JACC. Heart failure最新文献

英文中文

Sex Differences in Diabetic Cardiomyopathy and Treatment Response to AT-001 糖尿病性心肌病的性别差异和AT-001的治疗反应：来自rise - hf研究的见解

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.02.015

Vanessa Blumer MD , James L. Januzzi Jr. MD , Yuxi Liu MS , Javed Butler MD , Justin A. Ezekowitz MB, BCH , Riccardo Perfetti MD, PhD , Julio Rosenstock MD , Stefano Del Prato MD, MPH , W.H. Wilson Tang MD , Alessia Urbinati MD , Faiez Zannad MD, PhD , Gregory D. Lewis MD , Scott D. Solomon MD , Sheila Hedge MD , Nasrien E. Ibrahim MD, MPH , Carolyn S.P. Lam MBBS, PhD

Background

Diabetic cardiomyopathy (DbCM) is a significant cause of heart failure (HF) in individuals with type 2 diabetes mellitus. Although sex differences are noted in HF patients, it is unclear if such differences exist in those with DbCM and whether sex-based differences affect treatment responses.

Objectives

This analysis focuses on sex differences in baseline characteristics of study participants with DbCM at high risk for progression to overt HF and sex-based treatment responses to high-dose AT-001, a novel aldose reductase inhibitor.

Methods

The ARISE-HF trial was a Phase 3, randomized, international, placebo-controlled study designed to evaluate the efficacy and safety of AT-001 in study participants with DbCM.

Results

Of 691 participants, 348 (50.4%) were women. At baseline, women had higher N-terminal pro–B-type natriuretic peptide concentrations (92 vs 60 ng/L; P < 0.001), lower peak oxygen uptake (13.87 vs 17.59 mL/kg/min; P < 0.001), shorter cardiopulmonary exercise testing durations (8.47 vs 11.05 minutes; P < 0.001), and worse quality of life and health status (Kansas City Cardiomyopathy Questionnaire overall summary score 87.79 vs 92.55; P < 0.001; Physical Activity Scale for the Elderly score 137.87 vs 171.09; P < 0.001) compared with men. Despite these differences, there were no significant sex differences in the efficacy or tolerability of high-dose AT-001 compared with placebo. The placebo-corrected oxygen uptake change was 0.26 for women and 0.27 for men (P = 0.58), and changes from baseline to month 15 in Kansas City Cardiomyopathy Questionnaire and Physical Activity Scale for the Elderly scores showed no significant sex differences (all P > 0.05).

Conclusions

Despite baseline differences between women and men with DbCM, the efficacy and safety of high-dose AT-001 are comparable across sexes. These findings highlight the presence of sex-specific characteristics in DbCM and underscore the importance of further research to understand potential sex-specific mechanisms. (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure Trial [ARISE-HF]; NCT04083339)

背景：糖尿病性心肌病（DbCM）是2型糖尿病患者心衰（HF）的重要原因。尽管心衰患者存在性别差异，但尚不清楚DbCM患者是否存在这种差异，以及性别差异是否会影响治疗反应。目的：本分析侧重于研究参与者DbCM的基线特征的性别差异，这些参与者进展为明显HF的高风险，以及基于性别的对高剂量at -001（一种新型醛糖还原酶抑制剂）的治疗反应。方法：rise - hf试验是一项3期、随机、国际、安慰剂对照研究，旨在评估AT-001对DbCM患者的疗效和安全性。结果：691名参与者中，348名（50.4%）为女性。基线时，女性的n端前b型利钠肽浓度较高(92 vs 60 ng/L；P < 0.001)，峰值摄氧量较低(13.87 vs 17.59 mL/kg/min；P < 0.001)，较短的心肺运动试验持续时间(8.47 vs 11.05分钟；P < 0.001)，生活质量和健康状况更差(堪萨斯城心肌病问卷总总结得分87.79 vs 92.55；P < 0.001；老年人体力活动量表得分137.87比171.09；P < 0.001)。尽管存在这些差异，与安慰剂相比，高剂量AT-001的疗效或耐受性没有显著的性别差异。安慰剂校正后的摄氧量变化女性为0.26，男性为0.27 (P = 0.58)，从基线到第15个月，堪萨斯城心肌病问卷和老年人体力活动量表得分的变化没有显著的性别差异（P均为0.05）。结论：尽管女性和男性DbCM的基线存在差异，但高剂量AT-001的疗效和安全性在两性之间具有可比性。这些发现强调了DbCM中存在性别特异性特征，并强调了进一步研究以了解潜在的性别特异性机制的重要性。醛糖还原酶抑制对心力衰竭患者运动能力的稳定作用[rise - hf]；NCT04083339)。

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引用次数: 0

Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of CRD-740, a PDE9 Inhibitor, in Chronic Heart Failure PDE9抑制剂CRD-740治疗慢性心力衰竭的2期随机、双盲、安慰剂对照研究

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102706

James E. Udelson MD , Jan Bělohlávek MD, PhD , Andrej Dukát MD , Justin Ezekowitz MB, BCh, MSc , Sorel Goland MD , Bela Merkely MD, PhD , Eileen O’Meara MD , Mark C. Petrie MD , Piotr Ponikowski MD, PhD , Michele Senni MD , Mariya Tokmakova MD, PhD , Orly Vardeny PharmD, MS , Brian Claggett PhD , Elizabeth Moore DNP, CPNP-AC , Meghan Savard MPH , Hillary McKellar BA , Howard K. Surks MD , Scott D. Solomon MD , John J.V. McMurray BSc (Hons), MB ChB (Hons), MD

Background

The beneficial effects of natriuretic peptide receptor activation are mediated by cyclic guanosine monophosphate (cGMP). Phosphodiesterase 9 (PDE9) hydrolyzes cGMP and therefore its inhibition has the potential to increase intracellular cGMP signaling.

Objectives

The aim of this study is to assess the effects of the oral PDE9 inhibitor CRD-740 on plasma and urinary cGMP in patients with heart failure and reduced ejection fraction (HFrEF).

Methods

Patients with HFrEF of >6 months, NYHA functional class II/III, ejection fraction ≤40%, and elevated N-terminal pro–B-type natriuretic peptide were randomized 2:1 to CRD-740 (10 mg twice a day for 2 weeks, then 25 mg twice a day for 10 weeks) or placebo. The primary pharmacodynamic endpoint was the change in plasma cGMP to week 4.

Results

Sixty patients were randomized to CRD-740 (n = 40) or placebo (n = 20). Baseline characteristics included ejection fraction 28% ± 7%, with 73% of patients taking sacubitril/valsartan. The placebo-corrected change in plasma cGMP from baseline at week 4 increased with CRD-740, 19.1% ± 26.9% increase vs 8.8% (31.3%) decrease in area under the curve from 0 to 6 hours, respectively, for a least squared mean difference of 26.5% (95% CI: 7.8-45.1; P = 0.003). There was no interaction with the presence/absence of sacubitril/valsartan (P = 0.47). An increase in urinary cGMP was observed with CRD-740 at day 1 (P = 0.012), week 2 (P = 0.014), and week 4 (P = 0.09). No significant between-group differences in systolic blood pressure, hypotension, or serious adverse events were observed.

Conclusions

In this initial phase 2 trial, PDE9 inhibition with CRD-740 was well tolerated and resulted in elevations of plasma and urinary cGMP on top of standard care, including sacubitril/valsartan, supporting the potential of PDE9 inhibition to enhance the beneficial effects of the natriuretic peptide receptor-cGMP pathway incremental to existing heart failure treatments. (Effectiveness of CRD-740 in Heart Failure [CARDINAL-HF]; NCT05409183)

利钠肽受体激活的有益作用是由环鸟苷单磷酸（cGMP）介导的。磷酸二酯酶9 （PDE9）水解cGMP，因此其抑制有可能增加细胞内cGMP信号传导。目的：本研究的目的是评估口服PDE9抑制剂CRD-740对心力衰竭和射血分数降低（HFrEF）患者血浆和尿cGMP的影响。方法HFrEF为6个月，NYHA功能等级为II/III级，射血分数≤40%，n -末端前b型利钠肽升高的患者按2:1随机分配至CRD-740组（10 mg每日2次，持续2周，然后25 mg每日2次，持续10周）或安慰剂组。主要的药效学终点是第4周血浆cGMP的变化。结果60例患者随机分为CRD-740组（n = 40）和安慰剂组（n = 20）。基线特征包括射血分数28%±7%，73%的患者服用苏比利/缬沙坦。安慰剂校正后第4周血浆cGMP较基线的变化随crp -740增加，从0到6小时，曲线下面积分别增加19.1%±26.9%和减少8.8%(31.3%)，最小二乘法平均差为26.5% （95% CI: 7.8-45.1; P = 0.003）。与是否使用苏比里尔/缬沙坦无交互作用（P = 0.47）。CRD-740在第1天（P = 0.012）、第2周（P = 0.014）和第4周（P = 0.09）观察尿cGMP升高。在收缩压、低血压或严重不良事件方面，组间无显著差异。在这项初始2期试验中，CRD-740对PDE9的抑制具有良好的耐受性，并在标准治疗（包括苏比利/缬沙坦）的基础上导致血浆和尿液cGMP升高，支持PDE9抑制的潜力，以增强利钠肽受体-cGMP途径对现有心力衰竭治疗的有益作用。（CRD-740治疗心力衰竭的疗效[CARDINAL-HF]； NCT05409183）。

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引用次数: 0

Monitoring Disease Progression in Patients With Transthyretin Amyloid Cardiomyopathy 甲状腺素转淀粉样蛋白心肌病患者疾病进展的监测。

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102766

Pablo García-Pavía MD, PhD , Ronald M. Witteles MD , Thibaud Damy MD, PhD , Marianna Fontana MD, PhD , Giovanni Palladini MD, PhD , Kenichi Tsujita MD, PhD , Justin L. Grodin MD, MPH , Michel G. Khouri MD , Saurabh Malhotra MD, MPH , Vasvi Singh MD , Omar F. AbouEzzeddine MDCM, MS , Joban Vaishnav MD , Mazen Hanna MD , Mathew S. Maurer MD

Recognizing the lack of disease monitoring recommendations in transthyretin amyloid cardiomyopathy (ATTR-CM), international experts convened in 2021 to propose criteria for monitoring disease progression. Data have since been published demonstrating the prognostic value of certain parameters in ATTR-CM. Additionally, increased awareness and advances in diagnostic methods have led to a shift toward diagnosis at earlier stages of disease. In light of these developments, international experts with experience in treating ATTR-CM reviewed the available data, considered the feasibility of implementing evaluations in clinical practice, and proposed an update to the 2021 criteria. The criteria, with meaningful thresholds and monitoring frequency recommendations, are specifically designed to measure disease progression in patients with ATTR-CM, rather than to define progression of amyloid deposition. It remains unknown whether disease progression is an indicator for modifications to ATTR-CM treatment. Future studies should investigate whether changes in ATTR-CM disease-modifying treatment improve outcomes in patients demonstrating disease progression.

认识到甲状腺素淀粉样心肌病（atr - cm）缺乏疾病监测建议，国际专家于2021年召开会议，提出监测疾病进展的标准。此后发表的数据证明了atr - cm中某些参数的预后价值。此外，认识的提高和诊断方法的进步使人们转向在疾病的早期阶段进行诊断。鉴于这些发展，具有治疗atr - cm经验的国际专家审查了现有数据，考虑了在临床实践中实施评估的可行性，并提出了2021年标准的更新。该标准具有有意义的阈值和监测频率建议，专门用于测量atr - cm患者的疾病进展，而不是定义淀粉样蛋白沉积的进展。目前尚不清楚疾病进展是否是atr - cm治疗调整的指标。未来的研究应该调查atr - cm疾病改善治疗的改变是否能改善疾病进展患者的预后。

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引用次数: 0

Fulfilling the Promise of Cyclic GMP Signaling in Heart Failure With Reduced Ejection Fraction 循环GMP信号在心力衰竭伴射血分数降低中的应用前景

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102773

Yogesh N.V. Reddy MBBS, MS

引用次数: 0

Beyond Body Mass Index in Heart Transplantation 心脏移植中超过身体质量指数：比眼睛看到的更多。

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102764

Ann B. Nguyen MD , Michelle Kittleson MD, PhD

引用次数: 0

Population Stratification and Heterogeneity in NEXN Studies NEXN研究中的人口分层和异质性

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102735

Muhammad Mudasir Atif MBBS (Candidate)

引用次数: 0

NEXN-Related Cardiomyopathy NEXN-Related心肌病

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102736

Parth Aphale PhD, Shashank Dokania BHMS, Himanshu Shekhar BHMS

引用次数: 0

Incident Heart Failure in Adults With Mild to Moderate Chronic Kidney Disease 成人轻中度慢性肾病并发心力衰竭

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102616

Michael P. Girouard MD, MBA , Alan S. Go MD , Jane Y. Liu MPH , Rishi V. Parikh MPH , Thida C. Tan MPH , Emily S. Lee MD , Grace Sun BA , Rami Halaseh MD , Ankeet S. Bhatt MD, MBA, SM , Leonid Pravoverov MD , Sijie Zheng MD , Jana Svetlichnaya MD , Jesse K. Fitzpatrick MD , Harshith R. Avula MD, MPH , Keane K. Lee MD, MS , Sirtaz Adatya MD , David Ouyang MD , Parag Goyal MD, MS , Alexander T. Sandhu MD, MS , Andrew P. Ambrosy MD, MPH

引用次数: 0

Beyond the Pump 在泵之外：通过多系统机制透镜重构心力衰竭的心源性休克。

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102711

Ameesh Isath MD, Akshay S. Desai MD, MPH, Mandeep R. Mehra MD, MSc

Management of patients with cardiogenic shock (CS) has long focused on hemodynamic optimization, yet outcomes remain poor, particularly for those with acute-on-chronic heart failure (ACHF)-CS. This hemodynamic-centric paradigm is largely derived from ST-segment elevation myocardial infarction (STEMI)-CS, which inadequately captures the complex, multisystem physiology of ACHF-CS. The syndrome of ACHF-CS emerges from the simultaneous convergence of central hemodynamic abnormalities in concert with systemic inflammation and microcirculatory dysfunction. This primed convergence of aberrations fuels ongoing organ injury despite hemodynamic recovery—a phenomenon of hemodynamic dissonance. Unlike the acute and abrupt sequential trajectory of STEMI-CS, ACHF-CS is a distinctive mechanistic process shaped by longer-standing central and peripheral maladaptation with systemic stress at onset. This paper distinguishes ACHF-CS as a distinct shock phenotype, and highlights emerging therapeutic strategies aimed at modifying disease biology beyond a focus on solely rescuing hemodynamics. A mechanism-specific approach is essential to improve outcomes in ACHF-CS.

心源性休克（CS）患者的管理长期以来一直关注血流动力学优化，但结果仍然很差，特别是那些急性慢性心力衰竭(ACHF)-CS患者。这种以血流动力学为中心的范式主要来源于st段抬高型心肌梗死(STEMI)-CS，它不能充分捕捉到ACHF-CS复杂的多系统生理学。ACHF-CS综合征是中枢性血流动力学异常与全身性炎症和微循环功能障碍同时汇聚而成。尽管血流动力学得到了恢复，但这种畸变的启动趋同加剧了持续的器官损伤——一种血流动力学失调现象。与STEMI-CS的急性和突然顺序轨迹不同，ACHF-CS是一个独特的机制过程，由长期的中枢和外周不适应和发病时的系统性应激形成。本文将ACHF-CS区分为一种独特的休克表型，并强调了旨在改变疾病生物学的新兴治疗策略，而不仅仅是专注于挽救血液动力学。针对特定机制的方法对于改善ACHF-CS的预后至关重要。

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Toward a Streamlined Optimization Protocol for Patients With Heart Failure With Reduced Ejection Fraction 针对心力衰竭伴射血分数降低患者的简化优化方案：新证据。

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102724

Jolie Bruno MD , Aferdita Spahillari MD, MPH , Alexandre Mebazaa MD, PhD

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