Spinal cord stimulation causes potentiation of right vagus nerve effects on atrial chronotropic function and repolarization in canines.

INTRODUCTION: Experimental evidence suggests that spinal cord stimulation (SCS) can cause augmentation of parasympathetic influences on the heart via enhanced vagus nerve (VgN) activity. Herein, we investigated whether this might lead to enhanced inducibility of vagally mediated atrial tachyarrhythmias (AT) and whether such actions depend on intact autonomic neural connections with central neurons. METHOD AND RESULTS: Epidural SCS electrodes were implanted at T1-T4 in anesthetized canines. Sinus cycle length prolongation, atrial repolarization changes (191 epicardial electrode sites), and AT inducibility in response to right VgN stimuli applied at the cervical level were determined before and during SCS. VgN-induced sinus cycle length prolongation was potentiated during SCS among the animals with intact neural connections or bilateral vagotomy proximal to the stimulation site, whereas such prolongation was unaffected by SCS among animals with bilateral decentralization of stellate ganglia. Likewise, the atrial surface area in which VgN-induced repolarization wave form changes were identified was significantly augmented during SCS among the former but not among the latter. AT facilitation occurred during SCS in the majority of animals with intact neural connections, particularly among those displaying relatively greater potentiation of vagally mediated sinus cycle length prolongation. CONCLUSION: The data indicate that SCS may cause potentiation of parasympathetic influences on the atria in response to cervical VgN stimulation. Such SCS effects appear to be mediated via decreased tonic inhibitory sympathetic influences in the presence of intact stellate ganglion connections to central neurons.

Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of cardiac arrhythmia and a leading cause of cardiovascular morbidity, particularly stroke. The cardiac gap-junction protein connexin 40 is expressed selectively in atrial myocytes and mediates the coordinated electrical activation of the atria. We hypothesized that idiopathic atrial fibrillation has a genetic basis and that tissue-specific mutations in GJA5, the gene encoding connexin 40, may predispose the atria to fibrillation. METHODS: We sequenced GJA5 from genomic DNA isolated from resected cardiac tissue and peripheral lymphocytes from 15 patients with idiopathic atrial fibrillation. Identified GJA5 mutations were transfected into a gap-junction-deficient cell line to assess their functional effects on protein transport and intercellular electrical coupling. RESULTS: Four novel heterozygous missense mutations were identified in 4 of the 15 patients. In three patients, the mutations were found in the cardiac-tissue specimens but not in the lymphocytes, indicating a somatic source of the genetic defects. In the fourth patient, the sequence variant was detected in both cardiac tissue and lymphocytes, suggesting a germ-line origin. Analysis of the expression of mutant proteins revealed impaired intracellular transport or reduced intercellular electrical coupling. CONCLUSIONS: Mutations in GJA5 may predispose patients to idiopathic atrial fibrillation by impairing gap-junction assembly or electrical coupling. Our data suggest that common diseases traditionally considered to be idiopathic may have a genetic basis, with mutations confined to the diseased tissue.

Anatomical pitfalls during encircling cryoablation of the left atrium for atrial fibrillation therapy in the pig.

We previously published encircling endocardial cryo-isolation of the pulmonary vein (PV) region. This study documented mechanisms of isolation failure using CARTO mapping. Cryo-isolation used a modified Surgifrost introduced via a Universal Cardiac Introducer on the left atrial appendage. Of five pigs, two had incomplete isolation and repeat mapping: Activation was over Bachmann's bundle (BB) in one and the coronary sinus (CS) in the other. Repeat cryoablation failed to eliminate gaps. Histologically, the BB gap had nonlesioned sub-epicardial fibres and thick fat covering the cryolesioned BB: fat protecting the epicardium from cryoablation. The inferior gap had a large CS, and a thick myocardium bridging the isthmus: myocardial thickness and CS thermal sink preventing transmural cryolesions. CARTO mapping localized gaps. Although the CS is known to cause failure, its protective mechanism is not well documented. The BB gap is novel. These findings have important clinical implications for isolation of the PV region.

Ultrasound image and augmented reality guidance for off-pump, closed, beating, intracardiac surgery.

Our project is the reintroduction of off-pump intracardiac surgery using the Universal Cardiac Introducer (UCI) for safe intracardiac access. The purpose of this study was to evaluate multimodality visualization using three ultrasound modalities and ultrasound augmented with virtual reality. Image guidance was tested on implanting a mitral valve prosthesis via the UCI in 12 pigs. Initially, two-dimensional (2-D) transesophageal echocardiography (TEE) ultrasound, intravascular ultrasound (intracardiac echocardiography [ICE]), and three-dimensional (3-D) epicardial ultrasound were utilized. Ultrasound augmented with virtual reality was used in the last three experiments. A 2-D TEE assisted navigating the prosthesis into the orifice. Positioning was not intuitive and required trial and error method. A 3-D epicardial ultrasound allowed positioning of the valve into the orifice. Positioning of the clip was difficult because of artifacts with multiple reflections and shadowing. Augmented reality displayed the entire prosthesis and the tools without artifacts; provided intuitive information on navigation, positioning, and orientation of tools; and improved significantly image guidance and surgical skill. Augmented virtual reality, with tracked 2-D or 3-D ultrasound imaging, provides guidance that can effectively substitute for direct vision during beating heart intracardiac surgery.

Dose reduction for cardiac CT using a registration-based approach.

Two reasons for the recent rise in radiation exposure from CT are increases in its clinical applicability and the desire to maintain high SNR while acquiring smaller voxels. To address this emerging dose problem, several strategies for reducing patient exposure have already been proposed. One method employed in cardiac imaging is ECG-driven modulation of the tube current between 100% at one time point in the cardiac cycle and a reduced fraction at the remaining phases. In this paper, we describe how images obtained during such acquisition can be used to reconstruct 4D data of consistent high quality throughout the cardiac cycle. In our approach, we assume that the middiastole (MD) phase is imaged with full dose. The MD image is then independently registered to lower dose images (lower SNR) at other frames, resulting in a set of transformations. Finally, the transformations are used to warp the MD frame through the cardiac cycle to generate the full 4D image. In addition, the transformations may be interpolated to increase the temporal sampling or to generate images at arbitrary time points. Our approach was validated using various data obtained with simulated and scanner-implemented dose modulation. We determined that as little as 10% of the total dose was required to reproduce full quality images with a 1 mm spatial error and an error in intensity values on the order of the image noise. Thus, our technique offers considerable dose reductions compared to standard imaging protocols, with minimal effects on the quality of the final data.

Surgical treatment of Wolff-Parkinson-White syndrome: a timeless procedure?

Catheter-induced radiofrequency (RF) ablation has become the initial non-pharmacological treatment option for Wolff-Parkinson-White (WPW) syndrome. In this report, we present the successful surgical treatment of WPW syndrome in two patients in whom percutaneous ablation of the accessory pathway was not successful.

Revisiting heart activation-conduction physiology, part I: atria.

This discussion paper re-examines the conduction-activation of the atria, based on observations, with respect to the complexity of the heart as an organ with a brain, and its evolution from a peristaltic tube. The atria do not require a specialized conduction system because they use the subendocardial layer to produce centripetal transmural activation fronts, regardless of the anatomical and histological organization of the transmural atrial wall. This has been described as "two-layer" physiology which provides robust transmission of activation from the sinus to the AV node via a centripetal transmural activation front. New productive insights can come from re-examining the physiology, not only during sinus rhythm but also during atrial tachycardias, in particular atrial flutter and atrial fibrillation (AF). During common flutter, the areas of slow conduction, in the isthmus and following trabeculations, particularly the subendocardial layer confines conduction through the trabeculations which supports re-entry. During experimental or postoperative flutter, the circular 2D activation around the obstacle follows the physiological transmural activation. Understanding this physiology offers insights into AF. During acute or protracted AF, the presence of stationary or drifting rotors is characteristic and consistent with normal physiological 2D atrial activation, suggesting that suppressing physiological transmural activation of AF will permanently restore normal sinus node atrial activation. In contrast, during permanent AF, normal 2D activation is abolished; the presence of transmural, serpentine, and chaotic atrial activation suggests that the normal physiological activation pattern has been replaced by a new, irreversible variety of atrial conduction that is a new physiology, which is consistent with evolution of complex systems.

Revisiting right atrial isolation rationale for atrial fibrillation: functional anatomy of interatrial connections.

INTRODUCTION: Direct catheter ablation for atrial fibrillation does not yield reproducible permanent control as for other atrial arrhythmias. Therefore, there is a need for an alternative intervention, i.e., left atrial exclusion, based on elective ablation of the interatrial connecting bundles. METHODS AND RESULTS: We describe the "operative anatomy" of the three major interatrial connections: the Bachmann bundle, the coronary sinus bundle, and the left atrial-atrioventricular node connection, based on macroscopic dissections of human and porcine hearts and our previous experience. We identified the three right atrial attachments, with the coronary sinus (CS) and left atrial (LA)-atrioventricular (AV) nodal connection being most problematic for safe ablation. CONCLUSIONS: To obtain a complete isolation of the left from the right atrium, all three connections must be ablated. The CS connection must be ablated distal to the ostium. If present, the LA-AV nodal connection can be safely ablated from the left atrium.

Surface-Based CT-TEE Registration of the Aortic Root.

Transcatheter aortic valve implantation (TAVI) is a minimally invasive alternative to conventional aortic valve replacement for severe aortic stenosis in high-risk patients in which a stent-based bioprosthetic valve is delivered into the heart via a catheter. TAVI relies largely on single-plane fluoroscopy for intraoperative navigation and guidance, which provides only gross imaging of anatomical structures. Inadequate imaging leading to suboptimal valve positioning contributes to many of the early complications experienced by TAVI patients, including valve embolism, coronary ostia obstruction, paravalvular leak, heart block, and secondary nephrotoxicity from excessive contrast use. Improved visualization can be provided using intraoperative registration of a CT-derived surface to transesophageal echo (TEE) images. In this study, the accuracy and robustness of a surface-based registration method suitable for intraoperative use are evaluated, and the performances of different TEE surface extraction methods are compared. The use of cross-plane TEE contours demonstrated the best accuracy, with registration errors of less than 5 mm. This guidance system uses minimal intraoperative interaction and workflow modification, does not require tool calibration or additional intraoperative hardware, and can be implemented at all cardiac centers at extremely low cost.

Hybrid access to atria via the Guiraudon Universal Cardiac Introducer for arrhythmia ablation after total cavopulmonary derivation.

We report the first use of a new platform, the Guiraudon Universal Cardiac Introducer (GUCI), in humans for accessing the left atrium for catheter-based ablations in patients with resistant atrial arrhythmias after total cavopulmonary derivation. The GUCI was originally designed for intracardiac access for closed, beating instrumental intracardiac surgery.The patient was a 29-year-old man with problematic atrial arrhythmias resistant to antiarrhythmic drugs because of severe uncontrolled bradycardia and because his pacemaker was explanted for infection.The GUCI was attached to the left atrial appendage via an anterior left thoracotomy. The GUCI was modified to accommodate introduction and manipulation of multiple catheters. This allowed electrophysiologists to perform catheter-based exploration and ablation. A DDD pacemaker was implanted, with an atrial endocardial lead introduced via the GUCI cuff and a ventricular epicardial lead.Postoperative atrial arrhythmias were controlled using amiodarone and atrial pacing. At the 12-month follow-up, the patient was arrhythmia- and drug-free and returned to full employment.This new access offers an additional new alternative atrial access to treat resistant arrhythmia after total cavopulmonary derivation. The current state-of-the-art makes patient selection difficult and uncomfortable for the surgeons because of incomplete preoperative electrophysiological data, such as a return to the beginning of surgery for arrhythmia; however, more cumulative experience with intraoperative electrophysiological data and new mapping technologies should address these limitations.

US-fluoroscopy registration for transcatheter aortic valve implantation.

Transcatheter aortic valve implantation is a minimally invasive alternative to open-heart surgery for aortic stenosis in which a stent-based bioprosthetic valve is delivered into the heart on a catheter. Limited visualization during this procedure can lead to severe complications. Improved visualization can be provided by live registration of transesophageal echo (TEE) and fluoroscopy images intraoperatively. Since the TEE probe is always visible in the fluoroscopy image, it is possible to track it using fiducial-based single-perspective pose estimation. In this study, inherent probe tracking performance was assessed, and TEE to fluoroscopy registration accuracy and robustness were evaluated. Results demonstrated probe tracking errors of below 0.6 mm and 0.2°, a 2-D RMS registration error of 1.5 mm, and a tracking failure rate of below 1%. In addition to providing live registration and better accuracy and robustness compared to existing TEE probe tracking methods, this system is designed to be suitable for clinical use. It is fully automatic, requires no additional operating room hardware, does not require intraoperative calibration, maintains existing procedure and imaging workflow without modification, and can be implemented in all cardiac centers at extremely low cost.

Augmented reality image guidance improves navigation for beating heart mitral valve repair.

OBJECTIVE: Emerging off-pump beating heart valve repair techniques offer patients less invasive alternatives for mitral valve (MV) repair. However, most of these techniques rely on the limited spatial and temporal resolution of transesophageal echocardiography (TEE) alone, which can make tool visualization and guidance challenging. METHODS: Using a magnetic tracking system and integrated sensors, we created an augmented reality (AR) environment displaying virtual representations of important intracardiac landmarks registered to biplane TEE imaging. In a porcine model, we evaluated the AR guidance system versus TEE alone using the transapically delivered NeoChord DS1000 system to perform MV repair with chordal reconstruction. RESULTS: Successful tool navigation from left ventricular apex to MV leaflet was achieved in 12 of 12 and 9 of 12 (P = 0.2) attempts with AR imaging and TEE alone, respectively. The distance errors of the tracked tool tip from the intended midline trajectory (5.2 ± 2.4 mm vs 16.8 ± 10.9 mm, P = 0.003), navigation times (16.7 ± 8.0 seconds vs 92.0 ± 84.5 seconds, P = 0.004), and total path lengths (225.2 ± 120.3 mm vs 1128.9 ± 931.1 mm, P = 0.003) were significantly shorter in the AR-guided trials compared with navigation with TEE alone. Furthermore, the potential for injury to other intracardiac structures was nearly 40-fold lower when using the AR imaging for tool navigation. The AR guidance also seemed to shorten the learning curve for novice surgeons. CONCLUSIONS: Augmented reality-enhanced TEE facilitates more direct and safe intracardiac navigation of the NeoChord DS tool from left ventricular apex to MV leaflet. Tracked tool path results demonstrate fourfold improved accuracy, fivefold shorter navigation times, and overall improved safety with AR imaging guidance.

Virtual and augmented medical imaging environments: enabling technology for minimally invasive cardiac interventional guidance.

Virtual and augmented reality environments have been adopted in medicine as a means to enhance the clinician's view of the anatomy and facilitate the performance of minimally invasive procedures. Their value is truly appreciated during interventions where the surgeon cannot directly visualize the targets to be treated, such as during cardiac procedures performed on the beating heart. These environments must accurately represent the real surgical field and require seamless integration of pre- and intra-operative imaging, surgical tracking, and visualization technology in a common framework centered around the patient. This review begins with an overview of minimally invasive cardiac interventions, describes the architecture of a typical surgical guidance platform including imaging, tracking, registration and visualization, highlights both clinical and engineering accuracy limitations in cardiac image guidance, and discusses the translation of the work from the laboratory into the operating room together with typically encountered challenges.

Augmented reality image guidance during off-pump mitral valve replacement through the guiraudon universal cardiac introducer.

OBJECTIVE: : We report our experience with ultrasound augmented reality (US-AR) guidance for mitral valve prosthesis (MVP) implantation in the pig using off-pump, closed, beating intracardiac access through the Guiraudon Universal Cardiac Introducer attached to the left atrial appendage. METHODS: : Before testing US-AR guidance, a feasibility pilot study on nine pigs was performed using US alone. US-AR guidance, tested on a heart phantom, was subsequently used in three pigs (∼65 kg) using a tracked transesophageal echocardiography probe, augmented with registration of a 3D computed tomography scan, and virtual representation of the MVP and clip-delivering tool (Clipper); three pigs were used to test feature-based registration. RESULTS: : Navigation of the MVP was facilitated by the 3D anatomic display. AR displayed the MVP and the Clipper within the Atamai Viewer, with excellent accuracy for tool placement. Positioning the Clipper was hampered by the design of the MVP holder and Clipper. These limitations were well displayed by AR, which provided guidance for improved design of tools. CONCLUSIONS: : US-AR provided informative image guidance. It documented the flaws of the current implantation technology. This information could not be obtained by any other method of evaluation. These evaluations provided guidance for designing an integrated tool: combining an unobtrusive valve holder that allows the MVP to function properly as soon as positioned, and an anchoring system, with clips that can be released one at a time, and retracted if necessary, for optimal results. The portability of Real-time US-AR may prove to be the ideal practical image guidance system for all closed intracardiac interventions.

Off-pump positioning of a conventional aortic valve prosthesis through the left ventricular apex with the universal cardiac introducer under sole ultrasound guidance, in the pig.

OBJECTIVE: : To test an alternative to catheter and open-heart techniques, by documenting the feasibility of implanting an unmodified mechanical aortic valve (AoV) in the off pump, beating heart using the universal cardiac introducer (UCI) attached to the left ventricular (LV) apex. METHODS: : In six pigs, the LV apex was exposed by a median sternotomy. The UCI was attached to the apex. A 12-mm punching tool (punch), introduced through the UCI, was used to create a cylindrical opening through the apex. Then, the AoV, secured to a holder, was introduced into the LV, using transesophageal echocardiographic, guided through the apical LV opening, navigated into the LV outflow tract, and positioned within the aortic annulus. Transesophageal echocardiographic guidance was useful for navigation and positioning by superimposing the aortic annulus and prosthetic ring while Doppler imaging verified preserved prosthetic function and absence of perivalvular leaks. The valve function and hemodynamics were observed before termination for macroscopic evaluation. RESULTS: : The punch produced a clean opening without fragmentation or myocardial embolization. During advancement of the mechanical AoV, there were no arrhythmias, mitral valve dysfunctions, evidence of myocardial ischemia, or hemodynamic instability. The AoVs were well seated over the annulus, without obstructing the coronaries or contact with the conduction system. The ring of AoVs was well circumscribed by the aortic annulus. CONCLUSIONS: : This study documented the feasibility of positioning a mechanical AoV on the closed, beating heart. These results should encourage the development of adjunct technologies to deliver current tissue or mechanical AoV with minimal side effects.

Inside the beating heart: an in vivo feasibility study on fusing pre- and intra-operative imaging for minimally invasive therapy.

OBJECTIVE: An interventional system for minimally invasive cardiac surgery was developed for therapy delivery inside the beating heart, in absence of direct vision. METHOD: A system was developed to provide a virtual reality (VR) environment that integrates pre-operative imaging, real-time intra-operative guidance using 2D trans-esophageal ultrasound, and models of the surgical tools tracked using a magnetic tracking system. Detailed 3D dynamic cardiac models were synthesized from high-resolution pre-operative MR data and registered within the intra-operative imaging environment. The feature-based registration technique was employed to fuse pre- and intra-operative data during in vivo intracardiac procedures on porcine subjects. RESULTS: This method was found to be suitable for in vivo applications as it relies on easily identifiable landmarks, and hence, it ensures satisfactory alignment of pre- and intra-operative anatomy in the region of interest (4.8 mm RMS alignment accuracy) within the VR environment. Our initial experience in translating this work to guide intracardiac interventions, such as mitral valve implantation and atrial septal defect repair demonstrated feasibility of the methods. CONCLUSION: Surgical guidance in the absence of direct vision and with no exposure to ionizing radiation was achieved, so our virtual environment constitutes a feasible candidate for performing various off-pump intracardiac interventions.

Off-pump atrial septal defect closure using the universal cardiac introducer®: creation of models of atrial septal defects in the pig access and surgical technique.

OBJECTIVE: : Optimal atrial septal defect (ASD) closure should combine off-pump techniques with the effectiveness and versatility of open-heart techniques. We report our experience with off-pump ASD closure using the Universal Cardiac Introducer (UCI) in a porcine model. The goal was to create an ASD over the fossa ovale (FO) and position a patch over the ASD under ultrasound (US) imaging and augmented virtual reality guidance. METHODS: : An US probe (tracked with a magnetic tracking system) was positioned into the esophagus (transesophageal echocardiographic probe) for real-time image-guidance. The right atrium (RA) of six pigs was exposed via a right lateral thoracotomy or medial sternotomy. The UCI was attached to the RA wall. A punching tool was introduced via the UCI, navigated and positioned, under US guidance, to create an ASD into the FO. A patch with its holder and a stapling device were introduced into the RA via the UCI. The patch was positioned on the ASD. Occlusion of the ASD was determined using US and Doppler imaging. RESULTS: : The FO membrane was excised successfully in all animals. US image-guidance provided excellent visualization. The patch was positioned in all cases with complete occlusion of the ASD. The stapling device proved too bulky, impeding circumferential positioning. CONCLUSIONS: : Using the UCI, ASD closure was safe and feasible. US imaging, combined with virtual and augmented reality provided accurate navigating and positioning. This study also provided valuable information on the future design of anchoring devices for intracardiac procedures.