Catheter-based Renal Denervation as a Treatment for Pulmonary Hypertension: Hope or Hype?

Abstract

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance (PVR) that causes right ventricular (RV) failure and premature death. This hypertensive condition leads to precapillary pulmonary hypertension, defined as a mean pulmonary artery pressure (mPAP) 25 mmHg, pulmonary capillary wedge pressure 15 mmHg, and PVR > 3 Wood units at rest. The prevalence of PAH is estimated to range from 15 to 50 patients/million, with a female predominance (men:women, 1:2) and 1-year and 5-year survival rates of 85% and 57%, respectively. During the last 15 years, treatments for PAH have been studied in multiple clinical trials, with approval subsequently granted for 9 distinct drugs belonging to 4 pharmacological families: prostanoids (epoprostenol, iloprost, treprostinil), endothelin receptor antagonists (bosentan, ambrisentan, macitentan), phosphodiesterase-5 inhibitors (sildenafil, tadalafil), and adenylate cyclase stimulators (riociguat). Despite these therapeutic advances, many patients with PAH show disabling symptoms and an ominous prognosis, underscoring the need for new therapeutic strategies to combat PAH. The pathophysiology of PAH involves excessive vasoconstriction and vascular remodeling. The increased PVR is initially reversible and is due to an imbalance between vasodilatory and vasoconstrictive agents, but can become permanent in later stages. The vascular remodeling is characterized by intimal thickening and fibrosis and the proliferation and migration of vascular smooth muscle cells, with hypertrophy and fibrosis of the tunica media, inflammation, and in situ thrombosis, which trigger the formation of plexiform and obstructive lesions (the most characteristic finding of PAH), all of which lead to RV remodeling. Given our poor understanding of the pathophysiology of PAH, the development of new preclinical models of PAH and their evaluation using appropriate imaging techniques are essential to further our understanding of PAH.