<div><h4>Exercise-Induced Left Atrial Hypertension in Heart Failure With Preserved Ejection Fraction.</h4><i>Litwin SE, Komtebedde J, Hu M, Burkhoff D, ... Shah SJ, REDUCE LAP-HF Investigators and Research Staff</i><br /><b>Background</b><br />Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure.<br /><b>Objectives</b><br />This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH).<br /><b>Methods</b><br />The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH).<br /><b>Results</b><br />Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e\', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present.<br /><b>Conclusions</b><br />Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 14 Mar 2023; epub ahead of print</small></div>

<div><h4>Cardiovascular Disease and Mortality in Black Women Carrying the Amyloidogenic V122I Transthyretin Gene Variant.</h4><i>Haring B, Hunt RP, Shadyab AH, Eaton C, ... Kooperberg C, Wassertheil-Smoller S</i><br /><b>Background</b><br />Long-term data on cardiovascular disease (CVD) and mortality in female carriers of the transthyretin (TTR) V122I (pV142I) variant, one of the most common variants of hereditary transthyretin cardiac amyloidosis, are sparse and the effects of blood pressure, heart rate, body mass index, and physical activity on CVD outcomes remain largely unknown.<br /><b>Objectives</b><br />The aim was to first examine the relationship of TTR V122I (pV142I) carrier status with CVD and mortality and second to investigate the effects of blood pressure, heart rate, body mass index, and physical activity in a large cohort of postmenopausal women.<br /><b>Methods</b><br />The study population consisted of 9,862 non-Hispanic Black/African American women, 9,529 noncarriers and 333 TTR V122I carriers, enrolled in the Women\'s Health Initiative at 40 centers in the United States. Women were generally healthy and postmenopausal at the time of enrollment (1993-1998). CVD was defined as a composite endpoint consisting of coronary heart disease, stroke, acute heart failure or CVD death, and all-cause mortality. CVD cases were based on self-reported annual mailed health updates. All information was centrally adjudicated by trained physicians. HRs and 95% CIs were obtained from adjusted Cox proportional hazards models.<br /><b>Results</b><br />Among 9,862 Black female participants (mean age: 62 years [IQR: 56-67 years]), the population frequency of the TTR V122I variant was 3.4% (333 variant carriers and 9,529 noncarriers). During a mean follow-up of 16.1 years (IQR: 9.7-22.2 years), incident CVD occurred in 2,229 noncarriers and 96 carriers, whereas 2,689 noncarriers and 108 carriers died. In adjusted models including demographic, lifestyle, and medical history covariates, TTR V122I carriers were at higher risk of the composite endpoint CVD (HR: 1.52; 95% CI: 1.22-1.88), acute heart failure (HR: 2.21; 95% CI: 1.53-3.18), coronary heart disease (HR: 1.80; 95% CI: 1.30-2.47), CVD death (HR: 1.70; 95% CI: 1.26-2.30), and all-cause mortality (HR: 1.28; 95% CI: 1.04-1.56). The authors found a significant interaction by age but not by blood pressure, heart rate, body mass index, or physical activity.<br /><b>Conclusions</b><br />Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers. In case of clinical suspicion of amyloidosis, they should be screened for TTR V122I (pV142I) carrier status to ensure early treatment onset.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 05 Mar 2023; epub ahead of print</small></div>

<div><h4>Longer-Term Effects of Remote Patient Management Following Hospital Discharge After Acute Systolic Heart Failure: The Randomized E-INH Trial.</h4><i>Angermann CE, Sehner S, Faller H, Güder G, ... Störk ST, INH Study Group and of the Competence Network Heart Failure</i><br /><b>Background</b><br />The randomized INH (Interdisciplinary Network Heart Failure) trial (N = 715) reported that 6 months\' remote patient management (RPM) (HeartNetCare-HF) did not reduce the primary outcome (time to all-cause death/rehospitalization) vs usual care (UC) in patients discharged after admission for acute heart failure, but suggested lower mortality and better quality of life in the RPM group.<br /><b>Objectives</b><br />The Extended (E)-INH trial investigated the effects of 18 months\' HeartNetCare-HF on the same primary outcome in an expanded population (N = 1,022) and followed survivors up to 60 months (primary outcome events) or up to 120 months (mortality) after RPM termination.<br /><b>Methods</b><br />Eligible patients aged ≥18 years, hospitalized for acute heart failure, and with predischarge ejection fraction ≤40% were randomized to RPM (RPM+UC; n = 509) or control (UC; n = 513). Follow-up visits were every 6 months during RPM, and then at 36, 60, and 120 months.<br /><b>Results</b><br />The primary outcome did not differ between groups at 18 months (60.7% [95% CI: 56.5%-65.0%] vs 61.2% [95% CI: 57.0%-65.4%]) or 60 months (78.1% [95% CI: 74.4%-81.6%] vs 82.8% [95% CI: 79.5%-86.0%]). At 60 and 120 months, all-cause mortality was lower in patients previously undergoing RPM (41.1% [95% CI: 37.0%-45.5%] vs 47.4% [95% CI: 43.2%-51.8%]; P = 0.040 and 64.0% [95% CI: 59.8%-68.2%] vs 69.6% [95% CI: 65.6%-73.5%]; P = 0.019). At all visits, health-related quality of life was better in patients exposed to HeartNetCare-HF vs UC.<br /><b>Conclusions</b><br />Although 18 months\' HeartNetCare-HF did not significantly reduce the primary outcome of death or rehospitalization at 60 months, lower 120-month mortality in patients previously undergoing HeartNetCare-HF suggested beneficial longer-term effects, although the possibility of a chance finding remains.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Mar 2023; 11:191-206</small></div>

<div><h4>Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial.</h4><i>Chieng D, Sugumar H, Segan L, Tan C, ... Kaye DM, Ling LH</i><br /><b>Background</b><br />Patients with heart failure with preserved ejection fraction (HFpEF) frequently develop atrial fibrillation (AF). There are no randomized trials examining the effects of AF ablation on HFpEF outcomes.<br /><b>Objectives</b><br />The aim of this study is to compare the effects of AF ablation vs usual medical therapy on markers of HFpEF severity, including exercise hemodynamics, natriuretic peptide levels, and patient symptoms.<br /><b>Methods</b><br />Patients with concomitant AF and HFpEF underwent exercise right heart catheterization and cardiopulmonary exercise testing. HFpEF was confirmed with pulmonary capillary wedge pressure (PCWP) of 15 mm Hg at rest or ≥25 mm Hg on exercise. Patients were randomized to AF ablation vs medical therapy, with investigations repeated at 6 months. The primary outcome was change in peak exercise PCWP on follow-up.<br /><b>Results</b><br />A total of 31 patients (mean age: 66.1 years; 51.6% females, 80.6% persistent AF) were randomized to AF ablation (n = 16) vs medical therapy (n = 15). Baseline characteristics were comparable across both groups. At 6 months, ablation reduced the primary outcome of peak PCWP from baseline (30.4 ± 4.2 to 25.4 ± 4.5 mm Hg; P < 0.01). Improvements were also seen in peak relative VO<sub>2</sub> (20.2 ± 5.9 to 23.1 ± 7.2 mL/kg per minute; P < 0.01), N-terminal pro brain natriuretic peptide levels (794 ± 698 to 141 ± 60 ng/L; P = 0.04), and MLHF (Minnesota Living with Heart Failure) score (51 ± -21.9 to 16.6 ± 17.5; P < 0.01). No differences were detected in the medical arm. Following ablation, 50% no longer met exercise right heart catheterization-based criteria for HFpEF vs 7% in the medical arm (P = 0.02).<br /><b>Conclusions</b><br />AF ablation improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with concomitant AF and HFpEF.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 28 Feb 2023; epub ahead of print</small></div>

<div><h4>Recency of Heart Failure Hospitalization, Outcomes, and the Effect of Empagliflozin: An EMPEROR-Pooled Analysis.</h4><i>Ferreira JP, Zannad F, Butler J, Filippatos G, ... Anker SD, Packer M</i><br /><b>Background</b><br />Patients with a recent heart failure (HF) hospitalization have a high risk of rehospitalization and mortality. Early treatment may have a substantial impact on patient outcomes.<br /><b>Objectives</b><br />The study sought to study the outcomes and effect of empagliflozin according to timing of prior HF hospitalization.<br /><b>Methods</b><br />EMPEROR-Pooled (EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) and EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction) combined) included 9,718 HF patients who were grouped according to the recency of HF hospitalization (none, <3 months, 3-6 months, 6-12 months, >12 months). The primary outcome was a composite of time to first of HF hospitalization or cardiovascular death, over a median follow-up of 21 months.<br /><b>Results</b><br />The primary outcome event rates (per 100 person-years) in the placebo group were 26.7, 18.1, 13.7, and 2.8 for patients hospitalized within 3 months, 3-6 months, 6-12 months, and >12 months, respectively. The relative risk reduction of primary outcome events with empagliflozin was similar across HF hospitalization categories (P interaction = 0.67). The primary outcome absolute risk reduction was more pronounced among patients with a recent HF hospitalization but without statistical heterogeneity of treatment effect: -6.9, -5.5, -0.8, and -0.6 events prevented per 100 person-years for patients hospitalized within <3 months, 3-6 months, 6-12 months, and >12 months, respectively, and -2.4 events prevented per 100 person-years of follow-up in those without a prior HF hospitalization (P interaction = 0.64). Empagliflozin was safe irrespective of HF hospitalization recency.<br /><b>Conclusions</b><br />Patients with a recent HF hospitalization have a high risk of events. Empagliflozin reduced HF events regardless of HF hospitalization recency.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 20 Feb 2023; epub ahead of print</small></div>

<div><h4>Impact of the 2018 UNOS Heart Transplant Policy Changes on Patient Outcomes.</h4><i>Maitra NS, Dugger SJ, Balachandran IC, Civitello AB, Khazanie P, Rogers JG</i><br /><AbstractText>In 2018, the United Network for Organ Sharing implemented a 6-tier allocation policy to replace the prior 3-tier system. Given increasing listings of critically ill candidates for heart transplantation and lengthening waitlist times, the new policy aimed to better stratify candidates by waitlist mortality, shorten waiting times for high priority candidates, add objective criteria for common cardiac conditions, and further broaden sharing of donor hearts. There have been significant shifts in cardiac transplantation practices and patient outcomes following the implementation of the new policy, including changes in listing practices, waitlist time and mortality, transplant donor characteristics, post-transplantation outcomes, and mechanical circulatory support use. This review aims to highlight emerging trends in United States heart transplantation practice and outcomes following the implementation of the 2018 United Network for Organ Sharing heart allocation policy and to address areas for future modification.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 16 Feb 2023; epub ahead of print</small></div>

<div><h4>Effect of Training on Vascular Function and Repair in Heart Failure With Preserved Ejection Fraction.</h4><i>Gevaert AB, Böhm B, Hartmann H, Goovaerts I, ... Halle M, Van Craenenbroeck EM</i><br /><b>Background</b><br />Exercise training improves peak oxygen uptake (V̇O<sub>2</sub>peak) in heart failure with preserved ejection fraction (HFpEF). Multiple adaptations have been addressed, but the role of circulating endothelium-repairing cells and vascular function have not been well defined.<br /><b>Objectives</b><br />The authors investigated effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on vascular function and repair in HFpEF.<br /><b>Methods</b><br />This study is a subanalysis of the OptimEx-Clin Study randomizing patients with HFpEF (n = 180) to HIIT, MICT, or guideline control. At baseline, 3, and 12 months, the authors measured peripheral arterial tonometry (valid baseline measurement in n = 109), flow-mediated dilation (n = 59), augmentation index (n = 94), and flow cytometry (n = 136) for endothelial progenitor cells and angiogenic T cells. Abnormal values were defined as outside 90% of published sex-specific reference values.<br /><b>Results</b><br />At baseline, abnormal values (%) were observed for augmentation index in 66%, peripheral arterial tonometry in 17%, flow-mediated dilation in 25%, endothelial progenitor cells in 42%, and angiogenic T cells in 18%. These parameters did not change significantly after 3 or 12 months of HIIT or MICT. Results remained unchanged when confining analysis to patients with high adherence to training.<br /><b>Conclusions</b><br />In patients with HFpEF, high augmentation index was common, but endothelial function and levels of endothelium-repairing cells were normal in most patients. Aerobic exercise training did not change vascular function or cellular endothelial repair. Improved vascular function did not significantly contribute to the V̇O<sub>2</sub>peak improvement after different training intensities in HFpEF, contrary to previous studies in heart failure with reduced ejection fraction and coronary artery disease. (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure [OptimEx-Clin]; NCT02078947).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 15 Feb 2023; epub ahead of print</small></div>

<div><h4>Degree of Joint Risk Factor Control and Incident Heart Failure in Hypertensive Patients.</h4><i>Kou M, Wang X, Ma H, Li X, Heianza Y, Qi L</i><br /><b>Background</b><br />Heart failure (HF) is a major complication in patients with hypertension.<br /><b>Objectives</b><br />This study aimed to investigate the extent to which joint risk factor control could attenuate hypertension-related excess risk of HF.<br /><b>Methods</b><br />The study included a total of 75,293 participants with diagnosed hypertension from the UK Biobank and matched with 256,619 nonhypertensive control subjects, followed up until May 31, 2021. The degree of joint risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, body mass index, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, smoking, and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of HF.<br /><b>Results</b><br />Among hypertensive patients, joint risk factor control showed an association with a stepwise reduction of incident HF risk. Each additional risk factor control was related to a 20% lower risk, and the optimal risk factor control (controlling ≥6 risk factors) was associated with a 62% lower risk (HR: 0.38; 95% CI: 0.31-0.45). In addition, the study found that the hypertension-related excess risk of HF among participants jointly controlling ≥6 risk factors were even lower than in nonhypertensive control subjects (HR: 0.79; 95% CI: 0.67-0.94). The protective associations of joint risk factor control and risk of incident HF were broadly stronger among men than women and among medication users than nonusers (P for interaction < 0.05).<br /><b>Conclusions</b><br />The joint risk factor control is associated with a lower risk of incident HF in an accumulative and sex-specific manner. Optimal risk factor control may eliminate hypertension-related excess risk of HF.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 13 Feb 2023; epub ahead of print</small></div>

<div><h4>Cost-Effectiveness of Comprehensive Quadruple Therapy for Heart Failure With Reduced Ejection Fraction.</h4><i>Dixit NM, Parikh NU, Ziaeian B, Jackson N, Fonarow GC</i><br /><b>Background</b><br />Heart failure with reduced ejection fraction (HFrEF) is one of the most costly and deadly chronic disease states. The cost effectiveness of a comprehensive quadruple therapy regimen for HFrEF has not been studied.<br /><b>Objectives</b><br />The authors sought to determine the cost-effectiveness of quadruple therapy comprised of beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium glucose cotransporter-2 inhibitors vs regimens composed of only beta-blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists (triple therapy), and angiotensin-converting enzyme inhibitors and beta-blockers (double therapy).<br /><b>Methods</b><br />Using a 2-state Markov model, the authors performed a cost-effectiveness study using simulated populations of 1,000 patients with HFrEF based on the participants in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial and compared them by treatment strategy (quadruple therapy vs triple and double therapy) from a United States health care system perspective. The authors also performed 10,000 probabilistic simulations.<br /><b>Results</b><br />Treatment with quadruple therapy resulted in an increase of 1.73 and 2.87 life-years compared with triple therapy and double therapy, respectively, and an increase in quality-adjusted life-years of 1.12 and 1.85 years, respectively. The incremental cost-effectiveness ratios of quadruple therapy vs triple therapy and double therapy were $81,000 and $51,081, respectively. In 91.7% and 99.9% of probabilistic simulations quadruple therapy had an incremental cost-effectiveness ratio of <$150,000 compared with triple therapy and double therapy, respectively.<br /><b>Conclusions</b><br />At current pricing, the use of quadruple therapy in patients with HFrEF was cost effective compared with triple therapy and double therapy. These findings highlight the need for improved access and optimal implementation of comprehensive quadruple therapy in eligible patients with HFrEF.<br /><br />Copyright © 2023 American College of Cardiology Foundation. All rights reserved.<br /><br /><small>JACC Heart Fail: 10 Feb 2023; epub ahead of print</small></div>

<div><h4>Approaches to Genetic Screening in Cardiomyopathies: Practical Guidance for Clinicians.</h4><i>Kontorovich AR</i><br /><AbstractText>Patients and families benefit when the genetic etiology of cardiomyopathy is elucidated through a multidisciplinary approach including genetic counseling and judicious use of genetic testing. The yield of genetic testing is optimized when performed on a proband with a clear phenotype, and interrogates genes that are validated in association with that specific form of cardiomyopathy. Variants of uncertain significance are frequently uncovered and should not be overinterpreted. Identifying an impactful genetic variant as the cause of a patient\'s cardiomyopathy can have important prognostic impact, and enable streamlined cascade testing to highlight at risk relatives. Certain genotypes are associated with unique potential cardiac and noncardiac risk factors and may dictate personalized approaches to treatment.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Feb 2023; 11:133-142</small></div>

<div><h4>Applicability of Vericiguat to Patients Hospitalized for Heart Failure in the United States.</h4><i>Khan MS, Xu H, Fonarow GC, Lautsch D, ... Butler J, Greene SJ</i><br /><b>Background</b><br />In January 2021, vericiguat, a soluble guanylate cyclase stimulator, was approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of cardiovascular death and heart failure (HF) hospitalization among patients with a recent worsening HF event based on the VICTORIA (VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial.<br /><b>Objectives</b><br />This study sought to leverage a contemporary U.S. registry of patients hospitalized for heart failure (HF) to characterize patients who may be candidates for vericiguat based on FDA label and the VICTORIA trial eligibility criteria.<br /><b>Methods</b><br />The authors studied patients hospitalized for HF with ejection fraction (EF) <45% across 525 sites in the GWTG-HF (Get With The Guidelines-Heart Failure) registry between January 2014 and December 2020. Approximate FDA label criteria (excluding estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m<sup>2</sup>, dialysis, or patients with heart transplantation or durable mechanical circulatory support) and eligibility criteria for the VICTORIA trial were applied to the GWTG-HF cohort.<br /><b>Results</b><br />Among 241,057 patients with EF <45% in the GWTG-HF registry, 221,730 (92%) could be candidates for vericiguat under the FDA label and 92,249 (38%) would have been eligible for the VICTORIA trial. The most frequent reasons for ineligibility for the FDA label were eGFR <15 mL/min/1.73 m<sup>2</sup> (5.7%) and dialysis (1.6%). Although there were greater proportions of women and Black patients in the GWTG-HF registry, most clinical characteristics were qualitatively similar with patients enrolled in the VICTORIA trial. Among Medicare beneficiaries in the GWTG-HF registry eligible for vericiguat by either FDA label or VICTORIA trial criteria, 12-month postdischarge rates of mortality (36%-37%), HF hospitalization (33%-35%), all-cause hospitalization (64%-66%), and mean health care expenditure (U.S. $25,106-$25,428) were high.<br /><b>Conclusions</b><br />Data from a large, contemporary U.S. registry of patients actively hospitalized for HF with EF <45% suggest that approximately 4 in 10 patients meet the criteria of the VICTORIA trial and that more than 9 in 10 patients are potential candidates for vericiguat based on the FDA label. Contemporary Medicare beneficiaries hospitalized for HF with EF <45% and eligible for vericiguat face high rates of postdischarge mortality and readmission and accrue substantial health care costs.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Feb 2023; 11:211-223</small></div>

<div><h4>Association of Social Isolation and Loneliness With Incident Heart Failure in a Population-Based Cohort Study.</h4><i>Liang YY, Chen Y, Feng H, Liu X, ... Geng Q, Zhang J</i><br /><b>Background</b><br />Social isolation and loneliness have emerged as important risk factors for cardiovascular diseases, particularly during the coronavirus disease pandemic. However, it is unclear whether social isolation and loneliness had independent and joint associations with incident heart failure (HF).<br /><b>Objectives</b><br />This study sought to examine the association of social isolation, loneliness, and their combination with incident HF.<br /><b>Methods</b><br />The UK Biobank study is a population-based cohort study. Social isolation and loneliness were assessed using self-reported questionnaires. HF cases were identified by linking hospital records and death registries. The weighted polygenic risk score associated with HF was calculated.<br /><b>Results</b><br />Among the 464,773 participants (mean age: 56.5 ± 8.1 years, 45.3% male), 12,898 incident HF cases were documented during a median follow-up of 12.3 years. Social isolation (most vs least: adjusted HR: 1.17; 95% CI:1.11-1.23) and loneliness (yes vs no: adjusted HR: 1.19; 95% CI: 1.11-1.27) were significantly associated with an increased risk of incident HF. The association between an elevated risk of HF and social isolation was modified by loneliness (P<sub>interaction</sub> = 0.034). A gradient of association between social isolation and the risk of incident HF was found only among individuals without loneliness (P<sub>trend</sub> < 0.001), but not among those with loneliness (P<sub>trend</sub> = 0.829). These associations were independent of the genetic risk of HF.<br /><b>Conclusions</b><br />Social isolation and loneliness were independently associated with a higher likelihood of incident HF regardless of genetic risk. The association between social isolation and incident HF was potentially modified by loneliness status.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 20 Jan 2023; epub ahead of print</small></div>

<div><h4>Medication-Attributable Adverse Events in Heart Failure Trials.</h4><i>Harrington J, Fonarow GC, Khan MS, Hernandez A, ... Vaduganathan M, Butler J</i><br /><b>Background</b><br />Initiation and up-titration of guideline-directed medical therapies (GDMTs) for heart failure with reduced ejection fraction (HFrEF) remains suboptimal, in part because of concerns regarding tolerability and adverse events (AEs).<br /><b>Objectives</b><br />The authors sought to compare rates of AE in patients randomized to GDMT medication vs placebo in a meta-analysis of landmark cardiovascular outcomes trials.<br /><b>Methods</b><br />The authors assessed rates of reported AE in 17 landmark HFrEF clinical trials across each class of GDMT in the placebo and intervention arms. The overall rates of AE for each drug class, the absolute difference in frequency in AEs between the placebo and intervention arms, and the odds of each AE according based on randomization strata were calculated.<br /><b>Results</b><br />AE were reported commonly in trials across each class of GDMT, with 75% to 85% of participants reporting at least 1 AE. There was no significant difference in the frequency of AE between the intervention and placebo arms, except for angiotensin-converting enzyme inhibitors (87.0% [95% CI: 85.0%-88.8%] vs 82.0% [95% CI: 79.8%-84.0%], absolute difference: +5% with intervention; P < 0.001). There was no significant difference in drug discontinuation because of AE between placebo and intervention arms in angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists, sodium glucose cotransporter 2 inhibitors, or angiotensin receptor neprilysin inhibitor/angiotensin II receptor blocker trials. Patients randomized to beta-blocker were significantly less likely to stop study drug because of AE than placebo (11.3% [95% CI: 10.3%-12.3%] vs 13.7% [95% CI: 12.5%-14.9%], absolute difference: -1.1%; P = 0.015). When individual types of AE were assessed, the initiation of an intervention vs placebo resulted in small differences in absolute frequency of AE that were largely not statistically significant.<br /><b>Conclusions</b><br />In clinical trials of GDMT for HFrEF, AEs are observed frequently. However, rates of AE are similar between active medication and control, suggesting these may reflect the high risk nature of the heart failure disease state rather than be attributive to a specific therapy.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 12 Jan 2023; epub ahead of print</small></div>

<div><h4>Patient Eligibility for Established and Novel Guideline-Directed Medical Therapies After Acute Heart Failure Hospitalization.</h4><i>Moghaddam N, Hawkins NM, McKelvie R, Poon S, ... Zieroth S, Virani SA</i><br /><b>Background</b><br />Acute heart failure (AHF) hospitalization presents an opportunity to optimize pharmacotherapy to improve outcomes.<br /><b>Objectives</b><br />This study\'s aim was to define eligibility for initiation of guideline-directed medical therapy and newer heart failure (HF) agents from recent clinical trials in the AHF population.<br /><b>Methods</b><br />The authors analyzed patients with an AHF admission within the CAN-HF (Canadian Heart Failure) registry between January 2017 and April 2020. Heart failure with reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) ≤40% and heart failure with preserved ejection fraction (HFpEF) as LVEF >40%. Eligibility was assessed according to the major society guidelines or enrollment criteria from recent landmark clinical trials.<br /><b>Results</b><br />A total of 809 patients with documented LVEF were discharged alive from hospital: 455 with HFrEF and 354 with HFpEF; of these patients, 284 had a de novo presentation and 525 had chronic HF. In HFrEF patients, eligibility for therapies was 73.6% for angiotensin receptor-neprilysin inhibitors (ARNIs), 94.9% for beta-blockers, 84.4% for mineralocorticoid receptor antagonists (MRAs), 81.1% for sodium/glucose cotransporter 2 (SGLT2) inhibitors, and 15.6% for ivabradine. Additionally, 25.9% and 30.1% met trial criteria for vericiguat and omecamtiv mecarbil, respectively. Overall, 71.6% of patients with HFrEF (75.5% de novo, 69.5% chronic HF) were eligible for foundational quadruple therapy. In the HFpEF population, 37.6% and 59.9% were eligible for ARNIs and SGLT2 inhibitors based on recent trial criteria, respectively.<br /><b>Conclusions</b><br />The majority of patients admitted with AHF are eligible for foundational quadruple therapy and additional novel medications across a spectrum of HF phenotypes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 11 Jan 2023; epub ahead of print</small></div>

<div><h4>The End of Endomyocardial Biopsy?: A Practical Guide for Noninvasive Heart Transplant Rejection Surveillance.</h4><i>Holzhauser L, DeFilippis EM, Nikolova A, Byku M, ... Khush KK, Vest AR</i><br /><AbstractText>Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 11 Jan 2023; epub ahead of print</small></div>

<div><h4>Reclassification of Pre-Heart Failure Stages Using Cardiac Biomarkers: Atherosclerosis Risk in Communities (ARIC) Study.</h4><i>Jia X, Al Rifai M, Ndumele CE, Virani SS, ... Ballantyne CM, Nambi V</i><br /><b>Background</b><br />The recent heart failure (HF) guideline recommends the inclusion of cardiac biomarkers in defining Stage B HF.<br /><b>Objectives</b><br />The authors evaluated the impact of incorporating cardiac biomarkers to reclassify HF in 5,324 participants (mean age: 75.8 years) without prevalent HF enrolled in the Atherosclerosis Risk in Communities study and assessed prognosis of Stage B using cardiac biomarkers.<br /><b>Methods</b><br />Using N-terminal pro-B-type natriuretic peptide (<125 pg/mL or ≥125 pg/mL), high-sensitivity troponin T (<14 ng/L or ≥14 ng/L), and abnormal cardiac structure/function by echocardiography, individuals were classified as Stage A<sub>new</sub> and Stage B<sub>new</sub> HF, respectively. Stage B<sub>new</sub> was further evaluated as elevated biomarker only, abnormal echocardiogram only, and abnormalities in both (echo + biomarker). The authors assessed risk for incident HF and all-cause death using Cox regression.<br /><b>Results</b><br />Overall, 4,326 (81.3%) individuals were classified as Stage B<sub>new</sub> with 1,123 (21.1%) meeting criteria for elevated biomarkers only. Compared with Stage A<sub>new</sub>, Stage B<sub>new</sub> was associated with increased risk for incident HF (HR: 3.70 [95% CI: 2.58-5.30]) and death (HR: 1.94 [95% CI: 1.53-2.46]). Stage B<sub>biomarkers only</sub> and Stage B<sub>echo only</sub> were associated with increased HF risk, whereas Stage B<sub>biomarkers only</sub> was also associated with increased death. Stage B<sub>echo+biomarker</sub> had the highest risk for HF (HR: 6.34 [95% CI: 4.37-9.19]) and death (HR: 2.53 [95% CI: 1.98-3.23]).<br /><b>Conclusions</b><br />Incorporating biomarkers based on the new HF guideline reclassified approximately 1 in 5 older adults without prevalent HF to Stage B. The routine measurement of biomarkers can help to identify individuals at higher HF risk who may benefit most from HF prevention efforts.<br /><br />Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 09 Jan 2023; epub ahead of print</small></div>

<div><h4>Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF.</h4><i>Lanfear DE, Njoroge JN, Adams KF, Anand I, ... Malik FI, Teerlink JR</i><br /><b>Background</b><br />Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients.<br /><b>Methods</b><br />In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants.<br /><b>Results</b><br />Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro-B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs -0.7 mm Hg, P-interaction = 0.02).<br /><b>Conclusions</b><br />GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 04 Jan 2023; epub ahead of print</small></div>

<div><h4>Patient-Reported Frailty and Functional Status in Heart Failure With Preserved Ejection Fraction: Insights From VITALITY-HFpEF.</h4><i>Kaul P, Rathwell S, Lam CSP, Westerhout CM, ... Armstrong PW, VITALITY-HFpEF Study Group</i><br /><b>Background</b><br />The association between frailty and health status in patients with heart failure with preserved ejection fraction (HFpEF) is not well known.<br /><b>Objectives</b><br />The authors examined the association between: 1) patient-reported frailty, measured by the Fried frailty phenotype, Kansas City Cardiomyopathy Questionnaire physical limitation score (KCCQ-PLS), 6-minute walking distance (6MWD), and other baseline characteristics; 2) baseline frailty compared with KCCQ-PLS and 24-week 6MWD; 3) frailty and changes in KCCQ-PLS and 6MWD; and 4) vericiguat and frailty at 24 weeks.<br /><b>Methods</b><br />In a post hoc analysis, patients in the VITALITY-HFpEF (Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF) trial were categorized as not frail (0 symptoms), prefrail (1-2 symptoms), and frail (≥3 symptoms) according to patient-reported number of frailty symptoms. Correlations and linear regression models were used to examine the association between frailty and other measures, and between frailty and KCCQ-PLS at baseline with 24-week 6MWD.<br /><b>Results</b><br />Among 739 patients, 27.3% were not frail, 37.6% were prefrail, and 35.0% were frail at baseline. Frail patients were older, more likely to be women, and less likely to be from Asia. Baseline KCCQ-PLS and 6MWD (mean ± SD) among not frail, prefrail, and frail patients was 68.2 ± 23.2, 61.7 ± 22.6, and 48.4 ± 23.8 and 328.5 ± 117.1 m, 310.8 ± 98.9 m, and 250.7 ± 104.3 m (P < 0.01 for both). After accounting for baseline 6MWD, frailty status at baseline, but not KCCQ-PLS, was significantly associated with 6MWD at 24 weeks. By 24 weeks, 47.5% of patients had no change in frailty, 45.5% had become less frail, and 7.0% had become more frail. Treatment with vericiguat did not alter frailty status at 24 weeks.<br /><b>Conclusions</b><br />Patient-reported frailty is modestly correlated with both the KCCQ-PLS and 6MWD but offers prognostic insight into 6MWD at 24 weeks. (Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF [VITALITY-HFpEF]; NCT03547583).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 03 Jan 2023; epub ahead of print</small></div>

<div><h4>Blood Pressure and Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: DELIVER.</h4><i>Selvaraj S, Vaduganathan M, Claggett BL, Miao ZM, ... McMurray JJV, Solomon SD</i><br /><b>Background</b><br />Optimizing systolic blood pressure (SBP) in heart failure (HF) with preserved ejection fraction carries a Class I recommendation but with limited evidence. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have antihypertensive effects across cardiovascular disease.<br /><b>Objectives</b><br />The authors examined the interplay between SBP and treatment effects of dapagliflozin on SBP and cardiovascular outcomes.<br /><b>Methods</b><br />The authors analyzed 6,263 DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) participants and related baseline and mean achieved SBP categories (<120, 120-129, 130-139, ≥140 mm Hg) to the primary outcome (cardiovascular death or worsening HF), secondary outcomes, and safety events. They analyzed whether the blood pressure-lowering effects of dapagliflozin accounted for its treatment effects by adjusting for the change in SBP from baseline to 1 month.<br /><b>Results</b><br />The average age was 72 ± 10 years and 44% were women. SBP <120 mm Hg was associated with higher HF and mortality events, although amputation and stroke risk increased with higher SBP. Dapagliflozin reduced SBP by 1.8 (95% CI: 1.1-2.5) mm Hg compared with placebo at 1 month. The treatment effect of dapagliflozin on the primary outcome and Kansas City Cardiomyopathy Questionnaire total symptom score was consistent across SBP (interaction P = 0.15 and P = 0.98, respectively). Adverse events between arms were similar across SBP categories. The treatment effect was not accounted for by reducing blood pressure.<br /><b>Conclusions</b><br />In DELIVER, risk by SBP was augmented in the lowest and highest categories and varied by endpoint examined. Dapagliflozin modestly decreased SBP compared with placebo. Dapagliflozin was similarly efficacious and safe across the range of baseline SBP. The beneficial effects of dapagliflozin were not accounted for the changes in SBP. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Jan 2023; 11:76-89</small></div>

<div><h4>Race and Socioeconomic Bias in Pediatric Cardiac Transplantation.</h4><i>Amdani S, Conway J, Kleinmahon J, Auerbach S, ... Kirklin JK, Asante-Korang A</i><br /><b>Background</b><br />To date, no studies evaluated implicit bias among clinicians caring for children with advanced heart failure.<br /><b>Objectives</b><br />This study aims to evaluate implicit racial and socioeconomic bias among pediatric heart transplant clinicians.<br /><b>Methods</b><br />A cross-sectional survey of transplant clinicians from the Pediatric Heart Transplant Society was conducted between June and August 2021. The survey consisted of demographic questions along with explicit and validated race and socioeconomic status (SES) implicit association tests (IATs). Implicit and explicit biases among survey group members were studied and associations were tested between implicit and explicit measures.<br /><b>Results</b><br />Of 500 members, 91 (18.2%) individuals completed the race IAT and 70 (14%) completed the SES IAT. Race IAT scores indicated moderate levels of implicit bias (mean = 0.33, d = 0.76; P < 0.001; ie, preference for White individuals). SES IAT scores indicated strong implicit bias (mean = 0.52, d = 1.53; P < 0.001; ie, preference for people from upper SES). There were weak levels of explicit race and wealth bias. There was a strong level of explicit education bias (mean = 5.22, d = 1.19; P < 0.001; ie, preference for educated people). There were nonsignificant correlations between the race and the SES IAT and explicit measures (P > 0.05 for all).<br /><b>Conclusions</b><br />As observed across other health care disciplines, among a group of pediatric heart transplant clinicians, there is an implicit preference for individuals who are White and from higher SES, and an explicit preference for educated people. Future studies should evaluate how implicit biases affect clinician behavior and assess the impact of efforts to reduce such biases.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Jan 2023; 11:19-26</small></div>

<div><h4>Comparison of Demographic, Clinical, Biochemical, and Imaging Findings in Hypertrophic Cardiomyopathy Prognosis: A Network Meta-Analysis.</h4><i>Georgiopoulos G, Figliozzi S, Pateras K, Nicoli F, ... Masci PG, Olivotto I</i><br /><b>Background</b><br />Despite hypertrophic cardiomyopathy (HCM) being the most common inherited heart disease and conferring increased risk for heart failure (HF) and sudden cardiac death (SCD), risk assessment in HCM patients is still largely unresolved.<br /><b>Objectives</b><br />This study aims to synthesize and compare the prognostic impact of demographic, clinical, biochemical, and imaging findings in patients with HCM.<br /><b>Methods</b><br />The authors searched PubMed, Embase, and Cochrane Library for studies published from 1955 to November 2020, and the endpoints were: 1) all-cause death; 2) an arrhythmic endpoint including SCD, sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD; and 3) a composite endpoint including (1) or (2) plus hospitalization for HF or cardiac transplantation. The authors performed a pairwise meta-analysis obtaining the pooled estimate separately for the association between baseline variables and study endpoints. A random-effects network meta-analysis was subsequently used to comparatively assess the prognostic value of outcome associates.<br /><b>Results</b><br />A total of 112 studies with 58,732 HCM patients were included. Among others, increased brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide, late gadolinium enhancement (LGE), positive genotype, impaired global longitudinal strain, and presence of apical aneurysm conferred increased risk for the composite endpoint. At network meta-analysis, LGE showed the highest prognostic value for all endpoints and was superior to all other associates except New York Heart Association functional class >class II. A multiparametric imaging-based model was superior in predicting the composite endpoint compared to a prespecified model based on conventional risk factors.<br /><b>Conclusions</b><br />This network meta-analysis supports the development of multiparametric risk prediction algorithms, including advanced imaging markers additively to conventional risk factors, for refined risk stratification in HCM. (Long-term prognosis of hypertrophic cardiomyopathy according to genetic, clinical, biochemical and imaging findings: a systemic review and meta-analysis; CRD42020185219).<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Jan 2023; 11:30-41</small></div>

<div><h4>Prediction of Left Ventricular Ejection Fraction Change Following Treatment With Sacubitril/Valsartan.</h4><i>Mohebi R, Liu Y, Felker GM, Prescott MF, ... Solomon SD, Januzzi JL</i><br /><b>Background</b><br />Sacubitril/valsartan (Sac/Val) improves left ventricular ejection fraction (LVEF) in heart failure (HF) with reduced ejection fraction regardless of previous treatments. Improvements in LVEF may change eligibility for primary implantable cardioverter-defibrillator (ICD) placement. Awaiting LVEF improvement may expose patients to potential risks for arrhythmic complications.<br /><b>Objectives</b><br />The authors sought to develop a model predicting LVEF change after Sac/Val therapy.<br /><b>Methods</b><br />A total of 416 persons with HF and LVEF of <35% were included in this analysis. Following initiation of Sac/Val, echocardiographic parameters were measured serially for 1 year. A machine learning algorithm was implemented to develop a risk model for predicting the persistence of LVEF of <35% after 1 year and was validated in a separate group of study participants.<br /><b>Results</b><br />Baseline LVEF, left ventricular mass index, HF duration, age, N-terminal pro-B-type natriuretic peptide concentration at baseline and change by day 14, and body mass index were the most significant factors for identifying lack of LVEF improvement to ≥35% after 1 year. In the training and validation cohorts, the areas under the model curve for predicting lack of LVEF improvement were 0.92 and 0.86, respectively. Three categories of likelihood for LVEF of <35% after 1 year of Sac/Val treatment were developed based on the model predictions: 3.8%, 30.1%, and 83.7%. During follow-up, arrhythmia event rates were 0.9%, 2.9%, and 6.7% in these groups, respectively.<br /><b>Conclusions</b><br />Many persons with HF with reduced ejection fraction eligible for ICD insertion experience an increase in LVEF to ≥35% after treatment with Sac/Val. Early identification of those less likely to improve their LVEF might allow for more refined selection of primary ICD candidates. (Effects of Sacubitril/Valsartan Therapy on biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Jan 2023; 11:44-54</small></div>

<div><h4>Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides.</h4><i>Ravassa S, Lupón J, López B, Codina P, ... Bayés-Genís A, González A</i><br /><b>Background</b><br />Myocardial fibrosis may increase vulnerability to poor prognosis in patients with heart failure (HF), even in those patients exhibiting left ventricular reverse remodeling (LVRR) after guideline-based therapies.<br /><b>Objectives</b><br />This study sought to characterize fibrosis at baseline in patients with HF with left ventricular ejection fraction (LVEF) <50% by determining serum collagen type I-derived peptides (procollagen type I C-terminal propeptide [PICP] and ratio of collagen type I C-terminal telopeptide to matrix metalloproteinase-1) and to evaluate their association with LVRR and prognosis.<br /><b>Methods</b><br />Peptides were determined in 1,034 patients with HF at baseline. One-year echocardiography was available in 665 patients. Associations of peptides with 1-year changes in echocardiographic variables were analyzed by multivariable linear mixed models. LVEF was considered improved if it increased by ≥15% or to ≥50% or if it increased by ≥10% to >40% in patients with LVEF ≤40%. Cardiovascular death and HF-related outcomes were analyzed in all patients randomized to derivation (n = 648) and validation (n = 386) cohorts.<br /><b>Results</b><br />Continuous associations with echocardiographic changes were observed only for PICP. Compared with high-PICP (≥108.1 ng/mL) patients, low-PICP (<108.1 ng/mL) patients exhibited enhanced LVRR and a lower risk of HF-related outcomes (P ≤ 0.018), with women and nonischemic patients with HF showing a stronger LVEF increase (interaction P ≤ 0.010). LVEF increase was associated with a better prognosis, particularly in low-PICP patients (interaction P ≤ 0.029). Only patients with both low PICP and improved LVEF exhibited a better clinical evolution than patients with nonimproved LVEF (P < 0.001).<br /><b>Conclusions</b><br />Phenotyping with PICP, a peptide associated with myocardial fibrosis, may be useful to differentiate patients with HF who are more likely to experience clinical myocardial recovery from those with partial myocardial improvement.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Jan 2023; 11:58-72</small></div>

<div><h4>Predictors of Incident Heart Failure Diagnosis Setting: Insights From the Veterans Affairs Healthcare System.</h4><i>Tisdale RL, Fan J, Calma J, Cyr K, ... Heidenreich PA, Sandhu AT</i><br /><b>Background</b><br />Early recognition of heart failure (HF) can reduce morbidity, yet HF is often diagnosed only after symptoms require urgent treatment.<br /><b>Objectives</b><br />The authors sought to describe predictors of HF diagnosis in the acute care vs outpatient setting within the Veterans Health Administration (VHA).<br /><b>Methods</b><br />The authors estimated whether incident HF diagnoses occurred in acute care (inpatient hospital or emergency department) vs outpatient settings within the VHA between 2014 and 2019. After excluding new-onset HF potentially caused by acute concurrent conditions, they identified sociodemographic and clinical variables associated with diagnosis setting and assessed variation across 130 VHA facilities using multivariable regression analysis.<br /><b>Results</b><br />The authors identified 303,632 patients with new HF, with 160,454 (52.8%) diagnosed in acute care settings. In the prior year, 44% had HF symptoms and 11% had a natriuretic peptide tested, 88% of which were elevated. Patients with housing insecurity and high neighborhood social vulnerability had higher odds of acute care diagnosis (adjusted odds ratio: 1.22 [95% CI: 1.17-1.27] and 1.17 [95% CI: 1.14-1.21], respectively) adjusting for medical comorbidities. Better outpatient quality of care (blood pressure control and cholesterol and diabetes monitoring within the prior 2 years) predicted a lower odds of acute care diagnosis. Likelihood of acute care HF diagnosis varied from 41% to 68% across facilities after adjusting for patient-level risk factors.<br /><b>Conclusions</b><br />Many first HF diagnoses occur in the acute care setting, especially among socioeconomically vulnerable populations. Better outpatient care was associated with lower rates of an acute care diagnosis. These findings highlight opportunities for timelier HF diagnosis that may improve patient outcomes.<br /><br />Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 28 Dec 2022; epub ahead of print</small></div>

<div><h4>Comparison of Investigator-Reported and Centrally Adjudicated Heart Failure Outcomes in the EMPEROR-Reduced Trial.</h4><i>Carson P, Teerlink JR, Komajda M, Anand I, ... Zannad F, Packer M</i><br /><b>Background</b><br />There is limited published information on outcome adjudication in heart failure (HF).<br /><b>Objective</b><br />The authors sought to compare investigator reports (IRs) to a Clinical Events Committee (CEC) and the impact of Standardized Clinical Trial Initiative definitions (SCTI).<br /><b>Methods</b><br />In EMPEROR-Reduced, the authors compared IR to CEC for concordance; treatment effect on primary composite outcome events; and the components first event hospitalization primarily for HF (HHF) or cardiovascular mortality (CVM), prognosis after HHF, total HHFs, and trial duration with and without SCTI.<br /><b>Results</b><br />The CEC confirmed 76.3% of IR events for the primary outcome (CVM: 89.1%; HHF: 73.7%). The HR for treatment effect did not differ between adjudication methods for the primary outcome (IR: 0.75 [95% CI: 0.66-0.85]; CEC: 0.75 [95% CI: 0.65-0.86]), its components, or total HHFs. The prognosis after first HHF for all-cause mortality and CVM also did not differ between IR or CEC. Interestingly, IR primary HHF with different CEC primary cause had the highest subsequent fatal event rate. Full SCTI criteria were present in 90% of CEC HHFs-with a similar treatment effect to non-SCTI. The IR primary event reached the protocol target number (841) 3 months earlier than CEC (4 months with full SCTI criteria).<br /><b>Conclusions</b><br />Investigator adjudication is an alternative to a CEC with similar accuracy and faster event accumulation. The use of granular (SCTI) criteria did not improve trial performance. Finally, our data suggest that consideration be given to broadening the HHF definition to include \"for or with\" worsening disease. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 28 Dec 2022; epub ahead of print</small></div>