What are the common underlying etiologies of heart failure?

Common Underlying Etiologies of Heart Failure

Ischemic heart disease is the single most common cause of heart failure, accounting for approximately 40% of cases globally and 49-54% of heart failure with reduced ejection fraction in Western populations. 1, 2

Primary Myocardial Causes

Ischemic Heart Disease (Most Common)

• Ischemic cardiomyopathy represents the leading etiology worldwide, causing heart failure through multiple mechanisms including myocardial scarring, stunning/hibernation, epicardial coronary artery disease, abnormal coronary microcirculation, and endothelial dysfunction. 3, 1
• The prevalence varies substantially by geographic region, with Eastern Europe and the Middle East showing the highest rates (55-57%), while Africa shows the lowest ischemic rates (12%). 1
• Coronary artery disease is particularly common in patients with prior myocardial infarction, where left ventricular aneurysm or papillary muscle dysfunction may induce left ventricular dysfunction. 3, 4

Hypertension (Second Most Common)

• Hypertension accounts for 17-31% of heart failure cases, with higher prevalence in heart failure with preserved ejection fraction phenotypes. 1, 2
• Long-standing hypertension leads to pathological ventricular remodeling with increased wall thickness and eventual systolic and diastolic dysfunction. 1

Idiopathic Dilated Cardiomyopathy

• Idiopathic dilated cardiomyopathy represents approximately 30% of heart failure cases in European registries. 1, 2
• Up to 30% of dilated cardiomyopathy has a genetic cause, resulting from mutations in cytoskeletal, sarcolemmal, sarcomeric, and nuclear envelope proteins. 1, 2

Toxic and Medication-Related Causes

Cardiotoxic Substances

• Recreational substances including alcohol, cocaine, amphetamines, and anabolic steroids can cause heart failure. 3, 1
• Medications such as anthracycline chemotherapy (e.g., doxorubicin), immunomodulating drugs (interferons, monoclonal antibodies like trastuzumab and cetuximab), antidepressants, and antiarrhythmics are recognized causes. 3, 1
• Heavy metals (copper, iron, lead, cobalt) and radiation therapy to the chest can also induce myocardial damage. 3, 1

Metabolic and Hormonal Derangements

• Hormonal abnormalities including thyroid disease (both hypo- and hyperthyroidism), diabetes mellitus, metabolic syndrome, and pheochromocytoma can contribute to heart failure. 3, 1
• Nutritional deficiencies, particularly thiamine deficiency, as well as obesity and malnutrition, increase heart failure risk. 3, 1

Valvular Heart Disease

• Valvular disease accounts for 8-20% of heart failure cases, with higher prevalence in preserved ejection fraction (20%) versus reduced ejection fraction (4%). 1
• Rheumatic heart disease remains the greatest global burden of valvular disease, particularly in Sub-Saharan Africa where it causes up to 40% of heart failure cases. 1
• Both acquired and congenital valve abnormalities (mitral, aortic, tricuspid, and pulmonary valve diseases) can lead to heart failure through pressure or volume overload. 3, 1

Infectious and Immune-Mediated Causes

• Viral myocarditis represents a significant cause of heart failure, particularly in younger patients. 1
• Other infectious agents including bacteria, spirochetes, fungi, protozoa (Chagas disease in South America), parasites, rickettsiae, and viruses (HIV/AIDS) can cause myocardial damage. 3, 1
• Autoimmune conditions including lymphocytic/giant cell myocarditis, systemic lupus erythematosus, rheumatoid arthritis, Graves' disease, and hypersensitivity myocarditis (Churg-Strauss) can lead to heart failure. 3, 1

Arrhythmias

• Both tachyarrhythmias and bradyarrhythmias can cause or exacerbate heart failure. 3
• Sustained tachyarrhythmias can lead to tachycardia-induced cardiomyopathy. 1
• Sinus node dysfunction and conduction disorders may contribute to heart failure development. 3

Congenital Heart Disease in Adults

Adult congenital heart disease patients have specific substrates for late heart failure development, including: 3

• Severe aortic stenosis and/or regurgitation (bicuspid aortic valve and variants)
• Unoperated atrial septal defect or partial atrioventricular septal defect
• Congenitally corrected transposition of the great arteries
• D-transposition after Mustard or Senning operation (morphological right ventricle as systemic ventricle)
• Tetralogy of Fallot with early-era surgery or severe pulmonary regurgitation
• Single-ventricle physiology and Fontan surgery

Special Populations

• Peripartum cardiomyopathy occurs during pregnancy or the postpartum period, with incidence varying dramatically by geographic region. 1, 2
• Muscular dystrophies and laminopathies can lead to progressive cardiomyopathy. 3, 1

Geographic Variations

Critical geographic differences exist in heart failure etiology: 1, 2

• Eastern Europe and Middle East: highest ischemic etiology rates (55-57%)
• Africa: lowest ischemic rates (12%) but highest rates of rheumatic heart disease and dilated cardiomyopathy
• Sub-Saharan Africa: predominantly non-ischemic causes (75.5%)

Clinical Pitfall

A common pitfall is attributing heart failure symptoms solely to coronary disease when multiple etiologies may coexist. 3 Always obtain a detailed history to identify potential causes of cardiac damage, as heart failure is unusual in individuals with no relevant medical history, and previous myocardial infarction greatly increases the likelihood of heart failure in patients with appropriate symptoms and signs. 3