key: cord-0882370-cryyux9n
authors: Marginean, Alexandru; Masic, Dalila; Brailovsky, Yevgeniy; Fareed, Jawed; Darki, Amir
title: Difficulties of Managing Submassive and Massive Pulmonary Embolism in the era of COVID-19
date: 2020-05-19
journal: JACC Case Rep
DOI: 10.1016/j.jaccas.2020.05.017
sha: ac13de451f9515ee78cf5f70131c196d7b063910
doc_id: 882370
cord_uid: cryyux9n

Abstract: Acute pulmonary embolism (PE) is a potentially life-threatening manifestation of venous thromboembolic disease. SARS-COV2, a novel coronavirus that causes COVID-19, has been associated with increased risk of thrombosis. We describe the therapeutic challenges of three patients presenting with PE and suspected or confirmed COVID-19.

Pulmonary embolism (PE) is a life-threatening condition responsible for up to 15% of inhospital deaths annually in the United States. Clinical deterioration results from right sided heart failure, obstructive shock, hypoxia, and death in the most severe cases (1) . With a diverse range of clinical presentations, diagnosis and timely risk stratification is important. Low risk PE is defined by normotension, normal right ventricular function on CT or TTE, and no evidence of ischemia with biomarkers (troponin/BNP). Submassive PE manifests with RV dysfunction on imaging and/or abnormal biomarkers with normotension. Massive PE is characterized by hemodynamic collapse defined as systolic blood pressure (SBP) <90mmHg or a >40mmHg decrease in SBP for more than 15 minutes, or requiring inotropic support with associated RV dysfunction and ischemia (2) .

In December 2019 a novel coronavirus originating in Wuhan, China identified as SARS-COV2 was implicated as the causative agent in cases of severe pneumonia with ARDS. The virus has since been deemed a global pandemic by the WHO (3). Data published on its clinical manifestations and disease course have shown that patients with the most severe cases develop severe ARDS, sepsis-induced DIC, and cytokine storm. DIC manifests with elevated levels of Ddimer which are associated with increased mortality (4) . Hemorrhagic infarction and microthrombi formation in the pulmonary vasculature can be found in postmortem analyses of these patients (5) . Throughout the world clinicians modified their management strategies for suspected and confirmed PE in COVID-19 patients. We describe the therapeutic challenges of three patients presenting with PE and suspected or confirmed COVID-19.

A 75-year-old female with history of PE in 2018 treated with six months of apixaban was transferred to our institution after presenting to outside hospital with pleuritic chest pain and dyspnea and found to have hypotension and large, central PE extending into bilateral pulmonary arteries with an RV/LV ratio of 1.6. CT head identified a new brain lesion. Because of massive PE, shock, and contraindication to tPA, the patient was started on norepinephrine and transferred. On arrival to our institution, the patient was afebrile with BP of 109/80mmHg, pulse of 99 bpm, saturating 99% on 2L nasal cannula, and breathing 26 breaths/min. D-dimer was elevated at 7,348ng/mL (normal <500), lactate of 2.1mmol/L (normal <1.7), BNP of 614pg/mL (normal <100), and troponin I of 0.52ng/mL (normal <0.02). A rapid COVID-19 assay was drawn on arrival. Lower extremity doppler ultrasound revealed a mobile thrombus in the left common femoral vein (Video 1).

The patient was managed with intravenous UFH and dobutamine; however, lactate continued to rise. In the interim, her COVID-19 assay came back negative, so the decision was made to proceed with mechanical thrombectomy. She underwent successful aspiration thrombectomy of bilateral pulmonary arteries. (Figure 1 ). She was continued on anticoagulation and underwent workup of her brain mass and was discharged home.

This case identifies a therapeutic dilemma for the interventionalist in the era of COVID-19. There is paucity of data demonstrating clear association of interventional techniques with improvement in survival for acute PE. It is not clear when to safely escalate care to the catheterization lab, while limiting staff exposure to PUI with COVID-19. Aerosolized particles travel long distances, which may explain the extent of viral spread over the last few months (6) .

A patient's clinical condition must be weighed against the evidence of therapeutic approaches offered and safety of the healthcare team in determining the best course of action.

A 65-year-old female with history of PE treated with six months of warfarin presented to our institution with sudden onset dyspnea, subjective fevers, and one day of diarrhea. She was afebrile with a BP of 159/102mmHg, pulse of 122 bpm, oxygen saturation of 86% on 100% nonrebreather mask, and respiratory rate of 20 breaths/min. Troponin I was elevated at 0.16ng/mL, lactate was elevated at 3.9mmol/L, BNP was normal at 59pg/mL, and D-dimer was elevated at 6,629ng/mL. CT chest confirmed multiple central PE with extension into the bilateral lobar and subsegmental branches with an RV/LV ratio of 2.6. Her COVID-19 assay was drawn upon presentation. Based on clinical status, CDT was considered but deferred as she was a PUI for COVID-19.

Management involved initial airway stabilization with escalation to bilevel positive airway pressure and IV UFH for anticoagulation. Despite medical management, the patient had worsening hypoxia. In attempt to stave off intubation, which can be associated with acute RV decompensation due to increased RV afterload and risk of aerosolizing the COVID-19 virus if the patient was infected, we proceeded with half dose systemic fibrinolysis consisting of IV alteplase 10mg bolus followed by 40mg over two hours (7) . Following fibrinolysis, her work of breathing significantly improved and oxygen requirements decreased to 6lpm via nasal cannula.

The patient did not experience any bleeding. Her RV/LV ratio normalized on follow up echocardiogram and was discharged home.

This case of submassive PE highlights the difficulties of managing patients suspected of COVID-19 infection. CDT is associated with early improvement in RV function and hemodynamics in deteriorating patients with lower doses of tPA (8, 9) ; however, PUI for COVID-19 warrant infection rule out prior to proceeding with invasive procedures as already mentioned. Nevertheless, half or full dose systemic fibrinolysis are available in a physician's armamentarium to stabilize high-risk PE in PUI for COVID-19 without significantly increased risk of bleeding.

A 58-year-old female with history of asthma presented with dyspnea, pleuritic chest pain, diarrhea, and productive cough. She had exposure to COVID-19 at work 16 days before presentation with a positive viral assay 13 days prior. She was afebrile with a BP of 137/85mmHg, pulse of 117 bpm, oxygen saturation of 99% on 2L nasal cannula, and respiratory rate of 24 breaths/min. Troponin I was elevated at 0.38ng/mL, D-dimer was elevated at 16,400ng/mL, and BNP was elevated at 151pg/mL. Lactate was normal at 1.2mmol/L. CT chest revealed saddle PE with extension into bilateral pulmonary arteries. Lung windows demonstrated bilateral consolidations and ground glass opacities consistent with COVID-19 pneumonia.

( Figure 2) . She was diagnosed with submassive PE and was started on IV UFH. Her respiratory status improved on medical management alone and she was transitioned to apixaban prior to discharge.

Care of patients diagnosed with PE is complex and relies on risk stratification with biomarkers and imaging with CT and echocardiography to guide management. At our institution, all PE patients undergo TTE. However, TTE was deferred for this patient given her COVID-19 status. Patient isolation is vital to limit exposure and possible transmission. However, this practice can interfere with comprehensive patient care. Physicians managing venous thromboembolism must rely on clinical status, laboratory markers, and CT markers of severity, in lieu of TTE to make appropriate clinical decisions. In summary, as data continues to emerge in the COVID-19 pandemic, PE management algorithms must be revised to mitigate risks while maximizing patient care.

• To suspect PE early in the disease process in confirmed or suspected COVID-19 patients

• To identify high-risk patients early and to offer appropriate therapies while mitigating patient and provider risk 

Clinical, historical and diagnostic findings associated with right ventricular dysfunction in patients with central and non-massive pulmonary embolism

Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia

Clinical pathology of critical patients with novel coronavirus pneumonia (COVID-19)

COVID-19 may transmit through aerosol

Moderate pulmonary embolism treated with thrombolysis (from the "MOPETT" Trial)

Right Ventricular Outflow Doppler Predicts Low Cardiac Index in Intermediate Risk Pulmonary Embolism

Randomized, controlled trial of ultrasoundassisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism

Low left ventricular outflow tract velocity time integral is associated with poor outcomes in acute pulmonary embolism