Ken , Hideki , and Yoshio: Recurrence of Takotsubo Cardiomyopathy.

Introduction

Takotsubo cardiomyopathy (TC) is transient systolic dysfunction of the left ventricle (LV) occurring mainly in post-menopausal women after a stressful event. It is associated with characteristic LV contraction patterns, typically apical dyskinesia and basal hyperkinesia.1 The exact pathophysiology of TC is still unclear, although several hypotheses, such as multivessel coronary spasm, microvascular impairment, and direct catecholamine-mediated myocardial stunning, have been proposed.2 While the prognosis for TC patients is generally favorable, with complete recovery from LV wall motion abnormality, some patients experience recurrence of TC, once or sometimes multiple times. There is little information about the efficacy of chronic pharmacological therapy for preventing TC recurrence. This review summarizes current knowledge of TC recurrence.

Recurrence rate of takotsubo cardiomyopathy

The reported recurrence rate of TC has ranged from 0 to 10% (Table .1). Elesber et al. reported the highest recurrence rate within the first 4 years at 2.9% per year and subsequently it decreased at 1.3% per year.3 Singh et al. performed meta-analysis from 31 cohorts (1,664 TC patients) and reported that the annual incidence of recurrence was 1.5% and the cumulative recurrence rate increased from 1.2% at 6 months to nearly 5% at 6 years.4 Several cases of multiple recurrences have also been reported.5

Factors predicting recurrence of takotsubo cardiomyopathy:

Clinical or demographic features determining TC recurrence have not been clearly identified. Singh et al. demonstrated that the average LV ejection fraction during the first episode was significantly lower in patients with than without TC recurrence.4 It may be interpreted that severe LV dysfunction reflects increased susceptibility to stressful events. Patel et al. reported that the recurrence rate was 5-fold higher in female patients <50 years of age than in those aged 50 years old or more.6 The reason for higher recurrence rate in younger females is unknown. The recurrence of TC is more frequent in women but no statistically significant difference has shown between men and women, probably because of the low numbers of recurrence.7

Morphology and pathophysiology

Most cases of recurrent TC have the same ballooning pattern compared to that of the initial event.8-10 However, some case reports have documented recurrent TC with different ballooning patterns (i.e., apical ballooning to mid-ventricular ballooning,11,12 mid-ventricular ballooning to apical ballooning,13-15 and apical ballooning to basal ballooning.16 These observations are inconsistent with the currently proposed mechanisms of TC such as anatomic variations in sympathetic innervation and adrenergic receptor density. The exact pathophysiology of TC and its recurrence is unknown. Dynamic variation in the sensitivity of the cardiac adrenergic receptors or differences in the degree of stress and the subsequent level of catecholamine release may be responsible for different morphologic patterns between the initial and recurrent event.14 Other possible mechanisms are aging on adrenergic receptor location or density13 and a phenomenon analogous to regional ischemic preconditioning during the initial event.12

Table 1.

Recurrence rate of takotsubo cardiomyopathy

Authors Year Country No. of Patients Recurrence, No. Recurrence, %
Tsuchihashi et al.1 2001 Japan 72 2 2.8
Gianni et al.18 2006 Italy and Canada 169 6 3.6
Elesber et al.3 2007 USA 100 10 10.0
Regnante et al.19 2009 USA 70 2 2.9
Sharkey et al.20 2010 USA 136 7 5.1
Song et al.21 2010 Korea 87 0 0
Parodi et al.22 2011 Italy 116 2 1.7
Nunez-Gil et al.23 2012 Spain 100 4 4.0
Samardhi et al.24 2012 Australia 51 0 0
Bellandi et al.25 2012 Italy 105 0 0
Cacciotti et al.26 2012 Italy 75 1 1.3
Looi et al.27 2012 New Zealand 100 7 7.0
Patel et al.6 2013 USA 224 7 3.1
Murakami et al.28 2014 Japan 107 5 4.7
Nishida et al.29 2014 Japan 251 7 2.8
Templin et al.30 2015 Europe and USA 1750 N/A 1.8/patient-year

Prevention therapy

Prevention therapy for recurrence of TC has not been established. β-blockers are intuitively the most logical pharmacological prevention therapy. They may protect against stressful triggers and catecholamine surges. In fact, β-blockers are the most common discharge medication in patients with TC. However, two meta-analyses failed to show benefit of β-blockers for preventing recurrence of TC.4,17 It is postulated that the pathogenesis of TC is related to stimulation of β2- rather than β1-adrenergic receptors. β1-selective antagonists may be ineffective for preventing recurrence of TC. β-blockers might be useful for preventing recurrence of TC in selected patients especially with persistent anxiety and elevated sympathetic tone.

Singh et al. reported that there was a negative correlation between use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and recurrence of TC. Reduction of sympathetic activity through the renin-angiotensin system or the anti-inflammatory effect on myocardium may explain these results. In patients with multiple recurrent TC triggered by emotional stress or suffering from anxiety disorder, the psychological response to emotionally stressful triggers may be a therapeutic target. Psychological counseling or antianxiety drugs may be beneficial for preventing recurrence of TC.

Summary

Recurrence rate of TC has ranged from 0 to 10%. Although clinical correlates determining recurrence of TC have not been identified, patients with severe LV dysfunction during initial TC event or younger women should be followed up more carefully. Preventive therapy for recurrence of TC has not been established. β-blockers are commonly used in the prevention of TC recurrence but no evidence to date supports their efficacy. Angiotensin converting enzyme inhibitors or angiotensin receptor blockers and psychological counseling and/or antianxiety drugs may have a role to prevent recurrence of TC.

Declarations of Interest

The authors declare no conflicts of interest.

Acknowledgements

The authors state that they abide by the “Requirements for Ethical Publishing In Biomedical Journals”.31

References

1) 

Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I, Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. J Am Coll Cardiol 2001; 38: 11–8

2) 

Akashi YJ, Nef HM, Lyon AR, Epidemiology and pathophysiology of Takotsubo syndrome. Nat Rev Cardiol 2015; 12: 387–97 10.1038/nrcardio.2015.39

3) 

Elesber AA, Prasad A, Lennon RJ, Wright RS, Lerman A, Rihal CS, Four-year recurrence rate and prognosis of the apical ballooning syndrome. J Am Coll Cardiol 2007; 50: 448–52

4) 

Singh K, Carson K, Usmani Z, Sawhney G, Shah R, Horowitz J, Systematic review and meta-analysis of incidence and correlates of recurrence of takotsubo cardiomyopathy. Int J Cardiol 2014; 174: 696–701 10.1016/j.ijcard.2014.04.221

5) 

Sager HB, Schunkert H, Kurowski V, Recurrent mid-ventricular Tako-Tsubo cardiomyopathy: three episodes of a uniform cardiac response to varying stressors. Int J Cardiol 2011; 152: e22–4 10.1016/j.ijcard.2010.09.081

6) 

Patel SM, Chokka RG, Prasad K, Prasad A, Distinctive clinical characteristics according to age and gender in apical ballooning syndrome (takotsubo/ stress cardiomyopathy): an analysis focusing on men and young women. J Card Fail 2013; 19: 306–10 10.1016/j.cardfail.2013.03.007

7) 

Schneider B, Athanasiadis A, Stöllberger C, Pistner W, Schwab J, Gottwald U, Schoeller R, Gerecke B, Hoffmann E, Wegner C, Sechtem U, Gender differences in the manifestation of tako-tsubo cardiomyopathy. Int J Cardiol 2013; 166: 584–8 10.1016/j.ijcard.2011.11.027

8) 

Carigi S, Santarelli A, Baldazzi F, Grosseto D, Santoro D, Piovaccari G, Recurrent Takotsubo cardiomyopathy with similar clinical and instrumental signs. Int J Cardiol 2011; 148: 256–7 10.1016/j.ijcard.2010.05.008

9) 

Fenster BE, Freeman AM, Weinberger HD, Buckner JK, Recurrent transient mid-ventricular ballooning. Int J Cardiol 2011; 152: e35–6 10.1016/j.ijcard.2010.10.061

10) 

Kato K, Sakai Y, Ishibashi I, Kobayashi Y, Recurrent mid-ventricular takotsubo cardiomyopathy. Int J Cardiovasc Imaging 2014; 30: 1417–8 10.1007/s10554-014-0469-x

11) 

Gach O, Lempereur M, Pierard LA, Lancellotti P, Recurrent stress cardiomyopathy with variable pattern of left ventricle contraction abnormality. J Am Coll Cardiol 2012; 60: e5 10.1016/j.jacc.2011.10.911

12) 

Xu B, Williams PD, Brown M, Macisaac A, Takotsubo cardiomyopathy: does recurrence tend to occur in a previously unaffected ventricular wall region?. Circulation 2014; 129: e339–40 10.1161/CIRCULATIONAHA.113.007015

13) 

Mansencal N, El Mahmoud R, Pillière R, Dubourg O, Relationship between pattern of Tako-Tsubo cardiomyopathy and age: from midventricular to apical ballooning syndrome. Int J Cardiol 2010; 138: e18–20 10.1016/j.ijcard.2008.06.009

14) 

Wever-Pinzon O, Wever-Pinzon J, Tami L, Recurrent Takotsubo cardiomyopathy presenting with different morphologic patterns. Int J Cardiol 2011; 148: 379–81 10.1016/j.ijcard.2010.10.091

15) 

Kano S, Munakata R, Inami T, Takano M, Seino Y, Shimizu W, Recurrent Takotsubo cardiomyopathy with variable left ventricular obstruction and morphologies. J Am Coll Cardiol 2014; 63: e3 10.1016/j.Jacc.2013.07.112

16) 

Kaushik M, Alla VM, Madan R, Arouni AJ, Mohiuddin SM, Recurrent stress cardiomyopathy with variable regional involvement: insights into etiopathogenetic mechanisms. Circulation 2011; 124: e556–7 10.1161/CIRCULATIONAHA.111.059329

17) 

Santoro F, Ieva R, Musaico F, Ferraretti A, Triggiani G, Tarantino N, Di Biase M, Brunetti ND, Lack of efficacy of drug therapy in preventing takotsubo cardiomyopathy recurrence: a meta-analysis. Clin Cardiol 2014; 37: 434–9 10.1002/clc.22280

18) 

Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E, Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J 2006; 27: 1523–9

19) 

Regnante RA, Zuzek RW, Weinsier SB, Latif SR, Linsky RA, Ahmed HN, Sadiq I, Clinical characteristics and four-year outcomes of patients in the Rhode Island Takotsubo Cardiomyopathy Registry. Am J Cardiol 2009; 103: 1015–9 10.1016/j.amjcard.2008.12.020

20) 

Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, Haas TS, Hodges JS, Maron BJ, Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol 2010; 55: 333–41 10.1016/j.jacc.2009.08.057

21) 

Song BG, Hahn JY, Cho SJ, Park YH, Choi SM, Park JH, Choi SH, Choi JH, Park SW, Lee SH, Gwon HC, Clinical characteristics, ballooning pattern, and long-term prognosis of transient left ventricular ballooning syndrome. Heart Lung 2010; 39: 188–95 10.1016/j.hrtlng.2009.07.006

22) 

Parodi G, Bellandi B, Del Pace S, Barchielli A, Zampini L, Velluzzi S, Carrabba N, Gensini GF, Antoniucci D, Natural history of tako-tsubo cardiomyopathy. Chest 2011; 139: 887–92 10.1378/chest.10-1041

23) 

Núñez-Gil IJ, Molina M, Bernardo E, Ibañez B, Ruiz-Mateos B, García-Rubira JC, Vivas D, Feltes G, Luaces M, Alonso J, Zamorano J, Macaya C, Fernández-Ortiz A, Tako-tsubo syndrome and heart failure: long-term follow-up. Rev Esp Cardiol 2012; 65: 996–1002 10.1016/j.recesp.2012.04.016

24) 

Samardhi H, Raffel OC, Savage M, Sirisena T, Bett N, Pincus M, Small A, Walters DL, Takotsubo cardiomyopathy: an Australian single centre experience with medium term follow up. Intern Med J 2012; 42: 35–42 10.1111/j.1445-5994.2011.02474.x

25) 

Bellandi B, Salvadori C, Parodi G, Ebert AG, Petix N, Del Pace S, Boni A, Pestelli F, Fineschi M, Giomi A, Cresti A, Giuliani G, Venditti F, Querceto L, Gensini GF, Bolognese L, Bovenzi F, Epidemiology of Tako-tsubo cardiomyopathy: the Tuscany Registry for Tako-tsubo Cardiomyopathy. G Ital Cardiol 2012; 13: 59–66 10.1714/1015.11057

26) 

Cacciotti L, Passaseo I, Marazzi G, Camastra G, Campolongo G, Beni S, Lupparelli F, Ansalone G, Observational study on Takotsubo-like cardiomyopathy: clinical features, diagnosis, prognosis and follow-up. BMJ Open 2012; 2: pii: e001165 10.1136/bmjopen-2012-001165

27) 

Looi JL, Wong CW, Khan A, Webster M, Kerr AJ, Clinical characteristics and outcome of apical ballooning syndrome in Auckland, New Zealand. Heart Lung Circ 2012; 21: 143–9 10.1016/j.hlc.2011.11.010

28) 

Murakami T, Yoshikawa T, Maekawa Y, Ueda T, Isogai T, Konishi Y, Sakata K, Nagao K, Yamamoto T, Takayama M, Characterization of predictors of in-hospital cardiac complications of takotsubo cardiomyopathy: multi-center registry from Tokyo CCU Network. J Cardiol 2014; 63: 269–73 10.1016/j.jjcc.2013.09.003

29) 

Nishida J, Kouzu H, Hashimoto A, Fujito T, Kawamukai M, Mochizuki A, Muranaka A, Kokubu N, Shimoshige S, Yuda S, Hase M, Tsuchihashi K, Miura T, “Ballooning” patterns in takotsubo cardiomyopathy reflect different clinical backgrounds and outcomes: a BOREAS-TCM study. Heart Vessels 2015; 30: 789–97 10.1007/s00380-014-0548-x

30) 

Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschöpe C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Böhm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Lüscher TF, Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med 2015; 373: 929–38 10.1056/NEJMoa1406761

31) 

Shewan LG, Coats AJS, Henein M, Requirements for ethical publishing in biomedical journals. Int Cardiovasc Forum J 2015; 2: 2 10.17987/icfj.v2i1.4



Copyright (c) 2016 Ken Kato, Hideki Kitahara, Yoshio Kobayashi

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.