Overview
This lecture traces the evolving understanding, diagnosis, and treatment of heart failure with preserved ejection fraction (HFpEF), highlighting epidemiology, phenotypes, pathophysiology, clinical trials, and future directions.
History and Definition of HFpEF
- HFpEF emerged as a recognized condition in the 2000s, initially termed diastolic heart failure.
- Early skepticism existed about HFpEF, especially outside Western populations.
- Initial definitions focused on diastolic dysfunction, but this was neither sufficient nor specific.
- The term “HFpEF” focuses on preserved systolic (ejection fraction >40%) but recognizes that contraction can still be impaired.
Epidemiology and Phenotypes
- HFpEF now accounts for over half of heart failure cases and is rising.
- Typical Western HFpEF: older, hypertensive women; in Asia, younger, often obese males are also affected.
- Asian HFpEF patients have more diabetes and can have a lean-diabetic phenotype.
- Machine learning has identified three phenotypes: elderly/atrial fibrillation, obese/metabolic, and lean/diabetic (worst prognosis).
Pathophysiology Insights
- HFpEF involves both diastolic and systolic dysfunction, left atrial enlargement, raised natriuretic peptides, pulmonary hypertension, and increased filling pressures.
- Nitric oxide-cGMP pathway and inflammation are implicated in pathogenesis.
- Visceral and epicardial (around the heart) fat contribute to inflammation and fibrosis in HFpEF.
- Obesity paradox: higher BMI is protective in HFpEF, but central adiposity (high waist/height ratio) increases risk.
Treatment Evolution
- Early trials using therapies from HFrEF (e.g., ARBs, beta-blockers, MRAs) were neutral for HFpEF.
- Newer understanding emphasizes targeting inflammation and specific patient phenotypes.
- SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) have shown positive outcomes in HFpEF.
- Mineralocorticoid receptor antagonists and anti-inflammatory therapies are under investigation.
- Treatments may need to be tailored by phenotype (e.g., obese, inflammatory).
Classification and Sex Differences
- Heart failure with mid-range ejection fraction (HFmrEF) now recognized (EF 40-50%), with evidence to treat as HFrEF.
- Women have higher normal ejection fractions; guidelines suggest sex-specific cutoffs for reduced EF.
- New guidelines include SGLT2 inhibitors for both HFmrEF and HFpEF.
Future Directions and Research
- A focus on phenotype-specific treatments and precise diagnosis, including imaging and AI tools.
- Ongoing development of device therapies (e.g., atrial shunts, nerve modulation).
- Continued research into inflammation, microvascular dysfunction, and fat distribution.
Key Terms & Definitions
- HFpEF — Heart failure with preserved ejection fraction, typically EF >40-50%.
- HFrEF — Heart failure with reduced ejection fraction, EF <40%.
- Diastolic Dysfunction — Impaired relaxation/filling of the heart.
- Nitric Oxide-cGMP pathway — A signaling pathway involved in vascular and myocardial relaxation.
- Epicardial Fat — Fat around the heart, linked to inflammation and dysfunction.
- Obesity Paradox — The phenomenon where obesity increases risk for heart failure, but once present, higher BMI predicts better outcomes.
- SGLT2 Inhibitors — Medications originally for diabetes, now used in heart failure.
- HFmrEF — Heart failure with mildly reduced (mid-range) ejection fraction (EF 40-50%).
Action Items / Next Steps
- Review current heart failure guidelines for HFpEF, HFmrEF, and HFrEF.
- Stay updated on results from ongoing trials (e.g., SPIRIT, FINEARTS).
- Explore phenotype-specific management strategies in clinical practice.
- Study the impact of AI and imaging advances in heart failure diagnosis.
- Consider homework to summarize the three main HFpEF phenotypes and their clinical implications.