JACC. Heart failure最新文献

英文中文

“Arising” Above Heart Failure “产生”于心力衰竭之上

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.03.021

Ersilia M. DeFilippis MD , Eileen O’Meara MD

引用次数: 0

Finerenone Across the Spectrum of Kidney Risk in Heart Failure 芬尼烯酮在心力衰竭中肾脏风险的频谱：finhearts - hf试验。

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.03.006

John W. Ostrominski MD , Finnian R. Mc Causland MBBCh, MMSc , Brian L. Claggett PhD , Akshay S. Desai MD MPH , Pardeep S. Jhund MBChB, MSc, PhD , Carolyn S.P. Lam MD, PhD , Michele Senni MD , Sanjiv J. Shah MD , Adriaan A. Voors MD , Faiez Zannad MD , Bertram Pitt MD , Patrick Schloemer PhD , Meike Brinker MD , Markus F. Scheerer PhD , John J.V. McMurray MD , Scott D. Solomon MD , Muthiah Vaduganathan MD, MPH

Background

Estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio are complementary domains of kidney disease staging and independently associated with heart failure (HF) progression.

Objectives

The purpose of this study was to evaluate whether the efficacy and safety of finerenone varies according to kidney risk among patients with HF with mildly reduced or preserved ejection fraction.

Methods

In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), clinical outcomes and treatment effects of finerenone on the primary endpoint (cardiovascular death and total [first and recurrent] HF events) and key secondary endpoints were evaluated according to baseline KDIGO (Kidney Disease: Improving Global Outcomes) risk category (low, moderately increased, and high or very high). Key exclusion criteria in FINEARTS-HF were eGFR <25 mL/min/1.73 m² or serum potassium >5.0 mmol/L.

Results

Overall, 5,797 (97%) FINEARTS-HF participants had classifiable KDIGO risk category at baseline, of whom 2,022 (35%), 1,688 (29%), and 2,087 (36%) were low, moderate, and high/very high risk, respectively. Over a median follow-up of 2.7 years, higher kidney risk was associated with a higher rate of primary outcome events, with similar findings for other key endpoints, including the composite kidney outcome, new-onset atrial fibrillation, and vascular events. Benefits of finerenone vs placebo on the primary endpoint (P_interaction = 0.24) and Kansas City Cardiomyopathy Questionnaire–Total Symptom Score at 12 months (P_interaction = 0.36) were consistent irrespective of baseline kidney risk category. Participants with higher kidney risk experienced greater reductions in urine albumin-to-creatinine ratio after 6 months (P_interaction = 0.031), without differences in eGFR slope. Risks of safety events, including hyperkalemia, with finerenone vs placebo were not enhanced among participants with higher kidney risk.

Conclusions

Finerenone appears to consistently improve clinical outcomes, HF-related health status, and albuminuria across a broad spectrum of kidney risk in patients with HF with mildly reduced or preserved ejection fraction. (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure [FINEARTS-HF]; NCT04435626)

背景：估计的肾小球滤过率（eGFR）和尿白蛋白与肌酐比值是肾脏疾病分期的互补域，并且与心力衰竭（HF）进展独立相关。目的：本研究的目的是评估芬尼酮在射血分数轻度降低或保留的HF患者中是否根据肾脏风险而变化的疗效和安全性。方法：在这项预先指定的fineards -HF（芬尼烯酮试验，研究心力衰竭患者优于安慰剂的疗效和安全性）分析中，根据基线KDIGO（肾脏疾病：改善总体结局）风险类别（低、中等增加、高或极高）评估芬尼烯酮在主要终点（心血管死亡和总[首次和复发]心力衰竭事件）和关键次要终点的临床结局和治疗效果。FINEARTS-HF的主要排除标准是eGFR 2或血清钾>5.0 mmol/L。结果：总体而言，5,797（97%）名FINEARTS-HF参与者在基线时具有可分类的KDIGO风险类别，其中2,022（35%）、1,688（29%）和2,087（36%）分别为低、中、高/极高风险。在中位2.7年的随访中，较高的肾脏风险与较高的主要结局事件发生率相关，其他关键终点也有类似的发现，包括复合肾脏结局、新发房颤和血管事件。在主要终点（p相互作用= 0.24）和堪萨斯城心肌病问卷- 12个月总症状评分（p相互作用= 0.36）上，芬纳酮与安慰剂的获益是一致的，与基线肾脏风险类别无关。肾脏风险较高的参与者在6个月后尿白蛋白与肌酐比值下降更大（p相互作用= 0.031），eGFR斜率无差异。在肾脏风险较高的参与者中，芬尼酮与安慰剂的安全性事件风险（包括高钾血症）没有增加。结论：在射血分数轻度降低或保持的HF患者中，芬纳酮似乎可以持续改善临床结果、HF相关健康状况和广谱肾脏风险的蛋白尿。评价非那烯酮对心力衰竭和左心室射血分数（每次心脏卒中排出血液比例）大于或等于40%的患者发病率（疾病影响）和死亡率（死亡率）的疗效[疾病影响]和安全性的研究[fineards - hf]；NCT04435626)。

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引用次数: 0

Rapid Uptitration of Guideline-Directed Medical Therapy for Heart Failure 心衰药物治疗指南的快速升级

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102730

Prateeti Khazanie MD, MPH , Savitri E. Fedson MD, MA

引用次数: 0

Phase I Randomized Study of Cardiac Stem Cells in Patients With Hypoplastic Left Heart Syndrome 心脏干细胞在左心发育不良综合征患者中的I期随机研究：CHILD试验。

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure

Pub Date : 2026-01-01 DOI: 10.1016/j.jchf.2025.102723

Sunjay Kaushal MD, PhD , Joshua M. Hare MD , William T. Mahle MD , Aisha Khan PhD, MBA , Richard G. Ohye MD , Timothy C. Slesnick MD , Paul J. Chai MD , Subhadra Shashidharan MD , Joshua D. Robinson MD , Pei-Ni Jone MD , Tammy Doman BS , Ming-Sing Si MD , Jimmy C. Lu MD , Ketty Bacallao PhD , Adriana E. Nettina MS , Rejane Lamazares MS , Russell G. Saltzman MSPH , Lara M. Simpson PhD , Ruosha Li PhD , Judy E. Bettencourt MPH , Michael E. Davis PhD

Background

Hypoplastic left heart syndrome (HLHS) requires a series of 3-staged palliative operations, in which the right ventricle (RV) assumes systemic circulation under increased pressure-overload conditions. These patients have a shortened lifespan, often due to RV dysfunction. Neonatal cardiac progenitor cells (nCPCs) improve RV performance in animal models of pressure overload-induced RV dysfunction, as is experienced by HLHS patients.

Objectives

The authors conducted a phase 1 trial to assess the impact of autologous nCPCs injected into the RV myocardium during stage 2 operation. The primary endpoints were safety and feasibility, with efficacy assessed by evaluating RV size and function over a 1-year period.

Methods

The study enrolled HLHS patients in 2 groups. Group A consisted of 9 consecutive patients who received nCPC injections during their stage 2 operation. Group B involved a multicenter, randomized, double-blind trial comparing nCPC injections (n = 8) to standard-of-care (SOC) treatment (n = 8). The treatment arm received nCPC injections into the RV myocardium. All caregivers and cores except the surgeon were blinded to treatment.

Results

The trial met its primary safety and feasibility endpoints. However, the primary efficacy endpoint—changes in RV size or function measured by cardiac magnetic resonance and echocardiography—was not achieved. Despite this, secondary outcomes indicated potential clinical benefits. In group B, the mean major adverse cardiac events rates per 100 person-days were higher in the SOC arm (0.23) compared to the nCPC arm (0.00; P = 0.013) after stage 2 operation. The total 1-year in-hospital length of stay due to cardiac and vascular diseases was 15 days and 2 days per 100 person-days for the SOC and nCPC arms, respectively (P = 0.035). Mechanistic studies revealed that, on average, patients in the nCPC arm exhibited noticeable increases from baseline in plasma levels of VEGFC, VEGFD, TNF-α, and monocyte chemotactic protein-1 compared to the SOC arm by postoperative day 5, though the differences were not statistically significant after false discovery rate adjustment. Whereas subject numbers were insufficient to show significance for the composite endpoint of death or listed for transplantation for group B, when combining both groups A and B, no events were seen in the combined nCPC arms and 3 events were in the SOC arm (log-rank P = 0.005).

Conclusions

Injecting nCPCs into the RV during the stage 2 operation for HLHS patients appears to be safe but does not improve RV function. These findings warrant the initiation of a phase 2 trial. (The CHILD Trial: Hypoplastic Left Heart Syndrome Study [CHILD]; NCT03406884)

背景：左心发育不全综合征（HLHS）需要一系列3阶段的姑息性手术，其中右心室（RV）在压力过载增加的情况下承担体循环。这些患者的寿命缩短，通常是由于右心室功能障碍。新生儿心脏祖细胞（nCPCs）在压力过载诱导的左心室功能障碍动物模型中改善右心室功能，正如HLHS患者所经历的那样。目的：作者进行了一项1期试验，以评估在2期手术期间将自体nCPCs注射到RV心肌的影响。主要终点是安全性和可行性，在1年期间通过评估RV的大小和功能来评估疗效。方法将HLHS患者分为两组。A组为连续9例在二期手术中接受nCPC注射的患者。B组涉及一项多中心、随机、双盲试验，比较nCPC注射（n = 8）和标准护理（SOC）治疗（n = 8）。治疗组右心室心肌注射nCPC。除外科医生外，所有护理人员和核心人员对治疗不知情。结果该试验达到了主要的安全性和可行性终点。然而，主要疗效终点——通过心脏磁共振和超声心动图测量的右心室大小或功能的变化——没有达到。尽管如此，次要结果显示了潜在的临床益处。在B组，二期手术后，SOC组（0.23）比nCPC组（0.00;P = 0.013）每100人天的平均主要心脏不良事件发生率更高。SOC组和nCPC组因心血管疾病住院1年的总时间分别为15天和2天/ 100人日（P = 0.035）。机制研究显示，平均而言，术后第5天，与SOC组相比，nCPC组患者血浆中VEGFC、VEGFD、TNF-α和单核细胞趋化蛋白-1的水平明显高于基线水平，尽管在调整错误发现率后差异无统计学意义。虽然B组的受试者数量不足以显示死亡的综合终点或移植的显著性，但当A组和B组联合使用时，nCPC组中未见任何事件，SOC组中有3起事件（log-rank P = 0.005）。结论：在HLHS患者二期手术中向右心室注射ncpc是安全的，但不能改善右心室功能。这些发现为启动二期试验提供了依据。（CHILD试验：左心发育不良综合征研究[CHILD]； NCT03406884）。

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引用次数: 0

Venting the Venous Circulation 使静脉循环通畅