22 September 2022: Articles
Reverse Takotsubo Cardiomyopathy After Casirivimab-Imdevimab Therapy in a Patient with COVID-19: A Case Report
Challenging differential diagnosis, Unusual or unexpected effect of treatment, Unexpected drug reaction , Rare diseaseSalman Salehin1ABDEFG*, Deaa Abu Jazar1AEF, Syed Mustajab Hasan2EFG, Hussein Al-Sudani 3EF, Muhammad W. Raja2EFG
Am J Case Rep 2022; 23:e936886
BACKGROUND: Takotsubo cardiomyopathy, also referred to as apical ballooning syndrome (ABS), stress cardiomyopathy, or broken heart syndrome, initially described in Japan, is characterized by transient wall motion abnormalities involving the apical segment. Several variants have been described, including reverse type, mid-ventricular type, and the focal type. In the reverse type, there is basal hypokinesis and apical hyperkinesis. Stress cardiomyopathy is most likely to occur in middle-aged women and the underlying etiology is believed to be related to catecholamine release due to intense stress.
CASE REPORT: We report an extremely rare case of reverse takotsubo cardiomyopathy (rTTC) in a young woman with COVID-19 who was treated with Casirivimab-Imdevimab therapy. Our report is the second to reveal rTTC in a patient with COVID-19 in which obstructive coronary artery disease was definitively ruled out by coronary CT angiography.
CONCLUSIONS: Cardiovascular involvement in COVID-19 has been linked to increased morbidity and mortality rates. Recent reports have suggested the occasional occurrence of TTC and the rare occurrence of reverse takotsubo cardiomyopathy (rTTC) in patients with COVID-19. In fact, to the best of our knowledge, this is only the fifth reported case of rTTC in a patient with COVID-19; importantly, 3 out of the 4 of the previous reported cases lacked definitive ischemic work-up to rule out obstructive coronary artery disease due to the critical condition of the patients.
Keywords: casirivimab and imdevimab drug combination, COVID-19, takotsubo cardiomyopathy
The novel coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19), has now become the deadliest pandemic in the history of the United States, with a death toll surpassing that of the 1918 Spanish flu, as of September 2021, according to the COVID-19 Dashboard at Johns Hopkins University. In COVID-19, cardiac involvement manifests as cardiac myocyte injury, heart failure, arrhythmia, fulminant myocarditis, and pulmonary embolism (PE) [1,2]. Recent studies have suggested the occasional occurrence of TTC and the rare occurrence of reverse takotsubo cardiomyopathy (rTTC) in patients with COVID-19 . In fact, to the best of our knowledge, this is only the fifth reported case of rTTC in a patient with COVID-19 [4–7]; importantly, 3 out of the 4 previously reported cases lacked definitive ischemic work-up to rule out obstructive coronary artery disease due to the critical condition of the patients .
Our patient was a 24-year-old woman with history of uncomplicated C-section 7 weeks ago and recent diagnosis of COVID-19 confirmed by a positive real-time reverse transcriptase- polymerase chain reaction (RT-PCR) for SARS-CoV-2 3 days prior to admission. She initially presented to the out-patient infusion clinic for Casirivimab-Imdevimab therapy. However, upon returning home, she developed respiratory distress 3 h after receiving monoclonal antibody infusion therapy, and subsequently lost consciousness, for which she was taken to the Emergency Department. She was only minimally responsive when she arrived and was intubated due to ongoing dyspnea and for airway protection. She was also given 2 doses of intramuscular epinephrine and 1 dose of intravenous methylprednisolone for suspected anaphylactic reaction. Vital signs on admission were: temperature 37.5°C, pulse rate 123 beats per minute, respiratory rate 20 breaths per minute, blood pressure 141/106 mmHg, and oxyhemoglobin saturation of 100% on 15 L/min oxygen via bag valve mask. EKG (Figure 1A) showed new ST depression in leads V3–V6, suggestive of anterolateral wall ischemia, QTc of 450 ms, and sinus tachycardia with 103 beats per minute. Initial laboratory test results revealed troponin I elevation of 1.030 ng/ml (lab reference <0.034 ng/ml), which subsequently peaked at 6.8 ng/ml, elevated D-dimer of 0.77 µg/mL (lab reference <0.50 µg/mL), and elevated NT-proBNP of 1500 pg/ml (lab reference <125 pg/ml). A chest X-ray was grossly unremarkable (Figure 2). Empiric treatment with Remdesivir and Dexamethasone for COVID-19 pneumonia was commenced, as was aspirin (loading dose) plus heparin for possible non-ST elevation myocardial infarction (NSTEMI). The next day, transthoracic echocardiogram (TTE) revealed depressed left ventricular ejection fraction (EF) of 30–35%. The left ventricular basal to middle segments were severely hypokinetic while the distal segments and apex were hyperdynamic, consistent with rTTC (Figures 3, 4). An inferior vena cava (IVC) thrombus was noted as well. A repeat EKG 24 h later showed resolution of the ST depression (Figure 1B). A subsequent coronary CT angiogram ruled out obstructive coronary artery disease (CAD) and other coronary anatomical abnormalities, while CT pulmonary angiography ruled out pulmonary embolism, but did show subtle foci of inflammation in the superior segment of lower lobes, as evidenced by minimal ground-glass changes. Patient was successfully extubated the next day. She was treated with Metoprolol, Lisinopril, and Furosemide while an inpatient for left ventricular (LV) systolic dysfunction and received a therapeutic dose of low-molecular-weight heparin for IVC thrombus. She was discharged on guideline-directed medical therapy for heart failure with reduced LVEF, as well as Apixaban, for a total of 3 months for IVC thrombus. TTE was repeated 2 days after the first TTE, just prior to discharge, and the findings were unchanged. TTE was again repeated 2 weeks after the first TTE, and showed resolution of wall motion abnormalities and complete recovery of LVEF.
As previously mentioned, catecholamine surge is the central pathophysiologic mechanism of stress-induced cardiomyopathy. High concentrations of epinephrine trigger a switch in intracellular signal trafficking in ventricular cardiomyocytes from stimulatory Gs protein to inhibitory Gi protein signaling via the β2-adrenoceptor, which in turn protects against the proapoptotic effects of the intense activation of β1-adrenoceptors.
However, this change also causes a negative inotropic effect. Because β-adrenoceptor density is greatest at the apical myocardium, this effect is greatest in that region.
In older women, the apical variant of takotsubo occurs more frequently because the highest density of adrenoreceptors occurs in the cardiac apex in the postmenopausal age group. In younger females, the occurrence of reverse takotsubo cardiomyopathy may be due to the high density of adrenoreceptors at the cardiac base, as opposed to the apex in the elderly patients [4,5].
TTC AND THROMBOEMBOLISM:
The potential risk of intraventricular thrombus formation and systemic embolization should be addressed in patients with LV thrombus or severe LV systolic dysfunction. Echocardiography should include evaluation for potential thrombus as well as assessment of the extent of wall motion abnormality. According to the International Takotsubo Registry study, ventricular thrombus was detected in 1.3% of the 1750 patients with stress cardiomyopathy .
In our case, the patient had an IVC thrombus. The main underlying risk factors of thromboembolism for this patient were recent pregnancy  and ongoing COVID-19 . Recommended treatment includes anticoagulation for 3 months, with the duration of anticoagulation modified based on the rate of recovery of cardiac function and resolution of the thrombus.
TAKOTSUBO CARDIOMYOPATHY (TTC) VS PERIPARTUM CARDIOMYOPATHY (PPCM):
Peripartum cardiomyopathy (PPCM) can be defined as heart failure with reduced EF (<45%), which develops in the last month of pregnancy or within 5 months postpartum, with the absence of any prior heart disease and no identifiable cause of the heart failure. Given that the patient had C-section delivery prior to admission, PPCM would be a differential diagnosis for her systolic heart failure; however, a TTE is usually sufficient to differentiate these 2 entities. Although left ventricular (LV) dysfunction is similar at the initial diagnosis, PPCM is mostly associated with global or diffuse hypokinesis as compared to the regional wall motion abnormalities seen in TTC. In addition, the prognosis of LV recovery is better in TTC than in PPCM. Therefore, physicians should differentiate these 2 diseases entities, although they have several similarities in acute LV dysfunction .
TTE was repeated 2 weeks after the first TTE, and showed resolution of wall motion abnormalities and complete recovery of LVEF.
Cardiovascular involvement in COVID-19 is associated with increased morbidity and mortality rates. Recent studies have suggested the occasional occurrence of TTC and the rare occurrence of reverse takotsubo cardiomyopathy (rTTC) in patients with COVID-19. In fact, to the best of our knowledge, this is only the fifth reported case of rTTC in a patient with COVID-19, and only the second case where definitive ischemic work-up was done to rule out obstructive coronary artery disease. Of note, it cannot be confirmed whether the reverse takotsubo cardiomyopathy was a direct result of COVID-19 or if it was due to Casirivimab-Imdevimab therapy. Regardless, it would be very prudent to keep in mind that cardiomyopathies are possible consequences, albeit rare consequences, of COVID-19.
FiguresFigure 1.. Electrocardiogram on admission (A) showing ST depression in V3–V6 (anterolateral leads). Red arrows indicating ST depression. Repeat electrocardiogram 1 day after admission (B) showing normal sinus rhythm with resolution of ST depression in anterolateral leads (V3–V6). Green arrows indicate absence of ST depression. Figure 2.. CXR demonstrating unremarkable cardiomediastinal silhouette. Lungs expanded and clear. No pleural effusion seen. Figure 3.. 2D Transthoracic Echocardiogram with contrast at end-diastole (A) and without contrast at end-diastole (B). LV – left ventricle; LA – left atrium; RV – right ventricle. The red arrow indicates the cardiac apex while the blue arrow indicates interventricular septum. Figure 4.. 2D Transthoracic echocardiogram with contrast revealing basal ballooning in this case of rTTC at end-systole (A) and without contrast at end-systole (B). LV – left ventricle; LA – left atrium; RV – right ventricle. The red arrow indicates the cardiac apex while the blue arrow indicates interventricular septum. Video 1.. Transthoracic echocardiogram (TTE) with contrast showing regional wall motion abnormalities. Video 2.. TTE with contrast showing regional wall motion abnormalities. Video 3.. TTE with contrast showing regional wall motion abnormalities. Video 4.. TTE with contrast showing regional wall motion abnormalities. Video 5.. TTE without contrast showing regional wall motion abnormalities. Video 6.. TTE without contrast showing regional wall motion abnormalities.
1.. Inciardi RM, Lupi L, Zaccone G, Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19): JAMA Cardiol, 2020; 5(7); 819-24
2.. Kochi AN, Tagliari AP, Forleo GB, Cardiac and arrhythmic complications in patients with COVID-19: J Cardiovasc Electrophysiol, 2020; 31(5); 1003-8
3.. Gomez JMD, Nair G, Nanavaty P, COVID-19-associated takotsubo cardiomyopathy: BMJ Case Rep, 2020; 13; e236811
4.. Panchal A, Kyvernitakis A, Biederman R, An interesting case of COVID-19 induced reversed takotsubo cardiomyopathy and insight on cardiac bio-markers: Cureus, 2020; 12(11); e11296
5.. Demertzis ZD, Dagher C, Malette KM, Cardiac sequelae of novel coronavirus disease 2019 (COVID-19): A clinical case series: Eur Heart J Case Rep, 2020; 4(FI1); 1-6
6.. Faqihi F, Alharthy A, Alshaya R, Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: A case-report: BMC Cardiovasc Disord, 2020; 20(1); 389
7.. Sala S, Peretto G, Gramegna M, Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection: Eur Heart J, 2020; 41(19); 1861-62
8.. Ghadri JR, Wittstein IS, Prasad A, International expert consensus document on takotsubo syndrome (part I): Clinical characteristics, diagnostic criteria, and pathophysiology: Eur Heart J, 2018; 39(22); 2032-46
9.. Elesber AA, Prasad A, Bybee KA, Transient cardiac apical ballooning syndrome: Prevalence and clinical implications of right ventricular involvement: J Am Coll Cardiol, 2006; 47; 1082-83
10.. Citro R, Rigo F, D’Andrea A, Echocardiographic correlates of acute heart failure, cardiogenic shock, and in-hospital mortality in tako-tsubo cardiomyopathy: JACC Cardiovasc Imaging, 2014; 7; 119-29
11.. Ohba Y, Takemoto M, Nakano M, Takotsubo cardiomyopathy with left ventricular outflow tract obstruction: Int J Cardiol, 2006; 107; 120-22
12.. Haghi D, Rohm S, Suselbeck T, Incidence and clinical significance of mitral regurgitation in takotsubo cardiomyopathy: Clin Res Cardiol, 2010; 99; 93-98
13.. Syed FF, Asirvatham SJ, Francis J, Arrhythmia occurrence with takotsubo cardiomyopathy: A literature review: Europace, 2011; 13; 780-88
14.. Awad HH, McNeal AR, Goyal H, Reverse takotsubo cardiomyopathy: A comprehensive review: Ann Transl Med, 2018; 6(23); 460
15.. Paur H, Wright PT, Sikkel MB, High levels of circulating epinephrine trigger apical cardiodepression in a β2-adrenergic receptor/Gi-dependent manner: A new model of takotsubo cardiomyopathy: Circulation, 2012; 126(6); 697-706
16.. James AH, Pregnancy and thrombotic risk: Crit Care Med, 2010; 38(2 Suppl.); S57-63
17.. Schmidt M, Horvath-Puho E, Thomsen RW, Acute infections and venous thromboembolism: J Intern Med, 2012; 271(6); 608-18
18.. Yang WI, Moon JY, Shim M, Clinical features differentiating takotsubo cardiomyopathy in the peripartum period from peripartum cardiomyopathy: Heart Vessels, 2020; 35(5); 665-71
23 November 2022 : Case reportMepolizumab as a Potential Protective Factor of COVID-19 Mortality: A Case Report of Chronic Bronchitis and...
Am J Case Rep In Press; DOI: 10.12659/AJCR.938450
01 November 2022 : Case reportCentral Retinal Vein Occlusion After Discontinuation of Rivaroxaban Therapy in a Young Patient with COVID-1...
Am J Case Rep 2022; 23:e937739
25 October 2022 : Case reportInhaled Nitric Oxide in Acute Severe Pulmonary Hypertension and Severe Acute Respiratory Distress Syndrome ...
Am J Case Rep 2022; 23:e937147
25 Nov 2022 : Case reportA Case Report of Listeria Meningitis with Severe Rhabdomyolysis and Normal Renal Function
Am J Case Rep In Press; DOI: 10.12659/AJCR.938024
24 Nov 2022 : Case reportCardiac Arrest Following Torsades de Pointes Caused by Hypokalemia and Catecholamines in a Patient with Con...
Am J Case Rep In Press; DOI: 10.12659/AJCR.938609
24 Nov 2022 : Case reportA Large Pericardial Cyst in the Left Cardiophrenic Causing Persistent Chest Pain and Cough: A Case Report
Am J Case Rep In Press; DOI: 10.12659/AJCR.937785
Most Viewed Current Articles
13 Jul 2022 : Case reportWhistling Scrotum: An Unusual Presentation of Pneumomediastinum in the Setting of an Open Scrotal Wound
Am J Case Rep 2022; 23:e936441
23 Feb 2022 : Case reportPenile Necrosis Associated with Local Intravenous Injection of Cocaine
Am J Case Rep 2022; 23:e935250
06 Dec 2021 : Case reportLipedema Can Be Treated Non-Surgically: A Report of 5 Cases
Am J Case Rep 2021; 22:e934406