Targeting neurohumoral signaling to treat pulmonary hypertension: the right ventricle coming into focus.

Adverse remodeling of the right ventricle (RV) that affects RV systolic or diastolic function directly or indirectly by modulating changes to cavitary geometry is a principal determinant of poor outcome across the global spectrum of cardiopulmonary diseases.1,2 Indeed, even subclinical increases in RV mass are associated with substantially elevated risk for future heart failure and decreased lifespan.3 Unique embryological and anatomic features of the RV provide a pathophysiological basis by which to account for this observation. For example, precursor cells of the RV and left ventricle (LV) derive from the primary and anterior heart fields,4 respectively, indicating a different cellular lineage for each ventricle despite their close proximity and placement in series. In contrast to the LV, the RV is a triangular structure that is thin walled and noncompacted, and, thus, tolerates pressure-loading conditions poorly.5 Moreover, poor coronary blood flow reserve with increased RV strain due to elevations in wall tension is associated with decreased RV microvascular perfusion.6