Impaired Exercise Capacity in High-Risk Diabetic Cardiomyopathy: The ARISE-HF Cardiopulmonary Exercise Testing Subanalysis

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Abstract
BACKGROUND: Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF. METHODS: The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure). Cluster phenogroups with different comorbidities and their corresponding functional capacity profiles were identified. RESULTS: Among study participants (n=689), the median (Q1, Q3) peak oxygen uptake and ventilatory efficiency (slope of the ratio of minute ventilation/carbon dioxide production) were 15.7 (interquartile range, 13.0–18.0) mL/kg per minute and 31.2 (interquartile range, 27.2–34.1), respectively. Lower peak oxygen uptake was associated with older age, female sex, higher body mass index, higher N-terminal pro-B-type natriuretic peptide, and an increasing burden of noncardiac comorbid conditions but was not associated with cardiac troponin T or echocardiogram-derived strain, left atrial volume index, E/e′, or right ventricular systolic pressure. Elevated left ventricular mass index was the only echocardiographic abnormality associated with lower peak oxygen uptake. Multivariable analysis revealed that female sex, higher body mass index, and no history of dyslipidemia were independently associated with lower baseline peak oxygen uptake. Cluster analysis revealed 3 clusters with profiles of different cardiovascular/exercise parameters and health status profiles. CONCLUSIONS: Baseline cardiopulmonary exercise testing data from the ARISE-HF trial highlight predominant associations of extracardiac clinical and demographic variables with significant impairment in exercise capacity despite strict fulfillment of diagnostic criteria for stage B HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04083339.

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