Successful heart transplantation using a donor heart afflicted by takotsubo cardiomyopathy Yazhini Ravi, MD,* Ryan Campagna, MD,* Paola C. Rosas, MD, PhD, RPh, Essa Essa, MD, Ayesha K. Hasan, MD, Robert S. D. Higgins, MD, MHA, Sitaramesh Emani, MD, and Chittoor B. Sai-Sudhakar, MD
Takotsubo cardiomyopathy, also known as apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome, is a disease characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. Herein, we present a case in which a heart with mild takotsubo cardiomyopathy was utilized as the donor organ for an orthotopic heart transplant.
CASE REPORT A 61-year-old man with ischemic cardiomyopathy in New York Heart Association Class IV heart failure despite optimal therapy was listed for cardiac transplantation. Four months later, a donor heart became available from a 17-year-old woman without significant past medical history who was involved in a motor vehicle accident. During the evaluation for organ donation candidacy, echocardiography demonstrated apical ballooning suggestive of takotsubo cardiomyopathy (TC) (Figure 1). Because of the donor’s age and risk profile, epicardial coronary artery disease was not considered to be a factor in the causation of the localized wall motion abnormality. The left ventricular apical ballooning was directly observed at procurement as well, and palpation of the epicardial coronary arteries did not reveal any gross pathology, areas of atheromatous disease, or calcium. An orthotopic heart transplant was carried out in the recipient using the bicaval technique following closure of a patent foramen ovale in the donor heart. Total ischemic time was 240 minutes. Following the completion of the procedure, an intraoperative echocardiogram demonstrated complete resolution of the TC. The patient was extubated on postoperative day 1 and was weaned off all inotropic support within 48 hours. A transthoracic echocardiogram obtained on postoperative day 3 revealed no evidence of TC (Figure 2). The postoperative course was uneventful. Following the transplant, the patient continued to do well. The first biopsy done 1 week posttransplant showed grade 2 rejection (revised grade 1R) with evidence of reperfusion injury. Subsequent biopsies have been 1A-2 (revised grade 1R), with all biopsies after 24 months being 1A (revised grade 1R). Annual assessments of his left ventricular function have continued to show normal wall motion and function. To date, two annual angiographic assessments have shown no evidence of coronary allograft vasculopathy. The patient is doing well 46 months after his heart transplantation. Proc (Bayl Univ Med Cent) 2016;29(1):73–74
Figure 1. Echocardiography showing left ventricular apical ballooning in the donor.
DISCUSSION To date, there are no reports of TC in the context of cardiac transplantation. TC and cardiac transplantation have been From the Division of Cardiothoracic Surgery, Baylor Scott & White Healthcare, Temple, Texas (Ravi, Sai-Sudhakar); the College of Medicine, The Ohio State University, Columbus, Ohio (Campagna); the Department of Medical Physiology, Texas A&M Health Science Center, Temple, Texas (Rosas); the Division of Cardiology, The Ohio State University, Columbus, Ohio (Essa, Hasan, Emani); and the Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (Higgins). *Contributed equally. Corresponding author: Sitaramesh Emani, MD, Division of Cardiology, The Ohio State University, Wexner Medical Center, 473 W. 12th Avenue, Suite 200 DHLRI, Columbus, OH 43210 (e-mail: [email protected]). 73
Figure 2. Echocardiogram in the recipient showing normal wall motion.
indirectly associated with one another via brain death–induced cardiomyopathy (BDIC), a phenomenon that shares pathologic similarities with TC. Brain death is a common scenario within which cardiac donation is considered, yet the speculation of brain death–induced myocardial stunning as a reversible cardiomyopathy has only occurred recently (1).
BDIC and TC share a number of traits, the most important of which are excessive catecholamine exposure and transient ventricular dysfunction. The excess circulatory catecholamines present in BDIC and TC arise from different pathological etiologies, namely, stress-induced catecholamine release in TC and a loss of brainstem parasympathetic outflow/disinhibition of sympathetic tone in BDIC. The resultant “catecholamine surge” then imparts damage through a variety of proposed mechanisms, leading to clinically significant ventricular dysfunction. Despite differences in the most prevalent location of the ventricular dysfunction (right and left in BDIC and TC, respectively), the conditions share a plethora of additional pathological characteristics, including electrocardiographic findings, microscopic findings, and extracardiac features (1). We propose in this case that the donor’s cardiac function was affected by the intense physiologic stress caused by the motor vehicle accident and resultant fatal injuries. Many potential cardiac donors suffer traumatic brain injury, and poor cardiac function (often mediated by ventricular dysfunction) is the most common cause for declining a donor heart for transplant (2). Therefore, a better understanding of BDIC and its pathophysiological relation to reversible TC could lead to an increased use of donor hearts that would otherwise be rejected because of transient ventricular dysfunction. Future research efforts should aim to understand these phenomena both separately and alongside one another as reversible cardiomyopathies. 1.
2.
Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, Parameshwar J, Large S. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? J Heart Lung Transplant 2010;29(9):957–965. Taylor DO, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Rahmel AO, Kucheryavaya AY, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report—2008. J Heart Lung Transplant 2008;27(9):943–956.
Invited Commentary Using “broken hearts” for cardiac transplantation: a risky venture or fruitful endeavor?
F
irst described in 1990 (1), takotsubo cardiomyopathy (TC), known also as “broken heart syndrome” and “stress-induced cardiomyopathy,” remains a perplexing pathophysiologic condition. This transient clinical disorder is classically precipitated by intense emotional stress and manifests with signs and symptoms mimicking acute coronary syndrome in the absence of angiographically evident coronary disease. The echocardiographic sine qua non of TC includes left ventricular (LV) systolic dysfunction with apical ballooning that spontaneously resolves on serial exams over days to weeks. From a mechanistic standpoint, most postulate that TC is the culmi74
nation of a “perfect storm,” encompassing an intricate interplay between neurohormonal and/or other physiologic stressors that incite a catecholamine surge in susceptible patients with predisposing cardiovascular risk factors and comorbidities (2, 3). In the current issue of Baylor Proceedings, Ravi and colleagues (4) describe one of the only reported cases of a donor heart with TC successfully used for cardiac transplantation. The donor, a 17-year-old female with no prior cardiac history, suffered brain death following a high-impact motor vehicle collision. A confirmatory coronary angiogram was not performed, but the echocardiographic findings were clearly indicative of Proc (Bayl Univ Med Cent) 2016;29(1):74–75
TC, including both LV dysfunction and apical ballooning. The authors correctly surmised this was a reversible state and that once removed from the stressful catecholamine milieu of the donor, the heart function would normalize and the recipient would thrive. By the third postoperative day, this newly implanted heart exhibited no signs of TC and the patient had an uneventful course. While the authors should certainly be applauded for their courage and astute clinical judgment in this case, it is unfortunate to note that many, if not most, other transplant centers would likely have declined this donor heart offer. Such widespread reluctance is based largely on the prevalent concern that donor hearts with LV dysfunction will exhibit a greater proclivity for primary graft dysfunction following implantation. Such fears often persist, even when structural heart disease, such as coronary artery disease or valvular abnormalities, has been excluded as an etiologic factor. A number of studies examining outcomes of donor hearts with LV dysfunction would refute the notion that such hearts would have intrinsically worse outcomes (5–7). In a study by Mohamedali and colleagues (5) of 11 potential heart donors with compromised ejection fraction, LV systolic function normalized, regardless of the pattern of abnormalities. Similarly, in a Cleveland Clinic study of 50 donor hearts with >70 echocardiographic abnormalities (6), the vast majority exhibited normalized parameters following transplantation. When examining outcomes of “marginal donor hearts” in the alternative heart transplant program at Duke, we found no increased risk of subsequent graft dysfunction (7). These and other studies suggest that TC may very well be part of the spectrum of so-called neurogenic stress cardiomyopathy, an increasingly acknowledged phenomenon accompanying nearly 50% patients with brain death (8). The salient feature of this clinical entity is its reversibility, i.e., the spontaneous normalization of cardiac function. As such, potential heart donors exhibiting LV dysfunction should not be readily dismissed. Time permitting, serial echocardiographic evaluations should be conducted to document improvement. Conversely, the absence of structural heart disease, as confirmed by coronary angiography and echocardiography, along with the absence of cardiovascular risk factors, may itself justify acceptance for transplantation in many of these scenarios.
January 2016
Given the exponential growth in the number of patients with advanced heart failure and the purported shortage of donor organs, the therapeutic paradigm has increasingly evolved towards mechanical circulatory support to meet the growing demand. However, cardiac transplantation remains the gold standard therapy for these patients, and the oft-reported “shortage” of donor organs may be self-imposed, where clinically unfounded exclusion criteria are rampantly applied, thereby disqualifying many potentially viable donor hearts. In light of the published data, case reports such as this should not represent isolated aberrations in clinical practice, but a growing trend in our collective approach to heart donor selection. —Brian Lima, MD Department of Cardiac Surgery Baylor University Medical Center at Dallas (E-mail: [email protected]) 1.
2.
3. 4.
5.
6.
7.
8.
Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol 1991;21(2):203–214. Pelliccia F, Greco C, Vitale C, Rosano G, Gaudio C, Kaski JC. Takotsubo syndrome (stress cardiomyopathy): an intriguing clinical condition in search of its identity. Am J Med 2014;127(8):699–704. Peters MN, George P, Irimpen AM. The broken heart syndrome: takotsubo cardiomyopathy. Trends Cardiovasc Med 2015;25(4):351–357. Ravi Y, Campagna R, Rosas PC, Essa E, Hasan AK, Higgins RSD, Emani S, Sai-Sudhakar CB. Successful heart transplantation using a donor heart afflicted by takotsubo cardiomyopathy. Proc (Bayl Univ Med Cent) 2016;29(1):73–74. Mohamedali B, Bhat G, Zelinger A. Frequency and pattern of left ventricular dysfunction in potential heart donors: implications regarding use of dysfunctional hearts for successful transplantation. J Am Coll Cardiol 2012;60(3):235–236. Sopko N, Shea KJ, Ludrosky K, Smedira N, Hoercher K, Taylor DO, Starling RC, Gonzalez-Stawinski GV. Survival is not compromised in donor hearts with echocardiographic abnormalities. J Surg Res 2007;143(1):141–144. Lima B, Rajagopal K, Petersen RP, Shah AS, Soule B, Felker GM, Rogers JG, Lodge AJ, Milano CA. Marginal cardiac allografts do not have increased primary graft dysfunction in alternate list transplantation. Circulation 2006;114(1 Suppl):I27–I32. Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, Parameshwar J, Large S. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? J Heart Lung Transplant 2010;29(9):957–965.
Using “broken hearts” for cardiac transplantation: a risky venture or fruitful endeavor?
75
Takotsubo cardiomyopathy, also known as apical ballooning syndrome, stress cardiomyopathy, or broken heart syndrome, is a disease characterized by transient ventricular dysfunction in the absence of obstructive coronary artery disease. Herein, we present a case in which a heart with mild takotsubo cardiomyopathy was utilized as the donor organ for an orthotopic heart transplant.
CASE REPORT A 61-year-old man with ischemic cardiomyopathy in New York Heart Association Class IV heart failure despite optimal therapy was listed for cardiac transplantation. Four months later, a donor heart became available from a 17-year-old woman without significant past medical history who was involved in a motor vehicle accident. During the evaluation for organ donation candidacy, echocardiography demonstrated apical ballooning suggestive of takotsubo cardiomyopathy (TC) (Figure 1). Because of the donor’s age and risk profile, epicardial coronary artery disease was not considered to be a factor in the causation of the localized wall motion abnormality. The left ventricular apical ballooning was directly observed at procurement as well, and palpation of the epicardial coronary arteries did not reveal any gross pathology, areas of atheromatous disease, or calcium. An orthotopic heart transplant was carried out in the recipient using the bicaval technique following closure of a patent foramen ovale in the donor heart. Total ischemic time was 240 minutes. Following the completion of the procedure, an intraoperative echocardiogram demonstrated complete resolution of the TC. The patient was extubated on postoperative day 1 and was weaned off all inotropic support within 48 hours. A transthoracic echocardiogram obtained on postoperative day 3 revealed no evidence of TC (Figure 2). The postoperative course was uneventful. Following the transplant, the patient continued to do well. The first biopsy done 1 week posttransplant showed grade 2 rejection (revised grade 1R) with evidence of reperfusion injury. Subsequent biopsies have been 1A-2 (revised grade 1R), with all biopsies after 24 months being 1A (revised grade 1R). Annual assessments of his left ventricular function have continued to show normal wall motion and function. To date, two annual angiographic assessments have shown no evidence of coronary allograft vasculopathy. The patient is doing well 46 months after his heart transplantation. Proc (Bayl Univ Med Cent) 2016;29(1):73–74
Figure 1. Echocardiography showing left ventricular apical ballooning in the donor.
DISCUSSION To date, there are no reports of TC in the context of cardiac transplantation. TC and cardiac transplantation have been From the Division of Cardiothoracic Surgery, Baylor Scott & White Healthcare, Temple, Texas (Ravi, Sai-Sudhakar); the College of Medicine, The Ohio State University, Columbus, Ohio (Campagna); the Department of Medical Physiology, Texas A&M Health Science Center, Temple, Texas (Rosas); the Division of Cardiology, The Ohio State University, Columbus, Ohio (Essa, Hasan, Emani); and the Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (Higgins). *Contributed equally. Corresponding author: Sitaramesh Emani, MD, Division of Cardiology, The Ohio State University, Wexner Medical Center, 473 W. 12th Avenue, Suite 200 DHLRI, Columbus, OH 43210 (e-mail: [email protected]). 73
Figure 2. Echocardiogram in the recipient showing normal wall motion.
indirectly associated with one another via brain death–induced cardiomyopathy (BDIC), a phenomenon that shares pathologic similarities with TC. Brain death is a common scenario within which cardiac donation is considered, yet the speculation of brain death–induced myocardial stunning as a reversible cardiomyopathy has only occurred recently (1).
BDIC and TC share a number of traits, the most important of which are excessive catecholamine exposure and transient ventricular dysfunction. The excess circulatory catecholamines present in BDIC and TC arise from different pathological etiologies, namely, stress-induced catecholamine release in TC and a loss of brainstem parasympathetic outflow/disinhibition of sympathetic tone in BDIC. The resultant “catecholamine surge” then imparts damage through a variety of proposed mechanisms, leading to clinically significant ventricular dysfunction. Despite differences in the most prevalent location of the ventricular dysfunction (right and left in BDIC and TC, respectively), the conditions share a plethora of additional pathological characteristics, including electrocardiographic findings, microscopic findings, and extracardiac features (1). We propose in this case that the donor’s cardiac function was affected by the intense physiologic stress caused by the motor vehicle accident and resultant fatal injuries. Many potential cardiac donors suffer traumatic brain injury, and poor cardiac function (often mediated by ventricular dysfunction) is the most common cause for declining a donor heart for transplant (2). Therefore, a better understanding of BDIC and its pathophysiological relation to reversible TC could lead to an increased use of donor hearts that would otherwise be rejected because of transient ventricular dysfunction. Future research efforts should aim to understand these phenomena both separately and alongside one another as reversible cardiomyopathies. 1.
2.
Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, Parameshwar J, Large S. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? J Heart Lung Transplant 2010;29(9):957–965. Taylor DO, Edwards LB, Aurora P, Christie JD, Dobbels F, Kirk R, Rahmel AO, Kucheryavaya AY, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-fifth official adult heart transplant report—2008. J Heart Lung Transplant 2008;27(9):943–956.
Invited Commentary Using “broken hearts” for cardiac transplantation: a risky venture or fruitful endeavor?
F
irst described in 1990 (1), takotsubo cardiomyopathy (TC), known also as “broken heart syndrome” and “stress-induced cardiomyopathy,” remains a perplexing pathophysiologic condition. This transient clinical disorder is classically precipitated by intense emotional stress and manifests with signs and symptoms mimicking acute coronary syndrome in the absence of angiographically evident coronary disease. The echocardiographic sine qua non of TC includes left ventricular (LV) systolic dysfunction with apical ballooning that spontaneously resolves on serial exams over days to weeks. From a mechanistic standpoint, most postulate that TC is the culmi74
nation of a “perfect storm,” encompassing an intricate interplay between neurohormonal and/or other physiologic stressors that incite a catecholamine surge in susceptible patients with predisposing cardiovascular risk factors and comorbidities (2, 3). In the current issue of Baylor Proceedings, Ravi and colleagues (4) describe one of the only reported cases of a donor heart with TC successfully used for cardiac transplantation. The donor, a 17-year-old female with no prior cardiac history, suffered brain death following a high-impact motor vehicle collision. A confirmatory coronary angiogram was not performed, but the echocardiographic findings were clearly indicative of Proc (Bayl Univ Med Cent) 2016;29(1):74–75
TC, including both LV dysfunction and apical ballooning. The authors correctly surmised this was a reversible state and that once removed from the stressful catecholamine milieu of the donor, the heart function would normalize and the recipient would thrive. By the third postoperative day, this newly implanted heart exhibited no signs of TC and the patient had an uneventful course. While the authors should certainly be applauded for their courage and astute clinical judgment in this case, it is unfortunate to note that many, if not most, other transplant centers would likely have declined this donor heart offer. Such widespread reluctance is based largely on the prevalent concern that donor hearts with LV dysfunction will exhibit a greater proclivity for primary graft dysfunction following implantation. Such fears often persist, even when structural heart disease, such as coronary artery disease or valvular abnormalities, has been excluded as an etiologic factor. A number of studies examining outcomes of donor hearts with LV dysfunction would refute the notion that such hearts would have intrinsically worse outcomes (5–7). In a study by Mohamedali and colleagues (5) of 11 potential heart donors with compromised ejection fraction, LV systolic function normalized, regardless of the pattern of abnormalities. Similarly, in a Cleveland Clinic study of 50 donor hearts with >70 echocardiographic abnormalities (6), the vast majority exhibited normalized parameters following transplantation. When examining outcomes of “marginal donor hearts” in the alternative heart transplant program at Duke, we found no increased risk of subsequent graft dysfunction (7). These and other studies suggest that TC may very well be part of the spectrum of so-called neurogenic stress cardiomyopathy, an increasingly acknowledged phenomenon accompanying nearly 50% patients with brain death (8). The salient feature of this clinical entity is its reversibility, i.e., the spontaneous normalization of cardiac function. As such, potential heart donors exhibiting LV dysfunction should not be readily dismissed. Time permitting, serial echocardiographic evaluations should be conducted to document improvement. Conversely, the absence of structural heart disease, as confirmed by coronary angiography and echocardiography, along with the absence of cardiovascular risk factors, may itself justify acceptance for transplantation in many of these scenarios.
January 2016
Given the exponential growth in the number of patients with advanced heart failure and the purported shortage of donor organs, the therapeutic paradigm has increasingly evolved towards mechanical circulatory support to meet the growing demand. However, cardiac transplantation remains the gold standard therapy for these patients, and the oft-reported “shortage” of donor organs may be self-imposed, where clinically unfounded exclusion criteria are rampantly applied, thereby disqualifying many potentially viable donor hearts. In light of the published data, case reports such as this should not represent isolated aberrations in clinical practice, but a growing trend in our collective approach to heart donor selection. —Brian Lima, MD Department of Cardiac Surgery Baylor University Medical Center at Dallas (E-mail: [email protected]) 1.
2.
3. 4.
5.
6.
7.
8.
Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol 1991;21(2):203–214. Pelliccia F, Greco C, Vitale C, Rosano G, Gaudio C, Kaski JC. Takotsubo syndrome (stress cardiomyopathy): an intriguing clinical condition in search of its identity. Am J Med 2014;127(8):699–704. Peters MN, George P, Irimpen AM. The broken heart syndrome: takotsubo cardiomyopathy. Trends Cardiovasc Med 2015;25(4):351–357. Ravi Y, Campagna R, Rosas PC, Essa E, Hasan AK, Higgins RSD, Emani S, Sai-Sudhakar CB. Successful heart transplantation using a donor heart afflicted by takotsubo cardiomyopathy. Proc (Bayl Univ Med Cent) 2016;29(1):73–74. Mohamedali B, Bhat G, Zelinger A. Frequency and pattern of left ventricular dysfunction in potential heart donors: implications regarding use of dysfunctional hearts for successful transplantation. J Am Coll Cardiol 2012;60(3):235–236. Sopko N, Shea KJ, Ludrosky K, Smedira N, Hoercher K, Taylor DO, Starling RC, Gonzalez-Stawinski GV. Survival is not compromised in donor hearts with echocardiographic abnormalities. J Surg Res 2007;143(1):141–144. Lima B, Rajagopal K, Petersen RP, Shah AS, Soule B, Felker GM, Rogers JG, Lodge AJ, Milano CA. Marginal cardiac allografts do not have increased primary graft dysfunction in alternate list transplantation. Circulation 2006;114(1 Suppl):I27–I32. Berman M, Ali A, Ashley E, Freed D, Clarke K, Tsui S, Parameshwar J, Large S. Is stress cardiomyopathy the underlying cause of ventricular dysfunction associated with brain death? J Heart Lung Transplant 2010;29(9):957–965.
Using “broken hearts” for cardiac transplantation: a risky venture or fruitful endeavor?
75
