Original article
2D speckle tracking echocardiography for the assessment of regional contractile reserve after myocardial infarction Ewa Szymczyka, Piotr Lipieca, Błaz˙ej Michalskia, Konrad Szymczykb, Ahmed Shima, Bartłomiej Woz´niakowskib, Arkadiusz Rotkiewiczb, Ludomir Stefan´czykb and Jarosław D. Kasprzaka Aims To assess whether quantitative resting assessment of local myocardial function by 2D speckle tracking echocardiography may be helpful for the evaluation of myocardial viability in patients after ST-elevation myocardial infarction (STEMI) and for the prediction of left ventricular function recovery after 12-month follow-up. Methods The study group comprised 96 patients with first STEMI treated with successful primary percutaneous coronary intervention. Seven to 12 days after STEMI, all patients underwent resting echocardiography and low-dose dobutamine stress echocardiography (LDDSE) with visual assessment of contractile reserve which was the reference method for the evaluation of myocardial viability. After 12 months resting echocardiography with visual assessment of functional recovery was performed. Subsequently, acquired images were analyzed off-line using 2D speckle tracking echocardiography algorithm. Measurements included peak systolic longitudinal and transverse strain (SLS/STS), peak longitudinal and transverse strain (PLS/PTS), systolic longitudinal and transverse strain rate (SLSR/STSR) at baseline and after 12 months. Results All analyzed longitudinal parameters of strain had a very good diagnostic value, while transverse parameters
Introduction Myocardial ischemia may lead to a variety of tissue and global cardiac effects that impair cardiac function. It is well known that left ventricular dysfunction in patients with coronary artery disease may not represent irreversible myocardial necrosis, but rather still viable stunned or hibernating myocardium. ‘Stunned’ myocardium is defined as a transient postischemic dysfunction that persists for hours or days following reperfusion.1 ‘Hibernating’ myocardium is chronic but potentially reversible ischemic dysfunction as a result of long-duration reduced coronary blood flow that can be restored to normal by improving blood flow or by reducing oxygen demand.2 Dobutamine stress echocardiography (DSE), contrastenhanced MRI, single-photon emission computed tomography, and positron emission tomography are the most commonly used techniques for assessing myocardial viability in clinical practice. However, each mentioned technique detects a different feature of viable 1558-2027 ß 2016 Italian Federation of Cardiology. All rights reserved.
had only good diagnostic value for predicting myocardial viability defined on the basis of LDDSE. Moreover, SLS and PLS had good, whereas SLSR only satisfactory diagnostic value for predicting function recovery after 12-month follow-up. Conclusions 2D speckle tracking analysis applied during resting echocardiography can be helpful for the prediction of myocardial viability and functional recovery in patients after STEMI. Longitudinal strain parameters allow the prediction of local contractile reserve with SLS showing best correlation with DSE results functional recovery after 12-month follow-up. J Cardiovasc Med 2016, 17:374–381
Keywords: low-dose dobutamine stress echocardiography, speckle tracking echocardiography, stunned myocardium, viability a
Department of Cardiology, Medical University of Lodz and bDepartment of Radiology, Barlicki Teaching Hospital, Medical University of Lodz, Poland Correspondence to Ewa Szymczyk, MD, PhD, Department of Cardiology, Bieganski Hospital, Medical University of Lodz Kniaziewicza 1/5, 91–347 Lodz, Poland Tel: +48 42 251 6015; fax: +48 42 251 6015; e-mail: [email protected] Received 9 October 2013 Revised 21 July 2014 Accepted 21 July 2014
myocardium, which may not to be present simultaneously in each patient. It can be a reason for possible disagreements between different techniques.3 DSE has become a standard clinical tool because of its wide availability, relatively low cost, and absence of radiation exposure. However, when used for identification of contractile reserve, it requires administration of pharmacologic agents and involves a subjective interpretation of wall motion changes, requiring sufficient experience. 2D speckle tracking echocardiography (STE) is a non-Doppler method that rapidly developed from a research tool to an important part of clinical echocardiography that permits offline calculation of deformation parameters such as strain and strain rate, providing important insights into quantitative assessment of systolic and diastolic cardiac function.4 The aim of this study was to assess whether quantitative resting assessment of local myocardial function by 2D STE may be DOI:10.2459/JCM.0000000000000198
© 2016 Italian Federation of Cardiology. All rights reserved
2D STE for the assessment of regional contractile reserve Szymczyk et al. 375
helpful for the evaluation of myocardial viability in patients after ST-elevation myocardial infarction (STEMI) and for the prediction of left ventricular function recovery after 12-month follow-up.
Material and methods Study population
The study group comprised 96 consecutive patients (69 males, mean age 58 10 years) with first STEMI treated with successful primary percutaneous coronary intervention (defined as postprocedural flow Thrombolysis in Myocardial Infarction 3). STEMI was defined according to the universal definition of myocardial infarction.5 The criteria for enrollment were as follows: STEMI with onset of chest pain less than 12 h before primary percutaneous angioplasty, age over 18 years, and provision of patient’s informed written consent. The exclusion criteria were clinical instability on 7–12 days after STEMI, presence of severe, life-threatening arrhythmia, uncontrolled hypertension or hypotension, pregnancy, or breast-feeding. The research protocol was approved by the local bioethics committee. All patients received therapy according to European Society of Cardiology guidelines. Resting echocardiography, dobutamine stress echocardiography, and 12-month follow-up
Seven to 12 days after STEMI, all patients underwent resting echocardiography and subsequently DSE performed with incremental dobutamine infusion rates of 5, 10, and 20 mg/kg/min increased every 3 min according to the guidelines of Polish Cardiac Society.6 Criteria for terminating the test were completion of the protocol, heart rate increase of more than 15 bpm in comparison to baseline, evidence for severe ischemia (clinical, electrocardiographic, or echocardiographic), contractile reserve in all left ventricular segments, systolic blood pressure rise 240 mmHg or higher or drop 15 mmHg or lower from baseline, and patient request. Images were obtained at rest and at the end of each stage of DSE using a standard echocardiographic system Vivid 7 (General Electric, Vingmed, Horten, Norway) with the M4S probe. Images were acquired in apical four-chamber, three-chamber, and two-chamber views, and cine loops were digitally stored and postprocessed on EchoPAC workstation 6.1.0 (General Electric, Vingmed, Horten, Norway). Left ventricular ejection fraction was calculated using the biplane Simpson’s method. A 16-segment model of the left ventricle was used for wall motion analysis. Segments were graded as normokinetic, hypokinetic, akinetic, or dyskinetic on the basis of subjective assessment of wall motion amplitude and changes of left ventricular thickness. DSE performed by expert echocardiographer was used as a reference method for the evaluation of myocardial viability. In our study, left ventricular segments were defined as viable if they were normokinetic or hypokinetic in resting echocardiography or showed a
contractile reserve during DSE (improvement from akinesis or dyskinesis at baseline echocardiography to hypokinesis, normokinesis, or hyperkinesis at peak stage of DSE). According to baseline echocardiographic assessment of wall motion abnormalities, the myocardial viability was assessed in the group of all segments (normokinetic, hypokinetic, akinetic, and dyskinetic) and in the subgroup of akinetic and dyskinetic segments. After 12 months, each patient underwent control resting echocardiography with visual assessment of functional recovery in segments that were akinetic or dyskinetic at baseline resting echocardiography. 2D speckle tracking echocardiography
2D speckle tracking is a recent modality allowing nonDoppler calculation of regional myocardial velocities in any desired direction. Computer-based speckle tracking algorithms provide the value of displacement of pixel clusters between 2D image frames sampled at known refresh rate. Strain is a dimensionless quantity of myocardial deformation, which is expressed in percentage (%) and mathematically defined as the change of myocardial fiber length during end-systole compared with its original length in end-diastole.7 Strain rate expressed as 1 s1 is the spatial derivative of tissue velocity (mm/s).8 In our study, STE analysis was assessed in apical views with frame rate between 60 and 90 frames/s. The analyzed parameters included systolic longitudinal strain (SLS), systolic transverse strain (STS), peak longitudinal strain (PLS), peak transverse strain (PTS), SLS rate (SLSR), and STS rate (STSR). Systolic strain and strain rate were defined as the maximal value obtained prior to aortic valve closure, whereas peak strain and strain rate were measured as the maximal value of the parameter in physiological direction throughout cardiac cycle (Fig. 1). All parameters were measured automatically offline by expert echocardiographer using EchoPAC in each segment of the left ventricle. In each apical view, computer-assisted outlining of the left ventricular endocardial border was performed. Afterwards, the tracking of cardiac motion was done automatically by the software. Manual correction was done when judged necessary after visual verification of myocardial tracking accuracy. Segments with poor visualization were excluded from the further analysis. The software generated curves of longitudinal and transverse strain and strain rate for each segment of the left ventricle (Fig. 2). Statistical methods
Statistical analysis of data was performed using MedCalc version 9.5.2.0 (MedCalc Software, Frank Schoonjans 1993–2008, Belgium). In case of normal distribution, data were presented as means and standard deviation (SD); variables that did not follow normal distribution
© 2016 Italian Federation of Cardiology. All rights reserved
376 Journal of Cardiovascular Medicine 2016, Vol 17 No 5
Fig. 1 AVC
AVC
0
SLS –15 PLS
Transverse stran (%)
Transverse stran (%)
PTS
20
STS
0
Example curves of longitudinal (left panel) and transverse (right panel) strain. PLS, peak longitudinal strain; PTS, peak transverse strain; SLS, systolic longitudinal strain; STS, systolic transverse strain.
were presented as medians and upper and lower quartiles. A P value less than 0.05 was considered as statistically significant. Independent samples t-test was used for between-group comparisons. To determine the most accurate threshold value for systolic and peak longitudinal/transverse strain, and systolic longitudinal/transverse strain rate for viability detection, the results were analyzed with the use of four-field distribution table with variable threshold value, with the use of the receiveroperating characteristic (ROC) curve. The Youden’s index was used to identify the optimal cut-points of strain and strain rate for sensitivity and specificity.
Results Study group characterization
Arterial hypertension was diagnosed in 58 patients (60%), whereas obesity and diabetes were present in 30 (31%) and 19 (20%) patients, respectively. Over a half of patients (53%) were active smokers. The most frequent
localization of culprit lesions in coronary angiography was left anterior descending artery (49 patients, 51%), followed by right coronary artery (34 patients, 35%) and circumflex artery (13 patients, 14%). Baseline echocardiographic characteristic
The mean resting left ventricular ejection fraction measured with the biplane Simpson’s method was 50 7% (range 29–65%), whereas wall motion score index was 1.47 0.3 (range 1.1–2.5). Semiquantitative analysis of baseline left ventricular systolic function of 1536 segments revealed that 1111 segments (72.3%) were normokinetic, whereas 145 (9.4%) hypokinetic, 251 (16.3%) akinetic, and 13 (0.9%) dyskinetic. Only 16 segments (1.0%) were excluded from visual assessment of systolic function. However, precluding speckle tracking analysis, 211 segments (13.7%) were excluded from the analysis because of inadequate image quality in resting echocardiography.
Fig. 2
Example curves of longitudinal strain for six segments obtained from four-chamber apical view (panel a) and transverse strain for six segments from three-chamber apical view (panel b).
© 2016 Italian Federation of Cardiology. All rights reserved
2D STE for the assessment of regional contractile reserve Szymczyk et al. 377
Dobutamine stress echocardiography
2D speckle tracking echocardiography
Resting quantitative analysis with the use of 2D STE was performed in 96 patients from the study group (1536 segments). However, 211 segments (13.7%) were excluded from further analysis because of suboptimal image quality. Values of strain and strain rate were significantly lower for segments with impaired wall motion assessed by semiquantitative visual method (Table 1). Also, values of longitudinal strain and strain rate were significantly higher in segments with preserved myocardial viability. There was no statistically significant difference between mean values of STS and PTS in viable and nonviable segments (Table 2). Based on values of SLS (cutoff 10.6%), three of 11 (27.3%) Table 1
Comparison of resting values of strain and strain rate in viable and nonviable segments – analysis for normokinetic, hypokinetic, akinetic, and dyskinetic segments in baseline resting echocardiography
Table 2
The results of DSE were analyzed in 82 patients (1312 segments) because in 14 patients, DSE was inconclusive because of normal left ventricular function with no wall motion abnormalities on 7–12 days after STEMI (six patients), inadequate image quality (two patients), presence of left ventricular apical thrombus (two patients), uncontrolled hypertension (two patients), or earlier termination of DSE because of arrhythmia (two patients). The mean left ventricular ejection fraction measured with the biplane Simpson’s method increased from 50 7% at baseline to 60 8% at peak stage, whereas wall motion score index decreased from 1.47 0.3 at baseline to 1.33 0.3 (1.0–2.2) at peak stage. With the assumption that viable segments are those with normokinesis and hypokinesis at resting echocardiography (971 normokinetic segments and 117 hypokinetic segments), contractile reserve was assessed in 224 segments (eight segments with resting dyskinesis, 216 segments with resting akinesis) in DSE. At peak stage of DSE, normokinesis and hypokinesis were observed in 21 and 54 segments, whereas akinesis and dyskinesis were noted in 143 and 6 segments, respectively. Therefore, contractile reserve was confirmed during DSE in 75 (33.5%) segments. Taking into account data from resting (1088 viable segments) and stress echocardiography (75 viable segments), viability was confirmed in 1163 from 1312 segments (88.6%) in the group of 82 patients with performed DSE.
Parameter
Viable segments (n ¼ 1088)
Nonviable segments (n ¼ 224)
P
SLS (%) PLS (%) SLSR (s1) STS (%) PTS (%) STSR (s1)
14.9 7.16 16.05 6.32 1.07 0.40 25.68 24.56 23.17 23.78 2.07 1.28
2.93 6.07 4.98 5.42 0.58 0.32 23.99 24.5 20.76 24.1 1.61 1.16
3.25% 0.602 0.01 72.7% 45.2% PTS >14% 0.566 NS – – 0.540 NS – – STSR 1.75 s1
PPV
NPV
Accuracy
98.8% 99.3% 98.6% 24.8% 17.7% 15.8%
29.8% 21.9% 17.9% 93.2% 93.6% 92.5%
91.0% 85.5% 86.0% 76.4% 61.5% 59.2%
98.7% 98.7% 99.4% 65.2% – –
14.6% 25.1% 13.5% 54.0% – –
77.8% 88.3% 75.6% 61.3% – –
AUC, area under the curve; NPV, negative predictive value; PLS, peak longitudinal strain; PPV, positive predictive value; PTS, peak transverse strain; SLS, systolic longitudinal strain; SLSR, systolic longitudinal strain rate; STS, systolic transverse strain; STSR, systolic transverse strain rate.
© 2016 Italian Federation of Cardiology. All rights reserved
2D STE for the assessment of regional contractile reserve Szymczyk et al. 379
1.45 s1 in resting echocardiography could be recognized as indicators of myocardial viability. Longitudinal strain parameters allow the prediction of local contractile reserve with SLS showing high concordance with DSE results and functional recovery after 12-month follow-up. Cutoff values of SLS less than 10.1% and PLS less than 10.4% in resting echocardiography could be recognized as predictors of left ventricular function improvement after 12 months from STEMI. DSE is well recognized but requires expertise in diagnostic technique for the evaluation of myocardial viability in patients with impaired left ventricular function. The visual interpretation of wall motion abnormalities is semiquantitative and subjective, which is the reason for low interinstitutional observer agreement.9 The step toward objectification of results was the implementation of quantitative regional myocardial deformation parameters such as strain and strain rate obtained by tissue Doppler echocardiography and STE.10,11 Doppler-based ultrasound techniques quantify only the axial angle-dependent component of myocardial motion, along the direction of the transmitted ultrasound wave, and are prone to errors induced by random noise.12 STE is a newer echocardiographic approach based on high- resolution ultrasound imaging that allows accurate quantifying longitudinal, radial, and circumferential strain and strain rate regardless of limitations of Doppler technique.13,14 STE allows indepth evaluation of myocardial systolic and diastolic dynamics across a broad range of physiologic and pathologic conditions.15,16 One of the clinically important applications of STE is the assessment of myocardial viability not only during stress but also by resting echocardiography.17,18 Animal-based studies by Aarsæther et al. and Migrino et al.19,20 revealed that longitudinal, transverse, and circumferential strain values derived from STE correlated well with the extent of necrosis in myocardial segments following acute myocardial infarction and accurately reflected myocardial segmental viability, distinguishing infarcted from viable myocardium. Also, human studies revealed similar results. Tanimoto et al.21 analyzed transverse strain in patients 2 weeks after STEMI and observed significant inverse correlation between transmural extent of infarction determined by contrast-enhanced MRI and PTS value (r ¼ 0.74, P < 0.0001), proving that STE can be a useful and accurate method for evaluating myocardial viability. Gjesdal et al. studied the group of patients 9 months after first myocardial infarction using STE and MRI. Peak SLS was able to separate infarcted from noninfarcted myocardial segments, as assessed with contrastenhanced MRI. A value of 15% for peak SLS was demonstrated to be able to identify infarcted tissue with a sensitivity of 83% and a specificity of 93%. Accordingly, higher (more negative) strain values were associated with the presence of viable myocardium.22 Mollema et al. demonstrated that global longitudinal left ventricular
strain after acute infarction is strongly related to infarct size and may be a marker of myocardial viability. A cutoff value of 13.7% for baseline global longitudinal strain, with a sensitivity of 86% and a specificity of 74%, was able to predict left ventricular function recovery at 1-year follow-up.23 Similarly to all previously mentioned studies, our results revealed that longitudinal systolic and peak strain and strain rate had very good diagnostic value (85.5–91.0% for analysis of normokinetic, hypokinetic, akinetic, and dyskinetic segments; 75.6–88.3% for analysis of dyskinetic and akinetic segments), whereas transverse parameters only good (59.2–76.4% for analysis of normokinetic, hypokinetic, akinetic, and dyskinetic segments) diagnostic value for predicting myocardial viability determined by visual assessment of contractile reserve during DSE in patients 7–12 days after successfully reperfused STEMI. All longitudinal parameters had high positive predictive values for the assessment of myocardial viability, meaning that more negative values of longitudinal strain predicted higher probability of contractile reserve corresponding with myocardial viability. Respectively, transverse parameters had high negative predictive value (about 93%) for the assessment of myocardial viability, meaning that lower values of transverse strain predicted higher probability of lack of myocardial viability. Postsystolic shortening defined as myocardial shortening after aortic valve closure is considered a marker of disease with diagnostic potential for identifying actively contracting and hence viable myocardium.24,25 This was also observed in our study in analysis of akinetic and dyskinetic segments in which peak strain values were more predictive as compared with peak systolic values. However, for analysis of normokinetic, hypokinetic, akinetic, and dyskinetic segments, peak strain values were markedly less predictive as compared with peak systolic values. This may be a result of misleading contribution of postsystolic contraction of the myocardium, which is consistent with other authors stating that postsystolic shortening is not a specific marker of viability.26,27 In our study, 42% of akinetic or dyskinetic segments at baseline resting echocardiography showed functional recovery 12 months after STEMI. Among strain parameters, only SLS and PLS had good diagnostic value for predicting functional improvement 12 months after STEMI. The relatively high negative predictive value of longitudinal strain parameters (75–80%) indicates that less negative values correspond with lack of functional recovery. Those results are in concordance with observation of Caracciolo et al. of 42 patients with first STEMI, treated with percutaneus angioplasty. Likewise, the authors confirmed that longitudinal and circumferential (but not transverse) parameters were helpful in predicting functional recovery of left ventricular segments
© 2016 Italian Federation of Cardiology. All rights reserved
380 Journal of Cardiovascular Medicine 2016, Vol 17 No 5
5 months after STEMI.28 Also, Eek et al. and Antoni et al. had similar observation according longitudinal strain parameters.29,30 Although in our study transverse parameters of strain had nonsatisfactory diagnostic value for predicting functional recovery 12 months after STEMI, Hoffmann et al.31 confirmed predictive value of transverse parameters 9 months after revascularization. In comparison with other diagnostic methods such as dobutamine stress, myocardial contrast echocardiography, MRI, or positron emission tomography, STE based on resting echocardiography does not require the administration of pharmacological agents, radiation exposure, or sophisticated instruments and analysis. This well tolerated and relatively inexpensive technique can be widely applied in echocardiographic laboratories, which may facilitate the assessment of myocardial viability in everyday practice. Knowledge of myocardial viability is crucial for decision on possible revascularization or cardiac resynchronization therapy. Although echocardiographic quantitative analysis of the systolic function by speckle tracking is a well tolerated study, it is important to notice that the myocardial viability assessment was not possible in as many as 13.7% of the segments in our study, owing to suboptimal quality of the images usually obtained in the clinical practice. In comparison, Hurlburt et al. excluded from the analysis only 6% of segments, but their study group consisted of 60 healthy, young individuals, who, by definition, did not have obesity or obstructive lung disease.32 However, Marwick et al.33 excluded 21% of segments in the analysis of 242 healthy volunteers aged 18–80 years.
detecting myocardial viability at rest in all segments independent of wall motion alteration severity. Also, the results of this single-center study have been obtained from a relatively small group of 96 patients, although as many as 1536 segments were analyzed. Furthermore, in our study, there was only one expert echocardiographer who was analyzing 2D speckle tracking echocardiographic data and intraobserver and interobserver variability were not assessed, which is a strong limitation of the study. Finally, a novel method of speckle tracking based on complete volumetric datasets (4D strain) was not available for our study.
Conclusion 2D speckle tracking analysis applied during resting echocardiography can be helpful for the prediction of myocardial viability and functional recovery in patients after STEMI. Longitudinal strain parameters allow the prediction of local contractile reserve with SLS showing best correlation with DSE results for the assessment of functional recovery after 12-month follow-up. Compared with other diagnostic methods, measurements of strain parameters based on resting echocardiography offer an interesting alternative to dobutamine testing, but also may become competitive against other techniques because of wide availability and lower cost. This hypothesis requires, however, separate validation studies.
References 1
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Study limitations Several limitations of this study must be considered. First, the analysis of strain profile is largely dependent on image quality. Therefore, careful attention was given when recording the images, but still 13.7% of the segments were excluded from the analysis. Second, we used only low-dose DSE as a standard qualitative test to determine the myocardial viability and the subjectivity factor could play a role even though the assessment was performed by a cardiologist with extensive experience in stress echocardiography. The use of cardiac MRI for assessing the viability would be more accurate for a comparison between techniques. Also, we are concerned that the study design does not allow to demonstrate that 2D STE overcomes the limitation of subjective interpretation of DSE, but is rather able to provide similar information, without the administration of pharmacologic agents. Moreover, only apical views were obtained during rest and stress echocardiographic examination, enabling the analysis of longitudinal and transverse but not circumferential strain and strain rate or rotation parameters, which could provide additional information.34 Another limitation of this article is quite low values of sensitivity and negative predictive value of longitudinal strain in
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Voigt JU, Lindenmeier G, Exner B, et al. Incidence and characteristics of segmental postsystolic longitudinal shortening in normal, acutely ischemic, and scarred myocardium. J Am Soc Echocardiogr 2003; 16:415–423. Skulstad H, Edvardsen T, Urheim S, et al. Postsystolic shortening in ischemic myocardium: active contraction or passive recoil? Circulation 2002; 106:718–724. Terkelsen CJ, Poulsen SH, Nørgaard BL, et al. Does postsystolic motion or shortening predict recovery of myocardial function after primary percutanous coronary intervention? J Am Soc Echocardiogr 2007; 20:505–511. Lim P, Pasquet A, Gerber B, et al. Is postsystolic shortening a marker of viability in chronic left ventricular ischemic dysfunction? Comparison with late enhancement contrast magnetic resonance imaging. J Am Soc Echocardiogr 2008; 21:452–457. Caracciolo G, Eleid MF, Abe H, et al. Nonuniform recovery of left ventricular transmural mechanics in ST-segment elevation myocardial infarction. Cardiovasc Ultrasound 2010; 8:31. Eek C, Grenne B, Brunvand H, et al. Postsystolic shortening is a strong predictor of recovery of systolic function in patients with non-ST-elevation myocardial infarction. Eur J Echocardiogr 2011; 12:483–489. Antoni ML, Mollema SA, Atary JZ, et al. Time course of global left ventricular strain after acute myocardial infarction. Eur Heart J 2010; 31:2006–2013. Hoffmann R, Stempel K, Kuhl H, et al. Integrated analysis of cardiac tissue structure and function for improved identification of reversible myocardial dysfunction. Coron Artery Dis 2009; 20:21–26. Hurlburt HM, Aurigemma GP, Hill JC, et al. Direct ultrasound measurement of longitudinal, circumferential, and radial strain using 2-dimensional strain imaging in normal adults. Echocardiography 2007; 24:723–731. Marwick TH, Leano RL, Brown J, et al. Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging 2009; 2:80–84. Szymczyk E, Chrzanowski Ł, Krzemin´ska-Pakuła M, et al. Echokardiograficzna ocena rotacji lewej komory przy zastosowaniu techniki s´ledzenia markero´w akustycznych (speckle tracking). Pol Przegl Kardiol 2009; 11:31–35.
© 2016 Italian Federation of Cardiology. All rights reserved
2D speckle tracking echocardiography for the assessment of regional contractile reserve after myocardial infarction Ewa Szymczyka, Piotr Lipieca, Błaz˙ej Michalskia, Konrad Szymczykb, Ahmed Shima, Bartłomiej Woz´niakowskib, Arkadiusz Rotkiewiczb, Ludomir Stefan´czykb and Jarosław D. Kasprzaka Aims To assess whether quantitative resting assessment of local myocardial function by 2D speckle tracking echocardiography may be helpful for the evaluation of myocardial viability in patients after ST-elevation myocardial infarction (STEMI) and for the prediction of left ventricular function recovery after 12-month follow-up. Methods The study group comprised 96 patients with first STEMI treated with successful primary percutaneous coronary intervention. Seven to 12 days after STEMI, all patients underwent resting echocardiography and low-dose dobutamine stress echocardiography (LDDSE) with visual assessment of contractile reserve which was the reference method for the evaluation of myocardial viability. After 12 months resting echocardiography with visual assessment of functional recovery was performed. Subsequently, acquired images were analyzed off-line using 2D speckle tracking echocardiography algorithm. Measurements included peak systolic longitudinal and transverse strain (SLS/STS), peak longitudinal and transverse strain (PLS/PTS), systolic longitudinal and transverse strain rate (SLSR/STSR) at baseline and after 12 months. Results All analyzed longitudinal parameters of strain had a very good diagnostic value, while transverse parameters
Introduction Myocardial ischemia may lead to a variety of tissue and global cardiac effects that impair cardiac function. It is well known that left ventricular dysfunction in patients with coronary artery disease may not represent irreversible myocardial necrosis, but rather still viable stunned or hibernating myocardium. ‘Stunned’ myocardium is defined as a transient postischemic dysfunction that persists for hours or days following reperfusion.1 ‘Hibernating’ myocardium is chronic but potentially reversible ischemic dysfunction as a result of long-duration reduced coronary blood flow that can be restored to normal by improving blood flow or by reducing oxygen demand.2 Dobutamine stress echocardiography (DSE), contrastenhanced MRI, single-photon emission computed tomography, and positron emission tomography are the most commonly used techniques for assessing myocardial viability in clinical practice. However, each mentioned technique detects a different feature of viable 1558-2027 ß 2016 Italian Federation of Cardiology. All rights reserved.
had only good diagnostic value for predicting myocardial viability defined on the basis of LDDSE. Moreover, SLS and PLS had good, whereas SLSR only satisfactory diagnostic value for predicting function recovery after 12-month follow-up. Conclusions 2D speckle tracking analysis applied during resting echocardiography can be helpful for the prediction of myocardial viability and functional recovery in patients after STEMI. Longitudinal strain parameters allow the prediction of local contractile reserve with SLS showing best correlation with DSE results functional recovery after 12-month follow-up. J Cardiovasc Med 2016, 17:374–381
Keywords: low-dose dobutamine stress echocardiography, speckle tracking echocardiography, stunned myocardium, viability a
Department of Cardiology, Medical University of Lodz and bDepartment of Radiology, Barlicki Teaching Hospital, Medical University of Lodz, Poland Correspondence to Ewa Szymczyk, MD, PhD, Department of Cardiology, Bieganski Hospital, Medical University of Lodz Kniaziewicza 1/5, 91–347 Lodz, Poland Tel: +48 42 251 6015; fax: +48 42 251 6015; e-mail: [email protected] Received 9 October 2013 Revised 21 July 2014 Accepted 21 July 2014
myocardium, which may not to be present simultaneously in each patient. It can be a reason for possible disagreements between different techniques.3 DSE has become a standard clinical tool because of its wide availability, relatively low cost, and absence of radiation exposure. However, when used for identification of contractile reserve, it requires administration of pharmacologic agents and involves a subjective interpretation of wall motion changes, requiring sufficient experience. 2D speckle tracking echocardiography (STE) is a non-Doppler method that rapidly developed from a research tool to an important part of clinical echocardiography that permits offline calculation of deformation parameters such as strain and strain rate, providing important insights into quantitative assessment of systolic and diastolic cardiac function.4 The aim of this study was to assess whether quantitative resting assessment of local myocardial function by 2D STE may be DOI:10.2459/JCM.0000000000000198
© 2016 Italian Federation of Cardiology. All rights reserved
2D STE for the assessment of regional contractile reserve Szymczyk et al. 375
helpful for the evaluation of myocardial viability in patients after ST-elevation myocardial infarction (STEMI) and for the prediction of left ventricular function recovery after 12-month follow-up.
Material and methods Study population
The study group comprised 96 consecutive patients (69 males, mean age 58 10 years) with first STEMI treated with successful primary percutaneous coronary intervention (defined as postprocedural flow Thrombolysis in Myocardial Infarction 3). STEMI was defined according to the universal definition of myocardial infarction.5 The criteria for enrollment were as follows: STEMI with onset of chest pain less than 12 h before primary percutaneous angioplasty, age over 18 years, and provision of patient’s informed written consent. The exclusion criteria were clinical instability on 7–12 days after STEMI, presence of severe, life-threatening arrhythmia, uncontrolled hypertension or hypotension, pregnancy, or breast-feeding. The research protocol was approved by the local bioethics committee. All patients received therapy according to European Society of Cardiology guidelines. Resting echocardiography, dobutamine stress echocardiography, and 12-month follow-up
Seven to 12 days after STEMI, all patients underwent resting echocardiography and subsequently DSE performed with incremental dobutamine infusion rates of 5, 10, and 20 mg/kg/min increased every 3 min according to the guidelines of Polish Cardiac Society.6 Criteria for terminating the test were completion of the protocol, heart rate increase of more than 15 bpm in comparison to baseline, evidence for severe ischemia (clinical, electrocardiographic, or echocardiographic), contractile reserve in all left ventricular segments, systolic blood pressure rise 240 mmHg or higher or drop 15 mmHg or lower from baseline, and patient request. Images were obtained at rest and at the end of each stage of DSE using a standard echocardiographic system Vivid 7 (General Electric, Vingmed, Horten, Norway) with the M4S probe. Images were acquired in apical four-chamber, three-chamber, and two-chamber views, and cine loops were digitally stored and postprocessed on EchoPAC workstation 6.1.0 (General Electric, Vingmed, Horten, Norway). Left ventricular ejection fraction was calculated using the biplane Simpson’s method. A 16-segment model of the left ventricle was used for wall motion analysis. Segments were graded as normokinetic, hypokinetic, akinetic, or dyskinetic on the basis of subjective assessment of wall motion amplitude and changes of left ventricular thickness. DSE performed by expert echocardiographer was used as a reference method for the evaluation of myocardial viability. In our study, left ventricular segments were defined as viable if they were normokinetic or hypokinetic in resting echocardiography or showed a
contractile reserve during DSE (improvement from akinesis or dyskinesis at baseline echocardiography to hypokinesis, normokinesis, or hyperkinesis at peak stage of DSE). According to baseline echocardiographic assessment of wall motion abnormalities, the myocardial viability was assessed in the group of all segments (normokinetic, hypokinetic, akinetic, and dyskinetic) and in the subgroup of akinetic and dyskinetic segments. After 12 months, each patient underwent control resting echocardiography with visual assessment of functional recovery in segments that were akinetic or dyskinetic at baseline resting echocardiography. 2D speckle tracking echocardiography
2D speckle tracking is a recent modality allowing nonDoppler calculation of regional myocardial velocities in any desired direction. Computer-based speckle tracking algorithms provide the value of displacement of pixel clusters between 2D image frames sampled at known refresh rate. Strain is a dimensionless quantity of myocardial deformation, which is expressed in percentage (%) and mathematically defined as the change of myocardial fiber length during end-systole compared with its original length in end-diastole.7 Strain rate expressed as 1 s1 is the spatial derivative of tissue velocity (mm/s).8 In our study, STE analysis was assessed in apical views with frame rate between 60 and 90 frames/s. The analyzed parameters included systolic longitudinal strain (SLS), systolic transverse strain (STS), peak longitudinal strain (PLS), peak transverse strain (PTS), SLS rate (SLSR), and STS rate (STSR). Systolic strain and strain rate were defined as the maximal value obtained prior to aortic valve closure, whereas peak strain and strain rate were measured as the maximal value of the parameter in physiological direction throughout cardiac cycle (Fig. 1). All parameters were measured automatically offline by expert echocardiographer using EchoPAC in each segment of the left ventricle. In each apical view, computer-assisted outlining of the left ventricular endocardial border was performed. Afterwards, the tracking of cardiac motion was done automatically by the software. Manual correction was done when judged necessary after visual verification of myocardial tracking accuracy. Segments with poor visualization were excluded from the further analysis. The software generated curves of longitudinal and transverse strain and strain rate for each segment of the left ventricle (Fig. 2). Statistical methods
Statistical analysis of data was performed using MedCalc version 9.5.2.0 (MedCalc Software, Frank Schoonjans 1993–2008, Belgium). In case of normal distribution, data were presented as means and standard deviation (SD); variables that did not follow normal distribution
© 2016 Italian Federation of Cardiology. All rights reserved
376 Journal of Cardiovascular Medicine 2016, Vol 17 No 5
Fig. 1 AVC
AVC
0
SLS –15 PLS
Transverse stran (%)
Transverse stran (%)
PTS
20
STS
0
Example curves of longitudinal (left panel) and transverse (right panel) strain. PLS, peak longitudinal strain; PTS, peak transverse strain; SLS, systolic longitudinal strain; STS, systolic transverse strain.
were presented as medians and upper and lower quartiles. A P value less than 0.05 was considered as statistically significant. Independent samples t-test was used for between-group comparisons. To determine the most accurate threshold value for systolic and peak longitudinal/transverse strain, and systolic longitudinal/transverse strain rate for viability detection, the results were analyzed with the use of four-field distribution table with variable threshold value, with the use of the receiveroperating characteristic (ROC) curve. The Youden’s index was used to identify the optimal cut-points of strain and strain rate for sensitivity and specificity.
Results Study group characterization
Arterial hypertension was diagnosed in 58 patients (60%), whereas obesity and diabetes were present in 30 (31%) and 19 (20%) patients, respectively. Over a half of patients (53%) were active smokers. The most frequent
localization of culprit lesions in coronary angiography was left anterior descending artery (49 patients, 51%), followed by right coronary artery (34 patients, 35%) and circumflex artery (13 patients, 14%). Baseline echocardiographic characteristic
The mean resting left ventricular ejection fraction measured with the biplane Simpson’s method was 50 7% (range 29–65%), whereas wall motion score index was 1.47 0.3 (range 1.1–2.5). Semiquantitative analysis of baseline left ventricular systolic function of 1536 segments revealed that 1111 segments (72.3%) were normokinetic, whereas 145 (9.4%) hypokinetic, 251 (16.3%) akinetic, and 13 (0.9%) dyskinetic. Only 16 segments (1.0%) were excluded from visual assessment of systolic function. However, precluding speckle tracking analysis, 211 segments (13.7%) were excluded from the analysis because of inadequate image quality in resting echocardiography.
Fig. 2
Example curves of longitudinal strain for six segments obtained from four-chamber apical view (panel a) and transverse strain for six segments from three-chamber apical view (panel b).
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2D STE for the assessment of regional contractile reserve Szymczyk et al. 377
Dobutamine stress echocardiography
2D speckle tracking echocardiography
Resting quantitative analysis with the use of 2D STE was performed in 96 patients from the study group (1536 segments). However, 211 segments (13.7%) were excluded from further analysis because of suboptimal image quality. Values of strain and strain rate were significantly lower for segments with impaired wall motion assessed by semiquantitative visual method (Table 1). Also, values of longitudinal strain and strain rate were significantly higher in segments with preserved myocardial viability. There was no statistically significant difference between mean values of STS and PTS in viable and nonviable segments (Table 2). Based on values of SLS (cutoff 10.6%), three of 11 (27.3%) Table 1
Comparison of resting values of strain and strain rate in viable and nonviable segments – analysis for normokinetic, hypokinetic, akinetic, and dyskinetic segments in baseline resting echocardiography
Table 2
The results of DSE were analyzed in 82 patients (1312 segments) because in 14 patients, DSE was inconclusive because of normal left ventricular function with no wall motion abnormalities on 7–12 days after STEMI (six patients), inadequate image quality (two patients), presence of left ventricular apical thrombus (two patients), uncontrolled hypertension (two patients), or earlier termination of DSE because of arrhythmia (two patients). The mean left ventricular ejection fraction measured with the biplane Simpson’s method increased from 50 7% at baseline to 60 8% at peak stage, whereas wall motion score index decreased from 1.47 0.3 at baseline to 1.33 0.3 (1.0–2.2) at peak stage. With the assumption that viable segments are those with normokinesis and hypokinesis at resting echocardiography (971 normokinetic segments and 117 hypokinetic segments), contractile reserve was assessed in 224 segments (eight segments with resting dyskinesis, 216 segments with resting akinesis) in DSE. At peak stage of DSE, normokinesis and hypokinesis were observed in 21 and 54 segments, whereas akinesis and dyskinesis were noted in 143 and 6 segments, respectively. Therefore, contractile reserve was confirmed during DSE in 75 (33.5%) segments. Taking into account data from resting (1088 viable segments) and stress echocardiography (75 viable segments), viability was confirmed in 1163 from 1312 segments (88.6%) in the group of 82 patients with performed DSE.
Parameter
Viable segments (n ¼ 1088)
Nonviable segments (n ¼ 224)
P
SLS (%) PLS (%) SLSR (s1) STS (%) PTS (%) STSR (s1)
14.9 7.16 16.05 6.32 1.07 0.40 25.68 24.56 23.17 23.78 2.07 1.28
2.93 6.07 4.98 5.42 0.58 0.32 23.99 24.5 20.76 24.1 1.61 1.16
3.25% 0.602 0.01 72.7% 45.2% PTS >14% 0.566 NS – – 0.540 NS – – STSR 1.75 s1
PPV
NPV
Accuracy
98.8% 99.3% 98.6% 24.8% 17.7% 15.8%
29.8% 21.9% 17.9% 93.2% 93.6% 92.5%
91.0% 85.5% 86.0% 76.4% 61.5% 59.2%
98.7% 98.7% 99.4% 65.2% – –
14.6% 25.1% 13.5% 54.0% – –
77.8% 88.3% 75.6% 61.3% – –
AUC, area under the curve; NPV, negative predictive value; PLS, peak longitudinal strain; PPV, positive predictive value; PTS, peak transverse strain; SLS, systolic longitudinal strain; SLSR, systolic longitudinal strain rate; STS, systolic transverse strain; STSR, systolic transverse strain rate.
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2D STE for the assessment of regional contractile reserve Szymczyk et al. 379
1.45 s1 in resting echocardiography could be recognized as indicators of myocardial viability. Longitudinal strain parameters allow the prediction of local contractile reserve with SLS showing high concordance with DSE results and functional recovery after 12-month follow-up. Cutoff values of SLS less than 10.1% and PLS less than 10.4% in resting echocardiography could be recognized as predictors of left ventricular function improvement after 12 months from STEMI. DSE is well recognized but requires expertise in diagnostic technique for the evaluation of myocardial viability in patients with impaired left ventricular function. The visual interpretation of wall motion abnormalities is semiquantitative and subjective, which is the reason for low interinstitutional observer agreement.9 The step toward objectification of results was the implementation of quantitative regional myocardial deformation parameters such as strain and strain rate obtained by tissue Doppler echocardiography and STE.10,11 Doppler-based ultrasound techniques quantify only the axial angle-dependent component of myocardial motion, along the direction of the transmitted ultrasound wave, and are prone to errors induced by random noise.12 STE is a newer echocardiographic approach based on high- resolution ultrasound imaging that allows accurate quantifying longitudinal, radial, and circumferential strain and strain rate regardless of limitations of Doppler technique.13,14 STE allows indepth evaluation of myocardial systolic and diastolic dynamics across a broad range of physiologic and pathologic conditions.15,16 One of the clinically important applications of STE is the assessment of myocardial viability not only during stress but also by resting echocardiography.17,18 Animal-based studies by Aarsæther et al. and Migrino et al.19,20 revealed that longitudinal, transverse, and circumferential strain values derived from STE correlated well with the extent of necrosis in myocardial segments following acute myocardial infarction and accurately reflected myocardial segmental viability, distinguishing infarcted from viable myocardium. Also, human studies revealed similar results. Tanimoto et al.21 analyzed transverse strain in patients 2 weeks after STEMI and observed significant inverse correlation between transmural extent of infarction determined by contrast-enhanced MRI and PTS value (r ¼ 0.74, P < 0.0001), proving that STE can be a useful and accurate method for evaluating myocardial viability. Gjesdal et al. studied the group of patients 9 months after first myocardial infarction using STE and MRI. Peak SLS was able to separate infarcted from noninfarcted myocardial segments, as assessed with contrastenhanced MRI. A value of 15% for peak SLS was demonstrated to be able to identify infarcted tissue with a sensitivity of 83% and a specificity of 93%. Accordingly, higher (more negative) strain values were associated with the presence of viable myocardium.22 Mollema et al. demonstrated that global longitudinal left ventricular
strain after acute infarction is strongly related to infarct size and may be a marker of myocardial viability. A cutoff value of 13.7% for baseline global longitudinal strain, with a sensitivity of 86% and a specificity of 74%, was able to predict left ventricular function recovery at 1-year follow-up.23 Similarly to all previously mentioned studies, our results revealed that longitudinal systolic and peak strain and strain rate had very good diagnostic value (85.5–91.0% for analysis of normokinetic, hypokinetic, akinetic, and dyskinetic segments; 75.6–88.3% for analysis of dyskinetic and akinetic segments), whereas transverse parameters only good (59.2–76.4% for analysis of normokinetic, hypokinetic, akinetic, and dyskinetic segments) diagnostic value for predicting myocardial viability determined by visual assessment of contractile reserve during DSE in patients 7–12 days after successfully reperfused STEMI. All longitudinal parameters had high positive predictive values for the assessment of myocardial viability, meaning that more negative values of longitudinal strain predicted higher probability of contractile reserve corresponding with myocardial viability. Respectively, transverse parameters had high negative predictive value (about 93%) for the assessment of myocardial viability, meaning that lower values of transverse strain predicted higher probability of lack of myocardial viability. Postsystolic shortening defined as myocardial shortening after aortic valve closure is considered a marker of disease with diagnostic potential for identifying actively contracting and hence viable myocardium.24,25 This was also observed in our study in analysis of akinetic and dyskinetic segments in which peak strain values were more predictive as compared with peak systolic values. However, for analysis of normokinetic, hypokinetic, akinetic, and dyskinetic segments, peak strain values were markedly less predictive as compared with peak systolic values. This may be a result of misleading contribution of postsystolic contraction of the myocardium, which is consistent with other authors stating that postsystolic shortening is not a specific marker of viability.26,27 In our study, 42% of akinetic or dyskinetic segments at baseline resting echocardiography showed functional recovery 12 months after STEMI. Among strain parameters, only SLS and PLS had good diagnostic value for predicting functional improvement 12 months after STEMI. The relatively high negative predictive value of longitudinal strain parameters (75–80%) indicates that less negative values correspond with lack of functional recovery. Those results are in concordance with observation of Caracciolo et al. of 42 patients with first STEMI, treated with percutaneus angioplasty. Likewise, the authors confirmed that longitudinal and circumferential (but not transverse) parameters were helpful in predicting functional recovery of left ventricular segments
© 2016 Italian Federation of Cardiology. All rights reserved
380 Journal of Cardiovascular Medicine 2016, Vol 17 No 5
5 months after STEMI.28 Also, Eek et al. and Antoni et al. had similar observation according longitudinal strain parameters.29,30 Although in our study transverse parameters of strain had nonsatisfactory diagnostic value for predicting functional recovery 12 months after STEMI, Hoffmann et al.31 confirmed predictive value of transverse parameters 9 months after revascularization. In comparison with other diagnostic methods such as dobutamine stress, myocardial contrast echocardiography, MRI, or positron emission tomography, STE based on resting echocardiography does not require the administration of pharmacological agents, radiation exposure, or sophisticated instruments and analysis. This well tolerated and relatively inexpensive technique can be widely applied in echocardiographic laboratories, which may facilitate the assessment of myocardial viability in everyday practice. Knowledge of myocardial viability is crucial for decision on possible revascularization or cardiac resynchronization therapy. Although echocardiographic quantitative analysis of the systolic function by speckle tracking is a well tolerated study, it is important to notice that the myocardial viability assessment was not possible in as many as 13.7% of the segments in our study, owing to suboptimal quality of the images usually obtained in the clinical practice. In comparison, Hurlburt et al. excluded from the analysis only 6% of segments, but their study group consisted of 60 healthy, young individuals, who, by definition, did not have obesity or obstructive lung disease.32 However, Marwick et al.33 excluded 21% of segments in the analysis of 242 healthy volunteers aged 18–80 years.
detecting myocardial viability at rest in all segments independent of wall motion alteration severity. Also, the results of this single-center study have been obtained from a relatively small group of 96 patients, although as many as 1536 segments were analyzed. Furthermore, in our study, there was only one expert echocardiographer who was analyzing 2D speckle tracking echocardiographic data and intraobserver and interobserver variability were not assessed, which is a strong limitation of the study. Finally, a novel method of speckle tracking based on complete volumetric datasets (4D strain) was not available for our study.
Conclusion 2D speckle tracking analysis applied during resting echocardiography can be helpful for the prediction of myocardial viability and functional recovery in patients after STEMI. Longitudinal strain parameters allow the prediction of local contractile reserve with SLS showing best correlation with DSE results for the assessment of functional recovery after 12-month follow-up. Compared with other diagnostic methods, measurements of strain parameters based on resting echocardiography offer an interesting alternative to dobutamine testing, but also may become competitive against other techniques because of wide availability and lower cost. This hypothesis requires, however, separate validation studies.
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Study limitations Several limitations of this study must be considered. First, the analysis of strain profile is largely dependent on image quality. Therefore, careful attention was given when recording the images, but still 13.7% of the segments were excluded from the analysis. Second, we used only low-dose DSE as a standard qualitative test to determine the myocardial viability and the subjectivity factor could play a role even though the assessment was performed by a cardiologist with extensive experience in stress echocardiography. The use of cardiac MRI for assessing the viability would be more accurate for a comparison between techniques. Also, we are concerned that the study design does not allow to demonstrate that 2D STE overcomes the limitation of subjective interpretation of DSE, but is rather able to provide similar information, without the administration of pharmacologic agents. Moreover, only apical views were obtained during rest and stress echocardiographic examination, enabling the analysis of longitudinal and transverse but not circumferential strain and strain rate or rotation parameters, which could provide additional information.34 Another limitation of this article is quite low values of sensitivity and negative predictive value of longitudinal strain in
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