Incidence of recurrent venous thromboembolism and of chronic thromboembolic pulmonary hypertension in patients after a first episode of pulmonary embolism

Abstract

After a first episode of pulmonary embolism (PE), two major problems need to be considered: risk of recurrence when anticoagulation is stopped, and risk of chronic thromboembolic pulmonary hypertension (CTPH). We followed prospectively consecutive patients who survived a first episode of PE, with or without deep vein thrombosis, to assess the incidence of venous thromboembolism (VTE) recurrences and of symptomatic and asymptomatic CTPH. After 3-6 months of oral anticoagulant therapy (OAT) patients underwent transthoracic echocardiography for measuring transtricuspid (rV-rA) gradient. When rV-rA gradient was >35 mmHg further evaluations were performed to rule in or out CTPH. During follow-up patients who developed persistent dyspnea were re-evaluated. In patients who underwent OAT withdrawal D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), and thrombophilia were evaluated one month after warfarin discontinuation. Overall, 239 patients, 118 males, median age 59(16-89) years, were followed up for a median time of 36(9-192) months. Nine patients had rV-rA gradient >30 mmHg and ≤35 mmHg, and one of 37 mmHg. Among patients with normal rV-rA gradient, one developed persistent dyspnea 55 months after the first event and CPTH was confirmed. Among 206 patients who stopped OAT, 23(11.2%) had VTE recurrence, 11 PE(48%). Elevated DD and F1 + 2 levels after stopping OAT were significantly associated with recurrence. None of patients with recurrent VTE had elevated rV-rA gradient. In our series the incidence of CTPH after a first episode of PE was 0.4%. VTE recurrence and elevated DD and F1 + 2 levels seemed not to be related to the development of CTPH.

An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan

“…The proportion of patients who develop CTEPH following PE was reported in eight studies conducted in Europe and the USA [17,[45][46][47][48][49][50][51]. Japanese data were back-calculated, and further data were obtained from databases/registries.…”

Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding

“…However, an association between recurrent PE and CTEPH could have been underestimated: 1-yr mortality was high, and three out of four CTEPH patients had had documented episodes of DVT without any objective imaging tests for PE before entering the study. POLI et al [31] prospectively observed a cohort of 239 patients with a first episode of PE and found a 0.4% CTEPH incidence after a median follow-up of 3 yrs. VTE recurrences and high levels of D-dimer after withdrawal of anticoagulant therapy were not associated with an increased risk of CTEPH.…”

Epidemiology and Pathophysiology of Chronic Thromboembolic Pulmonary Hypertension: Risk Factors and Mechanisms

“…10 Subsequent studies have reported a prevalence ranging between 0.4% and 4.8%. [11][12][13][14][15][16][17] Differences in rates are likely due to differences in populations studied, screening methods for CTEPH, and length of follow-up.…”