This study is examining the use, safety and performance of an investigational, meaning not approved for commercial use or sale by the US Food and Drug Administration (FDA) device called Transcatheter Mitral Valve Replacement (TMVR). The TMVR is a device used to treat mitral valve disease in patients with heart failure (weakened heart muscle). The device is placed by a non surgical approach using a delivery catheter (hollow tube) placed in your blood vessel at the top of your leg and directed up to your heart. This five year study will include a screening process to determine you meet eligibility criteria. If you qualify you will then be seen for a baseline visit, undergo the procedure to place the device, day after procedure, at hospital discharge, 1,3,6, 12 months, then yearly for up to 5 years. Study related testing includes physical exams, medication review, 6 minute hall walk test, questionnaires, blood work, CT scans, electrocardiogram or ECG (recording of your heart's electrical activity) and echocardiogram (ultrasound test of your heart).

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 66:33 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.

This study is for participants who have tricuspid regurgitation, a condition in which your heart's tricuspid valve does not close tightly which causes blood to flow backwards in the incorrect direction. This condition increases the workload on the heart and if left untreated, it can increase the risk of worsening heart failure. In this study, a device called the PASCAL Transcatheter Valve Repair System will be used to treat the tricuspid regurgitation. The PASCAL Transcatheter Valve Repair System is an investigational device meaning it has not been approved for commercial use by the US Food and Drug Administration (FDA). In this study participants will be randomized, meaning randomly assigned like drawing straws, in a 2:1 fashion to either receive the PASCAL Transcatheter Valve Repair System (treatment group) or optimal medical therapy (OMT) (control group). OMT means your medications will be adjusted as needed to provide the most benefit possible. Participants randomized to the OMT group may be eligible to receive the device after completing 2 years of follow up. Participants not eligible for randomization may be eligible for the registry portion of the study if approved by the sponsor. The registry arm participants will not be randomized but will undergo the procedure to place the device.

Participation in this study will last about 5 years and involve up to 15 visits for those in the treatment or registry group and 11 visit for those in the control group. Study related procedures include a right heart catheterization (test to measure the pressures in the heart), echocardiograms (ultrasound test of heart), electrocardiogram or ECG (test of the heart's electrical system) blood work, questionnaires, hall walk test, and physical exam.

The purpose of this study is to evaluate the potential effectiveness, outcomes, and safety (before, during, and after study procedures) of the Inter Atrial Shunt Device (IASD) in the treatment of subjects with heart failure symptoms and relatively normal pumping of the heart. This study involves the use of an investigational medical device called the Corvia Atrial Shunt (CAS) System. The CAS is permanently implanted in the heart to reduce the increased pressure in the left side of the heart by creating a small opening between the two upper chambers of the heart. Participants will have a 50% chance of being in either group A having the CAS placed or group B and not receiving the device. Subjects will have 7 research clinic visits, and multiple telephone calls for a total of 5 years of follow-up. The research clinic visits will include medical exams, health questionnaires, ECG and echocardiogram of the heart and 6 minute hall walk tests.

The purpose of this study is to evaluate the potential effectiveness, outcomes, and safety (before, during, and after study procedures) of the Inter Atrial Shunt Device (IASD) in the treatment of subjects with heart failure symptoms and relatively normal pumping of the heart. This study involves the use of an investigational medical device called the Corvia Atrial Shunt (CAS) System. The CAS is permanently implanted in the heart to reduce the increased pressure in the left side of the heart by creating a small opening between the two upper chambers of the heart. Participants will have a 50% chance of being in either group A having the CAS placed or group B and not receiving the device. Subjects will have 7 research clinic visits, and multiple telephone calls for a total of 5 years of follow-up. The research clinic visits will include medical exams, health questionnaires, ECG and echocardiogram of the heart and 6 minute hall walk tests.

The purpose of the study is to evaluate the safety and how well the medication levosimenden works versus placebo in treating Pulmonary Hypertension and Heart Failure with a Preserved Ejection Fraction measured by a 6 minute walk. This is a condition where the lower left chamber (left ventricle) of the heart is not able to fill properly with blood during the filling phase and the amount of blood pumped out to the body is below normal. 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. Levosimendan is a drug that has been FDA-approved for intravenous (IV) delivery to your body. This study aims to determine if the tablet form of the drug is as effective as the IV route. Tablets are much more attainable for patients to manage their heart failure from home, rather than going to an infusion clinic for treatments. Participation in this study will last approximately 12 weeks with the option to continue to the stage 2 phase of the study. If the stage 2 phase is selected as well, participation will last approximately 26 months or a little over 2 years. These visits will include such activities as blood tests, questionnaires, physical evaluation by a study doctor, echocardiogram, and 6 minute hall walks.

Participants will be randomized to either the treatment group (and receive the medication) or the control group (receive an inactive medication). Subjects will have a 50:50 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.

This study involves research. You are being asked to participate in this research study to have your temperature taken. The purpose of the study is to collect data to test a temperature measurement module that is part of medical study device that measure's human body temperature.

This study is for participants who have tricuspid regurgitation, a condition in which your heart's tricuspid valve does not close tightly which causes blood to flow backwards in the incorrect direction. This condition increases the workload on the heart and if left untreated, it can increase the risk of worsening heart failure. In this study, a device called the VDyne Transcatheter Tricuspid Replacement System will be used to treat the tricuspid regurgitation. The VDyne Transcatheter Tricsupid Replacement System is an investigational device meaning it has not been approved for commercial use by the US Food and Drug Administration (FDA). In this study all eligible participants will be treated with the device.

Participation in this study will last about 5 years and involve up to 13 visits. Study related procedures include a right heart catheterization (test to measure the pressures in the heart), echocardiograms (ultrasound test of heart), electrocardiogram or ECG (test of the heart's electrical system) blood work, questionnaires, hall walk test, and physical exam.

There are risks associated with this study including potential risks with the device, implant procedure and study related procedures. There is also the risk of loss of confidentiality. The study may or may not benefit you but the information learned may benefit others with this condition in the future.

This study is for those with Transthyretin (TTR) Amyloidosis with Cardiomyopathy or ATTR-CM. ATTR-CM is a condition where the heart muscle does not pump your blood through your body as it should because of build up of abnormal protein between the muscle fibers in your heart. The specific protein is called transthyretin amyloid (TTR). The study involves an investigational drug called NTLA-2001. Investigational means it is not approved for commercial sale or use by the Food and Drug Administration. This study is a randomized study meaning participants will be assigned by chance to receive NTLA-2001 or placebo. A placebo looks like the investigational drug but contains no active ingredient. In this study, two out of three participants are assigned to receive NTLA-2001 and one out of three will receive placebo. NTLA-2001 or placebo are given by intravenous (IV) infusion meaning in your vein.

NTLA-2001 consists of a gene editing system which can "knockout" the TTR gene and permanently change the DNA (deoxyribonucleic acid, which contains information that determines parts in traits such as eye color or height, that are passed on from parent to child) so the gene stops making the TTR protein.

This study will last at least 18 months and include up to 17 visits. Study related procedures include physical exams, blood work including genetic testing, eye exam, hall walk test, electrocardiograms (ECGs), echocardiogram (echo) and vitamin A supplement. Study risks include infusion related risks like headache, fever, chills, or increased liver enzymes. Other study related risks include genetic risks, loss of confidentiality and unknown risks.

This study is an open label extension study for those who participated in the ION 682884-CS2 clinical trial for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a disease caused by change in a protein called transthyretin (TTR) which can result in a build up of this protein in parts of the body including the heart. This build up is called an amyloid deposit, and when this occurs in the heart it can lead to a condition called cardiomyopathy. This study involves the medication eplontersen, which is considered investigational meaning it is not approved for commercial use by the Food and Drug Administration (FDA). Eplontersen is aimed at preventing production of the TTR protein to slow or reverse disease progression. Eplontersen is given as an injection under the skin in the upper arm, stomach or thigh. This study will last about 3 1/2 years and include 16 clinic visits. Study procedures include physical exams, blood work, questionnaires, hall walk tests, electrocardiograms (tracing of the heart's electrical activity), echocardiogram (ultrasound test of the heart) and taking a Vitamin A supplement.