The purpose of the study is to evaluate the safety and how well the medication sotatercept works versus placebo in treating Heart Failure with a Preserved Ejection Fraction. The study will also look at information obtained from the tests performed as part of the study to see if subjects have improvement in symptoms of heart failure. Participation in this study will last approximately 26 months. During the study period subjects will be asked to attend regular study visits with the research coordinator. These visits will include such activities as blood tests, questionnaires, physical evaluation by a study doctor, a right heart catheterization with exercise, echocardiogram, and 6 minute hall walks. There will be 35 visits as part of participation in this clinical trial.

Participants will be randomized to either the treatment group (and receive the medication) or the control group (and not receive the medication). Subjects will have a 2:1 chance of receiving the study medication during their participation in the trial. The treatment assignment is determined by randomization, where a computer selects at random which treatment group you will be in (like drawing straws). Neither the subject, nor the blinded personnel will know which group subjects are in. Neither the subject nor the study doctor will decide what group subjects are assigned. Participants from the placebo group in CADENCE who enter HARMONIZE at Visit 9a will be randomized 1:1 to one of the active treatment groups. Participants from an active treatment group in CADENCE entering HARMONIZE after Visit 9a will be allocated to continue in the same treatment group (ie, sotatercept dose level) as in CADENCE.

This study is enrolling two different groups of individuals. The first group are those individuals referred for right heart catheterization (RHC), which is a procedure performed to check heart pressure taken inside the heart. The second group of individuals are those who have tricuspid regurgitation (TR) (blood that leaks due to improper valve closure) and are undergoing tricuspid valve intervention to correct the regurgitation. The RHC group will be referred to as the control group and the tricuspid intervention group will be the treatment group in this study. This study involves collecting existing medical records on both groups, as well as an arterial (from an artery) blood sample and venous (from a vein) blood sample from the vein that carries blood away from the liver. The control group will not involve any additional procedures or follow up. The TR population will perform a 6 minute hall walk test before their tricuspid valve intervention and again during the six month post procedure follow up. The TR group will also have repeat arterial and venous blood collection at the six month follow up. The TR group will have data collected for up to two years post tricuspid valve intervention.