Lymphocytic Myocarditis Research Articles

Focal myocardial fibrosis assessed by late gadolinium enhancement cardiovascular magnetic resonance in children and adolescents with dilated cardiomyopathy.

BackgroundDifferent patterns of late gadolinium enhancement (LGE) including mid-wall fibrosis using cardiovascular magnetic resonance (CMR) have been reported in adult patients presenting with non-ischemic dilated cardiomyopathy (DCM). In these studies, LGE was associated with pronounced LV remodelling and predicted adverse cardiac outcomes. Accordingly, the purpose of our study was to determine the presence and patterns of LGE in children and adolescents with DCM.MethodsPatients <18 years of age presenting with severe congestive heart failure who were admitted for evaluation of heart transplantation at our centre underwent CMR examination which consisted of ventricular functional analysis and assessment of LGE for detection of myocardial fibrosis. Ischemic DCM was excluded by coronary angiography, and right ventricular endomyocardial biopsies ruled out acute myocarditis.ResultsThirty-one patients (mean age 2.1 ± 4.2 years) with severe LV dilatation (mean indexed LVEDV 136 ± 48 ml/m2) and LV dysfunction (mean LV-EF 23 ± 8%) were examined. LGE was detected in 5 of the 31 patients (16%) appearing in various patterns characterized as mid-wall (n = 1), focal patchy (n = 1), RV insertion site (n = 1) and transmural (n = 2). Based on histopathological analysis, 4 of the 5 LGE positive patients had lymphocytic myocarditis, whereas one patient was diagnosed with idiopathic DCM.ConclusionsIn children and adolescents with DCM, focal histologically proven myocardial fibrosis is rarely detected by LGE CMR despite marked LV dilatation and severely depressed LV function. LGE occurred in various patterns and mostly in patients with inflammatory cardiomyopathy. It remains unclear whether myocardial fibrosis in childhood DCM reflects different endogenous repair mechanisms that enable favourable reverse remodelling. Larger trials are needed to assess the prognostic implications of LGE in childhood DCM.

Use of SPECT with &lt;sup&gt;99m&lt;/sup&gt;Tc-Pyrophosphate Combined with a Perfusion Myocardium Scintigraphy in the Evaluation of Inflammatory Changes of the Heart in Patients with Persistent Atrial Fibrillation

The purpose was to study the utility of technetium 99m - pyrophosphate in the diagnoses of inflammatory changes of the heart in patients with persistent atrial fibrillation. The study included 30 patients (20 men and 10 women, mean age is 46 ± 9.92 years) with idiopathic persistent atrial fibrillation. To identify the foci of inflammatory changes in the myocardium the scintigraphy with 99mTc-Pyrphotech and myocardial perfusion scintigraphy with 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) was performed before the operation. Later, both scintigrams were combined. During the surgical intervention, in all patients an endomyocardial sampling for histological and immunohistochemical study was performed. Pathological accumulation of 99mTc-Pyrphotech in the myocardium was detected in 8 (26%) of examined patients. In 20% of cases the cause of "idiopathic" form of AF is latent lymphocytic or polymorphocellular myocarditis of viral etiology. Scintigraphy with 99mTc-Pyrphotech can serve as one of the primary methods for non-invasive diagnosis of myocardial inflammation at the given form of arrhythmia.

Improvement of Idiopathic Cardiomyopathy After Colon Clear.

BackgroundThe study aimed to illustrate the effect of colon clear on idiopathic myocardial dysfunction. Helicobacter pylori colonized the stomach since an immemorial time, as if both the stomach and the bacterium used to live together in peace harmless to each other. H. pylori could migrate or get forced to migrate to the colon; antibiotics are seldom effective against extra-gastric H. pylori strains. The association of H. pylori and some cardiovascular diseases like myocarditis and cardiomyopaty has been sufficiently mentioned in literature. The role played by the increased mucosal production of inflammatory mediators (cytokines) induced by H. pylori among patients with ischemic heart diseases has been also clearly illustrated. The clinical association of gastritis and carditis is controversial. Active lymphocytic myocarditis manifested by intractable ventricular tachycardia, non-specific intra-ventricular block, and myocardial dysfunction has been described in a young woman infected with H. pylori; an immune influence has been emphasized in that patient as a possible etiology behind the development of autoimmune myocarditis. It has been reported also in literature that a possible role of autoimmunity induced by H. pylori in cardiomyopathy cannot be excluded.MethodsThree female patients with frank history of H. pylori dyspepsia and an age range of 41 - 47 years have developed myocaditis complicated with cardiomyopathy as confirmed by echocardiography (ECG) and magnetic resonance imaging (MRI). Existence of H. pylori in the colon was confirmed by H. pylori fecal antigen. Colon clear was done for them.ResultsSymptomatic improvement and clinical recovery to sinus rhythm with minimal supra-ventricular extra-systoles occurred for all patients after colon clear. Patients continued improvement to normal cardiac tracing and normal left ventricular ejection function within further 3 - 4 weeks.ConclusionColon clear could be a simple and safe measure to improve changes in cardiac rhythm, heart rate and myocardial function developing in association with H. pylori due to inflammatory, toxic or immune reasons.

Abstract 17506: A Young Man with a Great Fall: Putting the Pieces Together

A 35 year-old-male with hypertension and schizoaffective disorder presented with a first episode of non-prodromal syncope and traumatic fall resulting in a mandibular fracture. Physical examination revealed orthostatic tachycardia, normal cardiovascular examination, and no abnormalities with carotid sinus massage. Electrocardiogram showed NSR at 66 bpm, a single PVC, QTc interval 493 ms, and abnormal ST-T wave contour in V2-V3. Laboratory evaluation revealed normal electrolytes, mildly elevated troponin (0.763), and no leukocytosis. Postural orthostatic tachycardia syndrome was considered unlikely given that syncope did not occur after prolonged standing, and that his use of trazodone and risperidone can both cause orthostatic tachycardia. Transthoracic echocardiography (TTE) revealed decreased systolic function (EF 45%), paradoxical septal motion, normal LV wall thickness, and no valvular disease. Cardiac MRI showed moderate biventricular systolic dysfunction, LVEF 43%, RVEF 33%, mild 4-chamber dilatation, and a small pericardial effusion. Mild T2 hyperintensity in the mid-ventricular septum and anteroseptum, and scattered foci of patchy delayed gadolinium enhancement within the mid-anteroseptal, anterior and anterolateral LV segments were consistent with acute myocarditis. The reported prevalence of myocarditis among patients with sudden death is highly variable and ranges from 2-42%. Various types of myocarditis are associated with arrhythmias, including lymphocytic myocarditis which was the likely diagnosis in our patient. Despite lack of guideline recommendations, we opted to protect our patient with a wearable cardioverter-defibrillator given case reports of successful use for recurrent malignant arrhythmias in myocarditis. Follow-up TTE two months later was normal with EF 60%. Although syncope in the younger population is often appropriately attributed to a neurally-mediated etiology, the current case highlights the need for clinicians to be attuned to the possibility of subclinical myocarditis causing malignant arrhythmias in this setting, in which case the patient may be at risk for recurrent arrhythmia and sudden death and may benefit from the use of a wearable cardioverter-defibrillator.

Myocardial and microvascular inflammation/infection in patients with HIV-associated pulmonary artery hypertension.

Right ventricle compromise affects survival of patients with HIV-associated pulmonary artery hypertension (PAH). Myocardial histology with viral assessment may clarify the mechanism of right ventricular deterioration and provide clues on PAH origin. Fifteen patients with HIV infection, PAH and right ventricular dysfunction underwent cardiac magnetic resonance, catheterization, coronary with ventricular angiography and biventricular endomyocardial biopsy. Endothelial expression of HLA-DR, ICAM-1, E-selectin and VCAM-1 was semi-quantitatively evaluated. PCR for HIV, hepatitis C virus, human herpes virus-6, human herpes virus-8, Epstein-Barr virus, adenovirus, cytomegalovirus, enterovirus, influenza A/B and parvovirus B19 was performed. In PCR-positive hearts, viral protein adenovirus-1 and TORDJI-22 were assessed by immunohistology. New York Heart Association class was 2.4 ± 0.5, mean pulmonary artery pressure 49.93 ± 10.15 mmHg and wedge pressure 9.5 ± 2.19 mmHg. Coronaries were normal with slow flow. Left ventricular and/or right ventricular micro-aneurysms were seen in eight patients. Cardiac magnetic resonance documented increased right ventricular end-diastolic volume with reduced ejection fraction, normal left ventricular end-diastolic volume and left ventricular ejection fraction. Subepicardial/mesocardial oedema and delayed enhancement in the inter-ventricular junction and/or left ventricular inferolateral wall was detected in eight patients. Histology showed active lymphocytic myocarditis in 12 patients, with microvasculitis in three. Endothelial adhesion molecules were over-expressed in all patients. PCR was positive in four patients for hepatitis C virus and in two for adenovirus, and viruses localized both in cardiomyocytes and endothelial cells. Inflammation/infection of myocardium and intramural vessels is detectable in patients with HIV-associated PAH. It may adversely affect right ventricular function and have a role in the compromised pulmonary circulation.

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.

Electrogram Guidance: A Method to Increase the Precision and Diagnostic Yield of Endomyocardial Biopsy for Suspected Cardiac Sarcoidosis and Myocarditis

ObjectivesThe aim of this study was to describe the method used to perform electrogram-guided EMB and correlate electrogram characteristics with pathological and clinical outcomes. BackgroundEndomyocardial biopsy (EMB) is valuable in determining the underlying etiology of a cardiomyopathy. The sensitivity, however, for focal disorders, such as lymphocytic myocarditis and cardiac sarcoidosis (CS), is low. The sensitivity of routine fluoroscopically guided EMB is low. Abnormal intracardiac electrograms are seen at sites of myocardial disease. However, the exact value of electrogram-guided EMB is unknown. MethodsWe report 11 patients who underwent electrogram-guided EMB for evaluation of myocarditis and CS. ResultsOf 40 total biopsy specimens taken from 11 patients, 19 had electrogram voltage <5 mV, all of which resulted in histopathologic abnormality (100% specificity and positive predictive value). A voltage amplitude cutoff value of 5 mV had substantially higher sensitivity (70% vs. 26%) and negative predictive value (62%) than 1.5 mV. Abnormal electrogram appearance at biopsy site had good sensitivity (67%) and specificity (92%) in predicting abnormal myocardium. Normal signals with voltage >5 mV signified normal myocardium with no significant diagnostic yield. Biopsy results guided therapy in all patients, including 5 with active myocarditis or CS, all of whom subsequently received immunosuppressive therapy. There were no procedural complications. ConclusionsIn patients with suspected myocarditis or CS, electrogram-guided EMB targeting sites with abnormal or low-amplitude electrograms may increase the diagnostic yield for detecting abnormal pathological findings.

Lymphocytes Infiltrate the Quadriceps Muscle in Lymphocytic Myocarditis Patients: A Potential New Diagnostic Tool

BackgroundDiagnosing lymphocytic myocarditis (LM) is challenging because of the large variation in clinical presentation and the limitations inherent in current diagnostic tools. The objective of this study was to analyze infiltration of inflammatory cells in quadriceps skeletal muscle of LM patients and investigate the potential diagnostic value of assaying infiltrating inflammatory cells. MethodsQuadriceps muscle tissue, obtained at autopsy from control patients (n = 9) and LM patients (n = 21), was analyzed using immunohistochemistry for infiltration of lymphocytes (CD45), macrophages (CD68), neutrophilic granulocytes (myeloperoxidase), and several lymphocyte subtypes (CD3, CD4, CD8, CD20) and using polymerase chain reaction for a panel of myocarditis-associated viruses. Additionally, quadriceps muscle from mice with acute coxsackievirus B3-induced myocarditis and control mice was analyzed for presence of lymphocytes and virus. ResultsIn quadriceps muscle of LM patients the number of infiltrating lymphocytes were significantly increased and LM was diagnosed with specificity of 100% and sensitivity of 71%. Parvovirus B19 was the primary virus found in our patient groups, found in quadriceps tissue of 3 LM patients (although it was also found in 1 control patient). In the mice, enteroviral RNA was present in the quadriceps muscle, although enteroviral capsid proteins and lymphocyte infiltration were found primarily in the adipose tissue within and directly adjacent to the myocyte tissue, rather than in the myocyte tissue itself. ConclusionsLM is associated with lymphocyte infiltration and viral presence in quadriceps muscle. This indicates that skeletal muscle biopsy/lymphocyte quantification might be a potential diagnostic tool for LM patients.

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.

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.

Recurrent lymphocytic myocarditis in a young male with ulcerative colitis

Awareness of myocarditis in association with inflammatory bowel diseases is crucial as it bears a rare but serious risk for mortality. This report describes the case of a young Caucasian male, whose heart biopsy was tested negative for giant cells and bacterial or viral genomes or proteins. He was experiencing severe lymphocytic myocarditis (other than mesalamine-induced) along with cardiogenic shock during ulcerative colitis exacerbation. This is an extremely rare, if not unique, clinical constellation. We chose to study the epidemiologic grounds and all major aspects of differential pathogenesis and treatment of this serious health problem.

Correlation between Presence of Trypanosoma cruzi DNA in Heart Tissue of Baboons and Cynomolgus Monkeys, and Lymphocytic Myocarditis

Trypanosoma cruzi, the causative agent of Chagas' disease, preferentially infects cardiac and digestive tissues. Baboons living in Texas (Papio hamadryas) and cynomolgus monkeys (Macaca fascicularis) have been reported to be infected naturally with T. cruzi. In this study, we retrospectively reviewed cases of animals that were diagnosed with lymphocytic myocarditis and used a polymerase chain reaction (PCR)-based method (S36/S35 primer set) to amplify T. cruzi DNA from archived frozen and formalin-fixed paraffin-embedded (FFPE) cardiac tissues. We show that the PCR method is applicable in archived frozen and FFPE tissues and the sensitivity is in the femtogram range. A positive correlation between PCR positivity and lymphocytic myocarditis in both baboons and cynomolgus monkeys is shown. We also show epicarditis as a common finding in animals infected with T. cruzi.

Quantitative diagnosis of lymphocytic myocarditis in forensic medicine

The aim of this study was to establish quantitative diagnostic criteria for lymphocytic myocarditis on autopsy samples by using a stereological cell profile counting method. We quantified and compared the presence of lymphocytes and macrophages in myocardial autopsy specimens from 112 deceased individuals who had been diagnosed with myocarditis according to the Dallas criteria and 86 control subjects with morphologically normal hearts.We found the mean number to be 52.7lymphocyte profiles/mm2 (range 3.7–946; standard deviation 131) in the myocarditis group and 9.7 (range 2.1–25.9; standard deviation 4.6) in the control group. The cut-off value for the diagnosis of myocarditis was determined by calculating sensitivity plus specificity, which reached the highest combination at 13lymphocyte profiles/mm2 (sensitivity 68%; specificity 83%). A considerable proportion of subjects in both the myocarditis and control groups had lymphocyte profile counts below 30/mm2, representing a diagnostic challenge due to the increased risk of creating false negative or false positive results. We found it practically impossible to obtain a reliable macrophage count.The present data add new important information on lymphocyte counts in inflamed and non-inflamed myocardium. We suggest a cut-off value in the range of 11–16lymphocyte profiles/mm2 for a reliable diagnosis of lymphocytic myocarditis from autopsy samples. To evaluate small inflammatory changes at low lymphocyte counts, a multidisciplinary approach should be implemented, in which diagnostic tools are used ancillary to histological examination. We advise against semi-quantification of macrophages based on cell profile counting.

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.

Formation of the inflammasome in acute myocarditis

Acutemyocarditisisanin flammatorydisorderoftheheartmuscleinwhichtheseverityofinjurydependsbothonthenatureoftheoffendingagent(i.e.virus)andontheensuinginflammatoryresponse.Thede fini-tion excludes, however, the response to ischemic or toxic injury. Theheart, however, like other organs, may provide a stereotyped responsetoinjury.Followingischemicinjury,theformationoftheinfl ammasomein the heart promotes heart failure [1].Theinflammasome is a macro-molecular structure activated during injury that amplifies the responseby processing Interleukin-1β (IL-1β) and IL-18, and promotion of celldeath [2]. Viral infections may lead to either death of the virus and thecell (pyroptosis), or survival of both cell and virus with persistence ofthe infection through inhibition of the inflammasome (evasion) [3].Therearenoreportsoftheinflammasomeinacutemyocarditis.Wehy-pothesize that the viral infection or the ensuing cellular destructionleads to the formation of the inflammasome, providing an opportunityto explore inflammasome-related markers for diagnostic or prognosticpurposes. Furthermore at present day, there are no specific treatmentsfor acute myocarditis, and thus inhibitors of the inflammasome couldrepresent a new therapeutic approach.We studied samples obtainedthrough endomyocardialbiopsy in11patients with acute lymphocytic myocarditis (b4 weeks of symptomsonset) in Trieste, Italy. The diagnosis was based upon pathology exam-ination and clinical scenario (Table 1). As a comparison group westudied autopsy samples of 11 patients with acute myocarditis diag-nosed post mortem, and 5 control subjects who had died withoutacute myocarditis or other acute cardiac conditions.Weemployedimmunofluorescencestainingtodetectin flammasomeaggregatesusingantibodiesraisedagainstthescaffoldprotein,ApoptosisSpeck-like protein containing a caspase-1 recruiting domain (ASC), and/or the effector protein, caspase-1, as previously described [1].Tocharac-terizethetypeofcell,weusedadoublestainingtechniquewithantibod-ies against cardiac actin to identify cardiomyocytes, S100A4 to identifyfibroblasts, andCD31 forendothelialcells. To overcomefor the auto fluo-rescence of sarcomeric proteins, we used a solution of 1% Sudan black in70% ethanol for 5 min. Images of samples were acquired with an IX70microscope and cellSens Dimension di gital imaging software (Olympus,Central Valley, PA) using a 40× objective (400× magnification). Filtersets for each separate fluorescence-conjugated antibody were layeredtorenderacompositeimage.Theinflammasome “specks” were countedby cell type (cardiomyocyte, leukocytes, fibroblasts and endothelialcells) per high power field of view (40×). Data are presented as medianand interquartile range and non-parametric Mann–Whitney test wasused.Intracellularaggregates of ASC and/ or caspase-1 indicative of the for-mation of the inflammasome were seen in leukocytes, cardiomyocytes,fibroblasts and endothelial cells in heart biopsy samples of all 11 cases(100%), and in heart samples of 10 of 11 post-mortem cases (91%), andin none of the controls (0%, P b 0.002)(Fig. 1). ASC aggregates co-localized with caspase-1 aggregates in virtually all cases. The numberof inflammasomes was variable across cases ranging between 3 and 14specks in biopsies, and between 0 and 45 specks per field in autopsies,without statistically significant differences (data not shown). Some

Capabilities of 99mTc-pyrphotech single-photon emission computed tomography in combination with myocardial perfusion scintigraphy in the evaluation of inflammatory changes in the heart of patients with persistent atrial fibrillation

To estimate the capabilities of 99mTc-pyrphotech single-photon emission computed tomography (SPECT) in the diagnosis of myocardial inflammatory changes in patients with persistent atrial fibrillation (AF). Nineteen patients (11 males and 8 females, mean age 47.46 ± 9.92 years) with persistent idiopathic AF underwent preoperative complete clinical and instrumental examination. 99mTc-pyrphotech SPECT was performed to identify foci of myocardial inflammatory changes. After completing 99mTC-pyrphotech scanning, resting myocardial perfusion scintigraphy with 99mTC-methoxyisobutylisonitrile (99mTc-MIBI) was performed in accordance with the standard protocol. The scintigrams obtained in both studies were then combined using the applied programs Jet Stream Workspace Release 2.5 (Philips) and the application Fusion. During invasive intervention, endomyocardial samples were intraoperatively taken from all the patients for histological and immunohistochemical examinations. Abnormal 99mTc-pyrphotech myocardial accumulation was found in 7 (36.8%) of the examinees, multiple foci in 3 cases and single foci in 4. Analysis of perfusion scintigrams indicated that the mean abnormal accumulation of 99mTc-MIBI in the left ventricle was 3.75 ± 0.88% (maximum 9%). Histological examination of endomyocardial samples from 19 patients with persistent AF verified myocarditis in 4 (21%) patients and myocardial sclerosis concurrent with other abnormalities in 15 (78.9%) patients. Latent lymphocytic or polymorphic cellular myocarditis of viral etiology is a cause of idiopathic AF in 20% of the cases. 99mTc-pyrphotech scintigraphy may be one of the primary noninvasive diagnostic techniques for the detection of myocardial inflammation in this form of arrhythmia.

Myocardial extracellular space volume in patients with systemic sarcoidosis: quantitative measurement using a T1 mapping technique

Cardiac involvement is a major risk factor for sudden death in patients with systemic sarcoidosis. Pathologically, cardiac sarcoid lesions can be classified as early (mainly lymphocytic, similar to lymphocytic myocarditis), intermediate (active granulomatous), and late phase (primarily scar). These pathological processes can affect the myocardial extracellular space volume (ECV) in cardiac sarcoid. We hypothesize that quantitative measurement of ECV using a T1 mapping technique with CMR may yield new insights for the assessment of cardiac

Immunosuppressive therapy in myocarditis.

Although there is general agreement on the favorable effect of immunosuppression in eosinophilic, granulomatous, giant-cell myocarditis and in lymphocytic myocarditis associated with connective tissue disorders and with rejection of a transplanted heart, its therapeutic role in lymphocytic inflammatory cardiomyopathy (ICM) is still debated. Previous retrospective studies reported a relevant clinical benefit in 90% of patients with virus-negative ICM and no response or cardiac impairment in 85% of those with virus-positive ICM following immunosuppression. Other studies identified cardiomyocyte HLA upregulation as an additional indicator of ICM susceptibility to immunosuppressive therapy. Recently in a single-center randomized prospective double-blind trial using a combination of prednisone and azathioprine in addition to supportive treatment in 85 virus-negative ICM patients, a significant improvement in left ventricular (LV) ejection fraction and a significant reduction in LV dimensions in 88% of 43 treated patients compared with 42 patients receiving placebo who showed a cardiac impairment in 83% of cases (TIMIC study) was reported. These data confirm the efficacy of immunosuppression in virus-negative ICM. Lack of response in 12% of cases suggests the presence of unscreened viruses or mechanisms of damage and inflammation not susceptible to immunosuppression. Recovery of cardiac function in responders to immunosuppression was associated with inhibition of cardiomyocyte death, increased cell proliferation and with newly synthesized contractile material.

Fatal Subacute Myocarditis Associated with Human Bocavirus 2 in a 13-Month-Old Child

Human bocavirus has rarely been incriminated in fatal or life-threatening respiratory infections. We report a case of fatal disseminated infection with subacute lymphocytic myocarditis in a 13-month-old child. The human bocavirus 2 genome was detected by PCR analysis in nasal swab, plasma, urine, ascitic fluid, and mesenteric node, skeletal muscle, and lung tissue specimens.

Heart pathologies in dolphins stranded along the northwestern Italian coast

Nine striped dolphins Stenella coeruleoalba and 1 bottlenose dolphin Tursiops truncatus stranded along the Ligurian Sea coast of Italy were necropsied between February 2011 and April 2012. Macroscopic and histological findings were observed in the hearts of all animals and included saccular aneurysms of the pulmonary trunk (n = 3), cirsoid aneurysms (n = 1), right ventricular dilation (n = 1) associated with hypoplasia of the tricuspid chordae (n = 1), valvular fibrosis (n = 3), mitral leaflet thickening (n = 1), left ventricular hypertrophy (n = 1), lymphocytic myocarditis (n =1), and Lambl's excrescences (n = 4). To our best knowledge Lambl's excrescences, aneurysm of the pulmonary trunk, and cirsoid aneurysms have not previously been described in marine mammals, and some of these findings should be taken into account as possible causes of dolphin morbidity, mortality, and stranding.