Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
Duke Clinical Research Institute, Durham, NC, USA.
ESC Heart Fail. 2024 Oct;11(5):2813-2824. doi: 10.1002/ehf2.14777. Epub 2024 May 16.
Clinical trials in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) commonly have detailed eligibility criteria. This may contribute to challenges with efficient enrolment and questions regarding the generalizability of trial findings.
Patients with HFmrEF/HFpEF from a large US healthcare system were identified through a computable phenotype applied in linked imaging and electronic health record databases. We evaluated shared eligibility criteria from five recent/ongoing HFmrEF/HFpEF trials (PARAGON-HF, EMPEROR-Preserved, DELIVER, FINE-ARTS, and SPIRRIT-HFpEF) and compared clinical and echocardiographic features as well as outcomes between trial-eligible and trial-ineligible patients. Among 5552 patients with HFpEF/HFmrEF, 792 (14%) were eligible for trial consideration, having met all criteria assessed. Causes of ineligibility included lack of recent loop diuretics (37%), significant pulmonary disease (24%), reduced estimated glomerular filtration rate (17%), recent stroke/transient ischaemic attack (13%), or low natriuretic peptides (12%); 53% of ineligible patients had >1 reason for exclusion. Compared with eligible patients, ineligible patients were younger (age 71 vs. 75 years, P < 0.001) with higher rates of coronary artery disease (66% vs. 59%, P < 0.001) and peripheral vascular disease (40% vs. 33%, P < 0.001), but less mitral regurgitation, lower E/e' ratio, and smaller left atrial sizes. Both eligible and ineligible patients demonstrated high rates of structural heart disease consistent with HFpEF [elevated left atrial size or left ventricular (LV) hypertrophy/increased LV mass], although this was slightly higher among eligible patients (95% vs. 92%, P = 0.001). The two cohorts demonstrated similar LV global longitudinal strain along with a similar prevalence of atrial fibrillation/flutter, hypertension, and obesity. Ineligible patients had similar all-cause mortality (33% vs. 33% at 3 years) to those eligible but lower rates of heart failure hospitalization (20% vs. 28% at 3 years, P < 0.001).
Among patients with HFmrEF/HFpEF from a large health system, approximately one in seven were eligible for major trials based on key criteria applied through a clinical computable phenotype. These findings highlight the large proportion of patients with HFmrEF/HFpEF ineligible for contemporary trials for whom the generalizability of trial findings may be questioned and further investigation would be beneficial.
射血分数轻度降低或保留的心力衰竭（HFmrEF/HFpEF）的临床试验通常有详细的入选标准。这可能导致入组效率低下的挑战，并对试验结果的普遍性提出质疑。
通过应用于影像学和电子健康记录数据库的可计算表型，从美国大型医疗保健系统中确定了 HFmrEF/HFpEF 患者。我们评估了五项最近/正在进行的 HFmrEF/HFpEF 试验（PARAGON-HF、EMPEROR-Preserved、DELIVER、FINE-ARTS 和 SPIRRIT-HFpEF）的共同入选标准，并比较了试验入选和未入选患者的临床和超声心动图特征以及结局。在 5552 名 HFpEF/HFmrEF 患者中，有 792 名（14%）符合所有评估标准，有资格进行试验考虑。不符合入选标准的原因包括最近未使用袢利尿剂（37%）、严重肺部疾病（24%）、估算肾小球滤过率降低（17%）、近期卒中和短暂性脑缺血发作（13%）或低利钠肽（12%）；53%的不符合入选标准的患者有>1个排除原因。与入选患者相比，不符合入选标准的患者年龄较小（71 岁 vs. 75 岁，P<0.001），冠状动脉疾病（66% vs. 59%，P<0.001）和外周血管疾病（40% vs. 33%，P<0.001）发生率较高，但二尖瓣反流较少，E/e'比值较低，左心房大小较小。入选和未入选的患者均表现出与 HFpEF 一致的结构性心脏病高发生率[左心房增大或左心室（LV）肥厚/增加 LV 质量]，尽管入选患者的这一比例略高（95% vs. 92%，P=0.001）。两个队列的左心室整体纵向应变相似，心房颤动/扑动、高血压和肥胖的患病率相似。不符合入选标准的患者的全因死亡率与入选患者相似（3 年时为 33%），但心力衰竭住院率较低（3 年时为 20%，P<0.001）。
在来自大型医疗系统的 HFmrEF/HFpEF 患者中，约有七分之一的患者根据通过临床可计算表型应用的关键标准符合主要试验的入选标准。这些发现突出了 HFmrEF/HFpEF 患者中有很大一部分不符合当前试验的入选标准，可能对试验结果的普遍性提出质疑，进一步的研究将是有益的。
