Chronic thromboembolism phenotypes after acute pulmonary embolism: identification with the SEARCH algorithm

BACKGROUND: Chronic dyspnoea and exercise impairment are common after acute pulmonary embolism (PE) but poorly characterised. We performed a prospective observational study to validate an algorithm to diagnose discrete post-PE outcomes, including chronic thromboembolism phenotypes. METHODS: Six pulmonologists independently reviewed records from 150 consecutive patients ≥3 months after acute PE who had undergone a stepwise diagnostic algorithm (SEARCH), which incorporates Symptom screening, cardiopulmonary Exercise testing, pulmonary Arterial perfusion scans, Resting echocardiography, Confirmatory imaging, and Haemodynamic measurements by rest and exercise right heart catheterisation (RHC). Clinical data were reviewed after the first post-PE evaluation and then 6 months later. RESULTS: Symptomatic recovery was most common and occurred in 66.2% of patients during the final evaluation. Dyspnoea without discernible physiological defects occurred in 2.1% and dyspnoea from alternative diagnoses in 19.7%. Chronic thromboembolism phenotypes were diagnosed in 12.0% of patients. Chronic thromboembolism with ventilatory inefficiency and/or small stroke volume augmentation during exercise was seen in 6.3%: 2.1% without pulmonary hypertension on RHC and 4.2% in whom RHC was not performed. Chronic thromboembolic pulmonary hypertension and chronic thromboembolism with exercise-induced pulmonary hypertension occurred in 2.1% and 3.5%, respectively. Krippendorff's α among the readers was 0.984 (95% CI 0.9663-0.9960), signifying very high diagnostic reliability. No patient developed chronic thromboembolism between the first and final evaluations. CONCLUSIONS: Dyspnoea from chronic thromboembolism is common after acute PE, most of which is not associated with pulmonary hypertension. The SEARCH protocol reliably identifies chronic thromboembolism phenotypes after acute embolism. Validation of the SEARCH algorithm offers clinicians a straightforward method to diagnose post-PE conditions that are rarely distinguished clinically. Improved categorisation and definition of post-PE conditions will enhance clinical follow-up and allow more precise end-point adjudication in clinical trials of acute PE treatment.