key: cord-0867769-e1ian43y authors: Nicola, Bernardi; Emiliano, Calvi; Giuliana, Cimino; Greta, Pascariello; Matilde, Nardi; Dario, Cani; Pompilio, Faggiano; Enrico, Vizzardi; Di Meo, Nunzia; Marco Metra title: Covid-19 pneumonia, Takotsubo syndrome and left ventricle thrombi date: 2020-06-12 journal: JACC Case Rep DOI: 10.1016/j.jaccas.2020.06.008 sha: f79047c34a7792fd71c9e3bbd32186009ffd0471 doc_id: 867769 cord_uid: e1ian43y Left ventricle thrombus is considered a rare complication of Takotsubo syndrome. However, both a stress condition predisposing to Takotsubo syndrome and coagulation abnormalities coexist in COVID-19. We describe a case of COVID-19 patient with Takotsubo. COVID-19 = coronavirus interstitial disease cTnT = cardiac troponin T ECG = electrocardiogram PaO2 = oxygen partial pressure PaCO2 = carbon dioxide partial pressure NT-pro-BNP = N terminal pro-brain natriuretic peptide WBC = white blood cells STEMI = ST elevation myocardial infarction VTE = venous thromboembolism DVT = deep vein thrombosis LVEF = left ventricle ejection fraction calculated by Simpson's biplane method Abstract: Left ventricle thrombus is considered a rare complication of Takotsubo syndrome. However, both a stress condition predisposing to Takotsubo syndrome and coagulation abnormalities coexist in COVID-19. We describe a case of COVID-19 patient with Takotsubo. A 74-year-old male presented to the emergency department of a peripheral hospital with fever up to 38 C°, dyspnoea and cough. Physical examination revealed blood pressure of 135/85mmHg, heart rate of 95bpm. Arterial gas analysis showed pH=7.46, PaO2=57mmHg, PaCO2=36mmHg underlining respiratory failure. O2 therapy with C-PAP was started and the patient was hospitalized in the internal medicine unit. Chest X-ray was indicative of COVID pneumonia (Figure 1) . Therapy with azithromycin (500mg once daily), hydroxychloroquine (200mg twice daily) and dexamethasone (20mg once daily for 5 days and then 10mg once daily for 5 days) was started. A nasopharyngeal swab was positive for SARS-CoV-2 on real-time reverse transcriptase polymerase chain reaction assay. Five days later at his hospitalization, the patient presented retrosternal typical chest pain. ECG demonstrated ST segment elevation in antero-lateral leads suggesting an acute myocardial infarction (Figure 2 ). Arterial hypertension, dyslipidaemia and impaired fasting blood sugar. The differential diagnosis included acute myocardial infarction, Takotsubo syndrome, myocarditis and coronary embolism. The patient was transferred to our centre for an urgent coronary angiography which revealed non-significant coronary atherosclerosis. In order to make a diagnosis, a few days after, we performed a cardiac magnetic resonance which showed an increased tele-systolic volume with a severe systolic dysfunction Our priority was to treat the patient with Enoxaparin 7000UI twice daily as per patient's weight. During the first days of hospitalization, and taken into consideration that the patient was hypotensive (systolic blood pressure=80mmHg, mean blood pressure<65mmHg). He was treated with intravenous dobutamine at 5 mcg/kg/min with a progressive stabilization of pressure and heart rate. Heart-failure directed treatment was not started because of hypotension. COVID-19 rapidly spread worldwide with critical challenges for public health systems. The clinical course of this illness is mostly characterized by respiratory tract symptoms including fever, cough, fatigue, pharyngodynia and acute respiratory distress syndrome. Even though the presence of both extrapulmonary and other cardiovascular manifestations has been reported previously (1), coexistence of Takotsubo syndrome and COVID-19 have been reported only three cases, to date (2-3-4) . This is the first report of a case of symptomatic Takotsubo syndrome complicated by left ventricle thrombi. Ventricle thrombi are a very rare complication of stress cardiomyopathy (5) . There is growing evidence that COVID-19 may be associated with exaggerated inflammatory response with an abnormal activation of the coagulation system and signs of small vessel vasculitis and extensive micro thrombosis (6) . Although the specific mechanism of this response is not fully understood, it can cause profound changes in the patients' coagulation function; this pattern of presentation is associated with poor prognosis (7) . These observations are confirmed by changes in coagulation tests such as increased D-dimer and decreased fibrinogen. Interestingly, cases of small pulmonary embolism are reported in the literature, even in absence of DVT (8) . This evidence has oriented the therapeutic approach, which now includes a parenteral anticoagulant drug (such as unfractionated heparin or lowmolecular-weight heparin) as a thromboprophylaxis strategy to reduce hospital stay and mortality (9) . Accordingly, a study by Fei Zhou et al. showed a lower 28-day mortality in hospitalized patients who were treated with heparin than in those who were not (10). Our patient was treated with Enoxaparin leading to complete resolution of the thrombi in about two weeks. The use of heparin is recommended in COVID-19 patients. On the other hand, the use of NOAC is still being studied in thrombosis of the ventricle and in general these drugs are substituted by heparin in COVID patients (11) . Regarding Takotsubo cardiomyopathy, more evidence is needed to find a possible link between stress cardiomyopathy and COVID-19. Chest radiography was repeated in the following days and showed progressive reduction of interstitial pneumonia. Also, blood test revealed an improvement of inflammation indexes (table 1) . On day 7 of hospitalization, nasopharyngeal swab was repeated with a positive result. The first negative result was registered on day 15. On the 14th day, we performed another transthoracic echocardiography which showed the resolution of the two thrombi (Figure 7) and a complete restoration of left ventricle systolic function (LVEF=57%) (Video 5). The parenteral anticoagulant was then gradually switched to a long-term oral anticoagulant therapy with Warfarin (dosage adjustment according to INR values, with INR range of 2-3). Then, after three weeks of hospitalization, the patient, asymptomatic and in good hemodynamic compensation, was discharged. We consider clinically relevant to report this case of Takotsubo syndrome accompanying COVID-19; this may allow to improve the knowledge about this new disease. Furthermore, coagulation disorders in COVID-19 patients are very frequent and it is important to screen carefully. On the therapeutic side, in this case LMWH has proven effective in solving thrombosis. HB=Haemoglobin (g/dl); WBC=white blood cells (x10 3 /uL); Neutrophil (x10 3 /uL); Lymphocytes (x10 3 /uL); PLT=Platelets (x10 3 /uL); Creatinine (mg/dl); Fibrinogen (mg/dl); Ddimer (ng/ml); PCR (mg/L). 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A meta-summary of case reports DOACs in left ventricular thrombosis