Pulmonary, Allergy, and Critical Care Division.
Department of Biostatistics, Epidemiology, and Informatics, and.
Ann Am Thorac Soc. 2024 Jun;21(6):858-865. doi: 10.1513/AnnalsATS.202307-609OC.
Pulmonary arterial hypertension (PAH) is a progressive disease with manifestations including right atrial enlargement, right ventricular dysfunction, dilation, and hypertrophy. Electrocardiography (ECG) is a noninvasive, inexpensive test that is routinely performed in clinical settings. Prior studies have described separate abnormal findings in the electrocardiograms of patients with PAH. However, the role of composite ECG findings reflective of right heart disease (RHD) for risk stratification, clinical trial enrichment, and management of patients with PAH has not been explored. To describe a pattern of RHD on ECG in patients with PAH and to investigate the association of this pattern with clinical measures of disease severity and outcomes. We harmonized individual participant data from 18 phase III randomized clinical trials of therapies for PAH (1998-2013) submitted to the U.S. Food and Drug Administration. RHD was defined as the presence of right ventricular hypertrophy, right axis deviation, right atrial enlargement, or right bundle branch block on ECG. Random effects linear regression, multilevel ordinal regression (cumulative link model), and Cox proportional hazards models were used to assess the association of RHD by ECG with 6-minute walk distance (6MWD), World Health Organization (WHO) functional class, and clinical worsening after adjustment for age, sex, body mass index, and PAH etiology. Effect modification of treatment and ECG abnormalities was assessed by including an interaction term. A total of 4,439 patients had baseline ECG, and 68% of patients had evidence of RHD. RHD on ECG was associated with higher pulmonary vascular resistance ( < 0.001) and higher mean pulmonary artery pressures ( < 0.001). Patients with RHD on ECG had 10 meters shorter 6MWD ( = 0.005) and worse WHO functional class ( < 0.001) at baseline. RHD on baseline ECG was associated with increased risk of clinical worsening (hazard ratio, 1.42; 95% confidence interval; 1.21, 1.67; < 0.001). Patients with RHD had greater treatment effect in terms of 6MWD, WHO functional class, and time to clinical worsening than those without ( for interaction = 0.03, 0.001, and 0.03, respectively). RHD by ECG may be associated with worse outcomes and potentially greater treatment effect. Electrocardiograms could be an inexpensive, widely available noninvasive method to enrich clinical trial populations in PAH.
肺动脉高压（PAH）是一种进行性疾病，其表现包括右心房增大、右心室功能障碍、扩张和肥大。心电图（ECG）是一种非侵入性、廉价的测试，通常在临床环境中进行。先前的研究已经描述了 PAH 患者心电图中单独的异常发现。然而，反映右心疾病（RHD）的复合 ECG 结果在 PAH 患者的风险分层、临床试验富集和管理中的作用尚未得到探索。
本研究旨在描述 PAH 患者心电图中的 RHD 模式，并探讨该模式与疾病严重程度和结局的临床测量指标之间的关系。
我们对 1998 年至 2013 年提交给美国食品和药物管理局的 18 项 PAH 治疗的 III 期随机临床试验的个体参与者数据进行了协调。心电图上存在右心室肥厚、右轴偏移、右心房扩大或右束支传导阻滞定义为 RHD。使用随机效应线性回归、多级有序回归（累积链接模型）和 Cox 比例风险模型，在调整年龄、性别、体重指数和 PAH 病因后，评估 RHD 与 6 分钟步行距离（6MWD）、世界卫生组织（WHO）功能分级和临床恶化的关系。通过包括交互项来评估治疗和心电图异常的效应修饰。
共有 4439 例患者进行了基线心电图检查，其中 68%的患者存在 RHD 证据。心电图上的 RHD 与更高的肺血管阻力（ < 0.001）和更高的平均肺动脉压（ < 0.001）相关。心电图上有 RHD 的患者在基线时的 6MWD 短 10 米（ = 0.005），WHO 功能分级更差（ < 0.001）。心电图上的 RHD 与临床恶化的风险增加相关（危险比，1.42；95%置信区间，1.21，1.67； < 0.001）。与无 RHD 的患者相比，有 RHD 的患者在 6MWD、WHO 功能分级和临床恶化时间方面的治疗效果更好（交互项为 0.03、0.001 和 0.03）。
心电图上的 RHD 可能与更差的结局和潜在更大的治疗效果相关。心电图可能是一种廉价、广泛可用的非侵入性方法，可用于丰富 PAH 临床试验人群。
