Complications of 2-D echocardiography guided transfemoral right ventricular endomyocardial biopsy

Endomyocardial biopsy (EMBx) is a useful tool for diagnosing various cardiac pathologies. However, the routine use of EMBx has not gained widespread acceptance due to the possible complications related to the EMBx. Thus, not much information is available on the complications related to the EMBx. We prospectively evaluated 90 consecutive patients who underwent 2-D echocardiography guided transfemoral right ventricular EMBx at Kyungpook National University Hospital between March 2002 and November 2005 to determine the incidence, nature and subsequent management of complications related to EMBx. The clinical diagnoses before the EMBx were arrhythmogenic right ventricular dysplasia in 54, dilated cardiomyopathy in 19, Brugada syndrome in 9, myocarditis in 6 and miscellaneous in 2 patients. The overall major complication rate was 5.6% and no procedure-related mortality occurred. Myocardial perforation (n=3), which was the most frequent complication, did not progress to cardiac tamponade requiring pericardiocentesis in any patient. Hemodynamically unstable ventricular tachycardia occurred in 1 patient. New and persistent right bundle branch block occurred in another. Our findings suggest that 2-D echocardiography guided transfemoral right ventricular EMBx is a relatively safe procedure.     

Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis.

Giant cell myocarditis (GCM) is a serious condition that warrants immediate diagnosis and treatment. It often presents as rapidly progressive heart failure and/or malignant ventricular arrhythmias. Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma. A cardiac biopsy confirming the diagnosis was done within 3 days after admission. After institution of an aggressive immunosuppressive drug regimen, implantation of an implantable cardioverter defibrillator, and intensive cardiac rehabilitation, the patient recovered dramatically. In control biopsies after 4 weeks and 6 months, no more giant cells were found. We conclude that, in the case of nonischemic acute heart failure in young patients, a biopsy should be performed as soon as possible to prevent an unfavourable outcome of this often fatal disease.     

The endomyocardial biopsy

Endomyocardial biopsy (EMB) provides a safe, simple method of gathering unique information. Although the role of EMB continues to evolve rapidly, present consensus includes the following indications, based on the ability of EMB to provide diagnoses unobtainable by other means: assessment of early rejection following cardiac transplantation; determination of myocarditis as etiology of clinically obscure cardiac dysfunction; quantification of chemotherapeutic (especially anthracycline) cardiotoxicity; and distinction between constrictive and restrictive heart disease. Each of these indications carries major therapeutic as well as prognostic implications. Methods of processing EMB are presented, complications listed, artifacts described, findings and uses illustrated, and suggestions for future development addressed briefly.     

Pathology of endomyocardial biopsy

Endomyocardial biopsy (EMB) is routinely performed for cardiac transplant monitoring. Moreover, it can be a useful tool in the diagnostic work-up of myocarditis, cardiomyopathies, drug toxicity, unexplained arrhythmias, heart involvement in systemic disease, and to diagnose cardiac masses. Pathologic evaluation of EMB represents the gold standard in specific disorders, including myocarditis and cardiac involvement by amyloidosis and sarcoidosis. To increase the diagnostic yield of the procedure, multiple myocardial samples should be obtained, and processed in a fully-equipped laboratory, with access to immunohistochemical/histochemical analyses, molecular tests and transmission electron microscopy. We here review the main diagnostic features of myocarditis, cardiomyopathies and cardiac tumours on EMB, specifying the ancillary techniques required to reach the diagnosis in each specific cardiac disease.     

Right ventricular endomyocardial fibrosis

Endomyocardial fibrosis (EMF) is a neglected tropical cardiomyopathy of unknown etiology and pathogenesis that is common in certain tropical areas of Africa, Asia, and South America. It affects predominantly children and young adults. Endocardial fibrosis is the hallmark of this restrictive cardiomyopathy leading to restriction to diastolic filling of the ventricles with severe atrial dilatation.Endomyocardial fibrosis carries a poor prognosis, due to the late presentation of patients. The salient features of this condition are present in the case presented here of a 14-year-old boy who died from progressive heart failure due to right ventricular EMF. These pathological findings of advanced disease highlight the need for early diagnosis and better understanding of the pathogenesis in order to improve prognosis of this debilitating and fatal disease.     

Histomorphologic characteristics of endomyocardial fibrosis: an endomyocardial biopsy study

Endomyocardial biopsies from right, left, or both ventricles were performed in 13 angiographically documented cases of endomyocardial fibrosis. The endocardium was appreciably thickened due to acellular hyalinized collagen tissue in all cases. Variable amounts of elastic tissue intimately admixed with fibrous tissue were recognized. A "zonal layering" pattern of the endocardium was absent. Thrombus, inflammatory cells, and granulation tissue at the endomyocardial interphase, and eosinophils within the biopsy were not seen. In addition, lymphomononuclear interstitial inflammatory infiltrates were seen in five cases.     

An approach to endomyocardial biopsy interpretation

The endomyocardial biopsy (EMB) remains the gold standard mode of investigation for diagnosing many primary and secondary cardiac conditions. Through a percutaneous and transvenous route, tissue fragments are generally procured from the right ventricular septum, with very few complications. Widespread use of EMB followed the development of heart transplantation as a means to follow allograft rejection. It has since been useful in helping to diagnose conditions affecting the heart, including cardiomyopathies, myocarditis, infiltrative lesions, arrhythmias, and drug toxicities. The procedure has also been used as a research tool to investigate the natural history of disease and the cardiotoxicity of new medications. This review presents an approach to the evaluation of the EMB, which is particularly directed towards those who may be asked to interpret such biopsies, but are not dedicated cardiovascular pathologists. Through a systematic evaluation of the endocardium, myocardium, interstitium, and intramural vessels, in the context of a complete clinical history, enough information can be deduced to diagnose or exclude specific conditions of clinical value.     

Direct cocaine cardiotoxicity demonstrated by endomyocardial biopsy

The morbidity and mortality associated with cocaine abuse has markedly increased in recent years. Although several articles indicate a possible connection of cocaine with coronary spasm and acute myocardial infarction, this study in seven patients with a history of cocaine abuse, who underwent endomyocardial biopsy, suggests that cocaine may cause direct toxicity to the myocardium. Myocardial specimens from five of seven patients showed multifocal myocyte necrosis, of which two specimens revealed focal myocarditis, while three specimens had changes consistent with dilated cardiomyopathy. Ultrastructurally, extensive loss of myofibrils and sarcoplasmic vacuolization were observed. It is postulated that the pathogenesis of acute cocaine-induced toxicity is direct destruction of myofibrils resulting in myocyte necrosis and that these changes may or may not be associated with interstitial inflammatory cell infiltrates. Long-term abuse of cocaine may lead to interstitial fibrosis and eventually congestive heart failure.     

The role of endomyocardial biopsy in the diagnosis of cardiac disorders in infants and children

Endomyocardial biopsies from 26 children were studied by light and electron microscopy. Follow-up biopsies were obtained in 2 patients. The biopsy showed evidence of myocarditis in 6 patients, including 1 with features of sarcoidosis. Twelve biopsies showed features consistent with dilated cardiomyopathy. Endocardial fibroelastosis was documented in two of these biopsies. In two biopsies striking myocardial hypertrophy with prominent myofibrillar disarray suggested hypertrophic cardiomyopathy. Two biopsies from patients with clinical hypertrophic cardiomyopathy showed ultrastructural evidence of a mitochondrial abnormality. No morphological changes were detected in five biopsies, of which two had carnitine deficiency. A biopsy sampled the overlying myocardium in 1 patient with a cardiac fibroma, and a biopsy of the right ventricle was normal in a patient with Noonan's syndrome and hypertrophic cardiomyopathy limited to the left ventricle. Thus, of 28 biopsies in this series, the morphological changes were diagnostic in 10 (35%) and an additional 13 (46%) biopsies documented an abnormality of the myocardium. Endomyocardial biopsies can be of significant use in the diagnosis of selected cardiac disorders in childhood.     

Morphological changes in small vessels on endomyocardial biopsy

Small vessel disease has been described in various cardiac conditions including diabetes mellitus, amyloidosis, and connective tissue disease. Less well understood is the incidence and morphological features of small vessel disease in patients with myocardial disease of unknown etiology. This study examines the incidence, clinical presentation, and pathological changes of small vessel disease in patients with normal epicardial coronary arteries undergoing endomyocardial biopsy. Biopsy specimens in 110 consecutive patients were analyzed by light and electron microscopy. Small vessel abnormalities were present in 16 patients (14.6 percent) of whom five patients had associated hypertension and 11 patients had idiopathic small vessel disease. There were six males and 10 females with a mean age of 53 (26 to 76) years. Clinical presentations were arrhythmias, heart failure, or chest pain. The left ventricular ejection fraction was reduced (less than 50 percent) in 12 of these 16 patients. The morphological features of small vessel disease included marked thickening of the arterial wall owing to subendothelial deposits of heterogeneous electron dense materials consisting of microfibrils, collagen and elastic fibers, cellular debris, and other amorphous substances. Subendothelial deposits comprised a mean 60 percent (40 to 76 percent) of the arterial wall thickness.     

Diagnostic reliability of endomyocardial biopsy for assessment of cardiac allograft rejection

Endomyocardial biopsy (EMB) of the right ventricle has demonstrated clinical use primarily for the detection of allograft rejection. Since its introduction, the procedure has been demonstrated to be safe and adaptable to an ambulatory population. The detection and grading of rejection have relied heavily on the criteria originally proposed by the Stanford group. Similar criteria are under study for diagnosis of myocarditis. Using autopsy-acquired cardiac allograft specimens, we report the reliability of EMB for grading of rejection and establish the dependence on the morphologic features used as the diagnostic cut-off and the fragment number obtained at biopsy. The reliability of an interpretation protocol based on the pattern of inflammation present in the multiple fragments submitted is established. We compare the reliability for rejection prediction between this approach and the currently accepted approach based on the presence of myocyte necrosis.     

Pathology of heart transplant through endomyocardial biopsy.

Cardiac transplantation is most effective method for treatment of patients with end-stage heart disease. We present the experience of our institution with 1,564 biopsies and 11 autopsies of 105 orthotopic heart transplants. This report describes the morphological features and the grading systems of acute rejection. Also, we present the morphological characteristics of other complications of heart transplants such as chronic rejection, "Quilty" effect, interstitial fibrosis, heart hypertrophy, previous biopsy sites, calcification, cytomegalovirus infections, toxoplasmosis, and the appearance of malignancies, mainly, lymphomas. Actuarial survival of patients is 91% and 88% at 1 and 5 years' posttransplant, respectively.     

The diagnostics of arrhythmogenic right ventricular dysplasia by an endomiocardial biopsy and the role of viruses in the pathogenesis of disease

The comparative histologic, morphometric and immunohistochemical investigation of a right ventricular myocardium from 3 groups of patients has been carried out. The first group has included 12 patients with an arrythmogenic right ventricular dysplasia (ARVD) confirmed by an endomyocardial biopsy. The second group has consisted of 7 healthy people died a violent death. The third group has included 7 patients with a chronic alcoholism died from an acute alcoholic intoxication. The patients with ARVD and a chronic alcoholism have had an evident adiposis, a moderate fibrosis, and muscle atrophy with only 65% of cardiac hystiocytes. The patients with a chronic alcoholism have had only dystonia of intramural arteries. The cardiac hystiocytes of patients with ARVD have infected by enteroviruses (100%), parvoviruses B19 (58%), adenoviruses (25%), and hepatitis virus C (16%). 83% of observations have had a mixed viral infections.     

Diagnostic use of the endomyocardial biopsy: a consensus statement

The Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology created a task force to write a consensus document on when and how endomyocardial biopsy is of help for clinicians in the diagnosis and treatment of patients with heart failure, arrhythmias, and cardiac masses. Endomyocardial biopsy is the gold standard for a definitive diagnosis in disease entities like myocarditis, cardiac allograft rejection, and infiltration/storage myocardial disorders. Use of molecular biology techniques is mandatory to obtain specific information on etiology and pathogenesis and should be carried out as an investigation complementary to histology and immunohistochemistry. Given the complexity of these investigations, endomyocardial biopsy should be performed in or in collaboration with cardiac pathology referral centers, where the whole armamentarium of pathological investigation is available, including molecular techniques. Optimal use of the endomyocardial biopsy requires clinicopathologic correlations.