Right ventricular fibrosis: A pathophysiological factor in pulmonary hypertension?

S Andersen, JE Nielsen-Kudsk, A Vonk Noordegraaf… - Circulation, 2019 - Am Heart Assoc
S Andersen, JE Nielsen-Kudsk, A Vonk Noordegraaf, FS de Man
Circulation, 2019Am Heart Assoc
The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject
of ongoing discussion. Alterations of the collagen network of the extracellular matrix may
help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis
impairs cardiac function, and a growing body of experimental data suggests that fibrosis
plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial
hypertension and chronic thromboembolic PH, the RV is exposed to a≈ 5 times increased …
The role of right ventricular (RV) fibrosis in pulmonary hypertension (PH) remains a subject of ongoing discussion. Alterations of the collagen network of the extracellular matrix may help prevent ventricular dilatation in the pressure-overloaded RV. At the same time, fibrosis impairs cardiac function, and a growing body of experimental data suggests that fibrosis plays a crucial role in the development of RV failure. In idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, the RV is exposed to a ≈5 times increased afterload, which makes these conditions excellent models for studying the impact of pressure overload on RV structure. With this review, we present clinical evidence of RV fibrosis in idiopathic pulmonary arterial hypertension and chronic thromboembolic PH, explore the correlation between fibrosis and RV function, and discuss the clinical relevance of RV fibrosis in patients with PH. We postulate that RV fibrosis has a dual role in patients with pressure-overloaded RVs of idiopathic pulmonary arterial hypertension and chronic thromboembolic PH: as part of an adaptive response to prevent cardiomyocyte overstretch and to maintain RV shape for optimal function, and as part of a maladaptive response that increases diastolic stiffness, perturbs cardiomyocyte excitation-contraction coupling, and disrupts the coordination of myocardial contraction. Finally, we discuss potential novel therapeutic strategies and describe more sensitive techniques to quantify RV fibrosis, which may be used to clarify the causal relation between RV fibrosis and RV function in future research.
Am Heart Assoc