Mechanisms and Advances in the Treatment of Arrhythmias Associated With Pulmonary Hypertension.

Arrhythmias related to pulmonary hypertension (PH) are major complications of disease progression and are associated with a significantly increased risk of death. The pathophysiology of these arrhythmias involves complex, multifaceted mechanisms. Arrhythmic substrates include electrical remodeling (ion channel imbalance, gap junction protein connexin 43 (Cx43) dysfunction, and autonomic neuropathy), structural remodeling (right ventricular hypertrophy/fibrosis), metabolic disorders (mitochondrial dysfunction and the Warburg effect), and chronic inflammation. Clinically, PH-related atrial arrhythmias, particularly atrial fibrillation (AF)/flutter (AFL), are the most common. Diagnosis often requires combining ambulatory electrocardiography and implantable cardiac monitoring to detect subclinical events. Current treatment methods include optimizing PH-targeted therapy (e.g., dual- or triple-targeted drug therapy, soluble guanylate cyclase (sGC) stimulators), antiarrhythmic drugs, and catheter ablation, as well as emerging therapies such as Cx43 modulators, gene therapy (targeting bone morphogenetic protein receptor type 2 (BMPR2)/switch-independent 3A (SIN3A)), and microRNA (miRNA)-based regulation. Future work should focus on elucidating underlying mechanisms, developing precise risk stratification models, and formulating targeted individualized intervention strategies.