Risk assessment in inoperable chronic thromboembolic pulmonary hypertension
Authors: Yaylali Y , Kilickiran-Avci B , Akbulut M , Basarici I , Meric M , Atahan E , Sinan U Y , Kaya B , Ohtaroglu-Tokdil N K , Senol H , Mutlu B , Kucukoglu M S , Ongen Z 
Published: October 2022

Abstract

Background
Our objective was to investigate an abbreviated version of the the current European PH guidelines, noninvasive French model, an abridged version of the REVEAL 2.0 risk score calculator, REVEAL Lite 2, and a refined 4-strata risk assessment model, COMPERA 2.0 for inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Methods
We enrolled inoperable CTEPH patients from 8 PAH centers from December 2009 to June 2020 (n=123). 70% of patients were treated with PAH therapies. Noninvasive French model comprising WHO functional class (FC), 6-minute walk distance (6 MWD), and N-terminal pro–brain natriuretic peptide (NT-pro BNP) or BNP was used for 63 patients. REVEAL Lite 2 including FC, systolic blood pressure, heart rate, 6MWD, BNP/NT-pro BNP, and estimated glomerular filtration rate was used for 71 patients. COMPERA 2.0 including FC, 6MWD and BNP/NT-pro BNP was used for 71 patients. Patients were grouped into three categories according to the French model and REVEAL Lite 2 scores, and into four categories according to COMPERA 2.0. Kaplan-Meier (KM) survival was assessed in each risk group with all-cause mortality as the end point. Log-rank test was used to compare estimates.

Results
The mean age was 64±13 years at diagnosis. The median follow-up was 22.7 months. 26 patients had died. None of the patients had balloon pulmonary angioplasty. Most patients had received monotherapy (55%). 23.8% of patients were WHO FC I-II, 65.6% III, and 10.7% IV at initial evaluation (Table 1). All models discriminated risk in our cohort. Patients having none of low-risk criteria or high risk profiles by REVEAL Lite 2 and COMPERA 2.0 at follow-up had the worst survival. Figure 1 demonstrates KM survival curves for noninvasive French model (A), REVEAL Lite 2 (B), and COMPERA 2.0 (C). 37.3% of patients achieved 2 or more low risk criteria at follow-up. 44.8% of patients were in low risk at follow-up (REVEAL lite 2). 52.1% of patients were in low and intermediate-low risk at follow-up (COMPERA 2.0). The estimated survival rate at 5 years of patients meeting 2 and more low-risk criteria was 86% vs. 55% for patients meeting 0 low-risk criterion (p=0.04). The corresponding survival rate was 45% for high-risk patient, 79% for intermediate-risk patient, and 82% for low-risk patient (REVEAL lite 2) (p=0.029). The corresponding survival rates were 51.1% for high-risk patient and 91.6% for intermediate-low risk patient (COMPERA 2.0) (p=0.017). COMPERA 2.0 seems more accurate based on c-index. Survival was similar between patients treated and not treated with PAH therapies (p=0.735).

Conclusions
Noninvasive French model, REVEAL Lite 2, and COMPERA 2.0 may provide a simplified method of risk assessment for inoperable CTEPH. This analysis also supports the value of goal-oriented treatment in CTEPH. Patients who have not achieved low risk category at follow-up may benefit from escalation of their treatment regimen.

Funding Acknowledgement
Type of funding sources: None.