Despite advances in echocardiography, magnetic resonance imaging, and the ability to perform an endomyocardial biopsy, the underlying etiology of nonischemic left ventricular (LV) dysfunction often eludes clinical detection.¹ Takotsubo syndrome (also called apical ballooning) is a unique form of cardiomyopathy that tantalizes us with a rare glimpse into both the etiology and potential reversibility of myocardial dysfunction based on its association with adrenergic activation and its characteristic echocardiographic or ventriculographic appearance.

Although undoubtedly misdiagnosed as focal myocarditis or vasospasm prior to its description in a 1990 textbook by Sato,² our appreciation for the existence of Takotsubo syndrome has escalated in tandem with our desire to understand its underlying cause (Figure). Takotsubo syndrome typically presents in a postmenopausal, emotionally or physically distressed woman reporting acute chest pain or dyspnea, and manifesting mild enzymatic evidence of myocardial damage. Clinically, it may mimic an acute myocardial infarction or ventricular tachycardia. Although angiography reveals the absence of significant epicardial coronary artery disease, echocardiography or ventriculography reveal an end-systolic ventricular “ballooning” that may be heterogeneous.³ The syndrome is strikingly reminiscent of conditions seen in experimental animals that occur after acute increases in afterload or with catecholamine excess. Indeed, both an intraventricular pressure gradient and catecholamine excess have been described in Takotsubo patients.^4-7 Since additional mechanisms remain under consideration, including transient myocardial ischemia due to coronary vasospasm or difficult-to-detect thrombus in the territory of a “wrap around” left anterior descending artery (with its perfusion territory beyond the usual detection abilities of coronary angiography),^8,9 microcirculatory abnormalities, and even genetic predilections, it would be reasonable to assume that multiple forms of the disease may exist.

The case report by Nwachukwa demonstrates the need for precise diagnostic criteria for Takotsubo cardiomyopathy for both clinical and basic science investigation.¹⁰ The indolent presentation in this case report (progressive fatigue, dyspnea on exertion, and bilateral lower extremity swelling) is less common than the more fulminant presentation marked by acute dyspnea, chest pain, and often, cardiac arrest. The history also reveals the presence of celiac sprue, which raises the possibility that the cardiomyopathy may have been triggered by an electrolyte deficiency^9,11 or an anticardiolipin syndrome.¹² Electrocardiographic abnormalities, mimicking an acute inferior wall myocardial infarction, were present and the combination of echocardiography and ventriculography revealed apical akinesis with midventricular hyperkinesis. Classically, no angiographic evidence of an obstructive coronary lesion was present. However, we are not told if states of adrenergic excess, including pheochromocytoma or central nervous system disorders, were ruled out. Moreover, we are not told of the follow-up for this patient and potential reversibility of the LV dysfunction. Classic Takotsubo cardiomyopathy is associated with recovery of LV function, usually within 2-4 weeks of presentation.

Many questions concerning Takotsubo cardiomyopathy remain for both clinical and basic science researchers. These include an understanding of the heterogeneity of presentation, the optimal nature and duration of treatment, and whether the unique properties of Takotsubo cardiomyopathy will offer a window to more fully understand other forms of cardiomyopathy.

References
1. Felker GM, Hu W, Hare JM, et al. The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1278 patients. Medicine. 1999; 78:270-283.

2. Sato H, Tateishi H, Uchida T, et al. Tako-tsubo-like left ventricular dysfunction do to multivessel coronary spasm. In: Kodama K, Haxe K, Hori M, eds. Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure. Tokyo, Japan: Kagakuhyoronsha Publishing Company; 1990: 56-64.

3. Ibanez B, Benezet-Mazuecos J, Navarro F, et al. Takotsubo syndrome: a Bayesian approach to interpreting its pathogenesis. Mayo Clin Proc. 2006; 81: 732-735.

4. Villareal RP, Achari A, Wilansky S, et al. Anteroapical stunning and left ventricular outflow tract obstruction. Mayo Clin Proc. 2001; 76:79-83.

5. Tsuchihashi K, Ueshima K, Uchida T, et al on behalf of Angina Pectoris-Myocardial Infarction Investigations in Japan. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myocardial Infarction Investigations in Japan. J Am Coll Cardiol. 2001;38: 11-18.

6. Arora S, Alfayoumi F, Srinivasan V. Transient left ventricular apical ballooning after cocaine use: is catecholamine cardiotoxicity the pathologic link? Mayo Clin Proc. 2006; 81:829-832.

7. 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.

8. Ibanez B, Navarro F, Cordoba M, et al. Tako-tsubo transient left ventricular apical ballooning: is intravascular ultrasound the key to resolve the enigma? Heart. 2005; 91(1):102-104.

9. Desmet WJ, Adriaenssens BF, Dens JA. Apical ballooning of the left ventricle: first series in white patients. Heart. 2003; 89: 1027-1031.

10. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med. 2004; 141: 858-865.

11. De Bem RS, Da Ro Sa Utiyama SR, et al. Celiac disease prevalence in Brazilian dilated cardiomyopathy patients. Dig Dis Sci. 2006; 51: 1016-1019.

12. Makhdoom ZA, Randall NW. Dilated cardiomyopathy due to anticardiolipin syndrome in association with celiac sprue. J Clin Gastroenterol. 2000; 31: 91-92.

*With apologies to Kazakhstan.