2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T4e6,Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction (CpcPH-HFpEF) involves remodeling in both the heart and pulmonary vasculature. Despite significant mortality, there are no proven therapies. In this multicenter, randomized, placebo-controlled, phase 2 trial, adults received sotatercept (0.3 or 0.7 mg/kg) or placebo every 3 weeks. The primary end point was change in pulmonary vascular resistance at week 24. Hodges-Lehmann shift estimates described placebo-adjusted changes. 164 patients were randomized 54:55:55 to sotatercept 0.3 mg/kg, 0.7 mg/kg, and placebo, and baseline median pulmonary vascular resistance was 5.2 (interquartile range [IQR] 4.0-6.9) Wood units. The median change from baseline in pulmonary vascular resistance at week 24 was -0.67 Wood units in the sotatercept 0.3 mg/kg group, -0.33 Wood units in the sotatercept 0.7 mg/kg group, and 0.26 Wood units in the placebo group. The Hodges-Lehmann shift estimates in pulmonary vascular resistance were -1.02 Wood units (95% CI, -1.81 to -0.23; These findings provide proof of concept for improved pulmonary vascular and cardiac hemodynamics following activin signalling inhibition with sotatercept in patients with CpcPH-HFpEF.31:Tcc1, BACKGROUND: Combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction involves remodeling in both the heart and pulmonary vasculature. Despite significant mortality, there are no proven therapies. METHODS: In this multicenter, randomized, placebo-controlled, phase 2 trial, adults received sotatercept (0.3 or 0.7 mg/kg) or placebo every 3 weeks. The primary end point was change in pulmonary vascular resistance at week 24. Hodges-Lehmann shift estimates described placebo-adjusted changes. RESULTS: A total of 164 patients were randomized 54:55:55 to sotatercept 0.3 mg/kg, 0.7 mg/kg, and placebo, and baseline median pulmonary vascular resistance was 5.2 (interquartile range, 4.0–6.9) Wood units. The median change from baseline in pulmonary vascular resistance at week 24 was −0.67 Wood units in the sotatercept 0.3 mg/kg group, −0.33 Wood units in the sotatercept 0.7 mg/kg group, and 0.26 Wood units in the placebo group. The Hodges-Lehmann shift estimates in pulmonary vascular resistance were −1.02 Wood units (95% CI, −1.81 to −0.23; P =0.004) for 0.3 mg/kg and −0.75 Wood units (95% CI, −1.52 to 0.03; P =0.024) for 0.7 mg/kg sotatercept. Reductions were observed in mean pulmonary arterial pressure (0.3 and 0.7 mg/kg: −9.19 mm Hg [95% CI, −13.00 to −5.38] and −9.22 [95% CI, −12.97 to −5.46]) and pulmonary arterial wedge pressure (0.3 and 0.7 mg/kg: −3.04 mm Hg [95% CI, −5.77 to −0.32] and −2.53 [95% CI, −5.33 to 0.28]). Changes in 6-minute walk distance were 20.3 m (95% CI, 1.5–39.1) for 0.3 mg/kg and 5.8 m (95% CI, −17.3 to 28.9) for 0.7 mg/kg sotatercept. The most common adverse events with sotatercept (both groups) were increased hemoglobin and diarrhea. CONCLUSIONS: These findings provide proof of concept for improved pulmonary vascular and cardiac hemodynamics after activin signaling inhibition with sotatercept in patients with combined post- and precapillary pulmonary hypertension in heart failure with preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04945460. 32:T4dc,There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and of the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP-1 RAs and GIP/GLP-1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body weight alongside improvements in health status and exercise capacity. Whether these effects translate into fewer HF events or lower cardiovascular mortality remains uncertain, as current evidence is limited to two small trials with few observed events. In contrast, data regarding the efficacy and safety of these drugs in HF with reduced ejection fraction are scarce, with dedicated outcome trials yet to be launched. Finally, this document highlights knowledge gaps and outlines future research directions in this field.33:T4fb,There is growing clinical interest in strategies for improving clinical outcomes in patients with heart failure (HF) and obesity. The development of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and of the dual glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 RA has expanded therapeutic options for this population. This expert consensus provides a comprehensive and pragmatic framework for the use of GLP‐1 RAs and GIP/GLP‐1 RA in patients with HF, focusing on clinical integration, patient selection, safety, and tolerability. We review the evidence supporting their use in patients with HF with preserved ejection fraction (HFpEF), where clinical trials have demonstrated meaningful reductions in body weight alongside improvements in health status and exercise capacity. Whether these effects translate into fewer HF events or lower cardiovascular mortality remains uncertain, as current evidence is limited to two small trials with few observed events. In contrast, data regarding the efficacy and safety of these drugs in HF with reduced ejection fraction are scarce, with dedicated outcome trials yet to be launched. Finally, this document highlights knowledge gaps and outlines future research directions in this field.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Heart Failure With Preserved Ejection Fraction: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Heart Failure With Preserved Ejection Fraction (condition). Clinician-written summaries and actionable practice insights. 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the paper does not explicitly list brand names.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00186-5","tag_type":"warning","value":"No specific sample size is reported, as this is a review article synthesising across multiple studies.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00186-5","tag_type":"warning","value":"The paper is a narrative review using a triangulation framework — not a formal systematic review or meta-analysis — so the strength of causal inference varies by condition and evidence type.","value_numeric":null},{"paper_doi":"10.1016/s2213-8587(26)00186-5","tag_type":"warning","value":"The study design label 'Systematic Review / Narrative Review' reflects a hybrid approach; the authors describe triangulation of multiple evidence types rather than a preregistered systematic methodology.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates whether weight-loss interventions (lifestyle, surgical, and pharmacological — notably semaglutide and tirzepatide) can prevent or modify common obesity-related conditions across musculoskeletal, metabolic, cardiovascular, mental health, respiratory, and hepatic domains, using a triangulation framework of epidemiological, genetic (including Mendelian randomisation), and randomised trial evidence.","key_result":"Robust trial evidence supports weight loss as disease-modifying in type 2 diabetes and heart failure with preserved ejection fraction; incretin-based therapies (semaglutide, tirzepatide) now achieve ~14–20% average weight loss in people without diabetes and have generated the first large-scale randomised evidence of disease modification across several conditions, though many areas (musculoskeletal, respiratory, mental health, cardiovascular) remain under-investigated.","limitations":"- Many conditions lack adequate randomised trial evidence, limiting causal conclusions.\n- Evidence on varying magnitudes of weight loss with different agents, disease-stage effects, and long-term (legacy) outcomes is sparse.\n- Trials have not adequately addressed multimorbidity, mechanistic mediation, diverse global populations, or access equity.","practice_takeaway":"Clinicians have strong evidence to use weight-loss therapies — especially GLP-1 receptor agonists like semaglutide and dual GLP-1/GIP agonists like tirzepatide — for disease modification in type 2 diabetes and HFpEF, but should recognise that evidence for many other obesity-related conditions is still emerging. Individualised treatment targets and long-term follow-up remain important given persistent gaps in outcome data."}},{"doi":"10.1161/circheartfailure.126.014620","pmid":"42634934","title":"Multimodal Framework of Left Heart-Pulmonary Vascular Remodeling Underlying Right Ventricular Failure in PH-HFpEF","journal_title":"Circulation: Heart Failure","journal_issn":"1941-3289","published_at":"2026-08-24T00:00:00.000Z","url":"https://doi.org/10.1161/circheartfailure.126.014620","source_score":66,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-26T06:20:04.846Z","updated_at":"2026-08-26T06:20:04.846Z","tags":[{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"condition","value":"Pulmonary Hypertension Due To Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"condition","value":"Right Ventricular Failure","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"modality","value":"4D Flow MRI","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"modality","value":"Cardiac Magnetic Resonance Imaging","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"modality","value":"Invasive Cardiopulmonary Exercise Testing","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"modality","value":"Long-Read RNA Sequencing","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"modality","value":"Pulmonary Vascular Mechanics","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"sample_size","value":"n=48","value_numeric":48},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"study_design","value":"Observational Cohort Study (Retrospective with Prospective Subset)","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"warning","value":"Sex distribution was not explicitly reported in the abstract; the 'mixed' sex tag is inferred from typical HFpEF cohort composition.","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"warning","value":"Study design is mixed (mostly retrospective with a prospective subset), which introduces selection bias risk.","value_numeric":null},{"paper_doi":"10.1161/circheartfailure.126.014620","tag_type":"warning","value":"The biopsy/transcriptomics subgroup is very small (n=10); gene-level findings should be considered hypothesis-generating only.","value_numeric":null}],"summaries":{"what_studied":"A multimodal framework was used to evaluate mechanisms of RV failure in PH-HFpEF (n=48), stratifying patients by cardiac MRI-derived RV ejection fraction (<45% = RV dysfunction, n=19; normal RV, n=29), with subsets undergoing pulmonary vascular mechanics, 4D flow MRI, and endomyocardial biopsy with long-read RNA sequencing over a 1-year follow-up.","key_result":"RV dysfunction was associated with an 8.2-fold higher risk of mortality or first HF hospitalization at 1 year (HR 8.2, 95% CI 2.5–25.4), increased proximal pulmonary arterial stiffness, higher RV energy expenditure, disturbed 4D flow patterns, and RV myocardial pathway shifts (upregulated RNA metabolism, downregulated mitochondrial pathways).","limitations":"- Very small subgroup sample sizes (mechanics n=17, 4D flow n=15, biopsy n=10) severely limit statistical power for individual gene-level findings.\n- Predominantly retrospective cohort design with a prospective subset only.\n- Findings may not generalize beyond the specific PH-HFpEF phenotype studied.","practice_takeaway":"Cardiac MRI-derived RV ejection fraction <45% identifies PH-HFpEF patients at markedly higher risk of death or HF hospitalization within 1 year (HR 8.2), supporting its use as a prognostic stratifier. Segmental pulmonary vascular remodeling and mitochondrial pathway downregulation may represent future therapeutic targets, though validation in larger cohorts is needed before clinical translation."}},{"doi":"10.1161/jaha.124.041948","pmid":"42517500","title":"ECG‐Based Artificial Intelligence for Classifying Left Ventricular Dysfunction and Heart Failure With Preserved Ejection Fraction","journal_title":"Journal of the American Heart Association","journal_issn":"2047-9980","published_at":"2026-07-28T00:00:00.000Z","url":"https://doi.org/10.1161/jaha.124.041948","source_score":21,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-06T13:22:12.860Z","updated_at":"2026-08-06T13:22:12.860Z","tags":[{"paper_doi":"10.1161/jaha.124.041948","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"condition","value":"Heart Failure With Mildly Reduced Ejection Fraction","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"condition","value":"Heart Failure With Reduced Ejection Fraction","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"condition","value":"Left Ventricular Dysfunction","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"modality","value":"Artificial Intelligence / Machine Learning","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"modality","value":"Electrocardiography","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"sample_size","value":"n=208123","value_numeric":208123},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"study_design","value":"Retrospective Cohort Study with External Validation","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"warning","value":"HFpEF prevalence was only 1–2% in both cohorts; model performance in higher-prevalence clinical settings is unknown.","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"warning","value":"Pediatric validation is exploratory given only 142 cases; AUCs for mEF and HFpEF in children should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"warning","value":"Sample size tag reflects combined unique patient counts from both adult cohorts (165,243 + 42,880); ECG counts are much higher (~1.15M) — clinicians should note the distinction between patient-level and ECG-level data.","value_numeric":null},{"paper_doi":"10.1161/jaha.124.041948","tag_type":"warning","value":"The study design label 'Retrospective Cohort with External Validation' is an approximation; the paper describes a model development and validation study, which does not fit a single canonical study design label perfectly.","value_numeric":null}],"summaries":{"what_studied":"An AI model trained on 12-lead and single-lead (Lead I) ECG data was developed and externally validated to simultaneously classify four categories — reduced EF (rEF, EF<40%), midrange EF (mEF, 40–50%), HFpEF, and controls — using data from two health systems (Atrium Health Wake Forest Baptist: 1,078,198 ECGs / 165,243 patients; UTHSC: 72,832 ECGs / 42,880 patients), with additional pediatric validation.","key_result":"The 12-lead ECG-AI model achieved AUCs of 0.90 / 0.81 / 0.80 for rEF / mEF / HFpEF in internal holdout data and 0.92 / 0.76 / 0.73 in external validation; single Lead I performance was close (0.89 / 0.78 / 0.75 internally; 0.90 / 0.75 / 0.74 externally). In pediatric data, 12-lead AUCs were 0.97 / 0.71 / 0.64 for rEF / mEF / HFpEF. Adding clinical risk factors to ECG-AI did not significantly improve performance.","limitations":"- HFpEF prevalence was low (1–2%) in both cohorts, which may limit model calibration and real-world generalizability.\n- Clinical-only models lacked generalizability across sites, suggesting potential dataset-specific confounding.\n- Pediatric validation included only 142 cases, limiting conclusions for that population.","practice_takeaway":"A single ECG lead may be sufficient to screen for LV dysfunction and HFpEF with clinically meaningful accuracy, opening the door to low-cost, wearable-based screening. Clinicians should note that HFpEF detection performance (AUC ~0.73–0.80) is weaker than rEF detection and warrants confirmatory testing."}},{"doi":"10.3389/fendo.2026.1898812","pmid":null,"title":"Incretin analogues as cardiovascular agents: a state-of-the-art review","journal_title":"Frontiers in Endocrinology","journal_issn":"1664-2392","published_at":"2026-07-24T00:00:00.000Z","url":"https://doi.org/10.3389/fendo.2026.1898812","source_score":6,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-08-01T13:22:05.504Z","updated_at":"2026-08-01T13:22:05.504Z","tags":[{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"brand","value":"Mounjaro","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"brand","value":"Ozempic","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"category","value":"Endocrinology & Metabolism","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"condition","value":"Chronic Kidney Disease","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"condition","value":"Peripheral Artery Disease","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"condition","value":"Type 2 Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"generic","value":"orforglipron","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"generic","value":"retatrutide","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"generic","value":"semaglutide","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"generic","value":"tirzepatide","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"modality","value":"GIP/GLP-1 Dual Receptor Agonist","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"warning","value":"Brand name tags are inferred from common proprietary names for semaglutide and tirzepatide; the paper itself does not explicitly list all brand names.","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"warning","value":"Most full-text pages were rendered as images and were not machine-readable, so specific trial-level statistics (hazard ratios, confidence intervals, p-values) could not be extracted or verified.","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"warning","value":"Pipeline agent data (retatrutide, CagriSema, survodutide, orforglipron, zenagamtide, MariTide) reflects ongoing trials as of the publication date (July 2026); results may not yet be available.","value_numeric":null},{"paper_doi":"10.3389/fendo.2026.1898812","tag_type":"warning","value":"This is a narrative review, not a systematic review or meta-analysis; the level of evidence tag reflects the study design rather than the quality of the underlying trials reviewed.","value_numeric":null}],"summaries":{"what_studied":"This state-of-the-art review synthesizes the cardiovascular evidence base for GLP-1 receptor agonists and the dual GIP/GLP-1 agonist tirzepatide across five clinical scenarios: T2D with established ASCVD or high CV risk, overweight/obesity with CVD but without diabetes, obesity-related HFpEF, chronic kidney disease, and symptomatic peripheral artery disease. It also reviews pipeline agents and global access barriers in LMICs.","key_result":"Incretin analogues have demonstrated cardiovascular outcome benefit (reduced MACE, heart failure events, and kidney complications) across multiple clinical scenarios, with emerging data supporting improved walking ability in T2D with PAD; pipeline agents (retatrutide, CagriSema, survodutide, orforglipron, zenagamtide, MariTide) have ongoing cardiovascular outcome trials. Structural barriers—cost, reimbursement, underrepresentation in pivotal trials—limit access in LMICs despite high regional cardiometabolic burden.","limitations":"Full-text content is largely inaccessible (most pages rendered as figures/images), limiting extraction of specific trial-level numbers. The review covers a broad scope but does not appear to include a formal systematic search or meta-analysis, which reduces precision of synthesized estimates.","practice_takeaway":"Clinicians should consider incretin analogues (GLP-1 RAs and tirzepatide) not just as glucose-lowering drugs but as cardiovascular agents with proven benefit in T2D, obesity-related CVD, HFpEF, and CKD. A practical clinical algorithm is offered, but access barriers in lower-income settings must be factored into prescribing strategy."}},{"doi":"10.1016/j.jacc.2026.06.018","pmid":"42494134","title":"Management of Heart Failure With Preserved Ejection Fraction: 2026 ACC Expert Consensus Decision Pathway","journal_title":"JACC","journal_issn":"0735-1097","published_at":"2026-07-23T00:00:00.000Z","url":"https://doi.org/10.1016/j.jacc.2026.06.018","source_score":100,"is_retracted":false,"is_open_access":null,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":false},"created_at":"2026-07-26T13:44:37.835Z","updated_at":"2026-07-26T13:44:37.835Z","tags":[{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"modality","value":"Angiotensin Receptor Blocker","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"modality","value":"Angiotensin Receptor-Neprilysin Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"modality","value":"Diuretic","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"modality","value":"Mineralocorticoid Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"modality","value":"SGLT2 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"study_design","value":"Expert Consensus / Clinical Practice Guideline","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"warning","value":"Level of evidence assigned as '7' (expert consensus/opinion) because this is a guideline/pathway document, not a primary research study.","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"warning","value":"Only the publisher landing page and partial full text were available; specific trial names, drug dosages, and individual recommendation grades cited in the document could not be fully extracted.","value_numeric":null},{"paper_doi":"10.1016/j.jacc.2026.06.018","tag_type":"warning","value":"The document is dated July 23, 2026 — it is a 'Just Accepted' publication and may not yet reflect final copyedited content or supplemental appendix details.","value_numeric":null}],"summaries":{"what_studied":"This 2026 ACC Expert Consensus Decision Pathway (ECDP) updates the 2023 version, providing practical guidance on the diagnosis and management of HFpEF, including optimal medical therapy (SGLT2 inhibitors, nonsteroidal MRAs, incretin-based therapies, ARNIs, ARBs), nonpharmacologic strategies, device therapy, and comorbidity management.","key_result":"Key updates emphasize SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and incretin-based therapies (GLP-1 receptor agonists) as central pillars of optimal medical therapy in HFpEF, reflecting recent favorable trial data; HFpEF now accounts for >50% of all HF cases with outcomes comparable to HFrEF.","limitations":"This is a consensus/expert opinion document, not a systematic review or RCT; recommendations are derived from committee deliberation and may lag behind the most recent published trials. The pathway is primarily focused on the ambulatory setting and may not fully apply to acute inpatient care.","practice_takeaway":"Clinicians should prioritize SGLT2 inhibitors, nonsteroidal MRAs, and incretin-based therapies in eligible HFpEF patients, while also screening for and managing key comorbidities (obesity, diabetes, CKD, hypertension, atrial fibrillation, CAD). Use structured diagnostic scoring tools (HFA-PEFF, H2FPEF, HFpEF-ABA) to confirm diagnosis and exclude mimics before initiating therapy."}},{"doi":"10.1001/jamacardio.2026.2104","pmid":"42418169","title":"Finerenone and Blood Pressure in Heart Failure With Mildly Reduced or Preserved Ejection Fraction","journal_title":"JAMA Cardiology","journal_issn":"2380-6583","published_at":"2026-07-08T00:00:00.000Z","url":"https://eprints.gla.ac.uk/view/journal_volume/JAMA_Cardiology.html>,","source_score":50,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-17T13:33:01.465Z","updated_at":"2026-08-17T13:33:01.465Z","tags":[{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"brand","value":"Kerendia","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"condition","value":"Heart Failure With Mildly Reduced Ejection Fraction","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"generic","value":"finerenone","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"modality","value":"Mineralocorticoid Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"sample_size","value":"n=5999","value_numeric":5999},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"warning","value":"Multiple authors have financial relationships with Bayer AG, the trial sponsor, which funded the study and was involved in study supervision and data collection.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"warning","value":"The brand name 'Kerendia' is assigned based on known finerenone branding; the paper itself does not mention a brand name.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2104","tag_type":"warning","value":"This is a prespecified secondary/subgroup analysis of the FINEARTS-HF trial, not the primary trial report — causal mediation estimates should be interpreted cautiously given wide confidence intervals crossing zero.","value_numeric":null}],"summaries":{"what_studied":"This prespecified secondary analysis of the FINEARTS-HF RCT examined the blood pressure (BP) effects of finerenone vs placebo in 5,999 adults with HFmrEF/HFpEF (mean age 72 years, 45% female, mean baseline SBP 129 mmHg), and whether baseline BP or BP reduction mediated finerenone's cardiovascular benefits over up to 36 months.","key_result":"Finerenone produced an early, sustained SBP reduction (overall placebo-adjusted mean: −3.1 mmHg; 95% CI, −3.6 to −2.6; P<.001), consistent across all baseline SBP categories. Cardiovascular death and total HF events were reduced irrespective of baseline SBP or DBP (P for interaction .96 and .83, respectively), and causal mediation analysis showed only ~7.4% of finerenone's benefit was mediated by SBP change (95% CI, −0.7 to 27.0).","limitations":"- No 24-hour ambulatory BP monitoring, limiting BP characterization.\n- Exclusion of patients with symptomatic hypotension or uncontrolled SBP ≥160 mmHg (or ≥180 mmHg) may limit generalizability to extreme BP ranges.\n- Industry-sponsored trial (Bayer AG) with multiple author conflicts of interest.","practice_takeaway":"Finerenone lowers BP modestly but its cardiovascular benefit in HFmrEF/HFpEF is not driven by BP reduction — clinicians can use it across a broad baseline BP range without concern that only hypertensive patients benefit. The ~1.6–2.0× higher odds of SBP <100 mmHg events with finerenone vs placebo were consistent across BP subgroups, so monitoring for hypotension remains relevant regardless of baseline BP."}},{"doi":"10.1093/eurheartj/ehag450","pmid":"42390477","title":"Brain mineralocorticoid receptor activation and antagonism in heart failure with preserved ejection fraction: a hypothesis","journal_title":"European Heart Journal","journal_issn":"0195-668X","published_at":"2026-07-02T00:00:00.000Z","url":"https://doi.org/10.1093/eurheartj/ehag450","source_score":27,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-09T13:36:07.499Z","updated_at":"2026-07-09T13:36:07.499Z","tags":[{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"modality","value":"Mineralocorticoid Receptor Antagonist","value_numeric":null},{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"study_design","value":"Hypothesis / Narrative Review","value_numeric":null},{"paper_doi":"10.1093/eurheartj/ehag450","tag_type":"warning","value":"No patient data, sample size, or clinical outcomes are reported — this is a mechanistic hypothesis paper only. Tags for sample size, sex, and age group are omitted accordingly. Study design label reflects the conceptual/opinion nature of the publication.","value_numeric":null}],"summaries":{"what_studied":"This paper proposes a hypothesis about the role of brain mineralocorticoid receptor (MR) activation and its antagonism in the pathophysiology and treatment of heart failure with preserved ejection fraction (HFpEF).","key_result":"The authors hypothesize that brain MR activation contributes to the neurohormonal dysregulation seen in HFpEF, and that MR antagonism may exert beneficial effects partly through central nervous system mechanisms, beyond its known peripheral actions.","limitations":"This is a hypothesis paper, not an interventional or observational study — no clinical outcome data or patient cohort is presented. The proposed central MR mechanisms in HFpEF remain largely untested in humans.","practice_takeaway":"While MR antagonists are used in heart failure, this hypothesis suggests their brain-mediated effects may be an underappreciated therapeutic mechanism in HFpEF — clinicians should watch for emerging trial data testing this concept."}},{"doi":"10.1007/s10384-026-01381-w","pmid":"42217147","title":"Ocular microvascular alterations in patients with heart failure with preserved ejection fraction","journal_title":"Japanese Journal of Ophthalmology","journal_issn":"0021-5155","published_at":"2026-05-30T00:00:00.000Z","url":"https://doi.org/10.1007/s10384-026-01381-w","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:24:00.269Z","updated_at":"2026-06-10T14:24:00.269Z","tags":[{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"condition","value":"Left Ventricular Diastolic Dysfunction","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"modality","value":"Laser Speckle Flowgraphy","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"modality","value":"Optical Coherence Tomography Angiography","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"sample_size","value":"n=30","value_numeric":30},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"study_design","value":"Prospective Observational Study","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"warning","value":"Age and comorbidity matching between HFpEF and control groups is not described in detail, which may confound retinal and choroidal thickness comparisons.","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"warning","value":"Sample size is very small (n=15 per group), making effect size estimates and p-values unstable; results should be considered hypothesis-generating only.","value_numeric":null},{"paper_doi":"10.1007/s10384-026-01381-w","tag_type":"warning","value":"Sex breakdown of the cohort was not explicitly reported in the abstract; the 'mixed' sex tag is inferred from typical HFpEF demographics.","value_numeric":null}],"summaries":{"what_studied":"This prospective observational study compared ocular microvascular and structural parameters — including LSFG-derived blood flow, OCTA macular metrics, retinal thickness, and choroidal thickness — between 15 patients with HFpEF and 15 controls, with correlation analyses to echocardiographic markers of diastolic dysfunction.","key_result":"HFpEF patients showed significantly reduced optic nerve head (ONH) and macular blood flow by LSFG (p=0.0002 and p=0.0012), enlarged foveal avascular zone on OCTA (p=0.018), and thinner central retinal (p=0.011) and choroidal (p=0.010) thickness vs. controls; ONH blood flow correlated inversely with E/e' (r=−0.67, p=0.011), linking ocular perfusion to left ventricular diastolic dysfunction.","limitations":"Very small sample size (n=30 total; 15 per group) limits generalizability. Observational design precludes causal inference. Confounding from comorbidities common in HFpEF (e.g., hypertension, diabetes) was not fully addressed.","practice_takeaway":"Ocular imaging tools (LSFG, OCT/OCTA) may detect microvascular and structural changes in HFpEF that correlate with cardiac diastolic dysfunction — though findings are preliminary given the small sample. Clinicians should be aware that HFpEF patients may present with subtle retinal and choroidal thinning and reduced ocular perfusion."}},{"doi":"10.1093/ehjcvp/pvag024","pmid":"42213452","title":"Venous vascular pharmacology: how does it contribute to heart failure with preserved ejection fraction?","journal_title":"European Heart Journal - Cardiovascular Pharmacotherapy","journal_issn":"2055-6837","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1093/ehjcvp/pvag024","source_score":4,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-09T13:50:09.912Z","updated_at":"2026-06-09T13:50:09.912Z","tags":[{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"condition","value":"Venous Endothelial Dysfunction","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"modality","value":"Vasodilator","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"warning","value":"No specific drug names, brands, or sample sizes are reported — this is a narrative review without original patient or animal data.","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"warning","value":"Publication date is listed as 2026-05-29, which is in the future relative to most indexed literature but consistent with today's date of June 09, 2026.","value_numeric":null},{"paper_doi":"10.1093/ehjcvp/pvag024","tag_type":"warning","value":"Study design classified as 'Narrative Review'; it is not a systematic review or meta-analysis, so evidence synthesis may carry selection bias.","value_numeric":null}],"summaries":{"what_studied":"This review examines the role of venous vascular pharmacology — specifically the balance between endothelial-derived relaxing and contractile factors (EDRF/EDCF) — in the pathogenesis of HFpEF, and evaluates how current HFpEF therapies may target venous pathways in preclinical and clinical models.","key_result":"Evidence suggests venous endothelial dysfunction, elevated venous tone, and increased mean circulatory filling pressure contribute to ventricular-vascular mismatch in HFpEF; however, studies directly investigating EDRF/EDCF effects in validated HFpEF animal models are lacking.","limitations":"- No original data; findings are limited to synthesis of existing preclinical and clinical literature.\n- Preclinical evidence is largely from healthy or hypertensive animal models, not validated HFpEF models.\n- Clinical studies have not consistently used venous-specific endpoints (e.g., direct venous compliance measures), limiting translational conclusions.","practice_takeaway":"Clinicians managing HFpEF should be aware that venous tone and compliance may be under-targeted by current therapies; future trials should include venous-specific functional endpoints to better guide treatment strategies."}},{"doi":"10.1161/circulationaha.126.080833","pmid":"42104906","title":"Angiotensin Receptor Neprilysin Inhibitor in Heart Failure With Preserved Ejection Fraction and Secondary Mitral Regurgitation: The PRAISE-MR Randomized Trial","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2026-05-09T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.126.080833","source_score":19,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-01T13:27:23.427Z","updated_at":"2026-07-01T13:27:23.427Z","tags":[{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"brand","value":"Entresto","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"condition","value":"Atrial Functional Mitral Regurgitation","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"generic","value":"sacubitril/valsartan","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"modality","value":"Angiotensin Receptor-Neprilysin Inhibitor","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"sample_size","value":"n=84","value_numeric":84},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"warning","value":"Age breakdown and sex distribution of the 84 participants are not reported in the abstract; age_group tagged as 'adult' by inference from HFpEF population context.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"warning","value":"Brand name 'Entresto' inferred from sacubitril/valsartan; confirm if a different branded formulation was used in trial countries.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"warning","value":"Open-label design with blinded endpoint assessment (PROBE design) — performance bias cannot be excluded.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080833","tag_type":"warning","value":"The trial is recently published (May 2026) and has not yet been validated by independent replication; clinical adoption should await larger confirmatory trials.","value_numeric":null}],"summaries":{"what_studied":"This multicenter, open-label RCT (n=84) evaluated sacubitril/valsartan vs. standard of care over 6 months in patients with symptomatic HFpEF and at least moderate atrial functional mitral regurgitation (AFMR), using cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho) to assess exercise hemodynamics.","key_result":"Sacubitril/valsartan significantly improved the exercise mPAP/CO slope vs. SOC (adjusted difference: −0.93 mmHg/L/min; 95% CI −1.80 to −0.07; P=0.035), with better peak VO₂ (+0.9 vs. −0.6 mL/kg/min; P=0.002), KCCQ scores (+10 vs. +2 points; P=0.002), reduced NT-proBNP and LA volume (P<0.001 for both), and blunted exercise-induced MR increase (P=0.020).","limitations":"- Small sample (n=84); underpowered for clinical outcomes.\n- Open-label design with only blinded endpoint assessment introduces potential performance bias.\n- No placebo control; target dose reached in only 60% of patients, limiting generalizability.","practice_takeaway":"In HFpEF patients with AFMR, sacubitril/valsartan improved exercise hemodynamics and quality of life at 6 months — but the small, open-label design means these findings are hypothesis-generating only. Larger placebo-controlled trials are needed before changing practice."}},{"doi":"10.1016/j.jtcvs.2026.03.621","pmid":"42092503","title":"The 2026 American Association for Thoracic Surgery Expert Consensus Document: Management of atrial functional mitral regurgitation","journal_title":"The Journal of Thoracic and Cardiovascular Surgery","journal_issn":"0022-5223","published_at":"2026-05-04T00:00:00.000Z","url":"https://doi.org/10.1016/j.jtcvs.2026.03.621","source_score":28,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-31T13:35:40.972Z","updated_at":"2026-05-31T13:35:40.972Z","tags":[{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"condition","value":"Atrial Fibrillation","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"condition","value":"Atrial Functional Mitral Regurgitation","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"modality","value":"Antiarrhythmic Therapy","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"modality","value":"Anticoagulation","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"modality","value":"Surgical Mitral Valve Repair","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"modality","value":"Transcatheter Mitral Valve Intervention","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"study_design","value":"Expert Consensus Document","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"warning","value":"Full recommendation text and individual statement grades are not included in the abstract; specific class/level ratings cannot be extracted.","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"warning","value":"No sample size is applicable — this is a consensus document, not a clinical trial.","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"warning","value":"Sex distribution of the expert panel or patient populations referenced is not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1016/j.jtcvs.2026.03.621","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the novelty of a formal consensus framework for AFMR, but the underlying evidence base is largely observational/expert opinion.","value_numeric":null}],"summaries":{"what_studied":"An international multidisciplinary expert panel evaluated the diagnosis and management of atrial functional mitral regurgitation (AFMR) — MR secondary to left atrial dilation and annular remodeling without significant LV disease — using a systematic literature review and iterative Delphi consensus process.","key_result":"Consensus was reached on 18 statements across 5 domains: AFMR definition/pathophysiology/diagnosis; medical and rhythm management; surgical treatment and concomitant procedures; transcatheter and hybrid interventions; and postoperative rhythm and anticoagulation management.","limitations":"Consensus document rather than a primary study — recommendations reflect expert opinion and available evidence, which the authors acknowledge is limited; no prospective randomized trial data specific to AFMR underpins many statements. Grading by class of recommendation and level of evidence is applied, but the evidence base remains largely observational.","practice_takeaway":"Clinicians should recognize AFMR as a distinct secondary MR etiology driven by atrial remodeling — not LV disease — especially in patients with AF or HFpEF, and apply a multidisciplinary approach for timing and choice of intervention. Prospective research is still needed to optimize outcomes in this underrecognized population."}},{"doi":"10.1161/circulationaha.126.079918","pmid":"41904795","title":"Sotatercept for Combined Post- and Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From the Phase 2, Randomized, Placebo-Controlled CADENCE Study","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2026-03-29T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.126.079918","source_score":108,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-12","doi":"10.1161/circulationaha.126.079918","days":"7","issn":"0009-7322","rank":"3","field":"Clinical Medicine","score":"108","category":"Cardiac & Cardiovascular Systems","categories":["Cardiac & Cardiovascular Systems"],"_categories":["Cardiac & Cardiovascular Systems"]},"pubmed":{"doi":"10.1161/CIRCULATIONAHA.126.079918","title":"Sotatercept for Combined Post- and Pre-capillary Pulmonary Hypertension Associated With Heart Failure: Results from the Phase 2, Randomized, Placebo-Controlled CADENCE Study.","journal":"Circulation","methods":"","results":"164 patients were randomized 54:55:55 to sotatercept 0.3 mg/kg, 0.7 mg/kg, and placebo, and baseline median pulmonary vascular resistance was 5.2 (interquartile range [IQR] 4.0-6.9) Wood units. The median change from baseline in pulmonary vascular resistance at week 24 was -0.67 Wood units in the sotatercept 0.3 mg/kg group, -0.33 Wood units in the sotatercept 0.7 mg/kg group, and 0.26 Wood units in the placebo group. The Hodges-Lehmann shift estimates in pulmonary vascular resistance were -1.02 Wood units (95% CI, -1.81 to -0.23; ","abstract":"$30","keywords":[],"pubmed_id":"41904795","conclusions":"","publication_date":"2026-03-29T00:00:00"},"crossref":{"DOI":"10.1161/circulationaha.126.079918","URL":"https://doi.org/10.1161/circulationaha.126.079918","ISSN":["0009-7322","1524-4539"],"link":[{"URL":"https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.126.079918","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1446-1459","type":"journal-article","issue":"19","score":1,"title":["Sotatercept for Combined Post- and Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From the Phase 2, Randomized, Placebo-Controlled CADENCE Study"],"author":[{"given":"Mardi","family":"Gomberg-Maitland","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Cardiology, George Washington University School of Medicine and Health Sciences, Washington, DC (M.G-M.)."}]},{"given":"Ryan J.","family":"Tedford","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston (R.J.T.)."}]},{"given":"David","family":"Langleben","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiology, Center for Pulmonary Vascular Disease, Azrieli Heart Center, Jewish General Hospital, McGill University, Montreal, Canada (D.L.)."}]},{"given":"Stephan","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Heart Center, Department of Cardiology, Cologne University Hospital, Cologne Cardiovascular Research Center, Germany (S.R.)."}]},{"given":"Barry","family":"Miller","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}]},{"given":"Aaron D.","family":"Jones","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}]},{"given":"Alessia","family":"Urbinati","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}]},{"given":"Ciaran J.","family":"McMullan","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}]},{"given":"Alexandra G.","family":"Cornell","sequence":"additional","affiliation":[{"name":"Merck & Co, Inc, Rahway, NJ (B.M., A.D.J., A.U., C.J.M., A.G.C.)."}]},{"given":"Jean-Luc","family":"Vachiery","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hôpital Universitaire de Bruxelles Erasme, Brussels, Belgium (J-L.V.)."}]}],"funder":[{"name":"Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey, USA"}],"issued":{"date-parts":[[2026,5,12]]},"member":"276","prefix":"10.1161","source":"Crossref","volume":"153","created":{"date-time":"2026-03-29T16:00:30Z","timestamp":1774800030000,"date-parts":[[2026,3,29]]},"indexed":{"date-time":"2026-05-12T07:38:16Z","timestamp":1778571496338,"date-parts":[[2026,5,12]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079918"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2026-02-10"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":2,"value":"2026-03-18"},{"name":"published","group":{"name":"publication_history","label":"Publication 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The primary end point was change in pulmonary vascular resistance (PVR) at 24 weeks; baseline median PVR was 5.2 Wood units (IQR 4.0–6.9).","key_result":"At week 24, median change in PVR was −0.67 Wood units with sotatercept 0.3 mg/kg, −0.33 with 0.7 mg/kg, and +0.26 with placebo. A Hodges–Lehmann shift estimate in PVR was −1.02 Wood units (95% CI, −1.81 to −0.23).","limitations":"Phase 2 study with modest sample size (n=164) and 24-week follow-up. The dose–response was non-linear, with the 0.3 mg/kg group showing a larger median PVR reduction than 0.7 mg/kg.","practice_takeaway":"Sotatercept lowered PVR versus placebo over 24 weeks in adults with CpcPH-HFpEF, supporting proof-of-concept for activin pathway inhibition. 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Systems","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"condition","value":"Heart Failure With Reduced Ejection Fraction","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"modality","value":"Dual GIP/GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"modality","value":"GLP-1 Receptor Agonist","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"study_design","value":"Expert Consensus","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"warning","value":"Effects on heart failure events and cardiovascular mortality remain uncertain and are based on two small HFpEF trials with few events.","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"warning","value":"Evidence in HFrEF is sparse, and dedicated outcome trials had not launched at the time of publication.","value_numeric":null},{"paper_doi":"10.1002/ejhf.70082","tag_type":"warning","value":"Summary is based on an expert consensus abstract; quantitative effect sizes and trial sample sizes are not reported.","value_numeric":null}],"summaries":{"what_studied":"An expert consensus outlines practical use of GLP-1 receptor agonists and the dual GIP/GLP-1 agonist for patients with heart failure and obesity, emphasizing HFpEF, patient selection, safety, tolerability, and clinical integration.","key_result":"In HFpEF, trials reported weight loss and improvements in health status and exercise capacity, but effects on heart failure events and cardiovascular mortality are unknown because evidence comes from two small trials with few events. Data for HFrEF are scarce, and dedicated outcome trials have not yet launched.","limitations":"Findings for HFpEF rely on two small trials with few observed events. There is a lack of dedicated outcome trials, and evidence in HFrEF is minimal.","practice_takeaway":"GLP-1–based therapy can aid weight loss and symptom improvement in HFpEF with obesity, but event and mortality benefits are unproven. In HFrEF, evidence is insufficient; use these agents with careful attention to safety and tolerability while awaiting outcomes data."}}],"initialOffset":13,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Heart Failure With Preserved Ejection Fraction"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Heart Failure With Preserved Ejection Fraction"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Heart Failure With Preserved Ejection Fraction"}}}]]

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