Download The Two Extremes of Cardiac Sarcoidosis and the Effect of

The Two Extremes of Cardiac Sarcoidosis and the Effect
of Prednisone Therapy
Danielle Armstrong, DOa, Gonzalo V. Gonzalez-Stawinski, MDb, Jong Mi Ko, BAc,
Shelley A. Hall, MDd, and William C. Roberts, MDa,c,d,*
Described herein are clinical and morphologic findings in 2 patients who underwent heart
transplantation because of severe heart failure resulting from cardiac sarcoidosis. Although
the explanted hearts in each patient had characteristic gross changes of cardiac sarcoidosis,
one patient who had been treated with prednisone, had no residual sarcoid granulomas in
the myocardium, whereas the other patient, in whom diagnosis was not made until heart
transplantation, had innumerable sarcoid granulomas in her heart. This report suggests
that prednisone can eliminate sarcoid granulomas in the heart but that their replacement is
by dense fibrous tissue, something also likely the result of the granulomas themselves,
creating a situation where the treated (prednisone) and the non-treated sarcoid heart may
appear similar by gross examination. Ó 2015 Elsevier Inc. All rights reserved. (Am J
Cardiol 2015;115:150e153)
Although it is a systemic disease, sarcoidosis uncommonly
affects the heart and when it does the non-cardiac organs are
usually minimally affected and they function normally.1e6 On
occasion, cardiac sarcoidosis may lead to such severe heart
failure that heart transplantation (HT) is the only reasonable
therapy.3e5 In such situations, diagnosis of cardiac sarcoidosis is usually not made until HT, the usual pre-HT diagnosis
being “non-ischemic cardiomyopathy”.5 Recently, 2 patients
underwent HT at Baylor University Medical Center (BUMC)
in the same month and examination of the explanted heart in
one disclosed innumerable myocardial sarcoid granulomas
(not diagnosed clinically) and, in the other patient, despite
some similar gross findings in the heart, no myocardial
granulomas were seen (diagnosed clinically by an earlier biopsy). This report describes findings in these 2 patients to
point out the huge spectrum of myocardial changes in patients
with cardiac sarcoidosis, and the potential effect of long term
prednisone therapy in this condition.
Patients Studied
Pertinent findings in each of the 2 patients are detailed in
Table 1. Both patients were in their 50s; both were white;
both had severe (4þ/4þ) heart failure; both had evidence of
cardiac dysfunction for approximately 4 years; both had
periodic runs of non-sustained ventricular tachycardia; both
had some type of heart block (complete in case #1, and right
bundle branch block in case #2); neither had dysfunction of
a non-cardiac body organ, and neither patient had narrowing
a
b
d
Departments of Pathology, Cardiothoracic Surgery, and Internal
Medicine (Division of Cardiology), Baylor University Medical Center,
Dallas, Texas and cBaylor Heart and Vascular Institute, Baylor University
Medical Center, Dallas, Texas. Manuscript received September 2, 2014;
revised manuscript received and accepted October 5, 2014.
Support for this investigation was provided by the Baylor Health Care
System Foundation.
See page 153 for disclosure information.
*Corresponding author: Tel: 214-820-7911; fax: 214-820-7533.
E-mail address: [email protected] (W.C. Roberts).
0002-9149/14/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjcard.2014.10.003
of the epicardial coronary arteries. Diagnosis of sarcoidosis
before HT was made in patient #1 by biopsy of a mediastinal lymph node 21 months before HT although 2 years
earlier a cardiac biopsy had shown “granulomas”. Patient
#1, who had no granulomas in his explanted heart, was
placed on prednisone after the granulomas were seen in the
lymph node and he received this drug for 21 months,
at very high doses for 10 months before dose-tapering
Table 1
Clinical and morphologic findings in the 2 patients
Variable
Gender
Age (years)
At heart transplantation
Onset of symptoms
Electrophysiology
Heart block
Ventricular tachycardia
Pacemaker
Intracardiac defibrillator
Systemic hypertension
Body mass index (Kg/m2)
Hemodynamic data
Lowest left ventricular EF (%)
Cardiac index (L/min/m2)
Pressures (mm Hg)
Blood pressure, indirect (s/d)
Right atrial mean
Right ventricle (s/d)
Pulmonary artery (s/d)
Pulmonary artery wedge mean
Prednisone therapy (months)
Heart weight (g)
Cardiac granuloma (0-4þ)
Left ventricular cavity (cm)
Case
#1
#2
Man
Woman
53
49
57
53
Complete
þ
þ
þ
þ
31.8
RBBB
þ
0
þ
0
29.9
20
2.01
15
1.36
100/85
6
26/10
26/14
11
þ (21)
535
0
7.5
85/40
2
48/6
44/11
14
0
380
4þ
5.5
EF ¼ ejection fraction; RBBB ¼ right bundle branch block; s/d ¼ peak
systole/end diastole.
www.ajconline.org
Case Report/Cardiac Sarcoidosis With and Without Granulomas
151
Figure 1. Heart in patient #1. (A) View of the base of the heart showing marked dilatation of both right and left ventricular cavities and focal scars in the left and
right ventricular free walls and ventricular septum. (B) Transverse cuts of the cardiac ventricles caudal to the view shown in (A). (C) Close up view of the wall
of right ventricle showing extensive scarring and marked thinning of the wall (simulating arrhythmogenic right ventricular dysplasia/cardiomyopathy). (D)
View of the ventricular septum showing the scarring primarily on the right side of the septum. Because the biotome to biopsy the heart extracts tissue from the
right side of the ventricular septum that probably was the reason the biopsy was positive in this patient early in his course.
152
The American Journal of Cardiology (www.ajconline.org)
Figure 2. Photomicrographs of portions of the heart in patient #1. (A)
View of the epicardium, subepicardium, and outer myocardial wall in the
anterior portion of left ventricle. The left anterior descending coronary artery and also a coronary vein are shown. The deep blue color represents scar
tissue which is located primarily in the subepicardial region rather than the
sub-endocardial region. No granulomas were found in the dense fibrous
tissue despite examining numerous sections of myocardium. The coronary
vessels are surrounded by mainly adipose tissue. (B) View of the right
ventricular free wall also showing extensive scarring again involving the
subepicardial portion more than the subendocardial portion. Trichrome
stains, each 20.
began. Patient #2, whose sarcoidosis was not diagnosed
until HT, never received corticosteroid therapy before HT
and her explanted heart contained innumerable granulomas
typical of sarcoidosis. Photographs of the heart in each patient are shown in Figures 1 to 4.
Discussion
The explanted hearts in each of the 2 hitherto described
patients had gross features characteristic of cardiac sarcoidosis: involvement of the walls of both right and left ventricles
and the ventricular septum; multiple lesions in each of the
cardiac walls; a tendency for the gross lesions to involve the
subepicardial half of the left ventricular free wall and the right
ventricular half of the ventricular septum, dilation of both
ventricular cavities, and absence of narrowing of the epicardial coronary arteries. Yet one patient, who previously by
Figure 3. Views of the heart in case #2. (A) View of the opened basal portion
of the heart showing considerable dilatation of both ventricular cavities and
severe scarring of the ventricular septum, posterolateral left ventricular free
wall, and posterior wall of right ventricle. Numerous sarcoid granulomas were
present in the dense fibrous tissue. (B) One-cm thick slices of the ventricles
caudal to the upper view. Much of the left ventricular free wall, ventricular
septum and right ventricular free wall are replaced by sarcoid granulomas
with their surrounding fibrous tissue.
both cardiac and lymph node biopsies showed sarcoidosis,
had no granulomas in his explanted heart; the other patient had
innumerable sarcoid granulomas in her heart and diagnosis of
sarcoidosis was not made until examination of the explanted
heart. Patient #1 who had no granulomas in his explanted
heart had received prednisone therapy for 21 months, high
doses during 10 of those months. The quantity of scar tissue in
both patients’ hearts suggests that the sarcoid granulomas and
their adjacent lymphocytes are strong fibrous-tissue stimulants, and, moreover, that prednisone therapy is a strong
eliminator of sarcoid granulomas but the residue of that
healing is extensive replacement fibrosis. (Sarcoidosis in the
lung is also a strong fibrosis stimulator.7) It seems reasonable
to believe that the heart in patient #1 earlier had been loaded
with sarcoid granulomas as found in patient #2 but that the
prednisone treatment likely played a role in eliminating the
sarcoid granuloma by replacing them with dense fibrous
Case Report/Cardiac Sarcoidosis With and Without Granulomas
153
Figure 4. Photomicrographs in patient #2. (A) View of a portion of left ventricular free wall showing numerous granulomas surrounded by dense fibrous tissue. (B)
Close-up view of a single sarcoid granuloma. (C) Another view of sarcoid granulomas showing numerous nuclei in each of the giant cells. (D) Infiltration between
myocardial fibers of lymphocytes typical of sarcoid myocarditis. Trichrome stain, 40 (A); trichrome stain, 400 (B); hematoxylin/eosin stain, 400 (C), and
hematoxylin/eosin stain, 400 (D).
tissue. Such a demonstration to our knowledge has not been
provided previous to this report. Earlier we described a patient
with typical gross lesions of cardiac sarcoidosis but study of
numerous sections of the heart histologically failed to reveal
any granulomas.6 This earlier patient had never received
corticosteroid therapy,6 but earlier histologic examination of a
portion of the left ventricular free wall excised to insert a left
ventricular assist device did disclose sarcoid granulomas.
Disclosures
The authors have no conflicts of interest to disclose.
1. Roberts WC, McAllister HA Jr, Ferrans VJ. Sarcoidosis of the heart. A
clinicopathologic study of 35 necropsy patients (Group I) and review of
78 previously described necropsy patients (Group II). Am J Med
1977;63:86e108.
2. Virmani R, Bures JC, Roberts WC. Cardiac sarcoidosis: a major cause of
sudden death in young individuals. Chest 1980;77:423e428.
3. Donsky AS, Escobar J, Capehart J, Roberts WC. Heart Transplantation
for undiagnosed cardiac sarcoidosis. Am J Cardiol 2002;89:1447e1450.
4. Roberts WC, Vowels TJ, Ko JM, Capehard JE, Hall SA. Cardiac
transplantation for cardiac sarcoidosis with initial diagnosis by examination of the left ventricular apical “core” excised for insertion of a left
ventricular assist device for severe chronic heart failure. Am J Cardiol
2009;103:110e114.
5. Sharma PS, Lubahn JG, Donsky AS, Yoon AD, Carry MM, Grayburn
PA, Wood PB, Ko JM, Burton EC, Roberts WC. Diagnosing cardiac
sarcoidosis clinically without tissue confirmation. Proc (Bayl Univ Med
Cent) 2009;22:236e238.
6. Roberts WC, Chung MS, Ko JM, Capehart JE, Hall SA. Morphologic
features of cardiac sarcoidosis in native hearts of patients having cardiac
transplantation. Am J Cardiol 2014;113:706e712.
7. Crystal RG, Roberts WC, Hunninghake GW, Gadek JE, Fulmer JD,
Line BR. Pulmonary sarcoidosis: a disease characterized and perpetuated by activated lung T-lymphocytes. Ann Intern Med 1981;94:
73e94.