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      Echocardiography and cardiac resynchronisation therapy, friends or foes?

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          Abstract

          Echocardiography is used in cardiac resynchronisation therapy (CRT) to assess cardiac function, and in particular left ventricular (LV) volumetric status, and prediction of response. Despite its widespread applicability, LV volumes determined by echocardiography have inherent measurement errors, interobserver and intraobserver variability, and discrepancies with the gold standard magnetic resonance imaging. Echocardiographic predictors of CRT response are based on mechanical dyssynchrony. However, parameters are mainly tested in single-centre studies or lack feasibility. Speckle tracking echocardiography can guide LV lead placement, improving volumetric response and clinical outcome by guiding lead positioning towards the latest contracting segment. Results on optimisation of CRT device settings using echocardiographic indices have so far been rather disappointing, as results suffer from noise. Defining response by echocardiography seems valid, although re-assessment after 6 months is advisable, as patients can show both continuous improvement as well as deterioration after the initial response. Three-dimensional echocardiography is interesting for future implications, as it can determine volume, dyssynchrony and viability in a single recording, although image quality needs to be adequate. Deformation patterns from the septum and the derived parameters are promising, although validation in a multicentre trial is required. We conclude that echocardiography has a pivotal role in CRT, although clinicians should know its shortcomings.

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          Most cited references55

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          Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

          This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure

            Aims Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data. Methods and results An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58–73) years, QRS duration was 160 (146–176) ms, LVEF was 24 (20–28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value. Conclusion QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response. ClinicalTrials.gov numbers NCT00170300, NCT00271154, NCT00251251.
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              Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy.

              In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. Patients (n=141) with advanced heart failure (mean+/-SD age, 64+/-11 years; 73% men) who received CRT were followed up for a mean (+/-SD) of 695+/-491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of > or =9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank chi2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank chi2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank chi2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (beta=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (beta=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event. A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.
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                Author and article information

                Contributors
                w.m.vaneverdingen@umcutrecht.nl
                Journal
                Neth Heart J
                Neth Heart J
                Netherlands Heart Journal
                Bohn Stafleu van Loghum (Houten )
                1568-5888
                1876-6250
                8 December 2015
                8 December 2015
                January 2016
                : 24
                : 1
                : 25-38
                Affiliations
                Department of Cardiology, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA Utrecht, The Netherlands
                Article
                769
                10.1007/s12471-015-0769-3
                4692834
                26645707
                8da76b0f-be12-4158-9a91-71dcbab1a928
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2016

                Cardiovascular Medicine
                cardiac resynchronisation therapy,echocardiography,volume,optimisation,dyssynchrony,response,follow-up,interobserver variability,speckle tracking echocardiography,deformation imaging,3d echocardiography,septal strain

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