Selective Targeting of a Maladaptive Adipokine—But Not of a Traditional Hemodynamic Phenotype—Produces Predicted Left Heart Benefits in Patients With Heart Failure and Preserved Ejection Fraction

Dr. Milton Packer

“Treating elevated pulmonary vascular resistance (PVR) alone in patients with heart failure with preserved ejection fraction (HFpEF) and combined postcapillary and precapillary pulmonary hypertension (CpcPH-HFpEF) may target the wrong mechanism and only address downstream consequences. Instead, based on the adipokine hypothesis, therapies such as sotatercept that target activin A may lead to improved outcomes.”

Milton Packer

“This conceptual framework provides a coherent explanation of the effects of sotatercept on the left heart (and explains the disappointing results with conventional pulmonary vasodilators). It also underscores the advantages of adipokine-directed rather than phenotype-directed targeting in the treatment of HFpEF, even when the disease is clinically advanced.”