What are the causes of Heart Failure with Preserved Ejection Fraction (HFpEF)?

Causes of Heart Failure with Preserved Ejection Fraction (HFpEF)

The primary causes of HFpEF include hypertension, obesity, diabetes mellitus, advanced age, coronary artery disease, and specific cardiac conditions like infiltrative cardiomyopathies. These factors contribute to structural and functional cardiac changes that lead to heart failure despite preserved ejection fraction.

Major Risk Factors and Causes

Hypertension

• Present in >80% of HFpEF patients and is considered the single most significant predictor for HFpEF development 1
• Increases risk by approximately 50% and is potentially a prerequisite condition for most cases of HFpEF 1
• Sustained hypertension leads to left ventricular hypertrophy, increased ventricular stiffness, and impaired relaxation 1

Metabolic Disorders

• Obesity and metabolic syndrome:

  • Present in >80% of HFpEF patients 1
  • Associated with systemic inflammation that contributes to myocardial fibrosis and endothelial dysfunction 2
  • May represent a specific phenotype of HFpEF with unique hemodynamic and structural abnormalities 2

• Diabetes mellitus:

  • Present in 25-50% of HFpEF patients 1
  • Associated with worse prognosis due to overlapping pathophysiological mechanisms 1
  • Contributes to neurohormonal activation, inflammation, and impaired skeletal muscle function 1

Age and Gender Factors

• Advanced age is a strong predictor of HFpEF incidence, with rates up to 30% at advanced age (>80 years) 1
• Women are disproportionately affected compared to men 1

Cardiovascular Conditions

• Coronary artery disease:

  • Common in HFpEF patients and associated with greater deterioration in left ventricular systolic function 1
  • Prior myocardial infarction can lead to structural heart changes that contribute to HFpEF 3

• Atrial fibrillation:

  • Frequently associated with HFpEF and can both contribute to and result from HFpEF 3

Specific Cardiac Conditions ("HFpEF Mimics")

• Infiltrative/restrictive cardiomyopathies:

  • Cardiac amyloidosis (characterized by increased LV wall thickness) 3
  • Hemochromatosis 3
  • Fabry disease 3

• Other cardiac conditions:

  • Hypertrophic cardiomyopathy 3
  • Valvular heart disease 3
  • Pericardial disease 3

Non-Cardiac Causes

• Chronic kidney disease 3
• Liver disease 3
• Chronic venous insufficiency 3

Pathophysiological Mechanisms

Structural and Functional Changes

• Left ventricular hypertrophy and increased ventricular stiffness 1
• Impaired myocardial relaxation leading to elevated left ventricular filling pressures 1
• Myocardial fibrosis contributing to diastolic dysfunction 4
• Ventricular-vascular uncoupling 4

Inflammatory and Microvascular Dysfunction

• Chronic low-grade inflammation plays a vital role in the progression of HFpEF 5
• Microvascular dysfunction contributes to reduced cardiac perfusion 6
• Lymphatic vessel alterations may lead to myocardial edema and impaired cardiac function 6

Pulmonary Involvement

• Pulmonary hypertension commonly develops due to elevated left atrial pressures 1
• Progressive pulmonary vascular disease further complicates the condition 1

Diagnostic Approach to HFpEF Causes

When evaluating a patient with suspected HFpEF, it's important to:

1. Identify primary cardiovascular risk factors (hypertension, obesity, diabetes, advanced age)
2. Rule out specific cardiac conditions ("HFpEF mimics") that require targeted therapy:
   • Infiltrative cardiomyopathies (cardiac amyloidosis, hemochromatosis)
   • Hypertrophic cardiomyopathy
   • Valvular heart disease
   • Pericardial disease
3. Assess for non-cardiac causes of congestion (kidney disease, liver disease, chronic venous insufficiency)

Understanding the specific cause of HFpEF is crucial for appropriate management, as treatment strategies may differ based on the underlying etiology.