1. A review of MRI studies found myocarditis is associated with both COVID-19 infection and post-COVID vaccination. Myocarditis was seen in around 7% of autopsies of COVID patients but closer review found it in only 1.4%, suggesting COVID myocarditis may be overestimated. 2. Mandatory advanced cardiac testing of athletes after COVID found a 7.4% prevalence of myocarditis, much higher than previously thought. CMR criteria focusing on matching T1 and T2 abnormalities improved specificity for diagnosing myocarditis. 3. Myocarditis from COVID presents variably from no symptoms to chest pain and heart failure. Diagnosis relies on troponin, ECG, echo and gold

1. Duke Sports Cardiology / SCD Symposium
April 23, 2022
COVID-19 Myocarditis: Review of MRI Studies
Igor Klem, MD

2. 1. Myocarditis and myocardial involvement of COVID-19
2. Post COVID-19 vaccination myocarditis

3. Initial reports of myocarditis associated with covid-19
Eur Heart J, Volume 41, Issue 19, 14 May 2020, pp 1861–1862
• 43 y/o F no significant PMH
• Moderately ill w covid-19 pneumonia
• Tn elevated
• ECG w ectopic atrial rhythm, STE in V1-2, avR
• TTE EF 45%, inferolateral hypokinesia
• EMB: diffuse T-lymphocytic inflammatory
infiltrates (CD3þ >7/mm2 ) with huge interstitial
oedema and limited foci of necrosis. No
replacement fibrosis was detected, suggesting an
acute inflammatory process. Molecular analysis
showed absence of the SARS-CoV-2 genome.
• CMR: edema on T2-weighted images, and T1- and
T2-weighted parametric mapping. No LGE to
indicate scar/necrosis.
DIAGNOSIS: Acute virus-negative lymphocytic
myocarditis associated with SARS-CoV-2 respiratory
infection

4. GAINESVILLE, Fla. -- Florida forward
Keyontae Johnson, who collapsed on the
court during a game Dec. 12 at Florida
State, has been diagnosed with a heart
inflammation that may be related to an
earlier infection for COVID-19.
https://www.usatoday.com/story/sports/ncaab/sec/2020/12/22/floridas-keyontae-johnson-heart-acute-myocarditis-covid-19/4019276001/

5. Myocardial injury in hospitalized patients with COVID-19 is common
• Myocardial injury defined typically as cTn
concentration >99th percentile URL
• Prevalence ranges between 20-30% among
hospitalized patients, and 40% among
moderately/severely/critically ill patients.
• Occurs more often in older patients with chronic
cardiovascular conditions
• Myriad of conditions can cause myocardial injury
Sandoval et al., JACC 2020;76:1244-58

6. • 671 hospitalized patients with severe covid-19
infection in Renmin hospital Wuhan University
• Risk of death increased with myocardial injury
• Myocardial injury associated with senior age,
inflammatory response, and cardiovascular
comorbidities

7. Kotecha et al., Eur Heart J, 2021;42: 1866–1878
• 148 hospitalized patients with severe covid
(32% ventilated) and myocardial injury
imaged with CMR ~2 months after
recovery
• LVEF normal in 89% (67+/-11%)
• LGE and/or ischemia in 54%:
- Myocarditis 26%
- Infarct and/or ischemia 22%
- Mixed pathology 6%
CMR can help to understand the etiology of myocardial injury in moderate-severe covid

8. Case covid Multisystem inflammatory syndrome - C
11 y/o M, hx of asthma, COVID + on 9/1/2021
Admission to hospital w vomiting, po intolerance, diarrhea, sore throat, fever
Labs:
CRP 18 (ref<1)
ESR 76 (ref <10)
D-Dimer 1.29 (ref<0.5)
proBNP 386 (ref<100)
Troponin 1826 (ref<18)
Covid PCR negative
TTE: LVEF 45%, moderate RV dysfunction, normal origin of coronaries

9. T2-mapping LGE
Cine
Near normal LVEF
Abnormal T2 lateral:
Myocardial edema
Abnormal LGE lateral:
Myocardial necrosis
Case covid Multisystem inflammatory syndrome - C
T1-mapping
Abnormal T1 lateral:
Myocardial injury
CMR confirms myocarditis

10. • 74 seropositive health care workers with mild
symptoms or asymptomatic and 75 matched
healthy controls underwent a CMR study (6
months after symptom onset).
• No difference in LVEF, EDVi, LGE%, septal T1,
septal T2, LV mass, LA size, and other minor
parameters
• Mild covid does not result in excess
cardiovascular impact on LV structure, function,
scar burden.
Joy et al., JACC Cardio Img 2021;14:2155–2166
Myocardial injury in mild covid not as common as initially suspected

11. Myocarditis – inflammatory disease of the heart from infections, toxin, immune system activation
Diagnosis:
- Acute symptoms: chest pain (85-95%), dyspnea (19-49%), syncope (6%), fever (65%), flu-like or GI prodromi (18-18%)
- ECG: ST segment elevations (inferolateral), QRS>120ms, AV block, brady-, tachycardia, PVCs/NSVT
- Elevated cardiac troponin (hsTn), C-reactive protein (80-95%)
- TTE: LVEF normal or mildly reduced, regional WMA inferolateral, pericardial effusion
- EMB (min 5 samples): evidence of myocyte necrosis / degeneration with inflammatory infiltrate on
immunohistochemistry for leucocytes, macrophages, T and B cells (Dallas and Marburg criteria) with or without
fibrosis [NOTE: edema not a criterion]
- CMR
- Absence of flow-limiting coronary artery disease
Ammirati et al. Circulation: Heart Failure 2020;13e:e007405

12. Diagnostic criteria for myocarditis with CMR
Lake Louis Criteria: Sensitivity 78%, specificity 88%
validated in non-covid (viral) myocarditis
Differences between CMR and pathology:
• immunohistochemistry and PCR w EMB not w CMR
• surrogate of inflammation (edema, necrosis) w CMR
enough to replace EMB?
• EMB limited to few small samples

13. 222 patients with EMB-proven viral myocarditis and CMR
Follow-up 4.7 years
LGE+ 19.2% mortality
LGE+ HR 8.4 for all cause death, HR 12.8 for cardiac death
No patient w/o LGE had SCD
CMR findings (LGE) of myocarditis associated with adverse prognosis

14. • 97 cases of SCD due to myocarditis confirmed on autopsy from 2 large registries: 74 male, age 19.3+/- 6.2 years
• SCD in Athletes registry (age<40): 2406 cases, 7% of those assigned to cardiovascular death were due to myocarditis
• 58/97 (60%) died during or just after physical activity
• Only 46 (47%) had symptoms: viral illness/malaise (n=16), syncope (n=9), nausea/abdominal pain (n=7), chest pain
and palpitations (n=7)
• 9 patients consulted a cardiologist: None diagnosed myocarditis, rather PVC or “palpitations”.
• Myocarditis important under-recognized cause of SCD in young athletes,
• Clinical diagnosis challenging: viral prodrome in only 10%, nonspecific symptoms in only 40%, and often ignored
Harris, Am J Cardiol 2021;143:131-134
How common is myocarditis as cause of SCD among athletes?

15. • Summary of 22 studies including 277 cardiac autopsies
• Modest frequency of covid-19 related cardiovascular
histopathologies:
- Nonmyocarditis inflammatory infiltrate (12.6%)
- Single cell ischemia (13.7%)
- Acute myocardial infarction (4.7%)
- Myocarditis 7.2%
• Closer review by pathologist (excluding nonspecific
inflammatory infiltrates) frequency of myocarditis drops to
1.4%
How common is myocarditis related to covid-19 on autopsy?

16. Recommendations on testing and return to play for athletes after covid-19?
JAMA Cardiol. 2021;6(2):219-227.
No cardiac testing for asymptomatic / mild symptoms
RTP after 10 days gradually
Testing for athletes with prior moderate and severe
covid-19 infection w ECG, Tn, echo;
CMR confirmatory test with symptoms and moderate-
to-high pretest probability for myocarditis
If myocarditis confirmed:
- Repeat testing with TTE, 24 H Holter, exercise ECG
no less than 3-6 months after illness
- Ventricular function normalized
- Tn, CRP, proBNP normalized
- No clinically relevant arrhythmia on Holter and
exercise ECG

17. How common is myocarditis related to covid-19 in competitive athletes with recent covid19 infection?
Starting Sept 2020 mandate for advanced testing for
all athletes after covid-19 prior to RTP:
- ECG
- Echocardiogram
- Serum troponin level
- CMR
JAMA Cardiol. 2021;6(9):1078-1087
Myocarditis diagnosis definition:
Clinical myocarditis: cardiac symptoms
Subclinical probable myocarditis: no cardiac symptoms, with abnormal ECG, TTE, or Tn
Subclinical possible myocarditis: no cardiac symptoms, without abnormal ECG, TTE, or Tn and only abnormal CMR

18. Detection and prevalence of myocarditis related to covid-19 based on diagnostic strategy
JAMA Cardiol. 2021;6(9):1078-1087
7.4 fold higher prevalence of myocarditis

19. CMR criteria:
Positive for T1-based criteria and T2-based criteria in the same segment
Modified LLC to increase specificity and avoid interobserver variability
JAMA Cardiol. 2021;6(9):1078-1087