Article*
"Development of the European Network in Orphan Cardiovascular Diseases"
„Rozszerzenie Europejskiej Sieci Współpracy ds Sierocych Chorób Kardiologicznych”
Title: Endomyocardial biopsy
–
role,
techniques, indications, results, complications.
RCD code:
Author: Paweł Rubiś1,2,
Affiliation:
1
Department of Cardiac and Vascular Diseases, John Paul II Hospital, Institute of Cardiology
2
Center for Rare Cardiovascular Diseases, John Paul II Hospital
Date: 30/April/2014
John Paul II Hospital in Kraków
Jagiellonian University, Institute of Cardiology
80 Prądnicka Str., 31-202 Kraków;
tel. +48 (12) 614 33 99; 614 34 88; fax. +48 (12) 614 34 88
e-mail: rarediseases@szpitaljp2.krakow.pl
www.crcd.eu
The role of endomyocardial biopsy (EMB) in the management of cardiovascular
diseases has been recently defined by the joint scientific statement from the American Heart
Association (AHA), the American Collage of Cardiology (ACC), and the European Society of
Cardiology (ESC) [1]. According to this document, EMB should be used in one of fourteen
possible clinical scenarios in which the prognostic and diagnostic value of the information
obtained outweighs the risk of the procedure. Although EMB is considered as the gold
standard for in vivo diagnosis of myocardtitis, its invasiveness and potential serious
complications have greatly limited widespread application.
More than two decades ago Investigators for the US Myocarditis Treatment Trail
developed a working standard for the histologic analysis and interpretation of EMB samples,
called the Dallas criteria [2]. However, there are many concerns on the accuracy and utility of
the sole histologic evaluation, as the sensitivity of EMB for myocardtitis using the Dallas
criteria is low at 10 to 35%. Numerous reasons limit the value of “classic” histopathological
assessment and include focal and transient nature of inflammatory process, right ventricular
EMB of interventricular septum is preferable site of biopsy regardless the fact that most
common site of focal involvement is epicardial surface of the LV free wall, sampling error,
and last but not least variability of interpretation between expert pathologists [3].
Before every procedure indications for EMB should be verified with the source
document from AHA/ACC/ESC. In case of dilated cardiomyopathy, probably the most
common indications are clinical scenario 9 which stands for new-onset heart failure (HF) of 2
weeks to 3 months duration associated with dilated LV, without new ventricular arrhythmias,
or 2nd or 3rd degree heart block, and that responds to usual care within 1 to 2 weeks or clinical
scenario 10 which differs from scenario 9 only on the duration of the process (grater than 3
months). The guidelines state that in such clinical setting, EMB may be considered and
provide a weak recommendation of IIb B and IIb C, respectively. Naturally, other clinical
scenarios may occur, particularly scenarios 3, 4 and 5 (all class of recommendation IIa C).
Endomyocardial biopsy is performed under fluoroscopic guidance via a femoral venous
approach by experienced in the procedure interventional cardiologists in the catherization
laboratory with on-site Cardio-Thoracic Surgery Department. Long (104 cm), flexible,
disposable biopsy forceps 6 or 7 French (F) size with small jaws are used for the procedure.
According to the French size, forceps can remove tissue sample of approximately 1.85 mm
per 2.46 mm3 for the 6F and 2.3 mm per 5.2 mm3 for the 7F. The primary site for a biopsy is
usually right ventricular (RV) inter-ventricular septum (more than one region). Several
myocardial are obtained: two samples are submitted for light microscopic evaluation
according to the Dallas criteria and for an immunohistological evaluation of intramyocardial
inflammation, two samples are subject to DNA and RNA extraction for the amplification of
viral genomes and the remaining samples are submitted for studies of non-viral infectious
agents. Prior and after procedure echocardiography is frequently performed to asses the
presence of pericardial effusion or any other procedure-related complications.
The diagnosis of myocarditis and inflammatory cardiomyopathy is made according to
the Dallas criteria and confirmed by immunohistochemistry. Molecular biology studies are
used to detect the presence of cardio-tropic viruses.
Histological diagnosis of myocardtitis (Dallas criteria):
1. Active myocarditis – is defined as “an inflammatory infiltrate in of the myocardium
with necrosis and/or degeneration of adjacent myocytes not typical of the ischemic
damage associated with CAD’. In most cases infiltrates are mononuclear, but may be
John Paul II Hospital in Kraków
Jagiellonian University, Institute of Cardiology
80 Prądnicka Str., 31-202 Kraków;
tel. +48 (12) 614 33 99; 614 34 88; fax. +48 (12) 614 34 88
e-mail: rarediseases@szpitaljp2.krakow.pl
www.crcd.eu
neutrophilic, or eosinophilic (in rare cases of eosinophilic myocarditis).
2. Borderline myocarditis – is diagnosed when the inflammatory infiltrate is too sparse,
or myocyte injury is not demonstrated.
Immunohistochemical diagnosis and quantification of inflammatory process:
1. Abnormal findings – more than 2.0 CD3+ T-lymphocytes per high-power filed (HPF)
(400-fold magnification) or 7 per mm2.
2. Myocarditis – the presence of an inflammatory infiltrate of a minimum of 14
infiltrating leukocytes/mm2.
3. Active myocarditis – the presence of > 14 infiltrating leukocytes/mm2 and/or the
presence of more than 2.0 CD3+ T-lymphocytes per HPF, which are adherent to the
contour of cardiomyocytes and focally associated with cell necrosis.
Although rare, complications of EMB may occur and are sub-classified into major
complications which include pericardial tamponade with hemodynamic compromise and
requirement for pericardiocentesis, hemo- and pneumopericardium, permanent high-grade
atrio-ventricular block requiring pacemaker implantation, myocardial infarction, transient
ischemic attack (TIA) and stroke, severe tricuspid valve damage, and death, whereas minor
complications include transient chest pain, transient ECG abnormalities, transient
arrhythmias, transient hypotension, and small pericardial effusions [4]. The overall
complication rates range from less than 1 to as high as 6 percent [4, 5]. However, two recently
reported EMB safety studies reported lower rates of complications. In 755 patients with
myocardtitis or DCM the major complication rate for left ventricular EMB (LV-EMB) was
0.64% and for right ventricular EMB (RV-EMB) was 0.82%. Interestingly, in contrast to
common assumptions and earlier reports LV-EMB was not associated with grater risk of
complications than RV-EMB. In the larger study comprising of 6800 consecutive patients the
overall incidence of complication was 1.2%, with myocardial perforation in 0.42% and death
in only 0.03%.
References
1. Cooper LT, Baughman KL, Feldman AM, et al. 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.
2. Aretz HT. Myocarditis; the Dallas criteria. Hum Pathol 1987; 18: 619-24.
3. Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Circulation 2006; 113:
593.
4. Holzman M, Nicko A, Kuhl U, et al. 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 2008; 118:
1722.
5. Sekiguchi M, Take M. World survey of catheter biopsy of the heart. In: Cardiomyopathy:
Clinical, pathological and theoretical aspects, Sekiguchi M, Olsen EG (Eds), University
Park Press, Baltimore 1980. p. 217.
Paweł Rubiś …………………………..
Author’s signature**
[** Signing the article will mean an agreement for its publication]
John Paul II Hospital in Kraków
Jagiellonian University, Institute of Cardiology
80 Prądnicka Str., 31-202 Kraków;
tel. +48 (12) 614 33 99; 614 34 88; fax. +48 (12) 614 34 88
e-mail: rarediseases@szpitaljp2.krakow.pl
www.crcd.eu