iMAIL Figure 1D · 15/7/2020  · Begoña González de Marcos, MD Guillermo Reyes, MD Clara Salas,...

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COVID-19 “Fulminant Myocarditis”

Successfully Treated With Temporary

Mechanical Circulatory Support

A previously healthy 44-year-old man was admittedto our hospital for severe dyspnea and syncope onMarch 25, 2020. Seven days before, during the esca-lating Coronavirus Disease-2019 (COVID-19)pandemic in our country, he presented at the Emer-gency Department with fever, dry cough, diarrhea,and myalgia, being diagnosed as presumed COVID-19infection. He was discharged home with symptomatictherapy and isolation measures. However, symptomsworsened over the following days and finally he cameback with severe bradycardia, hypotension, and signsof peripheral hypoperfusion. The electrocardiogram(ECG) showed a third-degree atrioventricular block(Figure 1A) and an echocardiogram revealed a non-dilated but globally and severely dysfunctional leftventricle (left ventricular ejection fraction [LVEF]w15%) (Video 1). A temporary pacemaker wasimplanted and both dobutamine and norepinephrineperfusions were initiated but, eventually, intubationand mechanical ventilation were required. High-sensitive troponin T peak was 745 ng/l, creatine-kinase isoenzyme MB was 30 U/l, and N-terminalpro–B-type natriuretic peptide increased to 24,167pg/ml. Nasopharyngeal and oropharyngeal swabs forpolymerase chain reaction test of COVID-19 andother respiratory viral infections were obtained.Only SARS-CoV-2 had positive results, whereasinfluenza A virus, influenza A H1N1, influenza A H3N2,bocavirus, adenovirus, rhinovirus, parainfluenza,metapneumovirus, influenza B virus, other commoncoronaviruses, and respiratory syncytial virus werenegative. Legionella pneumophilla, Mycoplasmapneumoniae, and Chlamydophila pneumonia sero-logical test results were negative. Chest X-ray showedsigns of bilateral pneumonia (Figure 1B). In spite ofincreasing doses of vasoactive drugs, hemodynamicderangement ensued and in this dramatic clinicalscenario urgent coronary angiography revealednormal coronary arteries. Venous-arterial extracorpo-real membrane oxygenation (Figure 1C) and an intra-aortic balloon pump were implanted through femoralcannulation with drastic improvement of the hemo-dynamic condition. Several endomyocardial biopsy

samples were obtained (Figure 1D). A working diag-nosis of “fulminant myocarditis” was made, and a1,000-mg bolus of methylprednisolone was adminis-tered followed by treatment with tocilizumab,hydroxychloroquine, azithromycin, and lopinavir-ritonavir. Blood test results showed abnormal valuesof D-dimer (3.17 mg/ml), ferritin (1,135 ng/ml), andcirculating interleukin-6 (121.71 pg/l). Myocardialsamples showed no significant inflammatory in-filtrates, even after CD3, CD20, and CD68 staining(Figures 1E and 1F) and steroid therapy was withheld.Clinical status improved during the following days,with a rapid reduction of lactate levels to normalvalues, normalization of kidney and liver functions,and progressive recovery in left ventricular systolicfunction (Video 2). Blood test results showed reductionof high-sensitive troponin T levels to 221 ng/l and N-terminal pro–B-type natriuretic peptide to 7,624 pg/ml. Venous-arterial extracorporeal membraneoxygenation and the intra-aortic balloon could besuccessfully withdrawn 6 days after implantation andthe patient could be eventually weaned from ventila-tion 2 days later. On day 14 from admission, cardiacmagnetic resonance imaging was performed. A non-dilated left ventricle without regional wall motionabnormalities was seen (LVEFw75%) (Video 3). NativeT1 (mean, 1,120 ms), T2 signal intensity ratio (myocar-dium to serratus anterior muscle on T2 images pro-cessed using a signal intensity correction algorithm),and extracellular volume (mean, 36%) were diffuselyincreased with slightly less involvement of theinferolateral wall (Figures 1G to 1I). Late gadoliniumenhancement was negative (Supplemental Figure 1).These findings were suggestive of diffuse edemawithout macroscopic necrosis. Subsequent clinicalcourse was uneventful with a striking complete re-covery of left ventricular systolic function (LVEFw70%) on echocardiography.

The year 2020 will be remembered for the worldpandemic due to coronavirus-2019 (COVID-19) infec-tion. COVID-19 morbidity and mortality are mainlyassociated with lung involvement. However, under-lying cardiovascular conditions play a major role inclinical outcomes (1,2). Moreover, recent studiessuggest that cardiac injury has important prognosticimplications. Elevations in cardiac troponin levels arefrequently seen with clinically evident myocardialdamage demonstrated in most severe cases (1,2).However, so far, only a few cases of COVID-19–relatedmyocarditis have been described (3–5). Unspecificpathological findings have been described in isolated

FIGURE 1 ECG, Radiographic, Angiographic, Myocardial Biopsy, and Cardiac Magnetic Resonance Findings

AC

VC

VC

PM

EMB

LVRV

LVRV

LVRV

A B C D

E F G H I

(A) ECG showing complete atrio-ventricular block. (B) Chest X-ray depicting diffuse bilateral infiltrates. (C) Femoral access VA-ECMO. (D) Radiological image showing

the EMB forces. (E) EMB without necrosis, inflammation, or fibrosis (HEx200). (F) Isolated intersticial infiltrate with lymphocytes CD3þ (yellow arrows). (G,H)

T2-weighted and T2 signal intensity ratio mapping images (blue indicates a ratio more than 2) showing diffuse edema with slightly less involvement of the inferolateral

wall. (I) T1 mapping with diffuse increase of native T1 (septal T1 ¼ 1,120 ms) following the pattern of edema. AC ¼ arterial cannula; ECG ¼ electrocardiogram;

EMB ¼ endomyocardial biopsy; PM ¼ pacemaker; VA-ECMO ¼ veno-arterial extracorporeal membrane oxygenation; LV ¼ left ventricle; RV ¼ right ventricle;

VC ¼ venous cannula.

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reports with only 1 necropsy study reporting mildinflammatory infiltrate (5). However, we report thesuccessful treatment of cardiogenic shock withtemporary mechanical circulatory support in a pa-tient with a clear diagnosis of COVID-19 infectionpresenting as fulminant myocarditis. Takotsubocardiomyopathy remains a potential differentialdiagnosis considering the stressful situation, themyocardial edema, and the transient left ventriculardysfunction. A wide phenotypic presentation ofmyocardial damage appears to exist in patients withCOVID-19, ranging from mild myocardial injury(asymptomatic troponin elevation) to severe formsof myocarditis (likely secondary to the cytokinestorm). The absence of scar might be a clinicalmarker of myocardial recovery. The fact that cardiacfunction fully recovered after a few days of me-chanical circulatory support is of major interest,opening new avenues for the management of pa-tients critically ill with COVID-19 with fulminantmyocarditis because complete recovery of themyocardial function can be expected.

The patient provided informed consent to pub-lish his data but institutional review board approval

was not requested considering that this was aclinical observation obtained in a single patientwho was strictly treated according to standardclinical practice.

Jorge Salamanca, MDPablo Díez-Villanueva, MDPablo Martínez, MDAlberto Cecconi, MDBegoña González de Marcos, MDGuillermo Reyes, MDClara Salas, MDJavier Segovia, MDLuis Jesús Jiménez-Borreguero, MDFernando Alfonso, MD*

*Department of CardiologyHospital Universitario de La PrincesaInstituto de Investigación Sanitaria PrincesaCIBER-CV, Universidad Autónoma de MadridCalle Diego de León, 6228006 MadridSpainE-mail: falf@hotmail.comhttps://doi.org/10.1016/j.jcmg.2020.05.003

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All authors have reported that they have no relationships relevant to thecontents of this paper to disclose.The authors attest they are in compliance with human studies committees andanimal welfare regulations of the authors’ institutions and Food and DrugAdministration guidelines, including patient consent where appropriate. Formore information, visit the JACC: Cardiovascular Imaging author instructionspage.

RE F E RENCE S

1. Guo T, Fan Y, Chen M, et al. Cardiovascular implications of fatal outcomes ofpatients with Coronavirus Disease 2019 (COVID-19). JAMA Cardiol 2020;5:1–8.

2. Akhmerov A, Marban E. COVID-19 and the Heart. Circ Res 2020;126:1443–55.

3. Hu H, Ma F, Wei X, Fang Y. Coronavirus fulminant myocarditis saved withglucocorticoid and human immunoglobulin. Eur Heart J 2020 Mar 16 [E-pubahead of print].

4. Zeng JH, Liu YX, Yuan J, et al. First case of COVID-19 infection withfulminant myocarditis complication: case report and insights. Infection 2020Apr 10 [E-pub ahead of print].

5. Sala S, Peretto G, Gramegna M, et al. Acute myocarditis presenting as areverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratoryinfection. Eur Heart J 2020;41:1861–2.

APPENDIX For a supplemental figure and videos, please see theonline version of this paper.