Findings and Outcome of Transcatheter Right Ventricular Endomyocardial Biopsy and Hemodynamic Assessment in Children with Suspected Myocarditis or Cardiomyopathy.

OBJECTIVE: The study objective is assessing findings and outcome in children with suspected cardiomyopathy (CMP) or myocarditis undergoing cardiac catheterization with transcatheter right ventricular endomyocardial biopsy (RV-EMB). METHODS: All consecutive children undergoing cardiac catheterization with RV-EMB for suspected CMP/myocarditis between 2002-2021 were analysed regarding clinical presentation, cardiac biomarkers, periprocedural management, hemodynamic, histological/immunohistological findings, and outcome. RESULTS: Eighty-five RV-EMBs were performed in 81 patients at a median age of 6.8 (IQR 9.9) years and a bodyweight of 20 (32.2) kg. Histological/immunohistological findings of RV-EMB revealed dilated CMP in 10 (12%), chronic myocarditis in 28 (33%), healing myocarditis in 5 (6%), acute myocarditis in 9 (11%), other heart muscle diseases in 23 (27%) (7 restrictive CMP, 5 hypertrophic CMP, 4 toxic/anthracycline-induced CMP, 4 endocardfibroelastosis, 1 arrhythmogenic right ventricular CMP, 1 laminin CMP, 1 haemangioma), no conclusive histology in 7 (8%), and normal histology in 3 (4%) patients. Median LVEDP was 17 mmHg (IQR 9), LAP 15 mmHg (10), and PVR 1.83 (1.87) Wood Units/m2. There were 3 major complications (3%), all patients recovered without any sequelae. At follow-up (median 1153, IQR 1799 days) 47 (59%) patients were alive, 11 (13%) dead, 15 (18%) underwent cardiac transplantation, and 8 (9%) were lost to follow-up. Death/cardiac transplantation occurred within 3 years from RV-EMB. All patients with an acute myocarditis survived. NT-pro-BNP, echo parameters, and invasive hemodynamics correlate independently with death/cardiac transplant. CONCLUSION: Hemodynamic invasive data and morphological findings in RV-EMB complete clinical diagnosis in children with suspected CMP/myocarditis and provide important information for further clinical management.

Quantitative Assessment of Late Gadolinium Enhancement and Edema at Cardiac Magnetic Resonance in Low-Risk Myocarditis Patients.

In this study, we aimed to quantify LGE and edema at short-tau inversion recovery sequences on cardiac magnetic resonance (CMR) in patients with myocarditis. We retrospectively evaluated CMR examinations performed during the acute phase and at follow-up. Forty-seven patients were eligible for retrospective LGE assessment, and, among them, twenty-five patients were eligible for edema evaluation. Both groups were paired with age- and sex-matched controls. The median left ventricle LGE was 6.4% (interquartile range 5.0−9.2%) at the acute phase, 4.4% (3.3−7.2%) at follow-up, and 4.3% (3.0−5.3%) in controls, the acute phase being higher than both follow-up and controls (p < 0.001 for both), while follow-up and controls did not differ (p = 0.139). An optimal threshold of 5.0% was obtained for LGE with 87% sensitivity and 48% specificity; the positive likelihood ratio (LR) was 1.67, and the negative LR was 0.27. Edema was 12.8% (9.4−18.1%) at the acute phase, 7.3% (5.5−8.8%) at follow-up, and 6.7% (5.6−8.6%) in controls, the acute phase being higher than both follow-up and controls (both p < 0.001), while follow-up and controls did not differ (p = 0.900). An optimal threshold of 9.5% was obtained for edema with a sensitivity of 76% and a specificity of 88%; the positive LR was 6.33, and the negative LR was 0.27. LGE and edema thresholds are useful in cases of suspected mild myocarditis.

Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction.

PURPOSE: To test the diagnostic performance of cardiovascular magnetic resonance (CMR) tissue-tracking (TT) to detect the presence of late gadolinium enhancement (LGE) in patients with a diagnosis of myocardial infarction (MI) or myocarditis (MYO), preserved left ventricular ejection fraction (LVEF) and no visual regional wall motion abnormalities (RWMA). METHODS: We selected consecutive CMR studies of 50 MI, 50 MYO and 96 controls. Receiving operating characteristic (ROC) curve and net reclassification index (NRI) analyses were used to assess the predictive ability and the incremental diagnostic yield of 2D and 3D TT-derived strain parameters for the detection of LGE and to measure the best cut-off values of strain parameters. RESULTS: Overall, cases showed significantly reduced 2D global longitudinal strain (2D-GLS) values compared with controls (-20.1 ± 3.1% vs -21.6 ± 2.7%; p = 0.0008). 2D-GLS was also significantly reduced in MYO patients compared with healthy controls (-19.7 ± 2.9% vs -21.9 ± 2.4%; p = 0.0001). 3D global radial strain (3D-GRS) was significantly reduced in MI patients compared with controls with risk factors (34.3 ± 11.8% vs 40.3 ± 12.5%, p = 0.024) Overall, 2D-GLS yielded good diagnostic accuracy for the detection of LGE in the MYO subgroup (AUROC 0.79; NRI (95% CI) = 0.6 (0.3, 1.02) p = 0.0004), with incremental predictive value beyond risk factors and LV function parameters (p for AUROC difference = 0.048). In the MI subgroup, 2D-GRS (AUROC 0.81; NRI (95% CI) = 0.56 (0.17, 0.95) p = 0.004), 3D-GRS (AUROC 0.82; NRI (95% CI) = 0.57 (0.17, 0.97) p = 0.006) and 3D global circumferential strain (3D-GCS) (AUROC 0.81; NRI (95% CI) = 0.62 (0.22, 1.01) p = 0.002) emerged as potential markers of disease. The best cut-off for 2D-GLS was -21.1%, for 2D- and 3D-GRS were 39.1% and 37.7%, respectively, and for 3D-GCS was -16.4%. CONCLUSIONS: At CMR-tissue tracking analysis, 2D-GLS was a significant predictor of LGE in patients with myocarditis but preserved LVEF and no visual RWMA. Both 2D- and 3D-GRS and 2D-GCS yielded good diagnostic accuracy for LGE detection in patients with previous MI but preserved LVEF and no visual RWMA.

Fulminant Myocarditis: Epidemiology, Pathogenesis, Diagnosis, and Management.

Fulminant myocarditis (FM) is a rare, distinct form of myocarditis that has been difficult to classify. Since 1991, the definition of FM has evolved, and it is currently considered an acute illness with hemodynamic derangement and arrhythmias due to a severe inflammatory process requiring support of cardiac pump function and/or urgent management of serious arrhythmias. Diagnosis is aided through use of biomarkers and cardiac imaging, but endocardial biopsy remains the gold standard. Recent evidence has revealed that patients with FM are significantly more likely to die or require heart transplantation than those with the nonfulminant form, refuting previous studies proposing a paradoxically low mortality in patients with FM. Acute hemodynamic derangement is managed by intensive contemporary pharmacologic and interventional approaches, whereas the role of immunosuppressive therapy has not been clarified. Early recognition and aggressive management are essential for favorable outcomes. In conclusion, FM is an inflammatory process requiring intensive support, and it causes a higher morbidity and mortality than acute nonfulminant myocarditis.

LGE-MRI in the Assessment of Left-ventricular Remodelling in Myocarditis.

BACKGROUND: The exact morbidity of myocarditis is unknown, as the treatment is generally delayed in virtue of misdiagnosis or missed diagnosis. AIM: The aim of this study was to identify prognostic factors of left-ventricular remodeling on CMRI performed in patients with pathological proven myocarditis. METHODS: Sixty-two cases with various presentations of myocarditis (39 cases with heart failure; 23 cases with arrhythmias) were selected. All patients, who underwent coronary angiography, endomyocardial biopsy, were divided into positive-remodeling and negative-remodelling groups to analyse LGE and cardiac cine parameters at presentation and subsequent to 3 months. RESULTS: Comparison of two subgroups in CMRI is as follows: positive LGE (65.6% vs. 86.7%; p<0.05), LVEF (41.3±14.8% vs. 37.6±10.1%; p=0.62), (25.7±2.0% vs. 24.0±2.5%; p=0.81), (44.5±3.9mm vs. 46.3±5.4mm; p=0.76), (129.1±8.5ml vs. 135.3±12.2ml; p=0.26), (74.8±7.3ml vs. 79.1±10.0ml; p=0.55), (52.0±5.7g vs. 49.6±6.5g; p=0.71), (34.9±3.5ml vs. 32.4±6.2ml; p=0.68), (3.8±0.7L/min vs. 3.1±0.5L/min; p=0.64), (2.9±0.6L/min*m2 vs. 2.7±0.5L/min*m2; p=0.79). CONCLUSION: LGE-MRI is rewarding as an independent predictor in left-ventricular positive and negative remodelling of myocarditis.

The effects of flip angle optimization on the precision and reproducibility of feature tracking derived strain assessment in contrast enhanced bSSFP cine images.

OBJECTIVES: The aim of this study was to investigate whether a flip angle adaptation, which is known to improve SNR and CNR in post contrast SSFP imaging, improves the precision and reproducibility of Feature Tracking (FT) derived strain assessments in post contrast bSSFP imaging. METHODS AND RESULTS: At 1.5T balanced SSFP midventricular short axis cine images were acquired with various flip angles (FA) before (FA = 50°) and 5 min after (FAs = 50°, 80°, 90°, 100°) injection of double dose Gadobutrol. FT derived systolic circumferential strain was then calculated for all pre- and post-contrast images, the intra- and inter-observer variability of strain measurements was assessed. FT derived midventricular peak systolic circumferential strain (PSCS) derived from unadapted (FA: 50°) contrast enhanced bSSFP images was significantly lower than strain derived from unenhanced bSSFP images (-16.45 ±â€¯5.1% vs -20.57 ±â€¯6.2%; p < 0.001) and showed low agreement (mean difference of -4.13 ±â€¯2.4, 95% CI:-5.3 to -3) in all 20 subjects. After adaption of the flip angle (FA: 100°), agreement between strain derived from unenhanced and adapted contrast enhanced bSSFP images (-20.57 ±â€¯6%) was strong (0.01 ±â€¯0.9, CI:-0.43 to 0.41). In comparison to intra- and interobserver variability of strain derived from unenhanced images (intra 2.9%; inter: 3.9%), strain measurements derived from adapted contrast enhanced images (FA: 100°) showed a slightly lower variability (intra: 2.5%; inter: 2.3%). CONCLUSION: If flip angle adaptation is performed, FT based strain analysis may be performed on contrast enhanced bSSFP cine images without loss of precision and accuracy.

Assessment of edema using STIR+ via 3D cardiovascular magnetic resonance imaging in patients with suspected myocarditis.

OBJECTIVE: To evaluate three-dimensional T2-weighted fast spin echo triple inversion recovery sequences (STIR+) for the diagnosis of myocardial edema in patients with suspected early myocarditis after respiratory or gastrointestinal tract viral infection and at follow-up. MATERIALS AND METHODS: We prospectively examined 28 patients with suspected myocarditis and 37 controls matched for gender and age. An ECG-triggered STIR+ was used to cover the entire left ventricle in short-axis images with 10-mm slice thickness and no interslice gap. The global signal intensity ratio (heart muscle in relation to skeletal muscle) was calculated (global STIR+ ratio) to evaluate edema. All patients had repeat examinations at follow-up (mean interval 4.9 months, 1-12 months). RESULTS: The mean global STIR+ ratio was 2.15 ± 0.4 in the initial examination of patients as compared to 1.78 ± 0.3 in controls (p < 0.0001) and 1.89 ± 0.3 in patients at follow-up (p = 0.0001 vs. first visit). Left ventricular ejection fraction did not differ between patients and controls at baseline and at follow-up. CONCLUSION: We could identify a significantly higher global STIR+ ratio in patients with suspected myocarditis compared to controls, and a dynamic change during follow-up. The global STIR+ ratio may, therefore, be useful for the diagnosis of myocarditis and should be further explored.

Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models.

The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function. We established a physiological protocol for underwater zebrafish echocardiography using high frequency ultrasound, and evaluated its reliability in detecting altered cardiac function in two disease models. Serial assessment of cardiac function was performed in wild-type zebrafish aged 3 to 12 months and the effects of anesthetic agents, age, sex and background strain were evaluated. There was a varying extent of bradycardia and ventricular contractile impairment with different anesthetic drugs and doses, with tricaine 0.75 mmol l-1 having a relatively more favorable profile. When compared with males, female fish were larger and had more measurement variability. Although age-related increments in ventricular chamber size were greater in females than males, there were no sex differences when data were normalized to body size. Systolic ventricular function was similar in both sexes at all time points, but differences in diastolic function were evident from 6 months onwards. Wild-type fish of both sexes showed a reliance on atrial contraction for ventricular diastolic filling. Echocardiographic evaluation of adult zebrafish with diphtheria toxin-induced myocarditis or anemia-induced volume overload accurately identified ventricular dilation and altered contraction, with suites of B-mode, ventricular strain, pulsed-wave Doppler and tissue Doppler indices showing concordant changes indicative of myocardial hypocontractility or hypercontractility, respectively. Repeatability, intra-observer and inter-observer correlations for echocardiographic measurements were high. We demonstrate that high frequency echocardiography allows reliable in vivo cardiac assessment in adult zebrafish and make recommendations for optimizing data acquisition and analysis. This enabling technology reveals new insights into zebrafish cardiac physiology and provides an imaging platform for zebrafish-based translational research.

[Assessment of clinical-instrumental, morphological data and expression of coxsackie adenovirus receptor in patients with inflammatory cardiac pathology].

In 22 patients with heart failure and/or ventricular arrhythmias presumably of inflammatory etiology the results of clinical and instrumental investigation were analyzed and compared to the endomyocardial biopsy data. In the subgroup of patients with left bundle branch block (LBBB) we revealed features indicative of lesser contribution of inflammatory destruction in pathogenesis of cardiomyopathy. The only virus, detected in biopsy samples, was parvovirus B19. Its persistence in myocardium was not related to activity of inflammation and severity of clinical course. Increased expression of Coxsackie adenovirus receptor (CAR) was found in 20 patients. It was not related to inflammatory cells infiltration and virus persistence in myocardium. Patients with most prominent CAR expression were characteried by right heart dilatation, more severe heart failure and absence of LBBB. Enhancement of CAR expression could reflect the attempt of organism to repair intercellular communications between cardiomyocites and to protect cells from the products of necrotic lysis during long standing inflammation.

Noninvasive assessment of cardiac abnormalities in experimental autoimmune myocarditis by magnetic resonance microscopy imaging in the mouse.

Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice were imaged using a 9.4 T (400 MHz) 89 mm vertical core bore scanner equipped with a 4 cm millipede radio-frequency imaging probe and 100 G/cm triple axis gradients. Cardiac images were acquired from anesthetized animals using a gradient-echo-based cine pulse sequence, and the animals were monitored by respiration and pulse oximetry. The analysis revealed an increase in the thickness of the ventricular wall in EAM mice, with a corresponding decrease in the interior diameter of ventricles, when compared with healthy mice. The data suggest that morphological and functional changes in the inflamed hearts can be non-invasively monitored by MRM in live animals. In conclusion, MRM offers an advantage of assessing the progression and regression of myocardial injuries in diseases caused by infectious agents, as well as response to therapies.

Assessment of the anti-protozoal activity of crude Carica papaya seed extract against Trypanosoma cruzi.

In order to determine the in vivo activity against the protozoan Trypanosoma cruzi, two doses (50 and 75 mg/kg) of a chloroform extract of Carica papaya seeds were evaluated compared with a control group of allopurinol. The activity of a mixture of the three main compounds (oleic, palmitic and stearic acids in a proportion of 45.9% of oleic acid, 24.1% of palmitic and 8.52% of stearic acid previously identified in the crude extract of C. papaya was evaluated at doses of 100, 200 and 300 mg/kg. Both doses of the extracts were orally administered for 28 days. A significant reduction (p < 0.05) in the number of blood trypomastigotes was observed in animals treated with the evaluated doses of the C. papaya extract in comparison with the positive control group (allopurinol 8.5 mg/kg). Parasitemia in animals treated with the fatty acids mixture was also significantly reduced (p < 0.05), compared to negative control animals. These results demonstrate that the fatty acids identified in the seed extracts of C. papaya (from ripe fruit) are able to reduce the number of parasites from both parasite stages, blood trypomastigote and amastigote (intracellular stage).

Assessment of acute myocarditis by cardiovascular MR: diagnostic performance of shortened protocols.

The recommended cardiovascular magnetic resonance (CMR) diagnostic criteria for active myocarditis ("Lake Louise Criteria") are based on edema-sensitive (T2-weighted) imaging and two different contrast-enhanced techniques, the early gadolinium enhancement ratio (EGEr) and late gadolinium enhancement (LGE). Because fast spin echo sequences used for determining the EGEr and edema-sensitive T2-weighted sequences have inconsistent image quality, these components are often skipped in institutional standard protocols. We aimed to compare the diagnostic performance of the Lake Louise Criteria with and without T2-weighted or early gadolinium-enhanced CMR imaging in a clinical setting. We investigated 35 patients with suspected acute myocarditis (27 males; Age 39.8 ± 16.6) and 10 healthy controls (5 males; age 33.8 ± 10.4). CMR sequences investigated included an edema-sensitive short-T1 triple inversion recovery, T1-weighted turbo spin echo imaging before and within 4 min after gadolinium injection (EGEr), and a phase sensitive inversion-recovery gradient echo sequence 5-10 min after gadolinium injection (LGE). Quantitative and qualitative image analyses, respectively, were performed for EGEr and areas with increased signal in LGE and edema-sensitive images. EGEr, T2, and LGE burden were significantly higher in patients than in controls (EGEr: 5.8 ± 3.0 vs. 2.5 ± 1.7; p = 0.002, T2: 24 vs. 0; p < 0.001, LGE: 27 vs. 4; p < 0.05). The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were as follows: EGEr: 66, 90, 96, 43, and 72%; T2: 69, 100, 100, 53, and 76%; LGE: 77, 60, 87, 43 and 73%; T2 and/or LGE: 91, 60, 89, 67, 84% Lake Louise Criteria, "two out of three": 80, 90, 96, 53, and 82%. The sensitivity of "T2 and/or LGE" was significantly higher than the Lake Louise Criteria (p < 0.05), while the overall diagnostic accuracy was not statistically different. The overall diagnostic accuracy "T2 and/or LGE" was significantly better than that of LGE alone. The positive likelihood ratio was higher for the Lake Louise Criteria (7.7) than for EGE alone (6.3), T2 and/or LGE (2.3) or LGE alone (1.9). In patients with clinical evidence for relevant active myocarditis, skipping T2-weighted imaging or early GD enhancement is associated with a significantly lower positive likelihood ratio, while the removal of Early Gd Enhancement imaging does not change diagnostic overall accuracy, while reducing sensitivity. Thus, in patients where a high positive likelihood ratio is needed, the full Lake Louise Criteria including Early Gd enhancement and edema-sensitive T2-weighted imaging should be used until alternative approaches are developed.

Sex and gender differences in myocarditis and dilated cardiomyopathy.

Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is, in turn, a major cause of acute DCM in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of DCM differ between the sexes. This seminar provides a contemporary perspective on the immune mediators of myocarditis, including interdependent elements of the innate and adaptive immune response. The heart's acute response to injury is influenced by sex hormones that appear to determine the subsequent risk of chronic DCM. Preliminary data suggest additional genetic variations may account for some of the differences in epidemiology, left ventricular recovery, and survival between men and women. We highlight the gaps in our knowledge regarding the management of women with acute DCM and discuss emerging therapies, including bromocriptine for the treatment of peripartum cardiomyopathy.

Noninvasive assessment of myocardial inflammation by cardiovascular magnetic resonance in a rat model of experimental autoimmune myocarditis.

BACKGROUND: Limited availability of noninvasive and biologically precise diagnostic tools poses a challenge for the evaluation and management of patients with myocarditis. METHODS AND RESULTS: The feasibility of cardiovascular magnetic resonance (CMR) imaging with magneto-fluorescent nanoparticles (MNPs) for detection of myocarditis and its effectiveness in discriminating inflammation grades were assessed in experimental autoimmune myocarditis (EAM) (n=65) and control (n=10) rats. After undergoing CMR, rats were administered with MNPs, followed by a second CMR 24 hours later. Head-to-head comparison of MNP-CMR with T(2)-weighted, early and late gadolinium enhancement CMR was performed in additional EAM (n=10) and control (n=5) rats. Contrast-to-noise ratios were measured and compared between groups. Flow cytometry and microscopy demonstrated that infiltrating inflammatory cells engulfed MNPs, resulting in altered myocardial T(2)* effect. Changes in contrast-to-noise ratio between pre- and post-MNP CMR were significantly greater in EAM rats (1.08 ± 0.10 versus 0.48 ± 0.20; P<0.001). In addition, contrast-to-noise ratio measurement in MNP-CMR clearly detected the extent of inflammation (P<0.001) except for mild inflammation. Compared with conventional CMR, MNP-CMR provided better image contrast (CNR change 8% versus 46%, P<0.001) and detectability of focal myocardial inflammation. Notably, MNP-CMR successfully tracked the evolution of myocardial inflammation in the same EAM rats. CONCLUSIONS: Magneto-fluorescent nanoparticle CMR permitted effective visualization of myocardial inflammatory cellular infiltrates and distinction of the extent of inflammation compared with conventional CMR in a preclinical model of EAM. Magneto-fluorescent nanoparticle CMR performs best in EAM rats with at least moderate inflammatory response.

Rituximab reversed cardiac involvement of Wegener's granulomatosis: magnetic resonance imaging assessment.

INTRODUCTION: Cardiac involvement is a rare manifestation of Wegener granulomatosis (WG). Because its prognosis can be poor, it must be diagnosed early to be treated adequately. We report the disease course of a patient who received rituximab to treat cardiac involvement documented by contrast-enhanced cardiac magnetic resonance imaging (ceCMR). CASE: This WG patient developed myocarditis with atrioventricular block. CeCMR proved useful in the diagnosis and follow-up of cardiac involvement. Several unsuccessful regimens preceded the prescription of rituximab. Two months later, regression of the myocarditis shown by ceCMR images was correlated with electrophysiological improvement. DISCUSSION: CeCMR assessment of a heart conduction defect in a patient with WG showed that this tool was useful for the diagnosis and follow-up of cardiac involvement in this vasculitis. Rituximab was an effective treatment in this patient.

Assessment of the inflammatory process by endomyocardial biopsy in patients with dilated cardiomyopathy based on pathological and immunohistochemical methods.

INTRODUCTION: Myocarditis may lead to dilated cardiomyopathy (DCM) in immunogenetically predisposed individuals. The diagnosis of myocardial inflammation is currently based on histopathological and immunohistochemical methods. Previous studies indicate that inflammatory cardiomyopathy occurs in approximately 50% of patients with DCM. AIM: The goal of the study was to assess the inflammatory process in patients with DCM by endomyocardial biopsy using histopathological and immunohistochemical methods. METHODS: Endomyocardial biopsy specimens was examined using routine histopathological methods and immunochemical staining for T lymphocytes (CD3(+), n=84), major histocompatibility complex I (HLA ABC, n=48) and II (HLA DPQR, n=84) antigens and the adhesion molecules ICAM-1 (n=51) and VCAM-1 (n=48) in 84 patients (69 male, 15 female; mean age 35.0+/-10.5 years) with angiographically-confirmed DCM. Familial disease occurrence was noted in 14 (16.7%) patients. Cardiac samples obtained from 18 patients who died of non-cardiovascular causes were used as a control group. RESULTS: Myocarditis was diagnosed, according to the Dallas criteria, in 8 (9.5%) patients. The frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes per high-power field (hpf) in myocardial biopsy, was 14.3%. When broader criteria were applied (presence of >2.0 CD3(+) lymphocytes/hpf and/or 1.5 CD3(+) lymphocytes/hpf in multiple foci and increased expression of class I/II HLA), inflammatory cardiomyopathy was diagnosed in 32.1% of patients. Inflammatory activation of the endothelium, indicated by increased expression of at least three adhesion molecules (class I and II HLA, ICAM-1, VCAM-1), was present in 22 (45.8%) patients. The expression of HLA DPQR, HLA ABC and ICAM-1 was observed on the endothelium of capillaries and larger vessels, interstitial cells, and the surface of activated lymphocytes; immunohistochemical reactions were diffuse. In patients with markedly elevated expression of the aforementioned adhesion molecules, the expression was also present on cardiomyocyte cell membranes. VCAM-1 was restricted to the endothelium of individual small veins. The control group did not demonstrate any signs of myocarditis, inflammatory cardiomyopathy or inflammatory endothelial activation. CONCLUSIONS: The application of immunohistochemical methods to myocardial biopsy in order to identify the inflammatory cell phenotype and the presence of adhesion molecules permits the diagnosis of inflammatory cardiomyopathy in 14% or 32% of patients, depending on the criteria used, while conventional pathology allows for this diagnosis in 9% of patients. The observed frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes/hpf in the myocardium, was lower (14%) than in previous studies, while the frequency of inflammatory endothelial activation was similar (45%).

Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology.

BACKGROUND: Myocarditis can occasionally lead to sudden death and may progress to dilated cardiomyopathy in up to 10% of patients. Because the initial onset is difficult to recognize clinically and the diagnostic tools available are unsatisfactory, new strategies to diagnose myocarditis are needed. METHODS AND RESULTS: Cardiovascular MR imaging (CMR) was performed in 32 patients who were diagnosed with myocarditis by clinical criteria. To determine whether CMR visualizes areas of active myocarditis, endomyocardial biopsy was taken from the region of contrast enhancement and submitted to histopathologic analysis. Follow-up was performed 3 month later. Contrast enhancement was present in 28 patients (88%) and was usually seen with one or several foci in the myocardium. Foci were most frequently located in the lateral free wall. In the 21 patients in whom biopsy was obtained from the region of contrast enhancement, histopathologic analysis revealed active myocarditis in 19 patients (parvovirus B19, n=12; human herpes virus type 6 [HHV 6], n=5). Conversely, in the remaining 11 patients, in whom biopsy could not be taken from the region of contrast enhancement, active myocarditis was found in one case only (HHV6). At follow-up, the area of contrast enhancement decreased from 9+/-11% to 3+/-4% of left ventricular mass as the left ventricular ejection fraction improved from 47+/-19% to 60+/-10%. CONCLUSIONS: Contrast enhancement is a frequent finding in the clinical setting of suspected myocarditis and is associated with active inflammation defined by histopathology. Myocarditis occurs predominantly in the lateral free wall. Contrast CMR is a valuable tool for the evaluation and monitoring of inflammatory heart disease.

Significance of assessment of serum cardiac troponin I and interleukin-8 in scorpion envenomed children.

In the present study, 41 children in Upper Egypt were admitted to Pediatric Intensive Care Unit, Assiut University Hospital, for scorpion envenomation. They were compared with 15 apparently healthy children of matching age as controls. The victims and controls were subjected to complete clinical examination, full blood count and arterial blood gases analysis. According to severity of scorpion envenomation, 17 children had manifestations of severe envenomation and clinical signs of toxic myocarditis (severe cases), 14 children had moderate manifestations of envenomation without clinical evidence of carditis (moderate cases) and 10 cases showing only mild symptoms of envenomation (mild cases). The serum levels of cardiac troponin I (cTnI) and interleukin-8 (IL-8) beside the enzymatic activities of creatine phosphokinase (CPK), CPK-isoenzyme-MB (CPK-MB) and lactate dehydrogenase (LDH) were determined once for mild cases and controls on admission and twice for severe and moderate cases on admission and after 24. Electrocardiography and measurements of echocardiographic (Echo) of % fractional shortening of left ventricule (% SF), left ventricular ejection fraction (LVEF) and cardiac chambers dilatation were done for severe and moderate cases. All the envenomed victims showed significantly higher mean values of CPK, CPK-MB, LDH, and IL-8 on admission in comparison to control group. cTnI was not detectable in the sera of control group as well as patients of mild envenomation. The mean values of CPK, CPK-MB, LDH, and IL-8 were significantly higher in severe cases while only IL-8 and CPK-MB were significantly higher in moderate cases in comparison with mild cases. The mean values of IL-8, cTnI, CPK, CPK-MB and LDH were significantly higher in severe cases both on admission and on follow-up comparing with moderate cases. The case fatality rate was 12.5% and all were from severe cases with toxic myocarditis. The non-survivors victims showed significant higher mean values of only cTnI on admission and both cTnI and IL-8 on follow up in comparison to the survivors. Significant reduction of % SF and LVEF were noticed among the non-survivors in comparison to survivors. The cTnI showed 100% specificity and sensitivity for diagnosis of myocardial injury in relation to Echo finding in the envenomed victims. In severe cases, cTnI was positively correlated with IL-8 while negatively correlated with %SF and LVEF. In conclusion, cTnI is a specific marker for diagnosis of myocardial injury in scorpion envenomation while other biochemical markers did not show such specificity. Also, IL-8 may be involved in the pathogenesis of myocardial injury of scorpion envenomation. Both cTnI and IL-8 may be useful to forecast the fatal outcome in scorpion envenomation.

[Assessment of the protective effect of vitamin E during development of experimental myocardial damage]. / Otsinka zakhysnoï diï vitaminu E za rozvytku eksperymental'noho dribnovohnyshchevoho urazhennia miokarda.

It was shown that creatinphosphokinase activity of blood serum might be used as a criterion for evaluating the level of sparsely distributed damage in myocardium as a result of adrenaline administration. The protective effect of vitamin E under adrenaline-induced myocarditis was studied. The best effect was obtained after triple intramuscular injection of vitamin E before administration of pathological agent. Intravenous injection of the preparation has no benefits over that of intramuscular way of administration. Preventive action of vitamin E shows functioning itself in an increase of the quantity and activity of ubiquinone--the component of electron transport chain in mitochondria.