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Prolonged Ultrasound-Assisted Catheter-Directed Low-Dose Thrombolysis for Acute Pulmonary Embolism Unresponsive to Systemic Thrombolysis

Alessandro Beneduce, MD1;  Francesco Giannini, MD2;  Gianmarco Iannopollo, MD3;  Letizia Bertoldi, MD1;  Francesco Melillo, MD1;  Marta Panzeri, MD4;  Roberto Nicoletti, MD4;  Francesco De Cobelli, MD4;  Francesco Gentile, MD5;  Alberto Margonato, MD1;  Antonio Colombo, MD2;  Azeem Latib, MD3 

April 2019

J INVASIVE CARDIOL 2019;31(4):E56-E57.

Key words: EkoSonic, pulmonary embolism, pulmonary hypertension, thrombolysis


A 55-year-old man with previous idiopathic pulmonary embolism (PE) presented with acute dyspnea (PaO2, 60 mm Hg, PaCO2, 32 mm Hg), sinus tachycardia (heart rate, 130 bpm), and hypotension (blood pressure, 80/60 mm Hg) a few months after warfarin discontinuation. Transthoracic echocardiography (TTE) and computed tomography pulmonary angiography (CTPA) demonstrated massive bilateral PE, right ventricular (RV) hypertrophy, dilation (RV/left ventricular ratio, 1.6), and dysfunction (tricuspid annular plane systolic excursion [TAPSE], 12 mm) with  systolic pulmonary artery pressure of 126 mm Hg (Figures 1A-1C).

Systemic thrombolysis with alteplase 100 mg followed by unfractionated heparin (UFH) was administered. However, the patient developed RV failure, necessitating dobutamine administration. CTPA performed 48 hours later showed bilateral thrombus persistence. Ultrasound-assisted thrombolysis (USAT) with alteplase using the EkoSonic system (EKOS) was then administered at an initial dose of 1 mg/hr/catheter for 24 hours in addition to UFH to achieve an activated partial thromboplastin time of 60-80 sec. Considering partial hemodynamic improvement and the patient’s low bleeding risk profile, the treatment was continued at 0.5 mg/hr/catheter for a further 24 hours with echocardiographic monitoring of RV function and pulmonary artery pressures (Figure 1D).

After 48 hours of treatment with total alteplase dose of 72 mg, the patient’s hemodynamics improved, with blood pressure and arterial blood gas normalization. CTPA demonstrated significant reduction of thrombotic burden, with residual parietal thrombotic apposition, consistent with chronic PE, while RV function recovered (TAPSE, 22 mm) and pulmonary artery pressures progressively reduced to 55 mm Hg (Figures 1E-1G). The patient was discharged on day 8 on edoxaban 60 mg.

Our experience suggests that USAT with the EkoSonic system could be considered a valid bailout strategy in case of massive PE unresponsive to systemic thrombolysis and provides insights into the potential role of prolonged administration time in non-high bleeding risk patients with elevated thrombotic burden and initial suboptimal results. In this setting, multimodality imaging could guide patient selection and monitor treatment efficacy to individualize its duration in case of slow hemodynamic improvement.


From 1the Intensive Cardiac Care Unit, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Milan, Italy; 2Interventional Cardiology Unit, GVM Care & Research Maria Cecilia Hospital, Cotignola, Italy; 3Interventional Cardiology Unit, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute, Milan, Italy; 4Center for Experimental Imaging, Radiology Department, San Raffaele Scientific Institute, Milan, Italy; and 5Cardiology Unit, Edoardo Bassini Hospital, Cinisello Balsamo, Milan, Italy.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

The authors report that patient consent was provided for publication of the images used herein.

Manuscript accepted October 30, 2018.

Address for correspondence: Francesco Giannini, MD, Interventional Cardiology Unit, GVM Care & Research Maria Cecilia Hospital, Via Madonna di Genova 1, 48033 Cotignola (RA), Italy. Email: giannini_fra@yahoo.it


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