Dapagliflozin in Reducing Epicardial Adipose Tissue in Heart Failure with Preserved Ejection Fraction

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.

Conditions

• Heart Failure with Preserved Ejection Fraction

Interventions

DRUG

Dapagliflozin 10 mg once daily

Dapagliflozin 10 mg once daily will be given to all patients in symptomstic heart failure group

DRUG

Loop diuretics

Loop diuretics (IV or orally) will be given to all patients in symptomatic heart failure group

DRUG

Treatments of associated co-morbidities (e.g Anti-hypertensive, oral hypoglycemic)

Treatment of associated co-morbidities will be given to both arms (group) such as anti-hypertensive (B blockers, ACIE, ARBS, CA channel blockers, Diuretics), oral hypoglycemic (Metformins, sulfonyl urea,.......)

Sponsors & Collaborators

• Aswan University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-01

Primary Completion

2025-08-01

Completion

2025-10-01