A 67-year-old male patient with hypertension and chronic back pain saw his primary care physician for relatively new onset of shortness of breath. The patient first noticed these symptoms 1.5 weeks ago while doing regular household chores. The patient was a prior emergency medical technician and checked his vital signs. He was tachycardic (around 110 bpm) and had a blood pressure of 90/60 mmHg. Both findings were new for the patient. The patient denied ever having chest pain, peripheral edema, or fever. He works from home and sits most of the day. He is a life-long non-smoker. In the office, his blood pressure was 93/64 mmHg, his heart rate was 105 bpm, and his respiratory rate was 21 bpm with an O2 saturation of 97% on room air. There was a grade 2/6 holosystolic murmur best heard at the left lower sternal border and jugular venous distention slightly above the clavicle with the patient sitting upright. The lung fields were clear. An echocardiogram showed a right ventricular (RV) systolic pressure of 47 mmHg, with moderate tricuspid regurgitation and RV basal diameter of 53 mm. The patient was sent to the emergency department for further work-up, including a computed tomography pulmonary angiogram that revealed large emboli in both main pulmonary arteries with extension into the upper and lower lobes. Right to left ventricular dimension ratio on echocardiogram was 1.2. Troponin T was <0.02 ng/mL, B-type natriuretic peptide was 22 pg/mL, and creatinine was 1.3 mg/dL.
What is the best choice of treatment for this patient?
The correct answer is: C. IV heparin drip and catheter-directed thrombolysis
This patient has a submassive pulmonary embolism (PE) defined by systemic hypotension (systolic blood pressure ≥90 mmHg) but with either RV dysfunction (right to left ventricular dimension ratio >0.9) or myocardial necrosis.1 All patients with low-risk, submassive, and massive PE should be started on IV heparin. In patients with submassive PE, fibrinolytics should also be given if there are no contraindications and there is evidence of shock, respiratory failure, or moderate to severe RV strain based on 2011 American Heart Association (AHA) Scientific Statement on the management of massive and submassive PE.1 This patient has evidence of shock with a shock index >1.0 and moderate to severe RV strain with estimated RV systolic pressure >40.
Answer B is incorrect because systemic fibrinolytic therapy is given with IV heparin.1,2 In addition, the randomized double-blind trial PEITHO (Pulmonary Embolism Thrombolysis Study) compared tenecteplase plus heparin with placebo plus heparin in 1,005 intermediate risk normotensive PE patients with RV dysfunction on echocardiography or computed tomography as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T.3 Though fibrinolytic therapy prevented hemodynamic decompensation, risk of major hemorrhage and stroke was increased.
An alternative to systemic fibrinolysis is catheter-directed thrombolysis. This is a procedure performed by placing a multisided hole infusion catheter through the pulmonary embolus and infusing a thrombolytic drug over 12-24 hours. Catheters can have an ultrasound-emitting wire thought to accelerate thrombolysis by ultrasonically disrupting thrombus. SEATTLE II (A Prospective, Single-arm, Multi-center Trial of EkoSonic® Endovascular System and Activase for Treatment of Acute Pulmonary Embolism) is a single-arm prospective multicenter study in which 150 patients with massive (n = 31) and submassive (n = 19) PE were treated with ultrasound-assisted catheter-directed thrombolysis low-dose fibrinolysis.4 Results showed a decrease in right to left ventricular dimension ratio and pulmonary artery pressure with no intracranial or fatal bleeding.
Answer A, IV heparin drip alone, is not the best choice of treatment in submassive PE because fibrinolysis should be considered based on the 2011 AHA Scientific Statement. In the multicenter randomized ULTIMA (Ultrasound Accelerated Thrombolysis of Pulmonary Embolism) study, intermediate-risk PE patients saw an improvement of echocardiography-derived right to left ventricular dimension ratio with ultrasound-associated catheter-directed thrombolysis plus heparin (0.3 ± 0.2, p < 0.001) compared with heparin alone (0.03 ± 0.16, p = 0.31) at 24 hours without an increase in bleeding.5
Answer D, aspiration thrombectomy, would not be the correct choice because the patient is stable, and thrombectomy would expose the patient with needless risk of pulmonary artery injury when other therapies are indicated.2
Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123:1788-830.
Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of Pulmonary Embolism: An Update. J Am Coll Cardiol 2016;67:976-90.
Meyer G, Vicaut E, Danays T, et al. Fibrinolysis for patients with intermediate-risk pulmonary embolism. N Engl J Med 2014;370:1402-11.
Piazza G, Hohlfelder B, Jaff MR, et al. A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv 2015;8:1382-92.
Kucher N, Boekstegers P, Müller OJ, et al. Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism. Circulation 2014;129:479-86.