The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Patient 1 (P1)
3.2. Patient 2 (P2)
3.3. Patient 3 (P3)
3.4. Patient 4 (P4)
3.5. Patient 5 (P5)
3.6. Patient 6 (P6)
3.7. Patient 7 (P7)
4. Discussion
4.1. Main Findings
4.2. Diagnostic Workup
4.3. Disease Features and Etiology
4.4. Arrhythmias and Devices
4.5. Follow-Up and Treatment
4.6. Study Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
- Hendren, N.S.; Drazner, M.H.; Bozkurt, B.; Cooper, L.T., Jr. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation 2020, 141, 1903–1914. [Google Scholar] [CrossRef] [PubMed]
- Tschöpe, C.; Ammirati, E.; Bozkurt, B.; Caforio, A.L.P.; Cooper, L.T.; Felix, S.B.; Hare, J.M.; Heidecker, B.; Heymans, S.; Hübner, N.; et al. Myocarditis and inflammatory cardiomyopathy: Current evidence and future directions. Nat. Rev. Cardiol. 2020, 1–25. [Google Scholar] [CrossRef]
- Peretto, G.; Sala, S.; Caforio, A.L.P. Acute myocardial injury, MINOCA, or myocarditis? Improving characterization of coronavirus-associated myocardial involvement. Eur. Heart J. 2020, 41, 2124–2125. [Google Scholar] [CrossRef]
- Peretto, G.; De Luca, G.; Campochiaro, C.; Palmisano, A.; Busnardo, E.; Sartorelli, S.; Barzaghi, F.; Cicalese, M.P.; Esposito, A.; Sala, S. Telemedicine in myocarditis: Evolution of a mutidisciplinary "disease unit" at the time of COVID-19 pandemic. Am. Heart J. 2020, 229, 121–126. [Google Scholar] [CrossRef] [PubMed]
- Ferreira, V.M.; Schulz-Menger, J.; Holmvang, G.; Kramer, C.M.; Carbone, I.; Sechtem, U.; Kindermann, I.; Gutberlet, M.; Cooper, L.T.; Liu, P.; et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J. Am. Coll. Cardiol. 2018, 72, 3158–3176. [Google Scholar] [CrossRef] [PubMed]
- Caforio, A.L.; Pankuweit, S.; Arbustini, E.; Basso, C.; Gimeno-Blanes, J.; Felix, S.B.; Fu, M.; Heliö, T.; Heymans, S.; Jahns, R. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis. Eur. Heart J. 2013, 34, 2636–2648. [Google Scholar] [CrossRef]
- Peretto, G.; Sala, S.; Rizzo, S.; De Luca, G.; Campochiaro, C.; Sartorelli, S.; Benedetti, G.; Palmisano, A.; Esposito, A.; Tresoldi, M.; et al. Arrhythmias in myocarditis: State of the art. Heart Rhythm 2019, 16, 793–801. [Google Scholar] [CrossRef] [PubMed]
- Mazzone, P.; Peretto, G.; Radinovic, A.; Limite, L.R.; Marzi, A.; Sala, S.; Cireddu, M.; Vegara, P.; Baratto, F.; Paglino, G.; et al. The COVID-19 challenge to cardiac electrophysiologists: Optimizing resources at a referral center. J. Interv. Card Electrophysiol. 2020, 18, 1–7. [Google Scholar] [CrossRef]
- Esposito, A.; Palmisano, A.; Natale, L.; Ligabue, G.; Peretto, G.; Lovato, L.; Vignale, D.; Fiocchi, F.; Marano, R.; Russo, V. Cardiac Magnetic Resonance Characterization of Myocarditis-Like Acute Cardiac Syndrome in COVID-19. JACC Cardiovasc. Imaging 2020. [Google Scholar] [CrossRef]
- Ammirati, E.; Frigerio, M.; Adler, E.D.; Basso, C.; Birnie, D.H.; Brambatti, M.; Friedrich, M.G.; Klingel, K.; Lehtonen, J.; Moslehi, J.J.; et al. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circ. Heart Fail. 2020, 13, e007405. [Google Scholar] [CrossRef]
- Palmisano, A.; Vignale, D.; Peretto, G.; Busnardo, E.; Calcagno, C.; Campochiaro, C.; De Luca, G.; Sala, S.; Ferro, P.; Basso, C.; et al. Hybrid FDG-PET/MR or FDG-PET/CT to Detect Disease Activity in Patients With Persisting Arrhythmias After Myocarditis. JACC Cardiovasc. Imaging 2020, 10. [Google Scholar] [CrossRef] [PubMed]
- Basso, C.; Leone, O.; Rizzo, S.; De Gaspari, M.; van der Wal, A.C.; Aubry, M.C.; Bois, M.C.; Lin, P.T.; Maleszewski, J.J.; Stone, J.R. Pathological features of COVID-19-associated myocardial injury: A multicentre cardiovascular pathology study. Eur. Heart J. 2020, 41, 3827–3835. [Google Scholar] [CrossRef] [PubMed]
- Chu, D.K.W.; Pan, Y.; Cheng, S.M.S.; Hui, K.P.Y.; Krishnan, P.; Liu, Y.; Ng, D.Y.M.; Wan, C.K.C.; Yang, P.; Wang, Q.; et al. Molecular Diagnosis of a Novel Coronavirus (2019-nCoV) Causing an Outbreak of Pneumonia. Clin. Chem. 2020, 66, 549–555. [Google Scholar] [CrossRef] [Green Version]
- Koepsell, S.A.; Anderson, D.R.; Radio, S.J. Parvovirus B19 is a bystander in adult myocarditis. Cardiovasc. Pathol. 2012, 21, 476–481. [Google Scholar] [CrossRef] [PubMed]
- Del Nonno, F.; Frustaci, A.; Verardo, R.; Chimenti, C.; Nicastri, E.; Antinori, A.; Petrosillo, N.; Lalle, E.; Agrati, C.; Ippolito, G. Virus-Negative Myopericarditis in Human Coronavirus Infection: Report from an Autopsy Series. Circ. Heart Fail. 2020, 13. [Google Scholar] [CrossRef]
- Caforio, A.; Mahon, N.G.; Baig, M.K.; Tona, F.; Murphy, R.T.; Elliott, P.M.; McKenna, W.J. Prospective familial assessment in dilated cardiomyopathy—Cardiac autoantibodies predict disease development in asymptomatic relatives. Circulation 2007, 115, 76–83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sala, S.; Peretto, G.; Gramegna, M.; Palmisano, A.; Villatore, A.; Vignale, D.; De Cobelli, F.; Tresoldi, M.; Cappelletti, A.M.; Basso, C.; et al. Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection. Eur. Heart J. 2020, 41, 1861–1862. [Google Scholar] [CrossRef]
- Peretto, G.; Sala, S.; Rizzo, S.; Palmisano, A.; Esposito, A.; De Cobelli, F.; Campochiaro, C.; De Luca, G.; Foppoli, L.; Dagna, L.; et al. Ventricular Arrhythmias in Myocarditis: Characterization and Relationships with Myocardial Inflammation. J. Am. Coll. Cardiol. 2020, 75, 1046–1057. [Google Scholar] [CrossRef]
- Sala, S.; Peretto, G.; De Luca, G.; Farina, N.; Campochiaro, C.; Tresoldi, M.; Dagna, L.; Zangrillo, A.; Gulletta, S.; Della Bella, P. Low prevalence of arrhythmias in clinically stable COVID-19 patients. Pacing Clin. Electrophysiol. 2020, 16. [Google Scholar] [CrossRef]
- Oloriz, T.; Wellens, H.J.; Santagostino, G.; Trevisi, N.; Silberbauer, J.; Peretto, G.; Maccabelli, G.; Della Bella, P. The value of the 12-lead electrocardiogram in localizing the scar in non-ischaemic cardiomyopathy. Europace 2016, 18, 1850–1859. [Google Scholar] [CrossRef]
- Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA 2020, 323, 1824–1836. [Google Scholar] [CrossRef]
- De Luca, G.; Campochiaro, C.; Dinarello, C.A.; Dagna, L.; Cavalli, G. Treatment of Dilated Cardiomyopathy with Interleukin-1 Inhibition. Ann. Intern Med. 2018, 169, 819–820. [Google Scholar] [CrossRef]
- Frustaci, A.; Russo, M.A.; Chimenti, C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: The TIMIC study. Eur. Heart J 2009, 30, 1995–2002. [Google Scholar] [CrossRef] [PubMed]
- De Luca, G.; Campochiaro, C.; Sartorelli, S.; Peretto, G.; Dagna, L. Therapeutic strategies for virus-negative myocarditis: A comprehensive review. Eur. J. Int. Med. 2020, 77, 9–17. [Google Scholar] [CrossRef] [PubMed]
- Peretto, G.; Sala, S.; De Luca, G.; Marcolongo, R.; Campochiaro, C.; Sartorelli, S.; Tresoldi, M.; Foppoli, L.; Palmisano, A.; Esposito, A.; et al. Immunosuppressive Therapy and Risk Stratification of Patients with Myocarditis Presenting With Ventricular Arrhythmias. JACC Clin. Electrophysiol. 2020, 6, 1221–1234. [Google Scholar] [CrossRef] [PubMed]
Features | P1 | P2 | P3 | P4 | P5 | P6 | P7 |
---|---|---|---|---|---|---|---|
General features | |||||||
Age, y | 43 | 38 | 58 | 45 | 64 | 50 | 56 |
Gender | female | male | female | male | male | male | female |
Ethnicity | African American | African American | Caucasian | Caucasian | Caucasian | Caucasian | Caucasian |
COVID diagnosis | NPS | NPS | NPS | NPS, BAS, BAL | NPS | NPS | NPS |
Pneumonia diagnosis | XR, CT | XR, CT | XR, CT | XR, CT | negative | XR, CT | negative |
Delay from first cardiac abnormality to pneumonia, days | 0 | 6 | 0 | 8 | no | 12 | no |
Clinical presentation | |||||||
Myocarditis presentation | ACS-like | HF | ACS-like | HF | VA | HF | ACS-like, HF |
Sp02, % | 89 | 96 | 96 | 88 | 81 | 88 | 76 |
T, °C | 37.7 | 36.5 | 37.0 | 38.5 | 38.7 | 37.1 | 36.2 |
Prodromes | fever, vomit | cough | fever, vomit, diarrhea | fever, vomit, diarrhea | no | cough | fever |
Delay from prodromes to cardiac symptoms, days | 2 | 7 | 7 | 5 | 0 | 10 | 12 |
Coronary artery assessment | CT | no | CT | CT | CA | CA | CA |
Blood exams | |||||||
WBC peak, 106/ml | 18.9 | 8.7 | 4.4 | 19.8 | 28.6 | 9.0 | 28.7 |
CRP peak, mg/L | 21 | 208 | 52 | 309 | 233 | 12 | 79 |
T-Tn peak, ng/L | 135 | 26 | 222 | 39 | 487 | 29 | 13,722 |
NTproBNP peak, pg/mL | 1001 | 148 | 261 | 24,252 | 1170 | 1122 | 15,131 |
Screening for autoimmunity | AHA, anti-TPO | AHA | normal | ACL IgG | AHA, ANCA | normal | AHA |
Electrocardiogram (ECG) and arrhythmias | |||||||
Presentation rhythm | atrial ectopic | sinus | sinus | sinus | VF | sinus | sinus |
PQ, ms | 170 | 159 | 147 | 172 | 167 | 216 | 192 |
QRS, ms | 94 | 90 | 82 | 98 | 82 | 105 | 130 |
QTc, md | 452 | 444 | 392 | 378 | 421 | 456 | 445 |
Abnormal ST | yes | no | yes | no | yes | no | yes |
Abnormal T-waves | yes | yes | yes | no | yes | yes | yes |
BA | AJR (self-limited) | no | no | - | - | 1st-degree AVB | 3rd-degree AVB, LBBB |
SVA | no | no | no | - | - | - | AF |
VA | no | no | no | PVC, NSVT | VF, NSVT, PVC | PVC, NSVT | NSVT, VT |
Echocardiogram and CMR | |||||||
LVEDVi, mL/m2 | 52 | 61 | 47 | 77 | 82 | 115 | 44 |
LVEF, % | 43 | 41 | 59 | 34 | 15 | 20 | 30 |
Dominant WMA localization | IL, reverse TTS | AS | no | diffuse | diffuse | IL | AS |
TAPSE, mm | 18 | 18 | 22 | 12 | 14 | 23 | 8 |
RVEDD, mm | 27 | 26 | 25 | 38 | 32 | 40 | 50 |
CMR timing, day | 7 | 8 | 7 | 99 | 13 | - | 17 |
LGE | no | no | mid-basal AS (subepicardial) | 0 | mid-basal IL (subepicardial) | - | basal septal (midwall), RV |
STIR | mid-basal diffuse | diffuse basal, mid septal | AS | diffuse | mid-basal IL | - | mid-basal septal, RV |
T1 max, ms | 1234 | 1125 | 1311 | 1055 | 1159 | - | 1232 |
T2 max, ms | 67 | 58 | 62 | 54 | 67 | - | 65 |
Pericardial effusion | No | mild | no | mild | mild | - | mild |
EMB | |||||||
EMB timing, day | 7 | 9 | - | 17 | 9 | 118 | 7 |
Edema | Yes | yes | - | yes | yes | yes | yes |
Inflammatory infiltrates | yes | yes | - | yes | yes | yes | yes |
CD3+ > 7/mm2 | yes | no | - | yes | yes | yes | yes |
CD68+ > 4/mm2 | no | yes | - | yes | no | no | no |
Necrosis | mild | no | - | no | no | no | massive |
Replacement fibrosis | no | mild | - | mild | no | mild | no |
Viral genome | no | PVB19 (low-load), SARS-CoV2 (N+/ORF1−) | - | PVB19 (high-load) | no | no | EBV (high-load) |
Features | P1 | P2 | P3 | P4 | P5 | P6 | P7 |
---|---|---|---|---|---|---|---|
Acute-phase treatment | |||||||
ICU stay, days | 0 | 0 | 2 | 7 | 5 | 0 | 24 |
Iv diuretics | yes | yes | no | yes | yes | yes | yes |
Inotropes | no | no | no | Adr, Nor, Lev | Adr, Nor | dopamine | Adr, Nor, Lev |
MCS | no | no | no | IABP | no | no | IABP, VA-ECMO |
Mechanical ventilation | no | no | no | yes | no | no | yes |
Cardiac devices | no | no | no | no | ICD | S-ICD | temporary PM |
Etiology-driven treatment | HCQ, L/R | AZT | HCQ | HCQ, AKR | no | HCQ, AZT, AKR, PDN + AZA | PDN, IVIG |
Discharge assessment | |||||||
Hospitalization, days | 13 | 35 | 11 | 31 | 19 | 36 | 24 |
Symptoms | no | no | mild chest pain | no | dyspnea | dyspnea | dyspnea |
NYHA class | I | I | I | II | II | III | II |
T-Tn, ng/L | 11 | 10 | 5 | 13 | 24 | 8 | 1416 |
NTproBNP, pg/ml | 76 | 136 | 261 | 121 | 358 | 383 | 1937 |
LVEF, % | 65 | 61 | 60 | 45 | 40 | 20 | 65 |
TAPSE, mm | 20 | 22 | 24 | 16 | 18 | 20 | 10 |
RAAS inhibitors | no | no | no | ramipril | enalapril | valsartan | no |
Betablockers | no | no | bisoprolol | metoprolol | metoprolol | bisoprolol | no |
Antiarrhythmics | no | no | no | no | no | AMD | ivabradin |
Diuretics | no | no | SL | FS/SL | FS/SL | FS/SL | FS/CR |
Follow-up assessment | |||||||
Last follow-up, months | 9 | 6 | 6 | 6 | 6 | 6 | 3 |
Follow-up mode | IP, TM | TM | IP, TM | IP | IP, TM | IP, TM | TM |
Death | no | no | no | no | no | no | no |
Arrhythmias | no | no | no | no | PVC | PVC, NSVT | PVC, NSVT, AF |
End-stage heart failure | no | no | no | no | no | referred for HTx | referred for HTx |
New hospitalization | no | no | no | no | no | no | no |
Symptoms | no | no | dyspnea on effort | no | no | dyspnea | dyspnea |
NYHA class | I | I | II | I | I | III | II |
T-Tn, ng/L | 5 | 6 | 6 | 8 | 13 | 6 | 32 |
NTproBNP, pg/ml | 56 | 88 | 154 | 76 | 103 | 272 | 887 |
LVEF, % | 64 | 63 | 61 | 47 | 60 | 24 | 63 |
TAPSE, mm | 20 | 21 | 25 | 25 | 20 | 20 | 12 |
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Peretto, G.; Villatore, A.; Rizzo, S.; Esposito, A.; De Luca, G.; Palmisano, A.; Vignale, D.; Cappelletti, A.M.; Tresoldi, M.; Campochiaro, C.; et al. The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach. J. Clin. Med. 2021, 10, 1974. https://doi.org/10.3390/jcm10091974
Peretto G, Villatore A, Rizzo S, Esposito A, De Luca G, Palmisano A, Vignale D, Cappelletti AM, Tresoldi M, Campochiaro C, et al. The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach. Journal of Clinical Medicine. 2021; 10(9):1974. https://doi.org/10.3390/jcm10091974
Chicago/Turabian StylePeretto, Giovanni, Andrea Villatore, Stefania Rizzo, Antonio Esposito, Giacomo De Luca, Anna Palmisano, Davide Vignale, Alberto Maria Cappelletti, Moreno Tresoldi, Corrado Campochiaro, and et al. 2021. "The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach" Journal of Clinical Medicine 10, no. 9: 1974. https://doi.org/10.3390/jcm10091974