Electrocardiographic imaging demonstrates electrical synchrony improvement by dynamic atrioventricular delays in patients with left bundle branch block and preserved atrioventricular conduction

Aims: Cardiac resynchronization therapy programmed to dynamically fuse pacing with intrinsic conduction using atrioventricular (AV) timing algorithms (e.g. SyncAV) has shown promise; however, mechanistic data are lacking. This study assessed the impact of SyncAV on electrical dyssynchrony across various pacing modalities using non-invasive epicardial electrocardiographic imaging (ECGi). Methods and results: Twenty-five patients with left bundle-branch block (median QRS duration (QRSd) 162.7 ms) and intact AV conduction (PR interval 174.0 ms) were prospectively enrolled. ECGi was performed acutely during biventricular pacing with fixed nominal AV delays (BiV) and using SyncAV (optimized for the narrowest QRSd) during: BiV + SyncAV, LV-only single-site (LVSS + SyncAV), MultiPoint pacing (MPP + SyncAV), and LV-only MPP (LVMPP + SyncAV). Dyssynchrony was quantified via ECGi (LV activation time, LVAT; RV activation time, RVAT; LV electrical dispersion index, LVEDi; ventricular electrical uncoupling index, VEU; and biventricular total activation time, VVtat). Intrinsic conduction LVAT (124 ms) was significantly reduced by BiV pacing (109 ms) (P = 0.001) and further reduced by LVSS + SyncAV (103 ms), BiV + SyncAV (103 ms), LVMPP + SyncAV (95 ms), and MPP + SyncAV (90 ms). Intrinsic RVAT (93 ms), VVtat (130 ms), LVEDi (36 ms), VEU (50 ms), and QRSd (163 ms) were reduced by SyncAV across all pacing modes. More patients exhibited minimal LVAT, VVtat, LVEDi, and QRSd with MPP + SyncAV than any other modality. Conclusion: Dynamic AV delay programming targeting fusion with intrinsic conduction significantly reduced dyssynchrony, as quantified by ECGi and QRSd for all evaluated pacing modes. MPP + SyncAV achieved the greatest synchrony overall but not for all patients, highlighting the value of pacing mode individualization during fusion optimization

Novel implant designs in magnetic drug targeting

The lack of drug selectivity to a specific site has been one of the major limitations in current therapeutic treatments. To overcome these limitations, many approaches have been proposed, one of which is magnetic drug targeting (MDT). The concept of MDT is to use drug carriers that contain a magnetic component and guide these carriers to a specific site with the aid of an external magnetic source. These magnetic drug carrier particles (MDCP) can be used to deliver a drug to the desired site and increase the amount of treatment locally in the diseased tissue, subsequently reducing adverse side effects to healthy tissue and the required amount of pharmacological agents. Limitations in the traditional MDT approach, i.e. dynamic forces overcome magnetic forces, have led researchers to study the use of implants to increase magnetic forces and the collection of MDCPs. This method is termed implant assisted (IA)-MDT, which exploits basic principles of high gradient magnetic separation to improve local drug retention. The work herein will address the design and use of novel methods to improve the collection of MDCPs using IA-MDT. Ferromagnetic nanoparticles, wire filaments and stents were used in vitro as possible implants, showing that in their presence an increase of more than 15% collection of MDCPs was obtained, as opposed to the traditional MDT scenario. Biodegradable magnetic nanocomposite stents were also fabricated and proved to be a successful magnetic implant with comparable results to their metallic counterparts and the benefit of degrading naturally, thus preventing physiological complications, i.e. restenosis. Organ perfusion experiments were also carried out on swine heart tissue with stent implants in the right coronary artery. The results from this work with animal tissue under physiological conditions showed similar trends to previous theoretical studies and an increase of more than 30% of MDCPs collection in some cases, compared to controls in the absence of the magnetic field and the traditional MDT setup

On the geometrical relationship between global longitudinal strain and ejection fraction in the evaluation of cardiac contraction

Ejection fraction (EF) and global longitudinal strain (GLS) provide measures of left ventricle (LV) contraction that are closely related and also reflect different aspects of systolic function. Their comparative analysis can be informative about additional physiological properties on how LV contraction is achieved. The mathematical underlying relationship between EF and the GLS has been exploited and verified through data collected from recent literature. It was demonstrated that GLS and EF are bi-univocally related in the case of a self-similar systolic contraction. The deviation from this relationship, which can be quantified in terms of a shape function, characterizes the change of LV shape during the contraction. This analysis provides a firm ground to highlight the incremental information carried by GLS in the clinical evaluation of cardiac function

Comparative numerical study on left ventricular fluid dynamics after dilated cardiomyopathy

Introduction: The role of flow on the progression of left ventricular (LV) remodeling has been presumed, although measurements are still limited and the intraventricular flow pattern in remodeling hearts has not been systematically evaluated in a clinical setting. Comparative evaluation of intraventricular fluid dynamics is performed here between healthy subjects and dilated cardiomyopathy (DCM) patients. Methods: LV fluid dynamics is evaluated in 20 healthy young men and in 8 DCM patients by combination of 3D echocardiography with direct numerical simulations of the equation governing blood motion. Results are analyzed in terms of quantitative global indicators of flow energetics and blood transit properties that are representative of the qualitative fluid dynamics behaviors. Results: The flow in DCM exhibited qualitative differences due to the weakness of the formed vortices in the large LV chamber. DCM and healthy subjects show significant volumetric differences; these also reflect in flow properties like the vortex formation time, energy dissipation, and sub-volumes describing flow transit. Proper normalization permitted to define purely fluid dynamics indicators that are not influenced by volumetric measures. Conclusion: Cardiac fluid mechanics can be evaluated by a combination of imaging and numerical simulation. This pilot study on pathological changes in LV blood motion identified intraventricular flow indicators based on pure fluid mechanics that could potentially be integrated with existing indicators of cardiac mechanics in the evaluation of disease progression

Dynamic atrioventricular delay programming improves ventricular electrical synchronization as evaluated by 3D vectorcardiography

Background: Optimal timing of the atrioventricular delay in cardiac resynchronization therapy (CRT) can improve synchrony in patients suffering from heart failure. The purpose of this study was to evaluate the impact of SyncAV (TM) on electrical synchrony as measured by vectorcardiography (VCG) derived QRS metrics during biventricular (BiV) pacing. Methods: Patients implanted with a cardiac resynchronization therapy (CRT) device and quadripolar left ventricular (LV) lead underwent 12-lead ECG recordings. VCG metrics, including QRS duration (QRSd) and area, were derived from the ECG by a blinded observer during: intrinsic conduction, BiV with nominal atrioventricular delays (BiV Nominal), and BiV with SyncAV programmed to the optimal offset achieving maximal synchronization (BiV + SyncAV Opt). Results: One hundred patients (71% male, 40% ischemic, 65% LBBB, 32 +/- 9% ejection fraction) completed VCG assessment. QRSd during intrinsic conduction (166 +/- 25 ms) was narrowed successively by BiV Nominal (137 +/- 23 ms, p <.05 vs. intrinsic) and BiV + SyncAV Opt (122 +/- 22 ms, p Conclusion: With VCG-based, patient-specific optimization of the programmable offset, SyncAV reduced electrical dyssynchrony beyond conventional CRT. Crown Copyright (C) 2019 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Functional Strain-Line Pattern in the Human Left Ventricle

Analysis of deformations in terms of principal directions appears well suited for biological tissues that present an underlying anatomical structure of fiber arrangement. We applied this concept here to study deformation of the beating heart in vivo analyzing 30 subjects that underwent accurate three-dimensional echocardiographic recording of the left ventricle. Results show that strain develops predominantly along the principal direction with a much smaller transversal strain, indicating an underlying anisotropic, onedimensional contractile activity. The strain-line pattern closely resembles the helical anatomical structure of the heart muscle. These findings demonstrate that cardiac contraction occurs along spatially variable paths and suggest a potential clinical significance of the principal strain concept for the assessment of mechanical cardiac function. The same concept can help in characterizing the relation between functional and anatomical properties of biological tissues, as well as fiber-reinforced engineered materials