Mortality trends in pulmonary arterial hypertension in Canada: a temporal analysis of survival per ESC/ERS guideline era.

BACKGROUND: The evolution in pulmonary arterial hypertension (PAH) management has been summarised in three iterations of the European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines. No study has assessed whether changes in management, as reflected in the changing guidelines, has translated to improved long-term survival in PAH. METHODS: We performed a mixed retrospective/prospective analysis of treatment-naïve, incident PAH patients (n=392) diagnosed at three major centres in Canada from 2009 to 2021. Patients were divided into two groups based on their diagnosis date and in accordance with the 2009 and 2015 ESC/ERS guideline iterations. Overall survival was assessed based on date of diagnosis and initial treatment strategy (i.e. monotherapy versus combination therapy). RESULTS: There was a shift towards more aggressive upfront management with combination therapy in Canada after the publication of the 2015 ESC/ERS guidelines (10.4% and 30.8% in patients from 2009 to 2015 and 36.0% and 57.4% in patients diagnosed after 2015 for baseline and 2-year follow-up, respectively). A key factor associated with combination therapy after 2015 was higher pulmonary vascular resistance (p=0.009). The 1-, 3- and 5-year survival rates in Canada were 89.2%, 75.6% and 56.0%, respectively. Despite changes in management, there was no improvement in long-term survival before and after publication of the 2015 ESC/ERS guidelines (p=0.53). CONCLUSIONS: There was an increase in the use of initial and sequential combination therapy in Canada after publication of the 2015 ESC/ERS guidelines, which was not associated with improved long-term survival. These data highlight the continued difficulties of managing this aggressive pulmonary disease in an era without a cure.

Incorporation of renal function in mortality risk assessment for pulmonary arterial hypertension.

BACKGROUND: Risk assessment is important for prognostication and individualized treatment decisions for patients with pulmonary arterial hypertension (PAH). The purpose was (1) to compare contemporary risk assessment tools and (2) to determine the prognostic significance of risk parameters of kidney function and whether they can further improve risk prediction for patients with PAH. METHODS: We identified a cohort of treatment-naive patients (n = 211) who received an incident diagnosis of PAH at the University of Ottawa Heart Institute. Using demographics, disease characteristics, and hemodynamic data at diagnosis, we categorized patients as low, intermediate, or high risk according to current European guidelines (European Society of Cardiology [ESC]) and registry to evaluate early and long-term pulmonary arterial hypertension disease management (REVEAL) risk scores. The primary end-point was transplant-free survival (TFS). RESULTS: Patients were predominantly women (64.6%) with World Health Organization function Class III symptoms (66.5%). The median TFS was 7.09 years. There was little agreement between ESC- and REVEAL-based risk estimates (weighted kappa = 0.21-0.34). Although both the ESC (log-rank, p = 0.0002) and REVEAL algorithms stratified TFS risk (p < 0.0001), the REVEAL score provided superior discrimination (C-statistic = 0.70 vs 0.59, p = 0.004). Renal function at diagnosis (p < 0.0001) and Δ renal function at 6 months (p < 0.0001) were identified as novel risk parameters and served to reclassify some patients in the intermediate-risk category to a lower or higher risk stratum (p < 0.0001). CONCLUSION: REVEAL-based strategies provide superior TFS risk discrimination to ESC/European Respiratory Society-based approaches. However, the classification of intermediate-risk patients varied significantly across tools. We demonstrate the importance of renal function, which further improved the stratification of risk in patients with PAH, particularly in patients who are considered intermediate risk.