Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling

Shetty, Anoop; Duckett, Simon; Ginks, Matthew; Ma, Yinglaing; Sohal, Manav; Bostock, Julian; Kapetanakis, Stamatis; Singh, Jagmeet P.; Rhode, Kawal; Wright, Matthew; O’Neill, Mark; Gill, Jaswinder; Carr‐White, Gerald; Razavi, Reza; Rinaldi, Christopher Aldo

doi:10.1093/ehjci/jes270

Cited by 68 publications

(64 citation statements)

References 35 publications

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“…Expressing N2BAsc did not reverse anatomical remodeling of LV and LA chambers at 4 weeks post-surgery (Table 1). This might be explained by the continued pressure overload (the aortic constriction was not removed) or insufficient time for reversal of anatomical remodeling to take place 41–44 . The latter is supported by results from a pilot study in which TAC/DOCA cRbm20 Δ RRM mice were sacrificed 14 weeks after raloxifene injection and that showed normalization of left atrial dimension, as well as diastolic function recovery (results not shown).…”

Section: Discussionmentioning

confidence: 99%

Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction

et al. 2016

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Background Left Ventricular (LV) stiffening contributes to Heart Failure with preserved Ejection Fraction (HFpEF), a syndrome with no effective treatment options. Increasing titin’s compliance in the heart has become possible recently through inhibition of the splicing factor RBM20. Here we investigated the effects of increasing titin’s compliance in mice with diastolic dysfunction. Methods Mice in which the RNA recognition motif (RRM) of one of the RBM20 alleles was floxed and which expressed the MerCreMer transgene under control of the αMHC promoter (referred to as cRbm20ΔRRM mice) were used. Mice underwent transverse aortic constriction (TAC) surgery and deoxycorticosterone acetate (DOCA) pellet implantation (TAC/DOCA). RRM deletion in adult mice was triggered by injecting raloxifene (cRbm20ΔRRM-raloxifene) with DMSO injected mice (cRbm20ΔRRM-DMSO) as the control. Diastolic function was investigated using echocardiography and pressure volume analysis; passive stiffness was studied in LV muscle strips and isolated cardiac myocytes before and after elimination of titin-based stiffness. Treadmill exercise performance was also studied. Titin isoform expression was evaluated with Agarose gels. Results cRbm20ΔRRM-raloxifene mice expressed large titins in the hearts, named super compliant titin (N2BAsc), which, within 3 weeks after raloxifene injection, made up ~45% of total titin. TAC/DOCA cRbm20ΔRRM-DMSO mice developed LV hypertrophy and a marked increase in LV chamber stiffness as shown by both pressure-volume analysis and echocardiography. LV chamber stiffness was normalized in TAC/DOCA cRbm20ΔRRM-raloxifene mice that expressed N2BAsc. Passive stiffness measurements on muscle strips isolated from the LV free wall revealed that extracellular matrix (ECM) stiffness was equally increased in both groups of TAC/DOCA mice (cRbm20ΔRRM-DMSO and cRbm20ΔRRM-raloxifene). However, titin-based muscle stiffness was reduced in the mice that expressed N2BAsc (TAC/DOCA cRbm20ΔRRM-raloxifene). Exercise testing demonstrated significant improvement in exercise tolerance in TAC/DOCA mice that expressed N2BAsc. Conclusions Inhibition of the RBM20-based titin splicing system upregulates compliant titins, which improves diastolic function and exercise tolerance in the TAC/DOCA model. Titin holds promise as a therapeutic target for HFpEF.

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Section: Discussionmentioning

confidence: 99%

Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction

et al. 2016

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“…2,3,5,39,42 This article has focused on understanding the causative mechanisms of these clinical findings from a cardiac electrophysiological viewpoint. It has been argued that the benefit of LV endocardial pacing may be derived from the ability to access the optimal pacing site when the anatomy of the coronary sinus limits access to the epicardial site in the same region.…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effect on Cardiac Resynchronization From Left Ventricular Endocardial Pacing Is Mediated by Early Access to High Conduction Velocity Tissue

Hyde

Behar

Claridge

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Dyssynchronous heart failure (HF) is routinely treated with cardiac resynchronization therapy (CRT). During conventional biventricular (BV) CRT, pacing is applied to the right ventricle (RV) endocardium and the left ventricle (LV) epicardium via the coronary sinus (EPI-CRT BV ). Current best practice results in 30% to 40% of CRT patients failing to display improved clinical response.1 Recent clinical 2-5 and experimental 6,7 evidence suggests that BV CRT with an endocardial pacing strategy for the LV lead (ENDO-CRT BV ) can provide an improvement in acute hemodynamic response and stroke work over EPI-CRT BV and offers a novel approach for increasing CRT response rates. However, the relative importance of cardiac physiology or better access to optimal pacing sites in causing this improved outcome remains controversial. Identifying and understanding physiological mechanisms behind improved ENDO-CRT BV response are crucial for optimizing clinical procedures and identifying patients who will receive the maximal benefit from this therapy.In acute left bundle branch block (LBBB) canine studies, ENDO-CRT BV improved the systolic LV function over conventional EPI-CRT BV .6 Electric activation times (ATs) as measured by contact mapping were decreased with ENDO-CRT BV © 2015 American Heart Association, Inc. Original Article Circ Arrhythm Electrophysiol Background-Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute hemodynamic response compared with LV epicardial pacing (EPI-CRT).The role of cardiac anatomy and physiology in this improved response remains controversial. We used computational electrophysiological models to quantify the role of cardiac geometry, tissue anisotropy, and the presence of fast endocardial conduction on myocardial activation during ENDO-CRT and EPI-CRT. Methods and Results-Cardiac activation was simulated using the monodomain tissue excitation model in 2-dimensional (2D) canine and human and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) versus epicardial (ep) LV pacing (defined as %dLV=100×(LVLAT ep −LVLAT en )/LVLAT ep and %dT=100×(TLAT ep −TLAT en )/TLAT ep , respectively). Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodeled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular-paced canine model resulted in %dLV and %dT values of −7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding fast endocardial conduction to this model altered %dLV and %dT to 13.1% and 10.1%, respectively. Conclusions-Our results provide a physiological explanation for improved response to ENDO-CRT. We predict that patients with viable fast-conducting endocardial tissue or distal Purkinje network or both, as we...

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“…Neither of these studies evaluated or prescribed targets for the RV lead. The concept of using an intraprocedural model to guide lead delivery was recently described by Shetty et al 37 CMR was similarly exploited to identify optimal segmental targets for the LV lead based on both scar and mechanical dyssynchrony measures. Their approach was to incorporate this model into a vendor-based architecture to provide image fusion with live fluoroscopy.…”

Section: Discussionmentioning

confidence: 99%

Model-Based Navigation of Left and Right Ventricular Leads to Optimal Targets for Cardiac Resynchronization Therapy

Laksman

Yee

Stirrat

et al. 2014

Circ: Arrhythmia and Electrophysiology

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Background-Left ventricular (LV) and right ventricular pacing site characteristics have been shown to influence response to cardiac resynchronization therapy (CRT). This study aimed to determine the clinical feasibility of image-guided lead delivery using a 3-dimensional navigational model displaying both LV and right ventricular (RV) pacing targets. Serial echocardiographic measures of clinical response and procedural metrics were evaluated. Methods and Results-Thirty-one consecutive patients underwent preimplant cardiac MRI with the generation of a 3-dimensional navigational model depicting optimal segmental targets for LV and RV leads. Lead delivery was guided by the model in matched views to intraprocedural fluoroscopy. Blinded assessment of final lead tip location was performed from postprocedural cardiac computed tomography. Clinical and LV remodeling response criteria were assessed at baseline, 3 months, and 6 months using a 6-minute hall walk, quality of life questionnaire, and echocardiography. Mean age and LV ejection fraction was 66±8 years and 26±8%, respectively. LV leads were successfully delivered to a target or adjacent segment in 30 of 31 patients (97%), 68% being nonposterolateral. RV leads were delivered to a target or adjacent segment in 30 of 31 patients (97%), 26% being nonapical. Twenty-three patients (74%) met standard criteria for response (LV end-systolic volume reduction ≥15%), 18 patients (58%) for super-response (LV end-systolic volume reduction ≥30%). LV ejection fraction improved at 6 months (31±8 versus 26±8%, P=0.04). Conclusions-This study demonstrates clinical feasibility of dual cardiac resynchronization therapy lead delivery to optimal targets using a 3-dimensional navigational model. High procedural success, acceptable procedural times, and a low rate of early procedural complications were observed. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01640769.

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Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling

Cited by 68 publications

References 35 publications

Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction

Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a Mouse Model of Heart Failure With Preserved Ejection Fraction

Beneficial Effect on Cardiac Resynchronization From Left Ventricular Endocardial Pacing Is Mediated by Early Access to High Conduction Velocity Tissue

Model-Based Navigation of Left and Right Ventricular Leads to Optimal Targets for Cardiac Resynchronization Therapy

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