Sugrue, Alan

Background: Reentrant ventricular arrhythmias are a major cause of sudden death in patients with structural heart disease. Current treatments focus on electrically homogenizing regions of scar contributing to ventricular arrhythmia with ablation or altering conductive properties using antiarrhythmic drugs. The high conductivity of carbon nanotubes may allow restoration of conduction in regions where impaired electrical conduction results in functional abnormalities. We propose a new concept for arrhythmia treatment using a stretchable, flexible biopatch with conductive properties to attempt to restore conduction across regions in which activation is disrupted. Methods: Carbon nanotube patches composed of nanofibrillated cellulose/single-walled carbon nanotube ink 3-dimensionally printed in conductive patterns onto bacterial nanocellulose were developed and evaluated for conductivity, flexibility, and mechanical properties. The patches were applied on 6 canines to epicardium before and after surgical disruption. Electroanatomic mapping was performed on normal epicardium, then repeated over surgically disrupted epicardium, and then finally with the patch applied passively. Results: We developed a 3-dimensional printable carbon nanotube ink complexed on bacterial nanocellulose that was (1) expressable through 3-dimensional printer nozzles, (2) electrically conductive, (3) flexible, and (4) stretchable. Six canines underwent thoracotomy, and, during epicardial ventricular pacing, mapping was performed. We demonstrated disruption of conduction after surgical incision in all 6 canines based on activation mapping. The patch resulted in restored conduction based on mapping and assessment of conduction direction and velocities in all canines. Conclusions: We have demonstrated 3-dimensional custom-printed electrically conductive carbon nanotube patches can be surgically manipulated to improve cardiac conduction when passively applied to surgically disrupted epicardial myocardium in canines.

Background The Purkinje network appears to play a pivotal role in the triggering as well as maintenance of ventricular fibrillation. Irreversible electroporation ( IRE ) using direct current has shown promise as a nonthermal ablation modality in the heart, but its ability to target and ablate the Purkinje tissue is undefined. Our aim was to investigate the potential for selective ablation of Purkinje/fascicular fibers using IRE . Methods and Results In an ex vivo Langendorff model of canine heart (n=8), direct current was delivered in a unipolar manner at various dosages from 750 to 2500 V, in 10 pulses with a 90‐μs duration at a frequency of 1 Hz. The window of ventricular fibrillation vulnerability was assessed before and after delivery of electroporation energy using a shock on T‐wave method. IRE consistently eradicated all Purkinje potentials at voltages between 750 and 2500 V (minimum field strength of 250–833 V/cm). The ventricular electrogram amplitude was only minimally reduced by ablation: 0.6±2.3 mV ( P =0.03). In 4 hearts after IRE delivery, ventricular fibrillation could not be reinduced. At baseline, the lower limit of vulnerability to ventricular fibrillation was 1.8±0.4 J, and the upper limit of vulnerability was 19.5±3.0 J. The window of vulnerability was 17.8±2.9 J. Delivery of electroporation energy significantly reduced the window of vulnerability to 5.7±2.9 J ( P =0.0003), with a postablation lower limit of vulnerability=7.3±2.63 J, and the upper limit of vulnerability=18.8±5.2 J. Conclusions Our study highlights that Purkinje tissue can be ablated with IRE without any evidence of underlying myocardial damage.

Background Current thermal ablation methods for atrial fibrillation, including radiofrequency and cryoablation, have a suboptimal success rate. To avoid pulmonary vein (PV) stenosis, ablation is performed outside of the PV, despite the importance of triggers inside the vein. We previously reported on the acute effects of a novel direct current electroporation approach with a balloon catheter to create lesions inside the PVs in addition to the antrum. In this study, we aimed to determine whether the effects created by this nonthermal ablation method were associated with irreversible lesions and whether PV stenosis or other adverse effects occurred after a survival period. Methods and Results Initial and survival studies were performed in 5 canines. At the initial study, the balloon catheter was inflated to contact the antrum and interior of the PV. Direct current energy was delivered between 2 electrodes on the catheter in ECG‐gated 100 μs pulses. A total of 10 PVs were treated demonstrating significant acute local electrogram diminution (mean amplitude decrease of 61.2±19.8%). After the survival period (mean 27 days), computed tomography imaging showed no PV stenosis. On histologic evaluation, transmural, although not circumferential, lesions were seen in each treated vein. No PV stenosis or esophageal injury was present. Conclusions Irreversible, transmural lesions can be created inside the PV without evidence of stenosis after a 27‐day survival period using this balloon‐based direct current ablation approach. These early data show promise for an ablation approach that could directly treat PV triggers in addition to traditional PV antrum ablation.

AbstractBackgroundTransvenous lead implantation has multiple drawbacks and complications that can be overcome by epicardial lead placement. We aimed to design percutaneously implanted epicardial leads that are anchored through the transverse sinus (TS).Methods and resultsWe designed a novel multielectrode pacing device with four bipole electrode pairs. The device is advanced through the TS, with both ends externalized out of the pericardium. We tested the prototype in one proof‐of‐concept and 5 additional acute canine experiments.The TS device recorded ventricular and atrial electrograms. The median amplitude of near‐field ventricular electrograms was 3.3 mA (IQR 2.0–4.3) and of near‐field atrial electrograms was 2.1 mA (IQR 1.3–2.2). The median ventricular threshold (N = 30) was 1.1 mA (IQR 0.7–3.1) at a median pulse width of 0.5 ms (IQR 0.5–0.5). The median atrial threshold (N = 10) was 2.4 mA (IQR 1.1–7.8) at a median pulse width of 0.5 ms (IQR 0.5–0.9). Right and left ventricular and atrial pacing morphologies were noted while pacing electrodes adjacent to these chambers. Simultaneous left (LV) and right ventricular (RV) pacing showed reduction in QRS duration from 116 ms (RV) and 105 ms (LV) to 91 ms. On necropsy, the device was located in the TS in all animals. There were TS abrasions in one animal, and no other acute complications.ConclusionsThis study highlights a novel approach to epicardial pacing harnessing the unique anatomy of the transverse sinus as an anchoring point. Placement of this novel transverse sinus device was safe and feasible, with acceptable atrial and ventricular thresholds.

Background: Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases. Methods: The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death. RESULTS: The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function; P <0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57; P =0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91; P =0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12; P =0.003 and adjusted hazard ratio, 5.04; P <0.001, respectively). Conclusions: Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.

Background: Although the hallmark of long-QT syndrome (LQTS) is abnormal cardiac repolarization, there are varying degrees of phenotypic expression and arrhythmic risk. Our aim was to evaluate the performance of a morphological T-wave analysis program in defining breakthrough LQTS arrhythmic risk beyond the QTc value. Methods and Results: We analyzed 407 genetically confirmed patients with LQT1 (n=246; 43% men) and LQT2 (n=161; 41% men) over the mean follow-up period of 6.4±3.9 years. ECG analysis was conducted using a novel, proprietary T-wave analysis program. Time to a LQTS-associated cardiac event was analyzed using Cox proportional hazards regression methods. Twenty-three patients experienced ≥1 defined breakthrough cardiac arrhythmic events with 5- and 10-year event rates of 4% and 7%. Two independent predictors of future LQTS-associated cardiac events from the surface ECG were identified: left slope of T wave in lead V6 (hazard ratio=0.40 [0.24–0.69]; P <0.001) and T-wave center of gravity x axis (last 25% of wave) in lead I (hazard ratio=1.90 [1.21–2.99]; P =0.005), C statistic of 0.77 (0.65–0.89). When added to the QTc (C statistic 0.68 for QTc alone), discrimination improved to 0.78. Genotype analysis showed weaker association between these T-wave variables and LQT1-triggered events while these features were stronger in patients with LQT2 and significantly outperformed the QTc (C statistic, 0.82 [0.71–0.93]). Conclusion: Detailed morphological analysis of the T wave provides novel insights into risk of breakthrough arrhythmic events in LQTS, particularly LQT2. This observation has the potential to guide clinical decision making and further refine risk stratification.

BackgroundProlongation of the QT on the surface electrocardiogram can be due to either genetic or acquired causes. Distinguishing congenital long QT syndrome (LQTS) from acquired QT prolongation has important prognostic and management implications. We aimed to investigate if quantitative T‐wave analysis could provide a tool for the physician to differentiate between congenital and acquired QT prolongation.MethodsPatients were identified through an institution‐wide computer‐based QT screening system which alerts the physician if the QTc ≥ 500 ms. ECGs were retrospectively analyzed with an automated T‐wave analysis program. Congenital LQTS was compared in a 1:3 ratio to those with an identified acquired etiology for QT prolongation (electrolyte abnormality and/or prescription of known QT prolongation medications). Linear discriminant analysis was performed using 10‐fold cross‐validation to statistically test the selected features.ResultsThe 12‐lead ECG of 38 patients with congenital LQTS and 114 patients with drug‐induced and/or electrolyte‐mediated QT prolongation were analyzed. In lead V5, patients with acquired QT prolongation had a shallower T wave right slope (−2,322 vs. −3,593 mV/s), greater T‐peak‐Tend interval (109 vs. 92 ms), and smaller T wave center of gravity on the x axis (290 ms vs. 310 ms; p < .001). These features could distinguish congenital from acquired causes in 77% of cases (sensitivity 90%, specificity 58%).ConclusionT‐wave morphological analysis on lead V5 of the surface ECG could successfully differentiate congenital from acquired causes of QT prolongation.