Between June 2006 and October 2010, 3,100 patients were seen in our institutions with suspected acute coronary syndrome (ACS). Of these, 37 patients fulfilled the following criteria (1, 8) for SIC: 1) older than 18 yr; 2) transient akinesia/dyskinesia beyond a single major coronary artery vascular distribution; 3) absence of significant coronary artery disease upon coronary angiogram (CAG) and 4) the presence of definite antecedent physical or mental trigger factors, identified by the attending physicians. No patients had a preexisting cardiomyopathy, intracranial bleeding, or pheochromocytoma. We applied ergonovine echocardiography to all patients diagnosed with SIC to rule out coronary vasospasm within two days after CAG, and there was no patient with positive finding on the test.

We reviewed medical records for chief complaint, smoking history, and co-morbidities. We also investigated the presence of physical stress (septic shock, surgery, or intubation, etc.) or mental stress (anger management issues, death of loved one, or interpersonal conflicts, etc.). Body mass index (BMI), level of cardiac enzymes (creatine kinase MB fraction, CK-MB; troponin-I), high sensitive C-reactive protein (hsCRP), systolic and diastolic blood pressure (BP), heart rate (HR), and Killip class were evaluated at the time of diagnosis for SIC.

Standardized electrocardiography (ECG) and echocardiographic studies were examined at the time of diagnosis and one or two weeks later to confirm the status of recovery. If regional wall motion abnormality (RWMA), observed on the first echocardiogram, was not definitely improved on the second one, a third echocardiogram was performed a few weeks after the second one. All patients showed resolution of RWMA. In echocardiography studies, we measured the left ventricular ejection fraction (LVEF) and regional wall motion score index (WMSI) to determine the severity of cardiac dysfunction. The LVEF was measured using the modified Simpson's method, and WMSI was calculated using all views, including the parasternal short axis and long axis and apical four chamber views. We classified ventricular ballooning into two categories, typical and atypical apical ballooning, based on the location of ballooning. Standard 2-dimensional and Doppler echocardiography was performed using a 2.5 MHz transducer with harmonic imaging. We used a Philips iE33 system (Philips Medical Systems, USA) for patients admitted to the general ward and ViVid I (GE Ultrasound, Horten, Norway) for patients in the intensive care unit. We calculated the APACHE II score, with the worst physiologic parameters during the first 24 hr after the event, to measure the clinical severity of each patient's objective physical condition upon presentation. APACHE II is composed of vital signs, serum creatinine level, oxygen pressure in arterial blood gas analysis, blood acidity, degree of leukocytosis, level of hematocrit, severity of electrolyte imbalance, Glasgow coma scale (GCS; representing patient mental status), and age of patient, each recorded at the most severe level in 24 hr (7).

All statistical analyses were performed using SPSS software (version 18.0, SPSS Inc, Chicago, IL, USA). Continuous variables were expressed as mean ± SD or mean with interquartile ranges. Frequencies and percentages were used to describe categorical variables and were compared based on the result of ROC curve analysis with Fisher's exact test. Continuous variables of the two groups (Group I and II, divided by APACHE II score 20) were analyzed and compared using the student T-test. To estimate the sensitivity and specificity of the APACHE II score for predicting death, ROC curve analysis was done. Kaplan-Meier survival analysis was performed to estimate the mortality according to survival period. Statistical significance was defined as P < 0.05 in all of the analyses.

The institutional review board of Kyung-Hee University Hospital approved the protocal of this prospective SIC registry (KHNMC IRB 2011-026). The data were retrospectively reviewed and informed consents were provided by all patients.

To find out the variable which is able to predict the outcomes of patients exceedingly, we analyzed the baseline characteristics and the clinical factors of patients, including the cardiac functions, in terms of LVEF and WMSI, cardiac enzymes, such as CK-MB and TnI, and APACHE II score based on survival (Table 1). And we figured out that APACHE II score was significantly different between the dead and the survived among multiple clinical variables (22.5 ± 1.6 vs 11.7 ± 6.2, P value = 0.001). Even though SIC is a kind of cardiomyopathy, the abnormalities in ECG, the shape of apical ballooning, the heart functions and cardiac markers did not show any significant difference between two groups. And more male patients were included in the death group than survival group (67% vs 19%, P value = 0.035). Based on this result, we carried out receiver operating characteristics (ROC) curve analysis to confirm the availability of APACHE II score as a prognostic marker. According to the result of ROC curve analysis we divided the patients into group I (APACHE II score > 20) and group II (APACHE II score ≤ 20), because APACHE II score 20 showed higher sensitivity and specificity than any other scores (Fig. 1). The comparison between group I and group II was done to find out any other clinical factors, which is related to the prognosis, as described beneath.

The baseline characteristics of patients are presented in Table 2. The mean age was 66.1 ± 15.6 yr old, and the mean BMI was 21.5 ± 3.4 kg/m². Twenty-seven (73%) of 37 patients were female, and 31 (84%) were non-smokers. One third of the subjects had comorbidities, with cancer being most common (n = 6, 16%). Except for a few comorbidities, such as cancer or chronic obstructive pulmonary disease (COPD), most of them were not related to SIC itself.

The comparisons of clinical characteristics of the subjects are presented in Table 3. Physical stress, such as sepsis, surgery, or acidosis, was reported more often than mental stress in both groups (100% vs 0% in group I and 79% vs 21% in group II, respectively). Even though not described in the tables, operation was largest number of physical stress, followed by severe pneumonia, acute pyelonephritis, and acute exacerbation of COPD. And The most frequent initial symptom on presentation was chest pain (n = 14, 38%), followed by dyspnea, altered mentality and hypotension, with dyspnea in group I and chest pain in group II being the most common respectively. ECG on presentation showed no remarkable arrhythmia. Among ECG abnormalities, T wave inversion was most common (n = 16, 43%), followed by ST elevation and ST depression. Corrected QT interval (QTc) was prolonged at the time of diagnosis (485.3 ± 55.5 ms). Serum cardiac enzymes were elevated in all patients, and were not statistically different between groups. In the echocardiographic study at the time of diagnosis, mean LVEF was 42.5% ± 9.3%, and mean WMSI was 1.9 ± 0.3 and those are not significantly different between two groups (P value = 0.573 and 0.516, respectively). There was no significant difference in the proportion of typical ballooning between groups, although all patients in group I had typical ballooning at presentation (100% vs 79%, P value = 0.305). ROC curve indicated a high sensitivity (100%) and specificity (94%) of the APACHE II score for predicting death, with a threshold score of greater than 20 (Fig. 1). The APACHE II score at diagnosis was significantly higher in group I as compared to group II (22.1 ± 1.6 vs 11.0 ± 5.9, P = 0.001). Among multiple components of the APACHE II score, only maximal heart rate and Glascow coma scale were higher in group I. Six in group I and no one in group II died during hospitalization, all with physical stress and 4 of them were male (Table 4). Their mean APACHE II score and LVEF were 22.5 (range 21-25) and 40.5% (range 26%-49%), respectively. Mean time to death from diagnosis was 25 days (range 2-111 days). Kaplan-Meier survival curve shows significant difference in cumulative survival between two groups divided by APACHE II score 20 (Fig. 2).