Distinct Impact of Noncardiac Comorbidities on Exercise Capacity and Functional Status in Chronic Heart Failure.

BACKGROUND

Noncardiac comorbidities (NCCs) are common in patients with heart failure (HF), but how they jointly affect exercise capacity and functional status is relatively unexplored.

OBJECTIVES

This study sought to investigate the cumulative effects of NCC on exercise capacity and functional status in chronic HF.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.