Natural History of Cardiac Arrest in Patients With Takotsubo Cardiomyopathy Kuljit Singh, MDa,b,*, Kristin Carson, Dip Lab Medb, Benjamin Hibbert, MD, PhDa, and Michel Le May, MDa Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after CA, making it difﬁcult to distinguish if TTC is the precipitant or the consequence of the index event. In this systematic review, patient-level data were obtained to seek out the characteristics of patients in whom the underlying cause of CA is TTC. A comprehensive search of 4 major databases (Embase, Ovid MEDLINE, PubMed, and Google Scholar) was performed from their inception to the last week of September 2014. Of 186 citations, 62 case studies were included in the analysis, providing patient-level data on 77 patients. In 60 patients (78%), the diagnosis of TTC was made after CA. Patients presenting with CA were younger (mean age 49.5 – 16 vs 64.9 – 11 years, p 2,000 patients67 and various clinical studies2 have indicated the mean age of patients with TTC to be in the mid-60s, as found in the primary TTC group. The relatively young age in the secondary TTC group raises the suspicion of genetic
The American Journal of Cardiology (www.ajconline.org)
disorders and channelopathies as the real causes of CA. However, in patients in whom reliable histories of chest pain and dyspnea before CA are present, as found in nearly 20% of patients in our secondary TTC group, TTC as a cause of CA can be determined with certainty. These patients do not require AICDs, because the risk for recurrence of CA with TTC is extremely low. At the moment, there are no clinical guidelines for the long-term management of patients with TTC who experience CA. We noted that current practice of management differed signiﬁcantly among centers. Only 1/3 of patients underwent EP studies or device implantation. Patients who develop CA after TTC, when QTc interval duration is longest, probably do not require AICD placement or EP study. In contrast, in patients in whom there is no history of symptoms to suggest TTC and CA occurs at a relatively younger age, we recommend screening for other common causes for CA (Figure 2). The main purpose of this review was to identify characteristics of patients with TTC who develop CA. Furthermore, we wanted to clarify if patients presenting with CA, who are diagnosed with TTC, have other underlying reasons for CA and TTC changes to the left ventricle are not merely postresuscitation myocardial stunning. We found that in most patients, CA was triggered by TTC directly through prolongation of QTc and hypotension, or indirectly by noncardiac conditions that initially stimulated TTC, such as SAH and pheochromocytoma. However, occasional cases of TTC can unmask underlying iatrogenic or genetic long-QTc syndrome. Such cases can be suspected by extreme prolongation of QTc duration (>800 ms in 1 case), which is unusual for TTC. Only in 1 case was ARVD was found, but it is difﬁcult to ascertain if ARVD was the real cause of CA or just an incidental diagnosis. In patients who undergo AICD or pacemaker implantation, follow-up with device interrogation can help determine if these patients develop ventricular arrhythmias in the absence of TTC. This study had some limitations. First of all, it represents only a small proportion of the patients with TTC with CA who were hospitalized and underwent early invasive imaging to diagnose TTC. Second, detailed information on electrocardiographic, clinical, and biochemical parameters was not available in all the studies. Third, there was no control group available to ascertain whether the patients with TTC who developed CA were different from those who did not. Nonetheless, the data from the patients who developed CA and TTC while being monitored perioperatively provided strong support that hypotension is the triggering event of CA at the time of TTC development. Furthermore, this analysis not only consolidated the evidence that a long QTc interval is the underlying cause of CA during the subacute phase but also demonstrates that patients with QTc intervals >600 ms are those at risk for ventricular arrhythmias in the acute phase of TTC and should be monitored until the QTc interval stabilizes. Disclosures The authors have no conﬂicts of interest to disclose. 1. Akashi YJ, Nef HM, Mollmann H, Ueyama T. Stress cardiomyopathy. Annu Rev Med 2010;61:271e286.
2. Singh K, Neil CJ, Nguyen TH, Stansborough J, Chong CR, Dawson D, Frenneaux MP, Horowitz JD. Dissociation of early shock in takotsubo cardiomyopathy from either right or left ventricular systolic dysfunction. Heart Lung Circ 2014;23:1141e1148. 3. Singh K, Parsaik AK, Zeitz CJ. Takotsubo cardiomyopathy mid ventricle variant and cardiac arrest: chicken or the egg? Am J Emerg Med 2013;31:890.e1e890.e2. 4. Madias JE. Is Takotsubo syndrome one of the causes of sudden cardiac death? Pacing Clin Electrophysiol 2013;36:793e794. 5. Ahn JH, Park SH, Shin WY, Lee SW, Lee SJ, Jin DK, Lee HM, Eun JY. Long QT syndrome and torsade de pointes associated with Takotsubo cardiomyopathy. J Korean Med Sci 2011;26: 959e961. 6. Aregullin EO, Garg R, Berman D. Takotsubo cardiomyopathy after transcatheter Edwards Sapien pulmonary valve placement in a patient with tetralogy of Fallot. Pediatr Cardiol 2013;34:1972e1975. 7. Bahlmann E, Krause K, Harle T, van der Schalk H, Kuck KH. Cardiac arrest and successful resuscitation in a patient with tako-tsubo cardiomyopathy. Int J Cardiol 2008;130:e4ee6. 8. Bartoli CR, Nadar MM, Loyd GE, Kasdan ML. An atypical case of reverse Takotsubo cardiomyopathy during general anesthesia in a 30-year-old male with post-traumatic stress disorder. J Cardiothorac Vasc Anesth 2011;25:1116e1118. 9. Basselin C, Fontanges T, Descotes J, Chevalier P, Bui-Xuan B, Feinard G, Timour Q. 5-Fluorouracil-induced tako-tsubo-like syndrome. Pharmacotherapy 2011;31:226. 10. Bleser T, Weth C, Gorge G. [Reverse takotsubo cardiomyopathy-a life-threatening disease. Successful resuscitation of a 31-year-old woman with cardiologic shock after a visit to the dentist]. Med Klin Intensivmed Notfallmed 2013;108:675e678. 11. Boes M, Henning M, Urbach H, Simon M. Delayed diagnosis of subarachnoid hemorrhage associated with tako-tsubo cardiomyopathy. Cent Europ Neurosurg 2011;72:49e51. 12. Bomann S, Davies IO. ED echo of reverse tako-tsubo cardiomyopathy: a rare and misleading ﬁnding. Am J Emerg Med 2012;30:2088. e3e2088.e5. 13. Bortnik M, Verdoia M, Schaffer A, Occhetta E, Marino P. Ventricular ﬁbrillation as primary presentation of takotsubo cardiomyopathy after complicated cesarean delivery. World J Cardiol 2012;4:214e217. 14. Cabaton J, Rondelet B, Gergele L, Besnard C, Piriou V. [Tako-tsubo syndrome after anaphylaxis caused by succinylcholine during general anaesthesia]. Ann Fr Anesth Reanim 2008;27:854e857. 15. Cakici M, Cetin M, Polat M, Su Ner A. [Long QT-induced ventricular tachycardia associated with takotsubo cardiomyopathy]. Turk Kardiyol Dern Ars 2014;42:71e75. 16. Caudron J, Rey N, Dacher JN. Midventricular takotsubo cardiomyopathy associated with ventricular ﬁbrillation during general anaesthesia in a 34-year-old woman: insight from cardiac computed tomography and magnetic resonance imaging. Arch Cardiovasc Dis 2012;105:329e331. 17. Chadha S, Lodha A, Shetty V, Sadiq A, Hollander G, Shani J. Takotsubo cardiomyopathy: presentation with sudden cardiac arrest. Herz 2013;38:558e560. 18. Cho SC, Kim W, Park CS, Park SH, Jung AD, Hwang SH, Kim W. Stress-induced cardiomyopathy presenting as ventricular tachycardia. Korean J Intern Med 2012;27:107e110. 19. Cruvinel MG, Carneiro FS, Bessa RC Jr, Pereira e Silva Y, Marques MB. Tako-tsubo syndrome secondary to residual neuromuscular blockade. Case report. Rev Bras Anestesiol 2008;58:623e630. 20. Cunnington C, Garg S, Balachandran KP. Seizure-associated takotsubo cardiomyopathy presenting with unheralded ventricular ﬁbrillation. Int J Cardiol 2012;162:e21ee23. 21. Cvorovic V, Stankovic I, Panic M, Stipac AV, Zivkovic A, Neskovic AN, Putnikovic B. Establishing the diagnosis of inverted stress cardiomyopathy in a patient with cardiac arrest during general anesthesia: a potential role of myocardial strain? Echocardiography (Mount Kisco, NY) 2013;30:E161eE163. 22. D’Amato N, Colonna P, Brindicci P, Campagna MG, Petrillo C, Cafarelli A, D’Agostino C. Tako-tsubo syndrome in a pregnant woman. Eur J Echocardiogr 2008;9:700e703. 23. Dib C, Prasad A, Friedman PA, Ahmad E, Rihal CS, Hammill SC, Asirvatham SJ. Malignant arrhythmia in apical ballooning syndrome: risk factors and outcomes. Ind Pacing Electrophysiol J 2008;8: 182e192.
Review/Cardiac Arrest in Takotsubo Cardiomyopathy 24. Facciorusso A, Amico C, Vigna C, Santoro T, Potenza D, Massaro R, Stanislao M, Valle G, Cavaliere L, Fanelli R. Cardiac arrest caused by Barlow’s syndrome or by stress cardiomyopathy? Int J Cardiol 2010;140:e16ee18. 25. Finsterer J, Stollberger C, Demirtas D, Gencik M, Ohnutek I, Hornykewycz A. Recurrent takotsubo syndrome in a patient with myotonic dystrophy 1. Acute Card Care 2014;16:115e117. 26. Flam B, Broome M, Frenckner B, Branstrom R, Bell M. Pheochromocytoma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation. J Intensive Care Med 2014 [Article in press]. 27. Freitas HF, Renault R, Ribeiro ES, Andrade FM, Brito FS Jr, Velloso LG. Sudden cardiac arrest due to puerperal transient left ventricular apical ballooning syndrome. Int J Cardiol 2011;149:e12ee13. 28. Furushima H, Chinushi M, Sanada A, Aizawa Y. Ventricular repolarization gradients in a patient with takotsubo cardiomyopathy. Europace 2008;10:1112e1115. 29. Gotyo N, Kida M, Horiuchi T, Hirata Y. Torsade de pointes associated with recurrent ampulla cardiomyopathy in a patient with idiopathic ACTH deﬁciency. Endocr J 2009;56:807e815. 30. Harika R, Bermas K, Hughes C, Al-Khafaji A, Iyer M, Wallace DJ. Cardiac arrest after liver transplantation in a patient with takotsubo cardiomyopathy. Br J Anaesth 2014;112:594e595. 31. Hasdemir C, Vuran O, Yuksel A, Yavuzgil O. Stress cardiomyopathy (tako-tsubo) associated with sustained polymorphic ventricular tachycardia. Pacing Clin Electrophysiol 2013;36:e111ee114. 32. Hassid B, Azmoon S, Aronow WS, Palaniswamy C, Cohen M, Gass A. Hemodynamic support with TandemHeart in tako-tsubo cardiomyopathy—a case report. Arch Med Sci 2010;6:971e975. 33. Kalra N, Khetpal P, Sorrell VL. Seriously stressed. Am J Med 2009;122:735e737. 34. Kawagoe I, Odoh M, Koh K, Takada T, Inada E. [A case of intraoperative cardiac arrest in a patient with mitochondrial encephalomyopathy undergoing lung resection]. Jpn J Anesthesiol 2013;62: 431e434. 35. Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nakama Y, Kagawa E, Dai K, Ikenaga H. Tako-tsubo cardiomyopathy after successful resuscitation of out-of-hospital cardiac arrest. J Cardiovasc Med 2010;11:465e468. 36. Kwon SA, Yang JH, Kim MK, Park SW, Kim SH, Park KH, Park WJ. A case of takotsubo cardiomyopathy in a patient with iatrogenic thyrotoxicosis. Int J Cardiol 2010;145:e111ee113. 37. Liang JJ, Cha YM, Oh JK, Prasad A. Sudden cardiac death: an increasingly recognized presentation of apical ballooning syndrome (takotsubo cardiomyopathy). Heart Lung 2013;42:270e272. 38. Lieb M, Orr T, Gallagher C, Moten H, Tan JM. A case of intraoperative ventricular ﬁbrillation: electro-cauterization, undiagnosed Takotsubo cardiomyopathy or long QT syndrome? Int J Surg Case Rep 2012;3:155e157. 39. Lisi E, Guida V, Blengino S, Pedrazzi E, Ossoli D, Parati G. Intra-aortic balloon pump for treatment of refractory ventricular tachycardia in takotsubo cardiomyopathy: a case report. Int J Cardiol 2014;174:135e136. 40. Madias C, Fitzgibbons TP, Alsheikh-Ali AA, Bouchard JL, Kalsmith B, Garlitski AC, Tighe DA, Estes NA 3rd, Aurigemma GP, Link MS. Acquired long QT syndrome from stress cardiomyopathy is associated with ventricular arrhythmias and torsades de pointes. Heart Rhythm 2011;8:555e561. 41. Mahida S, Dalageorgou C, Behr ER. Long-QT syndrome and torsades de pointes in a patient with Takotsubo cardiomyopathy: an unusual case. Europace 2009;11:376e378. 42. Makaryus AN, Patrick C, Patcha R, Maccaro P. Cardiac arrest in a patient with normal coronary arteries. Am J Emerg Med 2008;26:734. e5e734.e7. 43. Mathew B, Villarreal D. Two unusual cases of takotsubo cardiomyopathy presenting with sudden cardiac death. Am J Med Sci 2009;337: 473e475. 44. Mrejen-Shakin K, Lopez R, Shenoy MM. Life-threatening takotsubo cardiomyopathy. Am Heart Hosp J 2011;9:119e121. 45. Nascimento FO, Krishna RK, Hrachian H, Santana O. Wearable cardioverter deﬁbrillator in stress cardiomyopathy and cardiac arrest. BMJ Case Rep 2013 [Article in press]. 46. Olivotti L, Moshiri S, Nicolino A, Chiarella F. Stress cardiomyopathy and arrhythmic storm in a 14-year-old boy. J Cardiovasc Med 2010;11: 519e521.
47. Pepe M, Zanna D, Quagliara D, Caiati C, Marzullo A, Palmiotto AI, Caruso G, Favale S. Sudden cardiac death secondary to demonstrated reperfusion ventricular ﬁbrillation in a woman with Takotsubo cardiomyopathy. Cardiovasc Pathol 2011;20:254e257. 48. Peters S, Klein HU. WCD LifeVest: risk stratiﬁcation in a case of Tako-Tsubo cardiomyopathy with QT interval prolongation. Herz 2012;37:219e221. 49. Peters S, Klein HU. Life-threatening ventricular arrhythmias due to atypical mid-ventricular tako tsubo cardiomyopathy in a patient with chronic QT interval prolongation under anti-psychotic medication. Int J Cardiol 2014;172:e534ee536. 50. Raddino R, Pedrinazzi C, Zanini G, Robba D, Portera C, Bonadei I, Vizzardi E, Dei Cas L. Out-of-hospital cardiac arrest caused by transient left ventricular apical ballooning syndrome. Int J Cardiol 2008;128:e31ee33. 51. Ritchie D, Trott T, Bryant J, Stearley S, Adkins B. Takutsubo cardiomyopathy and ﬂash pulmonary edema in a trauma patient. J Emerg Med 2013;45:530e532. 52. Russell L, Stockwell P. A case of intracranial hemorrhage causing stress-induced cardiomyopathy. R I Med J (2013) 2013;96:33e35. 53. Schimpf R, Meinhardt J, Borggrefe M, Haghi D. Catecholaminergic polymorphic ventricular tachycardia and midventricular takotsubo cardiomyopathy: a novel association? Herzschrittmacherther Elektrophysiol 2013;24:63e66. 54. Shimokawahara H, Sonoda M, Tanaka H, Kashima K, Nagayoshi S, Kawasaki D, Ikeda D, Nagano S, Tanaka Y, Nakamura K. Case of transient mid-ventricular ballooning syndrome with a rapid and uncommon recovery. J Cardiol 2009;54:311e316. 55. Siegfried JS, Bhusri S, Guttenplan N, Coplan NL. Takotsubo cardiomyopathy as a sequela of elective direct-current cardioversion for atrial ﬁbrillation. Tex Heart Inst J 2014;41:184e187. 56. Smedra-Kazmirska A, Barzdo M, Kowalski J, Szram S, Berent J. [Tako-tsubo cardiomyopathy in a man with cerebral haemorrhage]. Anestezjol Intens Ter 2010;42:85e89. 57. Sosnowska-Pasiarska B, Bakowski D, Woronowicz-Chrosciel A, Wozakowska-Kaplon B. Sudden cardiac arrest in takotsubo cardiomyopathy—a case study. Adv Interv Cardiol 2014;10:110e113. 58. Struzkova K, Stourac P, Kanovsky J, Krikava I, Toukalkova M, Sevcik P. An unusual reason for severe bradycardia leading to cardiac arrest during general anaesthesia: a case report. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013 [Article in Press]. 59. Suk EH, Kim DH, Kweon TD, Na SW, Shin JA. Stress-induced cardiomyopathy following cephalosporin-induced anaphylactic shock during general anesthesia. Can J Anaesth 2009;56:432e436. 60. Suzuki H, Sakurai M, Fujimoto M, Tsuchiya T, Sakaida H, Taki W. Complete recovery from aneurysmal subarachnoid hemorrhage associated with out-of-hospital cardiopulmonary arrest. Eur J Emerg Med 2010;17:42e44. 61. Tachotti Pires LJ, Cardoso Curiati MN, Vissoci Reiche F, Silvestre OM, Mangini S, Carballo Afonso R, Ferraz-Neto BH, Bacal F. Stressinduced cardiomyopathy (takotsubo cardiomyopathy) after liver transplantation-report of two cases. Transplant Proc 2012;44: 2497e2500. 62. Tran K, Milne N, Duhig E, Altman M. Inverted takotsubo cardiomyopathy—clinicopathologic correlation. Am J Forensic Med Pathol 2013;34:217e221. 63. Verdier F, Petitjeans F, Griffet V, Caignault JR, Guerard S. [Heart failure and anaphylactic shock. A report of two cases]. Ann Cardiol Angeiol 2011;60:113e117. 64. Vernick WJ, Hargrove WC, Augoustides JG, Horak J. Takotsubo cardiomyopathy associated with cardiac arrest following cardiac surgery: new variants of an unusual syndrome. J Card Surg 2010;25:679e683. 65. Zaman S, Ramesh N, Kovoor P. Arrhythmogenic right ventricular cardiomyopathy presenting with intra-operative aborted sudden cardiac death and takotsubolike left ventricular functional abnormalities. Hellenic J Cardiol 2009;50:330e334. 66. Duran-Cambra A, Sutil-Vega M, Fiol M, Nunez-Gil IJ, Vila M, Sans-Rosello J, Cinca J, Sionis A. Systematic review of the electrocardiographic changes in the takotsubo syndrome. Ann Noninvasive Electrocardiol 2015;20:1e6. 67. Singh K, Carson K, Shah R, Sawhney G, Singh B, Parsaik A, Gilutz H, Usmani Z, Horowitz J. Meta-analysis of clinical correlates of acute mortality in takotsubo cardiomyopathy. Am J Cardiol 2014;113: 1420e1428.