Long-Term Prognostic Impact of Pulmonary Hypertension After Venous Thromboembolism

Pulmonary embolism is a risk factor for chronic thromboembolic pulmonary hypertension (CTEPH), but the prognostic impact of CTEPH on venous thromboembolism (VTE) mortality remains unclear. We examined the impact of CTEPH and other pulmonary hypertension (PH) subtypes on long-term mortality after VTE. We conducted a nationwide, population-based cohort study of all adult Danish patients alive 2 years after incident VTE without previous PH from 1995 to 2020 (n = 129,040). We used inverse probability of treatment weights in a Cox model to calculate standardized mortality rate ratios (SMRs) of the association between receiving a first-time PH diagnosis ≤2 years after incident VTE and mortality (all-cause, cardiovascular, and cancer). We grouped PH as PH associated with left-sided cardiac disease (group II), PH associated with lung diseases and/or hypoxia (group III), CTEPH (group IV), and unclassified (remaining patients). Total follow-up was 858,954 years. The SMR associated with PH overall was 1.99 (95% confidence interval 1.75 to 2.27) for all-cause, 2.48 (1.90 to 3.23) for cardiovascular, and 0.84 (0.60 to 1.17) for cancer mortality. The SMR for all-cause mortality was 2.62 (1.77 to 3.88) for group II, 3.98 (2.85 to 5.56) for group III, 1.88 (1.11 to 3.20) for group IV, and 1.73 (1.47 to 2.04) for unclassified PH. The cardiovascular mortality rate was increased approximately threefold for groups II and III but was not increased for group IV. Only group III was associated with increased cancer mortality. In conclusion, PH diagnosed ≤2 years after incident VTE was associated with an overall twofold increased long-term mortality driven by cardiovascular causes.