Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes

Abstract

The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.

Keywords: Diabetes mellitus; Diabetic cardiomyopathies; Diagnosis; Epidemiology; Heart failure; Treatment.

Fig. 1.

The cardiovascular disease continuum. ASCVD, atherosclerotic cardiovascular disease. "Updated on 30 September 2021"

Fig. 2.

Pathophysiology for heart failure development in diabetes. AGE, advanced glycation end product; RAGE, receptors for AGE; ROS, reactive oxygen species; NO, nitric oxide; SNS, sympathetic nervous system; RAAS, renin-angiotensin-aldosterone system.

Fig. 3.

Diagnosis of heart failure. (A) Definition of heart failure types according to the ejection fraction. (B) Algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; LVEF, left ventricular ejection fraction; H₂FPEF, Heavy (a body mass index >30 kg/m² , 2 points), Hypertension (use of ≥2 antihypertensive medications, 1 point), atrial Fibrillation (3 points), Pulmonary hypertension (pulmonary artery systolic pressure >35 mm Hg, 1 point), Elderly (age >60 years, 1 point), and Filling pressures (E/e´ >9, 1 point); HFA-PEFF, Heart Failure Association—Pretest assessment, (ii) diagnostic workup with Echocardiogram and natriuretic peptide score, (iii) advanced workup with Functional testing in case of uncertainty, and (iv) Final etiological workup; BMI, body mass index; LAVI, left atrial volume index; LVMI, left ventricular mass index; NT-proBNP, N-terminal pro-B-type natriuretic peptide; BNP, B-type natriuretic peptide.

Fig. 4.

Treatment algorithm for guideline-directed medical therapy. HFrEF, heart failure with reduced ejection fraction; ARNI, angiotensin receptor-neprilysin inhibitor; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; eGFR, estimated glomerular filtration rate; NYHY, New York Heart Association; MRA, mineralocorticoid receptor antagonist; SGLT2, sodium-glucose cotransporter-2; HR, heart rate.