A LITERATURE ANALYSIS OF THE PATHOPHYSIOLOGY OF EMERGING THERAPIES FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION AND PRECISION MEDICINE

Heart Failure with Preserved Ejection Fraction (HFpEF) is a multifaceted and heterogeneous syndrome that accounts for more than half of all heart failure cases worldwide. It is primarily characterized by impaired diastolic relaxation and increased ventricular stiffness, leading to elevated filling pressures despite a normal ejection fraction. HFpEF predominantly affects older adults, women, and individuals with comorbidities such as hypertension, obesity, diabetes, atrial fibrillation, and chronic kidney disease. Despite its growing prevalence and significant contribution to morbidity, mortality, and healthcare costs, effective therapies for HFpEF have historically remained elusive. In recent years, however, substantial progress has been made in understanding the pathophysiology and management of this condition. The emergence of sodium–glucose cotransporter 2 (SGLT2) inhibitors, including empagliflozin and dapagliflozin, represents a major breakthrough, demonstrating consistent reductions in heart failure hospitalizations and improvements in symptoms irrespective of diabetic status. Angiotensin receptor–neprilysin inhibitors (ARNIs), particularly sacubitril/valsartan, have shown beneficial effects in select patient subgroups, while mineralocorticoid receptor antagonists (MRAs) continue to play an important role in carefully monitored patients. Furthermore, soluble guanylate cyclase (sGC) stimulators and disease-specific therapies such as tafamidis for transthyretin amyloid cardiomyopathy (ATTR-CM) highlight the shift toward targeted and precision-based treatment approaches. Despite these promising developments, no single therapy has yet demonstrated a universal mortality benefit in the diverse HFpEF population. Future strategies should emphasize precision phenotyping, integrating clinical data with multi-omics, artificial intelligence (AI), and machine learning to identify distinct HFpEF subtypes and optimize individualized therapy. Moreover, digital health technologies—including remote patient monitoring, predictive analytics, and wearable sensors—offer significant potential for early detection of decompensation and proactive management. The evolving therapeutic landscape of HFpEF signifies a paradigm shift from symptom management toward disease modification, personalization, and technology-driven care. Continued interdisciplinary collaboration and integration of advanced analytics into clinical practice will be essential to translate these emerging therapies into meaningful improvements in outcomes and quality of life for patients with HFpEF.