Myocarditis Patients Research Articles

34 Eosinophilic myocarditis in patients on dobutamine therapy: an underappreciated and not uncommon phenomenon

Background The phenomenon of eosinophilic myocarditis in explanted hearts was first reported in a series in 1991. The phenomenon remains under-recognised and the incidence uncertain, current published estimates ranging widely from 7 to 22%. Aims We sought to ascertain the incidence of eosinophilic myocarditis in our transplant centre and to assess if presence of an eosinophilic infiltrate was associated with dobutamine therapy prior to explant. Methods 76 sequential heart transplant recipients over a 9 year period were included. Clinical records were examined to detail any exposure to inotropic support prior to transplantation as well as presence or absence of peripheral blood eosinophilia. Pathology reports of explanted hearts as well as any pre-transplant endomyocardial biopsies were reviewed and the presence or absence of eosinophils on histology was documented. Results 28 patients (36.8%) of the group received dobutamine therapy prior to transplantation. Of these, 7 patients (25% of those receiving dobutamine, 9.2% of the total cohort) were found to have evidence of an eosinophilic infiltrate on myocardial histology (6 on explant, 1 on pre-transplant endomyocardia biopsy). All 7 patients had prolonged exposure to dobutamine prior to diagnosis of eosinophilic myocarditis. The duration of inotropic support ranged from 1 to 19 weeks; and the final maintenance dose of dobutamine ranged from 2.5 to 12.5 mcg/kg/min. One patient had a significant persistent peripheral blood eosinophilia for the duration of dobutamine therapy, 1.22 × 10 9 /L at peak (normal range 0.04 0.4 × 10 9 /L). A further 5 patients had short-lived ( 9 /L) in peripheral eosinophil count. Eosinophil count in these cases returned to normal without change in dobutamine dose or discontinuation. The patient with eosinophil infiltration on pre-transplant biopsy had dobutamine discontinued and histology of the explanted heart revealed complete resolution of the myocarditis. No eosinophilic infiltrates were identified in dobutamine-nave explants in the cohort, including 22 patients on prolonged therapy with intravenous milrinone. Conclusions One in four patients exposed to prolonged dobutamine therapy in this series developed eosinophilic myocarditis. Additionally, complete resolution of eosinophilic myocarditis after discontinuation of dobutamine was detailed in vivo in one case. The clinical impact of this process in a heart failure cohort is not clearly understood. Specific attention may need to be paid to peripheral blood eosinophil count in patients requiring prolonged inotropic support.

Eosinophils and IL-4 are essential drivers of inflammatory dilated cardiomyopathy (BA7P.160)

Abstract Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults, and patients often require a heart transplant. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. In wildtype (WT) BALB/cJ mice, experimental autoimmune myocarditis (EAM) progresses to DCMi with heart failure. Surprisingly, eosinophil-deficient ΔGATA1 mice developed myocarditis similar to WT mice, but were completely protected from DCMi. This indicates that eosinophils are crucial for progression of myocarditis to DCMi. Moreover, the level of eosinophilia correlated with DCMi severity. We used two models of eosinophilic myocarditis: mice expressing IL-5 under the CD3 promoter and IFNγ-IL-17A-double knockout mice. Both strains developed massive eosinophil infiltration in the heart and even more severe DCMi than WT mice. Recently, eosinophils were shown to affect several physiological processes through their production of IL-4. We therefore assessed IL-4 producing cell types in myocarditis using IL-4 reporter mice. Indeed, eosinophils were the major IL-4 expressing cell type in EAM. Additionally, IL-4-deficient mice developed myocarditis but were completely protected from DCMi, matching the phenotype of ΔGATA1 mice. In conclusion, eosinophils are required for progression of myocarditis to DCMi, drive severe DCMi when present in large numbers, and likely mediate this process through IL-4.

Cardiovascular magnetic resonance feature tracking in patients with acute myocarditis and normal ejection fraction: potential for improved diagnosis and prognosis

Background Myocarditis is the most common finding in patients presenting with chest pain, ECG changes, raised troponin and culprit-free coronary angiograms. Adverse events, such as arrhythmias, heart failure and death can occur in the absence of significant left ventricular (LV) impairment and myocarditis should not be considered benign when systolic function is normal at presentation. We currently do not know how to predict which patients will deteriorate. In addition, poorly understood risks of sudden death and cardiovascular events persist in this group. We sought to assess changes in cardiovascular magnetic resonance (CMR) feature tracking (FT) parameters between baseline and follow up scan in myocarditis patients with LV ejection fraction (EF) above 55% on admission to see if FT may help predict interval changes in ejection fraction and possibly adverse outcomes.

MYOCARDIAL BIOPSY IN GENERAL CARE CLINIC: PATIENTS SELECTION, THE RESULTS, SIGNIFICANCE FOR TREATMENT STRATEGY

Aim. To analyze the results of first 50 endomyocardial biopsies (EMB) in general care clinic, to clarify the selection criteria and procedure role in management decision in patients with various noncoronarogenic diseases of myocardium. Material and methods. Totally 50 patients included, who had been underwent EMB during 2007-2014 (31 men, mean age 44,3±13,5). Investigation included the level of anticardiac antibodies (n=49), DNA of herpes group viruses and parvovirus B19 by PCR in blood (n=40) and myocardium (n=49), scintigraphy of myocardium (n=20), MDCT (n=21), MRI (n=17), coronary arteriography (n=22), genetician consultation (n=15). EMB of the right ventricle was done using biopsy forceps STANDARD 5.5 F 104 FEMORAL (Cordis). The materials were coloured with hematoxyline-eosine, picrofucsine by Van Hison, Schiff reactives, Pearls, red congo. The study was approved by the Ethics Comitteeof FMSMU. Results. Indications for EMB were set for 3 groups of patients: 1. With dilated cardiomyopathy (DCMP) as a syndrome, including the probability of acute/ subacute myocarditis (n=7), allergic myocarditis (n=1), myocarditis with myocardial infarction (n=1), vasculitis (n=3), possible myocarditis in long-lasting course of DCMP (n=9), in patients with non-compact myocardium, myodystrophy of Emeri-Dreyfus and possible arrhythmogenic dysplasia of the right ventricle (n=7). 2. With "idiopathic" rhythm and conduction disorders (n=18), including high probability of myocarditis (n=13), vasculitis (n=2), necessity for differentiation of myocarditis and genetic cardiomyopathies (n=3). 3. With the syndrome of primary myocardial hypertrophy (n=3). EMB was informative in all patients, myocarditis found in 82,6%. Conclusion. The criteria for high diagnostic value of EMB is nosological way of selection. In addition to current scenarios it is aimfull to perform EMB if clinically significant ischemia with non-changed coronary arteries, with suspected myocarditis in patients with genetic cardiomyopathies, inborn defects, CHD and other established heart diseases. The EMB results define the tactics of medication and surgical treatment.

Myocarditis and inflammatory cardiomyopathy: from diagnosis to treatment.

Based on the definition in the European Society of Cardiology statement, myocarditis is an inflammatory disease of the myocardium diagnosed by established histological, immunological, and immunohistochemical criteria, whereas inflammatory cardiomyopathy is myocarditis in association with cardiac dysfunction. Actual incidences of myocarditis and CMi are difficult to determine. Studies addressing the issue of sudden cardiac death in young people report a highly variable autopsy prevalence of myocarditis, ranging from 2-42% of cases. Similarly, biopsy-proven myocarditis has been reported in 9-16% of adult patients with unexplained nonischemic dilated cardiomyopathy (DCM). In up to 30% of cases, biopsy-proven myocarditis can progress to DCM and is associated with a poor prognosis. Prognosis in myocarditis patients also varies according to underlying etiology.

Myocarditis: Pathologist's perspective

Myocarditis is a challenging diagnosis for both clinician and pathologist due to the extreme diversity of clinical presentation and low sensitivity of detection of myocarditis in the endomyocardial samples. The exact incidence of myocarditis is still not known as endomyocardial biopsy (EMB) is not performed in all suspected cases of myocarditis in majority of the centers. Identification of Dallas criteria in EMB is still considered as a gold standard in the diagnosis of myocarditis. Viral myocarditis is one of the most common causes of myocarditis next to idiopathic or primary myocarditis. Virtually any type of virus can affect the heart. Idiopathic myocarditis should be categorized depending upon the histopathological findings and clinical features as fulminant, chronic active, eosinophilic, granulomatous, or giant cell myocarditis. Hence, a thorough basic set of all relevant investigations including molecular study should be carried out in the evaluation of clinically suspected viral myocarditis patients to identify the active phase of the viral disease process which ultimately helps in the determination of treatment protocol and prognosis.

Analysis of Clinical Parameters and Cardiac Magnetic Resonance Imaging as Predictors of Outcome in Pediatric Myocarditis

Myocarditis causes significant morbidity and mortality in pediatric patients, with potential adverse outcomes including heart failure, transplantation requirement, and/or death. The objective of this study was to determine predictors of early and late poor outcomes, defined as requirement for extracorporeal membrane oxygenation, ventricular assist device, transplantation, or death in pediatric myocarditis patients. A retrospective cohort study was conducted to evaluate pediatric myocarditis presenting over a 5-year period at a pediatric institution. Patients were identified using an institutional heart failure database and International Classification of Diseases, Ninth Revision, discharge diagnosis codes for myocarditis and confirmed by review of medical records. Data extraction included epidemiologic factors, the presenting ejection fraction (EF), initial and peak troponin levels, brain natriuretic peptide (BNP) level, pathogen identification, cardiac magnetic resonance imaging (MRI), and outcomes. Univariate and multivariate regression was performed to identify variables predictive of outcomes. Because published pediatric cardiac MRI data are sparse, whether late enhancement was associated with specific clinical variables or predictive of outcomes was also evaluated. Fifty-eight patients were identified. The mean age was 10.5 years, 64% were male, 62% were Caucasian, 15% were African-American, and 23% were Hispanic or Asian. Eighty-one percent presented at the institution <1 week after symptom onset. Presenting EFs were normal (>50%) or mildly decreased (40% to 50%) in 48%, moderately decreased (30% to 40%) in 9%, and severely decreased (<30%) in 42%. Thirty patients (52%) underwent viral studies; 17 of these (56%) had acute viral origins of myocarditis identified, including 8 with parvovirus (2 with influenza coinfection), 7 with enterovirus, 1 with Epstein-Barr virus, and 1 with cytomegalovirus. Twenty-eight percent had poor outcomes. Univariate analysis identified Hispanic or Asian race (odds ratio [OR] 4.5, p = 0.05), a severely decreased EF (OR 13, p = 0.002), initial BNP >10,000 pg/ml (OR 5.6, p = 0.01), and peak BNP >10,000 pg/ml (OR 13.65, p = 0.001) as risk factors for poor outcomes; initial and peak troponin >1 ng/ml were correlated significantly with good outcomes (OR 0.22, p = 0.04, and OR 0.26, p = 0.05, respectively). Multivariate analysis adjusting for severe EF, troponin, BNP, and cardiac MRI revealed peak BNP >10,000 ng/L (OR 27.71, p = 0.04), a severely decreased EF (OR 12.8, p = 0.03), and late enhancement on cardiac MRI (OR 24.51, p = 0.04) as risk factors for poor outcomes. Thirty-four patients underwent cardiac MRI (50% with abnormal and 50% with normal results). No significant differences were found between these groups with respect to gender, race, symptom duration, the EF, BNP, troponin, inflammation on cardiac biopsy, or pathogen identification. In conclusion, this study provides data from a large cohort of pediatric myocarditis patients. A presenting EF <30%, peak BNP >10,000 ng/L, and cardiac MRI late enhancement were identified as predictors of poor outcomes.

The role of delayed contrast-enhanced cardiac magnetic resonance in differentiating myocarditis from myocardial infarction

A number of different conditions can present with symptoms that mimics acute coronary syndrome (ACS). Even after performing coronary angiography, diagnosis can still be challenging. The aim of this study was to evaluate the utility of contrast-enhanced cardiac magnetic resonance (CMR) to differentiate between myocarditis and myocardial infarction (MI) in patients presenting with acute chest pain syndrome, elevated cardiac markers, and unobstructed coronary arteries. We studied 26 consecutive patients (mean age 32.4+ 11.3 years, 80.1% males) presenting with acute symptoms, elevated cardiac markers, unobstructed coronary arteries, and referred for Gadolinium-enhanced CMR examinations. Myocarditis was ascertained by the presence of myocardial edema and/or epicardial or scattered intra-myocardial late gadolinium enhancement (LGE). Myocardial infarction was diagnosed if there was territorial subendocardial LGE with variable degrees of transmural involvement. In patients with no LGE, the diagnosis was uncertain. Of 26 patients, 15 (57.7%) were initially diagnosed with ACS, the majority (8 patients, 53.3%) had LGE pattern of myocarditis, 4 (26.7%) had LGE pattern of MI. The remaining 11 patients had suspected myocarditis, 2 (18.2%) had LGE pattern of MI, and 7 (63.6%) had LGE pattern of myocarditis. Five (19.2%) patients had no LGE and diagnosis was unclear. Cardiac magnetic resonance helped to reclassify more than half of our patients (57.7%). We demonstrated that contrast-enhanced CMR allows differentiation between MI and myocarditis in patients presenting with possible ACS and unobstructed coronary arteries. This, in turn, helps with planning long-term therapeutic strategies and redefines the patient’s future risk.

Passive transfer of affinity-purified anti-heart autoantibodies (AHA) from sera of patients with myocarditis induces experimental myocarditis in mice

BackgroundHuman autoimmune myocarditis is characterized by an increased frequency of serum organ and disease-specific anti-heart autoantibodies (AHA) in affected patients. To assess whether AHA are directly pathogenic, we used the passive transfer technique of AHA from patients to normal Balb/c mice to induce an experimental myocarditis. MethodsIn keeping with a classical passive transfer experiment, sera from 5 AHA positive myocarditis patients (3 male, mean age 30±11years, 3 with giant cell and 2 with lymphocytic myocarditis) were affinity purified and injected into 25 Balb/c mice. As controls, affinity purified sera from 5 healthy donors were passively transferred to 25 Balb/c mice. Further 15 control mice were injected with phosphate-buffered saline and 9 mice did not receive any injection. In all patients cardiac-specific AHA of IgG class had been previously detected by an indirect immunofluorescence (IFL) technique on cryostat sections of O blood group human heart. The animals were sacrificed after 4weeks and the hearts were blindly examined for histological evidence of myocarditis by an expert cardiac pathologist. ResultsMyocarditis was present in 13/25 (52%) of the mice which received affinity-purified IgG from patients. The findings of severe, moderate or mild myocarditis were more common in the mice which received affinity-purified IgG from patients (20%; 20% and 12%) than in control animals (2%, p=0.01; 0%, p=0.003; and 0%, p=0.04 respectively). ConclusionsThese findings provide a new evidence for AHA-mediated pathogenicity in human myocarditis, according to Rose–Witebsky criteria.

経皮的心肺補助法(PCPS)合併症を含めた，全身管理に苦慮した劇症型心筋炎の1例

経皮的心肺補助法(PCPS)合併症を含めた，全身管理に苦慮した劇症型心筋炎の1例

Historical assessment of diphtheritic myocarditis from a hospital in northeastern Thailand

Abstract Background: Although there have been many descriptive studies of diphtheria from resource limited countries, descriptions of the natural history of diphtheritic myocarditis in patients from these countries are scarce. Objective: To present the natural history of diphtheritic myocarditis from a hospital in northeastern Thailand. Methods: The clinical features of 38 patients with diphtheria admitted to the Khon Kaen University Hospital in northeastern Thailand between 1983 and 1996 were reviewed. Results: Of the 38 cases of diphtheria, 10 progressed to diphtheritic myocarditis (26%). Electrocardiographic findings of the 10 patients with myocarditis were myocardial and conduction abnormalities. The presence of a clinically severe (toxic) type (P &lt; 0.001) or a swollen neck (bull neck) (P = 0.001) was a predictor of the occurrence of myocarditis. Five (50%) of the 10 patients with myocarditis had conduction abnormalities (third-degree atrioventricular block 3, left bundle branch block 1, and right bundle branch block 1). Four patients with severe symptomatic bradyarrhythmia (third-degree atrioventricular block 3, and left bundle branch block 1) received ventricular pacing, and 3 patients died after this pacing. Echocardiographic abnormalities of left ventricular dilatation and myocardial hypertrophy were found in all 5 patients with conduction abnormalities. All 6 of 7 survivors of diphtheritic myocarditis had normal 12-lead electrocardiographic results at 1-month follow-up. A patient who was the survivor of third-degree AV block had an electrocardiographic finding of flat T waves, and with a complete echocardiographic normalization of left ventricular dilatation and myocardial hypertrophy. Conclusion: The present study confirms that increasing diphtheria immunization coverage in the population remains the most important strategy for the control of diphtheria. In resource limited countries, clinical findings, electrocardiography, and sometimes where available, echocardiography are helpful in assessing the severity of diphtheritic myocarditis, decision making of acute management, and predicting fatal outcome.

Letter by Mewton and Bresson Regarding Article, “Good Prognosis for Pericarditis With and Without Myocardial Involvement: Results From a Multicenter, Prospective Cohort Study”

We read with interest the article by Imazio et al1 on the prognosis of patients with myopericarditis, perimyocarditis, and pericarditis, excluding patients with pure myocarditis, in a prospective multicenter cohort. This article attempts to answer the question of long-term outcomes in patients with pericardial inflammatory syndromes. After a median follow-up of 36 months, the authors find that “the outcome of myopericardial inflammatory syndromes (excluding pure myocarditis) is good.” With the pioneer work of Mahrholdt, Sechtem, and their colleagues,2,3 we had significantly advanced in the assessment of myocarditis and pericarditis patients. In these reports, the systematic use of cardiac magnetic resonance improved the accuracy of the diagnosis of myocarditis and, to some extent, pericarditis and improved the diagnostic performance of endomyocardial biopsies. This …

Detailed pathologic evaluation on endomyocardial biopsy provides long-term prognostic information in patients with acute myocarditis

The long-term prognosis of biopsy-proven myocarditis is not well known. We hypothesized that a detailed pathological examination of an endomyocardial biopsy (EMB) would reveal prognostic information in patients with acute myocarditis. Fifty-four patients were diagnosed with acute myocarditis based on an EMB. Pathological diagnosis was categorized into lymphocytic dominant (29.6%), eosinophilic dominant (22.2%), and borderline myocarditis (48.1%). Masson's trichrome staining and further immunohistochemical staining for CD3, CD20, CD68, HLA-DR, TLR4, TLR8, enteroviral VP1, and caspase-3 expression were performed. The clinical outcomes were defined as all-cause and cardiovascular (CV) death. During the median 10.4 years of follow up (9.7±5.7 years), the overall all-cause mortality was 20.4% and the CV mortality was 14.8% in patients with acute myocarditis. Lymphocytic dominant myocarditis patients showed a poor clinical outcome when compared with eosinophilic dominant myocarditis patients for both all-cause (37.5% vs. 0%, p=0.015) and CV (31.2% vs. 0%, p=0.029) mortality. Among borderline myocarditis patients, the presence of fibrosis was linked with poor clinical outcomes in both all-cause (75.0% vs. 21.4%, p=0.045) and CV (100.0% vs. 25.0%, p=0.034) mortality. No significant associations between clinical outcome and all other immunohistochemical staining targets were observed. Detailed pathological evaluation on an EMB provides prognostic information in patients with acute myocarditis. EMB evaluation should be considered in patients with suspected myocarditis.

Sex Differences in Translocator Protein 18 kDa (TSPO) in the Heart: Implications for Imaging Myocardial Inflammation

Myocarditis is more severe in men than in women and difficult to diagnose due to a lack of imaging modalities that directly detect myocardial inflammation. Translocator protein 18 kDa (TSPO) is used extensively to image brain inflammation due to its presence in CD11b(+) brain microglia. In this study, we examined expression of TSPO and CD11b in mice with coxsackievirus B3 (CVB3) myocarditis and biopsy sections from myocarditis patients in order to determine if it could be used to image myocarditis. We found that male mice with CVB3 myocarditis upregulated more genes associated with TSPO activation than female mice. TSPO expression was increased in the heart of male mice and men with myocarditis compared with female subjects due to testosterone, where it was expressed predominantly in CD11b(+) immune cells. We show that TSPO ligands detect myocardial inflammation using microSPECT, with increased uptake of [(125)I]-IodoDPA-713 in male mice with CVB3 myocarditis compared with undiseased controls.

The Detectability for the Myocardial Fibrosis by Tagging Imaging on Cardiovascular Magnetic Resonance

Purpose: Myocardial fibrosis causes cardiac dysfunction, arrhythmias, and sudden death. Tagging imaging on cardiovascular MR can measure the intra-myocardial motion from the dynamic deformation of lines superimposed on the myocardium. The purpose of this study was to evaluate the detectability of myocardial fibrosis using tagging imaging and to compare this with conventional cine imaging. Materials and Methods: We reviewed 4 normal control (NML) subjects, 4 patients with myocarditis (MYO), and 4 patients with old myocardial infarction (ICM). We measured circumferential strain (Ecc) from tagging imaging, and regional wall thickening (rWT) from cine imaging. Fibrosis was determined from a late gadolinium enhancement (LGE) image. We evaluate diagnostic performance by comparing values of the area under curve (AUC) using ROC analysis. Results: Mean values of Ecc and rWT decreased in the area of LGE both in MYO and ICM patients. AUC values of Ecc and rWT in all subjects were 0.98 and 0.84, respectively (p < 0.0001). These values in MYO patients were 0.95 and 0.72 (p = 0.007), respectively, and 0.99 and 0.75, respectively, in ICM patients (p = 0.0008). Conclusions: Both Ecc and rWT decreased in the area with fibrosis in the patients with MYO and ICM. Tagging imaging showed better detectability of myocardial fibrosis than did cine imaging.

CONTEMPORARY MASKS OF THE MYOCARDITIS (FROM CLINICAL SIGNS TO DIAGNOSIS)

Contemporary myocarditis classifications are usually made up by morphological criteria due to a critical role of biopsy in its diagnostic. However in general medical practice this method is quite rare, though in the real practice internists and cardiologists meet this disease more and more ofted, including its non-classical forms. Clear connection of cardial symptomathic with an infection is the most specific sign of myocarditis, though its absence does not rule out the diagnosis. Using biopsy and complex algorhythm of diagnostics developed on the basis of biopsy we have usually seen these types: 1. Latent (without decompensation and general inflammatory changes) myocarditis in patients with so-called idiopathic rhythm and conduction disorders including atrial fibrillation; 2. Various clinical course and immunity-involvement types in patients with the dilated cardiomyopathy; 3. Paraneoplastic myocarditis; 4. Myocarditis with infarction-like manifesting (as acute and benevolent in its course and prognosis, as chronic with the outcome into severe heart failure), microvascular angina, and combination of myocarditis with coronary

National Survey of Influenza Myocarditis in Japanese Children in Three Seasons

An Influenza pandemic occurred in 2009. A nationwide, retrospective survey of Influenza myocarditis in Japanese children in 3 consecutive Influenza seasons was performed to compare Influenza myocarditis in the 2009/2010 season (the pandemic season), the 2010/2011 season, and the 2011/2012 season, by mailing questionnaires to 514 hospitals in Japan that have pediatric departments and collecting data from 285 hospitals. A questionnaire-based survey related to Influenza myocarditis was also conducted to evaluate the attitudes of Japanese pediatricians concerning the diagnosis of Influenza myocarditis. Fifteen Influenza myocarditis patients were reported, with 8 (H1N1pdm:6, type A:1, type B:1) from the 2009/10 season, 4 (type A:1, type B:3) from the 2010/11 season, and 3 (type B:3) from the 2011/12 season. Only 8 patients with Influenza A virus myocarditis were reported, with 7 patients from the 2009/2010 season, one from the 2010/2011 season, and none in the 2011/2012 season. Mortality was 33.3% (5/15) among the myocarditis patients. Twelve patients (12/15, 80%) were diagnosed with fulminant myocarditis with fatal arrhythmias and/or cardiogenic shock. In the pediatricians’ attitude survey, only 3.3% of pediatricians routinely examined the electrocardiograms of children hospitalized with Influenza infection in Japan. The number of Japanese children with myocarditis associated with Influenza A virus seemed to increase in the pandemic season. Increased awareness of Influenza myocarditis in children is needed during future Influenza pandemics.

Assessment of myocardial strain in patients with myocarditis by cardiac magnetic resonance imaging

Background Myocarditis is associated with a considerable morbidity and mortality in the acute phase as well as in the long term. It is found in up to 12% of young adults with sudden cardiac death and is regarded as a cause of dilated cardiomyopathy which is currently the most frequent reason for heart transplantation. Therefore, techniques for the diagnosis and the assessment of prognosis are of great interest. In this study we evaluate the novel post-procession feature tracking imaging (FTI) algorithm for strain analysis on patients with myocarditis. Methods We retrospectively included 36 patients (31 male, 5 female) who were admitted with acute myocarditis. A control group (31 male, 5 female) was drawn from a reference population of proven healthy volunteers and was matched with regard to age and gender. CMR imaging was performed on a 1.5 T whole-body MRI (Achieva, Philips Healthcare). Short axis views covering both ventricles as well as 2-, 3- and 4-chamber views were obtained using a SSFP sequence. Enddiastolic and endsystolic volumes as well as ejection fraction (EF) were derived from short axis segmentation. In addition we measured the circumferential und longitudinal strain applying a post-procession FTI algorithm (TomTec Imaging Systems). Results The study population and the control group showed similar characteristics regarding age and gender (40.3 ± 13.7 yrs. vs. 40.3 ± 15.7 yrs., p > 0.99). In patients with myocarditis the EF was significantly reduced compared to healthy controls (54.3 ± 8.4% vs. 67.8 ± 5.3%, p < 0.001). Furthermore the patients showed significantly lower values for the global circumferential strain (-24.4 ± 4.2% vs. -28.8 ± 3.8%, p < 0.001) as well as for the global longitudinal strain (-17.7 ± 4.5% vs. -23.6 ± 3.0%, p < 0.001). Global circumferential strain (r = -0.77, p < 0.001) and global longitudinal strain (r = -0.65, p < 0.001) correlated well with EF. In the subgroup of myocarditis patients with preserved ejection fraction (EF≥55%, 16 pts.) the global longitudinal strain (-20.4 ± 4.5% vs. -23.7 ± 2.6%, p < 0.05) was significantly reduced compared to the age- and gender matched control subgroup whereas the global circumferential strain did not show a significant difference (-27.3 ± 2.7% vs. -28.9 ± 3.8%, p = n.s.). Conclusions FTI strain analysis offers a fast quantitative assessment of myocardial strain patterns without the need for additional dedicated strain imaging sequences. Myocarditis patients with preserved EF show reduced longitudinal strain whereas the circumferential strain is not significantly

Foreword to special issue on “Myocarditis”

William Osler, with a very actual sentence, stated, back in year 1892, in its Medicine textbook: ‘‘There are three phases to treatment: diagnosis, diagnosis and diagnosis’’ [1]. This sentence clearly highlights that the best clinical management is based upon the most accurate diagnosis. Historically myocarditis has being considered a rare and poorly understood condition, a conundrum with polymorphic clinical presentation and variable prognosis ranging from spontaneous resolution to progressive heart failure and death. The first comprehensive review with a modern approach to etiopathogenesis was published in 1980 by Woodroof JF, who highlighted the possible etiological role of Coxsackie viruses and of the immune system in the progression of cardiac damage, with possible evolution to a dilated cardiomyopathy [2]. A major advance in diagnosis was the refinement of the endomyocardial biopsy technique using the King’s bioptome by Richardson [3]. Another important step was the development of a consensus pathological classification and histological definition of myocarditis by endomyocardial biopsy, known as the Dallas criteria [4]. Meanwhile, the first experimental observations were made by several investigators, suggesting a possible involvement of autoimmune mechanisms to cardiac autoantigens; in particular, a mouse model for myosin-induced autoimmune myocarditis was described by the Neu et al. [5]. In addition, various groups in the late 80s and early 90s reported the presence of circulating anti-heart autoantibodies against myosin as well as other autoantigens in acute and chronic myocarditis or dilated cardiomyopathy, in keeping with the hypothesis of autoimmunity being involved in a subset of patients [6–14]. A retrospective multicenter registry from the USA coordinated by Cooper et al. [15] reported the efficacy of immunosuppressive therapy in a rare but lethal form of myocarditis, e.g., giant cell myocarditis. On these premises, the multicenter Myocarditis Treatment Trial was designed using the Dallas criteria to recruit myocarditis patients to 6 months immunosuppression; the therapy with azathioprine and prednisone or cyclosporine A and prednisone was well tolerated, and no significant effect on survival was observed, although the study was not powered to detect differences in survival [16]. The results of the trial had a profoundly negative effect in the next decade on the use of endomyocardial biopsy to detect and treat myocarditis. However, researchers developed new diagnostic tools to be added to standard histology, in particular immunohistochemistry, to increase sensitivity of endomyocardial biopsy particularly in focal and chronic myocarditis and characterize the number and type of infiltrating inflammatory cells, and molecular detection of genomic material of infectious agents mainly by polymerase chain reaction (PCR), to diagnose infectious, particularly viral myocarditis [17–24]. This work leads to another major step forward, e.g., the 1995 WHO classification of cardiomyopathies, with the acknowledgment that myocarditis is diagnosed on endomyocardial biopsy by established histological, immunological and immunohistochemical criteria; molecular techniques on EMB were recommended to identify viral etiology [25]. In the WHO classification, infectious, autoimmune and idiopathic forms of myocarditis are recognized that may lead to dilated cardiomyopathy [25]. Using serum cardiac autoantibody testing as well as histology, immunohistology and viral PCR on endomyocardial biopsy, it is nowadays possible to define distinct etiopathogenetic A. L. P. Caforio (&) Division of Cardiology, Department of Cardiological, Thoracic and Vascular Sciences, Centro ‘‘V. Gallucci’’, University of Padova-Policlinico, Via Giustiniani, 2, 35128 Padua, Italy e-mail: alida.caforio@unipd.it

Myocarditis with fulminant type 1 diabetes mellitus diagnosed by cardiovascular magnetic resonance imaging: a case report

BackgroundFulminant type 1 diabetes is a non-autoimmune disorder characterized by sudden onset. This complication is rarely associated with myocarditis, suggesting an involvement of viral infection. We report a patient with myocarditis who was admitted for fulminant type 1 diabetes and diagnosed using a combination of non-invasive techniques.Case presentationWe describe the case of a 25-year-old Japanese man with fulminant type 1 diabetes complicated by myocarditis. The patient was admitted with flu-like symptoms and diabetic ketoacidosis, followed by chest pain the next day. Myocardial damage was suspected based on ST-segment elevation on electrocardiogram and elevation of cardiac enzymes. However, coronary angiography revealed no abnormality in the coronary arteries. We diagnosed myocarditis by a combination of echocardiography, cardiovascular magnetic resonance imaging (CMR), as well as Thallium-201 and Iodine-123 beta-methyl iodophenyl pentadecanoic acid (Tl-201 BMIPP and I-123 BMIPP) and myocardial imaging. More importantly, CMR revealed diffuse enhancement in the subepicardium of the left ventricle with late gadolinium enhancement, consistent with myocardial edema. The patient was successfully treated, received a two-week education program on diabetes and discharged without complication.ConclusionsThe rapid onset and flu-like symptoms strongly suggest the involvement of viral infection in the pathogenesis of fulminant type 1 diabetes and myocarditis. While cardiac muscle biopsy is routinely performed, this case demonstrates that a combination of non-invasive techniques, especially CMR, may successfully diagnose myocarditis in patients with fulminant type 1 diabetes.