key: cord-0853433-salizr5n authors: Horowitz, James M.; Yuriditsky, Eugene; Henderson, Ian J.; Stachel, Maxine Wallis; Kwok, Benjamin; Saric, Muhamed title: Clot in Transit on Transesophageal Echocardiography in a Prone Patient with COVID-19 Acute Respiratory Distress Syndrome date: 2020-05-16 journal: CASE (Phila) DOI: 10.1016/j.case.2020.05.007 sha: 8544ea2332efe39886ada02073fa6d586be37023 doc_id: 853433 cord_uid: salizr5n • The risk of thromboembolic events in COVID-19 is substantial; • Pulmonary embolism should be considered in cases of clinical deterioration; • Management of clot in transit is controversial. While a relatively infrequent entity, clot-in-transit (CIT) carries a considerable mortality; the ideal management for CIT remains controversial. We present a case of a patient admitted to the intensive care unit (ICU) with COVID-19 acute respiratory distress syndrome (ARDS) with deteriorating oxygenation and hemodynamics. An emergent transesophageal echocardiogram (TEE) was performed to better assess for etiologies of deterioration and demonstrated a CIT in the right ventricle. In this case, we highlight the utility of TEE in the evaluation of the unstable patient while in the prone position, and further demonstrate the consequences of the potential hypercoagulable state of COVID-19. A 62-year-old man without significant medical history presented to the emergency department with fevers, malaise, and dyspnea. His temperature was measured at 100.4 °F (38 °C) and he was found to be hypoxemic with 70% O 2 saturation on room air. A chest X-ray showed extensive patchy bilateral mid and lower lung airspace opacities. Laboratory data demonstrated a serum creatinine of 2.75 mg/dL, white blood cell count of 22.6 10^3/μL with lymphopenia (6% lymphocytes), and a D-dimer of 356 ng/mL (<230 ng/mL upper limit of normal). He was placed on high-flow nasal cannula and admitted to the general medicine service where he was found to be positive for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) by polymerase chain reaction (PCR). Patient was started on low molecular weight heparin (LMWH) at a dose of 40 mg every 24 hours as prophylaxis for venous thromboembolism. Lower extremity ultrasound on admission, ordered as a result of an elevated D-dimer level, did not reveal acute deep venous thrombosis. D-dimer rose to 4,070 mg/mL and the patient was transitioned to therapeutic LMWH at a dose of 1 mg/kg every 12 hours given the suspected increased risk of thrombosis among patients with COVID-19. The following day, he became progressively hypoxemic with increased work of breathing and worsening bilateral opacities on the chest X-ray leading to emergent endotracheal intubation and admission to the intensive care unit (ICU) (Figure 1 ). The diagnosis of COVID-19 acute respiratory distress syndrome (ARDS) was made. The patient had refractory hypoxemia with oxygen saturation of 84% despite inhaled nitric oxide (iNO) and prone positioning. He was hemodynamically unstable requiring vasopressor support. D-dimer rose further to >10,000 ng/mL. The possibility of extracorporeal membrane oxygenation (ECMO) was discussed however patient was not deemed a candidate in part related to significant acute renal failure. Given rapid hemodynamic and respiratory decompensation with a significantly elevated Ddimer level, an emergent TEE (Philips Affinity, X7 probe) was performed to exclude proximal pulmonary embolism (PE), and to evaluate for alternative causes of deterioration while patient remained in prone position (Figure 2) . For the purpose of provider safety, all team members donned an N-95 mask, face shield, gown, and 2 sets of gloves per our hospital protocol. Transthoracic echocardiography (TTE) was considered however, due to the emergent clinical status of the patient, TEE was selected as the initial imaging modality to obtain a greater amount of information upfront. Transportation for alternative imaging modalities such as a CT or VQ scan was not a safe option at this time. To facilitate probe insertion, the patient's head (Figure 6; Video 4) . The two working hypotheses were that the clot dissolved or embolized to the pulmonary artery. A heparin infusion was initiated, and the patient remained on mechanical ventilatory support for ARDS with persistent severe hypoxemia as well as worsening shock requiring escalating vasopressor therapies over the next 16 hours. While being transitioned to a supine position, he sustained asystolic cardiac arrest thought to be related to recurrent PE (i.e. CIT embolization) or, acute hypoxemia during repositioning from ARDS. Despite resuscitative efforts, the patient expired. An autopsy was offered to the family but declined. Venous thromboembolic events in patients with COVID-19 are thought to be the result of inflammation, hypoxia, and immobilization. Emerging pathologic evidence suggests endothelial dysfunction, dysregulated inflammation, and thrombotic microangiopathy contribute to the pathologic process [1] . The incidence of thrombotic complications among patients with COVID-19 is high. In a study of 184 ICU patients with COVID-19 pneumonia, 31% had thrombotic events despite prophylactic dose anticoagulation with pulmonary embolism (PE) being the most frequent (81% of thrombotic events) [2] . In case reports, PE has been noted among patients with COVID-19 pneumonia in the absence of other predisposing factors [3, 4] . Leonard-Lorant et al. have recently demonstrated the incidence of PE among COVID-19 patients to significantly exceed the rate of PE among critically ill patients without COVID-19 (30% v 1.3%) [5] . D-dimer, a marker of fibrin formation and degradation is elevated in conditions associated with thrombosis. Elevated D-dimer has been strongly linked with increased mortality among patients with COVID-19 infection [6, 7, 8] . It is postulated that elevated D-dimer levels may identify individuals at highest risk for embolic events. Therefore, it is common practice at many institutions to initiate therapeutic anticoagulation for patients with COVID-19 pneumonia and significantly elevated D-dimer levels. How best to identify those at the highest risk for venous thromboembolism remains unknown. The constellation of findings of elevated D-dimer, worsening hyoxemia and shock led to a strong suspicion for high-risk PE. While a CT scan would have been the optimal imaging modality to further evaluate for this concern, the patient's respiratory and hemodynamic instability created an unsafe scenario for patient transport. Prior studies have demonstrated the feasibility of prone TEE; in a report of 34 patients undergoing TEE in prone position in the setting of ARDS, standard views were able to be obtained in all but one patient [9] . Clots in transit are uncommon and occurring in ~4% of unselected patients with PE but are associated with a considerable 27-45% mortality rate [10, 11] . In patients with RV dysfunction, CIT raises significant suspicion for PE. While TEE is not the modality of choice for the diagnosis of PE, our imaging modalities were limited and TEE was further used to characterize chamber size and function to assist with the diagnosis. TEE can be instrumental in differentiating suspected CIT from other structures such as a Chiari network, Eustachian valve, or intracardiac tumors [12] . Optimal therapy for CIT is not defined as most data are based on case-series or registry results. However, meta-analysis data suggest superior results with thrombolytic therapy in these patients compared to alternative treatment modalities such as systemic anticoagulation or surgical embolectomy [13] . Our patient was hemodynamically unstable with a presumed diagnosis of PE, treatment with tPA was indicated. In general, thrombolytic therapy has been reported to lead to complete dissolution of CIT in <2 hours in 50% of cases while the remaining reach full resolution within 24 hours of treatment [14] . In an analysis of 177 patients with CIT, the mortality rate was 11.3% among patients receiving thrombolytics compared to 27.1% among the entire cohort treated with other therapeutic modalities such as heparin or surgical embolectomy [13] . We hypothesize the rapid deterioration and death of our patient was related to recurrent PE or acute hypoxemia related to ARDS. While the incidence of thrombotic complications among patients with COVID-19 is high, how best to identify the most high-risk individuals remains unknown. Our case highlights the need to maintain a high index of suspicion for pulmonary embolism in cases of COVID-19 with unexplained hemodynamic instability or respiratory decompensation. TEE can be performed emergently in such scnarios to gather a plethora of information such a chamber size and function and to evaluate for severe valvular lesions. Clear visualization of the pulmonary artery as well as rapid definition of CIT were added benfits of this imaging modality in our case. Performing a TEE in this patient who is mechanically ventilated in prone position TEE view of the main pulmonary artery. Simultaneous biplane transgastric TEE views demonstrate complete resolution of CIT post tPA. Simultaneous biplane transgastric TEE views demonstrate a CIT entrapped in the subvalvular apparatus. Midesophageal 4-chamber view demonstrates a markedly dilated RV with CIT entrapped in the subvalvular tricuspid valve apparatus. Midesophageal 4-chamber view demonstrates severe tricuspid regurgitation. Simultaneous biplane transgastric TEE views demonstrate complete resolution of CIT post tPA. Facing COVID-9 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research Acute pulmonary embolism and COVID-19 pneumonia: a random association? COVID-19 complicated by acute pulmonary embolism Acute Pulmonary Embolism in COVID-19 Patients on CT Angiography and Relationship to D-Dimer Levels Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia Anticoagulation treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Transesophageal echocardiography in prone position during severe acute respiratory distress syndrome Right ventricular thrombus in transit: Raising the stakes in the management of pulmonary embolism. 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