The aim of prospective, open label, single center, randomized controlled trial is to investigate the efficacy of enavogliflozin on exercise performance, diastolic dysfunction, and quality of life in patients with heart failure with preserved ejection fraction (HFpEF).
HFpEF is a clinically heterogenous syndrome and has unique characteristics that differ from the other entities of heart failure. Cardiovascular and non-cardiovascular comorbidities are known to contribute to the pathogenesis of HFpEF, and consequently, the importance of HFpEF is increasingly emphasized as the population ages. In fact, HFpEF occurs in approximately 5% of the general population aged over 60 years and account for half of hospitalization for heart failure. Notwithstanding, no medication has been found to be effective for HFpEF. Only recently, Sodium glucose cotransporter 2 (SGLT2) inhibitors was proven effective in patients with HFpEF in two landmark trials, EMPEROR-Preserved and DELIVER trials. In both trials, SGLT2 inhibitor was consistently associated with reduced risk of composite outcome of cardiovascular death and hospitalization for heart failure. In this regard, 2023 focused update of the 2021 European Society of Cardiology (ESC) guidelines for heart failure recommends SGLT2 inhibitor as class 1A recommendation in patients with HFpEF. Despite the solid evidence about the clinical benefit of SGLT2 inhibitor in patients with HFpEF, little is known about the mechanisms responsible for the beneficial cardiac effects of SGLT2 inhibitor. Patients with HFpEF are known to have impaired exercise and functional capacity, which lead to declined quality of life and debilitating symptoms. Along with unclear mechanisms responsible for the beneficial cardiac effect of SGLT2 inhibitor, the impacts of SGLT2 inhibitor on exercise and functional capacity in patients with HFpEF have also not been clearly evaluated. Therefore, this trial aim to evaluate the impact of SGLT2 inhibitor on exercise performance, diastolic function, and quality of life in patients with HFpEF using newly developed SGLT2 inhibitor, Enavogliflozin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
154
Enavogliflozin (0.3mg oral tablet once daily) will be administrated.
Samsung Medical Center
Seoul, South Korea
Change in peak oxygen consumption (VO2)
Change in peak oxygen consumption (VO2) from baseline to week 24
Time frame: Week 24
Change in minute ventilation to carbon dioxide output ratio (VE/VCO2 slope)
Change in minute ventilation to carbon dioxide output ratio (VE/VCO2 slope) from baseline to week 24
Time frame: Week 24
Change in Left atrial volume index (LAVI) before and after maximal exercise
Change in LAVI before and after maximal exercise from baseline to week 24
Time frame: Week 24
Change in Lateral Early diastolic transmitral filling velocity over early diastolic relaxation velocity at mitral annulus (E/e') before and after maximal exercise
Change in Lateral E/e' before and after maximal exercise from baseline to week 24
Time frame: Week 24
Change in Left ventricular mass index (LVMI) before and after maximal exercise
Change in LVMI before and after maximal exercise from baseline to week 24
Time frame: Week 24
Change in LV wall thickness before and after maximal exercise
Change in LV wall thickness before and after maximal exercise from baseline to week 24
Time frame: Week 24
Change in LV global longitudinal strain before and after maximal exercise
Change in LV global longitudinal strain before and after maximal exercise from baseline to week 24
Time frame: Week 24
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Change in LA strain before and after maximal exercise
Change in LA strain before and after maximal exercise from baseline to week 24
Time frame: Week 24
Change in right ventricular (RV) free wall strain before and after maximal exercise
Change in RV free wall strain before and after maximal exercise from baseline to week 24
Time frame: Week 24
Change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS)
Change in health-related quality of life assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS) from baseline to week 24 Score ranges from 0 to 100 and higher value represents better quality of life.
Time frame: Week 24
Change in N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP) level
Change in NT-proBNP level from baseline to week 24
Time frame: Week 24
Change in chronotropic response reserve assessed by change in heart rate from rest to peak exercise
Change in chronotropic response reserve assessed by change in heart rate from rest to peak exercise from baseline to week 24
Time frame: Week 24
Change in serum iron
Change in serum iron from baseline to week 24
Time frame: Week 24
Change in ferritin
Change in ferritin from baseline to week 24
Time frame: Week 24
Change in total iron binding capacity
Change in total iron binding capacity from baseline to week 24
Time frame: Week 24
Change in hemoglobin
Change in hemoglobin from baseline to week 24
Time frame: Week 24
All-cause death
All-cause death
Time frame: Week 24
Hospitalization for heart failure
Hospitalization for heart failure should include all of the following criteria: 1. Hospitalization with primary diagnosis of heart failure 2. Duration of hospitalization of at least 12 hours 3. New or worsening symptoms of heart failure 4. Objective evidence of new or worsening heart failure on physical examination or laboratory findings 5. Initiation or intensification of heart failure treatment.
Time frame: Week 24