Journal: JACC Heart Fail

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<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>
Holzhauser L, DeFilippis EM, Nikolova A, Byku M, ... Khush KK, Vest AR
JACC Heart Fail: 11 Jan 2023; epub ahead of print | PMID: 36682960
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<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>
Selvaraj S, Vaduganathan M, Claggett BL, Miao ZM, ... McMurray JJV, Solomon SD
JACC Heart Fail: 01 Jan 2023; 11:76-89 | PMID: 36599553
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<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>
Amdani S, Conway J, Kleinmahon J, Auerbach S, ... Kirklin JK, Asante-Korang A
JACC Heart Fail: 01 Jan 2023; 11:19-26 | PMID: 36599545
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<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>
Georgiopoulos G, Figliozzi S, Pateras K, Nicoli F, ... Masci PG, Olivotto I
JACC Heart Fail: 01 Jan 2023; 11:30-41 | PMID: 36599547
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<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>
Mohebi R, Liu Y, Felker GM, Prescott MF, ... Solomon SD, Januzzi JL
JACC Heart Fail: 01 Jan 2023; 11:44-54 | PMID: 36599549
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<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>
Ravassa S, Lupón J, López B, Codina P, ... Bayés-Genís A, González A
JACC Heart Fail: 01 Jan 2023; 11:58-72 | PMID: 36599551
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<div><h4>Negative Predictive Value and Prognostic Associations of Rb-82 PET/CT with Myocardial Blood Flow in CAV.</h4><i>Abadie BQ, Chan N, Sharalaya Z, Bhat P, ... Cremer PC, Jaber WA</i><br /><b>Background</b><br />Invasive coronary angiography (ICA) is the traditional screening modality for cardiac allograft vasculopathy (CAV). Positron emission tomography/computed tomography (PET/CT) scan with myocardial blood flow (MBF) quantification has emerged as a potential noninvasive alternative.<br /><b>Objectives</b><br />The aim of the study was to validate the diagnostic and prognostic value of a previously published algorithm for diagnosing CAV via PET/CT scans with MBF in a larger population. The study also sought to assess the downstream use of ICA when using PET/CT scanning as a screening modality.<br /><b>Methods</b><br />Patients with heart transplantation without prior revascularization who underwent PET/CT scans with MBF were identified retrospectively. The accuracy of the algorithm was assessed in patients who underwent PET/CT scanning within 1 year of ICA. The prognostic value was assessed via a composite outcome of heart failure hospitalization, myocardial infarction, retransplantation, and all-cause mortality.<br /><b>Results</b><br />A total of 88 patients for the diagnostic portion and 401 patients for the prognostic portion were included. PET CAV 0 had high negative predictive value for moderate to severe CAV (97%) and PET CAV 2/3 had a high positive predictive value for moderate to severe CAV (68%) by ICA. The cohort was followed for a median of 1.2 (IQR: 1.0-1.8) years with 46 patients having an adverse event. The annualized event rates were 6.9%, 9.3%, and 30.8% for PET CAV 0, 1, and 2/3, respectively (P < 0.001).<br /><b>Conclusions</b><br />An algorithm using PET/CT scanning with MBF demonstrates high a negative predictive value for CAV. PET CAV 2/3 is associated with a higher risk of adverse events and need for revascularization. PET/CT scanning with MBF is a reasonable alternative to ICA for screening for CAV.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 20 Dec 2022; epub ahead of print</small></div>
Abadie BQ, Chan N, Sharalaya Z, Bhat P, ... Cremer PC, Jaber WA
JACC Heart Fail: 20 Dec 2022; epub ahead of print | PMID: 36639302
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<div><h4>Functional and Symptomatic Clinical Trial Endpoints: The HFC-ARC Scientific Expert Panel.</h4><i>Psotka MA, Abraham WT, Fiuzat M, Filippatos G, ... Anker SD, O\'Connor CM</i><br /><AbstractText>The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and the Academic Research Consortium (ARC) composed of patients, academic investigators from the United States and Europe, the U.S. Food and Drug Administration, the National Institutes of Health, payers, and industry. Members discussed the measure, remote capture, and clinical utility of functional and quality-of-life endpoints for use in clinical trials of heart failure and cardiovascular therapeutics, with the goal of improving the efficiency of heart failure and cardiovascular clinical research, evidence generation, and thereby patient quality of life, functional status, and survival. Assessments of patient-reported outcomes and maximal and submaximal exercise tolerance are standardized and validated, but actigraphy remains inconsistent as a potential endpoint. This paper details those discussions and consensus recommendations.</AbstractText><br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Dec 2022; 10:889-901</small></div>
Psotka MA, Abraham WT, Fiuzat M, Filippatos G, ... Anker SD, O'Connor CM
JACC Heart Fail: 01 Dec 2022; 10:889-901 | PMID: 36456063
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<div><h4>Hemodynamically-Guided Management of Heart Failure Across the Ejection Fraction Spectrum: The GUIDE-HF Trial.</h4><i>Zile MR, Mehra MR, Ducharme A, Sears SF, ... Costanzo MR, Lindenfeld J</i><br /><b>Background</b><br />Hemodynamically-guided management using an implanted pulmonary artery pressure sensor is indicated to reduce heart failure (HF) hospitalizations in patients with New York Heart Association (NYHA) functional class II-III with a prior HF hospitalization or those with elevated natriuretic peptides.<br /><b>Objectives</b><br />The authors sought to evaluate the effect of left ventricular ejection fraction (EF) on treatment outcomes in the GUIDE-HF (Hemodynamic-GUIDEd management of Heart Failure) randomized trial.<br /><b>Methods</b><br />The GUIDE-HF randomized arm included 1,000 NYHA functional class II-IV patients (with HF hospitalization within the prior 12 months or elevated natriuretic peptides adjusted for EF and body mass index) implanted with a pulmonary artery pressure sensor, randomized 1:1 to a hemodynamically-guided management group (treatment) or a control group (control). The primary endpoint was the composite of HF hospitalizations, urgent HF visits, and all-cause mortality at 12 months. The authors assessed outcomes by EF in guideline-defined subgroups ≤40%, 41%-49%, and ≥50%, within the trial specified pre-COVID-19 period cohort.<br /><b>Results</b><br />There were 177 primary events (0.553/patient-year) in the treatment group and 224 events (0.682/patient-year) in the control group (HR: 0.81 [95% CI: 0.66-1.00]; P = 0.049); HF hospitalization was lower in the treatment vs control group (HR: 0.72 [95% CI: 0.57-0.92]; P = 0.0072). Within each EF subgroup, primary endpoint and HF hospitalization rates were lower in the treatment group (HR <1.0 across the EF spectrum). Event rate reduction by EF in the treatment groups was correlated with reduction in pulmonary artery pressures and medication changes.<br /><b>Conclusions</b><br />Hemodynamically-guided HF management decreases HF-related endpoints across the EF spectrum in an expanded patient population of patients with HF. (Hemodynamic-GUIDEd Management of Heart Failure [GUIDE-HF]; NCT03387813).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Dec 2022; 10:931-944</small></div>
Zile MR, Mehra MR, Ducharme A, Sears SF, ... Costanzo MR, Lindenfeld J
JACC Heart Fail: 01 Dec 2022; 10:931-944 | PMID: 36456066
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<div><h4>Prediction of Survival After Implantation of a Fully Magnetically Levitated Left Ventricular Assist Device.</h4><i>Mehra MR, Nayak A, Morris AA, Lanfear DE, ... Chuang J, Estep JD</i><br /><b>Background</b><br />Clinical trials inform on average efficacy, but individualized risk assessments for outcome prediction are important in guiding treatment implementation.<br /><b>Objectives</b><br />The authors developed and validated a patient-specific risk score to predict survival at 1 and 2 years after HeartMate 3 (HM3) left ventricular assist device (LVAD) implantation.<br /><b>Methods</b><br />The MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) trial includes 2,200 HM3 LVAD patients in the pivotal trial and Continued Access Protocol study (2014-2018). The authors randomly assigned all patients to a derivation cohort (n = 1,540) or validation cohort (n = 660). Univariate mortality predictors were screened for potential model inclusion, stepwise selection was used to build the multivariable Cox proportional hazards regression model, and performance (discrimination and calibration) was evaluated.<br /><b>Results</b><br />Age, prior cardiac surgery (coronary artery bypass grafting [CABG] or valve procedure), lower serum sodium, higher blood urea nitrogen (BUN), small left ventricular size, and right atrial pressure-to-pulmonary capillary wedge pressure (RAP/PCWP) ratio >0.6 were significant risk factors for mortality. Receiver-operating characteristic (ROC) analysis in the validation cohort demonstrated an area under the curve (AUC) of 0.76 (95% CI: 0.70-0.81) at 1 year and 0.71 (95% CI: 0.66-0.77) at 2 years. Calibration between predicted and observed survival of the risk quintiles was high, with Pearson correlation coefficients of 0.986 and 0.994 at 1 and 2 years, respectively. Patients were successfully stratified into tertiles with higher-than-average, average, and lower-than-average survival, and observed mortality risk increased by 2-fold from one tertile to the next.<br /><b>Conclusions</b><br />A practical, easy-to-use HM3 Survival Risk Score with 6 components was developed to accurately predict 1- and 2-year survival after HM3 LVAD implantation. The survival risk score can be used to provide individual survival estimates to facilitate shared decision making when considering HM3 LVAD therapy. (MOMENTUM 3 Trial Portfolio; NCT02224755, NCT02892955).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Dec 2022; 10:948-959</small></div>
Mehra MR, Nayak A, Morris AA, Lanfear DE, ... Chuang J, Estep JD
JACC Heart Fail: 01 Dec 2022; 10:948-959 | PMID: 36456068
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<div><h4>Safety of Right and Left Ventricular Endomyocardial Biopsy in Heart Transplantation and Cardiomyopathy Patients.</h4><i>Bermpeis K, Esposito G, Gallinoro E, Paolisso P, ... Bartunek J, Vanderheyden M</i><br /><b>Background</b><br />Endomyocardial biopsy (EMB) facilitates a histopathologic diagnosis with unique prognostic and therapeutic implications in both native and donor hearts. It is a relatively safe procedure, with an overall complication rate ranging from <1% to 6% depending on the experience of the operator, the clinical status of the patient, the presence or absence of left bundle branch block, the access site, and the site of procurement (right ventricular [RV] vs left ventricular [LV] approach).<br /><b>Objectives</b><br />This study aimed to assess the incidence of procedure-related complications in a real-world population. EMBs were performed either for surveillance of rejection episodes after heart transplantation or for diagnosis of etiology of cardiomyopathy.<br /><b>Methods</b><br />The authors retrospectively analyzed 1,368 biopsies obtained in 561 consecutive patients between May 2011 and May 2021. Patients were stratified according to the underlying heart disease, sex, age, access site, body mass index, and RV vs LV approach.<br /><b>Results</b><br />The analysis revealed an overall complication rate of 4.1%. Serious life-threatening cardiac complications occurred in <1% of EMBs, with tamponade necessitating pericardiocentesis in 0.2% and urgent cardiac surgery in 0.1% of the procedures. Minor complications occurred in 3.3% of the overall population and were more often encountered during LV EMBs (3.9%) and when the native heart was sampled (5.3%).<br /><b>Conclusions</b><br />In experienced hands, LV and RV EMB for heart transplantation rejection surveillance and cardiomyopathy diagnosis is a safe procedure with low risk of complications. Older, female patients and those undergoing native heart EMB were more prone to complications following EMB.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Dec 2022; 10:963-973</small></div>
Bermpeis K, Esposito G, Gallinoro E, Paolisso P, ... Bartunek J, Vanderheyden M
JACC Heart Fail: 01 Dec 2022; 10:963-973 | PMID: 36456070
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<div><h4>Age Differences in Effects of Sacubitril/Valsartan on Cardiac Remodeling, Biomarkers, and Health Status.</h4><i>Murphy SP, Ward JH, Piña IL, Felker GM, ... Solomon SD, Januzzi JL</i><br /><b>Background</b><br />Sacubitril/valsartan (Sac/Val) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Objectives</b><br />In this study, the authors sought to explore age differences in effects of Sac/Val on biomarkers, Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores and cardiac remodeling.<br /><b>Methods</b><br />After initiation and titration of Sac/Val, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-cTnT), and soluble suppressor of tumorigenicity 2 (sST2) were measured and KCCQ-23 scores obtained from baseline to 12 months. Left ventricular ejection fraction (LVEF), and indexed left ventricular end-systolic (LVESVi) and indexed left ventricular end-diastolic (LVEDVi) and left atrial volume index (LAVi) volumes were measured with the use of echocardiography. Safety end points were assessed. Age-stratified analysis was performed for groups aged <65, 65-74, and ≥75 years.<br /><b>Results</b><br />Among 794 participants with HFrEF (mean age 65.1 years, 28.5% women), compared with patients aged <65 years (n = 369), 65-74 years (n = 237), and those aged ≥75 years (n = 188), had similar reductions in hs-cTnT and sST2, but less NT-proBNP reduction (-45.6% vs -40.2% vs -30.5%, respectively; P = 0.02). Gains in KCCQ-23 were smaller (+11.8 vs +11.4 vs +6.0 points; P = 0.03) in patients aged ≥75 years, although similar proportions of each age group achieved ≥10-point and ≥20-point increases in KCCQ-23 by month 12. Improvements in LVEF, LVEDVi, LVESVi, and LAVi were similar among age groups. Incidence of safety end points was also similar.<br /><b>Conclusions</b><br />Sac/Val resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories. Older study participants showed somewhat blunted reduction in NT-proBNP and less improvement in KCCQ-23 overall summary scores. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Dec 2022; 10:976-988</small></div>
Murphy SP, Ward JH, Piña IL, Felker GM, ... Solomon SD, Januzzi JL
JACC Heart Fail: 01 Dec 2022; 10:976-988 | PMID: 36456072
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<div><h4>Plasma Amyloid-β in Relation to Cardiac Function and Risk of Heart Failure in General Population.</h4><i>Zhu F, Wolters FJ, Yaqub A, Leening MJG, ... Ikram MA, Kavousi M</i><br /><b>Background</b><br />Amyloid-β (Aβ) may be related to cardiac function. However, there are limited data on the association of plasma Aβ with cardiac function and risk of heart failure (HF) in the general population.<br /><b>Objectives</b><br />This study sought to determine the associations of plasma amyloid-β40 (Aβ40) and amyloid-β42 (Aβ42) with echocardiographic measurements of cardiac dysfunction and with incident HF in the general population.<br /><b>Methods</b><br />The study included 4,156 participants of the population-based Rotterdam Study (mean age: 71.4 years; 57.1% women), who had plasma Aβ samples collected between 2002 and 2005 and had no established dementia and HF at baseline. Multivariable linear regression models were used to explore the cross-sectional association of plasma Aβ with echocardiographic measures. Participants were followed up until December 2016. Cox proportional hazards models were used to assess the association of Aβ levels with incident HF. Models were adjusted for cardiovascular risk factors.<br /><b>Results</b><br />A per 1-SD increase in log-transformed plasma Aβ40 was associated with a 0.39% (95% CI: -0.68 to -0.10) lower left ventricular ejection fraction and a 0.70 g/m<sup>2</sup> (95% CI: 0.06-1.34) larger left ventricular mass indexed by body surface area. Aβ42 was not significantly associated with echocardiographic measures cross-sectionally. During follow-up (median: 10.2 years), 472 incident HF cases were identified. A per 1-SD increase in log-transformed Aβ40 was associated with a 32% greater risk of HF (HR: 1.32; 95% CI: 1.15-1.51), and the association was significant in men, but not in women. Higher plasma Aβ42 levels were associated with an increased risk of HF (HR: 1.12; 95% CI: 1.02-1.24), although the association was attenuated after further adjustment for concomitant Aβ40 (HR: 1.03; 95% CI: 0.92-1.16).<br /><b>Conclusions</b><br />Higher levels of Aβ40 were associated with worse cardiac function and higher risk of new onset HF in the general population, in particular among men.<br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 09 Nov 2022; epub ahead of print</small></div>
Zhu F, Wolters FJ, Yaqub A, Leening MJG, ... Ikram MA, Kavousi M
JACC Heart Fail: 09 Nov 2022; epub ahead of print | PMID: 36372727
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<div><h4>Potential Interactions When Prescribing SGLT2 Inhibitors and Intravenous Iron in Combination in Heart Failure.</h4><i>Packer M</i><br /><AbstractText>In patients with heart failure, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to decrease hepcidin and ferritin and increase transferrin receptor protein, changes that are typically indicative of worsening absolute iron deficiency, as would be seen with poor dietary intake or gastrointestinal bleeding, neither of which is provoked by SGLT2 inhibitors. Therefore, 2 alternative conceptual frameworks may explain the observed pattern of changes in iron homeostasis proteins. According to the \"cytosolic iron depletion hypothesis,\" the effect of SGLT2 inhibitors to decrease hepcidin and ferritin and increase transferrin receptor is related to a decline in cytosolic Fe<sup>2+</sup> that occurs after drug-induced erythropoietin-related increase in iron use. Erythropoietin-mimetics (eg, darbepoietin) elicit this type of iron-deficiency pattern of response, and it is typically accompanied by erythropoietin resistance that is alleviated by intravenous iron supplementation. In contrast, according to the \"cytosolic iron repletion hypothesis,\" the effect of SGLT2 inhibitors to decrease hepcidin and ferritin and increase transferrin receptor represents a direct action of these drugs: 1) to reverse inflammation-related increases in hepcidin and ferritin, and, thus, alleviate functional blocks on iron utilization; and 2) to increase in sirtuin-1 signaling, which suppresses hepcidin, accelerates the degradation of ferritin, and up-regulates transferrin receptor protein. Through either or both mechanisms, direct suppression of hepcidin and ferritin would be expected to increase cytosolic Fe<sup>2+</sup>, thus allowing an unattenuated erythrocytic response to erythropoietin without the need for intravenous iron supplementation. The totality of clinical evidence supports the \"cytosolic iron repletion hypothesis\" because SGLT2 inhibitors elicit a full and sustained erythrocytosis in response to erythropoietin, even in overtly iron-deficient patients and in the absence of intravenous iron therapy. Therefore, the emergence of an iron-deficiency pattern of response during SGLT2 inhibition does not reflect worsening iron stores that are in need of replenishment, but instead, represents potential alleviation of a state of inflammation-related functional iron deficiency that is commonly seen in patients with chronic heart failure. Treatment with intravenous iron may be unnecessary and theoretically deleterious.</AbstractText><br /><br />Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 05 Nov 2022; epub ahead of print</small></div>
Packer M
JACC Heart Fail: 05 Nov 2022; epub ahead of print | PMID: 36396554
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Abstract
<div><h4>Retinal Microvasculature: A Potential Window Into Heart Failure Prevention.</h4><i>Chaikijurajai T, Ehlers JP, Tang WHW</i><br /><AbstractText>Endothelial dysfunction and microvascular disease have been shown to play an important role in the development and progression of heart failure (HF). Retinal imaging provides a unique opportunity to noninvasively assess vascular structure and function, vessel features, and microcirculation within the retina. Accumulating evidence suggests that retinal vessel caliber, microvascular features, and vascular characteristics extracted from various imaging modalities are associated with alterations in left ventricular structure and function in stage B HF, as well as incident development of symptomatic HF in the general population. Moreover, dynamic retinal vessel analysis has been shown to differentiate HF patients based on their phenotypes. Given the increasing availability of rapid image acquisition devices (eg, nonmydriatic widefield systems and smartphone-based retinal cameras) and the integration of artificial intelligence-based interrogation/assessment techniques, retinal imaging is a promising noninvasive tool, in conjunction with cardiac imaging and biomarkers, to prevent HF and risk stratify those at risk of developing HF. This review focuses on the current evidence on retinal microvasculature changes, and potential clinical relevance and promising utility of retinal imaging in HF.</AbstractText><br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:785-791</small></div>
Chaikijurajai T, Ehlers JP, Tang WHW
JACC Heart Fail: 01 Nov 2022; 10:785-791 | PMID: 36328644
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<div><h4>Family Screening in Dilated Cardiomyopathy: Prevalence, Incidence, and Potential for Limiting Follow-Up.</h4><i>Vissing CR, Espersen K, Mills HL, Bartels ED, ... Christensen AH, Bundgaard H</i><br /><b>Background</b><br />According to patterns of inheritance and incomplete penetrance, fewer than half of relatives to dilated cardiomyopathy probands will develop disease.<br /><b>Objectives</b><br />The purpose of this study was to investigate the prevalence and incidence, and to identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening.<br /><b>Methods</b><br />The study was a retrospective, longitudinal cohort study of families screened and followed from 2006 to 2020 at a regional assembly of clinics for inherited cardiomyopathies.<br /><b>Results</b><br />In total, 211 families (563 relatives, 50% women) were included. At baseline, 124 relatives (22%) were diagnosed with FDC. Genetic sequencing identified the etiology in 37% of screened families and classified 101 (18%) relatives as unaffected carriers (n = 43) or noncarriers (ie, not at risk of FDC [n = 58]). The combined clinical and genetic baseline yield was 30%. During follow-up (2,313 person-years, median 5.0 years), 45 developed FDC (incidence rate of 2.0% per person-year; 95% CI: 1.4%-2.8%), increasing the overall yield to 34%. The incidence rate of FDC was high in relatives with baseline abnormalities on electrocardiogram or echocardiography compared with relatives with normal findings (4.7% vs 0.4% per person-year; HR: 12.9; P < 0.001). In total, baseline screening identified 326 (58%) relatives to be at low risk of FDC.<br /><b>Conclusions</b><br />Family screening identified a genetic predisposition to or overt FDC in 1 of 3 relatives at baseline. Genetic and clinical screening was normal in more than half of relatives, and these relatives had a low risk of developing FDC during follow-up. Thus, baseline screening identified a large proportion, in whom follow-up may safely be reduced, allowing focused follow-up of relatives at risk.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:792-803</small></div>
Vissing CR, Espersen K, Mills HL, Bartels ED, ... Christensen AH, Bundgaard H
JACC Heart Fail: 01 Nov 2022; 10:792-803 | PMID: 36328645
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<div><h4>Trends in Ischemic Evaluation in New-Onset Heart Failure Without Known Coronary Artery Disease.</h4><i>Andersson C, Schou M, Boden WE, Schwartz B, ... Gislason GH, Torp-Pedersen C</i><br /><b>Background</b><br />Guidelines recommend consideration of an ischemic evaluation (Class IIa-IIb) in new-onset heart failure (HF), but it is not well-known how often this is performed and leads to revascularization.<br /><b>Objectives</b><br />The authors investigated temporal trends in ischemic evaluation and revascularization within 90 days of HF onset in Denmark 2008-2018.<br /><b>Methods</b><br />From the Danish nationwide administrative registries, diagnostic tests and revascularizations within 90 days were identified among patients with new-onset HF between 2008 and 2018, alive 90 days after diagnosis.<br /><b>Results</b><br />Of 61,475 patients (mean age: 72.6 ± 13.8 years, 46% women), 12,503 (20%) underwent an ischemic evaluation, of whom 10,547 (84%) underwent invasive coronary angiography, and 1,956 (16%) underwent an initial noninvasive test, most frequently coronary computed tomographic angiography (n = 1,813, 93%). Of those who were initially referred for coronary computed tomographic angiography, 374 (21%) had a subsequent invasive coronary angiogram undertaken. Among individuals undergoing ischemic testing, percutaneous coronary intervention and coronary artery bypass graft surgery were performed in 1,354 (11%) and 619 (5%), respectively, corresponding to 2.2% and 1.0% of the entire sample. Between 2008 and 2018, the number of patients referred for ischemic evaluations increased, adjusted OR for 1.07 (95% CI: 1.06-1.07) per year high, and was greater among older versus younger individuals (OR: 1.01 [95% CI: 0.99-1.03], OR: 1.04 [95% CI: 1.03-1.06], OR: 1.06 [95% CI: 1.05-1.07], OR: 1.11 [95% CI: 1.09-1.12], and OR: 1.14 [95% CI: 1.10-1.18] per year increase for age group <50, 51-60, 61-75, 76-85, and >85 years, respectively, P for interaction <0.0001).<br /><b>Conclusions</b><br />In clinical practice, few patients with new-onset HF are referred for an ischemic evaluation and a minority undergo revascularization. Studies are needed to establish the appropriateness of this practice.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:807-815</small></div>
Andersson C, Schou M, Boden WE, Schwartz B, ... Gislason GH, Torp-Pedersen C
JACC Heart Fail: 01 Nov 2022; 10:807-815 | PMID: 36328647
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<div><h4>Risks of Depression and Suicide After Diagnosis With Heart Failure: A National Cohort Study.</h4><i>Crump C, Sundquist J, Kendler KS, Sieh W, Edwards AC, Sundquist K</i><br /><b>Background</b><br />Heart failure (HF) has been associated with psychosocial distress, but other long-term mental health sequelae are unclear.<br /><b>Objectives</b><br />In this study, the authors sought to determine risks of major depression and suicide, susceptible time periods, and sex-specific differences after HF diagnosis in a large population-based cohort.<br /><b>Methods</b><br />A national cohort study was conducted of all 154,572 persons diagnosed with HF at ages 18-75 years during 2002-2017 in Sweden and 1,545,720 age- and sex-matched population-based control subjects who were followed up for major depression and suicide ascertained from nationwide inpatient, outpatient, and death records through 2018. Poisson regression was used to compute incidence rate ratios (IRRs) while adjusting for sociodemographic factors and comorbidities.<br /><b>Results</b><br />HF was associated with increased risks of major depression and death by suicide in both men and women, with highest risks in the first 3 months, then declining to modest risks at ≥12 months after HF diagnosis. Within 3 months after HF diagnosis, adjusted IRRs for new-onset major depression were 3.34 (95% CI: 3.04-3.68) in men and 2.78 (95% CI: 2.51-3.09) in women, and for suicide death were 4.47 (95% CI: 2.62-7.62) in men and 2.82 (95% CI: 1.11-7.12) in women. These risks were elevated regardless of age at HF diagnosis. HF was associated with significantly more depression cases in women (P < 0.001).<br /><b>Conclusions</b><br />In this large national cohort, HF was associated with substantially increased risks of depression and suicide in men and women, with highest risks occurring within 3 months after HF diagnosis. Men and women with HF need timely detection and treatment of depression and suicidality.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:819-827</small></div>
Crump C, Sundquist J, Kendler KS, Sieh W, Edwards AC, Sundquist K
JACC Heart Fail: 01 Nov 2022; 10:819-827 | PMID: 36328649
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<div><h4>Posterior Wall Thickness Associates With Survival Following Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.</h4><i>Sun D, Schaff HV, Nishimura RA, Geske JB, ... Ducharme MT, Ommen SR</i><br /><b>Background</b><br />The left ventricular (LV) posterior wall thickness (PWT) is a predictor of sudden cardiac death in pediatric patients with hypertrophic cardiomyopathy (HCM), but the prognostic importance of PWT in adults has not been examined.<br /><b>Objectives</b><br />The goal of this study was to evaluate the association of LV PWT with late survival in adult patients undergoing septal myectomy for obstructive HCM.<br /><b>Methods</b><br />This single-center study reviewed 2,418 patients who underwent transaortic septal myectomy for obstructive HCM.<br /><b>Results</b><br />The median preoperative PWT was 13 (IQR: 11-15) mm. Patients with PWT >13 mm tended to have systemic hypertension (55.4% vs 49.1%; P = 0.002) and a larger body mass index (median: 30.8 [IQR: 27.1-35.1] kg/m<sup>2</sup> vs 29.6 [IQR: 26.1-33.9] kg/m<sup>2</sup>; P < 0.001). Preoperatively, PWT >13 mm was associated with increased septal thickness (median: 21 [IQR: 18-24] mm vs 19 [IQR: 17-22] mm; P < 0.001), greater maximum instantaneous left ventricular outflow tract (LVOT) gradient at rest (median: 67 [IQR: 36-96] mm Hg vs 47 [IQR: 19-79] mm Hg), and increased likelihood of moderate or greater mitral valve regurgitation (54.3% vs 47.3%; P = 0.001). However, PWT was not related to the severity of limitations measured by New York Heart Association functional class (P = 0.674). After adjusting for baseline covariates, greater PWT was an independent risk factor for late mortality after septal myectomy (P = 0.003).<br /><b>Conclusions</b><br />PWT is a newly identified predictor of reduced long-term survival after septal myectomy that is independent of septal thickness and severity of LVOT gradient. Future studies are warranted to investigate the mechanisms underlying the association and the potential usefulness of PWT in patient management.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:831-837</small></div>
Sun D, Schaff HV, Nishimura RA, Geske JB, ... Ducharme MT, Ommen SR
JACC Heart Fail: 01 Nov 2022; 10:831-837 | PMID: 36328651
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<div><h4>Steroidal MRA Across the Spectrum of Renal Function: A Pooled Analysis of RCTs.</h4><i>Ferreira JP, Pitt B, McMurray JJV, Pocock SJ, ... Zannad F, Rossignol P</i><br /><b>Background</b><br />Mineralocorticoid receptor antagonists (MRAs) are underused in patients with kidney dysfunction, and their efficacy among patients with chronic kidney disease (CKD) is uncertain.<br /><b>Objectives</b><br />The goal of this study was to analyze the efficacy and safety of steroidal MRAs across the spectrum of estimated glomerular filtration rates (eGFRs) in randomized controlled trials. The study included patients with heart failure (HF) or myocardial infarction and advanced CKD who participated in the RALES (Randomized Aldactone Evaluation Study), EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in the Americas, and EPHESUS (Eplerenone Post-AMI Heart Failure Efficacy and Survival Study) trials.<br /><b>Methods</b><br />This study used individual patient data meta-analysis using Cox models stratified by trial with treatment-by-eGFR interaction terms. eGFR was recalculated by using the Chronic Kidney Disease Epidemiology Collaboration creatinine formula.<br /><b>Results</b><br />A total of 12,700 patients were included, of whom 331 (2.6%) had an eGFR ≤30 mL/min/1.73 m<sup>2</sup> (mean eGFR: 26.8 ± 3.2 mL/min/1.73 m<sup>2</sup>). Patients with advanced CKD had higher annualized event rates for all studied outcomes: placebo event rate for the composite of cardiovascular death or HF hospitalization was ∼3-fold higher in patients with eGFR ≤30 compared with those with eGFR >90 mL/min/1.73 m<sup>2</sup>: 41.6 vs 14.6 events per 100 person-years. MRAs (vs placebo) reduced the composite of cardiovascular death or HF hospitalization, but the effect was attenuated as eGFR decreased: the corresponding HRs by eGFR categories were: HR for >90 mL/min/1.73 m<sup>2</sup>: 0.62 (95% CI: 0.49-0.78); HR for 61-90 mL/min/1.73 m<sup>2</sup>: 0.69 (95% CI: 0.61-0.77); HR for 46-60 mL/min/1.73 m<sup>2</sup>: 0.84 (95% CI: 0.74-0.95); HR for 31-45 mL/min/1.73 m<sup>2</sup>: 0.79 (95% CI: 0.68-0.91); and HR for ≤30 mL/min/1.73 m<sup>2</sup>: 0.96 (95% CI: 0.70-1.32) (treatment-by-eGFR interaction P for trend = 0.033). Investigator-reported hyperkalemia and worsening renal function were more frequent (2- to 3-fold) among MRA users, and hyperkalemia was more frequent as eGFR decreased (treatment-by-eGFR interaction P for trend = 0.002).<br /><b>Conclusions</b><br />Steroidal MRAs reduced HF hospitalizations and mortality across a wide range of eGFR. However, declining benefit and worsening safety may limit their use in patients with lower eGFR, particularly those with levels ≤30 mL/min/1.73 m<sup>2</sup>.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:842-850</small></div>
Ferreira JP, Pitt B, McMurray JJV, Pocock SJ, ... Zannad F, Rossignol P
JACC Heart Fail: 01 Nov 2022; 10:842-850 | PMID: 36328653
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<div><h4>Trends in Heart Failure-Related Mortality Among Older Adults in the United States From 1999-2019.</h4><i>Siddiqi TJ, Khan Minhas AM, Greene SJ, Van Spall HGC, ... Butler J, Khan MS</i><br /><b>Background</b><br />The U.S. population is aging with concurrent increases in heart failure (HF) burden. However, HF-related mortality trends among adults ≥75 years have not been investigated.<br /><b>Objectives</b><br />The purpose of this study was to assess the trends and regional differences in HF-related mortality among older adults in the United States.<br /><b>Methods</b><br />Death certificates from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database were examined from 1999 to 2019 for HF-related mortality in adults ≥75 years of age. Age-adjusted mortality rates (AAMRs) per 10,000 persons and annual percent change (APC) were calculated and stratified by year, sex, race/ethnicity, and geographic region.<br /><b>Results</b><br />Between 1999 and 2019, 5,014,919 HF-related deaths occurred among adults ≥75 years. The AAMR declined from 141.0 in 1999 to 108.3 in 2012 (APC: -2.1; 95% CI: -2.4 to -1.9), after which it increased to 121.3 in 2019 (APC: 1.7; 95% CI: 1.2-2.2). Men had consistently higher AAMR than women from 1999 (AAMR men: 158.3 vs women: 131.0) to 2019 (AAMR men: 141.1 vs women: 107.8). Non-Hispanic (NH) White adults had the highest overall AAMR (127.2), followed by NH Black (108.7), NH American Indian/Alaska Native (102.0), Hispanic or Latino (78.0), and NH Asian or Pacific Islander adults (57.1) AAMR also varied substantially by region (overall AAMR: Midwest 133.9; South: 119.2; West: 116.3; Northeast: 113.5), and nonmetropolitan areas had higher HF-related AAMR (147.0) than metropolitan areas (115.2). States in the top 90th percentile of HF-related AAMR were Mississippi, Oklahoma, West Virginia, Oregon, and Indiana, which had approximately double the AAMRs compared with states that fell into the lower 10th percentile.<br /><b>Conclusions</b><br />Following a period of steady decline, HF-related mortality in U.S. adults ≥75 years has increased since 2012. The highest AAMRs were observed among White adults and men, and among patients living in the Midwestern and nonmetropolitan United States. Targeted strategies are needed to prevent and treat HF among older adults to curb increasing levels of HF-related mortality.<br /><br />Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:851-859</small></div>
Siddiqi TJ, Khan Minhas AM, Greene SJ, Van Spall HGC, ... Butler J, Khan MS
JACC Heart Fail: 01 Nov 2022; 10:851-859 | PMID: 36328654
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<div><h4>Finerenone and Heart Failure Outcomes by Kidney Function/Albuminuria in Chronic Kidney Disease and Diabetes.</h4><i>Filippatos G, Anker SD, Pitt B, Rossing P, ... Ruilope LM, Agarwal R</i><br /><b>Background</b><br />In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis).<br /><b>Objectives</b><br />This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories.<br /><b>Methods</b><br />FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 m<sup>2</sup>) randomized to finerenone or placebo. Time-to-event outcomes were first hospitalization for heart failure (HHF), cardiovascular death or first HHF, recurrent HHF, and cardiovascular death or recurrent HHF, analyzed in subgroups by baseline eGFR (<60 and ≥60 mL/min/1.73 m<sup>2</sup>) and/or UACR (<300 and ≥300 mg/g).<br /><b>Results</b><br />Compared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 m<sup>2</sup> and a UACR <300 mg/g. Finerenone improved HF outcomes irrespective of baseline eGFR and/or UACR categories (all P interaction values >0.10).<br /><b>Conclusions</b><br />Compared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049).<br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 01 Nov 2022; 10:860-870</small></div>
Filippatos G, Anker SD, Pitt B, Rossing P, ... Ruilope LM, Agarwal R
JACC Heart Fail: 01 Nov 2022; 10:860-870 | PMID: 36328655
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This program is still in alpha version.