Retrospective evaluation of factors affecting early mortality and long-term chronic thromboembolic pulmonary hypertension (CTEPH) rates in patients with massive/submassive pulmonary embolism treated with thrombolytics

Introduction and Aim: Pulmonary embolism (PE) is the most common cause of cardiovascular death after myocardial infarction and stroke. In cases of massive PE, early hospital mortality exceeds 15%, and more than 50% of deaths occur within the first few hours. The cumulative incidence of CTEPH in the first two years following a PE attack ranges from 0.1% to 9.1%. This study aimed to determine early and late mortality and morbidity in patients receiving fibrinolytic therapy for massive/submassive PE and the clinical factors affecting these outcomes. Materials and Methods: All patients diagnosed with massive/submassive PE who received fibrinolytic therapy (alteplase) in our clinic between 2012 and 2024 were included in the study. All patients diagnosed with massive/submassive pulmonary embolism who received fibrinolytic therapy were identified and evaluated through the automated system. Results: A total of 50 cases (31 women, 62%; 19 men, 38%) were included in the study. The mean age of the cases was 64±16 years (min: 21 – max: 93), and the median follow-up period was 1661 days (min: 1 – max: 4566 days). D-dimer negativity was detected in 2% of massive/submassive PE cases, while elevated cardiac enzymes were detected in 52% of cases. Thirty-six patients (72%) had massive PE, and 14 (28%) had submassive PE. Fibrinolytic therapy was administered in the emergency department (18%), intensive care unit (24%), or ward (58%). Major bleeding (intracranial hemorrhage) was observed in 1 case (2%). Half-dose fibrinolytic therapy was administered to 26% of cases, and full-dose therapy to 74%. The 2-day mortality rate was 10% (5/50), the 10-day mortality rate was 26% (13/50), and the 30-day mortality rate was 28% (14/50). Early and late mortality rates were significantly higher in patients with a history of malignancy and heart failure. The 30-day mortality rate was significantly higher in patients receiving half-dose fibrinolytic therapy compared to those receiving full-dose therapy (53.8% vs. 18.9%, p=0.029). Elevated cardiac enzymes were also identified as a factor increasing the risk of 30-day mortality. Mortality rates were significantly lower in patients with hypertension and obesity. Age, gender, and the presence of massive or submassive clinical presentation were found to have no significant effect on early and late mortality. The administration of fibrinolytic therapy in the emergency department, ward, or intensive care unit did not affect mortality rates. In patients who died within 30 days due to massive/submassive PE, pulse rate, urea, and creatinine levels at the time of diagnosis were significantly higher than in surviving patients. No difference in early and late mortality was detected in massive and submassive cases treated with thrombolytics. The median survival for all cases treated with reperfusion therapy with a diagnosis of massive/submassive PE was found to be 2352 days (Standard Error- 304 days). In the Kaplan-Meier survival analysis, the median survival of patients with malignancy and heart failure was significantly lower. Median survival was significantly longer in obese patients, regardless of malignancy. According to Cox Regression analysis, malignancy was an independent risk factor negatively affecting survival, while obesity was a positive factor. KTEPH developed in 6 of the 21 patients (12% of the total cases; 6/50) who underwent KTEPH evaluation. The mean baseline pulmonary artery systolic pressure in patients who developed KTEPH was statistically significantly higher than in patients who did not develop KTEPH. Conclusion: The effects of factors such as malignancy, obesity, and half-dose fibrinolytic therapy on mortality and morbidity in patients undergoing reperfusion therapy with a diagnosis of massive/submassive PE should be investigated in more comprehensive studies.