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Selected Publication:
Douschan, P.
Clinical relevance of mildly elevated pulmonary arterial pressure
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2019. pp. 93
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- Authors Med Uni Graz:
- Advisor:
- Kovacs Gabor
- Olschewski Horst
- Stauber Rudolf
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- Abstract:
- Background and aims: Mean pulmonary arterial pressure (mPAP) is 14.0 ± 3.3mmHg (mean ± SD) under physiological conditions. As we initiated our study, the definition of pulmonary hypertension (PH) was an elevation of mPAP ≥ 25 mmHg. The clinical relevance of mildly elevated mPAP above 20 mmHg but below 25 mmHg was unclear. Accordingly, we aimed to assess the association of resting mPAP with all-cause mortality in a retrospective and a prospective cohort of patients with unexplained dyspnea and/or at risk of PH with special focus on patients not fulfilling the former hemodynamic criteria of PH. Methods: Prognostic cut-offs specific for our collective were first calculated by using regression tree (CART) analysis. In a second step mPAP cut-offs from the literature were used: lower-normal mPAP (≤ mean+ 1st SD), upper-normal mPAP (between mean + 1st SD and mean + 2nd SD), borderline (between mean + 2nd SD and 25 mmHg), and manifest PH (≥ 25 mmHg). We performed univariate and multivariate survival analysis adjusted for age and comorbidities. Results: Overall 547 patients were enrolled with 153 patients (26%) prospectively recruited. All patients underwent invasive assessment of pulmonary hemodynamics by means of right heart catheterization (RHC). N = 137, 56, 64 and 290 presented with lower-normal, upper-normal, borderline mPAP and manifest PH, respectively. The CART analysis on mPAP revealed three prognostic groups, mPAP < 17mmHg, 17 - 26 mmHg, and >26mmHg, with significantly decreasing survival. The univariate analysis based on thresholds from the literature showed that upper-normal, borderline mPAP and manifest PH were significantly associated with poor survival, compared to lower-normal mPAP. However, patients with mildly elevated pulmonary pressure were significantly older and had more cardiopulmonary comorbidities. In addition, they presented with lower exercise capacity and higher frequencies of exercise PH. In the multivariate model, corrected for age and comorbidities, only borderline mPAP [HR: 2.37, 95% CI: 1.14 - 4.97 (p = 0.022)] and manifest PH [HR: 5.05, 95% CI: 2.79 - 9.12 (p < 0.001)] were significantly associated with poor survival. Conclusion: In a combined retro- and prospective cohort at risk for PH and/or with unexplained dyspnea, unbiased CART analysis revealed prognostic cut-offs at a resting mPAP of 17 mmHg and 26mmHg. A mPAP between 20 mmHg and 25 mmHg represents an independent predictor of poor survival. Based on our results together with findings from other studies the definition for pulmonary hypertension was changed to mPAP > 20 mmHg at the 6th World Symposium on Pulmonary Hypertension in Nice, 2018.