What are the causes and treatment options for heart failure in patients with varying demographics and medical histories, including coronary artery disease, hypertension, diabetes, and cardiomyopathy?

Causes of Heart Failure

Heart failure results from structural or functional cardiac disorders that impair ventricular filling or ejection, with coronary artery disease, hypertension, and cardiomyopathy representing the three dominant etiologies in Western populations. 1

Primary Cardiac Causes

Coronary Artery Disease

• Ischemic heart disease is the single most common cause, accounting for approximately 40% of heart failure cases globally and 49-54% of cases with reduced ejection fraction in Western populations. 2, 3
• The mechanism involves myocardial scarring from prior infarction, stunning or hibernating myocardium, epicardial coronary disease, abnormal coronary microcirculation, and endothelial dysfunction. 2
• Coronary disease has become the predominant cause as hypertension treatment has improved and detection programs have expanded. 1

Hypertension

• Hypertension causes 17-31% of heart failure cases, with higher prevalence in heart failure with preserved ejection fraction. 2, 3
• Long-standing hypertension leads to pathological ventricular remodeling with increased wall thickness and eventual systolic and diastolic dysfunction. 2
• In elderly patients, hypertension acts as an accelerator of cardiovascular aging, often working synergistically with other risk factors. 4

Cardiomyopathies

• Idiopathic dilated cardiomyopathy accounts for approximately 30% of heart failure cases in European registries. 2, 3
• Up to 30% of dilated cardiomyopathy cases have a genetic cause, resulting from mutations in cytoskeletal, sarcolemmal, sarcomeric, and nuclear envelope proteins. 1, 2
• The diagnosis of idiopathic dilated cardiomyopathy should only be applied after excluding other specific etiologies through appropriate evaluation. 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%). 2
• 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. 2
• Aortic stenosis, mitral regurgitation, and other acquired or congenital valve abnormalities can lead to heart failure. 2

Toxic and Metabolic Causes

Cardiotoxic Substances

• Alcohol, cocaine, amphetamines, and anabolic steroids can cause heart failure. 2
• Chemotherapeutic agents, particularly anthracyclines (doxorubicin) and trastuzumab, are well-recognized causes. 1
• Antidepressants, antiarrhythmics, and immunomodulating drugs may contribute to cardiac dysfunction. 2
• Heavy metals including copper, iron, lead, and cobalt can cause heart failure. 2

Endocrine and Metabolic Disorders

• Diabetes mellitus contributes to heart failure development both directly and indirectly through accelerated coronary disease. 1, 4
• Thyroid disorders (both hypothyroidism and hyperthyroidism) can cause or exacerbate heart failure. 1, 2
• Metabolic syndrome and obesity accelerate cardiovascular aging and increase heart failure risk. 2, 4
• Nutritional deficiencies, particularly thiamine deficiency (beriberi), can cause high-output heart failure. 1, 2

Radiation Therapy

• Chest radiation increases the risk of heart failure through direct myocardial damage and accelerated coronary disease. 2

Infectious and Inflammatory Causes

Myocarditis

• Viral myocarditis represents a significant cause of heart failure, particularly in younger patients. 2
• Bacterial, fungal, protozoal, and parasitic infections can also cause myocarditis. 2
• Chagas disease is a major cause of heart failure in South America. 2
• Many patients with biopsy-proven myocarditis improve with supportive care alone, and the role of immunosuppression remains controversial. 1

Infiltrative Diseases

• Sarcoidosis, amyloidosis, and hemochromatosis can cause restrictive cardiomyopathy and heart failure. 1
• These conditions may be detected by endomyocardial biopsy when clinically suspected, though biopsy findings do not always alter management. 1

Autoimmune Disorders

• Systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and other collagen vascular disorders can cause heart failure. 1, 2
• Lymphocytic and giant cell myocarditis represent immune-mediated causes. 2

High-Output States

Several conditions mimic heart failure by creating high-output states rather than primary cardiac dysfunction: 1

• Anemia 1
• Thyrotoxicosis 1
• Septicemia 1
• Liver failure 1
• Arteriovenous shunts 1
• Paget's disease (affects approximately 3% of patients with extensive polyostotic disease) 5
• Beriberi (thiamine deficiency) 1

Special Populations

Peripartum Cardiomyopathy

• Occurs during pregnancy or the postpartum period with incidence varying dramatically by geographic region. 2, 3

Genetic and Congenital Conditions

• Muscular dystrophies and laminopathies can lead to cardiomyopathy. 2
• Adult congenital heart disease, including single ventricle syndromes, failed Fontan operations, and Eisenmenger's syndrome. 1
• Hypertrophic cardiomyopathy has a genetic basis and specific diagnostic criteria. 1

Geographic Variations

Critical geographic differences exist in heart failure etiology: 2

• Eastern Europe and Middle East show highest rates of ischemic etiology (55-57%). 2
• Africa shows lowest ischemic rates (12%) but highest rates of rheumatic heart disease and dilated cardiomyopathy. 2
• Sub-Saharan Africa has predominantly non-ischemic causes (75.5%). 2

Common Pitfalls

• Do not assume heart failure equals cardiomyopathy or left ventricular dysfunction—these describe structural reasons for heart failure, while heart failure itself is a clinical syndrome defined by symptoms (dyspnea, fatigue) and signs (edema, rales). 1
• Do not overlook reversible causes such as hibernating myocardium in coronary disease, which may show significant improvement after revascularization even with severe left ventricular dysfunction (ejection fraction <15-20%). 1
• Do not routinely perform endomyocardial biopsy unless specific infiltrative or inflammatory diseases are suspected based on clinical grounds, as nonspecific findings are common and rarely alter management. 1
• Recognize that multiple etiologies often coexist, particularly in elderly patients where hypertension, diabetes, obesity, and coronary disease frequently act synergistically. 4