Mechanistic Study of Nicotinamide Riboside on NAD+ Biology in Individuals With Combined Pulmonary Hypertension

The 6MWT measures the distance (in meters), a participant can walk at a comfortable speed on a flat, hard surface in 6 minutes. The intent of the 6MWD test is to evaluate exercise capacity associated with carrying out daily physical activities.

The New York Heart Association (NYHA) functional classification is a widely used system for assessing the severity of heart failure based on symptoms and their impact on physical activity. It is divided into four classes: Class I includes individuals with no limitations on physical activity and no symptoms during ordinary activities; Class II includes individuals with mild limitations on physical activity, where ordinary physical activity causes fatigue, shortness of breath, or other symptoms; Class III includes individuals with marked limitations on physical activity, where less-than-ordinary activity results in symptoms; and Class IV includes individuals who are unable to engage in any physical activity without discomfort and may experience symptoms even at rest. The NYHA functional class will be evaluated at Baseline and Visit 2. The NYHA functional classification is an ordinal scale ranging from Class I to Class IV, with lower class numbers indicating better functional status. Imp

The emPHasis-10 is a short and easy questionnaire that consists of 10 items that address breathlessness, fatigue, control, and confidence. Each item is scored on a semantic differential six-point scale (0-5), with contrasting adjectives at each end. A total emPHasis-10 score is derived using simple aggregation of the 10 items. emPHasis-10 scores range from 0 to 50, higher scores indicate worse quality of life

The SF36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical and emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. Remote subjects will complete the SF-36 at baseline and each subsequent visit during the study. Each SF-36 domain is scored using a standardized transformation to a 0-100 scale, with higher scores indicating better health status (i.e., fewer limitations, less pain, greater well-being, and higher vitality). Improvements over time are reflected by increases in domain scores relative to baseline.

The MLHF (Minnesota Living with Heart Failure Questionnaire) is a widely used disease-specific instrument designed to assess the impact of heart failure on an individual's quality of life. The MLHF includes 21 items that evaluate various aspects of physical, emotional, and social functioning as affected by heart failure. It focuses on areas such as 1) physical limitations due to heart failure symptoms; 2) the emotional impact of living with heart failure; 3) interference with social activities; 4) effects on usual daily activities; and 5) overall quality of life as perceived by the patient. Participants will complete the MLHF at baseline and during each subsequent visit to monitor changes in their quality of life throughout the study. Each MLHF item is scored on a 6-point Likert scale ranging from 0 ("no impact") to 5 ("very much"), reflecting how much heart failure has affected the patient during the past month. Item scores are summed to produce a total score ranging from 0 to 105, w

Right ventricular fractional area change (RV FAC) is a non-invasive measure of right ventricular systolic function assessed using transthoracic echocardiography. RV FAC is calculated from standard echocardiographic images by comparing right ventricular area during diastole and systole. Higher RV FAC values indicate better right ventricular function. Change in RV FAC from baseline will be used to assess changes in right ventricular systolic performance during the study.

Right ventricular longitudinal strain is a non-invasive measure of right ventricular myocardial function assessed using transthoracic echocardiography with strain analysis. RV longitudinal strain quantifies myocardial deformation of the right ventricle during systole. More negative strain values indicate better right ventricular systolic function. Change in RV longitudinal strain from baseline will be used to assess changes in right ventricular myocardial performance during the study.

This will be a measure of adverse events in the study