Hypercholesterolemia exacerbates in-stent restenosis in rabbits: Studies of the mitigating effect of stent surface modification with a CD47-derived peptide.

BACKGROUND AND AIMS: Hypercholesterolemia (HC) has previously been shown to augment the restenotic response in animal models and humans. However, the mechanistic aspects of in-stent restenosis (ISR) on a hypercholesterolemic background, including potential augmentation of systemic and local inflammation precipitated by HC, are not completely understood. CD47 is a transmembrane protein known to abort crucial inflammatory pathways. Our studies have examined the interrelation between HC, inflammation, and ISR and investigated the therapeutic potential of stents coated with a CD47-derived peptide (pepCD47) in the hypercholesterolemic rabbit model. METHODS: PepCD47 was immobilized on metal foils and stents using polybisphosphonate coordination chemistry and pyridyldithio/thiol conjugation. Cytokine expression in buffy coat-derived cells cultured over bare metal (BM) and pepCD47-derivatized foils demonstrated an M2/M1 macrophage shift with pepCD47 coating. HC and normocholesterolemic (NC) rabbit cohorts underwent bilateral implantation of BM and pepCD47 stents (HC) or BM stents only (NC) in the iliac location. RESULTS: A 40 % inhibition of cell attachment to pepCD47-modified compared to BM surfaces was observed. HC increased neointimal growth at 4 weeks post BM stenting. These untoward outcomes were mitigated in hypercholesterolemic rabbits treated with pepCD47-derivatized stents. Compared to NC animals, inflammatory cytokine immunopositivity and macrophage infiltration of peri-strut areas increased in HC animals and were attenuated in HC rabbits treated with pepCD47 stents. CONCLUSIONS: Augmented inflammatory responses underlie severe ISR morphology in hypercholesterolemic rabbits. Blockage of initial platelet and leukocyte attachment to stent struts through CD47 functionalization of stents mitigates the pro-restenotic effects of hypercholesterolemia.

Establishing a multicenter, preclinical consortium in resuscitation: A pilot experimental trial evaluating epinephrine in cardiac arrest.

BACKGROUND: Large animal studies are an important step in the translation pathway, but single laboratory experiments do not replicate the variability in patient populations. Our objective was to demonstrate the feasibility of performing a multicenter, preclinical, randomized, double-blinded, placebo-controlled cardiac arrest trial. We evaluated the effect of epinephrine on coronary perfusion pressure (CPP) as previous single laboratory studies have reported mixed results. METHODS: Forty-five swine from 5 different laboratories (Ann Arbor, MI; Baltimore, MD; Los Angeles, CA; Pittsburgh, PA; Toronto, ON) using a standard treatment protocol. Ventricular fibrillation was induced and left untreated for 6 min before starting continuous cardiopulmonary resuscitation (CPR). After 2 min of CPR, 9 animals from each lab were randomized to 1 of 3 interventions given over 12 minutes: (1) Continuous IV epinephrine infusion (0.00375 mg/kg/min) with placebo IV normal saline (NS) boluses every 4 min, (2) Continuous placebo IV NS infusion with IV epinephrine boluses (0.015 mg/kg) every 4 min or (3) Placebo IV NS for both infusion and boluses. The primary outcome was mean CPP during the 12 mins of drug therapy. RESULTS: There were no significant differences in mean CPP between the three groups: 14.4 ± 6.8 mmHg (epinephrine Infusion), 16.9 ± 5.9 mmHg (epinephrine bolus), and 14.4 ± 5.5 mmHg (placebo) (p = NS). Sensitivity analysis demonstrated inter-laboratory variability in the magnitude of the treatment effect (p = 0.004). CONCLUSION: This study demonstrated the feasibility of performing a multicenter, preclinical, randomized, double-blinded cardiac arrest trials. Standard dose epinephrine by bolus or continuous infusion did not increase coronary perfusion pressure during CPR when compared to placebo.

The Application of Virtual Reality for Preoperative Planning of Lymphovenous Anastomosis in a Patient with a Complex Lymphatic Malformation.

The management of lymphatic malformations (LMs) is challenging, particularly for large and complex lesions involving anatomical structures in the adjacent tissue. While lymphovenous anastomosis (LVA) has been reported as an effective treatment for lymphedema, it has hardly been described as a treatment for LM. Virtual reality has the ability to visualize human structures in three dimensions and can be used for the preoperative planning of complex cases. Here, we describe the first case of the management of an LM by LVA preoperatively planned with virtual reality. A young woman presented with an LM previously treated by gross excision. Following persistent complaints of swelling, a minimally invasive microsurgical intervention was planned. The results of the single photon emission tomography with computed tomography (SPECT-CT) and lymphoscintigraphy were analyzed using a virtual reality program, and a 3D patient-specific model was constructed. Based on the combined findings of this 3D model and lymphography with a fluorescent marker, a precise skin incision could be determined and one lymph vessel was anastomosed to a nearby vein. The swelling of the thigh reduced and the discomfort disappeared. Although more reports are needed to confirm its efficacy, LVA planned with virtual reality constructed images appears to be a valuable treatment option for complex lesions, including LMs.

A Magnetic Resonance Imaging-Conditional External Cardiac Defibrillator for Resuscitation Within the Magnetic Resonance Imaging Scanner Bore.

BACKGROUND: Subjects undergoing cardiac arrest within a magnetic resonance imaging (MRI) scanner are currently removed from the bore and then from the MRI suite, before the delivery of cardiopulmonary resuscitation and defibrillation, potentially increasing the risk of mortality. This precludes many higher-risk (acute ischemic and acute stroke) patients from undergoing MRI and MRI-guided intervention. An MRI-conditional cardiac defibrillator should enable scanning with defibrillation pads attached and the generator ON, enabling application of defibrillation within the seconds of MRI after a cardiac event. An MRI-conditional external defibrillator may improve patient acceptance for MRI procedures. METHODS AND RESULTS: A commercial external defibrillator was rendered 1.5 Tesla MRI-conditional by the addition of novel radiofrequency filters between the generator and commercial disposable surface pads. The radiofrequency filters reduced emission into the MRI scanner and prevented cable/surface pad heating during imaging, while preserving all the defibrillator monitoring and delivery functions. Human volunteers were imaged using high specific absorption rate sequences to validate MRI image quality and lack of heating. Swine were electrically fibrillated (n=4) and thereafter defibrillated both outside and inside the MRI bore. MRI image quality was reduced by 0.8 or 1.6 dB, with the generator in monitoring mode and operating on battery or AC power, respectively. Commercial surface pads did not create artifacts deeper than 6 mm below the skin surface. Radiofrequency heating was within US Food and Drug Administration guidelines. Defibrillation was completely successful inside and outside the MRI bore. CONCLUSIONS: A prototype MRI-conditional defibrillation system successfully defibrillated in the MRI without degrading the image quality or increasing the time needed for defibrillation. It can increase patient acceptance for MRI procedures.

New insight into scar-related ventricular tachycardia circuits in ischemic cardiomyopathy: Fat deposition after myocardial infarction on computed tomography--A pilot study.

BACKGROUND: Myocardial fat deposition (FAT-DEP) has been frequently observed in regions of chronic myocardial infarction in patients with ischemic cardiomyopathy. The role of FAT-DEP within scar-related ventricular tachycardia (VT) circuits has not been investigated. OBJECTIVE: This pilot study aimed to assess the impact of myocardial FAT-DEP on local electrograms and VT circuits in patients with ischemic cardiomyopathy. METHODS: Contrast-enhanced computed tomography was performed in 22 patients with ischemic VT. Electroanatomic map points were registered to the corresponding contrast-enhanced computed tomography images. Myocardial FAT-DEP was identified and characterized using a postprocessing image overlay that highlighted areas below 0 Hounsfield units (HU). The mean attenuation of local myocardial regions corresponding to sampled electrograms was measured on short-axis images. The associations of mean attenuation with bipolar and unipolar amplitudes, left ventricular wall thickness, and VT circuit sites were investigated. RESULTS: Of 1801 electroanatomic map points, 519 (28.8%) were located in regions with FAT-DEP. Significant differences were observed in mean intensity (23.2 ± 35.6 HU vs 81.7 ± 21.9 HU; P < .001), bipolar (0.75 ± 0.83 mV vs 2.9 ± 2.4 mV; P < .001) and unipolar (3.1 ± 1.7 mV vs 7.4 ± 4.3 mV; P < .001) amplitudes, and left ventricular wall thickness (5.2 ± 1.7 mm vs 8.2 ± 2.5 mm; P < .001) between regions with and without FAT-DEP. Lower HU was strongly associated with lower bipolar and unipolar amplitudes (P < .0001, respectively). Importantly, FAT-DEP was associated with critical VT circuit sites with fractionated or isolated potentials. CONCLUSION: FAT-DEP was associated with electrogram characteristics and VT circuit sites. Further work will be needed to determine whether FAT-DEP plays a causal role in the generation of ischemic scar-related VT circuits.

Dynamic contrast-enhanced MR lymphangiography: feasibility study in swine.

PURPOSE: To demonstrate the feasibility of dynamic four-dimensional ( 4D four-dimensional ) intranodal contrast material-enhanced magnetic resonance (MR) lymphangiography with inguinal lymph node injection of gadopentetate dimeglumine. MATERIALS AND METHODS: All procedures were performed in accordance with the guidelines on the use of animals in research and were approved by the animal care and use committee. Five swine underwent nonenhanced MR lymphangiography with a heavily T2-weighted MR sequence, bilateral inguinal lymph node injection of 2 mL of undiluted gadopentetate at a rate of 1 mL/min, and 60 minutes of MR imaging with T1-weighted high-spatial- and high-temporal-resolution MR angiography. Images were reviewed by a radiologist with expertise in lymphatic imaging and a pediatric cardiac MR imaging specialist for visualization of the thoracic duct ( TD thoracic duct ). Categorical variables were compared by using the exact conditional McNemar test. A difference with a P value less than .05 was considered significant. RESULTS: The TD thoracic duct was visualized in three of the five animals (60%) on T2-weighted images. In contrast, the TD thoracic duct was visualized in all five of the animals (100%) after contrast agent injection (P = .25). The median time for flow of the contrast agent through the lymphatic system to the TD thoracic duct outlet was 244 seconds (range, 201-387 seconds). Enhancement was seen in the TD thoracic duct up to 1 hour after injection. All animals survived without any complications. CONCLUSION: Dynamic 4D four-dimensional contrast-enhanced MR lymphangiography with intranodal injection of gadopentetate dimeglumine is feasible, produces good images of the central lymphatic system, and demonstrates the time course of flow of contrast agent up the central lymphatic ducts. On the basis of the results of this initial animal experiment, it appears that dynamic 4D four-dimensional contrast-enhanced MR lymphangiography is potentially feasible and safe with commercially available contrast agents.

Impact of nonischemic scar features on local ventricular electrograms and scar-related ventricular tachycardia circuits in patients with nonischemic cardiomyopathy.

BACKGROUND: The association of local electrogram features with scar morphology and distribution in nonischemic cardiomyopathy has not been investigated. We aimed to quantify the association of scar on late gadolinium-enhanced cardiac magnetic resonance with local electrograms and ventricular tachycardia circuit sites in patients with nonischemic cardiomyopathy. METHODS AND RESULTS: Fifteen patients with nonischemic cardiomyopathy underwent late gadolinium-enhanced cardiac magnetic resonance before ventricular tachycardia ablation. The transmural extent and intramural types (endocardial, midwall, epicardial, patchy, transmural) of scar were measured in late gadolinium-enhanced cardiac magnetic resonance short-axis planes. Electroanatomic map points were registered to late gadolinium-enhanced cardiac magnetic resonance images. Myocardial wall thickness, scar transmurality, and intramural scar types were independently associated with electrogram amplitude, duration, and deflections in linear mixed-effects multivariable models, clustered by patient. Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P<0.0001 by ANOVA) and in regions with patchy scar (versus endocardial, midwall, epicardial scar; P<0.05 by ANOVA). Most ventricular tachycardia circuit sites were located in scar with >25% scar transmurality. CONCLUSIONS: Electrogram features are associated with scar morphology and distribution in patients with nonischemic cardiomyopathy. Previous knowledge of electrogram image associations may optimize procedural strategies including the decision to obtain epicardial access.

Myocardial structural associations with local electrograms: a study of postinfarct ventricular tachycardia pathophysiology and magnetic resonance-based noninvasive mapping.

BACKGROUND: The association of scar on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) with local electrograms on electroanatomic mapping has been investigated. We aimed to quantify these associations to gain insights regarding LGE-CMR image characteristics of tissues and critical sites that support postinfarct ventricular tachycardia (VT). METHODS AND RESULTS: LGE-CMR was performed in 23 patients with ischemic cardiomyopathy before VT ablation. Left ventricular wall thickness and postinfarct scar thickness were measured in each of 20 sectors per LGE-CMR short-axis plane. Electroanatomic mapping points were retrospectively registered to the corresponding LGE-CMR images. Multivariable regression analysis, clustered by patient, revealed significant associations among left ventricular wall thickness, postinfarct scar thickness, and intramural scar location on LGE-CMR, and local endocardial electrogram bipolar/unipolar voltage, duration, and deflections on electroanatomic mapping. Anteroposterior and septal/lateral scar localization was also associated with bipolar and unipolar voltage. Antiarrhythmic drug use was associated with electrogram duration. Critical sites of postinfarct VT were associated with >25% scar transmurality, and slow conduction sites with >40 ms stimulus-QRS time were associated with >75% scar transmurality. CONCLUSIONS: Critical sites for maintenance of postinfarct VT are confined to areas with >25% scar transmurality. Our data provide insights into the structural substrates for delayed conduction and VT and may reduce procedural time devoted to substrate mapping, overcome limitations of invasive mapping because of sampling density, and enhance magnetic resonance-based ablation by feature extraction from complex images.

Impact of scar, viable myocardium, and epicardial fat on substrate identification of ventricular tachycardia in a case with nonischemic cardiomyopathy.

A 56-year-old man with nonischemic cardiomyopathy underwent orthotopic cardiac transplantation after endocardial and epicardial radiofrequency catheter ablation for pleomorphic ventricular tachycardia. The myocardial substrate and epicardial fat were comprehensively analyzed with three-dimensional electroanatomic maps, late gadolinium enhanced ex-vivo cardiac magnetic resonance, and histological examination. The association of scar, viable myocardium, and epicardial fat with endocardial and epicardial electrogram voltage and duration was quantitatively defined. This case provides a unique opportunity to explore the reliability of electrical surrogates of scar in nonischemic cardiomyopathy.

A prospective evaluation of a protocol for magnetic resonance imaging of patients with implanted cardiac devices.

BACKGROUND: Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns. OBJECTIVE: To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices. DESIGN: Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) SETTING: One center in the United States (94% of examinations) and one in Israel. PATIENTS: 438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies. INTERVENTION: Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachyarrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist. MEASUREMENTS: Activation or inhibition of pacing, symptoms, and device variables. RESULTS: In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, -0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, -2 Ω [IQR, -13 to 0 Ω], -4 Ω [IQR, -16 to 0 Ω], and -11 Ω [IQR, -40 to 0 Ω], respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, -1.1 to 0.3 mV]), decreased RV lead impedance (median, -3 Ω, [IQR, -29 to 15 Ω]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Ω]), and decreased battery voltage (median, -0.01 V, IQR, -0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming. LIMITATIONS: Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed. CONCLUSION: With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential.

Quantitative assessment of artifacts on cardiac magnetic resonance imaging of patients with pacemakers and implantable cardioverter-defibrillators.

BACKGROUND: The safety and clinical utility of MRI at 1.5 T in patients with cardiac implantable devices such as pacemakers (PM) and implantable cardioverter-defibrillators (ICD) have been reported. This study aims to evaluate the extent of artifacts on cardiac magnetic resonance (CMR) in patients with PM and ICD (PM/ICD). METHODS AND RESULTS: A total of 71 CMR studies were performed with an established safety protocol in patients with prepectoral PM/ICD. The artifact area around the PM/ICD generator was measured in all short-axis (SA), horizontal (HLA), and vertical long-axis (VLA) SSFP cine planes. The location and extent of artifacts were also assessed in all SA (20 sectors per plane), HLA, and VLA (6 sectors per plane) late gadolinium-enhanced CMR (LGE-CMR) planes. The artifact area on cine CMR was significantly larger with ICD versus PM generators in each plane (P<0.001, respectively). In patients with left-sided ICD or biventricular ICD systems, the percentages of sectors with any artifacts on LGE-CMR were 53.7%, 48.0%, and 49.2% in SA, HLA, and VLA planes, respectively. Patients with left-sided PM or right-sided PM/ICD had fewer artifacts. Anterior and apical regions were severely affected by artifact caused by left-sided PM/ICD generators. CONCLUSIONS: In contrast to patients with right-sided PM/ICD and left-sided PM, the anterior and apical left ventricle can be affected by susceptibility artifacts in patients with left-sided ICD. Artifact reduction methodologies will be necessary to improve the performance of CMR in patients with left sided ICD systems.

Gaps in the ablation line as a potential cause of recovery from electrical isolation and their visualization using MRI.

BACKGROUND: Ablation has become an important tool in treating atrial fibrillation and ventricular tachycardia, yet the recurrence rates remain high. It is well established that ablation lines can be discontinuous and that conduction through the gaps in ablation lines can be affected by tissue heating. In this study, we looked at the effect of tissue conductivity and propagation of electric wave fronts across ablation lines with gaps, using both simulations and an animal model. METHODS AND RESULTS: For the simulations, we implemented a 2-dimensional bidomain model of the cardiac syncytium, simulating ablation lines with gaps of varying lengths, conductivity, and orientation. For the animal model, transmural ablation lines with a gap were created in 7 mongrel dogs. The gap length was progressively decreased until there was conduction block. The ablation line with a gap was then imaged using MRI and was correlated with histology. With normal conductivity in the gap and the ablation line oriented parallel to the fiber direction, the simulation predicted that the maximum gap length that exhibited conduction block was 1.4 mm. As the conductivity was decreased, the maximum gap length with conduction block increased substantially, that is, with a conductivity of 67% of normal, the maximum gap length with conduction block increased to 4 mm. In the canine studies, the maximum gap length that displayed conduction block acutely as measured by gross pathology correlated well (R(2) of 0.81) with that measured by MRI. CONCLUSIONS: Conduction block can occur across discontinuous ablation lines. Moreover, with recovery of conductivity over time, ablation lines with large gaps exhibiting acute conduction block may recover propagation in the gap over time, allowing recurrences of arrhythmias. The ability to see gaps acutely using MRI will allow for targeting these sites for ablation.

Noninvasive assessment of tissue heating during cardiac radiofrequency ablation using MRI thermography.

BACKGROUND: Failure to achieve properly localized, permanent tissue destruction is a common cause of arrhythmia recurrence after cardiac ablation. Current methods of assessing lesion size and location during cardiac radiofrequency ablation are unreliable or not suited for repeated assessment during the procedure. MRI thermography could be used to delineate permanent ablation lesions because tissue heating above 50°C is the cause of permanent tissue destruction during radiofrequency ablation. However, image artifacts caused by cardiac motion, the ablation electrode, and radiofrequency ablation currently pose a challenge to MRI thermography in the heart. In the current study, we sought to demonstrate the feasibility of MRI thermography during cardiac ablation. METHODS AND RESULTS: An MRI-compatible electrophysiology catheter and filtered radiofrequency ablation system was used to perform ablation in the left ventricle of 6 mongrel dogs in a 1.5-T MRI system. Fast gradient-echo imaging was performed before and during radiofrequency ablation, and thermography images were derived from the preheating and postheating images. Lesion extent by thermography was within 20% of the gross pathology lesion. CONCLUSIONS: MR thermography appears to be a promising technique for monitoring lesion formation and may allow for more accurate placement and titration of ablation, possibly reducing arrhythmia recurrences.

QRS prolongation in myotonic muscular dystrophy and diffuse fibrosis on cardiac magnetic resonance.

Current noninvasive surrogates of cardiac involvement in myotonic muscular dystrophy have low positive predictive value for sudden death. We hypothesized that the cardiac MR signal-to-noise ratio variance (SNRV) is a surrogate of the spatial heterogeneity of myocardial fibrosis and correlates with electrocardiography changes in myotonic muscular dystrophy. The SNRV for contrast enhanced cardiac MR images was calculated over the entire left ventricle in 43 patients with myotonic muscular dystrophy. All patients underwent standard electrocardiography, and a subset of 23 patients underwent signal averaged electrocardiography. After correcting for body mass index, age, and ejection fraction, SNRV was predictive of QRS duration on standard electrocardiography (1.35-msec increased QRS duration/unit increase in SNRV, P < 0.001). SNRV was also predictive of the low-amplitude late-potential duration (1.49-msec increased low-amplitude late-potential duration/unit increase in SNRV, P < 0.001). Ten-fold cross-validation yielded an area under the receiver operating characteristic curve of 0.87 for the predictive value of SNRV for QRS duration greater than 120 msec. The SNRV of the left ventricle is associated with QRS prolongation, likely due to late depolarization of tissue within islands of patchy fibrosis. The association of SNRV with future clinical events warrants further study.

Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy.

AIMS: The ability of mesenchymal stem cells (MSCs) to heal the chronically injured heart remains controversial. Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function. METHODS AND RESULTS: Female adult Göttingen swine (n = 15) underwent left anterior descending coronary artery balloon occlusion to create reproducible ischaemia-reperfusion infarctions. Bone-marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks post-myocardial infarction (MI), animals were randomized to receive surgical injection of either phosphate buffered saline (placebo, n = 6), 20 million (low dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct and border zone. Injections were administered to the beating heart via left anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV) function. There was no difference in mortality, post-injection arrhythmias, cardiac enzyme release, or systemic inflammatory markers between groups. Whereas MI size remained constant in placebo and exhibited a trend towards reduction in low dose, high-dose MSC therapy reduced infarct size from 18.2 +/- 0.9 to 14.4 +/- 1.0% (P = 0.02) of LV mass. In addition, both low and high-dose treatments increased regional contractility and MBF in both infarct and border zones. Ectopic tissue formation was not observed with MSCs. CONCLUSION: Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.

Feasibility of endoscopic guidance for nonsurgical transthoracic atrial and ventricular epicardial ablation.

BACKGROUND: Epicardial catheter ablation via subxiphoid percutaneous access currently is used upon failure of endocardial catheter ablation. The safety, efficacy, and applicability of epicardial catheter ablation likely will improve with direct visualization of the pericardial space. OBJECTIVE: The purpose of this study was to assess the feasibility of percutaneous endoscopic guidance for identification of epicardial anatomic landmarks and epicardial catheter ablation. METHODS: Dual subxiphoid epicardial access and femoral venous and arterial access were obtained in six healthy swine. The endoscope and electrophysiology catheter were advanced to the pericardial space. Anatomic landmarks were identified via endoscopy and confirmed by multiview fluoroscopic assessment of proximity to endocardial catheters in the area of interest. Radiofrequency ablation of selected anatomic targets was performed under endoscopic guidance. Targeting of lesions was assessed by pathologic examination of the target and surrounding structures. RESULTS: Dual large-bore subxiphoid epicardial access was obtained without complications in all animals. The coronary sinus, left anterior descending coronary artery, left atrial appendage, and pulmonary veins were easily visualized in all animals. Catheter ablation of anatomic targets, including the right ventricular outflow tract, left atrial appendage, and pulmonary veins, was performed successfully under direct endoscopic observation. Endoscopic guidance of point and linear lesions near coronary vessels also was assessed. Pathology revealed successful targeting of lesions. CONCLUSION: Endoscopic guidance of percutaneous epicardial electrophysiologic procedures is feasible. Direct visualization of epicardial structures, catheters, and lesions may improve the safety and efficacy of epicardial catheter ablation and reduce staff and patient radiation exposure.

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 (approximately 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.

Determinants of gradient field-induced current in a pacemaker lead system in a magnetic resonance imaging environment.

BACKGROUND: The determinants of low-frequency-induced current by magnetic resonance imaging (MRI) gradient fields in a pacemaker lead system are largely unknown. OBJECTIVE: The purpose of this study was to determine the magnitude of MRI low-frequency-induced current in an implanted pacemaker lead system and to investigate in vivo determinants of low-frequency-induced current in an animal model. METHODS: Six mongrel dogs underwent conventional single-chamber pacemaker implantation with a current recorder connected in series. Pulse generator (PG) was programmed to VOO 120 bpm with subthreshold output. MRI was performed in a 1.5-T scanner. Low-frequency-induced current was recorded during unipolar pacing, bipolar pacing, and bipolar pacing with the PG case electrically isolated from the pocket. In each mode, low-frequency-induced current was recorded with and without a large loop of additional lead connected in series. RESULTS: With a conventional implant, low-frequency-induced current was < or =0.5 mA in all three pacing modes. With five external loops, the magnitude of low-frequency-induced current increased to >30 mA, with consistent myocardial capture in unipolar and bipolar pacing. However, in bipolar pacing with the PG electrically isolated from the pocket, low-frequency-induced current decreased to <0.5 mA with no myocardial capture even with additional looped leads. CONCLUSION: Under conventional implant conditions, the magnitude of low-frequency-induced current is <0.5 mA and is unlikely to cause myocardial capture; however, arrhythmia induction cannot be excluded. With sufficient increase in effective loop area (additional looped leads), direct myocardial capture by the low-frequency-induced current is possible. In this study, breaking the return pathway by electrically isolating the PG case from the circuit abolished low-frequency-induced current.

Novel electrode design for potentially painless internal defibrillation also allows for successful external defibrillation.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) save lives, but the defibrillation shocks delivered by these devices produce substantial pain, presumably due to skeletal muscle activation. In this study, we tested an electrode system composed of epicardial panels designed to shield skeletal muscles from internal defibrillation, but allow penetration of an external electric field to enable external defibrillation when required. METHODS AND RESULTS: Eleven adult mongrel dogs were studied under general anesthesia. Internal defibrillation threshold (DFT) and shock-induced skeletal muscle force at various biphasic shock strengths were compared between two electrode configurations: (1) a transvenous coil placed in the right ventricle (RV) as cathode and a dummy can placed subcutaneously in the left infraclavicular fossa as anode (control configuration) and (2) RV coil as cathode and the multielectrode epicardial sock with the panels connected together as anode (sock-connected). External DFT was also tested with these electrode configurations, as well as with the epicardial sock present, but with panels disconnected from each other (sock-disconnected). Internal DFT was higher with sock-connected than control (24 +/- 7 J vs. 16 +/- 6 J, P < 0.02), but muscle contraction force at DFT was greatly reduced (1.3 +/- 1.3 kg vs. 10.6 +/- 2.2 kg, P < 0.0001). External defibrillation was never successful, even at 360 J, with sock-connected, while always possible with sock-disconnected. CONCLUSION: Internal defibrillation with greatly reduced skeletal muscle stimulation can be achieved using a novel electrode system that also preserves the ability to externally defibrillate when required. This system may provide a means for painless ICD therapy.

Clinical utility and safety of a protocol for noncardiac and cardiac magnetic resonance imaging of patients with permanent pacemakers and implantable-cardioverter defibrillators at 1.5 tesla.

BACKGROUND: Magnetic resonance imaging (MRI) is an important diagnostic modality currently unavailable for millions of patients because of the presence of implantable cardiac devices. We sought to evaluate the diagnostic utility and safety of noncardiac and cardiac MRI at 1.5T using a protocol that incorporates device selection and programming and limits the estimated specific absorption rate of MRI sequences. METHODS AND RESULTS: Patients with no imaging alternative and with devices shown to be MRI safe by in vitro phantom and in vivo animal testing were enrolled. Of 55 patients who underwent 68 MRI studies, 31 had a pacemaker, and 24 had an implantable defibrillator. Pacing mode was changed to "asynchronous" for pacemaker-dependent patients and to "demand" for others. Magnet response and tachyarrhythmia functions were disabled. Blood pressure, ECG, oximetry, and symptoms were monitored. Efforts were made to limit the system-estimated whole-body average specific absorption rate to 2.0 W/kg (successful in >99% of sequences) while maintaining the diagnostic capability of MRI. No episodes of inappropriate inhibition or activation of pacing were observed. There were no significant differences between baseline and immediate or long-term (median 99 days after MRI) sensing amplitudes, lead impedances, or pacing thresholds. Diagnostic questions were answered in 100% of nonthoracic and 93% of thoracic studies. Clinical findings included diagnosis of vascular abnormalities (9 patients), diagnosis or staging of malignancy (9 patients), and assessment of cardiac viability (13 patients). CONCLUSIONS: Given appropriate precautions, noncardiac and cardiac MRI can potentially be safely performed in patients with selected implantable pacemaker and defibrillator systems.