Takotsubo Syndrome: An Opportunity to Better Understand Post-Infarction Myocardial Recovery?

In this issue of the Journal, Jabara et al1 provide an intriguing summary of differences between apical and non-apical Tako-tsubo syndrome based on case summaries of individuals with most often stress-induced ischemic events in the absence of major coronary vessel obstruction. The apical-type disorders are associated with larger defects, and not surprisingly, more severe complications. The apical patients probably show more intense ischemia with greater amounts of jeopardized muscle, and thus, the consequences of the ischemic insult are greater. Non-apical events appear more benign, presumably because they involve less heart muscle and in fact may even be a more vascular (small-vessel flow) event as opposed to the apical type, which may be a specific catecholamine-induced ischemic event. However, one cannot escape the fact that the remarkable recovery in both circumstances is something which should provide insight into potential salvage of damaged myocardium in other cardiac ischemic syndromes, including both transmural and non-transmural myocardial infarction. Reviewing the described differences in apical and non-apical syndrome, one wonders if the same mechanisms underlie each syndrome. For instance, both may occur in response to catecholamine excess,2 but the apical and non-apical presentations may depend on the most vulnerable site in that particular patient, which may vary. For instance, the apical events may be profoundly left ventricular catecholamine-induced stress for which the apical region is thought to be the most sensitive based on animal models of catecholamine-induced cardiomyopathy. Conversely, in some individuals, there may be qualitatively different defects in areas of the myocardium which produce transient large-vessel spasm, or more likely, may contribute to changes in small, intermyocardial vessels affecting local perfusion. As the authors point out, major vessel spasm seems unlikely, as clinical testing for spasm is most often negative, but the impact on small vessels is perhaps quite different and provides an explanation for the local non-apical events. Furthermore, given that Takotsubo patients are most frequently female, and current theories of ischemia in females in the absence of major vessel coronary disease focus on the role of small-vessel abnormalities, non-apical Takotsubo may relate to catecholamine autonomic ischemic abnormalities in small vessels affecting local flow. Therefore, Takotsubo syndrome may represent an extreme extension of small-vessel ischemia in women when it involves non-apical segments of the myocardium. Another important clinical point is that the excellent recovery in the absence of early morbid events in these patients is remarkable. Thus, particularly in the higher-risk, apical type of Takotsubo syndrome, intensive short-term observation with prevention and management of complications are critical, because if acute adverse events such as life-threatening arrhythmias or shock can be prevented, the long-term prognosis is excellent. A final point is that Takotsubo syndrome is unusual, but appears to have significant clinical relevance because it may well provide insights into other incompletely understood mechanisms of disease, including: 1) neurogenic ST changes seen after neurological or neurosurgical events; 2) early recovery of stunned myocardium in unstable ischemia; and finally, 3) insights into the prevention of apoptosis and adverse myocardial remodeling post myocardial infarction. Perhaps the transient nature of ischemia with early reperfusion, or the catecholamine-driven etiology of ischemia, underlies the rapid recovery of left ventricular function seen in these patients, but a better understanding of these mechanisms could clearly lead to new approaches to enhance myocardial recovery post ischemia and myocardial infarction.3,4 In summary, this series of cases is useful to our better understanding of Takotsubo syndrome and perhaps provides a beginning basis for better understanding the importance of ischemic reperfusion overall and how to optimize myocardial recovery.

1. Jabara R, Gadesam R, Pendyala L et al. Comparison of the clinical characteristics of apical and non-apical variants of broken heart (Takotsubo) syndrome in the United States. J Invasive Cardiol 2009;21:216–222.

2. Wittstein IS, Thiemann DR, Lima JA, et al Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005;352:539–548.

3. Carlson EB, Cowley MJ, Wolfgang TC, Ducey EF, Vetrovec GW. Acute changes in resting global and regional left ventricular function after successful percutaneous transluminal coronary angioplasty: Comparative results in stable and unstable angina. J Am Coll Cardiol 1989;13:1262–1269.

4. Abbate A, Bussani R, Amin MS, Vetrovec GW, Baldi A. Acute myocardial infarction and heart failure: Role of apoptosis. Int J Biochem Cell Biol 2006;38:1834–1840.