Acute myopericarditis and left shoulder capsulitis following second dose of mRNA SARS-CoV-2 Moderna vaccination.

Vaccination against mRNA SARS-CoV-2 has been administered on a very large scale and various side effects have been described. The increased risk of myopericarditis is known, and only a few cases of shoulder capsulitis have been reported after vaccination. These two pathologies have never been reported in the same patient after vaccination. Our article presents the history of a man in his 40s who presented with myopericarditis a few days after vaccination against SARS-CoV-2 with mRNA(Messenger RNA) Moderna® vaccine and who at the same time developed shoulder capsulitis. His cardiovascular symptoms resolved rapidly, and his shoulder symptoms improved/resolved within 1 year. This case should make physicians aware of the possibility of several concomitant side effects following vaccination against SARS-CoV-2.

Myocarditis and autoimmunity.

INTRODUCTION: Autoimmune myocarditis may develop due to heterogeneous causes. Myocarditis is often caused by viral infections, but it can also be caused by systemic autoimmune diseases. Immune checkpoint inhibitors and virus vaccines induce immune activation, and they can cause the development of myocarditis, as well as several immune-related adverse events. The development of myocarditis is dependent on the genetic factors of the host, and the major histocompatibility complex (MHC) may be an important determinant of the type and severity of the disease. However, non-MHC immunoregulatory genes may also play a role in determining susceptibility. AREA COVERED: This review summarizes the current knowledge of the etiology, pathogenesis, diagnosis, and treatment of autoimmune myocarditis with a particular focus on viral infection, autoimmunity, and biomarkers of myocarditis. EXPERT OPINION: An endomyocardial biopsy may not be the gold standard for the diagnosis of myocarditis. Cardiac magnetic resonance imaging is useful in diagnosing autoimmune myocarditis. Recently identified biomarkers of inflammation and myocyte injury are promising for the diagnosis of myocarditis when measured simultaneously. Future treatments should focus on the appropriate diagnosis of the etiologic agent, as well as on the specific stage of the evolution of immune and inflammatory processes.

Impact of Hypocalcemia on the Prognosis of Patients with Acute Myocarditis.

Acute viral myocarditis is a serious complication of viral infectious diseases, including coronavirus disease 2019 (COVID-19). To better understand the pathogenesis of acute viral myocarditis, we retrospectively analyzed the incidence and prognostic significance of hypocalcemia among patients with acute myocarditis, most of whom were considered to have acute viral myocarditis. We retrospectively reviewed the demographic and clinical data of patients with clinically confirmed acute myocarditis treated in our hospital over a 13-year period from 2006 to 2019, including laboratory results, cardiac imaging findings, and clinical outcomes. These data were compared between lower, middle, and higher calcium groups depending on the minimum calcium level measured during hospitalization. Among the 288 patients with acute myocarditis included, the hypocalcemia group (lower calcium group) had poorer clinical and laboratory results, received more medications and device support, and experienced poorer outcomes, including heart failure, arrhythmias, and death. Specifically, the left ventricular ejection fraction was significantly lower, and the length of hospital stay was significantly longer in the hypocalcemia group than in the other two groups. Furthermore, the incidence rates of atrioventricular block, ventricular tachycardia/ventricular fibrillation, cardiogenic shock, and mortality were significantly higher in the hypocalcemia group. Multivariate Cox regression analysis identified hypocalcemia as an independent risk factor for 30-day mortality in patients with acute myocarditis. In conclusion, the clinical evidence provided by the present study indicates that hypocalcemia is a risk factor for poorer outcomes in patients with acute myocarditis that should be considered carefully in the diagnosis and treatment of these patients.

COVID-19 myocarditis and long-term heart failure sequelae.

PURPOSE OF REVIEW: The clinical syndrome of coronavirus disease 2019 (COVID-19) has become a global pandemic leading to significant morbidity and mortality. Cardiac dysfunction is commonly seen in these patients, often presenting as clinical heart failure. Accordingly, we aim to provide a comprehensive review on COVID-19 myocarditis and its long-term heart failure sequelae. RECENT FINDINGS: Several suspected cases of COVID-19 myocarditis have been reported. It is often not clear if the acute myocardial dysfunction is caused by myocarditis or secondary to generalized inflammatory state of cytokine release or microvascular thrombotic angiopathy. Ischemia may also need to be ruled out. Regardless, myocardial dysfunction in these patients is associated with poor overall prognosis. Laboratory testing, echocardiography, cardiac magnetic resonance imaging, and even endomyocardial biopsy may be needed for timely diagnosis. Several treatment strategies have been described, including both supportive and targeted therapies. SUMMARY: COVID-19 can cause a spectrum of ventricular dysfunction ranging from mild disease to fulminant myocarditis with hemodynamic instability. Future research is needed to understand the true prevalence of COVID-19 myocarditis, as well as to better define various diagnostic protocols and treatment strategies.

Acute Myocarditis and Pericarditis After mRNA COVID-19 Vaccinations-A Single-Centre Retrospective Analysis.

BACKGROUND: With the rapid rollout of COVID-19 vaccinations, numerous associated and suspected adverse events have been reported nationally and worldwide. Literature reporting confirmed cases of pericarditis and myocarditis following SARS-CoV-2 mRNA vaccinations has evolved, with a predominance in adolescent males following the second dose. METHODS: This was a retrospective analysis of all patients presenting to St Vincent's Hospital, Sydney, Australia with suspected COVID-19 vaccine-related myocarditis and pericarditis. The Brighton Collaboration Case Definitions of Myocarditis and Pericarditis were used to categorise patients into groups based on diagnostic certainty. Cardiac magnetic resonance imaging findings were reviewed against updated Lake Louise Criteria for diagnosing patients with suspected myocarditis. RESULTS: We report 10 cases of confirmed, possible or probable myocarditis and pericarditis. The mean age of presentation in the vaccine group was 33±9.0 years. The most common presenting symptom was pleuritic chest pain (n=8, 80%). Eight patients (80%) had electrocardiogram (ECG) abnormalities (n=6 pericarditis, n=2 myocarditis). Five patients (50%) had a minimum 24 hours of cardiac monitoring. One patient had multisystem inflammatory syndrome following vaccination (MIS-V) with severely impaired left ventricular ejection fraction and required admission to the intensive care unit. DISCUSSION AND CONCLUSION: Cardiac complications post mRNA vaccines are rare. Our case series reflects the worldwide data that vaccine-related myocarditis and pericarditis most frequently occur in young males, following the second dose of the vaccine. These cardiac side effects are mild and self-limiting, with adequate responses to oral anti-inflammatories. One patient developed a severe reaction, with no fatal cases.

Cardiac inflammation associated with COVID-19 mRNA vaccination in patients with and without previous myocarditis.

BACKGROUND: mRNA COVID-19 vaccines have been associated with myocarditis in the general population. However, application of gold standard techniques is often missing, and data about patients with history of myocarditis have not been reported yet. METHODS: We evaluated 21 patients (median age 27, 86% males) for suspected myocarditis after receiving mRNA COVID-19 vaccine. We divided cases with previous diagnosis of myocarditis (PM, N.=7), from naïve controls (NM, N.=14). All patients were investigated thoroughly by cardiac magnetic resonance (100%) with or without endomyocardial biopsy (14%). RESULTS: Overall, 57% of patients met updated Lake Louise criteria and none fulfilled Dallas criteria, with no remarkable differences between groups. Acute coronary syndrome-like presentation was more frequent in NM with earlier normalization of troponin than PM. NM and PM already healed from myocarditis were clinically comparable, whereas PM with active inflammation had subtle presentation and were evaluated for immunosuppressive therapy modulation. None had fulminant myocarditis and/or malignant ventricular arrhythmia at presentation. No major cardiac events occurred by 3 months. CONCLUSIONS: In this study, the suspicion of mRNA COVID-19 vaccine-associated myocarditis was inconstantly confirmed by gold standard diagnostics. Myocarditis was uncomplicated in both PM and NM patients. Larger studies with longer follow-up are needed to validate COVID-19 vaccination in this population.

Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

Myocarditis related SARS-CoV-2 infection or vaccination: an expert consensus statement on its diagnosis and management.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has revealed several cardiovascular complications, including myocarditis caused by SARS-CoV-2 infection (COVID-19) or after messenger RNA vaccine administration. Because of the high prevalence of COVID-19, the expansion of vaccination programs, and the appearance of new information on myocarditis in these contexts, there is a need to condense the knowledge acquired since the start of the pandemic. To meet this need, this document was drafted by the Myocarditis Working Group of the Heart Failure Association of the Spanish Society of Cardiology, with the collaboration of the Spanish Agency for Medicines and Health Products (AEMPS). The document aims to address the diagnosis and treatment of cases of myocarditis associated with SARS-CoV-2 infection or messenger RNA vaccine administration.

Diagnosis and Treatment of Acute Myocarditis: A Review.

Importance: Acute myocarditis, defined as a sudden inflammatory injury to the myocardium, affects approximately 4 to 14 people per 100 000 each year globally and is associated with a mortality rate of approximately 1% to 7%. Observations: The most common causes of myocarditis are viruses, such as influenza and coronavirus; systemic autoimmune disorders, such as systemic lupus erythematosus; drugs, such as immune checkpoint inhibitors; and vaccines, including smallpox and mRNA COVID-19 vaccines. Approximately 82% to 95% of adult patients with acute myocarditis present with chest pain, while 19% to 49% present with dyspnea, and 5% to 7% with syncope. The diagnosis of myocarditis can be suggested by presenting symptoms, elevated biomarkers such as troponins, electrocardiographic changes of ST segments, and echocardiographic wall motion abnormalities or wall thickening. Cardiac magnetic resonance imaging or endomyocardial biopsy are required for definitive diagnosis. Treatment depends on acuity, severity, clinical presentation, and etiology. Approximately 75% of patients admitted with myocarditis have an uncomplicated course, with a mortality rate of approximately 0%. In contrast, acute myocarditis that is complicated by acute heart failure or ventricular arrhythmias is associated with a 12% rate of either in-hospital mortality or need for heart transplant. Approximately 2% to 9% of patients have hemodynamic instability, characterized by inability to maintain adequate end-organ perfusion, and require inotropic agents, or mechanical circulatory devices, such as extracorporeal life support, to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days. Immunosuppression (eg, corticosteroids) is appropriate for patients who have myocarditis characterized by eosinophilic or giant cell myocardial infiltrations or due to systemic autoimmune disorders. However, the specific immune cells that should be targeted to improve outcomes in patients with myocarditis remain unclear. Conclusions and Relevance: Acute myocarditis affects approximately 4 to 14 per 100 000 people per year. First-line therapy depends on acuity, severity, clinical presentation, and etiology and includes supportive care. While corticosteroids are often used for specific forms of myocarditis (eg, eosinophilic or giant cell infiltrations), this practice is based on anecdotal evidence, and randomized clinical trials of optimal therapeutic interventions for acute myocarditis are needed.

Ventricular Arrhythmia and COVID-19 Vaccine-associated Myocarditis.

17-year-old male presented with COVID-19 vaccine-associated myocarditis. Six months later, due to chest discomfort with exercise, the patient underwent an exercise stress test that revealed a 3-beat run of nonsustained ventricular tachycardia at 230 bpm at peak exercise. The long-term outcomes of COVID-19 vaccine-associated myocarditis are unclear. This patient had nonsustained ventricular tachycardia over 6 months after diagnosis.

Application of Magnetocardiography to Screen for Inflammatory Cardiomyopathy and Monitor Treatment Response.

Background Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine-related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine-related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days (P=0.010) and to 0.03 within 30 days (P<0.001). After 30 days, left ventricular ejection fraction improved from 42.2% at baseline to 53.8% (P<0.001). Conclusions Magnetocardiography has the potential to be used for diagnostic screening and to monitor early treatment response. The method is valuable in inflammatory cardiomyopathy, where there is a major unmet need for early diagnosis and monitoring response to immunosuppressive therapy.

COVID-19-associated myocardial injury: A case report.

Coronavirus disease 2019 (COVID-19) is often accompanied by pneumonia and can be fatal. We report a case of COVID-19-associated myocardial injury mimicking fulminant myocarditis. Endomyocardial biopsy revealed numerous von Willebrand factor-rich microthrombi with small myocardial necrotic areas, complement deposits in small vessels/microthrombi, and macrophage-predominant interstitial infiltration. These findings, distinct from those of typical lymphocytic myocarditis, show diffuse endothelial injury, complement activation, and activated macrophages as characteristic features of COVID-19-associated pathogenesis. Dysregulated serum cytokine profiles predicting severe/critical COVID-19-associated myocardial injury were also determined. This case emphasizes the occurrence of fatal cardiac manifestation with microthrombotic injury in the early stage of COVID-19.