Effect of Activin Type II Receptor Signaling in Patients With HFpEF and Pulmonary Hypertension: A Critical Analysis of Biological Mechanisms and Clinical Trials.

Sotatercept in CADENCE decreased pulmonary artery wedge pressures and left atrial volume index in patients with CpcPH-HFpEF, effects not explained by reduced pulmonary vascular resistance.

• Why it matters: Pulmonary vascular resistance increases in CpcPH-HFpEF differ from pulmonary arterial hypertension, and pulmonary venous/left atrial dysfunction may be central.
• What they did: The adipokine hypothesis centers activin A signaling through activin type II receptors; activin A promotes atrial myopathy and HFpEF in obesity-induced CpcPH-HFpEF models, and ligand traps alleviate left heart and pulmonary vascular abnormalities.
• The result: CADENCE validated that adipokine modulation can improve left heart measures in CpcPH-HFpEF, and phase III outcomes testing is underway to determine whether progression is slowed.