Background: Therapy in pulmonary embolism (PE) is mostly straight forward in stable low-risk and unstable high-risk patients. Trials like PEITHO-3 or HI-PEITHO evaluate reduced dosage one shot systemic or device-based prolonged lysis in intermediate-high risk patients. A different option is continuous infusion of low-dose rt-PA, with stopping the lysis after resolution of symptoms or echocardiographic defined criteria of RV-dysfunction. This strategy is successfully used in catheter-directed thrombolysis for deep vein thrombosis with favorable response on PE. This current retrospective feasibility study investigates administration of prolonged systemic reduced-dosage lysis in patients with intermediate high-risk pulmonary embolism.

Methods and results: This is a retrospective, observational single-center study of 13 patients with intermediate high-risk PE. All patients had significant right-heart distress and elevated cardiac biomarkers (Troponin I) at admission but were hemodynamically stable. Patients were treated at discretion of the treating physician. Continuous reduced dosage lysis (1mg rtPA/h for a maximum of 48 hours) in combination with therapeutic dosage of unfractionated heparin was administered. The effect of the treatment was assessed by clinical (blood pressure, oxygen saturation, heart rate) and echocardiographic (RV-Diameter, RV/LV-ratio, TAPSE, RV-FAC and pulmonary arterial pressure (PAPsys)) parameters at baseline and before hospital discharge. Clinical outcomes consisted of all-cause mortality, hemodynamic decompensation, collapse, need for full dose thrombolysis, myocardial infarction, stroke and bleeding (according to BARC classification). 360 days after study inclusion, the Pulmonary Embolism Quality of Life Questionnaire (PEmb-QoL) was sent to all patients.

Mean duration of lysis was 33.3 hours (±13.7) and mean dosage was 32.2 mg rtPA (±14.3). No patient suffered hemodynamic decompensation, myocardial infarction, stroke or syncope during hospital stay.  No patient required a full dose thrombolysis. 2 patients developed BARC type 2 bleeding. After therapy, RV-diameter had declined from 45.1 (±5.3) to 36.6mm (±8.3), p=0.006, RV/LV diameter from 1.4 (±0.2) for 0.9 (±0.2), p<0.001, PAPsys from 38.9 (±8.7) to 27.4mmHg (±11.8), p=0.013 and heart rate from 104 (±12.6) to 70 (±19.3), p<0.001, respectively. On the other hand, TAPSE improved from 14.5 (±4.4) to 22.5mm (±5.8), p=0.001, RV-FAC from 20.8 (±7.4) to 30.8% (±8.6), p=0.056 and SpO2 from 92.5 (±3.7) to 96.5% (±2.0), p=0.002, respectively (Figure 1). All patients survived for 360 days after the index event. The PEmb-QoL questionnaire showed that the majority of patients did well. However, up to 50% of patients still experienced chest discomfort and dyspnea while social activities and work were impaired to a lesser degree (Figure 2).

Conclusion: In the current study, we observed an extensive improvement in clinical and echocardiographic parameters in all patients. Continuous low dose lysis might offer a therapeutic strategy for intermediate high-risk patients. A substantial benefit lies in the steerability and thus possibility of cessation of lysis at any time. Thus, this concept might be applied in patients at higher bleeding risk, e.g. cancer patients, and warrants further studies with controlled design.