Background
Because stress-induced cardiomyopathy (SIC) is increasingly being observed during routine daily practice, we sought to explore the clinical features and factors that determine the outcome of SIC in a tertiary referral hospital.
Methods
Patients with typical left ventricular (LV) takotsubo (apical ballooning) or inverted takotsubo on 2-dimensional echocardiography were prospectively enrolled, and their clinical data were analyzed.
Results
Over a 63-month period, 56 consecutive patients (median age and interquartile range = 64 years [52-74 years]) were identified. Women comprised 79% (44/56) of all patients. The triggering events were acute medical illness, including sepsis and hypoxemia in 29 patients (52%, group A), in-hospital surgery/procedure in 17 patients (30%, group B), and emotional stress in 10 patients (18%, group C). Chest pain was more frequently observed in group C (50%) than in groups A (14%) and B (6%) ( P = .021), whereas dyspnea was the presenting symptom in groups A and B. Typical takotsubo and inverted takotsubo were observed in 48 and 8 patients, with a median ejection fraction of 33%. Other abnormalities included dynamic LV outflow tract obstruction (n = 2), LV thrombus (n = 2), and right ventricular dysfunction (n = 12). Nine deaths (16%) occurred during hospitalization. The groups did not differ in mortality. The Acute Physiology and Chronic Health Evaluation II score (odds ratio 1.405; 95% confidence interval, 1.091-1.810; P = .009) and absence of LV function recovery within 1 week (ejection fraction < 50%) (odds ratio 14.080; 95% confidence interval, 1.184-167.475; P = .036) were independent factors associated with mortality. During clinical follow-up up to 6 months, 3 more patients died, 2 of whom had recurrences of SIC.
Conclusions
SIC in a tertiary referral hospital was mainly associated with physical stressors and characterized by diverse clinical presentations, high mortality, and occasional fatal recurrences.
Stress-induced cardiomyopathy (SIC), a recently accepted benign form of reversible cardiomyopathy, was first described as a differential diagnosis of acute coronary syndrome and is increasingly being observed during routine daily practice, including diagnostic or therapeutic procedures, surgery, and intensive care. Moreover, the development of fatal arrhythmia, left ventricular (LV) perforation, and right ventricular dysfunction have also been reported. Thus, the clinical features of SIC and the factors determining prognosis need to be reassessed, and this issue is expected to be more important in a tertiary referral hospital. The present study explored the clinical features, outcomes, and factors determining the prognosis of patients with SIC in a tertiary referral hospital.
Materials and Methods
Subjects
From June 2003 to September 2008, all patients who underwent echocardiography during admission to the Asan Medical Center, a tertiary referral hospital in Seoul, South Korea, were assessed for their eligibility to enroll in this prospective study. Those who met the following inclusion criteria were enrolled: (1) development of typical takotsubo or inverted takotsubo on echocardiography ( Figure 1 , Videos 1-4 ; view video clips online); (2) no evidence of obstructive epicardial coronary artery disease, including no history of angina and a normal coronary angiogram or myocardial perfusion scan; for those patients who could not undergo invasive coronary angiography or myocardial perfusion scanning because of their condition, typical evolutionary electrocardiogram (ECG) changes, including prominent ST segment elevation and deep T-wave inversion with a marked discrepancy between the extent of wall motion abnormalities and cardiac biomarkers (peak troponin I level < 10 ng/mL), were used to indicate the absence of epicardial coronary artery obstruction; (3) the presence of a definite antecedent stressor, identified by the attending physicians; and (4) the absence of preexisting cardiomyopathy, head trauma, intracranial bleeding, pheochromocytoma, or catecholaminergic inotropic medication before echocardiography. Follow-up echocardiography was performed at least every week to assess LV function. Digitally stored echocardiographic images were reviewed again by experienced echocardiography specialists (JKS and JMS) to search for right ventricular dysfunction, LV thrombus, LV outflow tract obstruction, pericardial effusion, or inferior vena cava plethora (distended vena cava without inspiratory collapse). The severity of mitral regurgitation was assessed by using the ratio of distal jet area/left atrial area on color Doppler imaging, and grade ≥ 3 was defined as the ratio ≥ 35%.
![](https://i0.wp.com/thoracickey.com/wp-content/uploads/2018/06/gr1-475.jpg?w=960)
Clinical Data
The laboratory findings, hospital management, and outcome were determined by careful analysis of the medical records of all patients. The magnitude of systemic illness was quantified by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system, which was calculated using the worst physiologic parameters during the first 24 hours after the event. Shock was defined as a systolic blood pressure less than 90 mm Hg despite the administration of ≥ 40 mL/kg of isotonic fluid in 1 hour. Follow-up data were collected by direct telephone interviews and a detailed review of all medical records. The cause and date of death were confirmed by information from the National Population Registry of the Korea National Statistical Office, together with a review of all available clinical records at the time of death.
Data Analysis
Numeric variables are summarized by using median and interquartile range (IQR). Between-group comparisons were performed by using the Mann–Whitney U test or Kruskal–Wallis test as appropriate. Nominal variables were compared by using the Fisher exact test. In univariate analysis, 7 parameters showed a marginal association with a fatal outcome ( P < .10), and these variables were tested in backward stepwise multivariable logistic regression analysis to identify independent predictors of in-hospital death. All P values were 2-sided, and a probability value of P < .05 was considered significant. All statistical analyses were performed with SPSS (version 12.0; SPSS Inc, Chicago, IL).
Results
Triggering Events and Clinical Presentation
A total of 56 consecutive patients (median age of 64 years [IQR 52-74 years]) with typical takotsubo (n = 48) or inverted takotsubo (n = 8) on echocardiography were enrolled in this study. This cohort included 44 female patients (79%). Twenty-four patients (43%) underwent echocardiography in the emergency department, mainly because of chest pain or mild elevation of cardiac biomarkers. For the remaining 32 patients (57%), who underwent echocardiography during their hospital admission, echocardiography was requested because of the sudden development of dyspnea, ECG abnormalities, or pulmonary congestion documented by chest radiography. The triggering events were classified according to whether the stressors were emotional or physical ( Figure 2 ). The events involving physical stressors were further divided according to whether patients were admitted for a serious medical problem (acute medical illness group) or for prescheduled surgery or procedures (surgery/procedure group). Emotional stress was documented in 18% of patients (10/56), whereas acute medical illness and elective surgery/procedures were the precipitants in 52% of patients (29/56) and 30% of patients (17/56), respectively. Nine patients were taking a beta-receptor blocker (atenolol [n = 5], carvedilol [n = 3], and bisoprolol [n = 1]) to control blood pressure.
![](https://i0.wp.com/thoracickey.com/wp-content/uploads/2018/06/gr2-351.jpg?w=960)
Baseline Clinical Characteristics
The groups did not differ significantly in terms of age, gender ratio, and cardiovascular risk factors ( Table 1 ). Sudden development of chest pain was the most common clinical presentation in the emotional stress group (50%), but in the acute medical illness and surgery/procedure groups, the important clinical presentations were sudden dyspnea, ECG abnormality, hypotension, and oxygen desaturation. Shock developed only in the acute medical illness and surgery/procedure groups with a higher frequency of endotracheal intubation and significantly higher APACHE II scores compared with the emotional stress group.
Variables | Total | Emotional (n = 10) | Surgery or procedure (n = 17) | Acute medical illness (n = 29) | P value |
---|---|---|---|---|---|
Age, years (median and IQR) | 64 (52-74) | 63 (52-75) | 61 (44-70) | 68 (61-75) | .172 |
Female gender, n (%) | 44 (78.6) | 8 (80.0) | 16 (94.1) | 20 (69.0) | .137 |
Reasons for echocardiography, n (%) | |||||
Chest pain | 10 (17.9) | 5 (50.0) | 1 (5.9) | 4 (13.8) | .021 |
Dyspnea | 26 (46.4%) | 5 (50.0) | 5 (29.4) | 16 (55.2) | .280 |
ECG abnormality | 10 (17.9) | 0 | 8 (47.1) | 2 (6.9) | .001 |
Hypotension | 4 (7.1) | 0 | 1 (5.9) | 3 (10.3) | .812 |
Oxygen desaturation | 6 (10.7) | 0 | 2 (11.8) | 4 (13.8) | .723 |
Shock, n (%) | 13 (23.2) | 0 | 5 (29.4) | 8 (27.6) | .169 |
ICU care, n (%) | 49 (87.5) | 9 (90.0) | 17 (100) | 23 (79.3) | .101 |
Use of inotropic agents, n (%) | 33 (58.9) | 7 (70.0) | 12 (70.6) | 14 (48.3) | .275 |
Intubation, n (%) | 27 (48.2) | 1 (10.0) | 12 (70.6) | 14 (48.3) | .008 |
APACHE II score, median (IQR) | 15 (11-20) | 12 (10-17) | 13 (10-18) | 17 (14-23) | .005 |
Hospital stay, days (median [IQR]) | 17 (9-35) | 10 (6-16) | 18 (13-44) | 17 (11-35) | .061 |
In-hospital death, n (%) | 9 (16.1) | 1 (10.0) | 1 (5.9) | 7 (24.1) | .272 |
Table 2 compares the baseline laboratory findings of all patients and the patients in the 3 groups. The median (and IQR) LV ejection fraction and peak troponin I level of all patients were 33% (26-39) and 3.5 ng/mL (0.8-7.0), respectively, and there were no differences between the groups. The 3 groups did not differ in the frequency of ECG abnormalities, such as ST segment elevation mimicking acute myocardial infarction and deep T-wave inversion. The most frequent ECG abnormality was QT prolongation (n = 50 [89%]). Although typical takotsubo was the predominant pattern, the frequency of inverted takotsubo was significantly lower in the acute medical illness group than in the emotional stress and surgery/procedure groups.
Variables | Total | Emotional (n = 10) | Surgery or procedure (n = 17) | Acute medical illness (n = 29) | P value |
---|---|---|---|---|---|
ECG abnormalities, n (%) | |||||
ST-segment elevation | 16 (28.6) | 4 (40.0) | 4 (23.5) | 8 (27.6) | .675 |
T wave inversion | 45 (80.4) | 8 (80.0) | 13 (76.5) | 24 (82.8) | .902 |
QTc prolongation | 50 (89.3) | 9 (90.0) | 15 (88.2) | 26 (89.7) | 1.000 |
Atrial fibrillation | 6 (10.7) | 1 (10.0) | 2 (11.8) | 3 (10.3) | 1.000 |
Atrial flutter | 3 (5.4) | 1 (10.0) | 1 (5.9) | 1 (3.4) | .751 |
Ventricular tachycardia | 5 (8.9) | 0 | 2 (11.8) | 3 (10.3) | .693 |
Abnormality in chest x-ray, n (%) | |||||
Pulmonary edema | 27 (48.2) | 5 (50.0) | 8 (47.1) | 14 (48.3) | 1.000 |
Pleural effusion | 29 (51.8) | 4 (40.0) | 8 (47.1) | 17 (58.6) | .556 |
Peak troponin I, ng/mL (median [IQR]) | 3.5 (0.8-7.0) | 3.7 (0.6-11.5) | 4.2 (2.8-8.3) | 2.9 (0.4-6.7) | .213 |
Echocardiographic abnormalities, n (%) | |||||
Takotsubo | 48 (85.7) | 8 (80.0) | 12 (70.6) | 28 (96.6) | .026 |
Inverted takotsubo | 8 (14.3) | 2 (20.0) | 5 (29.4) | 1 (3.4) | .026 |
LV outflow tract obstruction | 2 (3.6) | 1 (10.0) | 1 (5.9) | 0 | .228 |
Mitral regurgitation grade ≥ 3 | 3 (5.4) | 1 (10.0) | 0 | 2 (6.9) | .573 |
RV dysfunction | 12 (21.4) | 3 (30.0) | 4 (23.5) | 5 (17.2) | .528 |
Pericardial effusion | 17 (30.4) | 2 (20.0) | 5 (29.4) | 10 (34.5) | .801 |
LV thrombus | 2 (3.6) | 0 | 1 (5.9) | 1 (3.4) | 1.000 |
TR jet velocity, m/s (median [IQR]) | 2.7 (2.4-3.0) | 2.7 (2.4-3.0) | 2.7 (2.3-3.2) | 2.7 (2.5-3.0) | .907 |
LV EF, % (median [IQR]) | 33 (26-39) | 35 (24-39) | 36 (28-43) | 31 (27-37) | .412 |
Follow-up LV EF, % (median [IQR]) | 59 (55-63) | 57 (52-61) | 58 (55-61) | 60 (54-63) | .536 |
Evaluation of obstructive CAD, n (%) | |||||
Coronary angiography | 22 (39.3) | 7 (70.0) | 8 (47.1) | 7 (24.1) | .029 |
Thallium 201 perfusion scan | 15 (26.8) | 2 (20.0) | 2 (11.8) | 11 (37.9) | .139 |
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