Estimation of global ventricular activation sequences by noninvasive three-dimensional electrical imaging: validation studies in a Swine model during pacing.

BACKGROUND: A novel noninvasive imaging technique, the heart-model-based three-dimensional cardiac electrical imaging (3DCEI) approach was previously developed and validated to estimate the initiation site (IS) of cardiac activity and the activation sequence (AS) from body surface potential maps (BSPMs) in a rabbit model. The aim of the present study was to validate the 3DCEI in an intact large mammalian model (swine) during acute ventricular pacing. METHODS AND RESULTS: The heart-torso geometries were constructed from preoperative magnetic resonance (MR) images acquired from each animal. Body surface potential mapping and intracavitary noncontact mapping (NCM) were performed simultaneously during pacing from both right ventricular (RV) (intramural) and left ventricular (LV) sites (endocardial). Subsequent 3DCEI analyses were performed from the measured BSPMs. The estimated ISs were compared with the precise pacing locations and estimated ASs were compared with those recorded by the NCM system. In total, five RV and five LV sites from control and heart failure (HF) animals were paced and sequences of 100 paced beats were analyzed (10 for each site). The averaged localization error (LE) of the RV and LV sites were 7.3 +/- 1.8 mm (n = 50) and 7.0 +/- 2.2 mm (n = 50), respectively. The global 3D ASs throughout the ventricular myocardium were also derived. The endocardial ASs as a subset of the estimated 3D ASs were consistent with those reconstructed from the NCM system. CONCLUSION: The present experimental results demonstrate that the noninvasive 3DCEI approach can localize the IS and estimate AS with good accuracy in an in vivo setting under control, paced, and/or diseased conditions.

Investigation of pacing site-related changes in global restitution dynamics by non-contact mapping.

AIMS: The determination of dynamic changes in ventricular repolarization may provide insight into arrhythmogenic mechanisms as a consequence of pacing site. This study investigated acute pacing site effects on global characteristics of electrical restitution using high resolution, non-contact mapping (NCM). METHODS AND RESULTS: Activation-recovery intervals (ARIs) were determined from reconstructed left ventricular electrograms by the NCM system and were analysed during pacing from the right atrial appendage (RAA, intrinsic), right ventricular apex (RVA), and right ventricular septum (RVS) with extrasystoles delivered at intermediate and short coupling intervals in anesthetized swine (n = 5). Electrical restitution curves were determined by the S1-S2 pacing protocol. Activation-recovery interval restitution slopes were determined by the overlapping linear segments regression method. Global distribution of repolarization was defined as the coefficient of variation of the ARIs during restitution. The maximum ARI slopes yielded by RVA pacing were significantly greater than RAA pacing (0.44 vs. 0.32; P < 0.05) and RVS pacing (0.44 vs. 0.37; P = 0.05). There was no significant difference between RAA and RVS pacing (0.32 vs. 0.37). The global distribution of ARIs during restitution from RVA pacing was significantly greater than RAA pacing (12.0 vs. 8.1%; P < 0.05). CONCLUSION: Right ventricular apex pacing is associated with impaired global repolarization patterns compared to RAA and RVS. These observations support the hypothesis that RVA pacing may be associated with increased risk of ventricular arrhythmias compared to RVS pacing.

Effects of pacing rate on mechanical restitution within the in vivo canine heart: study of the force-frequency relationship.

INTRODUCTION: It is known that as stimulation frequency is increased in a healthy heart, a corresponding increase in LV contractile function (dP/dt(max)) is observed, i.e., force-frequency relationship. The impact of this relationship on systolic and diastolic mechanical restitution in an ejecting, in vivo preparation has yet to be explored. Understanding this relationship may lead to further insight on the cellular processes that govern the contraction and relaxation of the heart, in addition to providing a safer, more feasible clinical diagnostic tool. METHODS AND RESULTS: Anesthetized canines (n = 8) were paced from the RA at rates of 130, 150, and 180 bpm. At each rate, extrasystoles were delivered at varying intervals. The LV dP/dt(max) and dP/dt(min) associated with the extrasystolic beat were expressed as a percentage of steady-state levels and plotted as a function of the extrasystolic interval to obtain mechanical restitution curves. The systolic restitution time constant length decreased significantly with all increases in heart rate, P < 0.05. In the diastolic case, significant decreases in restitution time constants were seen when heart rate was increased from 130 bpm to 180 bpm, and from 150 bpm to 180 bpm, P < 0.05. CONCLUSION: This study was the first to quantify the finding that the time constant of restitution significantly and consistently decreased with a consistent increase in heart rate. The identification of such behavior may be employed to develop stimulation protocols and chronic diagnostic tools to more safely and sensitively identify and optimize the clinical status of patients receiving pacing therapy.

Single-site ventricular and biventricular pacing: investigation of latest depolarization strategy.

Aims Cardiac resynchronization therapy with biventricular pacing has proved beneficial in symptomatic heart failure patients, yet the effects in patients with structurally normal hearts remain unknown. We hypothesized that, in an acute swine model with normal anatomy and function, single-site right ventricular (RV) pacing would better preserve haemodynamic function and electrical activation compared to biventricular pacing. Methods Endocardial single-site pacing was performed in anesthetized swine (n = 7) from the RV septum and RV apex. Biventricular pacing was performed using an epicardial left ventricular (LV) lead and a RV lead. High-resolution, non-contact mapping was employed to record LV activation sequences simultaneously with haemodynamic data after 5 min of consistent capture. Results All pacing interventions significantly prolonged QRS and total endocardial activation durations (P < 0.05) compared to intrinsic activation. Biventricular pacing with the RV apex lead significantly impaired LV systolic mechanics (dP/dt(max), max LV pressure; P < 0.05), and reduced LV relaxation to the greatest extent (dP/dt(min), P = ns). Right ventricular septal pacing conserved function better than other pacing interventions (P = ns) and elicited an intrinsic electrical activation sequence. Conclusion In intact, synchronous hearts, acute biventricular pacing resulted in systolic dysfunction and abnormal LV electrical activation.

Global electrophysiological and hemodynamic assessment of ventricular pacing employing non-contact mapping.

OBJECTIVE: Right ventricular (RV) pacing has been associated with abnormal cardiac electrical and mechanical dyssynchrony, resulting in impaired global and regional ventricular pump function. This study aimed to characterize the relative effects of pacing site on left ventricular (LV) activation patterns and associated hemodynamic performances. METHODS: Acute pacing was performed in anesthetized swine (n=10) instrumented for RV and LV pressure, noncontact mapping (NCM) of endocardial unipolar electrograms, surface ECG, aortic flow, and sonomicrometry. Bipolar endocardial pacing leads were positioned in the right atrial appendage (RAA), RV apex (RVA), and RV outflow tract (RVOT), while bipolar epicardial leads were positioned on the LV-free wall (LVFW) and LV apex (LVA). RESULTS: LVFW and RVA pacing induced the largest increase in intraventricular electrical dyssynchrony (IVED; 32.2+/-10 ms, 21.7+/-4.1 ms, respectively; both p<0.01), whereas pacing from all sites increased QRS and total endocardial LV activation durations (p<0.01). The largest impairment of LV and RV contractility (dP/dtmax) and relaxation (dP/dtmin) was observed during RVA pacing (p= ns). Synchronous electrical activation patterns were observed on NCM during RVOT and LVA pacing. LVFW pacing was the only site that significantly increased tau values as compared to RAA pacing (approximately 25%), whereas LVA pacing elicited only slight increases (approximately 1%). CONCLUSIONS: In swine with preserved ventricular conduction, in vivo pacing of the RVOT and LVA was associated with preserved, physiologically similar electrical activation sequences and LV function relative to RAA pacing. In contrast, RVA pacing caused widespread electrical dyssynchrony of the LV and prolonged activation durations, thereby impairing associated cardiac performance. Such insights into alternate site cardiac pacing, which employed the combination of high-resolution electrical mapping with real-time hemodynamic assessments, may further increase acute and long-term benefits in patients requiring permanent pacemaker support.

Left ventricular septal and left ventricular apical pacing chronically maintain cardiac contractile coordination, pump function and efficiency.

BACKGROUND: Conventional right ventricular (RV) apex pacing can lead to adverse clinical outcome associated with asynchronous activation and reduced left ventricular (LV) pump function. We investigated to what extent alternate RV (septum) and LV (septum, apex) pacing sites improve LV electric activation, mechanics, hemodynamic performance, and efficiency over 4 months of pacing. METHODS AND RESULTS: After AV nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex, RV septum, LV apex, or LV septum (transventricular septal approach). Electric activation maps (combined epicardial contact and endocardial noncontact) showed that RV apical and RV septal pacing induced significantly greater electric desynchronization than LV apical and LV septal pacing. RV apex and RV septal pacing also significantly increased mechanical dyssynchrony, discoordination (MRI tagging) and blood flow redistribution (microspheres) and reduced LV contractility, relaxation, and myocardial efficiency (stroke work/myocardial oxygen consumption). In contrast, LV apical and LV septal pacing did not significantly alter these parameters as compared with the values during intrinsic conduction. At 16 weeks, acute intrasubject comparison showed that single-site LV apical and LV septal pacing generally resulted in similar or better contractility, relaxation, and efficiency as compared with acute biventricular pacing. CONCLUSIONS: Acute and chronic LV apical and LV septal pacing maintain regional cardiac mechanics, contractility, relaxation, and efficiency near native levels, whereas RV apical or RV septal pacing diminish these variables. Acute LV apical and LV septal pacing tend to maintain or improve contractility and efficiency compared with biventricular pacing.

Noninvasive estimation of three-dimensional cardiac electrical activities from body surface potential maps.

A noninvasive three-dimensional (3D) cardiac electrical imaging (3DCEI) approach, which can estimate the location of the initiation site (IS) of activation and the resultant 3D activation sequence (AS) from body surface potential maps (BSPMs), was validated in an intact large mammalian model (swine) during acute ventricular pacing. Body surface potential mapping and intracavitary noncontact mapping (NCM) were performed simultaneously during pacing from both right ventricular (RV) sites (intramural) and left ventricular (LV) sites (endocardial). Subsequent 3DCEI analyses were performed on the measured BSPMs. In total, 5 RV and 5 LV sites from control and heart failure animals were paced. The averaged localization error of the RV and LV sites were 7.0+/-1.1 mm and 6.6+/-1.9 mm, respectively. The endocardial ASs as a subset of the estimated 3D ASs by 3DCEI were consistent with those reconstructed from the NCM system. The present experimental results demonstrate that the noninvasive 3DCEI approach can localize the initiation site and estimate cardiac activation sequence with good accuracy in an in vivo setting, under control, paced and/or diseased conditions.

Variation in pacing impedance: impact of implant site and measurement method.

BACKGROUND: Variations in pacing impedance may be observed during implantation of various active fixation pacing leads. However, these variations can be influenced by the nature of the fixation, the implant site, or the measurement method. Here we describe implant dynamics for a 4.1F, catheter-delivered pacemaker lead. METHODS: Endocardial active fixation leads were implanted under direct intracardiac visualization in two right atrial sites and three right ventricular sites in isolated swine (n = 6) and human (n = 4) hearts. Impedance measurements were recorded at each site employing three different measurement techniques-Pacing System Analyzer (PSA) 5311, PSA 2090, and the Impedance Tone Box (Medtronic, Inc., Minneapolis, MN, USA)-with four different degrees of lead fixation: helix touching, one turn fixed (1 TF), two turns fixed (2 TF), and overtorqued. RESULTS: Pacing impedances increased from touching to 1 TF to 2 TF at all implant sites in both swine and human hearts. Overtorquing applied to leads was associated with visible distortion at the endocardial tissue-lead interface in at least 60% of swine (18 of 30 implants) and human hearts (nine of 14 implants). Impedance values in the right atrial high septum were significantly larger than in any other implant site (P < 0.05). The three measurement methods did not yield significantly different impedance measurements. CONCLUSIONS: Variations in measured impedances were associated with the nature of implant fixation at all sites in both swine and human hearts.

Excitation of the intrinsic conduction system through his and interventricular septal pacing.

BACKGROUND: Direct His bundle pacing results in rapid synchronous ventricular activation. However, clinical experiences with such pacing have been associated with long procedure times and compromised pacing and sensing performance. METHODS: We evaluated myocardial activation sequences (AS) for pacing of the His bundle and peri-His region and assessed acute pacing performance using custom-designed plunge electrodes. Unipolar pacing was performed in isolated swine hearts (n = 10) using four quadripolar stimulation/sensing electrodes implanted into the interventricular septum and equally spaced between the membranous septum and the coronary sinus ostium (zones 1-4, respectively; electrode depth (ED) 1 = most distal, ED 4 = most proximal). Optimal pacing sites were defined as: pacing thresholds < or = 1.5 V, a P-R ratio of < or = 0.5, and > or = 50% occurrence of an intrinsic midseptal left ventricular (LV) endocardial electrical breakout (BO) and activation pattern. RESULTS: Pacing thresholds improved with greater depth of electrode location within the septum (ED 1: 1.51 +/- 0.8 V vs ED 4: 5.2 +/- 3.8 V, P < 0.001), as did the P-R ratio (0.34 +/- 0.6 vs 0.78 +/- 1.0, P < 0.05). His potentials were only observed in zone 1 and 2 electrodes (0.12 and 0.02 mV, respectively). Only electrodes in zones 1 and 2 produced LV endocardial electrical BOs in the midseptal region that demonstrated an intrinsic-like endocardial AS. Depth 1 and 2 electrodes (11.75 and 8.75 mm, respectively) in zone 1 satisfied all three optimal pacing site requirements. CONCLUSIONS: This study has shown that LV activation patterns similar to sinus rhythm may be achieved without direct activation of the His bundle, while maintaining acceptable pacing and sensing performance. These data indicate that pacing systems designed to stimulate the tissues below the point at which the His bundle penetrates the central fibrous body may provide improved system efficiency and LV performance in comparison to both direct His bundle pacing and traditional pacing sites.

A novel ex vivo heart model for the assessment of cardiac pacing systems.

BACKGROUND: Advances in endocardial device design have been limited by the inability to visualize the device-tissue interface. The purpose of this study was to assess the validity of an isolated heart approach, which allows direct ex vivo intracardiac visualization, as a research tool for studying endocardial pacing systems. METHOD OF APPROACH: Endocardial pacing leads were implanted in the right atria and ventricles of intact swine (n = 8) under fluoroscopic guidance. After collection of pacing and sensing performance parameters, the hearts were excised with the leads intact and reanimated on the isolated heart apparatus, and parameters again recorded. RESULTS: Atrial ex vivo parameters significantly decreased compared with in vivo measurements: P-wave amplitudes by 39%, slew rates by 61%, and pacing impedances by 42% (p < 0.05 for each). Similarly, several ventricular ex vivo parameters decreased: R-wave amplitudes by 39%, slew rates by 62%, and pacing impedances by 31%. In contrast, both atrial (4.4 +/- 2.8 vs 3.3 +/- 2.8 V; p = ns) and ventricular thresholds increased (1.2 +/- 0.7 vs 0.6 +/- 0.1 V; p < 0.05 for all). Three distinct phenomena were observed at the lead-tissue interface. Normal implants (70%) demonstrated minimal tissue distortion and resulted in elevated impedance and threshold values. Three implants (13%) resulted in severe tissue distortion and/or tissue wrapping and were associated with highly elevated pacing parameters. Tissue coring occurred in four implants (17%) where the lead would spin freely in the tissue after overtorquing of the lead. CONCLUSIONS: The utility of the isolated heart approach was demonstrated as a tool for the design and assessment of the performance of endocardial pacing systems. Specifically, the ability to visualize device-heart interactions allows new insights into the impact of product design and clinical factors on lead performance and successful implantation.

High pacing impedances: are you overtorquing your leads?

BACKGROUND: Variations in measured pacing impedances that occur at the time of lead implantation remain largely unexplained and may be due to the morphology of the tissue-lead interface. METHODS: An endocardial pacing lead was implanted under direct endoscopic visualization and parameters were measured for defined stages of implantation into multiple sites within the right atrium of in vitro swine hearts (n = 6, 38 implants), in vivo swine hearts (n = 2, 10 implants), and an in vitro human heart (n = 1, 15 implants). RESULTS: Steady increases in impedance values up to 2 turns fully fixed (2TF) were associated with minimal tissue distortion in all implants. Overtorquing of the in vitro swine implants resulted in severe distortion at the tissue-lead interface demonstrating either tissue wrapping (24 implants) or tissue coring (14 implants). Impedance and threshold values remained elevated (953 +/- 282 Omega, 7.86 +/- 3.0 V; both P < 0.05 vs 2TF) during tissue distortion/wrapping, while tissue-cored implants were associated with significant decreases (552 +/- 187 Omega, 6.2 +/- 2.2 V; both P < 0.05 vs 2TF). P-wave amplitudes demonstrated no significant changes or correlation to tissue distortion. Importantly, both swine in vivo and human in vitro data demonstrated similar trends compared with the swine in vitro data. CONCLUSIONS: In this study, one is able to directly observe and correlate the degree of distortion at the tissue-lead interface with measured electrical parameters. Instantaneous impedance values obtained during fixation serve as a superior indicator of an acceptable lead implantation, and should therefore be carefully monitored during implantation.

Biatrial and three-dimensional mapping of spontaneous atrial arrhythmias in patients with refractory atrial fibrillation.

INTRODUCTION: While atrial fibrillation (AF) initiation in the pulmonary veins has been well-studied, simultaneous biatrial and three-dimensional noncontact mapping (NCM) has not been performed. We hypothesized that these two techniques would provide novel information on triggers, initiation, and evolution of spontaneous AF and permit study of different AF populations. METHODS AND RESULTS: The origin of atrial premature beats (APBs), onset of spontaneous AF and its evolution were analyzed in 50 patients with AF in the presence or absence of structural heart disease (SHD) and in different AF presentations (group A: Persistent, group B: Paroxysmal). In 45 patients, spontaneous APBs in the right atrium (RA; n = 60) and left atrium (LA; n = 25) with similar regional distributions regardless of heart disease status were demonstrated. In total, 22 patients (44%) had > or =2 disparate regional origins. Biatrial regional foci were seen with equal frequency in patients with SHD (31%), without SHD (40%), in group A (32%), and in group B (36%). Biatrial mapping and NCM showed organized monomorphic atrial tachyarrhythmias arising in the RA (17), septum (17), or LA (21) and were classified as atrial flutter (RA = 34, LA = 8), macro-reentrant atrial tachycardia (RA = 1, LA = 3) or focal atrial tachycardia (RA = 2, LA = 7). Their regional distribution was more extensive in patients with SHD and persistent AF compared with patients without SHD or paroxysmal AF. Simultaneous biatrial tachycardias were observed only in group A patients and those with SHD. CONCLUSIONS: Simultaneous biatrial and NCM permits successful AF mapping in different AF populations and demonstrates a biatrial spectrum of spontaneous triggers and tachycardias. Organized monomorphic tachycardias with multiple unilateral or biatrial locations are commonly observed in human AF. Patients with heart disease or persistent AF have a more extensive distribution as well as simultaneous coexistence of multiple tachycardias during AF.

In vitro studies of human hearts.

BACKGROUND: Isolated mammalian hearts have been used in numerous studies that have led to many important discoveries in cardiac physiology, pharmacology, and surgery. Multiple methods of perfusion have been described including retrograde and/or antegrade flows and crystalloid or blood perfusates. Furthermore, multiple species have been utilized for such studies including the following: rat, rabbit, guinea pig, canine, and swine. The objective of this study was to describe a unique isolated heart preparation, utilizing human hearts not viable for transplant, which allows for physiologic perfusion and endocardial imaging. METHODS: Utilizing standard cardiac transplantation procedures, 12 human hearts deemed not viable for transplant were explanted to an isolated heart apparatus. A clear, modified Krebs-Henseleit buffer was used as a blood substitute, which allowed for endocardial imaging utilizing 6.0 mm endoscopic video cameras inserted into the cardiac chambers. The hearts were perfused in Langendorff (retrograde) and/or working (physiologic) mode. RESULTS: Eleven of 12 hearts achieved the following performance in working mode: peak left ventricular pressure of 21.5 to 75.8 mm Hg, with an average of 42.7 +/- 19.9 mm Hg. Intracardiac anatomical imaging was possible in all hearts, providing unique views of normal and pathological endocardial anatomy as well as biomedical device-heart interactions. CONCLUSIONS: We have described a unique isolated heart preparation with which we have successfully reanimated 11 human hearts deemed not viable for transplant, perfused them by working mode, and performed intracardiac anatomical imaging. This approach provides a novel means for obtaining images of functional human cardiac anatomy and various types of unique biomedical assessments.