (SD) follow-up of 9.4 (7.5) years included patients who were referred to the Molecular Cardiology Clinics of ICS Maugeri Hospital, Pavia, Italy. Participants included consecutive patients with CPVT who were carriers of a pathogenic or likely pathogenic RYR2 variant with long-term clinical follow-up.
Exposures
Treatment with selective and nonselective β-blocker only and ICD implant when indicated.
Main outcome and measures
The main outcome was the occurrence of the first LTAE while taking a β-blocker. LTAE was defined as a composite of 3 hard end points: sudden cardiac death, aborted cardiac arrest, and hemodynamically nontolerated ventricular tachycardia.
Results
The cohort included 216 patients with RYR2 CPVT (121 of 216 female [55%], median [IQR] age 14, [9-30] years). During a mean (SD) follow-up of 9.4 (7.5) years taking β-blockers only, 28 of 216 patients (13%) experienced an LTAE (annual rate, 1.9%; 95% CI, 1.3-2.7). In multivariable analysis, experiencing either an LTAE (hazard ratio [HR], 3.3; 95% CI, 1.2-8.9; P = .02) or syncope before diagnosis (HR, 4.5; 95% CI, 1.8-11.1; P = .001) and carrying a C-terminal domain variant (HR, 18.1; 95% CI, 4.1-80.8; P < .001) were associated with an increased LTAE risk during β-blocker therapy only. The risk of LTAE among those taking selective β-blockers vs nadolol was increased 6-fold (HR, 5.8; 95% CI, 2.1-16.3; P = .001). Conversely, no significant difference was present between propranolol and nadolol (HR, 1.8; 95% CI, 0.4-7.3; P = .44). An ICD was implanted in 79 of 216 patients (37%) who were followed up for a mean (SD) of 8.6 (6.3) years. At the occurrence of LTAE, ICD carriers were more likely to survive (18 of 18 [100%]) than non-ICD carriers (6 of 10 [60%]; P = .01).

Conclusions:
and relevance
In this cohort study, selective β-blockers were associated with a higher risk of LTAE as compared with nadolol. Independently from treatment, LTAE and syncope before diagnosis and C-terminal domain variants identified patients at higher risk of β-blocker failure, and the ICD was associated with reduced mortality in high-risk patients with CPVT.



JAMA Cardiol: 30 Mar 2022; epub ahead of print
Mazzanti A, Kukavica D, Trancuccio A, Memmi M, ... Monserrat L, Priori SG
JAMA Cardiol: 30 Mar 2022; epub ahead of print | PMID: 35353122
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Percutaneous Intramyocardial Septal Radiofrequency Ablation in Patients With Drug-Refractory Hypertrophic Obstructive Cardiomyopathy.

Zhou M, Ta S, Hahn RT, Hsi DH, ... Liu J, Liu L
Importance
Patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms and outflow gradients have limited nonsurgical treatment options. The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported previously; however, procedural and medium-term outcomes are unknown.
Objective
To describe the safety and medium-term outcomes of PIMSRA in a large patient cohort with drug-refractory HOCM.
Design, setting, and participants
This was a single-arm, open-label study of PIMSRA in patients with drug-refractory HOCM. Patients presenting to the Xijing Hospital in Xi\'an, China, between October 2016 to June 2020 with hypertrophic cardiomyopathy. Of 1314 patients presenting with HOCM, 244 fulfilled inclusion criteria of severe resting/provoked outflow gradients of 50 mm Hg or higher, and symptoms of New York Heart Association functional class of II or higher refractory to maximum tolerated medications. After discussion among the heart team, 40 patients underwent surgical or alcohol septal reduction therapy and 4 required treatment of significant coronary artery disease.
Interventions
PIMSRA performed in patients.
Main outcomes and measures
The primary outcome was 30-day major adverse clinical events: death, emergency surgery, severe effusion requiring intervention, procedure-related stroke, bleeding, and stroke. Secondary outcomes included 30-day technical success and 90-day improvement in outflow obstruction.
Results
The mean (SD) age of 200 patients was 46.9 (14.0) years, and 125 (62.5%) were men. Resting or provoked left ventricular outflow tract gradients were 50 mm Hg or higher. The median (IQR) follow-up for all patients was 19 (6-50) months. Thirty-day major adverse clinical events rate was 10.5% (n = 21): there were 2 in-hospital/30-day deaths (1.0%), 7 patients (3.5%) with pericardial effusion requiring mini-thoracotomy, 12 patients (6%) with pericardial effusion requiring pericardiocentesis, and no bleeding or strokes. Other periprocedural complications included permanent right bundle branch block in 5 patients (2.5%), resuscitated ventricular fibrillation in 2 (1.0%), and septal branch aneurysm in 2 (1.0%). There were no permanent pacemaker implantations. At follow-up, maximum septal thickness was reduced from a mean (SD) of 24.0 (5.1) mm to 17.3 (4.4) mm (P < .001), and left ventricular outflow tract gradient was decreased from a mean (SD) of 79.0 (53.0) mm Hg to 14.0 (24.0) mm Hg (P < .001). Overall, 190 patients (96%) with HOCM were in New York Heart Association functional class I or II at last follow-up.

Conclusions:
and relevance
This study found that PIMSRA in patients with drug-refractory HOCM may be an effective procedure for relief of left ventricular outflow tract obstruction and symptoms with acceptable complication rates. These results are encouraging and support the design of a randomized clinical trial against well-established septal reduction therapies.



JAMA Cardiol: 30 Mar 2022; epub ahead of print
Zhou M, Ta S, Hahn RT, Hsi DH, ... Liu J, Liu L
JAMA Cardiol: 30 Mar 2022; epub ahead of print | PMID: 35353129
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Improving Enrollment of Underrepresented Racial and Ethnic Populations in Heart Failure Trials: A Call to Action From the Heart Failure Collaboratory.

DeFilippis EM, Echols M, Adamson PB, Batchelor WB, ... Vardeny O, Vaduganathan M
Importance
Despite bearing a disproportionate burden of heart failure (HF), Black and Hispanic individuals have been poorly represented in HF clinical trials. Underrepresentation in clinical trials limits the generalizability of the findings to these populations and may even introduce uncertainties and hesitancy when translating trial data to the care of people from underrepresented groups. The Heart Failure Collaboratory, a consortium of stakeholders convened to enhance HF therapeutic development, has been dedicated to improving recruitment strategies for patients from diverse and historically underrepresented groups.
Observations
Despite federal policies from the US Food and Drug Administration and National Institutes of Health aimed at improving trial representation, gaps in trial enrollment proportionate to the racial and ethnic composition of the HF population have persisted. Increasing trial globalization with limited US enrollment is a major driver of these patterns. Additional barriers to representative enrollment include inequities in care access, logistical issues in participation, restrictive enrollment criteria, and English language requirements.

Conclusions:
and relevance
Strategies for improving diverse trial enrollment include methodical study design and site selection, diversification of research leadership and staff, broadening of eligibility criteria, community and patient engagement, and broad stakeholder commitment. In contemporary HF trials, diverse trial enrollment is not only feasible but can be efficiently achieved to improve the generalizability and translation of trial knowledge to clinical practice.



JAMA Cardiol: 23 Mar 2022; epub ahead of print
DeFilippis EM, Echols M, Adamson PB, Batchelor WB, ... Vardeny O, Vaduganathan M
JAMA Cardiol: 23 Mar 2022; epub ahead of print | PMID: 35319725
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Performance of Management Strategies With Class I Recommendations Among Patients Hospitalized With ST-Segment Elevation Myocardial Infarction in China.

Hao Y, Zhao D, Liu J, Liu J, ... Smith SC, CCC-ACS Investigators
Importance
Despite advances in the treatment of ST-segment elevation myocardial infarction (STEMI), little is known about how this evolving knowledge is applied in current clinical practice in China.
Objective
To evaluate hospital performance and temporal trends in the management of STEMI.
Design, setting, and participants
This study used data from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project, a nationwide quality improvement registry, in collaboration with the American Heart Association and the Chinese Society of Cardiology. Participants included patients with STEMI admitted to 143 tertiary hospitals across China from November 2014 to July 2019, and data were analyzed from November 2020 to December 2021.
Main outcomes and measures
Levels, hospital-level variations, and trends for utilization rates of the 9 management strategies with Class I recommendations in Chinese and US guidelines.
Results
A total of 57 560 hospitalizations with STEMI were included. Overall, 20.0% of patients received all the care according to the 9 guideline-recommended strategies. The performance rate of quality measures was low for reperfusion therapy (61.0%, 35 115/57 560 patients), β-blocker at discharge (68.3%, 37 750/55 285 patients), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker at discharge (55.1%, 2524/4578 patients), and smoking cessation counseling (36.5%, 9586/26 265 patients) among those who were eligible. Of 25 563 patients who underwent primary percutaneous coronary intervention (PCI), 66.8% underwent this procedure within 90 minutes of hospital arrival. Of 1128 patients who underwent fibrinolysis therapy, 253 (22.4%) underwent this treatment within 30 minutes of hospital arrival. Measures with high performance rates included receipt of dual antiplatelet therapy within 24 hours (95.5%, 54 263/56 848 patients) and at discharge (91.8%, 51 452/56 019 patients) and receipt of statin at discharge (93.0%, 52 214/56 141 patients) for those eligible. There was significant variation between hospitals in all-or-none score (ranging from 0 to 61.9%) and performance of individual measures. The quality of care improved during the study period, especially for reperfusion therapy, primary PCI within the first 90 minutes of hospital arrival, and smoking cessation counseling.

Conclusions:
and relevance
The quality of care for patients hospitalized with STEMI does not meet guideline-recommended strategies in China, with only 1 in 5 patients receiving all the care according to the 9 guideline-recommended strategies. Large disparities in the quality of care exist across hospitals.



JAMA Cardiol: 15 Mar 2022; epub ahead of print
Hao Y, Zhao D, Liu J, Liu J, ... Smith SC, CCC-ACS Investigators
JAMA Cardiol: 15 Mar 2022; epub ahead of print | PMID: 35293976
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prasugrel Dose De-escalation Therapy After Complex Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Post Hoc Analysis From the HOST-REDUCE-POLYTECH-ACS Trial.

Hwang D, Lim YH, Park KW, Chun KJ, ... Kim HS, HOST-RP-ACS investigators
Importance
De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. However, whether such benefits are similarly observed in those receiving complex procedures is unknown.
Objective
To investigate whether the benefits of prasugrel dose de-escalation therapy are maintained in the complex percutaneous coronary intervention (PCI) subgroup.
Design, setting, and participants
This was a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS trial, a randomized, open-label, adjudicator-blinded, multicenter trial performed at 35 hospitals in South Korea. Study participants included patients with ACS who were receiving PCI. Data were collected from September 30, 2014, to December 18, 2015, and analyzed from September 17, 2020, to June 15, 2021.
Interventions and exposures
Patients were randomized to a prasugrel dose de-escalation (5 mg daily) at 1 month post-PCI group or a conventional (10 mg daily) group. Complex PCI was defined as having at least 1 of the following features: 3 or more stents implanted, 3 or more lesions treated, bifurcation PCI, total stent length 60 mm or larger, left main PCI, or heavy calcification.
Main outcomes and measures
The main analysis end points were MACE (major adverse cardiac event, a composite of cardiovascular death, nonfatal myocardial infarction, stent thrombosis, and repeat revascularization) at 1 year for ischemic outcomes, and BARC (Bleeding Academic Research Consortium) class 2 or higher bleeding events at 1 year for bleeding outcomes.
Results
Of 2271 patients (mean [SD] age, 58.9 [9.0] years; 2024 [89%] male patients) for whom full procedural data were available, 705 patients received complex PCI, and 1566 patients received noncomplex PCI. Complex PCI was associated with higher rates of ischemic outcomes but not with bleeding outcomes. Prasugrel dose de-escalation did not increase the risk of MACE (hazard ratio [HR], 0.88; 95% CI, 0.47-1.66; P = .70 in complex PCI; HR, 0.81; 95% CI, 0.45-1.46; P = .48 in noncomplex PCI; P for interaction = .84) but decreased BARC class 2 or higher bleeding events (HR, 0.25; 95% CI, 0.10-0.61; P = .002 in complex PCI; HR, 0.62; 95% CI, 0.38-1.00; P = .05 in noncomplex PCI; P for interaction = .08), albeit with wide 95% CIs.

Conclusions:
and relevance
In this post hoc analysis of patients with ACS, prasugrel dose de-escalation compared with conventional therapy was not associated with an increased risk of ischemic outcomes but may reduce the risk of minor bleeding events at 1 year, irrespective of PCI complexity.
Trial registration
ClinicalTrials.gov Identifier: NCT02193971.



JAMA Cardiol: 08 Mar 2022; epub ahead of print
Hwang D, Lim YH, Park KW, Chun KJ, ... Kim HS, HOST-RP-ACS investigators
JAMA Cardiol: 08 Mar 2022; epub ahead of print | PMID: 35262625
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Comparison of Clopidogrel Monotherapy After 1 to 2 Months of Dual Antiplatelet Therapy With 12 Months of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndrome: The STOPDAPT-2 ACS Randomized Clinical Trial.

Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, ... Kimura T, STOPDAPT-2 ACS Investigators
Importance
Clopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS).
Objective
To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS.
Design, setting, and participants
This multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021.
Interventions
Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091).
Main outcomes and measures
The primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point.
Results
Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1- to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, -0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1- to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, -0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1- to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, -0.63% [95% CI, -1.20% to -0.06%]; HR, 0.46 [95% CI, 0.23-0.94]).

Conclusions:
and relevance
In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials.
Trial registration
ClinicalTrials.gov Identifiers: NCT02619760 and NCT03462498.



JAMA Cardiol: 01 Mar 2022; epub ahead of print
Watanabe H, Morimoto T, Natsuaki M, Yamamoto K, ... Kimura T, STOPDAPT-2 ACS Investigators
JAMA Cardiol: 01 Mar 2022; epub ahead of print | PMID: 35234821
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Fibrillar Collagen Variants in Spontaneous Coronary Artery Dissection.

Zekavat SM, Chou EL, Zekavat M, Pampana A, ... Natarajan P, Lindsay ME
Importance
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute myocardial infarction enriched among individuals with early-onset myocardial infarction but is of unclear etiology.
Objective
To assess which genes contribute to the development of SCAD.
Design, setting, and participants
To prioritize genes influencing risk for SCAD, whole-exome sequencing was performed among individuals with SCAD in the discovery and replication cohorts from a tertiary care hospital outpatient specialty clinic, and gene set enrichment analyses were also performed for disruptive coding variants. All patients were sequentially enrolled beginning July 2013. Aggregate prevalence of rare disruptive variants for prioritized gene sets was compared between individuals with SCAD with population-based controls comprising 46 468 UK Biobank participants with whole-exome sequencing. Complementary mice models were used for in vivo validation. Analysis took place between June 2020 and January 2021.
Main outcomes and measures
The frequency and identity of rare genetic variants in individuals with SCAD.
Results
Of 130 patients, 109 (83.8%) were female (26 of 32 [81.2%] in the discovery cohort and 83 of 98 [84.7%] in the replication cohort) with mean (SD) age at first SCAD event of 48.41 (8.76) years in the discovery cohort and 47.74 (10.09) years in the replication cohort. Across all patients with SCAD, rare disruptive variants were found within 10 collagen genes (COL3A1, COL5A1, COL4A1, COL6A1, COL5A2, COL12A1, COL4A5, COL1A1, COL1A2, and COL27A1) were 17-fold (P = 1.5 × 10-9) enriched among individuals with SCAD compared with a background of 2506 constrained genes expressed in coronary artery. Furthermore, compared with individuals from the UK Biobank, individuals with SCAD were 1.75-fold (P = .04) more likely to carry disruptive rare variants within fibrillar collagen genes. Complementary mice models haploinsufficient for Col3a1 or Col5a1, the 2 most common collagen gene variants identified in SCAD cases, demonstrated increased risk of arterial dissection and increased size of arterial diameters especially in female mice, with resulting changes in collagen fibril organization and diameter.

Conclusions:
and relevance
Unbiased gene discovery in patients with SCAD with independent human and murine validation highlights the role of the extracellular matrix dysfunction in SCAD.



JAMA Cardiol: 01 Mar 2022; epub ahead of print
Zekavat SM, Chou EL, Zekavat M, Pampana A, ... Natarajan P, Lindsay ME
JAMA Cardiol: 01 Mar 2022; epub ahead of print | PMID: 35234813
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Interventions to Mitigate Risk of Cardiovascular Disease After Adverse Pregnancy Outcomes: A Review.

Jowell AR, Sarma AA, Gulati M, Michos ED, ... Powe CE, Honigberg MC
Importance
A growing body of evidence suggests that adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy, gestational diabetes (GD), preterm birth, and intrauterine growth restriction, are associated with increased risk of cardiometabolic disease and cardiovascular disease (CVD) later in life. Adverse pregnancy outcomes may therefore represent an opportunity to intervene to prevent or delay onset of CVD. The objective of this review was to summarize the current evidence for targeted postpartum interventions and strategies to reduce CVD risk in women with a history of APOs.
Observations
A search of PubMed and Ovid for English-language randomized clinical trials, cohort studies, descriptive studies, and guidelines published from January 1, 2000, to April 30, 2021, was performed. Four broad categories of interventions were identified: transitional clinics, lifestyle interventions, pharmacotherapy, and patient and clinician education. Observational studies suggest that postpartum transitional clinics identify women who are at elevated risk for CVD and may aid in the transition to longitudinal primary care. Lifestyle interventions to increase physical activity and improve diet quality may help reduce the incidence of type 2 diabetes in women with prior GD; less is known about women with other prior APOs. Metformin hydrochloride may prevent development of type 2 diabetes in women with prior GD. Evidence is lacking in regard to specific pharmacotherapies after other APOs. Cardiovascular guidelines endorse using a history of APOs to refine CVD risk assessment and guide statin prescription for primary prevention in women with intermediate calculated 10-year CVD risk. Research suggests a low level of awareness of the link between APOs and CVD among both patients and clinicians.

Conclusions:
and relevance
These findings suggest that transitional clinics, lifestyle intervention, targeted pharmacotherapy, and clinician and patient education represent promising strategies for improving postpartum maternal cardiometabolic health in women with APOs; further research is needed to develop and rigorously evaluate these interventions. Future efforts should focus on strategies to increase maternal postpartum follow-up, improve accessibility to interventions across diverse racial and cultural groups, expand awareness of sex-specific CVD risk factors, and define evidence-based precision prevention strategies for this high-risk population.



JAMA Cardiol: 28 Feb 2022; 7:346-355
Jowell AR, Sarma AA, Gulati M, Michos ED, ... Powe CE, Honigberg MC
JAMA Cardiol: 28 Feb 2022; 7:346-355 | PMID: 34705020
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Apolipoprotein B-Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis: Distinguishing Between Particle Concentration, Type, and Content.

Marston NA, Giugliano RP, Melloni GEM, Park JG, ... Ruff CT, Sabatine MS
Importance
Lipid management typically focuses on levels of low-density lipoprotein cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). However, animal models and genetic studies suggest that the atherogenic particle subpopulations (LDL and very-low-density lipoprotein [VLDL]) are both important and that the number of particles is more predictive of cardiac events than their lipid content.
Objective
To determine whether common measures of cholesterol concentration, TG concentration, or their ratio are associated with cardiovascular risk beyond the number of apolipoprotein B (apoB)-containing lipoproteins.
Design, setting, and participants
This prospective cohort analysis included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The median (IQR) follow-up was 11.1 (10.4-11.8) years in UK Biobank and 2.5 (2.0-4.7) years in the clinical trials. Two populations were studied in this analysis: 389 529 individuals in the primary prevention group who were not taking lipid-lowering therapy and 40 430 patients with established atherosclerosis who were receiving statin treatment.
Exposures
ApoB, non-high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG.
Main outcome and measures
The primary study outcome was incident myocardial infarction (MI).
Results
Of the 389 529 individuals in the primary prevention group, 224 097 (58%) were female, and the median (IQR) age was 56.0 (49.5-62.5) years. Of the 40 430 patients with established atherosclerosis, 9647 (24%) were female, and the median (IQR) age was 63 (56.2-69.0) years. In the primary prevention cohort, apoB, non-HDL-C, and TG each individually were associated with incident MI. However, when assessed together, only apoB was associated (adjusted hazard ratio [aHR] per 1 SD, 1.27; 95% CI, 1.15-1.40; P < .001). Similarly, only apoB was associated with MI in the secondary prevention cohort. Adjusting for apoB, there was no association between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and risk of MI, implying that for a given concentration of apoB-containing lipoproteins, the relative proportions of particle subpopulations may no longer be a predictor of risk.

Conclusions:
and relevance
In this cohort study, risk of MI was best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). This suggests that apoB may be the primary driver of atherosclerosis and that lowering the concentration of all apoB-containing lipoproteins should be the focus of therapeutic strategies.



JAMA Cardiol: 28 Feb 2022; 7:250-256
Marston NA, Giugliano RP, Melloni GEM, Park JG, ... Ruff CT, Sabatine MS
JAMA Cardiol: 28 Feb 2022; 7:250-256 | PMID: 34773460
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

High-Throughput Precision Phenotyping of Left Ventricular Hypertrophy With Cardiovascular Deep Learning.

Duffy G, Cheng PP, Yuan N, He B, ... Cheng S, Ouyang D
Importance
Early detection and characterization of increased left ventricular (LV) wall thickness can markedly impact patient care but is limited by under-recognition of hypertrophy, measurement error and variability, and difficulty differentiating causes of increased wall thickness, such as hypertrophy, cardiomyopathy, and cardiac amyloidosis.
Objective
To assess the accuracy of a deep learning workflow in quantifying ventricular hypertrophy and predicting the cause of increased LV wall thickness.
Design, settings, and participants
This cohort study included physician-curated cohorts from the Stanford Amyloid Center and Cedars-Sinai Medical Center (CSMC) Advanced Heart Disease Clinic for cardiac amyloidosis and the Stanford Center for Inherited Cardiovascular Disease and the CSMC Hypertrophic Cardiomyopathy Clinic for hypertrophic cardiomyopathy from January 1, 2008, to December 31, 2020. The deep learning algorithm was trained and tested on retrospectively obtained independent echocardiogram videos from Stanford Healthcare, CSMC, and the Unity Imaging Collaborative.
Main outcomes and measures
The main outcome was the accuracy of the deep learning algorithm in measuring left ventricular dimensions and identifying patients with increased LV wall thickness diagnosed with hypertrophic cardiomyopathy and cardiac amyloidosis.
Results
The study included 23 745 patients: 12 001 from Stanford Health Care (6509 [54.2%] female; mean [SD] age, 61.6 [17.4] years) and 1309 from CSMC (808 [61.7%] female; mean [SD] age, 62.8 [17.2] years) with parasternal long-axis videos and 8084 from Stanford Health Care (4201 [54.0%] female; mean [SD] age, 69.1 [16.8] years) and 2351 from CSMS (6509 [54.2%] female; mean [SD] age, 69.6 [14.7] years) with apical 4-chamber videos. The deep learning algorithm accurately measured intraventricular wall thickness (mean absolute error [MAE], 1.2 mm; 95% CI, 1.1-1.3 mm), LV diameter (MAE, 2.4 mm; 95% CI, 2.2-2.6 mm), and posterior wall thickness (MAE, 1.4 mm; 95% CI, 1.2-1.5 mm) and classified cardiac amyloidosis (area under the curve [AUC], 0.83) and hypertrophic cardiomyopathy (AUC, 0.98) separately from other causes of LV hypertrophy. In external data sets from independent domestic and international health care systems, the deep learning algorithm accurately quantified ventricular parameters (domestic: R2, 0.96; international: R2, 0.90). For the domestic data set, the MAE was 1.7 mm (95% CI, 1.6-1.8 mm) for intraventricular septum thickness, 3.8 mm (95% CI, 3.5-4.0 mm) for LV internal dimension, and 1.8 mm (95% CI, 1.7-2.0 mm) for LV posterior wall thickness. For the international data set, the MAE was 1.7 mm (95% CI, 1.5-2.0 mm) for intraventricular septum thickness, 2.9 mm (95% CI, 2.4-3.3 mm) for LV internal dimension, and 2.3 mm (95% CI, 1.9-2.7 mm) for LV posterior wall thickness. The deep learning algorithm accurately detected cardiac amyloidosis (AUC, 0.79) and hypertrophic cardiomyopathy (AUC, 0.89) in the domestic external validation site.

Conclusions:
and relevance
In this cohort study, the deep learning model accurately identified subtle changes in LV wall geometric measurements and the causes of hypertrophy. Unlike with human experts, the deep learning workflow is fully automated, allowing for reproducible, precise measurements, and may provide a foundation for precision diagnosis of cardiac hypertrophy.



JAMA Cardiol: 22 Feb 2022; epub ahead of print
Duffy G, Cheng PP, Yuan N, He B, ... Cheng S, Ouyang D
JAMA Cardiol: 22 Feb 2022; epub ahead of print | PMID: 35195663
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Premature Ventricular Contraction Burden on Serial Holter Monitoring With Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

Gasperetti A, Cappelletto C, Carrick R, Targetti M, ... Casella M, Calkins H
Importance
A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce.
Objective
To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC.
Design, settings, and participants
In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021.
Main outcomes and measures
The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of β-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model.
Results
In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P < .001). A model including 24-hour PVC burden (odds ratio [OR] 1.50 [95% CI, 1.10-2.03]; P = .01), PVC spikes (OR, 6.20 [95 CI, 2.74-13.99]; P < .001), and NSVT (OR, 2.29 [95% CI, 1.10-4.51]; P = .03) at each follow-up Holter examination was associated with sustained ventricular arrhythmia occurrence in the following 12 months.

Conclusions:
and relevance
These findings suggest that in patients with ARVC, changes in parameters derived from each Holter examination performed during follow-up are associated with the risk of sustained ventricular arrhythmias within 12 months of disease diagnosis.



JAMA Cardiol: 22 Feb 2022; epub ahead of print
Gasperetti A, Cappelletto C, Carrick R, Targetti M, ... Casella M, Calkins H
JAMA Cardiol: 22 Feb 2022; epub ahead of print | PMID: 35195686
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.