Circulation: Arrhythmia and Electrophysiology April 2019 Issue - a podcast by Paul J. Wang, MD

Dr Paul Wang:                   Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor in Chief, with some of the key highlights from this month's issue.

                                                In our first paper Lucas Boersma and associates examined the final two-year outcome data from 47 centers, in 1,020 patients receiving the left atrial appendage occlusion watchman devices. Their study population had a mean age of 73.4 years, with 311 having prior ischemic stroke or TIA, 153 having prior hemorrhagic stroke, and 318 having prior major bleeding. 49% had a CHAS II vast score of 5 or greater, and 40% had a HAS-BLED score of three or greater. Oral anticoagulation was contraindicated in 72%. During follow up, 161 patients, or 16.4% died, 22 strokes were observed or 1.3 per 100 patient years representing an 83% reduction versus historic data. And 47 major non-procedural bleeding events were observed, or 2.7 per 100 patient years representing a 46% reduction versus historic data.

                                                Device thrombus was observed in 34 patients or 4.1%, and was not correlated to the drug regimen during follow up. P=0.28.

                                                In our next paper, Anish Amin and Associates examined whether high voltage impedance and subcutaneous or SICD system implant position are associated with ventricular fibrillation or VF conversion success with a sub-maximal joule shock. In the SICD investigational device exemption study, a successful conversion test required two consecutive VF conversions at 65 joules in either shock vector. Sub-optimal device position was defined as an inferior electrode or pulse generator, or electrode coil depth of greater than three mm anterior to the sternum, based on chest radiograph. Of 314 patients who underwent SICD implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 joules. 62 conversion failures, or 9.7%, occurred in 42 or 14.9% of patients.

                                                Lower body mass index or BMI, and lower shock impedance, were associated with higher conversion success rate. Whereas white race was associated with lower conversion success rate. Sub-optimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high BMI.

                                                In our next paper, Je-Wook Park and associates examined the left atrial pressure after repeat radiofrequency catheter ablation procedures. Among 1,848 patients who underwent atrial fibrillation or AF catheter ablation, the authors measured the left atrial pressure, LAP, immediately following the transseptal puncture in sinus rhythm in 1,687 patients before De novo ablation, median age 59 years, 72.4% male and 72.8% paroxysmal AF, and in 142 with second procedures. In the same 142 patients, the degree of left atrial stiffness, reflected by LAPP, the difference between LAP peak and LAP nater, was significantly higher in the second procedure than in the De novo procedure. P<0.001. The degree of LAPP increase, delta LAPP, was significantly higher in patients who underwent additional extra pulmonary vein left atrial ablation than in those who underwent circumferential PV isolation alone. P=0.01. Extra pulmonary vein left atrial ablation was independently associated with delta LAPP. P=0.045.

                                                An increase LAPP during repeat procedures was independently associated with a reduced diastolic function. P=0.041. However, the EQ5D symptom score did not change after de novo ablation.

                                                In our next paper, Adam Graham and associates examined a median of 711 electrocardiographic imaging, or ECGI, in cardiopirin points per patient to compare simultaneous epicardial mapping using CARTO and ECGI after geometrical co registration in 8 patients. They found that the correlation coefficient measuring the similarity of activation times we equal to 0.66, and the correlation coefficient for repolarization times was 0.55. The minimum distance between epicardial pacing sites, and the region of earliest activation in ECGI was 13.2 mm. Range 0 to 28.3 mm, from 25 pacing sites with stimulation to cuirass interval less than 40 milliseconds.

                                                In our next paper, Michael Barkagan and associates examined high-current, short-duration radiofrequency energy delivery using and expandable spheroid-shaped lattice electrode with effective service tenfold larger than standard irrigated electrodes. It incorporated nine surface temperature sensors, with ablation performed in temperature control mode. In phase one of the study, the authors found that six thigh muscle preparation experiments, ablation with the lattice catheter resulted in wider lesions at both low and high energy settings, 8.7 vs 12.2 mm. P<0.0001, and 19.4 vs 12.3 mm using standard irrigated catheter. P<0.0001.

                                                In phase two of the study, in Eighth Swan, the authors found that right atrial lines created in the posterior lateral walls using low and high-energy settings with the lattice catheter were wider, posterior 14.7 versus 9.2 mm, P<0.001, and lateral, 15.8 versus 5.7 mm, P<0.001.Lattice catheter ablation had 85% shorter ablation time, 12.4 second per centimeter line, versus 79.8 seconds per centimeter line.

                                                On phase three of the study, the authors found at 30 days, 100% of the ablation lines created with lattice catheter remained contiguous, compared to only 14.3% of lines created with a standard irrigated catheter. The authors reported that there were no steam pops or collateral tissue damage.

                                                In our next paper, Anett Ottesen and associated hypothesized that because circulating [inaudible] neuron concentrations are increased in patients with myocardial dysfunction, and predict poor outcome. And because secretive neuron inhibits calcium calmodulin dependent protein kinase ii delta activity, the up regulation of secretive neuron in patients protects against cardiomyocytes mechanisms arrhythmia.

                                                The authors found this secreting neuron levels were elevated in 8 patients with catecholaminergic polymorphic ventricular tachycardia, or in 155 patients after cardiac arrest. AAV9 induced over expression of secretive neuron, attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies map secreta neuron binding to the sub straight binding sight in catalyst region of calcium calmodulin dependent protein kinase ii delta.

                                                Secreta neuron attenuate in isoproterenol induced autophosphorylation of 3NE287 calcium calmodulin dependent protein kinase ii delta, in laying [inaudible] hearts, in inhibited calcium calmodulin dependent kinase ii dependent [inaudible] receptor phosphorylation. Secretor neuron treatment decreased calcium spark frequency in dimensions in cardiomyocytes during isoproterenol challenge, and reduced the instance of calcium wave delayed depolarizations in spontaneous action potentials.

                                                Secreta neuron treatment also lowered the incidence of early after depolarizations during isoproterenol paralleling a reduced magnitude of L type calcium current. Thus, the authors demonstrated that secreta neuron production is upregulated in conditions with cardiomyocytes calcium dysregulation and may provide compensatory protection against cardiomyocytes mechanisms of arrhythmia.

                                                In our final paper, Ne Gang and Shu Wang and associates examined whether Sorting Nexin-17, SNX17, regulates the trafficking process of protein voltage gated channel subfamily A member 5, which has been proposed as a target of interventions for atrial fibrillation. The authors curated a Sorting Nexin-17 knockout rat line. Sorting Nexin-17 hetero zygotes rat survived, and the level of Sorting Nexin-17 protein in the atrium was decreased by 50%.

                                                Sorting Nexin-17 deficiency increased the membrane expression of KV1.5 in atrial specific ultra-rapid delayed rectifier outward potassium current IKUR density, resulting in shorted actual potential duration, and eventually contribute to atrial fibrillation susceptibility.

                                                Sorting Nexin-17 facilitated the endocytic sorting of KV1.5 from the plasma membrane to early endosomes following the 4.1 ezrin radixin moesin called Firm domain. The authors concluded that Sorting Nexin-17 mediates susceptibility to atrial fibrillation through this mechanism, and thus may be a potent target for the development of new drugs for atrial fibrillation.

                                                That's it for this month, we hope that you'll find the journal the go to place for everyone interested in the field. See you next time.

                                                This program is copyright American Heart Association 2019.

 

Further episodes of Circulation: Arrhythmia and Electrophysiology On the Beat

Further podcasts by Paul J. Wang, MD

Website of Paul J. Wang, MD