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To read about:
Prevalence of Post-COVID-19 Vaccination Myocarditis Click here.
Diagnosis of Post-COVID-19 Vaccination Myocarditis Click here.
COVID-19 postvaccination myocarditis: Management
Narrative Driven Management Challenges
In their concise review Kornowski and Witberg acknowledge that management of COVID-19 postvaccination myocarditis is challenging (Kornowski & Witberg, 2022). They contribute those challenges to substantial “knowledge gaps”. Those authors are correct our knowledge about this type of myocarditis is limited. However, there is much more to the story. There is a striking trifecta of knowledge shortages related to postvaccination myocarditis. It seems that this relevant nosological entity is being neglected by the three main branches of mainstream medicine: research, clinical practice and teaching. First there is a paucity of basic research related to this subject. Second there is a scarcity of clinical investigations focused on this issue. Finally there is a disturbing unavailability of the comprehensive practice recommendations related to the management of the postvaccination myocarditis. Such absence is especially peculiar in the era of “the cook book medicine” in which the management of the most obscure condition is described in numerous EBM clinical guidelines, on-line textbooks, monographs and review articles, etc.
A frontline physician who is facing a possibility of having a patient with postvaccination myocarditis - will discover very soon that the resources to guide him are very scarce. A typical “go to sources” of information about clinical management will be very disappointing.
The most frequently used clinical database the “omniscient” Up To Date has only a brief section dedicated to the existence of postvaccination myocarditis:
Edwards, K & Orenstein, W. Myocarditis. In: Specific Safety Concerns COVID-19: Vaccines . UpToDate 2022. Wolters Kluver. Waltham, MA. (Accessed on 11/2/22)
As of November 2022 Up To Date does not have a separate chapter on management of this condition. Instead it refers a reader to generic texts on myocarditis. A situation which is rather unexpected given the well known comprehensiveness of Up To Date.
The other popular resources such as ClinicaKey and Medscape are the barren fields as well in this regards. The CDC WebPage dedicated to postvaccination myocarditis offers very little to the clinicians who want to learn details about the management of this condition. A determined physician after investing time in the NLM PubMed searches would be able to compile the following list of the most essential references:
Gluckman T, Bhave N, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play. J Am Coll Cardiol. 2022 May, 79 (17) 1717–1756.https://doi.org/10.1016/j.jacc.2022.02.003
Bozkurt, B., Kamat, I., & Hotez, P. J. (2021). Myocarditis With COVID-19 mRNA Vaccines. Circulation, 144(6), 471–484. https://doi.org/10.1161/CIRCULATIONAHA.121.056135
Luk A et al. Myocarditis and Pericarditis After COVID-19 mRNA Vaccination: Practical Considerations for Care Providers. Can J Cardiol. 2021 Oct;37(10):1629-1634. doi: 10.1016/j.cjca.2021.08.001. Epub 2021 Aug 8. PMID: 34375696; PMCID: PMC8349442.
Kornowski, R., & Witberg, G. (2022). Acute myocarditis caused by COVID-19 disease and following COVID-19 vaccination. Open Heart, 9(1), e001957. https://doi.org/10.1136/OPENHRT-2021-001957
And after reviewing those texts - most of the frontlile Primary Care Physicians will have to conclude that the best treatment option that can be offered to patients with this type of myocarditis - is to refer them to the experienced academic cardiologist. A relatively easy possibility for the large urban area but a problematic option for most underserved rural communities.
Why do we see this information vacuum? The answer is likely related to the impact of the politically driven narrative of the low significance and low prevalence of post vaccination myocarditis. Naturally, if the Powers That Be decided that certain medical condition is too inconvenient - the subservient to them medical expert will eagerly announce that the said condition is very rare and very benign. Hence, it is not worth neither time nor effort to study it and to teach how to manage it.
Conflicting Narratives of Postvaccination Myocarditis
As we discussed previously Political narrative is a term used to denote the manipulative method of storytelling. Such narratives are deliberately designed to change the perception of facts by the members of the public - in order to distort their understandings of reality.
There are two antagonistic narratives describing the Postvaccination Myocarditis as it is summarized on the Figure 2:
The Orthodoxy is in charge and it has all the administrative powers. Consequently, its narrative dominates and shapes the research programs and the standards of care related to the management of postvaccination myocarditis.
A Sensible Management of Postvaccination Myocarditis
After putting all types of narratives aside - the logic and prudence would dictate the following objective assessment of the circumstances related to the management of postvaccination myocarditis:
Postvaccination myocarditis is a novel iatrogenic disease.
Knowledge about its prevalence, pathomechanism, and clinical course, etc. is limited due to its recent emergence and politically motivated lack of interest in those matters.
There is a heated controversy about the described above characteristics of postvaccination myocarditis. In result a variety of biased opinions about those issues is circulating within medical profession and in general public.
Postvaccination myocarditis due to its nature of affecting a vital organ - has a high potential for causing substantial morbidity and mortality.
In the view of the above it is reasonable to conclude that:
Potential perils of postvaccination myocarditis should not be dismissed.
Preferably the management of patients diagnosed with this type of myocarditis should be directed by the experienced and unbiased cardiologist.
Primary Care Physicians practicing in the areas which are underserved in terms of cardiology services - should try to reach out for the remote help from the cardiologists who are willing to assist them through the use of tele-medicine. Furthermore they should strive to follow the evolving standards of care keeping the best interest of their patients in mind.
An Example of the Rational Management Paradigm of Postvaccination Myocarditis
This section contains the description of the general principles guiding the rational management of postvaccination myocarditis. This paradigm is based upon evidence contained in the most recent peer reviewed mainstream publications cited throughout this text and in its References section. It is presented for the informational purposes only. It should not be misconstrued as representing clinical guidelines, standards of care or any type of rigid treatment algorithm.
Management of patients who are diagnosed with postvaccination myocarditis has to be individualized and dictated by the specific clinical presentation and course with considerations given to the patients past medical history and current health status..
A proactive management plan should be put in place for those patients since any type of myocarditis is associated with a heightened risk of cardiac complications both early in the disease course and later on.
Management of Asymptomatic Postvaccination Myocarditis
Asymptomatic (subclinical) myocarditis has been reported following both SARS-CoV-2 infection and COVID-19 vaccinations. Such patients can be accidentally revealed during various types of cardiac screenings performed as parts of vocational or athletic assessment protocols
Number of such patients is rather small since most otherwise healthy people do not undergo such types of screenings. Nevertheless, it is reasonable to manage these individuals expectantly, rather than ignore results of screenings. This is because the long-term consequences of this asymptomatic condition are not known. Therefore those individuals should be given instructions to present for periodic re-assessments and to report any worrisome symptoms or signs (eg, chest pain, shortness of breath, syncope, edema) should they occur in the meantime.
Management of Symptomatic Postvaccination Myocarditis
The treatment approach for symptomatic myocardial involvement in the setting of COVID-19 vaccine side effects - depends upon the combination of patient’s clinical presentation and the nature of abnormalities revealed during ancillary testing.
Phases of Management
Most authors concur that the management of post-vaccination myocarditis consist of the following steps (Figure 1):
General Support
Cardiovascular Support
Heart failure therapy
Arrhythmias therapy
Anticoagulation
Mechanical circulatory support and transplantation - for fulminant cases.
Anti-Inflammatory Treatment
Judicious use of steroids
Short and long term Follow-up
General Support
General Support part of the management encompasses:
new symptoms surveillance,
symptomatic treatment aimed at safe relief of non-specific complaints,
education about self-care and required life style modification.
Surveillance. For both asymptomatic and symptomatic patients the detailed instruction shall be prepared about prompt reporting of any new worrisome symptoms or signs (eg, chest pain, shortness of breath, syncope, edema).
Symptomatic Treatment. Any nonspecific symptoms (fever, myalgias, etc) should be managed conservatively and with avoidance of NSAIDs.
Education. At minimum patient should be advised to modify their habits and activities in a way aimed at avoidance of potentially harmful factors. In general patients should be counseled to avoid:
NSAIDs overuse: Nonsteroidal anti-inflammatory drugs has been shown to be ineffective in the animal models of myocarditis. In fact, it has been demonstrated that they do enhance the burden of the myocarditis and hence can contribute to the increased morbidity and mortality. Furthermore, NSAIDS has been shown to increase the risk of the severe the Heart Failure (HF) leading to the increased mortality. Therefore the NSAIDs should be used sparingly or not used at all in individuals affected by HF.
Excessive alcohol intake: Heavy consumption of alcohol intake may enhance the severity of the myocarditis. Yet, the optimal recommendation for limiting the consumption of alcoholic beverages during myocarditis has not been established. However, it is reasonable to suggest alcohol restriction to the maximum of one or less alcoholic drink daily (14 to 15 g alcohol).
Strenuous exercise: It is extremely important to understand that physical activity should be restricted during myocarditis of any type. Such a restrictions is necessary to reduce the workload of the inflamed myocardium. Such restrictions are especially relevant when patients are febrile and/or show symptoms and signs of HF. The rationale for this approach has been confirmed in animal models. Unfortunately, to date the optimal duration of exercise restriction has not been established. Nevertheless, the American Heart Association/American College of Cardiology Foundation has issued a scientific statement about participation sports activities. AHA/ACCF and other experts recommends from 3 to 6 months abstinence from competitive sports after myocarditis. It is also advised that before clearing patients for the resumption of exercise activities - they should be evaluated with a symptom-limited exercise test, Holter monitor, and echocardiogram.
Cardiovascular Support
Cardiovascular Support shall include but not be limited to:
Heart failure therapy,
Arrhythmias therapy,
Anticoagulation,
Mechanical circulatory support and transplantation - for fulminant cases.
Heart failure therapy. Depending upon their clinical presentation, patients with myocarditis who presents with HF should receive standard cardiology therapy for acute and chronic HF. Discuss of the management of the acute and chronic HF is beyond the scope of this text. However, the detailed monographs on this matter are available elsewhere.
Following guiding principles of HF management shall be kept in mind:
Treatment of hemodynamically stable HF with reduced ejection fraction includes diuresis as needed, and early initiation of angiotensin converting enzyme (ACE) inhibitor (or angiotensin receptor blocker), and judicious use of beta blocker (carvedilol, extended release metoprolol, or bisoprolol) with addition of mineralocorticoid receptor antagonist in patients with persistent symptomatic HF with left ventricular ejection fraction ≤35 percent (excluding patients who are at risk for hyperkalemia).
However, use of beta blockers should be either decreased or withheld in myocarditis patients who presents with more than mildly decompensated HF.
ACE inhibitor and beta blocker therapy may have specific benefits in patients with myocarditis, in addition to their proven benefits in reducing morbidity and mortality in patients with systolic HF generally.
Digoxin is well known to provide a symptomatic benefit in patients with systolic HF in general. However, its efficacy and safety in management of HF associated with myocarditis is uncertain. Digoxin has been shown to increase mortality in a mouse model of myocarditis. For those reasons some authors avoid use of digoxin in the settings of myocarditis.
Arrhythmias therapy. It has been long recognized that patients with myocarditis can develop both tachy- and bradyarrhythmias. Because these arrhythmias typically resolve after the acute phase of myocarditis is over - therapy of those arrhythmias is generally supportive. Electrocardiographic monitoring can permit early detection of asymptomatic yet potentially life-threatening arrhythmias and/or conduction defects. For this reason, it is recommended that patients with acute and unstable myocarditis should be admitted to the hospital for monitoring.
Following generally suggested approach is consistent with the widely accepted guidelines:
Antiarrhythmic therapy should not be given for asymptomatic atrial and ventricular premature beats or for asymptomatic nonsustained arrhythmias.
When antiarrhythmic therapy is necessary (as indicated below), options include amiodarone, dofetilide (with precautions for potential proarrhythmia), and in patients without class IV HF, cautious use of beta blockers or calcium channel blockers. Due to the proarrhythmic and negative inotropic effects, other class I and III antiarrhythmic drugs are generally avoided in patients with acute myocarditis.
Supraventricular tachycardias (SVTs) can induce or aggravate HF. For sustained, symptomatic SVT, restoration of sinus rhythm is the recommended initial approach. For recurrent sustained SVT, options include rate control therapy and antiarrhythmic therapy. The specific approach to restoring sinus rhythm, controlling the ventricular rate, and selecting an antiarrhythmic drug depends upon the arrhythmia and the overall clinical scenario.
For ventricular arrhythmias:
Symptomatic nonsustained ventricular tachycardia can be treated with conservatively with standard antiarrhythmic drugs.
Sustained ventricular arrhythmias should be treated with urgent cardioversion, and recurrent arrhythmias should be treated with antiarrhythmic drugs.
Role of implantable cardioverter-defibrillator (ICD) therapy:
ICD implantation is generally deferred in patients with acute myocarditis since myocarditis and arrhythmia risk may resolve spontaneously. A potential role for a wearable cardioverter-defibrillator for patients at risk for sudden cardiac arrest has been suggested but the evidence to support such approach is limited.
ICD implantation can be beneficial in patients with life-threatening ventricular arrhythmias who are not in the acute phase of myocarditis, who are receiving optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than one year. Data are lacking regarding specific late risks of VT and sudden cardiac arrest in subjects with myocarditis who present with VT or sudden cardiac arrest, so this recommendation is based solely upon indirect data on patients with various types of heart disease (particularly ischemic heart disease).
Complete heart block and/or symptomatic bradycardia are indications for pacing during the acute phase of myocarditis. This conduction abnormality is often transient; as a result, use of a temporary pacemaker should be the first step.
Anticoagulation. Indications for anticoagulation in patients with myocarditis include standard general indications such as evidence of systemic embolism or presence of acute left ventricular thrombus. Standard criteria for anticoagulation for atrial fibrillation should be applied; most patients with atrial fibrillation and HF meet criteria for long-term anticoagulation due to the significantly increased risk of embolization. Indications for anticoagulation should be reassessed if atrial fibrillation and HF resolve. In contrast, HF and/or low ejection fraction in patients with sinus rhythm are not generally accepted as indications for anticoagulation.
Mechanical circulatory support and transplantation. Potential options for patients with fulminant myocarditis resulting in the refractory HF despite optimum medical therapy include mechanical circulatory support and cardiac transplantation:
Mechanical circulatory support (eg, ventricular assist device [VAD]) or extracorporeal membrane oxygenation maybe required for the hemodynamically unstable patients with HF. Mechanical circulatory support with a VAD should be considered when HF is intractable or when cardiogenic shock does not respond to medical therapy. Several reports suggest that in some patients, these devices can be used successfully as a bridge to spontaneous recovery in the setting of fulminant myocarditis. Among patients with fulminant myocarditis with cardiogenic shock treated with a VAD, a more rapid initial course is associated with greater likelihood of recovery.
Cardiac transplantation. Candidacy for cardiac transplantation should be considered in patients with chronic myocarditis presenting as an intractable cardiomyopathy with refractory HF. Although a case series of 12 patients with active lymphocytic myocarditis at the time of transplant suggested an increased surgical risk in such patients - patients with biopsy-proven myocarditis (n = 142) in the much larger United Network for Organ Sharing registry did at least as well as other cardiac transplantation patients over one-year follow-up.
Anti-Inflammatory Treatment
Steroids. Vaccine exposure, causes typically eosinophilic myocarditis (Cooper, 2020). standard treatment of the various types of eosinophilic myocarditis includes high-dose glucocorticoid therapy used as anti-inflammatory agents (Brambatti, 2017).
Several pre-COVID era reports demonstrated a dramatic improvement of eosinophilic myocarditis with both high and low dose steroid therapy (Eppenberger, 2013 ; Fozing, 2014 ; Hase, 2016 ; Chen, 2017 ).
Regarding steroid use in the cases of COVID-19 postvaccination myocarditis Kimora et al. reported a successful treatment of fulminant necrotizing eosinophilic myocarditis after COVID‐19 vaccination with steroid therapy and mechanical circulatory support. Moreover, Otsuka et al. described a case of fulminant eosinophilic myocarditis after Pfizer BNT162b2 vaccination that was successfully treated using steroid pulse therapy.
Colchicine for Postvaccination Pericarditis. For all patients who presents with the acute postvaccination pericarditis or my-pericarditis many authors recommend use of colchicine colchicine despite some past controversies. The skepticism was perhaps caused by the fact that for the patients who were diagnosed with the bacterial pericarditis, colchicine has not been proven efficacious and, on the contrary, ma theoretically impair the clearance of the infectious agent. Colchicine was also not proven to be efficacious in malignancy-related pericarditis and pericardial effusion. However, the etio-pathology of postvaccination pericarditis differs from the pathomechanism of those conditions.
In the settings of the postvaccination pericarditis, colchicine can be either used alone or added to the steroid therapy. Note that use of NSAIDs is discouraged in treatment of the myocarditis hence colchicine is a good alternative option for them. Indeed, the 2015 ESC guidelines concluded that the weight of evidence supported the efficacy of colchicine - in the treatment of acute pericarditis.
Moreover, the efficacy of colchicine in the primary management of acute pericarditis has been evaluated in the following randomized trials:
In the ICAP trial, a randomized, double-blind study of colchicine versus placebo in addition to standard antiinflammatory therapy for treatment of a first episode of acute pericarditis (77 percent idiopathic) in 240 patients, colchicine added to standard antiinflammatory therapy significantly reduced the risk of recurrence (17 versus 38 percent with antiinflammatory therapy alone; relative risk reduction 0.56, 95% CI 0.30-0.72). In addition, colchicine added to antiinflammatory treatment resulted in significantly better rates of remission and fewer hospitalizations compared with antiinflammatory treatment alone. No serious adverse events were observed.
In the open label COPE trial of 120 patients with a first episode of acute pericarditis (84 percent idiopathic), the recurrence rate of pericarditis within 18 months was significantly lower in the colchicine plus aspirin group (11 versus 32 percent with aspirin alone; number needed to treat to prevent one recurrence equals five)
In the 2019 open-label trial in 110 patients with a first episode of acute idiopathic pericarditis, the addition of colchicine to conventional antiinflammatory treatment did not reduce the recurrence rate. However, the study has important limitations to be acknowledged (eg, probably underpowered to test colchicine efficacy, diagnostic criteria for pericarditis not consistent with 2015 ESC guidelines, and possible significant delay in the administration of colchicine from symptoms onset) that may limit its clinical applicability.
In addition to those clinical trials , the efficacy of colchicine in the treatment of pericarditis has also been assessed in several systematic reviews and meta-analyses ( Imazio, 2012; Alabed,2014 ; Imazio, 2014; Melendo-Viu, 2022 ).
Based upon this stong line of evidence the use of colchicine in the treatment of postvaccination pericarditis appears to be justified.
However, it has to be mentioned that colchicine is not approved for the prevention of recurrent pericarditis in North America and as such its use is therefore considered to be “off-label”.
Follow-up
It is expected that many patients with the symptomatic postvaccination myocarditis will have partial or full clinical recovery. Based upon pre-COVID era observations it is possible that the process of myocarditis can continue initially sub-clinically, but ultimately becoming severe enough to produce symptoms, often with dilated cardiomyopathy. The likelihood of these late complications is increased in patients who present with greatly diminished left ventricular function.
Therefore, it is sensible to recommend short and long follow-up plan for the patients with with postvaccination myocarditis:
Short term follow-up. It is advisable that all patients with postvaccination myocarditis should be followed, initially at intervals of one to three months. Physical activity, especially competitive sports, should be permitted only gradually, and their tolerance monitored. The examiner should be alert to persistent or recurring S3 and S4 gallops. Echocardiography should be used for monitoring the size of the cardiac chambers, valve function, and the left ventricular ejection fraction. If the echocardiogram does not provide the necessary information, CMR, nuclear testing, or cardiac computed tomography are alternatives, depending upon availability.
Long term follow-up. After patients stability has been documented during short term follow-up depending upon circumstances their cardiac functions can be reevaluated at 6 months and then yearly or as indicated by the possible recurrence of symptoms.
However, the decision-making about the follow-up for each patients shell be individualized and based upon the specific for the given patient circumstances.
References and Suggested Readings
Most Essential Texts:
Gluckman T, Bhave N, et al. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play. J Am Coll Cardiol. 2022 May, 79 (17) 1717–1756.https://doi.org/10.1016/j.jacc.2022.02.003
Bozkurt, B., Kamat, I., & Hotez, P. J. (2021). Myocarditis With COVID-19 mRNA Vaccines. Circulation, 144(6), 471–484. https://doi.org/10.1161/CIRCULATIONAHA.121.056135
Luk A et al. Myocarditis and Pericarditis After COVID-19 mRNA Vaccination: Practical Considerations for Care Providers. Can J Cardiol. 2021 Oct;37(10):1629-1634. doi: 10.1016/j.cjca.2021.08.001. Epub 2021 Aug 8. PMID: 34375696; PMCID: PMC8349442.
Kornowski, R., & Witberg, G. (2022). Acute myocarditis caused by COVID-19 disease and following COVID-19 vaccination. Open Heart, 9(1), e001957. https://doi.org/10.1136/OPENHRT-2021-001957
Edwards K, & Orenstein, W. Myocarditis. In: Specific Safety Concerns COVID-19: Vaccines . UpToDate 2022. Wolters Kluver. Waltham, MA. (Accessed on 11/2/22)
Clinical Considerations: Myocarditis after mRNA COVID-19 Vaccines | CDC. (n.d.). Retrieved November 1, 2022, from https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html
Pillay J, Gaudet L, Wingert A, Bialy L, Mackie A S, Paterson D I et al. Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following covid-19 vaccination: living evidence syntheses and reviewBMJ 2022; 378 :e069445 doi:10.1136/bmj-2021-069445
Kounis NG, Koniari I, Mplani V, Plotas P, Velissaris D. Hypersensitivity Myocarditis and the Pathogenetic Conundrum of COVID-19 Vaccine-Related Myocarditis. Cardiology. 2022;147(4):413-415. doi: 10.1159/000524224. Epub 2022 Mar 22. PMID: 35316805; PMCID: PMC9393780.
Lima, P. Managing Cardiovascular Complications of COVID Vaccination Medscape 2022.
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