Which of the following is included in HFmrEF treatment as disease-modifying therapy?

• A. RASS blockade
• B. MRAs
• C. SGLT2 inhibitors
• D. Diuretics

Answer: (C)

In HFmrEF, disease-modifying therapy refers to treatments that improve long-term outcomes, not just symptoms. SGLT2 inhibitors fit this best because large trials have shown they reduce heart-failure hospitalizations and cardiovascular death across the heart failure spectrum, including mid-range ejection fraction. They appear to help with remodeling and overall heart function beyond simply relieving symptoms, which is why they’re emphasized as disease-modifying therapy for HFmrEF. Diuretics mainly alleviate congestion without altering disease progression. RASS blockade (ACE inhibitors/ARBs) and MRAs do have proven benefits in HFrEF and are used in HFmrEF in appropriate patients, but the strongest, specific disease-modifying evidence in HFmrEF points to SGLT2 inhibitors.