Journal: J Am Coll Cardiol

Sorted by: date / impact
Abstract

Predicting In-Hospital Mortality in Patients Undergoing Percutaneous Coronary Intervention.

Castro-Dominguez YS, Wang Y, Minges KE, McNamara RL, ... Curtis JP, Cavender MA
Background
Standardization of risk is critical in benchmarking and quality improvement efforts for percutaneous coronary interventions (PCIs). In 2018, the CathPCI Registry was updated to include additional variables to better classify higher-risk patients.
Objectives
This study sought to develop a model for predicting in-hospital mortality risk following PCI incorporating these additional variables.
Methods
Data from 706,263 PCIs performed between July 2018 and June 2019 at 1,608 sites were used to develop and validate a new full and pre-catheterization model to predict in-hospital mortality, and a simplified bedside risk score. The sample was randomly split into a development cohort (70%, n = 495,005) and a validation cohort (30%, n = 211,258). The authors created 1,000 bootstrapped samples of the development cohort and used stepwise selection logistic regression on each sample. The final model included variables that were selected in at least 70% of the bootstrapped samples and those identified a priori due to clinical relevance.
Results
In-hospital mortality following PCI varied based on clinical presentation. Procedural urgency, cardiovascular instability, and level of consciousness after cardiac arrest were most predictive of in-hospital mortality. The full model performed well, with excellent discrimination (C-index: 0.943) in the validation cohort and good calibration across different clinical and procedural risk cohorts. The median hospital risk-standardized mortality rate was 1.9% and ranged from 1.1% to 3.3% (interquartile range: 1.7% to 2.1%).
Conclusions
The risk of mortality following PCI can be predicted in contemporary practice by incorporating variables that reflect clinical acuity. This model, which includes data previously not captured, is a valid instrument for risk stratification and for quality improvement efforts.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:216-229
Castro-Dominguez YS, Wang Y, Minges KE, McNamara RL, ... Curtis JP, Cavender MA
J Am Coll Cardiol: 19 Jul 2021; 78:216-229 | PMID: 33957239
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Associations of Cardiac Mechanics With Exercise Capacity: The Multi-Ethnic Study of Atherosclerosis.

Patel RB, Freed BH, Beussink-Nelson L, Allen NB, ... Bertoni AG, Shah SJ
Background
Lower exercise capacity, as measured by 6-minute walk distance (6MWD), is associated with incident heart failure (HF). Among those without HF, the associations of measures of cardiac function with 6MWD are unclear, and may provide insight regarding the risk of incident HF.
Objectives
The purpose of this study was to understand the relationships between cardiac function and exercise capacity.
Methods
This study evaluated the associations of cardiac mechanics with 6MWD in the sixth examination of the Multi-Ethnic Study of Atherosclerosis. Echocardiography (2-dimensional, Doppler, and speckle-tracking) was performed at rest and after passive leg raise to evaluate functional reserve after intravascular volume challenge.
Results
Of 2,096 participants without HF (mean age 73 years, 48% men, 58% non-White), individuals with lower (worse) left atrial (LA) reservoir strain were older and had higher blood pressure. Lower resting LA reservoir strain (β coefficient per SD decrease: -5.0; 95% confidence interval [CI]: -8.8 to -1.3 m; p = 0.009), inability to augment LA reservoir strain after passive leg raise (β coefficient per SD decrease: -5.8; 95% CI: -9.1 to -2.5 m; p < 0.001), and lower right atrial reservoir strain (β coefficient per SD decrease: -4.4; 95% CI: -7.8 to -1.1 m; p = 0.01) were associated with shorter 6MWD. Worse left ventricular (LV) diastolic function was also associated with lower 6MWD. There were no independent associations of measures of LV systolic function (global longitudinal strain, circumferential strain, ejection fraction) with 6MWD.
Conclusions
Among individuals without HF, worse biatrial function, lack of LA functional reserve, and worse LV diastolic function were associated with reduced submaximal exercise capacity. Therapies aimed to improve these functional domains may increase exercise capacity and prevent HF.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:245-257
Patel RB, Freed BH, Beussink-Nelson L, Allen NB, ... Bertoni AG, Shah SJ
J Am Coll Cardiol: 19 Jul 2021; 78:245-257 | PMID: 33992746
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pathophysiology of the Lymphatic System in Patients With Heart Failure: JACC State-of-the-Art Review.

Itkin M, Rockson SG, Burkhoff D
The removal of interstitial fluid from the tissues is performed exclusively by the lymphatic system. Tissue edema in congestive heart failure occurs only when the lymphatic system fails or is overrun by fluid leaving the vascular space across the wall of the capillaries into the interstitial space. This process is driven by Starling forces determined by hydrostatic and osmotic pressures and organ-specific capillary permeabilities to proteins of different sizes. In this review, we summarize current knowledge of the generation of lymph in different organs, the mechanics by which lymph is returned to the circulation, and the consequences of the inadequacy of lymph flow. We review recent advances in imaging techniques that have allowed for new research, diagnostic, and therapeutic approaches to the lymphatic system. Finally, we review how efforts to increase lymph flow have demonstrated potential as a viable therapeutic approach for refractory heart failure.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:278-290
Itkin M, Rockson SG, Burkhoff D
J Am Coll Cardiol: 19 Jul 2021; 78:278-290 | PMID: 34266581
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Coronary Artery Risk Development In Young Adults (CARDIA) Study: JACC Focus Seminar 8/8.

Lloyd-Jones DM, Lewis CE, Schreiner PJ, Shikany JM, Sidney S, Reis JP
The CARDIA (Coronary Artery Risk Development in Young Adults) study began in 1985 to 1986 with enrollment of 5,115 Black or White men and women ages 18 to 30 years from 4 US communities. Over 35 years, CARDIA has contributed fundamentally to our understanding of the contemporary epidemiology and life course of cardiovascular health and disease, as well as pulmonary, renal, neurological, and other manifestations of aging. CARDIA has established associations between the neighborhood environment and the evolution of lifestyle behaviors with biological risk factors, subclinical disease, and early clinical events. CARDIA has also identified the nature and major determinants of Black-White differences in the development of cardiovascular risk. CARDIA will continue to be a unique resource for understanding determinants, mechanisms, and outcomes of cardiovascular health and disease across the life course, leveraging ongoing pan-omics work from genomics to metabolomics that will define mechanistic pathways involved in cardiometabolic aging.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:260-277
Lloyd-Jones DM, Lewis CE, Schreiner PJ, Shikany JM, Sidney S, Reis JP
J Am Coll Cardiol: 19 Jul 2021; 78:260-277 | PMID: 34266580
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Enhanced Assessment of Perioperative Mortality Risk in Adults With Congenital Heart Disease.

Constantine A, Costola G, Bianchi P, Chessa M, ... Ranucci M, Dimopoulos K
Background
In-hospital mortality is a rare, yet feared complication following cardiac surgery in adult congenital heart disease (ACHD). A risk score, developed and validated in ACHD, can be helpful to optimize risk assessment.
Objectives
The purpose of this study was to assess the performance of EuroSCORE II components and procedure-related Adult Congenital Heart Surgery (ACHS) score, identify additional risk factors, and develop a novel risk score for predicting in-hospital mortality after ACHD surgery.
Methods
We assessed perioperative survival in patients aged >16 years undergoing congenital heart surgery in a large tertiary center between 2003 and 2019. A risk variable-derived PEACH (PErioperative ACHd) score was calculated for each patient. Internal and external validation of the model was undertaken, including testing in a validation cohort of patients operated in a second European ACHD center.
Results
The development cohort comprised 1,782 procedures performed during the study period. Re-sternotomy was undertaken in 897 (50.3%). There were 31 (1.7%) in-hospital deaths. The PEACH score showed excellent discrimination ability (area under the curve [AUC]: 0.88; 95% CI: 0.83-0.94), and performed better than the ACHS score in our population (ACHS AUC: 0.69; 95% CI: 0.6-0.78; P = 0.0003). A simple 3-tiered risk stratification was formed: PEACH score 0 (in-hospital mortality 0.2%), 1-2 (3.6%), and ≥3 (17.2%). In a validation cohort of 975 procedures, the PEACH score retained its discriminative ability (AUC: 0.75; 95% CI: 0.72-0.77) and was well calibrated (Hosmer-Lemeshow chi-square goodness-of-fit P = 0.55). There was agreement in expected and observed perioperative mortality between cohorts.
Conclusions
The PEACH score is a simple, novel perioperative risk score developed and validated specifically for ACHD patients undergoing cardiac surgery.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:234-242
Constantine A, Costola G, Bianchi P, Chessa M, ... Ranucci M, Dimopoulos K
J Am Coll Cardiol: 19 Jul 2021; 78:234-242 | PMID: 34266577
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Population-Based Risk Factors for Ascending, Arch, Descending, and Abdominal Aortic Dilations for 60-74-Year-Old Individuals.

Obel LM, Diederichsen AC, Steffensen FH, Frost L, ... Bovling AS, Lindholt JS
Background
Aortic dilations (ectasias and aneurysms) may occur on any segment of the aorta. Pathogenesis varies between locations, suggesting that etiology and risk factors may differ. Despite this discrepancy, guidelines recommend screening of the whole aorta if 1 segmental dilation is discovered.
Objectives
The purpose of this study was to determine the most dominant predictors for dilations at the ascending, arch, descending, and abdominal part of the aorta, and to establish comprehensive risk factor profiles for each aortic segment.
Methods
Individuals aged 60-74 years were randomly selected to participate in DANCAVAS I+II (Danish Cardiovascular Multicenter Screening Trials). Participants underwent cardiovascular risk assessments, including blood samples, blood pressure readings, medical records, and noncontrast computed tomography scans. Adjusted odds ratios for potential risk factors of dilations were estimated by multivariate logistic analyses.
Results
The study population consisted of 14,989 participants (14,235 men, 754 women) with an average age of 68 ± 4 years. The highest adjusted odd ratios for having any aortic dilation were observed when coexisting aortic dilations were present. Other noteworthy predictors included coexisting iliac dilations, hypertension, increasing body surface area, male sex, familial disposition, and atrial fibrillation, which were present in various combinations for the different aortic parts. Smoking and acute myocardial infarction were inversely associated with ascending and abdominal dilations. Diabetes was a shared protective factor.
Conclusions
Risk factors differ for aortic dilations between locations. The most dominant predictor for having a dilation at any aortic segment is the presence of an aortic dilation elsewhere. This supports current guidelines when recommending a full screening of the aorta if a focal aortic dilation is discovered.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 19 Jul 2021; 78:201-211
Obel LM, Diederichsen AC, Steffensen FH, Frost L, ... Bovling AS, Lindholt JS
J Am Coll Cardiol: 19 Jul 2021; 78:201-211 | PMID: 34266574
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Transesophageal Echocardiography in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Metkus TS, Thibault D, Grant MC, Badhwar V, ... Zwischenberger B, Higgins R
Background
The impact of utilization of intraoperative transesophageal echocardiography (TEE) at the time of isolated coronary artery bypass grafting (CABG) on clinical decision making and associated outcomes is not well understood.
Objectives
The purpose of this study was to determine the association of TEE with post-CABG mortality and changes to the operative plan.
Methods
A retrospective cohort study of planned isolated CABG patients from the Society of Thoracic Surgeons Adult Cardiac Surgery Database between January 1, 2011, and June 30, 2019, was performed. The exposure variable of interest was use of intraoperative TEE during CABG compared with no TEE. The primary outcome was operative mortality. The association of TEE with unplanned valve surgery was also assessed.
Results
Of 1,255,860 planned isolated CABG procedures across 1218 centers, 676,803 (53.9%) had intraoperative TEE. The percentage of patients receiving intraoperative TEE increased over time from 39.9% in 2011 to 62.1% in 2019 (p trend <0.0001). CABG patients undergoing intraoperative TEE had lower odds of mortality (adjusted odds ratio: 0.95; 95% confidence interval: 0.91 to 0.99; p = 0.025), with heterogeneity across STS risk groups (p interaction = 0.015). TEE was associated with increased odds of unplanned valve procedure in lieu of planned isolated CABG (adjusted odds ratio: 4.98; 95% confidence interval: 3.98 to 6.22; p < 0.0001).
Conclusions
Intraoperative TEE usage during planned isolated CABG is associated with lower operative mortality, particularly in higher-risk patients, as well as greater odds of unplanned valve procedure. These findings support usage of TEE to improve outcomes for isolated CABG for high-risk patients.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2021; 78:112-122
Metkus TS, Thibault D, Grant MC, Badhwar V, ... Zwischenberger B, Higgins R
J Am Coll Cardiol: 12 Jul 2021; 78:112-122 | PMID: 33957241
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes.

Filippatos G, Bakris GL, Pitt B, Agarwal R, ... Anker SD, FIDELIO-DKD Investigators
Background
Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models.
Objectives
This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study.
Methods
Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF.
Results
Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively).
Conclusions
In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2021; 78:142-152
Filippatos G, Bakris GL, Pitt B, Agarwal R, ... Anker SD, FIDELIO-DKD Investigators
J Am Coll Cardiol: 12 Jul 2021; 78:142-152 | PMID: 34015478
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF.

Teerlink JR, Diaz R, Felker GM, McMurray JJV, ... Malik FI, GALACTIC-HF Investigators
Background
In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).
Objectives
The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.
Methods
Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.
Results
The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.
Conclusions
In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug\'s mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).

Published by Elsevier Inc.

J Am Coll Cardiol: 12 Jul 2021; 78:97-108
Teerlink JR, Diaz R, Felker GM, McMurray JJV, ... Malik FI, GALACTIC-HF Investigators
J Am Coll Cardiol: 12 Jul 2021; 78:97-108 | PMID: 34015475
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Improving Terminology to Describe Coronary Artery Procedures: JACC Review Topic of the Week.

Doenst T, Bonow RO, Bhatt DL, Falk V, Gaudino M
Coronary artery disease (CAD) is treated with medical therapy with or without percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The latter 2 options are commonly referred to as \"myocardial revascularization\" procedures. We reason that this term is inappropriate because it is suggestive of a single treatment effect of PCI and CABG (ie, the reestablishment of blood flow to ischemic myocardium) and obscures key mechanisms, such as the improvement in coronary flow capability in the absence of ongoing ischemia, the reperfusion in the presence of ischemia, and the prevention of myocardial infarction from CAD progression. We review the current evidence on the topic and suggest the use of a purely descriptive terminology (\"invasive treatment by PCI or CABG\") which has the potential to improve clinical decision making and guide future trial design.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2021; 78:180-188
Doenst T, Bonow RO, Bhatt DL, Falk V, Gaudino M
J Am Coll Cardiol: 12 Jul 2021; 78:180-188 | PMID: 34238439
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Progression of Early Subclinical Atherosclerosis (PESA) Study: JACC Focus Seminar 7/8.

Ibanez B, Fernández-Ortiz A, Fernández-Friera L, García-Lunar I, Andrés V, Fuster V
Atherosclerosis starts early in life and progresses silently for decades. Considering atherosclerosis as a \"systemic disease\" invites the use of noninvasive methodologies to detect disease in various regions before symptoms appear. The PESA-(Progression of Early Subclinical Atherosclerosis) CNIC-SANTANDER study is an ongoing prospective cohort study examining imaging, biological, and behavioral parameters associated with the presence and progression of early subclinical atherosclerosis. Between 2010 and 2014, PESA enrolled 4,184 asymptomatic middle-aged participants who undergo serial 3-yearly follow-up examinations including clinical interviews, lifestyle questionnaires, sampling, and noninvasive imaging assessment of multiterritorial subclinical atherosclerosis (carotids, iliofemorals, aorta, and coronaries). PESA tracks the trajectories of atherosclerosis and associated disorders from early stages to the transition to symptomatic phases. A joint venture between the CNIC and the Santander Bank, PESA is expected to run until at least 2029, and its significant contributions to date are presented in this review paper.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 12 Jul 2021; 78:156-179
Ibanez B, Fernández-Ortiz A, Fernández-Friera L, García-Lunar I, Andrés V, Fuster V
J Am Coll Cardiol: 12 Jul 2021; 78:156-179 | PMID: 34238438
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ablation Versus Drug Therapy for Atrial Fibrillation in Racial and Ethnic Minorities.

Thomas KL, Al-Khalidi HR, Silverstein AP, Monahan KH, ... Packer DL, CABANA Investigators
Background
Rhythm control strategies for atrial fibrillation (AF), including catheter ablation, are substantially underused in racial/ethnic minorities in North America.
Objectives
This study sought to describe outcomes in the CABANA trial as a function of race/ethnicity.
Methods
CABANA randomized 2,204 symptomatic participants with AF to ablation or drug therapy including rate and/or rhythm control drugs. Only participants in North America were included in the present analysis, and participants were subgrouped as racial/ethnic minority or nonminority with the use of National Institutes of Health definitions. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.
Results
Of 1,280 participants enrolled in CABANA in North America, 127 (9.9%) were racial and ethnic minorities. Compared with nonminorities, racial and ethnic minorities were younger with median age 65.6 versus 68.5 years, respectively, and had more symptomatic heart failure (37.0% vs 22.0%), hypertension (92.1% vs 76.8%, respectively), and ejection fraction <40% (20.8% vs 7.1%). Racial/ethnic minorities treated with ablation had a 68% relative reduction in the primary endpoint (adjusted hazard ratio [aHR]: 0.32; 95% confidence interval [CI]: 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR: 0.28; 95% CI: 0.10-0.79). Primary event rates in racial/ethnic minority and nonminority participants were similar in the ablation arm (4-year Kaplan-Meier event rates 12.3% vs 9.9%); however, racial and ethnic minorities randomized to drug therapy had a much higher event rate than nonminority participants (27.4% vs. 9.4%).
Conclusion
Among racial or ethnic minorities enrolled in the North American CABANA cohort, catheter ablation significantly improved major clinical outcomes compared with drug therapy. These benefits, which were not seen in nonminority participants, appear to be due to worse outcomes with drug therapy. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 12 Jul 2021; 78:126-138
Thomas KL, Al-Khalidi HR, Silverstein AP, Monahan KH, ... Packer DL, CABANA Investigators
J Am Coll Cardiol: 12 Jul 2021; 78:126-138 | PMID: 34238436
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

De-Escalation of Dual Antiplatelet Therapy in Patients With Acute Coronary Syndromes.

Shoji S, Kuno T, Fujisaki T, Takagi H, ... Latib A, Kohsaka S
Background
Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent P2Y12 inhibitors has become a cornerstone of acute coronary syndrome (ACS) management. Recent randomized controlled trials (RCTs) have investigated DAPT de-escalation to decrease the risk of bleeding outcomes.
Objectives
The aim of this study was to compare the efficacy and safety outcomes of various DAPT strategies in patients with ACS, including de-escalation from a potent P2Y12 inhibitor to clopidogrel or low-dose prasugrel.
Methods
MEDLINE and EMBASE were searched through January 2021 for RCTs investigating the efficacy and safety of DAPT in patients with ACS, and a network meta-analysis was conducted. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, and stroke. The primary bleeding outcome was trial-defined major or minor bleeding.
Results
Our search identified 15 eligible RCTs, including 55,798 patients with ACS. De-escalation therapy was associated with reduced risk of primary bleeding outcomes (HR: 0.48 [95% CI: 0.30-0.77] vs clopidogrel; HR: 0.32 [95% CI: 0.20-0.52] vs ticagrelor; HR: 0.36 [95% CI: 0.24-0.55] vs standard-dose prasugrel; and HR: 0.40 [95% CI: 0.22-0.75] vs low-dose prasugrel) without negatively affecting primary efficacy outcomes. There were no significant differences in ischemic or bleeding outcomes between de-escalation to clopidogrel or low-dose prasugrel.
Conclusions
Compared with other established uses of DAPT, de-escalation was the most effective strategy for ACS treatment, resulting in fewer bleeding events without increasing ischemic events.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 08 Jul 2021; epub ahead of print
Shoji S, Kuno T, Fujisaki T, Takagi H, ... Latib A, Kohsaka S
J Am Coll Cardiol: 08 Jul 2021; epub ahead of print | PMID: 34275697
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mitral Surgery After Transcatheter Edge-to-Edge Repair: Society of Thoracic Surgeons Database Analysis.

Chikwe J, O\'Gara P, Fremes S, Sundt TM, ... Mack M, Adams DH
Background
Transcatheter edge-to-edge (TEER) mitral repair may be complicated by residual or recurrent mitral regurgitation. An increasing need for surgical reintervention has been reported, but operative outcomes are ill defined.
Objectives
This study evaluated national outcomes of mitral surgery after TEER.
Methods
The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database was used to identify 524 adults who underwent mitral surgery after TEER between July 2014 and June 2020. Emergencies (5.0%; n = 26), previous mitral surgery (5.3%; n = 28), or open implantation of transcatheter prostheses (1.5%; n = 8) were excluded. The primary outcome was 30-day or in-hospital mortality.
Results
In the study cohort of 463 patients, the median age was 76 years (interquartile range [IQR]: 67 to 81 years), median left ventricular ejection fraction was 57% (IQR: 48% to 62%), and 177 (38.2%) patients had degenerative disease. Major concomitant cardiac surgery was performed in 137 (29.4%) patients: in patients undergoing isolated mitral surgery, the median STS-predicted mortality was 6.5% (IQR: 3.9% to 10.5%), the observed mortality was 10.2% (n = 23 of 225), and the ratio of observed to expected mortality was 1.2 (95% confidence interval [CI]: 0.8 to 1.9). Predictors of mortality included urgent surgery (odds ratio [OR]: 2.4; 95% CI: 1.3 to 4.6), nondegenerative/unknown etiology (OR: 2.2; 95% CI: 1.1 to 4.5), creatinine of >2.0 mg/dl (OR: 3.8; 95% CI: 1.9 to 7.9) and age of >80 years (OR: 2.1; 95% CI: 1.1 to 4.4). In a volume outcomes analysis in an expanded cohort of 591 patients at 227 hospitals, operative mortality was 2.6% (n = 2 of 76) in 4 centers that performed >10 cases versus 12.4% (n = 64 of 515) in centers performing fewer (p = 0.01). The surgical repair rate after failed TEER was 4.8% (n = 22) and was 6.8% (n = 12) in degenerative disease.
Conclusions
This study indicates that mitral repair is infrequently achieved after failed TEER, which may have implications for treatment choice in lower-risk and younger patients with degenerative disease. These findings should inform patient consent for TEER, clinical trial design, and clinical performance measures.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 05 Jul 2021; 78:1-9
Chikwe J, O'Gara P, Fremes S, Sundt TM, ... Mack M, Adams DH
J Am Coll Cardiol: 05 Jul 2021; 78:1-9 | PMID: 33945832
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lymphatic Dysregulation in Patients With Heart Failure: JACC Review Topic of the Week.

Fudim M, Salah HM, Sathananthan J, Bernier M, ... Virani SA, Patel MR
The lymphatic system is an integral part of the circulatory system and plays an important role in the volume homeostasis of the human body. The complex anatomy and physiology paired with a lack of simple diagnostic tools to study the lymphatic system have led to an underappreciation of the contribution of the lymphatic system to acute and chronic heart failure (HF). Herein, we discuss the physiological role of the lymphatic system in volume management and the evidence demonstrating the dysregulation of the lymphatic system in HF. Further, we discuss the opportunity to target the lymphatic system in the management of HF and different potential approaches to accessing the lymphatic system.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2021; 78:66-76
Fudim M, Salah HM, Sathananthan J, Bernier M, ... Virani SA, Patel MR
J Am Coll Cardiol: 05 Jul 2021; 78:66-76 | PMID: 34210416
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

United Kingdom Biobank (UK Biobank): JACC Focus Seminar 6/8.

Caleyachetty R, Littlejohns T, Lacey B, Bešević J, ... Collins R, Allen N
An increasing number of people are now living with cardiovascular disease (CVD), with concomitant CVD-related hospitalizations, operations, and prescriptions. To ultimately deliver optimal cardiovascular care, access to population-based biobanks with data on multiomics, phenotypes, and lifestyle risk factors are crucial. UK Biobank is a cohort study that incorporated data between 2006 and 2010 from over half a million individuals (40 to 69 years of age) at recruitment from across the United Kingdom. As one of the most accessible, largest, and in-depth cohort studies in the world, UK Biobank continues to enhance the resource with the addition of data from various omics platforms (eg, genomics, metabolomics, proteomics), multimodal imaging, self-reported risk factors and health outcomes, and linkage to electronic health records. The vision of UK Biobank is to allow as many researchers as possible to apply their expertise and imagination to undertake research to prevent, diagnose, and treat a wide range of chronic conditions, including CVD.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 05 Jul 2021; 78:56-65
Caleyachetty R, Littlejohns T, Lacey B, Bešević J, ... Collins R, Allen N
J Am Coll Cardiol: 05 Jul 2021; 78:56-65 | PMID: 34210415
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure.

Yu B, Roberts MB, Raffield LM, Zekavat SM, ... Lung, and Blood Institute TOPMed Consortium
Background
Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF).
Objectives
This study sought to evaluate whether CHIP is associated with incident HF.
Methods
CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses.
Results
Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction.
Conclusions
CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2021; 78:42-52
Yu B, Roberts MB, Raffield LM, Zekavat SM, ... Lung, and Blood Institute TOPMed Consortium
J Am Coll Cardiol: 05 Jul 2021; 78:42-52 | PMID: 34210413
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Optimal Medical Therapy on 10-Year Mortality After Coronary Revascularization.

Kawashima H, Serruys PW, Ono M, Hara H, ... Onuma Y, SYNTAX Extended Survival Investigators
Background
The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial.
Objectives
The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG.
Methods
This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality.
Results
In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without.
Conclusions
In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2021; 78:27-38
Kawashima H, Serruys PW, Ono M, Hara H, ... Onuma Y, SYNTAX Extended Survival Investigators
J Am Coll Cardiol: 05 Jul 2021; 78:27-38 | PMID: 34210411
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mortality Benefit of Rivaroxaban Plus Aspirin in Patients With Chronic Coronary or Peripheral Artery Disease.

Eikelboom JW, Bhatt DL, Fox KAA, Bosch J, ... Shestakovska O, Yusuf S
Background
The combination of 2.5 mg rivaroxaban twice daily and 100 mg aspirin once daily compared with 100 mg aspirin once daily reduces major adverse cardiovascular (CV) events in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD).
Objectives
The aim of this work was to report the effects of the combination on overall and cause-specific mortality.
Methods
The COMPASS trial enrolled 27,395 patients of whom 18,278 were randomized to the combination (n = 9,152) or aspirin alone (n = 9,126). Deaths were adjudicated by a committee blinded to treatment allocation. Previously identified high-risk baseline features were polyvascular disease, chronic kidney disease, mild or moderate heart failure, and diabetes.
Results
During a median of 23 months of follow-up (maximum 47 months), 313 patients (3.4%) allocated to the combination and 378 patients (4.1%) allocated to aspirin alone died (hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.71-0.96; P = 0.01). Compared with aspirin, the combination reduced CV death (160 [1.7%] vs 203 [2.2%]; HR: 0.78; 95% CI: 0.64-0.96; P = 0.02) but not non-CV death. There were fewer deaths following MI, stroke, and CV procedures, as well as fewer sudden cardiac, other, and unknown causes of CV deaths and coronary heart disease deaths. Patients with 0, 1, 2, and 3 or 4 high-risk features at baseline had 4.2, 4.8, 25.0, and 53.9 fewer deaths, respectively, per 1000 patients treated for 30 months.
Conclusions
The combination of rivaroxaban and aspirin compared with aspirin reduced overall and CV mortality with consistent reductions in cause specific CV mortality in patients with chronic CAD or PAD. The absolute mortality benefits are greater with increasing baseline risk. (Cardiovascular Outcomes for People Using Anticoagulant Strategies [COMPASS]; NCT01776424).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 05 Jul 2021; 78:14-23
Eikelboom JW, Bhatt DL, Fox KAA, Bosch J, ... Shestakovska O, Yusuf S
J Am Coll Cardiol: 05 Jul 2021; 78:14-23 | PMID: 34210409
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Classification of Heart Failure According to Ejection Fraction: JACC Review Topic of the Week.

Lam CSP, Solomon SD
The recent U.S. Food and Drug Administration expanded indication for sacubitril/valsartan introduces a new potential taxonomy for heart failure, with no reference to \"preserved\" ejection fraction but referring to \"below normal\" ejection fraction as those most likely to benefit. This review summarizes the evolution of nomenclature in heart failure and examines evidence showing that patients with ejection fraction in the \"mid range\" may benefit from neurohormonal blockade similar to those with more severely reduced (<40%) ejection fraction. Furthermore, prominent sex differences have been observed wherein the benefit of neurohormonal blockade appears to extend to a higher ejection fraction range in women compared to men. Based on emerging evidence, revised nomenclature is proposed defining heart failure with \"reduced\" (<40%), \"mildly reduced,\" and \"normal\" (≥55% in men, ≥60% in women) ejection fraction. Such nomenclature signals consideration of potentially beneficial therapies in the largest group of patients with reduced or mildly reduced ejection fraction.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2021; 77:3217-3225
Lam CSP, Solomon SD
J Am Coll Cardiol: 28 Jun 2021; 77:3217-3225 | PMID: 34167646
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Multi-Ethnic Study of Atherosclerosis (MESA): JACC Focus Seminar 5/8.

Blaha MJ, DeFilippis AP
The MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute-sponsored prospective study aimed at studying the prevalence, progression, determinants, and prognostic significance of subclinical cardiovascular disease in a sex-balanced, multiethnic, community-dwelling U.S. cohort. MESA helped usher in an era of noninvasive evaluation of subclinical atherosclerosis presence, burden, and progression for the evaluation of atherosclerotic cardiovascular disease risk, beyond what could be predicted by traditional risk factors alone. Concepts developed in MESA have informed international patient care guidelines, providing new tools to effectively guide public health policy, population screening, and clinical decision-making. MESA is grounded in an open science model that continues to be a beacon for collaborative science. In this review, we detail the original goals of MESA, and describe how the scope of MESA has evolved over time. We highlight 10 significant MESA contributions to cardiovascular medicine, and chart the path forward for MESA in the year 2021 and beyond.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2021; 77:3195-3216
Blaha MJ, DeFilippis AP
J Am Coll Cardiol: 28 Jun 2021; 77:3195-3216 | PMID: 34167645
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Automated Prediction of Cardiorespiratory Deterioration in Patients With Single Ventricle.

Rusin CG, Acosta SI, Vu EL, Ahmed M, Brady KM, Penny DJ
Background
Patients with single-ventricle physiology have a significant risk of cardiorespiratory deterioration between their first and second stage palliation surgeries.
Objectives
The objective of this study is to develop and validate a real-time computer algorithm that can automatically recognize physiological precursors of cardiorespiratory deterioration in children with single-ventricle physiology during their interstage hospitalization.
Methods
A retrospective study was conducted from prospectively collected physiological data of subjects with single-ventricle physiology. Deterioration events were defined as a cardiac arrest requiring cardiopulmonary resuscitation or an unplanned intubation. Physiological metrics were derived from the electrocardiogram (heart rate, heart rate variability, ST-segment elevation, and ST-segment variability) and the photoplethysmogram (peripheral oxygen saturation and pleth variability index). A logistic regression model was trained to separate the physiological dynamics of the pre-deterioration phase from all other data generated by study subjects. Data were split 50/50 into model training and validation sets to enable independent model validation.
Results
Our cohort consisted of 238 subjects admitted to the cardiac intensive care unit and stepdown units of Texas Children\'s Hospital over a period of 6 years. Approximately 300,000 h of high-resolution physiological waveform and vital sign data were collected using the Sickbay software platform (Medical Informatics Corp., Houston, Texas). A total of 112 cardiorespiratory deterioration events were observed. Seventy-two of the subjects experienced at least 1 deterioration event. The risk index metric generated by our optimized algorithm was found to be both sensitive and specific for detecting impending events 1 to 2 h in advance of overt extremis (receiver-operating characteristic curve area: 0.958; 95% confidence interval: 0.950 to 0.965).
Conclusions
Our algorithm can provide 1 to 2 h of advanced warning for 62% of all cardiorespiratory deterioration events in children with single-ventricle physiology during their interstage period, with only 1 alarm being generated at the bedside per patient per day.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2021; 77:3184-3192
Rusin CG, Acosta SI, Vu EL, Ahmed M, Brady KM, Penny DJ
J Am Coll Cardiol: 28 Jun 2021; 77:3184-3192 | PMID: 34167643
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Downstream Cascades of Care Following High-Sensitivity Troponin Test Implementation.

Ganguli I, Cui J, Thakore N, Orav EJ, ... Sequist TD, Wasfy JH
Background
Patients with chest pain are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value.
Objectives
This study sought to determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events.
Methods
Using electronic health record and billing data, this study examined patient-visits to 5 emergency departments from April 1, 2017, to April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n = 7,564) to patient-visits for other symptoms (n = 100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services.
Results
Following hs-cTn implementation, patients with chest pain had a 2.8% (95% confidence interval [CI]: 0.72% to 4.9%) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%; 95% CI: 9.0% to 12.0%) and electrocardiograms (7.1 per 100 patient-visits; 95% CI: 1.8 to 12.4). However, they received net fewer computed tomography scans (-1.5 per 100 patient-visits; 95% CI: -1.8 to -1.1), stress tests (-5.9 per 100 patient-visits; 95% CI: -6.5 to -5.3), and percutaneous coronary intervention (PCI) (-0.65 per 100 patient-visits; 95% CI: -1.01 to -0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (-3.5%; 95% CI: -4.5% to 2.6%), or be hospitalized (-5.8%; 95% CI: -7.7% to -3.8%). Patients with chest pain had lower net mean length of stay (-0.24 days; 95% CI: -0.32 to -0.16) but no net change in spending.
Conclusions
Hs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, PCI, cardiology evaluations, and hospital admissions in patients with chest pain relative to patients with other symptoms.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2021; 77:3171-3179
Ganguli I, Cui J, Thakore N, Orav EJ, ... Sequist TD, Wasfy JH
J Am Coll Cardiol: 28 Jun 2021; 77:3171-3179 | PMID: 34167642
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical Impact of High-Sensitivity Cardiac Troponin T Implementation in the Community.

Ola O, Akula A, De Michieli L, Dworak M, ... Jaffe AS, Sandoval Y
Background
Limited U.S. data exist regarding high-sensitivity cardiac troponin (cTn) implementation.
Objectives
This study sought to evaluate the impact of high-sensitivity cardiac troponin T (cTnT) implementation.
Methods
Observational U.S. cohort study of emergency department (ED) patients undergoing measurement of cTnT during the transition from 4th (pre-implementation March 12, 2018, to September 11, 2018) to 5th generation (Gen) cTnT (post-implementation September 12, 2018, to March 11, 2019). Diagnoses were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Resources evaluated included length of stay, hospitalizations, and cardiac testing.
Results
In this study, 3,536 unique patients were evaluated, including 2,069 and 2,491 ED encounters pre- and post-implementation. Compared with 4th Gen cTnT, encounters with ≥1 cTnT >99th percentile increased using 5th Gen cTnT (15% vs. 47%; p < 0.0001). Acute MI (3.3% vs. 8.1%; p < 0.0001) and myocardial injury (11% vs. 38%; p < 0.0001) increased. Although type 1 MIs increased (1.7% vs. 2.9%; p = 0.0097), the overall MI increase was largely due to more type 2 MIs (1.6% vs. 5.2%; p < 0.0001). Women were less likely than men to have MI using 4th Gen cTnT (2.3% vs. 4.4%; p = 0.008) but not 5th Gen cTnT (7.7% vs. 8.5%; p = 0.46). Overall length of stay and stress testing were reduced, and angiography was increased (all p < 0.05). Among those without cTnT increases, there were more ED discharges and a reduction in length of stay, echocardiography, and stress tests (all p < 0.05).
Conclusions
High-sensitivity cTnT implementation resulted in a marked increase in myocardial injury and MI, particularly in women and patients with type 2 MI. Despite this, except for angiography, overall resource use did not increase. Among those without cTnT increases, there were more ED discharges and fewer cardiac tests.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2021; 77:3160-3170
Ola O, Akula A, De Michieli L, Dworak M, ... Jaffe AS, Sandoval Y
J Am Coll Cardiol: 28 Jun 2021; 77:3160-3170 | PMID: 34167641
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults.

Zhou Z, Ryan J, Ernst ME, Zoungas S, ... Nelson MR, ASPREE Investigator Group
Background
The neurocognitive effect of statins in older adults remain uncertain.
Objectives
The aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults.
Methods
This analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer\'s disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer\'s disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified.
Results
Statin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02).
Conclusions
In adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 28 Jun 2021; 77:3145-3156
Zhou Z, Ryan J, Ernst ME, Zoungas S, ... Nelson MR, ASPREE Investigator Group
J Am Coll Cardiol: 28 Jun 2021; 77:3145-3156 | PMID: 34167639
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Current Status and Future Prospects of Transcatheter Mitral Valve Replacement: JACC State-of-the-Art Review.

Alperi A, Granada JF, Bernier M, Dagenais F, Rodés-Cabau J
Mitral regurgitation (MR) is the most prevalent valvular heart disease and, when left untreated, it confers a poorer prognosis. Catheter-based repair therapies face some limitations like their applicability on challenging anatomies and the potential recurrence of significant MR over time. Transcatheter mitral valve replacement (TMVR) has emerged as a less invasive approach potentially overcoming some of the current limitations associated with transcatheter mitral valve repair. Several devices are under clinical investigation, and a growing number of systems allow for a fully percutaneous transfemoral approach. In this review, the authors aimed to delineate the main challenges faced by the TMVR field, to highlight the key aspects for procedural planning, and to describe the clinical results of the TMVR systems under clinical investigation. Finally, they also discuss what the future perspectives are for this emerging field.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2021; 77:3058-3078
Alperi A, Granada JF, Bernier M, Dagenais F, Rodés-Cabau J
J Am Coll Cardiol: 21 Jun 2021; 77:3058-3078 | PMID: 34140110
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8.

Graham IM, Di Angelantonio E, Visseren F, De Bacquer D, ... Cooney MT, European Society of Cardiology Cardiovascular Risk Collaboration
Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology\'s (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC\'s Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2021; 77:3046-3057
Graham IM, Di Angelantonio E, Visseren F, De Bacquer D, ... Cooney MT, European Society of Cardiology Cardiovascular Risk Collaboration
J Am Coll Cardiol: 21 Jun 2021; 77:3046-3057 | PMID: 34140109
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Triglycerides and Residual Atherosclerotic Risk.

Raposeiras-Roubin S, Rosselló X, Oliva B, Fernández-Friera L, ... Ibáñez B, Fuster V
Background
Even when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.
Objectives
This study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.
Methods
An observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.
Results
Atherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).
Conclusions
In individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2021; 77:3031-3041
Raposeiras-Roubin S, Rosselló X, Oliva B, Fernández-Friera L, ... Ibáñez B, Fuster V
J Am Coll Cardiol: 21 Jun 2021; 77:3031-3041 | PMID: 34140107
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effectiveness of Blood Lipid Management in Patients With Peripheral Artery Disease.

Hess CN, Cannon CP, Beckman JA, Goodney PP, ... Shannon E, Bonaca MP
Background
Low-density lipoprotein cholesterol (LDL-C) is associated with heightened risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in peripheral artery disease (PAD). Lipid-lowering therapies (LLT) that reduce LDL-C decrease this risk.
Objectives
The authors examined LLT use and actual achieved LDL-C in PAD.
Methods
PAD patients in MarketScan from 2014 to 2018 were identified. Outcomes included LLT use, defined as high-intensity (HI) (high-intensity statin, statin plus ezetimibe, or PCSK9 inhibitor), low-intensity (any other lipid regimen), or no therapy, and follow-up LDL-C. Factors associated with LDL-C <70 mg/dl were identified with multivariable logistic regression.
Results
Among 250,103 PAD patients, 20.5% and 39.5% were treated at baseline with HI and low-intensity LLT, respectively; 40.0% were on no LLT. Over a 15-month median follow-up period, HI LLT use increased by 1.5%. Among 18,747 patients with LDL-C data, at baseline, 25.1% were on HI LLT, median LDL-C was 91 mg/dl, and 24.5% had LDL-C <70 mg/dl. Within the HI LLT subgroup, median LDL-C was 81 mg/dl, and 64% had LDL-C ≥70 mg/dl. At follow-up, HI LLT use increased by 3.7%, median LDL-C decreased by 4.0 mg/dl, and an additional 4.1% of patients had LDL-C <70 mg/dl. HI LLT use was greater after follow-up MACE (55.0%) or MALE (41.0%) versus no ischemic event (26.1%). After MACE or MALE, LDL-C was <70 mg/dl in 41.5% and 36.1% of patients, respectively, versus 27.1% in those without an event. Factors associated with follow-up LDL-C <70 mg/dl included smoking, hypertension, diabetes, prior lower extremity revascularization, and prior myocardial infarction but not prior acute or critical limb ischemia.
Conclusions
In PAD, LLT use is suboptimal, LDL-C remains elevated, and LLT intensity is a poor surrogate for achieved LDL-C. Less aggressive lipid management was observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies in PAD.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2021; 77:3016-3027
Hess CN, Cannon CP, Beckman JA, Goodney PP, ... Shannon E, Bonaca MP
J Am Coll Cardiol: 21 Jun 2021; 77:3016-3027 | PMID: 34140105
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Aortic Branch Aneurysms and Vascular Risk in Patients With Marfan Syndrome.

Lopez-Sainz A, Mila L, Rodriguez-Palomares J, Limeres J, ... Evangelista A, Teixido-Tura G
Background
Aortic branch aneurysms are not included in the diagnostic criteria for Marfan syndrome (MFS); however, their prevalence and eventual prognostic significance are unknown.
Objectives
The goal of this study was to assess the prevalence of aortic branch aneurysms in MFS and their relationship with aortic prognosis.
Methods
MFS patients with a pathogenic FBN1 genetic variant and at least one magnetic resonance or computed tomography angiography study assessing aortic branches were included. Aortic events and those related to aneurysm complications were recorded during follow-up.
Results
A total of 104 aneurysms were detected in 50 (26.7%) of the 187 patients with MFS (mean age 37.9 ± 14.4 years; 54% male) included in this study, with the iliac artery being the most common location (45 aneurysms). Thirty-one patients (62%) had >1 peripheral aneurysm, and surgery was performed in 5 (4.8%). Patients with aneurysms were older (41.9 ± 12.7 years vs. 36.7 ± 14.8 years; p = 0.040) and had more dilated aortic root (42.2 ± 6.4 mm vs. 38.8 ± 8.0 mm; p = 0.044) and dyslipidemia (31.0% vs. 9.7%; p = 0.001). In a subgroup of 95 patients with no previous aortic surgery or dissection followed up for 3.3 ± 2.6 years, the presence of arterial aneurysms was associated with a greater need for aortic surgery (hazard ratio: 3.4; 95% confidence interval: 1.1 to 10.3; p = 0.028) in a multivariable Cox analysis adjusted for age and aortic diameter.
Conclusions
Aortic branch aneurysms are present in one-quarter of patients with MFS and are related to age and aortic dilation, and they independently predict the need for aortic surgery. The systematic use of whole-body vascular assessment is recommended to identify other sites of vascular involvement at risk for complications and to define the subgroup of patients with more aggressive aortic disease.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 21 Jun 2021; 77:3005-3012
Lopez-Sainz A, Mila L, Rodriguez-Palomares J, Limeres J, ... Evangelista A, Teixido-Tura G
J Am Coll Cardiol: 21 Jun 2021; 77:3005-3012 | PMID: 34140103
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Meta-Analysis of Reversal Agents for Severe Bleeding Associated With Direct Oral Anticoagulants.

Gómez-Outes A, Alcubilla P, Calvo-Rojas G, Terleira-Fernández AI, ... Lecumberri R, Vargas-Castrillón E
Background
Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding.
Objectives
The aim of this study was to investigate clinical outcomes associated with the use of 4-factor prothrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding.
Methods
The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model.
Results
The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used.
Conclusions
The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 21 Jun 2021; 77:2987-3001
Gómez-Outes A, Alcubilla P, Calvo-Rojas G, Terleira-Fernández AI, ... Lecumberri R, Vargas-Castrillón E
J Am Coll Cardiol: 21 Jun 2021; 77:2987-3001 | PMID: 34140101
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation.

Mahfoud F, Townsend RR, Kandzari DE, Kario K, ... Böhm M, Weber MA
Background
The renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.
Objectives
The purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.
Methods
Analyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.
Results
Baseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (-0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (-1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.
Conclusions
Plasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2021; 77:2909-2919
Mahfoud F, Townsend RR, Kandzari DE, Kario K, ... Böhm M, Weber MA
J Am Coll Cardiol: 14 Jun 2021; 77:2909-2919 | PMID: 33957242
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ending Gender Inequality in Cardiovascular Clinical Trial Leadership: JACC Review Topic of the Week.

Van Spall HGC, Lala A, Deering TF, Casadei B, ... Bozkurt B, Global CardioVascular Clinical Trialists (CVCT) Forum and Women As One Scientific Expert Panel
Women are under-represented as leaders of cardiovascular randomized controlled trials, representing 1 in 10 lead authors of cardiovascular trials published in high-impact journals. Although the proportion of cardiovascular specialists who are women has increased in recent years, the proportion of cardiovascular clinical trialists who are women has not. This gap, underpinned by systemic sexism, has not been adequately addressed. The benefits of diverse randomized controlled trial leadership extend to patients and professionals. In this position statement, we present strategies adopted by some organizations to end gender inequality in research leadership. We offer an actionable roadmap for early-career researchers, scientists, academic institutions, professional societies, trial sponsors, and journals to follow, with the goal of harnessing the strength of women and under-represented groups as research leaders and facilitating a just culture in the cardiovascular clinical trial enterprise.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2021; 77:2960-2972
Van Spall HGC, Lala A, Deering TF, Casadei B, ... Bozkurt B, Global CardioVascular Clinical Trialists (CVCT) Forum and Women As One Scientific Expert Panel
J Am Coll Cardiol: 14 Jun 2021; 77:2960-2972 | PMID: 34112322
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3/8.

Wright JD, Folsom AR, Coresh J, Sharrett AR, ... Rosamond WD, Heiss G
ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health.

Published by Elsevier Inc.

J Am Coll Cardiol: 14 Jun 2021; 77:2939-2959
Wright JD, Folsom AR, Coresh J, Sharrett AR, ... Rosamond WD, Heiss G
J Am Coll Cardiol: 14 Jun 2021; 77:2939-2959 | PMID: 34112321
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction.

Hinkel R, Batkai S, Bähr A, Bozoglu T, ... Thum T, Kupatt C
Background
Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure.
Objectives
This study aimed to establish a novel porcine model of pressure-overload-induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model.
Methods
This study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28.
Results
At d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm2 in untreated hypertrophic hearts) and improved global cardiac function (ejection fraction 48.9 ± 1.0% vs. 36.1 ± 1.7% in control hearts). Moreover, at d56 antimiR-132-treated hearts displayed less increase of interstitial fibrosis compared with sham-operated hearts (Δsham 1.8 ± 0.5%) than control hearts (Δsham 10.8 ± 0.6%). Of note, cardiac platelet and endothelial cell adhesion molecule 1+ capillary density was higher in the antimiR-132-treated hearts (647 ± 20 cells/mm2) compared with in the control group (485 ± 23 cells/mm2).
Conclusions
The inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2021; 77:2923-2935
Hinkel R, Batkai S, Bähr A, Bozoglu T, ... Thum T, Kupatt C
J Am Coll Cardiol: 14 Jun 2021; 77:2923-2935 | PMID: 34112319
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Improved Risk Stratification for Ventricular Arrhythmias and Sudden Death in Patients With Nonischemic Dilated Cardiomyopathy.

Di Marco A, Brown PF, Bradley J, Nucifora G, ... Miller CA, Schmitt M
Background
Risk stratification for ventricular arrhythmias (VA) and sudden death in nonischemic dilated cardiomyopathy (DCM) remains suboptimal.
Objectives
The goal of this study was to provide an improved risk stratification algorithm for VA and sudden death in DCM.
Methods
This was a retrospective cohort study of consecutive patients with DCM who underwent cardiac magnetic resonance with late gadolinium enhancement (LGE) at 2 tertiary referral centers. The combined arrhythmic endpoint included appropriate implantable cardioverter-defibrillator therapies, sustained ventricular tachycardia, resuscitated cardiac arrest, and sudden death.
Results
In 1,165 patients with a median follow-up of 36 months, LGE was an independent and strong predictor of the arrhythmic endpoint (hazard ratio: 9.7; p < 0.001). This association was consistent across all strata of left ventricular ejection fraction (LVEF). Epicardial LGE, transmural LGE, and combined septal and free-wall LGE were all associated with heightened risk. A simple algorithm combining LGE and 3 LVEF strata (i.e., ≤20%, 21% to 35%, >35%) was significantly superior to LVEF with the 35% cutoff (Harrell\'s C statistic: 0.8 vs. 0.69; area under the curve: 0.82 vs. 0.7; p < 0.001) and reclassified the arrhythmic risk of 34% of patients with DCM. LGE-negative patients with LVEF 21% to 35% had low risk (annual event rate 0.7%), whereas those with high-risk LGE distributions and LVEF >35% had significantly higher risk (annual event rate 3%; p = 0.007).
Conclusions
In a large cohort of patients with DCM, LGE was found to be a significant, consistent, and strong predictor of VA or sudden death. Specific high-risk LGE distributions were identified. A new clinical algorithm integrating LGE and LVEF significantly improved the risk stratification for VA and sudden death, with relevant implications for implantable cardioverter-defibrillator allocation.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2021; 77:2890-2905
Di Marco A, Brown PF, Bradley J, Nucifora G, ... Miller CA, Schmitt M
J Am Coll Cardiol: 14 Jun 2021; 77:2890-2905 | PMID: 34112317
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prevalence of Left Atrial Thrombus in Anticoagulated Patients With Atrial Fibrillation.

Lurie A, Wang J, Hinnegan KJ, McIntyre WF, ... Connolly SJ, Wong JA
Background
The prevalence of left atrial (LA) thrombus in patients with atrial fibrillation (AF) or atrial flutter (AFL) on guideline-directed anticoagulation is not well known, yet this may inform transesophageal echocardiogram (TEE) use before cardioversion or catheter ablation.
Objectives
The purpose of this study was to quantify LA thrombus prevalence among patients with AF/AFL on guideline-directed anticoagulation and to identify high-risk subgroups.
Methods
EMBASE, MEDLINE, and CENTRAL were systematically searched from inception to July 2020 for studies reporting on LA thrombus prevalence among patients with AF/AFL undergoing TEE following at least 3 weeks of continuous therapeutic oral anticoagulation with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Meta-analysis was performed using random effects models.
Results
Thirty-five studies describing 14,653 patients were identified. The mean-weighted LA thrombus prevalence was 2.73% (95% confidence interval [CI]: 1.95% to 3.80%). LA thrombus prevalence was similar for VKA- and DOAC-treated patients (2.80%; 95% CI: 1.86% to 4.21% vs. 3.12%; 95% CI: 1.92% to 5.03%; p = 0.674). Patients with nonparoxysmal AF/AFL had a 4-fold higher LA thrombus prevalence compared with paroxysmal patients (4.81%; 95% CI: 3.35% to 6.86% vs. 1.03%; 95% CI: 0.52% to 2.03%; p < 0.001). LA thrombus prevalence was higher among patients undergoing cardioversion versus ablation (5.55%; 95% CI: 3.15% to 9.58% vs. 1.65%; 95% CI: 1.07% to 2.53%; p < 0.001). Patients with CHA2DS2-VASc scores ≥3 had a higher LA thrombus prevalence compared with patients with scores ≤2 (6.31%; 95% CI: 3.72% to 10.49% vs. 1.06%; 95% CI: 0.45% to 2.49%; p < 0.001).
Conclusions
LA thrombus prevalence is high in subgroups of anticoagulated patients with AF/AFL, who may benefit from routine pre-procedural TEE use before cardioversion or catheter ablation.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 14 Jun 2021; 77:2875-2886
Lurie A, Wang J, Hinnegan KJ, McIntyre WF, ... Connolly SJ, Wong JA
J Am Coll Cardiol: 14 Jun 2021; 77:2875-2886 | PMID: 34112315
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prevention of Pathological Atrial Remodeling and Atrial Fibrillation: JACC State-of-the-Art Review.

Chen YC, Voskoboinik A, Gerche A, Marwick TH, McMullen JR
Atrial enlargement in response to pathological stimuli (e.g., hypertension, mitral valve disease) and physiological stimuli (exercise, pregnancy) can be comparable in magnitude, but the diseased enlarged atria is associated with complications such as atrial fibrillation (AF), whereas physiological atrial enlargement is not. Pathological atrial enlargement and AF is also observed in a small percentage of athletes undergoing extreme/intense endurance sport and pregnant women with preeclampsia. Differences between physiological and pathological atrial enlargement and underlying mechanisms are poorly understood. This review describes human and animal studies characterizing atrial enlargement under physiological and pathological conditions and highlights key knowledge gaps and clinical challenges, including: 1) the limited ability of atria to reverse remodel; and 2) distinguishing physiological and pathological enlargement via imaging/biomarkers. Finally, this review discusses how targeting distinct molecular mechanisms underlying physiological and pathological atrial enlargement could provide new therapeutic and diagnostic strategies for preventing or reversing atrial enlargement and AF.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2021; 77:2846-2864
Chen YC, Voskoboinik A, Gerche A, Marwick TH, McMullen JR
J Am Coll Cardiol: 07 Jun 2021; 77:2846-2864 | PMID: 34082914
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Thrombolysis In Myocardial Infarction (TIMI) Study Group: JACC Focus Seminar 2/8.

Sabatine MS, Braunwald E
In 1984, the National Heart, Lung, and Blood Institute (NHLBI) decided to study the efficacy and safety of the treatment of acute myocardial infarction with an emerging therapy, coronary thrombolysis, and thus the TIMI (Thrombolysis In Myocardial Infarction) Study Group was born. Following completion of 3 clinical trials of thrombolytic therapy supported by the NHLBI, TIMI became an academic research organization headquartered at Brigham and Women\'s Hospital and subsequently branched out to study a wide range of patients, including those with stable coronary, cerebrovascular, and peripheral arterial disease; dyslipidemia; heart failure; atrial fibrillation; diabetes; and obesity. TIMI also began to study a wide range of interventions including thrombolytic, antithrombotic, lipid-modifying, anti-inflammatory, heart failure, glucose-lowering, and weight loss agents. TIMI, now in its 37th year, has completed >70 trials. This review describes the origins of the TIMI Study Group, summarizes several of its completed trials and the major lessons learned from them, and discusses ongoing trials and future directions.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2021; 77:2822-2845
Sabatine MS, Braunwald E
J Am Coll Cardiol: 07 Jun 2021; 77:2822-2845 | PMID: 34082913
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Systemic Sirolimus Therapy for Infants and Children With Pulmonary Vein Stenosis.

Patel JD, Briones M, Mandhani M, Jones S, ... Thomas A, Petit CJ
Background
Anatomic interventions for pulmonary vein stenosis (PVS) in infants and children have been met with limited success. Sirolimus, a mammalian target of rapamycin inhibitor, has demonstrated promise as a primary medical therapy for PVS, but the impact on patient survival is unknown.
Objectives
The authors sought to investigate whether mTOR inhibition with sirolimus as a primary medical therapy would improve outcomes in high-risk infants and children with PVS.
Methods
In this single-center study, patients with severe PVS were considered for systemic sirolimus therapy (SST) following a strict protocol while receiving standardized surveillance and anatomic therapies. The SST cohort was compared with a contemporary control group. The primary endpoint for this study was survival. The primary safety endpoint was adverse events (AEs) related to SST.
Results
Between 2015 and 2020, our PVS program diagnosed and treated 67 patients with ≥moderate PVS. Of these, 15 patients were treated with sirolimus, whereas the remaining patients represent the control group. There was 100% survival in the SST group compared with 45% survival in the control group (log-rank p = 0.004). A sensitivity analysis was completed to address survival bias using median time from diagnosis of PVS to SST. A survival advantage persisted (log-rank p = 0.027). Two patients on sirolimus developed treatable AEs. Patients in the SST group underwent frequent transcatheter interventions with 3.7 catheterizations per person-year (25th to 75th percentile: 2.7 to 4.4 person-years). Median follow up time was 2.2 years (25th to 75th percentile: 1.2 to 2.9 years) in the SST group versus 0.9 years (25th to 75th percentile: 0.5 to 2.7 years) in the control group.
Conclusions
The authors found a survival benefit associated with SST in infants and children with moderate-to-severe PVS. This survival benefit persisted after adjusting the analysis for survival bias. There were 2 mild AEs associated with SST during the study period; both patients were able to resume therapy without recurrence.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2021; 77:2807-2818
Patel JD, Briones M, Mandhani M, Jones S, ... Thomas A, Petit CJ
J Am Coll Cardiol: 07 Jun 2021; 77:2807-2818 | PMID: 34082911
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Moderate Aortic Stenosis in Patients With Heart Failure and Reduced Ejection Fraction.

Jean G, Van Mieghem NM, Gegenava T, van Gils L, ... Pibarot P, Clavel MA
Background
The study investigators previously reported that moderate aortic stenosis (AS) is associated with a poor prognosis in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF) (HFrEF). However, the respective contribution of moderate AS versus HFrEF to the outcomes of these patients is unknown.
Objectives
This study sought to determine the impact of moderate AS on outcomes in patients with HFrEF.
Methods
The study included 262 patients with moderate AS (aortic valve area >1.0 and <1.5 cm2; and peak aortic jet velocity >2 and <4 m/s, at rest or after dobutamine stress echocardiography) and HFrEF (LVEF <50%). These patients were matched 1:1 for sex, age, estimated glomerular filtration rate, New York Heart Association functional class III to IV, presence of diabetes, LVEF, and body mass index with patients with HFrEF but no AS (i.e., peak aortic jet velocity <2 m/s). The endpoints were all-cause mortality and the composite of death and HF hospitalization.
Results
A total of 262 patients with HFrEF and moderate AS were matched with 262 patients with HFrEF and no AS. Mean follow-up was 2.9 ± 2.2 years. In the moderate AS group, mean aortic valve area was 1.2 ± 0.2 cm2, and mean gradient was 14.5 ± 4.7 mm Hg. Moderate AS was associated with an increased risk of mortality (hazard ratio [HR]: 2.98; 95% confidence interval [CI]: 2.08 to 4.31; p < 0.0001) and of the composite of HF hospitalization and mortality (HR: 2.34; 95% CI: 1. 72 to 3.21; p < 0.0001). In the moderate AS group, aortic valve replacement (AVR) performed in 44 patients at a median follow-up time of 10.9 ± 16 months during follow-up was associated with improved survival (HR: 0.59; 95% CI: 0.35 to 0.98; p = 0.04). Notably, surgical AVR was not significantly associated with improved survival (p = 0.92), whereas transcatheter AVR was (HR: 0.43; 95% CI: 0.18 to 1.00; p = 0.05).
Conclusions
In this series of patients with HFrEF, moderate AS was associated with a marked incremental risk of mortality. AVR, and especially transcatheter AVR during follow-up, was associated with improved survival in patients with HFrEF and moderate AS. These findings provide support to the realization of a randomized trial to assess the effect of early transcatheter AVR in patients with HFrEF and moderate AS.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2021; 77:2796-2803
Jean G, Van Mieghem NM, Gegenava T, van Gils L, ... Pibarot P, Clavel MA
J Am Coll Cardiol: 07 Jun 2021; 77:2796-2803 | PMID: 34082909
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Glycated Hemoglobin and Subclinical Atherosclerosis in People Without Diabetes.

Rossello X, Raposeiras-Roubin S, Oliva B, Sánchez-Cabo F, ... Ibanez B, Fuster V
Background
The metabolic injury caused by protein glycation, monitored as the level of glycated hemoglobin (HbA1c), is not represented in most risk scores (i.e., Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease risk scale).
Objectives
The purpose of this study was to assess the association between HbA1c and the extent of subclinical atherosclerosis (SA) and to better identify individuals at higher risk of extensive SA using HbA1c on top of key cardiovascular risk factors (CVRFs).
Methods
A cohort of 3,973 middle-aged individuals from the PESA (Progression of Early Subclinical Atherosclerosis) study, with no history of cardiovascular disease and with HbA1c in the nondiabetic range, were assessed for the presence and extent of SA by 2-dimensional vascular ultrasound and noncontrast cardiac computed tomography.
Results
After adjusting for established CVRFs, HbA1c showed an association with the multiterritorial extent of SA (odds ratio: 1.05, 1.27, 1.27, 1.36, 1.80, 1.87, and 2.47 for HbA1c 4.9% to 5.0%, 5.1% to 5.2%, 5.3% to 5.4%, 5.5% to 5.6%, 5.7% to 5.8%, 5.9% to 6.0%, and 6.1% to 6.4%, respectively; reference HbA1c ≤4.8%; p < 0.001). The association was significant in all pre-diabetes groups and even below the pre-diabetes cut-off (HbA1c 5.5% to 5.6% odds ratio: 1.36 [95% confidence interval: 1.03 to 1.80]; p = 0.033). High HbA1c was associated with an increased risk of SA in low-risk individuals (p < 0.001), but not in moderate-risk individuals (p = 0.335). Relative risk estimations using Systematic Coronary Risk Estimation or atherosclerotic cardiovascular disease predictors confirmed that inclusion of HbA1c modified the risk of multiterritorial SA in most risk categories.
Conclusions
Routine use of HbA1c can identify asymptomatic individuals at higher risk of SA on top of traditional CVRFs. Lifestyle interventions and novel antidiabetic medications might be considered to reduce both HbA1c levels and SA in individuals without diabetes.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2021; 77:2777-2791
Rossello X, Raposeiras-Roubin S, Oliva B, Sánchez-Cabo F, ... Ibanez B, Fuster V
J Am Coll Cardiol: 07 Jun 2021; 77:2777-2791 | PMID: 34082907
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease.

Ono M, Serruys PW, Hara H, Kawashima H, ... Onuma Y, SYNTAX Extended Survival Investigators
Background
The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear.
Objectives
The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD).
Methods
In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models.
Results
Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; pinteraction = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; pinteraction = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: -0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients.
Conclusions
Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050) (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 07 Jun 2021; 77:2761-2773
Ono M, Serruys PW, Hara H, Kawashima H, ... Onuma Y, SYNTAX Extended Survival Investigators
J Am Coll Cardiol: 07 Jun 2021; 77:2761-2773 | PMID: 34082905
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Valve Academic Research Consortium 3: Updated Endpoint Definitions for Aortic Valve Clinical Research.

VARC-3 WRITING COMMITTEE:, Généreux P, Piazza N, Alu MC, ... Cohen DJ, Leon MB
Aims
The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research.
Methods and results
Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs.
Conclusions
Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 31 May 2021; 77:2717-2746
VARC-3 WRITING COMMITTEE:, Généreux P, Piazza N, Alu MC, ... Cohen DJ, Leon MB
J Am Coll Cardiol: 31 May 2021; 77:2717-2746 | PMID: 33888385
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical Approach to Cardiovascular Toxicity of Oral Antineoplastic Agents: JACC State-of-the-Art Review.

Rao VU, Reeves DJ, Chugh AR, O\'Quinn R, ... Barac A, Lenihan D
Precision medicine has ushered in a new era of targeted treatments for numerous malignancies, leading to improvements in overall survival. Unlike traditional chemotherapy, many molecular targeted antineoplastic agents are available in oral formulation, leading to enhanced patient convenience and a perception of reduced risk of adverse effects. Although oral antineoplastic agents are generally well-tolerated, cardiovascular toxicities are being reported with increasing frequency in part due to U.S. Food and Drug Administration and manufacturer recommended cardiac monitoring. Monitoring strategies have focused on left ventricular dysfunction, hypertension, and QT prolongation/arrhythmias. Given the rapid pace of development and availability of new oral antineoplastic agents, the purpose of this review is to provide clinicians with an up-to-date practical approach to monitoring and management of cardiovascular toxicities with the aim of improving overall outcomes for patients with cancer.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2021; 77:2693-2716
Rao VU, Reeves DJ, Chugh AR, O'Quinn R, ... Barac A, Lenihan D
J Am Coll Cardiol: 31 May 2021; 77:2693-2716 | PMID: 34045027
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Framingham Heart Study: JACC Focus Seminar, 1/8.

Andersson C, Nayor M, Tsao CW, Levy D, Vasan RS
The Framingham Heart Study is the longest-running cardiovascular epidemiological study, starting in 1948. This paper gives an overview of the various cohorts, collected data, and most important research findings to date. In brief, the Framingham Heart Study, funded by the National Institutes of Health and managed by Boston University, spans 3 generations of well phenotyped White persons and 2 cohorts comprised of racial and ethnic minority groups. These cohorts are densely phenotyped, with extensive longitudinal follow-up, and they continue to provide us with important information on human cardiovascular and noncardiovascular physiology over the lifespan, as well as to identify major risk factors for cardiovascular disease. This paper also summarizes some of the more recent progress in molecular epidemiology and discusses the future of the study.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 31 May 2021; 77:2680-2692
Andersson C, Nayor M, Tsao CW, Levy D, Vasan RS
J Am Coll Cardiol: 31 May 2021; 77:2680-2692 | PMID: 34045026
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Urinary Dickkopf-3 and Contrast-Associated Kidney Damage.

Roscigno G, Quintavalle C, Biondi-Zoccai G, De Micco F, ... Condorelli G, Briguori C
Background
Administration of iodinated contrast medium (CM) during invasive cardiovascular procedures may be associated with impairment of kidney function.
Objectives
Urinary dickkopf-3 (DKK3), a stress-induced renal tubular epithelium-derived glycoprotein, has been identified as a biomarker predicting both acute kidney injury (AKI) and persistent kidney dysfunction.
Methods
Urinary DKK3/creatinine ratio (uDKK3/uCr), urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) and serum cystatin C (sCyC) were assessed in 458 patients with chronic kidney disease scheduled for invasive cardiovascular procedures requiring CM administration with universal adoption of nephroprotective interventions. Contrast-associated AKI (CA-AKI) was defined as serum creatinine increase ≥0.3 mg/dl at 48 h after CM administration. Persistent kidney dysfunction was defined as persistent estimated glomerular filtration rate reduction ≥25% at 1 month compared with baseline.
Results
CA-AKI occurred in 64 or the 458 patients (14%), and baseline uDKK3/uCr ≥491 pg/mg was the best threshold for its prediction. Net reclassification improvement (NRI) was significantly increased by adding baseline uDKK3/uCr to the Mehran, Gurm, and National Cardiovascular Data Registry (NCDR) scores (all p < 0.05), and the same applied to integrated discrimination improvement (IDI) when adding uDKK3/uCr to the Gurm and NCDR scores (p < 0.001). Persistent kidney dysfunction occurred in 57 of the 458 patients (12%) and baseline uDKK3/uCr ≥322 pg/mg appeared as the best threshold for its prediction. Adding baseline uDKK3/uCr to the Mehran, Gurm, and NCDR scores significantly increased IDI and NRI (all p < 0.001).
Conclusions
Baseline uDKK3/uCr seems to be a reliable marker for improving the identification of patients with chronic kidney disease undergoing invasive coronary and peripheral procedures at risk for AKI and persistent kidney dysfunction.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2021; 77:2667-2676
Roscigno G, Quintavalle C, Biondi-Zoccai G, De Micco F, ... Condorelli G, Briguori C
J Am Coll Cardiol: 31 May 2021; 77:2667-2676 | PMID: 34045024
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk Associated With Valvular Regurgitation During Pregnancy.

Pfaller B, Dave Javier A, Grewal J, Gabarin N, ... Siu SC, Silversides CK
Background
Pregnancies in women with regurgitant valve lesions are generally considered low risk, but this has not been well studied.
Objectives
This study determined the frequency of adverse cardiac events (CEs) in pregnant women with moderate or severe regurgitant valve lesions.
Methods
Maternal and fetal outcomes in women with moderate or severe chronic valve regurgitation enrolled in a prospective multicenter study on pregnancy outcomes were examined. Adverse CEs included heart failure, sustained arrhythmias, cardiac arrest, or death. A multivariate logistic regression model was used to identify determinants of CEs in women at the highest risk.
Results
Outcomes of 430 pregnancies in women with moderate or severe regurgitant lesions were examined: 145 with mitral regurgitation (MR), 101 with pulmonary regurgitation (PR), 71 with multivalve disease, 73 with tricuspid regurgitation (TR), and 40 with aortic regurgitation (AR). Most women had associated congenital or acquired heart disease. Adverse CEs occurred in 13% of pregnancies: 27% of pregnancies with multivalve disease; 15% with MR; 15% with TR; 5% with AR; and 3% with PR. Maternal mortality was rare. In women with MR, TR, or multivalve disease (n = 289), left ventricular systolic dysfunction (p = 0.001), pulmonary hypertension (p = 0.005), and cardiac events before pregnancy (p < 0.001) were important determinants of CEs during pregnancy.
Conclusions
Women with AR and PR are at low risk for cardiac complications during pregnancy. While many women with MR, TR, and multivalve regurgitation do well during pregnancy, additional clinical variables help stratify those at highest risk. This new information will enhance the quality and precision of preconception counseling and pregnancy planning.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2021; 77:2656-2664
Pfaller B, Dave Javier A, Grewal J, Gabarin N, ... Siu SC, Silversides CK
J Am Coll Cardiol: 31 May 2021; 77:2656-2664 | PMID: 34045022
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pericardial Fat and the Risk of Heart Failure.

Kenchaiah S, Ding J, Carr JJ, Allison MA, ... Arai AE, Bluemke DA
Background
Obesity is a well-established risk factor for heart failure (HF). However, implications of pericardial fat on incident HF is unclear.
Objectives
This study sought to examine the association between pericardial fat volume (PFV) and newly diagnosed HF.
Methods
This study ascertained PFV using cardiac computed tomography in 6,785 participants (3,584 women and 3,201 men) without pre-existing cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis). Cox proportional hazards regression was used to evaluate PFV as continuous and dichotomous variable, maximizing the J-statistic: (Sensitivity + Specificity - 1).
Results
In 90,686 person-years (median: 15.7 years; interquartile range: 11.7 to 16.5 years), 385 participants (5.7%; 164 women and 221 men) developed newly diagnosed HF. PFV was lower in women than in men (69 ± 33 cm3 vs. 92 ± 47 cm3; p < 0.001). In multivariable analyses, every 1-SD (42 cm3) increase in PFV was associated with a higher risk of HF in women (hazard ratio [HR]: 1.44; 95% confidence interval [CI]: 1.21 to 1.71; p < 0.001) than in men (HR: 1.13; 95% CI: 1.01 to 1.27; p = 0.03) (interaction p = 0.01). High PFV (≥70 cm3 in women; ≥120 cm3 in men) conferred a 2-fold greater risk of HF in women (HR: 2.06; 95% CI: 1.48 to 2.87; p < 0.001) and a 53% higher risk in men (HR: 1.53; 95% CI: 1.13 to 2.07; p = 0.006). In sex-stratified analyses, greater risk of HF remained robust with additional adjustment for anthropometric indicators of obesity (p ≤ 0.008), abdominal subcutaneous or visceral fat (p ≤ 0.03) or biomarkers of inflammation and hemodynamic stress (p < 0.001) and was similar among Whites, Blacks, Hispanics, and Chinese (interaction p = 0.24). Elevated PFV predominantly augmented the risk of HF with preserved ejection fraction (p < 0.001) rather than reduced ejection fraction (p = 0.31).
Conclusions
In this large, community-based, ethnically diverse, prospective cohort study, pericardial fat was associated with an increased risk of HF, particularly HF with preserved ejection fraction, in women and men.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 31 May 2021; 77:2638-2652
Kenchaiah S, Ding J, Carr JJ, Allison MA, ... Arai AE, Bluemke DA
J Am Coll Cardiol: 31 May 2021; 77:2638-2652 | PMID: 34045020
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effects of Diet and Sodium Reduction on Cardiac Injury, Strain, and Inflammation: The DASH-Sodium Trial.

Juraschek SP, Kovell LC, Appel LJ, Miller ER, ... Rebuck H, Mukamal KJ
Background
The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.
Objectives
The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.
Methods
DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.
Results
Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: -27% to -7%) and hs-CRP by 13% (95% CI: -24% to -1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: -24% to -14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: -31% to -7%) and NT-proBNP by 23% (95% CI: -32% to -12%), whereas hs-CRP was not significantly changed (-7%; 95% CI: -22% to 9%) compared with the high sodium-control diet.
Conclusions
Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH - Sodium]; NCT00000608).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 31 May 2021; 77:2625-2634
Juraschek SP, Kovell LC, Appel LJ, Miller ER, ... Rebuck H, Mukamal KJ
J Am Coll Cardiol: 31 May 2021; 77:2625-2634 | PMID: 34045018
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Precision Medicine in Catecholaminergic Polymorphic Ventricular Tachycardia: JACC Focus Seminar 5/5.

Priori SG, Mazzanti A, Santiago DJ, Kukavica D, Trancuccio A, Kovacic JC
In this final of a 5-part Focus Seminar series on precision medicine, we focus on catecholaminergic polymorphic ventricular tachycardia (CPVT). This focus on CPVT allows us to take a \"deep dive\" and explore the full extent of the precision medicine opportunities for a single cardiovascular condition at a level that was not possible in the preceding articles. As a new paradigm presented in this article, it has become clear that CPVT can occur as either a typical or atypical form. Although there is a degree of overlap between the typical and atypical forms, it is notable that they arise due to different underlying genetic changes, likely exhibiting differing mechanisms of action, and presenting with different phenotypic features. The recognition of these differing forms of CPVT and their different etiologies and mechanisms is an important step toward implementing rapidly emerging precision medicine approaches that will tailor novel therapies to specific gene defects.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2592-2612
Priori SG, Mazzanti A, Santiago DJ, Kukavica D, Trancuccio A, Kovacic JC
J Am Coll Cardiol: 24 May 2021; 77:2592-2612 | PMID: 34016269
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Precision Medicine Approaches to Cardiac Arrhythmias: JACC Focus Seminar 4/5.

Giudicessi JR, Ackerman MJ, Fatkin D, Kovacic JC
In the initial 3 papers in this Focus Seminar series, the fundamentals and key concepts of precision medicine were reviewed, followed by a focus on precision medicine in the context of vascular disease and cardiomyopathy. For the remaining 2 papers, we focus on precision medicine in the context of arrhythmias. Specifically, in this fourth paper we focus on long QT syndrome, Brugada syndrome, and atrial fibrillation. The final (fifth) paper will deal with catecholaminergic polymorphic ventricular tachycardia. These arrhythmias represent a spectrum of disease ranging from common to relatively rare, with very different genetic and environmental causative factors, and with differing clinical manifestations that range from almost no consequences to lethality in childhood or adolescence if untreated. Accordingly, the emerging precision medicine approaches to these arrhythmias vary significantly, but several common themes include increased use of genetic testing, avoidance of triggers, and personalized risk stratification to guide the use of arrhythmia-specific therapies.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2573-2591
Giudicessi JR, Ackerman MJ, Fatkin D, Kovacic JC
J Am Coll Cardiol: 24 May 2021; 77:2573-2591 | PMID: 34016268
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Contemporary and Future Approaches to Precision Medicine in Inherited Cardiomyopathies: JACC Focus Seminar 3/5.

Fatkin D, Calkins H, Elliott P, James CA, Peters S, Kovacic JC
Inherited cardiomyopathies are commonly occurring myocardial disorders that are associated with substantial morbidity and mortality. Clinical management strategies have focused on treatment of heart failure and arrhythmic complications in symptomatic patients according to standardized guidelines. Clinicians are now being urged to implement precision medicine, but what does this involve? Advances in understanding of the genetic underpinnings of inherited cardiomyopathies have brought new possibilities for interventions that are tailored to genes, specific variants, or downstream mechanisms. However, the phenotypic variability that can occur with any given pathogenic variant suggests that factors other than single driver gene mutations are often involved. This is propelling a new imperative to elucidate the nuanced ways in which individual combinations of genetic variation, comorbidities, and lifestyle may influence cardiomyopathy phenotypes. Here, Part 3 of a 5-part precision medicine Focus Seminar series reviews the current status and future opportunities for precision medicine in the inherited cardiomyopathies.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2551-2572
Fatkin D, Calkins H, Elliott P, James CA, Peters S, Kovacic JC
J Am Coll Cardiol: 24 May 2021; 77:2551-2572 | PMID: 34016267
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Precision Medicine Approaches to Vascular Disease: JACC Focus Seminar 2/5.

Miller CL, Kontorovich AR, Hao K, Ma L, ... Björkegren JLM, Kovacic JC
In this second of a 5-part Focus Seminar series, we focus on precision medicine in the context of vascular disease. The most common vascular disease worldwide is atherosclerosis, which is the primary cause of coronary artery disease, peripheral vascular disease, and a large proportion of strokes and other disorders. Atherosclerosis is a complex genetic disease that likely involves many hundreds to thousands of single nucleotide polymorphisms, each with a relatively modest effect for causing disease. Conversely, although less prevalent, there are many vascular disorders that typically involve only a single genetic change, but these changes can often have a profound effect that is sufficient to cause disease. These are termed \"Mendelian vascular diseases,\" which include Marfan and Loeys-Dietz syndromes. Given the very different genetic basis of atherosclerosis versus Mendelian vascular diseases, this article was divided into 2 parts to cover the most promising precision medicine approaches for these disease types.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2531-2550
Miller CL, Kontorovich AR, Hao K, Ma L, ... Björkegren JLM, Kovacic JC
J Am Coll Cardiol: 24 May 2021; 77:2531-2550 | PMID: 34016266
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Precision Medicine in Cardiovascular Disease: Genetics and Impact on Phenotypes: JACC Focus Seminar 1/5.

Semsarian C, Ingles J, Ross SB, Dunwoodie SL, Bagnall RD, Kovacic JC
Our understanding of the genetic basis of cardiovascular diseases (CVDs) has evolved rapidly. This has resulted from a combination of dedicated research in well phenotyped CVD patients, the sequencing of the human genome, and the ready accessibility and decreasing cost of next-generation sequencing technologies. This increased knowledge of the genetic basis of CVDs has heralded the era of precision medicine. This encompasses many elements including improved diagnosis, family screening, assistance with reproductive decisions, targeted therapeutics guided by both phenotype and genotype, and providing important insights into risk stratification and prognosis. Furthermore, novel insights into genetic mechanisms, clinical rollout of polygenic risk scores for common CVDs, and the promise of genome editing approaches to effectively cure disease represent some of the exciting future endeavors that will change established clinical approaches. This Part 1 of a 5-part series focuses on the underpinnings and fundamental aspects of precision medicine.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2517-2530
Semsarian C, Ingles J, Ross SB, Dunwoodie SL, Bagnall RD, Kovacic JC
J Am Coll Cardiol: 24 May 2021; 77:2517-2530 | PMID: 34016265
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease.

Akawi N, Checa A, Antonopoulos AS, Akoumianakis I, ... Wheelock CE, Antoniades C
Background
Obesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown.
Objectives
The aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes.
Methods
A screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n = 48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints.
Results
Because ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C16:0-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular vesicles. High ThAT sphingolipid secretion was significantly associated with reduced endothelial nitric oxide bioavailability and increased superoxide generated in human vessels. Circulating C16:0-ceramide correlated positively with ThAT ceramides, dysregulated vascular redox signaling, and increased systemic inflammation in 633 patients with atherosclerosis. Exogenous C16:0-ceramide directly increased superoxide via tetrahydrobiopterin-mediated endothelial nitric oxide synthase uncoupling and dysregulated protein phosphatase 2 in human aortic endothelial cells. High plasma C16:0-ceramide and its glycosylated derivative were independently related with increased risk for cardiac mortality (adjusted hazard ratios: 1.394; 95% confidence interval: 1.030 to 1.886; p = 0.031 for C16:0-ceramide and 1.595; 95% confidence interval: 1.042 to 2.442; p = 0.032 for C16:0-glycosylceramide per 1 SD). In a randomized controlled clinical trial, 1-year treatment of obese patients with the glucagon-like peptide-1 analog liraglutide suppressed plasma C16:0-ceramide and C16:0-glycosylceramide changes compared with control subjects.
Conclusions
These results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2494-2513
Akawi N, Checa A, Antonopoulos AS, Akoumianakis I, ... Wheelock CE, Antoniades C
J Am Coll Cardiol: 24 May 2021; 77:2494-2513 | PMID: 34016263
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Integrated Clinical and Magnetic Resonance Imaging Assessments Late After Fontan Operation.

Meyer SL, St Clair N, Powell AJ, Geva T, Rathod RH
Background
Several clinical and cardiac magnetic resonance (CMR)-derived parameters have been shown to be associated with death or heart transplant late after the Fontan operation.
Objectives
The objective of this study was to identify the relative importance and interactions of clinical and CMR-based parameters for risk stratification after the Fontan operation.
Methods
Fontan patients were retrospectively reviewed. Clinical and CMR parameters were analyzed using univariable Cox regression. The primary endpoint was time to death or (listing for) heart transplant. To identify the patients at highest risk for the endpoint, classification and regression tree survival analysis was performed, including all significant variables from Cox regression.
Results
The cohort consisted of 416 patients (62% male) with a median age of 16 years (25th, 75th percentiles: 11, 23 years). Over a median follow-up of 5.4 years (25th, 75th percentiles: 2.4, 10.0 years) after CMR, 57 patients (14%) reached the endpoint (46 deaths, 7 heart transplants, 4 heart transplant listings). Lower total indexed end-diastolic volume (EDVi) was the strongest predictor of transplant-free survival. Among patients with dilated ventricles (EDVi ≥156 ml/BSA1.3), worse global circumferential strain (GCS) was the next most important predictor (73% vs. 44%). In patients with smaller ventricles (EDVi <156 ml/BSA1.3), New York Heart Association functional class ≥II was the next most important predictor (30% vs. 4%).
Conclusions
In this cohort of patients late after Fontan operation, increased ventricular dilation was the strongest independent predictor of death or transplant (listing). Patients with both ventricular dilation and worse GCS were at highest risk. These data highlight the value of integrating CMR and clinical parameters for risk stratification in this population.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2480-2489
Meyer SL, St Clair N, Powell AJ, Geva T, Rathod RH
J Am Coll Cardiol: 24 May 2021; 77:2480-2489 | PMID: 34016261
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Survival After Implantable Cardioverter-Defibrillator Shocks.

Aktaş MK, Younis A, Zareba W, Kutyifa V, ... Polonsky B, Goldenberg I
Background
There are conflicting data on the impact of implantable cardioverter-defibrillator (ICD) shocks on subsequent mortality.
Objectives
The aim of this study was to determine whether the arrhythmic substrate leading to ICD therapy or the therapy itself increases mortality.
Methods
The study cohort included 5,516 ICD recipients who were enrolled in 5 landmark ICD trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, RAID). The authors evaluated the association of device therapy with subsequent mortality in 4 separate time-dependent models: model I, type of ICD therapy; model II, type of arrhythmia for which ICD therapy was delivered; model III, combined assessment of all arrhythmia and therapy types during follow-up; and model IV, incremental risk associated with repeated ICD shocks.
Results
When analyzed by the type of ICD therapy (model I), a first appropriate ICD shock was associated with increased risk of subsequent mortality with or without concomitant occurrence of inappropriate shock during follow-up (hazard ratio [HR]: 2.78 and 2.31; p < 0.001 and p = 0.12), whereas inappropriate shock alone was not associated with mortality risk (HR: 1.23; p = 0.42). Similarly, ICD therapy for ventricular tachycardia (VT) ≥200 beats/min or ventricular fibrillation (VF) (model II) was associated with increased risk of death with or without concomitant therapy for VT <200 beats/min (HRs: 2.25 and 2.62; both p < 0.001), whereas appropriate therapy for VT <200 beats/min or inappropriate therapy (regardless of etiology) did not reach statistical significance (all p > 0.10). Combined assessment of all therapy and arrhythmia types during follow-up (model III) showed that appropriate ICD shocks for VF, shocks for fast VT (≥200 beats/min) without prior antitachycardia pacing (ATP), as well as shocks for fast VT delivered after failed ATP, were associated with the highest risk of subsequent death (HR: all >2.8; p < 0.001). Finally, 2 or more ICD appropriate shocks were not associated with incremental risk to the first appropriate ICD shock (model IV).
Conclusion
The combined data from 5 landmark ICD trials suggest that the underlying arrhythmic substrate rather than the ICD therapy is the more important determinant of mortality in ICD recipients.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 24 May 2021; 77:2453-2462
Aktaş MK, Younis A, Zareba W, Kutyifa V, ... Polonsky B, Goldenberg I
J Am Coll Cardiol: 24 May 2021; 77:2453-2462 | PMID: 34016257
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Percutaneous Coronary Intervention on Outcomes in Patients With Heart Failure: JACC State-of-the-Art Review.

Parikh PB, Bhatt DL, Bhasin V, Anker SD, ... Petrie MC, Butler J
Coronary artery disease (CAD) is highly prevalent in patients with heart failure (HF) and accounts for nearly two-thirds of cases. The use of percutaneous coronary intervention (PCI) in HF patients with CAD has markedly increased and has been suggested to be associated with improved outcomes in numerous observational studies. Randomized data comparing the impact of PCI with that of coronary artery bypass graft (CABG) or contemporary guideline-directed medical therapy alone on clinical outcomes and myocardial recovery in patients with HF are lacking. The purpose of this review is to describe the available evidence regarding the impact of PCI in acute HF (in the presence and absence of an acute coronary syndrome), chronic HF with reduced ejection fraction, and HF with preserved ejection fraction. Adequately-powered randomized clinical trials examining the outcomes with PCI in these distinct HF populations are warranted.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2021; 77:2432-2447
Parikh PB, Bhatt DL, Bhasin V, Anker SD, ... Petrie MC, Butler J
J Am Coll Cardiol: 17 May 2021; 77:2432-2447 | PMID: 33985688
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Vascular Lesion-Specific Drug Delivery Systems: JACC State-of-the-Art Review.

Marlevi D, Edelman ER
Drug delivery is central to modern cardiovascular care, where drug-eluting stents, bioresorbable scaffolds, and drug-coated balloons all aim to restore perfusion while inhibiting exuberant healing. The promise and enthusiasm of these devices has in some cases exceeded demonstration of efficacy and even understanding of driving mechanisms. The authors review the means of drug delivery in each device, outlining how the technologies affect vascular behavior. They focus on how drug retention and response are governed by lesion morphology: lipid displacing drug-specific binding sites, calcium inhibiting diffusion, blocking thrombi or promoting luminal washout, and vascular healing steering hyperplastic developments. In this regard, the authors outline the fundamental impact of vascular structure on drug delivery and review the development of contemporary and future devices for coronary and peripheral intervention. They look toward a future where incorporating information on lesion distribution is central to therapeutic success and envision a transition toward lesion-specific treatment for improved interventional outcomes.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2021; 77:2413-2431
Marlevi D, Edelman ER
J Am Coll Cardiol: 17 May 2021; 77:2413-2431 | PMID: 33985687
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Global Prevalence and Impact of Hostility, Discrimination, and Harassment in the Cardiology Workplace.

Sharma G, Douglas PS, Hayes SN, Mehran R, ... Blumenthal RS, Mehta LS
Background
Discrimination and emotional and sexual harassment create a hostile work environment (HWE). The global prevalence of HWE in cardiology is unknown, as is its impact.
Objectives
This study sought to evaluate emotional harassment, discrimination, and sexual harassment experienced by cardiologists and its impact on professional satisfaction and patient interactions worldwide.
Methods
The American College of Cardiology surveyed cardiologists from Africa, Asia, the Caribbean, Eastern Europe, the European Union, the Middle East, Oceana, and North, Central, and South America. Demographics, practice information, and HWE were tabulated and compared, and their impact was assessed. The p values were calculated using the chi-square, Fisher exact, and Mann-Whitney U tests. Univariate and multivariate logistic regression analysis determined the association of characteristics with HWE and its subtypes.
Results
Of 5,931 cardiologists (77% men; 23% women), 44% reported HWE. Higher rates were found among women (68% vs. 37%; odds ratio [OR]: 3.58 vs. men), Blacks (53% vs. 43%; OR: 1.46 vs. Whites), and North Americans (54% vs. 38%; OR: 1.90 vs. South Americans). Components of HWE included emotional harassment (29%; n = 1,743), discrimination (30%; n = 1,750), and sexual harassment (4%; n = 221), and they were more prevalent among women: emotional harassment (43% vs. 26%), discrimination (56% vs. 22%), and sexual harassment (12% vs. 1%). Gender was the most frequent cause of discrimination (44%), followed by age (37%), race (24%), religion (15%), and sexual orientation (5%). HWE adversely affected professional activities with colleagues (75%) and patients (53%). Multivariate analysis showed that women (OR: 3.39; 95% confidence interval: 2.97 to 3.86; p < 0.001) and cardiologists early in their career (OR: 1.27; 95% confidence interval: 1.14 to 1.43; p < 0.001) had the highest odds of experiencing HWE.
Conclusions
There is a high global prevalence of HWE in cardiology, including discrimination, emotional harassment, and sexual harassment. HWE has an adverse effect on professional and patient interactions, thus confirming concerns about well-being and optimizing patient care. Institutions and practices should prioritize combating HWE.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2021; 77:2398-2409
Sharma G, Douglas PS, Hayes SN, Mehran R, ... Blumenthal RS, Mehta LS
J Am Coll Cardiol: 17 May 2021; 77:2398-2409 | PMID: 33985685
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Major Residual Lesions on Outcomes After Surgery for Congenital Heart Disease.

Nathan M, Levine JC, Van Rompay MI, Lambert LM, ... Newburger JW, Pediatric Heart Network Investigators
Background
Many factors affect outcomes after congenital cardiac surgery.
Objectives
The RLS (Residual Lesion Score) study explored the impact of severity of residual lesions on post-operative outcomes across operations of varying complexity.
Methods
In a prospective, multicenter, observational study, 17 sites enrolled 1,149 infants undergoing 5 common operations: tetralogy of Fallot repair (n = 250), complete atrioventricular septal defect repair (n = 249), arterial switch operation (n = 251), coarctation or interrupted arch with ventricular septal defect (VSD) repair (n = 150), and Norwood operation (n = 249). The RLS was assigned based on post-operative echocardiography and clinical events: RLS 1 (trivial or no residual lesions), RLS 2 (minor residual lesions), or RLS 3 (reintervention for or major residual lesions before discharge). The primary outcome was days alive and out of hospital within 30 post-operative days (60 for Norwood). Secondary outcomes assessed post-operative course, including major medical events and days in hospital.
Results
RLS 3 (vs. RLS 1) was an independent risk factor for fewer days alive and out of hospital (p ≤ 0.008) and longer post-operative hospital stay (p ≤ 0.02) for all 5 operations, and for all secondary outcomes after coarctation or interrupted arch with VSD repair and Norwood (p ≤ 0.03). Outcomes for RLS 1 versus 2 did not differ consistently. RLS alone explained 5% (tetralogy of Fallot repair) to 20% (Norwood) of variation in the primary outcome.
Conclusions
Adjusting for pre-operative factors, residual lesions after congenital cardiac surgery impacted in-hospital outcomes across operative complexity with greatest impact following complex operations. Minor residual lesions had minimal impact. These findings may provide guidance for surgeons when considering short-term risks and benefits of returning to bypass to repair residual lesions.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 17 May 2021; 77:2382-2394
Nathan M, Levine JC, Van Rompay MI, Lambert LM, ... Newburger JW, Pediatric Heart Network Investigators
J Am Coll Cardiol: 17 May 2021; 77:2382-2394 | PMID: 33985683
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diabetes-Related Factors and the Effects of Ticagrelor Plus Aspirin in the THEMIS and THEMIS-PCI Trials.

Leiter LA, Bhatt DL, McGuire DK, Teoh H, ... Steg PG, THEMIS Steering Committee and Investigators
Background
THEMIS (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study) (n = 19,220) and its pre-specified THEMIS-PCI (The Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study-Percutaneous Coronary Intervention) (n = 11,154) subanalysis showed, in individuals with type 2 diabetes mellitus (median duration 10.0 years; HbA1c 7.1%) and stable coronary artery disease without prior myocardial infarction (MI) or stroke, that ticagrelor plus aspirin (compared with placebo plus aspirin) produced a favorable net clinical benefit (composite of all-cause mortality, MI, stroke, fatal bleeding, and intracranial bleeding) if the patients had a previous percutaneous coronary intervention.
Objectives
In these post hoc analyses, the authors examined whether the primary efficacy outcome (cardiovascular death, MI, stroke: 3-point major adverse cardiovascular events [MACE]), primary safety outcome (Thrombolysis In Myocardial Infarction-defined major bleeding) and net clinical benefit varied with diabetes-related factors.
Methods
Outcomes were analyzed across baseline diabetes duration, HbA1c, and antihyperglycemic medications.
Results
In THEMIS, the incidence of 3-point MACE increased with diabetes duration (6.7% for ≤5 years, 11.1% for >20 years) and HbA1c (6.4% for ≤6.0%, 11.8% for >10.0%). The relative benefits of ticagrelor plus aspirin on 3-point MACE reduction (hazard ratio [HR]: 0.90; p = 0.04) were generally consistent across subgroups. Major bleeding event rate (overall: 1.6%) did not vary by diabetes duration or HbA1c and was increased similarly by ticagrelor across all subgroups (HR: 2.32; p < 0.001). These findings were mirrored in THEMIS-PCI. The efficacy and safety of ticagrelor plus aspirin did not differ by baseline antihyperglycemic therapy. In THEMIS-PCI, but not THEMIS, ticagrelor generally produced favorable net clinical benefit across diabetes duration, HbA1c, and antihyperglycemic medications.
Conclusion
Ticagrelor plus aspirin yielded generally consistent and favorable net clinical benefit across the diabetes-related factors in THEMIS-PCI but not in the overall THEMIS population.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2021; 77:2366-2377
Leiter LA, Bhatt DL, McGuire DK, Teoh H, ... Steg PG, THEMIS Steering Committee and Investigators
J Am Coll Cardiol: 17 May 2021; 77:2366-2377 | PMID: 33985681
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Factors Predisposing to Survival After Resuscitation for Sudden Cardiac Arrest.

Ricceri S, Salazar JW, Vu AA, Vittinghoff E, Moffatt E, Tseng ZH
Background
In the POST SCD study, the authors autopsied all World Health Organization (WHO)-defined sudden cardiac deaths (SCDs) and found that only 56% had an arrhythmic cause; resuscitated sudden cardiac arrests (SCAs) were excluded because they did not die suddenly. They hypothesized that causes underlying resuscitated SCAs would be similarly heterogeneous.
Objectives
The aim of this study was to determine the causes and outcomes of resuscitated SCAs.
Methods
The authors identified all out-of-hospital cardiac arrests (OHCAs) from February 1, 2011, to January 1, 2015, of patients aged 18 to 90 years in San Francisco County. Resuscitated SCAs were OHCAs surviving to hospitalization and meeting WHO criteria for suddenness. Underlying cause was determined by comprehensive record review.
Results
The authors identified 734 OHCAs over 48 months; 239 met SCA criteria, 133 (55.6%) were resuscitated to hospitalization, and 47 (19.7%) survived to discharge. Arrhythmic causes accounted for significantly more resuscitated SCAs overall (92 of 133, 69.1%), particularly among survivors (43 of 47, 91.5%), than WHO-defined SCDs in POST SCD (293 of 525, 55.8%; p < 0.004 for both). Among resuscitated SCAs, arrhythmic cause, ventricular tachycardia/fibrillation initial rhythm, and white race were independent predictors of survival. None of the resuscitated SCAs due to neurologic causes survived.
Conclusions
In this 4-year countywide study of OHCAs, only one-third were sudden, of which one-half were resuscitated to hospitalization and 1 in 5 survived to discharge. Arrhythmic cause predicted survival and nearly one-half of nonsurvivors had nonarrhythmic causes, suggesting that SCA survivors are not equivalent to SCDs. Early identification of nonarrhythmic SCAs, such as neurologic emergencies, may be a target to improve OHCA survival.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 17 May 2021; 77:2353-2362
Ricceri S, Salazar JW, Vu AA, Vittinghoff E, Moffatt E, Tseng ZH
J Am Coll Cardiol: 17 May 2021; 77:2353-2362 | PMID: 33985679
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Autoregulation of Coronary Blood Supply in Response to Demand: JACC Review Topic of the Week.

Johnson NP, Gould KL, De Bruyne B
Although our coronary circulation evolved to meet demands during marked physical exertion for \"fight or flight\" survival, complex and multilayered control mechanisms reduce flow during other periods. Understanding homeostasis of resting flow provides essential insights into clinical pathophysiology. Several homeostatic mechanisms (myogenic, metabolic, endothelial, and neural) maintain sufficient baseline flow regardless of driving pressure (in aggregate, \"autoregulation\"). As a result, ventricular dysfunction does not arise until coronary perfusion pressure decreases to ∼40 mm Hg. Straightforward clinical parameters explain approximately one-half of observed absolute resting perfusion but with wide imprecision. Resting perfusion does not associate with clinical outcomes and remains unaffected by revascularization, recovery after myocardial infarction, and treating severe aortic stenosis, thereby supporting the notion that the heart was designed for peak performance.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2021; 77:2335-2345
Johnson NP, Gould KL, De Bruyne B
J Am Coll Cardiol: 10 May 2021; 77:2335-2345 | PMID: 33958131
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review.

Cannata A, Cantoni S, Sciortino A, Bruschi G, Russo CF
Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2021; 77:2323-2334
Cannata A, Cantoni S, Sciortino A, Bruschi G, Russo CF
J Am Coll Cardiol: 10 May 2021; 77:2323-2334 | PMID: 33958130
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Individualized Nutritional Support for Hospitalized Patients With Chronic Heart Failure.

Hersberger L, Dietz A, Bürgler H, Bargetzi A, ... Mueller B, Schuetz P
Background
Deterioration of nutritional status during hospitalization in patients with chronic heart failure increases mortality. Whether nutritional support during hospitalization reduces these risks, or on the contrary, may be harmful due to an increase in salt and fluid intake, remains unclear.
Objectives
The purpose of this trial was to study the effect of nutritional support on mortality in patients hospitalized with chronic heart failure who are at nutritional risk.
Methods
A total of 645 patients with chronic heart failure (36% [n = 234] with acute decompensation) participated in the investigator-initiated, open-label EFFORT (Effect of early nutritional support on Frailty, Functional Outcomes and Recovery of malnourished medical inpatients) trial. Patients were randomized to protocol-guided individualized nutritional support to reach energy, protein, and micronutrient goals (intervention group) or standard hospital food (control group). The primary endpoint was all-cause mortality at 30 days.
Results
Mortality over 180 days increased with higher severity of malnutrition (odds ratio per 1-point increase in Nutritional Risk Screening 2002 score: 1.65; 95% confidence interval [CI]: 1.21 to 2.24; p = 0.001). By 30 days, 27 of 321 intervention group patients (8.4%) died, compared with 48 of 324 (14.8%) control group patients (odds ratio: 0.44; 95% CI: 0.26 to 0.75; p = 0.002). Patients at high nutritional risk showed the most benefit from nutritional support. Mortality effects remained significant at 180-day follow-up. Intervention group patients also had a lower risk for major cardiovascular events at 30 days (17.4% vs. 26.9%; odds ratio: 0.50; 95% CI: 0.34 to 0.75; p = 0.001).
Conclusions
Among hospitalized patients with chronic heart failure at high nutritional risk, individualized nutritional support reduced the risk for mortality and major cardiovascular events compared with standard hospital food. These data support malnutrition screening upon hospital admission followed by an individualized nutritional support strategy in this vulnerable patient population. (Effect of Early Nutritional Therapy on Frailty, Functional Outcomes and Recovery of Undernourished Medical Inpatients Trial [EFFORT]; NCT02517476).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2021; 77:2307-2319
Hersberger L, Dietz A, Bürgler H, Bargetzi A, ... Mueller B, Schuetz P
J Am Coll Cardiol: 10 May 2021; 77:2307-2319 | PMID: 33958128
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Chronobiology of Natriuretic Peptides and Blood Pressure in Lean and Obese Individuals.

Parcha V, Patel N, Gutierrez OM, Li P, ... Arora G, Arora P
Background
Diurnal variation of natriuretic peptide (NP) levels and its relationship with 24-h blood pressure (BP) rhythm has not been established. Obese individuals have a relative NP deficiency and disturbed BP rhythmicity.
Objectives
This clinical trial evaluated the diurnal rhythmicity of NPs (B-type natriuretic peptide [BNP], mid-regional pro-atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [NT-proBNP]) and the relationship of NP rhythm with 24-h BP rhythm in healthy lean and obese individuals.
Methods
On the background of a standardized diet, healthy, normotensive, lean (body mass index 18.5 to 25 kg/m2) and obese (body mass index 30 to 45 kg/m2) individuals, age 18 to 40 years, underwent 24-h inpatient protocol involving ambulatory BP monitoring starting 24 h prior to the visit, controlled light intensity, and repeated blood draws for assessment of analytes. Cosinor analysis of normalized NP levels (normalized to 24-h mean value) was conducted to assess the diurnal NP rhythm and its relationship with systolic BP.
Results
Among 52 participants screened, 40 participants (18 lean, 22 obese; 50% women; 65% Black) completed the study. The median range spread (percentage difference between the minimum and maximum values) over 24 h for MR-proANP, BNP, and NT-proBNP levels was 72.0% (interquartile range [IQR]: 50.9% to 119.6%), 75.5% (IQR: 50.7% to 106.8%), and 135.0% (IQR: 66.3% to 270.4%), respectively. A cosine wave-shaped 24-h oscillation of normalized NP levels (BNP, MR-proANP, and NT-proBNP) was noted both in lean and obese individuals (prhythmicity <0.05 for all). A larger phase difference between MR-proANP BP rhythm (-4.9 h vs. -0.7 h) and BNP BP rhythm (-3.3 h vs. -0.9 h) was seen in obese compared with lean individuals.
Conclusions
This human physiological trial elucidates evidence of diurnal NP rhythmicity and the presence of an NP-BP rhythm axis. There exists a misalignment of the NP-BP diurnal rhythm in the obese, which may contribute to the disturbed diurnal BP pattern observed among obese individuals. (The Diurnal Rhythm in Natriuretic Peptide Levels; NCT03834168).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2021; 77:2291-2303
Parcha V, Patel N, Gutierrez OM, Li P, ... Arora G, Arora P
J Am Coll Cardiol: 10 May 2021; 77:2291-2303 | PMID: 33958126
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Stroke Complicating Infective Endocarditis After Transcatheter Aortic Valve Replacement.

Del Val D, Abdel-Wahab M, Mangner N, Durand E, ... Holzhey D, Rodés-Cabau J
Background
Stroke is one of the most common and potentially disabling complications of infective endocarditis (IE). However, scarce data exist about stroke complicating IE after transcatheter aortic valve replacement (TAVR).
Objectives
The purpose of this study was to determine the incidence, risk factors, clinical characteristics, management, and outcomes of patients with definite IE after TAVR complicated by stroke during index IE hospitalization.
Methods
Data from the Infectious Endocarditis after TAVR International Registry (including 569 patients who developed definite IE following TAVR from 59 centers in 11 countries) was analyzed. Patients were divided into two groups according to stroke occurrence during IE admission (stroke [S-IE] vs. no stroke [NS-IE]).
Results
A total of 57 (10%) patients had a stroke during IE hospitalization, with no differences in causative microorganism between groups. S-IE patients exhibited higher rates of acute renal failure, systemic embolization, and persistent bacteremia (p < 0.05 for all). Previous stroke before IE, residual aortic regurgitation ≥moderate after TAVR, balloon-expandable valves, IE within 30 days after TAVR, and vegetation size >8 mm were associated with a higher risk of stroke during the index IE hospitalization (p < 0.05 for all). Stroke rate in patients with no risk factors was 3.1% and increased up to 60% in the presence of >3 risk factors. S-IE patients had higher rates of in-hospital mortality (54.4% vs. 28.7%; p < 0.001) and overall mortality at 1 year (66.3% vs. 45.6%; p < 0.001). Surgical treatment was not associated with improved outcomes in S-IE patients (in-hospital mortality: 46.2% in surgical vs. 58.1% in no surgical treatment; p = 0.47).
Conclusions
Stroke occurred in 1 of 10 patients with IE post-TAVR. A history of stroke, short time between TAVR and IE, vegetation size, valve prosthesis type, and residual aortic regurgitation determined an increased risk. The occurrence of stroke was associated with increased in-hospital and 1-year mortality rates, and surgical treatment failed to improve clinical outcomes.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2021; 77:2276-2287
Del Val D, Abdel-Wahab M, Mangner N, Durand E, ... Holzhey D, Rodés-Cabau J
J Am Coll Cardiol: 10 May 2021; 77:2276-2287 | PMID: 33958124
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Permanent Pacemaker Implantation Following Valve-in-Valve Transcatheter Aortic Valve Replacement: VIVID Registry.

Alperi A, Rodés-Cabau J, Simonato M, Tchetche D, ... Webb JG, Dvir D
Background
Permanent pacemaker implantation (PPI) remains one of the main drawbacks of transcatheter aortic valve replacement (TAVR), but scarce data exist on PPI after valve-in-valve (ViV) TAVR, particularly with the use of newer-generation transcatheter heart valves (THVs).
Objectives
The goal of this study was to determine the incidence, factors associated with, and clinical impact of PPI in a large series of ViV-TAVR procedures.
Methods
Data were obtained from the multicenter VIVID Registry and included the main baseline and procedural characteristics, in-hospital and late (median follow-up: 13 months [interquartile range: 3 to 41 months]) outcomes analyzed according to the need of periprocedural PPI. All THVs except CoreValve, Cribier-Edwards, Sapien, and Sapien XT were considered to be new-generation THVs.
Results
A total of 1,987 patients without prior PPI undergoing ViV-TAVR from 2007 to 2020 were included. Of these, 128 patients (6.4%) had PPI after TAVR, with a significant decrease in the incidence of PPI with the use of new-generation THVs (4.7% vs. 7.4%; p = 0.017), mainly related to a reduced PPI rate with the Evolut R/Pro versus CoreValve (3.7% vs. 9.0%; p = 0.002). There were no significant differences in PPI rates between newer-generation balloon- and self-expanding THVs (6.1% vs. 3.9%; p = 0.18). In the multivariable analysis, older age (odds ratio [OR]: 1.05 for each increase of 1 year; 95% confidence interval [CI]: 1.02 to 1.07; p = 0.001), larger THV size (OR: 1.10; 95% CI: 1.01 to 1.20; p = 0.02), and previous right bundle branch block (OR: 2.04; 95% CI: 1.00 to 4.17; p = 0.05) were associated with an increased risk of PPI. There were no differences in 30-day mortality between the PPI (4.7%) and no-PPI (2.7%) groups (p = 0.19), but PPI patients exhibited a trend toward higher mortality risk at follow-up (hazard ratio: 1.39; 95% CI: 1.02 to 1.91; p = 0.04; p = 0.08 after adjusting for age differences between groups).
Conclusions
In a contemporary large series of ViV-TAVR patients, the rate of periprocedural PPI was relatively low, and its incidence decreased with the use of new-generation THV systems. PPI following ViV-TAVR was associated with a trend toward increased mortality at follow-up.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 10 May 2021; 77:2263-2273
Alperi A, Rodés-Cabau J, Simonato M, Tchetche D, ... Webb JG, Dvir D
J Am Coll Cardiol: 10 May 2021; 77:2263-2273 | PMID: 33958122
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiovascular and Kidney Outcomes across the Glycemic Spectrum: Insights from the UK Biobank.

Honigberg MC, Zekavat SM, Pirruccello JP, Natarajan P, Vaduganathan M
Background
Treatment guidelines for pre-diabetes primarily focus on glycemic control and lifestyle management. Few evidence-based cardiovascular and kidney risk-reduction strategies are available in this population.
Objectives
To characterize cardiovascular and kidney outcomes across the glycemic spectrum.
Methods
Among participants in the UK Biobank without prevalent type 1 diabetes, cardiovascular, or kidney disease, Cox models tested the association of glycemic exposures (type 2 diabetes [T2D], pre-diabetes, normoglycemia) with outcomes (ASCVD, chronic kidney disease [CKD], and heart failure), adjusting for demographic, lifestyle, and cardiometabolic risk factors.
Results
Among 336,709 individuals (mean age 56.3 years, 55.4% female), 46,911 (13.9%) had pre-diabetes and 12,717 (3.8%) had T2D. Over median follow-up of 11.1 years, 6,476 (13.8%) individuals with pre-diabetes developed ≥1 incident outcome, of whom only 802 (12.4%) developed T2D prior to an incident diagnosis. Pre-diabetes and T2D were independently associated with ASCVD (pre-diabetes: aHR 1.11 [95% CI 1.08-1.15], P<0.001; T2D: aHR 1.44 [95% CI 1.37-1.51], P<0.001), CKD (pre-diabetes: aHR 1.08 [95% CI 1.02-1.14], P<0.001; T2D: aHR 1.57 [95% CI 1.46-1.69], P<0.001), and heart failure (pre-diabetes: aHR 1.07 [95% CI 1.01-1.14], P=0.03; T2D: aHR 1.25 [95% CI 1.14-1.37], P<0.001). Compared with HbA1c <5.0%, covariate-adjusted risks increased significantly for ASCVD above HbA1c 5.4%, CKD above HbA1c 6.2%, and heart failure above HbA1c 7.0%.
Conclusions
Pre-diabetes and T2D were associated with ASCVD, CKD, and heart failure, but a substantial gradient of risk was observed across HbA1c levels below the threshold for diabetes. These findings highlight the need to design risk-reduction strategies across the glycemic spectrum.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 10 May 2021; epub ahead of print
Honigberg MC, Zekavat SM, Pirruccello JP, Natarajan P, Vaduganathan M
J Am Coll Cardiol: 10 May 2021; epub ahead of print | PMID: 34015477
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Total Ischemic Event Reduction with Rivaroxaban after Peripheral Arterial Revascularization in the VOYAGER PAD Trial.

Bauersachs RM, Szarek M, Brodmann M, Gudz I, ... Bonaca MP, VOYAGER PAD Committees and Investigators
Background
Patients with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population is unknown.
Objectives
To evaluate the total burden of vascular events in PAD patients after LER and the efficacy of low dose rivaroxaban on total events.
Methods
VOYAGER PAD randomized PAD patients undergoing LER to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone. The primary endpoint was time to first event of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or CV death. The current analysis considered all events (first and subsequent) for components of the primary endpoint as well as additional vascular events including peripheral revascularizations and venous thromboembolism. Hazard ratios were estimated by marginal proportional hazards models.
Results
Among 6564 randomized there were 4714 total first and subsequent vascular events including 1614 primary endpoint events and 3100 other vascular events. Rivaroxaban reduced total primary endpoint events (HR 0.86,95% CI 0.75-0.98; p=0.02) and total vascular events (HR 0.86,95% CI 0.79-0.95; p=0.003). An estimated 4.4 primary and 12.5 vascular events/100 participants were avoided with rivaroxaban over three years.
Conclusions
Symptomatic PAD patients undergoing LER have a high total event burden which is significantly reduced with rivaroxaban. Total event reduction may be useful metric to quantify the efficacy of rivaroxaban in this setting.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 06 May 2021; epub ahead of print
Bauersachs RM, Szarek M, Brodmann M, Gudz I, ... Bonaca MP, VOYAGER PAD Committees and Investigators
J Am Coll Cardiol: 06 May 2021; epub ahead of print | PMID: 34010631
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Management of Patients With Aortocoronary Saphenous Vein Graft Aneurysms: JACC State-of-the-Art Review.

Vinciguerra M, Spadaccio C, Tennyson C, Karuppannan M, ... Greco E, Rose D
Saphenous vein graft aneurysms (SVGAs) following coronary artery bypass grafting (CABG) surgery were first described in 1975. Although rare, in the absence of a prompt diagnosis, SVGAs can be responsible for serious complications and adverse outcomes. The clinical presentation of SVGAs described in the literature can vary from an asymptomatic patient with an incidental radiological finding to a profoundly shocked patient with life-threatening hemorrhage secondary to SVGA rupture. Improvements in diagnostic tools within the last decade, such as multislice computed tomographic scanning, has enabled early detection of SVGAs, and therefore, an expansion of the current management options. In this review, the current data and knowledge about clinical presentation, diagnosis, natural history, and treatment of SVGAs are updated, with a specific emphasis on the evolution of management strategies of this rare complication over the last 45 years. Finally, a clinical algorithm to guide decision-making and management is proposed.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2021; 77:2236-2253
Vinciguerra M, Spadaccio C, Tennyson C, Karuppannan M, ... Greco E, Rose D
J Am Coll Cardiol: 03 May 2021; 77:2236-2253 | PMID: 33926660
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lifespan Perspective on Congenital Heart Disease Research: JACC State-of-the-Art Review.

Diller GP, Arvanitaki A, Opotowsky AR, Jenkins K, ... Li Y, Marelli A
More than 90% of patients with congenital heart disease (CHD) are nowadays surviving to adulthood and adults account for over two-thirds of the contemporary CHD population in Western countries. Although outcomes are improved, surgery does not cure CHD. Decades of longitudinal observational data are currently motivating a paradigm shift toward a lifespan perspective and proactive approach to CHD care. The aim of this review is to operationalize these emerging concepts by presenting new constructs in CHD research. These concepts include long-term trajectories and a life course epidemiology framework. Focusing on a precision health, we propose to integrate our current knowledge on the genome, phenome, and environome across the CHD lifespan. We also summarize the potential of technology, especially machine learning, to facilitate longitudinal research by embracing big data and multicenter lifelong data collection.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 03 May 2021; 77:2219-2235
Diller GP, Arvanitaki A, Opotowsky AR, Jenkins K, ... Li Y, Marelli A
J Am Coll Cardiol: 03 May 2021; 77:2219-2235 | PMID: 33926659
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Anesthesia Strategy and Valve Type on Clinical Outcomes After Transcatheter Aortic Valve Replacement.

Feistritzer HJ, Kurz T, Stachel G, Hartung P, ... Thiele H, SOLVE-TAVI Investigators
Background
The randomized SOLVE-TAVI (compariSon of secOnd-generation seLf-expandable vs. balloon-expandable Valves and gEneral vs. local anesthesia in Transcatheter Aortic Valve Implantation) trial compared newer-generation self-expanding valves (SEV) and balloon-expandable valves (BEV) as well as local anesthesia with conscious sedation (CS) and general anesthesia (GA) in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). Both strategies showed similar outcomes at 30 days.
Objectives
The purpose of this study was to compare clinical outcomes during 1-year follow-up in the randomized SOLVE-TAVI trial.
Methods
Using a 2 × 2 factorial design 447 intermediate- to high-risk patients with severe, symptomatic aortic stenosis were randomly assigned to transfemoral TAVR using either the SEV (Evolut R, Medtronic Inc., Minneapolis, Minnesota) or the BEV (Sapien 3, Edwards Lifesciences, Irvine, California) as well as CS or GA at 7 sites.
Results
In the valve-comparison strategy, rates of the combined endpoint of all-cause mortality, stroke, moderate or severe paravalvular leakage, and permanent pacemaker implantation were similar between the BEV and SEV group (n = 84, 38.3% vs. n = 87, 40.4%; hazard ratio: 0.94; 95% confidence interval: 0.70 to 1.26; p = 0.66) at 1 year. Regarding the anesthesia comparison, the combined endpoint of all-cause mortality, stroke, myocardial infarction, and acute kidney injury occurred with similar rates in the GA and CS groups (n = 61, 25.7% vs. n = 54, 23.8%; hazard ratio: 1.09; 95% confidence interval: 0.76 to 1.57; p = 0.63).
Conclusions
In intermediate- to high-risk patients undergoing transfemoral TAVR, newer-generation SEV and BEV as well as CS and GA showed similar clinical outcomes at 1 year using a combined clinical endpoint. (SecOnd-generation seLf-expandable Versus Balloon-expandable Valves and gEneral Versus Local Anesthesia in TAVI [SOLVE-TAVI]; NCT02737150).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2021; 77:2204-2215
Feistritzer HJ, Kurz T, Stachel G, Hartung P, ... Thiele H, SOLVE-TAVI Investigators
J Am Coll Cardiol: 03 May 2021; 77:2204-2215 | PMID: 33926657
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

ST-Segment Elevation Myocardial Infarction Following Transcatheter Aortic Valve Replacement.

Faroux L, Lhermusier T, Vincent F, Nombela-Franco L, ... Campelo-Parada F, Rodés-Cabau J
Background
Among patients with acute coronary syndrome following transcatheter aortic valve replacement (TAVR), those presenting with ST-segment elevation myocardial infarction (STEMI) are at highest risk.
Objectives
The goal of this study was to determine the clinical characteristics, management, and outcomes of STEMI after TAVR.
Methods
This was a multicenter study including 118 patients presenting with STEMI at a median of 255 days (interquartile range: 9 to 680 days) after TAVR. Procedural features of STEMI after TAVR managed with primary percutaneous coronary intervention (PCI) were compared with all-comer STEMI: 439 non-TAVR patients who had primary PCI within the 2 weeks before and after each post-TAVR STEMI case in 5 participating centers from different countries.
Results
Median door-to-balloon time was higher in TAVR patients (40 min [interquartile range: 25 to 57 min] vs. 30 min [interquartile range: 25 to 35 min]; p = 0.003). Procedural time, fluoroscopy time, dose-area product, and contrast volume were also higher in TAVR patients (p < 0.01 for all). PCI failure occurred more frequently in patients with previous TAVR (16.5% vs. 3.9%; p < 0.001), including 5 patients in whom the culprit lesion was not revascularized owing to coronary ostia cannulation failure. In-hospital and late (median of 7 months [interquartile range: 1 to 21 months]) mortality rates were 25.4% and 42.4%, respectively (20.6% and 38.2% in primary PCI patients), and estimated glomerular filtration rate <60 ml/min (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.42 to 6.43; p = 0.004), Killip class ≥2 (HR: 2.74; 95% CI: 1.37 to 5.49; p = 0.004), and PCI failure (HR: 3.23; 95% CI: 1.42 to 7.31; p = 0.005) determined an increased risk.
Conclusions
STEMI after TAVR was associated with very high in-hospital and mid-term mortality. Longer door-to-balloon times and a higher PCI failure rate were observed in TAVR patients, partially due to coronary access issues specific to the TAVR population, and this was associated with poorer outcomes.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2021; 77:2187-2199
Faroux L, Lhermusier T, Vincent F, Nombela-Franco L, ... Campelo-Parada F, Rodés-Cabau J
J Am Coll Cardiol: 03 May 2021; 77:2187-2199 | PMID: 33926655
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome.

Garland EM, Gamboa A, Nwazue VC, Celedonio JE, ... Dupont WD, Raj SR
Background
High sodium intake is recommended for the treatment of postural tachycardia syndrome (POTS) to counteract the hypovolemia and elevated plasma norepinephrine that contribute to excessive orthostatic tachycardia, but evidence of its efficacy is not available.
Objectives
This study tested whether a high sodium (HS) diet reduces orthostatic tachycardia (Δ heart rate) and upright heart rate compared with a low sodium (LS) diet in POTS patients, and secondarily its effect on plasma volume (PV) and plasma norepinephrine.
Methods
A total of 14 POTS patients and 13 healthy control subjects (HC), age 23 to 49 years, were enrolled in a crossover study with 6 days of LS (10 mEq sodium/day) or HS (300 mEq sodium/day) diet. Supine and standing heart rate, blood pressure, serum aldosterone, plasma renin activity, blood volume, and plasma norepinephrine and epinephrine were measured.
Results
In POTS, the HS diet reduced upright heart rate and Δ heart rate compared with the LS diet. Total blood volume and PV increased, and standing norepinephrine decreased with the HS compared with the LS diet. However, upright heart rate, Δ heart rate, and upright norepinephrine remained higher in POTS than in HC on the HS diet (median 117 beats/min [interquartile range: 98 to 121 beats/min], 46 beats/min [interquartile range: 32 to 55 beats/min], and 753 pg/ml [interquartile range: 498 to 919 pg/ml] in POTS vs. 85 beats/min [interquartile range: 77 to 95 beats/min], 19 beats/min [interquartile range: 11 to 32 beats/min], and 387 pg/ml [interquartile range: 312 to 433 pg/ml] in HC, respectively), despite no difference in the measured PV.
Conclusions
In POTS patients, high dietary sodium intake compared with low dietary sodium intake increases plasma volume, lowers standing plasma norepinephrine, and decreases Δ heart rate. (Dietary Salt in Postural Tachycardia Syndrome; NCT01547117).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2021; 77:2174-2184
Garland EM, Gamboa A, Nwazue VC, Celedonio JE, ... Dupont WD, Raj SR
J Am Coll Cardiol: 03 May 2021; 77:2174-2184 | PMID: 33926653
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Myocardial Histopathology in Patients With Obstructive Hypertrophic Cardiomyopathy.

Cui H, Schaff HV, Lentz Carvalho J, Nishimura RA, ... Ommen SR, Maleszewski JJ
Background
Hypertrophic cardiomyopathy (HCM) is characterized by multiple pathological features including myocyte hypertrophy, myocyte disarray, and interstitial fibrosis.
Objectives
This study sought to correlate myocardial histopathology with clinical characteristics of patients with obstructive HCM and post-operative outcomes following septal myectomy.
Methods
The authors reviewed the pathological findings of the myocardial specimens from 1,836 patients with obstructive HCM who underwent septal myectomy from 2000 to 2016. Myocyte hypertrophy, myocyte disarray, interstitial fibrosis, and endocardial thickening were graded and analyzed.
Results
The median age at operation was 54.2 years (43.5 to 64.3 years), and 1,067 (58.1%) were men. A weak negative correlation between myocyte disarray and age at surgery was identified (ρ = -0.22; p < 0.001). Myocyte hypertrophy (p < 0.001), myocyte disarray (p < 0.001), and interstitial fibrosis (p < 0.001) were positively associated with implantable cardioverter-defibrillator implantation. Interstitial fibrosis (p < 0.001) and endocardial thickening (p < 0.001) were associated with atrial fibrillation pre-operatively. In the Cox survival model, older age (p < 0.001), lower degree of myocyte hypertrophy (severe vs. mild hazard ratio: 0.41; 95% confidence interval: 0.19 to 0.86; p = 0.040), and lower degree of endocardial thickening (moderate vs. mild hazard ratio: 0.75; 95% confidence interval: 0.58 to 0.97; p = 0.019) were independently associated with worse post-myectomy survival. Among 256 patients who had genotype analysis, patients with pathogenic or likely pathogenic variants (n = 62) had a greater degree of myocyte disarray (42% vs. 15% vs. 20%; p = 0.022). Notably, 13 patients with pathogenic or likely pathogenic genetic variants of HCM had no myocyte disarray.
Conclusions
Histopathology was associated with clinical manifestations including the age of disease onset and arrhythmias. Myocyte hypertrophy and endocardial thickening were negatively associated with post-myectomy mortality.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 03 May 2021; 77:2159-2170
Cui H, Schaff HV, Lentz Carvalho J, Nishimura RA, ... Ommen SR, Maleszewski JJ
J Am Coll Cardiol: 03 May 2021; 77:2159-2170 | PMID: 33926651
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Kidney Function and Outcomes in Patients Hospitalized with Heart Failure.

Patel RB, Fonarow GC, Greene SJ, Zhang S, ... Yancy CW, Vaduganathan M
Background
Few contemporary data exist evaluating care patterns and outcomes in HF across the spectrum of kidney function.
Objectives
To characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction.
Methods
We evaluated quality metrics among patients hospitalized with HF at 418 sites in the GWTG-HF registry from 2014-2019 by discharge CKD-EPI-derived eGFR. We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality.
Results
Among 365,494 hospitalizations (age 72±15y, LVEF 43±17%), median discharge eGFR was 51(34-72) mL/min/1.73m2, 234,332 (64%) had eGFR<60 mL/min/1.73m2, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014-2019. Among 157,439 patients with HFrEF(≤40%), discharge guideline-directed medical therapies, including β-blockers, were lowest in discharge eGFR<30 mL/min/1.73m2 or dialysis (P<0.001). \"Triple therapy\" with ACE inhibitor/ARB/ARNI+β-blocker+MRA was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60-89, 45-59, 30-44, <30 mL/min/1.73m2 and dialysis, respectively; P<0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; P<0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger in HFrEF compared with HF with mid-range or preserved EF (Pinteraction=0.045).
Conclusion
Despite facing elevated risks of mortality, patients with comorbid HFrEF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 03 May 2021; epub ahead of print
Patel RB, Fonarow GC, Greene SJ, Zhang S, ... Yancy CW, Vaduganathan M
J Am Coll Cardiol: 03 May 2021; epub ahead of print | PMID: 33989713
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial.

Herzog CA, Simegn MA, Xu Y, Costa SR, ... Hochman JS, Bangalore S
Background
Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing.
Objectives
In this post-hoc analysis from ISCHEMIA-CKD, we compared outcomes of patients not listed versus those listed according to management strategy.
Methods
In ISCHEMIA-CKD (n=777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction [MI]) and secondary (death, nonfatal MI, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed.
Results
Compared with those not listed, listed patients were younger (60 versus 65 years), less likely of Asian race (15% versus 29%), more likely on dialysis (83% versus 44%), had fewer anginal symptoms, and more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for the primary outcome were 0.91 (0.54-1.54) and 1.03 (0.78-1.37) for those listed and not listed, respectively (pinteraction=0.68). Adjusted HR for secondary outcomes were 0.89 (0.55-1.46) in listed and 1.17 (0.89-1.53) in those not listed (pinteraction=0.35).
Conclusions
In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 03 May 2021; epub ahead of print
Herzog CA, Simegn MA, Xu Y, Costa SR, ... Hochman JS, Bangalore S
J Am Coll Cardiol: 03 May 2021; epub ahead of print | PMID: 33989711
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

NHLBI-CMREF Workshop Report on Pulmonary Vascular Disease Classification: JACC State-of-the-Art Review.

Oldham WM, Hemnes AR, Aldred MA, Barnard J, ... Loscalzo J, Xiao L
The National Heart, Lung, and Blood Institute and the Cardiovascular Medical Research and Education Fund held a workshop on the application of pulmonary vascular disease omics data to the understanding, prevention, and treatment of pulmonary vascular disease. Experts in pulmonary vascular disease, omics, and data analytics met to identify knowledge gaps and formulate ideas for future research priorities in pulmonary vascular disease in line with National Heart, Lung, and Blood Institute Strategic Vision goals. The group identified opportunities to develop analytic approaches to multiomic datasets, to identify molecular pathways in pulmonary vascular disease pathobiology, and to link novel phenotypes to meaningful clinical outcomes. The committee suggested support for interdisciplinary research teams to develop and validate analytic methods, a national effort to coordinate biosamples and data, a consortium of preclinical investigators to expedite target evaluation and drug development, longitudinal assessment of molecular biomarkers in clinical trials, and a task force to develop a master clinical trials protocol for pulmonary vascular disease.

Copyright © 2021 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 26 Apr 2021; 77:2040-2052
Oldham WM, Hemnes AR, Aldred MA, Barnard J, ... Loscalzo J, Xiao L
J Am Coll Cardiol: 26 Apr 2021; 77:2040-2052 | PMID: 33888254
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Therapeutic Manipulation of Myocardial Metabolism: JACC State-of-the-Art Review.

Honka H, Solis-Herrera C, Triplitt C, Norton L, Butler J, DeFronzo RA
The mechanisms responsible for the positive and unexpected cardiovascular effects of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes remain to be defined. It is likely that some of the beneficial cardiac effects of these antidiabetic drugs are mediated, in part, by altered myocardial metabolism. Common cardiometabolic disorders, including the metabolic (insulin resistance) syndrome and type 2 diabetes, are associated with altered substrate utilization and energy transduction by the myocardium, predisposing to the development of heart disease. Thus, the failing heart is characterized by a substrate shift toward glycolysis and ketone oxidation in an attempt to meet the high energetic demand of the constantly contracting heart. This review examines the metabolic pathways and clinical implications of myocardial substrate utilization in the normal heart and in cardiometabolic disorders, and discusses mechanisms by which antidiabetic drugs and metabolic interventions improve cardiac function in the failing heart.

Copyright © 2021. Published by Elsevier Inc.

J Am Coll Cardiol: 26 Apr 2021; 77:2022-2039
Honka H, Solis-Herrera C, Triplitt C, Norton L, Butler J, DeFronzo RA
J Am Coll Cardiol: 26 Apr 2021; 77:2022-2039 | PMID: 33888253
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Group Medical Visit and Microfinance Intervention for Patients With Diabetes or Hypertension in Kenya.

Vedanthan R, Kamano JH, Chrysanthopoulou SA, Mugo R, ... Hogan JW, Fuster V
Background
Incorporating social determinants of health into care delivery for chronic diseases is a priority.
Objectives
The goal of this study was to evaluate the impact of group medical visits and/or microfinance on blood pressure reduction.
Methods
The authors conducted a cluster randomized trial with 4 arms and 24 clusters: 1) usual care (UC); 2) usual care plus microfinance (MF); 3) group medical visits (GMVs); and 4) GMV integrated into MF (GMV-MF). The primary outcome was 1-year change in systolic blood pressure (SBP). Mixed-effects intention-to-treat models were used to evaluate the outcomes.
Results
A total of 2,890 individuals (69.9% women) were enrolled (708 UC, 709 MF, 740 GMV, and 733 GMV-MF). Average baseline SBP was 157.5 mm Hg. Mean SBP declined -11.4, -14.8, -14.7, and -16.4 mm Hg in UC, MF, GMV, and GMV-MF, respectively. Adjusted estimates and multiplicity-adjusted 98.3% confidence intervals showed that, relative to UC, SBP reduction was 3.9 mm Hg (-8.5 to 0.7), 3.3 mm Hg (-7.8 to 1.2), and 2.3 mm Hg (-7.0 to 2.4) greater in GMV-MF, GMV, and MF, respectively. GMV and GMV-MF tended to benefit women, and MF and GMV-MF tended to benefit poorer individuals. Active participation in GMV-MF was associated with greater benefit.
Conclusions
A strategy combining GMV and MF for individuals with diabetes or hypertension in Kenya led to clinically meaningful SBP reductions associated with cardiovascular benefit. Although the significance threshold was not met in pairwise comparison hypothesis testing, confidence intervals for GMV-MF were consistent with impacts ranging from substantive benefit to neutral effect relative to UC. Incorporating social determinants of health into care delivery for chronic diseases has potential to improve outcomes. (Bridging Income Generation With Group Integrated Care [BIGPIC]; NCT02501746).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Apr 2021; 77:2007-2018
Vedanthan R, Kamano JH, Chrysanthopoulou SA, Mugo R, ... Hogan JW, Fuster V
J Am Coll Cardiol: 26 Apr 2021; 77:2007-2018 | PMID: 33888251
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Patient Selection for Intensive Blood Pressure Management Based on Benefit and Adverse Events.

Bress AP, Greene T, Derington CG, Shen J, ... Moran AE, SPRINT Research Group
Background
Intensive systolic blood pressure (SBP) treatment prevents cardiovascular disease (CVD) events in patients with high CVD risk on average, though benefits likely vary among patients.
Objectives
The aim of this study was to predict the magnitude of benefit (reduced CVD and all-cause mortality risk) along with adverse event (AE) risk from intensive versus standard SBP treatment.
Methods
This was a secondary analysis of SPRINT (Systolic Blood Pressure Intervention Trial). Separate benefit outcomes were the first occurrence of: 1) a CVD composite of acute myocardial infarction or other acute coronary syndrome, stroke, heart failure, or CVD death; and 2) all-cause mortality. Treatment-related AEs of interest included hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, and acute kidney injury. Modified elastic net Cox regression was used to predict absolute risk for each outcome and absolute risk differences on the basis of 36 baseline variables available at the point of care with intensive versus standard treatment.
Results
Among 8,828 SPRINT participants (mean age 67.9 years, 35% women), 600 CVD composite events, 363 all-cause deaths, and 481 treatment-related AEs occurred over a median follow-up period of 3.26 years. Individual participant risks were predicted for the CVD composite (C index = 0.71), all-cause mortality (C index = 0.75), and treatment-related AEs (C index = 0.69). Higher baseline CVD risk was associated with greater benefit (i.e., larger absolute CVD risk reduction). Predicted CVD benefit and predicted increased treatment-related AE risk were correlated (Spearman correlation coefficient = -0.72), and 95% of participants who fell into the highest tertile of predicted benefit also had high or moderate predicted increases in treatment-related AE risk. Few were predicted as high benefit with low AE risk (1.8%) or low benefit with high AE risk (1.5%). Similar results were obtained for all-cause mortality.
Conclusions
SPRINT participants with higher baseline predicted CVD risk gained greater absolute benefit from intensive treatment. Participants with high predicted benefit were also most likely to experience treatment-related AEs, but AEs were generally mild and transient. Patients should be prioritized for intensive SBP treatment on the basis of higher predicted benefit. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Apr 2021; 77:1977-1990
Bress AP, Greene T, Derington CG, Shen J, ... Moran AE, SPRINT Research Group
J Am Coll Cardiol: 26 Apr 2021; 77:1977-1990 | PMID: 33888247
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Incidence and Outcomes of Pneumonia in Patients With Heart Failure.

Shen L, Jhund PS, Anand IS, Bhatt AS, ... Solomon SD, McMurray JJV
Background
The incidence of pneumonia and subsequent outcomes has not been compared in patients with heart failure and reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF).
Objectives
This study aimed to examine the rate and impact of pneumonia in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in Heart Failure with Preserved Ejection Fraction) trials.
Methods
The authors analyzed the incidence of investigator-reported pneumonia and the rates of HF hospitalization, cardiovascular death, and all-cause death before and after the occurrence of pneumonia, and estimated risk after the first occurrence of pneumonia in unadjusted and adjusted analyses (the latter including N-terminal pro-B-type natriuretic peptide).
Results
In PARADIGM-HF, 528 patients (6.3%) developed pneumonia after randomization, giving an incidence rate of 29 (95% CI: 27 to 32) per 1,000 patient-years. In PARAGON-HF, 510 patients (10.6%) developed pneumonia, giving an incidence rate of 39 (95% CI: 36 to 42) per 1,000 patient-years. The subsequent risk of all trial outcomes was elevated after the occurrence of pneumonia. In PARADIGM-HF, the adjusted hazard ratio (HR) for the risk of death from any cause was 4.34 (95% CI: 3.73 to 5.05). The corresponding adjusted HR in PARAGON-HF was 3.76 (95% CI: 3.09 to 4.58).
Conclusions
The incidence of pneumonia was high in patients with HF, especially HFpEF, at around 3 times the expected rate. A first episode of pneumonia was associated with 4-fold higher mortality. (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF], NCT01035255; Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] With ARB [Angiotensin Receptor Blocker] Global Outcomes in Heart Failure With Preserved Ejection Fraction [PARAGON-HF], NCT01920711).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

J Am Coll Cardiol: 26 Apr 2021; 77:1961-1973
Shen L, Jhund PS, Anand IS, Bhatt AS, ... Solomon SD, McMurray JJV
J Am Coll Cardiol: 26 Apr 2021; 77:1961-1973 | PMID: 33888245
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.