Wolfram Doehner, Stefan D Anker, Javed Butler, Faiez Zannad, Gerasimos Filippatos, Andrew J S Coats, João Pedro Ferreira, Ingrid Henrichmoeller, Martina Brueckmann, Elke Schueler, Stuart J Pocock, James L Januzzi, Milton Packer
{"title":"Uric Acid and SGLT2 Inhibition With Empagliflozin in Heart Failure With Preserved Ejection Fraction: The EMPEROR-Preserved Trial.","authors":"Wolfram Doehner, Stefan D Anker, Javed Butler, Faiez Zannad, Gerasimos Filippatos, Andrew J S Coats, João Pedro Ferreira, Ingrid Henrichmoeller, Martina Brueckmann, Elke Schueler, Stuart J Pocock, James L Januzzi, Milton Packer","doi":"10.1016/j.jchf.2024.08.020","DOIUrl":"https://doi.org/10.1016/j.jchf.2024.08.020","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcome in patients with heart failure (HF) and reduce serum uric acid (SUA). The relevance of this metabolic effect in patients with heart failure with preserved ejection fraction (HFpEF) is unclear.</p><p><strong>Objectives: </strong>The authors investigated the effect of empagliflozin on SUA levels in relation to the therapeutic efficacy in patients with HFpEF.</p><p><strong>Methods: </strong>This post hoc analysis of the EMPEROR-Preserved (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction; NCT03057951) trial assessed the clinical effect of SUA reduction in relation to the outcome endpoints of the trial (composite primary outcome of cardiovascular mortality or hospitalization for HF, its individual components, and all-cause mortality in patients with HFpEF).</p><p><strong>Results: </strong>Hyperuricemia (SUA >5.7 mg/dL for women, >7.0 mg/dL for men) was prevalent in 49% of patients. Elevated SUA (highest tertile SUA 8.8 ± 1.4 g/dL) was associated with advanced HF severity and with higher risk of adverse outcome (primary endpoint HR: 1.23 [95% CI: 0.98-1.53]; P = 0.07; HF hospitalization HR: 1.42 [95% CI: 1.08-1.86]; P = 0.01). SUA was reduced early (after 4 weeks vs placebo -0.99 ± 0.03 mg/dL; P < 0.0001) and throughout follow-up, with reduction in all prespecified subgroups. Empagliflozin reduced clinical events of hyperuricemia (acute gout, gouty arthritis, or initiation of antigout therapy) by 38% (HR: 0.62 [95% CI: 0.51-0.76]; P < 0.0001). The treatment benefit on the primary endpoint was not influenced by baseline SUA (HR: 0.79 [95% CI: 0.69-0.90]; P = 0.0004). The change in SUA was an independent correlate of the treatment benefit on the primary endpoint (P = 0.07).</p><p><strong>Conclusions: </strong>Hyperuricemia is a common complication in HFpEF and is related to advanced disease severity and adverse outcome. Empagliflozin induced a rapid and sustained reduction of SUA levels and of clinical events related to hyperuricemia.</p>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophie L V M Stroeks, Michiel T H M Henkens, Fernando Dominguez, Marco Merlo, Debby M E I Hellebrekers, Esther Gonzalez-Lopez, Matteo Dal Ferro, Juan Pablo Ochoa, Francesco Venturelli, Godelieve R F Claes, Max F G H M Venner, Ingrid P C Krapels, Els K Vanhoutte, Pieter van Paassen, Arthur van den Wijngaard, Maurits A Sikking, Rick van Leeuwen, Myrurgia Abdul Hamid, Xiaofei Li, Han G Brunner, Gianfranco Sinagra, Pablo Garcia-Pavia, Stephane R B Heymans, Job A J Verdonschot
{"title":"Genetic Landscape of Patients With Dilated Cardiomyopathy and a Systemic Immune-Mediated Disease.","authors":"Sophie L V M Stroeks, Michiel T H M Henkens, Fernando Dominguez, Marco Merlo, Debby M E I Hellebrekers, Esther Gonzalez-Lopez, Matteo Dal Ferro, Juan Pablo Ochoa, Francesco Venturelli, Godelieve R F Claes, Max F G H M Venner, Ingrid P C Krapels, Els K Vanhoutte, Pieter van Paassen, Arthur van den Wijngaard, Maurits A Sikking, Rick van Leeuwen, Myrurgia Abdul Hamid, Xiaofei Li, Han G Brunner, Gianfranco Sinagra, Pablo Garcia-Pavia, Stephane R B Heymans, Job A J Verdonschot","doi":"10.1016/j.jchf.2024.08.011","DOIUrl":"https://doi.org/10.1016/j.jchf.2024.08.011","url":null,"abstract":"<p><strong>Background: </strong>Systemic immune-mediated diseases (SIDs) are a well-known cause of dilated cardiomyopathy (DCM), a cardiac phenotype influenced by genetic predispositions and environmental factors.</p><p><strong>Objectives: </strong>This study sought to examine if an underlying genetic predisposition is present in patients with DCM and SID.</p><p><strong>Methods: </strong>Genotyped DCM-SID patients (n = 183) were enrolled at 3 European centers. Genetic variants were compared with healthy control subjects (n = 20,917), DCM patients without SID (n = 560), and individuals with a suspicion of an SID (n = 1,333). Clinical outcomes included all-cause mortality, heart failure hospitalization, and life-threatening arrhythmias.</p><p><strong>Results: </strong>The SID diagnosis preceded the DCM diagnosis by 4.8 months (Q1-Q3: -68.4 to +2.4 months). The prevalence of pathogenic/likely pathogenic (P/LP) variants in DCM patients with an SID from the Maastricht cohort was 17.1%, compared with 1.9% in healthy control subjects (P < 0.001). In the Madrid/Trieste cohort, the prevalence was 20.5% (P < 0.001). Truncating variants showed the strongest enrichment (10.7% [OR: 24.5] (Maastricht) and 16% [OR: 116.6 (Madrid/Trieste); both P < 0.001), with truncating TTN (titin) variant (TTNtv) being the most prevalent. Left ventricular ejection fraction at presentation was reduced in TTNtv-SID patients compared with DCM patients with SID without a P/LP (P = 0.016). The presence of a P/LP variant in DCM-SID had no impact on clinical outcomes over a median follow-up of 8.4 years (Q1-Q3: 4.9-12.1 years).</p><p><strong>Conclusions: </strong>One in 6 DCM patients with an SID has an underlying P/LP variant in a DCM-associated gene. This highlights the role of genetic testing in those patients with immune-mediated DCM, and supports the concept that autoimmunity may play a role in unveiling a DCM phenotype in genotype-positive individuals.</p>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myocardial Mitochondrial Function Is Impaired in Cardiac Light-Chain Amyloidosis Compared to Transthyretin Amyloidosis","authors":"","doi":"10.1016/j.jchf.2024.03.012","DOIUrl":"10.1016/j.jchf.2024.03.012","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"12 10","pages":"Pages 1778-1780"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Combining Loop and Thiazide Diuretics Across the Left Ventricular Ejection Fraction Spectrum","authors":"","doi":"10.1016/j.jchf.2024.05.006","DOIUrl":"10.1016/j.jchf.2024.05.006","url":null,"abstract":"<div><h3>Background</h3><div><span><span>The addition of hydrochlorothiazide (HCTZ) to </span>furosemide in the CLOROTIC (Combining Loop with </span>Thiazide Diuretics<span><span> for Decompensated Heart Failure) trial improved the diuretic response in patients with </span>acute heart failure (AHF).</span></div></div><div><h3>Objectives</h3><div>This work aimed to evaluate if these results differ across the spectrum of left ventricular ejection fraction (LVEF).</div></div><div><h3>Methods</h3><div>This post hoc analysis<span> of the randomized, double-blind, placebo-controlled CLOROTIC trial enrolled 230 patients with AHF to receive either HCTZ or a placebo in addition to an intravenous furosemide regimen. The influence of LVEF on primary and secondary outcomes was evaluated.</span></div></div><div><h3>Results</h3><div><span><span>The median LVEF was 55%: 166 (72%) patients had LVEF >40%, and 64 (28%) had LVEF ≤40%. Patients with a lower LVEF were younger, more likely to be male, had a higher prevalence of ischemic heart disease, and had higher </span>natriuretic peptide<span><span> levels. The addition of HCTZ to furosemide was associated with the greatest weight loss at 72 of 96 hours, better metrics of diuretic response, and greater 24-hour </span>diuresis compared with placebo, with no significant differences according to the LVEF category (using 2 LVEF cutoff points: 40% and 50%) or LVEF as a continuous variable (all </span></span><em>P</em><span> values were insignificant). There were no significant differences observed with the addition of HCTZ in terms of mortality, rehospitalizations, or safety endpoints (impaired renal function, hyponatremia, and hypokalemia) among the 2 LVEF groups (all </span><em>P</em> values were insignificant).</div></div><div><h3>Conclusions</h3><div><span>Adding HCTZ to intravenous furosemide seems to be effective strategy for improving diuretic response in AHF without treatment effect modification according to baseline LVEF. (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure [CLOROTIC], </span><span><span>NCT01647932</span><svg><path></path></svg></span><span>; Randomized, double blinded, multicenter study, to asses Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics vs Loop diuretics with placebo in Patients With Decompensated, EudraCT Number </span><span><span>2013-001852-36</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"12 10","pages":"Pages 1719-1730"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Finding a Signal in the Noise","authors":"Anita Deswal MD, MPH, Salil Kumar MD","doi":"10.1016/j.jchf.2024.07.001","DOIUrl":"10.1016/j.jchf.2024.07.001","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"12 10","pages":"Pages 1775-1777"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status","authors":"","doi":"10.1016/j.jchf.2024.05.007","DOIUrl":"10.1016/j.jchf.2024.05.007","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis.</div></div><div><h3>Objectives</h3><div>This study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM.</div></div><div><h3>Methods</h3><div>Patients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first heart failure hospitalization (HFH). A Cox proportional hazards model was used to calculate HRs and 95% CIs to assess if the effect of vericiguat differed by history of T2DM.</div></div><div><h3>Results</h3><div><span>Of 5,050 patients enrolled, 3,683 (72.9%) had glycosylated hemoglobin (HbA</span><sub>1c</sub><span>) measured at baseline. Of these, 2,270 (61.6%) had T2DM, 741 (20.1%) had pre-T2DM, 449 (12.2%) did not have T2DM, and 178 (4.8%) had undiagnosed T2DM. The risks of the primary outcome, HFH, and all-cause and cardiovascular mortality were high across all categories. The efficacy of vericiguat on the primary outcome did not differ in patients stratified by T2DM by history (HR: 0.92; 95% CI: 0.81-1.04), T2DM measured by HbA</span><sub>1c</sub> (HR: 0.77; 95% CI: 0.49-1.20), and pre-T2DM measured by HbA<sub>1c</sub> (HR: 0.88; 95% CI: 0.68-1.13) and in those with normoglycemia (HR: 1.02: 95% CI: 0.75-1.39; <em>P</em> for interaction = 0.752). No significant differences were observed in subgroups with respect to the efficacy of vericiguat on HFH and all-cause or cardiovascular death.</div></div><div><h3>Conclusions</h3><div>In this post hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction regardless of T2DM status. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [Mk-1242-001] [VICTORIA]; <span><span>NCT02861534</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"12 10","pages":"Pages 1750-1759"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andriana P. Nikolova MD, PhD, Jon A. Kobashigawa MD
{"title":"The EVOLVeD Role of Cholesterol-Lowering Therapies in Cardiac Allograft Vasculopathy","authors":"Andriana P. Nikolova MD, PhD, Jon A. Kobashigawa MD","doi":"10.1016/j.jchf.2024.05.027","DOIUrl":"10.1016/j.jchf.2024.05.027","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"12 10","pages":"Pages 1689-1691"},"PeriodicalIF":10.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}