Mortality rates and cause of mortality in patients with mildly elevated pulmonary pressures versus PH: insights from the retrospective EVIDENCE-PAH study
Authors: Karia N , Howard L , Johnson M , Kiely D , Lordan J , McCabe C , Ong R , Pepke-Zaba J , Preiss M , Muthurangu V , Coghlan G 
Published: October 2022

Abstract

Background
Normal mean pulmonary artery pressure (mPAP) does not exceed 20 mmHg and normal pulmonary vascular resistance (PVR) does not exceed 2 Wood Units (WU). The thresholds used to define pre-capillary pulmonary hypertension (PH) – mPAP ≥25 mmHg and PVR &gt;3 WU – are being evaluated. It is unclear if treatment would benefit patients with mildly elevated mPAP (≥21–&lt;25 mmHg).

Purpose
The EVIDENCE-PAH study aims to describe mortality and hospitalisation outcomes, clinical characteristics, therapies, and quality of life during long-term follow-up of a national cohort of patients with different levels of mPAP and PVR. We report preliminary analyses focusing on mortality and its cause in patients stratified by their baseline (BL) mPAP.

Methods
This retrospective analysis included PAH-treatment-naïve patients with suspected PH who received a first right heart catheterisation (RHC) between 2009 and 2017 at any of the 7 UK tertiary PH centres, which assess all PH patients in the UK. A sample of patients with BL mPAP ≥25 mmHg (stratified by PVR and treatable versus non-treatable PH) was used as a control in this analysis. Baseline characteristics, mortality and cause of mortality were stratified by mPAP (&lt;21, ≥21–&lt;25, ≥25 mmHg) at BL (first RHC). Mortality was also stratified by BL PVR (&lt;1, 1–&lt;2, 2–&lt;3, 3–&lt;6, ≥6 WU). Mortality analysis was done without matching cohorts. Mortality data were obtained from the Office for National Statistics, NHS Digital.

Results
In total, 2926 patients were analysed (968, 689 and 1269 with mPAP &lt;21, ≥21–&lt;25, ≥25 mmHg, respectively). Mean observation was 6.1 years. BL characteristics are in Table. Survival worsened with increasing mPAP (p&lt;0.0001) and increasing PVR (p&lt;0.01) (Figure). After 5 years of follow-up, 187 (27.1%) patients with mPAP ≥21–&lt;25 mmHg had died, compared with 162 (16.7%) and 595 (46.9%) patients in the lower and higher mPAP groups, respectively. In patients with mPAP ≥21–&lt;25 mmHg, the most common main cause of death was respiratory disease (36.4%) – with scleroderma lung disease and interstitial lung disease accounting for 69.1% of these deaths – followed by cardiac disease (16.6%) and malignancy (15.0%) (Table). PH was the main cause of death for only 1.6% of patients with mildly elevated mPAP and it was a contributor to death in 6.8% (BL mPAP &lt;21 mmHg), 10.2% (≥21–&lt;25 mmHg), and 40.2% (≥25 mmHg) of cases.

Conclusion
Long-term survival in patients with mPAP ≥21–&lt;25 mmHg was worse than in those with normal mPAP, and better than in those with the current definition of PH. While the main cause of death was mostly unrelated to PH and further analysis is needed to understand the impact of underlying disease, mildly elevated mPAP appears to confer a worse prognosis and should be closely monitored. These data show the relevant disease burden in patients with mPAP ≥21–&lt;25 mmHg and the need to understand if they could benefit from treatment. PVR may be key in determining patients who might benefit.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson & Johnson.