Hiroshi Ashikaga

Feasibility of Real-Time Magnetic Resonance Imaging for Catheter Guidance in Electrophysiology Studies

Background— Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance. Methods and Results— An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images (≈5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients. Conclusions— To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.

Magnetic Resonance–Based Anatomical Analysis of Scar-Related Ventricular Tachycardia. Implications for Catheter Ablation

In catheter ablation of scar-related monomorphic ventricular tachycardia (VT), substrate voltage mapping is used to electrically define the scar during sinus rhythm. However, the electrically defined scar may not accurately reflect the anatomical scar. Magnetic resonance–based visualization of the scar may elucidate the 3D anatomical correlation between the fine structural details of the scar and scar-related VT circuits. We registered VT activation sequence with the 3D scar anatomy derived from high-resolution contrast-enhanced MRI in a swine model of chronic myocardial infarction using epicardial sock electrodes (n=6, epicardial group), which have direct contact with the myocardium where the electrical signal is recorded. In a separate group of animals (n=5, endocardial group), we also assessed the incidence of endocardial reentry in this model using endocardial basket catheters. Ten to 12 weeks after myocardial infarction, sustained monomorphic VT was reproducibly induced in all animals (n=11). In the epicardial group, 21 VT morphologies were induced, of which 4 (19.0%) showed epicardial reentry. The reentry isthmus was characterized by a relatively small volume of viable myocardium bound by the scar tissue at the infarct border zone or over the infarct. In the endocardial group (n=5), 6 VT morphologies were induced, of which 4 (66.7%) showed endocardial reentry. In conclusion, MRI revealed a scar with spatially complex structures, particularly at the isthmus, with substrate for multiple VT morphologies after a single ischemic episode. Magnetic resonance–based visualization of scar morphology would potentially contribute to preprocedural planning for catheter ablation of scar-related, unmappable VT.

Abnormal Sympathetic Innervation of Viable Myocardium and the Substrate of Ventricular Tachycardia After Myocardial Infarction

OBJECTIVES The aim of this study was to characterize the relationship between impaired sympathetic innervation and arrhythmia with noninvasive biologic imaging in an animal model of post-infarct ventricular tachycardia (VT). BACKGROUND Innervation might be abnormal in the normally perfused borderzone of myocardial infarction, contributing to myocardial catecholamine overexposure and arrhythmogenic risk. METHODS Myocardial infarction was induced by mid-left anterior descending coronary artery balloon occlusion in 11 pigs. Positron emission tomography (PET) of tissue perfusion and catecholamine uptake and storage was performed with [13N]-ammonia and [11C]-epinephrine 4 to 12 weeks later. Magnetic resonance imaging and invasive electrophysiology (electroanatomic mapping, basket catheter, VT inducibility) were performed within 1 week of PET. RESULTS When compared with a normal database of 9 healthy animals, reduced perfusion was observed in 37 +/- 7% of the left ventricle (LV). Epinephrine retention was reduced in 44 +/- 7% of LV, resulting in a perfusion/innervation mismatch of 7 +/- 4% LV. Sustained monomorphic VT was inducible in 7 of 11 animals. These animals showed a larger perfusion/innervation mismatch (10 +/- 4% vs. 4 +/- 2% LV for animals without VT; p = 0.02). Regionally, the degree of perfusion/innervation mismatch did not correlate with wall thickness or thickening but showed a significant correlation with reduced myocardial voltage (r = 0.93; p = 0.001) and with the site of earliest VT activation (chi-square 13.1; p < 0.001). CONCLUSIONS Noninvasive mapping of cardiac sympathetic nerve terminals reveals regionally impaired catecholamine uptake and storage in the normally perfused borderzone after experimental myocardial infarction. These areas might be useful to characterize the individual risk for ventricular arrhythmia.

Feasibility of image-based simulation to estimate ablation target in human ventricular arrhythmia

BACKGROUND Previous studies suggest that magnetic resonance imaging with late gadolinium enhancement (LGE) may identify slowly conducting tissues in scar-related ventricular tachycardia (VT). OBJECTIVE To test the feasibility of image-based simulation based on LGE to estimate ablation targets in VT. METHODS We conducted a retrospective study in 13 patients who had preablation magnetic resonance imaging for scar-related VT ablation. We used image-based simulation to induce VT and estimate target regions according to the simulated VT circuit. The estimated target regions were coregistered with the LGE scar map and the ablation sites from the electroanatomical map in the standard ablation approach. RESULTS In image-based simulation, VT was inducible in 12 (92.3%) patients. All VTs showed macroreentrant propagation patterns, and the narrowest width of estimated target region that an ablation line should span to prevent VT recurrence was 5.0 ± 3.4 mm. Of 11 patients who underwent ablation, the results of image-based simulation and the standard approach were consistent in 9 (82%) patients, where ablation within the estimated target region was associated with acute success (n = 8) and ablation outside the estimated target region was associated with failure (n = 1). In 1 (9%) case, the results of image-based simulation and the standard approach were inconsistent, where ablation outside the estimated target region was associated with acute success. CONCLUSIONS The image-based simulation can be used to estimate potential ablation targets of scar-related VT. The image-based simulation may be a powerful noninvasive tool for preprocedural planning of ablation procedures to potentially reduce the procedure time and complication rates.

The critical isthmus sites of ischemic ventricular tachycardia are in zones of tissue heterogeneity, visualized by magnetic resonance imaging

BACKGROUND A need exists to develop alternative approaches to VT ablation that provide an improved delineation of the arrhythmogenic substrate. OBJECTIVE The aim of this study was to evaluate the hypotheses that: (1) the heterogeneous zone (HZ, a mixture of normal-appearing tissue and scar) in magnetic resonance imaging (MRI) contains the critical isthmus(es) for ventricular tachycardia (VT), (2) successful ablation of VT would include ablation in the HZ, and (3) inadequate ablation of HZ allows for VT recurrence. METHODS MRI and an electrophysiology study (EP) were performed in a model of chronic myocardial infarction in 17 pigs. In animals that were inducible for VT, ablations were done guided by standard EP criteria and blinded to the MRI. After ablation, electroanatomic mapping results were co-registered with MRI. RESULTS In 8 animals, 22 sustained monomorphic VTs were generated. The HZ was substantially larger in inducible (n = 8) compared with noninducible animals (n = 9) [25% ± 10% vs 13% ± 5% of total scar, respectively, P = .007]. Acutely, all targeted VTs were successfully ablated, and postprocedure analysis showed that at least 1 ablation was in the HZ in each animal. In 5 animals, a second EP and MRI were performed 1 week after ablation. Three animals had inducible VTs, and MRI showed that the HZ had not been completely ablated. In contrast, the 2 animals without inducible VT revealed no remaining HZ. CONCLUSION These findings show that MRI can define an HZ and determine the location of ablated lesions. The HZ may be a promising ablation target to cure ischemic VTs. Remnants of HZ after ablation may be the substrate for clinical relapses.

Relationship between left atrial appendage morphology and stroke in patients with atrial fibrillation

BACKGROUND Atrial fibrillation (AF) is an important cause of stroke. Given the morbidity and mortality associated with stroke, the risk stratification of patients based on left atrial appendage (LAA) characteristics is of great interest. OBJECTIVE To explore the association between LAA morphology and LAA characteristics including the extent of trabeculations, orifice diameter, and length with prevalent stroke in a large cohort of patients with drug refractory AF who underwent AF ablation to develop mechanistic insight regarding the risk of stroke. METHODS An institutional cohort of 1063 patients referred for AF ablation from 2003 to 2012 was reviewed to identify patients that underwent preprocedural cardiac computed tomography (CT). LAA morphology was characterized as chicken wing, cactus, windsock, or cauliflower by using previously reported methodology. Left atrial size and LAA trabeculations, morphology, orifice diameter, and length were compared between patients with prevalent stroke and patients without prevalent stroke. RESULTS Of 678 patients with CT images, 65 (10%) had prior stroke or transient ischemic attack. In univariate analyses, prevalent heart failure (7.7% in cases vs 2.8% in controls; P = .033), smaller LAA orifice (2.26 ± 0.52 cm vs 2.78 ± 0.71 cm ; P < .001), shorter LAA length (5.06 ± 1.17 cm vs 5.61 ± 1.17 cm; P < .001), and extensive LAA trabeculations (27.7% vs 14.4%; P = .019) were associated with stroke. LAA morphologies were unassociated with stroke risk. In multivariable analysis, smaller LAA orifice diameter and extensive LAA trabeculations remained independently associated with thromboembolic events. CONCLUSIONS The extent of LAA trabeculations and smaller LAA orifice diameter are associated with prevalent stroke and may mediate the previously described association of cauliflower LAA morphology with stroke.

Transmural myocardial mechanics during isovolumic contraction.

OBJECTIVES We sought to resolve the 3-dimensional transmural heterogeneity in myocardial mechanics observed during the isovolumic contraction (IC) phase. BACKGROUND Although myocardial deformation during IC is expected to be little, recent tissue Doppler imaging studies suggest dynamic myocardial motions during this phase with biphasic longitudinal tissue velocities in left ventricular (LV) long-axis views. A unifying understanding of myocardial mechanics that would account for these dynamic aspects of IC is lacking. METHODS We determined the time course of 3-dimensional finite strains in the anterior LV of 14 adult mongrel dogs in vivo during IC and ejection with biplane cineradiography of implanted transmural markers. Transmural fiber orientations were histologically measured in the heart tissue postmortem. The strain time course was determined in the subepicardial, midwall, and subendocardial layers referenced to the end-diastolic configuration. RESULTS During IC, there was circumferential stretch in the subepicardial layer, whereas circumferential shortening was observed in the midwall and the subendocardial layer. There was significant longitudinal shortening and wall thickening across the wall. Although longitudinal tissue velocity showed a biphasic profile; tissue deformation in the longitudinal as well as other directions was almost linear during IC. Subendocardial fibers shortened, whereas subepicardial fibers lengthened. During ejection, all strain components showed a significant change over time that was greater in magnitude than that of IC. Significant transmural gradient was observed in all normal strains. CONCLUSIONS IC is a dynamic phase characterized by deformation in circumferential, longitudinal, and radial directions. Tissue mechanics during IC, including fiber shortening, appear uninterrupted by rapid longitudinal motion created by mitral valve closure. This study is the first to report layer-dependent deformation of circumferential strain, which results from layer-dependent deformation of myofibers during IC. Complex myofiber mechanics provide the mechanism of brief clockwise LV rotation (untwisting) and significant wall thickening during IC within the isovolumic constraint.

Association of Left Atrial Function and Left Atrial Enhancement in Patients With Atrial Fibrillation Cardiac Magnetic Resonance Study

Atrial fibrillation (AF) is associated with extensive abnormalities in atrial structure and function1-3. It is well-established that structural atrial changes precede the development of AF and progress with increased duration of sustained AF4. The changes in atrial function impair not only the booster pump function but also the atrial reservoir and conduit functions during ventricular systole and early diastole 5, 6. Progressive atrial remodeling includes fibrotic changes that promote AF maintenance7. This idea is supported by observations of increased left atrial (LA) fibrosis in patients with long-standing persistent AF 4. LA structural and functional remodeling is associated with increased incidence of AF, as well as AF recurrence after cardioversion or ablation8-11. Late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) can noninvasively quantify the extent of LA fibrosis12, 13. Atrial function is commonly evaluated by speckle-tracking echocardiography; however, the technique is limited for resolution of the thin and asymmetric LA myocardium and for the analysis of the posterior LA where most of the fibrosis is located7. In contrast, myocardial motion can be accurately tracked with CMR due to its ability to accurately define endocardial and epicardial borders14. CMR-feature tracking, a novel post–processing technique which tracks myocardial motion using cine CMR images, has recently been developed15-19. In this study, we sought to examine the association of LA fibrosis measured with LGE-CMR with phasic LA remodeling measured with feature-tracking CMR in patients with AF. We hypothesized that increased atrial LGE is associated with reduced LA function as assessed by feature tracking CMR.Background—Atrial fibrillation (AF) is associated with left atrial (LA) structural and functional changes. Cardiac magnetic resonance late gadolinium enhancement (LGE) and feature-tracking are capable of noninvasive quantification of LA fibrosis and myocardial motion, respectively. We sought to examine the association of phasic LA function with LA enhancement in patients with AF. Methods and Results—LA structure and function was measured in 90 patients with AF (age 61±10 years; 76% men) referred for ablation and 14 healthy volunteers. Peak global longitudinal LA strain, LA systolic strain rate, and early and late diastolic strain rates were measured using cine–cardiac magnetic resonance images acquired during sinus rhythm. The degree of LGE was quantified. Compared with patients with paroxysmal AF (60% of cohort), those with persistent AF had larger maximum LA volume index (56±17 versus 49±13 mL/m2; P=0.036), and increased LGE (27.1±11.7% versus 36.8±14.8%; P<0.001). Aside from LA active emptying fraction, all LA parameters (passive emptying fraction, peak global longitudinal LA strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate) were lower in patients with persistent AF (P<0.05 for all). Healthy volunteers had less LGE and higher LA functional parameters compared with patients with AF (P<0.05 for all). In multivariable analysis, increased LGE was associated with lower LA passive emptying fraction, peak global longitudinal LA strain, systolic strain rate, early diastolic strain rate, and late diastolic strain rate (P<0.05 for all). Conclusions—Increased LA enhancement is associated with decreased LA reservoir, conduit, and booster pump functions. Phasic measurement of LA function using feature-tracking cardiac magnetic resonance may add important information about the physiological importance of LA fibrosis.

Building maps of local apparent conductivity of the epicardium with a 2-D electrophysiological model of the heart

In this paper, we address the problem of estimating the parameters of an electrophysiological model of the heart from a set of electrical recordings. The chosen model is the reaction-diffusion model on the transmembrane potential proposed by Aliev and Panfilov. For this model of the transmembrane, we estimate a local apparent two-dimensional conductivity from a measured depolarization time distribution. First, we perform an initial adjustment including the choice of initial conditions and of a set of global parameters. We then propose a local estimation by minimizing the quadratic error between the depolarization time computed by the model and the measures. As a first step we address the problem on the epicardial surface in the case of an isotropic version of the Aliev and Panfilov model. The minimization is performed using Brent method without computing the derivative of the error. The feasibility of the approach is demonstrated on synthetic electrophysiological measurements. A proof of concept is obtained on real electrophysiological measures of normal and infarcted canine hearts

Myofiber Architecture of the Human Atria as Revealed by Submillimeter Diffusion Tensor Imaging

Background—Accurate knowledge of the human atrial fibrous structure is paramount in understanding the mechanisms of atrial electric function in health and disease. Thus far, such knowledge has been acquired from destructive sectioning, and there is a paucity of data about atrial fiber architecture variability in the human population. Methods and Results—In this study, we have developed a customized 3-dimensional diffusion tensor magnetic resonance imaging sequence on a clinical scanner that makes it possible to image an entire intact human heart specimen ex vivo at submillimeter resolution. The data from 8 human atrial specimens obtained with this technique present complete maps of the fibrous organization of the human atria. The findings demonstrate that the main features of atrial anatomy are mostly preserved across subjects although the exact location and orientation of atrial bundles vary. Using the full tractography data, we were able to cluster, visualize, and characterize the distinct major bundles in the human atria. Furthermore, quantitative characterization of the fiber angles across the atrial wall revealed that the transmural fiber angle distribution is heterogeneous throughout different regions of the atria. Conclusions—The application of submillimeter diffusion tensor magnetic resonance imaging provides an unprecedented level of information on both human atrial structure, as well as its intersubject variability. The high resolution and fidelity of this data could enhance our understanding of structural contributions to atrial rhythm and pump disorders and lead to improvements in their targeted treatment.