Pulmonary Hypertension in Left Heart Diseases: Pathophysiology, Hemodynamic Assessment and Therapeutic Management

Abstract

Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive backward transmission of elevated left heart pressures in the setting of heart failure, either with preserved (HFpEF) or reduced (HFrEF) ejection fraction, which increases the pulsatile afterload of the right ventricle (RV) by reducing pulmonary artery (PA) compliance. In a subset of patients, progressive remodeling of the pulmonary circulation resulted in a pre-capillary phenotype of PH, with elevated pulmonary vascular resistance (PVR) further increasing the RV afterload, eventually leading to RV-PA uncoupling and RV failure. The primary therapeutic objective in PH-LHD is to reduce left-sided pressures through the appropriate use of diuretics and guideline-directed medical therapies for heart failure. When pulmonary vascular remodeling is established, targeted therapies aiming to reduce PVR are theoretically appealing. So far, such targeted therapies have mostly failed to show significant positive effects in patients with PH-LHD, in contrast to their proven efficacy in other forms of pre-capillary PH. Whether such therapies may benefit some specific subgroups of patients (HFrEF, HFpEF) with specific hemodynamic phenotypes (post- or pre-capillary PH) and various degrees of RV dysfunction still needs to be addressed.

Left heart disease in pulmonary hypertension

“…In the CHAMPION study, an implantable sensor called CardioMEMS™ was used and provided for the funding [10]. The study enrolled patients with symptomatic heart failure irrespective of left ventricular ejection fraction in 64 centers across the USA.…”

“…The REDUCE LAP-HF II trial was a prospective randomized controlled trial with an intervention group treated with an interatrial shunt device. [10] 626 patients with heart failure with preserved ejection fraction with isolated post-capillary pulmonary hypertension were treated with the device or placebo for up to 24 months. The study showed no significant effects of the device on the primary composite outcomes, which included cardiovascular deaths.…”

Pressure Overload and Right Ventricular Failure: From Pathophysiology to Treatment

“…They must therefore be aggressively countered. In cases of bi-ventricular failure, diuretics should also aim at reducing left atrial pressure in order to decrease RV pulsatile load [88,89].…”