Study sample and procedures
DEL, BLOOD
This study was an investigator-initiated, multicenter, double-blind, randomized clinical trial designed to evaluate the effect of dapagliflozin on maximal functional capacity in patients with HFrEF. The patients were randomized 1:1 to receive either dapagliflozin or a placebo. Maximal functional capacity was evaluated at three time points: baseline, 1, and 3 months after initiation of treatment.The study protocol was approved by Agencia Española del Medicamento y Productos sanitarios (AEMPS) and by Comité Ético de Investigación Clínica (CEIC) del Hospital Clínico Universitario de Valencia. This study protocol was previously registered at The study population included patients with stable chronic HF in NYHA II or III class, and left ventricular ejection fraction (LVEF) ≤ 40%. The eligibility criteria, study procedures, and main findings were published elsewhereBriefly, randomized patients performed a baseline, 1 and 3-month maximal cardiopulmonary exercise test (CPET) using incremental and symptom-limited cardiopulmonary exercise testing on a bicycle ergometer, beginning with a workload of 10 W and gradually increasing in a ramp protocol of 10 W increments every 1 min.Blood samples were obtained the same day before CPET. NT-proBNP and CA125 were measured using standard commercial enzyme immune analysis (Roche Elecsys® NT-proBNP and Roche Elecsys® CA 125 assays). The values of both biomarkers were blinded to those researchers in charge of performing the CPET.