How does ischemic heart disease cause heart failure with reduced ejection fraction?

Pathophysiology of Ischemic Heart Disease Leading to Heart Failure with Reduced Ejection Fraction

Ischemic heart disease is the principal cause of heart failure with reduced ejection fraction (HFrEF) in men, leading to progressive myocardial damage, adverse cardiac remodeling, and ultimately impaired systolic function.

Pathophysiological Mechanisms

1. Myocardial Damage and Remodeling

• Acute Ischemic Injury: Coronary artery disease causes inadequate blood supply to the myocardium, leading to:

  • Myocyte death (infarction)
  • Replacement fibrosis
  • Loss of contractile tissue
  • Impaired systolic function

• Chronic Ischemia Effects:

  • Hibernating myocardium (chronically underperfused but viable tissue)
  • Stunned myocardium (temporary dysfunction following acute ischemia)
  • Progressive loss of functional myocardium over time

2. Adverse Ventricular Remodeling

• Structural Changes:

  • Left ventricular dilatation
  • Wall thinning at infarct sites
  • Compensatory hypertrophy of non-infarcted segments
  • Spherical ventricular shape (less efficient than elliptical)

• Molecular and Cellular Changes:

  • Activation of neurohormonal systems (renin-angiotensin-aldosterone, sympathetic)
  • Increased wall stress
  • Myocyte hypertrophy and apoptosis
  • Extracellular matrix changes and fibrosis

3. Hemodynamic Consequences

• Systolic Dysfunction:

  • Reduced contractility
  • Decreased ejection fraction (<40%)
  • Reduced stroke volume and cardiac output
  • Increased end-systolic and end-diastolic volumes

• Compensatory Mechanisms:

  • Frank-Starling mechanism (initially beneficial)
  • Neurohormonal activation (initially compensatory, later detrimental)
  • Increased heart rate (may worsen ischemia)

Gender Differences

• HFrEF is more prevalent in men, while women are more likely to develop heart failure with preserved ejection fraction (HFpEF) 1
• Men more often have ischemic cardiomyopathy as the etiology of heart failure 1
• Women tend to develop heart failure at an older age than men and have comparatively better outcomes 1

Clinical Implications

Diagnostic Considerations

• Left ventricular ejection fraction is a key diagnostic parameter but has limitations as a predictor of prognosis 1
• Other imaging parameters such as myocardial strain and strain rate are more sensitive markers of myocardial dysfunction 1
• Elevated natriuretic peptides and troponin levels indicate myocardial stress and injury

Treatment Approaches

• Pharmacological Therapy:

  • Beta-blockers and ACE inhibitors/ARBs as foundational therapy 2
  • Mineralocorticoid receptor antagonists for persistent symptoms
  • SGLT2 inhibitors significantly reduce cardiovascular mortality regardless of diabetes status 2
  • Ivabradine for patients with elevated heart rate despite optimal beta-blocker therapy 3

• Device Therapies:

  • Cardiac resynchronization therapy for patients with interventricular dyssynchrony 2
  • Implantable cardiac defibrillators for patients with severe LV dysfunction, particularly of ischemic etiology 2
  • Transcatheter mitral valve repair for severe secondary mitral regurgitation 2

Prognosis and Disease Trajectory

• Despite advances in therapy, HFrEF carries substantial morbidity and mortality
• 5-year survival rate of approximately 25% after hospitalization for HFrEF 2
• Patients with established ischemic heart disease have increased risk of further ischemic events and progression to lower EF categories over time 4

Key Pitfalls to Avoid

• Failing to recognize ischemic heart disease as the underlying cause of HFrEF
• Overlooking the importance of addressing the ischemic component in treatment strategies
• Relying solely on ejection fraction for prognostication and treatment decisions
• Underestimating the importance of comprehensive neurohormonal blockade in treatment

Understanding the pathophysiological link between ischemic heart disease and HFrEF is crucial for implementing effective prevention and treatment strategies to improve outcomes in this high-risk population.