Endomyocardial biopsy

INTRODUCTION — Endomyocardial biopsy (EMB) is a procedure used to obtain myocardial tissue to monitor for the occurrence of allograft rejection after cardiac transplantation or, less commonly, diagnose diseases of the myocardium. (see "Heart transplantation in adults: Diagnosis of allograft rejection").

This topic reviews the general description of the EMB procedure, complications of EMB, and indications for EMB.

TECHNIQUE

Access and imaging — EMB samples are typically obtained from the right ventricle (RV) via the internal jugular vein or the right internal jugular vein in the United States. EMB of the RV can also be performed via the femoral vein. Less commonly, EMB samples are obtained from the left ventricle (LV) via access from the femoral artery or at time of operative intervention.

EMB is usually performed with fluoroscopic guidance. Transthoracic echocardiography is increasingly used in conjunction with fluoroscopy to reduce the risk of cardiac perforation or valve injury. Echocardiography also allows visualization of biopsy location, which is important to confirm that the same site is not repeatedly biopsied and for conditions such as intracardiac mass.

Right or left ventricle — EMB specimens are usually obtained from the RV (figure 1). Biopsy of the RV septum has the advantage of posing a relatively low risk of cardiac perforation and, unlike LV biopsy (figure 2), it carries no risk for stroke [1,2]. The major limitation is sampling error, particularly for diseases that are patchy and primarily affect the LV.

LV biopsy is less commonly performed but can be obtained via an arterial approach (figure 2). Indications for LV biopsy include suspected cardiac sarcoidosis or myocarditis with primary LV involvement [3]. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

A two-center study found that biventricular biopsy provided an incremental diagnostic yield over RV biopsy [4]. 755 patients with suspected myocarditis and/or nonischemic cardiomyopathy underwent LV, RV, or biventricular EMB. Diagnostic EMB results were achieved more frequently in those undergoing biventricular EMB (79.3 percent) compared with those undergoing univentricular EMB (67.3 percent). In patients undergoing biventricular EMB, myocarditis was diagnosed by LV EMB in 18.7 percent, by RV EMB in 7.9 percent, and in both ventricles in 73.4 percent. Biopsy in the region of late gadolinium enhancement on cardiovascular magnetic resonance imaging did not increase the yield of diagnosis. Complication rates were similar for LV and RV biopsy.

A study reported safety and diagnostic data from the largest published case series of LV biopsies. A total of 4221 patients underwent EMB: 1153 LV EMBs, 672 RV EMBs, and 2369 both LV and RV EMBs. The overall risk of major complications was low (0.33 percent for LV EMB and 0.45 percent for RV EMB) [5]. The table summarizes the range of biopsy risks (table 1) [6].

Sampling and analysis — We agree with the following recommendations regarding EMB sampling and analysis based upon the 2007 American Heart Association/American College of Cardiology/European Society of Cardiology (AHA/ACC/ESC) scientific statement on the role of EMB [7] and the 2011 consensus statement on EMB from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology [8]:

●Samples should be obtained from more than one region of the RV septum (figure 1), and the number of samples should range from 5 to 10, depending upon the studies to be performed and size of the bioptome forceps.

●At least four to five samples should be submitted for light microscopic examination.

●Analysis by transmission electron microscopy (TEM) using a glutaraldehyde-based fixative is recommended if a storage disease, anthracycline, or hydroxychloroquine cardiotoxicity is suspected. TEM is occasionally helpful for identifying viral myocarditis.

●Tandem mass spectroscopy is useful to identify subtypes of amyloid protein [9]. (See "Overview of amyloidosis", section on 'Selection of biopsy site'.)

●The 2021 Heart Failure Association of the ESC, Heart Failure Society of America, and Japanese Heart Failure Society position statement on EMB recommends that the processing and staining of heart tissue obtained from EMB depends on the suspicion for specific disorders, listed in the table (table 2) [6].

INDICATIONS

Considerations — Indications for EMB are predicated upon two major considerations. The first is the anticipated yield of the procedure, given the presumed prebiopsy probability of a given disorder as well as the risk of sampling error (ie, not obtaining diagnostic samples from a diseased heart due to the patchy nature of disease). The second major consideration is the perceived availability of effective therapy for the diagnosis that is obtained. EMB is recommended in clinical scenarios in which the unique prognostic and diagnostic value of the information gained is felt to outweigh the procedural risks [10].

The diagnostic yield of a clinical evaluation that included EMB using exclusively histologic criteria (Dallas criteria) was retrospectively evaluated in a series of 1230 patients with an initially unexplained cardiomyopathy in which the following etiologies were noted [11]:

●Idiopathic – 50 percent

●Myocarditis – 9 percent

●Ischemic heart disease – 7 percent

●Infiltrative disease – 5 percent

●Peripartum cardiomyopathy – 4 percent

●Hypertension – 4 percent

●HIV infection – 4 percent

●Connective tissue disease – 3 percent

●Substance abuse – 3 percent

●Doxorubicin – 1 percent

●Other – 10 percent

Although a clinical diagnosis was established in 50 percent, a specific histologic diagnosis from EMB (mostly myocarditis and infiltrative disease (figure 3)) was obtained in only 15 percent of patients. This relatively low rate may be due in part to sampling error.

However, the diagnostic and prognostic value of EMB was likely underestimated by the above data [12-14]. The study did not include use of immunohistochemical and molecular techniques of viral genome analysis, which have led to substantially increased diagnostic yield compared with conventional histopathological evaluation (Dallas criteria). In addition, cardiovascular magnetic resonance (CMR) or endocardial voltage mapping may further increase the yield of EMB by identifying regions with inflammation for sampling in specific disorders [15-17]. The use of immunohistochemical and molecular EMB analysis to guide therapy is an area of active research [18-21].

In summary, the data suggest that the yield of therapeutically relevant information provided by EMB using histologic criteria (Dallas criteria) is low in the general heart failure (HF) population. Additional techniques such as immunohistochemistry and viral genome analysis can augment the diagnostic value of EMB in chronic unexplained cardiomyopathy, but limited data are available on therapy guided by such analysis. Therefore, patients with HF or cardiomyopathy should generally undergo a comprehensive evaluation, with EMB limited to those with specific indications [22,23]. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

The main value of EMB is in the diagnosis of certain uncommon myocardial disorders, such as giant cell myocarditis, that have unique prognoses and treatment and cannot be diagnosed by less invasive tests. Other special situations where EMB may provide unique information include disorders associated with hypereosinophilia, sarcoidosis, certain restrictive and infiltrative cardiomyopathies, and other types of myocarditis.

In patients with a strong indication for EMB, a repeat EMB procedure may be required if the first procedure is non-diagnostic. As an example, in a series of patients with giant cell myocarditis, the sensitivity of EMB increased from 68 percent after a single EMB procedure (with multiple samples) to 93 percent after two or three EMB procedures [24].

Given the limited available evidence, recommendations in the 2021 Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and Japanese Heart Failure Society position statement on EMB [6], 2016 American Heart Association Scientific statement on the Management of Specific Cardiomyopathies [25] and the 2007 American Heart Association/American College of Cardiology/European Society of Cardiology (AHA/ACC/ESC) scientific statement regarding the use of EMB were based mainly on expert opinion [7]. The clinical scenarios below have been adopted with modifications from these statements.

EMB recommended

Fulminant HF — EMB is recommended in patients with unexplained new-onset HF of less than two weeks' duration associated with a normal-sized or dilated LV with hemodynamic compromise [7,26]. In this setting, EMB may help establish prognosis and guide therapy. Since the cause of fulminant HF, such as giant cell myocarditis (GCM), may be missed on initial RV EMB, if the results of the first EMB are inconclusive or discordant with clinical findings and diagnostic uncertainty remains, then we suggest a repeat biopsy. If another biopsy is performed, a different biopsy site (eg, LV EMB) or a site identified by imaging (eg, CMR, voltage mapping) may reduce the likelihood of a false negative result [27].

GCM has traditionally had a poor prognosis, but combined immunosuppressive therapy has been associated with improved outcome [24]. When mechanical circulatory support is anticipated, a diagnosis of GCM may lead to use of a biventricular device because of the likelihood of progressive RV failure and to an early heart transplant listing. (See "Treatment and prognosis of myocarditis in adults".)

Early AV block, arrhythmias, or refractory HF — EMB is recommended in patients with unexplained new-onset HF of two weeks to three months' duration associated with a dilated LV and new ventricular arrhythmias, Mobitz type II second-degree atrioventricular (AV) block, third-degree AV block, or failure to respond to usual care within one to two weeks [7,28].

The acute onset of AV block, ventricular arrhythmias, or refractory HF are clinical manifestations associated with GCM. An EMB diagnosis of GCM would suggest risk of poor prognosis and may prompt immunosuppressive therapy as well as planning for cardiac transplantation. (See "Treatment and prognosis of myocarditis in adults", section on 'Giant cell myocarditis'.)

EMB suggested in selected cases

Late AV block, arrhythmias, or refractory HF — EMB is suggested in selected patients with unexplained HF of more than three months' duration associated with a dilated LV and new ventricular arrhythmias, Mobitz type II second-degree AV block, third-degree AV block, or failure to respond to usual care within one to two weeks.

This scenario is suggestive of cardiac sarcoidosis, GCM, or idiopathic granulomatous myocarditis. Although the sensitivity of EMB in cardiac sarcoidosis is low (eg, 20 percent), EMB may help distinguish sarcoidosis from GCM, which has diagnostic and therapeutic implications. However, the diagnosis of cardiac sarcoidosis can be made without EMB if clinical features are suggestive and non-caseating granulomas are identified elsewhere (table 3). (See "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

Cardiac sarcoidosis and GCM have similar rates of ventricular arrhythmias and heart block, but sarcoidosis is associated with a more chronic course and better prognosis. Sarcoidosis may respond to glucocorticoid therapy, whereas combination immunotherapies have been used to treat GCM. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis" and "Treatment and prognosis of myocarditis in adults", section on 'Giant cell myocarditis'.)

Support for EMB in patients with chronic (>6 months) dilated cardiomyopathy (DCM) unresponsive to conventional therapy comes from a randomized trial of 85 patients with EMB evidence of virus-negative myocarditis (inflammation present by immunohistology and viral genomes absent by polymerase chain reaction [PCR]) [18]. The patients were randomly assigned to a regimen of prednisone and azathioprine or to placebo. Patients receiving immunosuppressive therapy demonstrated significant improvements in LV ejection fraction (LVEF) and New York Heart Association functional class not observed in those receiving placebo. Two observational studies suggest that viral genome analysis may be useful to guide the use of immunosuppression for patients with a chronic inflammatory cardiomyopathy that has not responded to guideline-directed medical care for more than six months [19,20]. In a propensity score-matched study of 209 patients with inflammatory cardiomyopathy (>14 inflammatory cells/high power field), heart transplant free survival was greater with immunosuppression than with standard care alone [19].

DCM with eosinophilia — EMB is suggested in selected patients with unexplained HF with a DCM of any duration associated with a suspected allergic reaction in addition to eosinophilia [29]. This scenario is suggestive of hypersensitivity myocarditis (HSM), which is associated with a wide range of presentations. However, drug hypersensitivity may manifest as HSM, GCM, granulomatous myocarditis, or necrotizing eosinophilic myocarditis. EMB is reasonable when drug hypersensitivity is suspected, as it may help distinguish HSM from GCM and necrotizing myocarditis, both of which are associated with poor prognosis. Early diagnosis of HSM may lead to withdrawal of offending medications and administration of high-dose glucocorticoids. (See "Myocarditis: Causes and pathogenesis" and "Treatment and prognosis of myocarditis in adults".)

Anthracycline cardiotoxicity — Anthracycline cardiotoxicity is generally diagnosed via noninvasive monitoring. Although EMB is considered to be the most sensitive and specific method for evaluating anthracycline cardiotoxicity, it is reserved for situations in which the cause of cardiac dysfunction is uncertain, selected cases in which administration of greater than the usual upper limit of an agent is being considered, or clinical studies of toxicity of newer agents and regimens. (See "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity".)

Restrictive cardiomyopathy — EMB is suggested in selected patients with HF associated with restrictive cardiomyopathy if other work-up is inconclusive.

Patients with HF symptoms associated with preserved systolic function should undergo evaluation to determine whether restriction or constrictive pericarditis is present. Potentially reversible causes of restrictive cardiomyopathy, such as amyloidosis or hemochromatosis, may be suggested by associated clinical features and noninvasive imaging. Distinctive features of these disorders may be noted on echocardiography or CMR. If other evaluation is inconclusive, EMB may reveal a specific infiltrative disorder (eg, amyloidosis) or storage disease (eg, hemochromatosis) or myocardial fibrosis and myocyte hypertrophy consistent with idiopathic restrictive cardiomyopathy. (See "Definition and classification of the cardiomyopathies" and "Restrictive cardiomyopathies" and "Differentiating constrictive pericarditis and restrictive cardiomyopathy".)

Selected cardiac tumors — EMB is suggested for diagnosis of select cardiac tumors. Due to the risk of embolization, EMB should not be performed if features are suggestive of myxoma.

Cardiac tumors are generally identified and characterized by noninvasive imaging (eg, echocardiography, CMR, and computed tomography). Initial evaluation includes distinguishing tumor from cardiac structures, artifact, and thrombus. Surgical resection allows definite diagnosis from examination of the operative specimen. Occasionally, EMB-directed tissue diagnosis obviates the need for surgical resection and impacts management (eg, lymphoma).

The diagnostic yield and potential risks of EMB in this setting are not well defined because data are limited. In selected cases, EMB is suggested for diagnosis of a cardiac tumor. EMB is reasonable if the potential benefit from the procedure outweighs the potential risk with the following conditions:

●Artifact or normal variants have been excluded as potential causes for a tumor-like appearance

●The diagnosis cannot be established by noninvasive imaging

●It is unclear if surgical resection is indicated

●Tissue diagnosis can be expected to influence the course of therapy

●The chances of successful EMB are believed to be reasonably high

●The procedure is performed by an experienced operator

Guidance with transthoracic, transesophageal, or intracardiac echocardiography is advised; selection of imaging modality depends on tumor location and characteristics. Since myxomas can embolize with manipulation, we recommend against EMB if the tumor has features typical of a myxoma. (See "Cardiac tumors".)

Unexplained cardiomyopathy in children — EMB is suggested in selected children with fulminant or acute unexplained HF, or idiopathic DCM.

Rarely, EMB is performed in patients with other forms of cardiomyopathy, such as arrhythmogenic RV, restrictive, and hypertrophic cardiomyopathy. (See 'ARVC' below.)

A retrospective study found that early EMB in 40 children presenting with DCM and acute HF identified 14 individuals with myocarditis. Ten individuals with myocarditis responded to medical therapy and could be managed without heart transplantation [30]. Most myocarditis in children is presumed to be viral; various viruses have differing histopathologic findings and may be identified by PCR. Such identification may have prognostic value. Data are limited, so the assessment of EMB as reasonable in this setting is based upon expert opinion. (See "Clinical manifestations and diagnosis of myocarditis in children".)

HCM with HF — EMB is generally not needed to evaluate patients with unexplained hypertrophic cardiomyopathy. EMB is suggested in selected patients with HF with unexplained LV hypertrophy when a storage disease (such as Fabry disease) or an infiltrative process (such as amyloidosis) is suspected and noninvasive evaluation is inconclusive. (See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation" and "Fabry disease: Cardiovascular disease".)

ARVC — The diagnosis of arrhythmogenic RV cardiomyopathy is established by a multi-parametric noninvasive and invasive evaluation; occasionally, EMB is necessary. The potential role of EMB is this setting is discussed separately. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis".)

EMB of unproven value

General evaluation of heart failure — Since evidence of benefit of EMB is limited to specific clinical scenarios, routine EMB is not generally recommended in patients with new-onset HF. The 2013 ACC/AHA HF guidelines, the 2010 Heart Failure Society of America practice guidelines, and the 2012 ESC HF guidelines note that EMB should not be performed in the routine evaluation of patients with HF [26,31,32]. Although an expert panel on myocarditis suggested broadening the indications for EMB [33], the therapeutic impact of wider use of EMB is uncertain.

Recent onset DCM — EMB is not generally indicated in patients with unexplained new onset HF of two weeks to three months' duration associated with a DCM, without new ventricular arrhythmias or Mobitz type II second-degree AV block, or third-degree AV block, that responds to usual care within one to two weeks.

The utility of EMB in this setting is uncertain since many patients with this presentation improve with standard HF therapy. The prevalence of a pathologic diagnosis of lymphocytic myocarditis using exclusively the histologic criteria (Dallas criteria) has varied widely (0 to 63 percent) in this setting. Of note, the risk of death or heart transplantation in lymphocytic myocarditis with two weeks or more of symptoms and lack of viral prodrome is greater than in fulminant lymphocytic myocarditis described above in Clinical scenario 1.

EMB is not recommended for the routine evaluation of patients with recent onset DCM that is responsive to usual care. EMB in this setting is under investigation in certain specialized tertiary referral centers where immunohistochemistry and viral PCR are frequently performed to determine etiology and guide therapy [12-14,18]. (See "Treatment and prognosis of myocarditis in adults", section on 'Lymphocytic myocarditis'.)

DCM has been associated with a wide range of viruses including enteroviruses, adenoviruses, parvovirus B19, cytomegalovirus, Epstein-Barr virus, human herpes virus 6, HIV, and hepatitis C. EMB with combined histology (Dallas criteria), immunohistochemical, and molecular techniques of viral genome analysis is the gold standard to achieve etiopathogenetic diagnosis of viral versus autoreactive (virus-negative) inflammatory heart muscle disease [12-14,18]. However, the efficacy of etiology-directed therapy in this setting is uncertain.

Chronic DCM — EMB is not generally indicated in patients with unexplained HF of more than three months' duration associated with a DCM without new ventricular arrhythmias or Mobitz type II second-degree AV block, or third-degree AV block, that responds to usual care within one to two weeks.

Limited data are available on the efficacy of treatment guided by EMB analysis in patients with chronic DCM [14,18]. Some patients with symptomatic HF after six months of optimal therapy may show improvement in LVEF after immunosuppressive therapy, but more data are needed. The use of EMB to guide risk stratification and therapy in patients with chronic DCM is under investigation [12-14,18]. (See "Treatment and prognosis of myocarditis in adults", section on 'Immunosuppressive therapy'.)

Chronic DCM patients with myocardial iron overload due to hereditary or acquired hemochromatosis can usually be diagnosed by noninvasive evaluation, including laboratory testing and CMR. When noninvasive testing is nondiagnostic, EMB can be useful. Treatment of iron overload can reverse ventricular dysfunction. (See "Approach to the patient with suspected iron overload" and "Management and prognosis of hereditary hemochromatosis" and "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Cardiac iron overload'.)

Unexplained arrhythmias — The utility of performing EMB in patients with unexplained arrhythmias has not been established. Some patients with unexplained arrhythmias (supraventricular or ventricular) have myocarditis, and myocarditis may present as unexplained life-threatening arrhythmia or sudden cardiac death [18]. However, the yield of EMB is low using Dallas criteria. (See "Treatment and prognosis of myocarditis in adults".)

Unexplained atrial fibrillation — Scant data are available on the role of EMB in patients with unexplained atrial fibrillation [34]. We recommend against performing EMB in this setting; this recommendation is consistent with the 2007 AHA/ACC/ESC scientific statement [7].

COMPLICATIONS — Decisions regarding use of EMB should include consideration of the complications associated with the procedure.

The risks of EMB include myocardial perforation with pericardial tamponade, arrhythmias, heart block, pneumothorax, arterial puncture, pulmonary embolization, nerve block or injury, hematoma, damage to the tricuspid valve, creation of arteriovenous fistula, and deep venous thrombosis. Reported complication rates range from less than 1 to as high as 6 percent (table 1) [4,7]:

●In a single-center study, the major complications of RV and LV biopsy included:

•RV biopsy:

-Resuscitation – 0.1 percent

-Death – none

-Tamponade requiring pericardiocentesis – 0.1 percent

-Urgent cardiac surgery – none

-Pneumothorax – 0.1 percent

-Temporary AV block – 0.1 percent

-Tricuspid injury – 0.1 percent

•LV biopsy:

-Resuscitation – 0.4 percent

-Death – none

-Tamponade requiring pericardiocentesis – 0.8 percent

-Urgent cardiac surgery – 0.4 percent

-Pneumothorax – 0.4 percent

-Temporary AV block – none

-Mitral injury – 0.4 percent

Overall, there were more major complications with patients undergoing biopsy for diagnosis of cardiomyopathy when compared with patients undergoing biopsy for heart transplantation (1.9 versus 0.3 percent).

●In a study of 755 patients undergoing LV, RV, or biventricular EMB, LV EMB and RV EMB resulted in similar major complication rates (0.64 versus 0.82 percent, respectively) and similar minor complication rates (0.64 to 2.89 percent versus 2.24 to 5.10 percent, respectively) [4].

●A single-center experience of RV EMB via the femoral venous approach to evaluate unexplained LV dysfunction also demonstrated low complication rates [35]. The modified Cordis bioptome used is significantly more flexible and has smaller jaws than the standard Stanford-Caves bioptome. Retrospective study of 1919 patients undergoing 2505 EMB procedures and prospective study of 496 patients undergoing 543 EMB procedures revealed no patient deaths and no complications requiring emergency cardiac surgery. Major complications such as cardiac tamponade requiring pericardiocentesis or complete AV block requiring permanent pacing were very rare (0.12 percent total in the retrospective study and none in the prospective study). Minor complications such as pericardial effusion, conduction abnormalities, or arrhythmias occurred in 0.20 percent in the retrospective study and 5.5 percent in the prospective study.

A complication that is primarily seen in cardiac transplant recipients who undergo repeated surveillance biopsies is development of tricuspid valve regurgitation (TR). The TR is usually well tolerated but valve repair or replacement is occasionally required.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Myocarditis".)

SUMMARY AND RECOMMENDATIONS

●We recommend endomyocardial biopsy (EMB) in two clinical settings (in addition to monitoring for cardiac allograft rejection):

•Unexplained new-onset heart failure (HF) of less than two weeks' duration associated with a normal-sized or dilated left ventricle (LV) with hemodynamic compromise. (See 'Fulminant HF' above.)

•Unexplained new-onset HF of two weeks to three months' duration associated with a dilated LV and new ventricular arrhythmias, Mobitz type II second-degree atrioventricular (AV) block, third-degree AV block, or failure to respond to usual care within one to two weeks. (See 'Early AV block, arrhythmias, or refractory HF' above.)

●We suggest EMB in selected patients in the following clinical settings when other evaluation is inconclusive:

•Unexplained HF of more than three months' duration associated with a dilated LV and new ventricular arrhythmias, Mobitz type II second-degree AV block, third-degree AV block, or failure to respond to usual care within one to two weeks. (See 'Late AV block, arrhythmias, or refractory HF' above.)

•Unexplained HF with a dilated cardiomyopathy (DCM) of any duration associated with a suspected allergic reaction in addition to eosinophilia. (See 'DCM with eosinophilia' above.)

•HF associated with suspected anthracycline cardiomyopathy if the cause of cardiac dysfunction is uncertain, in selected cases in which administration of greater than the usual upper limit of an agent is being considered, or clinical studies of toxicity of newer agents and regimens. (See 'Anthracycline cardiotoxicity' above.)

•HF associated with unexplained restrictive cardiomyopathy. (See 'Restrictive cardiomyopathy' above.)

•In patients with cardiac tumors when indications for surgical removal are uncertain and EMB will likely alter management. Due to the risk of embolization, EMB should not be performed if features are suggestive of myxoma. (See 'Selected cardiac tumors' above.)

•In selected children presenting with fulminant or acute unexplained HF, or idiopathic DCM. (See 'Unexplained cardiomyopathy in children' above.)

•HF associated with unexplained ventricular hypertrophy, if an infiltrative or storage disease is suspected and other evaluation is inconclusive. (See 'HCM with HF' above.)

•Suspected arrhythmogenic right ventricular (RV) cardiomyopathy if other evaluation is inconclusive. (See 'ARVC' above and "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis".)

●EMB is of unproven value in the following settings:

•Recent onset (two weeks to three months' duration) DCM without new ventricular arrhythmias or Mobitz type II second-degree AV block, or third-degree AV block that responds to usual care within one to two weeks. (See 'Recent onset DCM' above.)

•EMB is generally not recommended for chronic DCM.

An exception is suspected myocardial iron overload for which EMB can be helpful when other evaluation is inconclusive. (See 'Chronic DCM' above and "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Cardiac iron overload'.)

•Unexplained arrhythmias. We suggest EMB in this setting only in exceptional cases in which the perceived likelihood of benefit outweighs the potential risk. (See 'Unexplained arrhythmias' above.)

•Unexplained atrial fibrillation. (See 'Unexplained atrial fibrillation' above.)