Heart Failure: Types and Causes
Definition
Heart failure is a complex clinical syndrome resulting from structural or functional impairment of ventricular filling or ejection of blood, manifesting primarily as dyspnea, fatigue, and fluid retention. 1
The syndrome arises from disorders affecting the pericardium, myocardium, endocardium, heart valves, or great vessels, though most cases stem from impaired left ventricular myocardial function. 1
Classification by Ejection Fraction
Heart failure is categorized into three distinct types based on left ventricular ejection fraction (LVEF):
Heart Failure with Reduced Ejection Fraction (HFrEF)
- LVEF ≤40% 2, 3
- Represents systolic dysfunction with impaired ventricular contraction 4
- Most extensively studied subtype with established evidence-based therapies 5
Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)
- LVEF 41-49% 2
- Previously termed "mid-range ejection fraction" until recent ESC guideline revision 6
- Emerging evidence suggests these patients benefit from similar therapies as HFrEF 6
Heart Failure with Preserved Ejection Fraction (HFpEF)
- LVEF ≥50% 2, 3
- Represents diastolic dysfunction with impaired ventricular filling 4
- More common in elderly patients, women, and those with hypertension or diabetes 1
- Both systolic and diastolic abnormalities typically coexist regardless of ejection fraction 1
Functional Classification
The New York Heart Association (NYHA) functional classification stratifies patients by symptom severity:
- Class I: No limitation of physical activity; no symptoms with ordinary exertion 1, 2
- Class II: Slight limitation of physical activity; symptoms with ordinary exertion 1
- Class III: Marked limitation of physical activity; symptoms with less-than-ordinary exertion 1
- Class IV: Unable to engage in any physical activity without symptoms; symptoms occur at rest 1
Staging System
The ACC/AHA staging system provides a progressive framework:
- Stage A: At risk for heart failure without structural heart disease or symptoms 1
- Stage B: Structural heart disease present without signs or symptoms of heart failure 1
- Stage C: Structural heart disease with current or prior heart failure symptoms 1
- Stage D: Refractory heart failure requiring specialized interventions 1
This staging system recognizes that patients advance through stages and rarely regress, even with symptom improvement. 1
Primary Causes
Ischemic Heart Disease
- Single most common etiology, accounting for approximately 40% of heart failure cases globally 7
- In Western populations, ischemic cardiomyopathy causes 49-54% of HFrEF cases 7
- Mechanisms include myocardial scarring, stunning/hibernation, epicardial coronary disease, abnormal coronary microcirculation, and endothelial dysfunction 7
- Coronary artery disease was the underlying cause in 60% of patients in the landmark PARADIGM-HF trial 8
Hypertension
- Represents the underlying cause in 17-31% of heart failure cases 7
- Higher prevalence in HFpEF phenotypes 7
- Long-standing hypertension leads to pathological ventricular remodeling with increased wall thickness and eventual systolic and diastolic dysfunction 7
- Present in 71% of patients in PARADIGM-HF 8
Cardiomyopathies
- Idiopathic dilated cardiomyopathy accounts for approximately 30% of heart failure cases in European registries 7
- Up to 30% of dilated cardiomyopathy has a genetic cause, resulting from mutations in cytoskeletal, sarcolemmal, sarcomeric, and nuclear envelope proteins 1, 7
- Muscular dystrophies and laminopathies can lead to cardiomyopathy 7
Valvular Heart Disease
- Accounts for 8-20% of heart failure cases 7
- Higher prevalence in HFpEF (20%) versus HFrEF (4%) 7
- 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 7
- Acquired and congenital valve abnormalities (mitral, aortic, tricuspid, pulmonary) contribute to heart failure development 7
Toxic and Metabolic Causes
Substance-Related
- Recreational substances: alcohol, cocaine, amphetamines, anabolic steroids 7
- Medications: anthracycline chemotherapy, immunomodulating drugs, antidepressants, antiarrhythmics 7
- Heavy metals: copper, iron, lead, cobalt 7
- Radiation therapy to the chest 7
Hormonal and Metabolic Abnormalities
- Hypothyroidism, hyperthyroidism, diabetes mellitus, metabolic syndrome 7
- Nutritional deficiencies: thiamine deficiency, obesity, malnutrition 7
- Diabetes mellitus was present in 35% of PARADIGM-HF patients 8
Infectious and Immune-Mediated Causes
- Viral myocarditis represents a significant cause of heart failure, particularly in younger patients 7
- Other infectious agents: bacteria, spirochetes, fungi, protozoa, parasites 7
- Chagas disease is a major cause of heart failure in South America 7
- Lymphocytic/giant cell myocarditis and systemic lupus erythematosus 7
Geographic and Demographic Variations
Critical geographic differences exist in heart failure etiology:
- Eastern Europe and Middle East: Highest rates of ischemic etiology (55-57%) 7
- Africa: Lowest ischemic rates (12%) but highest rates of rheumatic heart disease and dilated cardiomyopathy 7
- Sub-Saharan Africa: Predominantly non-ischemic causes (75.5%) 7
Special Populations
Peripartum Cardiomyopathy
Renal Dysfunction
- 37% of PARADIGM-HF patients had eGFR <60 mL/min/1.73m² 8
- Chronic renal insufficiency is a risk factor for HFpEF 4
Common Pitfalls
Do not confuse heart failure with cardiomyopathy or left ventricular dysfunction—these terms describe structural or functional abnormalities that may cause heart failure, but heart failure itself is a clinical syndrome diagnosed by symptoms (dyspnea, fatigue) and signs (edema, rales). 1
Recognize that "congestive heart failure" is outdated terminology—not all patients have volume overload at presentation, making "heart failure" the preferred term. 1
Understand that heart failure is a progressive disorder—cardiac remodeling generally precedes symptom development by months or years and continues despite treatment, contributing to symptom worsening. 1