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J Am Coll Cardiol, 2010; 55:700-701, doi:10.1016/j.jacc.2009.10.031
© 2010 by the American College of Cardiology Foundation
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CORRESPONDENCE: RESEARCH CORRESPONDENCE

Pre-Morbid Psychiatric and Cardiovascular Diseases in Apical Ballooning Syndrome (Tako-Tsubo/Stress-Induced Cardiomyopathy)

Potential Pre-Disposing Factors?

Matthew R. Summers, BS, Ryan J. Lennon, MS and Abhiram Prasad, MD*

* Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (Email: prasad.abhiram{at}mayo.edu).


To the Editor:

Apical ballooning syndrome (ABS), also referred to as Tako-Tsubo or stress-induced cardiomyopathy, is a unique reversible cardiovascular disease that mimics an acute myocardial infarction (1). Catecholamine-induced myocardial stunning has been postulated as a central mechanism, but the precise pathophysiology remains unknown (2,3). We hypothesized that the susceptibility to the cardiomyopathy may, in part, be related to pre-morbid chronic psychiatric and cardiovascular diseases, and our aim was to assess the burden of these diseases among patients who had suffered ABS.

A retrospective case-control study was conducted among patients who were prospectively diagnosed with ABS according to the Mayo Clinic diagnostic criteria (2). The study was restricted to Olmsted County, Minnesota, residents because the Mayo Clinic is the only tertiary heath care provider for the region; hence, their medical records would provide a complete past medical history for major acute and chronic diseases. Twenty-five female patients met inclusion criteria. Twenty-five Olmsted County residents with a prior history of an anterior ST-segment elevation myocardial infarction (STEMI) served as one control group. A second control group of 50 Olmsted County residents was drawn from the general population of patients seen at the Mayo Clinic in Rochester. Both control groups were matched for age, date of birth, and sex. The STEMI group was also matched for the index event date, and the general control subjects were seen at the Mayo Clinic within 5 years of the ABS patients' event date. The study was approved by the Mayo Clinic Institutional Review Board, and all subjects consented to the use of their medical records for research. We reviewed the complete medical records of each patient and control subject and documented details of the past psychiatric and cardiovascular history preceding the episode of ABS. The diagnosis of anxiety included generalized anxiety disorder, panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and social phobia. Substance abuse included alcohol and illicit drug use. Continuous variables are summarized as mean ± SD if they have roughly symmetric distributions; otherwise median (interquartile range) is the summary format. Categorical data are presented as frequency (group percentage); percentages are relative to those with data available. Differences between matched cases and control subjects were tested using conditional logistic regression.

The mean age of the ABS patients was 70.6 ± 12.2 years. There were no differences in the predominant presenting symptoms of chest pain and dyspnea or the occurrence of congestive heart failure and arrhythmias between the ABS patients and STEMI control subjects. Coronary atherosclerosis was present in 92% of ABS patients, although only 1 patient had a stenosis >70% in a major epicardial artery. The frequency of chronic anxiety disorders was significantly greater in patients with ABS compared with both control groups (Table 1). Compared with the general population control subjects, ABS patients were more likely to have been divorced (20% vs. 2%; p = 0.012) and to be living alone (52% vs. 24%, p = 0.024). The total number of conventional cardiovascular risk factors in patients with ABS was similar to that in STEMI patients, but higher when compared with the general population (Table 1).


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Table 1 Pre-Morbid Psychiatric and Cardiovascular History
 
The major findings of this study are that patients with ABS have: 1) a high prevalence of a chronic anxiety disorder that antecedes the onset of the cardiomyopathy; and 2) a high prevalence of comorbid cardiovascular risk factors with frequency similar to that seen in patients with STEMI. The present study is the first to report an association between chronic psychiatric illness and ABS; 56% of patients with ABS had been diagnosed with a chronic anxiety disorder by either a primary physician or a psychiatrist before the hospitalization for ABS. A diagnosis of either anxiety or depression was documented in more than two-thirds of patients with ABS. The frequency was significantly higher than that in the STEMI and general population control subjects. This observation, together with the higher frequency of a family history of anxiety or depression, and social isolation, suggests that psychosocial factors may be a pre-disposing risk factor in the pathophysiology of ABS. This is plausible given the fact that acute emotional stress is a well-recognized trigger for ABS (1,2). Thus, we speculate that chronic psychological stress may be a risk factor, whereas acute anxiety may ultimately trigger the syndrome. Proposed stress-related mechanisms that may promote atherogenesis include activation of the hypothalamic–pituitary–adrenal and sympathetic nervous systems, serotonergic dysfunction, secretion of proinflammatory cytokines, and platelet activation (4). The same mechanisms could also precipitate myocardial dysfunction that occurs in ABS.

Patients with ABS had a high prevalence of conventional cardiovascular risk factors. The majority had at least 2 of the following: hypertension, hyperlipidemia, diabetes mellitus, history of smoking, or a family history of cardiovascular disease. This may not seem unusual for an elderly cohort; however, it is noteworthy that the cumulative burden of cardiovascular risk was significantly greater in patients with ABS than that of the general population, and similar to that of the STEMI control subjects. The finding is consistent with the fact that 92% of patients with ABS had angiographic evidence of coronary atherosclerosis, although only 1 had an obstructive lesion. Because nonobstructive atherosclerosis and its risk factors seem to be ubiquitous in ABS, we speculate that endothelial dysfunction may play a role in the pathophysiology.

Further studies need to confirm our findings in larger cohorts, and if the associations are consistently present, detailed study of the psychosocial attributes, personality traits, and chronic life stress in ABS patients would be indicated. If chronic psychiatric conditions and cardiovascular risk factors were confirmed to play a role in the pathophysiology, it would be important to clearly identify and treat them with a view to preventing recurrence (1,2,5).


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 References
 
1. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes Circulation 2008;118:397-409.[Free Full Text]

2. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction Am Heart J 2008;155:408-417.[CrossRef][Web of Science][Medline]

3. Wittstein IS, Thiemann DR, Lima JAC, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress N Engl J Med 2005;352:539-548.[CrossRef][Web of Science][Medline]

4. Everson-Rose SA, Lewis TT. Psychosocial factors and cardiovascular diseases Annu Rev Public Health 2005;26:469-500.[CrossRef][Web of Science][Medline]

5. Roy-Byrne PP, Davidson KW, Kessler RC, et al. Anxiety disorders and comorbid medical illness Gen Hosp Psychiatry 2008;30:208-225.[CrossRef][Web of Science][Medline]




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