Hypereosinophilia and Left Ventricular Thrombus: A Case Report and Literature Review.

Left ventricular thrombus (LVT) has historically been reported as a complication of acute left ventricular (LV) myocardial infarction. It is most commonly observed in cases of LV systolic dysfunction attributed to ischemic or nonischemic etiologies. Conversely, the occurrence of LVT in normal LV systolic function is an exceptionally rare presentation and is predominantly associated with conditions such as hypereosinophilic syndrome (HES), cardiac amyloidosis, left ventricular noncompaction, hypertrophic cardiomyopathy (HCM), hypercoagulability states, immune-mediated disorders, and malignancies. Notably, hypereosinophilia (HE) has been linked with thrombotic events. Intracardiac thrombus is a well-known complication of eosinophilic myocarditis (EM) or Loeffler endomyocarditis, both of which are considered clinical manifestations of HES. We present a case of a 63-year-old male with normal LV systolic function, HE, and noncontributory hypercoagulability workup, who presented with thromboembolic complications arising from LVT. Interestingly, the diagnostic evaluation for EM and Loeffler endocarditis was nonconfirmatory. Additionally, we performed a literature review to delineate all similar cases. This article also outlines the pathophysiology, diagnosis, and treatment approaches for hypereosinophilic cardiac involvement with a specific focus on LVT.

'Hot phase' non-dilated left ventricular cardiomyopathy with atypical onset and recurrence: a case report.

Non-dilated left ventricular cardiomyopathy (NDLVC) is a newly categorized cardiomyopathy phenotype includingseveral aetiologies with a linking characteristic represented by the normal left ventricular volume. Inflammatory heart disease (InHD) is a heterogeneous process with variegate clinical manifestations, sometimes in overlap with NDLVC. A 26-year-old woman was admitted forcomplete heart block (CHB) and persistently raised troponin. Echocardiography and coronary angiography were normal. Extensive oedema and late gadolinium enhancement was found at cardiac magnetic resonance. Endomyocardial biopsy showed no signs of active myocarditis. Steroid therapy was started with restoration of atrioventricular conduction but subsequently the patient experienced a mild recurrence with a new troponin relapse. Genetic test was negative for mutations related with the clinical scenario. In this case of NDLVC with InHD the precise diagnostic work-up, including genetic test, was crucial for diagnostic, prognostic andtherapeutic purposes. Multimodality approach is crucial to detect and treat possible recurrences.

Severe Mitral Valve Regurgitation Secondary to Fulminant Myocarditis in the Setting of a Lupus Flare.

Systemic Lupus Erythematosus represents a chronic autoimmune disorder characterized by multiorgan involvement. Lupus myocarditis is a rare presentation of one of the cardiac complications of lupus with an incidence of 3-9%. It usually presents with non-specific symptoms such as dyspnea, orthopnea, chest pain, pedal edema, fever, diaphoresis, paroxysmal nocturnal dyspnea, nausea, vomiting, or palpitations. Even though endomyocardial biopsy is considered the gold standard diagnostic approach, other non-invasive diagnostic alternatives including cardiac magnetic resonance (CMR) have been studied. Therapeutic interventions may range from high-dose steroids, and IVIG, to the most advanced strategies such as mechanical circulatory support including VenoArterial Extracorporeal Membrane Oxygenation (VA-ECMO), and Impella, among others.

Cardiac magnetic resonance in a rare case of recurrent mesalazine-induced myocarditis.

Mesalazine represents a key treatment for intestinal bowel diseases and only in rare cases produces cardiac toxicity, with a not completely known mechanism. We report a case of a 25-year-old man with a first episode of myocarditis after 2 weeks from the first mesalazine intake, documented also by a characteristic cardiac magnetic resonance pattern. Then, after less than 1 month, he suffered myocarditis recurrence and so, guided by a multidisciplinary team evaluation, in the suspicion of mesalazine-induced myocarditis, the drug was promptly stopped, with consequent recovery of cardiac damage. In our patient, the recurrence of myocarditis because of the non-interruption of the drug is very peculiar (only three cases described in literature) and definitively confirms the diagnosis.

This paper reports an exemplary case of cardiac toxicity induced by mesalazine, a key treatment for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. In rare cases, this drug can lead to cardiac impairment, with a mechanism not yet clarified. The young patient described experiencing a first episode of myocarditis (inflammation of the heart muscle cells) after 2 weeks of starting mesalazine. The diagnosis was possible thanks to cardiac magnetic resonance, a noninvasive exam providing high-definition images associated with tissue characterization. Mesalazine was not discontinued because drug-induced etiology was not suspected, due to its rarity. Consequently, the patient suffered a second episode of myocarditis, diagnosed by endomyocardial biopsy, an invasive technique that can accurately assess the etiology of myocardial damage, leading to prompt cessation of treatment. Since myocarditis can have various causes, diagnosis was also facilitated through a multidisciplinary team, which ruled out other possible causes for this condition. This case report is highly educational and underscores the importance of clinicians being vigilant about this side effect and considering it in patients taking mesalazine who present with myocarditis, to promptly discontinue the treatment. Mesalazine interruption is otherwise the only effective therapy for this condition, in addition to anti-inflammatory and analgesic drugs. Furthermore, this paper highlights the increasing importance of multidisciplinary teams, comprising various specialists, for accurate diagnosis and therapeutic decisions. The authors also propose an algorithm for diagnosing mesalazine-induced myocarditis, with certainty derived from recurrence after drug rechallenge, either voluntarily or accidentally, as demonstrated in this case.

A challenging case of eosinophilic myocarditis leading to heart failure and transplantation.

The large spectrum of etiologies, severities, and histologic appearances of eosinophilic myocarditis (EoM) poses challenges to its diagnosis and management. Endomyocardial biopsy is the current gold standard for diagnosis. However, cardiovascular magnetic resonance imaging is becoming more frequently used to diagnose acute myocarditis because of enhanced sensitivity when compared to histopathologic examination, and its less invasive nature. We report a complicated case of EoM in a male in his mid-thirties that led to fulminant cardiogenic shock that required immunosuppressive therapy on day 5 of admission and implantation of a left ventricular assist device (LVAD) on day 30. EoM was diagnosed on histopathologic examination of the resected fragment of the left ventricular myocardium. Nine months after the initial presentation, the patient ultimately required heart transplantation. The explanted heart showed minimal residual interstitial inflammation with evidence of mildly active intimal arteritis and patchy areas of interstitial fibrosis. In this report, we describe our patient's clinical features and correlate them with imaging and histopathologic findings to illustrate the difficulty in diagnosing EoM, particularly in this complicated patient that ultimately required heart transplantation. The diagnosis can be challenging due to the variable histopathologic features, clinical presentation, and utilization of therapeutic medications and devices.

Are Endomyocardial Ventricular Biopsies Useful for Assessing Myocardial Fibrosis?

Myocardial fibrosis is an important factor in the progression of cardiovascular diseases. However, there is still no universal lifetime method of myocardial fibrosis assessment that has a high prognostic significance. The aim of the study was to determine the significance of ventricular endomyocardial biopsies for the assessment of myocardial fibrosis and to identify the severity of myocardial fibrosis in different cardiovascular diseases. Material and Methods: Endomyocardial biopsies (EMBs) of 20 patients with chronic lymphocytic myocarditis (CM), endomyocardial fragments obtained during septal reduction of 21 patients with hypertrophic cardiomyopathy (HCM), and 36 patients with a long history of hypertensive and ischemic heart disease (HHD + IHD) were included in the study. The control group was formed from EMBs taken on 12-14 days after heart transplantation (n = 28). Also, for one patient without clinical and morphological data for cardiovascular pathology, postmortem myocardial fragments were taken from typical EMB and septal reduction sites. The relative area of fibrosis was calculated as the ratio of the total area of collagen fibers to the area of the whole biopsy. Endocardium and subendocardial fibrosis were not included in the total biopsy area. Results: The relative fibrosis area in the EMBs in the CM patient group was 5.6 [3.3; 12.6]%, 11.1 [6.6; 15.9]% in the HHD + IHD patient group, 13.4 [8.8; 16.7]% in the HCM patient group, and 2.7 [1.5; 4.6]% in the control group. When comparing the fibrosis area of the CM patients in repeat EMBs, it was found that the fibrosis area in the first EMBs was 7.6 [4.8; 12.0]%, and in repeat EMBs, it was 5.3 [3.2; 7.6]%. No statistically significant differences were found between the primary and repeat EMBs (p = 0.15). In ROC analysis, the area of fibrosis in the myocardium of 1.1% (or lower than one) was found to be highly specific for the control group of patients compared to the study patients. Conclusions: EMB in the assessment of myocardial fibrosis has a questionable role because of the heterogeneity of fibrotic changes in the myocardium.

Epstein-Barr Virus Lytic Transcripts Correlate with the Degree of Myocardial Inflammation in Heart Failure Patients.

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected. EBV-specific transcripts from EMBs were enriched using a custom hybridization capture-based workflow and, subsequently, sequenced by NGS. The short-read sequencing revealed the presence of EBV-specific transcripts in 17 patients, of which 11 had only latent EBV genes and 6 presented with lytic transcription. The immunohistochemical staining for CD3+ T lymphocytes showed a significant increase in the degree of myocardial inflammation in the presence of EBV lytic transcripts, suggesting a possible influence on the clinical course. These results imply the important role of EBV lytic transcripts in the pathogenesis of inflammatory heart disease and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for specific treatment.

Diagnosis and treatment of myocarditis and inflammatory cardiomyopathy. Consensus document of the SEC-Working Group on Myocarditis.

Myocarditis is defined as myocardial inflammation and its etiology is highly diverse, including infectious agents, drugs, and autoimmune diseases. The clinical presentation also varies widely, extending beyond the classic clinical picture of acute chest pain, and includes cases of cardiomyopathy of unknown cause whose etiology may be inflammatory. Because certain patients may benefit from targeted treatments, the search for the etiology should begin when myocarditis is first suspected. There remain several areas of uncertainty in the diagnosis and treatment of this disease. Consequently, this consensus document aims to provide clear recommendations for its diagnosis and treatment. Hence, a diagnostic algorithm is proposed, specifying when non-invasive diagnosis with cardiac MR is appropriate vs a noninvasive approach with endomyocardial biopsy. In addition, more novel aspects are discussed, such as when to suspect an underlying genetic etiology. The recommendations cover the management of myocarditis and inflammatory cardiomyopathy, both for general complications and specific clinical entities.

Cardiac Sarcoidosis Presenting as Sustained Ventricular Tachycardia.

Introduction: Sarcoidosis has many possible clinical presentations since it can affect any organ, most commonly the lungs. The hallmark of the disease consists of the formation of non-necrotising granulomas. Pathogenesis is thought to rely on the interplay of genetic, environmental and epigenetic factors. This case highlights the importance of a thorough clinical history and physical examination, and the correlation with imaging findings in the diagnostic work-up of the non-ischaemic cardiomyopathy. Case description: A 57-year-old woman was admitted due to the sudden onset of malaise, dizziness, and chest discomfort. Sustained monomorphic ventricular tachycardia was evidenced and the patient rapidly evolved with haemodynamic instability; she underwent successful electrical cardioversion. The electrocardiogram afterwards showed a high-risk electrocardiographic pattern. Invasive coronary angiography excluded obstructive epicardial coronary lesions. Physical examination revealed skin lesions on the lower limbs which raised suspicion for erythema nodosum and therefore a biopsy was performed. Transthoracic echocardiography and cardiac magnetic resonance imaging revealed features consistent with an inflammatory cardiomyopathy, and an implantable cardioverter-defibrillator was placed. The histologic examination of the cutaneous lesions showed a non-necrotising granulomatous inflammatory process. Radionuclide imaging was inconclusive. The patient underwent an endomyocardial biopsy, which confirmed the diagnosis of systemic sarcoidosis with cardiac involvement. Conclusions: Systemic sarcoidosis with cardiac involvement is a challenging diagnosis. The role of imaging techniques such as transthoracic echocardiography, cardiac magnetic resonance imaging and radionuclide imaging is essential in raising suspicion and diagnosing this pathology. Endomyocardial biopsy is the 'gold standard' for its diagnosis; however, it has a low diagnostic yield. LEARNING POINTS: Systemic sarcoidosis with cardiac involvement is a challenging diagnosis as it may present in many different ways.The case presented highlights the importance of a thorough clinical history and physical examination, and the correlation with imaging findings.Imaging techniques such as transthoracic echocardiogram, cardiac magnetic resonance and radionuclide imaging are essential in raising suspicion and diagnosing cardiac sarcoidosis.

The Masquerading Myocarditis: A Case of Late Recurrence of Acute Myocarditis Presenting as "Peripartum Cardiomyopathy".

Myocarditis is a potentially fatal medical condition with varied etiologies. Peripartum cardiomyopathy (PPCM) refers to systolic dysfunction occurring toward the end of pregnancy or in the months following delivery; it is a diagnosis of exclusion. We present a patient with chest pain, bipedal edema, markedly elevated troponins, electrocardiogram (EKG) findings that were concerning for myocardial infarction, and a significantly reduced left ventricular ejection fraction (LVEF) on the echocardiogram. The patient's presentation in the postpartum period closely resembled peripartum cardiomyopathy and presented a peculiar diagnostic challenge to our team. The right diagnosis was possible with cardiac magnetic resonance imaging, which revealed late gadolinium enhancement. Additionally, the patient had positive Coxsackie B5 and Epstein Bar virus serologies. While the clinical course of the disease is often benign, it could rapidly deteriorate, so early recognition and diagnosis are important to ensure patients receive adequate therapeutic support.

Lymphomonocytic inflammatory infiltrate with numerous eosinophilic granulocytes in the interstitium in a surviving heart transplant recipient: a case report.

Findings of eosinophilic and lymphomonocytic inflammatory infiltrates in endomyocardial biopsies (EMBs) may help in myocardial disease diagnosis identification. Eosinophilic myocarditis (EM), a rare condition, is fatal if left untreated and has rarely been described in heart transplant recipients. An extensive work up is necessary to achieve an early etiological diagnosis; however, the underlying cause remains unexplained in nearly one-third of the patients. The cornerstone of treatment is corticosteroids, comprehensive therapy and heart failure management (including advanced mechanical support for fulminant myocarditis). We have described the case of a 17-year-old heart transplant recipient who presented with a cardiogenic shock. He was admitted to our intensive care unit and treated with inotropic drugs, such as milrinone, adrenaline, vasopressin, and levosimendan; the doses of these drugs were in accordance with our internal protocol. The patient underwent cardiac catheterization, coronarography, and right ventricular EMB. EMB revealed inflammatory lymphomonocytic and eosinophil granulocyte infiltrates; thus, steroid therapy was initiated, with complete recovery achieved after 15 days. Performing an early differential diagnosis among eosinophilic infiltration, acute cellular rejection (ACR), and possible chemotherapeutic damage is emerging as an important challenge. To our knowledge, this is the first reported case of a lymphomonocytic inflammatory infiltration with numerous eosinophilic granulocytes in the interstitium in a surviving heart transplant recipient.

COVID-19 mRNA Vaccination-Induced Myopericarditis in an Otherwise Healthy Young Male: An Evidence-Based Approach to Differentiating From Perimyocarditis.

A 29-year-old male, otherwise healthy with no past medical history, presented to the hospital after a two-day history of pleuritic chest pain with a fever. He had received his first dose of the mRNA-1273 coronavirus disease (COVID-19) vaccine (Moderna) two months prior without any adverse reactions. He received his second dose approximately 24 hours before symptom onset and hospital presentation. Work-up was unremarkable for respiratory, autoimmune, and rheumatological etiologies. The patient was found to have electrocardiogram features and symptoms in keeping with pericarditis, C-reactive protein elevation, and a peak high-sensitivity troponin level of 9,992 ng/L suggestive of a component of myocarditis. A dilemma arose regarding whether this patient should be diagnosed with perimyocarditis or myopericarditis, terms often used interchangeably without proper reference to the primary pathology, which can ultimately affect management. A subsequent echocardiogram was unremarkable, with a normal left ventricular systolic function, but cardiac resonance imaging revealed myocardial edema suggestive of myocarditis. Without convincing evidence for an alternative explanation after an extensive work-up of ischemic, autoimmune, rheumatological, and infectious etiologies, this patient was diagnosed with COVID-19 mRNA vaccine-induced myopericarditis. The patient fully recovered after receiving a treatment course of ibuprofen and colchicine. This case explores how the diagnosis of COVID-19 vaccine-induced myopericarditis was made and treated using an evidence-based approach, highlighting its differentiation from perimyocarditis.

Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study.

AIMS: Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS: Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS: Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Ten-Year Experience with Endomyocardial Biopsy after Orthotopic Heart Transplantation: Comparison between Trans-Jugular and Trans-Femoral Approach.

BACKGROUND: Endomyocardial biopsy (EMB) is considered the gold standard for monitoring allograft rejection after heart transplantation. EMB is an invasive procedure that may be performed via a trans-jugular or a trans-femoral approach with a complication rate reported as less than 6%. The aim of this study was to evaluate the complication rate after EMBs in heart recipients and to compare the results of EMBs performed via a trans-jugular or a trans-femoral approach. METHODS: Medical records of heart recipients undergoing EMBs between January 2012 and December 2022 were retrospectively reviewed. EMB-related complications were classified as major (death, pericardial effusion, hemopericardium, cardiac tamponade requiring a pericardiocentesis or an urgent cardiac surgery, ventricular arrythmias, permanent atrio-ventricular block requiring permanent pacing, hemothorax, pneumothorax and retroperitoneal bleeding) and minor (de novo tricuspid regurgitation, arrhythmias, coronary artery fistula, vascular access site complications). RESULTS: A total of 1698 EMBs were performed during the study period at our institution in 212 heart recipients. There were 927 (55%) EMBs performed through a trans-jugular approach (TJ group) and 771 (45%) EMBs performed through a trans-femoral approach (TF group). A total of 60 (3.5%) complications were recorded, including nine (0.5%) major complications (six cardiac tamponades, two pneumothorax and one retroperitoneal bleeding) and 51 (3%) minor complications (seven coronary fistulae, five de novo tricuspid regurgitation, four supraventricular arrythmias and thirty-five vascular access site complications). No difference was found in total (38 [4%] vs. 22 [3%]; p = 0.16) and major (6 [1%} vs. 3 [0.4%]; p = 0.65) complications (32 [3%] vs. 19 [2%]; p = 0.23) between the TJ group and the TF group. No difference was found in male sex, age at time of EMB and time from HT between complicated and not complicated EMBs. CONCLUSIONS: EMBs represent a safe procedure with a low risk of complications. In our experience, EMBs performed via a trans-jugular approach are as safe as the trans-femoral approach.

Storytelling of Myocarditis.

In 1900, Fiedler first reported autopsy cases with peculiar inflammation of the myocardium, which he named interstitial myocarditis. He postulated an isolated cardiac inflammation of the myocardium in the absence of multiorgan involvement and with a poor prognosis due to invisible microorganisms, which years later would have been identified as viruses. The revision of original histologic sections by Schmorl showed cases with lymphocytes and others with giant-cell inflammatory histotypes. The in vivo diagnosis of myocarditis became possible thanks to right cardiac catheterization with endomyocardial biopsy (EMB). The gold standard for diagnosis was achieved with the employment of immunohistochemistry and molecular investigation by Polymerase Chain Reaction (PCR), which allows for the detection of viruses as causal agents. Both RNA and DNA were revealed to be cardiotropic, with a common receptor (CAR). A protease, coded by coxsackie virus, disrupts the cytoskeleton and accounts for cell death. Unfortunately, vaccination, despite having been revealed to be effective in animal experiments, has not yet entered the clinical field for prevention. Cardiac Magnetic Resonance turned out to be a revolutionary tool for in vivo diagnosis through the detection of edema (inflammatory exudate). Myocarditis may be fulminant in terms of clinical presentation but not necessarily fatal. The application of ExtraCorporeal Membrane Oxygenation (ECMO) allows for relieving the overloaded native heart.

CMR Predictors of Favorable Outcome in Myocarditis: A Single-Center Experience.

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts.

Case report: acute myocarditis complicated with persistent complete heart block: a clinical dilemma when myocardial inflammation remains.

Background: Atrioventricular conduction abnormalities due to acute myocarditis are typically transient and do not require ventricular pacing beyond the acute phase of myocardial inflammation. Notwithstanding, selective injury and necrosis of the heart's conduction system may lead to persistent complete heart block (CHB) requiring device implantation. Case summary: We report the case of a 23-year-old man with acute lymphocytic myocarditis complicated by cardiogenic shock, cardiac arrest due to ventricular fibrillation, and persistent CHB. Endomyocardial biopsy (EMB) showed signs of subacute myocarditis, with no evidence of granulomas or giant cells, nor criteria for eosinophilic myocarditis. Aetiological work-up found serological evidence of previous Epstein-Barr virus (EBV) infection; Borrelia burgdorferi serology for Lyme disease was negative. The real time-polymerase chain reaction (RT-PCR) of the EMB was positive for the presence of EBV DNA, but in situ hybridization for viral ribosomal RNA (rRNA) was negative. The patient progressed favourably, and left ventricle ejection fraction recovered 2 weeks after initial presentation. However, CHB persisted for more than 3 weeks, and the patient underwent definitive pacemaker implantation with left bundle branch pacing. Discussion: Persistent CHB after acute myocarditis is generally considered unlikely, but in rare circumstances the damage portended by inflammation may be irreversible. Besides the play of chance, possible mechanisms behind the apparent predilection for the conduction system of the myocardium warrant further research.