Susan B. Mikell

Noninvasive potassium determination using a mathematically processed ECG: Proof of concept for a novel “blood-less, blood test”

OBJECTIVEnTo determine if ECG repolarization measures can be used to detect small changes in serum potassium levels in hemodialysis patients.nnnPATIENTS AND METHODSnSignal-averaged ECGs were obtained from standard ECG leads in 12 patients before, during, and after dialysis. Based on physiological considerations, five repolarization-related ECG measures were chosen and automatically extracted for analysis: the slope of the T wave downstroke (T right slope), the amplitude of the T wave (T amplitude), the center of gravity (COG) of the T wave (T COG), the ratio of the amplitude of the T wave to amplitude of the R wave (T/R amplitude), and the center of gravity of the last 25% of the area under the T wave curve (T4 COG) (Fig.xa01).nnnRESULTSnThe correlations with potassium were statistically significant for T right slope (P<0.0001), T COG (P=0.007), T amplitude (P=0.0006) and T/R amplitude (P=0.03), but not T4 COG (P=0.13). Potassium changes as small as 0.2mmol/L were detectable.nnnCONCLUSIONnSmall changes in blood potassium concentrations, within the normal range, resulted in quantifiable changes in the processed, signal-averaged ECG. This indicates that non-invasive, ECG-based potassium measurement is feasible and suggests that continuous or remote monitoring systems could be developed to detect early potassium deviations among high-risk patients, such as those with cardiovascular and renal diseases. The results of this feasibility study will need to be further confirmed in a larger cohort of patients.

Transvenous Stimulation of the Renal Sympathetic Nerves Increases Systemic Blood Pressure: A Potential New Treatment Option for Neurocardiogenic Syncope

Neurocardiogenic 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.

Novel balloon catheter device with pacing, ablating, electroporation, and drug-eluting capabilities for atrial fibrillation treatment--preliminary efficacy and safety studies in a canine model.

Pulmonary vein isolation is an established therapeutic procedure for symptomatic atrial fibrillation (AF). This approach involves ablation of atrial tissue just outside the pulmonary veins. However, patient outcomes are limited because of a high rate of arrhythmia recurrence. Ablation of electrically active tissue inside the pulmonary vein may improve procedural success, but is currently avoided because of the complication of postablation stenosis. An innovative device that can ablate inside pulmonary veins and prevent stenosis is a viable strategy to increase long-term efficacy. We have developed a prototypical balloon catheter device capable of nonthermal pulmonary vein ablation along with elution of an antifibrotic agent intended to eliminate arrhythmogenic substrate without the risk of stenosis and have demonstrated its functionality in 4 acute canine experiments. Further optimization of this device may provide an innovative means to simultaneously ablate and prevent pulmonary vein stenosis for improved AF treatment in humans.

Novel Percutaneous Epicardial Autonomic Modulation in the Canine for Atrial Fibrillation: Results of an Efficacy and Safety Study

Endocardial 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.

Direct pulmonary vein ablation with stenosis prevention therapy

The 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.

Advances in radiofrequency ablation of the cerebral cortex in primates using the venous system: Improvements for treating epilepsy with catheter ablation technology

BACKGROUNDnPharmacology frequently fails for the treatment of epilepsy. Although surgical techniques are effective, these procedures are highly invasive. We describe feasibility and efficacy of minimally invasive mapping and ablation for the treatment of epilepsy.nnnMETHODSnMapping and radiofrequency ablations were performed via the venous system in eleven baboons and three dogs.nnnRESULTSnMapping in deep cerebral areas was obtained in all animals. High-frequency pacing was able to induce seizure activity of local cerebral tissue in 72% of our attempts. Cerebral activity could be seen during mapping. Ablative lesions were deployed at deep brain sites without steam pops or sudden impedance rise. Histologic analysis showed necrosis at the sites of ablation in all primates.nnnCONCLUSIONnNavigation through the cerebral venous system to map seizure activity is feasible. Radiofrequency energy can be delivered transvenously or transcortically to successfully ablate cortical tissue in this animal model using this innovative approach.

Use of the Aortoatrial Continuity as Means of Providing Left Ventricular Assist Support Without Entering the Ventricle: A Feasibility Study

BACKGROUNDnLeft ventricular assist devices (LVADs) are increasingly used to treat patients with refractory heart failure. Current-generation LVADs have major limitations, including the need for open chest surgery, limiting their widespread use. We hypothesized that the aortoatrial continuity could be used as a unique anatomic vantage point for entirely percutaneous LVAD placement.nnnMETHODS AND RESULTSnForty human autopsied hearts were examined to ascertain the presence and define the dimensions of the continuity between the posterior aortic wall and the left atrium. In all cases, a septum between the aorta and left atrium was identified. In 3 animal experiments, a custom mechanical shunt was deployed in the wall between the left atrium and noncoronary cusp. With continuous intracardiac ultrasound imaging, and at necropsy, there was no evidence of device dislodgement, pericardial effusion, or aortic or coronary artery trauma noted.nnnCONCLUSIONSnIt is feasible to use the wall between the aorta and left atrium as an access route for a potentially entirely percutaneous LVAD. Such a system obviates the need for accessing the left ventricle, minimizing complications. In the future, such devices may allow widespread treatment of heart failure, malignant cardiac arrhythmia, and severe aortic and mitral valvular disease.

Compatibility of Electroanatomical Mapping Systems with a Concurrent Percutaneous Axial Flow Ventricular Assist Device

Hemodynamic instability hinders activation and entrainment mapping during ventricular tachycardia ablation. The Impella 2.5 microaxial flow device (MFD; Abiomed Inc., Danvers, MA, USA) is used to prevent hemodynamic instability during electrophysiologic study. However, electromagnetic interference (EMI) generated by this device can preclude accurate electroanatomic mapping.

Electroporation Ablation of Bronchial Smooth Muscle Cells: A Novel non-Thermal Asthma Therapy

OBJECTIVEnAsthma is a common disease which places significant burden on the US healthcare system and which can be associated with significant patient morbidity and mortality. Current medical therapies are costly and not curative. A new approach for a more permanent asthma treatment is the use of radiofrequency ablation. However, this radiofrequency approach is thermal-based and can result in deleterious effects to the airways, such as stenosis or ulceration. We describe a novel, improved therapeutic approach for smooth muscle ablation using non-thermal DC electroporation ablation.nnnMETHODSnWe developed and tested prototype electroporation ablation devices that access the airways both endoscopically and via a bronchoscope. We tested the feasibility of this approach and demonstrated proof-of-concept in 2 mongrel dogs. In order to assess for smooth muscle function, we performed functional studies pre and post ablation with methacholine challenge to assess for airway reversibility. We also evaluated bronchial lesions via direct vision with bronchoscopy.nnnRESULTSnWe developed novel electroporation catheters to delivery energy to the bronchial smooth muscle through an endoscopic approach. We tested these catheters in 2 acute canine studies and successfully demonstrated the ability to destroy smooth muscle tissue via novel prototypes and saline irrigation for widespread non-thermal electroporation ablation. Our functional studies demonstrate the efficacy of this approach.nnnCONCLUSIONnWe report a novel method for non-thermal bronchial smooth muscle ablation using novel prototypes and electroporation with normal saline. These early findings require further evaluation in larger, chronic canine studies to assess for use as a potential curative therapy.

Percutaneous ligation of the left atrial appendage results in atrial electrical substrate modification.

Debulking of electrically active atrial tissue may reduce the mass of fibrillating tissue during atrial fibrillation, eliminate triggers, and promote maintenance of normal sinus rhythm (NSR). We investigated whether left atrial appendage (LAA) ligation results in modification of atrial electrical substrate. Healthy male mongrel dogs (N = 20) underwent percutaneous epicardial LAA ligation. The ligation system grabber recorded LAA local electrograms (EGM) continuously before, during, and after closure. Successful ligation with a preloaded looped suture was confirmed intraprocedurally by LAA Doppler flow cessation on transesophageal echocardiography (TEE) and loss of LAA electrical activity, and after procedure by direct necropsic visualization. P-wave duration on surface electrocardiograms was measured immediately before and after LAA closure. Percent P-wave duration reduction was correlated with preclosure LAA internal dimensions measured by TEE and external dimensions measured on necropsy specimens to investigate associations of LAA geometry with the extent of electrical substrate modification. LAA ligation was successful in all dogs and accompanied by loss of LAA EGM. P-wave duration reduced immediately on ligation (mean 75 ms preligation to 63 ms postligation; mean difference ± standard error, 12 ± 1 ms; P < 0.0001). Percent P-wave reduction was associated with larger LAA longitudinal cross-sectional area (R(2) = 0.263, P = 0.04) and smaller external circumference (R(2) = 0.687, P = 0.04). All dogs were in sinus rhythm. Percutaneous LAA ligation results in its acute electrical isolation and atrial electrical substrate modification, the degree of which is associated with LAA geometry. These electrical changes raise the possibility that LAA ligation may promote NSR by removing LAA substrate and triggers.