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

ConditionHeart Failure with Preserved Ejection Fraction
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorAswan University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >18 years.

Patients with established diagnosis of HFpEF: (1. Signs and Symptoms of Heart Failure. 2. Preserved Ejection Fraction (EF): EF greater than or equal to 50% is generally considered preserved. 3.Echo-cardiography: Evidence of left ventricular hypertrophy (LVH) or Evidence of diastolic dysfunction, such as impaired relaxation or increased stiffness of the left ventricle. 4.Elevated Natriuretic Peptides: serum N-terminal pro-B type natriuretic peptide (NT-proBNP) ≥400 pg/mL or brain natriuretic peptide ≥100 pg/mL can support the diagnosis of HFpEF in the presence of symptoms and other findings).

BMI >27Kg/m2.

Adequate follow-up: Participants must be willing and able to comply with the study protocol and follow-up requirements.

Disqualifiers

1. Age <18 years. 2. Type 1 diabetes: Exclude individuals with type 1 diabetes, as dapagliflozin is primarily used for type 2 diabetes management.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Dapagliflozin 10 mg once daily

    Drug

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

  • Loop diuretics

    Drug

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

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

    Drug

    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,.......)

Treatment groups

70 Participants
are divided into 2 treatment groups
Group A: Symptomatic heart failureActive comparator 3 interventions
Group B: Asymptomatic Diastolic dysfunctionPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

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

Time frame
from enrollment (before stsrting dapagliflozin) to 6 month (while still on dapagliflozin)

Secondary outcomes

1

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

Time frame
At enrollement till 6 months latter
2

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

Time frame
From enrollement till 6 months latter
3

Cardio-vascular mortality

Cardiovascular mortality rate (due to stroke or MI) will be measured for both groups

Time frame
From enrollement till 6 months latter

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Aswan University

Lead sponsor

Aswan University Hospital

Sponsor institution

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: