Impact of Rehabilitation Program on PAH Patients Treated With Macitentan.

The Impact of Macitentan Therapy and Rehabilitation Program on Peak Oxygen Consumption in Patients With Severe Pulmonary Arterial Hypertension

48 patients, over the age of 18, with pulmonary arterial hypertension (PAH) classified as WHO III-IV, that are all stable under Macitentan therapy ( medication for treating PAH patients), will be recruited to the study through the pulmonary hypertension (PH) clinic at Soroka Medical Center. The patients will be randomly divided into an intervention group, which will exercise twice a week for 12 weeks, supervised by physiotherapists, and a control group, which will only receive the medication. Tests will be performed before the beginning of the intervention program, 6 weeks after it has begun, at the end of the 12 week program, and 3 months after finishing the program.

48 patients, over the age of 18, with PAH classified as WHO III-IV, that are all stable under Macitentan therapy, will be recruited to the study through the PH clinic at Soroka Medical Center. The patients will be randomly divided into intervention and control groups. The intervention group will exercise in a pulmonary rehabilitation program twice a week, for 12 weeks. The exercise protocol will include circuit training, with 2-3 minutes exercise intervals, including aerobic and strength training, and will be supervised by physiotherapists. The control group will continue to receive their usual Macitentan treatment. All study participants will undergo tests before the beginning of the intervention program, 6 weeks after it has begun, at the end of the 12 week program, and 3 months after finishing the program. The tests will include a cardio-pulmonary exercise test, 6 minute walk distance measurement, WHO functional class evaluation, levels of Brain natriuretic peptide (BNP), EMPHASIS10 questionnaire (emPHasis-10 questionnaire is a short questionnaire for assessing Health Related Quality of Life in pulmonary arterial hypertension), Short Form-36 (SF-36) quality of life questionnaire and echocardiography. Once data collection is completed, two way ANOVA repeated measures will be used to assess the changes in outcome measures.

Patients stable on Macitentan therapy will exercise twice a week for 12 weeks, supervised by physiotherapists. The exercise program includes aerobic and strength exercises, at 2-3 minutes intervals.

patients who are stable on Macitentan therapy (received in both groups before enrollment) and will exercise at a pulmonary rehabilitation program twice a week for 12 weeks

Cardio-pulmonary exercise test- measurements of VO2 , anaerobic threshold, respiratory exchange ratio, O2 pulse, ventilatory reserve, heart rate, End tidal CO2 and O2, work rate, ventilation (VE), VCO2 during exercise test

Echocardiography: dimensions and pressure of left and right ventricles, cardiac output, pulmonary arterial pressure (systolic, diastolic and mean), pulmonary capillary wedge pressure

Inclusion Criteria: PAH patients group 1 Patients Age > 18 years, Patients with WHO III Patients on Macitentan treatment who are stable on disease-targeted medication for at least 2 months prior to inclusion. Exclusion Criteria: Patients with other significant comorbidity such as Pulmonary veno-occlusive disease (PVOD) or pulmonary capillary haemangiomatosis, Malignancy, Recent myocardial infarction in the last 2 weeks. Patients on other PAH specific medications treatment.