Analysis of LV Lead Position in Cardiac Resynchronization Therapy Using Different Imaging Modalities

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1 JACC: CARDIOVASCULAR IMAGING VOL. 3, NO., BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN X/$36.00 PUBLISHED BY ELSEVIER INC. DOI: /j.jcmg Analysis of LV Lead Position in Cardiac Resynchronization Therapy Using Different Imaging Modalities Michael Becker, MD,* Ertunc Altiok, MD,* Christina Ocklenburg, MSC, Renate Krings, MD,* Dan Adams, PHD, Michael Lysansky, Barbara Vogel, MD,* Patrick Schauerte, MD,* Christian Knackstedt, MD,* Rainer Hoffmann, MD* Aachen, Germany; and Haifa, Israel OBJECTIVES This study sought to evaluate whether left ventricular (LV) lead position in cardiac resynchronization therapy (CRT) can be determined by myocardial deformation imaging during LV pacing and to compare imaging techniques for analysis of LV lead position. BACKGROUND LV lead position has a significant impact on effectiveness of CRT, but clinically applicable methods to determine LV lead position are less defined. METHODS In 6 patients (3 years, 34 men) undergoing CRT, fluoroscopy and 2 myocardial deformation imaging based approaches were applied to determine the LV lead position. Myocardial deformation imaging based techniques were used to determine 1) the segment with maximal temporal difference of peak circumferential strain before and while on biventricular CRT; and 2) the segment with earliest peak systolic circumferential strain during pure LV pacing. Twelve-month echocardiography was performed to determine LV remodeling and improvement in function. Optimal LV lead position was defined as concordance or immediate neighboring of the determined LV lead position to the segment with latest systolic strain prior to CRT. RESULTS LV lead position determined during LV pacing correlated to the position determined by fluoroscopy (kappa 0.761). Patients with optimal LV lead position had greater improvement in LV ejection fraction and decrease in end-diastolic volume than those with nonoptimal LV lead position (12 4% vs. 7 3%, p 0.001, and ml vs ml, p 0.001, respectively). Determination of the LV lead position based on myocardial deformation imaging during LV pacing showed greater discriminatory power for improvement of ejection fraction (difference optimal vs. nonoptimal lead position group: ml; p 0.001) than deformation imaging with biventricular pacing ( ml; p 0.007) and fluoroscopy ( ml; p 0.03). CONCLUSIONS Myocardial deformation imaging during LV pacing allows determination of the LV lead position in CRT. Improvement in LV function and remodeling as indicators of optimal LV lead position can be best predicted by LV lead position analysis during LV pacing. (Left Ventricular Lead Position in Cardiac Resynchronization Therapy; NCT ) (J Am Coll Cardiol Img 2010;3:472 81) 2010 by the American College of Cardiology Foundation From the *Department of Cardiology, Medical Engineering, and the Department of Medical Statistics, University RWTH Aachen, Aachen, Germany; and the Department of Biomedical Engineering, Technion Haifa, Haifa, Israel. This study was presented in part at the Scientific Sessions of the American Heart Association 2008, New Orleans, Louisiana. Manuscript received May 11, 2009; revised manuscript received November, 2009, accepted November 18, 2009.

2 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., Cardiac resynchronization therapy (CRT) has been shown to improve symptoms and left ventricular (LV) function, and induce reverse remodeling (1,2). However, about one-third of patients do not respond to CRT (1 ). LV pacing lead position has recently attracted attention and is likely to have a considerable impact on CRT success (6 11). The LV lead should be placed in the area of greatest delay in electrical activation and mechanical contraction to achieve optimal resynchronization effect (10). Thus, guidance of LV lead to this site is desirable. It would require an imaging modality that can identify the obtained LV lead position in relation to the site of maximal mechanical dyssynchrony (MMD). The LV lead position can be determined by fluoroscopy. However, the site of MMD prior to CRT is normally defined by echocardiography. We have recently described definition of LV lead position based on myocardial deformation imaging (MDI) before and while on biventricular CRT (8). Concordance of the LV lead position and the LV segment with latest contraction prior to CRT resulted in significantly better effectiveness of CRT (9). However, this analysis is complex. Determination of the LV area with earliest contraction during mere LV pacing may be an attractive alternative to define the LV lead position. This approach is based on the assumption that the LV lead induces the earliest electrical and mechanical activation. The LV lead position was determined in this study using: 1) fluoroscopy; 2) change in myocardial deformation sequence from pre-implant to on CRT; and 3) the site of earliest contraction during pure LV pacing. Improvement in LV ejection fraction (EF) and LV remodeling during a 12- month follow-up were evaluated. The imaging modality to most accurately define the LV lead position was determined based on the discriminatory power of the method for improvement in LVEF and LV remodeling during follow-up between an optimal and a nonoptimal LV lead position group. This end point was used because of previous experimental and clinical findings indicating that optimal LV lead position relative to the LV site with latest contraction prior to CRT results in highest CRT effectiveness (6 11). Thus, the highest discriminatory power of a technique for improvement in LVEF and remodeling is a function of accurate definition of the LV lead position relative to the LV site with MMD prior to CRT. METHODS Patients. Fifty-six consecutive patients (mean age 3 years, 34 men) with end-stage heart failure and sinus rhythm, scheduled for implantation of a biventricular pacemaker, were included in the study. Criteria for implantation were New York Heart Association (NYHA) functional class III (n 3) or IV (n 21) despite optimal pharmacologic therapy, LV systolic dysfunction with EF 3%, and a QRS width 120 ms due to left bundle branch block. Forty patients had a myocardial infarction within the last year. In 16 patients, the etiology of heart failure was nonischemic. This study was approved by the local ethical committee, and all subjects gave written informed consent. Biventricular device implantation. All patients received a biventricular cardioverter-defibrillator (Attain-System with InSync Marquis, Medtronic, Minneapolis, Minnesota, n 36; or Aesula-System with Epic HF AND V-339, St. Jude Medical, St. Paul, Minnesota, n 20). The LV lead was inserted by a transvenous approach through the coronary sinus into a cardiac vein of the free wall. The aim was to achieve an optimal LV lead position intraoperatively by minimizing the width of the QRS complex and optimizing hemodynamic parameters (increase arterial systolic pressure). An average of veins were evaluated for this purpose. The right atrial and ventricular leads were positioned conventionally. The ventrioventricular (VV) timing was set to 0. To determine the optimal atrioventricular (AV) time, Doppler echocardiography was used post-operatively as described before (8). Optimal AV time was between 100 and 10 ms (mean time ms) in 4 patients and between 70 and 8 ms (mean time 77 7 ms) in 2 patients. One day after CRT implantation, the device was reprogrammed to pure LV pacing for a short period to allow echocardiographic examination with this pacing setting. At 6- and 12-month follow-up, the device was controlled to ensure that no LV lead dislocation had occurred and that the AV timing was stable. Fluoroscopy. After CRT implantation, biplane fluoroscopy in orthogonal views (left anterior oblique [LAO] 60 and right anterior oblique [RAO] 30 ) was performed. These images were analyzed by 2 blinded readers to determine the anatomical location of the LV lead tip (Fig. 1) (12). ABBREVIATIONS ACRONYMS CRT cardiac resynchronization therapy CS circumferential strain EF ejection fraction LAO left anterior oblique LV left ventricular LVEDV left ventricular enddiastolic volume MMD maximal mechanical dyssynchrony RAO right anterior oblique VO 2 max maximum oxygen consumption

3 474 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., 2010 Figure 1. Determination of the LV Lead Position Using Fluoroscopy (Method 1) Orthogonal fluoroscopy views (right anterior oblique [RAO] 30 and left anterior oblique [LAO] 60 ) acquired after cardiac resynchronization therapy (CRT) implantation to determine the anatomical left ventricular (LV) lead position. The RAO view (left panel) was used to define the LV lead position in the basoapical direction (I: basal level, II: mid-ventricular level, III: apical level, IV: apex). The basal border of the basal level was defined as 1 cm apical to the LV lead course within the great cardiac vein. The LAO view (right panel) was subsequently used to define the position within the circumference of that level. For this purpose, the 17-segment scheme was projected onto the LAO view. The images show the tip of the LV lead (arrows) to be in the lateral medial segment. Adapted, with permission, from Cerqueira et al. (12). The intraobserver variability was found to be kappa 0.92 (9% confidence interval [CI]: 0.8 to 0.9), and interobserver variability was found to be kappa 0.89 (9% CI: 0.82 to 0.97). Echocardiography. All studies were performed before CRT, 1 day after CRT implantation, and at 12 2 months follow-up using a Vivid Seven digital ultrasound scanner (General Electric, Horten, Norway). Using apical 4- and 2-chamber views, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and EF were determined employing biplane Simpson s method. Patients with a reduction of 1% in LVEDV were considered to be adequate clinical responders. Definition of clinical response was not based on optimal LV lead positioning. Four parasternal short-axis views (mitral valve level, papillary muscle level, apical level, and an additional apex view) were acquired using 2-dimensional tissue harmonic imaging. For optimized characterization of myocardial tissue, the focus was adjusted to the center of the LV cavity, and the frame rate was between 6 and 92 frames/s. Analysis of myocardial deformation. Myocardial deformation analysis was performed offline on a personal computer with the aid of a customized software package (EchoPAC BT 0.2, General Electric) using 2 consecutive cardiac cycles as described before (9,13,14). Echocardiographic image quality was adequate for strain analysis in 89% of all segments. Time curves of circumferential strain (CS) were used to define the segment with latest peak negative CS before CRT in relation to the QRS complex within a 17-segment model. This segment was assumed to have the greatest need for resynchronization and to be the optimal LV lead position. Furthermore, based on strain curve analysis, 2 methods to determine the LV lead position were applied: 1) definition of the segment with maximal temporal difference in peak CS pre-implant before and while on biventricular CRT (Fig. 2); and 2) definition of the segment with earliest peak systolic CS during pure LV pacing 1 day after implantation of the CRT system (Fig. 3). Variability data were calculated as relative deviations between 2 measurements. For time-to-peak negative CS, intraobserver variability was found to be.3 1.9% of the absolute measured time values, and interobserver variability was %. Definition of optimal LV lead position. Considering the LV lead position defined either by fluoroscopy or the 2 deformation imaging based methods, the distance between the segment with MMD and the defined LV lead position was counted in number of segments referring to the 4 apicobasal levels and the up to 6 segments within 1 circumference. One distance step was related either to the apicobasal level or to the circumferential level. Optimal position of the LV lead was defined as concurrence or immediate neighboring ( 1 distance step) of the segment with MMD and the segment with assumed location of the LV lead. Definition of optimal LV lead position was not based on clinical success of CRT during follow-up.

4 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., Local: Circumferential Strain (%) Local: Circumferential Strain (%) t pre-post t pre t post Figure 2. Determination of the LV Lead Position From Deformation Imaging Before and With Biventricular Pacing (Method 2) Left panel: Myocardial deformation imaging prior to cardiac resynchronization therapy (CRT) demonstrating 6 circumferential strain tracings for the 6 evaluated segments within the circumference. The dotted black line indicates the mean circumferential strain of all 6 segments. The time difference between the segment with the earliest and the latest peak strain ( t pre) is marked with an orange arrow. Right panel: Myocardial deformation imaging demonstrating circumferential strain tracings from the 6 evaluated segments within the circumference while on biventricular pacing. The time difference between the segment with earliest and latest peak strain during CRT ( t post) is marked with a red arrow. The tracing obtained prior to CRT from the lateral segment (greatest change in time to peak strain from before to during CRT) is added as the dashed green line. The reduction in contraction delay with CRT compared with prior to therapy for this segment ( t pre-post) is marked by the yellow arrow. It was greatest among all 17 left ventricular (LV) segments of this patient indicating the LV lead position defined by this approach. Peak oxygen consumption. Patients underwent bicycle cardiopulmonary exercise testing (10 W per min increments) at baseline and after 12 ( 2) months of CRT. Maximum oxygen consumption (VO 2 max) at peak exercise was defined as the highest oxygen consumption measured during the symptomlimited exercise test and expressed as milliliters per kilogram per minute. Statistics. Continuous data are expressed as mean values SD and compared using the Student t test. We considered LVEDV and EF as relevant parameters to compare the ability of the imaging techniques to differentiate between optimal and nonoptimal lead position groups. Differences of the group means and the corresponding confidence limit were calculated, concluding that the farther away the mean difference is from 0 difference, the better the technique is able to discriminate between optimal and nonoptimal groups. Categorical data were presented as frequencies and compared with the Fisher exact test. Spearman rank correlation coefficient was used to show correlation between change in LVEDV and EF with distance between the segment with MMD and LV lead position. To evaluate agreement between anatomical LV lead position determined by fluoroscopy and assumed LV lead position determined by either method of CS analysis, we calculated Cohens kappa coefficient and weighted Cohens kappa coefficient with 9% CI as appropriate. To define intraobserver and interobserver variability in 10 subjects, analyses were repeated by the same observer and performed in addition by a second independent observer. A p value of 0.0 was considered statistically significant. RESULTS Baseline clinical characteristics prior to CRT are given in Table 1. Thirty-six of the 6 patients (64%) were classified as clinical responders (reduction of LVEDV 1%). Considering the LV lead position defined during LV pacing to determine patients with optimal and nonoptimal LV lead position, 31 of the 36 clinical responders had optimal LV lead position. In the clinical nonresponders, there were patients with optimal and 1 patients without optimal LV position. Location of MMD prior to CRT. The location of the segment with latest maximal systolic strain prior to CRT was as follows: 14 anterior (8 basal, 6 medial), 26 lateral (1 basal, 8 medial, 3 apical), 9 posterior (3 basal, 6 medial), 3 inferior (1 basal, 2 apical), and 4 at the apex. The distribution of the segment with

5 476 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., 2010 Local: Circumferential Strain (%)= T=929 msec Figure 3. Determination of the LV Lead Position From Deformation Imaging During Pure LV Pacing (Method 3) Circumferential strain tracings from the 6 evaluated segments within the circumference during pure left ventricular (LV) pacing. The segment with earliest peak circumferential strain among all 17 LV segments of this patient was defined as LV lead position by this approach (black arrow). latest contraction prior to CRT was not different between patients found to have optimal and those found to have nonoptimal LV lead position, independent of the imaging modality used. Table 1. Patient Characteristics at Baseline Before CRT Optimal LV Lead Position (n 36) Nonoptimal LV Lead Position (n 20) p Value Age, yrs Males/females 24 (66%) 12 (60%) 0.72 Ischemic cardiomyopathy 26 (71%) 1 (74%) QRS interval duration, ms NYHA functional classification LVEDV, ml LVESV, ml LVEF, % Concomitant therapy ACE inhibitors 28 (77%) 1 (73%) ARBs 6 (18%) 4 (21%) Beta-blockers 33 (91%) 18 (90%) 0.6 Digitalis 1 (43%) 8 (38%) Diuretics 17 (47%) 9 (44%) Aldosterone antagonists 2 (70%) 14 (68%) 0.16 Determination of optimal versus nonoptimal left ventricular (LV) lead position is based on myocardial deformation imaging during pure LV pacing. ACE angiotensin-converting enzyme; ARB angiotensin II receptor blocker; CRT cardiac resynchronization therapy; LVEDV left ventricular end-diastolic volume; LVEF left ventricular ejection fraction; LVESV left ventricular end-systolic volume; NYHA New York Heart Association. Location of the LV lead position. Figure 4 demonstrates the LV lead position based on findings by fluoroscopy and both strain analysis methods. LV lead position was found to be different in 6 patients by strain analysis before and while on CRT, and in 8 patients by fluoroscopy (Fig. 4). Kappa analysis demonstrated good agreement between the 3 different methods used to define LV lead position with regard to 1) segmental analysis; 2) distance between the segment with determined LV lead position and the segment with MMD prior to CRT; and 3) classification of the LV lead position as optimal or nonoptimal (Table 2). The distance between the LV lead position defined by fluoroscopy and the LV lead position defined by strain analysis during biventricular pacing or during pure LV pacing was (range: 0 to 2) segments and (range: 0 to 2) segments, respectively. Optimal versus nonoptimal LV lead position. Considering the location of MMD prior to CRT, the position of the LV lead was in agreement or in the immediate neighborhood (optimal LV lead position) in 33 patients using fluoroscopy, in 33 patients using strain analysis during biventricular pacing, and in 36 patients using strain analysis during pure LV pacing. Impact of CRT on LV dyssynchrony. Considering definition of optimal LV lead position in patients based on LV pacing analysis, the maximal temporal difference between the segment with earliest and latest peak negative CS before CRT was ms in the optimal LV lead position group and ms in the nonoptimal LV lead position group (p 0.689). With active CRT, this temporal difference was significantly reduced in both groups (optimal: ms, and nonoptimal: ms, p 0.001). The reduction was 21% higher in the optimal LV lead position group (48 11 ms vs ms, p 0.027). Impact of CRT on LV function, remodeling, and exercise capacity related to LV lead position. Comparison of baseline and 12-month follow-up results demonstrated a greater increase in LVEF, reverse remodeling, and VO 2 max for patients with optimal LV lead position compared with the nonoptimal LV lead position group. This benefit was present independent of the modality chosen for definition of the LV lead position (Table 3). Additionally, there was a significantly greater improvement in NYHA functional classification (optimal: classes and nonoptimal: classes, p 0.031). The improvement in LVEF at 12-month follow-up and the reduction in LVEDV at follow-up correlated to the distance between the

6 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., segment with MMD and the segment with LV lead position based on pure LV pacing (r 0.3, p and r 0.0, p 0.001, respectively) (Fig. ). Comparison of imaging modalities to determine LV lead position. Imaging modalities were compared with regards to their ability to accurately determine LV lead position. This analysis was based on the discriminatory power of each method for improvement in LVEF, LV remodeling, and VO 2 max during follow-up between an optimal and a nonoptimal LV lead position group. Determination of the LV lead position during LV pacing showed greatest differences, indicating greatest accuracy in the analysis of LV lead position (Table 3). DISCUSSION Septal Anteroseptal Inferior The major findings of this study are: 1) in 40% of patients undergoing CRT, the position of the LV lead did not match the site of MMD; 2) myocardial deformation analysis during pure LV pacing allowed definition of LV lead position; 3) a match of the identified LV lead position and the area demonstrating MMD prior to CRT resulted in significantly greater increase in LV function and negative LV remodeling; and 4) definition of the LV lead position based on myocardial deformation analysis during pure LV pacing allows better distinction between optimal and nonoptimal LV lead position, as indicated by the improvement in LV function and reverse remodeling at follow-up, than definition by fluoroscopy. Optimal LV lead position in CRT. Approximately 30% to 0% of patients remain unresponsive to CRT despite adherence to current guidelines. Optimal LV pacing site has increasingly been focused on as an important technical determinant of CRT success. Experimental data have demonstrated that the LV lead position should be in the area of the latest contraction prior to CRT (6,10). An animal study using cardiac magnetic resonance proved that regions with maximal resynchronization after CRT also exhibited maximum gain in systolic LV function (1). This should be the optimal region for the LV lead. One study showed that those patients (42%) who were paced at the site of latest activation achieved significant improvements in LVEF, LVESV, and exercise tolerance, whereas patients paced at different sites (8%) failed to show an improvement (6). In a study on 64 patients, Suffoletto et al. (16) demonstrated that patients with concordance between LV lead position and site of MMD had a larger increase in LVEF at follow-up. These findings were confirmed in a study by Murphy et al. (7) using 3-dimensional tissue synchronization imaging. Recently, a study on 244 patients demonstrated that a LV lead position concordant to the site of latest activation prior to CRT resulted in significantly more re Apex 3 8 Apical Medial Basal Anterior Posterior Lateral Figure 4. Allocation of LV Lead as Defined by Different Imaging Modalities Position of the left ventricular (LV) lead for all 6 patients in the 17-segment LV model as defined by fluoroscopy (anatomical lead position, shown in red), as defined by circumferential strain analysis before and with cardiac resynchronization therapy (shown in blue), and as defined by circumferential strain analysis during LV pacing (shown in black). Table 2. Concordance Between the 3 Different Modalities Used to Define LV Lead Position LV Lead Position (Segment) Distance (Number of Segments) Classification of Position (Optimal/ Nonoptimal) Weighted Kappa Value Weighted Kappa Value Kappa Value 9% CI Value 9% CI Value 9% CI A and B A and C B and C Concordance of the 3 methods is with regard to 1) segment with the left ventricular (LV) lead position; 2) distance between the segment with determined LV lead position and the segment with maximal dyssynchrony prior to cardiac resynchronization therapy; and 3) the classification of the LV lead position as optimal or nonoptimal. The methods are indicated as follows: A myocardial deformation imaging during biventricular pacing; B myocardial deformation imaging during LV pacing; and C fluoroscopy. CI confidence interval.

7 478 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., 2010 Table 3. LVEF, LVEDV, and VO 2 max Before CRT and at 12-Month Follow-Up Biventricular Pacing LV Pacing Fluoroscopy LVEF, % Optimal LV lead position group Baseline LVEF, % Follow-up LVEF, % LVEF, (%) Nonoptimal LV lead position group Baseline LVEF, % Follow-up LVEF, % LVEF, (%) Difference in LVEF, % (optimal nonoptimal group) (9% CI) 3.0 (0.9.2) 4.6 ( ) 2.2 (0.0 4.) p Value LVEF (optimal vs. nonoptimal LV lead group) LVEDV, ml LVEDV, ml Optimal LV lead position group Baseline LVEDV, ml Follow-up LVEDV, ml LVEDV, ml Nonoptimal LV lead position group Baseline LVEDV, ml Follow-up LVEDV, ml LVEDV, ml Difference in LVEDV, ml (optimal nonoptimal group) (9% CI) 6.6 ( ) 13.9 ( ) 7.6 ( ) p Value LVEDV (optimal vs. nonoptimal LV lead group) VO 2 max, ml/kg/min Optimal LV lead position group Baseline VO 2 max, ml/kg/min Follow-up VO 2 max, ml/kg/min VO 2 max, ml/kg/min Nonoptimal LV lead position group Baseline VO 2 max, ml/kg/min Follow-up VO 2 max, ml/kg/min VO 2 max, ml/kg/min Difference in VO 2 max, ml/kg/min (optimal nonoptimal group) (9% CI) 0.4 ( ) 0.9 ( ) 0.7 (0.1 1.) p Value for VO 2 max (optimal vs. nonoptimal LV lead group) Shown are the optimal and nonoptimal left ventricular (LV) lead position groups as defined by the different modalities to determine the LV lead position. For each parameter, the difference between optimal and nonoptimal LV lead position groups is greatest if deformation imaging during LV pacing is used to determine the LV lead position. CRT cardiac resynchronization therapy; VO 2 max maximum oxygen consumption; other abbreviations as in Tables 1 and 2. verse remodeling and lower hospitalization-free mortality rates during long-term follow-up (11). To overcome potential difficulties in the optimal placement of the LV lead, epicardial lead placement has been suggested (17 19). More recently, even the placement of 2 LV leads has been proposed to improve the effectiveness of CRT (20,21). Thus, a technique that will help to implant the LV lead into the area of greatest mechanical and electrical need is likely to improve the success rate of CRT. This would require accurate definition of the LV lead position relative to the site of MMD. Current difficulties relate to the problem of matching the LV lead site obtained in the catheterization lab with the area of MMD defined before by echocardiography or cardiac magnetic resonance. Fluoroscopy has limitations in defining the LV lead position in 3-dimensional space and lacks information on the area of MMD. We have recently described a technique to identify the LV lead position based on a detailed analysis of myocardial deformation before and while on CRT (8,9). The technique resulted in high agreement with the LV lead position defined by fluoroscopy and by computed tomography. It has the advantage of allowing definition of the area of MMD and the LV lead position within 1 imaging modality. However, the complex analysis limits its applicability. Thus, it has been impractical for optimization of the LV lead position during the implantation procedure. In this

8 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., LVEF Baseline Follow-up LVEDV Baseline Follow-up (%) -20 (ml) Number of Segments Between Maximal Dyssynchrony and LV Lead Position Number of Segments Between Maximal Dyssynchrony and LV Lead Position Figure. Changes in LVEF and LVEDV Related to Displacement of LV Lead (Left panel) change in left ventricular ejection fraction (LVEF) from baseline to 12-month follow-up related to distance between the segment with maximal dyssynchrony prior to cardiac resynchronization therapy (CRT) to the segment with LV lead position defined during pure LV pacing. (Right panel) change in LV end-diastolic volume (LVEDV) from baseline to 12-month follow-up related to distance between the segment with maximal dyssynchrony prior to CRT to the segment with LV lead position defined during pure LV pacing. study, we evaluated another approach based on MDI. The segment with earliest mechanical activity during pure LV pacing was assumed to represent the area of earliest electrical activation and thus the LV lead position. This technique, while still indirectly defining the LV lead position, is considerably easier. This study demonstrated that the spatial relationship between LV lead position defined by any of the 3 applied imaging modalities and the area of MMD prior to CRT is predictive for improvement in LV function and reverse remodeling with CRT. This finding supports the importance of the LV lead position for the CRT success. Furthermore, the spatial relationship of the LV lead position defined during LV pacing and the area of MMD prior to CRT had the best predictive power for improvement in LV function and reverse remodeling with CRT. This may be explained in part by the least complex analysis technique not requiring the matching of multiple imaging modalities or deformation imaging sets obtained at different time points. In this study, CS analysis was used because it has been proven to allow accurate analysis of LV dyssynchrony and assessment of the potential CRT benefit. Radial strain might also be used to evaluate dyssynchrony. However, this study was not intended to compare radial and CS for analysis of dyssynchrony. Future studies should compare radial, circumferential, and longitudinal strain parameters for prediction of improvement in EF and reduction in LV dimensions. Analysis of LV lead position during LV pacing has the potential to be used during CRT implantation for definition and optimization of the LV lead position, thereby improving the CRT success rate. Further studies will have to be performed to validate this concept. Study limitations. The segment with earliest contraction during LV pacing was considered the LV lead position. This is based on the hypothesis that the mechanical activation sequence will follow the electrical activation pathway. This hypothesis has not been proven in experimental studies. However, the considerable concordance of the LV lead position defined by this concept and the fluoroscopic results support this approach. Great improvement in LV function was used as indicator of optimal LV lead position. The comparison of imaging modalities regarding their ability to define the accurate LV lead position was done indirectly by considering their discriminating power for improvement in LV function and remodeling. This was done on the basis that only a modality that allows accurate definition of the LV lead position allows best analysis of the spatial relationship between LV lead position and the area of MMD prior to CRT. Spatial concordance is considered a requirement for greater CRT success. However, there are other parameters that might have an impact on

9 480 JACC: CARDIOVASCULAR IMAGING, VOL. 3, NO., 2010 CRT success. Lack of viability or scarring was not evaluated in this study as a potential mechanism for reduced CRT effect (22,23). However, the lack of viability analysis is unlikely to have an impact on the current results, because the distribution of ischemic cardiomyopathy was equal between the optimal and the nonoptimal LV lead position groups. The definition of the optimal LV lead position as concurrence or immediate neighborhood of the segment with maximal temporal difference in peak negative CS before and with CRT to the segment with MMD prior to CRT is arbitrary. A different definition of optimal lead position would have resulted in a higher number of patients with optimal lead position. However, there was a continuous reduction of LV reverse remodeling on CRT with increasing distance between LV lead position and the segment with latest contraction prior to CRT. There are technical factors that may limit the use of the described analysis method for optimal LV lead placement: some patients may have scar formation not allowing sufficient electrical response in the desired lead position, other patients have a maximal delayed segment in a region where a LV lead cannot be placed due to absence of a suitable vein or the impossibility of reaching that vein. CONCLUSIONS Analysis of the myocardial deformation sequence during pure LV pacing allows determination of CRT LV lead position. Concurrence of the LV lead position and the LV segment with MMD prior to CRT results in optimized effectiveness of CRT on LV function and reverse remodeling at 12-month follow-up. Definition of the LV lead position based on myocardial deformation analysis during pure LV pacing allows better distinction between optimal and nonoptimal LV lead position as indicated by the improvement in LV function and reverse remodeling at 12-month follow-up than definition of the LV lead position by fluoroscopy. Reprint requests and correspondence: Dr. Rainer Hoffmann, Medical Clinic I, University RWTH Aachen, Pauwelsstraße 30, 207 Aachen, Germany. rhoffmann@ukaachen.de. REFERENCES 1. Abraham WT, Fisher WG, Smith AL, et al.; MIRACLE Study Group. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346: Yu CM, Chau E, Sanderson JE, et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. 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