The Two Extremes of Cardiac Sarcoidosis and the Effect of Prednisone Therapy Danielle Armstrong, DO a , Gonzalo V. Gonzalez-Stawinski, MD b , Jong Mi Ko, BA c , Shelley A. Hall, MD d , and William C. Roberts, MD a,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 sarcoid- osis 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 bi- opsy). 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 of the epicardial coronary arteries. Diagnosis of sarcoidosis before HT was made in patient #1 by biopsy of a medias- tinal 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 Case #1 #2 Gender Man Woman Age (years) At heart transplantation 53 57 Onset of symptoms 49 53 Electrophysiology Heart block Complete RBBB Ventricular tachycardia þ þ Pacemaker þ 0 Intracardiac defibrillator þ þ Systemic hypertension þ 0 Body mass index (Kg/m 2 ) 31.8 29.9 Hemodynamic data Lowest left ventricular EF (%) 20 15 Cardiac index (L/min/m 2 ) 2.01 1.36 Pressures (mm Hg) Blood pressure, indirect (s/d) 100/85 85/40 Right atrial mean 6 2 Right ventricle (s/d) 26/10 48/6 Pulmonary artery (s/d) 26/14 44/11 Pulmonary artery wedge mean 11 14 Prednisone therapy (months) þ (21) 0 Heart weight (g) 535 380 Cardiac granuloma (0-4þ) 0 4þ Left ventricular cavity (cm) 7.5 5.5 EF ¼ ejection fraction; RBBB ¼ right bundle branch block; s/d ¼ peak systole/end diastole. Departments of a Pathology, b Cardiothoracic Surgery, and d Internal Medicine (Division of Cardiology), Baylor University Medical Center, Dallas, Texas and c Baylor 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. www.ajconline.org http://dx.doi.org/10.1016/j.amjcard.2014.10.003
Transcript
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The Two Extremes of Cardiac Sarcoidosis and the Effectof 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
ments o(Divisioas andenter, Dnuscript for thundatioge 153spondinaddres
/14/$ -i.org/1
transplantation because of severe heart failure resulting from cardiac sarcoidosis. Althoughthe 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 inthe myocardium, whereas the other patient, in whom diagnosis was not made until hearttransplantation, had innumerable sarcoid granulomas in her heart. This report suggeststhat prednisone can eliminate sarcoid granulomas in the heart but that their replacement isby 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 mayappear similar by gross examination. � 2015 Elsevier Inc. All rights reserved. (Am JCardiol 2015;115:150e153)
Table 1Clinical and morphologic findings in the 2 patients
Variable Case
#1 #2
Gender Man WomanAge (years)At heart transplantation 53 57Onset of symptoms 49 53
Systemic hypertension þ 0Body mass index (Kg/m2) 31.8 29.9Hemodynamic dataLowest left ventricular EF (%) 20 15Cardiac index (L/min/m2) 2.01 1.36Pressures (mm Hg)
Although it is a systemic disease, sarcoidosis uncommonlyaffects the heart and when it does the non-cardiac organs areusuallyminimally affected and they function normally.1e6Onoccasion, cardiac sarcoidosis may lead to such severe heartfailure that heart transplantation (HT) is the only reasonabletherapy.3e5 In such situations, diagnosis of cardiac sarcoid-osis is usually not made until HT, the usual pre-HT diagnosisbeing “non-ischemic cardiomyopathy”.5 Recently, 2 patientsunderwent HT at Baylor University Medical Center (BUMC)in the same month and examination of the explanted heart inone disclosed innumerable myocardial sarcoid granulomas(not diagnosed clinically) and, in the other patient, despitesome similar gross findings in the heart, no myocardialgranulomas were seen (diagnosed clinically by an earlier bi-opsy). This report describes findings in these 2 patients topoint out the huge spectrum ofmyocardial changes in patientswith cardiac sarcoidosis, and the potential effect of long termprednisone therapy in this condition.
Patients Studied
Pertinent findings in each of the 2 patients are detailed inTable 1. Both patients were in their 50s; both were white;both had severe (4þ/4þ) heart failure; both had evidence ofcardiac dysfunction for approximately 4 years; both hadperiodic runs of non-sustained ventricular tachycardia; bothhad some type of heart block (complete in case #1, and rightbundle branch block in case #2); neither had dysfunction ofa non-cardiac body organ, and neither patient had narrowing
f aPathology, bCardiothoracic Surgery, and dInternaln of Cardiology), Baylor University Medical Center,cBaylor Heart and Vascular Institute, Baylor Universityallas, Texas. Manuscript received September 2, 2014;t received and accepted October 5, 2014.is investigation was provided by the Baylor Health Caren.for disclosure information.g author: Tel: 214-820-7911; fax: 214-820-7533.s: [email protected] (W.C. Roberts).
see front matter � 2015 Elsevier Inc. All rights reserved.0.1016/j.amjcard.2014.10.003
of the epicardial coronary arteries. Diagnosis of sarcoidosisbefore HT was made in patient #1 by biopsy of a medias-tinal lymph node 21 months before HT although 2 yearsearlier a cardiac biopsy had shown “granulomas”. Patient#1, who had no granulomas in his explanted heart, wasplaced on prednisone after the granulomas were seen in thelymph node and he received this drug for 21 months,at very high doses for 10 months before dose-tapering
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 andright 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 wallof 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 theright side of the ventricular septum that probably was the reason the biopsy was positive in this patient early in his course.
Case Report/Cardiac Sarcoidosis With and Without Granulomas 151
Figure 2. Photomicrographs of portions of the heart in patient #1. (A)View of the epicardium, subepicardium, and outer myocardial wall in theanterior portion of left ventricle. The left anterior descending coronary ar-tery and also a coronary vein are shown. The deep blue color represents scartissue which is located primarily in the subepicardial region rather than thesub-endocardial region. No granulomas were found in the dense fibroustissue despite examining numerous sections of myocardium. The coronaryvessels are surrounded by mainly adipose tissue. (B) View of the rightventricular free wall also showing extensive scarring again involving thesubepicardial portion more than the subendocardial portion. Trichromestains, each �20.
Figure 3. Views of the heart in case #2. (A)View of the opened basal portionof the heart showing considerable dilatation of both ventricular cavities andsevere scarring of the ventricular septum, posterolateral left ventricular freewall, and posteriorwall of right ventricle.Numerous sarcoid granulomaswerepresent in the dense fibrous tissue. (B) One-cm thick slices of the ventriclescaudal to the upper view. Much of the left ventricular free wall, ventricularseptum and right ventricular free wall are replaced by sarcoid granulomaswith their surrounding fibrous tissue.
152 The American Journal of Cardiology (www.ajconline.org)
began. Patient #2, whose sarcoidosis was not diagnoseduntil HT, never received corticosteroid therapy before HTand her explanted heart contained innumerable granulomastypical of sarcoidosis. Photographs of the heart in each pa-tient are shown in Figures 1 to 4.
Discussion
The explanted hearts in each of the 2 hitherto describedpatients had gross features characteristic of cardiac sarcoid-osis: involvement of the walls of both right and left ventriclesand the ventricular septum; multiple lesions in each of thecardiac walls; a tendency for the gross lesions to involve thesubepicardial half of the left ventricular free wall and the rightventricular half of the ventricular septum, dilation of bothventricular cavities, and absence of narrowing of the epicar-dial coronary arteries. Yet one patient, who previously by
both cardiac and lymph node biopsies showed sarcoidosis,had no granulomas in his explanted heart; the other patient hadinnumerable sarcoid granulomas in her heart and diagnosis ofsarcoidosis was not made until examination of the explantedheart. Patient #1 who had no granulomas in his explantedheart had received prednisone therapy for 21 months, highdoses during 10 of thosemonths. The quantity of scar tissue inboth patients’ hearts suggests that the sarcoid granulomas andtheir adjacent lymphocytes are strong fibrous-tissue stimu-lants, and, moreover, that prednisone therapy is a strongeliminator of sarcoid granulomas but the residue of thathealing is extensive replacement fibrosis. (Sarcoidosis in thelung is also a strong fibrosis stimulator.7) It seems reasonableto believe that the heart in patient #1 earlier had been loadedwith sarcoid granulomas as found in patient #2 but that theprednisone treatment likely played a role in eliminating thesarcoid granuloma by replacing them with dense fibrous
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 betweenmyocardial fibers of lymphocytes typical of sarcoid myocarditis. Trichrome stain, �40 (A); trichrome stain, �400 (B); hematoxylin/eosin stain, �400 (C), andhematoxylin/eosin stain, �400 (D).
Case Report/Cardiac Sarcoidosis With and Without Granulomas 153
tissue. Such a demonstration to our knowledge has not beenprovided previous to this report. Earlier we described a patientwith typical gross lesions of cardiac sarcoidosis but study ofnumerous sections of the heart histologically failed to revealany granulomas.6 This earlier patient had never receivedcorticosteroid therapy,6 but earlier histologic examination of aportion of the left ventricular free wall excised to insert a leftventricular 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. Aclinicopathologic study of 35 necropsy patients (Group I) and review of78 previously described necropsy patients (Group II). Am J Med1977;63:86e108.
2. Virmani R, Bures JC, Roberts WC. Cardiac sarcoidosis: a major cause ofsudden death in young individuals. Chest 1980;77:423e428.
3. Donsky AS, Escobar J, Capehart J, Roberts WC. Heart Transplantationfor undiagnosed cardiac sarcoidosis. Am J Cardiol 2002;89:1447e1450.
4. Roberts WC, Vowels TJ, Ko JM, Capehard JE, Hall SA. Cardiactransplantation for cardiac sarcoidosis with initial diagnosis by exami-nation of the left ventricular apical “core” excised for insertion of a leftventricular assist device for severe chronic heart failure. Am J Cardiol2009;103:110e114.
5. Sharma PS, Lubahn JG, Donsky AS, Yoon AD, Carry MM, GrayburnPA, Wood PB, Ko JM, Burton EC, Roberts WC. Diagnosing cardiacsarcoidosis clinically without tissue confirmation. Proc (Bayl Univ MedCent) 2009;22:236e238.
6. Roberts WC, Chung MS, Ko JM, Capehart JE, Hall SA. Morphologicfeatures of cardiac sarcoidosis in native hearts of patients having cardiactransplantation. 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 perpet-uated by activated lung T-lymphocytes. Ann Intern Med 1981;94:73e94.
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