The Role of Endomyocardial Biopsy in the Management of
A Scientific Statement From the American Heart Association, the
American College of Cardiology, and the European Society of Cardiology
Leslie T. Cooper, MD, FAHA, FACC; Kenneth L. Baughman, MD, FAHA, FACC;
Arthur M. Feldman, MD, PhD, FAHA, FACC; Andrea Frustaci, MD;
Mariell Jessup, MD, FAHA, FACC; Uwe Kuhl, MD; Glenn N. Levine, MD, FAHA, FACC;
Jagat Narula, MD, PhD, FAHA; Randall C. Starling, MD, MPH;
Jeffrey Towbin, MD, FAHA, FACC; Renu Virmani, MD, FACC
Endorsed by the Heart Failure Society of America and the Heart Failure Association of the
European Society of Cardiology
vascular disease remains controversial, and the practice
varies widely even among cardiovascular centers of excel-
lence. A need for EMB exists because specific myocardial
disorders that have unique prognoses and treatment are
seldom diagnosed by noninvasive testing.1Informed clin-
ical decision making that weighs the risks of EMB against
the incremental diagnostic, prognostic, and therapeutic
value of the procedure is especially challenging for non-
specialists because the relevant published literature is
usually cited according to specific cardiac diseases, which
are only diagnosed after EMB. To define the current role
of EMB in the management of cardiovascular disease, a
multidisciplinary group of experts in cardiomyopathies
and cardiovascular pathology was convened by the Amer-
ican Heart Association (AHA), the American College of
Cardiology (ACC), and the European Society of Cardiology
(ESC). The present Writing Group was charged with reviewing
the published literature on the role of EMB in cardiovascular
diseases, summarizing this information, and making useful
he role of endomyocardial biopsy (EMB) in the
diagnosis and treatment of adult and pediatric cardio-
recommendations for clinical practice with classifications of
recommendations and levels of evidence.
The Writing Group identified 14 clinical scenarios in which
the incremental diagnostic, prognostic, and therapeutic value of
EMB could be estimated and compared with the procedural
risks. The recommendations contained in the present joint
Scientific Statement are derived from a comprehensive review
mias, and cardiac tumors and are categorized according to
presenting clinical syndrome rather than pathologically con-
an understanding of the range of acceptable approaches for the
use of EMB while recognizing that individual patient care
decisions depend on factors not well reflected in the published
literature, such as local availability of specialized facilities,
cardiovascular pathology expertise, and operator experience.
The use of EMB in the posttransplantation setting is beyond the
scope of this document.
This Scientific Statement was approved for publication by the
governing bodies of the American Heart Association, the Amer-
ican College of Cardiology, and the European Society of
The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside
relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required
to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This document was approved by the American Heart Association Science Advisory and Coordinating Committee on July 2, 2007; the American College
of Cardiology Foundation Board of Trustees on May 21, 2007; and the European Society of Cardiology Committee for Practice Guidelines on April 3,
When this document is cited, the American Heart Association, the American College of Cardiology Foundation, and the European Society of
Cardiology request that the following citation format be used: Cooper LT, Baughman K, Feldman AM, Frustaci A, Jessup M, Kuhl U, Levine GN, Narula
J, Starling RC, Towbin J, Virmani R. 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. 2007;116:2216–2233.
This article has been copublished in the Journal of the American College of Cardiology and the European Heart Journal.
Copies: This document is available on the World Wide Web sites of the American Heart Association (my.americanheart.org), the American College
of Cardiology (www.acc.org), and the European Society of Cardiology (www.escardio.org). A single reprint is available by calling 800-242-8721 (US
only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX 75231-4596. Ask for reprint No. 71-0421. To
purchase Circulation reprints, call 843-216-2533 or e-mail firstname.lastname@example.org.
Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express
permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml?
identifier?4431. A link to the “Permission Request Form” appears on the right side of the page.
© 2007 by the American Heart Association, Inc, the American College of Cardiology Foundation, and the European Society of Cardiology.
Circulation is available at http://circ.ahajournals.orgDOI: 10.1161/CIRCULATIONAHA.107.186093
AHA/ACCF/ESC Scientific Statement
Cardiology and has been officially endorsed by the Heart Failure
Society of America and the Heart Failure Association of the
European Society of Cardiology.
The classifications of recommendations used in this docu-
● Class I: conditions for which there is evidence or there is
general agreement that a given procedure is beneficial,
useful, and effective;
● Class II: conditions for which there is conflicting evidence
and/or a divergence of opinion about the usefulness/
efficacy of a procedure or treatment;
? Class IIa: conditions for which the weight of evi-
dence/opinion is in favor of usefulness/efficacy;
? Class IIb: conditions for which usefulness/efficacy is
less well established by evidence/opinion; and
● Class III: conditions for which there is evidence and/or
general agreement that a procedure/treatment is not
useful/effective and in some cases may be harmful.
The levels of evidence are
● Level A (highest): multiple randomized clinical trials;
● Level B (intermediate): limited number of randomized
trials, nonrandomized studies, and registries; and
● Level C (lowest): primarily expert consensus.
Technique and Risks of EMB
The first nonsurgical techniques for heart biopsy were re-
ported in 1958.2In the 1960s the safety of heart biopsy
improved, with vascular access through the right external or
internal jugular vein, sampling of the right interventricular
septum, and designation of the heart borders by right heart
catheterization before biopsy.3Sakakibara and Konno4intro-
duced the use of a flexible bioptome with sharpened cusps
that allowed EMB by a pinching as opposed to a cutting
technique. Caves et al5modified the Konno biopsy forceps
(Stanford Caves-Shulz bioptome) to allow percutaneous bi-
opsies through the right internal jugular vein with only local
anesthesia and rapid tissue removal. The reusable Stanford-
Caves bioptome and its subsequent modifications became the
standard device for EMB for approximately 2 decades.6,7
Single-use bioptomes and sheaths allow access through the
right and left jugular or subclavian veins, right and left
femoral veins, and right and left femoral arteries and may be
associated with lower risk of pyrogen reaction and transmis-
sion of infection than reusable bioptomes.
The right internal jugular vein is the most common
percutaneous access site for right ventricular EMB in the
United States. In Germany and Italy, the femoral vein is
commonly used for percutaneous access.8Sonographic tech-
niques to identify the location, size, and respirophasic varia-
tion in size of the internal jugular vein decrease the duration
of the procedure and complications.9,10Monitoring should
include electrocardiographic rhythm, blood pressure, and
pulse oximetry. The subclavian vein also may be used
The femoral artery may be used as a percutaneous access
site for left ventricular biopsy.11,12This approach requires
insertion of a preformed sheath to maintain arterial patency.
All arterial sheaths must be maintained under constant pres-
surized infusion to avoid embolic events. Aspirin or other
antiplatelet agents may be used in addition to heparin during
left heart biopsy procedures to decrease the risk of systemic
embolization. No comparative studies exist on which to base
a recommendation for left versus right ventricular biopsy;
however, left ventricular biopsy has been used in case series
to define cardiomyopathic processes limited to the left
EMB usually is performed safely under fluoroscopic guid-
ance. Fluoroscopy is generally better than 2-dimensional
echocardiography to guide EMB because it provides more
information to the operator about the course of the bioptome
and site of biopsy.14,15The echocardiographic technique
without fluoroscopy has been used primarily to biopsy
intracardiac masses. Some operators use fluoroscopy and
echocardiography in combination to enhance entry into the
right ventricle and direction of the bioptome. Noninvasive
computed tomography (CT) or cardiac magnetic resonance
(CMR) imaging may be of value in patients scheduled for
EMB. CT scanning may be used to assess the angle of the
intraventricular septum relative to the superior vena cava or
inferior vena cava. Knowledge of this angle may lessen the
risk of inadvertent biopsy of the right ventricular free wall
during a fluoroscopically directed biopsy. In addition, CMR
detection of a focal disease process may identify the area of
the left or right ventricle that would be most likely to
demonstrate the underlying pathological process.13,16Three-
dimensional echocardiography may enhance visualization
and reduce the reliance on radiographic imaging in the
The risks of EMB may be divided into those that are acute
and those that are delayed. Immediate risks of biopsy include
perforation with pericardial tamponade, ventricular or su-
praventricular arrhythmias, heart block, pneumothorax, punc-
ture of central arteries, pulmonary embolization, nerve pare-
sis, venous hematoma, damage to the tricuspid valve, and
creation of arterial venous fistula within the heart. The risks
of EMB likely vary with the experience of the operator,
clinical status of the patient, presence or absence of left
bundle-branch block, access site, and possibly bioptome. The
use of a long sheath that crosses the tricuspid valve may
decrease the risk of bioptome-induced tricuspid valve trauma.
Delayed complications include access site bleeding, damage
to the tricuspid valve, pericardial tamponade, and deep
venous thrombosis. Most complications are known from case
reports, and therefore the precise frequency of these events is
The data on EMB risks are derived from several single-
center experiences and registries that have been reported in
the literature. Fowles and Mason18reported an overall com-
plication rate of ?1% in ?4000 biopsies performed in
transplantation and cardiomyopathy patients, including 4 with
tamponade (0.14%), 3 pneumothorax, 3 atrial fibrillation, 1
ventricular arrhythmia, and 3 focal neurological complica-
tions.18Olsen, in an unpublished series referenced by Fowles
and Mason,18reported an overall complication rate of 1.55%
in 3097 cardiomyopathy patients biopsied in Europe. Sekigu-
chi and Take19reported a 1.17% complication rate in a
Cooper et al Endomyocardial Biopsy in Cardiovascular Disease
worldwide questionnaire of 6739 patients, including perfora-
tion in 28 patients (0.42%) and death in 2 patients (0.03%).
Deckers et al20prospectively recorded complications from
546 consecutive right heart biopsy procedures in patients with
new-onset unexplained cardiomyopathy. These are the most
reliable data in the literature20; the complication rates of
sheath insertion and biopsy procedure were reported as 2.7%
and 3.3%, as noted in Table 1.
The death rate associated with EMB is a result of perfora-
tion with pericardial tamponade.20Patients with increased
right ventricular systolic pressures, bleeding diathesis, recent
receipt of heparin, or right ventricular enlargement seem to be
at higher risk. Echocardiography is used to confirm myocar-
dial perforation and should be done in any patient in whom
the operator believes perforation may have occurred, even
without cardiovascular collapse, before central venous access
is removed or the patient leaves the catheterization labora-
tory. Immediate pericardiocentesis and the capability to
surgically evacuate the pericardial space should be available
at centers that perform EMB.
Careful attention to technique can minimize procedural
risks. The risk of pneumothorax can be minimized by taking
a relatively high internal jugular approach and avoiding the
immediate supra-clavicular location. Patients with preexistent
left bundle-branch block may develop complete heart block
when any catheter is placed into the right ventricle and
presses against the intraventricular septum.20If this occurs,
the bioptome and/or sheath must be removed, and the patient
may require temporary ventricular pacing. Rarely, the heart
block may be permanent. Lidocaine in the jugular venous and
carotid sheath may result in Horner syndrome, vocal paresis,
and, infrequently, weakness of the diaphragm. These compli-
cations last only for the duration of the lidocaine effect,
unless permanent damage has been done by trauma from the
The risks of EMB depend on the clinical state of the
patient, the experience of the operator, and the availability of
expertise in cardiac pathology. If a patient with an indication
for EMB presents at a medical center where expertise in EMB
and cardiac pathology is unavailable, transfer of the patient to
a medical center with such experience should be seriously
considered. Additionally, patients with cardiogenic shock or
unstable ventricular arrhythmias may require the care of
specialists in medical and surgical management of heart
failure, including ventricular assist device placement and
potentially heart transplantation.
Analysis of EMB Tissue
Samples should be obtained from ?1 region of the right
ventricular septum. The number of samples obtained should
range from 5 to 10, depending on the studies to be performed,
and each sample should be 1 to 2 mm3in size. The sample
must be handled carefully to minimize artifacts and trans-
ferred from the bioptome to fixative (10% neutral buffered
formalin) by use of a sterile needle and not with forceps.21,22
The fixative should be at room temperature to prevent
contraction band artifacts.23
The clinical reason for the biopsy determines how many
samples are removed and how they are fixed. In general, at
least 4 to 5 samples are submitted for light microscopic
examination, but more may be submitted for transmission
electron microscopy if the clinical question is anthracycline
cardiotoxicity.22,24,25Transmission electron microscopy may
also be helpful for the assessment of suspected infiltrative
disorders such as amyloidosis, glycogen storage diseases,
lysosomal storage diseases, and occasionally viral myocardi-
tis. For transmission electron microscopy, pieces are fixed in
4% glutaraldehyde at room temperature at the time of EMB.22
One or more pieces may be frozen for molecular studies,
immunofluorescence, or immunohistochemistry that may be
required for suspected myocarditis, storage diseases, tumor
typing, amyloid classification, or viral genome analysis.26
Pieces of myocardium can be snap-frozen in OCT-embedding
medium and stored at ?80° F for immunohistochemical or
liquid nitrogen molecular studies. Flash-freezing is suitable
for culture, polymerase chain reaction (PCR), or reverse
transcriptase PCR (rtPCR) for the identification of viruses,
but flash-freezing is not ideal for standard histological prep-
aration because of ice crystal artifacts and cell culture.
Light Microscopic Examination and Stains
For routine light microscopy examination, EMB tissue is
embedded in paraffin, and serial sections are obtained and
sequentially numbered.23For suspected myocarditis, many
laboratories will stain every third piece for hematoxylin and
eosin and the middle 2 pieces for Movat or elastic trichrome
stain to visualize collagen and elastic tissue. Many laborato-
ries also routinely stain 1 slide for iron on men and all
postmenopausal women, regardless of the indication for
EMB.23Congo red staining may be performed on 10- to
15-?m sections to rule out amyloidosis. The remaining slides
are usually preserved for immunohistochemistry.
Molecular Biological Detection of Viral Genomes
Recent advances in quantitative (qPCR) and qualitative
(nested PCR) molecular techniques can detect fewer than 10
gene copies of viral pathogens in the myocardium. These
highly sensitive techniques provide both challenges and
opportunities. The clinical impact on prognosis and treatment
Risks Associated With Endomyocardial Biopsy in 546
Overall 33 complications (6%)
Sheath insertion 15 (2.7%)
12 (2.0%) arterial puncture during local anesthesia
2 (0.4%) vasovagal reaction
1 (0.2%) prolonged venous oozing after sheath removal
Biopsy procedure 18 (3.3%)
6 (1.1%) arrhythmia
5 (1.0%) conduction abnormalities
4 (0.7%) possible perforation (pain)
3 (0.5%) definite perforation (pericardial fluid)
2 of 3 patients with definite perforation died
Reprinted from Deckers et al,20with permission from the American College
of Cardiology. © 1992.
November 6, 2007
antimyosin scintigraphy in suspected myocarditis. J Nucl Cardiol. 1996;
52. Shields RC, Tazelaar HD, Berry GJ, Cooper LT Jr. The role of right
ventricular endomyocardial biopsy for idiopathic giant cell myocarditis.
J Card Fail. 2002;8:74–78.
53. Kilgallen CM, Jackson E, Bankoff M, Salomon RN, Surks HK. A case
of giant cell myocarditis and malignant thymoma: a postmortem
diagnosis by needle biopsy. Clin Cardiol. 1998;21:48–51.
54. Daniels PR, Berry GJ, Tazelaar HD, Cooper LT. Giant cell myocarditis
as a manifestation of drug hypersensitivity. Cardiovasc Pathol. 2000;9:
55. Okura Y, Dec GW, Hare JM, Berry GR, Tazelaar HD, Cooper LT. A
multicenter registry comparison of cardiac sarcoidosis and idiopathic
giant-cell myocarditis. Circulation. 2000;102(18 suppl II):II-788.
56. Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: a clinico-
pathologic study of 84 unselected patients with systemic sarcoidosis.
57. Sekiguchi M, Yazaki Y, Isobe M, Hiroe M. Cardiac sarcoidosis: diag-
nostic, prognostic, and therapeutic considerations. Cardiovasc Drugs
58. Yazaki Y, Isobe M, Hiramitsu S, Morimoto S, Hiroe M, Omichi C,
Nakano T, Saeki M, Izumi T, Sekiguchi M. Comparison of clinical
features and prognosis of cardiac sarcoidosis and idiopathic dilated
cardiomyopathy. Am J Cardiol. 1998;82:537–540.
59. Fleming HA, Bailey SM. Sarcoid heart disease. J R Coll Physicians
Lond. 1981;15:245–246, 249–253.
60. Cooper L, Okura Y, Hare J, Grogen M. Survival in biopsy-proven
cardiac sarcoidosis is similar to survival in lymphocytic myocarditis and
dilated cardiomyopathy. In: Kimchi A, ed. Heart Disease: New Trends
in Research, Diagnosis, and Treatment: Proceedings of the 2nd Inter-
national Congress on Heart Disease. Englewood, NJ: Medimond
Medical Publications; 2001:491–496.
61. Okura Y, Dec GW, Hare JM, Kodama M, Berry GJ, Tazelaar HD,
Bailey KR, Cooper LT. A clinical and histopathologic comparison of
cardiac sarcoidosis and idiopathic giant cell myocarditis. J Am Coll
62. Litovsky SH, Burke AP, Virmani R. Giant cell myocarditis: an entity
distinct from sarcoidosis characterized by multiphasic myocyte
destruction by cytotoxic T cells and histiocytic giant cells. Mod Pathol.
63. Uemura A, Morimoto S, Hiramitsu S, Kato Y, Ito T, Hishida H. His-
tologic diagnostic rate of cardiac sarcoidosis: evaluation of endomyo-
cardial biopsies. Am Heart J. 1999;138(2 pt 1):299–302.
64. Sekiguchi M, Numao Y, Imai M, Furuie T, Mikami R. Clinical and
histopathological profile of sarcoidosis of the heart and acute idiopathic
myocarditis: concepts through a study employing endomyocardial
biopsy, I: sarcoidosis. Jpn Circ J. 1980;44:249–263.
65. Schulz-Menger J, Wassmuth R, Abdel-Aty H, Siegel I, Franke A, Dietz
R, Friedrich MG. Patterns of myocardial inflammation and scarring in
sarcoidosis as assessed by cardiovascular magnetic resonance. Heart.
66. Ardehali H, Howard DL, Hariri A, Qasim A, Hare JM, Baughman KL,
Kasper EK. A positive endomyocardial biopsy result for sarcoid is
associated with poor prognosis in patients with initially unexplained
cardiomyopathy. Am Heart J. 2005;150:459–463.
67. Takada K, Ina Y, Yamamoto M, Satoh T, Morishita M. Prognosis after
pacemaker implantation in cardiac sarcoidosis in Japan: clinical eval-
uation of corticosteroid therapy. Sarcoidosis. 1994;11:113–117.
68. Bellhassen B, Pines A, Laniado S. Failure of corticosteroids to prevent
induction of ventricular tachycardia in sarcoidosis. Chest. 1989;95:
69. Johns CJ, Michele TM. The clinical management of sarcoidosis: a
50-year experience at the Johns Hopkins Hospital. Medicine (Bal-
70. Bajaj AK, Kopelman HA, Echt DS. Cardiac sarcoidosis with sudden
death: treatment with the automatic implantable cardioverter defi-
brillator. Am Heart J. 1988;116(2 pt 1):557–560.
71. Winters SL, Cohen M, Greenberg S, Stein B, Curwin J, Pe E, Gomes JA.
Sustained ventricular tachycardia associated with sarcoidosis:
assessment of the underlying cardiac anatomy and the prospective utility
of programmed ventricular stimulation, drug therapy and an implantable
antitachycardia device. J Am Coll Cardiol. 1991;18:937–943.
72. Taliercio CP, Olney BA, Lie JT. Myocarditis related to drug hypersen-
sitivity. Mayo Clin Proc. 1985;60:463–468.
73. Hawkins ET, Levine TB, Goss SJ, Moosvi A, Levine AB. Hypersensi-
tivity myocarditis in the explanted hearts of transplant recipients: reap-
praisal of pathologic criteria and their clinical implications. Pathol
Annual. 1995;30(pt 1):287–304.
74. Spear GS. Eosinophilic explant carditis with eosinophilia: hypersensi-
tivity to dobutamine infusion. J Heart Lung Transplant. 1995;14:
75. Morimoto S, Kato S, Hiramitsu S, Uemura A, Ohtsuki M, Kato Y,
Sugiura A, Miyagishima K, Iwase M, Ito T, Hishida H. Narrowing of the
left ventricular cavity associated with transient ventricular wall
thickening reduces stroke volume in patients with acute myocarditis.
Circ J. 2003;67:490–494.
76. Meinardi MT, van der Graaf WT, van Veldhuisen DJ, Gietema JA, de
Vries EG, Sleijfer DT. Detection of anthracycline-induced cardio-
toxicity. Cancer Treat Rev. 1999;25:237–247.
77. Mason JW. Techniques for right and left ventricular endomyocardial
biopsy. Am J Cardiol. 1978;41:887–892.
78. Bristow MR, Lopez MB, Mason JW, Billingham ME, Winchester MA.
Efficacy and cost of cardiac monitoring in patients receiving doxo-
rubicin. Cancer. 1982;50:32–41.
79. Ewer MS, Ali MK, Mackay B, Wallace S, Valdivieso M, Legha SS,
Benjamin RS, Haynie TP. A comparison of cardiac biopsy grades and
ejection fraction estimations in patients receiving adriamycin. J Clin
80. Mackay B, Ewer MS, Carrasco CH, Benjamin RS. Assessment of
anthracycline cardiomyopathy by endomyocardial biopsy. Ultrastruct
81. Torti FM, Bristow MM, Lum BL, Carter SK, Howes AE, Aston DA,
Brown BW Jr, Hannigan JF Jr, Meyers FJ, Mitchell EP, et al. Cardio-
toxicity of epirubicin and doxorubicin: assessment by endomyocardial
biopsy. Cancer Res. 1986;46:3722–3727.
82. Umsawasdi T, Valdivieso M, Booser DJ, Barkley HT Jr, Ewer M,
MacKay B, Dhingra HM, Murphy WK, Spitzer G, Chiuten DF, et al.
Weekly doxorubicin versus doxorubicin every 3 weeks in cyclophos-
phamide, doxorubicin, and cisplatin chemotherapy for non-small cell
lung cancer. Cancer. 1989;64:1995–2000.
83. Valero V, Buzdar AU, Theriault RL, Azarnia N, Fonseca GA, Willey J,
Ewer M, Walters RS, Mackay B, Podoloff D, Booser D, Lee LW,
Hortobagyi GN. Phase II trial of liposome-encapsulated doxorubicin,
cyclophosphamide, and fluorouracil as first-line therapy in patients with
metastatic breast cancer. J Clin Oncol. 1999;17:1425–1434.
84. Hortobagyi GN, Willey J, Rahman Z, Holmes FA, Theriault RL, Buzdar
AU. Prospective assessment of cardiac toxicity during a randomized
phase II trial of doxorubicin and paclitaxel in metastatic breast cancer.
Semin Oncol 1997;24(5 suppl 17):S17-65–S17-68.
85. Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters
B, Shevtsov S, Pesant S, Clubb FJ, Rosenzweig A, Salomon RN, Van
Etten RA, Alroy J, Durand JB, Force T. Cardiotoxicity of the cancer
therapeutic agent imatinib mesylate. Nat Med. 2006;12:908–916.
86. Feldman AM, Lorell BH, Reis SE. Trastuzumab in the treatment of
metastatic breast cancer: anticancer therapy versus cardiotoxicity. Cir-
87. Kushwaha SS, Fallon JT, Fuster V. Restrictive cardiomyopathy. N Engl
J Med. 1997;336:267–276.
88. Asher CR, Klein AL. Diastolic heart failure: restrictive cardiomyopathy,
constrictive pericarditis, and cardiac tamponade: clinical and echocar-
diographic evaluation. Cardiol Rev. 2002;10:218–229.
89. Yazdani K, Maraj S, Amanullah AM. Differentiating constrictive peri-
carditis from restrictive cardiomyopathy. Rev Cardiovasc Med. 2005;6:
90. Alter P, Grimm W, Tontsch D, Maisch B. Diagnosis of primary cardiac
lymphoma by endomyocardial biopsy. Am J Med. 2001;110:593–594.
91. Iwaki T, Kanaya H, Namura M, Ikeda M, Uno Y, Terashima N, Ohka T,
Miura Y, Shimizu M, Mabuchi H. Right ventricular metastasis from a
primary cervical carcinoma. Jpn Circ J. 2001;65:761–763.
92. Malouf JF, Thompson RC, Maples WJ, Wolfe JT. Diagnosis of right
atrial metastatic melanoma by transesophageal echocardiographic-
guided transvenous biopsy. Mayo Clin Proc. 1996;71:1167–1170.
93. Flipse TR, Tazelaar HD, Holmes DR Jr. Diagnosis of malignant cardiac
disease by endomyocardial biopsy. Mayo Clin Proc. 1990;65:
94. Scott PJ, Ettles DF, Rees MR, Williams GJ. The use of combined
transesophageal echocardiography and fluoroscopy in the biopsy of a
right atrial mass. Br J Radiol. 1990;63:222–224.
Cooper et al Endomyocardial Biopsy in Cardiovascular Disease
95. Burling F, Devlin G, Heald S. Primary cardiac lymphoma diagnosed
with transesophageal echocardiography–guided endomyocardial biopsy.
96. Savoia MT, Liguori C, Nahar T, Marboe C, Weinberger J, Di Tullio
MR, Homma S. Transesophageal echocardiography–guided transvenous
biopsy of a cardiac sarcoma. J Am Soc Echocardiogr. 1997;10:752–755.
97. Hanley PC, Shub C, Seward JB, Wold LE. Intracavitary cardiac
melanoma diagnosed by endomyocardial left ventricular biopsy. Chest.
98. Hausheer FH, Josephson RA, Grochow LB, Weissman D, Brinker JA,
Weisman HF. Intracardiac sarcoma diagnosed by left ventricular endo-
myocardial biopsy. Chest. 1987;92:177–179.
99. Morrone A, Gaglione A, Bortone A, Iliceto S, Caruso G, Calabrese P,
Chiddo A. Endomyocardial biopsy diagnosis of a pulmonary micro-
cytoma metastasized to the atrium. Cardiologia. 1988;33:419–421.
100. Hammoudeh AJ, Chaaban F, Watson RM, Millman A. Transesophageal
echocardiography–guided transvenous endomyocardial biopsy used to
diagnose primary cardiac angiosarcoma. Cathet Cardiovasc Diagn.
101. Gosalakkal JA, Sugrue DD. Malignant melanoma of the right atrium,
antemortem diagnosis by transvenous biopsy. Br Heart J. 1989;62:
102. Miyashita T, Miyazawa I, Kawaguchi T, Kasai T, Yamaura T, Ito T,
Takei M, Kiyosawa K. A case of primary cardiac B cell lymphoma
associated with ventricular tachycardia, successfully treated with
systemic chemotherapy and radiotherapy: a long-term survival case. Jpn
Circ J. 2000;64:135–138.
103. Cooper DL, Sinard JH, Edelson RL, Flynn SD. Cardiogenic shock due
to progression of cutaneous T-cell lymphoma. South Med J. 1994;87:
104. Starr SK, Pugh DM, O’Brien-Ladner A, Stites S, Wilson DB. Right
atrial mass biopsy guided by transesophageal echocardiography. Chest.
105. Chan KL, Veinot J, Leach A, Bedard P, Smith S, Marquis JF. Diagnosis
of left atrial sarcoma by transvenous endocardial biopsy. Can J Cardiol.
106. Medolago G, Virotta G, Piti A, Tespili M, D’Adda F, Rottoli MR,
Comotti B, Motta T, Orlandi C, Bertocchi C. Abnormal uptake of
technetium-99m hexakis-2-methoxyisobutylisonitrile in a primary
cardiac lymphoma. Eur J Nucl Med. 1992;19:222–225.
107. Towbin J. Cardiomyopathy and heart transplantation in children. Curr
Opin Cardiol. 2002;17:274–279.
108. Shmorhun D, Fenrich A, Cecchin F, et al. Identification of viral causes
for ventricular arrhythmia in children using PCR analysis. Pacing Clin
109. Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearney D,
Zhang YH, Bodurtha J, Gelb B, Ni J, et al. Acute myocarditis: rapid
diagnosis by PCR in children. Circulation. 1994;90:330–339.
110. Shirali GS, Ni J, Chinnock RE, Johnston JK, Rosenthal GL, Bowles NE,
Towbin JA. Association of viral genome with graft loss in children after
cardiac transplantation. N Engl J Med. 2001;344:1498–1503.
111. Dec GW. Introduction to clinical myocarditis. In: Cooper LT, ed.
Myocarditis From Bench to Bedside. Totowa, NJ: Humana Press; 2003:
112. Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT,
Fenoglio JJ Jr, Olsen EG, Schoen FJ. Myocarditis: a histopathologic
definition and classification. Am J Cardiovasc Pathol. 1987;1:3–14.
113. Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Cir-
114. Grogan M, Redfield MM, Bailey KR, Reeder GS, Gersh BJ, Edwards
WD, Rodeheffer RJ. Long-term outcome of patients with biopsy-proved
myocarditis: comparison with idiopathic dilated cardiomyopathy. J Am
Coll Cardiol. 1995;26:80–84.
115. Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G,
Wilczewski P, Niklewski T, Zembala M, Polonski L, Rozek MM,
Wodniecki J. Randomized, placebo-controlled study for immunosup-
pressive treatment of inflammatory dilated cardiomyopathy: two-year
follow-up results. Circulation. 2001;104:39–45.
116. Staudt A, Schaper F, Stangl V, Plagemann A, Bohm M, Merkel K,
Wallukat G, Wernecke KD, Stangl K, Baumann G, Felix SB. Immuno-
histological changes in dilated cardiomyopathy induced by immunoad-
sorption therapy and subsequent immunoglobulin substitution. Circu-
117. Wojnicz R, Wilczek K, Nowalany-Kozielska E, Szygula-Jurkiewicz B,
Nowak J, Polonski L, Dyrbus K, Badzinski A, Mercik G, Zembala M,
Wodniecki J, Rozek MM. Usefulness of atorvastatin in patients with
heart failure due to inflammatory dilated cardiomyopathy and elevated
cholesterol levels. Am J Cardiol. 2006;97:899–904.
118. Herskowitz A, Ahmed-Ansari A, Neumann DA, Beschorner WE, Rose
NR, Soule LM, Burek CL, Sell KW, Baughman KL. Induction of major
histocompatibility complex antigens within the myocardium of patients
with active myocarditis: a nonhistologic marker of myocarditis. J Am
Coll Cardiol. 1990;15:624–632.
119. Parrillo JE. Inflammatory cardiomyopathy (myocarditis): which patients
should be treated with anti-inflammatory therapy? Circulation. 2001;
120. Olson LJ, Edwards WD, McCall JT, Ilstrup DM, Gersh BJ. Cardiac iron
deposition in idiopathic hemochromatosis: histologic and analytic
assessment of 14 hearts from autopsy. J Am Coll Cardiol. 1987;10:
121. Rahko PS, Salerni R, Uretsky BF. Successful reversal by chelation
therapy of congestive cardiomyopathy due to iron overload. J Am Coll
122. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D,
Moss AJ, Seidman CE, Young JB; American Heart Association; Council
on Clinical Cardiology, Heart Failure and Transplantation Committee;
Quality of Care and Outcomes Research and Functional Genomics and
Translational Biology Interdisciplinary Working Groups; Council on
Epidemiology and Prevention. Contemporary definitions and classifi-
cation of the cardiomyopathies: an American Heart Association Sci-
entific Statement from the Council on Clinical Cardiology, Heart Failure
and Transplantation Committee; Quality of Care and Outcomes
Research and Functional Genomics and Translational Biology Interdis-
ciplinary Working Groups; and Council on Epidemiology and Pre-
vention. Circulation. 2006;113:1807–1816.
123. Frustaci A, Chimenti C, Ricci R, Natale L, Russo MA, Pieroni M, Eng
CM, Desnick RJ. Improvement in cardiac function in the cardiac variant
of Fabry’s disease with galactose-infusion therapy. N Engl J Med.
124. Falk RH. Diagnosis and management of the cardiac amyloidoses. Cir-
125. Rahman JE, Helou EF, Gelzer-Bell R, Thompson RE, Kuo C, Rodriguez
ER, Hare JM, Baughman KL, Kasper EK. Noninvasive diagnosis of
biopsy-proven cardiac amyloidosis. J Am Coll Cardiol. 2004;43:
126. Dispenzieri A, Kyle RA, Gertz MA, Therneau TM, Miller WL, Chan-
drasekaran K, McConnell JP, Burritt MF, Jaffe AS. Survival in patients
with primary systemic amyloidosis and raised serum cardiac troponins.
127. Pellikka PA, Holmes DR Jr, Edwards WD, Nishimura RA, Tajik AJ,
Kyle RA. Endomyocardial biopsy in 30 patients with primary amy-
loidosis and suspected cardiac involvement. Arch Intern Med. 1988;148:
128. Kies P, Bootsma M, Bax J, Schalij MJ, van der Wall EE. Arrhyth-
mogenic right ventricular dysplasia/cardiomyopathy: screening,
diagnosis, and treatment. Heart Rhythm. 2006;3:225–234.
129. Basso C, Thiene G. Adipositas cordis, fatty infiltration of the right
ventricle, and arrhythmogenic right ventricular cardiomyopathy: just a
matter of fat? Cardiovasc Pathol. 2005;14:37–41.
130. Hulot JS, Jouven X, Empana JP, Frank R, Fontaine G. Natural history
and risk stratification of arrhythmogenic right ventricular dysplasia/car-
diomyopathy. Circulation. 2004;110:1879–1884.
131. Tandri H, Castillo E, Ferrari VA, Nasir K, Dalal D, Bomma C, Calkins
H, Bluemke DA. Magnetic resonance imaging of arrhythmogenic right
ventricular dysplasia: sensitivity, specificity, and observer variability of
fat detection versus functional analysis of the right ventricle. J Am Coll
132. Wichter T, Hindricks G, Lerch H, Bartenstein P, Borggrefe M, Schober
O, Breithardt G. Regional myocardial sympathetic dysinnervation in
arrhythmogenic right ventricular cardiomyopathy: an analysis using
123I-meta-iodobenzylguanidine scintigraphy. Circulation. 1994;89:
133. Chimenti C, Pieroni M, Maseri A, Frustaci A. Histologic findings in
patients with clinical and instrumental diagnosis of sporadic arrhyth-
mogenic right ventricular dysplasia. J Am Coll Cardiol. 2004;43:
November 6, 2007
134. Basso C, Ronco F, Abudureheman A, Thiene G. In vitro validation of
endomyocardial biopsy for the in vivo diagnosis of arrhythmogenic right
ventricular cardiomyopathy. Eur Heart J. 2006;27(suppl):960. Abstract.
135. Bowles NE, Ni J, Marcus F, Towbin JA. The detection of cardiotropic
viruses in the myocardium of patients with arrhythmogenic right ven-
tricular dysplasia/cardiomyopathy. J Am Coll Cardiol. 2002;39:
136. Mason JW, O’Connell JB. Clinical merit of endomyocardial biopsy.
137. Veinot JP. Diagnostic endomyocardial biopsy pathology: secondary
myocardial diseases and other clinical indications: a review. Can
J Cardiol. 2002;18:287–296.
138. Hosenpud JD, McAnulty JH, Niles NR. Unexpected myocardial disease
in patients with life threatening arrhythmias. Br Heart J. 1986;56:
139. Oakes DF, Manolis AS, Estes NA 3rd. Limited clinical utility of endo-
myocardial biopsy in patients presenting with ventricular tachycardia
without apparent structural heart disease. Clin Cardiol. 1992;15:24–28.
140. Sugrue DD, Holmes DR Jr, Gersh BJ, Edwards WD, McLaran CJ, Wood
DL, Osborn MJ, Hammill SC. Cardiac histologic findings in patients
with life-threatening ventricular arrhythmias of unknown origin. J Am
Coll Cardiol. 1984;4:952–957.
141. Vignola PA, Aonuma K, Swaye PS, Rozanski JJ, Blankstein RL, Benson
J, Gosselin AJ, Lister JW. Lymphocytic myocarditis presenting as unex-
plained ventricular arrhythmias: diagnosis with endomyocardial biopsy
and response to immunosuppression. J Am Coll Cardiol. 1984;4:
142. Frustaci A, Bellocci F, Olsen EG. Results of biventricular endomyocar-
dial biopsy in survivors of cardiac arrest with apparently normal hearts.
Am J Cardiol. 1994;74:890–895.
143. Yonesaka S, Takahashi T, Tomimoto K, Kinjo M, Sunagawa Y, Sato S,
Nakada T, Matubara T, Oura H, Koda M, Furukawa H. Clinical and
histopathological studies in children with supraventricular tachycardia.
Jpn Circ J. 1996;60:560–566.
144. Teragaki M, Toda I, Sakamoto K, Shimada K, Yamagishi H, Yoshiyama
M, Akioka K, Kawase Y, Nishimoto M, Takeuchi K, Yoshikawa J.
Endomyocardial biopsy findings in patients with atrioventricular block
in the absence of apparent heart disease. Heart Vessels. 1999;14:
145. Kobayashi Y, Yazawa T, Baba T, Mukai H, Inoue S, Takeyama Y,
Niitani H. Clinical, electrophysiological, and histopathological obser-
vations in supraventricular tachycardia. Pacing Clin Electrophysiol.
146. Uemura A, Morimoto S, Hiramitsu S, Hishida H. Endomyocardial
biopsy findings in 50 patients with idiopathic atrioventricular block:
presence of myocarditis. Jpn Heart J. 2001;42:691–700.
147. Frustaci A, Caldarulo M, Buffon A, Bellocci F, Fenici R, Melina D.
Cardiac biopsy in patients with “primary” atrial fibrillation: histologic
evidence of occult myocardial diseases. Chest. 1991;100:303–306.
148. Uemura A, Morimoto S, Hiramitsu S, Ohtsuki M, Kato S, Kato Y,
Sugiura A, Miyagishima K, Hishida H. Right ventricular endomyocar-
dial biopsy findings in 25 patients with sick sinus syndrome. Jpn
Heart J. 2004;45:73–80.
149. Feldman AM, Ray PE, Silan CM, Mercer JA, Minobe W, Bristow MR.
Selective gene expression in failing human heart: quantification of
steady-state levels of messenger RNA in endomyocardial biopsies using
the polymerase chain reaction. Circulation. 1991;83:1866–1872.
150. Ladenson PW, Sherman SI, Baughman KL, Ray PE, Feldman AM.
Reversible alterations in myocardial gene expression in a young man
with dilated cardiomyopathy and hypothyroidism [published correction
appears in Proc Natl Acad Sci U S A. 1992;89:8856]. Proc Natl Acad Sci
U S A. 1992;89:5251–5255.
151. Bristow MR, Minobe WA, Raynolds MV, Port JD, Rasmussen R, Ray
PE, Feldman AM. Reduced beta 1 receptor messenger RNA abundance
in the failing human heart. J Clin Invest. 1993;92:2737–2745.
152. Lowes BD, Zolty R, Minobe WA, Robertson AD, Leach S, Hunter L,
Bristow MR. Serial gene expression profiling in the intact human heart.
J Heart Lung Transplant. 2006;25:579–588.
153. Cook SA, Rosenzweig A. DNA microarrays: implications for cardio-
vascular medicine. Circ Res. 2002;91:559–564.
154. Napoli C, Lerman LO, Sica V, Lerman A, Tajana G, de Nigris F.
Microarray analysis: a novel research tool for cardiovascular scientists
and physicians. Heart. 2003;89:597–604.
155. Henriksen PA, Kotelevtsev Y. Application of gene expression profiling
to cardiovascular disease. Cardiovasc Res. 2002;54:16–24.
156. Slonim DK. From patterns to pathways: gene expression data analysis
comes of age. Nat Genet. 2002;32(suppl):502–508.
157. Strain JE, Grose RM, Factor SM, Fisher JD. Results of endomyocardial
biopsy in patients with spontaneous ventricular tachycardia but without
apparent structural heart disease. Circulation. 1983;68:1171–1181.
158. Morgera T, Salvi A, Alberti E, Silvestri F, Camerini F. Morphological
findings in apparently idiopathic ventricular tachycardia: an echocardio-
graphic haemodynamic and histologic study. Eur Heart J. 1985;6:
159. Dunnigan A, Staley NA, Smith SA, Pierpont ME, Judd D, Benditt DG,
Benson DW Jr. Cardiac and skeletal muscle abnormalities in cardiomy-
opathy: comparison of patients with ventricular tachycardia or con-
gestive heart failure. J Am Coll Cardiol. 1987;10:608–618.
160. Nishikawa T, Sekiguchi M, Hasumi M, Kasajima T, Nakazawa M, Ando
M, Takao A. Histopathologic findings of endomyocardial biopsies in
pediatric patients with arrhythmias or conduction disturbances. Heart
Vessels Suppl. 1990;5:24–27.
161. Sekiguchi M, Nishizawa M, Nunoda S, Hiroe M, Hosoda S. Endomyo-
cardial biopsy approach in cases with ventricular arrhythmias. Postgrad
Med J. 1991;68(suppl 1):S40–S43.
162. Thongtang V, Chiathiraphan S, Ratanarapee S, Panchavinnin P,
Srivanasont N, Jootar P, Sahasakul Y, Charoenchob N, Tresukosol D.
Prevalence of myocarditis in idiopathic dysrhythmias: role of endomyo-
cardial biopsy and efficacy of steroid therapy. J Med Assoc Thai.
KEY WORDS: AHA Scientific Statements ?biopsy ?transplantation ?heart
failure ? cardiomyopathy ? myocarditis
Cooper et al Endomyocardial Biopsy in Cardiovascular Disease