A dynamical model for heart remodeling during the two phases of pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension is a rare and lethal disease affecting small diameter pulmonary arteries and leading to a progressive increase of the right vascular resistances. Patients with such a disease have no specific symptom, a feature which delays the diagnosis by 18 months to 2 years in average. In most cases, pulmonary arterial hypertension is diagnosed when the cardiac output is already reduced, inevitably leading to death when the disease is not efficiently treated. During the evolution of the disease, the right ventricle is clearly affected in two different ways: first the thickness of its walls increases (compensation) and second the ventricle inflates (decompensation). The latter phase remained unexplained. We developed a dynamical model of the cardiovascular system in order to explain such a feature by regulation mechanisms. Since pulmonary arterial hypertension is a slowly evolving pathology, we took into account long-term regulation mechanisms as the myocardial development (muscular heart development); we only considered the heart rate variations among the short-term regulation mechanisms. Using a static model, we showed that the two phases observed during the evolution of pulmonary arterial hypertension can be explained by the interplay between the right and left ventricles. We then showed that our dynamical model can reproduce the heart remodeling during these two phases (compensation and decompensation of the right ventricle). After the compensation phase, the right ventricle can no longer maintain the cardiac output without the help of the left ventricle, which produces a part of the required work with the side effect of inflating the right ventricle. By taking into account slow regulation mechanisms, the cardiac remodeling during pulmonary arterial hypertension was reproduced. We thus showed that the two phases observed during the increase in the pulmonary arterial resistance result from an interplay between the left and right ventricles.