Pub Date : 2026-03-01Epub Date: 2025-03-11DOI: 10.1016/j.cardfail.2025.02.015
BART J. VAN ESSEN MD , JASPER TROMP MD, PhD , ANDREAS B. GEVAERT MD, PhD , TRISTAN V. De Jong PhD , WOUTER OUWERKERK PhD , ANDREA KOEKEMOER , DJORDJE DJORDJEVIC PhD , LUKAS BAUMHOVE MD , GANASH N. THARSHANA , KARIN CONDE-KNAPE PhD , MINTU NATH PhD , CHIM C. LANG MD, PhD , NILESH J. SAMANI MD, FRCP , NATASHA B.M. MICHAELSEN PhD , ADRIAAN A. VOORS MD, PhD
Introduction
Pathophysiological differences between heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) remain poorly understood. Therefore, we performed pathway analyses from whole-blood transcriptomics to distinguish HFpEF from HFrEF.
Methods and Results
Lexogen's QuantSeq was used to carry out whole-blood transcriptomics in 500 patients with HF (HFpEF n = 250, HFrEF n = 250). Differential gene expression analysis was performed on all protein-coding genes that met a predefined minimum expression level. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology over-representation analysis was utilized to identify upregulated and downregulated biological pathways. The findings were validated in an independent cohort of 727 patients with HF. Out of 7672 protein-coding transcripts, 217 were upregulated and 110 were downregulated in patients with HFpEF compared with HFrEF. The 3 most significantly upregulated genes were neutrophil-expressed elastase, defensin alpha 4, and pro-platelet basic protein. The 3 most significantly downregulated genes were lymphotoxin beta, bridging integrator 1, and V-set pre-B cell surrogate light chain 3. Translation of differentially expressed genes into biological pathways demonstrated that the most significantly activated KEGG pathway in HFpEF was neutrophil extracellular trap formation.
Discussion
Transcriptomics analyses suggest activation of neutrophil extracellular trap formation pathways in patients with HFpEF. This pathway is associated with endothelial and coronary microvascular dysfunction and might be a target for future drug development in patients with HFpEF.
{"title":"Activation of Neutrophil Extracellular Trap Formation in Patients with Heart Failure and a Preserved Ejection Fraction","authors":"BART J. VAN ESSEN MD , JASPER TROMP MD, PhD , ANDREAS B. GEVAERT MD, PhD , TRISTAN V. De Jong PhD , WOUTER OUWERKERK PhD , ANDREA KOEKEMOER , DJORDJE DJORDJEVIC PhD , LUKAS BAUMHOVE MD , GANASH N. THARSHANA , KARIN CONDE-KNAPE PhD , MINTU NATH PhD , CHIM C. LANG MD, PhD , NILESH J. SAMANI MD, FRCP , NATASHA B.M. MICHAELSEN PhD , ADRIAAN A. VOORS MD, PhD","doi":"10.1016/j.cardfail.2025.02.015","DOIUrl":"10.1016/j.cardfail.2025.02.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Pathophysiological differences between heart failure (HF) with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) remain poorly understood. Therefore, we performed pathway analyses from whole-blood transcriptomics to distinguish HFpEF from HFrEF.</div></div><div><h3>Methods and Results</h3><div>Lexogen's QuantSeq was used to carry out whole-blood transcriptomics in 500 patients with HF (HFpEF n = 250, HFrEF n = 250). Differential gene expression analysis was performed on all protein-coding genes that met a predefined minimum expression level. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology over-representation analysis was utilized to identify upregulated and downregulated biological pathways. The findings were validated in an independent cohort of 727 patients with HF. Out of 7672 protein-coding transcripts, 217 were upregulated and 110 were downregulated in patients with HFpEF compared with HFrEF. The 3 most significantly upregulated genes were neutrophil-expressed elastase, defensin alpha 4, and pro-platelet basic protein. The 3 most significantly downregulated genes were lymphotoxin beta, bridging integrator 1, and V-set pre-B cell surrogate light chain 3. Translation of differentially expressed genes into biological pathways demonstrated that the most significantly activated KEGG pathway in HFpEF was neutrophil extracellular trap formation.</div></div><div><h3>Discussion</h3><div>Transcriptomics analyses suggest activation of neutrophil extracellular trap formation pathways in patients with HFpEF. This pathway is associated with endothelial and coronary microvascular dysfunction and might be a target for future drug development in patients with HFpEF.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 3","pages":"Pages 596-604"},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-03-10DOI: 10.1016/j.cardfail.2026.02.001
Anuradha Lala MD , Robert J. Mentz MD
{"title":"Purpose, Presence and How We Work","authors":"Anuradha Lala MD , Robert J. Mentz MD","doi":"10.1016/j.cardfail.2026.02.001","DOIUrl":"10.1016/j.cardfail.2026.02.001","url":null,"abstract":"","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 3","pages":"Pages 555-556"},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147419082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-05-17DOI: 10.1016/j.cardfail.2025.05.002
JOÃO PEDRO FERREIRA MD, PhD , PEDRO MARQUES MD , ANA RITA LEITE MD , JOÃO SÉRGIO NEVES MD, PhD , FAIEZ ZANNAD MD, PhD , BERTRAM PITT MD
Steroidal (s) and nonsteroidal (ns) mineralocorticoid receptor antagonists (MRAs) and aldosterone synthase inhibitors (ASis) are either available for clinical use or are being tested in clinical trials in cardiovascular, kidney and metabolic (CKM) conditions. All agents block the actions of aldosterone, but they present important differences in terms of modes of action, pharmacokinetics and dynamics and side-effect profiles. Such differences may have clinical implications. To ascertain such potential differences, we performed a description and indirect comparison of MRA and ASi trial results in hypertension, chronic kidney disease and heart failure. Whenever possible, we used data from head-to-head comparisons. We then used this information to provide clinical guidance and to suggest how to improve clinical trials in the future. Notably, by performing more head-to-head comparison trials and trials with dual or triple combination therapies with sodium glucose co-transporter 2 inhibitors (SGLT2is) and/or oral glucagon-like peptide 1 receptor agonists (GLP1ras). In short, this article focuses on the similarities and potential differences among MRAs, nsMRAs and ASis, with implications for both clinical use and clinical trial design.
{"title":"Mineralocorticoid Receptor Antagonists and Aldosterone Synthase Inhibitors: Agent Comparison With Implications for Clinical Practice and Trial Design","authors":"JOÃO PEDRO FERREIRA MD, PhD , PEDRO MARQUES MD , ANA RITA LEITE MD , JOÃO SÉRGIO NEVES MD, PhD , FAIEZ ZANNAD MD, PhD , BERTRAM PITT MD","doi":"10.1016/j.cardfail.2025.05.002","DOIUrl":"10.1016/j.cardfail.2025.05.002","url":null,"abstract":"<div><div>Steroidal (s) and nonsteroidal (ns) mineralocorticoid receptor antagonists (MRAs) and aldosterone synthase inhibitors (ASis) are either available for clinical use or are being tested in clinical trials in cardiovascular, kidney and metabolic (CKM) conditions. All agents block the actions of aldosterone, but they present important differences in terms of modes of action, pharmacokinetics and dynamics and side-effect profiles. Such differences may have clinical implications. To ascertain such potential differences, we performed a description and indirect comparison of MRA and ASi trial results in hypertension, chronic kidney disease and heart failure. Whenever possible, we used data from head-to-head comparisons. We then used this information to provide clinical guidance and to suggest how to improve clinical trials in the future. Notably, by performing more head-to-head comparison trials and trials with dual or triple combination therapies with sodium glucose co-transporter 2 inhibitors (SGLT2is) and/or oral glucagon-like peptide 1 receptor agonists (GLP1ras). In short, this article focuses on the similarities and potential differences among MRAs, nsMRAs and ASis, with implications for both clinical use and clinical trial design.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 3","pages":"Pages 633-646"},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01DOI: 10.1016/j.cardfail.2026.02.032
Blain G Taffesse, Andrew P Ambrosy
{"title":"FAIR Enough for All? Intravenous Iron in Ischemic and Nonischemic Heart Failure with Reduced Ejection Fraction.","authors":"Blain G Taffesse, Andrew P Ambrosy","doi":"10.1016/j.cardfail.2026.02.032","DOIUrl":"https://doi.org/10.1016/j.cardfail.2026.02.032","url":null,"abstract":"","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01DOI: 10.1016/j.cardfail.2026.02.035
Olives Nguyen, Jack Wiedrick, Daniele Massera, Elizabeth Adlestein, Sumar Frejat, Matteo Castrichini, Said Alsidawi, John R Giudicessi, Jeffrey B Geske, Richard T Carrick, Jose Madrazo, Nicole Dellise, Mark A Zenker, Thomas A Boyle, Nosheen Reza, Anjali Tiku Owens, David S Frankel, Prabhjot Hundal, Jamil Tajik, Patrycja Galazka, Myra Lewontin, Michael Ayers, Timothy Wong, Michael Flanagan, Sumeet Singh Mitter, Arjun Kanwal, Ozlem Bilen, Sarah Baghdadi, Hirak Shah, Jared Kvapil, Paola Roldan, Loren Berenbom, Jill Jesurum, Denise Tootill, Alice Siqueira-Benzow, Mariko Harper, Danish Saleh, Lubna Choudhury, Isabela Valenta, Melissa Lang, Dermot M Phelan, Dmitry Prizand, Neal Lakdawala, Carolyn Y Ho, Lusha W Liang, Shepard D Weiner, Sririam Ravi, Ahmed Sami Abuzaid, Mohammed Makkiya, Jeremy S Markowitz, Mark Sherrid, Ahmad Masri
{"title":"Incidence and Outcomes of Atrial Fibrillation and Systolic Dysfunction in Patients Receiving Mavacamten for Obstructive Hypertrophic Cardiomyopathy: A Multicenter Study.","authors":"Olives Nguyen, Jack Wiedrick, Daniele Massera, Elizabeth Adlestein, Sumar Frejat, Matteo Castrichini, Said Alsidawi, John R Giudicessi, Jeffrey B Geske, Richard T Carrick, Jose Madrazo, Nicole Dellise, Mark A Zenker, Thomas A Boyle, Nosheen Reza, Anjali Tiku Owens, David S Frankel, Prabhjot Hundal, Jamil Tajik, Patrycja Galazka, Myra Lewontin, Michael Ayers, Timothy Wong, Michael Flanagan, Sumeet Singh Mitter, Arjun Kanwal, Ozlem Bilen, Sarah Baghdadi, Hirak Shah, Jared Kvapil, Paola Roldan, Loren Berenbom, Jill Jesurum, Denise Tootill, Alice Siqueira-Benzow, Mariko Harper, Danish Saleh, Lubna Choudhury, Isabela Valenta, Melissa Lang, Dermot M Phelan, Dmitry Prizand, Neal Lakdawala, Carolyn Y Ho, Lusha W Liang, Shepard D Weiner, Sririam Ravi, Ahmed Sami Abuzaid, Mohammed Makkiya, Jeremy S Markowitz, Mark Sherrid, Ahmad Masri","doi":"10.1016/j.cardfail.2026.02.035","DOIUrl":"10.1016/j.cardfail.2026.02.035","url":null,"abstract":"","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study investigated the effect of uptitration of sacubitril/valsartan (Sac/Val) compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level within current guideline-directed medical therapy in acute heart failure (AHF).
Methods and Results
This was the secondary analysis in the Program Angiotensin-Neprilysin Inhibition in Admitted Patients with Worsening Heart Failure (PREMIER) study. AHF patients were allocated to switch to Sac/Val or ACEIs/ARBs, and the Sac/Val group was divided into Sac/Val with or without uptitration group (Sac/Val >24/26 mg or ≤24/26 mg twice daily at week 8). The primary endpoint was the proportional change in geometric means of NT-proBNP levels at week 8. A total of 376 patients were included, consistent with the primary analysis in PREMIER. The percent changes in the NT-proBNP level were −51% (Sac/Val with uptitration), −39% (Sac/Val without uptitration), and −32% (ACEIs/ARBs). Their group ratios adjusted for baseline characteristics were 0.72 (Sac/Val with uptitration vs. ACEIs/ARBs, 95% confidence interval [CI], 0.59 to 0.89; P = .002) and 0.93 (Sac/Val without uptitration vs. ACEIs/ARBs, 95% CI, 0.76 to 1.13; P = .47). However, the Sac/Val without uptitration group yielded a greater NT-proBNP reduction than the ACEI/ARB group (adjusted ratio of change 0.72, 95% CI, 0.55 to 0.94; P = .016) in the subgroup of reduced ejection fraction. There were no adverse events associated with Sac/Val uptitration.
Conclusions
Uptitration of Sac/Val therapy yielded a greater NT-proBNP level reduction in AHF patients, but Sac/Val therapy without uptitration also reduced NT-proBNP levels in a subgroup with reduced ejection fraction compared with ACEI/ARB therapy.
目的：本研究探讨在急性心力衰竭（AHF）的现行指导药物治疗中，与血管紧张素转换酶抑制剂或血管紧张素受体阻阻剂（ACEI/ARB）相比，增加苏比利/缬沙坦（Sac/Val）对n端前b型利钠肽（NT-proBNP）水平的影响。方法和结果：这是血管紧张素- neprilysin抑制住院加重心力衰竭患者（PREMIER）研究项目的二级分析。AHF患者分为Sac/Val组和ACEI/ARB组，Sac/Val组分为Sac/Val加药组和不加药组（Sac/Val >24/26 mg或≤24/26 mg，第8周每日2次）。主要终点是第8周NT-proBNP水平几何平均值的比例变化。共纳入376例患者，与PREMIER的初步分析一致。NT-pro BNP水平变化百分比分别为-51% （Sac/Val升高）、-39% （Sac/Val未升高）和-32% (ACEI/ARB)，经基线特征调整后的组比为0.72 (Sac/Val升高vs. ACEI/ARB， 95%可信区间[CI] 0.59 ~ 0.89；p=0.002)和0.93(未上升的Sac/Val vs. ACEI/ARB, 95% CI 0.76 ~ 1.13；p = 0.47)。然而，Sac/Val无提升组的NT-proBNP降低幅度大于ACEI/ARB组(调整后的变化比0.72,95% CI 0.55 ~ 0.94；P =0.016)。没有与Sac/Val升高相关的不良事件。结论：与ACEI/ARB治疗相比，Sac/Val提高治疗可使AHF患者的NT-proBNP水平降低，但Sac/Val不提高治疗也可降低射血分数降低亚组的NT-proBNP水平。
{"title":"Uptitration of Sacubitril/Valsartan in Acute Heart Failure: Insight from the PREMIER Study","authors":"SHUNICHI DOI MD, PhD , ATSUSHI TANAKA MD, PhD , KEISUKE KIDA MD, PhD , TAKUMI IMAI PhD , YUSUKE UEDA MD , YUKIKO NAKANO MD, PhD , YOSHIHISA KIZAKI MD , DAIJU FUKUDA MD, PhD , YUYA MATSUE MD, PhD , YOSHIHIRO J. AKASHI MD, PhD , KOICHI NODE MD, PhD , PREMIER Study Investigators","doi":"10.1016/j.cardfail.2025.05.001","DOIUrl":"10.1016/j.cardfail.2025.05.001","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigated the effect of uptitration of sacubitril/valsartan (Sac/Val) compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level within current guideline-directed medical therapy in acute heart failure (AHF).</div></div><div><h3>Methods and Results</h3><div>This was the secondary analysis in the Program Angiotensin-Neprilysin Inhibition in Admitted Patients with Worsening Heart Failure (PREMIER) study. AHF patients were allocated to switch to Sac/Val or ACEIs/ARBs, and the Sac/Val group was divided into Sac/Val with or without uptitration group (Sac/Val >24/26 mg or ≤24/26 mg twice daily at week 8). The primary endpoint was the proportional change in geometric means of NT-proBNP levels at week 8. A total of 376 patients were included, consistent with the primary analysis in PREMIER. The percent changes in the NT-proBNP level were −51% (Sac/Val with uptitration), −39% (Sac/Val without uptitration), and −32% (ACEIs/ARBs). Their group ratios adjusted for baseline characteristics were 0.72 (Sac/Val with uptitration vs. ACEIs/ARBs, 95% confidence interval [CI], 0.59 to 0.89; <em>P</em> = .002) and 0.93 (Sac/Val without uptitration vs. ACEIs/ARBs, 95% CI, 0.76 to 1.13; <em>P</em> = .47). However, the Sac/Val without uptitration group yielded a greater NT-proBNP reduction than the ACEI/ARB group (adjusted ratio of change 0.72, 95% CI, 0.55 to 0.94; <em>P</em> = .016) in the subgroup of reduced ejection fraction. There were no adverse events associated with Sac/Val uptitration.</div></div><div><h3>Conclusions</h3><div>Uptitration of Sac/Val therapy yielded a greater NT-proBNP level reduction in AHF patients, but Sac/Val therapy without uptitration also reduced NT-proBNP levels in a subgroup with reduced ejection fraction compared with ACEI/ARB therapy.</div></div>","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 3","pages":"Pages 573-582"},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2025-11-07DOI: 10.1016/j.cardfail.2025.09.038
HUBERT B. HAYWOOD MD , IYANUOLUWA AYODELE MS , GREGG C. FONAROW MD , BROOKE ALHANTI , HARRIETTE GC VAN SPALL MD , AMBARISH PANDEY MD , SABRA C LEWSEY M.D., M.P.H. , JAVED BUTLER MD, MPH, MBA , STEPHEN J. GREENE MD
{"title":"Potential Patient Eligibility for Hospital at Home for Management of Worsening Heart Failure in the United States","authors":"HUBERT B. HAYWOOD MD , IYANUOLUWA AYODELE MS , GREGG C. FONAROW MD , BROOKE ALHANTI , HARRIETTE GC VAN SPALL MD , AMBARISH PANDEY MD , SABRA C LEWSEY M.D., M.P.H. , JAVED BUTLER MD, MPH, MBA , STEPHEN J. GREENE MD","doi":"10.1016/j.cardfail.2025.09.038","DOIUrl":"10.1016/j.cardfail.2025.09.038","url":null,"abstract":"","PeriodicalId":15204,"journal":{"name":"Journal of Cardiac Failure","volume":"32 3","pages":"Pages 670-674"},"PeriodicalIF":8.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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