Dapagliflozin in Reducing Epicardial Adipose Tissue in Heart Failure with Preserved Ejection Fraction
NCT Number: NCT06510270
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Heart Failure with Preserved Ejection Fraction
Sponsor: Aswan University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 70
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2025-10-01

Summary:
Heart failure with preserved ejection fraction (HFpEF) is becoming the most common cause of heart failure worldwide, in part, driven by a rising prevalence of obesity.

Although generalized and visceral adiposity is important in the pathogenesis of obesity-related HFpEF, there is increasing recognition of the potential role of epicardial adipose tissue (EAT) in disease pathogenesis. EAT is metabolically active tissue located directly on the surface of the myocardium underneath the visceral pericardium. By virtue of its anatomical interface with the heart and the lack of fascial separation between the underlying myocardium and epicardial fat, locally secreted adipokines directly bathe the surface of the heart and result in underlying myocardial remodeling.

Its position on the surface of the myocardium allows EAT to directly contribute to an increase in total heart size with stretch of the pericardium and results in relative pericardial restraint with constrictive physiology.

EAT is most commonly measured by echocardiography in the parasternal long axis view perpendicular to the right ventricle (RV) to quantify epicardial fat thickness and this has been correlated with worse haemodynamic derangements and adverse outcomes in HFpEF.

Alternatively, cardiac MRI or CT can provide a more complete volumetric assessment of epicardial fat volume and has also demonstrated associations with adverse outcomes and functional metrics in most but not all HFpEF studies.

Very little is understood about the impact of medical modulation of epicardial fat in HFpEF. The first proven agents to improve heart failure hospitalization and quality of life in HFpEF are the sodium-glucose cotransporter-2 inhibitors (SGLT2i) Although the mechanisms of benefit of these drugs are uncertain, they have demonstrated a reduction in epicardial fat despite only minimal weight loss suggesting a direct lipolytic effect on epicardial fat. The use of SGLT2i has also been associated with reduced incident AF, which may, in part, be due to the reduction in epicardial fat. The diuretic effect of SGLT2i may facilitate a reduction in plasma volume and mechanistic studies have shown that they also promote ventricular mass regression, which may cumulatively decrease pericardial restraint.

By this work we aims To determine whether the addition of 10 mg of Dapagliflozin to a patient with HFPEF can lead to a decrease in epicardial adipose tissue volume, which is a new approach to managing HFPEF or not.

Primary Outcome Measures: Reduction in Epicardial adipose tissue volume, epicardial adipose tissue volume (gm) will be measured by using CMR before starting Dapagliflozin in sympotomatic heart failure group and 6 months latter. In asymptomatic diastolic dysfunction CMR will be performed at enrollment and 6 month latter, from enrollment (before stsrting dapagliflozin) to 6 month (while still on dapagliflozin)
Secondary Outcome Measures: Change in Body mass index, body mass index (kg/m2) will be measured at enrollment for both groups and 6 month latter at the end of the study, At enrollement till 6 months latter|Recurrent hospital admission by heart failure, Number of recurrent hospital admission by heart failure for each participant from enrollment till th end of study (6 month latter) will be recorded, From enrollement till 6 months latter|Cardio-vascular mortality, Cardiovascular mortality rate (due to stroke or MI) will be measured for both groups, From enrollement till 6 months latter