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      Optimized Left Ventricular Endocardial Stimulation Is Superior to Optimized Epicardial Stimulation in Ischemic Patients With Poor Response to Cardiac Resynchronization Therapy : A Combined Magnetic Resonance Imaging, Electroanatomic Contact Mapping, and Hemodynamic Study to Target Endocardial Lead Placement

      research-article
      , MBBS, BSc , , MBBS, , PhD, , LLB, MBBS, , MD, , PhD, , MBBS, , MBBS, , MD, DPhil, , MD, , DPhil, , MD
      Jacc. Clinical Electrophysiology
      Elsevier Inc
      cardiac magnetic resonance imaging, CRT, electroanatomic map, endocardial pacing, AHR, acute hemodynamic response, CMR, cardiac magnetic resonance, CRT, cardiac resynchronization therapy, EAM, electroanatomic mapping, LV, left ventricle/ventricular, LVendo, left ventricular endocardium, LVepi, optimal epicardial response, LVepi1, implanted LV lead, LVepi2, temporary LV lead, Q-LV, first ventricular depolarization

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          Abstract

          Objectives

          The purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT).

          Background

          LV endocardial pacing may offer benefit over conventional CRT in ischemic patients.

          Methods

          We performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems.

          Results

          In all, 135 epicardial and endocardial pacing sites were tested in 8 patients. Endocardial pacing was superior to epicardial pacing with respect to mean AHR (% change in dP/dt max vs. baseline) (11.81 [-7.2 to 44.6] vs. 6.55 [-11.0 to 19.7]; p = 0.025). This was associated with a similar first ventricular depolarization (Q-LV) (75 ms [13 to 161 ms] vs. 75 ms [25 to 129 ms]; p = 0.354), shorter stimulation–QRS duration (15 ms [7 to 43 ms] vs. 19 ms [5 to 66 ms]; p = 0.010) and shorter paced QRS duration (149 ms [95 to 218 ms] vs. 171 ms [120 to 235 ms]; p < 0.001). The mean best achievable AHR was higher with endocardial pacing (25.64 ± 14.74% vs. 12.64 ± 6.76%; p = 0.044). Furthermore, AHR was significantly greater pacing the same site endocardially versus epicardially (15.2 ± 10.7% vs. 7.6 ± 6.3%; p = 0.014) with a shorter paced QRS duration (137 ± 22 ms vs. 166 ± 30 ms; p < 0.001) despite a similar Q-LV (70 ± 38 ms vs. 79 ± 34 ms; p = 0.512). Lack of capture due to areas of scar (corroborated by EAM and cardiac magnetic resonance) was associated with a poor AHR.

          Conclusions

          In ischemic patients with poor CRT response, biventricular endocardial pacing is superior to epicardial pacing. This may reflect accessibility to sites that cannot be reached via coronary sinus anatomy and/or by access to more rapidly conducting tissue. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as cardiac magnetic resonance to target delayed activating sites while avoiding scar.

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          Most cited references20

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          Defining left bundle branch block in the era of cardiac resynchronization therapy.

          Cardiac resynchronization therapy (CRT) has emerged as an attractive intervention to improve left ventricular mechanical function by changing the sequence of electrical activation. Unfortunately, many patients receiving CRT do not benefit but are subjected to device complications and costs. Thus, there is a need for better selection criteria. Current criteria for CRT eligibility include a QRS duration ≥ 120 ms. However, QRS morphology is not considered, although it can indicate the cause of delayed conduction. Recent studies have suggested that only patients with left bundle branch block (LBBB) benefit from CRT, and not patients with right bundle branch block or nonspecific intraventricular conduction delay. The authors review the pathophysiologic and clinical evidence supporting why only patients with complete LBBB benefit from CRT. Furthermore, they review how the threshold of 120 ms to define LBBB was derived subjectively at a time when criteria for LBBB and right bundle branch block were mistakenly reversed. Three key studies over the past 65 years have suggested that 1/3 of patients diagnosed with LBBB by conventional electrocardiographic criteria may not have true complete LBBB, but likely have a combination of left ventricular hypertrophy and left anterior fascicular block. On the basis of additional insights from computer simulations, the investigators propose stricter criteria for complete LBBB that include a QRS duration ≥ 140 ms for men and ≥ 130 ms for women, along with mid-QRS notching or slurring in ≥ 2 contiguous leads. Further studies are needed to reinvestigate the electrocardiographic criteria for complete LBBB and the implications of these criteria for selecting patients for CRT. Published by Elsevier Inc.
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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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              Echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy: results of the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region trial.

              Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable. The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28-0.82; P=0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls (P=0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22-0.71; P=0.002). A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00156390.
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                Author and article information

                Contributors
                Journal
                JACC Clin Electrophysiol
                JACC Clin Electrophysiol
                Jacc. Clinical Electrophysiology
                Elsevier Inc
                2405-500X
                2405-5018
                1 December 2016
                December 2016
                : 2
                : 7
                : 799-809
                Affiliations
                [1]Department of Imaging Sciences and Biomedical Engineering, King’s College London & Guy’s and St Thomas’ Hospital, London, United Kingdom
                Author notes
                [] Reprint requests and correspondence: Dr. Jonathan M. Behar, Imaging Sciences & Biomedical Engineering, St. Thomas’ Hospital, 4th Floor Lambeth Wing, London SE1 7EH, United Kingdom.Imaging Sciences & Biomedical Engineering, St. Thomas’ Hospital4th Floor Lambeth WingLondon SE1 7EHUnited Kingdom jonathan.behar@ 123456kcl.ac.uk
                Article
                S2405-500X(16)30108-6
                10.1016/j.jacep.2016.04.006
                5196018
                28066827
                e69dbd7c-052a-46ad-aeff-2e179094e1c9
                © 2016 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 December 2015
                : 31 March 2016
                : 7 April 2016
                Categories
                New Research Paper

                cardiac magnetic resonance imaging,crt,electroanatomic map,endocardial pacing,ahr, acute hemodynamic response,cmr, cardiac magnetic resonance,crt, cardiac resynchronization therapy,eam, electroanatomic mapping,lv, left ventricle/ventricular,lvendo, left ventricular endocardium,lvepi, optimal epicardial response,lvepi1, implanted lv lead,lvepi2, temporary lv lead,q-lv, first ventricular depolarization

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