Journal: J Am Coll Cardiol

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Abstract

Mendelian Randomization Study of PCSK9 and HMG-CoA Reductase Inhibition and Cognitive Function.

Rosoff DB, Bell AS, Jung J, Wagner J, Mavromatis LA, Lohoff FW
Background
Lipid-lowering therapy with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition are effective strategies in reducing cardiovascular disease risk; however, concerns remain about potential long-term adverse neurocognitive effects.
Objectives
This genetics-based study aimed to evaluate the relationships of long-term PCSK9 inhibition and statin use on neurocognitive outcomes.
Methods
We extracted single-nucleotide polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and PCSK9 from predominantly European ancestry-based genome-wide association studies summary-level statistics of low-density lipoprotein cholesterol and performed drug-target Mendelian randomization, proxying the potential neurocognitive impact of drug-based PCSK9 and HMGCR inhibition using a range of outcomes to capture the complex facets of cognition and dementia.
Results
Using data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area. Conversely, we observed several adverse associations for HMGCR inhibition with lowered cognitive performance (beta: -0.082; 95% CI: -0.16 to -0.0080; P = 0.03), reaction time (beta = 0.00064; 95% CI: 0.00030-0.00098; P = 0.0002), and cortical surface area (beta = -0.18; 95% CI: -0.35 to -0.014; P = 0.03). Neither PCSK9 nor HMGCR inhibition impacted biomarkers of Alzheimer\'s disease progression or Lewy body dementia risk. Consistency of findings across Mendelian randomization methods accommodating different assumptions about genetic pleiotropy strengthens causal inference.
Conclusions
Using a wide range of cognitive function and dementia endpoints, we failed to find genetic evidence of an adverse PCSK9-related impact, suggesting a neutral cognitive profile. In contrast, we observed adverse neurocognitive effects related to HMGCR inhibition, which may well be outweighed by the cardiovascular benefits of statin use, but nonetheless may warrant pharmacovigilance.

Published by Elsevier Inc.

J Am Coll Cardiol: 16 Aug 2022; 80:653-662
Rosoff DB, Bell AS, Jung J, Wagner J, Mavromatis LA, Lohoff FW
J Am Coll Cardiol: 16 Aug 2022; 80:653-662 | PMID: 35953131
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Abstract

Prevalence and Prognostic Implications of Discordant Grading and Flow-Gradient Patterns in Moderate Aortic Stenosis.

Stassen J, Ewe SH, Singh GK, Butcher SC, ... Marsan NA, Bax JJ
Background
The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown.
Objectives
The purpose of this study was to investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS.
Methods
Patients with moderate AS (aortic valve area >1.0 and ≤1.5 cm2) were identified and divided in 4 groups based on transvalvular mean gradient (MG), stroke volume index (SVi), and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mm Hg) and discordant moderate AS including 3 subgroups: normal-flow, low-gradient moderate AS (MG <20 mm Hg, SVi ≥35 mL/m2, and LVEF ≥50%); \"paradoxical\" low-flow, low-gradient moderate AS (MG <20 mm Hg, SVi <35 mL/m2, and LVEF ≥50%) and \"classical\" low-flow, low-gradient moderate AS (MG <20 mm Hg and LVEF <50%). The primary endpoint was all-cause mortality.
Results
Of 1,974 patients (age 73 ± 10 years, 51% men) with moderate AS, 788 (40%) had discordant grading, and these patients showed significantly higher mortality rates than patients with concordant moderate AS (P < 0.001). On multivariable analysis, \"paradoxical\" low-flow, low-gradient (HR: 1.458; 95% CI: 1.072-1.983; P = 0.014) and \"classical\" low-flow, low-gradient (HR: 1.710; 95% CI: 1.270-2.303; P < 0.001) patterns but not the normal-flow, low-gradient moderate AS pattern were independently associated with all-cause mortality.
Conclusions
Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Aug 2022; 80:666-676
Stassen J, Ewe SH, Singh GK, Butcher SC, ... Marsan NA, Bax JJ
J Am Coll Cardiol: 16 Aug 2022; 80:666-676 | PMID: 35953133
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Abstract

Clinical Characteristics and Transplant-Free Survival Across the Spectrum of Pulmonary Vascular Disease.

Hemnes AR, Leopold JA, Radeva MK, Beck GJ, ... Horn EM, PVDOMICS Study Group
Background
PVDOMICS (Pulmonary Vascular Disease Phenomics) is a precision medicine initiative to characterize pulmonary vascular disease (PVD) using deep phenotyping. PVDOMICS tests the hypothesis that integration of clinical metrics with omic measures will enhance understanding of PVD and facilitate an updated PVD classification.
Objectives
The purpose of this study was to describe clinical characteristics and transplant-free survival in the PVDOMICS cohort.
Methods
Subjects with World Symposium Pulmonary Hypertension (WSPH) group 1-5 PH, disease comparators with similar underlying diseases and mild or no PH and healthy control subjects enrolled in a cross-sectional study. PH groups, comparators were compared using standard statistical tests including log-rank tests for comparing time to transplant or death.
Results
A total of 1,193 subjects were included. Multiple WSPH groups were identified in 38.9% of PH subjects. Nocturnal desaturation was more frequently observed in groups 1, 3, and 4 PH vs comparators. A total of 50.2% of group 1 PH subjects had ground glass opacities on chest computed tomography. Diffusing capacity for carbon monoxide was significantly lower in groups 1-3 PH than their respective comparators. Right atrial volume index was higher in WSPH groups 1-4 than comparators. A total of 110 participants had a mean pulmonary artery pressure of 21-24 mm Hg. Transplant-free survival was poorest in group 3 PH.
Conclusions
PVDOMICS enrolled subjects across the spectrum of PVD, including mild and mixed etiology PH. Novel findings include low diffusing capacity for carbon monoxide and enlarged right atrial volume index as shared features of groups 1-3 and 1-4 PH, respectively; unexpected, frequent presence of ground glass opacities on computed tomography; and sleep alterations in group 1 PH, and poorest survival in group 3 PH. PVDOMICS will facilitate a new understanding of PVD and refine the current PVD classification. (Pulmonary Vascular Disease Phenomics Program PVDOMICS [PVDOMICS]; NCT02980887).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Aug 2022; 80:697-718
Hemnes AR, Leopold JA, Radeva MK, Beck GJ, ... Horn EM, PVDOMICS Study Group
J Am Coll Cardiol: 16 Aug 2022; 80:697-718 | PMID: 35953136
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Abstract

Management of Patients With Severe Mitral Annular Calcification: JACC State-of-the-Art Review.

Chehab O, Roberts-Thomson R, Bivona A, Gill H, ... Prendergast B, Rajani R
Mitral annular calcification (MAC) is a common and challenging pathologic condition, especially in the context of an aging society. Surgical mitral valve intervention in patients with MAC is difficult, with varying approaches to the calcified annular anatomy, and the advent of transcatheter valve interventions has provided additional treatment options. Advanced imaging provides the foundation for heart team discussions and management decisions concerning individual patients. This review focuses on the prognosis of, preoperative planning for, and management strategies for patients with MAC.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Aug 2022; 80:722-738
Chehab O, Roberts-Thomson R, Bivona A, Gill H, ... Prendergast B, Rajani R
J Am Coll Cardiol: 16 Aug 2022; 80:722-738 | PMID: 35953138
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Abstract

Mitral Valve Dysfunction in Patients With Annular Calcification: JACC Review Topic of the Week.

Churchill TW, Yucel E, Deferm S, Levine RA, Hung J, Bertrand PB
Mitral annular calcification (MAC) is a common clinical finding and is associated with adverse clinical outcomes, but the clinical impact of MAC-related mitral valve (MV) dysfunction remains underappreciated. Patients with MAC frequently have stenotic, regurgitant, or mixed valvular disease, and this valvular dysfunction is increasingly recognized to be independently associated with worse prognosis. MAC-related MV dysfunction is a distinct pathophysiologic entity, and importantly much of the diagnostic and therapeutic paradigm from published rheumatic MV disease research cannot be applied in this context, leaving important gaps in our knowledge. This review summarizes the current epidemiology, pathophysiology, diagnosis, and classification of MAC-related MV dysfunction and proposes both an integrative definition and an overarching approach to this important and increasingly recognized clinical condition.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 16 Aug 2022; 80:739-751
Churchill TW, Yucel E, Deferm S, Levine RA, Hung J, Bertrand PB
J Am Coll Cardiol: 16 Aug 2022; 80:739-751 | PMID: 35953139
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Abstract

Cardiovascular Disease Projections in the United States Based on the 2020 Census Estimates.

Mohebi R, Chen C, Ibrahim NE, McCarthy CP, ... Wasfy JH, Januzzi JL
Background
Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions.
Objectives
The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities.
Methods
The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060.
Results
By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities.
Conclusions
Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Aug 2022; 80:565-578
Mohebi R, Chen C, Ibrahim NE, McCarthy CP, ... Wasfy JH, Januzzi JL
J Am Coll Cardiol: 09 Aug 2022; 80:565-578 | PMID: 35926929
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Abstract

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure.

Ye F, Wang X, Wu S, Ma S, ... Wang J, FIRST Investigators
Background
Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.
Objectives
This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.
Methods
Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.
Results
We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.
Conclusions
The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Aug 2022; 80:584-594
Ye F, Wang X, Wu S, Ma S, ... Wang J, FIRST Investigators
J Am Coll Cardiol: 09 Aug 2022; 80:584-594 | PMID: 35926931
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Abstract

Cardiorespiratory Fitness and Mortality Risk Across the Spectra of Age, Race, and Sex.

Kokkinos P, Faselis C, Samuel IBH, Pittaras A, ... Zhang J, Myers J
Background
Cardiorespiratory fitness (CRF) is inversely associated with all-cause mortality. However, the association of CRF and mortality risk for different races, women, and elderly individuals has not been fully assessed.
Objectives
The aim of this study was to evaluate the association of CRF and mortality risk across the spectra of age, race, and sex.
Methods
A total of 750,302 U.S. veterans aged 30 to 95 years (mean age 61.3 ± 9.8 years) were studied, including septuagenarians (n = 110,637), octogenarians (n = 26,989), African Americans (n = 142,798), Hispanics (n = 35,197), Native Americans (n = 16,050), and women (n = 45,232). Age- and sex-specific CRF categories (quintiles and 98th percentile) were established objectively on the basis of peak METs achieved during a standardized exercise treadmill test. Multivariable Cox models were used to estimate HRs and 95% CIs for mortality across the CRF categories.
Results
During follow-up (median 10.2 years, 7,803,861 person-years of observation), 174,807 subjects died, averaging 22.4 events per 1,000 person-years. The adjusted association of CRF and mortality risk was inverse and graded across the age spectrum, sex, and race. The lowest mortality risk was observed at approximately 14.0 METs for men (HR: 0.24; 95% CI: 0.23-0.25) and women (HR: 0.23; 95% CI: 0.17-0.29), with no evidence of an increase in risk with extremely high CRF. The risk for least fit individuals (20th percentile) was 4-fold higher (HR: 4.09; 95% CI: 3.90-4.20) compared with extremely fit individuals.
Conclusions
The association of CRF and mortality risk across the age spectrum (including septuagenarians and octogenarians), men, women, and all races was inverse, independent, and graded. No increased risk was observed with extreme fitness. Being unfit carried a greater risk than any of the cardiac risk factors examined.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Aug 2022; 80:598-609
Kokkinos P, Faselis C, Samuel IBH, Pittaras A, ... Zhang J, Myers J
J Am Coll Cardiol: 09 Aug 2022; 80:598-609 | PMID: 35926933
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Abstract

Deep Learning Electrocardiographic Analysis for Detection of Left-Sided Valvular Heart Disease.

Elias P, Poterucha TJ, Rajaram V, Moller LM, ... Leon MB, Perotte AJ
Background
Valvular heart disease is an important contributor to cardiovascular morbidity and mortality and remains underdiagnosed. Deep learning analysis of electrocardiography (ECG) may be useful in detecting aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR).
Objectives
This study aimed to develop ECG deep learning algorithms to identify moderate or severe AS, AR, and MR alone and in combination.
Methods
A total of 77,163 patients undergoing ECG within 1 year before echocardiography from 2005-2021 were identified and split into train (n = 43,165), validation (n = 12,950), and test sets (n = 21,048; 7.8% with any of AS, AR, or MR). Model performance was assessed using area under the receiver-operating characteristic (AU-ROC) and precision-recall curves. Outside validation was conducted on an independent data set. Test accuracy was modeled using different disease prevalence levels to simulate screening efficacy using the deep learning model.
Results
The deep learning algorithm model accuracy was as follows: AS (AU-ROC: 0.88), AR (AU-ROC: 0.77), MR (AU-ROC: 0.83), and any of AS, AR, or MR (AU-ROC: 0.84; sensitivity 78%, specificity 73%) with similar accuracy in external validation. In screening program modeling, test characteristics were dependent on underlying prevalence and selected sensitivity levels. At a prevalence of 7.8%, the positive and negative predictive values were 20% and 97.6%, respectively.
Conclusions
Deep learning analysis of the ECG can accurately detect AS, AR, and MR in this multicenter cohort and may serve as the basis for the development of a valvular heart disease screening program.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Aug 2022; 80:613-626
Elias P, Poterucha TJ, Rajaram V, Moller LM, ... Leon MB, Perotte AJ
J Am Coll Cardiol: 09 Aug 2022; 80:613-626 | PMID: 35926935
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Abstract

Impact of the COVID-19 Pandemic on Cardiovascular Health in 2020: JACC State-of-the-Art Review.

Roth GA, Vaduganathan M, Mensah GA
The impact of COVID-19 on the burden of cardiovascular diseases (CVD) during the early pandemic remains unclear. COVID-19 has become one of the leading causes of global mortality, with a disproportionate impact on persons with CVD. Studies of health facility admissions for CVD found significant decreases during the pandemic. Studies of hospital mortality for CVD were more variable. Studies of population-level CVD mortality differed across countries, with most showing decreases, although some revealed increases in deaths. In some countries where large increases in CVD deaths were reported in vital registration systems, misclassification of COVID-19 as CVD may have occurred. Taken together, studies suggest heterogeneous effects of the COVID-19 pandemic on CVD without large increases in CVD mortality in 2020 for a number of countries. Clinical and population science research is needed to examine the ways in which the pandemic has affected CVD burden.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 09 Aug 2022; 80:631-640
Roth GA, Vaduganathan M, Mensah GA
J Am Coll Cardiol: 09 Aug 2022; 80:631-640 | PMID: 35926937
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Abstract

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations.

Whelton PK, Carey RM, Mancia G, Kreutz R, Bundy JD, Williams B
The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines are comprehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points recommended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline recommending a somewhat more intensive approach. Overall, there is substantial concordance in the recommendations provided by the 2 guideline-writing committees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore the commonality of their core recommendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

Copyright © 2022 American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 04 Aug 2022; epub ahead of print
Whelton PK, Carey RM, Mancia G, Kreutz R, Bundy JD, Williams B
J Am Coll Cardiol: 04 Aug 2022; epub ahead of print | PMID: 35965201
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Abstract

Impact of Peridevice Leak on 5-Year Outcomes After Left Atrial Appendage Closure.

Dukkipati SR, Holmes DR, Doshi SK, Kar S, ... Allocco DJ, Reddy VY
Background
In the U.S. Food and Drug Administration (FDA) clinical trials of left atrial appendage (LAA) closure, a postimplantation peridevice leak (PDL) of ≤5 mm (PDL≤5) was accepted as sufficient LAA \"closure.\" However, the clinical consequences of these PDLs on subsequent thromboembolism are poorly characterized.
Objectives
We sought to assess the impact of PDL≤5 on clinical outcomes after implantation of the Watchman device.
Methods
Using combined data from the FDA studies PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation), PREVAIL (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy), and CAP2 (Continued Access to PREVAIL), we assessed patients with successful device implantation for PDL by means of protocol-mandated transesophageal echocardiograms (TEEs) at 45 days and 1 year. Five-year outcomes were assessed as a function of the absence or presence of PDL≤5.
Results
The cohort included 1,054 patients: mean age 74 ± 8.3 years, 65% male, and CHA2DS2-VASc 4.1 ± 1.4. TEE imaging at 45 days revealed 634 patients (60.2%) without and 404 (38.3%) with PDL≤5, and 1-year TEE revealed 704 patients (71.6%) without and 272 (27.7%) with PDL≤5. The presence of PDL≤5 at 1 year, but not at 45 days, was associated with an increased 5-year risk of ischemic stroke or systemic embolism (adjusted HR: 1.94; 95% CI: 1.15-3.29; P = 0.014), largely driven by an increase in nondisabling stroke (HR: 1.97; 95% CI: 1.03-3.78; P = 0.04), while disabling or fatal stroke rates were similar (HR: 0.69; 95% CI: 0.19-2.46; P = 0.56). PDL≤5 was not associated with an increased risk of cardiovascular or unexplained death (HR: 1.20; P = 0.45) or all-cause death (HR: 0.87; P = 0.42).
Conclusions
PDL≤5 at 1 year after percutaneous LAA closure with the Watchman device are associated with increased thromboembolism, driven by increased nondisabling stroke, but similar mortality. (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [PROTECT-AF; NCT00129545]; Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation vs Long Term Warfarin Therapy [PREVAIL; NCT01182441]; Continued Access to PREVAIL [CAP2; NCT01760291]).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 02 Aug 2022; 80:469-483
Dukkipati SR, Holmes DR, Doshi SK, Kar S, ... Allocco DJ, Reddy VY
J Am Coll Cardiol: 02 Aug 2022; 80:469-483 | PMID: 35902169
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Abstract

Spatially Distinct Genetic Determinants of Aortic Dimensions Influence Risks of Aneurysm and Stenosis.

Nekoui M, Pirruccello JP, Di Achille P, Choi SH, ... Lindsay ME, Ellinor PT
Background
The left ventricular outflow tract (LVOT) and ascending aorta are spatially complex, with distinct pathologies and embryologic origins. Prior work examined the genetics of thoracic aortic diameter in a single plane.
Objectives
We sought to elucidate the genetic basis for the diameter of the LVOT, aortic root, and ascending aorta.
Methods
Using deep learning, we analyzed 2.3 million cardiac magnetic resonance images from 43,317 UK Biobank participants. We computed the diameters of the LVOT, the aortic root, and at 6 locations of ascending aorta. For each diameter, we conducted a genome-wide association study and generated a polygenic score. Finally, we investigated associations between these scores and disease incidence.
Results
A total of 79 loci were significantly associated with at least 1 diameter. Of these, 35 were novel, and most were associated with 1 or 2 diameters. A polygenic score of aortic diameter approximately 13 mm from the sinotubular junction most strongly predicted thoracic aortic aneurysm (n = 427,016; mean HR: 1.42 per SD; 95% CI: 1.34-1.50; P = 6.67 × 10-21). A polygenic score predicting a smaller aortic root was predictive of aortic stenosis (n = 426,502; mean HR: 1.08 per SD; 95% CI: 1.03-1.12; P = 5 × 10-6).
Conclusions
We detected distinct genetic loci underpinning the diameters of the LVOT, aortic root, and at several segments of ascending aorta. We spatially defined a region of aorta whose genetics may be most relevant to predicting thoracic aortic aneurysm. We further described a genetic signature that may predispose to aortic stenosis. Understanding genetic contributions to proximal aortic diameter may enable identification of individuals at risk for aortic disease and facilitate prioritization of therapeutic targets.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:486-497
Nekoui M, Pirruccello JP, Di Achille P, Choi SH, ... Lindsay ME, Ellinor PT
J Am Coll Cardiol: 02 Aug 2022; 80:486-497 | PMID: 35902171
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Abstract

Effects of Cyproheptadine on Mitral Valve Remodeling and Regurgitation After Myocardial Infarction.

Marsit O, Clavel MA, Paquin A, Deschênes V, ... Pibarot P, Beaudoin J
Background
Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR).
Objectives
This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology.
Methods
Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals.
Results
Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals.
Conclusions
Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:500-510
Marsit O, Clavel MA, Paquin A, Deschênes V, ... Pibarot P, Beaudoin J
J Am Coll Cardiol: 02 Aug 2022; 80:500-510 | PMID: 35902173
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Abstract

Nurse-Provided Lung and Inferior Vena Cava Assessment in Patients With Heart Failure.

Zisis G, Yang Y, Huynh Q, Whitmore K, ... Carrington MJ, Marwick TH
Background
Residual congestion detected using handheld ultrasound may be associated with increased risk of readmission and death after hospitalization for acute decompensated heart failure (ADHF). However, effective application necessitates routine use by nonexperts delivering clinical care.
Objectives
The objective of this study was to determine the ability of heart failure (HF) nurses to deliver a predischarge lung and inferior vena cava (IVC) assessment (LUICA) to predict 90-day outcomes.
Methods
In this multisite, prospective, observational study, HF nurses scanned 240 patients with ADHF (median age: 77 years; 56% men) using a 9-zone LUICA protocol. Obtained images were reviewed by independent nurses who were blinded to clinical characteristics and outcomes. Based on a B-line cut-off of 10, patients were dichotomized as congested (n = 115) or not congested (n = 125).
Results
Congested patients were more likely to have previous cardiac operations, long-standing HF (>6 months), and renal impairment. At 90 days, HF readmission or mortality occurred in 42 congested patients (37%) compared with 18 noncongested patients (14%). Pulmonary congestion increased at 30-day (OR: 3.86; 95% CI: 1.65-8.99; P < 0.01) and 90-day (OR: 3.42; 95% CI: 1.82-6.4; P < 0.01) HF readmission or mortality risk and 90-day mortality (OR: 5.18; 95% CI: 1.44-18.69; P < 0.01). Pulmonary congestion increased the 90-day odds of HF readmission and/or death by 3.3- to 4.2-fold (P < 0.01), independent of demographics, HF characteristics, comorbidities, and event risk score. Over 90 days, days alive out of hospital were fewer (78.3 ± 21.4 days vs 85.5 ± 12.4 days; P < 0.01) in congested patients.
Conclusions
LUICA can be a powerful tool for detection of predischarge residual congestion. HF nurses can obtain images and provide diagnostic reports that are predictive of ADHF outcomes.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:513-523
Zisis G, Yang Y, Huynh Q, Whitmore K, ... Carrington MJ, Marwick TH
J Am Coll Cardiol: 02 Aug 2022; 80:513-523 | PMID: 35902175
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Impact:
Abstract

Bioprosthetic Aortic Valve Hemodynamics: Definitions, Outcomes, and Evidence Gaps: JACC State-of-the-Art Review.

Herrmann HC, Pibarot P, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
A virtual workshop was organized by the Heart Valve Collaboratory to identify areas of expert consensus, areas of disagreement, and evidence gaps related to bioprosthetic aortic valve hemodynamics. Impaired functional performance of bioprosthetic aortic valve replacement is associated with adverse patient outcomes; however, this assessment is complicated by the lack of standardization for labelling, definitions, and measurement techniques, both after surgical and transcatheter valve replacement. Echocardiography remains the standard assessment methodology because of its ease of performance, widespread availability, ability to do serial measurements over time, and correlation with outcomes. Management of a high gradient after replacement requires integration of the patient\'s clinical status, physical examination, and multimodality imaging in addition to shared patient decisions regarding treatment options. Future priorities that are underway include efforts to standardize prosthesis sizing and labelling for both surgical and transcatheter valves as well as trials to characterize the consequences of adverse hemodynamics.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:527-544
Herrmann HC, Pibarot P, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
J Am Coll Cardiol: 02 Aug 2022; 80:527-544 | PMID: 35902177
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Impact:
Abstract

Standardized Definitions for Bioprosthetic Valve Dysfunction Following Aortic or Mitral Valve Replacement: JACC State-of-the-Art Review.

Pibarot P, Herrmann HC, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
Bioprosthetic valve dysfunction (BVD) and bioprosthetic valve failure (BVF) may be caused by structural or nonstructural valve dysfunction. Both surgical and transcatheter bioprosthetic valves have limited durability because of structural valve deterioration. The main objective of this summary of experts participating in a virtual workshop was to propose standardized definitions for nonstructural and structural BVD and BVF following aortic or mitral biological valve replacement with the goal of facilitating research reporting and implementation of these terms in clinical practice. Definitions of structural BVF, based on valve reintervention or death, underestimate the true incidence of BVF. However, definitions solely based on the presence of high transprosthetic gradient at a given echocardiogram during follow-up overestimate the incidence of structural BVD and BVF. Definitions of aortic or mitral structural BVD must therefore include the confirmation by imaging of permanent structural changes to the leaflets alongside evidence of deterioration in valve hemodynamic function at echocardiography follow-up.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 02 Aug 2022; 80:545-561
Pibarot P, Herrmann HC, Wu C, Hahn RT, ... Leon MB, Heart Valve Collaboratory
J Am Coll Cardiol: 02 Aug 2022; 80:545-561 | PMID: 35902178
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Abstract

Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy.

Goette A, Borof K, Breithardt G, Camm AJ, ... Kirchhof P, EAST-AFNET 4 Investigators
Background
Whether atrial fibrillation (AF) pattern or timing of AF therapy modifies the effectiveness of early rhythm control (ERC) is not known.
Objectives
This study sought to compare clinical characteristics and outcomes in patients presenting with different AF patterns on ERC vs usual care.
Methods
The effects of ERC were compared in first-diagnosed AF (FDAF), paroxysmal AF (paroxAF), and persistent AF (persAF) in this prespecified analysis of the EAST-AFNET 4 (Early treatment of atrial fibrillation for stroke prevention) trial. Associations between AF pattern and primary outcomes (first primary outcome: cardiovascular death, stroke, and hospitalization for heart failure and acute coronary syndrome; second primary outcome: nights spent in hospital per year) were compared over a mean follow-up of 5.1 years. Changes in health-related quality of life were assessed by the EQ-5D.
Results
FDAF patients (n = 1,048, enrolled 7 days after diagnosing AF) were slightly older (71 years of age, 48.0% female) than patients with paroxAF (n = 994, 70 years of age, 50.0% female) and persAF (n = 743, 70 years of age, 38.0% female). ERC reduced the primary outcome in all 3 AF patterns. Hospitalizations for acute coronary syndrome were highest in FDAF (incidence rate ratio [IRR]: 1.50; 95% CI: 0.83-2.69; P for interaction = 0.032) compared with paroxAF (IRR: 0.64; 95% CI: 0.32-1.25) and persAF (IRR: 0.50; 95% CI: 0.25-1.00). FDAF patients spent more nights in hospital (IRR: 1.38; 95% CI: 1.12-1.70; P for interaction = 0.004) than paroxAF (IRR: 0.84; 95% CI: 0.67-1.03), and persAF (IRR: 1.02; 95% CI: 0.80-1.30) patients. ERC improved health-related quality of life (EQ-5D score) in patients with paroxAF and persAF but not in patients with FDAF (P = 0.019).
Conclusions
ERC reduces the first primary composite outcome in all AF patterns. Patients with FDAF are at high risk for hospitalization and acute coronary syndrome, particularly on ERC. (Early treatment of atrial fibrillation for stroke prevention trial; ISRCTN04708680; Early Treatment of Atrial Fibrillation for Stroke Prevention Trial [EAST]; NCT01288352; Early treatment of Atrial fibrillation for Stroke prevention Trial [EAST]; EudraCT2010-021258-20).

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:283-295
Goette A, Borof K, Breithardt G, Camm AJ, ... Kirchhof P, EAST-AFNET 4 Investigators
J Am Coll Cardiol: 26 Jul 2022; 80:283-295 | PMID: 35863844
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Impact:
Abstract

Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults.

Barhoum P, Pineton de Chambrun M, Dorgham K, Kerneis M, ... Gorochov G, Hékimian G
Background
Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19-related myocarditis.
Objectives
This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19-related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A-).
Methods
A monocentric retrospective analysis of consecutive fulminant COVID-19-related myocarditis in a 26-bed intensive care unit (ICU).
Results
Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19-related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A- patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A- patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A- had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A- patients (54%) but in none of the MIS-A+ patients.
Conclusion
MIS-A+ and MIS-A- fulminant COVID-19-related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients\' management and further understanding of their pathophysiology.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:299-312
Barhoum P, Pineton de Chambrun M, Dorgham K, Kerneis M, ... Gorochov G, Hékimian G
J Am Coll Cardiol: 26 Jul 2022; 80:299-312 | PMID: 35863846
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Abstract

Association of Blood Viscosity With Mortality Among Patients Hospitalized With COVID-19.

Choi D, Waksman O, Shaik A, Mar P, ... Goonewardena SN, Rosenson RS
Background
Coronavirus disease-2019 (COVID-19) is characterized by a dysfunctional immune response and abnormal blood rheology that contribute to endothelial dysfunction and thrombotic complications. Whole blood viscosity (WBV) is a clinically validated measure of blood rheology and an established predictor of cardiovascular risk. We hypothesize that increased WBV is associated with mortality among patients hospitalized with COVID-19.
Objectives
This study sought to determine the association between estimated BV (eBV) and mortality among hospitalized COVID-19 patients.
Methods
The study population included 5,621 hospitalized COVID-19 patients at the Mount Sinai Health System from February 27, 2020, to November 27, 2021. eBV was calculated using the Walburn-Schneck model. Multivariate Cox proportional hazards models were used to evaluate the association between eBV and mortality. Considered covariates included age, sex, race, cardiovascular and metabolic comorbidities, in-house pharmacotherapy, and baseline inflammatory biomarkers.
Results
Estimated high-shear BV (eHSBV) and estimated low-shear BV were associated with increased in-hospital mortality. One-centipoise increases in eHSBV and estimated low-shear BV were associated with a 36.0% and 7.0% increase in death, respectively (P < 0.001). Compared with participants in the lowest quartile of eHSBV, those in the highest quartile of eHSBV had higher mortality (adjusted HR: 1.53; 95% CI: 1.27-1.84). The association was consistent among multiple subgroups, notably among patients without any comorbidities (adjusted HR: 1.69; 95% CI: 1.28-2.22).
Conclusions
Among hospitalized COVID-19 patients, increased eBV is significantly associated with higher mortality. This suggests that eBV can prognosticate patient outcomes in earlier stages of COVID-19, and that future therapeutics aimed at reducing WBV should be evaluated.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:316-328
Choi D, Waksman O, Shaik A, Mar P, ... Goonewardena SN, Rosenson RS
J Am Coll Cardiol: 26 Jul 2022; 80:316-328 | PMID: 35863848
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Abstract

Criteria for Referral of Patients With Advanced Heart Failure for Specialized Palliative Care.

Chang YK, Allen LA, McClung JA, Denvir MA, ... Collins A, Hui D
Background
Patients with advanced heart failure have substantial supportive care needs. Specialist palliative care can be beneficial, but it is unclear who is most appropriate for referral and when patients should be referred.
Objectives
We conducted a Delphi study of international experts to identify consensus referral criteria for specialist palliative care for patients with advanced heart failure.
Methods
Clinicians from 5 continents with expertise in the integration of cardiology and palliative care were asked to rate 34 disease-based, 24 needs-based, and 9 time-based criteria over 3 rounds. Consensus was defined a priori as ≥70% agreement. A criterion was coded as major if the experts endorsed that meeting that criterion alone was adequate to justify a referral.
Results
The response rate was 44 of 46 (96%), 41 of 46 (89%), and 43 of 46 (93%) in the first, second, and third rounds, respectively. Panelists reached consensus on 25 major criteria for specialist palliative care referral. The 25 major criteria were categorized under 6 topics, including \"advanced/refractory heart failure, comorbidities, and complications\" (eg, cardiac cachexia, cardiorenal syndrome) (n = 8), \"advanced heart failure therapies\" (eg, chronic inotropes, precardiac transplant) (n = 4), \"hospital utilization\" (eg, emergency room visits, hospitalization) (n = 2), \"prognostic estimate\" (n = 1), \"symptom burden/distress\" (eg, severe physical/emotional/spiritual distress) (n = 6), and \"decision making/social support\" (eg, goals-of-care discussions) (n = 4). The majority (68%) of major criteria had ≥90% agreement.
Conclusions
International experts reached consensus on a large number of criteria for referral to specialist palliative care. With further validation, these criteria may be useful for standardizing palliative care access in the inpatient and/or outpatient settings.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:332-344
Chang YK, Allen LA, McClung JA, Denvir MA, ... Collins A, Hui D
J Am Coll Cardiol: 26 Jul 2022; 80:332-344 | PMID: 35863850
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Impact:
Abstract

Coronary In-Stent Restenosis: JACC State-of-the-Art Review.

Giustino G, Colombo A, Camaj A, Yasumura K, ... Kini A, Sharma SK
The introduction and subsequent iterations of drug-eluting stent technologies have substantially improved the efficacy and safety of percutaneous coronary interventions. However, the incidence of in-stent restenosis (ISR) and the resultant need for repeated revascularization still occur at a rate of 1%-2% per year. Given that millions of drug-eluting stents are implanted each year around the globe, ISR can be considered as a pathologic entity of public health significance. The mechanisms of ISR are multifactorial. Since the first description of the angiographic patterns of ISR, the advent of intracoronary imaging has further elucidated the mechanisms and patterns of ISR. The armamentarium and treatment strategies of ISR have also evolved over time. Currently, an individualized approach using intracoronary imaging to characterize the underlying substrate of ISR is recommended. In this paper, we comprehensively reviewed the incidence, mechanisms, and imaging characterization of ISR and propose a contemporary treatment algorithm.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:348-372
Giustino G, Colombo A, Camaj A, Yasumura K, ... Kini A, Sharma SK
J Am Coll Cardiol: 26 Jul 2022; 80:348-372 | PMID: 35863852
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Impact:
Abstract

New Cardiovascular Risk Assessment Techniques for Primary Prevention: JACC Review Topic of the Week.

Verma KP, Inouye M, Meikle PJ, Nicholls SJ, Carrington MJ, Marwick TH
Risk factor-based models fail to accurately estimate risk in select populations, in particular younger individuals. A sizable number of people are also classified as being at intermediate risk, for whom the optimal preventive strategy could be more precise. Several personalized risk prediction tools, including coronary artery calcium scoring, polygenic risk scores, and metabolic risk scores may be able to improve risk assessment, pending supportive outcome data from clinical trials. Other tools may well emerge in the near future. A multidimensional approach to risk prediction holds the promise of precise risk prediction. This could allow for targeted prevention minimizing unnecessary costs and risks while maximizing benefits. High-risk individuals could also be identified early in life, creating opportunities to arrest the development of nascent coronary atherosclerosis and prevent future clinical events.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Jul 2022; 80:373-387
Verma KP, Inouye M, Meikle PJ, Nicholls SJ, Carrington MJ, Marwick TH
J Am Coll Cardiol: 26 Jul 2022; 80:373-387 | PMID: 35863853
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Impact:
Abstract

Criteria for Defining Stages of Cardiogenic Shock Severity.

Kapur NK, Kanwar M, Sinha SS, Thayer KL, ... Blumer V, Burkhoff D
Background
Risk-stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks uniform criteria defining each stage.
Objectives
The purpose of this study was to test parameters that define SCAI stages and explore their utility as predictors of in-hospital mortality in CS.
Methods
The CS Working Group registry includes patients from 17 hospitals enrolled between 2016 and 2021 and was used to define clinical profiles for CS. We selected parameters of hypotension and hypoperfusion and treatment intensity, confirmed their association with mortality, then defined formal criteria for each stage and tested the association between both baseline and maximum Stage and mortality.
Results
Of 3,455 patients, CS was caused by heart failure (52%) or myocardial infarction (32%). Mortality was 35% for the total cohort and higher among patients with myocardial infarction, out-of-hospital cardiac arrest, and treatment with increasing numbers of drugs and devices. Systolic blood pressure, lactate level, alanine transaminase level, and systemic pH were significantly associated with mortality and used to define each stage. Using these criteria, baseline and maximum stages were significantly associated with mortality (n = 1,890). Lower baseline stage was associated with a higher incidence of stage escalation and a shorter duration of time to reach maximum stage.
Conclusions
We report a novel approach to define SCAI stages and identify a significant association between baseline and maximum stage and mortality. This approach may improve clinical application of the staging system and provides new insight into the trajectory of hospitalized CS patients. (Cardiogenic Shock Working Group Registry [CSWG]; NCT04682483).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 19 Jul 2022; 80:185-198
Kapur NK, Kanwar M, Sinha SS, Thayer KL, ... Blumer V, Burkhoff D
J Am Coll Cardiol: 19 Jul 2022; 80:185-198 | PMID: 35835491
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Impact:
Abstract

Benefit of Early Revascularization Based on Inducible Ischemia and Left Ventricular Ejection Fraction.

Rozanski A, Miller RJH, Gransar H, Han D, ... Thomson L, Berman DS
Background
The utility of performing early myocardial revascularization among patients presenting with inducible myocardial ischemia and low left ventricular ejection fraction (LVEF) is currently unknown.
Objectives
In this study, we sought to assess the relationship between stress-induced myocardial ischemia, revascularization, and all-cause mortality (ACM) among patients with normal vs low LVEF.
Methods
We evaluated 43,443 patients undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging from 1998 to 2017. Median follow-up was 11.4 years. Myocardial ischemia was assessed for its interaction between early revascularization and mortality. A propensity score was used to adjust for nonrandomization to revascularization, followed by multivariable Cox modeling adjusted for the propensity score and clinical variables to predict ACM.
Results
The frequency of myocardial ischemia varied markedly according to LVEF and angina, ranging from 6.7% among patients with LVEF ≥55% and no typical angina to 64.0% among patients with LVEF <45% and typical angina (P < 0.001). Among 39,883 patients with LVEF ≥45%, early revascularization was associated with increased mortality risk among patients without ischemia and lower mortality risk among patients with severe (≥15%) ischemia (HR: 0.70; 95% CI: 0.52-0.95). Among 3,560 patients with LVEF <45%, revascularization was not associated with mortality benefit among patients with no or mild ischemia, and was associated with decreased mortality among patients with moderate (10%-14%) (HR: 0.67; 95% CI: 0.49-0.91) and severe (≥15%) (HR: 0.55; 95% CI: 0.38-0.80) ischemia.
Conclusions
Within this cohort, early myocardial revascularization was associated with a significant reduction in mortality among both patients with normal LVEF and severe inducible myocardial ischemia and patients with low LVEF and moderate or severe inducible myocardial ischemia.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 19 Jul 2022; 80:202-215
Rozanski A, Miller RJH, Gransar H, Han D, ... Thomson L, Berman DS
J Am Coll Cardiol: 19 Jul 2022; 80:202-215 | PMID: 35835493
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Impact:
Abstract

Subclinical Atherosclerosis in Young, Socioeconomically Vulnerable Hispanic and Non-Hispanic Black Adults.

Iglesies-Grau J, Fernandez-Jimenez R, Diaz-Munoz R, Jaslow R, ... Fayad ZA, Fuster V
Background
Non-Hispanic Black persons are at greater risk of cardiovascular (CV) events than other racial/ethnic groups; however, their differential vulnerability to early subclinical atherosclerosis is poorly understood.
Objectives
This work aims to study the impact of race/ethnicity on early subclinical atherosclerosis in young socioeconomically disadvantaged adults.
Methods
Bilateral carotid and femoral 3-dimensional vascular ultrasound examinations were performed on 436 adults (parents/caregivers and staff) with a mean age of 38.0 ± 11.1 years, 82.3% female, 66% self-reported as Hispanic, 34% self-reported as non-Hispanic Black, and no history of CV disease recruited in the FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) trial from 15 Head Start preschools in Harlem (neighborhood in New York, New York, USA). The 10-year Framingham CV risk score was calculated, and the relationship between race/ethnicity and the presence and extent of subclinical atherosclerosis was analyzed with multivariable logistic and linear regression models.
Results
The mean 10-year Framingham CV risk was 4.0%, with no differences by racial/ethnic category. The overall prevalence of subclinical atherosclerosis was significantly higher in the non-Hispanic Black (12.9%) than in the Hispanic subpopulation (6.6%). After adjusting for 10-year Framingham CV risk score, body mass index, fruit and vegetable consumption, physical activity, and employment status, non-Hispanic Black individuals were more likely than Hispanic individuals to have subclinical atherosclerosis (OR: 3.45; 95% CI: 1.44-8.29; P = 0.006) and multiterritorial disease (P = 0.026).
Conclusions
After adjustment for classic CV risk, lifestyle, and socioeconomic factors, non-Hispanic Black younger adults seem more vulnerable to early subclinical atherosclerosis than their Hispanic peers, suggesting that the existence of emerging or undiscovered CV factors underlying the residual excess risk (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA (Project 2)]; NCT02481401).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2022; 80:219-229
Iglesies-Grau J, Fernandez-Jimenez R, Diaz-Munoz R, Jaslow R, ... Fayad ZA, Fuster V
J Am Coll Cardiol: 19 Jul 2022; 80:219-229 | PMID: 35835495
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Impact:
Abstract

Contributions of the Women\'s Health Initiative to Cardiovascular Research: JACC State-of-the-Art Review.

LaMonte MJ, Manson JE, Anderson GL, Baker LD, ... Rossouw JE, WHI Investigators
The WHI (Women\'s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementation) for the primary prevention of major chronic diseases, including cardiovascular disease, in older women. In the WHI observational study, numerous clinical, behavioral, and social factors have been evaluated as predictors of incident chronic disease and mortality. Although the original interventions have been completed, the WHI data and biomarker resources continue to be leveraged and expanded through ancillary studies to yield novel insights regarding cardiovascular disease prevention and healthy aging in women.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2022; 80:256-275
LaMonte MJ, Manson JE, Anderson GL, Baker LD, ... Rossouw JE, WHI Investigators
J Am Coll Cardiol: 19 Jul 2022; 80:256-275 | PMID: 35835498
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Impact:
Abstract

Analysis of Worsening Heart Failure Events in an Integrated Health Care System.

Ambrosy AP, Parikh RV, Sung SH, Tan TC, ... Cristino J, Go AS
Background
There is growing interest to disentangle worsening heart failure (WHF) from location of care and move away from hospitalization as a surrogate for acuity.
Objectives
The purpose of this study was to describe the incidence of WHF events across the care continuum from ambulatory encounters to hospitalizations.
Methods
We studied calendar year cohorts of adults with diagnosed heart failure (HF) from 2010-2019 within a large, integrated health care delivery system. Electronic health record (EHR) data were accessed for outpatient encounters, emergency department (ED) visits/observation stays, and hospitalizations. WHF was defined as ≥1 symptom, ≥2 objective findings including ≥1 sign, and ≥1 change in HF-related therapy. Symptoms and signs were ascertained using natural language processing.
Results
We identified 103,138 eligible individuals with mean age 73.6 ± 13.7 years, 47.5% women, and mean left ventricular ejection fraction of 51.4% ± 13.7%. There were 1,136,750 unique encounters including 743,039 (65.4%) outpatient encounters, 224,670 (19.8%) ED visits/observation stays, and 169,041 (14.9%) hospitalizations. A total of 126,008 WHF episodes were identified, including 34,758 (27.6%) outpatient encounters, 28,301 (22.5%) ED visits/observation stays, and 62,949 (50.0%) hospitalizations. The annual incidence (events per 100 person-years) of WHF increased from 25 to 33 during the study period primarily caused by outpatient encounters (7 to 10) and ED visits/observation stays (4 to 7). The 30-day rate of hospitalizations for WHF ranged from 8.2% for outpatient encounters to 12.4% for hospitalizations.
Conclusions
ED visits/observation stays and outpatient encounters account for approximately one-half of WHF events, are driving the underlying growth in HF morbidity, and portend a poor short-term prognosis.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:111-122
Ambrosy AP, Parikh RV, Sung SH, Tan TC, ... Cristino J, Go AS
J Am Coll Cardiol: 12 Jul 2022; 80:111-122 | PMID: 35798445
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Impact:
Abstract

Secular Trends in Risk Profiles Among Adults With Cardiovascular Disease in the United States.

Gao Y, Isakadze N, Duffy E, Sheng Q, ... Matsushita K, Martin SS
Background
Documenting trends in risk factors among individuals with cardiovascular disease (CVD) may inform policy and secondary prevention initiatives.
Objectives
This study aimed to examine 20-year trends in risk profiles among U.S. adults with CVD and any racial/ethnic disparities.
Methods
In this serial cross-sectional analysis of 6,335 adults with self-reported CVD participating in the National Health and Nutrition Examination Survey from 1999 through 2018, we calculated age- and sex-adjusted proportions with ideal risk factor attainment.
Results
The proportions with ideal hemoglobin A1c (<7% if diabetes or <5.7% if not) and body mass index (<25 kg/m2) worsened from 58.7% (95% CI: 55.2%-62.1%) to 52.4% (95% CI: 48.2%-56.6%) and 23.9% (95% CI: 21.5%-26.4%) to 18.2% (95% CI: 15.6%-21.2%) from 1999-2002 to 2015-2018, respectively. After initial improvement, the proportion with blood pressure <130/80 mm Hg declined from 52.1% (95% CI: 48.9%-55.4%) in 2007-2010 to 48.6% (95% CI: 44.2%-52.7%) in 2015-2018. The proportion with non-high-density lipoprotein cholesterol levels <100 mg/dL increased from 7.3% (95% CI: 5.6%-9.5%) in 1999-2002 to 30.3% (95% CI: 25.7%-35.5%) in 2015-2018. The proportions with ideal smoking, physical activity, and diet profiles were unchanged over time, and in 2015-2018 were 77.8% (95% CI: 73.6%-81.4%), 22.4% (95% CI: 19.3%-25.9%), and 1.3% (95% CI: 0.7%-2.6%). Worsening trends were observed in Hispanic adults for cholesterol, and in Black adults for smoking (both P < 0.05 for nonlinear and linear trends). Persistently lower ideal risk factor attainment was observed for blood pressure in Black adults and for hemoglobin A1c levels in Asian adults compared with White adults (all P < 0.05 for differences).
Conclusions
Trends in cardiovascular risk factor profiles in U.S. adults with CVD were suboptimal from 1999 through 2018, with persistent racial/ethnic disparities.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:126-137
Gao Y, Isakadze N, Duffy E, Sheng Q, ... Matsushita K, Martin SS
J Am Coll Cardiol: 12 Jul 2022; 80:126-137 | PMID: 35798447
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Impact:
Abstract

Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999-2018.

O\'Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D
Background
Few studies have assessed U.S. cardiometabolic health trends-optimal levels of multiple risk factors and absence of clinical cardiovascular disease (CVD)-or its impact on health disparities.
Objectives
The purpose of this study was to investigate U.S. trends in optimal cardiometabolic health from 1999 to 2018.
Methods
We assessed proportions of adults with optimal cardiometabolic health, based on adiposity, blood glucose, blood lipids, blood pressure, and clinical CVD; and optimal, intermediate, and poor levels of each component among 55,081 U.S. adults in the National Health and Nutrition Examination Survey.
Results
In 2017-2018, only 6.8% (95% CI: 5.4%-8.1%) of U.S. adults had optimal cardiometabolic health, declining from 1999-2000 (P trend = 0.02). Among components of cardiometabolic health, the largest declines were for adiposity (optimal levels: 33.8%-24.0%; poor levels: 47.7%-61.9%) and glucose (optimal levels: 59.4%-36.9%; poor levels: 8.6%-13.7%) (P trend <0.001 for each). Optimal levels of blood lipids increased from 29.9%-37.0%, whereas poor decreased from 28.3%-14.7% (P trend <0.001). Trends over time for blood pressure and CVD were smaller. Disparities by age, sex, education, and race/ethnicity were evident in all years, and generally worsened over time. By 2017-2018, prevalence of optimal cardiometabolic health was lower among Americans with lower (5.0% [95% CI: 2.8%-7.2%]) vs higher education (10.3% [95% CI: 7.6%-13.0%]); and among Mexican American (3.2% [95% CI: 1.4%-4.9%]) vs non-Hispanic White (8.4% [95% CI: 6.3%-10.4%]) adults.
Conclusions
Between 1999 and 2000 and 2017 and 2018, U.S. cardiometabolic health has been poor and worsening, with only 6.8% of adults having optimal cardiometabolic health, and disparities by age, sex, education, and race/ethnicity. These novel findings inform the need for nationwide clinical and public health interventions to improve cardiometabolic health and health equity.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:138-151
O'Hearn M, Lauren BN, Wong JB, Kim DD, Mozaffarian D
J Am Coll Cardiol: 12 Jul 2022; 80:138-151 | PMID: 35798448
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Abstract

Carotid Artery Stenting: JACC State-of-the-Art Review.

White CJ, Brott TG, Gray WA, Heck D, ... Sachar R, Siddiqui A
Significant advances in the field of carotid artery stenting (CAS) have occurred, including new randomized trial data, recent professional societal statements for competency, new techniques and new devices that have been developed, and perhaps most importantly, our understanding of how to better select candidates for CAS to avoid periprocedural complications. The current Centers for Medicare and Medicaid Services coverage decision regarding CAS is outdated, and our review supports our recommendation to approve CAS in selected candidates who are symptomatic with a carotid stenosis ≥50% and ≤99% and for asymptomatic patients with carotid stenosis ≥70% and ≤99% for stroke prevention. Optimized CAS strategies have allowed experienced operators to better assess procedure risk before CAS and have led to continued improvement in CAS outcomes. New technologies including enhanced embolic protection devices and dual-layered stents should result in further improvement.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:155-170
White CJ, Brott TG, Gray WA, Heck D, ... Sachar R, Siddiqui A
J Am Coll Cardiol: 12 Jul 2022; 80:155-170 | PMID: 35798450
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Abstract

Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy.

Desai MY, Owens A, Geske JB, Wolski K, ... Sehnert AJ, Nissen SE
Background
Septal reduction therapy (SRT), surgical myectomy or alcohol ablation, is recommended for obstructive hypertrophic cardiomyopathy (oHCM) patients with intractable symptoms despite maximal medical therapy, but is associated with morbidity and mortality.
Objectives
This study sought to determine whether the oral myosin inhibitor mavacamten enables patients to improve sufficiently to no longer meet guideline criteria or choose to not undergo SRT.
Methods
Patients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at rest/provocation who met guideline criteria for SRT were randomized, double blind, to mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection fraction. The primary endpoint was the composite of the proportion of patients proceeding with SRT or who remained guideline-eligible after 16 weeks\' treatment.
Results
One hundred and twelve oHCM patients were enrolled, mean age 60 ± 12 years, 51% men, 93% New York Heart Association (NYHA) functional class III/IV, with a mean post-exercise LVOT gradient of 84 ± 35.8 mm Hg. After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients (17.9%) met guideline criteria or underwent SRT, difference (58.9%; 95% CI: 44.0%-73.9%; P < 0.001). Hierarchical testing of secondary outcomes showed significant differences (P < 0.001) favoring mavacamten, mean differences in post-exercise peak LVOT gradient -37.2 mm Hg; ≥1 NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53.
Conclusions
In oHCM patients with intractable symptoms, mavacamten significantly reduced the fraction of patients meeting guideline criteria for SRT after 16 weeks. Long-term freedom from SRT remains to be determined. (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [VALOR-HCM]; NCT04349072).

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2022; 80:95-108
Desai MY, Owens A, Geske JB, Wolski K, ... Sehnert AJ, Nissen SE
J Am Coll Cardiol: 12 Jul 2022; 80:95-108 | PMID: 35798455
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Abstract

Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age.

Böhm M, Butler J, Filippatos G, Ferreira JP, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators
Background
Empagliflozin reduces cardiovascular death (CVD) or heart failure (HF) hospitalization (HFH) in patients with HF and preserved ejection fraction. Treatment effects and safety in relation to age have not been studied.
Objectives
The purpose of this study was to evaluate the interplay of age and empagliflozin effects in EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).
Methods
We grouped patients (n = 5,988) according to their baseline age (<65 years [n = 1,199], 65-74 years [n = 2,214], 75-79 years [n = 1,276], ≥80 years [n = 1,299]). We explored the influence of age on empagliflozin effects on CVD or HFH (primary outcome), total HFH, rate of decline in estimated glomerular filtration rate, health-related quality of life with the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score, and frequency of adverse events.
Results
Considering only patients on placebo, the incidence of primary outcomes (P trend = 0.02) and CVD (P trend = 0.003) increased with age. Empagliflozin reduced primary outcomes (P trend = 0.33), first HFH (P trend = 0.22), and first and recurrent HFH (P trend = 0.11) across all age groups with an effect being similar at ≥75 years (P interaction = 0.22) or >80 years (P interaction = 0.51). Empagliflozin improved Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52 and attenuated the decline of estimated glomerular filtration rate without age interaction (P = 0.48 and P = 0.32, respectively). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the age groups.
Conclusions
Empagliflozin reduced primary outcomes and first and recurrent HFH and improved symptoms across a broad age spectrum. High age was not associated with reduced efficacy or meaningful intolerability. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction [EMPEROR-Preserved]; NCT0305951).

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:1-18
Böhm M, Butler J, Filippatos G, Ferreira JP, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators
J Am Coll Cardiol: 05 Jul 2022; 80:1-18 | PMID: 35772911
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Abstract

Cardiovascular Disease Risk Among Cancer Survivors: The Atherosclerosis Risk In Communities (ARIC) Study.

Florido R, Daya NR, Ndumele CE, Koton S, ... Platz EA, Selvin E
Background
More than 80% of adult patients diagnosed with cancer survive long term. Long-term complications of cancer and its therapies may increase the risk of cardiovascular disease (CVD), but prospective studies using adjudicated cancer and CVD events are lacking.
Objectives
The aim of this study was to assess the risk of CVD in cancer survivors in a prospective community-based study.
Methods
We included 12,414 ARIC (Atherosclerosis Risk In Communities) study participants. Cancer diagnoses were ascertained via linkage with state registries supplemented with medical records. Incident CVD outcomes were coronary heart disease (CHD), heart failure (HF), stroke, and a composite of these. We used multivariable Poisson and Cox regressions to estimate the association of cancer with incident CVD.
Results
Mean age was 54 years, 55% were female, and 25% were Black. A total of 3,250 participants (25%) had incident cancer over a median 13.6 years of follow-up. Age-adjusted incidence rates of CVD (per 1,000 person-years) were 23.1 (95% CI: 24.7-29.1) for cancer survivors and 12.0 (95% CI: 11.5-12.4) for subjects without cancer. After adjustment for cardiovascular risk factors, cancer survivors had significantly higher risks of CVD (HR: 1.37; 95% CI: 1.26-1.50), HF (HR: 1.52; 95% CI: 1.38-1.68), and stroke (HR: 1.22; 95% CI: 1.03-1.44), but not CHD (HR: 1.11; 95% CI: 0.97-1.28). Breast, lung, colorectal, and hematologic/lymphatic cancers, but not prostate cancer, were significantly associated with CVD risk.
Conclusions
Compared with persons without cancer, adult cancer survivors have significantly higher risk of CVD, especially HF, independent of traditional cardiovascular risk factors. There is an unmet need to define strategies for CVD prevention in this high-risk population.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:22-32
Florido R, Daya NR, Ndumele CE, Koton S, ... Platz EA, Selvin E
J Am Coll Cardiol: 05 Jul 2022; 80:22-32 | PMID: 35772913
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Abstract

Cardiovascular Risks of Hydroxychloroquine vs Methotrexate in Patients With Rheumatoid Arthritis.

D\'Andrea E, Desai RJ, He M, Glynn RJ, ... Weinblatt ME, Kim SC
Background
Hydroxychloroquine is often used as a first-line treatment of rheumatoid arthritis despite limited evidence on its cardiovascular risk.
Objectives
We conducted a cardiovascular safety evaluation comparing hydroxychloroquine to methotrexate among patients with rheumatoid arthritis.
Methods
Using Medicare data (2008-2016), we identified 54,462 propensity score-matched patients with rheumatoid arthritis, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrythmia (SCA/VA) and major adverse cardiovascular event (MACE). Secondary outcomes were cardiovascular mortality, all-cause mortality, myocardial infarction, stroke, and hospitalized heart failure (HF). We also examined treatment effect modification by history of HF.
Results
Hydroxychloroquine was not associated with risk of SCA/VA (HR: 1.03; 95% CI: 0.79-1.35) or MACE (HR: 1.07; 95% CI: 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR: 1.30; 95% CI: 1.08-1.56), cardiovascular mortality (HR: 1.34; 95% CI: 1.06-1.70), all-cause mortality (HR: 1.22; 95% CI: 1.04-1.43), myocardial infarction (HR: 1.74; 95% CI: 1.25-2.42), and hospitalized HF (HR: 1.29; 95% CI: 1.07-1.54) compared to methotrexate initiators. Cardiovascular risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR: 1.57; 95% CI: 1.30-1.90) among hydroxychloroquine initiators.
Conclusions
In older patients with rheumatoid arthritis, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, cardiovascular mortality, all-cause mortality, and myocardial infarction. An increased hospitalized HF risk was observed among hydroxychloroquine initiators regardless of an HF history.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:36-46
D'Andrea E, Desai RJ, He M, Glynn RJ, ... Weinblatt ME, Kim SC
J Am Coll Cardiol: 05 Jul 2022; 80:36-46 | PMID: 35772915
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Abstract

LMNA Variants and Risk of Adult-Onset Cardiac Disease.

Lazarte J, Jurgens SJ, Choi SH, Khurshid S, ... Lunetta KL, Lubitz SA
Background
Genetic variants in LMNA may cause cardiac disease, but population-level contributions of variants to cardiac disease burden are not well-characterized.
Objectives
We sought to determine the frequency and contribution of rare LMNA variants to cardiomyopathy and arrhythmia risk among ambulatory adults.
Methods
We included 185,990 UK Biobank participants with whole-exome sequencing. We annotated rare loss-of-function and missense LMNA variants for functional effect using 30 in silico prediction tools. We assigned a predicted functional effect weight to each variant and calculated a score for each carrier. We tested associations between the LMNA score and arrhythmia (atrial fibrillation, bradyarrhythmia, ventricular arrhythmia) or cardiomyopathy outcomes (dilated cardiomyopathy and heart failure). We also examined associations for variants located upstream vs downstream of the nuclear localization signal.
Results
Overall, 1,167 (0.63%) participants carried an LMNA variant and 15,079 (8.11%) had an arrhythmia or cardiomyopathy event during a median follow-up of 10.9 years. The LMNA score was associated with arrhythmia or cardiomyopathy (OR: 2.21; P < 0.001) and the association was more significant when restricted to variants upstream of the nuclear localization signal (OR: 5.05; P < 0.001). The incidence rate of arrhythmia or cardiomyopathy was 8.43 per 1,000 person-years (95% CI: 6.73-10.12 per 1,000 person-years) among LMNA variant carriers and 6.38 per 1,000 person-years (95% CI: 6.27-6.50 per 1,000 person-years) among noncarriers. Only 3 (1.2%) of the variants were reported as pathogenic in ClinVar.
Conclusions
Middle-aged adult carriers of rare missense or loss-of-function LMNA variants are at increased risk for arrhythmia and cardiomyopathy.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2022; 80:50-59
Lazarte J, Jurgens SJ, Choi SH, Khurshid S, ... Lunetta KL, Lubitz SA
J Am Coll Cardiol: 05 Jul 2022; 80:50-59 | PMID: 35772917
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Abstract

Preoperative Atrial Fibrillation and Cardiovascular Outcomes After Noncardiac Surgery.

Prasada S, Desai MY, Saad M, Smilowitz NR, ... Nakhla S, Mentias A
Background
The impact of pre-existing atrial fibrillation (AF) on outcomes after noncardiac surgery is not clear.
Objectives
We aimed to study the impact of AF on the risk of adverse outcomes after noncardiac surgery in a nationwide cohort.
Methods
We identified Medicare beneficiaries admitted for noncardiac surgery from 2015 to 2019 and divided the study cohort into 2 groups: with and without AF. Noncardiac surgery was classified into vascular, thoracic, general, genitourinary, gynecological, orthopedics and neurosurgery, breast, head and neck, and transplant. We used propensity score matching on exact age, sex, race, urgency and type of surgery, revised cardiac risk index (RCRI) and CHA2DS2-VASc score, and tight caliper on other comorbidities. The study outcomes were 30-day mortality, stroke, myocardial infarction, and heart failure. We examined the incremental utility of AF in addition to RCRI to predict adverse events after noncardiac surgery.
Results
The study cohort included 8,635,758 patients who underwent noncardiac surgery (16.4% with AF). Patients with AF were older, more likely to be men, and had higher prevalence of comorbidities. After propensity score matching, AF was associated with higher risk of mortality (OR: 1.31; 95% CI: 1.30-1.32), heart failure (OR: 1.31; 95% CI: 1.30-1.33), and stroke (OR: 1.40; 95% CI: 1.37-1.43) and lower risk of myocardial infarction (OR: 0.81; 95% CI: 0.79-0.82). Results were consistent in subgroup analysis by sex, race, type of surgery, and all strata of RCRI and CHA2DS2-VASc score. AF improved the discriminative ability of RCRI (C-statistic 0.73 to 0.76).
Conclusion
Pre-existing AF is independently associated with postoperative adverse outcomes after NCS.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2471-2485
Prasada S, Desai MY, Saad M, Smilowitz NR, ... Nakhla S, Mentias A
J Am Coll Cardiol: 28 Jun 2022; 79:2471-2485 | PMID: 35738707
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Abstract

Long-Term Outcomes of Patients Requiring Unplanned Repeated Interventions After Surgery for Congenital Heart Disease.

Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, ... Del Nido PJ, Nathan M
Background
Unplanned catheter-based or surgical reinterventions after congenital heart operations are independently associated with operative mortality and increased postoperative length of stay.
Objectives
This study assessed the long-term outcomes of transplant-free survivors of hospital discharge requiring predischarge reinterventions after congenital cardiac surgery.
Methods
Data from patients who required predischarge reinterventions in the anatomic area of repair after congenital cardiac surgery and survived to hospital discharge at a quaternary referral center from January 2011 to December 2019 were retrospectively reviewed. Previously published echocardiographic criteria were used to assess the severity of persistent residual lesions at discharge (Grade 1, no residua; Grade 2, minor residua; and Grade 3, major residua). Outcomes included postdischarge (late) mortality or transplant and unplanned reintervention. Associations between predischarge residual lesion severity and outcomes were assessed by using Cox or competing risk models, adjusting for baseline patient characteristics, case complexity, and preoperative risk factors.
Results
Among the 408 patients who met entry criteria, there were 58 (14.2%) postdischarge deaths or transplants and 208 (51.0%) late reinterventions at a median follow-up of 3.0 years (IQR: 1.1-6.8 years). Greater predischarge residual lesion severity was associated with worse transplant-free survival and freedom from reintervention (both, P < 0.05). On multivariable analyses, Grade 3 patients had an increased risk of postdischarge mortality or transplant (HR: 4.8; 95% CI: 2.0-11; P < 0.001) and late reintervention (subdistribution HR: 2.1; 95% CI: 1.4-3.1; P < 0.001) vs Grade 1 patients.
Conclusions
Among transplant-free survivors requiring predischarge reinterventions after congenital cardiac surgery, those with persistent major residua have significantly worse long-term outcomes. These high-risk patients warrant closer surveillance.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2489-2499
Sengupta A, Gauvreau K, Kohlsaat K, Colan SD, ... Del Nido PJ, Nathan M
J Am Coll Cardiol: 28 Jun 2022; 79:2489-2499 | PMID: 35738709
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Abstract

Socioeconomic Status and Risk of Bleeding After Mechanical Aortic Valve Replacement.

Dalén M, Persson M, Glaser N, Sartipy U
Background
Whether low socioeconomic status (SES) is associated with increased risk of anticoagulation-related adverse events in patients with mechanical heart valves is unknown.
Objectives
This study sought to investigate the impact of patients\' SES on the risk of bleeding after mechanical aortic valve replacement (AVR).
Methods
This nationwide population-based cohort study included all patients aged 18-70 years who underwent mechanical AVR in Sweden from 1997 to 2018. Data were obtained from the SWEDEHEART register and other national health data registers. The exposure was quartiles of household disposable income. The primary outcome was hospitalization for a bleeding event.
Results
Among 5974 patients, the absolute risk for bleeding after 20 years of follow-up was 20% (95% CI: 17%-24%) in the lowest income quartile (Q1) and 16% (95% CI: 13%-20%) in the highest quartile (Q4). The risk of bleeding decreased with increasing income level and was significantly lower in patients in income level Q3 (HR: 0.77; 95% CI: 0.60-0.99) and Q4 (HR: 0.68; 95% CI: 0.50-0.92) than Q1. The risk of death from intracranial hemorrhage was five times higher in the lowest income quartile than the age- and sex-matched general Swedish population (standardized mortality ratio: 5.0; 95% CI: 3.3-7.4).
Conclusions
We observed a strong association between SES and risk of bleeding among patients who underwent mechanical AVR. These findings suggest suboptimal anticoagulation treatment in patients with lower SES and the need for strategies to optimize anticoagulation treatment in patients with a mechanical heart valve. (Health-Data Register Studies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950).

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2502-2513
Dalén M, Persson M, Glaser N, Sartipy U
J Am Coll Cardiol: 28 Jun 2022; 79:2502-2513 | PMID: 35738711
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Abstract

Medicare Coverage and Out-of-Pocket Costs of Quadruple Drug Therapy for Heart Failure.

Faridi KF, Dayoub EJ, Ross JS, Dhruva SS, Ahmad T, Desai NR
Background
Beta-blockers, angiotensin receptor-neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2i), known as quadruple therapy, are recommended for patients with heart failure with reduced ejection fraction (HFrEF).
Objectives
This study sought to determine Medicare coverage and out-of-pocket (OOP) costs of quadruple therapy and regimens excluding ARNI or SGLT2i.
Methods
This study assessed cost sharing, prior authorization, and step therapy in all 4,068 Medicare prescription drug plans in 2020. OOP costs were determined during the standard coverage period and annually based on the Medicare Part D standard benefit, inclusive of deductible, standard coverage, coverage gap, and catastrophic coverage.
Results
Tier ≥3 cost sharing was required by 99.1% of plans for ARNI and 98.5% for at least 1 SGLT2i. Only ARNI required prior authorization (24.3% of plans), and step therapy was required only for SGLT2is (5.4%) and eplerenone (0.8%). The median 30-day standard coverage OOP cost of quadruple therapy was $94 (IQR: $84-$100), including $47 (IQR: $40-$47) for ARNI and $45 (IQR: $40-$47) for SGLT2i. The median annual OOP cost of quadruple therapy was $2,217 (IQR: $1,956-$2,579) compared with $1,319 (IQR: $1,067-$1,675) when excluding SGLT2i and $1,322 (IQR: $1,025-$1,588) when including SGLT2i and substituting an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ARNI. The median 30-day OOP cost of generic regimens was $3 (IQR: $0-$9).
Conclusions
Medicare drug plans restrict coverage of quadruple therapy through cost sharing, with OOP costs that are substantially higher than generic regimens. Quadruple therapy may be unaffordable for many Medicare patients with HFrEF unless medication prices and cost sharing are reduced.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2516-2525
Faridi KF, Dayoub EJ, Ross JS, Dhruva SS, Ahmad T, Desai NR
J Am Coll Cardiol: 28 Jun 2022; 79:2516-2525 | PMID: 35738713
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Abstract

Pericardial Effusion Provoking Atrial Fibrillation After Cardiac Surgery: JACC Review Topic of the Week.

Gaudino M, Di Franco A, Rong LQ, Cao D, ... DiMaio JM, Girardi LN
Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Patients who develop POAF are more likely to experience adverse outcomes, including increased rates of death, stroke, heart failure, and hospitalizations, and higher hospital costs. Understanding the mechanisms underlying POAF is important to improve patients\' outcome and optimize health systems\' efficiency. Beyond classic pathogenic hypotheses, emerging evidence suggests that postoperative pericardial effusion and localized pericardial inflammation may trigger POAF. This hypothesis is supported by data from nonhuman animal models and a growing body of evidence showing that reducing postoperative pericardial effusion might reduce POAF incidence. In this review, we summarize the classic pathophysiology theories of POAF following cardiac surgery and discuss new etiologic mechanisms with a specific focus on the role of pericardial effusion and inflammation.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2022; 79:2529-2539
Gaudino M, Di Franco A, Rong LQ, Cao D, ... DiMaio JM, Girardi LN
J Am Coll Cardiol: 28 Jun 2022; 79:2529-2539 | PMID: 35738715
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Abstract

Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols.

Takahashi T, Samuels BA, Li W, Parikh MA, ... Kobayashi Y, Microvascular Network
Background
Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm.
Objectives
We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols.
Methods
PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock.
Results
A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 μg and 200 μg.
Conclusions
Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2367-2378
Takahashi T, Samuels BA, Li W, Parikh MA, ... Kobayashi Y, Microvascular Network
J Am Coll Cardiol: 21 Jun 2022; 79:2367-2378 | PMID: 35710187
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Impact:
Abstract

Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction.

Doi T, Langsted A, Nordestgaard BG
Background
Elevated remnant cholesterol causes ischemic heart disease.
Objectives
We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.
Methods
For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use. Using predefined cut points for elevated remnant cholesterol, we calculated net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease defined as a composite of death from ischemic heart disease, myocardial infarction, and coronary revascularization.
Results
For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: -3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).
Conclusions
Elevated remnant cholesterol levels considerably improve myocardial infarction and ischemic heart disease risk prediction.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2383-2397
Doi T, Langsted A, Nordestgaard BG
J Am Coll Cardiol: 21 Jun 2022; 79:2383-2397 | PMID: 35710189
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Impact:
Abstract

Prospective Evaluation of Cardiovascular Risk 10 Years After a Hypertensive Disorder of Pregnancy.

Levine LD, Ky B, Chirinos JA, Koshinksi J, ... Koelper N, Lewey J
Background
Hypertensive disorders of pregnancy (HDP) are associated with increased risk of cardiovascular disease (CVD) 20-30 years later; however, cardiovascular (CV) risk in the decade after HDP is less studied.
Objectives
The purpose of this study was to evaluate differences in CV risk factors as well as subclinical CVD among a well-characterized group of racially diverse patients with and without a history of HDP 10 years earlier.
Methods
This is a prospective study of patients with and without a diagnosis of HDP ≥10 years earlier (2005-2007) who underwent in-person visits with echocardiography, arterial tonometry, and flow-mediated dilation of the brachial artery.
Results
A total of 135 patients completed assessments (84 with and 51 without a history of HDP); 85% self-identified as Black. Patients with a history of HDP had a 2.4-fold increased risk of new hypertension compared with those without HDP (56.0% vs. 23.5%; adjusted relative risk: 2.4; 95% CI: 1.39-4.14) with no differences in measures of left ventricular structure, global longitudinal strain, diastolic function, arterial stiffness, or endothelial function. Patients who developed hypertension, regardless of HDP history, had greater left ventricular remodeling, including greater relative wall thickness; worse diastolic function, including lower septal and lateral e\' and E/A ratio; more abnormal longitudinal strain; and higher effective arterial elastance than patients without hypertension.
Conclusions
We found a 2.4-fold increased risk of hypertension 10 years after HDP. Differences in noninvasive measures of CV risk were driven mostly by the hypertension diagnosis, regardless of HDP history, suggesting that the known long-term risk of CVD after HDP may primarily be a consequence of hypertension development.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2401-2411
Levine LD, Ky B, Chirinos JA, Koshinksi J, ... Koelper N, Lewey J
J Am Coll Cardiol: 21 Jun 2022; 79:2401-2411 | PMID: 35710191
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Impact:
Abstract

False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.

Evangelista A, Pineda V, Guala A, Bijnens B, ... Ferreira I, Rodríguez-Palomares J
Background
Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist.
Objectives
The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters.
Methods
One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD.
Results
After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events.
Conclusions
High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 21 Jun 2022; 79:2415-2427
Evangelista A, Pineda V, Guala A, Bijnens B, ... Ferreira I, Rodríguez-Palomares J
J Am Coll Cardiol: 21 Jun 2022; 79:2415-2427 | PMID: 35710193
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Impact:
Abstract

Causes, Angiographic Characteristics, and Management of Premature Myocardial Infarction: JACC State-of-the-Art Review.

Rallidis LS, Xenogiannis I, Brilakis ES, Bhatt DL
Among patients presenting with acute myocardial infarction (AMI), the proportion of young individuals has increased in recent years. Although coronary atherosclerosis is less extensive in young patients with AMI, with higher prevalence of single-vessel disease and rare left main involvement, the long-term prognosis is not benign. Young patients with AMI with obstructive coronary artery disease have similar risk factors as older patients except for higher prevalence of smoking, lipid disorders, and family history of premature coronary artery disease, and lower prevalence of diabetes mellitus and hypertension. Smoking cessation is by far the most effective secondary preventive measure. Myocardial infarction with nonobstructive coronary arteries is a relatively common clinical entity (10%-20%) among young patients with AMI, with intravascular and cardiac magnetic resonance imaging being key for diagnosis and potentially treatment. Spontaneous coronary artery dissection is a frequent pathogenetic mechanism of AMI among young women, requiring a high degree of suspicion, especially in the peripartum period.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2431-2449
Rallidis LS, Xenogiannis I, Brilakis ES, Bhatt DL
J Am Coll Cardiol: 21 Jun 2022; 79:2431-2449 | PMID: 35710195
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Abstract

Inappropriate Sinus Tachycardia: Etiology, Pathophysiology, and Management: JACC Review Topic of the Week.

Ahmed A, Pothineni NVK, Charate R, Garg J, ... Gopinathannair R, Lakkireddy D
Inappropriate sinus tachycardia (IST) is a clinical syndrome that generally affects young patients and is associated with distressing symptoms. Although the most common symptom is palpitations, it can be accompanied by a myriad of symptoms, including anxiety, dizziness, presyncope, and syncope. The pathogenesis of IST is not well understood and considered multifactorial, with autonomic dysfunction being the central abnormality. IST is a diagnosis of exclusion. Management presents a clinical challenge. The overall efficacy of lifestyle modifications and medical therapy may be limited. Recent advances in catheter and surgical sinus node sparing ablation techniques have led to improvement in outcomes. In addition, increased focus has led to development of multimodality team-based interventions to improve outcomes in this group of patients. In this review, we discuss the mechanistic basis of IST, review current approaches to diagnosis, and outline contemporary therapeutic approaches.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2022; 79:2450-2462
Ahmed A, Pothineni NVK, Charate R, Garg J, ... Gopinathannair R, Lakkireddy D
J Am Coll Cardiol: 21 Jun 2022; 79:2450-2462 | PMID: 35710196
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Abstract

Diabetes and Progression of Heart Failure: The Atherosclerosis Risk In Communities (ARIC) Study.

Echouffo-Tcheugui JB, Ndumele CE, Zhang S, Florido R, ... Shah AM, Selvin E
Background
The influence of diabetes on progression from preclinical heart failure (HF) stages to overt HF is poorly understood.
Objectives
The purpose of this study was to characterize the influence of diabetes on the progression from preclinical HF stages (A or B based on the 2021 Universal Definition) to overt HF.
Methods
We included 4,774 adults with preclinical HF (stage A [n = 1,551] or B [n = 3,223]) who attended the ARIC (Atherosclerosis Risk In Communities) study Visit 5 (2011-2013). Within each stage (A or B), we assessed the associations of diabetes and glycemic control (hemoglobin A1C [HbA1C] <7% vs ≥7%) with progression to HF, and of cross-categories of HF stages (A vs B), diabetes, and glycemic control with incident HF.
Results
Among the participants (mean age 75.4 years, 58% women, 20% Black), there were 470 HF events during 8.6 years of follow-up. Stage B participants with HbA1C ≥7% experienced clinical HF at a younger age than those with controlled diabetes or without diabetes (mean age 80 years vs 83 years vs 82 years; P < 0.001). HbA1C ≥7% was more strongly associated with HF in stage B (HR: 1.83; 95% CI: 1.33-2.51) compared with stage A (HR: 1.52; 95% CI: 0.53-4.38). In cross-categories of preclinical HF stage and HbA1C, participants with stage B and HbA1C ≥7% had increased risk of HF progression compared with stage A without diabetes (HR: 7.56; 95% CI: 4.68-12.20).
Conclusions
Among older adults with preclinical HF stages, uncontrolled diabetes was associated with substantial risk of HF progression. Our results suggest that targeting diabetes early in the HF process is critical.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2285-2293
Echouffo-Tcheugui JB, Ndumele CE, Zhang S, Florido R, ... Shah AM, Selvin E
J Am Coll Cardiol: 14 Jun 2022; 79:2285-2293 | PMID: 35680178
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Impact:
Abstract

Cigarette Smoking, Cessation, and Risk of Heart Failure With Preserved and Reduced Ejection Fraction.

Ding N, Shah AM, Blaha MJ, Chang PP, Rosamond WD, Matsushita K
Background
Smoking is well-recognized as a risk factor for heart failure (HF). However, few studies have evaluated the prospective association of cigarette smoking and smoking cessation with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) as distinct phenotypes.
Objectives
The aim of this study was to quantify the association of cigarette smoking and smoking cessation with the incidence of HFpEF and HFrEF.
Methods
In 9,345 ARIC (Atherosclerosis Risk In Communities) study White and Black participants without history of HF at baseline in 2005 (age range 61-81 years), we quantified the associations of several established cigarette smoking parameters (smoking status, pack-years, intensity, duration, and years since cessation) with physician-adjudicated incident acute decompensated HF using multivariable Cox models.
Results
Over a median follow-up of 13.0 years, there were 1,215 incident HF cases. Compared with never smokers, current cigarette smoking was similarly associated with HFpEF and HFrEF, with adjusted HRs ∼2. There was a dose-response relationship for pack-years of smoking and HF. A more extended period of smoking cessation was associated with a lower risk of HF, but significantly elevated risk persisted up to a few decades for HFpEF and HFrEF.
Conclusions
All cigarette smoking parameters consistently showed significant and similar associations with HFpEF and HFrEF. Smoking cessation significantly reduced the risk of HF, but excess HF risk persisted for a few decades. Our results strengthened the evidence that smoking is an important modifiable risk factor for HF and highlighted the importance of smoking prevention and cessation for the prevention of HF, including HFpEF.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2298-2305
Ding N, Shah AM, Blaha MJ, Chang PP, Rosamond WD, Matsushita K
J Am Coll Cardiol: 14 Jun 2022; 79:2298-2305 | PMID: 35680180
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Impact:
Abstract

Early Coronary Atherosclerosis in Women With Previous Preeclampsia.

Hauge MG, Damm P, Kofoed KF, Ersbøll AS, ... Gustafsson F, Linde JJ
Background
Women with previous preeclampsia have an increased risk of coronary artery disease later in life.
Objectives
This study aimed to determine the prevalence of coronary atherosclerosis in younger women with previous preeclampsia in comparison with women from the general population.
Methods
Women aged 40-55 years with previous preeclampsia were matched 1:1 on age and parity with women from the general population. Participants completed an extensive questionnaire, a clinical examination, and a coronary computed tomography angiography (CTA). The main study outcome was the prevalence of any coronary atherosclerosis on coronary CTA or a calcium score >0 in case of a nondiagnostic coronary CTA.
Results
A total of 1,417 women, with a mean age of 47 years, were included (708 women with previous preeclampsia and 709 control subjects from the general population). Women with previous preeclampsia were more likely to have hypertension (284 [40.1%] vs 162 [22.8%]; P < 0.001), dyslipidemia (338 [47.7%] vs 296 [41.7%]; P = 0.023), diabetes mellitus (24 [3.4%] vs 8 [1.1%]; P = 0.004), and high body mass index (27.3 ± 5.7 kg/m2 vs 25.0 ± 4.2 kg/m2; P < 0.001). Cardiac computed tomography was performed in all women. The prevalence of any coronary atherosclerosis was higher in the preeclampsia group (193 [27.4%] vs 141 [20.0%]; P = 0.001) with an OR: 1.41 (95% CI: 1.08-1.85; P = 0.012) after adjustment for age, dyslipidemia, diabetes mellitus, smoking, body mass index, menopause, and parity.
Conclusions
Younger women with previous preeclampsia had a slightly higher prevalence of coronary atherosclerosis compared with age- and parity-matched women from the general population. Preeclampsia remained an independent risk factor after adjustment for traditional cardiovascular risk factors. (The CoPenHagen PREeClampsia and cardIOvascUlar diSease study [CPH-PRECIOUS]; NCT03949829).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2310-2321
Hauge MG, Damm P, Kofoed KF, Ersbøll AS, ... Gustafsson F, Linde JJ
J Am Coll Cardiol: 14 Jun 2022; 79:2310-2321 | PMID: 35680182
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Impact:
Abstract

Care Models for Acute Chest Pain That Improve Outcomes and Efficiency: JACC State-of-the-Art Review.

Dawson LP, Smith K, Cullen L, Nehme Z, ... Taylor AJ, Stub D
Existing assessment pathways for acute chest pain are often resource-intensive, prolonged, and expensive. In this review, the authors describe existing chest pain pathways and current issues at the patient and system level, and provide an overview of recent advances in chest pain research that could inform improved outcomes for both patients and health systems. There are multiple avenues to improve existing models of chest pain care, including novel risk stratification pathways incorporating highly sensitive point-of-care troponin assays; new devices available before first medical contact that could allow clinicians to access vital signs and electrocardiogram data; artificial intelligence and precision medicine tools that may guide indications for further testing; and strategies to improve hospital benchmarking and performance monitoring to standardize care. Improving the speed and accuracy of chest pain diagnosis and management should be a priority for researchers and is likely to translate to substantive benefits for patients and health systems.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2333-2348
Dawson LP, Smith K, Cullen L, Nehme Z, ... Taylor AJ, Stub D
J Am Coll Cardiol: 14 Jun 2022; 79:2333-2348 | PMID: 35680185
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Impact:
Abstract

Inflammasome Signaling in Atrial Fibrillation: JACC State-of-the-Art Review.

Ajoolabady A, Nattel S, Lip GYH, Ren J
As the most prevalent form of arrhythmia, atrial fibrillation (AF) increases the risk of heart failure, thromboembolism, and stroke, contributing to the raising mortality and morbidity in patients with cardiovascular diseases. Despite the multifaceted nature of AF pathogenesis and complexity of AF pathophysiology, a growing body of evidence indicates that the NLRP3 inflammasome activation contributes to onset and progression of AF. Herein, the authors aim at reviewing the current literature on the role of inflammasome signaling in AF pathogenesis, and novel therapeutic options in the management of AF.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2022; 79:2349-2366
Ajoolabady A, Nattel S, Lip GYH, Ren J
J Am Coll Cardiol: 14 Jun 2022; 79:2349-2366 | PMID: 35680186
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Impact:
Abstract

Precision Phenotyping of Dilated Cardiomyopathy Using Multidimensional Data.

Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, ... Heymans SRB, Prasad SK
Background
Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction.
Objectives
The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification.
Methods
Longitudinal, observational UK-derivation (n = 426; median age 54 years; 67% men) and Dutch-validation (n = 239; median age 56 years; 64% men) cohorts of DCM patients (enrolled 2009-2016) with clinical, genetic, cardiovascular magnetic resonance, and proteomic assessments. Machine learning with profile regression identified novel disease subtypes. Penalized multinomial logistic regression was used for validation. Nested Cox models compared novel groupings to conventional risk measures. Primary composite outcome was cardiovascular death, heart failure, or arrhythmia events (median follow-up 4 years).
Results
In total, 3 novel DCM subtypes were identified: profibrotic metabolic, mild nonfibrotic, and biventricular impairment. Prognosis differed between subtypes in both the derivation (P < 0.0001) and validation cohorts. The novel profibrotic metabolic subtype had more diabetes, universal myocardial fibrosis, preserved right ventricular function, and elevated creatinine. For clinical application, 5 variables were sufficient for classification (left and right ventricular end-systolic volumes, left atrial volume, myocardial fibrosis, and creatinine). Adding the novel DCM subtype improved the C-statistic from 0.60 to 0.76. Interleukin-4 receptor-alpha was identified as a novel prognostic biomarker in derivation (HR: 3.6; 95% CI: 1.9-6.5; P = 0.00002) and validation cohorts (HR: 1.94; 95% CI: 1.3-2.8; P = 0.00005).
Conclusions
Three reproducible, mechanistically distinct DCM subtypes were identified using widely available clinical and biological data, adding prognostic value to traditional risk models. They may improve patient selection for novel interventions, thereby enabling precision medicine.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2219-2232
Tayal U, Verdonschot JAJ, Hazebroek MR, Howard J, ... Heymans SRB, Prasad SK
J Am Coll Cardiol: 07 Jun 2022; 79:2219-2232 | PMID: 35654493
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Abstract

Transcatheter Closure of Atrial and Ventricular Septal Defects: JACC Focus Seminar.

Turner ME, Bouhout I, Petit CJ, Kalfa D
The field of congenital interventional cardiology has experienced tremendous growth in recent years. Beginning with the development of early devices for transcatheter closure of septal defects in the 1970s and 1980s, such technologies have evolved to become a mainstay of treatment for many atrial septal defects (ASDs) and ventricular septal defects (VSDs). Percutaneous device closure is now the preferred approach for the majority of secundum ASDs. It is also a viable treatment option for selected VSDs, though limitations still exist. In this review, the authors describe the current state of transcatheter closure of ASDs and VSDs in children and adults, including patient selection, procedural approach, and outcomes. Potential areas for future evolution and innovation are also discussed.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2247-2258
Turner ME, Bouhout I, Petit CJ, Kalfa D
J Am Coll Cardiol: 07 Jun 2022; 79:2247-2258 | PMID: 35654496
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Impact:
Abstract

Interventions for Congenital Atrioventricular Valve Dysfunction: JACC Focus Seminar.

Barry OM, Bouhout I, Kodali SK, George I, ... Petit CJ, Kalfa D
Innovation and creativity have led to tremendous advancements in the care and management of patients with congenital heart disease (CHD) that have resulted in considerably increased survival. Catheter-based interventions have contributed significantly to these advancements. However, catheter-based interventions for congenital lesions of the atrioventricular (AV) valves have been limited in scope and effectiveness mainly because of patient size and anatomical challenges. Thus, surgical repair and replacement for congenital AV valve lesions have remained the preferred therapy. However, the ongoing transcatheter heart valve revolution has led to techniques and technologies that are changing the landscape, particularly for adult CHD patients. Many devices for AV valve repair and replacement are being studied in adult patients without CHD, and translation of select practices to CHD patients has begun, with many more to come. Transcatheter AV valve interventions represent exciting opportunities for the growing numbers of adult CHD patients.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2259-2269
Barry OM, Bouhout I, Kodali SK, George I, ... Petit CJ, Kalfa D
J Am Coll Cardiol: 07 Jun 2022; 79:2259-2269 | PMID: 35654497
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Impact:
Abstract

Transcatheter Cardiac Interventions in the Newborn: JACC Focus Seminar.

Barry OM, Bouhout I, Turner ME, Petit CJ, Kalfa DM
For neonates with critical congenital heart disease requiring intervention, transcatheter approaches for many conditions have been established over the past decades. These interventions may serve to stabilize or palliate to surgical next steps or effectively primarily treat the condition. Many transcatheter interventions have evidence-based records of effectiveness and safety, which have led to widespread acceptance as first-line therapies. Other techniques continue to innovatively push the envelope and challenge the optimal strategies for high-risk neonates with right ventricular outflow tract obstruction or ductal-dependent pulmonary blood flow. In this review, the most commonly performed neonatal transcatheter interventions will be described to illustrate the current state of the field and highlight areas of future opportunity.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2022; 79:2270-2283
Barry OM, Bouhout I, Turner ME, Petit CJ, Kalfa DM
J Am Coll Cardiol: 07 Jun 2022; 79:2270-2283 | PMID: 35654498
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Impact:
Abstract

Cardiovascular Outcomes in Aortopathy: GenTAC Registry of Genetically Triggered Aortic Aneurysms and Related Conditions.

Holmes KW, Markwardt S, Eagle KA, Devereux RB, ... Roman MJ, GenTAC Investigators
Background
The GenTAC (Genetically Triggered Thoracic Aortic Aneurysm and Cardiovascular Conditions) Registry enrolled patients with genetic aortopathies between 2007 and 2016.
Objectives
The purpose of this study was to compare age distribution and probability of elective surgery for proximal aortic aneurysm, any dissection surgery, and cardiovascular mortality among aortopathy etiologies.
Methods
The GenTAC study had a retrospective/prospective design. Participants with bicuspid aortic valve (BAV) with aneurysm (n = 879), Marfan syndrome (MFS) (n = 861), nonsyndromic heritable thoracic aortic disease (nsHTAD) (n = 378), Turner syndrome (TS) (n = 298), vascular Ehlers-Danlos syndrome (vEDS) (n = 149), and Loeys-Dietz syndrome (LDS) (n = 121) were analyzed.
Results
The 25% probability of elective proximal aortic aneurysm surgery was 30 years for LDS (95% CI: 18-37 years), followed by MFS (34 years; 95% CI: 32-36 years), nsHTAD (52 years; 95% CI: 48-56 years), and BAV (55 years; 95% CI: 53-58 years). Any dissection surgery 25% probability was highest in LDS (38 years; 95% CI: 33-53 years) followed by MFS (51 years; 95% CI: 46-57 years) and nsHTAD (54 years; 95% CI: 51-61 years). BAV experienced the largest relative frequency of elective surgery to any dissection surgery (254/33 = 7.7), compared with MFS (273/112 = 2.4), LDS (35/16 = 2.2), or nsHTAD (82/76 = 1.1). With MFS as the reference population, risk of any dissection surgery or cardiovascular mortality was lowest in BAV patients (HR: 0.13; 95% CI: 0.08-0.18; HR: 0.13; 95%: CI: 0.06-0.27, respectively). The greatest risk of mortality was seen in patients with vEDS.
Conclusions
Marfan and LDS cohorts demonstrate age and event profiles congruent with the current understanding of syndromic aortopathies. BAV events weigh toward elective replacement with relatively few dissection surgeries. Nonsyndromic HTAD patients experience near equal probability of dissection vs prophylactic surgery, possibly because of failure of early diagnosis.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2069-2081
Holmes KW, Markwardt S, Eagle KA, Devereux RB, ... Roman MJ, GenTAC Investigators
J Am Coll Cardiol: 31 May 2022; 79:2069-2081 | PMID: 35618343
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Impact:
Abstract

Gender Differences in Takotsubo Syndrome.

Arcari L, Núñez Gil IJ, Stiermaier T, El-Battrawy I, ... Eitel I, Santoro F
Background
Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized.
Objectives
The aim of the present study is to describe TTS sex differences.
Methods
TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger.
Results
In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52).
Conclusions
Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2085-2093
Arcari L, Núñez Gil IJ, Stiermaier T, El-Battrawy I, ... Eitel I, Santoro F
J Am Coll Cardiol: 31 May 2022; 79:2085-2093 | PMID: 35618345
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Impact:
Abstract

Disruption of Circadian Rhythms by Shift Work Exacerbates Reperfusion Injury in Myocardial Infarction.

Zhao Y, Lu X, Wan F, Gao L, ... Ji Y, Pu J
Background
Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear.
Objectives
This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI.
Methods
Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models.
Results
Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (β = 5.94%; 95% CI: 2.94-8.94; P < 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury.
Conclusions
The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2097-2115
Zhao Y, Lu X, Wan F, Gao L, ... Ji Y, Pu J
J Am Coll Cardiol: 31 May 2022; 79:2097-2115 | PMID: 35618347
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Impact:
Abstract

Becoming a Parent During Cardiovascular Training.

Oliveros E, Burgess S, Nadella N, Davidson L, ... DeFaria Yeh D, Park K
Background
Specialty training in cardiovascular diseases is consistently perceived to have adverse job conditions and interfere with family life. There is a dearth of universal workforce support for trainees who become parents during training.
Objectives
This study sought to identify parental policies across cardiovascular training programs internationally.
Methods
An Internet-based international survey study available from August 2020 to October 2020 was sent via social media. The survey was administered 1 time and anonymously. Participants shared experiences regarding parental benefits/policies and perception of barriers for trainees. Participants were divided into 3 groups: training program directors, trainees pregnant during cardiology fellowship, and trainees not pregnant during training.
Results
A total of 417 replies were received from physicians, including 47 responses (11.3%) from training program directors, 146 responses (35%) from current or former trainees pregnant during cardiology training, and 224 responses (53.7%) from current or former trainees that were not pregnant during cardiology training. Among trainees, 280 (67.1%) were parents during training. Family benefits and policies were not uniformly available across institutions, and knowledge regarding the existence of such policies was low. Average parental leave ranged from 1 to 2 months in the United States compared with >4 months outside the United States, and in all countries, paternity leave was uncommon (only 11 participants [2.6%]). Coverage during family leave was primarily provided by peers (n = 184 [44.1%]), and 168 (91.3%) were without additional monetary or time compensation.
Conclusions
This is the first international survey evaluating and comparing parental benefits and policies among cardiovascular training programs. There is great variability among institutions, highlighting disparities in real-world experiences.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2119-2126
Oliveros E, Burgess S, Nadella N, Davidson L, ... DeFaria Yeh D, Park K
J Am Coll Cardiol: 31 May 2022; 79:2119-2126 | PMID: 35618349
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Impact:
Abstract

Call for Formalized Pathways in Vascular Medicine Training: JACC Review Topic of the Week.

Eberhardt RT, Bonaca MP, Abu Daya H, Garcia LA, ... Young MN, Piazza G
The burden of vascular diseases and complexity of their management have been growing. Vascular medicine specialists may help to bridge gaps in care, especially as part of multidisciplinary teams. However, there is a limited number of vascular medicine specialists because of constraints in training. Despite established pathways for training in vascular medicine, there are obstacles that restrict completion of training in dedicated programs. A key factor is lack of funding as a result of inadequate recognition by key national accrediting and credentialing organizations. A concerted effort is required to overcome the obstacles to expand vascular medicine training programs and ultimately the pool of vascular medicine specialists. Well-trained vascular medicine specialists will be well positioned to ease the burden of vascular disease and optimize patient outcomes.

Copyright © 2022 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 31 May 2022; 79:2129-2139
Eberhardt RT, Bonaca MP, Abu Daya H, Garcia LA, ... Young MN, Piazza G
J Am Coll Cardiol: 31 May 2022; 79:2129-2139 | PMID: 35618351
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Impact:
Abstract

Association of Thromboxane Generation With Survival in Aspirin Users and Nonusers.

Rade JJ, Barton BA, Vasan RS, Kronsberg SS, ... Kakouros N, Kickler TA
Background
Persistent systemic thromboxane generation, predominantly from nonplatelet sources, in aspirin (ASA) users with cardiovascular disease (CVD) is a mortality risk factor.
Objectives
This study sought to determine the mortality risk associated with systemic thromboxane generation in an unselected population irrespective of ASA use.
Methods
Stable thromboxane B2 metabolites (TXB2-M) were measured by enzyme-linked immunosorbent assay in banked urine from 3,044 participants (mean age 66 ± 9 years, 53.8% women) in the Framingham Heart Study. The association of TXB2-M to survival over a median observation period of 11.9 years (IQR: 10.6-12.7 years) was determined by multivariable modeling.
Results
In 1,363 (44.8%) participants taking ASA at the index examination, median TXB2-M were lower than in ASA nonusers (1,147 pg/mg creatinine vs 4,179 pg/mg creatinine; P < 0.0001). TXB2-M were significantly associated with all-cause and cardiovascular mortality irrespective of ASA use (HR: 1.96 and 2.41, respectively; P < 0.0001 for both) for TXB2-M in the highest quartile based on ASA use compared with lower quartiles, and remained significant after adjustment for mortality risk factors for similarly aged individuals (HR: 1.49 and 1.82, respectively; P ≤ 0.005 for both). In 2,353 participants without CVD, TXB2-M were associated with cardiovascular mortality in ASA nonusers (adjusted HR: 3.04; 95% CI: 1.29-7.16) but not in ASA users, while ASA use was associated with all-cause mortality in those with low (adjusted HR: 1.46; 95% CI: 1.14-1.87) but not elevated TXB2-M.
Conclusions
Systemic thromboxane generation is an independent risk factor for all-cause and cardiovascular mortality irrespective of ASA use, and its measurement may be useful for therapy modification, particularly in those without CVD.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; epub ahead of print
Rade JJ, Barton BA, Vasan RS, Kronsberg SS, ... Kakouros N, Kickler TA
J Am Coll Cardiol: 24 May 2022; epub ahead of print | PMID: 35660296
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Impact:
Abstract

Arterial Ultrasound Testing to Predict Atherosclerotic Cardiovascular Events.

Nicolaides AN, Panayiotou AG, Griffin M, Tyllis T, ... Avraamides C, Martin RM
Background
Studies have indicated that the presence and size of subclinical atherosclerotic plaques improve the prediction of atherosclerotic cardiovascular events (ASCVE) over and above that provided by conventional risk factors alone. However, the relative contribution of different ultrasonographic measurements and sites of measurements on the 10-year ASCVD risk is largely unknown.
Objectives
Our aims were to determine the relative performance of carotid intima-media thickness, plaque thickness, and plaque area in 10-year ASCVD prediction when added to conventional risk factors as well as whether the vascular territory of these measurements, carotid or common femoral bifurcation, and the number of bifurcations with plaque (NBP) influence prediction.
Methods
We enrolled 985 adults (mean age: 58.1 ± 10.2 years) free of atherosclerotic cardiovascular disease. Conventional risk factors were recorded, and both carotid and common femoral bifurcations were scanned with ultrasonography. The primary endpoint was a composite of first-time fatal or nonfatal ASCVE.
Results
Over a mean ± SD follow-up of 13.2 ± 3.7 years, ASCVE occurred in 154 (15.6%) participants. By adding different plaque measurements to conventional risk factors in a Cox model, net reclassification improvement was 10.4% with maximum intima-media thickness, 9.5% with carotid plaque thickness, and 14.2% with carotid plaque area. It increased to 16.1%, 16.6%, and 16.6% (P < 0.0001) by adding measurements from 4 bifurcations: NBP, total plaque thickness, and total plaque area, respectively.
Conclusions
NBP, total plaque thickness, or total plaque area from both the carotid and common femoral bifurcations provides a better prediction of future ASCVE than measurements from a single site. The results need to be validated in an independent cohort.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:1969-1982
Nicolaides AN, Panayiotou AG, Griffin M, Tyllis T, ... Avraamides C, Martin RM
J Am Coll Cardiol: 24 May 2022; 79:1969-1982 | PMID: 35589158
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Abstract

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy.

Norrish G, Cleary A, Field E, Cervi E, ... Elliott PM, Kaski JP
Background
Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized.
Objectives
The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years.
Methods
Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years.
Results
At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age.
Conclusions
Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:1986-1997
Norrish G, Cleary A, Field E, Cervi E, ... Elliott PM, Kaski JP
J Am Coll Cardiol: 24 May 2022; 79:1986-1997 | PMID: 35589160
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Impact:
Abstract

Worldwide Disparities in Recovery of Cardiac Testing 1 Year Into COVID-19.

Einstein AJ, Hirschfeld C, Williams MC, Vitola JV, ... Paez D, INCAPS COVID 2 Investigators Group
Background
The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown.
Objectives
The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide.
Methods
The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic\'s onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery.
Results
Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians\' psychological stress were significant in predicting recovery of cardiac testing.
Conclusions
Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:2001-2017
Einstein AJ, Hirschfeld C, Williams MC, Vitola JV, ... Paez D, INCAPS COVID 2 Investigators Group
J Am Coll Cardiol: 24 May 2022; 79:2001-2017 | PMID: 35589162
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Abstract

Reduced Heart Failure and Mortality in Patients Receiving Statin Therapy Before Initial Acute Coronary Syndrome.

Bugiardini R, Yoon J, Mendieta G, Kedev S, ... Badimon L, Cenko E
Background
There is uncertainty regarding the impact of statins on the risk of atherosclerotic cardiovascular disease (ASCVD) and its major complication, acute heart failure (AHF).
Objectives
The aim of this study was to investigate whether previous statin therapy translates into lower AHF events and improved survival from AHF among patients presenting with an acute coronary syndrome (ACS) as a first manifestation of ASCVD.
Methods
Data were drawn from the International Survey of Acute Coronary Syndromes Archives. The study participants consisted of 14,542 Caucasian patients presenting with ACS without previous ASCVD events. Statin users before the index event were compared with nonusers by using inverse probability weighting models. Estimates were compared by test of interaction on the log scale. Main outcome measures were the incidence of AHF according to Killip class and the rate of 30-day all-cause mortality in patients presenting with AHF.
Results
Previous statin therapy was associated with a significantly decreased rate of AHF on admission (4.3% absolute risk reduction; risk ratio [RR]: 0.72; 95% CI: 0.62-0.83) regardless of younger (40-75 years) or older age (interaction P = 0.27) and sex (interaction P = 0.22). Moreover, previous statin therapy predicted a lower risk of 30-day mortality in the subset of patients presenting with AHF on admission (5.2 % absolute risk reduction; RR: 0.71; 95% CI: 0.50-0.99).
Conclusions
Among adults presenting with ACS as a first manifestation of ASCVD, previous statin therapy is associated with a reduced risk of AHF and improved survival from AHF. (International Survey of Acute Coronary Syndromes [ISACS] Archives; NCT04008173).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:2021-2033
Bugiardini R, Yoon J, Mendieta G, Kedev S, ... Badimon L, Cenko E
J Am Coll Cardiol: 24 May 2022; 79:2021-2033 | PMID: 35589164
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Impact:
Abstract

Diagnosis and Management of Infective Endocarditis in People Who Inject Drugs: JACC State-of-the-Art Review.

Yucel E, Bearnot B, Paras ML, Zern EK, ... Wakeman SE, Sundt T
The incidence of injection drug use-associated infective endocarditis has been increasing rapidly over the last decade. Patients with drug use-associated infective endocarditis present an increasingly common clinical challenge with poor long-term outcomes and high reinfection and readmission rates. Their care raises issues unique to this population, including antibiotic selection and administration, indications for and ethical issues surrounding surgical intervention, and importantly management of the underlying substance use disorder to minimize the risk of reinfection. Successful treatment of these patients requires a broad understanding of these concerns. A multidisciplinary, collaborative approach providing a holistic approach to treating both the acute infection along with effectively addressing substance use disorder is needed to improve short-term and longer-term outcomes.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:2037-2057
Yucel E, Bearnot B, Paras ML, Zern EK, ... Wakeman SE, Sundt T
J Am Coll Cardiol: 24 May 2022; 79:2037-2057 | PMID: 35589166
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Impact:
Abstract

Sodium Glucose Cotransporter-2 Inhibition for Acute Myocardial Infarction: JACC Review Topic of the Week.

Udell JA, Jones WS, Petrie MC, Harrington J, ... Hernandez AF, Butler J
Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and chronic heart failure. SGLT2 inhibitors also reduce the risk of cardiovascular mortality and hospitalization for heart failure among patients with type 2 diabetes mellitus and a remote history of myocardial infarction (MI). As a result of the growing body of evidence in diverse disease states, and the hypothesized mechanisms of action, it is reasonable to consider the potential of SGLT2 inhibition to improve outcomes in patients with acute MI as well if initiated early after presentation. Whether these therapies are efficacious and safe to use early in the course of acute coronary heart disease remains relatively unexplored. Here, we describe the contemporary data and continuing evidence gap for considering the use of SGLT2 inhibitors early following an acute MI to reduce cardiovascular morbidity and mortality.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2022; 79:2058-2068
Udell JA, Jones WS, Petrie MC, Harrington J, ... Hernandez AF, Butler J
J Am Coll Cardiol: 24 May 2022; 79:2058-2068 | PMID: 35589167
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Impact:
Abstract

Distribution of Coronary Artery Calcium by Age, Sex, and Race Among Patients 30-45 Years Old.

Javaid A, Dardari ZA, Mitchell JD, Whelton SP, ... Villines TC, Blaha MJ
Background
Coronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged <45 years.
Objectives
The purpose of this study was to determine the probability of CAC >0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years.
Methods
We harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques.
Results
The prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile.
Conclusions
In a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2022; 79:1873-1886
Javaid A, Dardari ZA, Mitchell JD, Whelton SP, ... Villines TC, Blaha MJ
J Am Coll Cardiol: 17 May 2022; 79:1873-1886 | PMID: 35550683
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Impact:
Abstract

Location of Aortic Enlargement and Risk of Type A Dissection at Smaller Diameters.

Ganapathi AM, Ranney DN, Peterson MD, Lindsay ME, ... Isselbacher EM, Hughes GC
Background
Previous work has demonstrated that more than one-half of acute type A aortic dissections (ATADs) occur at a maximal aortic diameter (MAD) of <5.5 cm. However, no analysis has investigated whether ATAD risk at smaller MADs is more common with modest dilation of the aortic root (AR) or supracoronary ascending aorta (AA) in patients without genetically triggered aortopathy.
Objectives
This study sought to determine if the segment of modest aortic dilation affects risk of ATAD.
Methods
Using the International Registry of Acute Aortic Dissection (IRAD) database from May 1996 to October 2016, we identified 667 ATAD patients with MAD <5.5 cm. Patients were stratified by location of the largest proximal aortic segment (AR or AA). Patients with known genetically triggered aortopathy were excluded. MADs at time of dissection were compared between AR and AA groups. Secondary outcomes included operation, postoperative outcomes, and long-term survival.
Results
Of patients with ATAD at an MAD <5.5 cm, 79.5% (n = 530) were in the AA group and 20.5% (n = 137) in the AR group. Modestly dilated ARs (median MAD 4.6 cm [IQR: 4.1-5.0 cm]) dissected at a significantly smaller diameter than modestly dilated AAs (median MAD 4.8 cm [IQR: 4.4-5.1 cm]) (P < 0.01). AR patients were significantly younger than AA patients (58.5 ± 13.0 years vs 63.2 ± 13.3 years; P < 0.01) and more commonly male (78% vs 65%; P < 0.01). Postoperative and long-term outcomes did not differ between groups.
Conclusions
ATAD appears to occur at smaller diameters in patients with modest dilation in the AR vs the AA (4.6 vs 4.8 cm). These findings may have implications for future consensus guidelines regarding the management of patients with aortic disease.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2022; 79:1890-1897
Ganapathi AM, Ranney DN, Peterson MD, Lindsay ME, ... Isselbacher EM, Hughes GC
J Am Coll Cardiol: 17 May 2022; 79:1890-1897 | PMID: 35550685
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Impact:
Abstract

Cardiovascular Risk Factors Mediate the Long-Term Maternal Risk Associated With Hypertensive Disorders of Pregnancy.

Stuart JJ, Tanz LJ, Rimm EB, Spiegelman D, ... Rexrode KM, Rich-Edwards JW
Background
Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, are associated with an increased risk of CVD.
Objectives
The purpose of this study was to evaluate associations between HDP and long-term CVD and identify the proportion of the association mediated by established CVD risk factors.
Methods
Parous participants without CVD in the Nurses\' Health Study II (n = 60,379) were followed for incident CVD from first birth through 2017. Cox proportional hazards models estimated HRs and 95% CIs for the relationship between HDP and CVD, adjusting for potential confounders, including prepregnancy body mass index, smoking, and parental history of CVD. To evaluate the proportion of the association jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes, and changes in body mass index, we used the difference method.
Results
Women with HDP in first pregnancy had a 63% higher rate of CVD (95% CI: 1.37-1.94) compared with women with normotensive pregnancies. This association was mediated by established CVD risk factors (proportion mediated = 64%). The increased rate of CVD was higher for preeclampsia (HR: 1.72; 95% CI: 1.42-2.10) than gestational hypertension (HR: 1.41; 95% CI: 1.03-1.93). Established CVD risk factors accounted for 57% of the increased rate of CVD for preeclampsia but 84% for gestational hypertension (both P < 0.0001).
Conclusions
Established CVD risk factors arising after pregnancy explained most (84%) of the increased risk of CVD conferred by gestational hypertension and 57% of the risk among women with preeclampsia. Screening for chronic hypertension, hypercholesterolemia, type 2 diabetes, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2022; 79:1901-1913
Stuart JJ, Tanz LJ, Rimm EB, Spiegelman D, ... Rexrode KM, Rich-Edwards JW
J Am Coll Cardiol: 17 May 2022; 79:1901-1913 | PMID: 35550687
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Impact:
Abstract

Burden of Pediatric Heart Failure in the United States.

Amdani S, Marino BS, Rossano J, Lopez R, Schold JD, Tang WHW
Background
There are currently limited accurate national estimates for pediatric heart failure (HF).
Objectives
This study aims to describe the current burden of primary and comorbid pediatric HF in the United States.
Methods
International Classification of Diseases, Clinical Modification codes were used to identify HF cases and comorbidities from the Kids\' Inpatient Database, National Inpatient Sample, National Emergency Department (ED) Sample, and National Vital Statistics System for 2012 and 2016. To describe HF events, all visits/events among pediatric and adult subjects were included in the analysis. HF events were classified into 1 of 3 groups: 1) no HF; 2) primary HF; or 3) comorbid HF. We compared patients with and without HF and calculated unique event rates with age and sex standardization.
Results
Congenital heart disease, conduction disorders/arrhythmias, and cardiomyopathy were responsible for the majority of pediatric HF-related ED visits and hospitalizations. Compared to 2012, in 2016, there was an increase in comorbid HF ED visits (rate ratio: 1.93; P < 0.001) and primary HF hospitalizations (rate ratio: 1.14; P = 0.002). Pediatric HF burden was lower compared to adult HF; however, deaths in the ED and in-hospital were significantly more likely in children presenting with HF than adults.
Conclusions
The burden of pediatric HF continues to increase. Compared to adults with HF presenting to the ED and in-hospital, outcomes are inferior and per patient resource use is higher for children hospitalized with HF. National initiatives to understand risk factors for morbidity and mortality in pediatric HF and continued surveillance and mitigation of preventable risk factors may attenuate this uptrend.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2022; 79:1917-1928
Amdani S, Marino BS, Rossano J, Lopez R, Schold JD, Tang WHW
J Am Coll Cardiol: 17 May 2022; 79:1917-1928 | PMID: 35550689
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Impact:
Abstract

The Increasing Role of Rhythm Control in Patients With Atrial Fibrillation: JACC State-of-the-Art Review.

Camm AJ, Naccarelli GV, Mittal S, Crijns HJGM, ... Turakhia MP, Kirchhof P
The considerable mortality and morbidity associated with atrial fibrillation (AF) pose a substantial burden on patients and health care services. Although the management of AF historically focused on decreasing AF recurrence, it evolved over time in favor of rate control. Recently, more emphasis has been placed on reducing adverse cardiovascular outcomes using rhythm control, generally by using safe and effective rhythm-control therapies (typically antiarrhythmic drugs and/or AF ablation). Evidence increasingly supports early rhythm control in patients with AF that has not become long-standing, but current clinical practice and guidelines do not yet fully reflect this change. Early rhythm control may effectively reduce irreversible atrial remodeling and prevent AF-related deaths, heart failure, and strokes in high-risk patients. It has the potential to halt progression and potentially save patients from years of symptomatic AF; therefore, it should be offered more widely.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2022; 79:1932-1948
Camm AJ, Naccarelli GV, Mittal S, Crijns HJGM, ... Turakhia MP, Kirchhof P
J Am Coll Cardiol: 17 May 2022; 79:1932-1948 | PMID: 35550691
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Impact:
Abstract

Anticoagulation for Percutaneous Ventricular Assist Device-Supported Cardiogenic Shock: JACC Review Topic of the Week.

Vandenbriele C, Arachchillage DJ, Frederiks P, Giustino G, ... Price S, Chieffo A
Interest in the use of mechanical circulatory support for patients presenting with cardiogenic shock is growing rapidly. The Impella (Abiomed Inc), a microaxial, continuous-flow, short-term, ventricular assist device (VAD), requires meticulous postimplantation management. Because systemic anticoagulation is needed to prevent pump thrombosis, patients are exposed to increased bleeding risk, further aggravated by sepsis, thrombocytopenia, and high shear stress-induced acquired von Willebrand syndrome. The precarious balance between bleeding and thrombosis in percutaneous VAD-supported cardiogenic shock patients is often the main reason that patient outcomes are jeopardized, and there is a lack of data addressing optimal anticoagulation management strategies during percutaneous VAD support. Here, we present a parallel anti-Factor Xa/activated partial thromboplastin time-guided anticoagulation algorithm and discuss pitfalls of heparin monitoring in critically ill patients. This review will guide physicians toward a more standardized (anti)coagulation approach to tackle device-related morbidity and mortality in this critically ill patient group.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2022; 79:1949-1962
Vandenbriele C, Arachchillage DJ, Frederiks P, Giustino G, ... Price S, Chieffo A
J Am Coll Cardiol: 17 May 2022; 79:1949-1962 | PMID: 35550692
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Impact:
Abstract

Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement.

Généreux P, Pibarot P, Redfors B, Bax JJ, ... Leon MB, Cohen DJ
Background
The impact of aortic valve replacement (AVR) on progression/regression of extra-valvular cardiac damage and its association with subsequent prognosis is unknown.
Objectives
To describe evolution of cardiac damage post-AVR and its association with outcomes.
Methods
Patients undergoing transcatheter or surgical AVR from the PARTNER 2 and 3 trials were pooled and classified by cardiac damage stage at baseline and 1-year (Stage 0, no damage; Stage 1, left ventricular damage; Stage 2, left atrial or mitral valve damage; Stage 3, pulmonary vasculature or tricuspid valve damage; Stage 4, right ventricular damage). Proportional hazards models determined association between change in cardiac damage post-AVR and 2-year outcomes.
Results
Among 1974 patients, 121 (6.1%) were Stage 0, 287 (14.5%) Stage 1, 1014 (51.4%) Stage 2, 412 (20.9%) Stage 3, and 140 (7.1%) Stage 4 pre-AVR. Two-year mortality was associated with extent of cardiac damage at baseline and 1-year. Compared with baseline, cardiac damage improved in ∼15%, remained unchanged in ∼60%, and worsened in ∼25% of patients at 1-year. One-year change in cardiac damage stage was independently associated with mortality (adjHR for improvement=0.49; no change=1.0; worsening=1.95; p=0.023) and composite of death or heart failure hospitalization (adjHR for improvement=0.60; no change=1.0; worsening=2.25; p<0.001) at 2 years.
Conclusion
In patients undergoing AVR, extent of extravalvular cardiac damage at baseline and its change at 1-year have important prognostic implications. These findings suggest that earlier detection of AS and intervention prior to development of irreversible cardiac damage may improve global cardiac function and prognosis.

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 14 May 2022; epub ahead of print
Généreux P, Pibarot P, Redfors B, Bax JJ, ... Leon MB, Cohen DJ
J Am Coll Cardiol: 14 May 2022; epub ahead of print | PMID: 35595203
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Impact:
Abstract

Balloon- Versus Self-Expanding Valve Systems for Treating Small Failed Surgical Aortic Bioprostheses: The LYTEN Trial.

Rodés-Cabau J, Abbas A, Serra V, Vilalta V, ... Pelletier-Beaumont E, Pibarot P
Background
Data comparing valve systems in the valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) field has been obtained from retrospective studies.
Objectives
To compare the hemodynamic results between the balloon-expandable SAPIEN (3/ULTRA) (BEV) and self-expanding Evolut (R/PRO/PRO+) (SEV) valves in ViV-TAVR.
Methods
Patients with a failed small (≤23 mm) surgical valve. were randomized to receive a BEV or a SEV. The primary endpoint was valve hemodynamics (maximal/mean residual gradients; severe prosthesis patient mismatch [PPM] or moderate-severe aortic regurgitation [AR]) at 30 days as evaluated by Doppler-echocardiography.
Results
A total of 102 patients were randomized, and of these, 98 patients finally underwent a ViV-TAVR procedure (BEV: 46, SEV: 52). The procedure was successful in all cases, with no differences in clinical outcomes at 30 days between groups (no death or stroke events). Patients in the SEV group exhibited lower mean and maximal transvalvular gradient values (15±8 vs 23±8 mmHg, p˂0.001; 28±16 vs 40±13 mmHg, p ˂0.001), and a tendency towards a lower rate of severe PPM (44% vs. 64%, p=0.07). There were no cases of moderate-severe AR. 55 consecutive patients (SEV: 27, BEV: 28) underwent invasive valve hemodynamic evaluation during the procedure, with no differences in mean and peak transvalvular gradients between both groups (p=0.41 and p=0.70, respectively).
Conclusions
In patients with small failed aortic bioprostheses, ViV-TAVR with a SEV was associated with improved valve hemodynamics as evaluated by echocardiography. There were no differences between groups in intra-procedural invasive valve hemodynamics and 30-day clinical outcomes (NCT03520101).

Copyright © 2022. Published by Elsevier Inc.

J Am Coll Cardiol: 13 May 2022; epub ahead of print
Rodés-Cabau J, Abbas A, Serra V, Vilalta V, ... Pelletier-Beaumont E, Pibarot P
J Am Coll Cardiol: 13 May 2022; epub ahead of print | PMID: 35597385
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Abstract

Definitions and Standardized Endpoints for Treatment of Coronary Bifurcations.

Lunardi M, Louvard Y, Lefèvre T, Stankovic G, ... Onuma Y, Bifurcation Academic Research Consortium and European Bifurcation Club
The Bifurcation Academic Research Consortium (Bif-ARC) project originated from the need to overcome the paucity of standardization and comparability between studies involving bifurcation coronary lesions. This document is the result of a collaborative effort between academic research organizations and the most renowned interventional cardiology societies focused on bifurcation lesions in Europe, the United States, and Asia. This consensus provides standardized definitions for bifurcation lesions; the criteria to judge the side branch relevance; the procedural, mechanistic, and clinical endpoints for every type of bifurcation study; and the follow-up methods. Considering the complexity of bifurcation lesions and their evaluation, detailed instructions and technical aspects for site and core laboratory analysis of bifurcation lesions are also reported. The recommendations included within this consensus will facilitate pooled analyses and the effective comparison of data in the future, improving the clinical relevance of trials in bifurcation lesions, and the quality of care in this subset of patients.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 13 May 2022; epub ahead of print
Lunardi M, Louvard Y, Lefèvre T, Stankovic G, ... Onuma Y, Bifurcation Academic Research Consortium and European Bifurcation Club
J Am Coll Cardiol: 13 May 2022; epub ahead of print | PMID: 35597684
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Abstract

Antithrombotic Therapy After Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation.

Freeman JV, Higgins AY, Wang Y, Du C, ... Masoudi FA, Curtis JP
Background
Pivotal trials of percutaneous left atrial appendage occlusion (LAAO) used specific postprocedure treatment protocols.
Objectives
This study sought to evaluate patterns of postprocedure care after LAAO with the Watchman device in clinical practice and compare the risk of adverse events for different discharge antithrombotic strategies.
Methods
We evaluated patients in the LAAO Registry of the National Cardiovascular Data Registry who underwent LAAO with the Watchman device between 2016 and 2018. We assessed adherence to the full postprocedure trial protocol including standardized follow-up, imaging, and antithrombotic agents and then evaluated the most commonly used antithrombotic strategies and compared the rates and risk of adverse events at 45 days and 6 months by means of multivariable COX frailty regression.
Results
Among 31,994 patients undergoing successful LAAO, only 12.2% received the full postprocedure treatment protocol studied in pivotal trials; the most common protocol deviations were with discharge antithrombotic medications. The most common discharge medication strategies were warfarin and aspirin (36.9%), direct oral anticoagulant (DOAC) and aspirin (20.8%), warfarin only (13.5%), DOAC only (12.3%), and dual antiplatelet therapy (5.0%). In multivariable Cox frailty regression, the adjusted risk of any adverse event through the 45-day follow-up visit were significantly lower for discharge on warfarin alone (HR: 0.692; 95% CI: 0.569-0.841) and DOAC alone (HR: 0.731; 95% CI: 0.574-0.930) compared with warfarin and aspirin. Warfarin alone retained lower risk at the 6-month follow-up.
Conclusions
In contemporary U.S. practice, practitioners rarely used the full U.S. Food and Drug Administration-approved postprocedure treatment protocols studied in pivotal trials of the Watchman device. Discharge after implantation on warfarin or DOAC without concomitant aspirin was associated with lower risk of adverse outcomes.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2022; 79:1785-1798
Freeman JV, Higgins AY, Wang Y, Du C, ... Masoudi FA, Curtis JP
J Am Coll Cardiol: 10 May 2022; 79:1785-1798 | PMID: 35512858
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Abstract

High-Intensity Statin Use Among Patients With Atherosclerosis in the U.S.

Nelson AJ, Haynes K, Shambhu S, Eapen Z, ... Pagidipati NJ, Granger CB
Background
Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have improved the use of high-intensity statins is unknown.
Objectives
This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD.
Methods
In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities.
Results
Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence.
Conclusions
Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2022; 79:1802-1813
Nelson AJ, Haynes K, Shambhu S, Eapen Z, ... Pagidipati NJ, Granger CB
J Am Coll Cardiol: 10 May 2022; 79:1802-1813 | PMID: 35512860
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Abstract

Incidence of Sudden Cardiac Death in the European Union.

Jean-Philippe E, Lerner I, Valentin E, Folke F, ... Jouven X, ESCAPE-NET Investigators
Background
Although sudden cardiac death (SCD) is recognized as a high-priority public health topic, reliable estimates of the incidence of SCD or, more broadly, out-of-hospital cardiac arrest (OHCA), in the population are scarce, especially in the European Union.
Objectives
The study objective was to determine the incidence of SCD and OHCA in the European Union.
Methods
The study examined 4 large (ie, >2 million inhabitants) European population-based prospective registries collecting emergency medical services (EMS)-attended (ie, with attempted resuscitation) OHCA and SCD (OHCA without obvious extracardiac causes) for >5 consecutive years from January 2012 to December 2017 in the Paris region (France), the North Holland region (the Netherlands), the Stockholm region (Sweden), and in all of Denmark.
Results
The average annual incidence of SCD in the 4 registries ranged from 36.8 per 100,000 (95% CI: 23.5-50.1 per 100,000) to 39.7 per 100,000 (95% CI: 32.6-46.8 per 100,000). When extrapolating to each European country and accounting for age and sex, this yields to 249,538 SCD cases per year (95% CI: 155,377-343,719 SCD cases per year). The average annual incidence of OHCA in the 4 registries ranged from 47.8 per 100,000 (95% CI: 21.2-74.4 per 100,000) to 57.9 per 100,000 (95% CI: 19.6-96.3 per 100,000), corresponding to 343,496 OHCA cases per year (95% CI: 216,472-464,922 OHCA cases per year) in the European Union. Incidence rates of SCD and OHCA increased with age and were systematically higher in men compared with women.
Conclusions
By combining data from 4 large, population-based registries with at least 5 years of data collection, this study provided an estimate of the incidence of SCD and OHCA in the European Union.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2022; 79:1818-1827
Jean-Philippe E, Lerner I, Valentin E, Folke F, ... Jouven X, ESCAPE-NET Investigators
J Am Coll Cardiol: 10 May 2022; 79:1818-1827 | PMID: 35512862
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Abstract

Guidelines for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes: JACC Guideline Comparison.

Kelsey MD, Nelson AJ, Green JB, Granger CB, ... McGuire DK, Pagidipati NJ
Cardiovascular disease is a leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus. These high-risk patients benefit from aggressive risk factor management, with blood pressure and low-density lipoprotein-cholesterol treatment, glycemic control, kidney protection, and lifestyle intervention. There are several recommendation and guideline documents across cardiology, endocrinology, nephrology, and general medicine professional societies from the United States and Europe with recommendations for cardiovascular risk reduction in patients with type 2 diabetes mellitus. Although there are some noteworthy differences, particularly in risk stratification, low-density lipoprotein-cholesterol and blood pressure treatment targets, and the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, overall there is considerable alignment across recommendations from different professional societies.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2022; 79:1849-1857
Kelsey MD, Nelson AJ, Green JB, Granger CB, ... McGuire DK, Pagidipati NJ
J Am Coll Cardiol: 10 May 2022; 79:1849-1857 | PMID: 35512864
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Abstract

Venous Tone and Stressed Blood Volume in Heart Failure: JACC Review Topic of the Week.

Fudim M, Kaye DM, Borlaug BA, Shah SJ, ... Sunagawa K, Burkhoff D
A number of pathologic processes contribute to the elevation in cardiac filling pressures in heart failure (HF), including myocardial dysfunction and primary volume overload. In this review, we discuss the important role of the venous system and the concepts of stressed blood volume and unstressed blood volume. We review how regulation of venous tone modifies the distribution of blood between these 2 functional compartments, the physical distribution of blood between the pulmonary and systemic circulations, and how these relate to the hemodynamic abnormalities observed in HF. Finally, we review recently applied methods for estimating stressed blood volume and how they are being applied to the results of clinical studies to provide new insights into resting and exercise hemodynamics and therapeutics for HF.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2022; 79:1858-1869
Fudim M, Kaye DM, Borlaug BA, Shah SJ, ... Sunagawa K, Burkhoff D
J Am Coll Cardiol: 10 May 2022; 79:1858-1869 | PMID: 35512865
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Abstract

Survival Following Alcohol Septal Ablation or Septal Myectomy for Patients With Obstructive Hypertrophic Cardiomyopathy.

Cui H, Schaff HV, Wang S, Lahr BD, ... Ommen SR, Maron MS
Background
There is little information regarding long-term mortality comparing the 2 most common procedures for septal reduction for obstructive hypertrophic cardiomyopathy (HCM), alcohol septal ablation (ASA), and septal myectomy.
Objectives
This study sought to compare the long-term mortality of patients with obstructive HCM following septal myectomy or ASA.
Methods
We evaluated outcomes of 3,859 patients who underwent ASA or septal myectomy in 3 specialized HCM centers. All-cause mortality was the primary endpoint of the study.
Results
In the study cohort, 585 (15.2%) patients underwent ASA, and 3,274 (84.8%) underwent septal myectomy. Patients undergoing ASA were significantly older (median age: 63.0 years [IQR: 52.7-72.8 years] vs 53.7 years [IQR: 44.9-62.8 years]; P < 0.001) and had smaller septal thickness (19.0 mm [IQR: 17.0-22.0 mm] vs 20.0 mm [IQR: 17.0-23.0 mm]; P = 0.007). Patients undergoing ASA also had more comorbidities, including renal failure, diabetes, hypertension, and coronary artery disease. There were 4 (0.7%) early deaths in the ASA group and 9 (0.3%) in the myectomy group. Over a median follow-up of 6.4 years (IQR: 3.6-10.2 years), the 10-year all-cause mortality rate was 26.1% in the ASA group and 8.2% in the myectomy group. After adjustment for age, sex, and comorbidities, the mortality remained greater in patients having septal reduction by ASA (HR: 1.68; 95% CI: 1.29-2.19; P < 0.001).
Conclusions
In patients with obstructive hypertrophic cardiomyopathy, ASA is associated with increased long-term all-cause mortality compared with septal myectomy. This impact on survival is independent of other known factors but may be influenced by unmeasured confounding patient characteristics.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2022; 79:1647-1655
Cui H, Schaff HV, Wang S, Lahr BD, ... Ommen SR, Maron MS
J Am Coll Cardiol: 03 May 2022; 79:1647-1655 | PMID: 35483751
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Abstract

Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction.

Gaba P, Bhatt DL, Steg PG, Miller M, ... Ballantyne CM, REDUCE-IT Investigators
Background
REDUCE-IT was a double-blind trial that randomized 8,179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. There was a significant reduction in the primary endpoint, including death from cardiovascular (CV) causes. The specific impact of IPE among patients with prior myocardial infarction (MI) was unknown.
Objectives
Our goal was to examine the benefit of IPE on ischemic events among patients with prior MI in REDUCE-IT.
Methods
We performed post hoc analyses of patients with prior MI. The primary endpoint was CV death, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary endpoint was CV death, MI, or stroke.
Results
A total of 3,693 patients had a history of prior MI. The primary endpoint was reduced from 26.1% to 20.2% with IPE vs placebo; HR: 0.74 (95% CI: 0.65-0.85; P = 0.00001). The key secondary endpoint was reduced from 18.0% to 13.3%; HR: 0.71 (95% CI: 0.61-0.84; P = 0.00006). There was also a significant 35% relative risk reduction in total ischemic events (P = 0.0000001), a 34% reduction in MI (P = 0.00009), a 30% reduction in CV death (P = 0.01), and a 20% lower rate of all-cause mortality (P = 0.054), although there was a slight increase in atrial fibrillation. Sudden cardiac death and cardiac arrest were also significantly reduced by 40% and 56%, respectively.
Conclusions
Patients with a history of prior MI in REDUCE-IT treated with IPE demonstrated large and significant relative and absolute risk reductions in ischemic events, including CV death. (A Study of AMR101 to Evaluate Its Ability to Reduce Cardiovascular Events in High Risk Patients With Hypertriglyceridemia and on Statin. The Primary Objective is to Evaluate the Effect of 4 g/Day AMR101 for Preventing the Occurrence of a First Major Cardiovascular Event. [REDUCE-IT]; NCT01492361).

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2022; 79:1660-1671
Gaba P, Bhatt DL, Steg PG, Miller M, ... Ballantyne CM, REDUCE-IT Investigators
J Am Coll Cardiol: 03 May 2022; 79:1660-1671 | PMID: 35483753
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Abstract

Cardiovascular Implications of the 2021 KDIGO Blood Pressure Guideline for Adults With Chronic Kidney Disease.

Lee HH, Lee H, Townsend RR, Kim DW, Park S, Kim HC
Background
The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommends a systolic blood pressure (BP) target of <120 mm Hg for nondialysis chronic kidney disease (CKD).
Objectives
We sought to examine the potential implications of the 2021 KDIGO BP target, compared with the 2012 KDIGO and 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP targets, as related to cardiovascular disease (CVD) outcomes.
Methods
From the cross-sectional Korea National Health and Nutrition Examination Survey (KNHANES) and longitudinal National Health Insurance Service (NHIS) data, adults with nondialysis CKD were identified and categorized into 4 groups based on concordance/discordance between guidelines: 1) above both targets; 2) above 2021 KDIGO only; 3) above 2012 KDIGO or 2017 ACC/AHA only; and 4) controlled within both targets. We determined the nationally representative proportion and CVD risk of each group.
Results
In KNHANES (n = 1,939), 50.2% had BP above both 2021 and 2012 KDIGO targets, 15.9% above the 2021 KDIGO target only, 3.5% above the 2012 KDIGO target only, and 30.4% controlled within both targets. In NHIS (n = 412,167; median follow-up: 10.0 years), multivariable-adjusted HRs for CVD events were 1.52 (95% CI: 1.47-1.58) among participants with BP above both targets, 1.28 (95% CI: 1.24-1.32) among those with BP above 2021 KDIGO only, and 1.07 (95% CI: 0.61-1.89) among those with BP above 2012 KDIGO only, compared to those with BP controlled within both targets. Results were similar for comparison between 2021 KDIGO and 2017 ACC/AHA BP targets.
Conclusions
New candidates for BP-lowering treatment per the 2021 KDIGO guideline account for a substantial proportion of the total CKD population and bear significantly high CVD risk.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2022; 79:1675-1686
Lee HH, Lee H, Townsend RR, Kim DW, Park S, Kim HC
J Am Coll Cardiol: 03 May 2022; 79:1675-1686 | PMID: 35483755
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Abstract

Systematic Review of Physical Activity Trajectories and Mortality in Patients With Coronary Artery Disease.

Gonzalez-Jaramillo N, Wilhelm M, Arango-Rivas AM, Gonzalez-Jaramillo V, ... Franco OH, Bano A
Background
The role of lifestyle physical activity (PA) trajectories in the mortality risk of patients with coronary heart disease (CHD) remains unclear.
Objectives
The purpose of this study was to determine the association of longitudinal PA trajectories with all-cause and cardiovascular disease (CVD) mortality in patients with CHD.
Methods
Longitudinal cohorts reporting the association of PA trajectories with mortality in patients with CHD were identified in April 2021 by searching 5 databases without language restrictions. Published HRs and 95% CIs were pooled using random effects models and bias assessed by Egger regression.
Results
A total of 9 prospective cohorts included 33,576 patients. The mean age was 62.5 years. The maximum follow-up was 15.7 years. All of the studies assessed PA through validated questionnaires, and mortality was well documented. Changes in PA defined 4 nominal PA trajectories. Compared with always-inactive patients, the risk of all-cause mortality was 50% lower in those who remained active (HR: 0.50; 95% CI: 0.39-0.63); 45% lower in those who were inactive but became active (HR: 0.55; 95% CI: 0.44-0.7); and 20% lower in those who were active but became inactive (HR: 0.80; 95% CI: 0.64-0.99). Similar results were observed for CVD mortality, except for the category of decreased activity (HR: 0.91; 95% CI: 0.67-1.24). The overall risk of bias was low. No evidence of publication bias was found. Multiple sensitivity analyses provided consistent results.
Conclusions
This study illustrates how patients with CHD may benefit by preserving or adopting an active lifestyle. The observation that the benefits of past activity can be weakened or lost if PA is not maintained may be confounded by disease progression.

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2022; 79:1690-1700
Gonzalez-Jaramillo N, Wilhelm M, Arango-Rivas AM, Gonzalez-Jaramillo V, ... Franco OH, Bano A
J Am Coll Cardiol: 03 May 2022; 79:1690-1700 | PMID: 35483757
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Abstract

The National Cardiovascular Data Registry Data Quality Program 2020: JACC State-of-the-Art Review.

Malenka DJ, Bhatt DL, Bradley SM, Shahian DM, ... Roe M, Masoudi FA
The National Cardiovascular Data Registry is a group of registries maintained by the American College of Cardiology Foundation. These registries are used by a diverse constituency to improve the quality and outcomes of cardiovascular care, to assess the safety and effectiveness of new therapies, and for research. To achieve these goals, registry data must be complete and reliable. In this article, we review the process of National Cardiovascular Data Registry data collection, assess data completeness and integrity, and report on the current state of the data. Registry data are complete. Accuracy is very good but variable, and there is room for improvement. Knowledge of the quality of data is essential to ensuring its appropriate use.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2022; 79:1704-1712
Malenka DJ, Bhatt DL, Bradley SM, Shahian DM, ... Roe M, Masoudi FA
J Am Coll Cardiol: 03 May 2022; 79:1704-1712 | PMID: 35483759
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Abstract

Complicated Carotid Artery Plaques and Risk of Recurrent Ischemic Stroke or TIA.

Kopczak A, Schindler A, Sepp D, Bayer-Karpinska A, ... Saam T, Dichgans M
Background
Complicated nonstenosing carotid artery plaques (CAPs) are an under-recognized cause of stroke.
Objectives
The purpose of this study was to determine whether complicated CAP ipsilateral to acute ischemic anterior circulation stroke (icCAP) are associated with recurrent ischemic stroke or transient ischemic attack (TIA).
Methods
The CAPIAS (Carotid Plaque Imaging in Acute Stroke) multicenter study prospectively recruited patients with ischemic stroke restricted to the territory of a single carotid artery. Complicated (AHA-lesion type VI) CAP were defined by multisequence, contrast-enhanced carotid magnetic resonance imaging obtained within 10 days from stroke onset. Recurrent events were assessed after 3, 12, 24, and 36 months. The primary outcome was recurrent ischemic stroke or TIA.
Results
Among 196 patients enrolled, 104 patients had cryptogenic stroke and nonstenosing CAP. During a mean follow-up of 30 months, recurrent ischemic stroke or TIA occurred in 21 patients. Recurrent events were significantly more frequent in patients with icCAP than in patients without icCAP, both in the overall cohort (incidence rate [3-year interval]: 9.50 vs 3.61 per 100 patient-years; P = 0.025, log-rank test) and in patients with cryptogenic stroke (10.92 vs 1.82 per 100 patient-years; P = 0.003). The results were driven by ipsilateral events. A ruptured fibrous cap (HR: 4.91; 95% CI: 1.31-18.45; P = 0.018) and intraplaque hemorrhage (HR: 4.37; 95% CI: 1.20-15.97; P = 0.026) were associated with a significantly increased risk of recurrent events in patients with cryptogenic stroke.
Conclusions
Complicated CAP ipsilateral to acute ischemic anterior circulation stroke are associated with an increased risk of recurrent ischemic stroke or TIA. Carotid plaque imaging identifies high-risk patients who might be suited for inclusion into future secondary prevention trials. (Carotid Plaque Imaging in Acute Stroke [CAPIAS]; NCT01284933).

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 27 Apr 2022; epub ahead of print
Kopczak A, Schindler A, Sepp D, Bayer-Karpinska A, ... Saam T, Dichgans M
J Am Coll Cardiol: 27 Apr 2022; epub ahead of print | PMID: 35523659
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Abstract

Association of Left Atrial Structure and Function With Heart Failure in Older Adults.

Inciardi RM, Claggett B, Minamisawa M, Shin SH, ... Chen LY, Solomon SD
Background
Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF).
Objectives
The aim was to assess reference range of LA measures, their associations with N-terminal pro-B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death.
Methods
We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5.5 years) in the whole ARIC cohort.
Results
Approximately 20% of the overall population had LA abnormalities according to the ARIC-based reference limit. Each LA measure was associated with NT-proBNP and, except for LAViMax, with incident HF or death after multivariable adjustment (including left ventricular function and NT-proBNP). Results were consistent in participants with normal LAViMax (P for interaction > 0.05). LA measures were prognostic for both incident HF with preserved ejection fraction or death and incident HF with reduced ejection fraction or death. When added to HF risk factors and NT-proBNP (baseline C-statistics = 0.74) all LA measures, except for LAViMax, significantly enhanced the prognostic accuracy.
Conclusions
Novel measures of LA structure and function, but not standard assessment by LAViMax, are associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP.

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Apr 2022; 79:1549-1561
Inciardi RM, Claggett B, Minamisawa M, Shin SH, ... Chen LY, Solomon SD
J Am Coll Cardiol: 26 Apr 2022; 79:1549-1561 | PMID: 35450571
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Abstract

Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy.

Dybro AM, Rasmussen TB, Nielsen RR, Ladefoged BT, ... Jensen MK, Poulsen SH
Background
The relationship between exercise hemodynamics, loading conditions, and medical treatment in patients with obstructive hypertrophic cardiomyopathy (HCM) is incompletely understood.
Objectives
This study aimed to investigate the effect of metoprolol on invasive hemodynamic parameters at rest and during exercise in patients with obstructive HCM.
Methods
This randomized, double-blind, placebo-controlled crossover trial enrolled 28 patients with obstructive HCM and New York Heart Association functional class ≥II. Patients were randomized to initiate either metoprolol 150 mg or placebo for 2 consecutive 2-week periods. Right-heart catheterization and echocardiography were performed at rest and during exercise at the end of each treatment period. The primary outcome was the difference in pulmonary capillary wedge pressure (ΔPCWP) between peak exercise and rest.
Results
No treatment effect on ΔPCWP was observed between metoprolol and placebo treatment (21 ± 9 mm Hg vs 23 ± 9 mm Hg; P = 0.12). At rest, metoprolol lowered heart rate (P < 0.0001), left ventricular outflow tract (LVOT) gradient (P = 0.01), and increased left ventricular end-diastolic volume (P = 0.02) and stroke volume (SV) (+6.4; 95% CI: 0.02-17.7; P = 0.049). During peak exercise, metoprolol was associated with a lower heart rate (P < 0.0001), a lower LVOT gradient (P = 0.0005), lesser degree of mitral regurgitation (P = 0.004), and increased SV (+9 mL; 95% CI: 2-15 mL; P = 0.008).
Conclusions
In patients with obstructive HCM, exercise was associated with an abnormal rise in PCWP, which was unaffected by metoprolol. However, metoprolol increased SV at rest and peak exercise following changes in end-diastolic volume, LVOT gradient, and degree of mitral regurgitation. (The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy [TEMPO]; NCT03532802).

Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Apr 2022; 79:1565-1575
Dybro AM, Rasmussen TB, Nielsen RR, Ladefoged BT, ... Jensen MK, Poulsen SH
J Am Coll Cardiol: 26 Apr 2022; 79:1565-1575 | PMID: 35450573
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Impact:
Older ...

This program is still in alpha version.