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.

Ventricular activation patterns during intrinsic conduction and right ventricular pacing in cardiac resynchronization therapy patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) involves stimulation of both right ventricle (RV) and left ventricle (LV). LV pacing from the sites of delayed electrical activation improves CRT response. The RV-LV conduction is typically measured in intrinsic rhythm. The differences in RV-LV conduction patterns and timing between intrinsic rhythm and during paced RV activation, these differences are not fully understood. METHODS: Enrolled patients were implanted with a de novo CRT device and quadripolar LV lead, with lead implant locations at the implanting physician's discretion. QRS duration and conduction delay between the RV lead and each of the four LV electrodes (D1, M2, M3, and P4) were measured during intrinsic conduction and RV pacing. RESULTS: Conduction measurements were collected from 275 patients across 14 international centers (68 ± 13 years of age, 73% male, 45% ischemic, 158 ± 22 ms QRS duration). Mean RV-LV conduction time was shorter during intrinsic conduction versus RV pacing by 59.6 ms (106.5 ± 36.5 versus 166.1 ± 32.1 ms, p < 0.001). The intra-LV activation delay between the latest and earliest activating LV electrode was also shorter during intrinsic conduction versus RV pacing by 6.6 ms (20.6 ± 13.1 vs. 27.2 ± 21.2 ms, p < 0.001). Intrinsic conduction and RV pacing resulted in a different activation order in 72.7% of patients, and the same LV activation order in 27.3%. CONCLUSIONS: Differences in RV-LV conduction time, intra-LV conduction time, and activation pattern were observed between intrinsic conduction and RV pacing. These findings highlight the importance of evaluating intrinsic versus paced ventricular activation to guide LV pacing site selection in CRT patients.

Electrical synchronization achieved by multipoint pacing combined with dynamic atrioventricular delay.

PURPOSE: Multipoint pacing (MPP) improves left ventricular (LV) electrical synchrony in cardiac resynchronization therapy (CRT). SyncAV automatically adjusts atrioventricular delay (AVD) according to intrinsic AV intervals and may further improve synchrony. Their combination has not been assessed. The objective was to evaluate the improvement in electrical synchrony achieved by SyncAV combined with MPP in an international, multicenter study. METHODS: Patients with LBBB undergoing CRT implant with a quadripolar lead (Abbott Quartet™) were prospectively enrolled. QRS duration (QRSd) was measured by blinded observers from 12-lead ECG during: intrinsic conduction, BiV pacing (conventional biventricular pacing, nominal static AVD), MPP (2 LV cathodes maximally spaced, nominal static AVD), BiV + SyncAV, and MPP + SyncAV. All SyncAV offsets were individualized for each patient to yield the narrowest QRSd during BiV pacing. QRSd changes were compared by ANOVA and post hoc Tukey-Kramer tests. RESULTS: One hundred and three patients were enrolled (65.7 ± 12.1 years, 67% male, 37% ischemic, EF 26.4 ± 6.5%, PR 190.3 ± 39.1 ms). Relative to intrinsic conduction (QRSd of 165 ± 16 ms), BiV reduced QRSd by 11.9% to 145 ± 18 ms (P < 0.001 vs intrinsic), and MPP reduced QRSd by 13.3% to 142 ± 19 ms (P < 0.001 vs intrinsic). However, enabling SyncAV with a patient-optimized offset nearly doubled this QRSd reduction. BiV + SyncAV reduced QRSd by 22.0% to 128 ± 13 ms (P < 0.001 vs BiV), while MPP + SyncAV reduced QRSd further by 25.6% to 122 ± 14 ms (P < 0.05 vs BiV + SyncAV). CONCLUSION: SyncAV can significantly improve acute electrical synchrony beyond conventional CRT, with further improvement achieved by superimposing MPP.

Non-paroxysmal atrial fibrillation mapping: characterization of the electrophysiological substrate using a novel integrated mapping technique.

AIMS: Clinical outcomes after radiofrequency catheter ablation (RFCA) remain suboptimal in the treatment of non-paroxysmal atrial fibrillation (AF). Electrophysiological mapping may improve understanding of the underlying mechanisms. To describe the arrhythmia substrate in patients with persistent (Pers) and long-standing persistent (LSPers) AF, undergoing RFCA, using an integrated mechanism mapping technique. METHODS AND RESULTS: Patients underwent high-density electroanatomical mapping before and after catheter ablation. Integrated maps characterized electrogram (EGM) cycle length (CL) in regions with repetitive-regular (RR) activations, stable wavefront propagation, fragmentation, and peak-to-peak bipolar voltage. Among 83 patients (72% male, 60 ± 11 years old), RR activations were identified in 376 regions (mean CL 180 ± 31 ms). PersAF patients (n = 43) showed more RR sites per patient (5.3 ± 2.4 vs. 3.7 ± 2.1, P = 0.002) with faster CL (166 ± 29 vs. 190 ± 29 ms; P < 0.001) and smaller surface area of fragmented EGMs (15 ± 14% vs. 27 ± 17%, P < 0.001) compared with LSPersAF. The post-ablation map in 50 patients remaining in AF, documented reduction of the RR activities per patient (1.5 ± 0.7 vs. 3.7 ± 1.4, P < 0.001) and area of fragmentation (22 ± 17% vs. 8 ± 9%, P < 0.001). Atrial fibrillation termination during ablation occurred at RR sites (0.48 ± 0.24 mV; 170.5 ± 20.2 ms CL) in 31/33 patients (94%). At the latest follow-up, arrhythmia freedom was higher among patients receiving ablation >75% of RR sites (Q4 82.6%, Q3 63.1%, Q2 35.1%, and Q1 0%; P < 0.001). CONCLUSION: The integrated mapping technique allowed characterization of multiple arrhythmic substrates in non-paroxysmal AF patients. This technique might serve as tool for a substrate-targeted ablation approach.

Dynamic programming of atrioventricular delay improves electrical synchrony in a multicenter cardiac resynchronization therapy study.

BACKGROUND: Patient-specific programming of cardiac resynchronization therapy (CRT) is often neglected, despite significant nonresponse rates. The device-based SyncAV CRT algorithm dynamically adjusts atrioventricular delays to the intrinsic AV interval, reduced by a programmable offset, to accommodate each patient's changing needs. OBJECTIVE: The purpose of this study was to evaluate the acute effect of biventricular (BiV) pacing enhanced by SyncAV on electrical synchrony in a broad patient population. METHODS: Patients with existing CRT implants were prospectively evaluated at 5 international centers. Blinded 12-lead electrocardiographic QRS duration (QRSd) measurements were used to compare intrinsic conduction with nominal BiV pacing, BiV + SyncAV (default 50 ms offset), and BiV + SyncAV (optimized, patient-specific offset). BiV configurations were tested twice using the latest activating and earliest activating left ventricular (LV) electrodes as cathodes. RESULTS: Ninety patients (mean age 67.1 ± 9.5 years; 67 (74%) men; 55 (63%) with left bundle branch block; 37 (43%) with ischemic cardiomyopathy; LV ejection fraction 32% ± 9%) with intact atrioventricular conduction (PR interval 195 ± 45 ms) were enrolled. With BiV pacing from the latest activating LV electrode, the intrinsic QRSd of 155 ± 29 ms was reduced by 9% ± 20% to 138 ± 27 ms using traditional BiV pacing and by 13% ± 14% to 133 ± 25 ms using BiV + SyncAV (50 ms offset). The maximal QRSd reduction by 20% ± 10% to 123 ± 22 ms was achieved by BiV + SyncAV with an optimized offset. Similar QRSd reductions were observed with BiV pacing from the earliest activating LV electrode across all settings. Of all baseline characteristics, intrinsic QRSd was the only significant predictor of QRSd reduction magnitude. CONCLUSION: SyncAV improved acute electrical synchrony beyond conventional CRT, particularly with patient-specific optimization. The degree of synchrony restored was contingent on intrinsic QRSd, but not limited by other baseline characteristics or by the LV pacing electrode used.

Clinical Outcome of Electrophysiologically Guided Ablation for Nonparoxysmal Atrial Fibrillation Using a Novel Real-Time 3-Dimensional Mapping Technique: Results From a Prospective Randomized Trial.

BACKGROUND: Clinical outcomes after ablation of persistent atrial fibrillation remain suboptimal. Identification of AF drivers using a novel integrated mapping technique may be crucial to ameliorate the clinical outcome. METHODS AND RESULTS: Persistent AF patients were prospectively enrolled to undergo high-density electrophysiological mapping to identify repetitive-regular activities (RRas) before modified circumferential pulmonary vein (PV) ablation. They have been randomly assigned (1:1 ratio) to ablation of RRa followed by modified circumferential PV ablation (mapping group; n=41) or modified circumferential PV ablation alone (control group; n=40). The primary end point was freedom from arrhythmic recurrences at 1 year. In total, 81 persistent AF patients (74% male; mean age, 61.7±10.6 years) underwent mapping/ablation procedure. The regions exhibiting RRa were 479 in 81 patients (5.9±2.4 RRa per patient): 232 regions in the mapping group (n=41) and 247 in the control group (n=40). Overall, 185 of 479 (39%) RRas were identified within the PVs, whereas 294 of 479 (61%) in non-PV regions. Mapping-guided ablation resulted in higher arrhythmia termination rate when compared with conventional strategy (25/41, 61% versus 12/40, 30%; P<0.007). Total radiofrequency duration (P=0.38), mapping (P=0.46), and fluoroscopy times (P=0.69) were not significantly different between the groups. No major procedure-related adverse events occurred. After 1 year, 73.2% of mapping group patients were free from recurrences versus 50% of control group (P=0.03). CONCLUSIONS: Targeted ablation of regions showing RRa provided an adjunctive benefit in terms of arrhythmia freedom at 1-year follow-up in the treatment of persistent AF. These findings might support a patient-tailored strategy in subjects with nonparoxysmal AF and should be confirmed by additional larger, randomized, multicenter studies. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier NCT02571218.

Aging does not affect radial viscoelastic behavior of the left ventricle.

OBJECTIVES: This study investigates the effect of aging on the radial viscoelastic behavior of the left ventricle (LV) based on a previously validated model that uses myocardial tissue phase mapping (TPM) of cine phase-contrast MRI. METHODS: Previous studies suggest that aging remarkably influences regional myocardial motion, mostly myocardial velocities in both radial and long-axis directions. However, the effect of aging on cardiac viscoelasticity, which exhibits time-dependent strain, has not been elucidated yet. In this study, myocardial velocity and displacement mapping of the LV was performed using TPM in 39 healthy subjects divided into three age groups. The viscoelasticity parameters were obtained for each segment of the LV and compared among the studied groups. RESULTS: The analyses showed that myocardial elasticity ranged from approximately 20 to -20 dyne/cm2 during a cardiac cycle, and the myocardial viscous-damping component ranged from -1 to 1 dyne × s/cm2. Overall, no statistically significant difference was observed in the viscoelasticity components among the subjects in the different age groups (p > 0.05). CONCLUSION: Myocardial viscoelastic behavior of the LV in radial direction was found to be considerably similar in pattern and magnitude among the studied subjects of different age groups with no statistically significant difference, despite the fact that the regional myocardial velocities change due to aging.

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 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 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 inflow 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.

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, one-dimensional 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.

Modeling radial viscoelastic behavior of left ventricle based on MRI tissue phase mapping.

The viscoelastic behavior of myocardial tissue is a measure that has recently found to be a deterministic factor in quality of contraction. Parameters imposing the viscoelastic behavior of the heart are influenced in part by sarcomere function and myocardial composition. Despite the overall agreement on significance of cardiac viscoelasticity, a practical model that can measure and characterize the viscoelastic behavior of the myocardial segments does not yet exist. Pressure-Volume (P-V) curves are currently the only measure for stiffness/compliance of the left ventricle. However, obtaining P-V curves requires invasive cardiac catheterization, and only provides qualitative information on how pressure and volume change with respect to each other. For accurate assessment of myocardial mechanical behavior, it is required to obtain quantitative measures for viscoelasticity. In this work, we have devised a model that yields myocardial elastic and viscous damping coefficient functions through the cardiac cycle. The required inputs for this model are kinematic information with respect to changes in LV short axes that were obtained by Magnetic Resonance Imaging (MRI) using a tissue phase mapping (TPM) pulse sequence. We evaluated viscoelastic coefficients of LV myocardium in two different age groups of 20-40 and greater than 60. We found that the magnitude of stiffness coefficients is noticeably greater in the older subjects. Additionally, we found that slope of viscous damping functions follow similar patterns for each individual age group. This method may shed light on dynamics of contraction through MRI in conditions where composition of myocardium is changed such as in aging, adverse remodeling, and cardiomyopathies.

Isolated swine heart ventricle perfusion model for implant assisted-magnetic drug targeting.

An isolated swine heart ventricle perfusion model was developed and used under physiologically relevant conditions to study implant assisted-magnetic drug targeting (IA-MDT). A stent coil was fabricated from a ferromagnetic SS 430 wire and used to capture 100-nm diameter magnetite particles that mimicked magnetic drug carrier particles (MDCPs). Four key cases were studied: (1) no stent and no magnet (control), (2) no magnet but with a stent, (3) no stent but with a magnet (traditional MDT), and (4) with a stent and a magnet (IA-MDT). When applied, the magnetic field was fixed at 0.125T. The performance of the system was based on the capture efficiency (CE) of the magnetite nanoparticles. The experiments done in the absence of the magnetic field showed minimal retention of any nanoparticles whether the stent was present or not. The experiments done in the presence of the magnetic field showed a statistically significant increase in the retention of the nanoparticles, with a marked difference between the traditional and IA-MDT cases. Compared to the control case, in one case there was nearly an 11-fold increase in CE for the IA-MDT case compared to only a threefold increase in CE for the traditional MDT case. This enhanced performance by the IA-MDT case was typical of all the experiments. Histology images of the cross-section of the coronary artery revealed that the nanoparticles were captured mainly in the vicinity of the stent. Overall, the IA-MDT results from this work with actual tissue were very encouraging and similar to those obtained from other non-tissue and theoretical studies; but, they did point to the need for further studies of IA-MDT.