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Treatment of Tako-tsubo cardiomyopathy
International Journal of Cardiology 130 (2008) 475 – 476 www.elsevier.com/locate/ijcard
Letter to the Editor
Treatment of Tako-tsubo cardiomyopathy Giovanni Fazio ⁎, Giuseppina Novo, Giuseppe Barbaro, Loredana Sutera, Salvatore Azzarelli, Tomas Palecek, Gabriele Di Gesaro, Yoshihiro Akashi, Salvatore Novo Department of Cardiology, University of Palermo, Italy Cardiology Service, Department of Physiopatology, La Sapienza University, Rome, Italy Department of Cardiology, “Cannizzaro” Hospital, Catania, Italy 2nd Department of Internal Cardiovascular Medicine, General University Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan Received 3 July 2007; received in revised form 7 July 2007; accepted 8 July 2007 Available online 26 November 2007
Keywords: Takotsubo; Treatment; Drug; ACE inhibitors, Beta-blokers; Inotropics
No guidelines presently exist concerning the treatment of takotsubo cardiomiopathy. In future many efforts and some clinical trials must be realized to determine the most effective therapies [1–3]. Concerning therapy, in 2002 Kyume et al. [1] described, in an interesting article, 3 patients treated with beta-blockers: in two cases these drugs improved the clinical findings, while in another case they did not. There are no other reports about the treatment of this particular disease. We performed a retrospective analysis of 45 patients affected by Takotsubo cardiomyopathy (TC), with 36 followed for a mean period of 1 month. The diagnosis of TC was based on the symptomatology, the clinical history, the echocardiogram and the hemodynamic study. All data were mailed to the Palermo centre, where the diagnosis was verified. In this retrospective analysis, first, we investigated the benefits of dopamine, dobutamine, levosimendan, ACE inhibitors and diuretics, administrated at the admission in hospital, subdividing the patients into 7 groups, and evaluating the efficacy of these different treatments compared to control group of non treated patients. Statistical analysis was performed using Student t-test, with a significant statistical point of p:0.05.The 7 groups were: low dose dobutamine group, dobutamine + dopamine group, levosimendan group, ⁎ Corresponding author. Via santa maria di Gesu' 25, 90124 Palermo, Italy. Tel.: +39 3334439962. E-mail address: [email protected] (G. Fazio). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.07.162
ACE inhibitors group, diuretics group, beta-blockers group and control (untreated) group. The clinical findings at admission in hospital were similar in the different groups. A combined endpoint was chosen: survival + improvement of the EF (comparing discharge to admission values).We selected only the patients treated with a single drug. The results are shown in Table 1.The use of a drug therapy with inotropics, ACE-inhibitors or beta-blockers, did not give any advantage in the improvement of cardiac performance. Instead, we noticed a reduction of the improvement time in two treated groups: low dose of dobutamine and diuretics group. While the physiopathologic action of the diuretics [2] is easy to accept and to understand, the benefit of the low dose of dobutamine is less clear. Several works published in literature have supposed a catecholamine-mediated origin of the disease [1–6]. In our registry the benefit of the low dose dobutamine was been associated with an ineffectiveness of the beta-blockers or high dose inotropic drugs (dobutamine + dopamine). The improvement of hospitalization time might depend on the modifications of blood sympathetic-mimetic concentrations, implicated in the etio-pathogenesis of this disease [1–6]. We agree that there may be perceived to be a necessity to treat these patients during the acute left ventricular dysfunction. Concerning the long term treatment [3] of these patients, no sudden death was reported, and a very low incidence of recurrence has been reported. In our series 3 patients of 45 reported new episodes of reversible
476
G. Fazio et al. / International Journal of Cardiology 130 (2008) 475–476
Table 1 Drug
Patients
FE at the admission
FE at the discharge
Improvement
Deaths
P
Days of hospitalisation
P
Dobutamine Dopamine + dobutamine Levosimendan ACE inhibitors Diuretics Beta-blockers Control group
4 5 1 9 3 7 16
44 40 44 43 43 46 43
62 62 63 62 62 65 63
18 22 19 20 19 19 20
0 2 0 0 0 0 0
0.75 0.60 0.88 0.82 0.83 0.78 –
12 22 22 22 12 19 20
0.04 0.45 0.51 0.90 0.04 0.32 –
left ventricular dysfunction. We strongly agree about the necessity to perform randomized trials, but, until these are available we do think that long term therapy is indicated. References [1] Kyuma M, Tsuchihashi K, Shinshi Y, et al. Effect of intravenous propranolol on left ventricular apical ballooning without coronary artery stenosis (ampulla cardiomyopathy): three cases. Circ J 2002;66:1181–4. [2] Splendiani G, Condo S. Diuretic therapy in heart failure. G Ital Nefrol 2006;34:S74–6.
[3] Fazio G, Pizzuto C, Barbaro G, et al. Chronic pharmacological treatment in takotsubo cardiomyopathy. Int J Cardiol 2008;127:121–3. [4] Guttormsen B, Nee L, Makielski JC, Keevil JG. Transient left ventricular apical ballooning: a review of the literature. WMJ 2006;105:49–54. [5] 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. [6] Barbaro G, Pellicelli A, Barbarini G, Akashi YJ. Takotsubo-like left ventricular dysfunction in an HIV-infected patient. Curr HIV Res 2006;4:239–41.
Letter to the Editor
Treatment of Tako-tsubo cardiomyopathy Giovanni Fazio ⁎, Giuseppina Novo, Giuseppe Barbaro, Loredana Sutera, Salvatore Azzarelli, Tomas Palecek, Gabriele Di Gesaro, Yoshihiro Akashi, Salvatore Novo Department of Cardiology, University of Palermo, Italy Cardiology Service, Department of Physiopatology, La Sapienza University, Rome, Italy Department of Cardiology, “Cannizzaro” Hospital, Catania, Italy 2nd Department of Internal Cardiovascular Medicine, General University Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan Received 3 July 2007; received in revised form 7 July 2007; accepted 8 July 2007 Available online 26 November 2007
Keywords: Takotsubo; Treatment; Drug; ACE inhibitors, Beta-blokers; Inotropics
No guidelines presently exist concerning the treatment of takotsubo cardiomiopathy. In future many efforts and some clinical trials must be realized to determine the most effective therapies [1–3]. Concerning therapy, in 2002 Kyume et al. [1] described, in an interesting article, 3 patients treated with beta-blockers: in two cases these drugs improved the clinical findings, while in another case they did not. There are no other reports about the treatment of this particular disease. We performed a retrospective analysis of 45 patients affected by Takotsubo cardiomyopathy (TC), with 36 followed for a mean period of 1 month. The diagnosis of TC was based on the symptomatology, the clinical history, the echocardiogram and the hemodynamic study. All data were mailed to the Palermo centre, where the diagnosis was verified. In this retrospective analysis, first, we investigated the benefits of dopamine, dobutamine, levosimendan, ACE inhibitors and diuretics, administrated at the admission in hospital, subdividing the patients into 7 groups, and evaluating the efficacy of these different treatments compared to control group of non treated patients. Statistical analysis was performed using Student t-test, with a significant statistical point of p:0.05.The 7 groups were: low dose dobutamine group, dobutamine + dopamine group, levosimendan group, ⁎ Corresponding author. Via santa maria di Gesu' 25, 90124 Palermo, Italy. Tel.: +39 3334439962. E-mail address: [email protected] (G. Fazio). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.07.162
ACE inhibitors group, diuretics group, beta-blockers group and control (untreated) group. The clinical findings at admission in hospital were similar in the different groups. A combined endpoint was chosen: survival + improvement of the EF (comparing discharge to admission values).We selected only the patients treated with a single drug. The results are shown in Table 1.The use of a drug therapy with inotropics, ACE-inhibitors or beta-blockers, did not give any advantage in the improvement of cardiac performance. Instead, we noticed a reduction of the improvement time in two treated groups: low dose of dobutamine and diuretics group. While the physiopathologic action of the diuretics [2] is easy to accept and to understand, the benefit of the low dose of dobutamine is less clear. Several works published in literature have supposed a catecholamine-mediated origin of the disease [1–6]. In our registry the benefit of the low dose dobutamine was been associated with an ineffectiveness of the beta-blockers or high dose inotropic drugs (dobutamine + dopamine). The improvement of hospitalization time might depend on the modifications of blood sympathetic-mimetic concentrations, implicated in the etio-pathogenesis of this disease [1–6]. We agree that there may be perceived to be a necessity to treat these patients during the acute left ventricular dysfunction. Concerning the long term treatment [3] of these patients, no sudden death was reported, and a very low incidence of recurrence has been reported. In our series 3 patients of 45 reported new episodes of reversible
476
G. Fazio et al. / International Journal of Cardiology 130 (2008) 475–476
Table 1 Drug
Patients
FE at the admission
FE at the discharge
Improvement
Deaths
P
Days of hospitalisation
P
Dobutamine Dopamine + dobutamine Levosimendan ACE inhibitors Diuretics Beta-blockers Control group
4 5 1 9 3 7 16
44 40 44 43 43 46 43
62 62 63 62 62 65 63
18 22 19 20 19 19 20
0 2 0 0 0 0 0
0.75 0.60 0.88 0.82 0.83 0.78 –
12 22 22 22 12 19 20
0.04 0.45 0.51 0.90 0.04 0.32 –
left ventricular dysfunction. We strongly agree about the necessity to perform randomized trials, but, until these are available we do think that long term therapy is indicated. References [1] Kyuma M, Tsuchihashi K, Shinshi Y, et al. Effect of intravenous propranolol on left ventricular apical ballooning without coronary artery stenosis (ampulla cardiomyopathy): three cases. Circ J 2002;66:1181–4. [2] Splendiani G, Condo S. Diuretic therapy in heart failure. G Ital Nefrol 2006;34:S74–6.
[3] Fazio G, Pizzuto C, Barbaro G, et al. Chronic pharmacological treatment in takotsubo cardiomyopathy. Int J Cardiol 2008;127:121–3. [4] Guttormsen B, Nee L, Makielski JC, Keevil JG. Transient left ventricular apical ballooning: a review of the literature. WMJ 2006;105:49–54. [5] 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. [6] Barbaro G, Pellicelli A, Barbarini G, Akashi YJ. Takotsubo-like left ventricular dysfunction in an HIV-infected patient. Curr HIV Res 2006;4:239–41.