Caution in the use of sedation and endomyocardial biopsy for the management of pediatric acute heart failure caused by endocardial fibroelastosis

Endocardial fibroelastosis(EFE)is commonly considered to be an inflammatory reactive lesion of hyperplasia and deposition of tissue fibers and collagen in the endocardium and/or subendocardium,which is strongly associated with endocardial sclerosis,ventricular remodeling and acute and chronic heart failure,and is one of the important causes for pediatric heart transplantation.Early diagnosis and treatment are the key factors in determining the prognosis of the children.In this paper,we would like to highlight the potential unintended consequences of the use of sedation and biopsy for pediatric acute heart failure caused by EFE and the comprehensive considerations prior to clinical diagnosis.

Clinical profile of patients with advanced age and inflammatoric dilated cardiomyopathy on endomyocardial biopsy

Background Endomyocardial biopsy （EMB） is an important tool when patients with inflammatoric cardiomyopathy （DCMi） are evaluated. We aimed to assess the clinical profile of elderly patients with DCMi on EMB. Methods Retrospective study of all consecutive patients hospitalized from January 2007 to December 2011 with clinical suspicion of DCMi undergoing EMB. Patients with evidence of DCMi on EMB （Group 1 〉 70 years, n = 85; Group 3 〈 70 years; n = 418） were compared to patients of the same age group without evi- dence of DCMi on EMB （Group 2 〉 70 years, n = 45; Group 4 〈 70 years; n = 147）. Results Among 24,275 patients treated at our institu- tion during the study period, 695 had clinical suspicion of DCMi and underwent EMB; 503 （2.1%） patients had DCMi on EMB. There were more male patients in Group 1, mean age was 74 ~ 2.8 years, mean ejection fraction was 38% q- 14%. On presentation, signs of hemody- namic compromise （NYHA functional class IIUIV, low cardiac output/index, and low cardiac power index） were more frequent in Group 1. EMB revealed viral genome in 78% of the patients, parvovirus B 19 （PVB） was frequently encountered in both age groups （Group 1： 69.4% vs. Group 2： 59.6%）; detection of more than one viral genome was more frequent in Group 1 （21.2% vs. 11.2%; P = 0.02） whereas the extent of immune response was significantly lower in individuals with advanced age. Conclusions In patients 〉 70 years with DCMi on EMB signs of hemodynamic compromise, detection of multiple viral genomes together with an overall lower extent of immune response were more frequently observed.

Feasibility of real-time magnetic resonance imaging-guided endomyocardial biopsies:An in-vitro study

AIM: To investigate if magnetic resonance(MR)-guided biopsy can improve the performance and safety of such procedures. METHODS: A novel MR-compatible bioptome was evaluated in a series of in-vitro experiments in a 1.5T magnetic resonance imaging(MRI) system. The bioptome was inserted into explanted porcine and bovine hearts under real-time MR-guidance employing a steady state free precession sequence. The artifact produced by the metal element at the tip and the signal voids caused by the bioptome were visually tracked for navigation and allowed its constant and precise localization. RESULTS: Cardiac structural elements and the target regions for the biopsy were clearly visible. Our method allowed a significantly better spatial visualization of the bioptoms tip compared to conventional X-ray guidance. The specific device design of the bioptome avoided inducible currents and therefore subsequent heating. The novel MR-compatible bioptome provided a superior cardiovascular magnetic resonance(imaging) soft-tissue visualization for MR-guided myocardial biopsies. Not at least the use of MRI guidance for endomyocardial biopsies completely avoided radiation exposure for both patients and interventionalists.CONCLUSION: MRI-guided endomyocardial biopsies provide a better than conventional X-ray guided navigation and could therefore improve the specificity and reproducibility of cardiac biopsies in future studies.

Autoradiographic Analysis of β-Adrenoceptors in Endomyocardial Biopsy Samples

We have studied the [125I] Pindolol ([125I]-PIN) binding to β-adrenergic receptors on endomyocardial biopsy samples through autoradiographic analysis. Minusculc amount of human endomyocardial tissues Was sectioned and incubated in [125I]-PIN, emulsion-coatcd covcrslips Were attached to the slides and then developed, fixed and staincd after exposure. The grain density was quantified using a computer image analyzer.The autoradiograms demonstrated the sites of cardiac β-receptorbinding with clear grains, and the non-specific binding was below 10%-20%' of the total binding. Linearregression analysis for the plot of specific cpm against specific grains at each concentration of [125I]-PINgave ay value of 0.99. Using this technique, we identified down-regulation of cardiac β-receptors inpatients with dilated cardiomyopathy (DCM) as compared with that of normal human subjects.

Tropical Coronary Artery Disease and Arrhythmogenic Potentials—The Changing Pattern towards Endomyocardial Fibrosis—An Analysis

Aim: To analyse the increasing burden of coronary artery disease (CAD) in tropical and subtropical belts of the Equator since it remains blurred and carries a grim prognosis. Introduction: Endomyocardial fibrosis [EMF] is a tropical febrile disorder, confined to peculiar and limited geographical areas. Plaque buildup in endocardium and coronary arteries, causing ischemic injury and arrhythmic episodes, is a vanishing mystery in its pathogenesis and emphasizing alternative routes for understanding and treatment of this enigmatic disease. Case Report: 15 cases in various age groups were reported with potential complications of coronary artery disease and arrhythmias, associated with endocardial lesions, the characteristic feature of endomyocardial fibrosis. Conclusion: The narrowing of coronary arteries as a result of thickening of the walls, spasm, inflammation, plaques and its rupture produce ischemic episodes which can occur slowly or suddenly in a devastating pattern with arrhythmogenic potentials. The important steps to prevent and decrease the risk of CAD is to reduce the chance of getting this disorder by epidemiological measures with an advice of blood thinning medications such as small daily dose aspirin, antibiotics in susceptible individuals and revascularization in established myocardial infarction.

Myocarditis—Personalized Medicine by Expanded Endomyocardial Biopsy Diagnostics

Myocarditis and dilated cardiomyopathy (DCM) are acute or chronic disorders of myocardium. The gold standard for final confirmation of causative reasons of these heart muscle diseases is the endomyocardial biopsy (EMB) analysis. Due to focal pathology, diagnostics are failing if the EMB does not contain the area of interest. Personalized medicine comprises the genetic information together with the phenotypic and environmental factors to yield a tailored healthcare for each individual and removes the limitations of the “one-size-fits-all” therapy approach. This provides the opportunity to translate therapies from bench to bedside, to diagnose and predict disease, and to improve patient-tailored treatments based on the unique signatures of a patient’s disease. Furthermore, novel treatment schedules can be identified which have eventually the chance to enhance long-term survivals. Global biomarkers such as specific gene expression signatures or miRNA profiles not only have the potential to reduce this problem but also add valuable information for individualized therapy decisions. In future, multiplex approaches allowing rapid and absolutely reliable identification of inflammatory or virally-induced myocardial diseases will replace singleplex methods such as direct detection of viral genomes in one single biopsy. Gene or miRNA profiles are upcoming diagnostic biomarkers for cardiomyopathies which are not only detectable in tissue samples but in body fluids as well. Consequently, a systemic diagnostic approach by determination of distinct expression pattern in e.g., peripheral blood samples will support the characterization of distinct cardiomyopathies by means of non-invasive methods.

“Burnt-Out” Endomyocardial Fibrosis—An Overview

Tropical endomyocardial fibrosis (EMF) is a public health problem affecting the children, young adults and elderly individuals in an epidemic fashion in the coastal districts of south India. Due to lack of resources for research in these endemic areas, its etiology remains elusive and hypotheses ranging from infections and allergic causes to malnutrition and toxins have not been tested rigorously. The disease is characterized by endocardial fibrosis and the right ventricle is the cardiac chamber most frequently affected. Patients may present clinically with heart failure and an associated AV (atrioventricular) valve regurgitation is common. Several features of the advanced disease called as “burnt-out” stage of endomyocardial fibrosis (EMF) are not fully understood. Background of these case studies described the clinical presentation, echocardiographic features and management of this late stage of the disease.

DETECTION OF CYTOMEGALOVIRUS GENOME BY IN SITU HYBRIDIZATION IN PARAFFIN EMBEDDED ENDOMYOCARDIAL BIOPSY SPECIMENS OF VIRAL MYOCARDITIS

Cytomegalovirus (CMV) genes were detected by in situ hybridization in 25 Chinese patients with viral myocarditis (VMC). The positive hybridization signals werre found in cardiomyocytes (6 cases, 24%), capillary endothelial cells (4 cases, 16%) and interstitial cells (7 cases, 28%). The difference between VMC and control group (16 cases died of brain trauma and 10 cases of congenital heart diseases was statistically significant. There was no definite pathomorphological relationship between the detection of CMV genes and myocardial lesions. The results suggest that CMV infection may be one of the causes of myocarditis and chronic stimulation of the immune system induced by CMV may be a possible pathogenesis of this disease.

EXPRESSION OF MHC-Ⅰ AND MHC-Ⅱ ANTIGENS IN ENDOMYOCARDIAL BIOPSIES FROM PATIENTS WITH VIRAL MYOCARDITIS AND CARDIOMYOPATHY

In situ expression of major histocompatibility complex (MHC) Ⅰ and Ⅱ antigens were examined in endomyocardial biopsy samples from 35 patients with viral myocarditis (VMC) and dilated cardiomyopathy (DCM). Increased expressions of these 2 antigens were observed on endocardia, capillary endothelia, dentritic and mononuclear cell membranes. The expression of sarcolemma was also found in specimens of VMC and DCM. Thus the abnormal expression of MHC is a new marker of autoimmune reactivity directed against cardiac structures.

Standard Operation Procedure of Percutaneous Endomyocardial Biopsy in Peking Union Medical College Hospital

Percutaneous endomyocardial biopsy (EMB) is a technique that biopsy samples are obtained using bioptome through peripheral blood vessel. This technique has been used and refined more than 50 years in clinical application. Now EMB has become an important diagnostic tool in the diagnosis of myocarditis and cardiomyopathy. Department of cardiology, Peking Union Medical College Hospital (PUMCH) has performed more than 500 cases of EMB and accumulated abundant practical experience. The clinical practice guideline of percutaneous EMB in PUMCH was also established, including indications, contradictions, operation key points, sample handling and processing, post-procedure monitoring, and treatment strategy for potential complications, etc. Due to the limitation of EMB, cardiologists should collaborate with experts in echocardiography, cardiac magnetic resonance and cardiac pathology to avoid missed diagnosis and misdiagnosis. Cardiologists should pay more attention to the value of EMB and actively perform EMB to improve the diagnosis level for myocarditis and cardiomyopathy in China.

Fulminant isolated cardiac sarcoidosis with pericardial effusion and acute heart failure: Challenging aspects of diagnosis and treatment

This case report illustrates challenging aspects of diagnosis and treatment of isolated sarcoid heart disease(SHD) and the role of cardiovascular magnetic resonance(CMR) imaging. Here, we present a previously healthy 45-year-old man, who was admitted with pericardial effusion and symptoms of acute heart failure. CMR followed by targeted left ventricular endomyocardial biopsy(EMB) revealed the diagnosis of isolated SHD. The combined use of CMR and EMB was crucial in diagnosing SHD. Furthermore, this case report demonstrates the value of CMR for monitoring response to therapy and lesion healing.

Predictors of long-term outcome in patients with biopsy proven inflammatory cardiomyopathy

Background The objective of this study was to identify prognostic indicators in patients with inflammatory cardiomyopathy （iCM） on endomyocardial biopsy （EMB）. Methods and results Between 2007 and 2011 all consecutive patients with diagnosed with iCM at EMB were retrospectively analyzed. The combined primary endpoint （EP） （1E°P） was cardiac death, aborted sudden cardiac death/appropriate implantable cardioverter defibrillator （ICD） shock, progressive heart failure requiring left venWicular assist device （LVAD） implantation and heart transplantation. 503 patients （mean age 58 ° 12 years, 73% male） were available for analysis. Genomes of cardiotrophic viruses were detected in 396 patients （79%） and immuno-histochemical signs of inflammation were present in 223 individuals （44%）. After 3.6 ° 2.4 years of follow-up, cardiac mortality was 3.0% （n = 14） and a total of 8.6% （n = 40） reached the primary endpoint. Independent predictors for the 1 °EP were： age 〉 50 years, presence and duration （〈 28 days） of symptomatic heart failure. A risk stratification approach based on the results of the multivariate analysis demonstrated that absence of signs and/or symptoms of congestive heart failure in younger （〈 50 years） patients with longer （〉 28 days） duration of disease appear to have an excellent prognosis with 100% survival and no events during follow-up The presence of all above mentioned independent risk factors results in an 1°EP occurrence of 35.9%. Conclusions Symptoms of heart fail- ure, short duration of disease, and older age are indicators of poor outcome in patients with iCM.

Pomolidomide for relapsed/refractory light chain amyloidosis after resistance to both bortezomib and daratumumab:A case report

BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes.Despite the administration of immunotherapeutic agents,in particular bortezomib and daratumumab,which have improved the outcomes of AL amyloidosis,antiplasma cell therapy remains suboptimal for some patients.CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy.He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen.The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion,in which flow cytometry analysis showed abnormal plasma cells.After two cycles of this regimen,the pleural effusion was controlled effectively with no recurrence.CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.

Protective Effects of Berberine on Cerebral Ischemia in Mice and Rats

We have studied the [125I] Pindolol ([125I]-PIN) binding to β-adrenergic receptors on endomyocardial biopsy samples through autoradiographic analysis. Minusculc amount of human endomyocardial tissues Was sectioned and incubated in [125I]-PIN, emulsion-coatcd covcrslips Were attached to the slides and then developed, fixed and staincd after exposure. The grain density was quantified using a computer image analyzer.The autoradiograms demonstrated the sites of cardiac β-receptorbinding with clear grains, and the non-specific binding was below 10%-20%' of the total binding. Linearregression analysis for the plot of specific cpm against specific grains at each concentration of [125I]-PINgave ay value of 0.99. Using this technique, we identified down-regulation of cardiac β-receptors inpatients with dilated cardiomyopathy (DCM) as compared with that of normal human subjects.

Idiopathic Giant Cell Myocarditis: State of the Art

Giant cell myocarditis (GCM) is a rare, rapidly progressive and highly lethal disease in young and middle-aged adults. It is attributed to an inflammation of the heart muscle, and mediated by T lymphocytes and anti-myosin autoantibodies. Making diagnosis of GCM with multiple noninvasive imaging modalities is possible in a small percentage of patients, so myocardial tissue diagnosis is often required. An early diagnosis is very important, because immunosuppressive treatment may significantly improve clinical course and survival of these patients. GCM often escapes diagnosis until autopsy or transplantation and has defied proper treatment trials for its rarity and deadly behavior. This review will focus on the diagnostic approach to patients with suspected GCM and currently evidence-based treatment strategy for this disease.

Right Ventricular Thrombus and Tricuspid Valve Dysfunction in a Patient with Behçet’s Disease

Background: Behçet’s disease (BD) is a multisystemic, chronic inflammatory disorder with a broad range of manifestations including within the cardiovascular system. Cardiac involvement like intracardiac thrombus (ICT) and valvular involvement in BD are rarely seen entities and often associated with poor prognosis. Case Presentation: We present the case of a young patient with vascular-Behçet diagnosed by the presence of intracardiac thrombus in the right ventricle, unresponsive to medical treatment. Even though the intracardiac lesion was successfully treated by surgical excision, he presented a severe tricuspid dysfunction some years later due to the extension of fibrosis with no surgical therapeutic option. Conclusion: Intracardiac thrombosis is a rare but early manifestation of Behçet’s disease, which is difficult to diagnose and has a poor prognosis.

Recent Advances in Molecular Diagnostics and Treatment of Heart Muscle Diseases--From Biopsy-Focused to Systemic Diagnostics

Cardiomyopathies are acute or chronic disorders of myocardium. Diagnostic characterization of disease entities demands endomyocardial biopsy analyses with histological, immunohistochemical and molecular biological tissue evaluations to establish a final diagnosis. Only such biopsy-based information allows so far a specific treatment of distinct cardiomyopathy subgroups. In order to reduce sampling error, tissue specimens have to be obtained and analyzed to get clinically relevant data for specific treatment options. Specific gene expression and microRNA (miRNAs) profiles as well as genetic markers add additional valuable information which not only reduce the sampling error but also improve patient management. Advantages of such biomarkers result from their general expression within the entire altered myocardium. Thus, obtained information does not depend on small tissue areas reached by biopsy. This very fact allows prediction of a myocardial infection even in virus-negative areas adjoining positive biopsy specimen. The combination of multiple deregulated miRNAs or genes into one disease specific diagnostic profile demands the integration of new profiling technologies in the routine workflows of cardiological laboratories. In future, multiplex approaches allowing rapid and absolutely reliable identification of inflammatory or virally-induced myocardial diseases will replace singleplex methods such as direct detection of viral genomes in one single biopsy. miRNAs are stable biomarkers which are not only detectable in tissue samples but also in body fluids. Consequently, the determination of distinct miRNA patterns in e.g. peripheral blood samples will provide a systemic diagnostic approach for the characterization of distinct cardiomyopathies by means of non-invasive methods. This will reduce the number of undiagnosed patients who have to undergo endomyocardial biopsy for final confirmation of their myocardial complaints. The resulting molecular diagnostics will pave the way from biopsy focused interpretation to systemic analysis of cardiomyopathies. To reach this goal, the set-up of modern diagnostics harks back to the broad portfolio of high-end analytical techniques and tools.

Cardiomyopathies in Tropical Countries:Causes and Nosological Perspective

Background: Cardiomyopathy is the main cause of heart failure in developing countries, mainly in Africa. In those areas the concept of “tropical cardiomyopathy” is still used to design all unexplained cardiomyopathy. The primary aim of this review is first to review the main etiologies of cardiomyopathies observed in tropical countries and second to gain a better understanding of the nosological place of the so-called “tropical cardiomyopathies” in the current framework of cardiomyopathies. Methods and Results: We reviewed relevant references over the last forty years (June, 1976 to May 2012). Given literature data, endomyocardial fibrosis (EMF) is mainly diagnosed in sub-Saharan countries, as well as Brazil and India. Peripartum cardiomyopathy (PPCM) is observed with a higher prevalence than in temperate countries. Sickle cell anemia does not induce specific cardiomyopathy in all echocardiographic studies. Malnutrition and chronic anemia can induce reversible cardiac dysfunction. Myocardial involvement in parasitic infections is restricted to Chagas disease and probably to human African trypanosomiasis. Helminthiasis is not involved in the pathogenesis of cardiomyopathy except for the deleterious effect of high eosinophilia induced by some endemic diseases (filariasis, schistosomiasis). Primary cardiomyopathies (dilated, hypertrophic, and restrictive cardiomyopathy) have no specificity. Arrhythmogenic right ventricular dysplasia and left ventricular noncompaction are also reported and do not differ from elsewhere. Conclusions: The concept of tropical cardiomyopathy is no longer relevant as most of the cardiomyopathies observed in tropical countries have no specificity, with few exceptions (PPCM, EMF, Chagas disease). In this context, the European Society of Cardiology classification offers a simpler clinical approach and allows the inclusion of the rare tropical specificities.

Monitoring of Acute Rejection after Orthotopic Heart Tranplantation

Objectives To study the monitoting of rejection after orthotopic heart thansplantation. Methods From 1998 to 2005, 10 othotopic heart thansplans were performed, and acute rejection was monitored by endomyocardial biopsy as well as by clinical features, ECG, ultrasonocardiography and blood serum determination of Tropin Ⅰ, and by the combination of these methods, we analysed the monitoring of acute rejection after the heart transplantation. Results With the combination of clinical features, ECG, ultrasonocardiography and blood serum test, 5 occurences of acute rejection were judged in the postoperative course, which were comfirmed by endomyocardial biopsy to be 2 acute rejections in Ⅰ b degree, 3 acute rejections in Ⅲa degree. Endomyocardial biopsy were routinely performed 21 times postoperatively in which there were 1 acute rejection in Ⅰa degree and 5 acute rejections in Ⅰ b degree. Conclusions Acute rejection is an important factor influencing the postoperative course of heart transplantation, so it is imperative to have an intime, effective and planned monitoring procedure for acute rejection. Endomyocardial biopsy is a sensitive and reliable method in diagnosis of acute rejection, but it is invasive and probable for some complications. The noninvasive method such as clinical features, ECG, ultrasonocardiography and blood serum test can be used as additive means in the diagnosis of acute rejection. Endomyocardial biopsy should be combined with some noninvasive methods in monitoring acute rejection after the heart transplantation.