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

Epidemiology

The presence of diabetes means a 2–4-fold risk of heart failure (HF) compared to the general population. According to the Framingham Heart Study, the incidence of HF is 2-fold in men and 4-fold in women with diabetes, even when adjusted for other cardiovascular (CV) risk factors. Among patients with identified ischemic heart disease (IHD) in the Heart and Soul Study, individuals with diabetes had a 3.3-fold risk of developing HF. Diabetes is a significant risk factor that accelerates the progression of CV disease at every stage of the CV continuum. Additional risk factors include age, duration of diabetes, IHD, higher body weight, and higher creatinine levels.

It is also true that among patients with HF, the prevalence of diabetes is 2–2.5 times higher than in the general population. The prevalence of diabetes among HF patients in Europe, according to the EuroHeart Failure Survey II, is 33%, and in the USA, according to the Acute Decompensated Heart Failure National Registry (ADHERE), it is 44%. Patients with concurrent HF and diabetes have less favorable characteristics than those without diabetes. They more often suffer from HF of ischemic etiology, have higher BMI, heart rate, systolic blood pressure, creatinine levels, and NT-proBNP levels. This may explain the poorer outcomes achieved in their treatment.

Pathophysiology

Diabetes affects the development of HF through micro- and macrovasculopathy leading to ischemic cardiomyopathy or through direct effects on the myocardium via diabetic cardiomyopathy.

In the pathophysiology of HF development in patients with diabetes, hyperglycemia, hyperinsulinemia, and insulin resistance play roles, disrupting vascular homeostasis. Hyperglycemia leads to the formation of advanced glycation end products that promote fibrosis development and impair myocardial relaxation. They also lead to the creation of oxygen radicals that promote inflammation and atherosclerosis progression. Oxygen radicals, through their impact on mitochondria and subsequent disruption of intracellular calcium utilization, reduce myocardial energy efficiency.

In diabetes, there is also excessive activation of the renin-angiotensin-aldosterone system (RAAS), which induces vasoconstriction and supports left ventricular hypertrophy.

All these mechanisms contribute to anatomical and functional myocardial damage and the development of diabetic cardiomyopathy.

Diagnosis and Treatment

The classification, diagnosis, and treatment of HF in patients with diabetes are the same as those for non-diabetics.

According to data from the Korean registry KorAHF, 59.1% of HF patients have heart failure with reduced ejection fraction of the left ventricle (HFrEF), 15.8% have mildly reduced ejection fraction (HFmrEF), and 25.1% have preserved ejection fraction (HFpEF). Among patients with HF and diabetes, these values are 64%, 14.4%, and 21.6%, respectively.

In the treatment of HF in both diabetics and non-diabetics, seven classes of drugs are used: RAAS inhibitors, AT₁ receptor and neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists (MRA), beta-blockers, If channel blockers in the sinus node, SGLT2 inhibitors, and soluble guanylate cyclase (sGC) stimulators. Drugs targeting neurohumoral and metabolic pathways have so far demonstrated a reduction in mortality and morbidity in HFrEF. Therefore, these patients should be treated according to existing recommendations regardless of diabetes presence. On the other hand, drugs affecting neurohumoral pathways do not improve survival in HFpEF patients. Studies with SGLT2i in these patients are still ongoing.

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Source: Park J. J. Epidemiology, pathophysiology, diagnosis, and treatment of heart failure in diabetes. Diabetes Metab J 2021 Mar; 45 (2): 146–157, doi: 10.4093/dmj.2020.0282.