Association Between Functional Status and Cardiac Function in Chronic Heart Failure: Insights from the C-MIC II Trial

Abstract Background Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response. Methods This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25-35%. Correlations between changes in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), 6-minute walk distance (6MWD), core lab-assessed LVEF (primary measure) and site-assessed LVEF, and peak oxygen uptake (peak VO2) were evaluated at 4 weeks, 2 months, 3 months, 4 months, and 6 months using Pearson coefficients with 95% confidence intervals (CI). Results The mean age was 60.0±9.7 years and baseline LVEF was 29.8±3.3%. Baseline 6MWD was 291.4±61.6m and KCCQ-OSS was 42.6±22.7. From baseline to 6 months, changes in KCCQ-OSS (n=63) and 6MWD (n=61) showed modest correlations with core lab-assessed LVEF (r=0.39; 95% CI: 0.16-0.58; p=0.0015 and r=0.39; 95% CI: 0.15-0.58; p = 0.0022, respectively). Changes in KCCQ-OSS and 6MWD correlated strongly (n=62; r=0.63; 95% CI: 0.46-0.76; p0.0001). Changes in KCCQ-OSS and 6MWD did not correlate significantly with changes in peak VO2 (p=0.06 and p=0.30, respectively). Changes in LVEF and peak VO2 (n=55) demonstrated modest correlation (r=0.41; 95% CI: 0.16-0.61; p=0.002). Baseline correlations with peak VO2 were weak to modest but increased at 6 months for LVEF (n=59; r=0.56; 95% CI: 0.35-0.71; p0.0001). Conclusions In advanced HF, improvements in health status and submaximal functional capacity associate modestly with LVEF, while LVEF correlates more closely with peak VO2. Cardiac function, functional capacity, and health status represent related but distinct domains, supporting multidimensional assessment in HF trials.