Background: Group 2 pulmonary hypertension (PH), defined as PH caused due to left heart disease, remains a challenging condition. However, its prognostic impact and implications for emerging therapies are unclear. We aimed to evaluate the real-world relationship between pulmonary vascular resistance (PVR) and prognosis in Group 2 PH and assess the efficacy of emerging therapies.
Methods: Two prospective registries supported by Japanese PH societies were analyzed: a current (2018-2024; n=563) and a previous (2012-2016; n=425) registry. The composite end points were hospitalization for heart failure, all-cause death, ventricular assist device implantation, or cardiac transplantation.
Results: Stratified analyses using propensity score-matched data demonstrated a significant association between PVR >3 Wood units and prognosis in patients with Group 2 PH (6-year event-free rates, PVR >3 Wood units versus PVR ≦3 Wood units, previous registry: 72.9% versus 61.4%; current registry: 75.2% versus 55.4%). Consistent patterns were observed in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction subgroups. The use of SGLT2 (sodium-glucose cotransporter-2) inhibitors in the current registry was associated with improved outcomes in patients with elevated PVR, showing event-free rates of 73.8% versus 35.5% in those without treatment. Among multivariate analyses including major treatment options, SGLT2 inhibitor treatment exhibited significant associations with improvement of composite end points.
Conclusions: Elevated PVR (>3 Wood units) identified a high-risk subset of patients with Group 2 PH. The association between the use of SGLT2 inhibitors and better outcomes suggests a potential therapeutic role that warrants further investigation through controlled studies.
Keywords: SGLT2 inhibitors; ejection fraction; pulmonary hypertension; pulmonary vascular remodeling; pulmonary vascular resistance.