Endomyocardial biopsy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

## Contents

* 1 Overview
* 2 Disease States that can be Diagnosed Using Endomyocardial Biopsy
* 3 Endomyocardial biopsy
* 4 Standardizing the Interpretation of Endomyocardial Biopsies: The Dallas Criteria
* 5 Scenarios in Which Endomyocardial Biopsy May Be Useful[8][9]
* 6 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults (DO NOT EDIT) [11]
* 7 The AHA/ACCF/ESC Scientific Statement: The role of Endomyocardial Biopsy in fourteen clinical scenarios (DO NOT EDIT) [12]
* 8 The Biopsy Procedure
* 8.1 Approach from the neck
* 8.2 Approach from the femoral vein
* 9 Evaluation of Biopsy Specimen
* 10 Grading of Rejection
* 11 Categories of cellular rejection
* 12 Complications of Endomyocardial Biopsy[12][13]
* 13 References

## Overview

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An endomyocardial biopsy is an invasive heart procedure that is performed to obtain a small piece of myocardial tissue for pathologic evaluation. Endomyocardial biopsy remains the gold standard test to evaluate for the presence of and to subclassify the type of myocarditis. A small tissue sample of the endocardium and myocardium is obtained via right sided cardiac catheterization. The sample is then evaluated by a pathologist using immunochemistry and special staining techniques as necessary. Histopathological features include abundant edema in the myocardial interstitium and an inflammatory infiltrate which is rich in lymphocytes and macrophages. Focal destruction of myocytes as a result of the inflammatory process results in left ventricular dysfunction.[1] Endomyocardial biopsy is recommended when the results would identify an underlying disease that is amenable to therapy. Routine performance of endomyocardial biopsy is not recommended in all patients with myocarditis.

## Disease States that can be Diagnosed Using Endomyocardial Biopsy

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* Myocarditis
* Sarcoidosis
* Hemachromatosis
* Amyloidosis
* Heart transplant rejection

## Endomyocardial biopsy

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The Heart Failure Society of America recommends that performance of endomyocardial biopsy should be considered when cardiac function deteriorates acutely with an unknown etiology that is unresponsive to medical therapy (Strength of Evidence = B)[2].

Non-specific findings such as hypertrophy, cell loss and fibrosis may be noted on biopsy. However, biopsy findings that significantly impact patient management have not been conclusively established[3]. For example, although inflammatory changes in the myocardium may be detected in viral myocarditis, the majority of patients with biopsy proven myocarditis improve with supportive therapy alone without the need for antiviral or anti-inflammatory treatment[4]. Endomyocardial biopsy has a low sensitivity and specificity which could be explained by the focal and transient nature of the inflammatory infiltrates[5][6].

## Standardizing the Interpretation of Endomyocardial Biopsies: The Dallas Criteria

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Histologically, both active inflammatory infiltrate within the myocardium and associated myocyte necrosis (the Dallas pathologic criteria)[7] are present in myocarditis. Despite its limitations, the Dallas criteria have established uniform histologic criteria diagnosing myocarditis and have substantially reduced the variability in diagnosing the disease. Some of the criteria are as follows:

“  |

* Active myocarditis: the presence of an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of the ischaemic damage associated with coronary artery disease.
* Borderline myocarditis: the presence of an inflammatory infiltrate of the myocardium without necrosis or degeneration of adjacent myocytes.

| ”

|
|

## Scenarios in Which Endomyocardial Biopsy May Be Useful[8][9]

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* Subacute or acute symptoms of heart failure refractory to standard management
* Rapid worsening of ejection fraction despite standard pharmacological therapy
* Development of cardiac arrhythmias such as ventricular tachycardia and/or heart block
* Heart failure with concomitant rash, fever, or peripheral eosinophilia
* Cardiac dysfunction thought to be secondary to the following conditions as the results of endomyocardial biopsy may alter the therapy:
* Collagen vascular disease:
* Systemic lupus erythematosus
* Scleroderma
* Polyarteritis nodosum
* Infiltrative diseases:
* Amyloidosis: These patients are no eligible for cardiac transplantation
* Sarcoidosis
* Hemachromatosis
* Giant cell myocarditisThese patients generally progress rapidly to either cardiac transplantation or death and are poorly responsive to treatment. Myocardial biopsy may optimize the management of these patients by identifying patients who may benefit from early heart transplantation[10]..

## 2009 Focused Update Incorporated Into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults (DO NOT EDIT) [11]

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Class III (Harm)

"1. Endomyocardial biopsy should not be performed in the routine evaluation of patients with heart failure.[12] (Level of Evidence: C) "
Class IIa

"1. Endomyocardial biopsy can be useful in patients presenting with heart failure when a specific diagnosis is suspected that would influence therapy.[12] (Level of Evidence: C)  "

## The AHA/ACCF/ESC Scientific Statement: The role of Endomyocardial Biopsy in fourteen clinical scenarios (DO NOT EDIT) [12]

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Class I

"1. New-onset heart failure of <2 weeks’ duration associated with a normal-sized or dilated left ventricle and hemodynamic compromise. (Level of Evidence: B) "
"2. New-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks. (Level of Evidence: B) "
Class III (Harm)

"1. Unexplained atrial fibrillation. (Level of Evidence: C) "
Class IIa

"1. Heart failure of >3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks. (Level of Evidence: C) "
"2. Heart failure associated with a DCM of any duration associated with suspected allergic reaction and/or eosinophilia. (Level of Evidence: C) "
"3. Heart failure associated with suspected anthracycline cardiomyopathy. (Level of Evidence: C) "
"4. Heart failure associated with unexplained restrictive cardiomyopathy. (Level of Evidence: C) "
"5. Suspected cardiac tumors. (Level of Evidence: C) "
"6. Unexplained cardiomyopathy in children. (Level of Evidence: C) "
Class IIb

"1. New-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle, without new ventricular arrhythmias or second- or third-degree heart block, that responds to usual care within 1 to 2 weeks. (Level of Evidence: B) "
"2. Heart failure of >3 months’ duration associated with a dilated left ventricle, without new ventricular arrhythmias or second- or third-degree heart block, that responds to usual care within 1 to 2 weeks. (Level of Evidence: C) "
"3. Heart failure associated with unexplained HCM. (Level of Evidence: C) "
"4. Suspected ARVD/C. (Level of Evidence: C) "
"5. Unexplained ventricular arrhythmias. (Level of Evidence: C) "

## The Biopsy Procedure

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The procedure can be performed either from the neck (using the jugular vein), or from the femoral vein.

### Approach from the neck

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* Jugular vein approach (especially right internal jugular vein). Endomyocardial biopsy is performed in a supine position with local anesthesia.
* Subclavian vein approach is not preferable for a variety of reasons as: local anesthesia is less effective, because of the clavicle, the risk of pneumothorax is significantly higher as compared to puncture of the internal jugular vein and due to the anatomical course of the great veins, direction of the bioptome is more difficult.

### Approach from the femoral vein

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The femoral triangle is prepped and draped in the usual sterile fashion. The Seldinger approach is used to puncture the femoral vein. An 8 french sheath is then introduced over a long exchange length J wire. The x-ray gantry is placed in the straight anteroposterior angulation.

A pigtail catheter is next advanced into the right atrium. An exchange length J wire is then inserted so that the pigtail straightens (similar to the maneuver used to cross the aortic valve). The exchange length J wire is then advanced across the tricuspid valve into the right ventricle. The pigtail catheter is then advanced over this wire to the apex of the right ventricle. Once the catheter is at the apex of the right ventricle, the pigtail catheter is removed, and the wire remains near the apex of the right ventricle. The long sheath used to advance the bioptome is now advanced over the exchange length J wire to the apex of the right ventricle. The bioptome is next inserted into the long bioptome sheath, and is advanced to the apex of the right ventricle. The x-ray gantry is now rotated into the left anterior oblique (LAO) position. In this angulation, the operator is looking straight down the barrel of the heart from the apex. The right ventricle is on the left-hand side of the screen and the left ventricle is on the right-hand side of the screen. At this point care must be taken to ensure that the bioptome is pointing to the right on the screen which is towards the left ventricle. This assures that if a deep bite of the myocardium is taken then this will result in perforation of the septum rather than the free wall of the right ventricle. This reduces the risk of cardiac tamponade, a catastrophic complication of the procedure.

Once the position of the bioptome is verified, the jaws of the bioptome are opened (this usually requires that the handles of the bioptome are pulled apart), and the open bioptome is now advanced into the apex of the right ventricle until premature ventricular contractions (PVCs) are stimulated. Once PVCs are stimulated, the handle of the bioptone is quickly squeezed to entrap myocardial tissue in the device. In other words, squeezing the handle rapidly closes the mouth of the bioptome around a piece of the myocardium. The operator then tugs on the bioptome apparatus to take a "bite" out of or biopsy the myocardium. There should be resistance as the operator tugs on the bioptome. This resistance assures that a successful bite" of the myocardium has been obtained. The bioptome is now removed from the body and saline is used to wash the specimen of myocardium into a container to send to pathology. Three to five specimens should be obtained for pathologic evaluation.

## Evaluation of Biopsy Specimen

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Biopsy specimens are prepared for light microscopy by hematoxiline – eosine staining.

## Grading of Rejection

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Morphologically, acute rejection is a mononuclear inflammatory reaction of predominantly lymphocytes against the myocardium. Grading of rejection is performed according to the guidelines of the International Society for Heart and Lung Transplantation (ISHLT) as follows:

* Grade 0: no evidence of rejection
* Grade Ia: focal perivascular or interstitial infiltrate without myocardial injury
* Grade Ib: multifocal or diffuse sparse infiltrate without myocardial injury
* Grade II: single focus or dense infiltrate with myocyte injury
* Grade IIIa: multifocal dense infiltrates with myocyte injury
* Grade IIIb: diffuse, dense infiltrates with myocyte injury
* Grade IV: diffuse and extensive polymorphous infiltrate with myocyte injury; may have hemorrhage, edema, and microvascular injury

## Categories of cellular rejection

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* Grade 0 R: no rejection
* Grade 1 R: mild rejection (Grades I A, I B and II)
* Grade 2 R: moderate rejection (Grade III A)
* Grade 3 R: severe rejection (Grade III B and IV)

## Complications of Endomyocardial Biopsy[12][13]

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Complications may be as high as 6% as observed in a series where 546 patients with cardiomyopathy underwent right ventricular endomyocardial biopsy[14]. Several other studies reported the incidence of complications to be 0.5 to 1.5%[13][15].

* Myocardial perforation leading to pericardial tamponade
* Heart block
* Pulmonary embolization
* Pneumothorax
* Nerve injury
* Hematoma
* Tricuspid valve damage
* Arteriovenous fistula
* Deep venous thrombosis
* Bleeding at the puncture site (venous/arterial due to accidental arterial puncture)
* Arrhythmias (supraventricular tachycardia/ventricular tachycardia/complete heart block)
* Tricuspid valve damage
* Coronary artery to right ventricle fistula

## References

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1. ↑ Feldman AM, McNamara D (2000). "Myocarditis". N Engl J Med. 343 (19): 1388–98. doi:10.1056/NEJM200011093431908. PMID 11070105.
2. ↑ Heart Failure Society of America. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA; et al. (2010). "HFSA 2010 Comprehensive Heart Failure Practice Guideline". J Card Fail. 16 (6): e1–194. doi:10.1016/j.cardfail.2010.04.004. PMID 20610207.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
3. ↑ Chow LC, Dittrich HC, Shabetai R (1988). "Endomyocardial biopsy in patients with unexplained congestive heart failure". Ann Intern Med. 109 (7): 535–9. PMID 3421562.CS1 maint: Multiple names: authors list (link)
4. ↑ Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME; et al. (1995). "A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators". N Engl J Med. 333 (5): 269–75. doi:10.1056/NEJM199508033330501. PMID 7596370.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
5. ↑ Mahrholdt H, Goedecke C, Wagner A, Meinhardt G, Athanasiadis A, Vogelsberg H; et al. (2004). "Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology". Circulation. 109 (10): 1250–8. doi:10.1161/01.CIR.0000118493.13323.81. PMID 14993139.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
6. ↑ Hauck AJ, Kearney DL, Edwards WD (1989). "Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error". Mayo Clin Proc. 64 (10): 1235–45. PMID 2593714.CS1 maint: Multiple names: authors list (link)
7. ↑ Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ; et al. (1987). "Myocarditis. A histopathologic definition and classification". Am J Cardiovasc Pathol. 1 (1): 3–14. PMID 3455232.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
8. ↑ Wu LA, Lapeyre AC, Cooper LT (2001). "Current role of endomyocardial biopsy in the management of dilated cardiomyopathy and myocarditis". Mayo Clin Proc. 76 (10): 1030–8. PMID 11605687.CS1 maint: Multiple names: authors list (link)
9. ↑ Magnani JW, Dec GW (2006). "Myocarditis: current trends in diagnosis and treatment". Circulation. 113 (6): 876–90. doi:10.1161/CIRCULATIONAHA.105.584532. PMID 16476862.
10. ↑ Cooper LT, Berry GJ, Shabetai R (1997). "Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators". N Engl J Med. 336 (26): 1860–6. doi:10.1056/NEJM199706263362603. PMID 9197214.CS1 maint: Multiple names: authors list (link)
11. ↑ Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, Ganiats TG; et al. (2009). "2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation". Circulation. 119 (14): e391–479. doi:10.1161/CIRCULATIONAHA.109.192065. PMID 19324966.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
12. ↑ 12.0 12.1 12.2 12.3 Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U; et al. (2007). "The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology". Circulation. 116 (19): 2216–33. doi:10.1161/CIRCULATIONAHA.107.186093. PMID 17959655.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
13. ↑ 13.0 13.1 Yilmaz A, Kindermann I, Kindermann M, Mahfoud F, Ukena C, Athanasiadis A; et al. (2010). "Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance". Circulation. 122 (9): 900–9. doi:10.1161/CIRCULATIONAHA.109.924167. PMID 20713901.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
14. ↑ Deckers JW, Hare JM, Baughman KL (1992). "Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center". J Am Coll Cardiol. 19 (1): 43–7. PMID 1729344.CS1 maint: Multiple names: authors list (link)
15. ↑ Holzmann M, Nicko A, Kühl U, Noutsias M, Poller W, Hoffmann W; et al. (2008). "Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period". Circulation. 118 (17): 1722–8. doi:10.1161/CIRCULATIONAHA.107.743427. PMID 18838566.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)

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