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Predictors of Outcomes in Mild Pulmonary Hypertension
Quick Takes
- Patients referred to pulmonary hypertension (PH) programs who have a mean pulmonary artery pressure (mPAP) of 21–24 mm Hg or a pulmonary vascular resistance (PVR) of >2–≤3 WU have an increased mortality compared to those with normal hemodynamics.
- Mild elevation in mPAP (21–24 mm Hg) and PVR (>2–≤3 WU) are independently associated with higher mortality.
- These data support the changes made by the ESC/ERS 2022 guidelines in the definition of precapillary PH (mPAP >20 mm Hg and PVR >2 WU).
Study Questions:
What is the impact on prognosis of the 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) pulmonary hypertension (PH) guidelines on the new redefined hemodynamic threshold (mean pulmonary artery pressure [mPAP] >20 mm Hg and pulmonary vascular resistance [PVR] >2 Wood units [WU]) for the diagnosis of precapillary PH?
Methods:
EVIDENCE-PAH UK is a United Kingdom (UK) cohort national study that aims to phenotype and determine drivers of outcome in patients with mild elevations in PAP and PVR. All seven adult tertiary PH centers across the UK were included in this study. Data collected prospectively for the UK national audit between January 2009 and December 2017 were analyzed. Hemodynamic data collected in all patients included mPAP, cardiac output (CO), pulmonary arterial wedge pressure (PAWP), and PVR, calculated as mPAP–PAWP/CO (with thermodilution values used for CO, where possible). Data obtained from NHS Digital and the UK Office for National Statistics provided mortality data.
Results:
The median age of the population was 65 (interquartile range, 53–73) years. A total of 2,929 patients were included in the study, with 968 patients (33%) in the mPAP <21 mm Hg group, 689 patients (23.5%) in the mPAP 21–24 mm Hg group, and 1,272 (43.4%) in the mPAP ≥25 mm Hg group. In the mPAP 21–24 mm Hg group, 68.2% (n = 437) had comorbid lung and/or left heart disease, compared to 51.4% (n = 466) in the mPAP <21 mm Hg group and 78.8% (n = 975) in the stratified mPAP ≥25 mm Hg group. Connective tissue disease (CTD) was present in 37.4%, 35.3%, and 29.6% in the three mPAP groups, respectively.
During the observation period (median of 6.1 years), there were 1,383 deaths (47.2%): 30.8% of the mPAP <21 mm Hg group, 43.3% of the mPAP 21–24 mm Hg group, and 61.8% of the mPAP ≥25 mm Hg group. On multivariable regression models, the excess mortality in the mPAP 21-24 mm Hg and >25 mm Hg groups remained significant when compared to the mPAP <21 mm Hg group, after adjustment of lung disease, left heart disease, CTD, age, and gender.
When analyzing PVR, 1,253 (42.8%) had a PVR ≤2 WU, 735 (25.1%) had a PVR >2–≤3 WU, and 941 (32.1%) had a PVR >3 WU. A stepwise worsening of unadjusted survival with each increase in PVR group (PVR ≤2 WU, PVR >2–≤3 WU and PVR > 3 WU) was noted. Excess mortality (compared to PVR ≤2 WU) remained significant for PVR >2–≤3 WU, and PVR >3 WU, when individually adjusted for lung disease, left heart disease and CTD, age, and gender.
When focusing on the mPAP 21–24 mm Hg population, 315 patients (45.7%) had a PVR ≤2 WU, 231 patients (33.5%) had a PVR >2–≤3 WU, and 143 patients (20.8%) had a PVR >3 WU. The Kaplan–Meier curves reveal that a PVR >2–≤3 WU confers higher mortality compared to a PVR of ≤2 WU, but lower than among patients with a PVR >3 WU.
Conclusions:
Patients referred for PH evaluation who have an mPAP 21-24 mm Hg or a PVR >2–≤3 WU have an increased mortality compared to those with normal hemodynamics.
Perspective:
Recently, the 2022 ESC/ERS PH guidelines redefined the hemodynamics threshold for the diagnosis of precapillary PH to mPAP >20 mm Hg and PVR >2 WU. The proposed change is based on the observation that mPAP and PVR rarely exceed 20 mm Hg and 2 WU, respectively, in healthy individuals. The initial definition of PH (mPAP ≥25 mm Hg) was considered to be arbitrary, made by expert opinion and not based on clinical data. The 2015 ESC/ERS guidelines added PVR >3 WU and PAWP ≤15 mm Hg, for the diagnosis of precapillary PH and the 6th World Symposium on PH proposed defining precapillary PH an mPAP >20 mm Hg, PAWP ≤15 mm Hg, and PVR ≥3 WU.
Karia et al. provide convincing data that even mild elevations in mPA and PVR significantly affect survival and support the lower threshold for defining precapillary PH implemented by the 2022 ESC/ERS PH guidelines. A previous US Veterans Affairs Health System–based study (Maron BA, et al., J Am Heart Assoc 2018;7e009729) highlighted the continuum of clinical risk for mortality with PVR >2.2 WU even in the presence of mild PH. This study had a significant male bias (96.7%) and with a high proportion of left heart disease and parenchymal lung disease.
Karia and colleagues provide additional supporting evidence that in a more traditional PH referral population with a female prevalence (65.8%) and less significant comorbidities (37.2% left heart disease, 45.3% lung disease, CTD 33.5%), an mPAP >20 mm Hg and a PVR >2 WU are strongly associated with mortality, despite multiple variable adjustments.
The evidence that even mild hemodynamic derangements are associated with worse clinical outcomes raises the very important question of whether current PH-specific medical therapy can be beneficial in this population. Unfortunately, there are no firm data supporting this concept at this point. Further clinical research will be important in understanding how outcomes can be improved in this patient population.
Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Pulmonary Hypertension, Hypertension
Keywords: Hypertension, Pulmonary
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