Predictors of chronic thromboembolic pulmonary hypertension in patients with submassive pulmonary embolism treated with catheter-directed thrombolysis versus anticoagulation alone: A secondary analysis of the SUNSET sPE trial

Abstract

Objective: Chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is a morbid complication with suboptimal treatment. We aimed to evaluate the biomarker profile and functional outcomes in patients with submassive PE (sPE) treated with catheter-directed thrombolysis (CDT) compared with anticoagulation alone (ACA). We performed a secondary biomarker and survey analysis of the SUNSET sPE (standard vs ultrasound-assisted catheter thrombolysis for submassive pulmonary embolism) randomized trial comparing standard CDT to ultrasound-assisted thrombolysis in patients with sPE.

Methods: As a part of the SUNSET sPE study, patients who did not receive an intervention were enrolled in the medical (ACA) arm. The biomarkers associated with CTEPH in the literature (ie, CCL2, CXCL10, PTX3, GDF-15, RAGE, BCA-1, TFPI) were collected and measured using a multiplex assay at diagnosis, discharge, and 3-month follow-up. Patients underwent a 6-minute walk test and answered quality-of-life questionnaires (pulmonary embolism quality of life; University of California, San Diego, shortness of breath questionnaire; 36-item short-form survey) at 3 months after diagnosis. Comparisons were made using the Student t test. Nonparametric tests were used when the distributions were not normal. Significance was set at P ≤ .05.

Results: A total of 72 patients (age, 56 ± 15 years; 40.3% women) were included in the present analysis. Of these 72 patients, 53 underwent CDT and 19 were included in the ACA arm. The baseline right ventricle/left ventricle ratios were similar between the two groups (CST, 1.8; ACA, 1.7). The survival and complication rates were similar between the two groups. At discharge, CXCL10 (768.9 ± 148.6 pg/mL vs 3032.0 ± 1201.0 pg/mL; P = .018) and PTX3 (3203.5 ± 1298.0 pg/mL vs 12,716.2 ± 6961.5 pg/mL; P = .029) were lower in the CDT group and displayed a quicker return to baseline than in the ACA group. This trend, although not significant, was also seen with the other biomarkers. At 3 months, the 6-minute walking distance and quality-of-life scores were similar between both groups.

Conclusions: In patients with sPE, the biomarkers of CTEPH were lower with CDT compared with ACA. At 3 months, both groups demonstrated similar biomarker levels, 6-minute walking distances, and quality-of-life scores.

Trial registration: ClinicalTrials.gov NCT02758574.

Keywords: Biomarkers; Catheter-directed thrombolysis; Chronic thromboembolic pulmonary hypertension; Pulmonary embolism.

Figure 1.. Flow chart displaying study enrollment and outcome measurements.

Figure was constructed using biorender.com.

Figure 2.. Circulating concentrations of CXCL10 and PTX 3 reduce earlier following catheter directed thrombolysis (CDT) compared to anticoagulation along (AC).

(A) Circulating concentration of CXCL10, (B) PTX-3, (C) RAGE, (D) MCP-1, (E) BCA-1, and (F) GDF-15. All concentrations result in pg/ml. *p<.05, error bars represent standard error of the mean (SEM).

Figure 3.. Short term physiologic outcomes including RV/LV ratio resolution and six-minute do not change between groups.

(A) Reduction in right ventricle (RV) to left ventricle (LV) diameter ratio at time of diagnosis compared to the measurement at three-month follow-up. (B) Six-minute walk test distance completed at three-month follow-up. Error bars represent standard error of the mean (SEM).

Figure 4.. Short term quality of life does not differ between catheter directed thrombolysis (CDT) and anticoagulation monotherapy (AC).

(A) Transformed PEmb quality of life scores three months after pulmonary embolism diagnosis. Higher scores represent worse quality of life. (B) SF36 health related quality of life questionnaire score. Higher scores represent better quality of life. (C) University of California San Diego Shortness of Breath questionnaire (UCSDSOBQ) score three months after pulmonary embolism diagnosis. Higher scores represent more debilitating shortness of breath. Error bars represent standard error of the mean (SEM).