Heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) represent a significant and growing burden for patients and the healthcare system, not only in cardiovascular medicine, but also in the context of cardio-kidney-metabolic (CKM) syndrome. Trials are underway evaluating new therapies that may offer benefits to patients with HFmrEF/HFpEF and may also have broader, multisystem effects. Tune in to stay up to date!