Acute Heart Failure in Apical Ballooning Syndrome (TakoTsubo/Stress Cardiomyopathy)

Clinical Correlates and Mayo Clinic Risk Score

To the Editor:

Apical ballooning syndrome (ABS) is an acute cardiac syndrome characterized by transient regional systolic dysfunction of the left ventricle (LV) in the absence of obstructive coronary artery disease (1). Systolic heart failure (HF) is the most common complication and merits early detection and treatment. However, the clinical correlates and outcomes of acute HF in ABS have not been systematically studied. Thus, the primary aim of our study was to examine the frequency of, risk factors for, and prognosis of patients with acute HF complicating ABS.

A retrospective analysis was conducted among 118 consecutive, prospectively identified patients with ABS diagnosed using the Mayo Clinic criteria from January 2002 to January 2008 (1). The study was approved by the Institutional Review Board and all patients consented to the use of their medical records for research purposes. Acute heart failure was defined as a clinical syndrome characterized by new onset of symptoms such as dyspnea, and at least 2 of the following physical signs: pulmonary rales, elevated central venous pressure, and a third heart sound on cardiac auscultation; cardiogenic shock was defined using standard criteria (2). Coronary angiography was performed on hospital days 1, 2, 3, and 4 in 98, 15, 4, and 1 patient, respectively. Ejection fraction (EF) was measured by LV angiography in 92 patients. Echocardiography was performed in 106 patients at a mean interval of 1.7 ± 1.0 days. A follow-up echocardiogram was available in 94 patients at a mean interval of 75 ± 14 days. Independent predictors for the development of acute HF were identified using the Cox proportional hazards regression model. Five clinical characteristics (age, presence of physical stressor, ST-segment elevation, troponin T level at admission, and EF) that had a statistically significant association with acute HF by univariate analysis were included in the multivariate model. The risk score for acute HF was developed by allocating 1 point each for 3 factors that were significant (p < 0.05) in multivariate analysis arranged in a dichotomous fashion (age >70 years, presence of physical stressor, and EF <40%). Troponin T level was not included in the risk score due to the heterogeneity in the assays and cutoff values used in different institutions. The chi-square test was used to assess differences in the event rates for increasing risk score, and its predictive performance was evaluated using the C-statistic. The risk score was validated in a second cohort of 52 ABS patients identified between February 2008 and December 2009.

Fifty-three (45%) patients demonstrated clinical evidence of acute HF during the hospitalization (Table 1). Among patients with acute HF, 23 (43%), 5 (9%), and 25 (47%) patients had Killip class II, III, and IV HF, respectively. Patients with acute HF were older, more likely to have experienced a preceding physically stressful event, and had higher admission and peak cardiac troponin T levels, more frequent ST-segment elevation, and lower EF at presentation. By multivariate analysis, age (odds ratio [OR]: 1.06 [95% confidence interval (CI): 1.02 to 1.11], p = 0.001), a physical stressor (OR: 4.01 [95% CI: 1.64 to 10.36], p = 0.002), admission troponin T level (OR: 2.43 [95% CI: 1.05 to 6.59], p = 0.04), and lower EF (OR: 0.96 [95% CI: 0.92 to 0.99], p = 0.01) were independent predictors of acute HF. There was a significant positive correlation between the frequency of acute HF and the risk score in the development cohort (C-statistic 0.77, p < 0.001) (Fig. 1). Twenty (38%) patients in the validation cohort (age 71 ± 12 years, 46% physical trigger, EF: 42 ± 12%) developed HF, and there was a significant increase in the frequency of HF as the risk score increased (C-statistic 0.77, p = 0.002) (Fig. 1). Patients with HF were more likely to require inotrope (38% vs. 0%), intra-aortic balloon pump support (17% vs. 0%), mechanical ventilation (28% vs. 5%), and experienced longer hospitalization (11.2 ± 5.4 days vs. 5.4 ± 8.7 days, p = 0.0004) compared to those without HF. Three (3%) patients died in hospital due to multi-organ failure secondary to cardiogenic shock. The majority (92%) of patients had complete resolution of acute HF at discharge from the hospital. Patients with and without HF had similar EF (60 ± 10% vs. 62 ± 6%, p = 0.3) on follow-up. None of the patients had ongoing or recurrent HF at follow-up.

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Figure 1

Acute Heart Failure in Apical Ballooning Syndrome

Frequency of heart failure stratified by the risk score in the development (A) and validation (B) cohorts.

Our study is the first, to our knowledge, to provide a measure of the severity of HF in ABS. We report that approximately 45% of patients had clinical HF, and approximately 1 in 5 developed cardiogenic shock. Patients who developed acute HF had greater myocardial injury and stunning, and were more likely to have a physical stressor and advanced age. There are several potential explanations for these observations. First, patients with physical stressors had significant underlying comorbid conditions that not only triggered ABS, but may have contributed to the development of HF. Second, physical stressors such as post-operative state may be associated with a more sustained surge in catecholamines compared with emotional stress which may be short lived. Third, advancing age is often associated with higher prevalence of pre-existing cardiac abnormalities such as diastolic dysfunction and coronary endothelial dysfunction, which may increase the likelihood of developing HF.

We also developed and validated a simple risk score that can be calculated at the time of presentation. The presence of 1, 2, and 3 points was associated with a 28%, 58%, and 85% risk of acute HF, respectively. Despite the limitations of retrospective analysis, the model had good predictive value in the validation cohort, which suggests that it may be widely applicable to patients with ABS that are diagnosed according to the Mayo Clinic diagnostic criteria. Risk stratification using this data may assist in triaging patients at high risk to an intensive care unit for initial management. In addition, it may allow physicians to identify patients in whom early initiation of beta-adrenergic blockers may be harmful. Moreover, since ABS is believed to be catecholamine mediated, the use of inotropic agents in those with hypotension or HF, or at increased risk for developing HF may potentially be deleterious. Thus, inotropic agents should be used with caution in ABS, and the use of intra-aortic balloon pump counterpulsation may be the preferred treatment strategy for moderate or severe hemodynamic compromise.

• American College of Cardiology Foundation