Vaccine Induced Carditis  

Vaccine Induced Carditis  

Inflammatory reaction of the cardiac muscle (myocardium) and/or outer lining of the heart (pericardium) triggered by vaccine administration.

Synonyms

• Vaccine-induced myocarditis
• Vaccine-induced pericarditis
• Vaccine-induced myopericarditis

Epidemiology & Demographics

• •Between 1990 and 2018, before the COVID-19 pandemic, the prevalence of vaccine-induced myopericarditis was 0.1%, mainly attributed to the smallpox, influenza, and hepatitis B vaccines. ¹
• •The overall incidence of carditis after vaccination with mRNA COVID-19 vaccine is 0.3 to 5.0 cases per 100,000 individuals. ² A relation between the Novavax (protein subunit vaccine) and carditis has also been made, but data are limited at this time. ³
• •Vaccine-induced carditis typically affects males under the age of 30 yr old. ^4 , 5
• •The peak incidence of carditis is 22 to 35.9 per 100,000 cases in males between the ages of 12 and 17 yr old after the second dose of mRNA COVID-19 vaccination. ^2 , 6

Physical Findings & Clinical Presentation

• •Individuals typically present 3 to 4 days after vaccination. ²
• •Clinical presentation is typically mild but rarely can present with fulminant myocarditis and/or cardiogenic shock.
• •Symptoms are similar to non–vaccine-related carditis.
  • 1.If inflammation of the pericardium is involved, patients can present with chest pain that is typically described as pleuritic. It is exacerbated by taking a deep breath or lying down and improves with leaning forward.
  • 2.Palpitations, presyncope, or syncope can be present due to arrhythmias.
  • 3.Shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, and lower extremity edema can be seen in the setting of heart failure.
  • 4.Rarely, patients can present with additional signs of a low-output state including fatigue, altered mental status, and oliguria in the setting of cardiogenic shock. ⁴

Etiology

What causes this condition?

• •Several potential mechanisms of mRNA vaccine-induced carditis have been postulated:
  • 1.The COVID-19 mRNA vaccines induce expression of the IgG spike protein antibody on the outer portion of the host cell, which prevents virus attachment and therefore entry into the cell. It has been postulated that antibodies to the mRNA induced IgG spike protein may cross react with myocardial contractile proteins leading to carditis. ²
  • 2.An alternate theory is that the immune system mistakes the mRNA in the vaccine as an antigen, which triggers the immune cascade. ² However, this hypothesis does not explain why some organ systems are affected and others are not.
• •The increased prevalence of carditis in males has been attributed to hormone-mediated factors including increased levels of testosterone leading to a more aggressive T-cell–mediated immune response. ²

Differential Diagnosis

• Myocardial infarction
• Alternate etiologies of cardiomyopathy (e.g., ischemic-mediated, alcohol-induced, infiltrative disease, hypertension related)
• Non–vaccine-mediated carditis (e.g., viral carditis, bacterial carditis, malignancy-associated carditis)

Workup

• •ECG is helpful to assess for myocardial injury and arrhythmias.
• •Endomyocardial biopsy is not required, but can be considered if alternate etiologies of myocarditis such as giant cell myocarditis (GCM) is on the differential because the biopsy results would guide treatment in GCM.
  • 1.If performed, the endomyocardial biopsy of vaccine-induced carditis demonstrates areas of inflammation and myocyte necrosis. ⁷

Laboratory tests

• Troponin should be obtained to assess for myocardial involvement and myocardial injury.
• C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) should be obtained as baseline markers of inflammation and monitored over time to assess response to therapy.
• Brain natriuretic peptide (BNP) can be used to assess for myocardial distension in the setting of heart failure.
• White blood cell count (WBC) and differential can be helpful to assess for an underlying infectious process.
• Comprehensive respiratory viral pathogen testing should be obtained to assess for alternate etiologies of carditis.
• Refer to the “Myocarditis” chapter for further testing to rule out other etiologies of non–vaccine-induced carditis.

Imaging Studies

• Chest x-ray should be obtained to assess for cardiomegaly and pulmonary edema.
• Echocardiogram can assess for pericardial effusion as well as left ventricular assessment.
• Cardiac MRI can be considered to further support the diagnosis but is not required. Findings that would suggest carditis would include late gadolinium enhancement and myocardial edema.

Treatment

Non Pharmacologic Therapy

• In individuals presenting with heart failure: Strict low-salt diet and fluid restriction can be helpful.
• Limited physical activity during the acute phase should be recommended.
• In individuals presenting with cardiogenic shock:
  • 1.Consider placement of a pulmonary artery catheter for hemodynamic guided management.
  • 2.Mechanical circulatory support with left ventricular (LV) support devices or ECMO can be considered in advanced cases.

Acute General Treatment

• •In patients with rapid improvement in symptoms, no LV dysfunction, and normal or resolving cardiac biomarkers, therapy may be deferred. ¹
• •In symptomatic patients, acute treatment includes diuretics, inotropes, and antiarrhythmics as needed.
• •Colchicine, NSAIDs, and/or steroids are typically considered in patients with persistent mild symptoms. ¹
• •Steroids, IVIG, and mechanical circulatory support can be considered in patients with evidence of significant LV dysfunction or heart failure, hemodynamic instability, or new-onset arrhythmias. ¹

Chronic Treatment

• •If LV dysfunction is present, guideline-directed medical therapy for heart failure should be initiated, including ACE inhibitors and beta-blockers.
• •Based on literature from non–vaccine-induced myocarditis, patients should refrain from participating in competitive sports for at least 3 to 6 mo and receive clearance from their physician before resuming competitive activities.

Disposition

• •Typically symptoms are mild. If admission is required, most patients are discharged within 4 days.
• •If cardiogenic shock or persistent arrhythmias are present, patients should be referred to a center with cardiac intensive care and the ability to provide mechanical circulatory support if needed.

Referral

• •Patients with LV dysfunction or arrhythmias should be referred to a cardiologist for evaluation and follow-up. Guideline-directed medications for heart failure with reduced ejection fraction will need to be titrated to the maximum tolerated doses. Follow-up echocardiograms will need to be obtained as an outpatient to assess for LV recovery.
• •Referral to an infectious disease specialist may be considered as well for guidance regarding future vaccinations and workup of alternate etiologies of carditis.

Pearls & Considerations

• •Males between the ages of 12 and 17 yr old are at highest risk of vaccine-induced carditis.
• •Clinical symptoms are typically mild, but rare cases of significant LV dysfunction and cardiogenic shock have been reported.
• •The addition of IVIG or steroids to standard treatment of carditis can be considered in individuals with significant LV dysfunction, hemodynamic instability, or new-onset arrhythmias; however, data are limited.

Prevention

• •Waiting a longer period of time (up to 8 wk) between vaccinations with the mRNA or Novavax COVID-19 vaccine may be considered in high-risk individuals, especially young males, to possibly lower the risk of vaccine-induced carditis. This risk must be weighed against the rate of COVID-19 infection in the individual’s community. ³

Patient & Family education

• •Studies have shown that infection with the COVID-19 virus has a rate of carditis that matches or exceeds the risk of vaccine-induced carditis in most populations. ⁸
• •It is currently recommended by the CDC that all individuals older than 6 mo of age receive COVID-19 vaccination.
• •Underlying cardiac conditions are not a contraindication to undergoing vaccination.
• •Patients with abnormal testing or evidence of myocarditis should be referred to a specialist for discussion regarding risks/benefits of future COVID-19 vaccinations with mRNA or Novavax vaccines; alternate forms of vaccination may be recommended depending on the individual’s risk.
• •Based on expert review by the CDC, future vaccinations with mRNA COVID-19 or Novavax should be avoided in patients with a history of vaccine-induced carditis. ³
• •In individuals with mRNA-associated carditis who do not have an abnormal ECG, troponin, or inflammatory markers, repeat vaccination can be considered after discussion with their clinical team. ³

REFERENCES

1.Bozkurt B., et al.: Myocarditis with COVID-19 mRNA vaccines . Circulation 2021; 144 (6): pp. 471-484.

2.Heymans S., Cooper L.T.: Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms . Nat Rev Cardiol 2022; 19 (2): pp. 75-77.

3.Centers for Disease Control and Prevention: Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States. Updated August 22, 2022. Accessed August 30, 2022. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html#myocarditis-pericarditis .

4.Witberg G., et al.: Myocarditis after COVID-19 vaccination in a large health care organization . N Engl J Med 2021; 385 (23): pp. 2132-2139.

5.Mevorach D., et al.: Myocarditis after BNT162b2 mRNA vaccine against COVID-19 in Israel . N Engl J Med 2021; 385 (23): pp. 2140-2149.

6.Block J.P., et al.: Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination—PCORnet, United States, January 2021-January 2022 . MMWR Morb Mortal Wkly Rep 2022; 71 (14): pp. 517-523.

7.Ehrlich P., et al.: Biopsy-proven lymphocytic myocarditis following first mRNA COVID-19 vaccination in a 40-year-old male: case report . Clin Res Cardiol 2021; 110 (11): pp. 1855-1859.

8.Stecker E, Mullen B: Vaccine-associated myocarditis risk in context: emerging evidence, American College of Cardiology, February 9, 2022. Accessed August 30, 2022. https://www.acc.org/latest-in-cardiology/articles/2022/02/09/12/56/vaccine-associated-myocarditis-risk-in-context .