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Multisite pacing (MSP) of the left ventricle is proposed as an alternative to conventional single-site LV pacing in cardiac resynchronization therapy (CRT). Reports on the benefits of MSP have been conflicting. A paradigm whereby not all patients derive benefit from MSP is emerging.We sought to compare the hemodynamic and electrical effects of MSP with the aim of identifying a subgroup of patients more likely to derive benefit from MSP.Sixteen patients with implanted CRT systems incorporating a quadripolar LV pacing lead were studied. Invasive hemodynamic and electroanatomic assessment was performed during the following rhythms: baseline (non-CRT); biventricular (BIV) pacing delivered via the implanted CRT system (BIV(implanted)); BIV pacing delivered via an alternative temporary LV lead (BIV(alternative)); dual-vein MSP delivered via 2 LV leads; MultiPoint Pacing delivered via 2 vectors of the quadripolar LV lead.Seven patients had an acute hemodynamic response (AHR) of10% over baseline rhythm with BIV(implanted) and were deemed nonresponders. AHR in responders vs nonresponders was 21.4% ± 10.4% vs 2.0% ± 5.2% (P.001). In responders, neither form of MSP provided incremental hemodynamic benefit over BIV(implanted). Dual-vein MSP (8.8% ± 5.7%; P = .036 vs BIV(implanted)) and MultiPoint Pacing (10.0% ± 12.2%; P = .064 vs BIV(implanted)) both improved AHR in nonresponders. Seven of 9 responders to BIV(implanted) had LV endocardial activation characterized by a functional line of block during intrinsic rhythm that was abolished with BIV pacing. All these patients met strict criteria for left bundle branch block (LBBB). No nonresponders exhibited this line of block or met strict criteria for LBBB.Patients not meeting strict criteria for LBBB appear most likely to derive benefit from MSP.

ECG imaging is an emerging technology for the reconstruction of cardiac electric activity from non-invasively measured body surface potential maps. In this case report, we present the first evaluation of transmurally imaged activation times against endocardially reconstructed isochrones for a case of sustained monomorphic ventricular tachycardia (VT). Computer models of the thorax and whole heart were produced from MR images. A recently published approach was applied to facilitate electrode localization in the catheter laboratory, which allows for the acquisition of body surface potential maps while performing non-contact mapping for the reconstruction of local activation times. ECG imaging was then realized using Tikhonov regularization with spatio-temporal smoothing as proposed by Huiskamp and Greensite and further with the spline-based approach by Erem et al. Activation times were computed from transmurally reconstructed transmembrane voltages. The results showed good qualitative agreement between the non-invasively and invasively reconstructed activation times. Also, low amplitudes in the imaged transmembrane voltages were found to correlate with volumes of scar and grey zone in delayed gadolinium enhancement cardiac MR. The study underlines the ability of ECG imaging to produce activation times of ventricular electric activity-and to represent effects of scar tissue in the imaged transmembrane voltages.

Cardiac Resynchronisation Therapy (CRT) causes changes in cardiac anatomy, electrophysiology and mechanics of the heart after 3-6 months of treatment. Multi-pole pacing (MPP) and multi-vein pacing (MVP) are new technologies that offer the ability to change the location of the pacing site post implant, however, the long term benefits of shifting the left ventricle (LV) pacing site are still uncertain. A personalised biophysical electromechanical model of a patient's heart was developed from MRI, echocardiogram, ECG and pressure catheter recordings, before and after sustained CRT treatment. Simulations of biventricular pacing of the heart were performed for 49 pacing sites across the LV free wall, in the model of the patient prior to- and after sustained pacing. The optimal region for LV pacing was determined by the acute haemodynamic response (AHR). After sustained CRT treatment the heart remodels and the models predict that the optimal region for pacing the LV would expand by 46% after this remodeling. The expansion in the optimal LV pacing region after remodeling predicts that if LV lead location was placed within the optimal region prior to CRT treatment, it will remain within the optimal region after sustained pacing.

Aims Problems with implanting a left ventricular (LV) lead during cardiac resynchronization therapy (CRT) procedures are not uncommon and may occur for a variety of reasons including phrenic nerve stimulation (PNS) and high capture thresholds. We aimed to perform successful CRT in patients with previous LV lead problems using the multiple pacing configurations available with the St Jude Quartet model 1458Q quadripolar LV lead to overcome PNS or high capture thresholds. Methods and results Four patients with previous failed attempts at LV lead implantation underwent a further attempt at CRT using a Quartet lead. In all four cases, successful CRT was achieved using a Quartet lead placed in a branch of the coronary sinus. Problems with PNS or high capture thresholds were seen in all four patients but were successfully overcome. Satisfactory lead parameters were seen at implant, pre-discharge, and at short-term follow-up (8.5 ± 5 weeks). Conclusion The Quartet lead allows 10 different pacing vectors to be used and may overcome common pacing problems because of the multiple pacing configurations available. Problems with either PNS or unsatisfactory pacing parameters experienced during CRT may be resolved simply by changing the pacing configuration using this quadripolar lead system.

Background Cardiac magnetic resonance (CMR) imaging enables characterization of myocardial scar and the ‘grey zone’, an admixture of scar and healthy myocardium, which is an independent predictor of ventricular arrhythmia. We explored the relationship between the grey zone and ventricular tachycardia circuits (VT) in ischaemic cardiomyopathy. Methods Two patients with previous myocardial infarct underwent high-resolution late gadolinium enhanced CMR scar imaging (1.2x1.2x2.6mm) and a VT-stimulation study. The LV scar core was segmented using full-width-half-maximum method; and the grey zone was segmented with a cut-off signal intensity below that of the scar core and above 2 standard-deviation of the remote healthy myocardium. A multi-electrode array (MEA) was positioned in the LV cavity for simultaneous electroanatomical mapping during the study. The MEA shell was registered with the CMR-derived LV shell using anatomical landmark registration (Figure 1a,b) for comparison. Results Sustained monomorphic VT (SMVT) was induced in both patients. Scar core and grey zone regions correlated well with the low voltage area (≤ 30% maximum voltage) seen on the MEA (Figure 1a,c,d). The exit point during SMVT

Background ICD implantation is known to improve prognosis in patients with ischemic cardiomyopathy (ICM). Determining which patients are at high risk of ventricular arrhythmias and sudden death remains difficult. The presence and extent of grey zone detected by CMR has been linked to ventricular arrhythmias and may be useful in determining which patients should have an ICD. Several processing methods to define the area of grey zone based on traditional late enhancement sequences (LGE) have been developed. Recently, a novel delayed enhancement sequence (MCDE) combined with an automated segmentation method was introduced to more accurately assess the peri-infarct area. 1,2 One limitation of this technique is the presence of cardiac motion in the image making the analysis cumbersome as the images from the same point in the cardiac cycle need to be filtered out of the dataset during postprocessing. An alternative option for the quantitative T1 measurement of the grey zone is the modified look-locker (MOLLI), which is not affected by cardiac motion. In the current study, the MCDE and MOLLI sequences were compared for the evaluation of the grey zone.

It is known that 30-40% of heart failure patients that undergo cardiac resynchronization therapy (CRT) do not derive significant clinical benefit. Using cine imaging a measure of volume change over the cardiac cycle can be derived called the Systolic Dyssynchrony Index (SDI). This has the potential to improve patient selection pre CRT.

Myocardial stiffness is a valuable clinical biomarker for the monitoring and stratification of heart failure (HF). Cardiac finite element models provide a biomechanical framework for the assessment of stiffness through the determination of the myocardial constitutive model parameters. The reported parameter intercorrelations in popular constitutive relations, however, obstruct the unique estimation of material parameters and limit the reliable translation of this stiffness metric to clinical practice. Focusing on the role of the cost function (CF) in parameter identifiability, we investigate the performance of a set of geometric indices (based on displacements, strains, cavity volume, wall thickness and apicobasal dimension of the ventricle) and a novel CF derived from energy conservation. Our results, with a commonly used transversely isotropic material model (proposed by Guccione et al.), demonstrate that a single geometry-based CF is unable to uniquely constrain the parameter space. The energy-based CF, conversely, isolates one of the parameters and in conjunction with one of the geometric metrics provides a unique estimation of the parameter set. This gives rise to a new methodology for estimating myocardial material parameters based on the combination of deformation and energetics analysis. The accuracy of the pipeline is demonstrated in silico, and its robustness in vivo, in a total of 8 clinical data sets (7 HF and one control). The mean identified parameters of the Guccione material law were \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$C_1=3000\pm 1700\,\hbox {Pa}$$\end{document}C1=3000±1700Pa and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\alpha =45\pm 25$$\end{document}α=45±25 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_f=25\pm 14$$\end{document}bf=25±14, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_{ft}=11\pm 6$$\end{document}bft=11±6, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_{t}=9\pm 5$$\end{document}bt=9±5) for the HF cases and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$C_1=1700\,\hbox {Pa}$$\end{document}C1=1700Pa and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\alpha =15$$\end{document}α=15 (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_f=8$$\end{document}bf=8, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_{ft}=4$$\end{document}bft=4, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$b_{t}=3$$\end{document}bt=3) for the healthy case.

Background Acute indicators of response to cardiac resynchronisation therapy (CRT) are critical for developing lead optimisation algorithms and evaluating novel multi-polar, multi-lead and endocardial pacing protocols. Accounting for beat-to-beat variability in measures of acute haemodynamic response (AHR) may help clinicians understand the link between acute measurements of cardiac function and long term clinical outcome. Methods and results A retrospective study of invasive pressure tracings from 38 patients receiving an acute pacing and electrophysiological study was performed. 602 pacing protocols for left ventricle (LV) (n = 38), atria–ventricle (AV) (n = 9), ventricle–ventricle (VV) (n = 12) and endocardial (ENDO) (n = 8) optimisation were performed. AHR was measured as the maximal rate of LV pressure development (dP/dtMx) for each beat. The range of the 95% confidence interval (CI) of mean AHR was ~ 7% across all optimisation protocols compared with the reported CRT response cut off value of 10%. A single clear optimal protocol was identifiable in 61%, 22%, 25% and 50% for LV, AV, VV and ENDO optimisation cases, respectively. A level of service (LOS) optimisation that aimed to maximise the expected AHR 5th percentile, minimising variability and maximising AHR, led to distinct optimal protocols from conventional mean AHR optimisation in 34%, 78%, 67% and 12.5% of LV, AV, VV and ENDO optimisation cases, respectively. Conclusion The beat-to-beat variation in AHR is significant in the context of CRT cut off values. A LOS optimisation offers a novel index to identify the optimal pacing site that accounts for both the mean and variation of the baseline measurement and pacing protocol.

Background Many patients with electrical dyssynchrony who undergo cardiac resynchronization therapy (CRT) do not obtain substantial benefit. Assessing mechanical dyssynchrony may improve patient selection. Results from studies using echocardiographic imaging to measure dyssynchrony have ultimately proved disappointing. We sought to evaluate cardiac motion in patients with heart failure and electrical dyssynchrony using cardiovascular magnetic resonance (CMR). We developed a framework for comparing measures of myocardial mechanics and evaluated how well they predicted response to CRT. Methods CMR was performed at 1.5 Tesla prior to CRT. Steady-state free precession (SSFP) cine images and complementary modulation of magnetization (CSPAMM) tagged cine images were acquired. Images were processed using a novel framework to extract regional ventricular volume-change, thickening and deformation fields (strain). A systolic dyssynchrony index (SDI) for all parameters within a 16-segment model of the ventricle was computed with high SDI denoting more dyssynchrony. Once identified, the optimal measure was applied to a second patient population to determine its utility as a predictor of CRT response compared to current accepted predictors (QRS duration, LBBB morphology and scar burden). Results Forty-four patients were recruited in the first phase (91% male, 63.3 ± 14.1 years; 80% NYHA class III) with mean QRSd 154 ± 24 ms. Twenty-one out of 44 (48%) patients showed reverse remodelling (RR) with a decrease in end systolic volume (ESV) ≥ 15% at 6 months. Volume-change SDI was the strongest predictor of RR (PR 5.67; 95% CI 1.95-16.5; P = 0.003). SDI derived from myocardial strain was least predictive. Volume-change SDI was applied as a predictor of RR to a second population of 50 patients (70% male, mean age 68.6 ± 12.2 years, 76% NYHA class III) with mean QRSd 146 ± 21 ms. When compared to QRSd, LBBB morphology and scar burden, volume-change SDI was the only statistically significant predictor of RR in this group. Conclusion A systolic dyssynchrony index derived from volume-change is a highly reproducible measurement that can be derived from routinely acquired SSFP cine images and predicts RR following CRT whilst an SDI of regional strain does not. ISSN:1097-6647 ISSN:1532-429X