Heart failure (HF) with preserved ejection fraction (HFpEF) is a distinct phenotype
hallmarked by clinical signs and symptoms of HF coupled with a normal ejection faction (EF ≥
50%) and evidence of increased left ventricular (LV) pressures and impaired LV filling on
echocardiography. HFpEF is highly prevalent, accounting for up to 50% of all patients with
HF, and is associated with significant morbidity and mortality. HFpEF is a heterogenous
disorder, contributed to by comorbidities that include hypertension, diabetes, obesity,
coronary artery disease (CAD), chronic kidney disease (CKD), and specific causes such as
cardiac amyloidosis. These chronic conditions complicate the management of HF and have a
significant impact on its prognosis. How to generate specific recommendations addressing many
of these conditions in the setting of HF is challenging given the current state of the
evidence.
Obesity is a growing global concern, and is a common finding in the progression of HFpEF.
According to the World Health Organization (WHO), percentage of adult population that is
obese in Egypt is 32% which makes it ranks 18th with the highest prevalence of obesity
worldwide. Very few studies have been published about the burden of diseases in Egypt in
general, and the burden of obesity is even more complex as the impact of obesity is a result
of its comorbidities rather than a direct effect. Several studies have provided evidence for
the distinct obesity related HFpEF phenotype, and its unique pathophysiology based on the
obesity criteria for the European and American population with a body mass index (BMI)
greater than 30 kg/m2. Obesity is a commonly occurring comorbidity in patients with HFpEF,
and has many deleterious effects on the cardiovascular system, mediated by changes in volume
overload, cardiac load, energy substrate utilization, tissue metabolism, and systemic
inflammation. However, based on latest heart failure guidelines, evidence gaps and future
research directions are needed to assess efficacy and safety of weight loss management and
treatment strategies in patients with HF and obesity.
Metformin is a common anti-diabetic drug with both systemic and cardioprotective benefits in
addition to its hypoglycaemic effect. At the cellular level metformin activates adenosine
monophosphate-activated protein kinase (AMPK) an important regulator of several metabolic
pathways resulting in enhanced glucose utilisation, reduction of protein synthesis and
improvement of mitochondrial function. Furthermore, metformin has been shown to reduce
collagen accumulation and potentially reduce LV hypertrophy and improve diastolic function in
the diabetic myocardium. The cardio protection afforded by metformin treatment seems to
result from interference with TGF-beta signaling pathway and activation of the AMP-kinase
signaling cascade. A recent systematic review and meta regression analysis have shown that
metformin treatment was associated with a reduction in mortality in patients with HFpEF. In
addition, treatment with metformin of non-diabetic metabolic syndrome patients with diastolic
dysfunction, on top of lifestyle counseling, was associated with improved diastolic function.
Moreover, some studies have shown that metformin can reduce body weight. However, metformin
has not been officially approved as a medicine for weight loss because its effect on
different populations remains inconsistent. No studies to date assessed the role of metformin
in obese non-diabetic patients with HFpEF Accordingly, investigators aimed to evaluate if
metformin can improve diastolic function in non-diabetic obese patients with HFpEF.
Investigators also aimed to assess the impact of this therapy in functional capacity, weight
loss and health-related quality of life (HRQoL).