Percutaneous cryoablation for papillary muscle ventricular arrhythmias after failed radiofrequency catheter ablation.

BACKGROUND: Catheter ablation of ventricular arrhythmias (VA) from the papillary muscles (PM) is challenging due to limited catheter stability and contact on the PMs with their anatomic complexity and mobility. OBJECTIVE: This study aimed to evaluate the effectiveness of cryoablation as an adjunctive therapy for PM VAs when radiofrequency (RF) ablation has failed. METHODS: We evaluated a retrospective series of patients who underwent cryoablation for PM VAs when RF ablation had failed. The decision to switch to cryoablation was at the operator's discretion when intracardiac echocardiography (ICE) suggested that cryoablation might be more effective in achieving catheter stability and energy delivery. RESULTS: Sixteen patients underwent cryoablation of PM VAs between 2014 and 2016 after RF ablation was unsuccessful. VAs originated from the anterolateral left ventricle (LV) PM (six patients), posterolateral LV PM (six patients), and right ventricle PM (four patients). VAs were predominantly frequent premature ventricular complexes (PVCs); however, patients with sustained ventricular tachycardia and PVC-triggered VF were also represented. Fifteen of the 16 patients were treated with cryoablation; in one patient, a procedural complication with retrograde aortic access precluded treatment. In all patients treated with cryoablation, contact and stability was confirmed with ICE to be superior to the RF catheter, and there was acute and long-term elimination of VAs. CONCLUSION: Cryoablation is a useful adjunctive therapy in ablation of PM VAs, providing excellent procedural outcomes even when RF ablation has failed. Cryoablation catheters are less maneuverable than RF ablation catheters and care is required to avoid complications.

Development of new anatomy reconstruction software to localize cardiac isochrones to the cardiac surface from the 12 lead ECG.

Non-invasive electrocardiographic imaging (ECGI) of the cardiac muscle can help the pre-procedure planning of the ablation of ventricular arrhythmias by reducing the time to localize the origin. Our non-invasive ECGI system, the cardiac isochrone positioning system (CIPS), requires non-intersecting meshes of the heart, lungs and torso. However, software to reconstruct the meshes of the heart, lungs and torso with the capability to check and prevent these intersections is currently lacking. Consequently the reconstruction of a patient specific model with realistic atrial and ventricular wall thickness and incorporating blood cavities, lungs and torso usually requires additional several days of manual work. Therefore new software was developed that checks and prevents any intersections, and thus enables the use of accurate reconstructed anatomical models within CIPS. In this preliminary study we investigated the accuracy of the created patient specific anatomical models from MRI or CT. During the manual segmentation of the MRI data the boundaries of the relevant tissues are determined. The resulting contour lines are used to automatically morph reference meshes of the heart, lungs or torso to match the boundaries of the morphed tissue. Five patients were included in the study; models of the heart, lungs and torso were reconstructed from standard cardiac MRI images. The accuracy was determined by computing the distance between the segmentation contours and the morphed meshes. The average accuracy of the reconstructed cardiac geometry was within 2mm with respect to the manual segmentation contours on the MRI images. Derived wall volumes and left ventricular wall thickness were within the range reported in literature. For each reconstructed heart model the anatomical heart axis was computed using the automatically determined anatomical landmarks of the left apex and the mitral valve. The accuracy of the reconstructed heart models was well within the accuracy of the used medical image data (pixel size <1.5mm). For the lungs and torso the number of triangles in the mesh was reduced, thus decreasing the accuracy of the reconstructed mesh. A novel software tool has been introduced, which is able to reconstruct accurate cardiac anatomical models from MRI or CT within only a few hours. This new anatomical reconstruction tool might reduce the modeling errors within the cardiac isochrone positioning system and thus enable the clinical application of CIPS to localize the PVC/VT focus to the ventricular myocardium from only the standard 12 lead ECG.

Sensitivity of CIPS-computed PVC location to measurement errors in ECG electrode position: the need for the 3D camera.

BACKGROUND: The Cardiac Isochrone Positioning System (CIPS) is a non-invasive method able to localize the origins of PVCs, VT and WPW from the 12 lead ECG. The CIPS model integrates a standard 12-lead ECG with an MRI derived model of the heart, lungs, and torso in order to compute the precise electrical origin of a PVC from within the myocardium. To make these calculations, CIPS uses virtually represented ECG electrode positions. These virtual electrode positions, however, are currently assumed to represent the standard 12 lead positions in the model without taking into account the actual, anatomical locations on a patient. The degree of error introduced into the CIPS model by movement of the virtual electrodes is unknown. Therefore, we conducted a model-based study to determine the sensitivity of CIPS to changes in its virtually represented ECG electrode positions. METHODS: Previously, CIPS was tested on 9 patients undergoing PVC ablation, producing a precise myocardial PVC location for each patient. These initial results were used as controls in two different simulation experiments. The first moved all virtual precordial leads in CIPS simultaneously up and down to recalculate a PVC origin. The second moved each virtual precordial lead individually, using 8 points on multiple concentric circles of increasing radius to recalculate a PVC origin. The distance of the newly calculated PVC origin from the control origin was used as a metric. RESULTS: Moving either all electrodes simultaneously or each V1-6 precordial electrode independently resulted in non-linear and unpredictable shifts of the CIPS-computed PVC origin. Simultaneously moving all V1-6 precordial electrodes by 10mm increments produced a shift in CIPS-computed PVC origin between 0 and 62mm. Independently moving an electrode, a shift of more than 10mm resulted in an unpredictable CIPS-computed PVC origin relocation between 0 and 40mm. The effect of moving the virtual electrodes on CIPS modeling more pronounced the closer the virtual electrode was positioned to the actual PVC origin. CONCLUSIONS: Slight changes in the virtual positions of the V1-6 precordial electrodes produce marked, non-linear and unpredictable shifts in the CIPS-computed PVC origin. Thus, any variation in the physical ECG electrode placement on a patient can result in significant error within the CIPS model. These large errors would make CIPS useless and underscore the need for accurate, patient specific measurement of electrode position relative to the patient specific torso geometries. A potential solution to this problem could be the introduction of a 3D camera to incorporate accurate measurement of physical electrode placement into the CIPS model. Since the 3D camera software integrates the 3D imaged position of the electrode with the MRI derived torso model, it is conveniently incorporated in the next generation CIPS software to decrease the errors in modeled location of the electrodes. Thus, the 3D camera will be the III(rd) component of the CIPS to increase its accuracy in PVC, VT, and WPW localization.

SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells.

Knockdown or inhibition of SIRT2 enhances biological stress-tolerance. We extend this phenotype showing that SIRT2 knockdown reduces anoxia-reoxygenation injury in H9c2 cells. Gene array analysis following SIRT2 siRNA knockdown identifies 14-3-3 zeta as the most robustly induced gene. SIRT2 knockdown evokes induction of this chaperone, facilitating cytosolic sequestration of BAD with a corresponding reduction in mitochondrial BAD localization. Concurrent siRNA against SIRT2 and 14-3-3 zeta abolishes the SIRT2-depleted cytoprotective phenotype. SIRT2 functions to moderate cellular stress-tolerance, in part, by modulating the levels of 14-3-3 zeta with the concordant control of BAD subcellular localization.