Endomyocardial biopsy (EMB) has been in use to aid in diagnosing cardiac pathology since the early 1960s. Improvements in biopsy equipment to the current flexible, single-use bioptomes and sheaths allow access to the right ventricular septum via the internal jugular veins (most common access site used in the USA), femoral veins, and subclavian veins [1]. Arterial access may also be used for biopsy of the left ventricle. EMB is required and most commonly used in surveillance of allograft rejection in heart transplant patients. Native heart biopsy is less frequently performed, with considerable variability among medical centers in frequency and indication for use.

The AHA/ACC/ESC joint statement has identified 13 clinical scenarios where EMB may be indicated in native hearts [2]. Of these, 2 are class I recommendations: new-onset heart failure of <2 weeks’ duration associated with a normal-sized or dilated left ventricle and hemodynamic compromise; and 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 1–2 weeks. An additional 6 are class IIa recommendations, including evaluation of heart failure with suspected restrictive/infiltrative cardiomyopathy.

The likelihood of a specific pathologic diagnosis from an EMB of a native heart varies depending on the pre-test probability of pathology, location and number of samples obtained, and timing of biopsy relative to clinical decompensation [3]. The addition of immunohistochemistry and PCR to standard histologic analysis has enhanced the sensitivity of EMB. Specific diagnoses where EMB may be useful in native hearts include myocarditis (viral, giant cell, eosinophilic), amyloidosis, sarcoidosis, ARVC, and Fabry’s disease. Advancements in echocardiography and cardiac MRI have significantly enhanced noninvasive diagnosis of some of these diseases; however, there often remains a role for EMB. A recent retrospective analysis was performed on 100 consecutive patients who presented to a tertiary care center with unexplained cardiomyopathy (ischemic and valvular etiologies ruled out). These patients underwent cardiac MRI which suggested a diagnosis in 53% of cases. The combination of cardiac MRI and EMB was able to increase that number to 86% [4].

In this issue, Shah and colleagues report their results on the trends in use and complications of EMB in a large number of patients in the Nationwide Inpatient Sample. They looked at over 50,000 inpatient procedures over a 7-year period, the breakdown of which included approximately 24,000 procedures in heart transplant patients and 17,000 in native hearts. Around 10,000 procedures done during the index transplant hospitalization were excluded from analysis as were outpatient EMB procedures (the vast majority of surveillance EMBs in transplant hearts are performed as an outpatient). They reported the rate of serious complications from EMB which was defined as pericardial effusion, hemopericardium and/or cardiac tamponade that required pericardiocentesis or pericardial window on the same day or the day following EMB. They found a significantly lower rate of serious complications in the heart transplant group compared to the native heart group: 0.19 versus 0.70%. When broken down by the type of medical center the EMB was performed in, they showed a significantly higher complication rate in nonteaching hospitals versus teaching hospitals: 1 versus 0.18% in transplant hearts and 3.4 versus 0.53% in native hearts. The overwhelming majority of EMBs were performed in teaching hospitals: 99% of transplant EMBs and 94% of native heart EMBs. They also found that native heart EMBs increased by 48% over the time period studied (2007–2014).

Several key points emerge from this study. First, there was a significantly increased rate of serious complications from EMB in native hearts as compared to transplant hearts. A recently published review from Singh et al. [5] in Boston studied the trends in utilization and complications of EMB using the Nationwide Inpatient Sample from 2002 to 2014 and found similar findings. This makes sense when considering the anatomy of native hearts that are undergoing indicated EMBs. Patients with intact pericardium will develop tamponade quickly relative to a transplant patient with an open pericardium. Patients with unexplained new-onset cardiomyopathy and/or cardiogenic shock often have dilated ventricles with thin walls lending to a higher risk of perforation and dysrhythmias. Second, Shah and colleagues show the significant disparity in the number of EMBs performed at teaching versus nonteaching hospitals and the attendant increase in serious complications with procedures performed at nonteaching hospitals: 3.4% of the 1,000 patients undergoing native heart EMB at a nonteaching required pericardiocentesis or pericardial window compared to 0.53% of the over 15,000 native heart EMBs performed at teaching hospitals. Teaching hospitals with transplant programs frequently perform outpatient surveillance EMBs in transplant hearts and the increased experience very likely contributes strongly to the lower rate of complications in native heart inpatient EMBs. On-site cardiac surgery in the case of pericardial window is needed and pathology departments with experience in interpreting and performing specialized testing on EMBs are also more commonly present at teaching hospitals. Third, there was a notable 48% increase in native heart EMBs during the study period. This is an interesting finding given the continued progression of noninvasive diagnostic imaging modalities such as cardiac MRI. As mentioned previously, the ability to detect certain diagnoses by EMB (such as various etiologies of infectious cardiomyopathy) has improved in recent years with the emergence and improvement of immunohistochemical and PCR analysis of biopsies.

What implications do these findings have concerning the role of EMB in native hearts? One diagnosis from EMB that has increased in recent years is cardiac amyloid. This may reflect increased recognition of the disease as well as improved treatment options. The recently published landmark randomized trial of tafamidis (an oral medication that binds to transthyretin and prevents tetramer dissociation and amyloid formation) for patients with transthyretin amyloid cardiomyopathy showed dramatic results: tafamidis was associated with a decreased all-cause mortality over the 30-month study period of 29.5% compared to 42.9% with placebo [6]. This corresponds with a number needed to treat of 7 to prevent one death – a substantial improvement. Add to that significant reductions in hospitalizations, improved functional status, and no increased risk of adverse events and it is evident that this new therapeutic option can have significant benefit to patients with this debilitating cause of heart failure.

EMB use in native hearts will likely continue to increase in frequency. While the absolute number of serious complications remains low when performed at centers with high volume, they are increased relative to transplant heart EMB[7]. Judicious patient selection, timing, technique, and awareness of and ability to manage complications will remain vital.

The authors declare no conflicts of interest related to this paper.

1.
From
AM
,
Maleszewski
JJ
,
Rihal
CS
.
Current status of endomyocardial biopsy
.
Mayo Clin Proc
.
2011
Nov
;
86
(
11
):
1095
102
.
[PubMed]
0025-6196
2.
Cooper
LT
,
Baughman
KL
,
Feldman
AM
,
Frustaci
A
,
Jessup
M
,
Kuhl
U
, et al;
American Heart Association
;
American College of Cardiology
;
European Society of Cardiology
.
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
Nov
;
116
(
19
):
2216
33
.
[PubMed]
0009-7322
3.
Khan
T
,
Selvakumar
D
,
Trivedi
S
,
Rao
K
,
Harapoz
M
,
Thiagalingam
A
, et al
The value of endomyocardial biopsy in diagnosis and guiding therapy
.
Pathology
.
2017
Dec
;
49
(
7
):
750
6
.
[PubMed]
0031-3025
4.
Sotiriou
E
,
Heiner
S
,
Jansen
T
,
Brandt
M
,
Schmidt
KH
,
Kreitner
KF
, et al
Therapeutic implications of a combined diagnostic workup including endomyocardial biopsy in an all-comer population of patients with heart failure: a retrospective analysis
.
ESC Heart Fail
.
2018
Aug
;
5
(
4
):
630
41
.
[PubMed]
2055-5822
5.
Singh
V
,
Mendirichaga
R
,
Savani
GT
, et al
Comparison of utilization trends, indications, and complications of endomyocardial biopsy in native versus donor hearts (from the Nationwide Inpatient Sample 2002 to 2014). Am J Card
2017
:10.021
6.
Maurer
MS
,
Schwartz
JH
,
Gundapaneni
B
,
Elliott
PM
,
Merlini
G
,
Waddington-Cruz
M
, et al;
ATTR-ACT Study Investigators
.
Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy
.
N Engl J Med
.
2018
Sep
;
379
(
11
):
1007
16
.
[PubMed]
0028-4793
7.
Shah
Z
,
Vuddanda
V
,
Rali
AS
, et al
National trends and procedural complications from endomyocardial biopsy: results from the National Inpatient Sample, 2007.
Publication pending
.
Clin Res Cardiol
.
2014
.1861-0684
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.