Optimization of CRT programming using non-invasive electrocardiographic imaging to assess the acute electrical effects of multipoint pacing.

AIM: Quadripolar lead technology and multi-point pacing (MPP) are important clinical adjuncts in cardiac resynchronization therapy (CRT) pacing aimed at reducing the rate of non-response to therapy. Mixed results have been achieved using MPP and it is critical to identify which patients require this approach and how to configure their MPP stimulation, in order to achieve optimal electrical resynchronization. METHODS & RESULTS: We sought to investigate whether electrocardiographic imaging (ECGi), using the CARDIOINSIGHT ™ inverse ECG mapping system, could identify alterations in electrical resynchronization during different methods of device optimization. In no patient did a single form of programming optimization provide the best electrical response. The effects of utilizing MPP were idiosyncratic and highly patient specific. ECGi activation maps were clearly able to discern changes in bulk LV activation during differing MPP programming. In two of the five subjects, MPP resulted in more rapid activation of the left ventricle compared to standard CRT; however, in the remaining three patients, the use of MPP did not appear to acutely improve electrical resynchronization. Crucially, this cohort showed evidence of extensive LV scarring which was well visualized using both CMR and ECGi voltage mapping. CONCLUSIONS: Our work suggests a potential role for ECGi in the optimization of non-responders to CRT, as it allows the fusion of activation maps and scar analysis above and beyond interrogation of the 12 lead ECG.

Variation in activation time during bipolar vs extended bipolar left ventricular pacing.

BACKGROUND: Cardiac resynchronization therapy (CRT) is typically delivered via quadripolar leads that allow stimulation using either true bipolar pacing, where stimulation occurs between two electrodes (BP) on the quadripolar lead, or extended bipole (EBP) left ventricular (LV) pacing, with the quadripolar electrodes and right ventricular coil acting as the cathode and anode, respectively. True bipolar pacing is associated with reductions in mortality and it has been postulated that these differences are the result of enhanced electrical activation. MATERIALS AND METHODS: Patients undergoing a CRT underwent an electrocardiographic imaging study where electrical activation data were recorded while different LV pacing vectors were temporarily programmed. RESULTS: There were no differences in the total electrical activation times or dispersion of electrical activation between biventricular pacing with bipolar or corresponding EBP LV vector configurations (left ventricular total activation time [LVtat] BP 74.70 ± 18.07 vs EBP 72.4 ± 22.64; P = 0.45). When dichotomized according to etiology, no difference was observed in the activation time with either BP or EBP pacing (LVtat BP ischemic cardiomyopathy 72.2 ± 17.4 vs BP dilated cardiomyopathy 79.9 ± 18.9; P = 0.38). CONCLUSIONS: Bipolar pacing alters the mechanical activation sequence of the LV and is associated with reductions in all-cause mortality. It has been postulated these benefits derive from improvements in electromechanical activation of the LV. Our study would suggest that true bipolar pacing does not necessarily result in more favorable activation of the LV or improved electrical resynchronization and other mechanisms should be explored.

Optimal site selection and image fusion guidance technology to facilitate cardiac resynchronization therapy.

INTRODUCTION: Cardiac resynchronization therapy (CRT) has emerged as one of the few effective treatments for heart failure. However, up to 50% of patients derive no benefit. Suboptimal left ventricle (LV) lead position is a potential cause of poor outcomes while targeted lead deployment has been associated with enhanced response rates. Image-fusion guidance systems represent a novel approach to CRT delivery, allowing physicians to both accurately track and target a specific location during LV lead deployment. AREAS COVERED: This review will provide a comprehensive evaluation of how to define the optimal pacing site. We will evaluate the evidence for delivering targeted LV stimulation at sites displaying favorable viability or advantageous mechanical or electrical properties. Finally, we will evaluate several emerging image-fusion guidance systems which aim to facilitate optimal site selection during CRT. EXPERT COMMENTARY: Targeted LV lead deployment is associated with reductions in morbidity and mortality. Assessment of tissue characterization and electrical latency are critical and can be achieved in a number of ways. Ultimately, the constraints of coronary sinus anatomy have forced the exploration of novel means of delivering CRT including endocardial pacing which hold promise for the future of CRT delivery.

Guidance for Optimal Site Selection of a Leadless Left Ventricular Endocardial Electrode Improves Acute Hemodynamic Response and Chronic Remodeling.

OBJECTIVES: This study hypothesized that guided implants, in which the optimal left ventricular endocardial (LVENDO) pacing location was identified and targeted, would improve acute markers of contractility and chronic markers of cardiac resynchronization (CRT) response. BACKGROUND: Biventricular endocardial (BiVENDO) pacing may offer a potential benefit over standard CRT; however, the optimal LVENDO pacing site is highly variable. Indiscriminately delivered BiVENDO pacing is associated with a reverse remodeling response rate of between 40% and 60%. METHODS: Registry of centers implanting a wireless, LVENDO pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California); John Radcliffe Hospital (Oxford, United Kingdom), Guy's and St. Thomas' Hospital (London, United Kingdom), and The James Cook University Hospital (Middlesbrough, United Kingdom). Centers used a combination of preprocedural imaging and electroanatomical mapping the identify the optimal LVENDO site. RESULTS: A total of 26 patients across the 3 centers underwent a guided implant. Patients were predominantly male with a mean age of 68.8 ± 8.4 years, the mean LV ejection fraction was 34.2 ± 7.8%. The mean QRS duration was 163.8 ± 26.7 ms, and 30.8% of patients had an ischemic etiology. It proved technically feasible to selectively target and deploy the pacing electrode in a chosen endocardial segment in almost all cases, with a similar complication rate to that observed during indiscriminate BiVENDO. Ninety percent of patients met the definition of echocardiographic responder. Reverse remodeling was observed in 71%. CONCLUSIONS: Guided endocardial implants were associated with a higher degree of chronic LV remodeling compared with historical nonguided approaches.

Lesion Index-Guided Ablation Facilitates Continuous, Transmural, and Durable Lesions in a Porcine Recovery Model.

BACKGROUND: The Lesion Index (LSI) is a proprietary algorithm from Abbott Medical combining contact force, radiofrequency application duration, and radiofrequency current. It can be displayed during ablation with the TactiCath contact force catheter. The LSI Index was designed to provide real-time lesion formation feedback and is hypothesized to estimate the lesion diameter. METHODS AND RESULTS: Before ablation, animals underwent cardiac computed tomography to assess atrial tissue thickness. Ablation lines (n=2-3 per animal) were created in the right atrium of 7 Göttingen mini pigs with point lesions (25 W). Within each line of ablation, the catheter tip was moved a prescribed distance (D/mm) according to 1 of 3 strategies: D=LSI+0 mm; D=LSI+2 mm; or D=LSI+4 mm. Two weeks after ablation, serial sections of targeted atrial tissue were examined histologically to identify gaps in transmural ablation. LSI-guided lines had a lower incidence of histological gaps (4 gaps in 69 catheter moves, 5.8%) than LSI+2 mm lines (7 gaps in 33 catheter moves, 21.2%) and LSI+4 mm lines (15 gaps in 23 catheter moves, 65.2%, P<0.05 versus D=LSI). ΔLSI was calculated retrospectively as the distance between 2 adjacent lesions above the mean LSI of the 2 lesions. ΔLSI values of ≤1.5 were associated with no gaps in transmural ablation. CONCLUSIONS: In this model of chronic atrial ablation, delivery of uninterrupted transmural linear lesions may be facilitated by using LSI to guide catheter movement. When ΔLSI between adjacent lesions is ≤1.5 mm, no gaps in atrial linear lesions should be expected.

Electrical latency predicts the optimal left ventricular endocardial pacing site: results from a multicentre international registry.

Aims: The optimal site for biventricular endocardial (BIVENDO) pacing remains undefined. Acute haemodynamic response (AHR) is reproducible marker of left ventricular (LV) contractility, best expressed as the change in the maximum rate of LV pressure (LV-dp/dtmax), from a baseline state. We examined the relationship between factors known to impact LV contractility, whilst delivering BIVENDO pacing at a variety of LV endocardial (LVENDO) locations. Methods and results: We compiled a registry of acute LVENDO pacing studies from five international centres: Johns Hopkins-USA, Bordeaux-France, Eindhoven-The Netherlands, Oxford-United Kingdom, and Guys and St Thomas' NHS Foundation Trust, London-UK. In all, 104 patients incorporating 687 endocardial and 93 epicardial pacing locations were studied. Mean age was 66 ± 11 years, mean left ventricular ejection fraction 24.6 ± 7.7% and mean QRS duration of 163 ± 30 ms. In all, 50% were ischaemic [ischaemic cardiomyopathy (ICM)]. Scarred segments were associated with worse haemodynamics (dp/dtmax; 890 mmHg/s vs. 982 mmHg/s, P < 0.01). Delivering BiVENDO pacing in areas of electrical latency was associated with greater improvements in AHR (P < 0.01). Stimulating late activating tissue (LVLED >50%) achieved greater increases in AHR than non-late activating tissue (LVLED < 50%) (8.6 ± 9.6% vs. 16.1 ± 16.2%, P = 0.002). However, the LVENDO pacing location with the latest Q-LV, was associated with the optimal AHR in just 62% of cases. Conclusions: Identifying viable LVENDO tissue which displays late electrical activation is crucial to identifying the optimal BiVENDO pacing site. Stimulating late activating tissue (LVLED >50%) yields greater improvements in AHR however, the optimal location is frequently not the site of latest activation.

Comprehensive use of cardiac computed tomography to guide left ventricular lead placement in cardiac resynchronization therapy.

BACKGROUND: Optimal lead positioning is an important determinant of cardiac resynchronization therapy (CRT) response. OBJECTIVE: The purpose of this study was to evaluate cardiac computed tomography (CT) selection of the optimal epicardial vein for left ventricular (LV) lead placement by targeting regions of late mechanical activation and avoiding myocardial scar. METHODS: Eighteen patients undergoing CRT upgrade with existing pacing systems underwent preimplant electrocardiogram-gated cardiac CT to assess wall thickness, hypoperfusion, late mechanical activation, and regions of myocardial scar by the derivation of the stretch quantifier for endocardial engraved zones (SQUEEZ) algorithm. Cardiac venous anatomy was mapped to individualized American Heart Association (AHA) bull's-eye plots to identify the optimal venous target and compared with acute hemodynamic response (AHR) in each coronary venous target using an LV pressure wire. RESULTS: Fifteen data sets were evaluable. CT-SQUEEZ-derived targets produced a similar mean AHR compared with the best achievable AHR (20.4% ± 13.7% vs 24.9% ± 11.1%; P = .36). SQUEEZ-derived guidance produced a positive AHR in 92% of target segments, and pacing in a CT-SQUEEZ target vein produced a greater clinical response rate vs nontarget segments (90% vs 60%). CONCLUSION: Preprocedural CT-SQUEEZ-derived target selection may be a valuable tool to predict the optimal venous site for LV lead placement in patients undergoing CRT upgrade.

Cardiac computational modeling of ventricular tachycardia and cardiac resynchronization therapy: a clinical perspective.

Computational modeling has contributed to the understanding of the normal cardiac electrophysiology and the mechanisms underlying arrhythmogenesis and arrhythmia maintenance. Our improved understanding of cardiac physiology and access to faster computational power have allowed us to integrate many layers of biological systems, gain further insight into the mechanism of cardiac pathology and moved from small scale molecular and cellular models to integrated three-dimensional models representing the anatomy, electrophysiology and hemodynamic parameters on an organ scale. The ultimate goal of cardiac modeling is to create personalized patient-specific models that would allow clinicians to better understand the disease pathology, aid diagnosis and plan treatment strategy on a case-by-case basis. Pioneers in the field have demonstrated that such approach have already impacted on the diagnosis and therapeutic treatment for ventricular arrhythmia and heart failure. This review demonstrates the feasibility to integrate computational modeling with clinical investigations in a clinical environment and to guide therapeutic treatment of cardiac arrhythmia and heart failure in real time for individual patients.

Coupling of ventricular action potential duration and local strain patterns during reverse remodeling in responders and nonresponders to cardiac resynchronization therapy.

BACKGROUND: The high risk of ventricular arrhythmias in patients with heart failure remains despite the benefit of cardiac resynchronization therapy (CRT). An electromechanical interaction between regional myocardial strain patterns and the electrophysiological substrate is thought to be important. OBJECTIVE: We investigated the in vivo relation between left ventricular activation recovery interval (ARI), as a surrogate measure of action potential duration (APD), and local myocardial strain patterns in responders and nonresponders to CRT. METHODS: ARIs were recorded from the left ventricular epicardium in 20 patients with CRT 6 weeks and 6 months post implantation. Two-dimensional speckle tracking echocardiography was performed at the same time to assess myocardial strains. Patients with ≥15% reduction in end-systolic volume at 6 months were classified as responders. RESULTS: ARI decreased in responders (263 ± 46 ms vs 246 ± 47 ms, P < .01) and increased in nonresponders (235 ± 23 ms vs 261 ± 20 ms; P < .01). Time-to-peak radial, circumferential, and longitudinal strains increased in responders (41 ± 27, 35 ± 25, 56 ± 37 ms; P < .01) and decreased in nonresponders (-58 ± 26, -47 ± 26, -64 ± 27 ms; P < .01). There was a nonlinear correlation between changes in time-to-peak strain and ARIs (Spearman correlation coefficient r ≥ 0.70; P < .01). Baseline QRS duration >145 ms and QRS duration shortening with biventricular pacing were associated with ARI shortening following CRT. CONCLUSION: Changes in ventricular wall mechanics predict local APD lengthening or shortening during CRT. Nonresponders have a worsening of myocardial strain and local APD. Baseline QRS duration >145 ms and QRS duration shortening with biventricular pacing identified patients who exhibited improvement in APD.

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.

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/dtmax 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.

Effects of Epicardial and Endocardial Cardiac Resynchronization Therapy on Coronary Flow: Insights From Wave Intensity Analysis.

BACKGROUND: The increase in global coronary flow seen with conventional biventricular pacing is mediated by an increase in the dominant backward expansion wave (BEW). Little is known about the determinants of flow in the left-sided epicardial coronary arteries beyond this or the effect of endocardial pacing stimulation on coronary physiology. METHODS AND RESULTS: Eleven patients with a chronically implanted biventricular pacemaker underwent an acute hemodynamic and electrophysiological study. Five of 11 patients also took part in a left ventricular endocardial pacing protocol at the same time. Conventional biventricular pacing, delivered epicardially from the coronary sinus, resulted in a 9% increase in flow (average peak velocity) in the left anterior descending artery (LAD), mediated by a 13% increase in the area under the BEW (P=0.004). Endocardial pacing resulted in a 27% increase in LAD flow, mediated by a 112% increase in the area under the forward compression wave (FCW) and a 43% increase in the area under the BEW (P=0.048 and P=0.036, respectively). There were no significant changes in circumflex parameters. Conventional biventricular pacing resulted in homogenization of timing of coronary flow compared with baseline (mean difference in time to peak in the LAD versus circumflex artery: FCW 39 ms [baseline] versus 3 ms [conventional biventricular pacing], P=0.008; BEW 47 ms [baseline] versus 8 ms [conventional biventricular pacing], P=0.004). CONCLUSIONS: Epicardial and endocardial pacing result in increased coronary flow in the left anterior descending artery and homogenization of the timing of waves that determine flow in the LAD and the circumflex artery. The increase in both the FCW and the BEW with endocardial pacing may be the result of a more physiological activation pattern than that of epicardial pacing, which resulted in an increase of only the BEW.

Images as drivers of progress in cardiac computational modelling.

Computational models have become a fundamental tool in cardiac research. Models are evolving to cover multiple scales and physical mechanisms. They are moving towards mechanistic descriptions of personalised structure and function, including effects of natural variability. These developments are underpinned to a large extent by advances in imaging technologies. This article reviews how novel imaging technologies, or the innovative use and extension of established ones, integrate with computational models and drive novel insights into cardiac biophysics. In terms of structural characterization, we discuss how imaging is allowing a wide range of scales to be considered, from cellular levels to whole organs. We analyse how the evolution from structural to functional imaging is opening new avenues for computational models, and in this respect we review methods for measurement of electrical activity, mechanics and flow. Finally, we consider ways in which combined imaging and modelling research is likely to continue advancing cardiac research, and identify some of the main challenges that remain to be solved.

An automatic service for the personalization of ventricular cardiac meshes.

Computational cardiac physiology has great potential to improve the management of cardiovascular diseases. One of the main bottlenecks in this field is the customization of the computational model to the anatomical and physiological status of the patient. We present a fully automatic service for the geometrical personalization of cardiac ventricular meshes with high-order interpolation from segmented images. The method is versatile (able to work with different species and disease conditions) and robust (fully automatic results fulfilling accuracy and quality requirements in 87% of 255 cases). Results also illustrate the capability to minimize the impact of segmentation errors, to overcome the sparse resolution of dynamic studies and to remove the sometimes unnecessary anatomical detail of papillary and trabecular structures. The smooth meshes produced can be used to simulate cardiac function, and in particular mechanics, or can be used as diagnostic descriptors of anatomical shape by cardiologists. This fully automatic service is deployed in a cloud infrastructure, and has been made available and accessible to the scientific community.

Share and enjoy: anatomical models database--generating and sharing cardiovascular model data using web services.

Sharing data between scientists and with clinicians in cardiac research has been facilitated significantly by the use of web technologies. The potential of this technology has meant that information sharing has been routinely promoted through databases that have encouraged stakeholder participation in communities around these services. In this paper we discuss the Anatomical Model Database (AMDB) (Gianni et al. Functional imaging and modeling of the heart. Springer, Heidelberg, 2009; Gianni et al. Phil Trans Ser A Math Phys Eng Sci 368:3039-3056, 2010) which both facilitate a database-centric approach to collaboration, and also extends this framework with new capabilities for creating new mesh data. AMDB currently stores cardiac geometric models described in Gianni et al. (Functional imaging and modelling of the heart. Springer, Heidelberg, 2009), a number of additional cardiac models describing geometry and functional properties, and most recently models generated using a web service. The functional models represent data from simulations in geometric form, such as electrophysiology or mechanics, many of which are present in AMDB as part of a benchmark study. Finally, the heartgen service has been added for producing left or bi-ventricle models derived from binary image data using the methods described in Lamata et al. (Med Image Anal 15:801-813, 2011). The results can optionally be hosted on AMDB alongside other community-provided anatomical models. AMDB is, therefore, a unique database storing geometric data (rather than abstract models or image data) combined with a powerful web service for generating new geometric models.