What is the etiology of congestive heart failure?

Etiology of Congestive Heart Failure

Congestive heart failure results from a broad spectrum of primary myocardial diseases and abnormal loading conditions, with ischemic heart disease, hypertension, and dilated cardiomyopathy representing the most common causes in developed countries. 1

Primary Myocardial Diseases

Ischemic Heart Disease

• Ischemic heart disease is the single most common etiology, accounting for approximately 40% of heart failure cases worldwide, though this varies substantially by geographic region 1
• In Western populations, ischemic cardiomyopathy (from coronary artery disease and prior myocardial infarction) causes heart failure in 49-54% of patients with reduced ejection fraction 1
• The mechanism involves myocardial scarring, stunning/hibernation, epicardial coronary disease, abnormal coronary microcirculation, and endothelial dysfunction 1
• Ischemic etiology is less common in heart failure with preserved ejection fraction (24-32%) compared to reduced ejection fraction 1

Hypertension and Hypertensive Heart Disease

• Hypertension represents the underlying cause in 17-31% of heart failure cases, with higher prevalence in preserved ejection fraction phenotypes 1
• Long-standing hypertension leads to pathological ventricular remodeling with increased wall thickness and eventual systolic and diastolic dysfunction 1
• Geographic variation is substantial: hypertensive heart disease accounts for 35% of cases in Africa, 21% in South America, but lower percentages in developed nations 1

Dilated Cardiomyopathy

• Idiopathic dilated cardiomyopathy accounts for approximately 30% of heart failure cases in European registries 1
• Primary (genetic) cardiomyopathies result from mutations in cytoskeletal, sarcolemmal, sarcomeric, and nuclear envelope proteins, with up to 30% of dilated cardiomyopathy having a genetic cause 1
• Specific genetic forms include hypertrophic cardiomyopathy, left ventricular non-compaction, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, muscular dystrophies, and laminopathies 1

Toxic and Metabolic Causes

Cardiotoxic Substances

• Recreational substances: alcohol (most common), cocaine, amphetamines, anabolic steroids 1
• Medications: anthracycline chemotherapy, immunomodulating drugs (trastuzumab, cetuximab, interferons), antidepressants, antiarrhythmics 1
• Heavy metals: copper, iron, lead, cobalt 1
• Radiation therapy to the chest 1

Metabolic and Endocrine Disorders

• Hormonal abnormalities: hypothyroidism, hyperthyroidism (Graves' disease), diabetes mellitus, metabolic syndrome, pheochromocytoma, Addison disease 1
• Nutritional deficiencies: thiamine deficiency, obesity, malnutrition from malignancy or anorexia nervosa 1
• Infiltrative diseases: amyloidosis, sarcoidosis, hemochromatosis, glycogen storage diseases (Pompe), lysosomal storage diseases (Fabry) 1

Infectious and Immune-Mediated Causes

Myocarditis

• Viral myocarditis (especially) represents a significant cause, particularly in younger patients 1
• Other infectious agents: bacteria, spirochetes, fungi, protozoa, parasites (Chagas disease in endemic areas), rickettsiae, HIV/AIDS 1
• Chagas disease is a major cause in South America 1

Autoimmune Disorders

• Lymphocytic/giant cell myocarditis 1
• Systemic lupus erythematosus, rheumatoid arthritis, other connective tissue disorders 1
• Hypersensitivity and eosinophilic myocarditis (Churg-Strauss syndrome) 1

Abnormal Loading Conditions

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
• Acquired and congenital valve abnormalities: mitral, aortic, tricuspid, and pulmonary valve diseases 1
• Mechanisms include pressure overload (stenosis) and volume overload (regurgitation) 1

Other Structural Abnormalities

• Congenital heart disease: atrial and ventricular septal defects, coarctation of aorta, bicuspid aortic valve 1
• Pericardial diseases: constrictive pericarditis, pericardial effusion 1
• Endomyocardial pathologies: endomyocardial fibrosis, eosinophilic cardiomyopathy 1

Arrhythmia-Induced Cardiomyopathy

• Sustained and inappropriate tachycardia (tachycardia-induced cardiomyopathy) 1
• Chronic bradyarrhythmias 1
• Atrial fibrillation as both cause and consequence 1

Special Populations and Conditions

Peripartum Cardiomyopathy

• Occurs during pregnancy or postpartum period 1
• Incidence varies dramatically: 1/100-1/1000 in Africa versus 1/15,000 in the United States 1

Neuromuscular Disorders

• Muscular dystrophies and laminopathies can lead to cardiomyopathy 1

Geographic and Demographic Variations

Critical geographic differences exist: Eastern Europe and Middle East show highest rates of ischemic etiology (55-57%), Africa shows lowest ischemic rates (12%) but highest rates of rheumatic heart disease and dilated cardiomyopathy, and Sub-Saharan Africa has predominantly non-ischemic causes (75.5%) 1

Multifactorial Nature

Heart failure etiology is typically pluricausal rather than singular 2:

• Patients average 1.5-1.9 contributory factors beyond the primary etiology 2
• Common overlapping factors include hypertension, diabetes mellitus, atrial fibrillation, and alcohol consumption 2
• In 40% of non-ischemic cases, the primary etiology remains unclear due to multiple probable contributing factors 2