Clinical Characteristics and Outcome of Left Ventricular Ballooning Syndrome in a European Population

We assessed the clinical characteristics and determinants of the prognosis of patients with left ventricular ballooning syndrome (LVBS) in an European population. A total of 128 patients with LVBS (98% women, age 67 ± 11 years) were prospectively followed up for a median of 13 months. A trigger event was identifiable in 58% of the patients. Anterior ST-segment elevation was documented in 38% and negative T waves in 41% of the patients. Apical ballooning was present in 82% and midventricular ballooning in 18%. The initial LV ejection fraction was 41 ± 9%. In-hospital events included the death of 1 patient (0.8%), LV failure in 13 (10%), LV thrombi in 4 (3.1%), sustained ventricular or supraventricular tachyarrhythmias in 6 (4.7%) and asystole in 2 patients (1.6%). The extent of wall motion abnormalities (odds ratio 4.16, p = 0.012), dyspnea at presentation (odds ratio 3.42, p = 0.01), and treatment with nitrates (odds ratio 0.30, p = 0.015) were significant univariate predictors of in-hospital events. The recovery of regional wall motion abnormalities occurred within 1 month of the event in 73% of patients. During follow-up, events occurred in 7 (6%) of 121 patients, including noncardiac death in 1 (0.8%), recurrent LVBS in 2 (1.6%), heart failure in 1 (0.8%), and recurrent chest pain in 3 (2.5%). In conclusion, in a European population, LVBS was characterized by a significant rate of in-hospital events, mainly related to pump failure, and low short-term mortality. The extent of wall motion abnormalities was the best predictor of acute events. Contractile recovery occurred within 1 month in most patients. The long-term prognosis was good, with a recurrence rate of <2%/year.

Left ventricular ballooning syndrome (LVBS) is an acute cardiac syndrome mimicking acute myocardial infarction. It was initially described in Japan and was subsequently also recognized in white populations. The clinical presentation of LVBS can vary, both in relation to the presence of a psychological or physical stress as a trigger event and in relation to the type and extent of regional wall motion abnormalities (WMAs). Several studies have reported a significant rate of complications in the acute phase ; however, the determinants of the short-term outcome have not been clearly defined. Furthermore, data on the long-term prognosis are limited. The data have mainly been retrospective and mostly collected from Japanese and American populations. Thus, the aim of the present study was to assess the clinical characteristics and determinants of the short- and long-term outcomes of patients with LVBS in a large, prospectively studied population of European patients.


From October 2003 to December 2008, 132 patients were prospectively recruited from 15 cardiological centers participating in the Italian Multicenter LVBS Registry. The clinical data and angiographic examinations of the patients were reviewed by 2 of us (A.R. and M.P.) at the core laboratory to verify adherence to the diagnostic criteria of LVBS proposed by the Mayo Clinic group. These criteria included (1) transient akinesia and dilation of the mid- and apical LV segments (apical ballooning) or of the midventricular segments only (midventricular ballooning), with hyperkinesis of the basal segments; (2) the absence of significant (≥50%) obstructive coronary artery disease or angiographic evidence of plaque rupture; (3) new electrocardiographic (ECG) abnormalities, including ST-segment elevation and/or T-wave inversion or an increase in cardiac troponin; and (4) the absence of pheochromocytoma, recent head trauma, intracranial bleeding, myocarditis, and hypertrophic cardiomyopathy. Of the 132 patients initially considered, 4 (1 with hypertrophic cardiomyopathy and 3 with minor WMAs) did not fulfill the diagnostic criteria for LVBS and were excluded, leaving a final study population of 128 patients. The study complied with the Declaration of Helsinki, and the locally appointed ethics committee approved the research protocol. All subjects provided informed consent.

The clinical, echocardiographic, angiographic, and follow-up data of the study population were collected using a standardized case report form. Hypertension was considered present when the blood pressure was >140/90 mm Hg or when patients were receiving antihypertensive treatment. Hyperlipidemia was considered present when the total cholesterol level was >200 mg/dl or the patients were treated with antihyperlipidemic drugs. ST-segment elevation was defined as a new >1 mm ST deviation measured 80 ms after the J point in ≥2 contiguous leads and T-wave inversion as negative T waves >3 mm in amplitude in ≥2 contiguous leads not present on previous electrocardiograms. All other ECG changes not fulfilling these criteria were defined as nonspecific ST–T-wave changes. Multiplane coronary angiography was performed on admission in 64 patients (50%) and within 72 hours of admission in the remaining 64. Coronary artery disease was defined as a ≥50% reduction in the luminal diameter of a major coronary artery. Coronary artery spasm was defined as a >50% focal or diffuse narrowing of an epicardial coronary artery not caused by a catheter that resolved after intracoronary nitroglycerin. Left ventriculography in the right anterior oblique projection was performed in 104 (81%) of the 128 patients. The LV ejection fraction was calculated using the area-length method. The remaining 24 patients underwent 2-dimensional echocardiography after coronary angiography for evaluation of the LV ejection fraction and regional WMAs. Standard 2-dimensional Doppler echocardiography was performed in the acute phase in all patients. The LV end-systolic and end-diastolic volumes were measured from the apical 4-chamber view using the area-length method, and the ejection fraction was calculated using the standard formula. LV regional wall motion was evaluated, and the wall motion score index was calculated in accordance with a previously described method. Mitral valve regurgitation was graded from mild (grade 1) to severe (grade 4) according to the evaluation of regurgitant flow with color flow imaging and measurement of the color flow Doppler maximal regurgitant area/left atrial area ratio in a 4-chamber apical view. It was considered significant (grade 3 and 4) when the maximal regurgitant area/left atrial area ratio was >50%. Significant dynamic LV obstruction was diagnosed in the presence of a gradient >30 mm Hg by continuous wave Doppler localized in the outflow tract or at the midventricular level. After discharge, the patients were followed up with outpatient ECG and echocardiographic examinations at 1, 3 to 6, and 12 months. The in-hospital events and complications included cardiac and noncardiac death, heart failure and cardiogenic shock, sustained symptomatic supraventricular and ventricular arrhythmias, and LV thrombi. The events considered during long-term follow-up were death from any cause, the recurrence of LVBS, the recurrence of chest pain with or without ECG abnormalities, and hospitalization for heart failure.

Continuous data are reported as the mean ± SD or median and twenty-fifth to seventy-fifth percentiles, according to their distribution. Categorical data are reported using numbers and percentages. Continuous data were compared between the clinical subgroups using the Student t test or Mann-Whitney U test and categorical data using the Fisher exact test. The determinants of short prognosis were assessed using univariate and multivariate logistic regression analyses. On univariate analysis, the clinical, ECG, echocardiographic, and coronary angiographic variables were evaluated. The variables with p <0.1 on univariate analysis were included in the multivariate analysis. The presence of collinearity between these variables was verified. Cox regression analysis was used to assess the determinants of long-term prognosis. Odds ratios (ORs) and hazard ratios were computed, together with their 95% confidence intervals (CIs). Kaplan-Meier survival analysis with the log-rank test was used to compare the long-term survival of patients with and without complications during the acute phase. Stata, version 10 (StataCorp, College Station, Texas) was used for computation. A 2-sided p value <0.05 was considered statistically significant.


The main clinical characteristics of the patients are listed in Table 1 . The mean patient age was 67 ± 11 years (range 24 to 97), and 98% were women. Co-morbidities included chronic gastrointestinal disease in 19 patients (15%), hypo- or hyperthyroidism in 10 (8%), bronchial asthma and chronic obstructive lung disease in 9 (7%), uterine fibromatosis or previous hysterectomy in 7 (5%), hepatitis C virus-hepatitis B virus–related hepatic disease in 6 (4%), and anxiety-depressive disorders in 3 (2%). A trigger (defined as an unusual emotional or physical stress occurring <12 hours before symptom onset) was identified in 75 patients (59%). Of the 75 patients, 45 had an emotional stressor, including death of a close relative for 13, a violent argument for 13, a physical attack for 7, stress at home or work for 7, disease of a relative for 3, and public speaking for 2. The remaining 30 reported a physical stressor, including unusually heavy exercise in 10, noncardiac medical or surgical procedures in 10, exacerbation of a chronic illness in 5, delivery in 2, dancing in 2, and multiple bee stings in 1. The troponin I plasma levels were elevated in all 117 patients in whom they were measured. The remaining 11 patients had elevated creatine kinase-MB levels, with a mean peak value of 39 ± 22 mU/ml. Coronary angiography showed normal coronary arteries in 112 patients (88%) and a <50% disease of 1 or 2 vessels in 16 patients (12%). Stenosis of the left anterior descending artery was present in 9 of 12 patients with 1-vessel and 4 of 4 with 2-vessel disease. No patient had a spontaneous coronary artery spasm. An apical ballooning pattern was documented in 105 patients (82%) and a midventricular ballooning pattern in 23 (18%). At Doppler echocardiography, grade 3 to 4 mitral regurgitation was documented in 9 (7%) of 128 patients, all with apical ballooning. Significant dynamic LV obstruction was observed in 6 patients (5%), all of whom had significant mitral regurgitation. In-hospital treatment is listed in Table 1 ; 20% of patients required diuretics and 5% intravenous catecholamines. The 4 patients with LV thrombi received intravenous or subcutaneous heparin plus oral anticoagulation in 2.

Table 1

Clinical patient characteristics

Variable Value
Age (years) 67 ± 11
Women 125 (98%)
Hypertension 75 (59%)
Hyperlipidemia 57 (45%)
Diabetes mellitus 9 (7%)
Tobacco use 30 (23%)
Presenting symptoms
Chest pain 88 (69%)
Dyspnea 29 (23%)
Presyncope or syncope 11 (8%)
Triggering event
Emotional 45 (36%)
Physical 30 (23%)
No trigger 53 (41%)
Admission electrocardiographic findings
ST-segment elevation 49 (38%)
Negative T waves 52 (41%)
Nonspecific ST-T changes 27 (21%)
Admission QTc interval (ms) 438 ± 50
Peak troponin I (ng/ml) 4.4 ± 7.8
Coronary and left ventricular angiographic findings
Normal coronary arteries 112 (88%)
<50% stenosis 1-2 vessel 16 (12%)
Left ventricular ejection fraction (%) (n =104) 42 ± 9
Doppler 2-dimensional echocardiographic findings
Left ventricular ejection fraction (%) (n =128) 41 ± 9
Wall motion score index 1.8 ± 0.4
Significant (grade 3-4) mitral regurgitation 9 (7%)
Dynamic left ventricular obstruction 6 (5%)
In-hospital treatment
Aspirin 111 (87%)
Clopidogrel 29 (23%)
Intravenous or subcutaneous heparin 127 (99%)
Oral anticoagulation 2 (2%)
β Blockers 87 (68%)
Nitrates 87 (68%)
Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 59 (46%)
Calcium antagonists 13 (10%)
Diuretics 25 (20%)
Statins 42 (33%)
Intravenous catecholamines 7 (5%)
Intra-aortic balloon counterpulsation 1 (1%)

In-hospital events occurred in 26 patients (20%) and included death from stroke 48 hours after admission for 1 patient (0.8%), heart failure or cardiogenic shock in 13 (10%), LV apical thrombi in 4 (3.1%), ventricular fibrillation and ventricular tachycardia in 3 (2.3%), sustained symptomatic atrial fibrillation in 3 (2.3%), and syncope due to severe bradycardia and asystole in 2 (1.6%). The patient who died had had no heart failure, atrial fibrillation, or LV thrombus. On univariate analysis ( Table 2 ), the extent of WMAs evaluated using the wall motion score index (OR 4.16, 95% CI 1.28 to 13.45, p = 0.012), dyspnea at presentation (OR 3.42, 95% CI 1.35 to 8.67, p = 0.01), and treatment with nitrates (OR 0.30, 95% CI 0.11 to 0.79, p = 0.015) were significant predictors of in-hospital events. Treatment with β blockers (OR 0.38, 95% CI 0.15 to 1.0, p = 0.05) showed a trend toward statistical significance. Also, grade 3 to 4 mitral regurgitation was associated with a high rate of complications (44% vs 18% in patients without regurgitation) but was not a significant predictor of in-hospital events (OR 3.52, 95% CI 0.87 to 14.2, p = 0.08). On multivariate analysis, the model including the wall motion score index, dyspnea at presentation, and grade 3 to 4 mitral regurgitation significantly predicted the short-term outcome (p = 0.008; Table 3 ). No collinearity was found between the variables selected for multivariate analysis.

Table 2

Predictors of in-hospital complications on univariate analysis

Variable OR 95% CI p Value
Age 1.02 0.98–1.07 NS
Women 2.00 0.17–22.94 NS
Hypertension 1.77 0.70–4.45 NS
Diabetes mellitus 1.13 0.22–5.79 NS
Tobacco use 0.73 0.25–2.14 NS
Main presenting symptoms
Chest pain 0.36 0.11–1.11 NS
Dyspnea 3.42 1.35–8.67 0.01
Presyncope or syncope 0.97 0.19–4.91 NS
ST-segment elevation 1.09 0.45–2.61 NS
Apical ballooning 1.11 0.37–3.34 NS
Triggering event 0.53 0.22–1.26 NS
Peak troponin I 1.00 0.96–1.03 NS
Left ventricular ejection fraction 0.97 .092–1.01 NS
Wall motion score index 4.16 1.28–13.45 0.012
Significant (grade 3-4) mitral regurgitation 3.52 0.87–4.21 NS
In-hospital treatment
Aspirin 1.62 0.33–7.78 NS
β Blockers 0.38 0.15–1.00 0.05
Nitrates 0.30 0.11–0.79 0.015
Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers 1.21 0.47–3.07 NS

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Dec 22, 2016 | Posted by in CARDIOLOGY | Comments Off on Clinical Characteristics and Outcome of Left Ventricular Ballooning Syndrome in a European Population

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