Heart failure with preserved ejection fraction (HFpEF) constitutes approximately 50% of heart failure patients. The prevalence of\ndiabetes mellitus in HFpEF is high at 30-40%. The paper provides a systematic review of the pathophysiological features\nunderlying HFpEF in diabetes mellitus. The importance of mechanisms other than left ventricular diastolic dysfunction underlying\nthis important condition is emphasised. Thus, ventricular-arterial coupling & vascular dysfunction together with chronotropic\nincompetence & cardiovascular reserve dysfunction play an important role. The various morphologic and molecular features\noccurring in the myocardium and vasculature in diabetes secondary to hyperglycaemia and other metabolic disturbances are also\ndiscussed. These include microangiopathy, myocardial fibrosis, increased oxidative stress, impaired calcium homeostasis,\nactivation of the cardiac renin-angiotensin system, autonomic neuropathy, endothelial dysfunction, re-expression of foetal gene\nresponse as well as stem cell involvement. Nonetheless, a lot is still unknown and further studies are needed to establish the\nunderlying pathophysiological mechanisms with the hope that novel pharmacotherapies targeting this disease will be\ndeveloped. In the meantime, cardiometabolic factors, including hyperglycaemia, hypertension and dyslipidaemia should be\ntargeted and aggressively treated.
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