Summary
Background
Tako-Tsubo cardiomyopathy is a clinical entity mimicking acute coronary syndrome. Assessment of left ventricular function may be difficult using conventional echocardiography.
Aims
To characterize left ventricular systolic function using contrast echocardiography in Tako-Tsubo cardiomyopathy.
Methods
We prospectively studied 63 consecutive women admitted for suspected acute coronary syndrome who underwent coronary arteriography, biplane left ventricular angiography and conventional and contrast echocardiography; 25 women had Tako-Tsubo cardiomyopathy (group 1), 25 women had proven coronary artery disease (group 2) and 13 women had no significant coronary lesion (group 3). Echocardiographic interpretation was performed by two observers: a physician trainee (observer 1) and an experienced investigator (observer 2).
Results
Left ventricular segments were assessed for wall motion abnormalities, which were present in 70 and 88% (observer 1) and in 91 and 99% (observer 2), using conventional and contrast echocardiography, respectively ( P < 0.0001). Accuracy for the diagnosis of Tako-Tsubo cardiomyopathy was improved significantly for both observers using contrast echocardiography: for observer 1, sensitivity was 56 and 88%, respectively, using conventional and contrast echocardiography ( P = 0.01), whereas for observer 2, sensitivity was 72 and 96%, respectively ( P = 0.04). Interobserver agreement was excellent using contrast agent (kappa = 0.85 vs 0.34 using conventional echocardiography). The blinded review of left ventriculograms distinguished Tako-Tsubo cardiomyopathy from coronary artery disease correctly in 96% of cases.
Conclusions
Contrast echocardiography could be used in routine practice to replace left ventricular angiography in Tako-Tsubo cardiomyopathy.
Résumé
Contexte
La cardiomyopathie de Tako-Tsubo (CTT) est une entité clinique qui mime un syndrome coronaire aigu. L’évaluation de la fonction ventriculaire gauche (VG) peut être difficile en échocardiographie conventionnelle.
Objectif
Étudier la fonction VG dans la CTT en échocardiographie de contraste.
Méthode
Nous avons étudié de manière prospective 63 femmes admises pour une suspicion de syndrome coronaire aigu, qui ont bénéficié d’une coronarographie, d’une ventriculographie biplan et d’une échocardiographie conventionnelle et de contraste: 25 femmes présentaient une CTT (groupe 1), 25 avaient une cardiopathie ischémique (groupe 2) et 13 femmes ne présentaient pas de lésion coronaire significative (groupe 3). L’interprétation des échocardiographies était réalisée par deux observateurs: un en cours de formation (observateur 1) et un expérimenté (observateur 2).
Résultats
Les anomalies segmentaires VG étaient retrouvées dans 70 et 88 % (observateur 1) et 91 et 99 % (observateur 2) respectivement en échocardiographie conventionnelle et en échocardiographie de contraste ( p < 0,0001). La valeur diagnostique de l’échocardiographie était significativement améliorée en utilisant du produit de contraste quel que soit l’observateur: pour l’observateur 1, la sensibilité était de 56 et 88 % en utilisant respectivement l’échocardiographie conventionnelle et l’échocardiographie de contraste ( p = 0,01) alors qu’avec l’observateur 2, la sensibilité était respectivement de 72 et 96 % ( p = 0,04). La concordance interobservateur était excellente en échocardiographie de contraste (kappa = 0,85 versus 0,34 en échocardiographie conventionnelle). La relecture en aveugle des ventriculographies permettait de différencier correctement les CTT des cardiopathies ischémiques dans 96 % des cas.
Conclusions
L’échocardiographie de contraste pourrait être utilisée en pratique quotidienne pour remplacer la ventriculographie dans la CTT.
Background
Tako-Tsubo cardiomyopathy (TTC) is characterized by transient stress-induced left ventricular (LV) dysfunction in the absence of significant coronary lesions . The pathogenesis of this disease is still uncertain and several hypotheses have been proposed . The LV dysfunction does not correspond to a single coronary artery distribution, suggesting that it cannot be explained by coronary artery occlusion. However, the clinical presentation usually mimics an acute coronary syndrome (ACS) and an occlusion of the left anterior descending coronary artery, and may lead to misdiagnosis. Postmenopausal women are most likely to be affected by TTC, resulting in a TTC prevalence of 3% among women with a suspicion of ACS . This elderly population may thus be fragile and may present renal failure. Biplane LV angiography and cardiac magnetic resonance are two imaging tools used for the analysis of global and regional LV dysfunction in TTC, allowing confirmation of LV regional wall motion abnormalities extending beyond a single epicardial coronary distribution. However, these two examinations have several limitations: LV angiography is invasive, renal failure is a contraindication and complications may occur, whereas cardiac magnetic resonance is of limited availability and cannot be performed in case of claustrophobia.
Echocardiography is used in TTC for the assessment of LV systolic function and to detect cardiac complications . However, routine echocardiography may provide suboptimal images of the LV endocardial borders. New contrast agents may improve echocardiographic imaging quality, leading to its use for left heart opacification and myocardial characterization . LV contrast cavity opacification has been shown to assess regional wall motion abnormalities accurately in patients with coronary artery disease (CAD) . Patients with TTC have regional wall motion abnormalities without significant coronary artery stenosis . The role of contrast echocardiography in TTC has not been evaluated previously. The objective of this prospective single-centre study was to assess the accuracy of contrast echocardiography in the detection of TTC in patients who presented with suspected ACS.
Methods
Study population
From January 2005 to December 2008, among 3466 patients referred for coronary angiography, 1298 patients presented with suspected ACS ( Fig. 1 ). A diagnosis of TTC was made in 25 consecutive women. From this population with suspected ACS, 63 women were enrolled prospectively. These women were divided into three groups: 25 women with acute TTC (group 1), 25 women with proven CAD (group 2) and 13 women without significant coronary lesion or LV dysfunction (group 3). Groups 2 and 3 were age- and sex- matched with group 1.
All included patients ( n = 63) underwent coronary arteriography, biplane LV angiography, conventional transthoracic echocardiography and contrast echocardiography; for patients presenting with TTC ( n = 25), all these examinations were performed less than 24 hours after the onset of symptoms . Contrast echocardiography was used for LV opacification and perfusion analysis. The diagnosis of TTC was defined as: an acute chest pain during a stressful incident associated with ST-segment abnormalities and/or increased serum troponin level; transient regional LV systolic dysfunction with regional wall motion abnormalities extending beyond a single epicardial coronary distribution assessed by LV angiography; and no coronary artery lesions . All patients from group 2 presented with single-vessel disease with chronic occlusion of the left anterior descending coronary artery associated with LV systolic dysfunction, documented by coronary arteriography and LV angiography. Patients from group 3 had no significant CAD and no LV wall motion abnormalities. The study was approved by our institutional review board.
Left ventricular angiography
At the end of coronary arteriography, biplane LV angiography (i.e. right anterior oblique and left anterior oblique) was performed and provided the diagnostic gold standard for the assessment of LV systolic function in this study. LV ejection fraction was calculated using biplane LV volumes, according to Simpson’s rules. LV regional wall motion (presence or not of abnormalities) was assessed systematically for each LV segment. To compare the reliability of echocardiography, the left ventriculograms from groups 1 and 2 were also evaluated by an independent experienced reviewer (R.E.M.), who was unaware of the clinical and coronary angiographic findings. This blinded reading classified each patient as having TTC or CAD.
Echocardiographic protocol
The same echocardiographic protocol was performed in all patients using a Siemens/Sequoia Acuson C512 system (Acuson, Mountain View, CA, USA) equipped with multifrequency transducers and capable of low energy (0.2 to 0.3 mechanical index). All echocardiographic studies were performed by two experienced physicians (N.M. and O.D.). The apical four-chamber and two-chamber views were assessed systematically by conventional and contrast transthoracic echocardiography in all patients. Echocardiography was performed according to the recommendations of the American Society of Echocardiography . LV ejection fraction was calculated using Simpson’s biplane method. All conventional echocardiographic examinations were performed using second harmonic imaging with a 1.9-mechanical index. At the end of conventional transthoracic echocardiography, LV contrast cavity opacification was performed by peripheral venous injection of Sonovue (Bracco Altana, Inc., Milan, Italy), using a low mechanical index (0.2 to 0.3), to avoid the destruction of microbubbles. An initial bolus of 1.0 ml was followed if necessary by a second intravenous bolus (0.5 ml); CPS software (Siemens/Acuson, Mountain View, CA, USA) was used for LV analysis.
All echocardiographic studies were recorded digitally and stocked on a TomTec workstation (TomTec Imaging Systems GmbH, Unterschleissheim, Germany). Interpretation was performed by two observers: a physician trainee (observer 1) and an experienced investigator (observer 2). The two observers were blinded to clinical data and diagnosis. Three cardiac cycles of the parasternal long- and short-axis views, and apical four-chamber and two-chamber views were stored in cineloop format for offline analysis. The quality of endocardial delineation in 17 LV segments was assessed by observer 2 and used to determine the number of well-visualized LV segments by conventional and contrast echocardiography. Both observers assessed systematically LV regional wall motion (presence or not of abnormalities) in each segment using conventional and contrast echocardiography and then classified each patient as having TTC or CAD. TTC was defined as a circular LV dysfunction , whereas LV wall motion abnormalities corresponding to a single epicardial coronary artery suggested the presence of CAD.
To measure myocardial signal intensity, frames were analysed using the offline software Syngo AutoTracking Contrast Quantification (Axius, Siemens Medical Solutions USA, Inc., Malvern, PA, USA). Peak myocardial signal intensity was measured in the different parts of the left ventricle in all patients. Regions of interest were placed in segments with and without wall motion abnormalities. At least three measurements were performed in each segment. Myocardial signal intensity was analysed according to the presence (or not) of wall motion abnormalities; the contrast intensity of the LV cavity was also measured.
Statistical analysis
Continuous variables are presented as mean ± standard deviation and ranges, unless otherwise specified. Categorical data are presented as absolute values and percentages. Continuous and categorical variables were compared with use of the Chi 2 test, paired t tests, unpaired t tests or Fisher’s exact test, as appropriate. Confidence intervals were calculated using the confidence interval analysis software version 2.1.2 (BMJ, London, UK). Interobserver agreement in the interpretation of contrast echocardiography was assessed by the kappa statistic. A P -value <0.05 was considered significant. Statistical analysis was performed using StatView version 4.5 (Abacus Concepts, Inc., Cary, NC, USA).
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