Search

Clozapine is effective in up to 50 % of patients resistant to other antipsychotics. Its use is restricted to third-line due to adverse effects which include myocarditis. Australia reports the highest incidence of clozapine-associated myocarditis (CAM) in the context of pharmacovigilance and relatively rapid titration. An audit of patients commenced on clozapine within the Central Adelaide Local Health Network (CALHN) between 2012 and 2015 found an incidence of 8.6 %. We present here a case series from a follow up audit considering titration relevant risk factors for CAM. We reviewed anecdotal cases and data from all hospital-based commencements of clozapine across CALHN for the period July 2021 to June 2022 using pharmacy and medical record databases. We identified 5 cases of CAM and all had risk factors impacting on clozapine metabolism, including rapid titration, elevated baseline CRP, Asian ethnicity and concomitant treatment with inhibitors of clozapine metabolism. While personalisation of clozapine treatment needs further investigation in prospective trials, slower titration to lower targets for risk groups may not impact on hospital length of stay and has the potential to significantly reduce the burden of adverse events. Australian manufacturer approved titration rates exceed those recommended for personalised dosing and may not be safe for patients with risk factors. Early clozapine levels at week two could identify slow metabolisers for dose adjustment. Closer ties between psychiatrists and cardiologists are critical for the development of protocols for safely maintaining clozapine treatment during low level cardiac inflammation and to support safe rechallenge. [ABSTRACT FROM AUTHOR]

Higher frequencies of inflammatory adverse effects of clozapine have been reported in Japan. As the international titration protocol for Asians has set slower dose titration than the Japanese package insert, we hypothesized that a dose titration speed slower than the recommendation of the guideline would be associated with fewer inflammatory-related adverse events. The medical records of all 272 patients who were first started on clozapine at seven hospitals between 2009 and 2023 were studied retrospectively. Of those, 241 were included in the analysis. The patients were divided into two groups regarding whether the titration speed was faster or slower than the guideline for Asians. The incidence of inflammatory adverse events with clozapine was compared between the groups. The frequency of inflammatory adverse events was 34 % (37/110) in the faster titration group and 13 % (17/131) in the slower titration group, and a significant difference was observed by Fisher exact test (odds ratio 3.38; 95 % confidence interval 1.71–6.91; p < 0.001). Serious adverse effects, fever for more than five days, and clozapine discontinuation were significantly more frequent in the faster titration group. Logistic regression analysis indicated significantly more inflammatory adverse events in the faster titration group (adjusted odds ratio 4.01; 95 % confidence interval 2.02–7.87; p < 0.001) considering age, sex, body mass index, concomitant valproic acid, and smoking as confounding factors. Clozapine-induced inflammatory adverse events were less frequent in Japanese individuals when a titration rate was more gradual than the protocol recommended in the Japanese package insert. [Display omitted] [ABSTRACT FROM AUTHOR]

Vaccines are vital for public health, but concerns about adverse effects, particularly myocarditis and pericarditis linked to COVID-19 vaccines-, persist. This study investigates the application of Brighton Collaboration case definition to national vaccine safety data related to post-COVID-19 vaccine myo/pericarditis, utilizing claims under the Korea National Vaccine Injury Compensation Program (NIVCP). This study analyzed 190 medical records of individuals who claimed to have developed myo/pericarditis after receiving the COVID-19 vaccine, as reported to the NVICP between specified dates, categorizing cases based on the Brighton criteria for myocarditis or pericarditis. Between 2021–2022, NVICP received 190 cases meeting the Brighton criteria for myocarditis or pericarditis at levels 1, 2, or 3. Most cases fell into Level 2 (70%), followed by Level 1 (29%), and one at Level 3 (1%), with Level 1 cases showing a higher hospitalization rate (87.3%) and a notable proportion requiring admission to the Intensive Care Unit (25.5%). Chest pain and Troponin-I/T elevation were common findings in Level 1 cases, while Level 2 cases exhibited similar patterns but at a slightly lower frequency. Electrocardiogram and echocardiography findings differed between the two levels. The Brighton Collaboration case definition proved valuable for classifying and assessing AEFI data, enhancing our understanding of the potential relationship between myocarditis and the COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 – 2.82; SCRI post 2.13, 95 %CI – 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 – 2.44, extended SCCS 1.52, 95 %CI = 1.08 – 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures. [ABSTRACT FROM AUTHOR]

• Rare cases of myocarditis/pericarditis after vaccination with COVID-19 vaccine NVX-CoV2373 have been documented. • This analysis provides a benefit-risk assessment for vaccination with NVX-CoV2373 based on data from clinical studies and recent real-world burden of disease data. • Results indicate that the benefits of vaccination with NVX-Cov2373 outweigh the risks of myocarditis/pericarditis. A benefit–risk assessment of NVX-CoV2373, a vaccine to prevent COVID-19, was conducted to determine if the benefits of vaccination outweigh the risks of myocarditis/pericarditis. This analysis used data on myocarditis/pericarditis cases observed in the NVX-CoV2373 clinical studies, real-world data of mRNA COVID vaccine effectiveness against predominant SARS-CoV-2 strains in early 2023, and recent COVID-19 burden of disease data from the United States. The benefits of NVX-CoV2373 vaccination were estimated as the number of COVID-19 cases, hospitalizations, and deaths prevented. The risks of myocarditis/pericarditis cases and related hospitalizations and deaths occurring within 7 days of vaccination were also estimated. In our analysis, vaccination with NVX-CoV2373, per 100,000 vaccinated, resulted in an estimated 1805 COVID-19 cases prevented compared with an estimated 5.3 excess myocarditis/pericarditis cases. The number of COVID-19 hospitalizations and deaths prevented were also greater than vaccine-associated myocarditis/pericarditis hospitalizations and deaths. Our analysis indicates a positive benefit–risk balance for NVX-CoV2373. [ABSTRACT FROM AUTHOR]

To investigate the anti-inflammatory actions and molecular mechanisms of the sodium/glucose cotransporter 2 (SGLT-2) inhibitor empagliflozin on autoimmune myocarditis. The experimental autoimmune myocarditis (EAM) mouse model was constructed using peptides, and the therapeutic effects of empagliflozin on cardiac inflammation and fibrosis were observed using hematoxylin and eosin (HE), Sirius red staining, and Masson's trichome staining. Western blotting was used to identify the actions of empagliflozin on the surface marker expression levels of M2 macrophages and inflammatory factors. In vitro, experiments were completed using lentiviral overexpression of SGLT-2 in macrophages. Macrophage inflammation and anti-inflammatory models were constructed using lipopolysaccharide and interleukin-4, respectively. Enzyme-linked immunosorbent assay, immunofluorescence staining, and reverse-transcription polymerase chain reaction were applied to detect the effects of empagliflozin on the levels of inflammatory factors and macrophage surface markers. Western blotting was used to identify variability in SGLT-2 expression and the role of empagliflozin on the signal transducer and activator of the transcription 3 (STAT3) pathway. The Genomic Spatial Event 142564 dataset was studied in an EAM mouse model. We selected single-cell sequencing results from day 0 and day 21 of modeling to visualize differentially expressed genes. Immune cell infiltration correlation analysis was implemented to explore the expression of inflammatory factors and phenotypic markers. Empagliflozin increased the expression of the M2 macrophage surface marker CD206 and reduced the level of inflammatory factors in the EAM mouse model while reducing the levels of inflammation and fibrosis. In vitro experiments revealed that the phosphorylation of STAT3 pathway was enhanced after macrophages were polarized to M1 phenotype by LPS, the phosphorylation of STAT3 pathway was inhibited after empagliflozin intervention, and the levels of inflammatory factors were decreased. Empagliflozin can reduce the level of inflammation in autoimmune myocarditis through the STAT3 pathway and macrophage phenotype transformation. These results indicate the expression of SGLT-2 can be a target for autoimmune myocarditis therapy. • An autoimmune myocarditis mouse model using scRNA-seq data was analysed. • Lentiviral overexpression of SGLT-2 was also performed in vitro in macrophages. • Empagliflozin reduced the expression of inflammatory factors as well as fibrosis. • STAT3 pathway phosphorylation was inhibited by empagliflozin administration. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammation of the heart muscle often associated with viral infections and can lead to dilated cardiomyopathy. Interferon-induced transmembrane protein 3 (IFITM3) is a small endosomal membrane protein with anti-viral activity against multiple viruses and is also implicated in non-infectious diseases such as cancer and Alzheimer's Disease. Since the IFITM3 proteins are expressed both in T cells and in cardiomyocytes, it is reasonable to hypothesize that these molecules could affect myocarditis either through their effect on the autoimmune response or through direct modulation of cardiomyocyte damage. The aim of this study was to investigate the role of IFITM3 in experimental autoimmune myocarditis (EAM)-mediated myocardial injury. Immunization of rats with cardiac myosin results in substantial cardiac inflammation and is associated with increased expression of IFITM3 after 21 days. In vivo IFITM3 shRNA knockdown using the lentivirus transfection method reduced cardiac injury while restoring IFITM3 expression reversed the protective effect of IFITM3 RNA interference. To determine the direct impact of IFITM3, the rat ventricular cell line, H9c2, was treated with palmitic acid which causes apoptosis in these cells. Suppressing IFITM3 expression protects H9c2 cells while overexpressing IFITM3 enhances cell injury. JAK inhibitors reduced IFITM3-mediated myocardial cell injury. In conclusion, IFITM3 may mediate myocardial injury in EAM rats and palmitic acid-induced damage to H9c2 cells through the JAK2/STAT3 pathway. [Display omitted] • IFITM3 may mediate myocardial injury in EAM rats and palmitic acid-induced damage to H9c2 cells through the JAK2/STAT3 pathway. • IFITM3 may be an effective target for the prevention and treatment of myocardial injury. • IFITM3 is expected to provide effective drug development strategies. [ABSTRACT FROM AUTHOR]

Dysregulated cell death machinery and an excessive inflammatory response in Coxsackievirus B3(CVB3)-infected myocarditis are hallmarks of an abnormal host response. Complement C4 and C3 are considered the central components of the classical activation pathway and often participate in the response process in the early stages of virus infection. In our study, we constructed a mouse model of CVB3-related viral myocarditis via intraperitoneal injection of Fer-1 and detected myocarditis and ferroptosis markers in the mouse myocardium. Then, we performed co-IP and protein mass spectrometry analyses to explore which components interact with the ferroptosis gene transferrin receptor (TFRC). Finally, functional experiments were conducted to verify the role of complement components in regulating ferroptosis in CVB3 infection. It showed that the ferroptosis inhibitor Fer-1 could alleviate the inflammation in viral myocarditis as well as ferroptosis. Mechanistically, during CVB3 infection, the key factor TFRC was activated and inhibited by Fer-1. Fer-1 effectively prevented the consumption of complement C3 and overload of the complement product C4b. Interestingly, we found that TFRC directly interacts with complement C4, leading to an increase in the product of C4b and a decrease in the downstream complement C3. Functional experiments have also confirmed that regulating the complement C4/C3 pathway can effectively rescue cell ferroptosis caused by CVB3 infection. In this study, we found that ferroptosis occurs through crosstalk with complement C4 in viral myocarditis through interaction with TFRC and that regulating the complement C4/C3 pathway may rescue ferroptosis in CVB3-infected cardiomyocytes. [Display omitted] • This research showed that the expression of the component C3 decreased and that of C4b increased on the 14th days of post-CVB3 infection in myocardium. • It has been confirmed for the first time that ferroptosis regulates myocarditis damage through its interaction with complements in CVB3 induced myocarditis. • This may provide a new method for the clinical treatment of myocardial cell death in patients with viral myocarditis. [ABSTRACT FROM AUTHOR]

• The third dose of the BNT162b2 vaccine increases the risk of myocarditis, particularly in adolescent males. • The risk of myocarditis from BNT162b2, whether as an initial or booster dose following the BBIBP-CorV series, is close. • The risk of myocarditis after vaccination is less marked in children aged 5–11. Due to the data scarcity in low- and middle-income countries, we aimed to examine the incidence rate of myocarditis and pericarditis within 30 days after each dose of homologous (3 × BNT162b2) and heterologous prime-boost (2 × BBIBP-CorV/BNT162b2) vaccine regimen among individuals younger than 40 years. We conducted a historical control cohort using routinely recorded data from Thai national vaccine and insurance claims databases. Sex-specific incidence rate ratios (IRRs) for myocarditis and pericarditis were calculated for each vaccination strategy and contrasted with incidence rates among the non-immunised population in the pre-COVID-19 period. From August 2021 to September 2022, we tracked the incidence of myocarditis and pericarditis within 30 days after vaccinations using < 40-year-old national population databases. Our reference was the average monthly incidence of these conditions in the non-immunised population from August to October 2019. The exposure of interest was immunisation against the SARS-CoV-2 virus, incorporating the following vaccination strategies: three-dose 3 × BNT162b2 regimen, three-dose 2 × BBIBP-CorV/BNT162b2 regimen, and non-immunisation. For myocarditis, a total of 215 cases were identified among 7,594,965 individuals in the 3 × BNT162b2 cohort, 5 cases among 2,914,643 individuals in the 2 × BBIBP-CorV/BNT162b2 cohort, and 115 cases among 32,424,780 non-immunised individuals. The sex-specific IRRs (95 % confidence intervals) of myocarditis and pericarditis after the homologous vaccination were 3.09 (1.61, 5.93) and 1.84 (0.72, 4.73) for females and 7.43 (3.11, 17.73) and 10.48 (3.90, 28.15) for males, respectively. Conversely, the IRRs of myocarditis after the heterologous vaccination were not significant (females: 2.24 (0.70, 7.17); males: 1.99 (0.48, 8.21)). IRRs could not be obtained for pericarditis after the heterologous vaccination because of the small number of observed events. The study observed a significantly increased risk of myocarditis and pericarditis following homologous 3 × BNT162b2 vaccination but had insufficient power to confirm an increased risk for myocarditis following the heterologous prime-boost 2 × BBIBP-CorV/BNT162b2 vaccination. The incidence of pericarditis following the heterologous vaccination was too rare to evaluate. [ABSTRACT FROM AUTHOR]

To study the causes of clozapine treatment discontinuation and measure clozapine-induced myocarditis (CIM) rates in an Australian region, to compare the observed rates of CMI with reports from Australia and the world, and discuss factors related to CIM incidence rates in the region. The study is a retrospective clinical audit of 327 patients prescribed clozapine. All patients were monitored by the mandatory CIM monitoring protocol for the first six weeks of treatment. The validity of a diagnosis of CIM was assessed using six criteria. Socio-demographic and clinical factors and clozapine prescription practices were analysed for their association with CIM. The study could not examine co-existing medical illness, co-prescribed psychotropic medication, genetics, and environmental factors. CIM occurred in 9.8 % of the cohort after a mean treatment duration of 19.5 days. The diagnosis of CIM was considered valid in all cases. Gender, age at the start of treatment, ethnicity, cumulative clozapine dose, dose titration, and clozapine/norclozapine ratio were unrelated to CIM. The CIM rate in the Hunter region was higher than in the rest of Australia and the world and increased after adopting the monitoring protocol. Over-diagnosis, patient's age and gender, ethnicity, cumulative clozapine dose, dosing titration, and clozapine metabolism rate were unrelated to the high occurrence rates. The possible role of comorbid illnesses, co-prescribed psychiatric medications, genetic, and environmental factors in the etiology of CIM requires further study. The reasons underlying the high rates of CIM in the Hunter region need further exploration. [ABSTRACT FROM AUTHOR]

• Myocarditis is a well known adverse events of special interest following COVID-19 vaccines. • Limited information has been published regarding medium and longer term outcomes. • This clinical survey study found around half of patients still experience symptoms at 6 months. • There are distinct phenotypic differences between genders and age groups. Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort. Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1–3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. 87.5 % (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9 % of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8 % (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9 % of male respondents reported symptom resolution compared to 22.6 % of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations. There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data. [ABSTRACT FROM AUTHOR]

Exploring the immune mechanism of coxsackievirus B3 (CVB3)-induced myocarditis may provide a promising therapeutic strategy. Here, we investigated the regulatory role of macrophage CAPN4 in the phenotypic transformation of macrophages and NOD-like receptor protein 3 (NLRP3) inflammasome activation. We found that CAPN4 was the most upregulated subtype of the calpain family in CVB3-infected bone marrow-derived macrophages (BMDMs) and Raw 264.7 cells after CVB3 infection and was upregulated in cardiac macrophages from CVB3-infected mice. Conditional knockout of CAPN4 (CAPN4flox/flox; LYZ2-Cre, CAPN4-cKO mice) ameliorated inflammation and myocardial injury and improved cardiac function and survival after CVB3 infection. Enrichment analysis revealed that macrophage differentiation and the interleukin signaling pathway were the most predominant biological processes in macrophages after CVB3 infection. We further found that CVB3 infection and the overexpression of CAPN4 promoted macrophage M1 polarization and NLRP3 inflammasome activation, while CAPN4 knockdown reversed these changes. Correspondingly, CAPN4-cKO alleviated CVB3-induced M1 macrophage transformation and NLRP3 expression and moderately increased M2 transformation in vivo. The culture supernatant of CAPN4-overexpressing or CVB3-infected macrophages impaired cardiac fibroblast function and viability. Moreover, macrophage CAPN4 could upregulate C/EBP-homologous protein (chop) expression, which increased proinflammatory cytokine release by activating the phosphorylation of transducer of activator of transcription 1 (STAT1) and 3 (STAT3). Overall, these results suggest that CAPN4 increases M1-type and inhibits M2-type macrophage polarization through the chop-STAT1/STAT3 signaling pathway to mediate CVB3-induced myocardial inflammation and injury. CAPN4 may be a novel target for viral myocarditis treatment. [Display omitted] • Macrophage CAPN4 regulates cell polarization and NLRP3 inflammasome activation after coxsackievirus B3 (CVB3) infection. • Chop expression was altered by the effects of CAPN4 and CVB3 infection. • Chop regulates M1 polarization and NLRP3 inflammasome activation via the STAT1/STAT3 signaling pathway. • Macrophage CAPN4 is a novel therapeutic target for infectious, inflammatory diseases. [ABSTRACT FROM AUTHOR]

Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that typically develops within the first month after commencing an antipsychotic drug. Although the precise mechanism of this severe adverse drug reaction is unknown, multiple theories have been proposed with varying levels of support from cellular or animal studies. We conducted a systematic review, in accordance with PRISMA guidelines, of published preclinical and clinical studies investigating the cellular mechanism by which antipsychotic drugs induce myocarditis. A literature search including all studies available before December 10, 2022, yielded 15 studies that met our inclusion criteria. Antipsychotics examined in the included studies included clozapine (n = 13), ziprasidone (n = 1), amisulpride (n = 1), haloperidol (n = 1), levomepromazine (n = 1), olanzapine (n = 1), and sertindole (n = 1). The evidence suggests several overlapping mechanistic cascades involving: (1) increased levels of catecholamines, (2) increased proinflammatory cytokines, (3) increased reactive oxygen species (ROS), (4) reduced antioxidant levels and activity, and (5) mitochondrial damage. Notable limitations such as, a focus on clozapine, sample heterogeneity, and use of supratherapeutic doses will need to be addressed in future studies. Discovery of the mechanism by which antipsychotic drugs induce myocarditis will allow the development of clinically-useful biomarkers to identify those patients at increased risk prior to drug exposure. The development or repurposing of therapeutics to prevent or treat drug-induced myocarditis will also be possible and this will enable increased and safe use of antipsychotics for those patients in need. [ABSTRACT FROM AUTHOR]

Electrocardiographic (ECG) findings of T-wave inversions in V1–V3, with or without accompanying epsilon waves, often raise concerns for the rare, but potentially lethal, arrhythmogenic right ventricular cardiomyopathy (ARVC). However, this pattern may be found in pericardial agenesis, an even rarer pathology. Concomitant myocarditis can confuse this presentation further. We report a case of a previously healthy man who presented with left-sided chest pain, ECG findings suggestive of ARVC, and a final diagnosis of myocarditis with underlying partial pericardial agenesis. A growing number of cases have reported pericardial agenesis demonstrating ECG changes similar to ARVC. We discuss an approach to a diagnostically challenging patient. This case emphasizes the importance of a broad differential and the danger of premature closure. [ABSTRACT FROM AUTHOR]

A paradigm shift in cancer treatment occurred with the advent of immune checkpoint inhibitors (ICI). ICI therapy has improved tumor response and increased overall survival in patients with solid tumors and hematologic malignancies. While ICI therapy has improved overall patient outcomes in oncology, it has also introduced novel adverse effects called immune-related adverse effects (irAEs). Studies have shown that the development of irAEs is associated with improved overall survival, but certain irAEs like pneumonitis and myocarditis are life threatening, and could result in death if not identified and treated early. Therefore, it is important for radiologists to be aware of complications arising from ICI administration, especially those related to the heart and lungs as they are associated with greater mortality. This paper will review the imaging features of cardiothoracic toxicities, recurrent and chronic irAEs, and atypical tumor responses associated with irAEs. • Imaging plays a key role in identifying the cardiothoracic complications of immunotherapy. • Some cardiothoracic complications are associated with high mortality and imaging plays a crucial role in their diagnosis. • Early detection of complications can prompt early initiation of treatment, allowing patients to continue immunotherapy. [ABSTRACT FROM AUTHOR]

To evaluate the role of quantitative cardiac magnetic resonance imaging (CMRI) parameters in myocarditis, including acute and chronic myocarditis (AM and CM), for children and adolescents. PRISMA principles were followed. PubMed, EMBASE, Web of Science, Cochrane Library, and grey literature were searched. The Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) checklist were utilised for quality assessment. Quantitative CMRI parameters were extracted and a meta-analysis was performed in comparison with healthy controls. The overall effect size was measured as the weighted mean difference (WMD). Ten quantitative CMRI parameters of seven studies were analysed. Compared with the control group, the myocarditis group reported longer native T1 relaxation time (WMD=54.00, 95% confidence interval [CI]: 33.21,74.79, p< 0.001), longer T2 relaxation time (WMD=2.13, 95% CI: 0.98, 3.28, p< 0.001), increased extracellular volume (ECV; WMD=3.13, 95% CI: 1.34,4.91, p= 0.001), elevated early gadolinium enhancement (EGE) ratio (WMD=1.47, 95% CI: 0.65,2.28, p< 0.001), and increased T2-weighted ratio (WMD=0.43, 95% CI: 0.21,0.64, p< 0.001). The AM group had longer native T1 relaxation times (WMD=72.02, 95% CI: 32.78,111.27, p< 0.001), increased T2-weighted ratios (WMD=0.52, 95% CI: 0.21,0.84 p= 0.001), and impaired left ventricular ejection fractions (LVEF; WMD= – 5.84, 95% CI: -9.69, -1.99, p =0.003). Impaired LVEF (WMD= – 2.24, 95% CI: -3.32, -1.17, p <0.001) was observed in the CM group. Statistical differences can be observed in some CMRI parameters between patients with myocarditis and healthy controls; however, apart from native T1 mapping, there were no large differences in other parameters between two groups, which may reveal the limited benefit of CMRI in assessing myocarditis in children and adolescents. • Aim to assess the value of CMR in myocarditis for children & adolescents. • Native myocardial T1 mapping is higher in myocarditis than healthy controls. • No large difference between patients and control of EGE ratio and T2-weighted ratio. • No large difference between patients and control of T2 mapping. [ABSTRACT FROM AUTHOR]

Orthotopic heart transplantation for cardiac sarcoidosis (CS) is becoming increasingly common. Historically, there have been concerns regarding disease recurrence within the allograft. Although rarely reported in the literature, cases of recurrent CS tend to be observed in patients after dose reduction of immunosuppressive therapy and cessation of corticosteroids. Here, we present 2 cases of recurrent CS after orthotopic heart transplantation, confirmed on endomyocardial biopsy. Case 1 reports a 50-year-old man with a fulminant course of giant cell myocarditis who developed allograft recurrence with granulomas 5 years after transplantation despite maintenance corticosteroid therapy. Case 2 reports a 47-year-old man with CS who developed recurrence with the presence of giant cells 2 years after transplantation, with a benign clinical course. With these cases, we demonstrate the clinical overlap between CS and giant cell myocarditis and highlight the spectrum of the disease process. We also demonstrate that CS can recur despite corticosteroid maintenance therapy. [ABSTRACT FROM AUTHOR]

• Myocarditis after messenger RNA (mRNA) COVID-19 vaccination is rare. • The myocarditis rate after an mRNA vaccine booster is lower than the second dose. • No association detected between mRNA COVID-19 booster vaccine type and myocarditis. We aimed to estimate the rate of myocarditis after the messenger RNA (mRNA) COVID-19 booster vaccination by vaccine type, age, and sex. We used data from the British Columbia COVID-19 Cohort, a population-based cohort surveillance platform. The exposure was a booster dose of an mRNA vaccine. The outcome was diagnosis of myocarditis during hospitalization or an emergency department visit within 7-21 days of booster vaccination. The overall rate of myocarditis was lower for the booster dose (6.41, 95% confidence interval [CI]: 3.50-10.75) than the second dose (17.97, 95% CI: 13.78-23.04); (Rate ratio booster vs dose-2 = 0.34, 95% CI: 0.17-0.61). This difference was more apparent for the mRNA-1273 vaccine type. After the second dose, the myocarditis rate in males was significantly lower for BNT162b2 than mRNA-1273 overall and among those aged 18-39 years. In contrast, after the booster dose, no significant differences between myocarditis and vaccine type was observed overall or within the specific age groups among males or females. Myocarditis after mRNA COVID-19 vaccines is a rare event. A lower absolute risk of myocarditis was observed after a booster dose of mRNA vaccine than the primary series second dose. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Myocarditis and inflammatory bowel diseases (IBD) are rare conditions, but may coexist. Myocarditis in IBD may be infective, immune-mediated, or due to mesalamine toxicity. A gap of knowledge exists on the clinical features of patients that present myocarditis in association with IBD, especially for endomyocardial biopsy-proven cases. Our aims are: 1) to describe the clinical characteristics of patients with an associated diagnosis of myocarditis and IBD in a single-center hospital, 2) to perform a systematic review of the literature of analogous cases. We retrospectively analyzed data of patients followed up at the outpatient Cardio-immunology and Gastroenterology Clinic of Padua University Hospital, to identify those with an associated diagnosis of myocarditis and IBD. In addition, a systematic review of the literature was conducted. We performed a qualitative analysis of the overall study population. The study included 104 patients (21 from our single center cohort, 83 from the literature review). Myocarditis in IBD more frequently affects young (median age 31 years) males (72%), predominantly with infarct-like presentation (58%), within an acute phase of the IBD (67%) and with an overall benign clinical course (87%). Nevertheless, a not negligible quote of patients may present giant cell myocarditis, deserve immunosuppression and have a chronic, or even fatal course. Histological evidence of mesalamine hypersensitivity is scarce and its incidence may be overestimated. Our study shows that myocarditis in association with IBD, if correctly managed, may have a spontaneous benign course, but predictors of worse prognosis must be promptly recognized. [Display omitted] • Myocarditis and IBD may coexist, raising concerns for prognosis and management. • Myocarditis associated to IBD generally has a spontaneous benign course. • A sizable quote of patients deserve immunosuppression and have a severe prognosis. • Mesalamine toxicity should be investigated, if myocarditis presents during IBD. [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy with left ventricular involvement (ACM-LV), particularly in case of isolated left ventricular involvement (i.e. left dominant arrhythmogenic cardiomyopathy, LDAC) and previous infectious myocarditis (pIM) may have overlapping clinical and cardiac magnetic resonance (CMR) features. To date, there are no validated CMR criteria for the differential diagnosis between these conditions. The present study aimed to identify CMR characteristics to distinguish ACM-LV from pIM. This observational, retrospective, single-centre study included 30 pIM patients and 30 ACM-LV patients. In ACM-LV patients CMR was performed at diagnosis; in patients with pIM, CMR was performed six months after acute infection. CMR analysis included quantitative assessment of left ventricle (LV) volumes, systolic function and wall thicknesses, qualitative and quantitative assessment of late gadolinium enhancement (LGE) sequences. Compared with pIM, ACM-LV patients showed slightly larger LV volumes, more frequent regional wall motion anomalies and reduced wall thicknesses. ACM-LV patients had higher amounts of LV LGE and extension. Notably, the LDAC subgroup had the highest amount of LV LGE. LV LGE amount > 15 g and a LV LGE percentage > 30% of LV mass discriminated ACM-LV from pIM with a 100% specificity. LGE segmental distribution was superimposable among the groups, except for septal segments that were more frequently involved in ACM-LV and LDAC patients. A great extension of LV LGE (a cut-off of LGE >15 g and a percentage above 30% of LV LGE in relation to total myocardial mass) discriminates ACM-LV from pIM with extremely high specificity. • Quantification of late gadolinium enhancement is crucial in the differential diagnosis between arrhythmogenic cardiomyopathy with left ventricular involvement and previous infectious myocarditis. • Integration of several morpho-functional parameters together with late gadolinium enhancement analysis can help in distinguishing left dominant arrhythmogenic cardiomyopathy from previous infectious myocarditis. • Both the layer location and the distribution pattern of the late gadolinium enhancement are not useful elements in the differential diagnosis between arrhythmogenic cardiomyopathy with left ventricular involvement and previous myocarditis. [ABSTRACT FROM AUTHOR]

• 1883 vaccinated and unvaccinated post-COVID patients evaluated by echocardiogram. • 2.92% presented pathological TTE findings consistent with post-COVID cardiac injury. • Unvaccinated patients presented more cardiac injury than vaccinated (4.1% vs 1.3%) • 15% of the patients reported persistent symptoms at the post-COVID control. • Complete vaccination was associated with 48% reduction in risk of long-COVID symptoms. After the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms. Methods : All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis. Results : From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17–0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40–0.69, p<0.001). Conclusion: Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population. [ABSTRACT FROM AUTHOR]

There have been reports of potential negative cardiovascular effects from the COVID-19 vaccine, such as myocarditis or pericarditis. This study sought to ascertain the risk of myocarditis/pericarditis after COVID-19 vaccination by conducting an extensive meta-analysis of published cases. A systematic literature search was conducted in 7 online databases by March 31, 2022. Heterogeneity was tested by I 2 index. RR and 95% CI were pooled through either random-effect or fixed-effect models. Sensitivity analysis and publication bias were also conducted. A total of 11 studies with 58,620,611 subjects were included. COVID-19 vaccination correlated with an increased risk of myocarditis or pericarditis (RR=2.04; 95% CI=1.33, 3.14). In addition, an increased risk of myocarditis or pericarditis in people who received the second dose of COVID-19 vaccine compared with that in those who received only the first dose of COVID-19 vaccine was also found (RR=4.06; 95% CI=2.08, 7.92). An increased incidence of pericarditis or myocarditis was noted predominantly in those who received BNT162b2 and mRNA-1273 vaccines (RR=2.19; 95% CI=1.46, 3.29 and RR=4.15; 95% CI=1.87, 9.22, respectively). Study results indicate that a higher incidence of myocarditis or pericarditis was found after COVID-19 vaccination. In addition, the risk of developing myocarditis or pericarditis was greater after the second dose than after the first dose. Nevertheless, the risks of myocarditis and pericarditis in COVID-19 vaccine recipients are still significantly lower than the health risks observed in patients with COVID-19. Therefore, the benefits and harms must be carefully assessed to determine the best management option for patients who are in the high-risk group of myocarditis or pericarditis. [ABSTRACT FROM AUTHOR]

A substantial number of patients present with a suspected ACS and non-obstructive coronary arteries; sex differences in these patients are not well understood. This study aims to evaluate the impact of sex on clinical presentation and outcome in patients with suspected acute coronary syndrome (ACS) and non-obstructive coronary arteries with a final diagnosis confirmed by cardiovascular magnetic resonance imaging (CMR). Consecutive patients with ACS and non-obstructive coronary arteries (n = 719) with an unclear cause from a single tertiary centre who were referred for CMR were included. The primary endpoint was all-cause mortality. CMR was performed at a median time of 30 days after presentation and identified a diagnosis in 74% of patients. All-cause mortality was 9.5% over a median follow up of 4.9 years, with no significant difference between sexes (8.8% versus 10.1%; p = 0.456). Men were more likely to have non-ischaemic aetiology on CMR than women (55% v 41%, p < 0.001), but were equally likely to have an ischaemic cause (25% v 27%, p = 0.462). Age group (HR 1.58, p < 0.001) and LV ejection fraction (HR 0.98, p = 0.023) were independent predictors of mortality. There is no difference in all-cause mortality between sexes in patients presenting with suspected ACS and non-obstructive coronary arteries. • All-cause mortality was 9.5% over a median follow up of 4.9 years. • There was no overall difference in mortality by sex. • Mortality is highest in the non-ischaemic group in both sexes. • Men were more likely to have a non-ischaemic aetiology on CMR driven by a higher incidence of myocarditis. [ABSTRACT FROM AUTHOR]

To assess the outcomes and risk factors for adult patients with acute fulminant myocarditis (AFM) supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) in China mainland. Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Data from adult patients who were diagnosed with AFM and needed VA ECMO in the database were retrospectively analyzed. The primary outcome was 90-day mortality after ECMO initiation in patients with AFM supported with VA ECMO. Cox proportional hazard regression model was used to examine the risk factors associated with 90-day mortality. Among 221 patients enrolled and followed up to 90 days, 186 (84.2%) patients weaned from ECMO and 159 (71.9%) patients survived and discharged home. The median age was 38 years (IQR 29–49) and males (n = 115) represented 52.0% of the total accounted patients. The median ECMO duration was 134 h (IQR 96–177 h). The main adverse event during ECMO course was bleeding (16.3%), followed by infection (15.4%). In the multivariate Cox model analysis, cardiac arrest prior to ECMO initiation (adjusted HR 2.529; 95%CI: 1.341–4.767, p = 0.004), lower pH value (adjusted HR 0.016; 95%CI: 0.010–0.059, p < 0.001) and higher lactate concentration at 24 h after ECMO initiation (adjusted HR 1.146; 95%CI: 1.075–1.221, p < 0.001) were associated with 90-day mortality. 71.9% patients with AFM (clinical diagnosed) supported with VA ECMO survived. Cardiac arrest prior to ECMO, lower pH and higher lactate concentration at 24 h after ECMO initiation were correlated with 90-day mortality of AFM patients supported with VA ECMO. • >70% of adult patients with acute fulminant myocarditis supported with VA ECMO survived in China mainland. • The median ECMO duration was 134 h. • Cardiac arrest prior to ECMO, pH and lactate after ECMO were independent risk factors correlated with 90-day mortality. [ABSTRACT FROM AUTHOR]

The burden of cardiovascular diseases is sharply rising in low- and middle-income countries (LMICs). Along with the increasing rates of cardiovascular risk factors in these regions, there is a growing recognition of the contribution of neglected tropical diseases and other infections. Several cardiac implications of these infections have been reported but have not yet been validated by robust population data. This is in part due to limited access to health care and insufficient data collection infrastructure in many LMICs. Therefore, the true impact of these infections on the cardiovascular system may be underestimated, because of both underdiagnosis and underreporting bias. There is an urgent need to thoroughly delineate the cardiac impact of these conditions with elevated prevalence in LMICs and to propose strategies to reduce the negative consequences of these diseases in health systems with limited resources. [Display omitted] • Tropical infections can adversely affect the cardiovascular system in multiple ways, and their impact may be underestimated. • Better understanding of the cardiovascular effects of tropical infectious diseases can facilitate development of preventive, diagnostic, and therapeutic strategies. • Collaboration between public and non-governmental sectors is crucial to reducing the detrimental impact of tropical infectious diseases. [ABSTRACT FROM AUTHOR]

Cardiac involvement in Takayasu arteritis (TA) is the major cause of morbidity and mortality. Cardiovascular magnetic resonance (CMR) is an excellent modality for the assessment of myocardial involvement. Studies have shown myocardial involvement in 25%–27% of patients. To evaluate the prevalence and pattern of myocardial involvement in TA on CMR. We also evaluated any correlation between CMR changes and disease activity score (ITAS 2010 and ITAS-A) assessed at the time of CMR. Patients classified as Takayasu arteritis according to Sharma et al. criteria were enrolled in the study. Demographic, clinical, and laboratory data were documented in the predesigned proforma. CMR was performed on a dedicated cardiac 3 Tesla MR machine. Disease activity was recorded by ITAS2010 and ITAS-A. A total of 37 TA patients were included. Mean (±SD) age was 29 ± 11 years. Female to male ratio was 3:1. Five patients (14%) had myocardial involvement on CMR. Two (2/5) had myocarditis and three (3/5) patients had features of ischaemic myocardial fibrosis. The myocardium is affected in TA, however the prevalence of subclinical myocardial involvement in our study was less (8% vs. 25%–27%) compared to the previous studies. Myocardial involvement trends towards early age of onset, less disease duration, lack of classical risk factors, and more with disease activity. [ABSTRACT FROM AUTHOR]

There is limited and conflicting information on waitlist and transplant outcomes for children with myocarditis. Retrospective review included children with myocarditis and dilated cardiomyopathy (DCM) listed for HT from January 01, 1993 to December 31, 2019 in the Pediatric Heart Transplant Society database. Clinical characteristics, waitlist and post-HT outcomes (graft loss, rejection, cardiac allograft vasculopathy, infection and malignancy) for children listed from early (1993-2008) and current era (2009-2019) with myocarditis were evaluated and compared to those with DCM. Of 9755 children listed, 322 (3.3%) had myocarditis and 3178 (32.6%) DCM. Compared to DCM, children with myocarditis in the early and the current era were significantly more likely to be listed at higher urgency; be in intensive care unit; on mechanical ventilation; extracorporeal membrane oxygenation and ventricular assist device (p < 0.05 for all). While unadjusted analysis revealed lower transplant rates and higher waitlist mortality for children with myocarditis, in multivariable analysis, myocarditis was not a risk factor for waitlist mortality. Myocarditis, however, was a significant risk factor for early phase post-HT graft loss (HR 2.46; p = 0.003). Waitlist and post-HT survival for children with myocarditis were similar for those listed and transplanted in the early era to those listed and transplanted in the current era (p > 0.05 for both). Children with myocarditis have a higher acuity of illness at listing and at HT and have inferior post-HT survival compared to children with DCM. Outcomes for children with myocarditis have not improved over the 3 decades and efforts are needed to improve outcomes for this cohort. [ABSTRACT FROM AUTHOR]

Myocardial injury (MINJ) is a well-recognized prognostic marker in different acute cardio-respiratory illnesses, nonetheless, its relevance in Influenza remains poorly defined. Our aim was to assess incidence, correlates, short and mid-term prognostic role of MINJ in Influenza. Hospitalized patients (pts) with laboratory confirmed Influenza A or B underwent highly sensitive cardiac T Troponin (hs-cTnT) measurement at admission in four regional Swiss hospitals during the 2018–2019 epidemic. MINJ was defined as hs-cTnT >14 ng/L. Clinical, laboratory and outcome data were prospectively collected. The primary endpoint was mortality at 28 days while the composite of mortality, admission to intensive care unit (ICU) or need for mechanical ventilation at 28-days and mortality at 30-months were set as secondary endpoints. The presence of MINJ was assessed within 48 h from admission in 145 consecutive hospitalized pts, being evident in 94 (65.5%) pts and associated with older age, higher C-reactive protein levels, renal impairment or chronic obstructive pulmonary disease. At a 28-days follow-up, 7 deaths (4.8%) occurred, all in patients with MINJ at admission (log-rank p = 0.048). MINJ was strongly associated with occurrence of death, ICU admission or mechanical ventilation (OR 5.74, 95% CI 1.28–53.29; p = 0.015). After a median follow-up of 32.7 months (IQR 32.2–33.4), 15 (10.3%) deaths occurred, all among pts with MINJ at index hospitalization leading to a higher mortality at follow-up among patients with MINJ (log-rank p = 0.003). MINJ is common in patients hospitalized for Influenza and is able to stratify the risk of short-term adverse events and mid-term mortality. • Myocardial injury is a prognostic factor in critically ill patients with Influenza. • Myocardial injury is common in Influenza, evident in 65.5% of hospitalized patients. • Influenza associated myocardial injury stratifies short term risk of adverse events. • Mid term mortality is higher in patients with Influenza associated myocardial injury. [ABSTRACT FROM AUTHOR]

Association between messenger RNA (mRNA) COVID-19 vaccines and myocarditis has aroused public concern over vaccine safety. The goal of this study was to compare the prognosis of this condition with viral infection–related myocarditis over 180 days. A territory-wide electronic public health care database in Hong Kong linked with population-based vaccination records was used to conduct a retrospective cohort study. Since the roll-out of BNT162b2 (Pfizer-BioNTech), patients aged ≥12 years hospitalized with myocarditis within 28 days after BNT162b2 vaccination were compared against viral infection–related myocarditis recorded before the pandemic (2000-2019), over a 180-day follow-up period (starting from diagnosis of myocarditis). All-cause mortality, heart failure, dilated cardiomyopathy, heart transplant, and postdischarge health care utilization were examined with Cox proportional hazards models. A total of 866 patients were included for analysis. Over the follow-up period, 1 death (1.0%) of 104 patients with postvaccination myocarditis and 84 deaths (11.0%) of 762 patients with viral infection–related myocarditis were identified. One case (1.0%) of dilated cardiomyopathy and 2 cases (1.9%) of heart failure were identified in the postvaccination group, compared with 28 (3.7%) and 93 (12.2%) in the viral infection–related myocarditis group, respectively. Adjusted analysis showed that the postvaccination myocarditis group had a 92% lower mortality risk (adjusted HR: 0.08; 95% CI: 0.01-0.57). No significant differences in other prognostic outcomes were seen. This study found a significantly lower rate of mortality among individuals with myocarditis after mRNA vaccination compared with those with viral infection–related myocarditis. Prognosis of this iatrogenic condition may be less severe than naturally acquired viral infection–related myocarditis. [Display omitted] [ABSTRACT FROM AUTHOR]

Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis. An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram. Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84–8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98–3.61, p = 0.057). CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis. • ICB-myocarditis can clinically present similarly to acute coronary syndrome. • Diagnostic steps are similar; treatment of both entities is substantially different. • Delay in appropriate treatments of severe ICB-myocarditis should be avoided. [ABSTRACT FROM AUTHOR]

Cardiac magnetic resonance imaging (CMR) became over the last 30 years an essential tool in the management of patients with myocarditis. Noninvasive diagnosis of acute myocarditis relies on a clinical picture compatible with myocarditis and fulfilling of the updated 2018 Lake Louise criteria. These criteria include highlights of myocardial edema by conventional T2-weighted sequences or by T2 mapping in one hand and evidence of myocardial injury using late gadolinium enhancement sequences, T1 mapping or extra-cellular volume measurement in the other hand. It is recommended to perform basal examination in the 2 or 3 weeks following acute episode and to repeat CMR during follow-up. The literature reports excellent diagnostic accuracy, between 80% and 90%, making CMR a robust and reliable noninvasive alternative to endomyocardial biopsy. Besides, beyond its diagnostic performance, CMR can also help to identify patients with unfavourable long-term outcome. For instance, medio-ventricular and septal location of late gadolinium enhancement, degree of late gadolinium enhancement extent or high T2 mapping values are independent predictive factors of major cardio-vascular events. [ABSTRACT FROM AUTHOR]

Cardiac Magnetic Resonance (CMR) imaging is recommended as the reference diagnostic non-invasive modality for myocarditis but is often limited by patients' compliance. The purpose of this study is to evaluate the validity of Radiomics applied to Short Tau Inversion Recovery (STIR) sequences, in predicting the presence of LGE in patients with suspected acute myocarditis. 171 STIR images on short-axis view were segmented with "MaZda" software ver 4.6, by placing a region of interest (ROI) on the left ventricle by two radiologists in consensus. Images were classified according to the presence of LGE in the equivalent short-axis T1-IR slice. A total of 337 ROI features were extracted for each image. Dataset was then split into two parts (train and test set) with 70:30 ratio. Eleven classification models were trained. An Ensemble Machine Learning (EML) model was obtained by averaging the predictions of models with accuracy on test set >70%. The EML documented accuracy of 0.75, sensitivity of 0.8 and a specificity of 0.73 with a NPV of 0.81 and a PPV of 0.7, with AUC of 0.79 (95% CI: 0.66–0.92). Radiomics and machine learning analysis could be a promising approach in reducing scan times without reducing diagnostic accuracy in predicting LGE in patients with acute myocarditis. [ABSTRACT FROM AUTHOR]

In patients with de novo acute heart failure (AHF) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO), endomyocardial biopsy (EMB) has been recently shown to be feasible and a helpful method to clarify differential diagnoses, including acute myocarditis. This study aimed to evaluate the feasibility and safety of EMB in patients with a left ventricular (LV) implanted Impella® device. This retrospective, single-center study involves 22 cardiogenic shock patients [SCAI shock stage: C (91%)] requiring mechanical circulatory support (MCS) either by Impella® axial pumps [20 patients (91%)] alone or in combination with VA-ECMO [2 patients (9%)] between December 2017 and January 2022. Coronary artery disease (CAD) or severe valvular heart disease were excluded. The study's primary endpoint was to verify the safety of EMB during MCS. Furthermore, histopathological analysis of the EMB samples was described. 30 LV-EMB procedures were performed. No major complications were reported (death, sustained ventricular tachycardia, need for cardiopulmonary resuscitation, cardiac tamponade, stroke, major bleeding). In 14 patients (64%), EMB-derived histology/immunohistology led to the definitive diagnosis of acute myocarditis. EMB can be safely performed in patients suffering from cardiogenic shock requiring an Impella®-based MCS without the risk of major complications. In about 50% of the patients, relevant inflammatory heart disease could be detected, which required a change in treatment decisions. • LV EMBs can be safely performed in patients requiring Impella® support. • Immuno−/histology led to the diagnosis of acute myocarditis in about 50% of patients. • Detection of relevant cardiac inflammation required a change in treatment decisions. [ABSTRACT FROM AUTHOR]

Background: Postmarketing evaluations have linked myocarditis to COVID-19 mRNA vaccines. However, few population-based analyses have directly compared the safety of the 2 mRNA COVID-19 vaccines.Objectives: This study aimed to compare the risk of myocarditis, pericarditis, and myopericarditis between BNT162b2 and mRNA-1273.Methods: We used data from the British Columbia COVID-19 Cohort (BCC19C), a population-based cohort study. The exposure was the second dose of an mRNA vaccine. The outcome was diagnosis of myocarditis, pericarditis, or myopericarditis during a hospitalization or an emergency department visit within 21 days of the second vaccination dose. We performed multivariable logistic regression to assess the association between vaccine product and the outcomes of interest.Results: The rates of myocarditis and pericarditis per million second doses were higher for mRNA-1273 (n = 31, rate 35.6; 95% CI: 24.1-50.5; and n = 20, rate 22.9; 95% CI: 14.0-35.4, respectively) than BNT162b2 (n = 28, rate 12.6; 95% CI: 8.4-18.2 and n = 21, rate 9.4; 95% CI: 5.8-14.4, respectively). mRNA-1273 vs BNT162b2 had significantly higher odds of myocarditis (adjusted OR [aOR]: 2.78; 95% CI: 1.67-4.62), pericarditis (aOR: 2.42; 95% CI: 1.31-4.46) and myopericarditis (aOR: 2.63; 95% CI: 1.76-3.93). The association between mRNA-1273 and myocarditis was stronger for men (aOR: 3.21; 95% CI: 1.77-5.83) and younger age group (18-39 years; aOR: 5.09; 95% CI: 2.68-9.66).Conclusions: Myocarditis/pericarditis following mRNA COVID-19 vaccines is rare, but we observed a 2- to 3-fold higher odds among individuals who received mRNA-1273 vs BNT162b2. The rate of myocarditis following mRNA-1273 receipt is highest among younger men (age 18-39 years) and does not seem to be present at older ages. Our findings may have policy implications regarding the choice of vaccine offered. [ABSTRACT FROM AUTHOR]

L'atteinte cardiaque au cours du lupus systémique (LS) et du syndrome des antiphospholipides (SAPL) peut être de mécanisme et de présentation très variable. Les péricardites représentent la manifestation lupique la plus fréquente et surviennent chez 16 à 25 % des patients. Elles sont très corticosensibles. La colchicine permet une épargne cortisonique. Les myocardites lupiques vraies sont rares et souvent inaugurales. Elles peuvent se manifester par une douleur thoracique, une insuffisance cardiaque aiguë, des troubles du rythme ou de la conduction, et peuvent évoluer vers une cardiomyopathie dilatée et/ou une insuffisance cardiaque définitive. Leur pronostic est cependant généralement bon, même en l'absence de traitement par cyclophosphamide pour les formes les moins graves. Enfin, l'atteinte coronarienne au cours du lupus est le plus souvent d'origine athéroscléreuse, thrombotique (généralement dans le cadre d'un SAPL associé), et exceptionnellement expliquée par une authentique vascularite coronarienne. Au cours du SAPL, les valvulopathies sont fréquentes et dans la majorité des cas asymptomatiques. Les atteintes thrombotiques peuvent être (1) coronariennes se manifestant typiquement par un infarctus du myocarde chez un sujet jeune à coronaires saines, (2) intracardiaques beaucoup plus rarement, ou (3) microcirculatoires généralement dans le cadre d'un syndrome catastrophique des antiphospholipides (CAPS) pouvant aboutir à un tableau de défaillance multiviscérale. Enfin, les manifestations cardiaques iatrogéniques peuvent exceptionnellement se voir au cours d'un traitement par cyclophosphamide ou par antimalariques caractérisés par des troubles conductifs et/ou une insuffisance cardiaque. Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure. [ABSTRACT FROM AUTHOR]

• ·COVID-19 vaccines have been developed to restrain the rapid spread of SARS-CoV-2. • ·Adverse responses occur from COVID-19 vaccines, including fatal thrombotic events. • ·Messenger RNA–based vaccines trigger pericarditis/myocarditis and it is more predominant in young adults. • ·Cardiovascular events also include hypertension, arrhythmia, and acute coronary syndrome. SARS-CoV-2 is responsible for the global COVID-19 pandemic, with little prevention or treatment options. More than 600 million mortalities have been documented from SARS-CoV-2 infection, with the majority of fatalities occurring among elderly patients (aged >65 years). A number of vaccines have been developed in an effort to restrain the rapid spread of SARS-CoV-2. Considering the widespread administration of these vaccines, substantial side or undesired effects in multiple organ systems have emerged, necessitating essential critical care. Herein, we tabulate the adverse cardiovascular responses resulting from COVID-19 vaccines. We searched PubMed for articles published through April, 2022, with the terms "SARS-CoV-2", "COVID-19", "cardiovascular", "SARS-CoV-2 vaccines", "COVID-19 vaccines", "myocarditis", "pericarditis", "thrombosis", "thrombocytopenia", "vaccine-induced thrombotic thrombocytopenia", "acute coronary syndrome", "myocardial infarction", "hypertension", "arrythmia", "postural orthostatic tachycardia syndrome", "Takotsubo cardiomyopathy", "cardiac arrest" and "death". We mainly selected publications from the past 3 years, but did not exclude widely referenced and highly regarded older publications. Besides, we searched the reference lists of articles identified by above search method and chose those we considered relevant. COVID-19 vaccines evoke rare but fatal thrombotic events, whereas messenger RNA\055based vaccines appear to be associated with risks of pericarditis/myocarditis, with the latter being more predominant in young adults following the second dose. Reports of other cardiovascular responses, including hypertension, arrhythmia, acute coronary syndrome, and cardiac arrest, have also been indicated. The undesired cardiovascular complications remain infrequent, giveng the large number of vaccinations inoculated to general population. And lower mortality takes precedence over the undesired cardiovascular complications. [ABSTRACT FROM AUTHOR]

The aim of our work, developed within the Tunisian Football Federation (TFF), was to study the clinical manifestations and the possible cardiac complications in professional footballers of the first league having contracted an infection by SARS-CoV2. This is a retrospective, descriptive, and analytical study. Professional Premier League football players who contracted COVID-19 from the onset of the pandemic through June 2021 were included. Among the 1388 players of the Tunisian first professional league, 102 players (7.35%) had COVID-19. Three were excluded for lack of clinical data. The average age of the subjects included was 26 ± 4 years with extremes ranging from 19 to 37 years. The most frequent clinical manifestations were anosmia, agueusia and muscle fatigue. The clinical examination was normal in all the subjects included except for the presence of fever among 37 (37.9%) subjects. All subjects' electrocardiogram did not show any unusual abnormality. As for the imaging data, two players presented a pericardial effusion without signs of severity. In the other players, echocardiography was normal. Cardiac magnetic resonance imaging did not reveal any abnormality. The results of our study showed that there was no severe form of COVID-19 among professional soccer players. Larger scale studies integrating other leagues and different sport categories may provide more information on the clinical impact of this disease in high level athletes. [ABSTRACT FROM AUTHOR]

The world is experiencing a pandemic linked to the respiratory spread of SARS-CoV2 which can affect the heart with elevated troponins, ECG abnormalities and kinetic disturbances in echocardiography, of ischemic or non-ischemic origin (most often fulminant myocarditis). To describe the evolutionary modalities of post-COVID-19 myocarditis and to identify factors of poor ejection fraction (EF) recovery under treatment of heart failure. Monocentric observational study including patients with post-COVID-19 non-fulminant myocarditis confirmed by cardiac MRI. These patients were divided into 2 groups according to the evolution of their EF at 3 months (EF > 50% vs EF < 50%). 33 patients (19♂/14♀) aged from 30 to 61 were included, all of whom had repolarization disorder; mean EF at baseline was 44.3% (30–52%) with a troponin level 480 times normal (20–2100). Conventional treatment for heart failure was initiated in all patients with clinical, electrical and echocardiographic monitoring at 1 and 3 months. A significant improvement (EF > 50%) was observed in 29 patients. Gender, congestive signs, electrical and angiographic abnormalities do not seem to influence the evolution of EF (P > 0.10). Age > 60 years, troponins > 1200 times normal, pericardial effusion and a combined criterion of the three seem to be associated with poor evolution of EF (P at 0.07, 0.02, 0.035 and 0.01 respectively). Non-fulminant post-COVID-19 myocarditis have a good prognosis (EF recovery in 87.88%). Factors of poor recovery are age > 60 years, elevated troponins, appearance of pericardial effusion and the combined criterion of the three. Non-fulminant post-COVID-19 myocarditis seems to have a favorable course. Patients presenting factors of poor evolution had to have a longer follow-up. [ABSTRACT FROM AUTHOR]

A 45 years old female patient was admitted to our facility for COVID -19 infection complicated by fulminant cardiac injury and refractory cardiogemic shock. She had echographic findings of reverse takotsubo cardiomyopathy. She was successfully treated by VA-ECMO allowing complete revocery of the left ventricule function and weaning from support [ABSTRACT FROM AUTHOR]