Clinical Diagnosis Of Myocarditis Research Articles

Abstract 4140148: Genetic Influence in Patients Transplanted for Myocarditis in the TOPMed-TOPCHeF Cohort of Explanted Hearts

Background: Myocarditis is a leading cause of secondary cardiomyopathy and stems from infection, medications, or immune etiologies. Recent reports identify an overlap between myocarditis and pathogenic / likely pathogenic (P/LP) genetic variants of dilated and arrhythmogenic cardiomyopathies (DCM/ACM). Hypothesis: We hypothesized that myocarditis leading to heart failure and transplantation could be influenced by P/LP mutations for DCM/ACM. Aims: To evaluate the impact of genetics in myocarditis, we investigated a series of patients presenting with symptoms consistent with myocarditis who were found to have P/LP genetic signatures for dilated and arrhythmogenic cardiomyopathies DCM/ACM. Methods: Patients with myocarditis, defined by retrospective clinical diagnosis, were selected from the NHLBI Trans-Omics for Precision Medicine (TOPMed) - Trans-Omics for Precision Medicine for Congestive Heart Failure (TOPCHeF) cohort. After informed consent, patients’ explanted hearts were collected in the University of Colorado Heart Tissue Bank. A total of 837 hearts (697 failing and 140 control hearts) underwent whole genome DNA sequencing (WGS). Results: 11 patients had a diagnosis of myocarditis based on clinical history. None had acute myocarditis at time of transplantation. P/LP variants in DCM/ACM genes were found in 6 patients. The average age at transplantation was 42.8 years for patients with genetic variants and 38.9 without. Demographics are included in table 1. The most common genetic variants were Titin truncations. Full genetic data are included in table 2. Conclusion: 50% of patients undergoing transplantation with a clinical diagnosis of myocarditis in the TOPMed-TOPCHeF population had P/LP variants in DCM/ACM genes. This underscores the importance of genetic testing in patients with a clinical presentation of myocarditis for future management implications.

COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur.

COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur.

Myocarditis following COVID-19 vaccination in adolescents: Cardiac magnetic resonance imaging study.

IntroductionVaccination-associated myocarditis was reported following COVID-19 vaccine initially among persons aged 16 or older and recently among adolescents aged 12–15.ObjectivesTo describe the clinical and cardiac magnetic resonance (CMR) characteristics of adolescents aged 12–15 with myocarditis following the administration of the BNT162b2 mRNA COVID-19 vaccine.MethodsCMR of adolescents (age 12–15) with a clinical diagnosis of myocarditis within 42 days following the first COVID-19 vaccine were analyzed.ResultsA total of 182,605 adolescent were vaccinated, out of which 9 were diagnosed with clinically adjudicated myocarditis while CMR was performed in 5/9 patients (56%). Median age was 15 years (range 13–15), 4/5 (80%) males. All the patients we previously healthy. The ECG upon presentation was abnormal in 3/5 (60%) of patients. All cases were classified as clinically mild and no patient required inotropes or mechanical circulatory support treatment. The median follow-up time, for the 5-included patients, was 206 (IQR 192–229, range 179–233) days. During the follow-up, no re-admissions, deaths, or any other cardiac events have occurred.The median time between the diagnosis to the CMR was 104 days (range 27–149). The median left ventricular ejection fraction was within normal range 65% (range 62–69). Native T1 was available in four patients, the local T1 value was increased in three of them. T2 values were available in two patients and were all within normal range. The median late gadolinium enhancement (LGE) was 2% (range 0–6%) with inferolateral wall being the most common location (3/5). The patterns of the LGE were as following: (i) mid-wall in 3 patients; (ii) epicardial in 1-patient. LGE in the pericardium was present in 2/5 patients with pericardial effusion present in 4/5 patients with a median diameter of 4 mm (range 3–5 mm) at end-systole.ConclusionsCMR findings and clinical course of adolescents with COVID-19 vaccination associated myocarditis, are similar to those of older patients, being relatively mild and potentially implying favorable outcomes.

A Case Series of Myocarditis Following Third (Booster) Dose of COVID-19 Vaccination: Magnetic Resonance Imaging Study.

BackgroundMyocarditis has been reported following the first two doses of Pfizer-BNT162b2 messenger RNA (mRNA) COVID-19 vaccination. Administration of a third dose (booster) of the vaccine was initiated recently in Israel.ObjectiveThe aim of this study was to describe the characteristics of patients referred for cardiac magnetic resonance (CMR) imaging with myocarditis following the booster.MethodsPatients referred for CMR imaging with a clinical diagnosis of myocarditis within 21 days following the booster, between July 13 and November 11, 2021, were analyzed.ResultsOverall, 4 patients were included, 3/4 (75%) were men, and the mean age was 27 ± 10 years. The time from booster administration to the onset of symptoms was 5.75 ± 4.8 days (range 2–14). Obstructive coronary artery disease was excluded in 3 of the patients (75%). CMR was performed 34 ± 15 days (range 8-47 days) following the 3rd vaccination. The mean left ventricular ejection fraction was 61 ± 7% (range 53–71%), and regional wall motion abnormalities were present in one of the patients. Global T1 was increased in one of the patients, while focal T1 values were increased in 3 of the patients. Global T2 was increased in one of the patients, while focal T2 values were increased in all the patients. Global ECV was increased in 3 of the patients, while focal ECV was increased in all the patients. Median late gadolinium enhancement (LGE) was 4 ± 3% (range 1–9%), with the inferolateral segment as the most common location (3 of the 4 patients). All the patients met the Updated Lake Louise Criteria.ConclusionsPatient characteristics and CMR imaging findings of myocarditis following the administration of the booster vaccine are relatively mild and consistent with those observed with the first two doses. Although larger-scale prospective studies are necessary, these initial findings are somewhat reassuring.

Sex differences in incidence, management, and outcomes in adult patients aged over 20 years with clinically diagnosed myocarditis in the last 10 years: data from the MYO‑PL nationwide database.

Comprehensive epidemiological data about the course of myocarditis and sex differ-ences are lacking. We aimed to investigate the current differences in the incidence, clinical characteristics, management, and outcomes of men and women with a clinical diagnosis of myocarditis in Poland in the last 10 years. The nationwide MYO‑PL (Occurrence, Trends, Management, and Outcomes of Patients with Myocarditis in Poland) database identified hospitalization records with a primary diag-nosis of myocarditis following the International Classification of Diseases and Related Health Problems, 10th Revision (ICD‑10), derived from the database of the national health care insurer; ClinicalTrials.gov identifier: NCT04827706. A total of 16 319 patients (4208 [25.8%] women and 12 111 [74.2%] men) aged over 20 years with a hospital‑based clinical diagnosis of myocarditis were included in the study. The women were older than the men (median age, 54 (36-70) and 35 (28-47) years, respectively). The incidence of myocarditis was age-, sex-, and season‑dependent. The incidence rate of myocarditis increased over time only in men. Although women were more symptomatic and demonstrated more comorbidities than men, they were less likely to be admitted to a cardiology ward or undergo diagnostic tests. Regardless of the age and sex, the patients with myocarditis had a poorer prognosis than the general population. The women aged 21-40 years had a poorer prognosis than the men of the same age. The incidence of myocarditis was age-, sex-, and season‑dependent. Significant improve-ment is required in the management of myocarditis, including the initial diagnostic process, as well as short-and long‑term therapy, particularly in women.

Sex Differences in Incidence, Clinical Characteristics and Outcomes in Children and Young Adults Hospitalized for Clinically Suspected Myocarditis in the Last Ten Years-Data from the MYO-PL Nationwide Database.

There is a widespread lack of systematic knowledge about myocarditis in children and young adults in European populations. The MYO-PL nationwide study aimed to evaluate sex differences in the incidence, clinical characteristics, management and outcomes of all young patients with a clinical diagnosis of myocarditis, hospitalized in the last ten years. The study involved data (from the only public healthcare insurer in Poland) of all (n = 3659) patients aged 0–20 years hospitalized for myocarditis in the years 2011–2019. We assessed clinical characteristics, management and five-year outcomes. Males comprised 75.4% of the study population. The standardized incidence rate of myocarditis increased over the last ten years and was, on average, 7.8 and 2.5 (in males and females, respectively). It was the highest (19.5) in males aged 16–20 years. The highest rates of hospital admissions occurred from late autumn to early spring. Most myocarditis-directed diagnostic procedures, including laboratory tests, echocardiography, coronary angiography, cardiac magnetic resonance and endomyocardial biopsy, were performed in a low number of patients, particularly in females. Most patients required rehospitalization for cardiovascular reasons. The results of this large epidemiological study showed an increasing incidence of myocarditis hospitalizations in young patients over last ten years and that it was sex-, age- and season-dependent. Survival in young patients with myocarditis was age- and sex-related and usually it was worse than in the national population. The general management of myocarditis requires significant improvement.

Abstract 12952: Global Longitudinal Strain is Simple, Effective & Sensitive Assessment of Cardiac Chamber Function in Patients With Acute-phase Myocarditis

Introduction: Myocarditis is an inflammatory disease process with growing clinical relevance in the current COVID-19 pandemic. Acute-phase myocarditis is known to result in subclinical changes in left ventricular (LV) function despite normal LV ejection fraction (LVEF), as assessed by myocardial deformation indices. The presence of right ventricular (RV) and left atrial (LA) subclinical dysfunction however has not been well described in current literature. Hypothesis: Myocarditis patients have subclinical impairment of LV, RV and LA function as assessed by global longitudinal strain (GLS) on speckle tracking echocardiography. Methods: Consecutive patients with clinical diagnosis of myocarditis admitted to our institution during 2013-2018 were assessed (n=76). Patients who did not meet appropriate diagnostic criteria (n=14), had impaired LVEF or prior cardiac disease (n=8) or poor transthoracic echocardiogram images (n=14) were excluded from analysis. Clinical and echocardiographic parameters were compared to age- , gender- and risk factor- matched controls. GLS was performed by two independent observers using vendor independent software (TomTec Arena, Germany v4.6). Results: The final cohort consisted 40 patients with myocarditis (age 44.3±16.7, 60% male) and 40 matched controls (44.5±16.6, 60% male). No significant differences in baseline clinical characteristics were observed between groups. No differences in LVEF, indexed LV mass, RV fractional area change, indexed LA volume or TR pressure gradient (p>0.05 for all) were demonstrated between the two groups. Patients with myocarditis had a lower mean LV strain (GLS%: -16.4±2.9 vs -19.7±2.7, p=0.0001), a lower mean RV Free Wall Strain (FWS) (GLS%: -22.1±4.1 vs -26.2±6.9, p=0.03) and a lower mean LA reservoir strain (GLS%: 27.5±4.6 vs. 33.7±6.3, p<0.0001) when compared to controls. Conclusions: Our results demonstrate the presence of significant subclinical global myocardial dysfunction despite normal traditional echocardiographic indices, in patients with acute-phase myocarditis. Routine assessment of GLS may identify such patients for early targeted cardiac therapy.

Myocarditis and arrhythmogenic right ventricular cardiomyopathy: a diagnostic challenge

Abstract Background Current arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnostic criteria are mostly based on ventricle function and dimension. Previous studies have reported a significant overlap between ARVC and chronic myocarditis, at non-invasive assessment. Purpose Tto compare biopsy-proven ARVC and myocarditis patients, in order to identify clinical, imaging and invasive electroanatomic voltage mapping (EVM) differences between the two groups. Methods Patients with borderline diagnosis of ARVC or suspected myocarditis underwent compete assessment with cardiac magnetic resonance (CMR). All patients underwent endomyocardial biopsy (EMB) with targeted tissue sampling guided by EVM. All patients with an histological diagnosis of myocarditis or ARVC were included. Results 83 patients were included, divided into 35 (42.2%) ARVC and 48 (57.8%) myocarditis. Among ARVC patients, 25 (71.4%) had right dominant ARVC, 5 (14.3%) left dominant patter and 5 (14.3%) bi-ventricular involvement. Nine patients (23.1%) with suspected clinic diagnosis of ARVC before EMB, received and histological diagnosis of myocarditis. Two (5.7%) patients with suspected myocarditis were proven to have ARVC. When comparing patients with ARVC and patients with myocarditis, univariate analysis showed that age, sex, family history, arrhythmic disorders at presentation and ECG abnormalities were similar between the two groups (P>0.05 for all the variables). There was also no significant difference with regards to bi-ventricular function and dimension at CMR evaluation. More patients with myocarditis resulted positive at late gadolinium enhancement (LGE) evaluation, although non-significantly (P=0.082). Oedema was more frequently present in patients with myocarditis (P=0.01), while adipose tissue infiltration and segmental wall motion abnormalities were more often observed in patients with ARVC (P=0.002 and P<0.001 respectively). At EVM analysis, a significant greater number of patients had a pathological uni- and bi-polar EVM (P<0.05 in all cases) and the scar-area was greater in patients with ARVC: 18.8 vs 11.0 cmq (P=0.041). Conclusion(s) A significant number of patients who received a clinical diagnosis of Myocarditis or ARVC according to current guidelines, were subsequently reclassified after histological analysis. Patients with ARVC and myocarditis were not distinguishable on the basis of clinical features and ventricular function and dimensions. Conversely, tissue analysis with CMR demonstrated how patient with ARVC had less oedema, more adipose tissue infiltration and had more extensive scar at EVM evaluation. Funding Acknowledgement Type of funding source: None

5035Comparative assessment of diagnostic algorithms of myocardial inflammation by endomyocardial biopsy and tissue mapping by CMR against high-sensitive troponin in viral myocarditis

Abstract Background Myocarditis is defined by inflammatory involvement of the myocardium, either histologically by evidence of myocardial necrosis and cellular infiltration on endomyocardial biopsy (EMB), or non-invasively by presence of myocardial oedema using tissue mapping with cardiovascular magnetic resonance (CMR). Objective: to undertake intra-individual comparisons of EMB vs. CMR diagnostic algorithms of myocardial inflammation, as well as against an independent gold-standard of myocardial injury, high-sensitive troponin (hs-TropT). Methods Prospective multicentre study of consecutive patients (n=109) with clinical diagnosis of myocarditis. EMBs were analysed by 2 reference centres using the ESC diagnostic and their local algorithms. The CMR criteria used sequence-specific cut-offs for native T1 and T2 (standard deviation, SD); myocardial inflammation T1 ≥2SD, T2 ≥2SD and no inflammation: T1 and T2<2SD, with subcategories for acute/high-grade: T1 ≥5SD, T2 ≥2SD; chronic/low-grade: T1 ≥2SD, T2 ≥2SD; healed: T1 <2SD, T2 <2SD but myocardial impairment and non-inflammatory cardiomyopathy: T1 ≥2SD, T2 <2SD. Results The agreement between ESC criteria and CMR criteria (AUC: 0.56, p=0.381) was poor. There was a significant agreement between myocardial injury (hs-TropT ≥13.9 ng/L) and CMR criteria (AUC: 0.84, p<0.001), but not ESC algorithm. hs-TropT levels had significant associations with native T1 and T2 (r=0.37 and 0.35, p<0.001), but not with immunohistochemical inflammatory markers. Viral presence was similarly proportioned between inflammatory/non-inflammatory subjects, irrespective of the algorithm. AUC of CMR and EMB versus hs-TroponinT Conclusions Poor agreement between CMR and EMB-based diagnostic algorithms suggests non-overlapping definitions of myocardial inflammatory involvement. Excellent agreement between CMR algorithm and hs-TropT reiterates its high sensitivity for inflammatory myocardial injury. Acknowledgement/Funding 1. National Institute for Health Research (NIHR) Biomedical Research Centre 2. German Centre for Cardiovascular Research (DZHK)

Utility of cardiac MRI in paediatric myocarditis.

The diagnostic role of cardiac MRI in myocarditis is evolving, however with extremely limited data in paediatrics. The goal of this study was to assess the utility of cardiac MRI in paediatric myocarditis and present a new prognostic score for risk stratification. The present study is a retrospective investigation of children with a clinical diagnosis of myocarditis, including analysis of demographics, clinical presentation, diagnostic studies, including cardiac MRI, and outcomes. A total of 44 patients met the inclusion criteria, of whom 20 had undergone cardiac MRI. Patients who underwent cardiac MRI were older (median 15.6 versus 11.1 years, p=0.004), had a shorter length of hospital stay (median 4.0 versus 12.5 days, p=0.004), had overall less-severe illness at presentation as evidenced by a higher left-ventricular ejection fraction on echocardiography, had lower peak brain-type natriuretic peptide, were less likely to require advanced mechanical support, and were less likely to experience cardiac death or transplant. In patients who had undergone cardiac MRI, the most common findings were increased early gadolinium enhancement (n=9) or late gadolinium enhancement (n=9). Cardiac MRI findings did not predict a worse outcome. Independent predictors of the need for heart-failure medications at 1-year follow-up included inotrope requirement, extracorporeal membrane oxygenator requirement, and antiarrhythmic requirement at presentation (p<0.05). In paediatric myocarditis, cardiac MRI is not used uniformly, has a low yield, and does not predict worse outcomes. Future research should evaluate clinical decision-making and the cost-benefit analysis of cardiac MRI in the diagnosis of paediatric myocarditis.

Native T1 in Discrimination of Acute and Convalescent Stages in Patients With Clinical Diagnosis of Myocarditis: A Proposed Diagnostic Algorithm Using CMR

ObjectivesThis study investigated whether T1 mapping by cardiac magnetic resonance (CMR) reflects the clinical evolution of disease in myocarditis and supports its diagnosis independently of the disease stages. BackgroundAcute viral myocarditis is characterized by a range of intracellular changes due to viral replication and extracellular spill of debris within days of viral infection. Convalescence may be characterized by a chronic low-grade inflammation leading to ventricular remodelling, but also a complete resolution of myocardial changes. MethodsPatients with clinical diagnosis of viral myocarditis (N = 165) underwent routine clinical CMR protocol (1.5- and 3.0-T) for assessment of cardiac function and structure, and tissue characterization with T2-weighted imaging and late gadolinium enhancement. T1 mapping was obtained in a mid-ventricular short-axis slice before and >20 min after administration of 0.2 mmol/kg of gadobutrol. ResultsCompared with control subjects (n = 40), T1 indexes were increased in patients with myocarditis. Patients with acute symptoms (n = 61) had higher values of T1 indexes compared with patients in clinical convalescence (n = 67). Native T1 is an independent discriminator between health and disease, as well as a discriminator between acute and convalescent stage of the disease. Native T1- was superior to T2-weighted imaging and late gadolinium enhancement with high diagnostic accuracy and positive and negative predictive values. Using pre-defined cutoff values for normal ranges, we demonstrated that acute myocarditis can be independently identified by native T1 of >5 SD above the mean of normal range, whereas convalescence is best defined by either abnormal native T1 (>2 SD) or presence of late gadolinium enhancement. We prospectively tested a new diagnostic algorithm in an independent dataset of patients with clinical diagnosis of myocarditis and achieved similar diagnostic performance. ConclusionsThe new diagnostic algorithm using native T1 can reliably discriminate between health and disease and determine the clinical disease stage in patients with a clinical diagnosis of myocarditis.

Etiology, diagnosis, management, and treatment of myocarditis. Position paper from the ESC Working Group on Myocardial and Pericardial Diseases

Despite great advances in the pathophysiology and etiology of myocarditis, the clinical diagnosis of myocarditis in daily clinical practise remains challenging. Often the diagnosis was not clear because of the heterogeneity of clinical symptoms and the lack of guidelines for adequate diagnostic requirements and consecutive treatment options. The European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases established a working group of experts to improve the diagnosis and management of myocarditis and to provide a common consensus statement as a reference for future registries and controlled trials. The goal was to bridge the gap between clinical- and tissue-based diagnosis by formulating a concept concerning essential diagnostics and treatment of these patients that would be accepted across Europe. Only in this manner is it possible to establish a basis for national and international registries and double-blind randomized treatment trials for the etiologically differentiated treatment of myocarditis, which appear promising due to numerous studies in recent years. In this paper, two members from the expert working group summarize the most important aspects of this position paper on the etiology, diagnosis, management, and treatment of myocarditis, which were published in the July 2013 issue of European Heart Joumal.

Diagnostic capability of CMR for the diagnosis of acute myocarditis in young patients is determined by the presence of elevated cardiac enzymes

Summary Only in patients with elevated levels of cardiac troponin CMR can reliably corroborate the clinical diagnosis of acute myocarditis Background Diagnosis of myocarditis remains a difficult clinical challenge, since the clinical spectrum of myocarditis is multifaceted. As clinical presentation and ECG-changes tend to be non-specific, cardiovascular magnetic resonance (CMR) has proven to be av aluable diagnostic tool regarding non-invasive diagnosis of myocarditis. However, CMR studies are time- and cost-intensive. Hence, further parameters are warranted to identify those individuals in whom a CMR study is likely to add crucial information regarding correct and timely diagnosis of acute myocarditis. The current study sought to elucidate the diagnostic yield of CMR in young patients aged ≤ 40 yrs with clinical diagnosis of myocarditis based on symptoms and ECG in relation to the presence or absence of elevated levels of cardiac troponin as an additional marker of acute myocardial injury. Methods Between 2009 and 2011, young patients aged ≤ 40 yrs presenting with acute or subacute chest pain and significant new-onset ST-segment changes suggestive of myocarditis, prospectively underwent CMR studies after obstructive coronary artery disease (CAD) was ruled out by coronary angiography if risk factors were present. Black-blood T2-weighted turbo-spin-echo (TSE) sequences were obtained to detect myocardial edema. Late gadolinium enhancement (LGE) imaging was performed in order to detect focal areas of contrast enhancement. Studies were performed on a 1.5 Tesla MR-Scanner (Siemens Sonata). Results During the recruitment period, 106 consecutive patients aged 17 to 40 yrs were included. Mean age was 29±7 yrs. In 19 patients additional cardiac catheterization was performed in order to definitely rule out obstructive CAD. LGE was successfully performed in all patients while in one patient T2-weighted edema images could not be obtained due to insufficient image quality. 13 (12%) patients showed significantly elevated levels of cardiac troponin. 15 (14%) patients showed focal late gadolinium enhancement (LGE) indicating myocarditis. All patients (100%) who presented with elevated levels of troponin showed presence of focal LGE. T2-weighted edema imaging showed correlating myocardial edema in 7 of these 13 individuals (54%). However, none of the 2 patients demonstrating LGE in the absence of elevated cardiac enzymes had signs of myocardial edema assessed by T2-weighted edema imaging but both turned out to have anamnestic evidence of subsided myocarditis in the past requiring exclusion of “acute” myocarditis. Moreover, the remaining 91 young patients with an unequivocal clinical diagnosis of myocarditis - but normal troponin levels - demonstrated normal findings by both T2-weighted edema and LGE imaging.

Histopathological diagnosis of myocarditis in a dengue outbreak in Sri Lanka, 2009

BackgroundIn 2009, an outbreak of dengue caused high fatality in Sri Lanka. We conducted 5 autopsies of clinically suspected myocarditis cases at the General Hospital, Peradeniya to describe the histopathology of the heart and other organs.MethodsThe diagnosis of dengue was confirmed with specific IgM and IgG ELISA, HAI and RT-PCR techniques. The histology was done in tissue sections stained with hematoxylin and eosin.ResultsOf the 319 cases of dengue fever, 166(52%) had severe infection. Of them, 149 patients (90%) had secondary dengue infection and in 5 patients, DEN-1 was identified as the causative serotype. The clinical diagnosis of myocarditis was considered in 45(27%) patients. The autopsies were done in 5 patients who succumbed to shock (3 females and 2 males) aged 13- 31 years. All had pleural effusions, ascites, bleeding patches in tissue planes and histological evidence of myocarditis. The main histological findings of the heart were interstitial oedema with inflammatory cell infiltration and necrosis of myocardial fibers. One patient had pericarditis. The concurrent pulmonary abnormalities were septal congestion, pulmonary haemorrhage and diffuse alveolar damage; one case showed massive necrosis of liver.ConclusionsThe histology supports occurrence of myocarditis in dengue infection.

Heart and Skeletal Muscle Are Targets of Dengue Virus Infection

Dengue fever is one of the most significant re-emerging tropical diseases, despite our expanding knowledge of the disease, viral tropism is still not known to target heart tissues or muscle. A prospective pediatric clinical cohort of 102 dengue hemorrhagic fever patients from Colombia, South America, was followed for 1 year. Clinical diagnosis of myocarditis was routinely performed. Electrocardiograph and echocardiograph analysis were performed to confirm those cases. Immunohistochemistry for detection of dengue virus and inflammatory markers was performed on autopsied heart tissue. In vitro studies of human striated skeletal fibers (myotubes) infected with dengue virus were used as a model for myocyte infection. Measurements of intracellular Ca2+ concentration as well as immunodetection of dengue virus and inflammation markers in infected myotubes were performed. Eleven children with dengue hemorrhagic fever presented with symptoms of myocarditis. Widespread viral infection of the heart, myocardial endothelium, and cardiomyocytes, accompanied by inflammation was observed in 1 fatal case. Immunofluorescence confocal microscopy showed that myotubes were infected by dengue virus and had increased expression of the inflammatory genes and protein IP-10. The infected myotubes also had increases in intracellular Ca2+ concentration. Vigorous infection of heart tissues in vivo and striated skeletal cells in vitro are demonstrated. Derangements of Ca2+ storage in the infected cells may directly contribute to the presentation of myocarditis in pediatric patients.

Towards understanding the phenotypes of myocardial involvement in the presence of self-limiting and sustained systemic inflammation: a magnetic resonance imaging study

Objective. To investigate the patterns of myocardial involvement in the presence of self-limiting and sustained systemic inflammation, using MRI.Methods. Ninety-four subjects, with a clinical diagnosis of myocarditis (n = 36), RA (n = 24) and apparently healthy subjects (n = 34, control group), underwent standardized cardiac MRI protocol for the assessment of global and regional morphology and systolic function using balanced steady-state free precession sequences, T2-weighted images and late gadolinium enhancement (LGE) studies.Results. The three groups were well matched for age, gender and cardiovascular risk factors. The RA group showed markedly increased end-diastolic volumes and reduced ejection fraction (P < 0.05). Antero/inferolateral wall thickness was greater in the myocarditis group and reduced in RA, associated with reduced radial and longitudinal thickening (P < 0.01), and markedly raised T2-oedema ratio and global LGE scores (P < 0.05).Conclusions. Our results may signify the phenotypic features of myocardial plasticity and deformation in response to self-limiting and sustained inflammatory injury.

Myocarditis exacerbation in a child undergoing inguinal hernioplasty after viral infection

Immunosuppressive effects of general anaesthesia and surgery could have unexpected consequences in a child with recent infection. The incidence of myocarditis in childhood is unknown. During general anaesthesia for inguinal hernia repair, a seven-year-old boy suddenly developed heart failure. Clinical presentation included hypotension, pulmonary oedema, drop in haemoglobin oxygen saturation, ST segment elevation and premature ventricular contractions. Haemodynamic stability and adequate oxygenation were achieved with dopamine and furosemide. Preoperative history, physical examination and complete blood count were unremarkable. Moderate cardiomegaly and pulmonary oedema were present on chest radiography. Diminished left ventricular contractility found on echocardiography increased troponin I and CK-MB levels suggested myocardial injury. Increased C-reactive protein with lymphocytosis suggested inflammation as its cause. Parents failed to report rubella 10 days before the operation. A clinical diagnosis of myocarditis as a complication of rubella was based on increased titer of IgM to rubella. With intravenous immunoglobulin, corticosteroids and symptomatic treatment for heart failure, his condition improved and ejection fraction reached 68% one month after operation. In future, we need protocols with instructions for paediatric patients undergoing elective surgery and anaesthesia after viral infections.

Gated myocardial perfusion scintigraphy in children with myocarditis: can it be considered as an indicator of clinical outcome?

Myocarditis is an inflammation of the heart muscle and represents a challenge for diagnosis and treatment. On account of the lack of sensitivity and specificity of routine cardiac tests, there is a need for accurate diagnostic imaging. The aim of this study is to review the role of gated 99Tc-methoxyisobutylisonitrile myocardial perfusion scintigraphy (G-MPS) in the diagnosis and follow-up of the patients with myocarditis in comparison with gallium scintigraphy. Thirteen patients with a clinical diagnosis of myocarditis were included in the study. All underwent rest G-MPS and the images were then evaluated by quantitative perfusion single-photon emission computed tomography and quantitative gated single photon emission computed tomography software program. Visual evaluation of perfusion was performed as well as analysis of motion with thickening function [expressed as summed rest score, summed motion score, and summed thickening score (STS)] with calculation of ejection fraction (EF) and lung-to-heart (L/H) ratio. Eight patients underwent 67Ga scintigraphy. Clinical, echocardiography, and cardiac enzymes (creatinine kinase-MB, myoglobulin, troponin T, brain natriuretic peptide) data were gathered from the patients' charts. Clinical outcome was grouped according to prognosis. Spearman's correlation (SC) test was used for comparison analysis. Myocardial perfusion defects were observed in eight patients. Perfusion defects in the left ventricle involve a mean of 7.25% (range: 1-11%), whereas wall motion abnormality on G-MPS was more prominent, which showed to be a better marker for myocardial inflammation and necrosis. The 67Ga scintigraphy findings were normal in all, but two. The G-MPS EF (33+/-21%) was slightly lower than the echocardiography EF (40+/-15%), but with close correlation (SC coefficient: 0.635). Comparison of scintigraphic findings with clinical parameters showed that summed motion score with G-MPS EF and STS with L/H ratios were highly correlated (0.932 and 0.622, respectively). The maximum brain natriuretic peptide and L/H ratio with STS were highly correlated with the patients' outcomes (SC coefficient: -0.621, 0.821, and 0.579, respectively), as well. Tc-methoxyisobutylisonitrile G-MPS is therefore helpful in providing additional diagnostic and prognostic information in patients with myocarditis.

Myocarditis

Myocarditis is clinically and pathologically defined as “inflammation of the myocardium.” Despite its rather clear-cut definition, the classification, diagnosis, and treatment of myocarditis continue to prompt considerable debate. The more routine use of endomyocardial biopsy has helped to better define the natural history of human myocarditis and to clarify clinicopathological correlations. Clinical presentations of the disease range from nonspecific systemic symptoms (fever, myalgias, palpitations, or exertional dyspnea) to fulminant hemodynamic collapse and sudden death. The extreme diversity of clinical manifestations has made the true incidence of myocarditis difficult to determine. Recent prospective postmortem data have implicated myocarditis in sudden cardiac death of young adults at rates of 8.6% to 12%.1,2 Furthermore, it has been identified as a cause of dilated cardiomyopathy in 9% of cases in a large prospective series.3 Recent molecular techniques have facilitated new insights into inflammatory autoimmune processes that affect the myocardium and ultimately result in acute or chronic dilated cardiomyopathy. Despite the well-established morbidity and mortality associated with myocarditis,4–7 clinical practice guidelines with regard to its evaluation and treatment are lacking.8 The wide variety of etiologies implicated in myocarditis and its heterogeneous clinical presentations5,7,9 have impeded patient identification and consensus on the most appropriate diagnostic criteria. The Dallas pathological criteria, published in 1986, served as the first attempt to develop standardized diagnostic guidelines for the histopathological classification of myocarditis.10 Active myocarditis is characterized by an inflammatory cellular infiltrate with evidence of myocyte necrosis (Figure 1), whereas borderline myocarditis demonstrates an inflammatory cellular infiltrate without evidence of myocyte injury (Figure 2). The inflammatory infiltrate should be further described as lymphocytic, eosinophilic, or granulomatous (Figure 3). The amount of inflammation may be mild, moderate, or severe, and its distribution may be focal, confluent, or diffuse, respectively. A retrospective study of 112 consecutive …

The incidence of myocarditis in endomyocardial biopsy samples from patients with congestive heart failure

We present the combined experience of three Yugosiavian cardiovascular centers in the application of endomyocardial biopsy for the diagnosis of myocarditis in patients who present clinically with congestive heart failure. The study group comprised 107 patients (mean age, 40.8 years; range, 19 to 61 years). On the basis of patient history and diagnostic tests, the following clinical diagnoses were established: dilated cardiomyopathy (85), myocarditis (16), and alcohol-induced heart disease (6). EMB samples were taken from the left ventricle (95) or both ventricles (12) by use of a King's College bioptome, with a mean of 3.2 samples per patient. Histologic evidence of myocarditis was noted in 10 of 85 patients (12%) with a clinical diagnosis of dilated cardiomyopathy, in 2 of 6 patients (33%) with alcohol-induced heart disease, and in 12 of 16 patients (75%) with a clinical diagnosis of myocarditis. There was confirmation of the clinically suspected diagnosis in 63% of cases, a change of diagnosis based on histology in 15% of cases, and nonspecific findings in 22%. However, useful information was obtained in 78% of the cases, and there was a 22% incidence of histologically proven myocarditis for the entire group. Our results indicate that endomyocardial biopsy is beneficial in determining the true incidence of myocarditis in patients with a clinical presentation of dilated cardiomyopathy.