Exploring a New Systematic Route for Left Ventricular Pacing in Cardiac Resynchronization Therapy.

BACKGROUND: Frequency and distribution of left ventricular (LV) venous collaterals were studied in vivo to evaluate the ease and feasibility of implanting a new ultra-thin LV quadripolar microlead for cardiac resynchronization therapy (CRT).Methods and Results:Evaluable venograms were analyzed to define the prevalence of venous collaterals (>0.5 mm diameter) between: (1) different LV segments; and (2) different major LV veins in: unselected patients who underwent CRT from 2008 to 2012 at Rouen Hospital, France (retrospective); and CRT patients from the Axone Acute pilot study in 2018 (prospective). In prospective patients with evaluable venograms, LV microlead implantation was attempted. Thirty-six (21/65 retrospective, 15/20 prospective) patients had evaluable venograms with ≥1 visible venous collaterals. Collaterals were found between LV veins in all CRT patients with evaluable venograms. Regionally, prevalence was highest between: the apical inferior and apical lateral (42%); and mid inferior and mid inferolateral (42%) segments. Collateral connections were most prevalent between: the inferior interventricular vein (IIV) and lateral vein (64% [23/36]); and IIV and infero-lateral vein (36% [13/36]). Cross-vein microlead implantation was possible in 18 patients (90%), and single-vein implantation was conducted in the other 2 patients (10%). CONCLUSIONS: Venous collaterals were found in vivo between LV veins in all CRT patients with evaluable venograms, making this network an option for accessing multiple LV sites using a single LV microlead.

Regional Left Ventricular Fiber Stress Analysis for Cardiac Resynchronization Therapy Response.

Cardiac resynchronization therapy (CRT) is an effective treatment for a subgroup of heart failure (HF) patients, but more than 30% of those selected do not improve after CRT implantation. Imperfect pre-procedural criteria for patient selection and optimization are the main causes of the high non-response rate. In this study, we evaluated a novel measure for assessing CRT response. We used a computational modeling framework to calculate the regional stress of the left ventricular wall of seven CRT patients and seven healthy controls. The standard deviation of regional wall stress at the time of mitral valve closure (SD_MVC) was used to quantify dyssynchrony and compared between patients and controls and among the patients. The results show that SD_MVC is significantly lower in controls than patients and correlates with long-term response in patients, based on end-diastolic volume reduction. In contrast to our initial hypothesis, patients with lower SD_MVC respond better to therapy. The patient with the highest SD_MVC was the only non-responder in the patient cohort. The distribution of fiber stress at the beginning of the isovolumetric phase seems to correlate with the degree of response and the use of this measurement could potentially improve selection criteria for CRT implantation. Further studies with a larger cohort of patients are needed to validate these results.

Optimal pacing sites in cardiac resynchronization by left ventricular activation front analysis.

Cardiac resynchronization therapy (CRT) can substantially improve dyssynchronous heart failure and reduce mortality. However, about one-third of patients who are implanted, derive no measurable benefit from CRT. Non-response may partly be due to suboptimal activation of the left ventricle (LV) caused by electrophysiological heterogeneities. The goal of this study is to investigate the performance of a newly developed method used to analyze electrical wavefront propagation in a heart model including myocardial scar and compare this to clinical benchmark studies. We used computational models to measure the maximum activation front (MAF) in the LV during different pacing scenarios. Different heart geometries and scars were created based on cardiac MR images of three patients. The right ventricle (RV) was paced from the apex and the LV was paced from 12 different sites, single site, dual-site and triple site. Our results showed that for single LV site pacing, the pacing site with the largest MAF corresponded with the latest activated regions of the LV demonstrated during RV pacing, which also agrees with previous markers used for predicting optimal single-site pacing location. We then demonstrated the utility of MAF in predicting optimal electrode placements in more complex scenarios including scar and multi-site LV pacing. This study demonstrates the potential value of computational simulations in understanding and planning CRT.

Wide Frequency Characterization of Intra-Body Communication for Leadless Pacemakers.

Leadless Cardiac Pacemakers (LCP) have the potential to revolutionize Cardiac Rhythm Management (CRM). Current LCPs can only pace a single location of the heart limiting their use to patients requiring single-chamber stimulation. A Multi-node system of synchronized LCPs could be used in a significantly larger patient population. Synchronization using standard communication techniques involves high power consumption decreasing the longevity of the device. In this work, we investigate Galvanic Intra Body Communication (IBC) as a method to synchronize multi-node LCP systems. First, an accurate computational torso model was used for quasi-static simulations to estimate channel pathloss in the frequency range [40 kHz-20 MHz]. The model was then verified with in-vivo measurements using a novel experimental setup, where two LCP devices were placed in the right atrium, right ventricle and left ventricle. All channels involved in a potential multi-node LCP system were characterized. The orientation of the transducers relative to each other had a great impact on the results, with the attenuation level ranging between 55 dB and 70 dB between the best and worst orientations. The best results were achieved in the MHz range. Coupled with the fact that it does not require additional electrodes, this study suggests Galvanic IBC be superior to conventional communication methods for LCP devices. This analysis defines a methodology for galvanic IBC channel characterization for LCP systems, which is an important step for the design of efficient transceivers for IBC applications. More experiments with larger datasets are needed to bring this method to practice.

Multisite pacing and myocardial scars: a computational study.

Cardiac resynchronization therapy (CRT) is a frequently effective treatment modality for dyssynchronous heart failure, however, 30% of patients do not respond, usually due to suboptimal activation of the left ventricle (LV). Multisite pacing (MSP) may increase the response rate, but its effect in the presence of myocardial scars is not fully understood. We use a computational model to study the outcome of MSP in an LV with scars in two different locations and of two different sizes. The LV was stimulated from anterior, posterior and lateral locations individually and in pairs, while a septal stimulation site represented right ventricular (RV) pacing. Intraventricular pressures were measured, and outcomes evaluated in terms of maximum LV pressure gradient (dP/dtmax)- change compared to isolated RV pacing. The best result obtained using various LV pacing locations included a combination of sites remote from scars and the septum. The highest dP/dtmax increase was achieved, regardless of scar size, using MSP with one pacing site located on the LV free wall opposite to the scar and one site opposite to the septum. These in silico modelling results suggest that making placement of pacing electrodes dependent on location of scarring, may alter acute haemodynamics and that such modelling may contribute to future CRT optimization.

RF Channel Modeling for Implant-to-Implant Communication and Implant to Subcutaneous Implant Communication for Future Leadless Cardiac Pacemakers.

Propagation of radio-frequency signals inside human body is demanding to analyze as it is a highly complex medium consisting of different frequency-dependent lossy materials of varying thickness. Moreover, experimental analyses are also unfeasible because that requires probes to be placed inside a human body to collect the signals. This paper focuses on in-body to in-body implant communication for future multinodal capsule-like leadless cardiac pacemaker technology. The frequency range of 0.3-3 GHz is analyzed using very detailed numerical simulations of digital human models. The results show that the Industrial, Scientific, and Medical radio band of the frequency range of 2.4-2.5 GHz is optimal, having the least attenuation of signals considering the size constraints of the implant antenna. Furthermore, the placement of an additional subcutaneous implant transceiver is studied. The analysis shows that the abdominal wall is the optimal position for the placement of the implant compared to shoulder and lateral side of the body. This result is further validated by an in vivo experiment on an adult pig. The other novelty of the study is the investigation of the channel behavior based on ventricular blood volume of the heart to find out the appropriate timing of the transmission of signals between the implants. The results show that the attenuation of the signal increases with the increase in blood volume inside the heart.

Electromechanical Model to Predict Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) can substantially improve dyssynchronous heart failure and reduce mortality. However, one-third of the CRT patients derive no measurable benefit from CRT, due to suboptimal placement of the left ventricular (LV) lead. We introduce a pipeline for improved CRT-therapy by creating an electromechanical model using patient-specific geometric parameters allowing individualization of therapy. The model successfully mimics expected changes when variables for tension, stiffness, and conduction are entered. Changing LV pacing site had a notable effect on maximum pressure gradient (dP/dtmax) in the presence of cardiac scarring, causing non-uniform excitation propagation through the LV. Tailoring CRT to the individual requires simulations with patient-specific biventricular meshes including cardiac geometry and conductivity properties.

Towards Non-Invasive Extraction and Determination of Blood Glucose Levels.

Diabetes is a condition where the body is incapable of proper utilization of glucose and one that, if not properly managed, can lead to critical illness. Glucose monitoring and decision support is vital in avoiding potential adverse health effects. Current methods mainly involve invasive blood extraction for the purposes of blood glucose level notification, yet such methods rely on active user participation and subjective interpretation of the result. This paper reviews existing research in methods of extraction and monitoring of glucose levels. The purpose of this paper is to examine blood glucose extraction methods in addition to indicators of blood glucose level, toward development of an innovative, non-invasive extraction technology. Decision support methods are also analyzed toward customized, automated, and intelligent diabetic management.