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Echocardiographic assessment of regional left ventricular wall motion abnormalities in patients with tako-tsubo cardiomyopathy: comparison with anterior myocardial infarction

Rodolfo Citro, Fausto Rigo, Quirino Ciampi, Antonello D'Andrea, Gennaro Provenza, Marco Mirra, Roberta Giudice, Francesco Silvestri, Giuseppe Di Benedetto, Eduardo Bossone
DOI: http://dx.doi.org/10.1093/ejechocard/jer059 542-549 First published online: 23 May 2011

Abstract

Aims The aim of this study was to assess the echocardiographic distribution of regional wall motion abnormalities (RWMA) in patients with tako-tsubo cardiomyopathy (TTC) compared with anterior ST-elevation myocardial infarction (ant-STEMI).

Methods and results Thirty-seven TTC and 37 ant-STEMI patients underwent standard echocardiographic examination at the time of hospital admission. RWMA and the involvement of the left ventricular territories supplied by each coronary artery according to the American Society of Echocardiography classification were reported. TTC patients showed a lower left ventricular ejection fraction (37.6 ± 5.1 vs. 40.9 ± 3.7%; P = 0.002) and a higher wall motion score index (WMSI; 1.98 ± 0.2 vs. 1.51 ± 0.14; P < 0.001) compared with ant-STEMI patients. No significant differences were observed between groups with regard to detection of RWMA in the territory supplied by the left anterior descending coronary artery (LAD) (37 vs. 37; P = 1). Conversely, in TTC patients, the territories supplied by the LAD/left circumflex coronary artery (LCX) (37 vs. 31; P = 0.011), LAD/right coronary artery (RCA) (34 vs. 13; P < 0.001), RCA (33 vs. 5; P < 0.001), and RCA/LCX (31 vs. 2; P < 0.001) were more frequently involved. A cut-off value of WMSI ≥1.75 (area under the curve 0.956) and for the number of territories with RWMA ≥4 (AUC = 0.928) predicted TTC with a sensitivity of 83 and 84% and a specificity of 100 and 97%, respectively.

Conclusion Echocardiography revealed a distinctive pattern of contractility in TTC patients, characterized by symmetrical RWMA extending equally into the territory of distribution of all coronary arteries.

  • Tako-tsubo syndrome
  • Apical ballooning syndrome
  • Stress cardiomyopathy
  • Myocardial infarction

Introduction

Tako-tsubo cardiomyopathy (TTC), also known as transient left ventricular (LV) apical ballooning syndrome, is an uncommon acute cardiac condition characterized by transient, severe LV dysfunction mimicking myocardial infarction.14 It typically occurs in postmenopausal women in the seventh or eighth decade of life and is often triggered by an emotional or physical stressful event.5,6 In recent years it has been increasingly recognized, accounting for 2.2% of all patients admitted with a presumed diagnosis of acute coronary syndrome; this rate increases up to 6–7% if only females are considered.6 However, the overall incidence is still unknown and most likely underestimated. TTC patients usually present with substernal chest pain, ischaemic electrocardiogram (ECG) changes, and mild cardiac enzyme elevation, making the differential diagnosis with anterior ST-elevation myocardial infarction (ant-STEMI) challenging.3,4 The widespread use of echocardiography has contributed to more frequent recognition of TTC.7 The typical LV apical ballooning (a/hypokinesis of the mid-apical segments with hyperkinesis of the basal segments and reduced ejection fraction) can be usually detected non-invasively by two-dimensional echocardiography, or invasively by LV angiography during the acute phase.8 Although several authors suggest that myocardial dysfunction in TTC occurs beyond the territory of distribution of the single coronary artery, only few data are available to support this hypothesis. The aim of this study was to assess the echocardiographic distribution of regional wall motion abnormalities (RWMA) in TTC patients at presentation compared with ant-STEMI patients.

Methods

Patient selection

We compared 37 patients with TTC enrolled in Mestre, Salerno, Benevento and Naples Hospitals with 37 patients with ant-STEMI prospectively enrolled in the study and admitted to the catheterization laboratory of Mestre and Salerno Hospitals within 12 h after hospital admission for urgent coronary angiography. The inclusion criteria for TTC patients were as follows: (i) balloon-like morphology of the left ventricle with hypokinesis, akinesis, or dyskinesis of the apical and/or midventricular segments; (ii) no angiographic evidence of coronary narrowing with ≥50% stenosis and/or plaque rupture or intracoronary thrombus formation; (iii) new ECG abnormalities (dynamic ST-T changes or T-wave inversion); (iv) absence of pheochromocytoma and myocarditis.

The inclusion criteria for ant-STEMI patients were as follows: (i) ST-segment elevation in at least two anterior precordial leads on admission ECG; (ii) first myocardial infarction; (iii) significant coronary artery disease with ≥70% stenosis of the left anterior descending coronary artery (LAD) as the culprit lesion on coronary angiography.

Patients with poor acoustic windows (suboptimal visualization of the endocardial borders), significant valvular heart disease, arrhythmia (including atrial fibrillation or flutter), and hypertrophic cardiomyopathy were excluded. Patient demographics, presenting symptoms, triggering stress factors, and clinical, laboratory, and ECG findings were collected on a standard case-report form. All participants provided informed written consent and the study was approved by the local ethics committee.

Echocardiography

All echocardiographic examinations were performed at hospital admission before coronary angiography. A commercially available cardiac ultrasonography system with a 2.5–4.5 MHz phased-array transducer with second harmonic capability was used for complete two-dimensional Doppler echocardiography. All echocardiographic images were digitally recorded and reviewed by two expert readers (R.C. and F.R.). Three cardiac cycles from the apical four- and two-chamber view and the parasternal short-axis view at the level of the mitral valve and papillary muscles were stored in cine-loop format for off-line analysis.

RWMA were evaluated by visual assessment of multiple apical and short-axis views as in routine clinical practice. The left ventricle was divided into 17 segments (6 basal, 6 midventricular, 5 apical). LV segment nomenclature is as follows, as recommended9: (1) basal antero-septal; (2) basal postero-septal; (3) basal inferior; (4) basal infero-lateral; (5) basal lateral; (6) basal anterior; (7) mid antero-septal; (8) mid postero-septal; (9) mid inferior; (10) mid infero-lateral; (11) mid lateral; (12) mid anterior; (13) apical septal; (14) apical inferior (15) apical lateral; (16) apical anterior; (17) apex.9 Each segment was analysed individually and scored by motion and systolic thickening as follows: 1 = normal/hyperkinesis, 2 = hypokinesis, 3 = akinesis, 4 = dyskinesis, 5 = aneurysmal. LV wall motion score index (WMSI) was derived from the sum of all scores divided by the number of LV segments. According to the American Society of Echocardiography classification of territories supplied by each coronary artery, LV segments were assigned to five different territories in order to evaluate the extent of myocardial dyssynergy (Figure 1).9,10 The territory supplied by the LAD includes segments 1, 6, 7, 12, 13, 16, and 17. The territory supplied by the right coronary artery (RCA) includes segments 2, 3, and 9. The territory supplied by the LAD or left circumflex coronary artery (LCX) includes segments 5, 11, and 15. The territory supplied by the RCA or LAD includes segments 8 and 14. The territory supplied by the RCA or LCX includes segments 4 and 10. The vascular territories with RWMA (hypokinesis, akinesis, and/or dyskinesis) detected in at least one segment were considered as involved. LV volume and ejection fraction (EF) were calculated using biplane Simpson's method from the apical four- and two-chamber view. Right ventricular systolic function was evaluated by visual assessment for the detection of right ventricular involvement.11,12 LV outflow tract obstruction was detected by continuous wave Doppler. Using the modified Bernoulli equation, a cut-off value of 20 mmHg for dynamic intraventricular pressure gradient was considered to indicate significant LV outflow tract obstruction.13

Figure 1

Left ventricular segmentation in apical (1, 2, 3) and short-axis (4, 5, 6) views according to typical coronary artery distribution (modified from Cerqueira et al.9).

Statistical analysis

Data are expressed as mean ± standard deviation for continuous variables and as numbers (per cent) for categorical variables. Continuous variables were compared by the paired-samples t-test. Proportions were compared by χ2 statistics; Fisher's exact test was used where appropriate. To determine the best cut-off value for the number of involved territories in predicting the presence of TTC, and to determine the best cut-off value of WMSI in predicting the presence of TTC, receiver operating characteristic (ROC) curves were plotted for the clinical variables included in the analysis. The C statistics, a measure of the area under the ROC curve, was calculated. Calculations of sensitivity, specificity, and accuracy were performed according to standard definitions. The 95% confidence intervals (CIs) were calculated for each technique, and the individual intervals were compared. Differences were considered significant at the 0.05 level when their CI did not overlap. Reproducibility of RWMA measurement was determined in all patients. Intraobserver and interobserver variabilities were assessed using both Pearson's bivariate two-tailed correlation test and Bland–Altman analysis. Relation coefficients, 95% confidence limits, and per cent errors were reported. A probability value of <0.05 was considered statistically significant. All statistical calculations were performed using SPSS for Windows, version 12.0 (SPSS Inc., Chicago, IL, USA).

Results

Demographic and clinical findings

TTC patients were more often female, older, and had a lower systolic blood pressure and a lower incidence of diabetes mellitus (Table 1). In the overall population, the most common presenting symptoms were chest pain (62 patients, 83.7%; 30 TTC vs. 32 ant-STEMI; P = 0.528) and dyspnoea (12 patients, 16.3%; 7 TTC vs. 5 ant-STEMI; P = 0.528). Trigger events and ST-segment elevation were documented in the majority of TTC patients. The magnitude of ST-segment elevation and troponin levels were significantly lower in TTC patients than in ant-STEMI patients. However, among patients with TTC, troponin levels were higher in patients showing ST-segment elevation than in those without ST-segment elevation (6.91 ± 2.74 vs. 2.66 ± 2.94 ng/mL; P < 0.001).

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Table 1

Demographic and clinical characteristics

In ant-STEMI patients, single-vessel disease (with LAD involvement) was detected in 27 cases. Multivessel disease was found in 10 cases (LAD and RCA involvement in 5, LAD and LCX involvement in 3, and three-vessel involvement in 2). In most patients (n = 22) primary percutaneous coronary intervention (PCI) with stent implantation was performed; eight patients underwent rescue PCI of the infarct-related artery (LAD) after failed thrombolysis, and seven patients had repeat PCI with stenting of the LAD within 24 h of symptom onset and following vessel reopening after successful thrombolysis.

Echocardiographic findings

The TTC cohort showed higher LV diastolic and systolic volumes, a lower LV EF, and a higher WMSI than ant-STEMI patients (Table 2). RWMA involving the apex with sparing of the base were detected in 29% and 2% of patients with TTC and ant-STEMI, respectively (P = 0.002). Right ventricular involvement and LV outflow tract obstruction were more frequently detected in TTC patients.

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Table 2

Echocardiographic findings

Regional left ventricular wall motion abnormalities

Hypokinesis of the basal segments was more often observed in ant-STEMI patients (Table 3). Only a few TTC patients showed hypokinesis in the basal segments of the antero-septal (2 vs. 11; P = 0.006), postero-septal (1 vs. 1; P = 1), and inferior (4 vs. 1; P = 0.165) walls (Figure 2A). On the other hand, TTC patients showed more often involvement of the mid postero-septal (31 vs. 6; P < 0.001), inferior (31 vs. 0; P < 0.001), infero-lateral (33 vs. 5; P < 0.001), and lateral (34 vs. 7; P < 0.001) walls (Figure 2B). The majority of the apical segments were similarly involved in both groups, with the exception of the apical inferior and lateral segments (34 vs. 13, P < 0.001, and 37 vs. 31, P < 0.011, respectively), which were more often involved in TTC patients (Figure 2C).

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Table 3

Prevalence of patients with involvement of the basal, mid, and apical segments

Figure 2

Wall motion abnormalities of left ventricular segments in TTC vs. ant-STEMI patients: (A) basal; (B) mid; (C) apical. Ant-STEMI, anterior ST-elevation myocardial infarction; TTC, tako-tsubo cardiomyopathy.

In the territory supplied by the LAD, no significant differences in RWMA extent were observed between groups (37 vs. 37; P = 1). However, in TTC patients, the territories supplied by LAD/LCX or LAD/RCA (37 vs. 32; P = 0.021) and above all by RCA (31 vs. 2; P < 0.001) and RCA/LCX (33 vs. 5; P < 0.001) were more frequently involved (Figure 3). A cut-off value of WMSI ≥1.75 (area under the curve 0.956) predicted TTC with a sensitivity of 83%, a specificity of 100%, and a positive and negative predictive value of 100 and 86%, respectively. According to coronary distribution, a cut-off value for the number of territories with RWMA ≥4 (area under the curve 0.928) predicted TTC with a sensitivity of 84%, a specificity of 97%, and a positive and negative predictive value of 97 and 86%, respectively.

Figure 3

Left ventricular segmental systolic dysfunction according to coronary artery distribution in TTC vs. STEMI patients. In TTC patients, the territories not exclusively supplied by the LAD are more significantly involved. Ant-STEMI, anterior ST-elevation myocardial infarction; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; RCA, right coronary artery; TTC, tako-tsubo cardiomyopathy.

As for RWMA assessment, interobserver variability was r = 0.88; P < 0.00001 (Pearson's correlation); 95% CI ±0.7; per cent error 5.1% (Bland–Altman analysis), whereas intraobserver variability was r = 0.90; P < 0.00001 (Pearson's correlation); 95% CI ±0.5; per cent error 4.1% (Bland–Altman analysis).

At 1-month follow-up, WMSI and LV EF markedly improved in both TTC and ant-STEMI groups (1.02 ± 0.34 and 1.30 ± 0.17, P < 0.001; and 56.9 ± 2.2% and 50.7 ± 6.7%, P < 0.001, respectively), and a significantly greater recovery of LV function was observed in TTC patients.

Discussion

At present, the diagnosis of TTC requires awareness and clinical judgement and does not rely on ECG changes or laboratory findings alone as for acute coronary syndromes.2,3,14 The detection of persistent myocardial stunning resulting in diffuse RWMA despite the absence of significant obstructive coronary artery disease along with spontaneous myocardial function recovery within days or weeks are fundamental criteria to diagnose TTC.15 Over the last decades, echocardiography has been shown to play a key role in the assessment of LV function in patients with ischaemic heart disease as well as in several cardiomyopathies including TTC.7,1619

By using two-dimensional echocardiography, our study demonstrated that TTC patients show (i) more diffuse RWMA than ant-STEMI patients despite a slight increase in troponin values, and (ii) a distinctive pattern of regional systolic myocardial dysfunction. As previously demonstrated by cardiac magnetic resonance,20 in our TTC patients, involvement of the basal segments, especially of the anterior wall and interventricular septum, was rarely observed. Conversely, in ant-STEMI patients, the middle segments of the inferior and postero-lateral wall were significantly less frequently affected. In particular, when considering the extent of RWMA according to coronary artery distribution, most TTC patients showed myocardial systolic dysfunction in the territories supplied either by the LAD or non-LAD coronary artery vessels, with involvement of ≥4 territories. The topography of LV segmental myocardial dysfunction characterized by symmetrical RWMA extending equally into the anterior, inferior, and lateral walls supports the hypothesis of extensive myocardial stunning in the pathogenesis of TTC. This also highlights the difference with ant-STEMI where RWMA are usually confined to the territory supplied only by the LAD as the culprit lesion15,21 (Figure 4). In this respect, Mansencal et al.22 assessed LV dysfunction by means of speckle tracking echocardiography in a small population of TTC patients compared with patients with chronic LAD occlusion. They demonstrated that systolic dysfunction in TTC during the acute phase is ‘circular' and completely different from LV myocardial contractility observed in patients with coronary artery occlusion, suggesting that TTC is not related to coronary artery disease.22

Figure 4

Apical four-chamber view (top) and two-chamber view (bottom) in TTC (left) and ant-STEMI (right). In TTC patients, akinesis of both apical and mid segments of the opposite walls (interventricular septum and lateral wall in four-chamber view; inferior and anterior walls in two-chamber view) can be appreciated. Conversely, in ant-STEMI patients only the mid and apical segments of the interventricular septum and anterior wall (supplied only by the left anterior descending coronary artery) are involved (arrows). Ant-STEMI, anterior ST-elevation myocardial infarction; TTC, tako-tsubo cardiomyopathy.

In accordance with Park et al.,21 also in our series TTC patients were characterized by larger volumes, a lower LV EF, and a higher WMSI despite a slight increase in troponin levels. Furthermore, a WMSI of ≥1.75 showed a high positive predictive value for the diagnosis of TTC. The detection of a higher WMSI is consistent with the findings by Elesber et al.23 and reinforces the concept of diffuse injury in TTC. Additionally, among patients with TTC, WMSI values were higher in those with ST-segment elevation, suggesting an association between ST-segment elevation and more severe myocardial dysfunction. Finally, an accurate evaluation of right ventricular wall motion should be recommended in TTC because also right ventricular ‘ballooning' may be observed at echocardiography. As previously reported, about one-quarter of patients with TTC show right ventricular dysfunction, which results in prolonged hospital stay and haemodynamic instability. In our study population, right ventricular involvement was identified in only 1 ant-STEMI patient vs. 11 TTC patients. Such a finding may be considered as an additional diagnostic indicator of TTC. Prompt recognition of TTC can be challenging. The differential diagnosis with ant-STEMI due to LAD occlusion is difficult even with LV angiography and is usually clarified by the absence of significant coronary artery narrowing or plaque rupture at coronary arteriography.24 Echocardiographic detection of a peculiar pattern of LV systolic dysfunction in the acute phase may be useful in arousing an early suspicion of TTC. However, at present coronary angiography still remains an essential method for the definitive diagnosis.

Study limitations

Some study limitations should be addressed. Firstly, only patients with first myocardial infarction, typical form of TTC, and good quality of acoustic windows were enrolled. Secondly, in patients with multivessel disease the differential diagnosis between TTC and acute myocardial infarction might be more difficult on the basis of RWMA distribution alone. Furthermore, evaluation of wall motion contraction may be affected by the tethering phenomenon and by the human factor related to visual assessment. A major advantage of echocardiography, especially in the acute care setting, is the possibility of a rapid visual assessment of LV RWMA and global systolic function. Nevertheless, a wide range of reproducibility that limits diagnostic accuracy of the echocardiographic parameters has been reported. However, a recent report confirms that visual interpretation of WMSI and LV EF has good interobserver reliability among expert echocardiographic readers and seems to be adequate for clinical decision making.25 It should also be underlined that sensitivity and specificity are the best-case scenarios because they were calculated in the same group of patients in which the ROC curves were derived. Although new ultrasound technologies such as speckle tracking and three-dimensional echocardiography may provide new insights into the regional wall motion analysis, they are not yet recommended by current guidelines.26 Finally, our study population included a limited number of patients in each subgroup, and our results need to be confirmed in a larger study sample.

Conclusions

Our results demonstrate that a systematic evaluation by two-dimensional echocardiography reveals a distinctive pattern of LV contractility in TTC characterized by symmetrical RWMA extending equally into the anterior, inferior, and lateral walls. A large area of dysfunctional myocardium beyond the territory of distribution of a single coronary artery detected in TTC is in contrast to the typical distribution of RWMA generally described in acute coronary syndromes. In addition, the simultaneous detection of LV and right ventricular apical involvment (biventricular ballooning) should be considered a diagnostic marker of TTC. The possibility of rapidly distinguishing patients with TTC and no epicardial coronary artery lesions from patients with ant-STEMI may facilitate timely and appropriate management. Our results combined with other peculiar clinical characteristics, such as postmenopausal women with a precipitating stressful event, may be helpful in the early differential diagnosis between TTC (especially in patients with ST-segment elevation at presentation) and ant-STEMI.

Conflict of interest: none declared.

References

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