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Circumferential 2D-strain imaging for the prediction of long term response to cardiac resynchronization therapy
Cardiovascular Ultrasoundvolume 6, Article number: 28 (2008)
Cardiac Resynchronization Therapy (CRT) leads to hemodynamic and clinical improvement in heart failure patients. The established methods to evaluate myocardial asynchrony analyze longitudinal and radial myocardial function. This study evaluates the new method of circumferential 2D-strain imaging in the prediction of the long-term response to CRT.
Methods and results
38 heart failure patients (NYHA II-III, QRS > 120 ms, LVEF < 0.35) received CRT and echocardiographic evaluation with a mean follow-up of 9.4 months. 18 (47.4%) of the patients were hemodynamic responders to long-term CRT. In the responder group, the maximum delay in the circumferential 2D-strain in the basal segments decreased (246 ± 94 to 123 ± 92 ms, p < 0.001). In the non-responder group there was no significant change (pre CRT: 195 ± 86, post CRT 135 ± 136 ms, p = 0.84). This was paralleled by a reduction of the maximum delay in the radial and longitudinal 2D strain in the basal segments. In ROC analysis, the baseline delay of circumferential 2D strain (AUC 0.66 (± 0.14)) does not predict a long-term response to CRT (p = 0.37).
There is a significant decrease in the circumferential 2D-strain derived delays after CRT, indicating that resynchronization induces improvement in all three dimensions of myocardial contraction. However, the resulting predictive values of 2D strain delays are not superior to longitudinal and radial 2D-strain or TDI delays.
Cardiac resynchronisation therapy (CRT) is an effective therapy for advanced chronic heart failure. Randomized, controlled trials indicate that CRT improves hemodynamics, reverse remodelling, quality of life, hospitalisation and mortality [1–7]. However, in the large CRT studies, the responder rates were low (43–63%) [6, 8, 9]. In the CARE-HF (2005): about 50% of the patients responded clinically. The COMPANION study did not publish the responder rates (2004) .
In this context, it is essential to select patients for CRT carefully and to define predictors. Several studies have focused on prospectively predicting successful CRT by echocardiography. However, only parameters of longitudinal and radial myocardial function were used [8, 10].
There are conflicting data about the best predictor for hemodynamic and clinical improvement. Several echocardiographic (including 3D echocardiography) and clinical predictors were assessed recently [10–14].
Myocardial contraction is a complex three-dimensional motion. Fibre architecture includes longitudinal, radial and circumferential oriented fibres. The majority of fibres have a longitudinal orientation. However, radial and circumferential fibres contribute to myocardial systolic function [15, 16].
Circumferential myocardial function can be analysed by 2D ("speckle tracking") derived echocardiography. Unlike Tissue Doppler derived velocity and strain, 2D-derived analysis  is angle-independent and allows the measurement of circumferential strain [18, 19].
The aim of this study is to examine the improvement of circumferential myocardial contractility after CRT is analysed.
Patients and methods
In this monocentric study, we included 38 heart failure patients (NYHA II-IV) with a LVEF < 0.35 and a QRS width > 120 ms. All patients received a CRT-device with automatic defibrillator (ICD) function and were fully documented by 2D and Tissue Doppler echocardiography. Follow-up was at least 6 months. The heart failure medication was unchanged three months prior to implantation of the CRT-ICD to obtain unbiased data regarding cardiac improvement after CRT.
Successful resynchronization therapy was defined as a relative reduction of the left-ventricular end-systolic volume (LV-ESV) of more than 15% [20, 21] and a relative increase of the LVEF of more than 25% compared to baseline . The latter has been evaluated to a follow-up interval of 6 months.
Echocardiography was performed by Vivid 5 and Vivid 7 (GE Vingmed, Horton, Norway). The images were stored digitally and analyzed off-line by EchoPac PC Dimension (GE Vingmed, Horton Norway). For TDI and 2D echocardiography analysis, three beats were stored.
Circumferential 2D strain was measured in the parasternal short axis at the level of the papillary muscles. The endocardial border of the end-systole was traced manually. The following six segments were analysed: antero-septal, anterior, lateral, posterior, inferior, septal. The maximal delays in opposite segments (anterior-septal/posterior, anterior/inferior, septal/lateral) were then calculated. The maximum delay was then used for further analyses.
The maximal longitudinal delays were obtained from apical and the maximal radial delays were measured in the parasternal short axis views.
Written consent was obtained from each patient, and the ethics committee of the Charité University Hospital approved the protocol.
Statistics were calculated by SPSS (version 12.0, Chicago, Ill, USA). Results are expressed as mean (± standard deviation). Comparisons of parametric variables between the responders and the non-responders were calculated by paired Student's t-test. The comparison of echocardiographic parameters between groups was calculated by unpaired t-test. Dichotomized data were analyzed by the Chi2-test. The level of significance was p = 0.05.
Eighteen (47.4%) of the 38 patients were hemodynamic responders to long-term CRT. The baseline characteristics in the responder and non-responder group did not differ significantly. Baseline characteristics see Table 1.
The hemodynamics of the responder and non-responder group: see Table 2. After CRT, there is a significant reverse remodelling in the responder group. The placement of the left ventricular lead was in posterolateral position in 52.6% of the patients. The lead placement was not different in the responder and the non-responder group (p = 0.34).
2D strain echocardiography
The maximum delay in the circumferential, longitudinal and radial 2D-strain decreased significantly in the responder group but not in the non-responder group (Table 3, Figure 2). Figure 1 illustrates a responder in the long-term follow-up with improvement of circumferential synchrony. Two videoclips showing circumferential 2D strain in the parasternal short axis of a patient with DCM (See additional file 1) and a healthy control (See additional file 2) are attached.
Tissue Doppler echocardiography
The maximum delay in the peak systolic velocities in the basal segments decreased in the responder group but not in the non-responder group. The maximum delay in the peak systolic strain in the basal segments did not change significantly in the responder group or in the non-responder group. The s-wave velocity in the basal septum and the TDI-based strain did not change significantly in the two patient groups (Table 2).
ROC (Receiver Operator Characteristic) curve analysis (Figure 3) was performed to calculate the best cut-off value to predict response to CRT (Table 3). The area under the curve is 0.664 (± 0.144) for baseline maximum delay of circumferential 2D strain in the prediction of CRT response, which indicates a fair accuracy. The predictive value of circumferential 2D strain is not significant (p = 0.365) The best cut-off for this discrimination is a delay of 141.5 ms (sensitivity 93.3%, specificity 46.3%).
Intra- and Interobserver variability
Intra- and interobserver reliabilities were calculated by the intraclass correlation coefficient (ICC). There were good correlations for Tissue Doppler measurements (ICC = 0.94, p < 0.001 and 0.96, p < 0.001, respectively) and circumferential (non-Doppler) 2 D strain measurements (ICC = 0.92, p < 0001 and 0.91, p < 0.001, respectively).
The main finding of this study is that circumferential 2D Strain delays decrease significantly in the responders but not in the non-responders to CRT. The analysis of circumferential 2D strain broadens the view of three-dimensional myocardial motion and indicates that circumferential myocardial synchrony is improved by CRT.
The majority of myocardial fibres have longitudinal orientation. Early in the development of heart failure, longitudinal function is impaired, with a compensation of radial and circumferential (= short axis) function . The progressive dilated heart in heart failure is the result of impaired radial and circumferential function . Our study indicates that circumferential function can be partially restored by CRT.
Circumferential asynchrony might play an important role in the measurement of overall asynchrony. A TAGGED-MRT-study found that asynchrony assessed by longitudinal motion is less sensitive, follows different time courses than circumferential asynchrony, and may manifest CRT benefit during specific cardiac phases depending on pacing mode. These results underscore the limitations of longitudinal analyses of asynchrony .
There are technical issues of circumferential 2D Strain of importance. The rather low frame rate (50–100/min) can impair the detection of myocardial contraction peaks. Despite the low temporal resolution of 2D-Strain, significant changes in our study and of previous studies [11, 27, 28] support that the method of 2D strain allows detection of myocardial asynchrony. The intra- and inter-observer variability is low and therefore, it seems unlikely that the observed differences in echocardiography are related to this.
This is supported by a recent study by Becker . Circumferential 2D strain analysis was prospectively used to determine to optimal LV-lead position. The authors found that the optimal lead position led to more favourable reverse remodelling.
In contrast to our results, Zhang  found an improvement of the absolute value of circumferential (but not radial and longitudinal) 2D strain after three months of successful CRT. In our study, neither the longitudinal nor the radial or circumferential 2D strain values changed in the long-term follow up. We have used 2 D strain as a tool to measure asynchrony (i.e. we have analysed the maximum delays) and not of systolic myocardial performance (i.e. absolute values).
Neither circumferential nor radial and longitudinal 2D strain delays are able to predict CRT response. The 2 D Strain parameters are not superior to Tissue Doppler derived asynchrony. We conclude that no single parameter is able to help in patient selection for CRT.
The future role of echocardiography in selection of CRT candidates is not yet resolved. The recently published consensus statement of the American Society of Echocardiography points out that echocardiographic selection of CRT candidates should only be performed in borderline cases with difficult decision making .
The results from the CRT patients in our institution have led to the strategy currently used: an integration of seven parameters of inter- and intra-ventricular asynchrony in addition to the established parameters. If more than two parameters are indicative of myocardial asynchrony, a CRT indication supported by echocardiography is seen. We hypothesize that not single parameters of myocardial asynchrony but the integration of multiple echocardiographic parameters of asynchrony will facilitate the selection of CRT candidates.
In conclusion, circumferential 2D Strain delays decrease significantly after CRT, indicating an improvement in all three dimensions of myocardial contraction. However, the resulting predictive values of 2D strain delays are not superior to longitudinal and radial 2D-strain or TDI delays.
Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM: Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac Resynchronization Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure. N Eng J Med. 2004, 350: 2140-2150. 10.1056/NEJMoa032423.
Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S, McKenna W, Fitzgerald M, Deharo JC, Alonso C, Walker S, Braunschweig F, Bailleul C, Daubert JC: Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol. 2002, 40: 111-118. 10.1016/S0735-1097(02)01932-0.
Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Trupp RJ, Underwood J, Pickering F, Truex C, McAtee P, Messenger J: (MIRACLE Study Group). Multicenter InSync Randomized Clinical evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002, 346: 1845-1853. 10.1056/NEJMoa013168.
Saxon LA, De Marco T, Schafer J, Chatterjee K, Kumar UN, Foster E, (VIGOR Congestive Heart Failure Investigators): Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling. Circulation. 2002, 105: 1304-1310. 10.1161/hc1102.105730.
Sundell J, Engblom E, Koistinen J, Ylitalo A, Naum A, Stolen KQ, Kalliokoski R, Nekolla SG, Airaksinen KE, Bax JJ, Knuuti J: The effects of cardiac resynchronization therapy on left ventricular function, myocardial energetics, and metabolic reserve in patients with dilated cardiomyopathy and heart failure. J Am Coll Cardiol. 2004, 43 (6): 1027-1033. 10.1016/j.jacc.2003.10.044.
Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, Tavazzi L, Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators: The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005, 352 (15): 1539-49. 10.1056/NEJMoa050496.
Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K, Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) Trial Investigators: Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure. JAMA. 2003, 289: 2685-2694. 10.1001/jama.289.20.2685.
Beshai JF, Grimm RA, Nagueh SF, Baker JH, Beau SL, Greenberg SM, Pires LA, Tchou PJ: RethinQ Study Investigators. Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med. 2007, 357 (24): 2461-2471. 10.1056/NEJMoa0706695.
Yu CM, Abraham WT, Bax J, Chung E, Fedewa M, Ghio S, Leclercq C, León AR, Merlino J, Nihoyannopoulos P, Notabartolo D, Sun JP, Tavazzi L, PROSPECT Investigators: Predictors of response to cardiac resynchronization therapy (PROSPECT) – study design. Am Heart J. 2005, 149: 600-605. 10.1016/j.ahj.2004.12.013.
Linde C: Results of the predictors of response to CRT (PROSPECT) trial. Hotline Session III (Number: 3222). 4 September 2007, [http://www.escardio.org/knowledge/congresses/CongressReports/2007/hl-ctu/3222-linde-hotline2.htm]
Knebel F, Schattke S, Bondke H, Walde T, Eddicks S, Reibis R, Baumann G, Borges AC: Evaluation of longitudinal and radial two-dimensional strain imaging versus Doppler tissue echocardiography in predicting long-term response to cardiac resynchronization therapy. J Am Soc Echocardiogr. 2007, 20 (4): 335-341. 10.1016/j.echo.2006.09.007.
Kapetanakis S, Kearney MT, Siva A, Gall N, Cooklin M, Monaghan MJ: Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony. Circulation. 2005, 112: 992-1000. 10.1161/CIRCULATIONAHA.104.474445.
Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, Wall van der EE, Chan YS, Kong SL, Bax JJ: Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation. 2005, 112: 1580-1586. 10.1161/CIRCULATIONAHA.105.538272.
Dohi K, Suffoletto MS, Schwartzman D, Ganz L, Pinsky MR, Gorcsan J: Utility of echocardiographic radial strain imaging to quantify left ventricular dyssynchrony and predict acute response to cardiac resynchronization therapy. Am J Cardiol. 2005, 96 (1): 112-116. 10.1016/j.amjcard.2005.03.032.
Reese TG, Weisskoff RM, Smith RN, Rosen BR, Dinsmore RE, Wedeen VJ: Imaging myocardial fiber architecture in vivo with magnetic resonance. Magn Reson Med. 1995, 34 (6): 786-791. 10.1002/mrm.1910340603.
van Doorn A, Bovendeerd PH, Nicolay K, Drost MR, Janssen JD: Determination of muscle fibre orientation using Diffusion-Weighted MRI. Eur J Morphol. 1996, 34 (1): 5-10. 10.1076/ejom.220.127.116.1156. Erratum in: Eur J Morphol 199; 34(4):325.
Leitman M, Lysyansky P, Sidenko S, Shir V, Peleg E, Binenbaum M, Kaluski E, Krakover R, Vered Z: Two-dimensional strain-a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr. 10: 1021-1029.
Helle-Valle T, Crosby J, Edvardsen T, Lyseggen E, Amundsen BH, Smith HJ, Rosen BD, Lima JA, Torp H, Ihlen H, Smiseth OA: New noninvasive method for assessment of left ventricular rotation: speckle tracking echocardiography. Circulation. 2005, 112 (20): 3149-3156. 10.1161/CIRCULATIONAHA.104.531558.
Amundsen BH, Helle-Valle T, Edvardsen T, Torp H, Crosby J, Lyseggen E, Støylen A, Ihlen H, Lima JA, Smiseth OA, Slørdahl SA: Noninvasive myocardial strain measurement by speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol. 2006, 47 (4): 789-793. 10.1016/j.jacc.2005.10.040.
Yu CM, Wing-Hong Fung J, Zhang Q, Sanderson JE: Understanding nonresponders of cardiac resynchronization therapy – current and future perspectives. J Cardiovasc Electrophysiol. 2005, 10: 1117-1124. 10.1111/j.1540-8167.2005.40829.x.
Yu CM, Fung JW, Zhang Q, Chan CK, Chan YS, Lin H, Kum LC, Kong SL, Zhang Y, Sanderson JE: Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation. 2004, 110: 66-73. 10.1161/01.CIR.0000133276.45198.A5.
Penicka M, Bartunek J, De Bruyne B, Vanderheyden M, Goethals M, De Zutter M, Brugada P, Geelen P: Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography. Circulation. 2004, 109: 978-983. 10.1161/01.CIR.0000116765.43251.D7.
Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H: Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989, 5: 358-367.
Yu CM, Lin H, Yang H, Kong SL, Zhang Q, Lee SW: Progression of systolic abnormalities in patients with "isolated" diastolic heart failure and diastolic dysfunction. Circulation. 2002, 105 (10): 1195-1201. 10.1161/hc1002.105185.
Greenbaum RA, Ho SY, Gibson DG, Becker AE, Anderson RH: Left ventricular fibre architecture in man. Br Heart J. 1981, 45 (3): 248-263. 10.1136/hrt.45.3.248.
Helm RH, Leclercq C, Faris OP, Ozturk C, McVeigh E, Lardo AC, Kass DA: Cardiac dyssynchrony analysis using circumferential versus longitudinal strain: implications for assessing cardiac resynchronization. Circulation. 2005, 111 (21): 2760-2767. 10.1161/CIRCULATIONAHA.104.508457.
Becker M, Kramann R, Franke A, Breithardt OA, Heussen N, Knackstedt C, Stellbrink C, Schauerte P, Kelm M, Hoffmann R: Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography. Eur Heart J. 2007, 28 (10): 1211-1220. 10.1093/eurheartj/ehm034.
Zhang Q, Fung JW, Yip GW, Chan JY, Lee AP, Lam YY, Wu LW, Wu EB, Yu CM: Improvement of Left Ventricular Myocardial Short-axis, but not Long-axis Function or Torsion after Cardiac Resynchronization Therapy-An Assessment by Two-Dimensional Speckle Tracking. Heart. 2008
Gorcsan J, Abraham T, Agler DA, Bax JJ, Derumeaux G, Grimm RA, Martin R, Steinberg JS, Sutton MS, Yu CM, American Society of Echocardiography Dyssynchrony Writing Group: Echocardiography for cardiac resynchronization therapy: recommendations for performance and reporting – a report from the American Society of Echocardiography Dyssynchrony Writing Group endorsed by the Heart Rhythm Society. J Am Soc Echocardiogr. 2008, 21 (3): 191-213. 10.1016/j.echo.2008.01.003.
The authors like to thank Christine Scholz for excellent technical assistance.
FK and SS have equally contributed to the study. FK, SS, ACB, AG, SE participated in contributions to conception, analysis and interpretation of data, the follow-up echocardiographic examinations and made comments to the manuscript. HB has implanted the CRT systems and has analyzed data. BG has supervised and commented the study. ACB was the supervisor of echo examinations, is head of the echo lab, contributed by revising the manuscript critically.