Granulomatous Myocarditis Research Articles

Granulomatous myocarditis arising from intravesical Bacillus Calmette–Guérin therapy leading to death diagnosed by postmortem examination: a case report

BackgroundIntravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach.Case presentationWe present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus.ConclusionGranulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

Eosinophilic Granulomatous Myocarditis in Two Pigs

Eosinophilic myocarditis is a human condition that has been rarely documented in animals. We now report two unrelated porcine cases of idiopathic eosinophilic granulomatous myocarditis that resembled the human disease and which were associated with sudden death. The most relevant gross finding in both cases was marked cardiomegaly, accompanied by raised, multifocal to coalescent small white nodules (1-2mm) and poorly demarcated multifocal pale areas in the epicardium. Histologically, there were multifocal to coalescent areas of cardiomyocyte loss with replacement by an intense inflammatory infiltrate of eosinophils and epithelioid macrophages, and proliferation of fibrous connective tissue. Immunohistochemistry for porcine circovirus type 2 (PCV2) and Toxoplasma gondii, in-situhybridization and quantitative polymerase chain reaction tests for PCV2 and porcine circovirus type 3 and aerobic bacterial culture on myocardium samples were negative.

Listeriosis with viral coinfections in 8 gray foxes, 8 wild turkeys, and 2 young cervids in the southeastern United States.

Listeria monocytogenes is a bacterium that can cause disease in many species, including humans, livestock, and wildlife. Increased interactions via shared habitats may promote pathogen transmission among these groups. Our objectives were to evaluate the Southeastern Cooperative Wildlife Disease Study diagnostic data to characterize and compare L. monocytogenes-induced lesions and comorbidities in gray foxes and wild turkeys, and to describe cases of listeriosis in 2 cervids. From 1991-2020, 8 gray foxes, 8 wild turkeys, a neonatal elk, and a white-tailed deer fawn from several eastern states in the United States were diagnosed with listeriosis. All 8 foxes had hepatitis and/or hepatic necrosis with intralesional gram-positive bacilli, and concurrent canine distemper virus (CDV) infection; 2 of the foxes had been vaccinated recently for CDV. L. monocytogenes was cultured from the liver (6 of 8) or lung (2 of 8) of foxes. Lesions in wild turkeys included hepatocellular necrosis (3 of 8), heterophilic hepatitis (1 of 8), heterophilic granulomas (1 of 8), intrasinusoidal gram-positive bacilli without hepatic lesions (1 of 8), granulomatous dermatitis (1 of 8), and/or granulomatous myocarditis (2 of 8). Lymphoproliferative disease viral DNA was detected in 5 of 6 turkeys tested; reticuloendotheliosis viral DNA was detected in 2 of 3 turkeys tested. Both cervids had systemic listeriosis, with L. monocytogenes isolated from liver. Immunohistochemistry for Listeria spp. on select cases revealed immunolabeling in affected organs. Listeriosis was thus established as a cause of morbidity and mortality in 3 wildlife species, which often suffered from concurrent infections and likely immunosuppression.

Granulomatous Myocarditis After Cardiac Transplantation for Giant Cell Myocarditis

<h3>Introduction</h3> Cardiac sarcoidosis and idiopathic giant cell myocarditis are uncommon but serious inflammatory cardiomyopathies which share some clinical and histopathologic features. We present the case of a patient who developed end-stage heart failure due to giant cell myocarditis requiring heart transplant, and years after transplantation, developed cardiac sarcoidosis <h3>Case Report</h3> A 45-year-old man with no significant medical history was preparing for a triathlon but began to experience subacute heart failure symptoms culminating in a sudden cardiac arrest shortly after endomyocardial biopsy (EMBx) revealing giant cell myocarditis. He required ECMO cannulation as a bridge to biventricular HeartWare HVADs and was treated with cyclosporin. After 10 months of biventricular support, he underwent heart transplant. Post-operative course was uneventful and was maintained on standard immunosuppression with tacrolimus, mycophenolate, and prednisone. At three-years post-transplant, he was transitioned to sirolimus and remained stable. During his sixth annual visit, he noted exertional intolerance. His echocardiogram revealed a drop in his left ventricular ejection fraction from 58% to 47%, an increase LVIDd from 41 mm to 51 mm, and an increase in LV mass index from 70 to 80 g/m2. He also had a cardiopulmonary exercise stress test and his peak VO2 went from 36 ml/(min/kg) to 32.9 (ml/min/kg). Event monitor showed PVC's and non-sustained VT. Coronary angiogram showed mild non obstructive cardiac allograft vasculopathy. Endomyocardial biopsy revealed an active granulomatous myocarditis which had the appearance of sarcoidosis. His steroid regimen was augmented to prednisone 30 mg daily, then tapered. Three months after immunosuppression changes, cardiac PET scan revealed findings compatible with an inflammatory cardiomyopathy process associated with edema, fibrosis and scar. Tacrolimus was added to his regimen, mycophenolate dose was increased and received 3 days of pulse dose steroids <h3>Summary</h3> While previous descriptions of recurrent sarcoidosis in cardiac allografts have been described, the unique features of GCM on native heart explantation and clear features of sarcoidosis in the allograft despite adequate immunosuppression highlight not only the challenges with regard to management of active myocarditis after transplant but also the overlap of the two disease entities

Epidemiology, Pathogenesis, and Diagnosis of Cardiac Sarcoidosis

Cardiac sarcoidosis (CS) is a widely underdiagnosed yet clinically significant form of granulomatous myocarditis associated with significant morbidity and mortality. Clinical presentation ranges from silent cardiac involvement detected on imaging to cardiomyopathy or sudden cardiac death. Diagnosis of CS remains challenging due to the lack of sensitivity and specificity of any single diagnostic method, underscoring the importance of elevated clinical suspicion and the use of multimodality imaging to guide diagnosis and treatment. In this review, we discuss the epidemiology, pathogenesis, clinical features, and diagnosis of this clinically evading and enigmatic disease.

Recurrent Granulomatous Myocarditis after Heart Transplant

<h3>Introduction</h3> Recurrent granulomatous myocarditis is an uncommon phenomenon after heart transplantation. We present a case of late recurrent granulomatous myocarditis after heart transplant. <h3>Case Report</h3> A previously healthy gentleman presented with complete heart block requiring placement of a permanent pacemaker. He subsequently developed reduced left ventricular function and progressive heart failure, prompting an endomyocardial biopsy which revealed granulomatous myocarditis. He was treated with steroids but his symptoms progressed and ultimately underwent orthotopic heart transplant. Pathologic examination of the explanted heart revealed "Florid granulomatous inflammation throughout the myocardium, with dense scar that is patchy and irregularly distributed." 7 Years after transplant he developed severe rapid onset heart failure symptoms. Transthoracic echocardiography revealed a newly reduced left ventricular ejection fraction of 35 %. Urgent catheterization and endomyocardial biopsy was performed revealing mild single vessel allograft vasculopathy, mildly elevated filling pressures and a cardiac index of 2 liters per minute per meter squared. Pathologic examination of the biopsy revealed myocardium with significant inflammation including numerous eosinophils and scattered multinucleated giant cells with myocyte damage. Cardiac magnetic resonance imaging (CMR) was performed revealing late gadolinium enhancement in the apical lateral, and basal anteroseptal walls [Figure] with prolonged T2 time suggestive of edema. He was treated with high dose steroids, intravenous diuretics were administered, and he clinically recovered symptomatically and continues to follow in clinic. <h3>Summary</h3> Granulomatous myocarditis caused by giant cell myocarditis or cardiac sarcoidosis can lead to end stage heart failure and necessity for heart transplant. Recurrence of the granulomatous inflammation can lead to graft dysfunction and can be identified by endomyocardial biopsy as well as noninvasive imaging with CMR.

Pre-Treatment Myocardial 18FDG Uptake Predicts Response to Immunosuppression in Patients With Cardiac Sarcoidosis

ObjectivesThis study identified predictors of clinical (CR) and echocardiographic response (ER) following immunosuppressive therapy (IST) in patients with cardiac sarcoidosis (CS). BackgroundIST has been the cornerstone of treatment for patients with CS and active myocardial inflammation. However, there are little data to explain the variable response to IST in CS. MethodsData of 96 consecutive patients with CS from the Granulomatous Myocarditis Registry were analyzed. All patients underwent a 18fluorodeoxy glucose positron emission tomography−computed tomography (18FDG-PET-CT) before initiation of IST. Response was assessed after 4 to 6 months of therapy. CR was defined as an improvement in functional class (New York Heart Association functional class ≥I) and freedom from ventricular arrhythmias and heart failure hospitalizations. ER was defined as an improvement in left ventricular ejection fraction (LVEF) ≥10%. ER was assessed only in patients with a LVEF <50%. Complete responders had no residual myocardial FDG uptake and fulfilled both response criteria. Partial responders fulfilled only 1 response criteria or had residual FDG uptake. Nonresponders did not fulfill either CR or ER criteria. The uptake index (UI) was defined as the product of maximum standardized uptake value and the number of LV segments with abnormal uptake on 18FDG-PET-CT. ResultsAmong 91 patients included in the final analysis, 54.9%, 20.9%, and 24.2% of patients were classified as complete and partial responders and nonresponders, respectively. Cox regression analysis (all responders vs. nonresponders) identified the following as independent predictors of response following immunosuppression: LVEF >40% (hazard ratio: 1.61; 95% confidence interval: 1.06 to 7.69; p = 0.031) and myocardial UI >30 (hazard ratio: 1.28; 95% confidence interval: 1.05 to 6.12; p = 0.010). The final model had a good discriminative power (area under the curve [AUC]: 0.85) and predictive accuracy (sensitivity: 85.5%; specificity: 86.4%). Pre-treatment myocardial UI had a strong positive correlation with change in LVEF following immunosuppression. ConclusionsPre-treatment 18FDG myocardial uptake was a predictor of CR and ER response to immunosuppression in patients with CS.

Putative role of prosthetic dental implants in the development of cardiac sarcoidosis: A case-control study.

Background:Etiopathogenesis of cardiac sarcoidosis is poorly understood. The objective of this study is to examine a possible role of previous dental procedures on the development of cardiac sarcoidosis (CS).Methods:Clinical details of 73 patients with CS from the Granulomatous Myocarditis Registry were extracted. Data regarding clinical presentation, comorbidities, baseline electrocardiogram, echocardiogram, and 18fluorodeoxyglucose(FDG) PET-CT was extracted from the registry database. A comprehensive history of dental procedures for all patients was recorded. The two control groups comprised of 79 patients with idiopathic ventricular tachycardia and/or complete heart block (with similar clinical presentation) and 145 healthy age and sex matched patients, respectively.Results:Dental evaluation revealed that patients with CS had undergone a previous prosthetic dental implant(PI) (OR 12.4, 95% CI 4.0-38.1, p<0.001) or root canal treatment (RCT) (OR 2.43, 95% CI 1.12-5.26, p=0.025) more often than the healthy controls. The patients with CS and previous dental procedures had higher18FDG uptake in the LV myocardium (SUV max 8.6±3.3vs.5.5 ±1.8 (mean±SD), p<0.001) and mediastinal lymph nodes (9.3±4.6vs.5.4±1.7 (mean±SD), p<0.001) as compared to patients who did not undergo a dental procedure. The subset of CS patients with a previous PI or RCT had higher uptake levels in the myocardium (max SUV 9.4±3.1vs.6.7±2.0, p=0.011, number of abnormal LV Segments 10.3±3.1vs.6.5±2.8(mean±SD), p=0.008) and mediastinal lymph nodes(max SUV 10.5±4.8vs. 7.2±1.8,p=0.002) compared to those who underwent crowning or extraction. In addition, CS was diagnosed after a shorter latency period (47.3±21.0vs.81.6±25.3 months (mean±SD), p<0.001) following PI and RCT compared to other dental procedures.Conclusions:We observed a significant association between PI and RCT and the occurrence of CS. This group of patients also appear to have a more severe form of the disease.

Stroke in cardiac sarcoidosis: Need to worry?

ObjectivesThe occurrence of stroke in patients with cardiac sarcoidosis (CS) is an under-recognized entity. The objective of this study is to evaluate the clinical presentation, risk factors, etiology, temporal relationship and management of stroke in patients with CS. MethodsThe data of 111 patients with CS from the Granulomatous Myocarditis Registry was analyzed. Clinical data regarding the clinical presentation, risk factors for vascular disease, electrocardiogram, echocardiogram and 18 Fluorodeoxyglucose (FDG) PET-CT were extracted from the registry database. ResultsAmong the 111 patients with CS, 8 patients (7.2%) had a history of ischemic stroke.Six of the eight patients with ischemic stroke were young (<50 years) without conventional risk factors for vascular disease. In five patients, stroke occurred prior to the diagnosis of CS. In all except one patient the ischemic stroke occurred in the anterior cerebral circulation. LV dysfunction was noted in all patients at the time of stroke, with the presence of an LV apical clot in four of the eight patients. Atrial fibrillation was documented in 2 patients. Two patients received thrombolysis and mechanical thrombectomy, while the others were treated with standard antiplatelets and statins. There was a significant improvement in the LV Ejection fraction (33.6 ± 15.2 to 49.1 ± 13.8%, p = 0.043) following immunosuppression. Two patients developed refractory HF and respiratory sepsis, respectively, and succumbed following prolonged ICU admissions. ConclusionsIschemic stroke in patients with CS can be attributed to a cardioembolic phenomenon. A high index of clinical suspicion is needed for early diagnosis and management of these patients.

Serum angiotensin converting enzyme, Erythrocyte sedimentation rate and high sensitive-C reactive protein levels in diagnosis of cardiac sarcoidosis- where do we stand?

BackgroundCardiac sarcoidosis (CS) is increasingly being recognized in the last two decades. The diagnosis of CS depends on clustering of multiple symptoms, investigations and demonstration of a non-caseating granuloma on histopathology. Serum Angiotensin Converting Enzyme (SACE) level, one of the serological markers, is often elevated in systemic sarcoidosis. However, the yield of SACE level among patients with isolated or predominant CS is unclear. We conducted a retrospective study to assess the prevalence of elevated SACE level among patients with proven CS. Materials and methodsFrom our Granulomatous myocarditis (GM) registry, 45 biopsy proven CS patients were enrolled. Inclusion criteria: Clinical diagnosis of CS [HRS definition + Lymph Node biopsy/Endomyocardial biopsy (non-caseating granuloma)]. Exclusion criteria - Other causes of GM like cardiac tuberculosis (TB culture/AFB smear -positive) and patients taking medications affecting SACE level. ResultsAmong 143 GM cases, 45 CS were analyzed. Mean age:42 ± 11 years (Range 22–63 years, 19 females). With our laboratory reference of SACE (Normal range: 20–70 U/L), 3 out of 45 (6.7%) patients of CS had elevated SACE. In a comparative analysis we found, Erythrocyte Sedimentation Rate (ESR) and High sensitive-C Reactive Protein (Hs-CRP) are much more sensitive, although not specific for CS. Patients with pulmonary involvement more often had elevated SACE level. ConclusionSerum ACE is elevated only in approximately 6.7% of patients with biopsy proven CS. Hence, it is insensitive serological tool for diagnosis of CS even in the active phase of the disease. In contrast, ESR and Hs-CRP emerges to be more sensitive markers of active CS.

GIANT CELL MYOCARDITIS: A SILENT BUT DEADLY KILLER

SESSION TITLE: Cardiovascular Cases SESSION TYPE: Med Student/Res Case Report PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Giant cell myocarditis (GCM) usually affects previously healthy adults and is a rapidly progressive and frequently fatal disease, accounting for approximately 17% of all myocarditis fatalities. Early diagnosis is critical, with evidence showing rapidly instituted cyclosporine-based immunosuppression can improve transplant-free survival. CASE PRESENTATION: A 56 year old male with a history of Type 2 Diabetes presented with 1 week of exertional dyspnea and lightheadedness. Initial exam and tests were remarkable for a mild Troponin leak. EKG revealed Left bundle branch block and transthoracic echocardiogram (TTE) showed a normal ejection fraction (EF) and Left Ventricular (LV) internal Dimension-Diastole of 5.4cm. Stress test, nuclear imaging and Left Heart Catheterization were normal. An event monitor documented exercise induced bradycardia leading to the placement of a dual chamber pacemaker. Repeat ECHO done at the time showed normal EF and a mild circumferential pericardial effusion. In the following two months the patient developed worsening exertional dyspnea (NYHA III). A CT angiogram revealed a large pericardial effusion with tamponade physiology. The aspirate showed 304 cells with 94% monocytes, protein of 4.4g/dl, and cytology revealed reactive mesothelial and chronic inflammatory cells. CRP was elevated. Repeat ECHO showed LV EF of 30% with akinesis of inferior and inferolateral wall as well as diffuse hypokinesis and severely increased RV size and RV thrombus. He was begun on anticoagulation. Subsequently, right heart catherization showed elevated RA pressures and cardiac MRI showed Biventricular dilation and nondiagnostic delayed gadolinium enhancement imaging. Endomyocardial biopsy from RV was not suggestive of GCM. Patient subsequently developed progressive cardiogenic shock requiring dual Ventricular Assist Device placement. On analysing excised core of LV apex for cannula placement, it revealed granulomatous myocarditis with Giant cell formation and pericarditis. He was started on milrinone, high dose steroids and anticoagulation for suspected GCM. An RVAD was placed. Eventually patient returned with fulminant septic shock and died. DISCUSSION: This case reveals the rapidly progressive nature of GCM,which from presentation, has a median survival of 3 months to death or transplant without appropriate therapy. Biopsy is diagnostic in >70% cases if done early, however false negatives are frequent due to the patchy nature of the disease CONCLUSIONS: With immunotherapy, the 5-year survival rate free of transplant is between 52-72%. Transplant is an effective strategy however GCM can recur in around 25% of transplanted hearts. Reference #1: Giant Cell Myocarditis: A Brief Review ; Arch Pathol Lab Med. 2016 Dec;140(12):1429-1434 : Xu J, Brooks EG Reference #2: Diagnosis, Treatment, and Outcome of Giant-Cell Myocarditis in the Era of Combined Immunosuppression;Riina Kandolin, Jukka Lehtonen, Kaisa Salmenkivi: DOI:10.1161/CIRCHEARTFAILURE.112.969261 Reference #3: Idiopathic Giant-Cell Myocarditis — Natural History and Treatment; Leslie T. Cooper, Jr., Gerald J. Berry : N Engl J Med 1997; 336:1860-1866 DISCLOSURES: No relevant relationships by Tanya Chandra, source=Web Response No relevant relationships by Abhas Khurana, source=Web Response No relevant relationships by Osama Mukarram, source=Web Response No relevant relationships by Anand Muthu Krishnan, source=Web Response No relevant relationships by Rudra Ramanathan, source=Web Response No relevant relationships by Nitya Sthalekar, source=Web Response

Prognostic value of fluorine-18 fluoro-2-deoxyglucose positron emission computed tomography in patients with unexplained atrioventricular block

The cause of atrioventricular conduction block (AVB) remains unexplained in a significant number of patients. Granulomatous myocarditis is an uncommon but important cause of AVB. Fluorine-18 fluoro-2-deoxyglucose positron emission computed tomography (18-FDG PET) scan has emerged as a sensitive tool for diagnosing granulomatous myocarditis. The purpose of this study was to evaluate the prognostic value of 18-FDG PET scan in patients with unexplained AVB. Patients age 18-55 years presenting with unexplained AVB and requiring a permanent pacemaker were evaluated with a fasting 18-FDG PET scan. Transthoracic echocardiography was performed at baseline and at follow-up. Major adverse cardiac events (ventricular tachycardia, heart failure, cardiac death) were noted during follow-up. Over a period of 3 years, 35 patients (20 females, 15 males; mean age 43.67 ± 11.21 years) were included in the study. Abnormal myocardial FDG uptake was noted in 15 patients (42.8%). Four patients consented for biopsy of paracardiac FDG avid lymph nodes, which revealed granulomatous inflammation (one of which grew Mycobacterium tuberculosis in culture). Mean follow-up period was 24 months. Major adverse cardiac events were significantly higher in the patients with abnormal PET uptake (P < .01) compared to those with normal scans. Patients with high-degree AVB and abnormal myocardial 18-FDG PET uptake have more adverse cardiac events and worse outcomes. Early screening for myocardial inflammation and appropriate treatment may prevent these complications. Tuberculosis may be an important cause of unexplained AVB, apart from sarcoidosis, in developing countries such as India.

THE ROLE OF IMMUNITY SUPPRESSION IN TREATMENT OF MYOCARDITIS

Regardless the common consensus on the benefits of immunity suppression in eosinophilic, granulomatous, giant cell and lymphocyte myocarditis, associated with systemic connective tissue diseases, and in rejection of transplanted heart, role of immune suppression therapy (IST) in treatment of lymphocyte inflammatory cardiomyopathy remains controversial. Previous retrospective studies revealed clinical improvement in 90% of patients with virus-negative inflammatory cardiomyopathy and absence of response or worsening of heart function in 85% of virus-positive inflammatory cardiomyopathy after immunity suppression. Other studies identified the enhanced expression of HLA in cardiomyocytes as an additional indicator of sensitivity of inflammatory cardiomyopathy to IST. Recently, the singlecenter randomized study was performed with double blind application of prednisone and azatioprin as addition to maintenance therapy in 85 patients with virus-negative inflammatory cardiomyopathy. The results of the study showed significant improvement of the left ventricle ejection fraction and decrease of the left ventricle dimensions in 88% patients among 43 of treated comparing to 42 patients on placebo demonstrated worsening of cardiac functioning in 83% cases (the TIMIC study). This data confirms the efficacy of immunity suppression in virus-negative inflammatory cardiomyopathy. Insufficiency of response in 12% cases undermines existence of non-revealed viruses and mechanisms of damage and inflammation, non-sensitive to immunity suppression. Restoring of cardiac function in patients actively responded to immunity suppression, was determined by inhibition of cardiomyocytes death and increase of cells proliferation with ad novo synthesized contractile material.

Safety and efficacy of epicardial approach to catheter ablation of ventricular tachycardia – An institutional experience

Background and aimEpicardial approach to VT ablation increases the success rate of ablation but is not without complications. We studied the safety and efficacy of epicardial VT ablations performed at our institute. MethodsAll patients who underwent epicardial VT ablation at our institute were studied retrospectively. The outcome of VT ablation was among three groups: ischaemic cardiomyopathy (ICM), non-ischaemic cardiomyopathy (NICM) and granulomatous myocarditis (GM). Safety outcomes assessed included all complications considered to be due to pericardial access or epicardial mapping/ablation. ResultsA total of 54 patients (total 119 VTs, mean 2.2 (0.9)) were taken up for ablation procedure through epicardial access. Mean age: 47 (10) years, males: 83%. All patients had drug resistant recurrent VTs. The epicardial procedure was abandoned in three patients due to access issues; percutaneous sub-xiphoid access was employed in 48 and surgical approach in four patients. Complete success was achieved in 59% and partial success in 76%. The outcomes were poor in ICM patients as compared to those with GM and NICM. Overall success rates for all clinical VTs were 89% in GM, 90% in NICM and 67% in ICM. Success rates for epicardial VT ablation were 94%, 85% and 78% respectively for GM, NICM and ICM. Procedure related complications occurred in six patients. ConclusionEpicardial ablation for VT offers good immediate outcomes with acceptable safety profile.

Differential diagnosis of arrhythmogenic right ventricular cardiomyopathy and granulomatous myocarditis by advanced ECG analysis

In nearly 12% of cases arrhythmogenic cardiomyopathy can be diagnosed without any typical ECG changes [1]. In the latest classification published by Frank Marcus in 2010 epsilon waves and T-wave inversions in right precordial leads are major ECG criteria that leads together with imaging techniques, formation of ventricular extrasystole and genetic information to the diagnosis of arrhythmogenic cardiomyopathy [2]. If typical ECG findings are missing atypical ECG changes like localized right precordial QRS prolongation, QRS fragmentation and typical changes in lead aVR (amplitude of Q wave 3 mm or more and R wave 2 mm or less and inverted T-waves) have been described [3]. We report a 50-year-old male patient whowas admitted to hospital because of chest pain and ventricular extrasystole. ECG revealed incomplete right bundle branchblock and no typical or atypical sign for arrhythmogenic cardiomyopathy (Fig. 1). Echocardiography showed normal contracting left ventricle and no signs of valvular dysfunction. The right ventricle had a sacculation in the right ventricular outflow tract without dilatation, a dilatation of the inferior region and sacculations of the apical area (Fig. 2). Coronary angiography showed normal coronary arteries and left ventricular angiography revealed normal contracting left ventricular without any segmental contraction impairment. But right ventricular angiography was abnormal with sacculation of the inferior region and a deep horizontal fissure of the apical segment.

FQRS as a marker of granulomatous disease in patients presenting with ventricular tachycardia and normal left ventricular ejection fraction

BackgroundGranulomatous myocarditis may present with sustained monomorphic ventricular tachycardia (SMVT) in the presence of normal left ventricular ejection fraction (LVEF), and could be mistaken for idiopathic ventricular tachycardia (IVT). The use of cardiac imaging for diagnosis can be limited by availability and high cost. ECG is readily available and inexpensive. Fragmented QRS (fQRS) on ECG has been found to be associated with myocardial scar. We hypothesized that fQRS could be useful in the diagnosis of granulomatous VT (GVT). MethodsWe compared the 12-lead ECG of 16 patients with GVT and 42 patients with IVT who presented with SMVT. ResultsThe presence of fQRS was significantly higher in the GVT group compared to the IVT group (75% versus 19.1%, p < 0.001). The location of fQRS correlated with delayed enhancement cardiac magnetic resonance imaging (DE-CMR) in the same segment in 4/16 patients in the GVT group. It correlated with an affected segment on either DE-CMR or 18FDG positron emission computed tomography in 4/11 patients in the GVT group who had both imaging modality. Whenever fQRS was present in contiguous leads other than the inferior leads, it always corresponded to an affected segment on imaging. ConclusionsIn patients presenting with SMVT and no structural heart disease, the presence of fQRS is strongly associated with granulomatous myocarditis. fQRS on the surface ECG is a helpful tool the presence of which should prompt a CMR for a definitive diagnosis.

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.

Giant cell and granulomatous myocarditis necessitating cardiac transplantation: clinical, gross, and histopathological findings

Giant cell myocarditis and granulomatous myocarditis are rare diseases, leading to severe heart symptoms like tachyarrhythmia or atrial fibrillation with frequently fatal outcome. Typically, diagnosis is confirmed at necropsy or in explanted hearts, as the majority of cases remain clinically unrecognized. Explanted heart specimens of 355 heart transplant recipients receiving cardiac transplantation between January 1994 and December 2011 were examined. Unexpected granulomatous myocarditis was found in the explanted hearts of three patients and giant cell myocarditis in four patients. We investigated preoperative and postoperative course and gross and histopathological findings of these two different disorders, which were thought to be the same disease for a long time. Preoperatively, both groups suffered from mild to severe symptoms of heart failure. Gross findings of resected heart specimens showed right and left ventricular hypertrophy. Histological examination revealed a left ventricular endomyocardial fibrosis and inflammation infiltrates including giant cells with the presence or absence of granulomas. All patients with granulomatous myocarditis are alive. Three patients suffering from giant cell myocarditis showed a complicated postoperative clinical course, one heart transplant recipient developed Guillain–Barre syndrome due to cytomegalovirus reactivation 6 months after heart transplantation, another patient died due to cerebral edema shortly after transplantation, and another one died because of myocardial and cerebral infarction after tricuspid valve replacement. In consideration of the limitation of this study that a small number of patients were included, our results suggest that patients suffering from granulomatous myocarditis are older at heart transplantation and have a more favorable outcome compared with heart transplant recipients with giant cell myocarditis.

Porcine Circovirus Type 2 Infection in a Piglet Born from a Surrogate Mother

A 4-week-old male piglet being maintained in a research facility was found dead without any previous clinical signs. The piglet had been born from a surrogate mother after somatic nuclear transfer as part of a xenotransplantation study. Ovaries for nuclear transfer were obtained from a private farm outside the research facility. Histopathologically, multifocal to coalescing granulomatous myocarditis was observed in the heart, characterized by infiltration of lymphocytes, macrophages and multinucleated giant cells, and by myocardial necrosis and fibrosis. Lymphoid tissues showed marked lymphoid depletion with infiltration by histiocytes or giant cells. Immunohistochemistry showed PCV-2 antigens in necrotic myocytes, macrophages and multinucleated giant cells in the heart, as well as in macrophages and giant cells in lymphoid depleted areas of lymphoid tissues. Reproductive failure associated with PCV-2 in aborted or stillborn piglets is frequently characterized by myocarditis, and similar lesions were observed in this 4-week-old piglet with PCV-2 infection. The PCV-2 infection in this piglet may have been due to contamination or infection of an ovary from the pig farm.

Equine Pulmonary Aspergillosis with Encephalitic, Myocardial, and Renal Dissemination

The cause of the death of a 16-month-old Brasileiro-de-Hipismo filly and a 3-year-old male Paint Horse with clinical manifestations of anemia and apathy from southern Brazil was investigated. These horses were maintained at the same stable; received hay as part of their diet and were submitted for routine necropsy evaluations. Significant gross findings included several nodules randomly distributed throughout the pulmonary lobes of both horses, and the kidneys, myocardium, and the frontal lobes of the cerebrum of the filly. Histopathological evaluation revealed pyogranulomatous bronchopneumonia in both horses; granulomatous interstitial nephritis, myocarditis, and encephalitis were observed in the filly. All lesions contained vasculitis and thrombosis associated with myriads of intralesional, branching, septate fungi consistent with Aspergillus spp.; intralesional fungi were more easily identified by the Grocott methenamine silver stain. Mycological culture of fresh pulmonary sections from both horses and the brain of the filly revealed pure growths of A. fumigatus. These findings confirmed the participation of A. fumigatus in the etiopathogenesis of the lesions observed in the lungs of both horses, and the cerebrum, myocardium and kidneys of the filly and might represent the first description of A. fumigatus-induced encephalitis in horses. Additionally, we believe that infection occurred during the ingestion of contaminated hay or by inhalation of spores within contaminated bedding that resulted in transient nasal mycosis, which progressed to pyogranulomatous bronchopneumonia in both horses with embolic encephalitic, myocardial, and renal dissemination of A. fumigatus occurring only in the filly.