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 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.

Volunteers are being asked to participate in a clinical research study to find out if the drug mavacamten is safe and effective in treating elevated biomarker levels that occur in patients who have Heart Failure with Preserved Ejection Fraction (HFpEF). HFpEF is a syndrome that leads to stiffening in the left bottom chamber of the heart. This stiffening makes it difficult for the chamber to relax enough to fill up with blood, leading to increased pressure inside of the heart. MyoKardia is doing this research to find out if the new medication called mavacamten will work and be safe for the treatment of heart failure patients with the elevated levels the biomarkers NT-proBNP (a marker of wall stress inside the heart) and/or cardiac troponin (a marker of heart muscle injury). Biomarkers are biological molecules found in bodily fluids that can indicate abnormal conditions within the body. The study is planned to go on for about 2 years and include 35 patients from about 30 different study sites.

This research study will be evaluating whether liquid nitrogen sprayed on the cells lining the airways (cryotherapy) can reduce the mucus produced in the lungs of patients with chronic obstructive pulmonary disease (COPD). The study involves bronchoscopies, (placement of a lighted, flexible scope into the lungs) under general anesthesia to deliver the treatment to the lungs. The study is randomized such that 2/3 of individuals get the cryotherapy and the other 1/3 get a sham (control) treatment with no cryotherapy. Participants in the sham control group will be evaluated for eligible for cryotherapy at end of year one. The Study duration is 36 months. Those initially randomized to the treatment group, they will have 7 clinic visits and 2 treatment visits. Participants randomized to sham group will have 11 clinic visits and 4 treatment visits.

This research study aims to determine a less invasive way to assess heart function by taking measurements of the heart while subjects are performing an exercise cardiac MRI. Subjects will undergo two exercise phases and MRI measurements will be taken after each exercise phase. These measurements will be compared to available clinical data (including demographic, hemodynamic, radiologic, and functional) and future outcome data.

The primary purpose of this study is to see if the Targeted Lung Denervation (TLD) therapy (Active Treatment) is more effective than a sham procedure (Sham Control/no TLD therapy) at decreasing moderate or severe exacerbations in patients with COPD on optimal medical care. In addition, the study seeks to compare long-term safety, and other efficacy assessments, between the Active Treatment arm and the Sham Control arm.

TLD Therapy is done by passing a bronchoscope, with a special device (catheter) inserted through it, into the lungs. This special catheter delivers a type of electrical energy called radio frequency (or RF) energy to the nerves located on the outside of the airways. As with many bronchoscopic procedures, this is done while under anesthesia.

Participants will be randomly assigned (like flipping a coin) to receive one of two different treatments, either TLD Therapy in addition to optimal medical care (Active Treatment) or optimal medical care only (Sham Control). No matter which treatment you receive, you will undergo the same type of procedure, testing and follow-up while remaining on optimal medical care for COPD. You will have an equal chance of being assigned to either Active Treatment or the Sham Control group (1:1 randomization). Neither you or your study doctor will know which treatment you have received until after your 12-month follow-up visit. After the 12-month visit you will find out whether you received the active or sham procedure. If you received the sham procedure you have the option of crossing over into the treatment group and receiving TLD therapy.

Participation in the study will last for approximately 62 months. Depending on which group you are randomized to and if you decide to crossover to the treatment group, there will be 1-2 visits for TLD Therapy or sham control (non-active) procedure, 9-12 in-person clinic visits, and 13-23 phone visits.

Individuals with alpha-1 antitrypsin (AAT) deficiency (AAT blood level lower than 11 micro-moles) and emphysema will be invited to participate in this study. This study will determine the impact of IV Alpha-1 proteinase inhibitor (Alpha-1 MP) on the progression of emphysema in patients with AAT deficiency. A participant in this study would receive any one of the following three therapies: 1) Alpha-1 MP dosed at 60mg/Kg, 2) Alpha-1 MP dosed at 120mg/Kg, or 3) Placebo. Once a subject is enrolled into this study, he/she will be randomly selected to receive only one of the above three therapies. Neither the study investigators nor the participants will know the actual therapy being given to the participants. All the study participants will receive serial chest CT scans to determine if their emphysema progresses over the following 3 years. Participants will have the IV therapies given to them weekly, with some infusions given at MUSC and some at home. Safety and side effects of all therapies will be monitored.