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Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis
Cardiovascular Pathology 15 (2006) 228 – 230
Case Report
Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis Paul L. van Haelst4, Johan Brqgemann, Gilles F. Diercks, Albert Suurmeijer, Dirk J. van Veldhuisen Department of Cardiology, University Medical Center Groningen, NL-9700RB Groningen, The Netherlands Department of Pathology, University Medical Center Groningen, NL-9700RB Groningen, The Netherlands Received 20 June 2005; received in revised form 14 March 2006; accepted 23 March 2006
Abstract Giant cell myocarditis (GCM) is a serious condition that warrants immediate diagnosis and treatment. It often presents as rapidly progressive heart failure and/or malignant ventricular arrhythmias. Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma. A cardiac biopsy confirming the diagnosis was done within 3 days after admission. After institution of an aggressive immunosuppressive drug regimen, implantation of an implantable cardioverter defibrillator, and intensive cardiac rehabilitation, the patient recovered dramatically. In control biopsies after 4 weeks and 6 months, no more giant cells were found. We conclude that, in the case of nonischemic acute heart failure in young patients, a biopsy should be performed as soon as possible to prevent an unfavourable outcome of this often fatal disease. D 2006 Elsevier Inc. All rights reserved. Keywords: Giant cell myocarditis; Follow-up; Treatment; Endomyocardial biopsy; Implantable cardioverter defibrillator
1. Case A 34-year-old man presented with a 3-day history of shortness of breath. Two weeks before, he had undergone an uncomplicated resection of a type B2 (cortical) thymoma with invasion in the visceral pleura. There was no cardiac involvement of the thymoma, nor had the pericardium been manipulated during operation. The postoperative course had been uneventful, and he was discharged after 6 days. On admission, a severely distressed patient was seen with symptoms of heart failure. There was no history of chest pain, palpitations, or dizziness. No symptoms indicating infectious disease were reported. The night before admission, he had not been able to sleep because of dyspnea and
4 Corresponding author. Thoraxcenter, Department of Cardiology, University Hospital Groningen, PO Box 30001, NL-9700RB Groningen, The Netherlands. Tel.: +31 50 3612355; fax: +31 50 3614391. E-mail address: [email protected] (P.L. van Haelst). 1054-8807/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2006.03.005
massive perspiration. He had no cardiovascular risk factors whatsoever. Physical examination revealed a lean, profusely perspiring patient with a breathing frequency of 20/min. His blood pressure was 120/70 mmHg, the pulse frequency was a regular sinustachycardia (106 beats per minute), and body temperature was 378C. The central venous pressure was not elevated. On auscultation, a third heart sound was heard without any murmurs. Examination of the lungs revealed diffuse rales. The chest wound was neatly cured. Peripheral edema was not present, and the extremities felt damp. The electrocardiogram (ECG) was changed, compared to the preoperative ECG, and now showed microvoltages along with pathological Qs in leads V1–3 and II, III, and aVF. Echocardiography revealed a small heart with diffusely thickened walls of both ventricles. The contraction pattern was adequate, except for the anterior and basal part of the septum that was akinetic. The right ventricular function was normal. The patient was admitted to the cardiac care unit for the symptomatic treatment of heart failure and further diagnos-
P.L. van Haelst et al. / Cardiovascular Pathology 15 (2006) 228 – 230
229
tics. A coronary angiography showed no signs of coronary artery disease. On the day after admission, he suffered from progressive sustained polymorphic ventricular arrhythmias leading to hemodynamic instability requiring cardiopulmonary resuscitation. The patient was sedated, intubated, ventilated, and electrocardioverted to sinus rhythm. Therapy with intravenous amiodarone was instituted, and after several electroshocks for recurrent ventricular tachycardias, the arrhythmias declined in severity and frequency. The combination of acute-onset heart failure in combination with malignant ventricular arrhythmias raised a strong suspicion of giant cell myocarditis (GCM) [1]. Therapy was expanded with 1000 mg of methylprednisolone intravenously for 3 days, and a myocardial biopsy was performed at the third day of admission. Right ventricular endomyocardial biopsy revealed a GCM (Fig. 1A). Treatment was started with cyclosporine and azathioprine and, after consulting his neurologist, plasmapheresis to prevent a relapse of the myasthenia. Respiratory support was continued for 6 days. A control biopsy after 4 weeks of treatment showed a decrease in inflammatory cells, and giant cells were no longer detectable. However, fibrosis was more pronounced (Fig. 1B). The patient was discharged, but after several weeks, he was readmitted because of a septic shock due to an atypical pneumonia. In the intensive care ward, the immunosuppressive treatment was discontinued for 4 days. A control echocardiography revealed a severely worsened left ventricular function [left ventricular ejection fraction (LVEF) estimated at 20– 25%]. Immunosuppressive therapy was reinstituted. Because of the worsened LVEF and the fact that a Holter ECG showed multiple nonsustained ventricular tachycardias, an implantable cardioverter defibrillator (ICD) was positioned. The patient successfully underwent a cardiac rehabilitation program, and 6 months later, his LVEF was 45%, and myocardial biopsies showed no more signs of GCM, with only a very sparse inflammatory infiltrate (Fig. 1C). Now, 15 months after the diagnosis, the patient is in an excellent clinical condition. He still uses cyclosporine, azathioprine, and prednisolone next to an angiotensinconverting enzyme inhibitor and beta-blocker. The ICD has not discharged since implantation.
2. Discussion Fig. 1. (A) Right ventricular endomyocardial biopsy before treatment. GCM: a dense inflammatory interstitial infiltrate which contains lymphocytes, epitheloid histiocytes, and Langhans giant cells. This infiltrate is associated with myocyte damage. Importantly, no granulomas were seen. (B) Right ventricular endomyocardial biopsy after 2 weeks of treatment. The inflammatory interstitial infiltrate is clearly less present. No giant cells are present anymore, but fibrosis is more pronounced. This biopsy shows a resolving myocarditis. (C) Right ventricular endomyocardial biopsy after 6 months. The biopsy contains hypertrophic cardiomyocytes with interstitial fibrosis and a very sparse inflammatory interstitial infiltrate. This biopsy shows a resolved myocarditis.
GCM is a disease of young, predominantly healthy adults. Males and females are equally affected. The disease is associated with a number of autoimmune diseases such as myasthenia gravis, ulcerative colitis, Crohn’s disease, Hashimoto’s thyroiditis, rheumatoid arthritis, pernicious anemia, and Takayasu’s arteritis. GCM generally presents as heart failure of a very sudden onset with dyspnea, hypotension, orthopnea, and peripheral edema [2]. In some
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P.L. van Haelst et al. / Cardiovascular Pathology 15 (2006) 228 – 230
cases, it presents with ventricular tachycardias, complete heart block, and symptoms mimicking myocardial infarction. Importantly, an association exists with thymoma, as was excellently reviewed by Kilgallen et al. [3]. Histologically, myocyte necrosis, giant cells, and inflammatory infiltrates are seen, while granulomatous lesions should not be present since they are a hallmark of cardiac sarcoidosis, a disease mimicking GCM histologically. The course of the disease is almost invariably fatal unless strong immunosuppressive therapy is started or heart transplantation is done. A study that included 63 patients worldwide showed a rate of death or cardiac transplantation of 89% after 5 years, with a median survival of 5.5 months [1]. The posttransplantation survival rate after 3 years is 74%, comparable to groups that underwent cardiac transplantation for other reasons. However, GCM may recur in the transplanted heart [4]. An endomyocardial biopsy is not routinely advocated in patients with a myocarditis because of a low diagnostic yield [5,6]. However, it was suggested that biopsy in patients with a fulminant clinical course who presented early (as in this case) had a sensitivity for GCM of as high as 80% [7]. Since the implications for further treatment are significant, we feel that in patients who present with rapidly progressive heart failure of an unknown cause, a right ventricular endomyocardial biopsy should be performed. Moreover, as was done in this case, the results of the biopsy may guide the clinician in choosing the right immunosuppressive regimen. The association of thymoma and GCM is not novel [3]. Kilgallen et al describe GCM after thymoma resection only in women. It has also been reported that the time course of GCM after resection of the thymoma is not within any time frame; it may occur immediately after the operation, or even years later. Clinicians who follow these patients should be aware of this.
3. Conclusion GCM is a rare cause of heart failure, which may occur in patients after the resection of a thymoma at any time point. Because the histological diagnosis enables aggressive therapeutic measures, an early cardiac tissue sample is warranted. We recommend that, in a case of unexplained rapidly progressive heart failure with or without malignant arrhythmias, especially in the presence of a history of an autoimmune condition, a myocardial biopsy should be performed within several days in order to start early treatment and prevent a fatal course of the disease. Follow-up endomyocardial biopsies may guide the clinician in deciding what immunosuppressive treatment the patients ought to receive. References [1] Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis— natural history and treatment Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med 1997;336:1860 – 6. [2] van Haelst PL, van Rossem M, Valentijn RM, et al. Giant cell myocarditis: a fatal cause of dyspnea in pregnancy. Eur J Obstet Gynecol Reprod Biol 2001;100:105 – 7. [3] Kilgallen CM, Jackson E, Bankoff M, et al. A case of giant cell myocarditis and malignant thymoma: a postmortem diagnosis by needle biopsy. Clin Cardiol 1998;21:48 – 51. [4] Davies RA, Veinot JP, Smith S, et al. Giant cell myocarditis: clinical presentation, bridge to transplantation with mechanical circulatory support, and long-term outcome. J Heart Lung Transplant 2002;21: 674 – 9. [5] Feldman AM, McNamara D. Myocarditis. N Engl J Med 2000;343: 1388 – 98. [6] Kasper EK, Agema WR, Hutchins GM, et al. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol 1994;23:586 – 90. [7] Shields RC, Tazelaar HD, Berry GJ, et al. The role of right ventricular endomyocardial biopsy for idiopathic giant cell myocarditis. J Card Fail 2002;8:74 – 8.
Case Report
Serial right ventricular endomyocardial biopsy in rapid-onset severe heart failure due to giant cell myocarditis Paul L. van Haelst4, Johan Brqgemann, Gilles F. Diercks, Albert Suurmeijer, Dirk J. van Veldhuisen Department of Cardiology, University Medical Center Groningen, NL-9700RB Groningen, The Netherlands Department of Pathology, University Medical Center Groningen, NL-9700RB Groningen, The Netherlands Received 20 June 2005; received in revised form 14 March 2006; accepted 23 March 2006
Abstract Giant cell myocarditis (GCM) is a serious condition that warrants immediate diagnosis and treatment. It often presents as rapidly progressive heart failure and/or malignant ventricular arrhythmias. Here, we describe a 34-year-old patient with myasthenia gravis who presented with GCM 2 weeks after resection of a thymoma. A cardiac biopsy confirming the diagnosis was done within 3 days after admission. After institution of an aggressive immunosuppressive drug regimen, implantation of an implantable cardioverter defibrillator, and intensive cardiac rehabilitation, the patient recovered dramatically. In control biopsies after 4 weeks and 6 months, no more giant cells were found. We conclude that, in the case of nonischemic acute heart failure in young patients, a biopsy should be performed as soon as possible to prevent an unfavourable outcome of this often fatal disease. D 2006 Elsevier Inc. All rights reserved. Keywords: Giant cell myocarditis; Follow-up; Treatment; Endomyocardial biopsy; Implantable cardioverter defibrillator
1. Case A 34-year-old man presented with a 3-day history of shortness of breath. Two weeks before, he had undergone an uncomplicated resection of a type B2 (cortical) thymoma with invasion in the visceral pleura. There was no cardiac involvement of the thymoma, nor had the pericardium been manipulated during operation. The postoperative course had been uneventful, and he was discharged after 6 days. On admission, a severely distressed patient was seen with symptoms of heart failure. There was no history of chest pain, palpitations, or dizziness. No symptoms indicating infectious disease were reported. The night before admission, he had not been able to sleep because of dyspnea and
4 Corresponding author. Thoraxcenter, Department of Cardiology, University Hospital Groningen, PO Box 30001, NL-9700RB Groningen, The Netherlands. Tel.: +31 50 3612355; fax: +31 50 3614391. E-mail address: [email protected] (P.L. van Haelst). 1054-8807/06/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2006.03.005
massive perspiration. He had no cardiovascular risk factors whatsoever. Physical examination revealed a lean, profusely perspiring patient with a breathing frequency of 20/min. His blood pressure was 120/70 mmHg, the pulse frequency was a regular sinustachycardia (106 beats per minute), and body temperature was 378C. The central venous pressure was not elevated. On auscultation, a third heart sound was heard without any murmurs. Examination of the lungs revealed diffuse rales. The chest wound was neatly cured. Peripheral edema was not present, and the extremities felt damp. The electrocardiogram (ECG) was changed, compared to the preoperative ECG, and now showed microvoltages along with pathological Qs in leads V1–3 and II, III, and aVF. Echocardiography revealed a small heart with diffusely thickened walls of both ventricles. The contraction pattern was adequate, except for the anterior and basal part of the septum that was akinetic. The right ventricular function was normal. The patient was admitted to the cardiac care unit for the symptomatic treatment of heart failure and further diagnos-
P.L. van Haelst et al. / Cardiovascular Pathology 15 (2006) 228 – 230
229
tics. A coronary angiography showed no signs of coronary artery disease. On the day after admission, he suffered from progressive sustained polymorphic ventricular arrhythmias leading to hemodynamic instability requiring cardiopulmonary resuscitation. The patient was sedated, intubated, ventilated, and electrocardioverted to sinus rhythm. Therapy with intravenous amiodarone was instituted, and after several electroshocks for recurrent ventricular tachycardias, the arrhythmias declined in severity and frequency. The combination of acute-onset heart failure in combination with malignant ventricular arrhythmias raised a strong suspicion of giant cell myocarditis (GCM) [1]. Therapy was expanded with 1000 mg of methylprednisolone intravenously for 3 days, and a myocardial biopsy was performed at the third day of admission. Right ventricular endomyocardial biopsy revealed a GCM (Fig. 1A). Treatment was started with cyclosporine and azathioprine and, after consulting his neurologist, plasmapheresis to prevent a relapse of the myasthenia. Respiratory support was continued for 6 days. A control biopsy after 4 weeks of treatment showed a decrease in inflammatory cells, and giant cells were no longer detectable. However, fibrosis was more pronounced (Fig. 1B). The patient was discharged, but after several weeks, he was readmitted because of a septic shock due to an atypical pneumonia. In the intensive care ward, the immunosuppressive treatment was discontinued for 4 days. A control echocardiography revealed a severely worsened left ventricular function [left ventricular ejection fraction (LVEF) estimated at 20– 25%]. Immunosuppressive therapy was reinstituted. Because of the worsened LVEF and the fact that a Holter ECG showed multiple nonsustained ventricular tachycardias, an implantable cardioverter defibrillator (ICD) was positioned. The patient successfully underwent a cardiac rehabilitation program, and 6 months later, his LVEF was 45%, and myocardial biopsies showed no more signs of GCM, with only a very sparse inflammatory infiltrate (Fig. 1C). Now, 15 months after the diagnosis, the patient is in an excellent clinical condition. He still uses cyclosporine, azathioprine, and prednisolone next to an angiotensinconverting enzyme inhibitor and beta-blocker. The ICD has not discharged since implantation.
2. Discussion Fig. 1. (A) Right ventricular endomyocardial biopsy before treatment. GCM: a dense inflammatory interstitial infiltrate which contains lymphocytes, epitheloid histiocytes, and Langhans giant cells. This infiltrate is associated with myocyte damage. Importantly, no granulomas were seen. (B) Right ventricular endomyocardial biopsy after 2 weeks of treatment. The inflammatory interstitial infiltrate is clearly less present. No giant cells are present anymore, but fibrosis is more pronounced. This biopsy shows a resolving myocarditis. (C) Right ventricular endomyocardial biopsy after 6 months. The biopsy contains hypertrophic cardiomyocytes with interstitial fibrosis and a very sparse inflammatory interstitial infiltrate. This biopsy shows a resolved myocarditis.
GCM is a disease of young, predominantly healthy adults. Males and females are equally affected. The disease is associated with a number of autoimmune diseases such as myasthenia gravis, ulcerative colitis, Crohn’s disease, Hashimoto’s thyroiditis, rheumatoid arthritis, pernicious anemia, and Takayasu’s arteritis. GCM generally presents as heart failure of a very sudden onset with dyspnea, hypotension, orthopnea, and peripheral edema [2]. In some
230
P.L. van Haelst et al. / Cardiovascular Pathology 15 (2006) 228 – 230
cases, it presents with ventricular tachycardias, complete heart block, and symptoms mimicking myocardial infarction. Importantly, an association exists with thymoma, as was excellently reviewed by Kilgallen et al. [3]. Histologically, myocyte necrosis, giant cells, and inflammatory infiltrates are seen, while granulomatous lesions should not be present since they are a hallmark of cardiac sarcoidosis, a disease mimicking GCM histologically. The course of the disease is almost invariably fatal unless strong immunosuppressive therapy is started or heart transplantation is done. A study that included 63 patients worldwide showed a rate of death or cardiac transplantation of 89% after 5 years, with a median survival of 5.5 months [1]. The posttransplantation survival rate after 3 years is 74%, comparable to groups that underwent cardiac transplantation for other reasons. However, GCM may recur in the transplanted heart [4]. An endomyocardial biopsy is not routinely advocated in patients with a myocarditis because of a low diagnostic yield [5,6]. However, it was suggested that biopsy in patients with a fulminant clinical course who presented early (as in this case) had a sensitivity for GCM of as high as 80% [7]. Since the implications for further treatment are significant, we feel that in patients who present with rapidly progressive heart failure of an unknown cause, a right ventricular endomyocardial biopsy should be performed. Moreover, as was done in this case, the results of the biopsy may guide the clinician in choosing the right immunosuppressive regimen. The association of thymoma and GCM is not novel [3]. Kilgallen et al describe GCM after thymoma resection only in women. It has also been reported that the time course of GCM after resection of the thymoma is not within any time frame; it may occur immediately after the operation, or even years later. Clinicians who follow these patients should be aware of this.
3. Conclusion GCM is a rare cause of heart failure, which may occur in patients after the resection of a thymoma at any time point. Because the histological diagnosis enables aggressive therapeutic measures, an early cardiac tissue sample is warranted. We recommend that, in a case of unexplained rapidly progressive heart failure with or without malignant arrhythmias, especially in the presence of a history of an autoimmune condition, a myocardial biopsy should be performed within several days in order to start early treatment and prevent a fatal course of the disease. Follow-up endomyocardial biopsies may guide the clinician in deciding what immunosuppressive treatment the patients ought to receive. References [1] Cooper LT, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis— natural history and treatment Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med 1997;336:1860 – 6. [2] van Haelst PL, van Rossem M, Valentijn RM, et al. Giant cell myocarditis: a fatal cause of dyspnea in pregnancy. Eur J Obstet Gynecol Reprod Biol 2001;100:105 – 7. [3] Kilgallen CM, Jackson E, Bankoff M, et al. A case of giant cell myocarditis and malignant thymoma: a postmortem diagnosis by needle biopsy. Clin Cardiol 1998;21:48 – 51. [4] Davies RA, Veinot JP, Smith S, et al. Giant cell myocarditis: clinical presentation, bridge to transplantation with mechanical circulatory support, and long-term outcome. J Heart Lung Transplant 2002;21: 674 – 9. [5] Feldman AM, McNamara D. Myocarditis. N Engl J Med 2000;343: 1388 – 98. [6] Kasper EK, Agema WR, Hutchins GM, et al. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol 1994;23:586 – 90. [7] Shields RC, Tazelaar HD, Berry GJ, et al. The role of right ventricular endomyocardial biopsy for idiopathic giant cell myocarditis. J Card Fail 2002;8:74 – 8.