Postgraduate Program in Cardiology and Cardiovascular Sciences, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
JAMA Cardiol. 2023 Feb 1;8(2):150-158. doi: 10.1001/jamacardio.2022.4427.
Heart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies.
To assess within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of HF severity (N-terminal pro-B-type natriuretic peptide [NT-proBNP] level), and their association with long-term prognosis in the PARADIGM-HF trial.
DESIGN, SETTING, AND PARTICIPANTS: All patients in PARADIGM-HF were in NYHA class II or higher at baseline and were treated with sacubitril-valsartan during a 6- to 10-week run-in period before randomization. Patients classified as NYHA class I, II, and III in PARADIGM-HF were compared at randomization.
NYHA class at randomization after 6 to 10 weeks of the run-in period.
Primary outcome was cardiovascular death or first HF hospitalization. Logistic regression models, areas under the receiver operating characteristic curve (AUC), kernel density estimation overlaps, and Cox proportional hazards models were used.
The analysis included 8326 patients with known NYHA classification at randomization. Of 389 patients in NYHA class I, 228 (58%) changed functional class during the first year after randomization. Level of NT-proBNP was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51 (95% CI, 0.48-0.54). For NT-proBNP level, estimated kernel density overlap was 93% between NYHA class I vs II, 79% between NYHA I vs III, and 83% between NYHA II vs III. Patients classified as NYHA III displayed a distinctively higher rate of cardiovascular events (NYHA III vs I, hazard ratio [HR], 1.84; 95% CI, 1.44-2.37; NYHA III vs II, HR, 1.49; 95% CI, 1.35-1.64). Patients in NYHA class I and II revealed lower event rates (NYHA II vs I, HR, 1.24; 95% CI, 0.97-1.58). Stratification by NT-proBNP level (<1600 pg/mL or ≥1600 pg/mL) identified subgroups with distinctive risk, such that NYHA class I patients with high NT-proBNP levels (n = 175) had a numerically higher event rate than patients with low NT-proBNP levels from any NYHA class (vs I, HR, 3.43; 95% CI, 2.03-5.87; vs II, HR, 2.12; 95% CI, 1.58-2.86; vs III, HR, 1.37; 95% CI, 1.00-1.88).
In this study, patients in NYHA class I and II overlapped substantially in objective measures and long-term prognosis. Physician-defined "asymptomatic" functional class concealed patients who were at substantial risk for adverse outcomes. NYHA classification might be limited to differentiate mild forms of HF.
ClinicalTrials.gov Identifier: NCT01035255.
心力衰竭 (HF) 治疗建议以纽约心脏协会 (NYHA) 分类为中心，因此大多数明显无症状的患者不符合疾病修正治疗的条件。
评估患者在时间内 NYHA 分类的变化，NYHA 类别与 HF 严重程度的客观测量（N 末端 pro-B 型利钠肽 [NT-proBNP] 水平）之间的关系，以及它们与 PARADIGM-HF 试验中的长期预后的关系。
设计、地点和参与者：PARADIGM-HF 中的所有患者在基线时均处于 NYHA Ⅱ级或更高级别，在随机分组前的 6 至 10 周的跑入期内接受沙库巴曲缬沙坦治疗。在随机分组时比较 PARADIGM-HF 中被分类为 NYHA Ⅰ、Ⅱ和Ⅲ的患者。
跑入期后随机分组时的 NYHA 类别。
主要结局是心血管死亡或首次 HF 住院。使用逻辑回归模型、接受者操作特征曲线下的面积 (AUC)、核密度估计重叠和 Cox 比例风险模型。
该分析包括 8326 名随机分组时已知 NYHA 分类的患者。在 389 名 NYHA Ⅰ级患者中，228 名（58%）在随机分组后第一年的功能分类发生了变化。NT-proBNP 水平是 NYHA 分类的一个很差的判别器：对于 NYHA Ⅰ级与Ⅱ级，AUC 为 0.51（95%CI，0.48-0.54）。对于 NT-proBNP 水平，估计的核密度重叠在 NYHA Ⅰ级与Ⅱ级之间为 93%，在 NYHA Ⅰ级与Ⅲ级之间为 79%，在 NYHA Ⅱ级与Ⅲ级之间为 83%。被分类为 NYHA Ⅲ级的患者显示出明显更高的心血管事件发生率（NYHA Ⅲ级与Ⅰ级，HR，1.84；95%CI，1.44-2.37；NYHA Ⅲ级与Ⅱ级，HR，1.49；95%CI，1.35-1.64）。NYHA Ⅰ级和Ⅱ级的患者显示出较低的事件发生率（NYHA Ⅱ级与Ⅰ级，HR，1.24；95%CI，0.97-1.58）。按 NT-proBNP 水平分层（<1600 pg/mL 或≥1600 pg/mL）可确定具有独特风险的亚组，例如 NT-proBNP 水平较高（n=175）的 NYHA Ⅰ级患者的事件发生率高于任何 NYHA 级别的 NT-proBNP 水平较低的患者（与Ⅰ级相比，HR，3.43；95%CI，2.03-5.87；与Ⅱ级相比，HR，2.12；95%CI，1.58-2.86；与Ⅲ级相比，HR，1.37；95%CI，1.00-1.88）。
在这项研究中，NYHA Ⅰ级和Ⅱ级的患者在客观测量和长期预后方面有很大的重叠。医生定义的“无症状”功能分类掩盖了有不良结局风险的患者。NYHA 分类可能无法区分轻度 HF。
ClinicalTrials.gov 标识符：NCT01035255。
