Prognostic relevance of elevated pulmonary arterial pressure assessed non-invasively: Analysis in a large patient cohort with invasive measurements in near temporal proximity

Abstract

Background: The clinical relevance of non-invasively derived pulmonary arterial pressure (PAP) by Doppler echocardiography (DE) has been questioned in the past. However, transthoracic echocardiography is used as a cornerstone examination for patients with dyspnea and suspected pulmonary hypertension (PH). This study aimed to evaluate the prognostic value of non-invasive assessed PAP in a large population of patients with known or suspected cardiopulmonary disease.

Methods: The analyses are based on data of patients of a tertiary cardiology center that received right heart catheterization (RHC) as well as non-invasively assessed PAP by DE within five days, and includes serological and clinical parameters in a retrospective follow-up for up to eight years.

Results: Of 1,237 patients, clinical follow-up was possible in 1,038 patients who were included in the statistical analysis. The mean-follow up time was 1,002 days. The composite endpoint of heart transplantation (HTx) or death occurred in n = 308 patients. Elevated PAP measured non-invasively as well as invasively had significant prognostic impact (hazard ratio (HR) 2.32; 95% confidence interval (CI) 1.78-3.04; χ2 = 37.9; p<0.001 versus HR 2.84; 95%CI 2.11-3.82; χ2 = 51.9; p<0.001, respectively). By multivariate analysis, NYHA functional class, N-terminal pro-brain natriuretic peptide, cardiac troponin T, left ventricular ejection fraction, and right ventricular dysfunction remained independently predictive. Incremental prognostic information in a multimodal approach was highly relevant.

Conclusions: In this comprehensive study, elevated pulmonary arterial pressure measured by DE offers similar prognostic information on survival or need for HTx as right heart catheterization. Furthermore, the addition of functional capacity and serological biomarkers delivered incremental prognostic information.

Fig 1. Study protocol.

Flow chart with inclusion criteria from catheter and echocardiography databases, identification of individual patients, and exclusion due to loss of clinical follow-up. Abbreviation: RHC right heart catheterization.

Fig 2. Survival of patients with or without PH as diagnosed by RHC visualized by Kaplan-Meier curves.

Abbreviations: PH pulmonary hypertension, RHC right heart catheterization, mPAP mean pulmonary arterial pressure, HR hazard ratio, 95%CI 95% confidence interval.

Fig 3. Survival of patients with or without PH as suggested by Doppler echocardiography visualized by Kaplan-Meier curves.

Abbreviations: PH pulmonary hypertension, sPAP systolic pulmonary arterial pressure, HR hazard ratio, 95%CI 95% confidence interval.

Fig 4

Outcome differentiated by PAP for subgroup of patients: left ventricular cardiomyopathy (CMP):A,B; valvular heart disease: C,D; ischemic heart disease (IHD): E,F and rare cardiac diseases: G;H. Invasive measurements by RHC (A,C,E,G) are compared to non-invasively assessment by DE (B,D,F,G). Abbreviations: m/sPAP mean/systolic pulmonary arterial pressure, HR hazard ratio, 95%CI 95% confidence interval, ns not significant.

Fig 5

Kaplan-Meier curves for survival of patients with PH due to LHD or precapillary PH defined by RHC according to mPAP and PCWP (A) or elevated PVR (≥ 250 dyn^xs^xcm^-5 or 3.1 WU, B). Abbreviations: PH pulmonary hypertension, LHD left heart disease, RHC right heart catheterization, PAP pulmonary arterial pressure, mPAP mean pulmonary arterial pressure, PVR pulmonary vascular resistance, WU Wood Units, HR hazard ratio, 95%CI 95% confidence interval, ns not significant.

Fig 6. Incremental predictive information for survival of multimodal clinical settings based on complete-case data (n = 395).

Abbreviations: Clin: clinical assessment (age, sex, NYHA functional class), Clin+Echo: clinical assessment and transthoracic (Doppler) echocardiography (LV-EF, RV dysfunction, sPAP, RAP), Clin+Sero: clinical assessment and cardiac serological parameters (NT-proBNP, cTnT); Clin+Sero+Echo: clinical assessment, cardiac serological parameters and transthoracic echocardiography combined; Clin+Sero+Echo+RHC: Non-invasive diagnostics and RHC (CI, mPAP, RAP) combined; Clin+RHC: clinical assessment and RHC (CI, mPAP, RAP) combined. **p<0.001. NYHA New York Heart Association, LV-EF left ventricular ejection fraction, sPAP systolic pulmonary arterial pressure, RAP right atrial pressure, NT-proBNP N-terminal pro brain natriuretic peptide, cTnT cardiac troponin T, CI cardiac index, mPAP mean pulmonary arterial pressure, RHC right heart catheterization.