Chronic Active Myocarditis Research Articles

Different Phases of Disease in Lymphocytic Myocarditis: Clinical and Electrophysiological Characteristics.

Endomyocardial biopsy (EMB) is required to make a definite diagnosis of lymphocytic myocarditis (LM), to identify its etiology, and to classify LM into different phases. This study aims to characterize and compare clinical and electrophysiological characteristics of different biopsy-proven LM phases, namely acute myocarditis (AM), chronic active myocarditis (CAM), and healed myocarditis (HM). All patients with a diagnosis of LM at 3 Italian referral centers were prospectively enrolled. According to EMB findings, LM was classified as AM, CAM, or HM; per-group comparisons of clinical presentations, noninvasive, and invasive findings are reported. Among the 122 enrolled patients (AM, n=44; CAM, n=42; HM, n=36), complex ventricular arrhythmias were very common overall (n=109, 89%), but ventricular fibrillation was slightly more prevalent in AM (P=0.028). Cardiac magnetic resonance imaging showed late gadolinium enhancement in more patients with HM and CAM than AM (94.4% vs 92.9% vs 50%; P< 0.001), whereas edema was more common in AM than in CAM, being absent in HM (90.9% vs 50% vs 0%; P< 0.001). Accordingly, edema was the strongest independent clinical predictor of EMB-proven active inflammation. Electroanatomical mapping revealed a lower prevalence of low-voltage areas in AM than in CAM or HM. We observed a strong association between edema at a specific myocardial segment and normal voltages at that site (odds ratio: 0.24; 95%CI: 0.10-0.54; P< 0.01), as well as between late gadolinium enhancement and low-voltage areas (odds ratio: 2.86; 95%CI: 1.19-6.97; P=0.019). LM is a highly heterogeneous disease, and its different phases are characterized by diverse clinical, morphological, and electrophysiological features. Further research is required to identify electroanatomical markers of inflammation.

369 PENTRAXIN 3 AS A DIAGNOSTIC AND PROGNOSTIC MARKER OF ACTIVE MYOCARDITIS

Abstract Background Pentraxin 3 (PTX3) is an acute phase protein, which regulates the outcomes of inflammation. Currently, there are no myocarditis-typical biomarkers that allow a non-invasive diagnosis, and endomyocardial biopsy (EMB) is still the gold standard. Finally, risk stratification is often challenging in these patients. Aim To investigate whether PTX3 could be expressed in cardiomyocytes and released during myocarditis, serving as a novel and independent diagnostic indicator of myocardial inflammation, and contributing to prognosis prediction. Methods Fifty-five patients with a diagnosis of acute or chronic active myocarditis proven by cardiac magnetic resonance (CMR) and/or endomyocardial biopsy (EMB), were included. First, we evaluated tissue PTX3 expression by immunohistochemistry (IHC). Then, we assessed circulating blood PTX3 by ELISA technique. Results On cardiac tissue, PTX3 at IHC did not localize in the interstitium, and showed an inconstant expression in the vascular endothelium, but a marked staining by cardiomyocytes in all myocarditis patients. The only exception was represented by two patients with systemic COVID-19, with SARS-CoV-2 and PVB-19 intracardiac genomes, respectively, who showed a diffuse cardiac PTX3 expression. Remarkably, at semi-quantitative pixel analysis, viral aetiology showed higher levels of tissue expression, rather than the autoimmune one. Circulating PTX3 levels were significantly higher in myocarditis patients than controls, with pathologic values in 87% of myocarditis patients, and none among controls. Remarkably, plasma PTX3 proved to be more sensitive in myocarditis detection than CRP, ESR, troponin T, and NT-proBNP. As regards of prognosis, we observed that patients with heart failure (HF) presentation all had elevated PTX3 levels, as compared with chest pain or arrhythmia. Remarkably, patients with reduced LVEF (&amp;lt;50%) at admission who recovered during follow-up had higher baseline PTX3 levels, rather than those whose systolic function did not improve. Conclusions Tissue PTX3 is mostly expressed by cardiomyocytes in patients with active myocarditis on EMB samples. In addition, plasma PTX3 is a sensitive diagnostic and prognostic marker in patients with inflammatory cardiomyopathy.

MAGNETIC RESONANCE IMAGING OF THE HEART IN DIAGNOSTICS OF VARIOUS TYPES OF MYOCARDITIS

Aim. To study the radiation semiotics of various clinical and morphological types of myocarditis with magnetic resonance imaging (MRI). Material and methods. Totally, 70 patients included, with suspected by clinical and lab data myocarditis (28 females, 42 males; mean age 37,0±13,1 y.o). All patients underwent endomyocardial biopsy (EMB) and MRI with intravenous contrasting. Sensitivity of MRI method was evaluated with relation to EMB. Exclusion criteria had been the comorbid ischemic heart disease. Results. Among 70 patients with histologically verified myocarditis, only 47 had this diagnosis by MRI data, sensitivity was set as 67%. In acute active and acute borderline myocardities there is high sensitivity of MRI — 86%; in chronic active myocarditis — 74%, in patients with chronic borderline myocarditis — 55%. Three MRI-criteria of myocarditis were found in acute active myocarditis. Acute borderline myocarditis in most cases presented with 2 signs: edema and delayed contrast enhancement. Significant difference of active myocarditis from other clinical and morphological types is dominance of transmural pattern of delayed contrasting. Also, there is interdependence of inflammation activity by EMB and severity of myocardium edema (64,3% vs. 40,5%, p=0,005). The main differentiating factor of chronic myocarditis is collecting kind of the delayed contrasting areas, which spread more than the zone of myocardium edema. Conclusion. Magnetic resonance imaging shows the highest sensitivity in revealing of acute myocarditis, and in cases of chronic myocarditis the sensitivity depends on activity of inflammation. The overlap of the areas of delayed contrasting and myocardial edema make it to differentiate acute and chronic process in myocardium. Dignostics of chronic borderline myocarditis is impossible unless EMB is done.

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.

MYOCARDITIS AS A CAUSE OF VENTRICULAR ARRHYTHMIAS

Objective. To study the etiology of nonischemic ventricular arrhythmias and to improve diagnostic evaluation of inlammatory myocardial disease using endomyocardial biopsy.Design and methods. We performed 100 endomyocardial biopsies during catheter ablation in patients with nonischemic ventricular arrythmias. Results. Myocarditis was veriied in 58 cases, and postinlammatory ibrosis — in 24 cases. Twenty three patients (67 %) demonstrated active myocarditis, 1 (2,9 %) had chronic active myocarditis, and 10 subjects (29 %) — chronic non-active myocarditis. Conclusion. Endomyocardial biopsy contributes to better veriication of the etiology of ventricular arrhythmias. Late gadolinium enhancement during magnetic resonance imaging shows 74 % sensitivity and 46,9 % speciicity in the evaluation of myocarditis, and 52,4 % sensitivity and 38,9 % speciicity in veriication of postinlammatory ibrosis. Presence of CD-8+ cells, Ig M, patchy dystrophin expression can be additional features for veriication of active myocarditis.

臨床 病理組織学的に多数の著明なリンパ球集簇を認め“慢性活動性心筋炎(chronic activemyocarditis)”と考えられた3剖検例

臨床 病理組織学的に多数の著明なリンパ球集簇を認め“慢性活動性心筋炎(chronic activemyocarditis)”と考えられた3剖検例

Electrical storm of ventricular tachycardia associated with chronic active myocarditis

Electrical storm of ventricular tachycardia associated with chronic active myocarditis

A fatal case of Human Herpesvirus 6 chronic myocarditis in an immunocompetent adult

Background Human Herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis in immunocompromised or immunocompetent patients. However the physiopathological mechanisms of HHV-6 related acute myocarditis and the involvement of subsequent HHV-6 reactivation phases in the development of chronic cardiomyopathies remain to be assessed. Objectives To describe a case of fatal HHV-6 chronic myocarditis in an immunocompetent adult. Study design Case report and detailed histological and viral diagnoses by combination of histology/immunohistochemistry and polymerase chain reaction techniques on cardiac tissues. Results Histopathological analysis of ventricular tissues showed large interstitial and scarring fibrotic areas with a moderate mononuclear cell infiltrate compatible with histological aspect of chronic myocarditis. Detection of both HHV-6 by real-time PCR and viral glycoproteins in mononuclear and endothelial cells by immunohistochemistry evidenced an ongoing cardiac HHV-6 replication with viral late protein synthesis activity. Conclusions This case report indicates that HHV-6 can establish a chronic active myocarditis leading to heart failure in immunocompetent subjects.

Right-Sided Heart Wall Thickening and Delayed Enhancement Caused by Chronic Active Myocarditis Complicated by Sustained Monomorphic Ventricular Tachycardia

An asymptomatic healthy 65-year-old man was referred to a hospital for inverted T waves in the precordial leads (Figure 1) with paroxysmal advanced atrioventricular block in the ECG. Chest x-ray showed mild cardiac enlargement (Figure 2), and an echocardiogram showed right ventricular (RV) wall thickening (arrow in Figure 3). Five months later, the patient was referred to another hospital complaining of chest discomfort. Coronary angiogram was normal, but sustained monomorphic ventricular tachycardia (VT) occurred. Suffering from incessant VT, the patient was transferred to our hospital. The ECG and echocardiogram were …

Active myocarditis in a patient with chronic active Epstein–Barr virus infection

Chronic active Epstein–Barr virus (CAEBV) infection is characterized by chronic or recurrent infectious mononucleosis-like symptoms and the prognosis of CAEBV infection is quite poor. The incidence of myocarditis as a complication of EBV infection is not so high and it is unusual that heart failure appears as the initial symptom. However, it is very important to detect and treat chronic active myocarditis in the early phase of CAEBV infection because chronic active myocarditis disorganizes and decreases cardiomyocytes, resulting in the progression to heart failure. We report a case of a 45-year-old man with CAEBV infection for 5 years. Echocardiography revealed moderate left ventricular systolic dysfunction with mild pericardial effusion. Endomyocardial biopsies demonstrated massive lymphocytic infiltration with adjacent myocytolysis and necrosis of cardiomyocytes suggesting active myocarditis. Immunohistological analysis of biopsies revealed that the infiltrating cells were mainly T lymphocytes. And some of the infiltrating cells showed a positive signal for the EBV-encoded small nuclear RNA by in situ hybridization. Positron emission tomography using 18F-fluoro-2-deoxyglucose ( 18F-FDG) performed revealed increased uptake of 18F-FDG of whole left ventricular wall with mild heterogeneity.

Interferon-γ Induces Chronic Active Myocarditis and Cardiomyopathy in Transgenic Mice

Chronic heart failure is associated with an activation of the immune system characterized among other factors by the cardiac synthesis and serum expression of proinflammatory cytokines. There is unequivocal clinical and experimental evidence that the cytokine tumor necrosis factor-alpha is involved in the development of chronic heart failure, but a putative cardiotoxic potential of the proinflammatory cytokine interferon (IFN)-gamma remains primarily unknown. To investigate this issue we analyzed the cardiac phenotype of SAP-IFN-gamma transgenic mice, which constitutively express IFN-gamma in their livers and hence exhibit high circulating serum levels of this cytokine. SAP-IFN-gamma mice spontaneously developed chronic active myocarditis, characterized by the infiltration of not only CD4(+) and CD8(+) T cells but also Mac2(+) (galectin 3(+)) macrophages and CD11c(+) dendritic cells, eventually culminating in cardiomyopathy. Echocardiographic analyses exhibited a left ventricular dilation and impaired systolic function induced by IFN-gamma overexpression. IFN-gamma-mediated cardiotoxicity was associated with high-level cardiac transcription of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-12 and the macrophage-attracting chemokines MCP1 and MIP1-alpha. Myotoxic IFN-gamma effects could not be detected in smooth or striated muscle tissue, suggesting cardiomyocellular specificity of the toxic IFN-gamma effect. The precise mechanism of IFN-gamma cardiotoxicity remains to be elucidated.

Diagnosis of Myocarditis

Determining the etiology of cardiac dysfunction in patients with heart failure influences management and prognosis.1 Myocarditis, diagnosed by the current histopathological Dallas criteria, accounts for &10% of patients with new-onset cardiac dysfunction submitted to endomyocardial biopsy.1,2 Despite complete evaluation including history, physical examination, blood work, echocardiography, coronary angiography, and endomyocardial biopsy, &50% of patients with dilated cardiomyopathy have no etiology identified.1 Recent data suggest that patients in the “idiopathic” category may be suffering from myocardial inflammation due to persistent viral replication or autoimmune activation after a viral infection. These studies raise the question of whether the current histopathological criteria for myocardial inflammation (the Dallas criteria) are sensitive enough to identify the population with viral or autoimmune-related heart compromise. The Dallas criteria were proposed in 1986 and provided a histopathological categorization by which the diagnosis of myocarditis could be established. Dallas criteria myocarditis requires an inflammatory infiltrate and associated myocyte necrosis or damage not characteristic of an ischemic event. Borderline myocarditis requires a less intense inflammatory infiltrate and no light microscopic evidence of myocyte destruction.3 These criteria have been used exclusively by American investigators over the last 2 decades. Sampling error, variation in expert interpretation, variance with other markers of viral infection and immune activation in the heart, and variance with treatment outcomes all suggest that the Dallas criteria are no longer adequate. Chow et al and Hauck et al4,5 demonstrated by biopsying postmortem hearts of patients who had died with myocarditis that, from a single endomyocardial biopsy, histological myocarditis could be demonstrated in only 25% of samples. With >5 biopsies, Dallas criteria myocarditis could be diagnosed in approximately two thirds of subjects. A recent MRI study used focal imaging abnormalities to guide heart biopsy investigation of possible myocarditis. The authors showed that the earliest myocardial …

Sudden death in Whipple's disease.

Despite antibiotic therapy, some patients with uncomplicated Whipple's disease die suddenly and inexplicably. We describe one such patient who died following unexplained cardiorespiratory arrest and was found to have chronic...

Chronic variant of myocarditis associated with hepatitis C virus infection.

Although molecular biological studies suggest a pathogenic link between enterovirus infection and dilated cardiomyopathy (DCM), the frequency of detection of enteroviral RNA is not consistently high in myocardial tissue from patients with DCM. A recent study has suggested that hepatitis C virus (HCV) may also be involved in the development of DCM. We performed genomic analysis for HCV in three patients with chronic active myocarditis. In all three patients, serum aminotransferase activities remained within normal ranges until the terminal stage of heart failure. At necropsy, all three livers showed evidence of tissue damage caused by chronic congestion, and one liver had evidence of chronic hepatitis. Routinely processed, paraffin-embedded tissue blocks of myocardium and liver were analyzed. Renal specimens were also analyzed to exclude the possibility of myocardial contamination with HCV material from the circulating blood. RNA extracted from the heart, liver, and kidney was subjected to strand-specific reverse transcription and amplified by semi-nested polymerase chain reaction. The target nucleotide sequence was a 178-bp fragment of the highly conserved 5'-noncoding region. Both positive- (genomic) and negative-strand RNA (replicative intermediates) were present in myocardial and liver tissue samples from all three patients. However, negative-strand RNA was undetectable in renal tissue from one patient. These findings suggest that HCV replicated in myocardial tissue of these patients with myocarditis. Thus, HCV infection may contribute to the development of this unusual form of myocarditis.

Cardioscopic spectrum of the left ventricular endocardial surface and its relation to histologic changes in idiopathic myocarditis

To examine feasibility of percutaneous cardioscopy for diagnosis of idiopathic myocarditis, cardioscopic appearance of the left ventricle and biopsy findings were compared in 21 such patients. The endocardial surface was milky white, red, pink, or reddish brown and edematous at the segments that exhibited histologic changes of acute myocarditis; purplish red in those that exhibited chronic active myocarditis; and yellow in those that exhibited chronic inactive or healed myocarditis. Follow-up study by repeated cardioscopy and biopsy in six patients revealed that the milky white surface disappeared and that the red, pink, and reddish brown surfaces changed to purplish red and then to yellow or white. The results indicate that the endocardial coloration of the left ventricle represents histologic changes and that cardioscopy is feasible for macroscopic pathologic diagnosis and for follow-up of idiopathic myocarditis.

Early recurrence of chronic active myocarditis after heart transplantation

Early recurrence of chronic active myocarditis after heart transplantation

Successive infection of coxsackievirus B3 and encephalomyocarditis virus: an animal model of chronic myocarditis.

Successive infection of coxsackievirus B3 and encephalomyocarditis virus was investigated as a disease model of chronic myocarditis. Four-week-old C3H/He mice were inoculated with coxsackievirus B3 and then inoculated with encephalomyocarditis virus at 8 weeks old. The hearts were evaluated on histopathological changes compared with those of non-infected mice and mice infected with either virus alone. At 10 weeks old, the hearts of the mice infected successively with both viruses showed co-existence of fibrosis surrounding calcified lesions and marked cellular infiltration with myocardial necrosis. These findings resembled chronic active myocarditis in humans, unlike the lesions due to either virus alone. At 12 weeks old, the hearts of all the infected mice showed fibrosis with scarce cellular infiltration. The successively infected hearts also showed a significantly higher heart weight to body weight ratio than that of the non-infected control mice, and localized wall thinning in the damaged regions. Thus, we conclude that successive infection additively causes myocardial damage that resembles chronic myocarditis and may produce a heart condition similar to dilated cardiomyopathy.

Lymphocytic active myocarditis characterized by numerous clusters of lymphocytes: A chronic variant of myocarditis?

We report three patients with a particular form of myocarditis characterized by numerous clusters of lymphocytes. Their common clinical manifestation was progressive and fatal heart failure with a 3- to 6-year duration. Atrioventricular and intraventricular conduction disturbances were observed in two patients. At necropsy, the hearts weighed 480, 530, and 430 gm, respectively, and showed marked dilatation of the bilateral ventricles and atria, with frequent mural thrombi. Histologic examination revealed numerous lymphocytic clusters and scattered foci of acute myocardial cell damage on a background of extensive fibrosis. We propose the term “chronic active myocarditis” to denote clinicopathologic characteristics of the present cases.

Clinicopathoiogic description of myocarditis

Histologic evidence of myocarditis was demonstrated in 35 of 348 patients submitted to endomyocardial biopsy over 5 years. Analysis of the histologic findings and clinical course of these patients resulted in a new clinicopathologic classification of myocarditis in which four distinct subgroups are identified. Patients with fulminant myocarditis become acutely ill after a distinct viral prodrome, have severe cardiovascular compromise, multiple foci of active myocarditis by histologic study and ventricular dysfunction that either resolves spontaneously or results in death. Patients with acute, chronic active and chronic persistent myocarditis have a less distinct onset of illness.Patients with acute myocarditis present with established ventricular dysfunction and may respond to immunosuppressive therapy or their condition may progress to dilated cardiomyopathy. Those with chronic active myocarditis initially respond to immunosuppressive therapy, but they have clinical and histologic relapses and develop ventricular dysfunction associated with chronic inflammatory changes including giant cells on histologic study. Chronic persistent myocarditis is characterized by a persistent histologic infiltrate, often with foci of myocyte necrosis but without ventricular dysfunction despite other cardiovascular symptoms such as chest pain or palpitation.

Pathogenesis of Sarcocystis falcatula (Apicomplexa: Sarcocystidae) in the Budgerigar (Melopsittacus undulatus) III. Pathologic and Quantitative Parasitologic Analysis of Extrapulmonary Disease

Forty-four budgerigars (Melopsittacus undulatus) were administered sporocysts of Sarcocystis falcatula orally and were examined at necropsy intervals from less than 12 hr to 168 days. Tissue were examined by touch preparations (of organ cut surfaces), light microscopy, and electron microscopy. Meront and cyst burdens were determined in various organs and correlated with duration of infection, inoculum, and the meront or cyst burdens of other organs. Host inflammatory tissue reactions were quantitated and correlated with meront and cyst burdens. Quantitation of meronts was more accurate in tissue sections than in touch preparations, but quantitation of merozoites was better in touch preparations. More than 97% of meronts were found in capillary, venular, and venous endothelial cells. Cysts were found only in cardiac and skeletal myocytes. Merogony began in the lamina propria of the small intestine less than 12 hr postinoculation (PI). Meronts were in liver and lung by the second day PI and in other organs by 3-7 days PI. Mean meront burdens were highest in lung (33 meronts/mm2), lower in liver and kidney (1-3 meronts/mm2), and infrequent in other organs (less than 0.9 meronts/mm2). Cysts were first seen in cardiac myocytes 7 days PI. They developed through the metrocyte stage and then degenerated, rarely reaching maturity. Cysts were first noted in skeletal muscle at 8 days PI. In leg, upper esophagus, and tongue, cysts matured between 44 and 77 days PI. In pectoral muscles, the majority of cysts degenerated during the late metrocyte and early intermediate stages (28-42 days PI). In addition to a previously reported and often fatal acute interstitial pneumonitis, S. falcatula-infected budgerigars also sustained a chronic active hepatitis, interstitial myocarditis, myositis, nephritis, splenitis, and encephalitis. These lesions weakly correlated with meront burdens in most sites during early infection (up to 50 days PI).