Cause Of Myocarditis Research Articles

Myocarditis following administration of COVID-19 Vaccine: Should we be worried?

The COVID-19 vaccines have raised scepticism surrounding their accelerated approval due to their suspected adverse side effects.(1) Recently emerging clinical cases such as flu, fever, tachycardia, Bell’s palsy, and swelling of the lymph nodes have further heightened public distrust. Interestingly, the United States Food and Drug Administration has recently announced an inflammatory heart disease, Myocarditis, as a potential risk of the Pfizer-BioNTech COVID-19 vaccine. In efforts to find an association between the Pfizer vaccine and Myocarditis, researchers recently carried out extensive clinical trials; two new studies tracked cases having biomarker evidence of myocardial injury and Cardiac Magnetic Resonance Imaging.(2,3) Moreover, the United States Centers for Disease Control and Prevention (CDC) has recorded 323 confirmed cases of myocarditis, most documented within a week after each patient had received the Pfizer-BioNTech COVID-19 vaccine.(4) A recent emergent theory suggests a cytokine response as the leading cause of myocarditis; the immune system identifies the mRNA in the vaccine as an antigen, leading to the activation of proinflammatory cascades and immunological pathways. The expression of cytokines and activation markers is due to the exposure of the dendritic cells to mRNA, which eventually causes inflammation of the heart muscle.(4) Furthermore, according to the CDC, the myocarditis is mainly observed in male adolescents and young adults, more often after getting the second dose of the COVID-19 vaccine. A week after administrating the vaccine, symptoms such as chest pain, shortness of breath, and tachycardia may appear, which tend to resolve following conservative treatment with nonsteroidal anti-inflammatory drugs.(3) Despite the previously mentioned occurrences of myocarditis after administration of the Pfizer-BioNtech vaccine, we would like to highlight the results of a large-scale cohort study in Israel with 2.5 million participants, where the estimated incidence of myocarditis after the administration of the Pfizer vaccine was only 2.13 cases per 100,000 persons.(5) These statistics allow us to draw the readers’ attention towards the benefits of the COVID-19 vaccination, which outweigh potential adverse risks such as Myocarditis. The Pfizer-BioNtech vaccine has proven to be 95% effective and to keep track of other possible complications, patients are advised to report to the Vaccine Adverse Event Reporting System (VAERS) to document any unusual side effects.(4) Despite the few reported complications, we would further like to emphasize the importance of population- wide vaccination to overcome the COVID-19 pandemic with a minimum mortality rate.

A Real Circuit Breaker: Hyperhemolysis Syndrome Related to the VA-ECMO Circuit?

<h3>Introduction</h3> Myocarditis is an inflammatory disease of cardiac muscle caused by a variety of infectious and non-infectious conditions. Viral infection is the most frequent cause of myocarditis; however, herpes simplex virus 1 (HSV-1) infection causing myocarditis has been rarely described. We present a case of a young woman with HSV-1 viremia and fulminant myocarditis presenting with cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO), complicated by hyperhemolysis. <h3>Case Report</h3> A 35 year-old immunocompetent woman with moderate alcohol consumption presented to hospital with a 4-day history of fever and flu-like symptoms. She was fully vaccinated for COVID-19 two months prior to symptom onset. Her COVID-19 testing was negative and she was discharged home. She returned to hospital 4 days later in cardiogenic shock. Transthoracic echocardiogram demonstrated LVEF of 30% with a small pericardial effusion. Coronary angiogram revealed normal coronaries. She was placed on peripheral VA-ECMO for worsening cardiogenic shock. Due to inadequate LV unloading, she underwent atrial septostomy. Five days after VA-ECMO cannulation, HSV-1 was detected in the blood and she was started on intravenous acyclovir. Her ECMO course was complicated by acute kidney injury requiring dialysis, and hyperhemolysis with a peak LDH of 12,000 U/L. The mechanism of hemolysis was attributed to an intravascular process (plasma free hemoglobin 7487 mg/L, normal < 150 mg/L) likely from a combination cold agglutinins and the mechanical circuit. Interestingly the membrane pressure gradient was within normal. The patient received treatment with plasmapheresis (Table 1), and was eventually decannulated after 12 days following hemodynamic improvement. <h3>Summary</h3> This case report highlights a rare viral cause of fulminant myocarditis and emphasizes the need for collaboration among various specialists in the management of complex cases.

Role Of Immunomodulators And Early Mechanical Circulation Support In A Life Threatening Presentation Of Fulminant Lymphocytic Myocarditis

Introduction Lymphocytic Myocarditis is a rare cause of myocarditis with an incidence of 22 cases per 100,000. There is limited data in terms of role of immunomodulators and protocolized initiation of mechanical circulation support (MCS). We present a case to emphasize early recognition and prompt initiation of MCS to manage the hemodynamic derangements caused by fulminant myocarditis. Case Description A 19-year-old female with no significant past medical history presented to the ED due to a four-day history of chest pain, dyspnea, fatigue, and palpitations associated with leukocytosis, elevated lactate, and troponins. Initial EKG and telemetry showed SVT with heart rate in the 140s. Treatment with diltiazem led to hypotension, syncope, and clinical deterioration necessitating a transfer to the CVICU. Initial echocardiogram showed mild left ventricular thickness due to edema, minimal LV enlargement, and estimated ejection fraction at 25%. Patient's right heart catheterization showed a CI of 1.09 with a SVR of 2275 dynes on ionotropic support. Due to third degree heart block and junctional escape rhythm, a transvenous pacemaker was placed. Intra-aortic balloon pump (IABP) was placed to unload the left ventricle and endomyocardial biopsy (EMB) was performed. Patient further deteriorated due to development of refractory sustained ventricular tachycardia (VT) unresponsive to defibrillation. A decision was made to escalate to peripheral veno-arterial extracorporeal membrane oxygenation (ECMO). In addition, patient also developed multiorgan failure; AKI, altered mental status and shock liver which were monitored closely. EMB showed extensive lymphocytic infiltration, myocardial edema associated with myocardial cell necrosis and patient was diagnosed with lymphocytic myocarditis. Patient was initiated on 0.5 mg per kg of IVIG for two days and scheduled steroids followed by a taper. Her lactate cleared after 48 hours of ECMO, BNP and ALT down-trended significantly and creatinine improved subsequently. She was weaned off ECMO, and eventually IABP and inotropes. She was downgraded and eventually discharged after a total stay of 12 days. Conclusion Though there is scarce data regarding management of myocarditis, our case illustrates improvement in hemodynamics with prompt initiation of IVIG and steroids combined with ECMO support. We advocate quick escalation to MCS before the electrical storm sets in place from cardioversion of ventricular arrythmias. Additionally, it emphasizes the role of bedside echocardiogram, troponins, BNP, and EKG in an ED setting for early recognition and timely initiation of hemodynamic support can be lifesaving. The role of EMB is paramount. Lymphocytic Myocarditis is a rare cause of myocarditis with an incidence of 22 cases per 100,000. There is limited data in terms of role of immunomodulators and protocolized initiation of mechanical circulation support (MCS). We present a case to emphasize early recognition and prompt initiation of MCS to manage the hemodynamic derangements caused by fulminant myocarditis. A 19-year-old female with no significant past medical history presented to the ED due to a four-day history of chest pain, dyspnea, fatigue, and palpitations associated with leukocytosis, elevated lactate, and troponins. Initial EKG and telemetry showed SVT with heart rate in the 140s. Treatment with diltiazem led to hypotension, syncope, and clinical deterioration necessitating a transfer to the CVICU. Initial echocardiogram showed mild left ventricular thickness due to edema, minimal LV enlargement, and estimated ejection fraction at 25%. Patient's right heart catheterization showed a CI of 1.09 with a SVR of 2275 dynes on ionotropic support. Due to third degree heart block and junctional escape rhythm, a transvenous pacemaker was placed. Intra-aortic balloon pump (IABP) was placed to unload the left ventricle and endomyocardial biopsy (EMB) was performed. Patient further deteriorated due to development of refractory sustained ventricular tachycardia (VT) unresponsive to defibrillation. A decision was made to escalate to peripheral veno-arterial extracorporeal membrane oxygenation (ECMO). In addition, patient also developed multiorgan failure; AKI, altered mental status and shock liver which were monitored closely. EMB showed extensive lymphocytic infiltration, myocardial edema associated with myocardial cell necrosis and patient was diagnosed with lymphocytic myocarditis. Patient was initiated on 0.5 mg per kg of IVIG for two days and scheduled steroids followed by a taper. Her lactate cleared after 48 hours of ECMO, BNP and ALT down-trended significantly and creatinine improved subsequently. She was weaned off ECMO, and eventually IABP and inotropes. She was downgraded and eventually discharged after a total stay of 12 days. Though there is scarce data regarding management of myocarditis, our case illustrates improvement in hemodynamics with prompt initiation of IVIG and steroids combined with ECMO support. We advocate quick escalation to MCS before the electrical storm sets in place from cardioversion of ventricular arrythmias. Additionally, it emphasizes the role of bedside echocardiogram, troponins, BNP, and EKG in an ED setting for early recognition and timely initiation of hemodynamic support can be lifesaving. The role of EMB is paramount.

RNA Virus Gene Signatures Detected in Patients With Cardiomyopathy After Chemotherapy; A Pilot Study.

BackgroundViral infections are pervasive and leading causes of myocarditis. Immune-suppression after chemotherapy increases opportunistic infections, but the incidence of virus-induced myocarditis is unknown.ObjectiveAn unbiased, blinded screening for RNA viruses was performed after chemotherapy with correlation to cardiac function.MethodsHigh-throughput sequencing of RNA isolated from blood samples was analyzed following chemotherapy for hematological malignancies (N = 28) and compared with left ventricular ejection fraction (LVEF).ResultsOn initial rigorous analysis, low levels of influenza orthomyxovirus and avian paramyxovirus sequences were detectable, but without significant correlation to LVEF (r = 0.208). A secondary broad data mining analysis for virus sequences, without filtering human sequences, detected significant correlations for paramyxovirus with LVEF after chemotherapy (r = 0.592, P < 0.0096). Correlations were similar for LVEF pre- and post- chemotherapy for orthomyxovirus (R = 0.483, P < 0.0421). Retrovirus detection also correlated with LVEF post (r = 0.453, p < 0.0591), but not pre-chemotherapy, but is suspect due to potential host contamination. Detectable phage and anellovirus had no correlation. Combined sequence reads (all viruses) demonstrated significant correlation (r = 0.621, P < 0.0078). Reduced LVEF was not associated with chemotherapy (P = NS).ConclusionsThis is the first report of RNA virus screening in circulating blood and association with changes in cardiac function among patients post chemotherapy, using unbiased, blinded, high-throughput sequencing. Influenza orthomyxovirus, avian paramyxovirus and retrovirus sequences were detectable in patients with reduced LVEF. Further analysis for RNA virus infections in patients with cardiomyopathy after chemotherapy is warranted.

Cardiac MRI Findings of Myocarditis After COVID-19 mRNA Vaccination in Adolescents

BACKGROUND. A possible association has been reported between COVID-19 messenger RNA (mRNA) vaccination and myocarditis. OBJECTIVE. The purpose of our study was to describe cardiac MRI findings in patients with myocarditis after COVID-19 mRNA vaccination. METHODS. This retrospective study included patients without known prior SARS-CoV-2 infection who underwent cardiac MRI between May 14, 2021, and June 14, 2021, for suspected myocarditis within 2 weeks of COVID-19 mRNA vaccination. Information regarding clinical presentation, hospital course, and events after hospital discharge were recorded. A cardiothoracic imaging fellow and cardiothoracic radiologist reviewed cardiac MRI examinations in consensus. Data were summarized descriptively. RESULTS. Of 52 patients without known prior SARS-CoV-2 infection who underwent cardiac MRI during the study period, five underwent MRI for suspected myocarditis after recent COVID-19 mRNA vaccination. All five patients were male patients ranging in age from 16 to 19 years (mean, 17.2 ± 1.0 [SD] years) who presented within 4 days of receiving the second dose of a COVID-19 mRNA vaccine. Troponin levels were elevated in all patients (mean peak troponin I value, 6.82 ± 4.13 ng/mL). Alternate possible causes of myocarditis were deemed clinically unlikely on the basis of medical history, physical examination findings, myocarditis viral panel, and toxicology screening. Cardiac MRI findings were consistent with myocarditis in all five patients on the basis of the Lake Louise criteria, including early gadolinium enhancement and late gadolinium enhancement (LGE) in all patients and corresponding myocardial edema in four patients. All five patients had a favorable hospital course and were discharged from the hospital in stable condition with improved or resolved symptoms after hospitalization (mean length of hospital stay, 4.8 days). Two patients underwent repeat cardiac MRI that showed persistent, although decreased, LGE. Three patients reported mild intermittent self-resolving chest pain after hospital discharge, and two patients had no recurrent symptoms after discharge. CONCLUSION. In this small case series, all patients with myocarditis after COVID-19 vaccination were male adolescents and had a favorable initial clinical course. All patients showed cardiac MRI findings typical of myocarditis from other causes. LGE persisted in two patients who underwent repeat MRI. These observations do not establish causality. CLINICAL IMPACT. Radiologists should be aware of a possible association of COVID-19 mRNA vaccination and myocarditis and recognize the role of cardiac MRI in the assessment of suspected myocarditis after COVID-19 vaccination.

Myocardial Injury Pattern at MRI in COVID-19 Vaccine-Associated Myocarditis.

BackgroundThere is limited data on the pattern and severity of myocardial injury in patients with COVID-19 vaccination associated myocarditis.PurposeTo describe myocardial injury following COVID-19 vaccination and to compare these findings to other causes of myocarditis.MethodsIn this retrospective cohort study, consecutive adult patients with myocarditis with at least one T1-based and at least one T2-based abnormality on cardiac MRI performed at a tertiary referral hospital between 2019-2021 were included. Patients were classified into one of three groups: myocarditis following COVID-19 vaccination, myocarditis following COVID-19 illness, and other myocarditis not associated COVID-19 vaccination or illness.ResultsOf the 92 included patients, 21 (22%) had myocarditis following COVID-19 vaccination (mean age 31 years ±14 [standard deviation]; 17 men; mRNA-1273 in 12 [57%] and BNT162b2 in 9 [43%]). Ten patients (11%) had myocarditis following COVID-19 illness (mean age 51 years ±14; 3 men), and 61 (66%) had other myocarditis (mean age 44 years ±18; 36 men). MRI findings in vaccine associated myocarditis included late gadolinium enhancement (LGE) in 17 (81%) and left ventricular dysfunction in 6 (29%). Compared with other causes of myocarditis, patients with vaccine associated myocarditis had higher left ventricular ejection fraction and less extensive LGE, even after controlling for age, sex, and duration between symptom onset and MRI. The most frequent location of LGE in all groups was subepicardial at the basal inferolateral wall, although septal involvement was less common in vaccine associated myocarditis. At short-term follow-up (median 22 [IQR 7-48] days), all patients with vaccine associated myocarditis were asymptomatic with no adverse events.ConclusionsCardiac MRI demonstrated a similar pattern of myocardial injury in vaccine associated myocarditis compared to other causes, although abnormalities were less severe, with less frequent septal involvement, and no adverse events over short-term follow-up.See also the editorial by Raman and Neubauer.

Fatal Toxoplasma gondii myocarditis in an urban pet dog.

A 70-day-old Boxer dog from a household in Montevideo, Uruguay, died after presenting neurologic, respiratory, and gastrointestinal signs for 6days. Autopsy findings included lymphadenomegaly, ascites and hepatomegaly. Histopathology revealed severe widespread lymphohistiocytic and plasmacytic myocarditis with cardiomyocyte necrosis, mineralization and numerous intrasarcoplasmic protozoa immunoreactive with anti-Toxoplasma gondii antisera on immunohistochemistry. The protozoa were ultrastructurally confirmed as T. gondii by transmission electron microscopy. Other lesions included diffuse centrilobular hepatocellular necrosis, multifocal lymphohistiocytic portal hepatitis and interstitial nephritis. Other causes of myocarditis, including Neospora caninum, Trypanosoma cruzi, Sarcocystis neurona, canine distemper virus, and canine parvovirus were ruled out by immunohistochemistry. Toxoplasma gondii infections in dogs are usually subclinical; however, clinical disease with fatal outcome can occur. To our knowledge, this is the first report of fatal toxoplasmosis in a dog in Uruguay. This case raises awareness for dogs as sentinels and possible sources of human toxoplasmosis in urban settings in Uruguay.

Rhinovirus as a rare cause of acute onset dilated cardiomyopathy due to myocarditis in a newborn: case report and review of the literature

Cardiomyopathies account for 1% of cardiac diseases that mainly originate from myocarditis in the form of dilated cardiomyopathy in the neonatal period. Viruses are the main cause of myocarditis resulting in dilated cardiomyopathy. Rhinovirus is the leading cause of viral respiratory infections though it is rarely severe. We report a 17 day old newborn with acute onset dilated cardiomyopathy due to myocarditis that developed after a viral respiratory infection caused by Rhinovirus who was admitted to the emergency ward with shock due to heart failure and recovered without any complications. This is the first case reporting the causal role of rhinovirus and myocarditis in the neonatal period. A comprehensive approach is needed for the diagnosis of myocarditis in the case of unknown etiology and an extensive respiratory panel may be taken into consideration if there is a history or clinical symptoms of respiratory infection.

Reversible myocardial injury aggravated by complex arrhythmias in three Toxoplasma gondii-positive dogs.

Although Toxoplasma gondii represents an oft-cited cause of myocarditis in veterinary medicine, the existing literature on the pre-mortem demonstration of T. gondii-associated myocardial injury (MI) in dogs is scant. In this case series, we provide detailed clinical, laboratory, echocardiographic and electrocardiographic description of three T. gondii-positive dogs diagnosed with MI. In all cases, etiological diagnosis was based on the antibody screening test (all dogs had IgM titres ≥1:64) and MI was demonstrated by a concomitant increase of the serum concentration of cardiac troponin I (0.25–9.6 ng/ml, upper hospital limit <0.15 ng/ml). In all dogs, MI was aggravated by complex arrhythmias (ventricular in two dogs, and either ventricular and supraventricular in the remaining dog). In one case, left ventricular systolic dysfunction was also present. All dogs underwent an extensive diagnostic work-up aimed at excluding additional comorbidities, either cardiac and extra-cardiac, possibly able to contribute to MI, arrhythmias and systolic dysfunction. All dogs received appropriate antiprotozoal (i.e., clindamycin) and antiarrhythmic (i.e., amiodarone, sotalol) therapy. This was systematically followed by a simultaneous decline in T. gondii serology titres, normalisation of troponin level and left ventricular systolic function, and the resolution of clinical and electrocardiographic abnormalities. In light of this result, therapies were interrupted and subsequent controls ruled out any disease relapse. In these cases, the clinical and instrumental findings obtained at admission and rechecks strongly supported the clinical suspicion of toxoplasmic myocarditis.

Cardiac MRI Assessment of Nonischemic Myocardial Inflammation: State of the Art Review and Update on Myocarditis Associated with COVID-19 Vaccination.

Myocarditis is a nonischemic inflammatory disease of the myocardium that can be triggered by a multitude of events, including viral infection and toxins. Recently, there has been heightened interest in myocarditis given its association with COVID-19 vaccination. Timely identification of myocarditis can affect patient management and prognosis. Therefore, it is crucial for radiologists and cardiac imagers to understand the role of cardiac imaging to establish a diagnosis and inform treatment decisions. Cardiac MRI is the most important noninvasive imaging modality for evaluation of myocarditis, with typical findings of focal or diffuse myocardial edema and myocardial damage, including presence of late gadolinium enhancement. There are currently limited data available to indicate that the pattern of myocardial injury following COVID-19 vaccination is similar to other causes of myocarditis, although the severity of disease may be relatively mild. A description of the role of imaging and typical imaging features will be reviewed here, with a focus on emerging data in the setting of myocarditis after COVID-19 vaccination.Keywords: MRI, Heart, Inflammation© RSNA, 2021

Cardiovascular consequences of viral infections: from COVID to other viral diseases.

Infection of the heart muscle with cardiotropic viruses is one of the major aetiologies of myocarditis and acute and chronic inflammatory cardiomyopathy (DCMi). However, viral myocarditis and subsequent dilated cardiomyopathy is still a challenging disease to diagnose and to treat and is therefore a significant public health issue globally. Advances in clinical examination and thorough molecular genetic analysis of intramyocardial viruses and their activation status have incrementally improved our understanding of molecular pathogenesis and pathophysiology of viral infections of the heart muscle. To date, several cardiotropic viruses have been implicated as causes of myocarditis and DCMi. These include, among others, classical cardiotropic enteroviruses (Coxsackieviruses B), the most commonly detected parvovirus B19, and human herpes virus 6. A newcomer is the respiratory virus that has triggered the worst pandemic in a century, SARS-CoV-2, whose involvement and impact in viral cardiovascular disease is under scrutiny. Despite extensive research into the pathomechanisms of viral infections of the cardiovascular system, our knowledge regarding their treatment and management is still incomplete. Accordingly, in this review, we aim to explore and summarize the current knowledge and available evidence on viral infections of the heart. We focus on diagnostics, clinical relevance and cardiovascular consequences, pathophysiology, and current and novel treatment strategies.

39-YEAR-OLD WITH LEGIONELLA MYOCARDITIS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Myocarditis is an inflammatory condition of the myocardium. Legionella is a known rare infectious cause of myocarditis. Additionally, it has been implicated with pericarditis and prosthetic valve endocarditis. We present a case of a 39-year-old male with legionella pneumonia with myocarditis, acute renal failure, and rhabdomyolysis. CASE PRESENTATION: A 39-year-old male with no known past medical history presented to the emergency department with worsening dyspnea after a viral syndrome for 3 weeks. He was intubated in the emergency department for respiratory failure. Chest x-ray showed multifocal atypical infiltrates. Electrocardiogram significant for diffuse ST depressions. Echocardiogram revealed severe left ventricular systolic dysfunction with ejection fraction of 30% with no valvular abnormalities. Lab analysis revealed hyponatremia, elevated troponins and acute renal failure with rhabdomyolysis requiring hemodialysis. Atypical serology was positive for Legionella which was treated with levofloxacin and azithromycin. SARS-CoV-2 PCR was negative and urine drug screen was negative. He was diagnosed with myocarditis given the legionella culture, elevated troponins, significant for electrocardiogram and echocardiogram findings. DISCUSSION: The first case of Legionella myocarditis was reported in 1981 by Gross [1]. Symptoms of myocarditis can range from a mild flu-like illness to cardiogenic shock or sudden death. Myocarditis is the cause of 12% of sudden deaths in young adults [2]. Diagnosis is typically made clinically with non-diagnostic exams, as endomyocardial biopsy is only used for special circumstances when other testing are non-diagnostic. A literature review of Legionella myocarditis as of 2017 portrayed ten patients with positive Legionella urine antigens, with eight having reduced left ventricular ejection fraction on echocardiogram. Only two of those cases were based on cardiac biopsy [3]. CONCLUSIONS: Extrapulmonary manifestations of Legionella such as myocarditis have been reported even in the absence of overt pneumonia, and most often in immunocompromised patients. Clinicians should be aware of Legionella in the setting of unexplained myocarditis with findings as above. Treatment should be initiated for this reversible cause of myocarditis without delay, resulting in favorable prognosis. REFERENCE #1: Armengol, S., Domingo, C., Messales, E., (1992). Myocarditis: a rare complication during Legionella infection. DOI: 10.1016/0167-5273(92)90276-9 REFERENCE #2: Damasio, A.F, Rodriguez, L., Miranda, L/, Coelho, P., Banazol, N., Colaco, J., Fragata, J. (2014). Fulminant myocarditis caused by Legionella pneumophila: Case report. Revista Portuguesa de Cardiologia. Vol 33, Issue 3. https://doi.org/10.1016/j.repce.2013.09.015 REFERENCE #3: Erdogan, Haluk & Eldem, Halil. (2017). A Patient with Suspected Myocarditis Associated with Legionnaires' Disease: A Case Report and Review of the Literature. Mediterr J Infect Microb Antimicrob. 6. 10.4274/mjima.2017.2. DISCLOSURES: No relevant relationships by James McGee, source=Web Response No relevant relationships by Visala Natarajan, source=Web Response no disclosure on file for Ben Shamian

Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data - United States, March 2020-January 2021.

Viral infections are a common cause of myocarditis, an inflammation of the heart muscle (myocardium) that can result in hospitalization, heart failure, and sudden death (1). Emerging data suggest an association between COVID-19 and myocarditis (2-5). CDC assessed this association using a large, U.S. hospital-based administrative database of health care encounters from >900 hospitals. Myocarditis inpatient encounters were 42.3% higher in 2020 than in 2019. During March 2020-January 2021, the period that coincided with the COVID-19 pandemic, the risk for myocarditis was 0.146% among patients diagnosed with COVID-19 during an inpatient or hospital-based outpatient encounter and 0.009% among patients who were not diagnosed with COVID-19. After adjusting for patient and hospital characteristics, patients with COVID-19 during March 2020-January 2021 had, on average, 15.7 times the risk for myocarditis compared with those without COVID-19 (95% confidence interval [CI]=14.1-17.2); by age, risk ratios ranged from approximately 7.0 for patients aged 16-39 years to >30.0 for patients aged <16 years or ≥75 years. Overall, myocarditis was uncommon among persons with and without COVID-19; however, COVID-19 was significantly associated with an increased risk for myocarditis, with risk varying by age group. These findings underscore the importance of implementing evidence-based COVID-19 prevention strategies, including vaccination, to reduce the public health impact of COVID-19 and its associated complications.

Differences between genetic dilated cardiomyopathy and myocarditis in children presenting with severe cardiac dysfunction.

Acute myocarditis is an inflammatory disease of the myocardium, and it can present as severe heart failure in children. Differential diagnosis with genetic cardiomyopathy can be difficult. The objective of this study is to identify patterns of clinical presentation and to assess invasive and non-invasive measures to differentiate patients with acute myocarditis from patients with dilated genetic cardiomyopathy. We performed a retrospective descriptive study of all paediatric patients (0–16 years old) that presented with new-onset heart failure with left ventricle ejection fraction < 35% in whom we performed an endomyocardial biopsy (EMB) during the period from April 2007 to December 2020. The patients were classified into two groups: Group 1 included 18 patients with myocarditis. Group 2 included 9 patients with genetic cardiomyopathy. Findings favouring a diagnosis of myocarditis included a fulminant or acute presentation (77.8% vs 33.3%, p = 0.01), higher degree of cardiac enzyme elevation (p = 0.011), lower left ventricular dimension z-score (2.2 vs 5.4, p = 0.03) increase of ventricular wall thickness (88.8% vs 33.3%, p = 0.03) and oedema in the EMB. Seven (77.8%) patients with genetic cardiomyopathy had inflammation in the endomyocardial biopsy fulfilling the diagnostic criteria of inflammatory cardiomyopathy.Conclusion: Differentiating patients with a myocarditis from those with genetic cardiomyopathy can be challenging, even performing an EMB. Some patients with genetic cardiomyopathy fulfil the diagnostic criteria of inflammatory cardiomyopathy. Using invasive and non-invasive measures may be useful to develop a predictive model to differentiate myocarditis from genetic cardiomyopathy. What is Known:• Acute myocarditis could present with cardiogenic shock in paediatric patients.• Parvovirus B19 is the main cause of myocarditis in this population.What is New:• Current diagnostic criteria for myocarditis have limited use in paediatric patients presenting with new-onset heart failure.• Some patients with a genetic cardiomyopathy and a new-onset heart failure fulfill the diagnostic criteria of inflammatory cardiomyopathy.Supplementary informationThe online version contains supplementary material available at 10.1007/s00431-021-04175-z.

Recurrent Marijuana Induced Myocarditis: A Case Report

Thirty-Three states in the US have passed laws to legalize marijuana usage, increasing its prevalence by 50% within the last year. Though society generally regards cannabis as safe, the exponential increase in users can evince dangerous side effects in patients presenting to physicians, such as the case presented below. A 37-year-old female presented to the ED with chest pain and an initial troponin of 24 that peaked at 29. The coronary arteries were found to be angiographically normal. She was discharged without any definitive diagnosis. Now 38, she again presented with complaints of crushing, substernal chest pain radiating down her left arm, unrelieved by nitro. Since the onset of pain, she progressively developed shortness of breath, nausea, diaphoresis, and anxiety, stating that she felt like she “was going to die.” Her presentation and impending sense of doom were ominous harbingers for a myocardial infarction; concerns that were validated with an initial troponin of 11.4. EKG showed normal sinus rhythm with nonspecific ST changes. CT Angiogram showed no evidence of pulmonary thrombo-embolism or dissection. Significant CAD leading to this extent of troponin elevation was not suspected as the patient had a normal angiogram a year prior. Stress-Induced Cardiomyopathy was unlikely based on the unremarkable echocardiogram findings. Coronary-Thrombus was considered, however, the hypercoagulable workup was negative along with lack of coronary thrombus on prior angiogram. Under these circumstances, the only explanation for the extent of troponin elevation was myocarditis. Viral infections are the most common cause of myocarditis, however the patient denied any associated symptoms. After ruling out viral etiologies, we subsequently evaluated and eliminated rheumatological disorders and medication-induced myocarditis. The patient’s history revealed that she led a healthy lifestyle, but had struggled with chronic back pain, which led to her cannabis use. By the time of her admission, she smoked up to 1.5 grams of cannabis a day, and stated that chest pain began immediately following smoking cannabis. Her previous episodes also correlated with her cannabis usage. Given the strong correlation of the patient’s symptoms with cannabis use, we theorized her cardiac stress was resultant from it, and recommended that she discontinue its use. To date there have been four reported cases of cannabis-induced myocarditis, making this a fifth case. Of note, the contaminants of marijuana may be variable and include substances like aluminum from soil or pesticides in grass that could traverse the marijuana plant. Inhaling such components has been correlated with an upregulation of cannabinoid receptors in platelets, vascular smooth muscle, and endothelium. CB1R activation has been observed to induce oxidative stress, inflammation, and fibrosis of the cardiomyocyte. With increased cannabis use, it is imperative that we document adverse events to definitively connect its use to cardiac damage.

Fatal Enterovirus-related Myocarditis in a Patient with Devic's Syndrome Treated with Rituximab.

Enteroviruses are a frequent source of infection and among the most common central nervous system viral pathogens. Enteroviruses – in particular, the Coxsackie B viruses – are a known cause of myocarditis. Rituximab is a genetically engineered chimeric anti-CD20 monoclonal antibody. Many reports in the literature suggest a higher risk of infection following repeated rituximab therapy, including viral infection. However, observations of enterovirus-related myocarditis in the context of rituximab treatment are scarce. The authors describe the case of a patient with neuromyelitis optica spectrum disorder who developed severe and fatal enterovirus-related myocarditis after rituximab therapy with a difficult differential diagnosis of autoimmune or giant-cell myocarditis. This case highlights the importance of complete diagnostic workup in difficult cases of myocarditis, including endomyocardial biopsies.

A Rare Case of Myocarditis Induced by Cannabis Use

Cannabis is one of the most commonly abused drugs in the world and there is a widespread misconception that cannabis is a safe drug without adverse effects. Tetrahydrocannabinol (THC) is one of the main chemicals of cannabis and considerable research suggests that cannabis and THC may have severe consequences on mental as well as physical health. However, the cardiovascular effects of cannabis are not well known. This article outlines the first reported case of pediatric death due to myocarditis induced by cannabis exposure. The subject is an 11-month-old male without any previous medical history that presented to the emergency department with central nervous system depression. The patient then went into cardiac arrest and died. Autopsy revealed myocarditis as the cause of death. Post-mortem blood analysis further revealed high concentrations of Δ-9-THC which is a metabolite of THC that can be detected for 24 hours after exposure. Considering that no other alternate causes of myocarditis have been confirmed, this raises cannabis exposure as the most likely cause. Although this is the first case of death from cannabis-induced myocarditis, there have been other cases wherein which cannabis exposure lead to myocarditis in young males. Altogether, these cases highlight the need for further investigation into the cardiovascular effects of cannabis and to consider cannabis in the diagnosis of myocarditis.

Recurrent HHV-7 myocarditis in a 16-year-old boy

Recurrent myocarditis is very rare, with most cases reported in adults. We present a case of a 16-year-old boy with 2 episodes of myocarditis 4 months apart. The aetiological factor of the first episode was not detected, whereas the second episode was caused by HHV-7 infection, which, according to literature reports, is an extremely rare cause of myocarditis. We described the evolution of changes in electrocardiography, changes in echocardiography and magnetic resonance as well as laboratory abnormalities, with particular focus on the differences between the first and the second episode. The patient was treated with bed rest and enalapril. Metoprolol was included during the second episode. The left ventricular function returned to normal after both episodes. This rare course of disease indicates the need for further clinical follow-up and periodic cardiac check-up in children considered to be cured.

ANMCO/SIC Consensus document on the management of myocarditis

Myocarditis is an inflammatory heart disease that can occur acutely, as in acute myocarditis, or persistently, as in chronic myocarditis or chronic inflammatory cardiomyopathy. Different agents can induce myocarditis, with viruses being the most common triggers. Generally, acute myocarditis affects relatively young people and men more than women. Myocarditis has a broad spectrum of clinical presentations and evolution trajectories, although most cases resolve spontaneously. Patients with reduced left ventricular ejection fraction, heart failure symptoms, advanced atrioventricular block, sustained ventricular arrhythmias or cardiogenic shock (the latter known as fulminant myocarditis) are at increased risk for death and heart transplantation. The presentation of chronic inflammatory cardiomyopathy may be more subtle, with progressive symptoms of heart failure or appearance of rhythm disturbance, not rarely preceded by an infective episode. Autoimmune disorder or systemic inflammatory conditions can be another significant predisposing substrate of myocarditis, especially in women. Emerging causes of myocarditis are drug-related like the new anticancer therapies, the immune checkpoint inhibitors. In this Italian Association of Hospital Cardiologists (ANMCO) and Italian Society of Cardiology (SIC) expert consensus document on myocarditis, we propose diagnostic strategies for identifying possible causes of the disease and factors associated with increased risk. Finally, we propose potential treatments and when referring patients to tertiary centers, especially for high-risk patients. Even if endomyocardial biopsy is the invasive diagnostic tool for making definitive diagnosis and differentiation of histological subtypes (i.e., lymphocytic vs eosinophilic vs giant cell myocarditis), it is not always readily available in all centers. Thus, we propose when this exam is mandatory or when it can be postponed or substituted by cardiac magnetic resonance imaging. This document reflects the Italian perspective on managing patients with myocarditis and their follow-up, considering also current US and European scientific position statements.

Case report of severe PCR-confirmed COVID-19 myocarditis in a European patient manifesting in mid January 2020.

BackgroundViral genesis is the most common cause of myocarditis. COVID-19-associated myocarditis seems to be a notable extrapulmonary manifestation, which may result in the need for a different treatment. There has been no positive polymerase chain reaction (PCR) testing of SARS-CoV-2 in heart specimens, thus far.Case summaryA 48-year-old male patient presented with fever, dyspnoea, and haemoptysis. Laboratory findings showed highly elevated inflammatory and cardiac damage markers. Thoracic computed tomography (CT) revealed bilateral, patchy peripheral ground-glass opacities with a crazy-paving pattern, focal consolidations, and mild pleural effusions. Cardiac imaging with echocardiography and magnetic resonance imaging (MRI) detected a reduced biventricular function. MRI additionally showed myocardial oedema and late gadolinium enhancement. Lung and heart biopsies were performed, revealing alveolitis with necrosis and acute lymphocytic myocarditis. Testing for usual cardiotropic viruses was negative, and no aspects of vasculitis or granuloma could be found. Due to fulfilling the criteria, the patient was diagnosed with rheumatic vasculitis. Treatment with cyclophosphamide and steroids was initiated. Later, the patient reported a history of travel to Tyrol in mid January. Consequently, PCR testing for SARS-CoV-2 was performed, which was positive in the heart specimen. Immunosuppressive treatment was discontinued. During a follow-up visit at the end of April, the patient’s recovery was stable.DiscussionIn COVID-19 infections, myocardial inflammation can be present as an extrapulmonary manifestation. Positive PCR testing confirms myocardial invasion of the virus. Imaging and laboratory studies correlate with the histopathological findings, and thus should be performed in COVID-19 patients who are suspicious for myocarditis. Supportive treatment with steroids may be useful in these patients.