Muscle strengthening may complement PAH therapies
Study finds persistent exercise intolerance linked with impaired muscle function
Persistent exercise intolerance in pulmonary arterial hypertension (PAH) patients with treatment-related improvements in blood pressure was associated with impaired muscle function and strength, a study revealed.
Because many of the study’s participants have lived with PAH for many years, muscle function may have been compromised, the researchers noted.
Interventions that target muscle function and strength may improve exercise abilities in treatment-responsive PAH patients, they suggested in “Exercise Capacity and Ventilatory Efficiency in Patients With Pulmonary Arterial Hypertension,” which was published in the Journal of the American Heart Association.
In PAH, narrowing of blood vessels that pass through the lungs, called the pulmonary arteries, elevates blood pressure, making it harder for the heart to pump blood.
One of the earliest PAH symptoms is shortness of breath on exertion, leading to exercise intolerance — a reduced ability to perform strenuous activities.
PAH‐specific therapies, designed to widen blood vessels, improve blood flow and lower blood pressure, have extended survival in people with the disease. But exercise intolerance persists in many cases despite treatment-related improvements in blood flow (hemodynamic) measurements.
To understand what contributes to exercise intolerance in treatment-responsive PAH, researchers in Japan assessed patients with near-normal pulmonary blood pressure at rest. Among the 82 participants, ages 39-51, 59 (72%) were women and 16 (20%) needed oxygen therapy to engage in activities. The time from a diagnosis to the study’s exercise test ranged from four to 12 years.
Factors affecting exercise with PAH
Cardiopulmonary exercise testing without supplemental oxygen involved a cycling machine while lying down with the patient’s legs elevated. A three-minute rest period was followed by a three-minute warmup, then with increased exercise difficulty until symptom-limiting peak levels were reached. The six-minute walking test (6MWD), or the distance walked in six minutes, and upper leg muscle (quadricep) strength were also measured.
Arterial blood pressure was recorded, as well as oxygen consumption, carbon dioxide output, minute ventilation — the amount of air that enters the lungs per minute — and cardiac output, an indicator of heart function.
From these data, the arterial mixed venous oxygen content difference (C(a‐v)O2) was calculated. It’s defined as the difference in blood oxygen levels between the arteries and veins. It estimated how much oxygen the muscles removed from the blood to fuel the exercise. Higher C(a‐v)O2 values during peak exercise were best able to predict a longer six-minute walking distance, adjusted statistical analysis showed.
“6MWD performance was strongly associated with muscular O2 extraction,” the researchers said.
During peak exercise, higher oxygen consumption was best predicted by a higher peak cardiac output and peak C(a‐v)O2 values.
Lower mean blood pressure in the pulmonary arteries while resting was associated with higher peak oxygen consumption. Lower blood pressure was also linked to a more downward slope (ratio) of minute ventilation versus carbon dioxide output (VE/VCO2), a measure of breathing efficiency. Here, lower VE/VCO2 values indicated better heart-lung function (more CO2 release per breath).
Stronger upper leg muscles significantly correlated with higher C(a‐v)O2 values (more muscular O2 uptake), elevated oxygen consumption during peak exercise, and a longer six-minute walking distance. Muscle strength was also linked to lower VE/VCO2 (better breathing efficiency) and resting pulmonary arterial blood pressure.
“The present study demonstrated that peripheral factors, including O2 extraction and muscle strength, could be the chief determinants of exercise capacity, even in low‐risk patients with hemodynamically normalized PAH,” the researchers wrote. “Many cases in our study had a long disease duration; therefore, peripheral functions may have become more damaged throughout the disease course.”