Site Of Latest Mechanical Activation Research Articles

Cardiac resynchronization therapy outcomes with left ventricular lead concordant with latest mechanical activation: A meta-analysis.

For cardiac resynchronization therapy (CRT), image-guided approaches targeting left ventricular (LV) lead placement at the site of latest mechanical activation had inconsistent outcomes. We examined evidence for improved CRT outcomes when LV lead placement concordant with latest mechanical activation occurred. A review of EMBASE and PubMed was performed for randomized controlled trials or prospective observational studies from October 2008 through October 2020 comparing outcomes with concordant versus discordant LV lead placement. Meta-analyses were performed to assess the association between concordance and death, death or heart failure (HF) hospitalization,≥15% reduction in LV end systolic volume (LVESV), and changes in LVESV or ejection fraction (LVEF). From 5897 citations, nine publications (eight studies) with 1355 patients were selected; 975 with a concordant LV lead and 380 with a discordant lead. Mean age was 66-68 years, 82% were male, and 64% had ischemic cardiomyopathy. Meta-analyses demonstrated a statistically significant reduction in death/HF hospitalization at 2 years (OR 0.38; 95% CI 0.16, 0.92) and LVESV at 6 months (mean difference [MD] -13.4%; 95% CI -6.7%, -20.0%), and an increase in LVEF (MD 4.03; 95% CI 0.77, 7.30) with the concordant LV lead. There were trends toward decreased death at 2 years (OR 0.49; 95% CI 0.19, 1.23) and≥15% reduction in LVESV at 6 months (OR 3.81; 95% CI 0.24, 61.24) with concordant LV lead placement. A concordant LV lead was associated with better CRT outcomes. Further study of feasible methods to achieve LV lead concordance is needed.

Outcomes of Cardiac Resynchronization Therapy with Image-Guided Left Ventricular Lead Placement at the Site of Latest Mechanical Activation: A Systematic Review and Meta-Analysis.

Aim To assess evidence for an image-guided approach for cardiac resynchronization therapy (CRT) that targets left ventricular (LV) lead placement at the segment of latest mechanical activation. Methods A systematic review of EMBASE and PubMed was performed for randomized controlled trials (RCTs) and prospective observational studies from October 2008 through October 2020 that compared an image-guided CRT approach with a non-image-guided approach for LV lead placement. Meta-analyses were performed to assess the association between the image-guided approach and NYHA class improvement or changes in end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF). Results From 5897 citations, 5 RCTs including 818 patients (426 image-guided and 392 non-image-guided) were identified. The mean age ranged from 66 to 71 years, 76% were male, and 53% had ischemic cardiomyopathy. Speckle tracking echocardiography was the primary image-guided method in all studies. LV lead placement within the segment of the latest mechanical activation (concordant) was achieved in the image-guided arm in 45% of the evaluable patients. There was a statistically significant improvement in the NYHA class at 6 months (odds ratio 1.66; 95% confidence interval (CI) [1.02, 2.69]) with the image-guided approach, but no statistically significant change in LVESV (MD −7.1%; 95% CI [−16.0, 1.8]), LVEDV (MD −5.2%; 95% CI [−15.8, 5.4]), or LVEF (MD 0.68; 95% CI [−4.36, 5.73]) versus the non-image-guided approach. Conclusion The image-guided CRT approach was associated with improvement in the NYHA class but not echocardiographic measures, possibly due to the small sample size and a low rate of concordant LV lead placement despite using the image-guided approach. Therefore, our meta-analysis was not able to identify consistent improvement in CRT outcomes with an image-guided approach.

Targeting the latest site of left ventricular mechanical activation is associated with improved long-term outcomes for recipients of cardiac resynchronization therapy.

BackgroundPrevious studies have suggested that targeting the site of latest mechanical activation of the left ventricle (LV) results in improved cardiac resynchronization therapy (CRT) outcomes. It is not known whether these benefits are sustained over medium-term follow-up.ObjectiveTo assess the clinical outcome of imaging-guided LV lead position.MethodsWe sought to assess the medium-term clinical outcome by performing a patient-level meta-analysis of 2 previously published randomized controlled trials (the “STARTER” trial and the “CRT Clinic” trial). These 2 trials compared imaging-guided LV lead placement in the latest activated scar-free segment (intervention group) to standard of care (control). Mortality and heart failure hospitalization outcomes over extended follow-up were gathered from the medical records and merged. Results were stratified for native electrocardiogram (ECG) morphology.ResultsA total of 289 patients were followed for a median of 6.3 years. Seven years post implant, 47 (28%) in the intervention group had died, vs 47 (38%) in the control group (P = .13); 49 (30%) vs 53 (42%) had been hospitalized for heart failure (P = .035); and 47% vs 59% (P = .057) had reached the combined endpoint. In Kaplan-Meier analysis, patients in the intervention group had better survival free of heart failure hospitalization (P = .045) and lower risk of heart failure hospitalization (P = .019).ConclusionTargeting the latest mechanically activated segment in CRT results in better medium-term clinical outcome, mainly driven by a reduced risk of hospitalization for heart failure. The effect was seen regardless of native ECG morphology.

Abstract 9509: Is Left Ventricular Lead Placement at Site of Latest Mechanical Activation Associated with Cardiac Resynchronization Therapy Outcomes? Results of a Meta-Analysis

Introduction: CRT outcomes with image-guided left ventricular (LV) lead placement within the LV segment of latest mechanical activation have been assessed in several randomized controlled trials (RCTs) with equivocal results, possibly due to variable achievement of concordant LV lead placement in the image-guided and comparator arms. We conducted meta-analyses to assess CRT outcomes associated with concordant LV lead placement. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that reported outcomes in those with LV lead placement at or adjacent to the site of latest mechanical activation (concordant) versus those with LV lead placement distant to the site of latest mechanical activation (discordant) as determined by any imaging method. Two independent reviewers screened titles and abstracts then reviewed full text for inclusion/exclusion. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses for death, death or HF hospitalization, and changes in LVESV and LVEF were performed using random effects models. Results: Among 5715 citations identified, 9 papers from 8 studies (including 4 RCTs) were selected that included 1004 patients with concordant LV lead placement and 380 with discordant LV lead placement. Mean patient age ranged from 66 to 68 years, 82% were male, and 64% had ischemic cardiomyopathy. Segment of latest activation was determined by speckle tracking echocardiography (STE) in 7 (88%) studies. Meta-analyses demonstrated statistically significant lower all-cause mortality or HF hospitalization and reduction in LVESV with a concordant LV lead (Figure). There were trends toward lower all-cause mortality and increased LVEF. Conclusion: A concordant LV lead, as determined primarily by STE, was associated with better CRT outcomes. Further study of feasible methods to achieve concordance in clinical practice is needed.

Optimal left ventricular lead positioning during cardiac resynchronisation therapy; a comparison of 2 methods

Abstract Background/Introduction Superior response to CRT and improved clinical outcomes can be achieved when placing the left ventricular (LV) lead at the site of latest mechanical activation and avoiding regions of scar during cardiac resynchronisation therapy (CRT). The site of latest mechanical activation can be identified using speckle-tracking echocardiography, whilst the area of latest electrical activation can be assessed by measuring QLV, the time from the initial deflection of the surface QRS complex to sensing at the LV lead electrode. It remains unclear if the two techniques are interchangeable and whether the site of latest mechanical activation is related to the site of latest electrical activation, or sensed electrical signals correspond to sites of scar. Purpose To determine whether electrical targeting of LV lead position corresponds to echo-guided mechanical targeting and whether myocardial electrogram signals can predict areas of myocardial scar Methods This was a pilot study of patients receiving CRT, in sinus rhythm with severe LV impairment (ejection fraction ≤35%) and left bundle branch block (LBBB) with QRS ≥130ms. Ethics approval was obtained, and written consent was sought. Participants underwent echocardiographic speckle-tracking 2-dimensional radial strain imaging to identify amplitude and time to peak contraction of posterior, posterolateral, lateral, anterolateral and anterior segments. During CRT implant, the sensed R wave and QLV were measured at the respective branch of the coronary sinus, where the anatomy permitted. The site of latest mechanical was compared to the site of latest electrical activation and classified as concordant (same site), adjacent (within 1 segment), or remote (2 segments away). The strain amplitude was compared to the sensed R wave and time to mechanical activation with QLV. Results Seventeen patients (13 male) were studied, mean age 74.2 (SD 8.7). Mean QRS was 161 ms (SD 18), mean PR 186 ms (SD 37). A modest and significant positive correlation was found between the site of latest mechanical and latest electrical activation (Pearson r=0.66, p 0.004). The site of latest electrical activation was concordant with latest mechanical activation in 13 patients (76.5%), adjacent in 4 patients (23.5%) and remote in none. There was no apparent association between sensed R wave and strain amplitude (Pearson r=0.2, p=0.12) or between QLV and time to mechanical activation (Pearson r=0.1, p=0.5). Conclusion A significant positive correlation was found between the site of latest mechanical and latest electrical activation in patients undergoing CRT implant. Electrical targeting might be a suitable alternative to mechanical targeting particularly when imaging is not available, however, does not appear to discriminate scar. Future larger studies are needed to confirm our findings and determine whether QLV can be used as an alternative method for targeting LV lead placement. Funding Acknowledgement Type of funding sources: None.

Prognostic Benefit of Optimum Left Ventricular Lead Position in Cardiac Resynchronization Therapy: Follow-Up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy)

This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). An optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited. Data from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up. An optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024). An optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up.

The Association of Left Ventricular Lead Position Related to Regional Scar by Speckle-Tracking Echocardiography with Clinical Outcomes in Patients Receiving Cardiac Resynchronization Therapy

Response to cardiac resynchronization therapy is variable. The aim of this study was to test the hypothesis that left ventricular (LV) lead position in proximity to myocardial scar is associated with less favorable outcomes. A total of 149 patients were included in this substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial using echocardiographic radial strain for basal and middle LV segments and transverse strain for apical segments to estimate scar. Sixty-four patients with high-dose rest (99m)Tc sestamibi single-photon emission computed tomographic imaging were used for validation in 508 LV free-wall segments. The relationship of LV lead position to segments estimated as scar was defined as concordant, adjacent, or remote. The prespecified primary end point was heart failure hospitalization or death over 2 years. Wall thickening < 10% by radial strain in LV free wall segments was associated with absent (99m)Tc sestamibi uptake indicative of scar with 77% sensitivity and 89% specificity and strain < 10% was accordingly used as the surrogate for scar. Event-free survival was most favorable in patients with nonischemic disease (79%), similarly favorable in patients with ischemic disease and LV leads remote from scar (74%), but significantly worse in patients with ischemic disease and LV leads adjacent to (61%) or within scar (41%) (P= .004). Preserved wall thickening at the LV lead site was independently associated with favorable outcome and additive to pacing at the site of latest mechanical activation (P= .001) and remained significant after adjusting for scar burden. Echocardiographic speckle-tracking strain has the potential to estimate free wall scar in patients with ischemic cardiomyopathy and influence LV lead positioning away from scar to improve clinical outcomes after cardiac resynchronization therapy.

Effect of Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy on Mortality and Risk of Defibrillator Therapy for Ventricular Arrhythmias in Heart Failure Patients (from the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region [STARTER] Trial)

Echocardiography-guided left ventricular (LV) lead placement at the site of latest mechanical activation improves heart failure outcomes in patients receiving a cardiac resynchronization therapy defibrillator (CRT-D). In this study, we test the hypothesis that a strategy of echocardiography-guided LV lead placement improves patient survival rate free from appropriate CRT-D therapy for ventricular arrhythmias. Patients enrolled in the prospective, randomized Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial and treated with a CRT-D device (108 with the echo-guided strategy and 75 with the routine strategy) were followed to the end point of death or first appropriate CRT-D therapy. Over a follow-up period of 3.7 ± 2.1years, 62 patients (33%) died and 40(22%) received appropriate CRT-D therapy. Compared with the routine group, patients in the echo-guided group had improved CRT-D therapy-free survival rate (hazard ratio= 0.64, 95% confidence interval= 0.42 to 0.98, p= 0.038). Patients randomized to the echo-guided LV lead placement were more likely to resynchronize their LV compared with the routine group (72% vs 48%, respectively, p= 0.006). Patients whose LV did resynchronize after CRT-D had improved therapy-free survival rate compared with those whose LV did not resynchronize (hazard ratio= 0.49, 95% confidence interval= 0.28 to 0.86, p= 0.012). In conclusion, a strategy of echo-guided LV lead placement improved the patient survival rate free from defibrillator therapy in CRT-D recipients.

Echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy in ischemic vs nonischemic cardiomyopathy patients

Echocardiography-guided (EG) left ventricular (LV) lead placement at the site of latest mechanical activation improves outcome in heart failure (HF) patients receiving a cardiac resynchronization therapy (CRT)-defibrillator (CRT-D). The purpose of this study was to examine the effect of a strategy of EG LV lead placement in each of ischemic (ICM) vs nonischemic (NICM) cardiomyopathy patients. Patients enrolled in the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized trial who were treated with a CRT-D device (108 EG strategy and 75 routine strategy) were followed to the end-points of death, appropriate CRT-D therapy, or HF hospitalization. Of the patients enrolled in STARTER, 115 had ICM and 68 had NICM. Over mean follow-up of 3.7 ± 2.1 years, 62 patients died, 40 received appropriate CRT-D therapy, and 67 had HF hospitalizations. Compared to NICM patients, patients with ICM had worse survival (P = .0003), worse survival free from implantable cardioverter-defibrillator therapy (P = .004), and survival free from HF hospitalization (P = .0001). A strategy of EG LV lead placement improved the outcome of CRT-D therapy-free survival primarily in ICM patients and the outcome of HF hospitalization-free survival in both ICM and NICM patients. Achieving LV resynchronization was most critical in ICM patients in whom arrhythmic and HF outcomes improve with resynchronization to levels comparable to those of NICM patients. A strategy of EG LV lead placement improves HF-free survival equally in ICM and NICM patients and CRT-D therapy-free survival more favorably in ICM patients to levels comparable to those of NICM patients.

Utility of Speckle Tracking Echocardiography to Characterize Dysfunctional Myocardium in Patients with Ischemic Cardiomyopathy Referred for Cardiac Resynchronization Therapy

Assessment of transmural scar at the site of latest mechanical activation is relevant to maximize outcomes in cardiac resynchronization therapy (CRT). Few studies have assessed the ability of speckle tracking echocardiography (STE)-derived short-axis strain to identify segmental myocardial scar, defined by contrast-enhanced cardiac magnetic resonance imaging (CMR), in patients referred for CRT. A total of 26 patients with ischemic cardiomyopathy who underwent preprocedure echocardiography and CMR were studied. Extent of transmural scar was assessed using contrast-enhanced CMR and corresponding peak segmental radial and circumferential strains were derived using two-dimensional (2D) STE. Total left ventricle (LV) scar volume was compared with parameters of global strain. CRT response was defined as >15% reduction in LV end systolic volume (LVESV) at 6months. Speckle tracking short-axis strain analysis was technically possible in over 90% of LV segments. Applying a segmental radial strain cutoff value of 10% distinguished segments with >50% scar area with a high negative predictive value (98%). Global longitudinal strain <-5% predicted CRT response. Two-dimensional STE offers potential to characterize dysfunctional myocardium and define segmental scar offering an integrated imaging approach to guide LV lead placement for CRT.

Usefulness of Echocardiographically Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy in Patients With Intermediate QRS Width and Non–Left Bundle Branch Block Morphology

The current guidelines most strongly support cardiac resynchronization therapy (CRT) for patients with heart failure with a QRS width of ≥150 ms and left bundle branch block (LBBB). Our objective was to assess the potential benefit of echocardiographically guided left ventricular (LV) lead positioning for patients with a QRS width <150 ms or non-LBBB as a substudy of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized controlled trial. The STARTER trial randomized 187 patients with heart failure, a QRS of ≥120 ms, and ejection fraction of ≤35% to LV lead guided to the site of latest mechanical activation by speckle tracking radial strain versus routine implantation. The predefined primary end point was heart failure hospitalization or death within 2 years. This substudy included 151 CRT patients with matching echocardiographic and LV lead position data and complete follow-up data. Patients with a QRS width of 120 to 149 ms or non-LBBB and LV lead concordant or adjacent to the site of latest mechanical activation had favorable outcomes after CRT similar to those with LBBB or a QRS width of ≥150 ms. In contrast, patients with a QRS of 120 to 149 ms or non-LBBB and remote LV leads had unfavorable outcomes (hazard ratio 5.45, 95% confidence interval 2.36 to 12.6, p <0.001, and hazard ratio 4.92, 95% confidence interval 2.12 to 11.39, p <0.001, respectively, with significant interaction after adjusting for baseline variables, p = 0.038 and p = 0.008). In conclusion, LV lead positioning with respect to the echocardiographic site of latest activation was significantly associated with more favorable clinical outcomes in patients with a QRS duration <150 ms and/or non-LBBB. Additional prospective study is warranted.

Individually tailored left ventricular lead placement: lessons from multimodality integration between three-dimensional echocardiography and coronary sinus angiogram

Non-responder rates for cardiac resynchronization therapy (CRT) vary from 11% to 46%. Retrospective data imply a better outcome with stimulation of the latest contracting left ventricular (LV) region. Our study analysed the feasibility, safety and clinical outcome of prospectively planned LV lead placement at the site of latest mechanical activation. Thirty-eight heart failure patients with CRT indication were assessed by three-dimensional (3D) transoesophageal echocardiography and rotation angiography of the coronary sinus (CS). Both images were merged into a single 3D-model to identify CS target veins close to the site of latest mechanical activation. Subsequently, LV lead deployment was attempted at the desired target position. Patients were clinically and echocardiographically evaluated at baseline, after 3 and 6 months. The area of latest mechanical activation covered 6 ± 2 segments (38 ± 13% of LV surface) and was found lateral in 24 of 37 (65%), anterior in 11 of 37 (30%), inferior in 2 of 37 (5%), and septal in 1 of 37 (3%) patients. In 36 of 37 (97%) patients an appropriate target vein was identified and successful implantation could be performed in 34 of 37 (92%) patients. Among those patients clinical and echocardiographic response was observed in 91% and 81%, respectively. Individualized lead placement at the latest contracting LV site can be performed safely and successfully in the majority of patients. Initial clinical outcome data are encouraging. Identification of target sites requires multimodality integration between LV wall motion data and CS anatomy. Future developments need to improve those technologies and require randomized data on clinical outcome parameters.

The role of 3D wall motion tracking in heart failure

Heart failure is a major health problem in developed countries and a growing one in developing countries. Cardiac remodeling in heart failure affects myocardial mechanics, which requires comprehensive evaluation in three dimensions. The novel technique of 3D wall motion tracking applies speckle tracking technology to full volume, 3D echocardiographic datasets. Quantification of conventional and novel left ventricular (LV) parameters including volumes, ejection fraction, global and regional 3D strain, endocardial area strain, twist, and dyssynchrony, and identification of the site of latest mechanical activation are feasible on the basis of a single acquisition of a full-volume dataset. Clinical applications of 3D wall motion tracking include the assessment of global and regional LV performance in ischemic and nonischemic heart diseases, evaluation of mechanics in cardiomyopathies and congenital heart disease, potential selection of patients for cardiac resynchronization therapy and prediction of their response, and detection of subclinical cardiac dysfunction in diseases with likelihood of progression to heart failure. Technological advances with improvement in spatial and temporal resolution of this novel imaging modality are expected. Although 3D wall motion tracking is still in its infancy, this method has begun to provide new insights into LV mechanics and has already found clinical applications. Future developments in 3D assessment of right ventricular and myocardial layer-specific mechanics are awaited.

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Non-contrast magnetic resonance imaging for guiding left ventricular lead position in cardiac resynchronization therapy

A left ventricular lead position concordant to viable myocardium at the site of latest mechanical activation is associated with a better response to cardiac resynchronization therapy (CRT). The present study aimed to guide left ventricular (LV) lead implantation into a vein over the area of latest mechanical activation with no transmural scar as determined by radial strain measured by non-contrast magnetic resonance imaging (MRI). Patients admitted for CRT implantation underwent MRI on the day before pacemaker implantation. Time to peak radial strain in ventricular segments was measured to define the site of latest mechanical activation. Areas with peak radial strain less than 16.5% were defined as transmural scar. Venograms were visualized to define the optimal vein for LV lead positioning. Echocardiograms, 6-min hall walk test, and NYHA class were obtained at baseline and after 6 months of follow-up. Sixteen patients were included. In nine patients the lead was positioned at the primary target site, and in six patients a secondary was used owing to phrenic nerve stimulation (one patient), unstable lead position (two patients) and lack of suitable vein (three patients) at the primary target site. In three patients pre-implant MRI changed the implanters primary target vein. Non-contrast MRI can be used to detect the site of latest mechanical activation by radial strain to guide LV lead positioning in candidates for CRT. Image guided LV lead implantation in CRT patients may in some patients change the primary target tributary of the coronary sinus.

Baseline asynchrony, assessed circumferentially using temporal uniformity of strain, besides coincidence between site of latest mechanical activation and presumed left ventricular lead position, predicts favourable prognosis after resynchronization therapy

Traditional indexes of LV dyssynchrony (DYS) in pts to be resynchronized are sensitive to noise, while the concordance between LV lead position and site of latest mechanical activation is suggested to be, in these patients, clinically relevant. Both aspects, asynchrony and lead position have been addressed separately but unclear is their potential synergistic role in the clinical evolution of CRT patients. We assessed clinical and echocardiographic outcome, as well as mid-term prognosis, in a population of CHF patients submitted to CRT, stratified according to a novel asynchrony quantitation (temporal uniformity of strain: TUS) method and concordance or not between presumed LV lead position and site of latest mechanical activation. TUS was computed in 85 pts (QRS > 120 ms, EF < 0.35) in whom we measured circumferential and longitudinal strains using speckle-tracking 2D-echocardiography before and 3-6 months after CRT, together with triplane apical LV volumes. Optimal LV lead position in short axis view was defined as concordance of the segment with latest systolic circumferential strain prior-CRT and segment with assumed LV lead position. Assumed LV lead position was defined from a chest X-ray obtained 1 day after implantation and scored as anterior, lateral, posterior or inferior using 2 orthogonal views (antero-posterior and lateral). Following CRT, LV volume decreased (diastolic -8 ± 20%) and EF improved (+6 ± 9%, P < 0.001 for both). Two-way ANOVA revealed TUS improvement post-CRT (+22 ± 68%, P = 0.025), with a clear evidence for more marked asynchrony detectable at circumferential (from 0.53 ± 0.20 to 0.55 ± 0.19) as compared with longitudinal level (from 0.56 ± 0.14 to 0.62 ± 0.14) (P = 0.017). Multivariate analysis revealed that greater baseline asynchrony, as assessed circumferentially (P = 0.079), together with concordance between LV lead position and site of activation (P = 0.012), besides younger age (P = 0.051), longer QRS duration (P = 0.021) and higher baseline EF (P = 0.04),), but not longitudinal TUS (P = 0.231) did predict death from any cause or new episodes of pulmonary or systemic congestion requiring i.v. diuretics during a 529 ± 357 days clinical follow-up. We conclude that DYS indexed by circumferential TUS yields CRT benefits, supporting the idea of targeting TUS-measured DYS as the informative asynchrony quantitative measurement in CRT pts. Significant predictability in medium-term clinical follow-up of patients to be resynchronized is also associated with concordance between site of latest mechanical activation and presumed LV lead position in the present study.

A Guide to the Use of Left Ventricular Analysis with 3D Echo in Dyssynchrony

Data from single-centre studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronisation therapy (CRT). To our knowledge, the only published multicentre trial that compared 12 echocardiographic methods, the Predictors of response to cardiac resynchronization therapy (PROSPECT) trial, stated that none of the echocardiographic measurements of ventricular dyssynchrony applied in the study were able to distinguish responders from non-responders. Realtime 3D echocardiography is able to measure left ventricular (LV) size, function and dyssynchrony to identify the presence and extension of scar tissue and to evaluate where the site of latest mechanical activation is. After CRT device implantation, it also allows physicians to detect where the first mechanical activation secondary to LV pacing is located. Indeed, it can be useful in interventricular (VV) delay optimisation of the device after the implantation and, in single-centre studies, it was able to predict response to CRT and to identify responders from non-responders. Care must be taken to optimise temporal resolution, but now volume rates of 70–80vps can be easily obtained in the majority of cases. VV optimisation using realtime 3D echocardiography is feasible and intuitive, but time-consuming compared with traditional methods based on Doppler or algorithms. In this article we illustrate our approach to LV analysis with realtime 3D echocardiography in the study of dyssynchrony.

Finding Pieces of the Puzzle of Nonresponse to Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an exciting advance for heart failure patients. As a result of a wealth of evidence from randomized clinical trials, guidelines for selecting patients for CRT have been established, including New York Heart Association functional class III or IV on optimal medical therapy, QRS width ≥120 ms, and ejection fraction ≤35%.1,2 The landmark Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial published in 2002 reported a 67% improvement in the group randomized to CRT using a clinical composite score in which patients were judged to be improved, unchanged, or worsened.1 Interestingly, the very recent Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trial, designed to assess strategies for atrioventricular (AV) and interventricular (VV) interval optimization, reported a 67.5% improvement after CRT using the same clinical composite score.3 Despite tremendous advances in knowledge and experience with CRT, the proportion of patients considered clinical nonresponders has remained at one third over the last 8 years. Puzzling questions remain: Why are there nonresponders to CRT? Can we improve on current patient selection for CRT to reduce nonresponders? The important article by Delgado et al4 in this issue finds some pieces of the puzzle of nonresponse by focusing on a large series of patients with ischemic heart failure. They reported that mortality and heart failure hospitalizations after CRT in patients with routine indications are associated with dyssynchrony, left ventricular (LV) lead position, and estimates of regional scar. It is worthwhile to consider these factors individually, in combination, and in context of other variables that may influence response to CRT (the Figure). Figure. The puzzle of nonresponse to CRT. Article see p 70 There is an abundance of data to support dyssynchrony as the major pathological derangement associated with mechanical inefficiency and deleterious biological effects that …

Optimal left ventricular lead position assessed with phase analysis on gated myocardial perfusion SPECT

PurposeThe aim of the current study was to evaluate the relationship between the site of latest mechanical activation as assessed with gated myocardial perfusion SPECT (GMPS), left ventricular (LV) lead position and response to cardiac resynchronization therapy (CRT).MethodsThe patient population consisted of consecutive patients with advanced heart failure in whom CRT was currently indicated. Before implantation, 2-D echocardiography and GMPS were performed. The echocardiography was performed to assess LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). The site of latest mechanical activation was assessed by phase analysis of GMPS studies and related to LV lead position on fluoroscopy. Echocardiography was repeated after 6 months of CRT. CRT response was defined as a decrease of ≥15% in LVESV.ResultsEnrolled in the study were 90 patients (72% men, 67±10 years) with advanced heart failure. In 52 patients (58%), the LV lead was positioned at the site of latest mechanical activation (concordant), and in 38 patients (42%) the LV lead was positioned outside the site of latest mechanical activation (discordant). CRT response was significantly more often documented in patients with a concordant LV lead position than in patients with a discordant LV lead position (79% vs. 26%, p<0.01). After 6 months, patients with a concordant LV lead position showed significant improvement in LVEF, LVESV and LVEDV (p<0.05), whereas patients with a discordant LV lead position showed no significant improvement in these variables.ConclusionPatients with a concordant LV lead position showed significant improvement in LV volumes and LV systolic function, whereas patients with a discordant LV lead position showed no significant improvements.

Usefulness of Three-Dimensional Speckle Tracking Strain to Quantify Dyssynchrony and the Site of Latest Mechanical Activation

Previous methods to quantify dyssynchrony could not determine regional 3-dimensional (3-D) strain. We hypothesized that a novel 3-D speckle tracking strain imaging system can quantify left ventricular (LV) dyssynchrony and site of latest mechanical activation. We studied 64 subjects; 54 patients with heart failure were referred for cardiac resynchronization therapy (CRT) with an ejection fraction 25 +/- 6% and QRS interval 165 +/- 29 ms and 10 healthy volunteer controls. The 3-D speckle tracking system determined radial strain using a 16-segment model from a pyramidal 3-D dataset. Dyssynchrony was quantified as maximal opposing wall delay and SD in time to peak strain. The 3-D analysis was compared to standard 2-dimensional (2-D) strain datasets and site of 3-D latest mechanical activation, not possible by 2D was quantified. As expected, dyssynchrony in patients on CRT was significantly greater than in controls (maximal opposing wall delay 316 +/- 112 vs 59 +/- 12 ms and SD 124 +/- 48 vs 28 +/- 11 ms, p <0.001 vs normal). The 3-D opposing wall delay was closely correlated with 3-D 16-segment SD (r = 0.95) and 2-D mid-LV strain (r = 0.83) and SD (r = 0.85, all p values <0.001). The 3-D site of the latest mechanical activation was most commonly midposterior (26%), basal posterior (22%), midlateral (20%), and basal lateral (17%). Eleven patients studied after CRT demonstrated improvements in 3-D synchrony (300 +/- 124 to 94 +/- 37 ms) and ejection fraction (24 +/- 6% to 31 +/- 7%, p <0.05). In conclusion, 3-D speckle tracking can successfully quantify 3-D dyssynchrony and site the latest mechanical activation. This approach may play a clinical role in management of patients on CRT.