Clinical Characteristics and Prognostic Factors of Stress-Induced Cardiomyopathy

The stress-induced cardiomyopathy (SCM) is characterized by acute, reversible, and transient left ventricular (LV) systolic dysfunction mimicking acute coronary syndrome without significant stenosis on coronary angiogram.1), 2) This syndrome was first described by Satoh et al.3) and was named Takotsubo-cardiomyopathy because its shape resembles the tako-tsubo (Japanese octopus trap).4) The majority of patients are postmenopausal women who present with acute emotional or physical stress.1), 2) Clinical features are acute onset chest pain or dyspnea, electrocardiographic ST changes with T-wave inversion, elevated cardiac biomarkers, elevated B-type natruretic peptide (BNP), apical or midventricular wall motion abnormality by echocardiography and favorable prognosis.1) The underlying etiology is unclear. There are limited data for clinical manifestations and prognostic factors of SCM in Korea.5), 6) Therefore, we sought to clarify the clinical features and prognosis in SCM.

We retrospectively reviewed and analyzed 39 patients diagnosed with SCM from May, 2004, to January, 2009, in Wonju Christian Hospital. SCM was diagnosed as: 1) no previous history of cardiac disease, 2) acute onset, 3) a regional wall motion abnormality, typically in the takotsubo or inverted takotsubo shape by echocardiography, and 4) no significant stenosis in the coronary angiogram. We investigated baseline clinical characteristics, laboratory data, hospital course, complications, and clinical outcomes.

We defined ST-elevation as deviation >1 mm higher than the baseline in ≥2 contiguous leads. We defined T-wave inversion as a change from the previous electrocardiogram (EKG) in ≥2 contiguous leads. Echocardiography was performed at admission and rechecked at discharge or improved symptoms. Coronary angiography and left ventriculography were performed to evaluate coronary artery disease or LV systolic function. Significant stenosis was defined as >50% diameter stenosis by coronary angiography. Shock was defined as systolic blood pressure <90 mm Hg with signs of end-organ hypoperfusion requiring the use of vasopressor agents. Adverse clinical events were defined as death or cardiogenic shock.

Cardiac biomarkers {creatinine kinase MB (CK-MB) fraction and troponin-I}, high sensitive C-reactive protein (hs-CRP), and BNP were collected at admission and cardiac biomarkers were rechecked until normalization. EKG was performed daily. The trigger factor was categorized as emotional or physical stress. After discharge, all patients were followed in an out-patient clinic to reevaluate symptoms, LV systolic function, and adverse events. SCM patients were grouped in 4 seasons to evaluate seasonal variation.

Continuous data were summarized as mean±SD and were compared by Student's t-test. Multivariate logistic regression analysis was performed to determine the independent variables associated with the occurrence of adverse events.

Our study shows that elevated hs-CRP levels and initial impairment of LV systolic function relate to poor clinical outcome. Elevated CRP levels are found in SCM patients and related to impaired LV systolic function with BNP release.7) Enhanced production of acute-phase proteins in the liver by catecholamines may result from direct stimulation or may be mediated by cytokines such as tumor necrosis factor-α or interleukin 6.8) Pathologic findings of SCM revealed the infiltration of inflammatory cells, including activated macrophages.9) Collectively, our findings and previous reports suggest that systemic or local inflammatory processes may affect myocardial dysfunction and clinical outcomes in SCM.

We had different gender-related differences, triggering factors, and initial symptoms than previous studies (Table 4). Postmenopausal females predominate in SCM due to estrogen deficiency after menopause. In animal models, postmenopausal females are more vulnerable to sympathetically mediated myocardial stunning.16) Ovariectomised female rats with estradiol supplementation had significantly less stress-induced ventricular dysfunction, suggesting that estrogen possibly downregulates myocardial adrenoreceptors. New animal models propose that estrogen (via immunoreactive estrogen receptors in the central sympathetic neurons) directly attenuates the hypothalamo-sympathoadrenal axis, and also gives rise to cardioprotective substances such as atrial natruretic peptide, and heat shock protein 70.17), 18) We found a lower percentage of women (female 69%) with SCM, and physical stress was more common than emotional stress. Another SCM study has mostly male patients (65%) and LV apical ballooning developed in a considerable number of patients with severe physical stress who were admitted to the medical intensive care unit.19) Hahn et al.20) also showed that the triggering factors were physical stress (69%) rather than emotional stress. Thus, SCM also occurs in men after physical stress, and inflammation (high CRP), leading to the development and poor clinical outcome for SCM regardless of gender difference.

Table 4
Clinical characteristics of published data with stress-induced cardiomyopathy

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Previous studies have reported that chest pain is a more frequent symptom than dyspnea.1), 2), 20) But, our study showed that dyspnea was more frequent at initial presentation. The patients with dyspnea showed longer hospitalization than patients with chest pain (18±18 vs. 10±8 days). And dyspnea group showed an elevated BNP level (966±1,118 vs. 779±773 pg/mL), higher hs-CRP level (53±77 vs. 22±29 mg/L) and decreased initial LVEF (42±17 vs. 50±15%), but none significant. The discrepancy between our data and previous reports is unclear, but could relate to the small sample size and wide range of standard deviation. A further large study is needed to reveal this phenomenon in the future.

We found atypical types of SCM. There are 3 cases of inverted takotsubo type, 4 cases of transient LV outflow obstruction type, and 1 case of apical thrombus (Fig. 2). Variations in regional wall motion in transient LV apical ballooning, transient mid-ventricular ballooning, and other entities involving excess catecholamines relate more to differences in the anatomic location of cardiac adrenergic receptors, the degree of excess sympathetic activity, or individual differences.21) Transient severe LV dysfunction can cause serious complication such as cerebrovascular attack, renal infarct, and peripheral arterial obstruction that originates from an LV apical thrombus. Early evaluation of echocardiogram and anticoagulation therapy are important.

Fig. 2
A case of inverted stress-induced cardiomyopathy {systolic (A) and diastolic (B) phase}. Left ventriculogram (right anterior oblique view) shows hyper-contractility of the basal and apical segments and ballooning of the mid-segments.

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Our study is restricted to a single center experience and it cannot represent general characteristics of the Korea population. So, a multicenter prospective study needs to reveal the clinical characteristics and outcomes in Korean patients with SCM.