CHF patients are divided into two main groups: those with reduced ejection fraction (HFrEF) and those with preserved ejection fraction (HFpEF), as defined by the measurement of left ventricular ejection fraction, the central measure of left ventricular systolic function. The LVEF cut-off has varied over time, but AHA/ACC/HFSA and ESC guidelines now utilize ≤40% for HFrEF and ≥50% for HFpEF, with a third group in the middle having mildly reduced EF (HFmrEF). Despite similar symptoms and disabilities, HFrEF and HFpEF appear to have features of distinct syndromes, with differing epidemiology, LV morphology and cellular changes, though some have challenged this view. 

Drug treatment of chronic heart failure (CHF) is dominated by well-established and widely genericized classes, including angiotensin-converting enzyme (ACE) inhibitors and beta blockers. Polypharmacy with these older classes is common owing to the numerous functional and structural problems that contribute to the HF syndrome. However, in recent years, several new products have become available for CHF that have demonstrated additional benefits in terms of cardiovascular (CV) outcomes and are now recommended in treatment guidelines. These products include Novartis’ angiotensin receptor-neprilysin inhibitor (ARNi) Entresto (sacubitril/vaslsartan), Merck and Bayer’s soluble guanylate cyclase (sGC) stimulator Verquvo (vericiguat), and the sodium-glucose cotransporter-2 (SGLT-2) inhibitors, AstraZeneca’s Farxiga (dapagliflozin), Eli Lilly and Boehringer Ingelheim’s Jardiance (empagliflozin), and Lexicon Pharmaceuticals’ SGLT-1/SGLT-2 inhibitor Inpefa (sotagliflozin). Currently, there are more approved therapies for HFrEF, but the unmet need for HFpEF patients is driving new research and leading to drug approvals and label expansions.