Comparative assessment of myocarditis and pericarditis reporting rates related to mRNA COVID-19 vaccines in Europe and the United States.

OBJECTIVES: The novel mRNA vaccines proved to be safe and effective in averting severe COVID-19. Vaccine-related complications recorded by pharmacovigilance systems, such as 'EudraVigilance' in Europe and 'VAERS' in the United States (US), rarely include myocarditis and pericarditis. Given the novelty of the platform and the increasing global-scale vaccine production needs, we assessed their reporting rates comparatively across continents. METHODS: Data of myocarditis and pericarditis cases post COVID-19 vaccination reported from week 52/2020 (December 21 to 27, 2020) to week 40/2021 (October 4 to 10, 2021) were collected for mRNA vaccines from EudraVigilance and VAERS. The corresponding administered vaccine doses were used as denominators to estimate reporting rates for comparison purposes. Cross-tabulation analysis was employed to compare the reporting rates of mRNA vaccines-associated myocarditis and pericarditis between EudraVigilance and VAERS. RESULTS: Low reporting rates of myocarditis (7.64/million vaccine doses) and pericarditis (5.32/million) were found, with higher rates of both disorders in EudraVigilance compared to VAERS; these differences were more pronounced post-mRNA-1273 (5-6-fold, p=0.000 for myocarditis and p<0.001 for pericarditis) than post-BNT162b2 vaccination (1.5-2-fold, p<0.001 for both conditions). Most myocarditis cases occurred in males <30 years. Pericarditis affected predominantly males <40 and both sexes >40 years. The extremely rare fatalities related to myocarditis (0.102/million) or pericarditis (0.017/million) were also higher in EudraVigilance versus VAERS. CONCLUSIONS: Understanding the underlying causes of the observed differences could provide guidance for the enhanced quality of mRNA vaccines that would also foster vaccine acceptance.

Cardiovascular Risk Assessment after COVID-19 Infection before Resuming Sports Activities - Practical Flowchart and Meta-Analysis

Abstract Background: The risk of sports-related sudden cardiac arrest after COVID-19 infection can be a serious problem. There is an urgent need for evidence-based criteria to ensure patient safety before resuming exercise. Objective: To estimate the pooled prevalence of acute myocardial injury caused by COVID-19 and to provide an easy-to-use cardiovascular risk assessment toolkit prior to resuming sports activities after COVID-19 infection. Methods: We searched the Medline and Cochrane databases for articles on the prevalence of acute myocardial injury associated with COVID-19 infection. The pooled prevalence of acute myocardial injury was calculated for hospitalized patients treated in different settings (non-intensive care unit [ICU], ICU, overall hospitalization, and non-survivors). Statistical significance was accepted for p values <0.05. We propose a practical flowchart to assess the cardiovascular risk of individuals who recovered from COVID-19 before resuming sports activities. Results: A total of 20 studies (6,573 patients) were included. The overall pooled prevalence of acute myocardial injury in hospitalized patients was 21.7% (95% CI 17.3-26.5%). The non-ICU setting had the lowest prevalence (9.5%, 95% CI 1.5-23.4%), followed by the ICU setting (44.9%, 95% CI 27.7-62.8%), and the cohort of non-survivors (57.7% with 95% CI 38.5-75.7%). We provide an approach to assess cardiovascular risk based on the prevalence of acute myocardial injury in each setting. Conclusions: Acute myocardial injury is frequent and associated with more severe disease and hospital admissions. Cardiac involvement could be a potential trigger for exercise-induced clinical complications after COVID-19 infection. We created a toolkit to assist with clinical decision-making prior to resuming sports activities after COVID-19 infection.

A review of diagnosis, etiology, assessment, and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

Myocardial infarction (MI) in the absence of obstructive coronary artery disease (MINOCA) is prevalent in around 5% of acute myocardial infarction (AMI) presentations. MINOCA is a heterogeneous entity with many different etiologies. It is important for health care providers to familiarize themselves with the disease process, presentation, and possible underlying causes in order to guide appropriate management strategies. In this article, the authors review the contemporary definition, etiologies and assessment, and management for AMI patients with MINOCA.

Long-Term Arrhythmic Risk Assessment in Biopsy-Proven Myocarditis.

OBJECTIVES: This study sought to assess long-term arrhythmic risk in patients with myocarditis who received an implantable cardioverter-defibrillator (ICD). BACKGROUND: The arrhythmic risk of patients with myocarditis overtime remains poorly known. METHODS: The study enrolled 56 patients with biopsy-proven myocarditis who received an ICD for either primary (57%) or secondary prevention (43%) according to current guidelines. Clinical characteristics, biopsy findings, electrophysiological data from endocardial 3-dimensional electroanatomic voltage mapping, and device interrogation data were analyzed to detect arrhythmic events overtime. Coronary angiography excluded significant coronary artery disease in all patients. RESULTS: At a mean follow-up of 74 ± 60 months (median 65 months), 25 (45%) patients had major ventricular arrhythmias treated by ICD intervention (76% being terminated by ICD shock and 24% by antitachyarrhythmia burst pacing). At multivariable analysis, the presence of sustained ventricular tachycardia on admission (hazard ratio: 13.0; 95% confidence interval: 2.0 to 35.0; p = 0.032) and the extension of the areas of low potentials at the bipolar endocardial mapping (hazard ratio: 1.19; 95% confidence interval: 1.04 to 1.37; p = 0.013) were the only independent predictors of appropriate ICD interventions. A cutoff value of 10% of abnormal bipolar area at electroanatomical ventricular mapping discriminated patients with appropriate ICD interventions with a sensitivity of 89% and a specificity of 85%. CONCLUSIONS: The study demonstrates that the prevalence of life-threatening ventricular arrhythmias in patients with myocarditis receiving an ICD according to current guidelines is high and the arrhythmic risk persists late overtime. Electroanatomical ventricular mapping may be a useful tool to identify patients at greater arrhythmic risk.

Assessment of acute myocarditis by cardiac magnetic resonance imaging: Comparison of qualitative and quantitative analysis methods.

BACKGROUND: To compare cardiac magnetic resonance (CMR) qualitative and quantitative analysis methods for the noninvasive assessment of myocardial inflammation in patients with suspected acute myocarditis (AM). METHODS: A total of 61 patients with suspected AM underwent coronary angiography and CMR. Qualitative analysis was performed applying Lake-Louise Criteria (LLC), followed by quantitative analysis based on the evaluation of edema ratio (ER) and global relative enhancement (RE). Diagnostic performance was assessed for each method by measuring the area under the curves (AUC) of the receiver operating characteristic analyses. The final diagnosis of AM was based on symptoms and signs suggestive of cardiac disease, evidence of myocardial injury as defined by electrocardiogram changes, elevated troponin I, exclusion of coronary artery disease by coronary angiography, and clinical and echocardiographic follow-up at 3 months after admission to the chest pain unit. RESULTS: In all patients, coronary angiography did not show significant coronary artery stenosis. Troponin I levels and creatine kinase were higher in patients with AM compared to those without (both P < .001). There were no significant differences among LLC, T2-weighted short inversion time inversion recovery (STIR) sequences, early (EGE), and late (LGE) gadolinium-enhancement sequences for diagnosis of AM. The AUC for qualitative (T2-weighted STIR 0.92, EGE 0.87 and LGE 0.88) and quantitative (ER 0.89 and global RE 0.80) analyses were also similar. CONCLUSIONS: Qualitative and quantitative CMR analysis methods show similar diagnostic accuracy for the diagnosis of AM. These findings suggest that a simplified approach using a shortened CMR protocol including only T2-weighted STIR sequences might be useful to rule out AM in patients with acute coronary syndrome and normal coronary angiography.

Predictors, Burden, and the Impact of Arrhythmia on Patients Admitted for Acute Myocarditis.

A significant proportion of patients with acute myocarditis experience sudden cardiac death presumably due to cardiac arrhythmia. In this study, we explore the burden, the predictors of arrhythmia in acute myocarditis and the association between arrhythmias and adverse in-hospital outcomes. After evaluating the frequency of various tachyarrhythmias and bradyarrhythmia in myocarditis population, we built a logistic model to determine the independent predictors of arrhythmias in myocarditis and a 1:1 propensity-matched analysis to examine the impact of arrhythmias. Overall, cardiac arrhythmias were identified in 33.71% of the hospitalized myocarditis cases. Ventricular tachycardia and atrial fibrillation were most common arrhythmias. There were increased odds of in-hospital mortality, cardiogenic shock, use of mechanical circulatory support, pacemaker implantation, and nonroutine hospital discharges in the arrhythmia cohorts. Length of stay and cost of hospitalization were also significantly higher. A significant proportion of patients with myocarditis have cardiac arrhythmias. As the occurrence of arrhythmias in myocarditis is associated with worse outcomes, it may be important to risk stratify patient to identify those who will benefit from early intervention.

Assessment of edema using STIR+ via 3D cardiovascular magnetic resonance imaging in patients with suspected myocarditis.

OBJECTIVE: To evaluate three-dimensional T2-weighted fast spin echo triple inversion recovery sequences (STIR+) for the diagnosis of myocardial edema in patients with suspected early myocarditis after respiratory or gastrointestinal tract viral infection and at follow-up. MATERIALS AND METHODS: We prospectively examined 28 patients with suspected myocarditis and 37 controls matched for gender and age. An ECG-triggered STIR+ was used to cover the entire left ventricle in short-axis images with 10-mm slice thickness and no interslice gap. The global signal intensity ratio (heart muscle in relation to skeletal muscle) was calculated (global STIR+ ratio) to evaluate edema. All patients had repeat examinations at follow-up (mean interval 4.9 months, 1-12 months). RESULTS: The mean global STIR+ ratio was 2.15 ± 0.4 in the initial examination of patients as compared to 1.78 ± 0.3 in controls (p < 0.0001) and 1.89 ± 0.3 in patients at follow-up (p = 0.0001 vs. first visit). Left ventricular ejection fraction did not differ between patients and controls at baseline and at follow-up. CONCLUSION: We could identify a significantly higher global STIR+ ratio in patients with suspected myocarditis compared to controls, and a dynamic change during follow-up. The global STIR+ ratio may, therefore, be useful for the diagnosis of myocarditis and should be further explored.

Assessment of radiological techniques application possibility for non-invasive diagnostics of latent inflammatory processes in myocardium in patients with atrial fibrillation.

OBJECTIVE: Aim was to study the performance of single-photon emission computed tomography (SPECT) with 99mTc-pyrophosphate (99mTc-PYP) in diagnostics of chronic latent inflammation in myocardium of patients with atrial fibrillation (AF). METHODS: The research included 70 patients (the average age of 49.3 ± 10.2 years) with persistent form of idiopathic AF. All patients underwent myocardium SPECT with 99mTc-PYP and cardiac magnetic resonance imaging (CMR) before the ablation. During the ablation endomyocardium sampling for histological and immunohistochemical verification of myocarditis was performed. RESULTS: Sensitivity of SPECT with 99mTc-PYP in diagnoses of chronic latent myocarditis in patients with AF in relation to endomyocardial biopsy was 80 %, specificity-83 % and diagnostic accuracy-82 %. Sensitivity, specificity and diagnostic accuracy of myocardium perfusion scintigraphy for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 30, 50 and 50 % correspondingly. Also the close correlation between the size of the perfusion defect and the severity of myocardial fibrosis in patients with AF was revealed. Specificity of the Lake Louise criteria for diagnostics of latent myocarditis in relation to endomyocardial biopsy was 77.6 %, sensitivity-60 % and diagnostic accuracy-74.5 %. For only LGE specificity was 16 %, sensitivity-90 % and diagnostic accuracy-28 %. CONCLUSIONS: The study showed the possibility of successful application of radionuclide methods for diagnoses of chronic latent myocarditis at AF. Taking into account high informative values the results of scintigraphy can be also considered as a promising additional criteria for selecting patients with AF of unexplained etiology for non-invasive endomyocardial biopsy procedure.

[Assessment of clinical-instrumental, morphological data and expression of coxsackie adenovirus receptor in patients with inflammatory cardiac pathology].

In 22 patients with heart failure and/or ventricular arrhythmias presumably of inflammatory etiology the results of clinical and instrumental investigation were analyzed and compared to the endomyocardial biopsy data. In the subgroup of patients with left bundle branch block (LBBB) we revealed features indicative of lesser contribution of inflammatory destruction in pathogenesis of cardiomyopathy. The only virus, detected in biopsy samples, was parvovirus B19. Its persistence in myocardium was not related to activity of inflammation and severity of clinical course. Increased expression of Coxsackie adenovirus receptor (CAR) was found in 20 patients. It was not related to inflammatory cells infiltration and virus persistence in myocardium. Patients with most prominent CAR expression were characteried by right heart dilatation, more severe heart failure and absence of LBBB. Enhancement of CAR expression could reflect the attempt of organism to repair intercellular communications between cardiomyocites and to protect cells from the products of necrotic lysis during long standing inflammation.

Outcomes, long-term quality of life, and psychologic assessment of fulminant myocarditis patients rescued by mechanical circulatory support.

OBJECTIVE: Myocarditis is a rare disease that may progress rapidly to refractory cardiogenic shock and death. In such situations, emergent initiation of mechanical circulatory assistance is the only therapeutic option to rescue these dying patients. This study was designed to evaluate the outcomes, health-related quality of life and frequencies of anxiety, depression and posttraumatic stress disorder symptoms in fulminant myocarditis patients rescued by mechanical circulatory assistance, since these major components of outcome evaluation after serious illnesses have not yet been assessed in this setting. DESIGN: A retrospective, single-center, observational study and a cross-sectional survey to assess health-related quality of life by the Short Form-36 questionnaire and frequencies of anxiety, depression and posttraumatic stress disorder symptoms by the Hospital Anxiety and Depression Scale and the Impact of Event Scale, respectively. SETTING: An 18-bed tertiary intensive care unit in a university hospital. PATIENTS: We analyzed the short- and long-term outcomes of 41 patients hospitalized at our institution between 2003 and 2009 and who received either a Thoratec BiVAD (Thoratec, Pleasanton, CA) (n = 6) or extracorporeal membrane oxygenation (n = 35) to combat refractory cardiogenic shock due to fulminant myocarditis. MEASUREMENTS AND MAIN RESULTS: Intensive care unit survival was 68%, and four (10%) patients underwent heart transplantation. Independent predictors of in-intensive care unit death were Simplified Acute Physiology Score II ≥56 (odds ratio = 10.23) and troponin Ic ≥12 µg/L (odds ratio = 7.49) at admission. Complete follow-up (median, 525 days) was available for 26 of 28 survivors. Compared to age- and sex-matched controls, Short Form-36 evaluation of health-related quality of life revealed satisfactory mental health and vitality but persistent physical and psychosocial-related difficulties. Lastly, anxiety, depression, and/or posttraumatic stress disorder symptoms were reported by 38%, 27% and 27% of the patients, respectively. CONCLUSIONS: Mechanical circulatory assistance rescued 68% of patients with refractory circulatory failure due to fulminant myocarditis. Greater disease severity and higher troponin Ic levels at extracorporeal membrane oxygenation initiation predicted poorer prognosis. Because up to one-third of the patients reported anxiety, depression, and/or posttraumatic stress disorder symptoms, strategies aimed at attenuating their emotional and psychologic distress might significantly improve their long-lasting well-being.

[Transthoracic echocardiographic assessment of a biventricular assist device]. / Badanie echokardiograficzne po implantacji sztucznych komór serca.

We present the results of standard transthoracic echocardiographic assessment of a biventricular assist device implanted in a patient with progressive heart failure caused by acute giant-cell myocarditis.

[Fulminant myocarditis: clinical value of extracorporeal life support]. / Myocardites fulminantes : intérêt de l'assistance circulatoire temporaire.

Fulminant myocarditis is a rare cause of cardiogenic shock which usually occurs in young adults without known cardiac disease. Initial course may be complicated by a cardiogenic shock refractory to optimal medical treatment. Temporary circulatory assistance using an extracorporeal life support is of great clinical value in this setting, since myocardial systolic function usually fully recovers after a short time delay.

Risk of sudden cardiac death in young athletes: which screening strategies are appropriate?

Resources are not available to comprehensively evaluate all young athletes before participation in competitive sports. Therefore, the cardiovascular evaluation of young athletes needs to be targeted at high-risk areas and focus on the individuals who are at greatest possible risk: those who have suggestive, even if minor, symptoms, and those who have a family history of sudden death or premature cardiac disease.

Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology.

BACKGROUND: Myocarditis can occasionally lead to sudden death and may progress to dilated cardiomyopathy in up to 10% of patients. Because the initial onset is difficult to recognize clinically and the diagnostic tools available are unsatisfactory, new strategies to diagnose myocarditis are needed. METHODS AND RESULTS: Cardiovascular MR imaging (CMR) was performed in 32 patients who were diagnosed with myocarditis by clinical criteria. To determine whether CMR visualizes areas of active myocarditis, endomyocardial biopsy was taken from the region of contrast enhancement and submitted to histopathologic analysis. Follow-up was performed 3 month later. Contrast enhancement was present in 28 patients (88%) and was usually seen with one or several foci in the myocardium. Foci were most frequently located in the lateral free wall. In the 21 patients in whom biopsy was obtained from the region of contrast enhancement, histopathologic analysis revealed active myocarditis in 19 patients (parvovirus B19, n=12; human herpes virus type 6 [HHV 6], n=5). Conversely, in the remaining 11 patients, in whom biopsy could not be taken from the region of contrast enhancement, active myocarditis was found in one case only (HHV6). At follow-up, the area of contrast enhancement decreased from 9+/-11% to 3+/-4% of left ventricular mass as the left ventricular ejection fraction improved from 47+/-19% to 60+/-10%. CONCLUSIONS: Contrast enhancement is a frequent finding in the clinical setting of suspected myocarditis and is associated with active inflammation defined by histopathology. Myocarditis occurs predominantly in the lateral free wall. Contrast CMR is a valuable tool for the evaluation and monitoring of inflammatory heart disease.

Prognosis in patients with diphtheric myocarditis and bradyarrhythmias: assessment of results of ventricular pacing.

OBJECTIVE: To determine the prognosis in patients with diphtherial myocarditis and bradyarrhythmias and to assess the results of ventricular pacing in those with third degree atrioventricular block. DESIGN: Case series. SETTING: Referral department of cardiology in a teaching hospital. PATIENTS: Twenty four out of 46 patients admitted with diphtherial myocarditis over 10 years had bradyarrhythmias. Six had sinus bradycardia, 15 atrioventricular or intraventricular conduction disturbances, and three atrioventricular dissociation. MAIN OUTCOME MEASURE: Death rate. RESULTS: Eleven patients died (46%): all seven patients with third degree atrioventricular block, the patient with bifascicular block, and three of the six patients with bundle branch block. Seven died of cardiogenic shock and four of ventricular fibrillation. All nine patients with sinus bradycardia or atrioventricular dissociation survived. CONCLUSION: Conduction system disturbances in patients with diphtherial myocarditis are markers of severe myocardial damage and a poor prognosis. In addition, ventricular pacing does not improve survival.

[Value of endomyocardial biopsy in the assessment of the degree of the changes in myocarditis]. / Znaczenie biopsji endomiokardialnej dla oceny nasilenia zmian w stanach zapalnych miesnia sercowego.

Right ventricular diagnostic biopsy was performed in 25 patients (12 females and 13 males) aged 19-48 (mean 32) with suspicion of acute or subacute myocarditis for definitive diagnosis verification and to determine indications for therapy with corticosteroids or azathioprine. 3-4 specimens taken from different sites of ventricle were estimated under the light microscope according to Dallas classification distinguishing active myocarditis with or without fibrosis from borderline myocarditis with inflammatory infiltration not causing myocytes damage. Routine clinical and laboratory tests, echocardiographic examination, ECG Holter monitoring and nuclear examination to evaluate left ventricular ejection fraction were performed in all patients. 6 patients underwent coronarography to exclude atherosclerotic changes in coronary arteries. Bioptic examination result confirmed myocarditis suspicion in all patients. Active inflammation was stated in 18 patients including 7 with coexisting fibrosis. Borderline myocarditis was stated in 7 cases. Comparison of clinical examination results with those of pathomorphologic study made possible to state, that tachycardia, cardiac murmur, arrhythmias and left ventricular function impairment were frequent observed in the group of active myocarditis. Ejection fraction less than 30% was observed only in patients with active myocarditis and mainly in those with coexisting fibrosis. Based on performed study we consider that myocardial biopsy allows not only to diagnose myocarditis but also is helpful for lesion extent assessment in myocardium with all clinical implications.