Fabry disease patients struggle with physical exercise — measured by a cardiopulmonary exercise test — due to an impairment in cardiac function as a direct consequence of Fabry-associated heart disease, a study shows.
The study, “Cardiopulmonary fitness assessment on maximal and submaximal exercise testing in patients with Fabry disease,” was published in the American Journal of Medical Genetics.
Fabry disease is a a rare genetic disorder caused by mutations in the GLA gene — located on the X chromosome — that provides instructions for the production of an enzyme called alpha-galactosidase A (GLA). These mutations typically affect the function of GLA, leading to the accumulation of a type of fat called globotriaosylceramide (Gb3) in several organs, including the heart and kidneys.
Fabry patients have difficulties with physical exercise and, depending on disease severity and cardiac function impairment, rapidly experience fatigue.
The cardiopulmonary exercise test (CPET) is a method designed to evaluate patients’ aerobic fitness (the body’s ability to use oxygen as an energy source to fuel metabolism), cardiac function, and heart response to physical strain. However, very few studies have used CPET to assess cardiopulmonary exercise capacity in this patient population.
In this retrospective study, researchers reviewed and compared clinical data from Fabry patients obtained between 2001 and 2016, to age- and gender-matched healthy control individuals.
The study enrolled 29 Fabry patients and 29 healthy control subjects who were evaluated using two different CPET protocols: the Bruce protocol, involving treadmill exercise (18 Fabry patients and 18 controls); and the ramp protocol, involving cycling exercise (11 Fabry patients and 11 controls).
Results showed that Fabry patients had a significantly lower heart rate at peak exercise (151.2 vs. 178.6), maximal oxygen consumption (23.7 vs. 33.9) and peak oxygen pulse (volume of blood pumped by the heart, 12.1 vs. 15.2), compared with healthy controls. These statistically significant differences were maintained in all parameters comparing Fabry patients to control subjects who had been included in the same exercise protocol.
In addition, when researchers looked more closely at patients who were also assessed using cardiac magnetic resonance imaging — an imaging method that depicts the structures within and around the heart — they found a positive correlation between maximal oxygen consumption and the volume of blood in the right heart ventricle after relaxation, called diastole, and after a contraction, or systole, indicating a possible link between heart disease and exercise performance in Fabry patients.
“Additional research should be performed to further delineate the precise mechanism for exercise intolerance in these patients as well as to determine if the exercise intolerance is correctable with either pharmacotherapy or cardiopulmonary conditioning and rehabilitation,” the researchers concluded.