Right Ventricle Thrombus in a Massive Pulmonary Embolism COVID-19 Patient

The coronavirus disease 2019 (COVID-19) infection presents with a wild range of clinical manifestations. Increased inflammatory response and thrombotic risk have been described, being pulmonary embolism a potential cause of death in these patients. Pulmonary embolisms with right ventricle thrombus are rare and have higher mortality rates. This case report concerns a rare clinical presentation of a 75-year-old male with a medical history of right renal transplantation 36 years ago, that presented with a ten-day history of asthenia, followed by fever, shortness of breath, and cough since the day before. He was admitted with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia and respiratory insufficiency. The next morning the patient worsened, he presented with hypotension, tachycardia, severe refractory hypoxemia, and chest pain. Contrast CT showed a massive pulmonary embolism with a right ventricle thrombus, confirmed by an echocardiogram. Anticoagulation and IV fluids were started, and the patient was transferred to the ICU. He developed obstructive shock, so thrombolysis was performed with a full dose of alteplase. The outcome was good with complete recovery. Posterior investigation excluded other causes for pulmonary embolism. The severity of pulmonary parenchymal disease secondary to COVID-19 correlates with thromboembolic complications, which demand a swift response to avoid death. An abrupt deterioration in oxygenation should raise suspicion for PE in COVID-19 patients, and mostly in the presence of hypotension and tachycardia. In our case report, there was a massive pulmonary embolism with a rare right ventricle thrombus that had a good outcome with medical treatment.


Introduction
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus presents with a wide range of clinical manifestations [1].The typical presentation of severe infection is viral pneumonia with respiratory insufficiency.It can also affect multiple systems, including the cardiovascular system [2,3].
An abrupt deterioration in oxygenation should raise suspicion for PE in COVID-19 patients, and mostly in the presence of hypotension and tachycardia [2,3].The early diagnosis of PE and prompt treatment are vital [2].The treatment of intracardiac thrombi can be with either anticoagulation, fibrinolytic therapy, and/or surgical embolectomy depending on the stability of the patient as well as the balance of its risks and benefits [17,19].

Case Presentation
The patient was a 75-year-old male that presented to the emergency with a ten-day history of asthenia followed by fever, shortness of breath, and cough since the day before.His past medical history included right renal transplantation 36 years ago, with no complications and regular use of prednisolone and azathioprine.The vital signs showed tachycardia (HR 100 bpm), normal blood pressure (BP 100/67 mmHg), apirexia (TT 36.4 ºC), and low O 2 saturation (91% in a 28% Venturi mask) with a respiratory rate of 14 breaths per minute.Physical examination revealed bilateral rales and the use of accessory muscles.Chest xray revealed a normal cardiac silhouette and evidence of bilateral pneumonia.Chest CT showed extensive bilateral pneumonia with ground-glass opacities and consolidation and crazy-paving pattern.Laboratory investigation revealed an elevated C-reactive protein at 156 mg/L (normal range <6 mg/L), elevated white blood cells of 11.6 x 10 9 /L (normal range 4 -10 x10 9 /L) with prominent neutrophilia (78%); hemoglobin was normal (14 g/dL) as well as procalcitonin (0.15 ng/mL) and renal function (creatinine 1 mg/dL, urea 53 mg/dL); it also revealed an elevated high sensitivity troponin I of 2,397 ng/L (normal range < 14 ng/L), an Nterminal pro-brain natriuretic peptide (NT-proBNP) of 13,287 pg/mL (normal range <100 pg/mL).The SARS-CoV-2 PCR test was positive.Arterial blood gas (FiO 2 28%) showed type I respiratory insufficiency (pH 7.48, PaCO 2 27 mmHg, PaO 2 68 mmHg, HCO 3 24 mmHg, lactate 1.3 mmol/L).An electrocardiogram (ECG) showed sinus tachycardia, with right brunch block, without evidence of ischemia.Urine antigen tests for Legionella pneumophila and Streptococcus pneumoniae were negative.Blood cultures were also negative.The patient was transferred to the intensive care unit (ICU).The patient worsened a few hours later with refractory hypotension and respiratory difficulty despite proper oxygenation, so it was admitted that the PE was causing obstructive shock.Thrombolysis was performed with full dose alteplase (100mg) for two hours, followed by non-fractionated heparin (NFH) in the dose of 18 U/kg/h for three days and posterior switch to LMVH.A venous Doppler ruled out deep vein thrombosis.The ICU stay was complicated with a minor hematoma of the right superior arm with no vascular or neurologic compromise, nor hemodynamic instability or even significant hemoglobin decrease.The control TTE in the fourth day of admission showed improvement and the RV thrombus was no longer detected.Ceftriaxone and dexamethasone were maintained for eight days and azithromycin for five days with reduction of the inflammatory markers.Clinical improvement allowed oxygen reduction and step-down of care and anticoagulation was switched to apixaban.
The patient was discharged with a normal TTE and reevaluated in outpatient clinic.Malignancy was ruled out by complete body CT and upper and lower gastrointestinal endoscopy.Hypercoagulable state was also ruled out with negative anticardiolipin, antinuclear, antiphospholipid, and beta-2-glycoprotein antibodies, as well as normal homocysteine, antithrombin, protein C and protein S. Anticoagulation was maintained for six months.No other thrombotic events were registered.The COVID-19 infection appeared to be the cause of the RV thrombus and massive PE.

Discussion
Though affecting mostly, the respiratory system, causing severe pneumonia and even acute respiratory distress syndrome (ARDS) [1].COVID-19 infection may cause hypercoagulopathy and thrombotic complications that have been well-accessed in the literature [2,4,5].
McFadyen et al. supported this by showing that the thrombotic manifestations of severe COVID-19 are related to the endothelial dysfunction caused by the SARS-CoV-2 ability to directly infect endothelial cells via ACE-2 receptors expressed on the endothelial cell surface in the lungs, vessels, and heart [4].Trepa et al. reviewed as PE is one of the most severe thrombotic complications of COVID-19, and that its incidence is likely higher than other known viral infections.The incidence varies in the literature, but there is a consensus that is higher in critical patients [2,10,14,16].
Ogren et al. studied the prevalence and risk of PE in patients with intracardiac thrombosis [11].As Sakellariou et al. reviewed right heart thrombi are detected in approximately 4% of patients with PE [17].RV thrombus is even rarer than right atria, but both have been described [6][7][8][9][10][11][12][13].The treatment of intracardiac varies with each case, each patient, their hemodynamic stability, and the balance of their risks and benefits.The treatment includes anticoagulation, fibrinolytic therapy, and/or surgical embolectomy [17,19].
Sakellariou et al. reviewed that mobile right heart thrombi require rapid therapeutic choices between surgical thrombectomy and thrombolysis.They also presented a successful case of medical thrombolysis [4].The absence of cardiothoracic surgery service in our hospital, as well as the high distance to a center where thrombectomy was feasible, ruled out that option.The fast deterioration of the patient's status with evolution to cardiac shock demanded fast action, and the prompt start of fibrinolytic therapy with a full dose of alteplase was successful.
Wichmann et al. established that PE was the direct cause of death in a third of COVID-19 patients that were autopsied [18].Tang et al. associated raised d-dimers with severe presentation and death [5].Despite these risk factors and also the increased risk associated with the presence of intracardiac thrombus, our patient had a good outcome.In the present case, the patient was admitted at the end of 2020, to a secondary hospital in Portugal, at the peak second wave of COVID-19.The available resources were scarce, both human and material resources (echocardiogram was not usually available outside working hours, and its use on COVID-19 patients was very limited; hemodialysis was also not available for COVID-19 patients), and supply shortages of medical resources were even more exacerbated by disruptions to the global supply chain [20,21].Nevertheless, reviewing the case, this patient should have had a contrast CT at admission.

Conclusions
Hypercoagulability is a known complication of COVID-19 and thrombosis can occur in various forms, including PE and RV thrombus.These complications are more frequent in critically ill patients, and their severity is linked with the severity of COVID-19 pneumonia.Despite being potentially fatal, a massive PE with an RV thrombus can be successfully treated with medical treatment.
The patient was admitted to the COVID-19 ward and started on dexamethasone and IV ceftriaxone and azithromycin for COVID-19 pneumonia with suspected secondary bacterial infection.The next morning patient deteriorated with hypotension (BP 89/53 mmHg), tachycardia (HR 110 bpm), increased respiratory rate (18 breaths per minute) with the use of accessory muscles, shortness of breath while speaking, and desaturation.He also complained of sharp and stabbing type chest pain 8/10, that radiated to the back.The patient was hypoxic so non-rebreather mask at 15 L/min was started.ECG showed sinus tachycardia, with right bundle branch block, with inframillimetric ST elevation in AVR and DIII, and inframillimetric ST depression in DI, AVL, V5, and V6 (Figure1).Blood arterial gas (FiO 2 60%) showed respiratory alkalemia with hypoxemia and (pH 7.49, PaCO 2 23 mmHg, PaO 2 75 mmHg, HCO 3 21 mmHg, lactate 2.2 mmol/L).Anticoagulation with low-molecular-weight heparin (LMWH) and IV fluids was started.

FIGURE 2 :FIGURE 3 :
FIGURE 2: CT pulmonary angiography showing massive pulmonary embolism Klok et al. and Trepa et al.  both explored the importance of prevention with thrombosis prophylaxis in COVID-19 as well as the vital importance of monitoring these patients for signs of thrombotic complications[2,3].In our case, the suspicion of PE should have been made at admission, especially on the presence of tachycardia, and elevation of troponin and BNP, despite the uncharacteristic initial ECG.D-dimers should have been tested to rule out PE, the diagnosis would probably have been made some hours earlier.