Takotsubo Syndrome After Mitral Valve Replacement: Case Report and Brief Review of the Literature Amedeo Pergolini, MD,* Giordano Zampi, MD,† Giovanni Casali, MD,* Andrea Madeo, MD,‡ Claudia Luisa Visconti, MD,§ Pier Luigi Cipullo, MD,* Paolo Giuseppe Pino, MD,* and Francesco Musumeci, MD*


RANSIENT LEFT VENTRICULAR apical ballooning syndrome, also known as Takotsubo or stress-induced cardiomyopathy, is a cardiac disease characterized by transient left ventricular dysfunction, electrocardiographic changes mimicking an acute coronary syndrome, and release of myocardial cellular necrosis enzymes in the absence of significant lesions of coronary arteries.1 Takotsubo cardiomyopathy in the perioperative period increasingly is being recognized, but its association with cardiac surgery remains a rare event. In this report, the authors describe a case of Takotsubo syndrome occurring after elective minimally invasive mitral valve replacement (MVR). CASE REPORT A 66-year-old Caucasian woman was admitted to the authors’ department for elective mitral valve replacement due to severe rheumatic mitral stenosis and regurgitation. The routine preoperative assessment did not reveal remarkable findings; the electrocardiogram (ECG) showed atrial fibrillation and no other associated alterations (Fig 1A), transthoracic echocardiography (TTE) confirmed the mitral disease, showing normal left ventricular (LV) systolic function, and the coronary angiography revealed no coronary lesions. Minimally invasive mitral valve replacement was performed through a small right lateral thoracotomy in the fourth intercostal space. Cardiopulmonary bypass (CPB) was established with venous drainage through the right femoral vein with a multistage 25Fr cannula (Medtronic BioMedicus, Minneapolis, MN) and arterial return through the right femoral artery with a 19Fr cannula (Medtronic Bio-Medicus, Minneapolis, MN). The aorta was cross-clamped with a Cygnet clamp, and myocardial protection was achieved by infusing cold crystalloid cardioplegia in the aortic root (Bretshmeider’s HTK solution; 25 mL/kg at 5-81C). The surgical field was flooded with carbon dioxide in order to minimize air embolism. The mitral valve was replaced with a mechanical prosthesis (St. Jude Medical 27 mm), preserving the posterior mitral leaflet and, therefore, maintaining the annuloventricular continuity. The heart was deaired through the left atriotomy by inflating the lungs and filling the right side by reducing the venous drainage. An aortic root vent was maintained after discontinuing CPB until an optimal de-airing was achieved under transesophageal echocardiographic (TEE) monitoring. Following the heart reperfusion, the patient experienced 2 episodes of ventricular fibrillation (VF) successfully treated by DC shock with restoration of sinus rhythm. Weaning from CPB easily was achieved on a low dose of dobutamine (3 μg/kg/min). The intraoperative TEE showed normal prosthesis positioning and function and no wall motion abnormalities of the left ventricle. CPB time was 133 minutes and aortic cross-clamp time was 82 minutes. The patient was transferred to the intensive care unit (ICU) and extubated 9 hours later. The early postoperative course was uneventful, the arterial oxygen saturation was normal (SaO2 97%), and only a mild sinus tachycardia (90/min) was observed. On postoperative day 4, a significant

arterial oxygen desaturation (SaO2 88%) was noticed at a routine gas analysis, the patient remained asymptomatic, and the vital signs were stable. A TTE showed severe left ventriular dysfunction (EF 30%) with akinesia of the apical and mid-ventricular segments, hyperkinesia of the basal segments (Fig 2A-D) (Video Clips 1-2), and moderate pulmonary hypertension (estimated pulmonary arterial systolic pressure of 55 mmHg) (Fig 2E-F). An ECG showed sinus rhythm with a ventricular rate of 100 bpm and inverted T-waves in leads II, III, and aVF and in precordial leads (Fig 1B). Maximal troponin T was 1.78 ng/mL, and creatine phosphokinase-MB was 11 ng/mL; BNP value was high (1,100 pg/mL). Based on the typical findings of apical ballooning on echocardiography, low elevation of cardiac enzymes, and previous detection of no coronary artery disease, Takotsubo cardiomyopathy was diagnosed. Beta-blocker treatment immediately was initiated. Daily transthoracic echocardiography showed gradual improvement of LV function. On postoperative day 12, TTE showed normal LV function (EF of about 55%) with normal regional wall motion (Fig 3A-D) (Video Clips 3-4) and normal pulmonary arterial pressure (Fig 3E-F); the patient was, therefore, transferred to a standard hospitalization area.


Four diagnostic criteria have been proposed by the Mayo Clinic2 for the diagnosis of Takotsubo cardiomyopathy: (1) Absence of obstructive coronary disease, (2) new electrocardiographic abnormalities (either ST-segment elevation or T-wave inversion), (3) transient akinesia or dyskinesia of the left ventricular apical and mid-ventricular segments with regional wall-motion abnormalities extending beyond a single epicardial vascular distribution, and (4) absence of recent significant head trauma, intracranial bleeding, pheochromocytoma, obstructive epicardial coronary artery disease, myocarditis, and hypertrophic cardiomyopathy.

From the *Department of Cardiovascular Sciences, “S. CamilloForlanini” Hospital, Rome, †U.O.C. Cardiologia ed Emodinamica Ospedale Belcolle, Viterbo, ‡Dipartimento Cuore e Grossi Vasi “A. Reale,” Università Sapienza, Rome; and §Università degli Studi di Palermo, Palermo, Italy. Address reprint requests to Giordano Zampi, MD, U.O.C. Cardiologia ed Emodinamica Ospedale Belcolle, Strada Sammartinese s.n.c. Viterbo, Italy. E-mail: [email protected] © 2013 Elsevier Inc. All rights reserved. 1053-0770/2602-0033$36.00/0 Key words: Takotsubo syndrome, Takotsubo cardiomyopathy, mitral valve replacement, stress-induced cardiomyopathy, postoperative complications, cardiogenic shock

Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), 2013: pp ]]]–]]]




Fig 1.

A. Preoperative Electrocardiogram; B. Electrocardiogram during Takotsubo syndrome.

Patients with Takotsubo syndrome usually are menopausal women, experiencing a stressful event; stress has been implicated in its physiopathology as well as alterations in endothelial function related to low concentrations of estrogen. The exact etiology and physiopathology of this syndrome remain unknown even if several mechanisms have been proposed to explain the unusual features of this syndrome such as multivessel coronary vasospasm, abnormalities in coronary microvascular function, and, more importantly, catecholaminemediated cardiotoxicity.3–4 The prognosis generally is excellent with full recovery in most patients, and the main therapy includes beta-blocker titration.5 Takotsubo cardiomyopathy in the perioperative period increasingly is being recognized, but its association with cardiac surgery mostly is unseen and poorly described in the literature. This syndrome also has been described in the setting of anesthesia and noncardiac procedures such as tooth extraction, preparation for colonoscopy, laparotomy, thoracotomy,

pulmonary lobectomy, and so forth. A PubMed search of the terms Takotsubo, Tako-Tsubo, and cardiac surgery or mitral valve replacement was conducted; only 8 cases have been reported presenting a correlation with cardiac surgery (Table 1). The possible mechanisms associated with its occurrence in this specific population of patients are probably multiple and multifactorial, even if the correlation with mitral surgery appears to be relevant. As written in the very interesting ecomment by Bockeria and coworkers, “The mechanism of this modality remains unclear, although exaggerated sympathetic simulation has been considered to play a major role. Several mechanisms were suggested as the leading factors: coronary vasospasm (epicardial and microvascular ischemia), catecholamine mediated toxicity, excessive sympathetic activation.”6 Physical and psychological stress is relevant and always present in cardiac surgery, especially in an emergency setting, and it could be one of the triggers. Although the echocardiographic pattern of LV wall-motion abnormalities and clinical course are characteristics, other



Fig 2. Transthoracic echocardiography during Takotsubo syndrome. A. Apical 4-chambers view, diastolic frame; B. Systolic frame; C. Apical 2-chambers view, diastolic frame; D. Systolic frame; E. Color Doppler of tricuspid regurgitation; F. Continuous-wave Doppler of tricuspid regurgitation showing moderate pulmonary hypertension estimated on V max of tricuspid regurgitation.

differential diagnoses, such as poor myocardial protection and coronary air embolism, should be considered. Moreover, the loss of the mitral annuloventricular continuity, described in the past after conventional mitral valve replacement (MVR) with excision of both leaflets and papillary muscles, may lead to a sphericalization of the left ventricle and impairment of its function.7 In the authors’ case, suboptimal myocardial protection is unlikely (CPB 133 min; ACC 83 min), and coronary air embolism is also improbable because the wall motion abnormalities observed were more extensive than a single coronary artery territory. Many factors have been investigated to better understand what really caused it; desaturation and tachycardia have to be

considered epiphenomena, and no other relevant events happened before discovering the cardiomyopathy, including no brady- or tachyarrhythmias and no pain. Inotropic infusion with dobutamine remains a probable trigger of Takotsubo syndrome. In the cases reported previously in the literature, 7 were postmenopausal women, and almost all the patients received inotropic therapy in the perioperative period.8–14 There was only 1 case in which the authors recognized preoperative emotional stress as the possible trigger.14 Frequently, this syndrome occurs soon after the surgery, ranging from a few hours from extubation9–12 to a couple of days13; only in 1 case did it have a late onset.8



Fig 3. Transthoracic echocardiography after resolution of Takotsubo syndrome, A. Apical 4-chambers view, diastolic frame; B. Systolic frame; C. Apical 2-chambers view, diastolic frame; D. Systolic frame; E. Color Doppler of tricuspid regurgitation; F. Continuous-wave Doppler of tricuspid regurgitation showing normal systolic arterial pressure estimated on V max of tricuspid regurgitation.

In the setting of cardiac surgery this cardiomyopathy seems to be linked very closely to mitral valve surgery; almost all the cases reported regard replacement or plasty of the mitral valve. Often the presentation of this syndrome is dramatic with sudden cardiogenic shock or hemodynamic instability in patients with an uneventful postoperative period. However, in all the previously reported cases, the surgical technique, the myocardial protection, and the de-airing procedures have not been described in detail. It is very important to consider Takotsubo cardiomyopathy in patients presenting with cardiogenic shock after cardiac surgery. A correct diagnosis can lead to a different therapeutic

strategy, trying to avoid inotropes, promptly prescribing betablockers as well as fluid infusion if pulmonary congestion is not present. The immediate discontinuation of all inotropes after diagnosis, even if they have not been imputed as cause, has been argued by several authors. This strategy may cause more harm than good in post-cardiac surgical patients who need hemodynamic support.12 However, once Takotsubo cardiomyopathy occurs, mechanical circulatory assistance with IABP could be recommended to minimize the use of inotropes. Itoh and co-workers,5 first describing Takotsubo syndrome after cardiac surgery, suggested that “it could be prevented by



Table 1. Cases Reported in the Literature of Takotsubo Cardiomyopathy After Cardiac Surgery Author

Clinical Presentation

Myocardial Protection

Pharmacological Support pre-TK

Itoh H. (2007) Kogan A. (2008)


59/W 62/W


Type of Intervention

Hemodynamic instability Hemodynamic instability

Wong C.P. (2008)


Hemodynamic instability

NR Dobutamine, noradrenaline and adrenaline Adrenaline

Blazquez J.A. (2010)


Left atrial myxoma excision MVR

NR CPB: 153 min ACC: 101 min NR

Hemodinamic instability

Adrenaline, noradrenaline

Yamane K. (2011) Gariboldi V. (2011)

68/W 66/W


Congestive heart failure Cardiogenic shock

Farber G. (2011) Vernick W. (2012)

69/W 78/M


Cardiogenic shock Cardiogenic shock

CPB: 83 min ACC: 68 min NR CPB: 103 min ACC: 80 min NR NR

Inotropes Dobutamine, noradrenaline Adrenaline, noradrenaline Adrenaline, noradrenaline

Abbreviations: ACC, aortic cross-clamp; CBP, cardiopulmonary bypass; MVP, mitral valve plasty; MVR, mitral valve replacement; NR, not reported; TK, Takotsubo cardiomyopathy.

administration of angiotensin-converting enzyme inhibitors before surgery and by the use of superior biocompatible cardiopulmonary bypass components.” It is possible that some cases of transient LV sphericalization after mitral valve replacement surgery described previously were cases of Takotsubo syndrome. Based on the limited number of cases, it appears that the clinical course of this cardiomyopathy in

cardiac surgery patients is self limited with rapid recovery, although studies investigating a larger series of patients are needed. APPENDIX A. SUPPLEMENTARY DATA

Supplementary data associated with this article can be found in the online version at 09.005.

REFERENCES 1. Gianni M, Dentali F, Grandi A, et al: Apical ballooning syndrome or Takotsubo cardiomyopathy: A systematic review. Eur Heart J27: 1523-1529, 2006 2. Bybee KA, Kara T, Prasad A, et al: Transient left ventricular apical ballooning: A syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 141:858-865, 2004 3. Satoh H, Tateishi H, Uchida T: Takotsubo-type cardiomyopathy due to multivessel spasm. In: Kodama K, Haze K, Hon M, eds: Clinical aspects of myocardial injury: From ischemia to heart failure. Tokyo, Kagakuyouronsya Co; 56-64, 1990. 4. Looi JL, Gabriel R, Khan A, et al: Left ventricular morphology and response to beta-adrenergic stimulation in apical ballooning syndrome. Eur Heart J 13:510-516, 2012 5. Itoh H, Miyake Y, Hioki I, et al: Report of Takotsubo cardiomyopathy occurring during cardiopulmonary bypass. J Extra Corpor Technol 39:109-111, 2007 6. Bockeria LA, Bockeria OL, Goustova IA: eComment: Re: Takotsubo cardiomyopathy after elective mitral valve replacement. Interact Cardiovasc Thorac Surg 11:119, 2010 7. Ghosh PK, Kogan A, Raanani E: Mitral valve replacement and Takotsubo syndrome. Eur J Cardiothorac Surg 34:466-471, 2008

8. Farber G, Muhle A, Doenst T, et al: Late onset Takotsubo cardiomyopathy after mitral valve replacement. Thorac Cardiovasc Surg 59: 500-503, 2011 9. Vernick WJ, Hargrove WC, Augoustides JG, et al: Takotsubo cardiomyopathy associated with cardiac arrest following cardiac surgery: New variants of an unusual syndrome. J Card Surg 25: 679-683, 2010 10. Blazquez JA, Gonzalez JM, Dalmau MJ, et al: Takotsubo cardiomyopathy after elective mitral valve replacement. Interact Cardiovasc Thorac Surg 11:117-119, 2010 11. Gariboldi V, Jop B, Grisoli D, et al: Takotsubo syndrome after mitral valve replacement for acute endocarditis. Ann Thorac Surg 91: e31-e32, 2011 12. Kogan A, Ghosh P, Schwammenthal E, et al: Takotsubo syndrome after cardiac surgery. Ann Thorac Surg 85:1439-1441, 2008. 13. Wong CP, Jim MH, Chan AO, et al: Iatrogenic Tako-Tsubo cardiomyopathy. Int J Cardiol 125:e16-e18, 2008 14. Yamane K, Hirose H, Reeves GR, et al: Left ventricular dysfunction mimicking Takotsubo cardiomyopathy following cardiac surgery. J Heart Valve Dis 20:471-473, 2011

Takotsubo syndrome after mitral valve replacement: case report and brief review of the literature.

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