Introduction
Efficacy of medical treatment in pulmonary hypertension has traditionally been evaluated using the 6-Minute Walk Test (6MWT). The 6-Minute Walk Distance (6MWD) gives a measure of the exercise tolerance of a PH patient and correlates with the mean number of daily steps and duration of physical activities.
Due to the limited physical capabilities of PH patients and an increased risk of adverse cardiopulmonary events with exercise, the use of exercise regimens to improve exercise capacity and tolerance has only recently been attempted. Early clinical recommendations against exercise testing and activity in PAH patients was based on concerns that the risk of adverse cardiopulmonary events outweighed the potential benefits given by exercise training. The concern that there would be more risk than benefit was thought to result from exercise-induced increases in blood flow through a restricted and presumably noncompliant pulmonary vascular bed, leading to possible ischemic events in non-pulmonary organ systems.
Rationale for Cardiopulmonary Exercise as a Rehabilitative Measure in PH
In spite of advances in medical care for PAH, patients often still demonstrate progressive deterioration in exercise tolerance. Results from cardiopulmonary exercise testing in PAH patients show similar abnormalities to those seen in patients with severe heart failure, including reduced maximal O2 uptake, early anaerobic threshold onset, and increased ventilation.
The ability to distend pulmonary arteries and decrease pulmonary vascular resistance (PVR) during exercise (to increase pulmonary blood flow and cardiac output to match increased metabolic demand and O2 delivery to tissues) is lost in PAH patients due to impaired vasodilation and effective reduction in the size of the pulmonary vascular bed. Beneficial effects of exercise training and rehabilitation are established for other chronic cardiopulmonary disease states wherein patients report deficiencies in exercise tolerance; similar to that seen in pulmonary hypertension.
In other cardiopulmonary disease states, aerobic exercise, resistance training, and training of the muscles of respiration (esp. inspiration) all act to improve the overall physiological function of the pulmonary, cardiac and skeletal muscle. Meta-analyses have described positive effects of cardiac rehabilitation in patients with systolic heart failure; improvements in tolerance of exercise, endurance, and quality-of-life have been observed.
Efficacy and Safety of Exercise-Based Pulmonary Rehabilitation
A pivotal randomized, controlled study published in 2006 by Mereles et al. studied the efficacy and safety of respiratory and exercise training in patients with severe chronic PH who were stable using optimized usual therapy (ERAs, prostacyclins, sildenafil, CCBs, diuretics, anticoagulants, and O2). Patients included were WHO functional class II to IV (without recent syncope or skeletal/muscle abnormalities). The study was 15 weeks duration, and the primary endpoint of the study was change from baseline to week 15 in 6MWD and change in QoL via questionnaire. Secondary endpoints included changes in WHO functional classification and various hemodynamic and echocardiographic parameters.
Intervention: For the first 3 weeks of the study patients remained in the hospital; the remaining 12 weeks of the study were conducted at home. Control group patients received standard rehabilitation therapy (nutrition, physical therapy, counseling, and muscular relaxation therapy). Patients in the primary training group participated in an exercise program 7 days weekly at low workloads supervised by physical therapists and physicians. Training involved interval bicycle training titrated to participant tolerability and improvement. Additionally, 60 minutes of walking was performed 5 days weekly (flat ground and uphill).Strength training was also performed 5 days per week using dumbbells, along with 30 min of respiratory training (stretching, breathing techniques, yoga, etc.).
Results: 30 patients were included in the study.
6MWD-After 3 weeks of treatment, the 6-minute walking distance increase was significantly larger in the primary training group (85+/-56 m) than in the control group (12+/-37 m; p=0.0003; Figure 1). After 15 weeks of treatment, the distance walked in 6 minutes decreased in the control group (-15+/-54 m), whereas patients in the primary training group revealed a further improvement (96+/-61 m; P<0.0001; Figure 1); the mean difference between groups was 111 m (95% CI, 65 to 139; P<0.001).
*P=0.0003 for primary training vs. control group after 3 weeks of training;
**P<0.0001 for primary training vs. control group after 15 weeks of training.
Figure reproduced from Mereles et al. Circulation 2006;114:1482-1489.
Quality of Life – At baseline, all 30 patients had significantly compromised quality-of-life scores compared with the general population and showed a >40% score reduction in the 2 summation scores (the physical and mental component scales) and in 3 of 8 SF-36 scales. Exercise and respiratory training significantly
improved the physical (p=0.013) and mental (p=0.027) component scale summation scores and the subscale scores for physical functioning (p=0.018), role-physical (p=0.003), social functioning (p=0.002), mental health (p=0.017), and vitality (p=0.001) compared with the control group, in which these parameters remained virtually unchanged. In the primary training group, the largest increase occurred in the score for physical functioning and vitality. No significant changes occurred in the subscales of role functioning emotional, bodily pain, and general health perception.
Hemodynamics and Gas Exchange – Hemodynamic parameters did not change significantly within the groups during the study period. PASP values at rest and during exercise, however, were significantly lower after 3 and 15 weeks of exercise and respiratory training compared with the values of the control group. Peak oxygen consumption, peak oxygen consumption in percent of the predicted value, oxygen consumption at the anaerobic threshold, and the achieved workload at the anaerobic threshold significantly improved.
Safety: All patients tolerated exercise training, and there were no progression of symptoms in the training groups. Two patients experienced dizziness without fainting following bicycle training, and one patient had a drop in O2 saturation during exercise, despite wearing an oxygen mask.
Conclusions: Low-dose exercise and respiratory training significantly improved exercise capacity, 6-minute walking test, quality of life, WHO functional class, and peak oxygen consumption. Thus, the exercise and respiratory training program shows promise as a safe and powerful potential adjunct therapy
in patients with advanced PH.
Treatment effect on 6MWD was higher than has been observed with medications for PAH. Exercise training in PAH patients also provides significant benefits to patients’ psychological perspectives. Although it is possible that, due to small sample size, important safety concerns were not brought out, the results suggest
that respiratory and exercise training may potentially add to optimized medical therapy.
Approaches to Exercise Training in Patients with Pulmonary Hypertension
- Exercise training for PAH patients should be performed under close monitoring and supervision by qualified staff and with necessary safety equipment at hand.
- Aerobic exercise training relies on rhythmic and continuous large muscle group movement.
- Defining optimal intensity of exercise is not a precise process but proposed intensities should be between 40% and 85% of a patient’s maximal aerobic capacity.
- Setting training intensity at the point of ventilatory threshold may help optimize physiologic adaptation to the exercise.
- Patients, who have a sedentary lifestyle due to PAH, ILD, or COPD may be seriously de-conditioned and thus the initiation of a training program at the above level is not realistic, but can be attained.
- Current evidence supports initiation of programs 3-5 times per week.
- Attainment of the above stated levels of exercise should be undertaken as a long-term goal.
- The ideal aerobic exercises should be tailored to the individual patient’s capabilities and progressed as appropriate.
- Various modes of exercise may lend themselves to achievement of these training goals, such as walking, biking, and elliptical training, with patient preferences determining the best exercise mode.
- Inspiratory muscle training and resistance training should also not be ignored if undertaken with appropriate supervision.
- Several recent analyses suggest that multidisciplinary exercise programs may provide significant benefit.
Conclusions
PAH patients, particularly those in higher WHO functional classes, exhibit significant impairment in aerobic and functional capacities. Aerobic and resistance training can produce numerous and significant clinical benefits, such as increased physical capacity for exertion and improved quality of life. Current opinion suggests that such training programs be considered as a standard of care for PAH patients, provided they are managed under appropriate supervision to ensure patient safety.
If, when undertaking exercise programs with PAH, a patient experiences syncope, chest pain, hypotension or cardiac arrhythmias, such exercise programs should be discontinued and professionally reevaluated. Training programs should be performed under close monitoring and supervision by qualified staff and with appropriate safety equipment always on hand.
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