The Association of Cystatin C-based eGFR with Functional Exercise Capacity and Patient-Reported Outcomes in Heart Failure.

INTRODUCTION: Lower estimated glomerular filtration rate (eGFR) is associated with worse clinical outcomes in people with heart failure (HF) with reduced (HFrEF) and preserved (HFpEF) ejection fractions. Data on the association of functional exercise capacity and patient-reported outcomes in HF with eGFR measures using Cr (eGFRcr) are conflicted and scarce using cystatin C (eGFRcys). METHODS: We evaluated the association between baseline eGFR and scores on 6-minute walk test (6MWT), Kansas City Cardiomyopathy Questionnaire (KCCQ), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) at baseline and 6 months in 769 participants from EXACT-HF, RELAX, and FIGHT trials. eGFR measures were eGFRcr, eGFRcys, a combination (eGFRcr-cys), and discordance in eGFR (eGFRcys at least 30% lower than eGFRcr, i.e. eGFRcys/GFRcr<0.7). Multivariable linear regression adjusted for age, sex, diabetes, BMI, NYHA class, NT-proBNP, and treatment arm. RESULTS: Median eGFRcr was 54 [40, 74], eGFRcys 49 [34, 70], and eGFRcr-cys 54 [38, 72] ml/min/1.73m2. eGFRcys/eGFRcr was <0.7 in 20%. Lower eGFR using all measures was associated with 6MWT at baseline. Only cystatin C-derived measures were associated with 6MWT at 6 months in adjusted models: eGFRcys, β (95% CI), 8.7 (4.1, 13.4), p<0.001; eGFRcr-cys, 7.7 (3.0, 12.5), p=0.001; per 10 ml/min/1.73m2 increase in eGFR). Discordance in eGFR was associated with a 34.9 (10.4, 59.4) meter drop in distance walked at 6 months (p=0.005). Only cystatin C-derived eGFR measures were associated with KCCQ at 6 months (eGFRcys/eGFRcr <0.7: 7.8 (-13.9, -1.7), p=0.01; eGFRcys: 1.9 (0.9, 2.9), p<0.001; eGFRcr-cys: 1.7 (0.6, 2.8), p=0.003; per 10 ml/min/1.73m2 increase in eGFR). Only eGFRcys/eGFRcr was associated with an improvement in MLHFQ score on fully adjusted analysis. CONCLUSION: Lower eGFR measures using cystatin C but not creatinine predicted worse performance at 6 months on functional and patient-reported outcomes in people with HF. These findings highlight the prognostic importance of cystatin C-based eGFR measures in HF.