Response
Sir,We greatly appreciate Dr Arora's response to our study.1 We always try to diagnose patients with takotsubo cardiomyopathy (TC) prospectively. Cardiac catheterization is the most reliable method to diagnose TC, but we confirm TC using not only the catheter findings in the acute phase, but also pathological findings and/or clinical causes, including electrocardiogram (ECG) pattern. It is quite difficult to distinguish a patient with TC from one with acute coronary syndrome, but we often find elevated ST segment on ECG without severe chest pain in TC patients. Patients are finally diagnosed as TC according to the criteria of the Mayo Clinic.2 When TC patients have other diseases, e.g. phaeochromocytoma, intracranial bleedings, etc., we change their diagnosis from TC to takotsubo-like left ventricular (LV) dysfunction complicated by these diseases.
We usually keep TC patients under observation for 2–3 weeks in our hospital until such time as their wall motions return to normal. As mentioned in a previous presentation,3 we observe these patients in the coronary care unit for at least 3 days after onset, following the protocol for patients with acute myocardial infarction (AMI), because sometimes TC causes sudden cardiac death3. However, administration of medications is still a matter of debate. There is no consensus for the treatment of TC patients, because this type of left ventricular dysfunction can be normalized within a few weeks. We doubt the necessity in elderly patients (>80 years) to take many agents after the wall motion has normalized. As we have previously shown, prognosis in TC patients is generally favourable without any additional medications,4 and only a handful of recurrent cases have been reported. The effectiveness and safety of ACE-inhibitor and/or ß-blocker administration have not been established in TC patients. Moreover, the use of ß-blockers is still controversial because it may prolong the QT interval on ECG. A case has been reported with lethal ventricular arrhythmia of TC due to prolonged QT interval.5 When TC patients have severe heart failure and/or severe low output syndrome, we treat them with a standard therapy for heart failure. In fact, we did not experience such severe TC cases in our recent report.1 It is vital to investigate a large number of TC patients treated with medications that are usually administered to the patients with acute myocardial infarction. Experiments with animal models of TC suggest that 
- and ß- blockers can reduce stress-induced LV dysfunction, in a rat model.6 The same researchers are also investigating the possible use of oestrogen administration to attenuate left ventricular dysfunction in rats under stress.7 Results from these animal studies may help us to decide whether to prescribe these agents to TC patients in the future.
We believe that our heart rate variability (HRV) findings support our previous nuclear findings and hypotheses. As previously reported, HRV parameters of TC patients are somewhat different from those of the patients with acute coronary syndrome, although we could not completely distinguish these parameters in our study. Since HRV parameters in cardiac patients are significantly altered by pharmacological interventions, we prefer to present the actual HRV data of TC patients treated without any drugs at this time. Non-invasive measurement of HRV in TC patients in the coronary care unit is a reasonable choice to assess the strength of the modulation of the cardiac autonomic system. Although high levels of sympathetic activation have been already observed, the decrease in low frequency may be caused by abnormalities in central autonomic regulation and impairment of ß-adrenergic receptor sensitivity. As our study failed to clarify the reason for this difference, it is necessary to examine HRV data to investigate the mechanism of the autonomic dysfunction.
The actual reason for this distinctive contractile pattern is still unknown and the onset mechanism of TC is still controversial. The elevated systemic level of catecholamines is presumed to be part of the pathophysiology of this disorder. Excessive catecholamine production in patients with phaeochromocytoma can induce similar reversible LV dysfunction. Persistent activation of Ca2+ channel triggers these changes, and Ca2+ overload in the myocardial cell membrane is a possible mechanism for the ventricular dysfunction in patients with catecholamine cardiotoxicity. Accordingly, we have suggested that the cause of dysfunction in TC may partly relate to increased catecholamines, but we are unable to explain why catecholamines were not increased in our study1. Based on experimental and anatomical findings, we presume that a variety of ß-receptors or their reactivity may contribute to the formation of ventricular dysfunction. Therefore, we suggest that it is not only the status of catecholamine cardiotoxicity, but also the neurogenic myocardial stun due to autonomic imbalance that is important. According to the results of our studies,1,8 we would like to suggest that altered autonomic regulation due to stress is the main mechanism of this syndrome. In our study, we observed the consecutive occurrences of high levels of plasma catecholamine concentrations, cardiac adrenoceptor hyper-reactivity and coronary microvascular insufficiency, respectively. These facts lead to the conclusion of 'chicken and egg' theory concerning the onset of this syndrome, as discussed by many investigators.
Division of Cardiology
Department of Internal Medicine
St Marianna University School of Medicine
Kawasaki
Japan
email: johnny{at}marianna-u.ac.jp
References
1. Akashi YJ, Barbaro G, Sakurai T, Nakazawa K, Miyake F. Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy. Q J Med (2007) 100:335–43.[ISI]
2. Bybee KA, Kara T, Prasad A, Lerman A, Barsness GW, Wright RS, Rihal CS. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med (2004) 141:858–65.
3. Akashi YJ, Tejima T, Sakurada H, Matsuda H, Suzuki K, Kawasaki K, Tsuchiya K, Hashimoto N, Musha H, Sakakibara M, Nakazawa K, Miyake F. Left ventricular rupture associated with Takotsubo cardiomyopathy. Mayo Clin Proc (2004) 79:821–4.[ISI][Medline]
4. Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Koike H, Sasaka K. The clinical features of takotsubo cardiomyopathy. Q J Med (2003) 96:563–73.[ISI]
5. Denney SD, Lakkireddy DR, Khan IA. Long QT syndrome and torsade de pointes in transient left ventricular apical ballooning syndrome. Int J Cardiol (2005) 100:499–501.[CrossRef][ISI][Medline]
6. Ueyama T, Kasamatsu K, Hano T, Yamamoto K, Tsuruo Y, Nishio I. Emotional stress induces transient left ventricular hypocontraction in the rat via activation of cardiac adrenoceptors: a possible animal model of ‘tako-tsubo’ cardiomyopathy. Circ J (2002) 66:712–13.[CrossRef][ISI][Medline]
7. Ueyama T, Hano T, Kasamatsu K, Yamamoto K, Tsuruo Y, Nishio I. Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Tako-tsubo (Ampulla) cardiomyopathy. J Cardiovasc Pharmacol (2003) 42(Suppl. 1):S117–19.[ISI][Medline]
8. Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Musha H, Sasaka K. 123I-MIBG myocardial scintigraphy in patients with ‘takotsubo’ cardiomyopathy. J Nucl Med (2004) 45:1121–7.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||