The Interplay Between Pulmonary Hypertension and Atrial Fibrillation: A Comprehensive Overview

Pulmonary hypertension (PH) is a progressive lung disease characterized by abnormal pulmonary vascular pressure and right ventricular (RV) dysfunction. Atrial arrhythmias, including atrial fibrillation (AF) and atrial flutter, are common in patients with PH and significantly contribute to disease progression and mortality. A bidirectional pathophysiological link exists between PH and AF, encompassing shared mechanisms such as endothelial dysfunction, DNA damage, autophagy, inflammation, and oxidative stress, as well as mutual risk factors, including diabetes, obesity, heart disease, and aging. Despite these shared pathways, limited research has been conducted to fully understand the intertwined relationship between PH and AF, hindering the development of effective treatments. In this review, we provide a comprehensive overview of the epidemiology of PH, the molecular mechanisms underlying the development of AF in PH, and the overlap in their pathophysiology. We also identify novel druggable targets and propose mechanism-based therapeutic approaches to treat this specific patient group. By shedding light on the molecular connection between PH and AF, this review aims to fuel the design and validation of innovative treatments to address this challenging comorbidity.