Kaufman Center for Heart Failure Treatment and Recovery, Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
JACC Heart Fail. 2023 Oct;11(10):1365-1376. doi: 10.1016/j.jchf.2023.05.018. Epub 2023 Jun 28.
Noncardiac comorbidities (NCCs) are common in patients with heart failure (HF), but how they jointly affect exercise capacity and functional status is relatively unexplored.
This study sought to investigate the cumulative effects of NCC on exercise capacity and functional status in chronic HF.
Baseline NCC-status was assessed in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), IRONOUT-HF (Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure), NEAT-HFpEF (Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction), INDIE-HFpEF (Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF), and RELAX-HFpEF (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) trials, and relations with peak Vo and 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and all-cause death were determined according to HF type (with reduced vs preserved ejection fraction). Cluster analysis of the different NCCs was performed.
A total of 2,777 patients were evaluated (mean age: 60 ± 13 years; median NCC burden in HF with preserved vs reduced ejection fraction: 3 [IQR: 2-4] vs 2 [IQR: 1-3]; P < 0.001). Obesity played a more important role in HF with preserved ejection fraction in limiting peak Vo and 6MWT. There was a progressive decline in peak Vo, 6MWT, and KCCQ with increasing NCC burden. Cluster analysis revealed 3 NCC clusters: cluster 1: predominance of stroke and cancer; cluster 2: predominance of chronic kidney disease and peripheral vascular disease; and cluster 3: predominance of obesity and diabetes. Patients in cluster 3 had the worst peak Vo, 6MWT, and KCCQ despite having the lowest N-terminal pro-B-type natriuretic peptide and exhibited diminished response to aerobic exercise training (peak VoP = 0.045); however, it had similar risk for all-cause death as cluster 1, whereas cluster 2 had higher risk of death than cluster 1 (HR: 1.60 [95% CI: 1.25-2.04]; P < 0.001).
NCC type and burden have a significant and cumulative effect on exercise capacity, occur in clusters, and are associated with clinical outcomes in patients with chronic HF.
非心脏合并症（NCCs）在心力衰竭（HF）患者中很常见，但它们如何共同影响运动能力和功能状态还相对未知。
本研究旨在探讨 NCC 对慢性 HF 患者运动能力和功能状态的累积影响。
在 HF-ACTION（心力衰竭：一项控制试验，研究运动训练的结果）、IRONOUT-HF（口服铁补充对心力衰竭中摄氧量的影响）、NEAT-HFpEF（硝酸盐对心力衰竭保留射血分数时活动耐量的影响）、INDIE-HFpEF（无机亚硝酸盐输送以改善 HFpEF 中的运动能力）和 RELAX-HFpEF（磷酸二酯酶-5 抑制以改善射血分数保留心力衰竭的临床状况和运动能力）试验中评估了基线 NCC 状态，并根据 HF 类型（射血分数降低与保留）确定了与峰值 Vo 和 6 分钟步行试验（6MWT）、堪萨斯城心肌病问卷（KCCQ）和全因死亡的关系。对不同的 NCC 进行了聚类分析。
共评估了 2777 名患者（平均年龄：60±13 岁；HF 保留与降低射血分数的中位数 NCC 负担：3[IQR：2-4] vs 2[IQR：1-3]；P<0.001）。肥胖在限制 HF 保留射血分数患者的峰值 Vo 和 6MWT 方面发挥了更重要的作用。随着 NCC 负担的增加，峰值 Vo、6MWT 和 KCCQ 逐渐下降。聚类分析显示 3 个 NCC 聚类：聚类 1：中风和癌症为主；聚类 2：以慢性肾脏病和外周血管疾病为主；聚类 3：以肥胖和糖尿病为主。尽管 N 端脑利钠肽前体最低，但聚类 3 患者的峰值 Vo、6MWT 和 KCCQ 最差，并且对有氧运动训练的反应减弱（峰值 VoP=0.045）；然而，它的全因死亡风险与聚类 1 相似，而聚类 2 的死亡风险高于聚类 1（HR：1.60[95%CI：1.25-2.04]；P<0.001）。
NCC 类型和负担对慢性 HF 患者的运动能力有显著且累积的影响，以聚类形式出现，并与患者的临床结局相关。
