Suddendorf, Scott H.

Background: Conduction tissue in the ventricles is closely intertwined with myocardium. Owing to high velocity of conduction, there is near simultaneous activation , making it difficult to discern. Restricted sampling rates and limited dynamic range make real time signal processing challenging for these signals in routine recording systems. Objectives: We aimed to use novel signal processing techniques in a new system to isolate the conduction tissue signals from the rest of the myocardial activation. Methods: We used the PURE-EP™ (BioSig Technologies, MN) signal processing system to record endocardial and epicardial signals from 6 anesthetized canines in an acute study setting. A novel filter based on proprietary algorithms to isolate the high frequency signal was applied at sites where the electrogram signals were thought to have a conduction tissue component to them. . In addition, ventricular fibrillation (VF) was induced at the end of the experiment and signals were then recorded from the endocardium and the conduction system. Results: This filter was successfully able to isolate conduction tissue signals in the myocardium from those of the ventricular muscle. It did over sense atrial signals at the basal left ventricular septum owing to the high frequency components of the atrial signal at this location. When applied to epicardial signals, it did not pick up any conduction tissue signals. In VF, we could discern signals originating from the conduction system endocardially. (Figure 1) Conclusions: This filter can isolate conduction tissue signals from those of the myocardium and may prove to be a useful adjunct in mapping arrhythmias originating near the conduction system.

Background: Ablation in the sinuses of Valsalva (SoV) within the aorta is fraught with risk, owing to the proximity of the coronary arteries. Assessment of catheter tip position is not very easy at this location owing to complex local anatomy and poor images from available modalities. Objectives: We propose the use of novel local unipolar electrogram characteristics using a new signal recording system to guide the assessment of catheter tip position in this region. Methods: We recorded unipolar signals from above the SoV, within the coronaries and below the SoV using the PURE-EP™ (BioSig Technologies, MN) signal processing system in 4 anesthetized canines in the setting of an acute study. We used fluoroscopy, intracardiac echocardiography and angiography for confirmation of the position of the catheter tip. We recorded changes in the signals when transitioning between (1) the coronary arteries and the SoV and (2) the SoV and below the SoV. Results: The unipolar signal showed a negative current of injury (COI) when the catheter tip was present in the SoV, whereas within the coronary artery or below the SoV, the COI was positive. We propose that the difference in the distribution of ventricular muscle below and above the SoV is responsible for this phenomenon. These changes in the COI were noted immediately when transitioning from one location to another and were present reproducibly in all the dogs. ( Figure 1 ) Conclusions: Analysis of the changes on the local electrogram can provide information about the location of the catheter tip which could prove critical in saving lives.

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.

BackgroundAutomated external defibrillators can provide life‐saving therapies to treat ventricular fibrillation. We developed a prototype unit that can deliver a unique shock waveform produced by four independent capacitors that is delivered through two shock vectors, with the rationale of providing more robust shock pathways during emergent defibrillation. We describe the initial testing and feasibility of this unique defibrillation unit, features of which may enable downsizing of current defibrillator devices.MethodsWe tested our defibrillation unit in four large animal models (two canine and two swine) under general anesthesia. Experimental defibrillation thresholds (DFT) were obtained by delivery of a unique waveform shock pulse via a dual‐vector pathway with four defibrillation pads (placed across the chest). DFTs were measured and compared with those of a commercially available biphasic defibrillator (Zoll M series, Zoll Medical, Chelmsford, MA, USA) tested in two different vectors. Shocks were delivered after 10 seconds of stable ventricular fibrillation and the output characteristics and shock outcome recorded. Each defibrillation series used a step‐down to failure protocol to define the defibrillation threshold.ResultsA total of 96 shocks were delivered during ventricular fibrillation in four large animals. In comparison to the Zoll M series, which delivered a single‐vector, biphasic shock, the energy required for successful defibrillation using the unique dual‐vector biphasic waveform did not differ significantly (P = 0.65).ConclusionsOur early findings support the feasibility of a unique external defibrillation unit using a dual‐vector biphasic waveform approach. This warrants further study to leverage this unique concept and work toward a miniaturized, portable shock delivery system.

Percutaneous Pericardiotomy ToolIntroductionEpicardial procedures frequently require pericardial manipulation. We aimed to develop a nonsurgical percutaneous pericardial modification tool that may (1) facilitate epicardial‐based procedures by enabling adhesiolysis or (2) attenuate the myocardial constraining effect of the pericardium.MethodsThree novel devices were developed to enable pericardiotomy, all of which can be deployed in over‐the‐wire fashion following percutaneous epicardial access. The grasper permits us to seize the pericardial membrane providing leverage for incision. The scissors enables anterograde cutting maneuvers. The reverse‐slitter allows retrograde incisions; in addition, this device has a deflectable tip that increases the potential cutting area. We optimized these tools for safety by including electrodes to test for phrenic nerve stimulation as well as myocardial stimulation to determine directionality of the cutting devices. The base of the scissors and reverse‐slitter are also blunt ensuring that the cutting element is always away from the myocardium.ResultsFollowing 5 nonbeating heart bench test experiments for prototype development, 11 animal (9 canine, 2 swine) studies were performed. Of these 2 were proof‐of‐concept open chest studies; the remaining 9 were entirely closed‐chest, percutaneous procedures allowing for remodification of the prototypes. The tools successfully permitted incision of the pericardium in all studies. Hemodynamic measurements were assessed postincision and showed no compromise of systolic function. No coronary artery or phrenic nerve damage was seen in any study.ConclusionPercutaneous pericardiotomy is feasible and appears to be safe. It may provide leverage in epicardial‐based procedures and offer treatment options in disease processes characterized by pericardial restraint.

Endovascular Stimulation for Treatment of HypotensionBackgroundWe have previously shown that sympathetic ganglia stimulation via the renal vein rapidly increases blood pressure. This study further investigated the optimal target sites and effective energy levels for stimulation of the renal vasculatures and nearby sympathetic ganglia for rapid increase in blood pressure.MethodsThe pre‐study protocol for endovascular stimulations included 2 minutes of stimulation (1–150 V and 10 pulses per second) and at least 2 minutes of rest during poststimulation. If blood pressure and/or heart rate were changed during the stimulation, time to return to baseline was allowed prior to the next stimulation.ResultsIn 11 acute canine studies, we performed 85 renal artery, 30 renal vein, and 8 hepatic vasculature stimulations. The mean arterial pressure (MAP) rapidly increased during stimulation of renal artery (95 ± 18 mmHg vs. 103 ± 15 mmHg; P < 0.0001), renal vein (90 ± 16 mmHg vs. 102 ± 20 mmHg; P = 0.001), and hepatic vasculatures (74 ± 8 mmHg vs. 82 ± 11 mmHg; P = 0.04). Predictors of a significant increase in MAP were energy >10 V focused on the left renal artery, bilateral renal arteries, and bilateral renal veins (especially the mid segment). Overall, heart rate was unchanged, but muscle fasciculation was observed in 22.0% with an output >10 V (range 15–150 V). Analysis after excluding the stimulations that resulted in fasciculation yielded similar results to the main findings.ConclusionsStimulation of intra‐abdominal vasculatures promptly increased the MAP and thus may be a potential treatment option for hypotension in autonomic disorders. Predictors of optimal stimulation include energy delivery and the site of stimulation (for the renal vasculatures), which informs the design of subsequent research.

BackgroundEndocardial ablation of atrial ganglionated plexi (GP) has been described for treatment of atrial fibrillation (AF). Our objective in this study was to develop percutaneous epicardial GP ablation in a canine model using novel energy sources and catheters.MethodsPhase 1: The efficacy of several modalities to ablate the GP was tested in an open chest canine model (n = 10). Phase 2: Percutaneous epicardial ablation of GP was done in six dogs using the most efficacious modality identified in phase 1 using two novel catheters.ResultsPhase 1: Direct current (DC) in varying doses (blocking [7–12 μA], electroporation [300–500 μA], ablation [3,000–7,500 μA]), radiofrequency ablation (25–50 W), ultrasound (1.5 MHz), and alcohol (2–5 mL) injection were successful at 0/8, 4/12, 5/7, 3/8, 1/5, and 5/7 GP sites. DC (500–5,000 μA) along with alcohol irrigation was tested in phase 2. Phase 2: Percutaneous epicardial ablation of the right atrium, oblique sinus, vein of Marshall, and transverse sinus GP was successful in 5/6 dogs. One dog died of ventricular fibrillation during DC ablation at 5,000 μA. Programmed stimulation induced AF in six dogs, preablation and no atrial arrhythmia in three, flutter in one, and AF in one postablation. Heart rate, blood pressure, effective atrial refractory period, and local atrial electrogram amplitude did not change significantly postablation. Microscopic examination showed elimination of GP, and minimal injury to atrial myocardium.ConclusionPercutaneous epicardial ablation of GP using DC and novel catheters is safe and feasible and may be used as an adjunct to pulmonary vein isolation in the treatment of AF in order to minimize additional atrial myocardial ablation.

Direct Pulmonary Vein Ablation With Stenosis Prevention TherapyIntroductionThe dominant location of electrical triggers for initiating atrial fibrillation (AF) originates from the muscle sleeves inside pulmonary veins (PVs). Currently, radiofrequency ablation (RFA) is performed outside of the PVs to isolate, rather than directly ablate these tissues, due to the risk of intraluminal PV stenosis.MethodsIn 4 chronic canine experiments, we performed direct PV muscle sleeve RFA ± postablation drug‐coated balloon (DCB) treatment with paclitaxel/everolimus. Of the 4 PVs, 2 PVs were ablated and treated with DCB, 1 PV was ablated without DCB treatment (positive control), and 1 PV was left as a negative control. Local electrograms were assessed in PVs for near‐field signals and were targeted for ablation. After 12–14 weeks survival, PVs were interrogated for absence of near‐field PV potentials, and each PV was assessed for stenosis.ResultsAll canines survived the study period without cardiorespiratory complications, and remained ambulatory. In all canines, PVs that were ablated and treated with DCB remained without any significant intraluminal stenosis. In contrast, PVs that were ablated and not treated with DCB showed near or complete intraluminal stenosis. At terminal study, PV potentials remained undetectable. A blinded, histologic analysis demonstrated that ablated PVs without DCB treatment had extensive thrombus, fibrin, mineralization, and elastin disruption.ConclusionOur chronic canine data suggest that direct PV tissue ablation without subsequent stenosis is feasible with the use of postablation DCBs.

Renal Vein Stimulation Increases Blood PressureBackgroundNeurocardiogenic syncope (NCS) is a common and sometimes debilitating disorder, with no consistently effective treatment. NCS is due to a combination of bradycardia and vasodilation leading to syncope. Although pacemaker devices have been tried in treating the bradycardic aspect of NCS, no device‐based therapy exists to treat the coexistent vasodilation that occurs. The renal sympathetic innervation has been the target of denervation to treat hypertension. We hypothesized that stimulation of the renal sympathetic nerves can increase blood pressure and counteract vasodilation in NCS.Methods and ResultsHigh‐frequency stimulation (800–900 pps, 10 V, 30–200 seconds) was performed using a quadripolar catheter in the renal vein of 7 dogs and 1 baboon. A significant increase in blood pressure (BP; mean [SD] systolic BP 117 [±28] vs. 128 [±33], diastolic BP 75 [±19] vs. 87 [±29] mmHg) was noted during the stimulation, which returned to baseline after cessation of stimulation. The mean increase in systolic and diastolic BP was 13.0 (±3.3) (P = 0.006) and 10.2 (±4.6) (P = 0.08), respectively.ConclusionWe report the first ever study of feasibility and safety of high‐frequency electrical stimulation of the renal sympathetic innervation to increase BP in animal models. This has potential applications in the treatment of hypotensive states such as NCS.