Functional Capacity Improvement on Patent Ductus Arteriosus with Pulmonary Arterial Hypertension : A Case Report and Literature Review

Pulmonary artery hypertension (PAH) is a pathophysiological disorder involving a wide range of clinical conditions. This can be a condition of complications from heart disease and respiratory system. Pulmonary arterial hypertension is defined as an increase in mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest assessed by right heart catheterization. The cardiovascular rehabilitation program is a set of efforts to improve the underlying cause of cardiovascular disease such that it can maintain or restore the best conditions and secondary prevention. Cardiac rehabilitation and physical exercise programs have the benefit of improving pulmonary vascular endothelial function, physical activity capacity and quality of life parameters for PAH patients. A 6-minute walk test can be used to assess the functional capacity of PAH patients.


INTRODUCTION
Pulmonary artery hypertension (PAH) is characterized by an increase in pulmonary vascular resistance that lead to decrease right ventricular function or death. 1 In addition to medical therapy for PAH, there are studies of cardiovascular rehabilitation programs and physical exercise programs in PAH patients that have positive effects because these programs can improve endothelial function, physical activity capacity, and life quality parameters. 2 These programs include a series of physical, educational, psychosocial and secondary prevention activities. 3This case reports the improvement of functional capacity in patient with patent ductus arteriosus (PDA) bidirectional shunt with PAH, by means of home-based exercise program.

CASE PRESENTATION
A 23-year-old woman came with postpartum shortness of breath.She was reffered from a district hospital with a suspicion of atrial septal defect (ASD) on P1A0 5 days postpartum.Shortness of breath was felt since 32 weeks of gestation that increased during activity, improves at rest.The legs were swollen and the activity was limited.Patient routinely checked the pregnancy at local Primary Health Care and was advised to give birth at a district hospital due to suspicion of congenital heart disease.She delivered normally; the baby was in a good condition.After delivery her baby, her complain about shortness of breath and swollen legs still persisted, therefore she was referred to Dr. Sardjito General Hospital for further treatment.History of fatigue had been felt since childhood, no disturbance of growth.At 9 years old of age, she visited a cardiologist and was diagnosed with congenital heart disease.She was advised to do a surgery due to congenital heart disease then, but the patient's family were refused.
On physical examination, we found that she was compos mentis.The blood pressure was 120/70 mmHg, heart rate 95 beats per minute (bpm), respiration rate 32 times per minute and temperature 36.5 ⁰C, SpO 2 86%.Jugular venous pressure was 2 cmH 2 O, no lymphadenopathy.Examination of the lungs showed vesicular voices in both the lung fields, there was no rales.Cardiac examination revealed cardiomegaly, prominent right ventricle heaving, continuous murmur in left infraclavicle area.Examination of both lower extremities showed peripheral edema.
Patient was educated about homebased exercise to walk 30 minutes/day, 5-7 times/week accompanied by observing SpO 2 before and after exercise.The exercise should be stopped when the patient feel shortness of breath or decrease of SpO 2 >10% from the baseline (before exercise) or fatigue (Table 1).Evaluation of the exercise should be done in 4 weeks.The patient was discharged and received sildenafil 40 mg t.i.d, bosentan 12.5 mg b.i.d, furosemide 40 mg q.i.d, and spironolacton 25 mg q.i.d.

DISCUSSION
Pulmonary hypertension (PH) is a pathophysiological disorder involving a wide range of clinical conditions and can be a complication of heart disease and respiratory system.Pulmonary hypertension is defined as an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest and assessed by heart catheterization. 1 Pulmonary hypertension is classified into five major groups.They are PAH, PH due to left heart disease, PH due to chronic lung disease and or hypoxic conditions, PH due to chronic thromboembolic disease or other pulmonary artery obstruction, and PH of unknown cause. 1 Echocardiography studies found that the prevalence of PH is 10.5%, including PH from left heart disease 78.7%, PH of lung disease and hypoxia 9.7%, PAH 4.2% and PH due to chronic thromboembolism 0.6% with average mortality in cases of PH are 4.5 to 12.3 per 100,000 population. 1 There are many pathophysiology mechanism involved in the cell and tissue level of PAH.The overall interaction of initiation and progression of the pathology process is not well understood.Hemodynamic changes of PAH patients are associated with complex pathophysiology and multifactorial pathobiology involving multiple biochemical pathways.Increased of pulmonary vascular resistance (PVR) is associated with vasoconstriction, proliferation, pulmonary vascular wall obstruction, inflammation, and thrombosis.This change involves endothelial cells, smooth muscle cells and adventitial resident cells. 4In adventitial layer, there is increase of extracellular matrix production including collagen, elastin, fibronectin and tenacillin. 1 Inflammatory cells and platelets (via serotonin pathway) also play a role in the pathophysiology of PAH. 1 They substantially decreased quality of life and experienced shortness of breath then decreased tolerance to physical activity or exercise.This condition occurs due to disruption of the gas exchange process associated with ventilation-perfusion mismatch as well as decreased pulmonary venous return flow resulting in decreased cardiac output. 4These result in hypoxia, decreased oxygen delivery to muscle, decreased maximal oxygen consumption, anaerobic metabolism and ultimately increased ventilation. 4he patient complained of fatigue during activity since childhood and shortness of breath since 32 weeks of gestation.
There have been many studies of medical therapy on PAH, but there are also other studies suggest that cardiovascular rehabilitation and physical exercise program have the benefit of improving pulmonary vascular endothelial function, physical activity capacity and quality of life of PAH patients. 2ardiovascular rehabilitation programs are a set of efforts undertaken to improve the underlying cause of heart disease, the physical, mental and social conditions of patients or who have a risk of cardiovascular disease than perform secondary prevention.Its goals are restoring the patient with heart disease or risk factors for heart disease as soon as possible to an active and productive life, maintaining the patient's best condition, stop or slow the progression of cardiovascular disease process and reduce the risk of mortality and morbidity of heart disease. 3mplementation of cardiovascular rehabilitation program consists of 4 phases, they are phase I, phase II, phase III and phase IV.Phase I program is a rehabilitation program conducted to patients who are still hospitalized.In this phase, the rehabilitation program is conducted in inpatient room until the patient is discharge in order to overcome or reduce the negative effects of bed rest during hospitalization, reduce the anxiety or depression problems caused by the illness and the patient is able to perform basic activity daily life. 3The programs include education of the patient's condition, gradual mobilization, physiotherapy according to the patient's condition as well as evaluation of fitness level and stratification ability before discharge. 5n this case, during hospitalization, patients and family were educated about the patient's condition, gradual mobilization begins by sitting, walking around the bed and bathroom as well as around the treatment room.

Table 1. The result of home based exercise datasheet performed by patient and supervised by family member
The phase II program is a rehabilitation program for patients after returning home for secondary prevention, preparing the patient to return to work, perform optimal daily activities and make the exercise program safely and effectively for the patient. 5Training programs conducted in this phase include education and counseling for patients and family, controlling for patient risk factors, prescribing and implementing physical exercise programs, evaluating the ability or level of fitness of the patient, and occupational physiotherapy programs.The duration of exercise in phase II is 1-2 months in 12 practice sessions. 6In this case, after returning home, she was educated for home based exercise with prescription from the hospital.Evaluation was done within 30 days post discharge.
The phase III program is a further rehabilitation program after undergoing an evaluation of the Phase II program.Rehabilitation at this phase can be performed at cardiac and vascular rehabilitation centers or at home.This phase aims to continue the program to overcome disease progression, optimize physical exercise and continue healthy lifestyle independently.Programs in Phase III include counseling and education for patients and family, controlling risk factors for patients, measuring fitness and advanced physical exercise programs, outdoor exercise, functional level evaluation and further programs as well as advanced physiotherapy, occupational therapy and other necessary interventions.The duration of the Phase III is 1-3 months. 6In this case, a phase III rehabilitation program had not been evaluated yet.The phase IV program is a rehabilitation program conducted independently by the patient.This program can be done at home or in a community environment such as in a heart healthy club.The purpose of phase IV is to maintain the patient's health condition at the most optimal level.The length of the program is a lifetime of patients with regular fitness level evaluations every 6 to 12 months. 7In this case, the phase IV rehabilitation program had not been implemented yet.

Physical
exercise on cardiovascular rehabilitation program should consider the contraindications for physical exercise.These include unstable angina pectoris, systolic blood pressure ≥ 200 mmHg and diastolic ≥ 100 mmHg, decreased systolic blood pressure ≥20 mmHg from daily average blood pressure, moderate to severe aortic valve stenosis, uncontrolled ventricular heart rhythm disorders, uncontrolled tachycardia (heart rate ≥120 beats/minute), uncompensated congestive heart failure, total atrioventricular block without a pacemaker, acute pericarditis, acute myocarditis, new embolism, thrombophlebitis, ST depression ≥2 mm on resting ECG, and presence of limb problems that cause the patient can't perform physical exercise. 7PAH itself is not a contraindication for physical exercise.In this case, there was no contraindication to perform physical exercise.
Cardiovascular rehabilitation and physical exercise programs in PAH patients have positive effects, where these will lead to improve endothelial function, physical activity capacity and quality of life. 2 In addition, these reduce the oxidative stress that occurs in blood vessels through increased activity of endothelial nitric oxide synthesis which will benefit for pulmonary vascular. 2Evaluation of the rehabilitation program in PAH patients are significant increase of 6MWD test distance, improved patient quality of life, maximal work rate, maximum heart rate, peak VO 2 and VO 2 threshold and anaerobic work rate (calculated by gas exchange in patients). 2hese programs can be tolerated without reported incidents or adverse events. 2 In this case, there was a significant increase of 6MWD distance for 30 days of exercise without complications during and after exercise.
The prescription of physical exercise program in PAH patients use the principles of FITT (Frequency, Intensity, Time and Type), depend on the patient's abilities, specific limitations of underlying illness as well as the goal of physical exercise.Physical exercise in PAH patients can be started by warming up for 5-10 minutes with low-moderate intensity then ended by cooling down for 3-10 minutes.This warming up period is useful for warm-up exercises of muscles, increased muscle temperature, oxygen exchange and increased transmission of nerve impulses. 6he cooling down period to restore the condition of the body after physical exercise, as well as avoiding the risk of post-action bronchial spasms.Physical exercise in PAH patients can be done in frequency of 3-5 times per week, with the supervision of cardiovascular rehabilitation expert.Duration of initial physical exercise time in PAH patients is recommended for 30 minutes (range 20-60 minutes) with a gradual increase up to 60-90 minutes duration if the patient can tolerate exercise. 6he study by Newman and  Robbins (2006) showed that PAH patients who underwent 12-15 weeks of physical exercise program, the average 6MWD test distance were 439±82 meters. 8In this case, the average distance of 6MWD test was 400±82 meters during 30 days of physical exercise.The 6MWD test is considered a test that can be well tolerated by the patient.The American College of Chest Physicians (ACCP) recommends a serial assessment of the physical and functional capacity of PAH patients using the 6MWD test to assess severity of thedisease and response to therapy. 9The 6MWD test measures the distance that the patient can walk on a flat surface within 6 minutes.The test also assess the patient's functional capacity at the submaximal level. 10Based on several previous studies, the distance of the 6MWD test was considered as an appropriate predictor of patient mortality. 11xygen saturation assessment during the 6MWD test can use pulse oximetry and oxygen saturation during the 6MWD test can be used to determine the degree of hypoxemia in PAH patients during the activity.The desaturation conditions during the 6MWD test is considered as a better predictor factor for mortality.Paciocco et al. (2001) published that 10% reduction of oxygen saturation during the 6MWD test predicted a higher mortality rate. 12While other research stated that each 10% decrease of arterial oxygen saturation level during the 6MWD would increase26% of mortality risk.In this case, there was no oxygen saturation decrease>10% after exercise. 10ardio Pulmonary Exercise Test (CPET) tests can be safely used in patients with advanced respiratory diseases, including PAH, with some indications such as prognosis assessment, disability evaluation and monitoring response to therapy. 13The peak VO2 assessment during the CPET test is a gold standard in the assessment of PAH patients.In the CPET test, the patient will perform a training test using a static ergometer bicycle and the patient is asked to breathe through the mouthpiece.This test include assessment of the respiratory rate, VE, VO

Figure 2 .
Figure 2. Chest X-ray showed cardiomegaly with enlargement of right atrium and right ventricle, pulmonary hypertension and right lung partial infiltrate due to pneumonia.