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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]

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]

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]

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]

The presence of myocardial late gadolinium enhancement (LGE) indicates myocyte necrosis, and assists with the diagnosis of acute myocarditis (AM). Cardiac magnetic resonance (CMR) measures other than LGE i.e. tissue characterization and myocardial structural and functional parameters, play an important diagnostic role in assessment for inflammation, as seen in AM. The aim of this systematic review was to appraise the evidence for the use of quantitative CMR measures to identify myocardial inflammation in order to diagnose AM in adult patients. A systematic literature search of medical databases was performed using PRISMA principles to identify relevant CMR studies on AM in adults (2005-2020; English; PROSPERO registration CRD42020180605). Data for a range of quantitative CMR measures were extracted. Continuous variables with low heterogeneity were meta-analyzed using a random-effects model for overall effect size measured as the standard mean difference (SMD). Available data from 25 studies reporting continuous quantitative 1.5-T CMR measures revealed that AM is most reliably differentiated from healthy controls using T1 mapping (SMD 1.80, p <0.01) and T2 mapping (SMD 1.63, p <0.01), respectively. All other measures examined including T2-weighted ratio, extracellular volume, early gadolinium enhancement ratio, right ventricular ejection fraction, and LV end-diastolic volume, mass, ejection fraction, longitudinal strain, circumferential strain, and radial strain also had discriminatory ability although with smaller standard mean difference values (|SMD| 0.32–0.96, p < 0.01 for all). Meta-analysis shows that myocardial tissue characterization (T1 mapping>T2 mapping) followed by measures of left ventricular structure and function demonstrate diagnostic discriminatory ability in AM. • Myocardial structure, function and tissue characterization on cardiac magnetic resonance (CMR) plays an important diagnostic role in assessment of inflammation. • This meta-analysis demonstrated that beyond late gadolinium enhancement, acute myocarditis is most reliably differentiated from healthy controls using T1 and T2 mapping (greatest overall effect sizes). • CMR measures of extra-cellular volume, right ventricular ejection fraction, early gadolinium enhancement ratio and left ventricular volume, ejection fraction & strain all demonstrated smaller effect sizes, compared to T1 and T2 mapping. [ABSTRACT FROM AUTHOR]

Coronary spasm has been suggested to be the underlying mechanism of chest pain in patients with myocarditis and unobstructed coronary arteries. Here we sought to investigate a potential association between virus type and coronary spasm endotype in patients with biopsy-proven viral myocarditis. A total of 618 consecutive patients with unobstructed coronary arteries who underwent endomyocardial biopsy between 2008 and 2018 were screened. Viral myocarditis defined as (immuno-)histological evidence of myocardial inflammation and proof of viral genome by PCR was confirmed in 114 patients. Of these, 34 patients had undergone additional intracoronary acetylcholine (ACh) testing and served as the final study cohort. Patients in this study were 51 ± 27 years old, 41% were female and mean left ventricular ejection fraction was 58 ± 23%. Most frequently, virus DNA was detected by PCR from parvovirus B19 (PVB19, 59%) and human herpesvirus 6 (HHV6, 26%). ACh testing revealed epicardial spasm in 10 patients (29%) and microvascular spasm in 11 patients (32%). The rate of coronary spasm was higher in patients with PVB19-associated myocarditis compared to those with HHV6-associated myocarditis (80% vs. 33%, p = 0.031). In particular, there was a higher prevalence of microvascular spasm in patients with PVB19 compared to HHV6 infection (45% vs. 0%, p = 0.018). Coronary spasm is a frequent finding in patients with biopsy-proven viral myocarditis supporting the hypothesis that coronary spasm may contribute to chest pain in these patients. We observed a particular association of microvascular spasm with PVB19 infection. • Patients with viral myocarditis often present with chest pain. • Most frequently in lymphocytic myocarditis, PVB19 and HHV6 DNA is detected. • Coronary artery spasm could contribute to chest pain in myocarditis. • We observed an association of PVB19 DNA-positive myocarditis with coronary microvascular spasm. [ABSTRACT FROM AUTHOR]

Acute myocarditis is an acute inflammatory cardiomyopathy associated with cardiac damage triggered by a virus or a pathological immune activation. It may present with a wide range of clinical presentations, ranging from mild symptoms to severe forms like fulminant myocarditis, characterized by hemodynamic compromise and cardiogenic shock. The immune system plays a central role in the pathogenesis of myocarditis. In fact, while its function is primarily protective, aberrant responses can be detrimental. In this context, both innate and adaptive immunity play pivotal roles; notably, the innate system offers a non-specific and immediate defense, while the adaptive provides specialized protection with immunological memory. However, dysregulation in these systems can misidentify cardiac tissue, triggering autoimmune reactions and possibly leading to significant cardiac tissue damage. This review highlights the importance of innate and adaptive immune responses in the progression and treatment of acute myocarditis. • Acute myocarditis derives from immune dysregulation, often after a viral infection. • Pathologic immune reaction involves both innate and adaptive immunity. • NLRP3 inflammasome and IL-1β are key players in the innate immune response. • Adaptive immunity involves antigen mimicry and expansion of pathologic T cell. [ABSTRACT FROM AUTHOR]

Clozapine-induced myocarditis and cardiomyopathy are difficult to detect clinically and may be fatal if not detected early. The current/routine biomarkers for clozapine-induced myocarditis are non-specific indicators of inflammation (C-reactive protein) or cardiomyocyte damage (troponins I and T) that lack sensitivity, and for which changes often arise too late to be clinically useful. The C lozapine S afety S tudy was a prospective, longitudinal, observational study to determine what, if any, the plasma concentrations of clozapine, N -desmethylclozapine, and clozapine- N -oxide in patients contribute to cardiotoxicity. Samples were collected and analysed using liquid chromatography mass spectrometry over a 41-month period from patients in the Auckland District Health Board. Sixty-seven patients were included. Six patients were diagnosed with myocarditis; none were diagnosed with cardiomyopathy in the study period. In patients not undergoing dose titration, clozapine biotransformation may shift to the N -oxide pathway rather than the N -desmethyl pathway with increasing dose. During dose titration, the timeframe in which myocarditis occurs, the rate of increase in the plasma concentration of clozapine- N- oxide, as well as the ratio of N -oxidation relative to N -desmethylation, were significantly higher in patients diagnosed with myocarditis. The assessment of clozapine- N- oxide formation, and N -oxidation relative to N -desmethylation ratios during treatment, may help identify a biomarker to aid the early detection of patients at risk of developing clozapine-induced cardiotoxicity. • As clozapine dose increases biotransformation may shift from the N- demethyl to the N -oxide pathway. • The routes of clozapine metabolism may be altered in clozapine-induced myocarditis. • The clozapine N -oxide route appears to be favoured in cases of clozapine-induced myocarditis. • Assessment of metabolite ratios may help identify a biomarker of clozapine-induced myocarditis. [ABSTRACT FROM AUTHOR]

Complications following COVID-19 vaccination, particularly with mRNA vaccines, rarely include myocarditis and pericarditis. This work principally aimed at defining a realistic temporal relationship between vaccination and myocarditis/pericarditis development. All relevant cases reported from week 52/2020 through week 41/2021 in the VAERS database were retrieved and analyzed for licensed vaccines. These included BNT162b2, mRNA-1273, and AD26.COV2·S. Incidence rates were calculated using the corresponding administered vaccine doses as denominators. Additionally, analyzed parameters included demographics, dose series, hospitalization length and outcome. Overall, 2016 myocarditis and 1380 pericarditis cases, (4.96/106 and 3.40/106 administered vaccine doses, respectively), were recorded. Most myocarditis cases occurred following BNT162b2 (5.60/106 doses) in males <30 years. Pericarditis affected predominantly males <40, both sexes >40 years, and was most common post AD26.COV2·S (4.78/106 doses). Hospitalization was required for 40.3% and 27.2% of myocarditis and pericarditis cases, respectively. A bimodal pattern was found for both myocarditis and pericarditis, with two peaks that coincided temporally, but were reversed in intensity. The first peak was recorded 1–3 days post-vaccination and was more pronounced in myocarditis, while the second was recorded 15–30 days post-vaccination and was more intense in pericarditis. Myocarditis/pericarditis after COVID-19 vaccination is rare and depicts a bimodal pattern. • Myocarditis and pericarditis are rare side effects of vaccination against COVID-19. • A bimodal pattern was found for both myocarditis and pericarditis. • The first peak appeared 1–3 days post vaccination and was more pronounced for myocarditis. • The second peak was observed 15–30 days post vaccination and was more intense in pericarditis. • This bimodal pattern was common for all COVID-19 vaccines, irrespectively of platform. [ABSTRACT FROM AUTHOR]

Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4–15.9) years. Time from symptom-onset to EMB was 11.0 (4.0–29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE. • High cardiac immune cell levels are present in young age & heart failure patients. • Children with fulminant clinical presentation & young age have the highest risks. • Myocardial virus genome detection had no significant influence on outcome. • Weaning rate from MCS is high in acute myocarditis. • In myocarditis with persistent cardiac impairment immunotherapy should be discussed. [ABSTRACT FROM AUTHOR]

The incidence of myocarditis after RNA-based vaccines for coronavirus has gained social and medical interest. We performed an intention-to-treat meta-analysis, following the PRISMA statement. After a systematic search, without language restriction, 9 publications were selected. Two were excluded (one was only in subjects with age 12–17 and other might had included subjects from a larger publication). We followed the PRISMA guidelines for abstracting data and assessing data quality and validity. Data was verified by 2 investigators. We analyzed 17,704,413 subjects, from 7 studies, that included 627 cases of confirmed myocarditis). The incidence of myocarditis was 0.0035% (95% CI 0.0034–0.0035). Mean incidence rate was 10.69 per 100.000 persons-year. Cases reported from Israel represented 45.14% from total (283 out of the 627). Only 1 case of fatal myocarditis or death was reported. There was significant heterogeneity between results. The meta-regression analysis excluded mean age, region, number of cases or number of people included as sources of heterogeneity. No small-study effect was observed (p = 0.19). Myocarditis incidence after RNA vaccines is very rare (0.0035%) and has a very favorable clinical course. [Display omitted] • I ncidence of myocarditis after RNA-based vaccines for coronavirus has gained social and medical interest. • We performed a meta-analysis with 17,704,413 subjects that included 627 confirmed myocarditis. • The incidence of myocarditis was 0.0035% (95% CI 0.0034–0.0035). • Mean incidence rate was 10.69 per 100.000 persons-year. • Only 1 case of fatal myocarditis or death was reported. [ABSTRACT FROM AUTHOR]

Acute myocarditis (AM) may be the heralding manifestation of autoimmune and inflammatory disorders (AIID). We aimed to describe the clinical presentation and outcome of patients with AM revealing AIID. All consecutive adult patients with AM admitted in a department of Cardiology (Bichat Hospital, Paris, France) from January 2011 to January 2019 were included. Diagnosis of AM was based on clinical manifestations, elevated Troponin, myocardial inflammation on CMR and no evidence for coronary artery disease. AIID were classified using international criteria. Two-hundred and eighteen (35.3 [26.4–47.1] years, 75.2% males) patients with AM were included. Overall, AM revealed AIID in 15 (6.9%), including systemic lupus erythematosus (n = 3), adult onset Still's disease (n = 3), sarcoidosis (n = 2), mixed connective tissue disease (n = 1), anti-Jo1 syndrome (n = 1), eosinophilic granulomatosis with polyangiitis (n = 1), antiphospholipid syndrome (n = 1), reactive arthritis (n = 1), Graves' disease (n = 1) and Crohn's colitis (n = 1). Left ventricular ejection fraction (LVEF) at onset was <30% in 5 (33.3%) patients with AIID. All but 2 patients with AIID were treated with steroids, immunosuppressive and/or immunomodulatory drugs and LVEF normalized in all by the end of follow-up. By comparing patients with AIID to patients with idiopathic AM (n = 203), multivariable analysis showed that pericardial effusion, lack of chest pain and high CRP level at onset were independently associated with AIID. Acute myocarditis revealing AIID may be life-threatening at the acute phase but has an overall good prognosis under specific treatment. Pericardial effusion and CRP level at admission suggest an AIID as the cause for AM. • Acute myocarditis (AM) may reveal autoimmune and inflammatory disorders (AIID). • Myocarditis revealing AIID may be life-threatening at the acute phase. • AIID-associated myocarditis has a good prognosis under specific treatment. • Pericardial effusion and high CRP level suggest an AIID as the cause for AM. [ABSTRACT FROM AUTHOR]

Myocardial infarction with non-obstructed coronary arteries (MINOCA) is a distinct entity among patients presenting with troponin-positive acute chest pain. We have previously reported on the incremental diagnostic capability of cardiovascular magnetic resonance (CMR) in this cohort. There is paucity of evidence on the long-term (> 5 years) clinical outcomes of these patients as graded by their acute CMR diagnosis. A total of 229 patients with a working diagnosis of MINOCA who underwent CMR assessment during the acute admission (2010–2017) were prospectively studied. The primary endpoint was major adverse cardiac events (MACE) defined as a composite of all-cause mortality and cardiovascular readmissions, identified from hospital and primary care records. CMR performed at a median of 6 days (IQR 2, 8) from presentation provided a diagnosis in 85% of the patients (38% myocarditis, 28% acute myocardial infarction and 19% Takotsubo cardiomyopathy). Over a median follow-up of 7.1 years (IQR 3.7, 8.2), 56 (24%) patients experienced a MACE. We found a strong association between CMR diagnosis and MACE (log rank 30.47, p < 0.001). In multivariate analysis, age (hazard ratio = 1.07; 95% confidence interval = 1.05, 1.10; p < 0.001) and CMR diagnosis of acute myocardial infarction (hazard ratio = 8.87; 95% confidence interval = 2.58, 30.4; p = 0.001) were independent predictors of MACE. In a large cohort of patients with a working diagnosis of MINOCA, one in four suffer a MACE during long-term clinical follow-up. CMR diagnosis of acute myocardial infarction and age were significant predictors of MACE even in the absence of significant coronary artery obstruction. [Display omitted] • MINOCA is a distinct clinical entity with different pathophysiological causes. • CMR is a key investigation in patients presenting with a working diagnosis of MINOCA. • One in four patients suffer a MACE during long-term clinical follow-up. • In patients with a working diagnosis of MINOCA, CMR diagnosis of AMI is a significant predictor of MACE. [ABSTRACT FROM AUTHOR]

Traditional cardiomyopathy paradigms segregate inflammatory etiologies from those caused by genetic variants. An identified or presumed trigger is implicated in acute myocarditis or chronic inflammatory cardiomyopathy but growing evidence suggests a significant proportion of patients have an underlying cardiomyopathy-associated genetic variant often even when a clear inflammatory trigger is identified. Recognizing a possible genetic contribution to inflammatory cardiomyopathy may have major downstream implications for both the patient and family. The presenting features of myocarditis (i.e. chest pain, arrhythmia, and/or heart failure) may provide insight into diagnostic considerations. One example is isolated cardiac sarcoidosis, a distinct inflammatory cardiomyopathy that carries diagnostic challenges and clinical overlap; genetic testing has increasingly reclassified cases of isolated cardiac sarcoidosis as genetic cardiomyopathy, notably altering management. On the other side, inflammatory presentations of genetic cardiomyopathies are likewise underappreciated and a growing area of investigation. Inflammation plays an important role in the pathogenesis of several familial cardiomyopathies, especially arrhythmogenic phenotypes. Given these clinical scenarios, and the implications on clinical decision making such as initiation of immunosuppression, sudden cardiac death prevention, and family screening, it is important to recognize when genetics may be playing a role. • Some inflammatory cardiomyopathies may be influenced by cardiovascular genetic abnormalities • Identification of a genetic variant has implications for management and family screening • Patient factors may suggest an underlying genetic cause; recognition may avoid ineffective and potentially harmful treatments • Known genetic cardiomyopathies may have inflammatory presentations that are important to recognize • Increased recognition of genetic and inflammatory cardiomyopathy overlap may help future research to help refine treatment [ABSTRACT FROM AUTHOR]

Cardiomyopathy is an important cause of heart failure, however, there is notable lack of data on causes and manifestations of cardiomyopathy in Africa. The African Cardiomyopathy and Myocarditis Registry Program (IMHOTEP) aims to address the knowledge gap on etiology, treatment, and outcomes of cardiomyopathy in sub-Saharan Africa. We conducted a single-center pilot study to delineate the clinical and cardiovascular magnetic resonance (CMR) phenotypes of cardiomyopathy in South African patients. Assessment of the first 99 adult incident cases [mean age 36.8 ± 12.5 years; females 53.5%] enrolled in IMHOTEP showed that dilated cardiomyopathy (n = 77) was commonest, followed by hypertrophic (n = 13), restrictive (n = 5) and arrhythmogenic (n = 4) cardiomyopathies. A broad range of etiologies were encountered with secondary causes identified in 42% of patients. Onset of symptoms in the peripartum period was observed in 47% of women, and peripartum cardiomyopathy was diagnosed in 32.1% of women recruited. In addition to electrocardiography and echocardiography, CMR was performed in 67 cases and contributed diagnostically in a third of cases. Acute inflammation was rarely observed [2%] on CMR, however, late gadolinium enhancement (LGE) was noted in 92% of cases. We report a diverse spectrum of causes of cardiomyopathy in the South African population, with secondary, potentially treatable, etiologies in a significant proportion of cases. CMR was useful in delineating specific phenotypes and etiologies, influencing clinical care. A higher-than-expected burden of LGE was observed in this young patient cohort - the implications of which are yet to be determined. • The IMHOTEP study represents the first step in addressing current knowledge deficits around cardiomyopathies in Africans. • Secondary, potentially treatable, causes play an important role in development of dilated cardiomyopathy in South Africa. • We observe a higher-than-expected burden of myocardial fibrosis in South African patients with cardiomyopathies. [ABSTRACT FROM AUTHOR]

Gene therapy is a technique to correct genetic abnormalities, through introduction of a functional gene or through direct genome editing. Adeno-associated virus (AAV)-mediated gene replacement shows promise for targeted therapies in treatment of inherited cardiomyopathies and is the most used approach in clinical trials. However, immune responses from the host to the virus and gene product pose delivery and safety challenges. This review explores the immunological reactions to AAV-based gene therapy, their potential toxic effects, with a focus on myocarditis, and future directions for gene therapy. Central Illustration: Mechanisms of gene therapy toxicity. TLR: toll-like receptor. PAMP: pathogen-associated molecular patterns, APC: antigen-presenting cell, NF-kB: nuclear factor kappa B, ITR: inverted terminal repeats, pA: poly-A tail. Created with BioRender.com [Display omitted] • AAV-delivered gene therapy has shown promising results in clinical trials for inherited diseases. • Immune reactions may develop against the transgene or vector, leading to possible adverse events. • Standardized immunosuppressive regimens may be important for increasing gene therapy safety. [ABSTRACT FROM AUTHOR]

Cardiac magnetic resonance (CMR) is central in the diagnosis and prognostic stratification of acute myocarditis (AM) but the timing of repeated CMR scans to assess edema resolution and late gadolinium enhancement (LGE) stabilization remain unclear. We assessed edema and LGE evolution over 12 months to identify the optimal timing of repeat CMR evaluation in AM. Thirty-three consecutive patients with AM underwent CMR at clinical presentation (CMR-1), after 3 months (CMR-2) and after 12-months (CMR-3). CMR included assessment of edema and LGE, left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMi). After CMR-3 patients were followed-up every three-months by clinical evaluation, Holter-monitoring, and echocardiography. All patients had edema and LGE at CMR-1. At CMR-2 edema-positive segments (0.42 ± 0.34 vs. 3.18 ± 2.33, p < 0.005), LGE (4.98 ± 4.56 vs. 9.60 ± 8.58 g, and 4.22 ± 3.97% vs 7.50 ± 5.61%) and LVMi (69.82 ± 11.83 vs 76.06 ± 13.13 g/m2) (all p < 0.0001) significantly reduced, while LVEF (63.12 ± 5.47% vs.61.15 ± 6.87% p < 0.05) significantly improved, compared to CMR-1. At CMR-2 edema persisted in 7 patients (21%) but resolved at CMR-3 with no further changes of LVMi, LVEF and LGE. During follow-up (85 ± 15 months), 5 (15%) patients showed persistent ventricular arrhythmias. Univariate predictors of arrhythmic persistence were LGE extension at CMR-2 and CMR-3 (both p < 0.05), but not at CMR-1 (p = 0.07). Most patients with uncomplicated AM show edema resolution with LGE stabilization after 3 months. Further CMR evaluations should be limited to patients with persisting edema at this time. LGE extent measured after edema resolution is associated with persistent ventricular arrhythmias. • In most uncomplicated acute myocarditis, myocardial edema resolved after 3 months. • Edema resolution is associated with increase of LVEF and reduction of LVMi. • LGE extent reduced after 3 months with no further changes after 12 months. • LGE measured after edema resolution is the definitive post-myocarditis scar. • The extent of definitive LGE is associated with ventricular arrhythmia persistence. [ABSTRACT FROM AUTHOR]

Immune-checkpoint inhibitors (ICIs), a unique antibody-based therapeutic strategy, have revolutionized the treatment landscape of solid and hematological cancers. Despite the proven benefits of ICIs, the cardiotoxicity from unspecific immune activation (uncommon but potentially fatal) is a continuing concern. Accumulating preclinical research has demonstrated that ICIs initiate inflammation in the myocardium, while clinically significant cardiotoxicity were reported in few patients receiving ICI therapy, probably due to the low incidence and unspecific symptoms. The subtle signs and symptoms (e.g., chest pain, dizziness, and dyspnea) were likely attributed to cancer and/or non-cardiac events by previous studies, thus limiting the understanding of the incidence, outcomes, risk factors, and management of ICI-related cardiotoxicity. The heterogeneous clinical presentation and complex diagnostic procedure further make it challenging to accurately identify ICI-related cardiac events in clinical trials. Therefore, ICI-related cardiotoxicity, whose incidence is probably underestimated, has not been well recognized. In this article, we provide an overview of potential mechanisms underlying ICI-related cardiotoxicity and review accumulating clinical evidence of ICI-related cardiotoxicity, with a focus on myocarditis. Moreover, we discuss possible strategies to manage ICI-related cardiotoxicity and highlight the importance of developing cardio-oncology. • Introduce possible mechanisms underlying immune-checkpoint inhibitors-induced cardiotoxicity. • Summarize recent clinical evidence of immune-checkpoint inhibitors-related cardiotoxicity, with a focus on myocarditis. • Discuss possible strategies to manage immune-checkpoint inhibitors-related cardiotoxicity. • Highlight the significance of developing cardio-oncology. [ABSTRACT FROM AUTHOR]

Myocarditis has been reported following the second dose of COVID-19 mRNA vaccination. Whether administration of additional doses of COVID-19 vaccines further increases the risk of myocarditis is unknown. We included individuals who received one to three doses of BNT162b2 or mRNA-1273 mRNA vaccine between 12/14/2020 and 2/18/2022. Myocarditis within 21 days of vaccine administration was identified using electronic medical records. Incidence rate ratios were calculated by comparing the observed incidence with the expected incidence from the same population during a 365-day baseline period. Of 3,076,660 KPSC members who received at least one dose of COVID-19 mRNA vaccines, 2,916,739 (94.5%) received at least two doses, and 1,146,254 (47.0%) received three doses. The incidence rate ratio for myocarditis was 0.86 (95% CI 0.31–1.93) for the first dose, 4.22 (95% CI 2.63–6.53) for the second dose, and 2.61 (1.13–5.29) for the third dose. Most myocarditis cases following the second and third dose occurred within seven days of vaccination. Myocarditis was a rare event observed after the second or third dose of vaccination. Most cases presented within seven days of vaccination. The incidence of myocarditis following the third dose was not significantly higher than that observed after the second dose. • Whether administration of additional doses of COVID-19 vaccines increases the risk of myocarditis is not known. • Among 3,076,660 individuals, an increased risk of myocarditis was observed after the second and the third dose of COVID-19 mRNA vaccination. • Most cases presented within seven days of vaccination • The incidence of myocarditis following the third dose was not significantly higher than that observed after the second dose. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up. Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up. Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms. Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors. [Display omitted] • Cardiovascular involvement is common in hospitalized COVID-19 patients. • The occurrence of cardiovascular disease increases the risk of in-hospital mortality. • Cardiovascular evaluation in COVID-19 identifies patients who could benefit from specific treatment. • Short and long-term cardiovascular sequelae suggest the need for monitoring COVID-19 survivors. [ABSTRACT FROM AUTHOR]

Histologic evidence is required for a definitive diagnosis of cardiac sarcoidosis (CS) by published guidelines; however, the sporadic nature of the disease may produce false negative biopsy results, causing CS to be underdiagnosed. We sought to establish a clinical category of CS absent histologic findings. Patients evaluated for CS were stratified into 3 groups: probable CS and definite CS based on Heart Rhythm Society (HRS) criteria and presumed CS, ie, patients without any histologic evidence of sarcoidosis, but with unexplained high-grade atrioventricular block or ventricular arrhythmia and findings suggestive of CS on either cardiac magnetic resonance imaging or positron emission tomography. The primary end point was hospitalization-free and overall survival at 10 years. A total of 383 patients were included in the study: 59, definite CS; 223, probable CS; and 101, presumed CS (62, isolated CS and 39, systemic CS). Compared with patients meeting HRS criteria for CS, patients with presumed CS had lower odds of New York Heart Association class III or IV symptoms (odds ratio [OR], 0.44 [95% CI, 0.23–0.83]; P =.01) but greater odds of previous ventricular tachycardia (OR, 2.4 [95% CI, 1.4–4.0]; P =.001) or history of resuscitated sudden cardiac arrest (OR, 2.9 [95% CI, 1.0–8.6]; P =.05). Hospitalization-free and overall survival were similar among groups (P =.51 and P =.71, respectively). Clinical categorization of patients with presumed CS identified a high-risk cohort comparable to patients with histologic evidence of disease, although caution should be exercised in reaching this diagnosis without paying due diligence to the differential diagnosis. • Cardiac sarcoidosis (CS) may be underdiagnosed. • A "presumed" CS category incorporates characteristic clinical and imaging findings. • The presumed cohort has similar presentation and symptomatology. • No difference in a composite CV outcome was identified among the cohorts. • Cardiac sarcoid diagnosis absent histology identifies patients warranting treatment. [ABSTRACT FROM AUTHOR]

Heart failure (HF), the dominant form of cardiovascular disease in Africans, is mainly due to hypertension, rheumatic heart disease and cardiomyopathy. Cardiomyopathies pose a great challenge because of poor prognosis and high prevalence in low- and middle-income countries (LMICs). Little is known about the etiology and outcome of cardiomyopathy in Africa. Specifically, the role of myocarditis and the genetic causes of cardiomyopathy are largely unidentified in Africans. The Afr i can Cardio m yopat h y and My o cardi t is R e gistry P rogram (the IMHOTEP study) is a pan-African multi-centre, hospital-based cohort study, designed with the primary aim of describing the clinical characteristics, genetic causes, prevalence, management and outcome of cardiomyopathy and myocarditis in children and adults. The secondary aim is to identify barriers to the implementation of evidence-based care and provide a platform for trials and other intervention studies to reduce morbidity and mortality in cardiomyopathy. The registry consists of a prospective cohort of newly diagnosed (i.e., incident) cases and a retrospective (i.e., prevalent) cohort of existing cases from participating centres. Patients with cardiomyopathy and myocarditis will be subjected to a standardized 3-stage diagnostic process. To date, 750 patients have been recruited into the multi-centre pilot phase of the study. The IMHOTEP study will provide comprehensive and novel data on clinical features, genetic causes, prevalence and outcome of African children and adults with all forms of cardiomyopathy and myocarditis in Africa. Based on these findings, appropriate strategies for management and prevention of the cardiomyopathies in LMICs are likely to emerge. • There are limited data on etiology, treatment and outcome of cardiomyopathy and myocarditis which limits diagnosis, management and prevention. • IMHOTEP is a hospital-based study of clinical features, genetics and outcomes of cardiomyopathy in children and adults. • IMHOTEP consists of prospectively and retrospectively recruited cases; over 750 participants recruited in the pilot phase. • IMHOTEP as a pan-African, multi-centre, single registry that includes all forms of cardiomyopathies. • IMHOTEP is a hospital-based investigation and will not address disease burden at the population level. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease associated with increased glucose uptake. The hypothesis of this study assumes that 18F-2-fluoro-2-deoxy- d -glucose positron emission tomography/computed tomography (FDG-PET/CT) may improve specificity and sensitivity in the diagnosis of myocarditis and referral for endomyocardial biopsy (EMB), adding additional information for post-discharge risk stratification. The aim of the study is to assess the diagnostic and prognostic feasibility of FDG-PET/CT in comparison to cardiac magnetic resonance (CMR) (alone or in combination) in patients with clinically suspected myocarditis undergoing EMB. Fifty hospitalized patients with clinically suspected myocarditis who meet the inclusion/exclusion criteria will be enrolled in a prospective, observational, multicentre, cohort study (NCT04085718). The primary endpoint is the sensitivity and specificity of FDG-PET/CT imaging in the diagnosis of myocarditis. The main secondary endpoints include correlation of FDG-PET/CT imaging with CMR, echocardiography, and EMB results. The patients will undergo the following evaluations: clinical examination, blood tests (including biomarkers of fibrosis and anti-heart autoantibodies (AHA)), ECG, 24 h Holter ECG, echocardiography, CMR, as well as resting single photon emission computed tomography (SPECT) to assess possible myocardial perfusion defects, cardiac FDG-PET/CT and right ventricular EMB. After 6-months a follow-up visit will be performed (including 24 h Holter ECG, echocardiography and CMR). Investigators evaluating individual studies (CMR, SPECT, FDG-PET/CT and EMB) are to be blinded to the other tests' results. We believe that FDG-PET/CT alone or in combination with CMR may be a useful tool for improving diagnostic accuracy in patients with clinically suspected myocarditis. • Making a reliable diagnosis of myocarditis is still a challenge. • CMR is the reference method of imaging in myocarditis, but it has limitations in chronic myocarditis and patients with contraindications to CMR. • FDG-PET/CT is another promising non-invasive method that may be a useful tool in the diagnosis of myocarditis. • Use of FDG-PET/CT may help to choose patients that should be referred for endomyocardial biopsy. [ABSTRACT FROM AUTHOR]

Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis. CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214–923) days. LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70–746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08–10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16–18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery. In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome. • We present data from a large multicentric cohort of pediatric patients submitted to CMR for acute myocarditis with a mean follow-up time of 745 days. • Recover of function was attained in about 2/3 of patients and is inversely correlated with the presence of a midwall or mixed LGE pattern. • A complete recovery from functional and tissue abnormalities found only in a third of patients. [ABSTRACT FROM AUTHOR]

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested. • FM is a form of acute myocardial inflammation leading to rapid-onset clinical presentation requiring circulatory support. • Although FM is associated with poor outcomes, a paucity of evidence-based management strategies exists for this disease. • The present report highlights both agreements and controversies in FM management across the world. • International efforts should be made to launch prospective interventional studies specifically oriented to FM patients. [ABSTRACT FROM AUTHOR]

Previous literature suggests that both SARS-CoV-2 infection and COVID-19 mRNA vaccine are associated with myocarditis, in which the incidence is higher in the infection group. COVID-19 mRNA vaccine-related myocarditis is noted to have a more benign course. Despite these findings, there is a need for a larger population systematic review that compares the outcomes to pre-pandemic acute myocarditis to better understand the extent of the current post-COVID state. We performed a literature search with PubMed and EMBASE and identified studies investigating COVID-19 and its vaccinated population, and the population prior to the pandemic (control group) who had myocarditis. We performed a one-group meta-analysis of the incidence, baseline demographics, and outcomes of myocarditis for each group. The incidence in the SARS-CoV-2 infection group was 2.76 per thousand (95% CI, 0.85–8.92), 19.7 per million (95% CI, 12.3–31.6) in the vaccine group, and 0.861 per million (95% CI, 0.04–16.7) in the control group. The majority of patients were male, with the highest proportion in the vaccine group. The mean age was the youngest in the vaccine group (24.8, 95% CI, 19.1–30.6). The vaccine group had the lowest mortality (2.0%, 95% CI, 1.3–2.7) followed by the control and the SARS-CoV-2 infection group. The vaccine group had the lowest proportion of immunoglobulin and glucocorticoid use, mechanical circulatory support, and cardiogenic shock. Our study showed favorable outcomes of myocarditis in patients with COVID-19 mRNA vaccination, despite a higher incidence than pre-COVID controls. Further studies with standardized myocarditis diagnostic criteria assessing long-term outcomes are necessary. • COVID-19 is associated with myocarditis as well as its vaccines. • COVID-19 vaccine associated myocarditis had a favorable outcome. • COVID-19 associated myocarditis may have a worse cardiac and mortality outcome [ABSTRACT FROM AUTHOR]

Although the incidence of immune checkpoint inhibitor (ICI)-related cardiovascular (CV) toxicity is low, the overall burden of CV events after ICI is unknown. Risk factors for CV events after ICI have yet to be identified. We sought to evaluate the association between vascular calcification on routine baseline computed tomography (CT) imaging and CV events following ICI. This was a single-center, retrospective cohort study of 76 patients referred to Cardio-Oncology with prior ICI treatment. Coronary and aortic calcification on non-gated chest and abdominal CT imaging were qualitatively assessed. The association of baseline clinical parameters and vascular calcification with symptomatic heart failure (HF), acute coronary syndrome, myocarditis, symptomatic arrhythmia, or pericardial effusion after ICI was evaluated. Over 11 months of follow-up, there were 80 CV events that occurred in 49 patients. Worse coronary and aortic calcification on pre-treatment CT imaging was seen in patients with a CV event (p =.018 and p =.014, respectively). There were no differences in traditional CV risk factors between those with and without a CV event. Eighteen patients (37%) were restarted on ICI therapy after a non- myocarditis or symptomatic systolic HF CV event without recurrent events or mortality over 13 months of follow-up. Symptomatic HF was the most common CV event seen after ICI therapy. Worse coronary and aortic calcification on baseline CT imaging was associated with CV events following ICI. With careful clinical evaluation, selected patients may be re-treated with ICI following a non- myocarditis or symptomatic systolic HF CV event. • A broad range of cardiovascular events may be seen in patients receiving immune checkpoint inhibitor (ICI) therapy. • Vascular calcification on baseline non-gated CT scans are associated with the occurrence of cardiovascular events on ICI therapy. • Selected patients may be re-treated with ICI after a non-myocarditis or symptomatic systolic heart failure event on ICI therapy. [ABSTRACT FROM AUTHOR]

Time from first symptoms to diagnosis, called time to diagnosis, is related to prognosis in several diseases. The aim of this study was to assess time to diagnosis in children with new-onset heart failure (HF) and assess its consequences and determinants. A retrospective population-based observational study was conducted between 2007 and 2016 in a French tertiary care center. We included all children under 16 years old with no known heart disease, and HF confirmed by echocardiography. With logistic regression used for outcomes and a Cox proportional-hazards model for determinants, analyses were stratified by HF etiology: congenital heart diseases (CHD) and cardiomyopathies/myocarditis (CM). A total of 117 children were included (median age [interquartile range (IQR)] 25 days (6–146), 50.4% were male, 60 had CHD and 57 had CM). Overall median (IQR) time to diagnosis was 3.3 days (1.0–21.2). The frequency of 1-year mortality was 17% and 1-year neuromotor sequel 18%. Death at 1 year was associated with low birth weight for all patients (adjusted odds ratio 0.24, 95% confidence interval [CI] 0.08–0.68) and time to diagnosis below the median with CM (0.09, 0.01–0.87) but not time to diagnosis above the median for all patients (0.59, 0.13-2.66). Short time to diagnosis was associated with clinical severity on the first day of symptoms for all patients (adjusted hazard ratio 3.39, 95% CI 2.01–5.72), and young age with CM (0.09, 0.02–0.41). In children with new-onset HF presenting in our region, median time to diagnosis was short. Long time to diagnosis was not associated with poor outcome. • In pediatric new-onset heart failure, median time to diagnosis was short. • Excess mortality was not associated with long time to diagnosis but with low birth weight. • Early severity signs were the main determinant of short time to diagnosis. [ABSTRACT FROM AUTHOR]

Although immune checkpoint inhibitors (ICIs) have made an immense breakthrough in cancer therapeutics, they can exert unique, immune-related adverse events. Among them, myocarditis is less frequent, but it is serious and often follows a lethal course. To examine the changes in cardiac autoimmunity after ICI administration, we developed a mouse experimental autoimmune myocarditis (EAM) model via intraperitoneal administration of murine α-cardiac myosin heavy chain (MyHC-α) fragment. Thereafter, the mouse anti-PD-1 antibody (mPD1ab) was administered at two time points, subsequent to and concurrent with MyHC-α fragment administration. Severe EAM developed in 3 weeks; wide inflammatory lesions were observed in the cardiac sections. Furthermore, inflammatory/fibrotic genes, such as interleukin 1β, interleukin 6, and collagen 1, were upregulated, although the cardiac function was not significantly affected. The subsequent administration of mPD1ab at 2 weeks post administration of the first MyHC-α fragment exacerbated EAM, whereas the administration of mPD1ab concurrent with MyHC-α fragment administration did not exacerbate EAM. The subsequent administration of mPD1ab significantly increased the infiltration of cluster of differentiation (CD)4- and F4/80-positive cells, whereas the concurrent administration of mPD1ab significantly decreased the infiltration of CD4-positive cells, indicating that the concurrent and subsequent administration of mPD1ab had opposite effects on immune/inflammatory cell infiltration. These data suggest that the appearance of ICI-induced autoimmune myocarditis might be related to autoimmune system activity before ICI administration. Although ICIs do not adversely affect patients with normal immune systems, we propose that ICI administration should be avoided in patients with autoimmune disorders. • We developed a mouse experimental autoimmune myocarditis (EAM) model. • Exacerbation of autoimmune myocarditis by an immune checkpoint inhibitor (ICI) is dependent on its time of administration. • The appearance of ICI-induced autoimmune myocarditis is related to autoimmune system activity before ICI administration. • We propose that ICI administration should be avoided in patients with autoimmune disorders. [ABSTRACT FROM AUTHOR]

Immune-mediated myocardial injury following Severe Acute Respiratory Syndrome Coronavirys-2 (SARS-CoV2) infection has been described in adults and children. Cases of myocarditis following immunization for SARS-CoV2 have recently been documented, mostly associated with mild severity and spontaneous recovery. We herein report two cases of fulminant myocarditis following BNT162b2 mRNA Covid-19 vaccination associated with systemic hyperinflammatory syndrome and refractory shock requiring support with veno-arterial extracorporeal membrane oxygenation. • Fulminant myocarditis may occur following SARS-CoV2 mRNA vaccination requiring mechanical cardiac support. • It is important to recognize features of systemic hyperinflammatory syndrome following SARS-CoV2 mRNA vaccination. [ABSTRACT FROM AUTHOR]

A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community. Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients. Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19. We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes. Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis. 112 COVID-19 patients were enrolled in our study. There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis. Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died. Troponin levels were significantly increased in the week preceding the death. 15 (13.4%) patients have presented signs of pulmonary hypertension. Typical signs of myocarditis were absent on echocardiography and electrocardiogram. The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus. The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients. • The evidence from clinical standpoint and front-line data in Wuhan for COVID-19. • The novel coronavirus in COVID-19 less likely caused myocardial injury directly. • Elevation in cardiac markers is the warning sign of adverse outcomes for COVID-19. [ABSTRACT FROM AUTHOR]

Endomyocardial biopsies (EMB) are the gold standard for the diagnosis of myocarditis in children and adults. The existing WHO/ISFC criteria for lymphocytic cell infiltrates by are based on the myocardium of adults. The aim of this study was to present a paediatric control cohort for the evaluation of inflammation in EMB of children. In this study endomyocardial tissue from 62 children under 4 years of age was investigated, being collected during a planned open heart surgery with routine resection from ventricular site. Patients had no history of infection or myocardial inflammation. The heart tissue was formalin fixed and embedded in paraffin. Four μm thick tissue sections were stained with haematoxylin and eosin, Masson's trichrome, and Giemsa. Immunohistochemical stainings included quantitative evaluation of CD3+ T cells, CD20+ B cells, CD68+ macrophages and MHCII expression. The myocardium was obtained in 96.8% (n = 60) of the cases from the right and in 3.2% (n = 2) from the left ventricle. The median age (interquartile range) at biopsy was 0.5 years (0.3–0.9), 66.1% male. Within this cohort, a median of 2.5/mm2 (1.0–4.0) CD3+ T cells, 0.5/mm2 (0.0–0.6) CD20+ B cells and 4.0/mm2 (2.5–6.0) CD68+ macrophages were detected. The MHC II grade was 0 in 71.0% (n = 44) and 1 in 29.0% (n = 18). This is the first paediatric control cohort being relevant for the correct interpretation of inflammatory heart diseases in EMB. The lymphocytic cell numbers in children needing congenital heart surgery without myocardial inflammation are below the existing values in adults. • First paediatric reference cohort to interpret inflammation in myocardial tissue. • Median reference values: CD3+ T cells 2.5/mm2 & CD68+ macrophages 4.0/mm2. • The lymphocytic cell numbers lie below the existing values in adults. [ABSTRACT FROM AUTHOR]

Myocarditis is a rare but severe adverse event associated with immune checkpoint inhibitors, its diagnosis depending on a high index of suspicion and appropriate investigations. Our objective was to systematically review the diagnostic approaches to myocarditis associated with immune checkpoint inhibitors. The systematic review was conducted according to the PRISMA guidelines (PROSPERO Registration: CRD42018097247). We searched Medline and Embase for case reports, case series, and observational studies published in journal articles or presented as conference abstracts that describe patients who developed myocarditis after immune checkpoint inhibitor therapy. After a review of 2326 citations, we included 88 cases (53 case reports/series published in journal articles and 35 cases in the observational study). Serum troponin was elevated in 98% of the case reports and 94% of participants in the observational study. ST changes including ST elevation were present in almost a third of case reports. Echocardiography revealed preserved left ventricular ejection fraction in 32% of case reports and 51% of cases in the observational study; however, preserved systolic function did not predict greater survival. Patients who suffered poorer prognosis tended to have major conduction defects or ventricular arrhythmias more frequently than patients who did not. Acute myocardial ischemia was ruled out in all cases (n = 31) when the diagnostic workup included coronary angiography. Immune checkpoint inhibitor-associated myocarditis is characterized by elevation of cardiac troponin levels and non-specific electrocardiographic changes. Early coronary angiography may distinguish it from myocardial ischemia or myocardial infarction. • Largest systematic review of immune checkpoint inhibitor-induced myocarditis cases • Cases show elevated cardiac biomarkers, nonspecific electrocardiographic changes. • Cases with poor prognosis reported conduction defects and arrhythmias. • High negative predictive value of coronary angiography may help in prompt diagnosis. [ABSTRACT FROM AUTHOR]

Myocarditis was discovered as heart disease at autopsy with the use of microscope. In 1900, with the name of acute interstitial myocarditis, Carl Ludwig Alfred Fiedler first reported the history of a sudden cardiac heart failure, in the absence of coronary, valve, pericardial disease or classical specific infections with multiorgan involvement. He postulated a peculiar isolated acute inflammation of the myocardium with poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. Subsequent revision of Fiedler original histologic slides by Schmorl showed cases with either lymphocytic or giant cell infiltrates. The in vivo diagnosis became possible with the right heart catheterism and endomyocardial biopsy. Employment of immunohistochemistry and molecular techniques improved the diagnosis and etiology identification. The mechanism of myocyte injury by coxsackie virus was identified in protease 2A coded by the virus and disrupting the dystrophin in the cytoskeleton. Both RNA and DNA viruses may be cardiotropic, and coxsackie and adenovirus share a common receptor (CAR). Unfortunately, vaccination is not yet available. Cardiac Magnetic Resonance is a revolutionary diagnostic tool by detecting edema, of myocardial inflammation. However endomyocardial biopsy remains the gold standard for etiological and histotype diagnosis, with limited sensitivity due to sampling error. Viral lymphocytic fulminant myocarditis may not be fatal and the employment of mechanical assistant device – ECMO in acute phase for temporary support may be lifesaving with good prognosis. • Myocarditis was discovered as heart disease at autopsy with the use of microscope. • In 1900, Carl Ludwig Alfred Fiedler first reported with the name of acute interstitial myocarditis a sudden heart failure. • Histology, immunohistochemistry and PCR are now considered a gold standard tool for the diagnosis of viral myocarditis. • Cardiac resonance magnetic may be of help in identifying inflammatory edema. [ABSTRACT FROM AUTHOR]

Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare inflammatory diseases of the myocardium with poor prognosis. Little is known about the cardiovascular magnetic resonance (CMR) appearance of GCM and the methods ability to distinguish the two rare entities from one another. We assessed a total of 40 patients with endomyocardial biopsy-proven GCM (n = 14) and CS (n = 26) concerning their clinical and CMR appearance in a blinded manner. Patients with GCM and CS were of similar median age (55 vs 56 years), and a male predominance was observed in both groups. In GCM, median levels of troponin T (313 vs 31 ng/L, p < 0.001), and natriuretic peptides (6560 vs 676 pg/mL, p < 0.001) were higher than in CS, and the clinical outcome worse (p = 0.04). On CMR imaging, the observed alterations of left and right ventricular (LV/RV) dimensions and function were similar. GCM showed multifocal LV late gadolinium enhancement (LGE) with a similar longitudinal, circumferential, and radial distribution as in CS, including suggested signature imaging biomarkers of CS like the "hook sign" (71% vs 77%, p = 0.702). The median LV LGE enhanced volume was 17% and 22% in GCM and CS (p = 0.150), respectively. The number of RV segments with pathologically increased T2 signal and/or LGE were most extensive in GCM. The CMR appearance of both GCM and CS is highly similar, making the differentiation between the two rare entities solely based on CMR challenging. This stands in contrast to the clinical appearance, which seems to be more severe in GCM. • Giant cell myocarditis and cardiac sarcoidosis are rare inflammatory diseases of the myocardium with poor prognosis. • Their CMR appearance is highly similar including the presence of suggested signature imaging biomarkers of cardiac sarcoidosis like the "hook sign". • This overlap in phenotypes makes the differentiation between the two rare entities solely based on CMR challenging and underlines the need for additional imaging and/or endomyocardial biopsy. • This stands in contrast to the clinical appearance, which seems to be more severe in giant cell myocarditis. [ABSTRACT FROM AUTHOR]

Abstract Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disease that causes sudden cardiac death in the young. Inflammatory myocardial infiltrates have been described at autopsy and on biopsy, but there are few data on the presence of myocarditis in living patients with ARVC using non-invasive imaging techniques. FDG-PET is a validated technique for detecting myocardial inflammation in clinically suspected myocarditis. We aimed to determine the prevalence of myocardial inflammation in patients with ARVC using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods and results We performed a retrospective analysis of a single centre cohort of patients with ARVC referred for FDG-PET scans between 2012 and 2017 for investigation of symptoms or suspected device infection. Sixteen patients (12 male; age 42 ± 13 years) with a definite diagnosis of ARVC were identified. Seven had positive FDG-PET scans, two of whom had cardiac sarcoidosis on endomyocardial biopsy. Of the remaining five, two carried pathogenic desmoplakin mutations. FDG uptake was found in the left ventricular myocardium in all cases. One patient also had right ventricular uptake. Conclusion In this exploratory study, we show that some patients with ARVC have evidence for myocardial inflammation on FDG-PET, suggesting that myocarditis plays a role in disease pathogenesis. Highlights • This is the first study to demonstrate the prevalence of FDG-PET imaging findings in ARVC. • This study provides the first in vivo evidence of myocardial inflammation in patients with ARVC using non-invasive imaging. • FDG uptake is usually present in the left ventricle and coincides with the affected areas as demonstrated by LGE uptake on CMR. [ABSTRACT FROM AUTHOR]

Abstract Introduction Myocarditis has been described in association with many systemic immune-mediated diseases (SIDs). However, the role of SIDs in influencing clinical presentation and outcome of patients with a new diagnosis of biopsy-proved myocarditis, has never been investigated so far. Methods We enrolled 25 consecutive cases with biopsy-proved myocarditis in the context of SIDs, and controls with isolated myocarditis, matched 1:1 by age, gender, ethnicity and clinical presentation. All of the patients presented with acute symptoms, normal coronary arteries, and no previous history of myocarditis. Detailed diagnostic workup, including blood exams, echocardiogram, arrhythmia monitoring and cardiac magnetic resonance (CMR) were obtained at baseline and at defined time points, up to 12-month follow-up (FU). Results At presentation, patients with SIDs had more commonly inflammatory biomarkers elevation, signs of associated pericarditis, and replacement fibrosis at histology, as compared to controls (18 vs. 6, 20 vs. 12, and 21 vs. 11, respectively; all p < 0.05). The Lake Louise criteria at CMR were negative in 19 vs. 10 patients with and without underlying SIDs, respectively (p = 0.021). Baseline ECG, in-hospital arrhythmia telemonitoring and echocardiographic findings were not significantly different between groups (all p = n.s.). At 12-month FU, the composite major endpoint of cardiac death, end-stage heart failure or malignant ventricular arrhythmias was significantly more common in cases than in controls (7 vs. 1, respectively, p = 0.049). Conclusion In patients with a new diagnosis of myocarditis, the presence of underlying SIDs is associated with distinct baseline clinical features and a significantly worse 1-year outcome. Highlights • Heart involvement in systemic immune-mediated diseases (SIDs) is a relevant but often neglected clinical issue. • In particular, little is known about baseline manifestations and prognosis of inflammatory heart disease in the context of SIDs. • We present here a prospective study on 25 patients with biopsy-proved myocarditis in the context of SIDs, compared to matched controls with isolated myocarditis. • Interestingly, patients with SIDs had distinct clinical features at onset, and grater occurrence of major and minor events in follow-up. [ABSTRACT FROM AUTHOR]

Abstract Background Myocarditis may be self-limited but has been identified as an important contributor to downstream cardiomyopathy. Aldosterone mediates myocardial damage in various conditions, but has not been considered specifically as a therapeutic target for inflammatory damage in acute myocarditis. We sought to demonstrate local aldosterone synthesis in human myocardium affected by acute myocarditis. Methods We evaluated myocardial samples obtained via endomyocardial biopsy (EMB) for expression of CYP11B2, the final and key enzyme for aldosterone synthesis, from patients with acute myocarditis and from stable heart transplant recipients with no evidence of rejection as negative controls. Excised adrenal glands from patients with aldosterone-secreting adenomas were used as positive controls. An experienced cardiovascular pathologist blinded to clinical information rated CYP11B2 stains as negative, positive, or borderline, also recording location of any CYP11B2-positivity. Results Sixteen patients' EMB samples showing definite acute myocarditis were identified (50% female). CYP11B2 was positive in 13/16 cases (81%), typically showing diffuse intracardiomyocyte cytoplasmic staining, vs. 2/16 borderline stains in transplant controls (p < 0.001 myocarditis vs. negative controls). All 3 adrenalectomy samples stained positive for CYP11B2 (diffuse intracellular staining). Importantly, no myocarditis or transplant patients were on aldosterone antagonist therapy at the time of biopsy. Conclusions In this proof-of-concept study, myocardium from patients with acute myocarditis demonstrates evidence and high prevalence of local aldosterone synthesis by immunohistochemistry that showed high accuracy, specificity, and sensitivity. Aldosterone warrants consideration as a specific target for therapy in patients with myocardial damage due to inflammation towards strategies that reduce downstream complications. Highlights • In-vivo, local production of aldosterone has never been demonstrated in subjects affected by biopsy-proven acute myocarditis. • This work shows for the first time in humans local tissue synthesis of aldosterone in myocarditis not present in controls. • These findings support further studies of aldosterone synthesis as a potential therapeutic target in acute myocarditis. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory heart disease is known to be associated with ventricular arrhythmias (VA) and impaired ventricular function at presentation or during follow-up. We aimed to investigate the need for implanted cardioverter defibrillator (ICD) due to ventricular dysfunction and occurrence of VA during long-term follow-up in patients admitted with suspected myocarditis. Methods Between 2000 and 2016, 191 patients (age 43 ± 13 years, 71% male, mean left ventricular ejection fraction (LVEF) 33 ± 15%) with clinically suspected myocarditis, who underwent endomyocardial biopsies (EMB), were prospectively enrolled and followed up in 6-months-intervals (median follow-up was 83 (49–156) months). The primary endpoint was deterioration of cardiac function (LVEF ≤ 35%) or occurrence of VA leading to ICD implantation. Results According to EMB results, patients were stratified in three diagnostic groups: acute myocarditis (5%), chronic myocarditis (50%) and dilated cardiomyopathy (DCM) (45%). An ICD implantation was performed in 58 patients (30%, n = 38 for primary prevention). Besides LVEF at baseline, chronic myocardial inflammation was the only independent predictor of ICD implantation for primary prevention (hazard ratio 2.48 (95% confidence interval 1.02–5.5); p = 0.045). VA requiring ICD therapy occurred in 29 of 58 patients (50%) after a median of 14 (2–37) months without a significant difference between presence and absence of myocardial inflammation. Conclusions Nearly one third of patients with suspected myocarditis require an ICD due to impaired LVEF or occurrence of VA. Half of these patients experienced VA with adequate ICD therapy. Highlights • About 30% of patients with suspected myocarditis undergoing endomyocardial biopsy receive an ICD during long-term follow. • Patients with biopsy-proven myocardial inflammation are at increased risk to receive an ICD for primary prevention. • Half of all ICD recipients experience ventricular arrhythmias requiring ICD therapy. [ABSTRACT FROM AUTHOR]

Abstract Aim To characterize cases of myocarditis (MC) and pericarditis (PC) recorded in the Vaccine Adverse Event Reporting System (VAERS). Methods Cases were extracted from VAERS (2011–2015) and assessed for causality using standardized WHO algorithm. Disproportionality analysis was performed through reporting odds ratio (ROR) with 95%CI. MEDLINE was also searched. Results In VAERS, 199 cases of MC or PC were collected, among which 149 reported smallpox vaccine. The remaining were: 15 cases in 'YOUNGER GROUP' (YG; <18 years old) and 35 in 'OLDER GROUP' (OG; >18 years old). Main reported vaccines were against Human Papilloma Virus (n = 6) in YG and influenza (n = 16) in OG. Causality always resulted "undeterminate" for YG, whereas either "undetermined" (30 cases) and "correlated" (3 cases) for OG. Statistically significant ROR was found in YG for meningococcal vaccine (ROR = 3.55; 95%CI = 1.23–10.24) and in OG for thyphoid vaccine (11.13; 7.73–16.03), Japanese encephalitis vaccine (8.54; 2.7–27.01), anthrax (25.5; 18.8–34.5), and, as expected, smallpox (71.88; 49.25–104.89). In MEDLINE, 91 articles were found: positive/possible causality was frequently reported. Conclusions MC and PC after immunization appear extremely rare; only in very few cases can a role of vaccine be actually identified. Signals for vaccines against typhus, Japanese encephalitis, anthrax and meningococcus warrant monitoring. Highlights • For both literature and VAERS, myo/pericarditis after immunization are extremely rare. • Cases frequently present abnormalities in ECG and in myocardial necrosis markers. • Chest pain in a recently immunized young is useful for differential diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease with an elusive association with myocardial inflammation. A myocarditis phenotype has been well established without systematic evidence of a viral trigger. We intend to study the relationship between myocardial inflammation detected by Cardiac magnetic resonance (CMR) and ARVC in a paediatric population. Methods Retrospective case series of all patients <18 years admitted to two CMR units for clinical suspicion of myocarditis from March 2012 to June 2017 who had genetic testing for inherited cardiomyopathies including analysis for known ARVC genes. Results Six patients were identified experiencing myocarditis-like episodes with chest pain and troponin elevation. All had CMR evidence of active myocardial inflammation often affecting the left ventricle without identification of an infectious trigger. These episodes were likely exercise-induced in 50% of our patients and were multiple in all but one. Conclusion We provide evidence that ARVC can present as recurrent myocarditis-like episodes with CMR evidence of myocardial inflammation despite absent infectious trigger in children. We believe they represent an active hot phase of the disease and may lead to disease progression. Highlights • Paediatric Patients presenting with clinical and mri evidence of myocarditis may later develop diagnostic criteria for Arrhythmogenic Right Ventricular Cardiomyopathy. • These myocarditis episodes seem to be exercise-induced rather than infectious, are often multiple and may lead to disease progression. • We believe these episodes to be active phases of the disease and part of its natural history. [ABSTRACT FROM AUTHOR]

Abstract Objectives Right ventricular (RV) myocarditis (MY) is unrecognized, and its prevalence is unknown. We evaluated the prevalence of RV involvement in acute MY and its association with cardiac events (cardiac death, cardiac arrest, ventricular assist device, transplantation, and appropriate ICD intervention). Methods We enrolled 151 patients who underwent cardiac magnetic resonance for clinical suspicion of acute MY. The CMR protocol included T2-STIR images for edema detection, post-contrast cine-SSFP for hyperemia detection and late gadolinium enhancement (LGE) images. Results Signs of RV MY were found in 27 patients (17.8%): RV edema at T2-STIR in all of these 27 patients; RV LGE was detected in 11 patients (7.3%). The median RV myocardial segment involved was 2 (1–3). In 13 patients, RV edema was in direct continuity with LV edema of septum and inferior wall or with anterior septum and anterior wall. In 2 patients RV myocarditis was found without any signs of LV involvement. Patients with RV MY had higher RV end-diastolic volume index (p = 0.04) and RV mass index (p = 0.03), and lower RV ejection fraction (p < 0.001) than others. At Kaplan-Meier survival curve patients with RV MY had more cardiac events than those without RV involvement (p = 0.015). RV involvement, anteroseptal LGE and RV LGE were associated with cardiac events. Conclusion RV involvement in acute MY is more frequent than previously hypothesized. RV MY was associated with cardiac events. Highlights • Right ventricular myocarditis at magnetic resonance was in 17.8% of patients myocarditis • Patients with right ventricular myocarditis had worse prognosis than those without. • Right ventricular myocarditis was an independent predictor of worse prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Left Anterior Fascicular Block (LAFB) occurs frequently among the elderly, and have a correlation with coronary artery disease (CAD), yet controversies regarding its clinical significance still remain. Methods We carried on a retrospective study involving 92 LAFB and 478 non-LAFB patients, in which anatomic, clinical and electrocardiographic characteristics were compared. Results LAFB subjects had more pathological CAD (66.3% vs 54.6%, P = 0.039), myocardial infarction (MI) (53.3% vs 37.9%, P = 0.007) and myocarditis (5.4% vs 1.7%, P = 0.043). Among the LAFB group, 58.1% of patients with CAD and 30.2% of patients with MI were clinically misdiagnosed, while 42.9% of patients with MI were clinically missed. Logistic regression showed CAD had no independent relevance with LAFB. LAFB subjects displayed heavier hearts [(451.1 ± 101.3)g vs (407.1 ± 102.3)g, P < 0.001], thicker left ventricular walls [(1.6 ± 0.4)cm vs (1.4 ± 0.3)cm, P = 0.001]. Kaplan-Meier survival analysis indicated significant differences in long-term survival time (χ2 = 12.223, P < 0.001) and cardiac mortality (χ2 = 20.982, P < 0.001) between LAFB and non-LAFB group. Cox multivariate analysis demonstrated LAFB was an independent risk factor of all-cause death (HR = 1.552, 95% CI = 1.208–1.994, P = 0.001) and cardiac death (HR = 2.287, 95% CI = 1.545–3.386, P < 0.001). The major death cause of LAFB was cardiac death (46.7%), including more MI (28.3% vs 13.4%, P = 0.008), myocarditis (4.3% vs 1.0%, P = 0.042) and cardiac rupture (6.7% vs 1.9%, P = 0.022). Conclusions LAFB subjects had more pathological CAD and MI, but LAFB was not an independent relevant factor of CAD. LAFB lowered the accuracy to clinically diagnose CAD. LAFB patients gained heavier hearts, thicker left ventricular walls, and suffered increased risk of death and cardiac death. Highlights • Left anterior fascicular block (LAFB) increased all-cause death and cardiac death. • LAFB was not independently relevant with coronary artery disease (CAD). • LAFB lowered the accuracy to clinically diagnose CAD. • LAFB patients had greater heart mass and more left ventricle hypertrophy. • The CAD, cardiac structure and death cause were determined precisely by autopsy. [ABSTRACT FROM AUTHOR]