Heart failure: A preventable and treatable complication of type 2 diabetes

Abstract

Chronic heart failure (CHF) is a complex syndrome in which impaired emptying or filling of the heart results in a clinical picture of fatigue, breathless and fluid retention. Chronic heart failure is a common, preventable, and treatable complication of type 2 diabetes (T2D). Diabetes is approximately three to four times more prevalent in patients with heart failure than the general population. Not only is T2D a risk factor for the development of CHF, but impaired glucose tolerance may be a consequence of the systemic perturbations of the CHF syndrome. Type 2 diabetes is an independent risk factor for progressive heart failure and cardiovascular death, and patients with T2D have higher New York Heart Association (NYHA) class and symptom burden than nondiabetic patients with similar ejection fractions. The most common comorbidities leading to CHF in patients with T2D are coronary artery disease (CAD) and hypertension. Although multivessel CAD is a major cause of CHF in patients with diabetes and a strong adverse predictor of survival, the adverse effect of T2D on outcomes in CHF patients is of a similar magnitude in patients with and without CAD. This suggests an additional direct effect on the myocardium, a “diabetic cardiomyopathy”. Although several mechanisms have been proposed, and impaired cardiac glucose metabolism is a strong candidate, the underlying pathogenesis is only partially understood and there is no accepted clinical definition. Overall, the pathophysiology of heart failure and diabetes overlap; both are associated with insulin resistance, impaired glucose metabolism and the metabolic syndrome. Heart failure is classified based upon the presence of reduced left ventricular function as heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction. In both descriptions, reduced cardiac output and a fall in blood pressure are sensed by baroreceptors and renal afferent arterioles. These, in turn, trigger activation of the reninangiotensin-aldosterone system (RAAS), secretion of antidiuretic hormone (ADH), vasoconstriction, activation of the sympathetic nervous system, and release of epinephrine and norepinephrine. It is these physiological adaptations that result in the clinical syndrome of heart failure. Activation of the RAAS leads to secretion of aldosterone and ADH, promoting sodium and water retention. This augments preload, resulting in pulmonary congestion and fluid overload. Vasoconstriction maintains blood pressure to achieve organ perfusion at the expense of excessive afterload, which exacerbates pump failure. Sympathetic stimulation increases heart rate and contractility, initially improving ejection fraction but ultimately increasing the heart s metabolic requirements and predisposing to dysrhythmia and sudden cardiac death. Conversely, natriuretic peptide secretion promotes beneficial structural remodeling, natriuresis, and diuresis and reduces sympathetic tone (Figure 1). Contemporary therapies aim to limit these physiological adaptations, reduce symptoms and improve survival. Diuretics provide symptomatic relief from fluid retention. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists inhibit the RAAS. Neprilysin inhibitors reduce the degradation of natriuretic peptides to promote structural remodeling, vasodilation, and natriuresis. β-Adrenoreceptor antagonists (beta-blockers) counteract sympathetic activation, reduce heart rate and contractility and, largely by their DOI: 10.1111/1753-0407.12930