Circulation: Arrhythmia and Electrophysiology December 2018 Issue

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 for this month's issue.

                                                In our first paper, Pasquale Vergara and Associates develop a predictive risk score to assess the outcome of ventricular tachycardia ablation creating what they call the IVT score. The authors examined 16 demographics, clinical, and procedural related variables in 1,251 patients. They used a technique called survival tree analysis, which uses a recursive partitioning algorithm to find relationships among variables.

                                                They then compared the survival time and time to VT recurrence in groups derived from survival tree analysis using a log rank test. A random forest analysis was then run to extract a variable importance index and internally validate the survival tree models. They found that the left ventricular ejection fraction, ICD, or CRT device, previous ablation were the best predictors of ventricular tachycardia recurrence. While left ventricular ejection fraction, previous ablation, electrical storm was identified as best predictors of mortality.

                                                They identified a high-risk group in which 65% of patients survived and 52.1% were free from VT occurrence. A medium risk group in which 84% survived and 72% were free of VT, and a low risk group in which 97% of patients survived and 88% were free of VT recurrence.

                                                In our next paper, Alwin Zweerink and Associates examined the relationship between cure restoration and left ventricular dimension as predictors of outcomes after cardiac re-synchronization therapy. The present study evaluates the effect of normalization of the cure restoration to left ventricular dimension on the prediction of survival after CRT implantation. They study 250 heart failure patients with left ventricular ejection fraction less than or equal to 35% in cure restoration greater than or equal to 120 milliseconds, and they normalize the cure restoration based on the left ventricular dimension. The left ventricular and diastolic volumes obtained using cardiac magnetic resonance imaging.

                                                Before CRT implantation were used for cure restoration normalization. During a follow up period of 3.9 years, 79 patients or 32% reached the primary end point, which combined death, left ventricular assist device, or heart transplantation. Using univariable cox regression they found that although the unadjusted cure restoration was unrelated to CRT outcome, P=0.116, the normalized cure restoration was a strong predictor of survival. Hazard ratio 0.81 per 0.1 milliseconds per milliliter, P=0.008.

                                                Women demonstrated higher normalized cure restorations than men, 0.2 milliseconds per milliliter, versus 0.55 millisecond per milliliter, P=0.003, and showed better survival after CRT. Hazard ratio 0.52 with P=0.018.

                                                In our next study, Markus Linhart and Associates examined the impact of catheter ablation gaps on outcomes after first pulmonary vein isolation. Using delayed gadolinium enhancement cardiac magnetic resonance imaging three months after radio frequency ablation, they found that in 94 patients, 62% with paroxysmal atrial fibrillation, that there was a mean number of 5.4 gaps per patients. Atrial fibrillation recurrence within the first year of ablation was observed in 21 patients with paroxysmal AF, 36%, and 19 patients with persistent atrial fibrillation, 53%.

                                                In the unit variate analysis, CHA2DS2 -VASc score, afib type and relative gap length were predictors of recurrence. In multi-variant analysis, only relative gap length was significantly associated with recurrence. Hazard ratio 1.16 per each 10% of the gap.

                                                In our next paper, Antonius van Stipdonk, Iris ter Horst, Marielle Kloosterman, Alexander Maass, Kevin Vernooy and Associates examined the value of cueres area compared to that of cure restoration and morphology as predictors of clinical echocardiographical outcomes following cardiac resynchronization therapy. The authors found that in 1,492 cardiac resynchronization therapy patients during a mean follow up of 3.4 years, 32% of patients reached the combined prior endpoint of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation.

                                                The authors found that cure restoration identified patients that did not experience the primary endpoint better than QRS morphology in cure restoration area under the curve 0.61 versus 0.55 and 0.51, P value less than 0.001. They also found that QRS area identifies patients with echocardiograph remodeling in response to CRT better than the QRS morphology and duration, area under the curve 0.69 versus 0.58 and 0.58, P < 0.001. In addition, QRS area was the only independent electrocardiographic determine associated with the primary endpoint. Hazard ratio 0.50 QRS area retained its significant associative outcomes in both patients with and without left bundle branch block in cure restoration greater than 150 milliseconds.

                                                Our next paper is a research letter in which Brian Hansen, Ning Li and Associates report the first in-vivo use in a canine model of near infrared optical mapping. In-vivo optical action potential showed a sharp upstroke that corresponded with atrial activation at a neighboring electrode. Imaging during in-vivo atrial fibrillation episodes showed re-entrant activation around the sinoatrial region minimizing the effect of motion artifact in validation in structurally remodeled hearts would be the next steps for this promising technology.

                                                Also, in a research letter, James Hummel and Associates studied whether infrared thermography over a six-centimeter segment can be effectively used to guide atrial fibrillation ablation. Thermography continuously sampled 7,680 points over a full 360 degree and refreshed every second. Ablation was guided by 3D mapping and performed using a 3.5-millimeter irrigated tip. Power was reduced to 25-watts on the left atrial posterior wall and could be further reduced to 20-watts in areas where there was excessive esophageal temperature rise. Esophageal temperature cutoff for radio frequency power delivery was initially 46 degrees and progressively raised to 50 degrees throughout the study at the discretion of the operators.

                                                All patients underwent upper endoscopy on post-ablation day one to three by a gastroenterologist blinded to temperature data. Thirty-four patients were studied, 94% of patients had luminal esophageal temperatures above 40 degrees during ablation of the posterior wall. Thermal events with Tmex greater than 40 degrees occurred commonly averaging 6.5 seconds during a procedure. On average, 231 seconds of ablation were performed with Tmex greater than 40 degrees centigrade. However, the excursions above threshold cutoff Tmex greater than 50 degrees centigrade lasted only 1.5 seconds per patient. In total, 38% of patients, 13 out of 34 had at least one energy delivery discontinued for exceeding threshold. This occurred eight out of 17 times or 47% when the cutoff was 46 degrees centigrade and five out of 15, or 33% at 50 degrees centigrade.

                                                On endoscopy one patient, 3% had thermal injury related to malpositioning of the infrared thermal probe below the region of ablation. Another patient had three lesions spanning 16 centimeters likely related to mechanical trauma with probe placement. The authors concluded that esophageal injury does not seem to occur with esophageal temperatures less than 50 degrees centigrade using thermography.

                                                In a review paper in this issue, Bruce Lerman and Associates discussed adenosine as a potent but underutilized tool that is useful in clarifying in clinical diagnoses of arrhythmias. Adenosine mediates its electrophysiological effect through binding to the cell surface adenosine receptor A1R, a G-protein receptor. In the sinoatrial node, activation of IKADO by adenosine results in negative chronotrophy, a manifestation of its modern effects on membrane hyperpolarization and a decrease in the rate of phase four depolarization. Adenosine also mediates its cellular effects in atrial and AV nodal cells predominantly through activation of IKADO. In atrial myocytes, this results in a shortening of action potential duration in decrease in refractoriness. By shortening the atrial refractory period without changing atrial conduction velocity, the wavelength of activation is shortened. A mechanism through which adenosine can facilitate induction of atrial fibrillation. Adenosine also exerts an antiadrenergic effect in atrial tissue, reducing cyclic AMP stimulated levels of L-type calcium current.

                                                Adenosine has a negative dromotropic effect on the AV node. The most potent effects of adenosine are expressed in N-cells. In these cells, as well as AN-cells, adenosine decreases excitability by reducing the plateau amplitude in abbreviating action potential duration. In addition, it reduces the rate of rise of the upstroke of N-cells. NH-cells are insensitive to adenosine. Adenosine terminates permanent form of junctional recipriatachycardia in the retrograde accessory pathway limb. The mechanism in which adenosine causes block in the retrograde decremental accessory pathway is thought to be by hyper-polarizing the pathways membrane potential. Adenosine has been helpful in illuminating differences in etiology of decremental conduction in three predominant antigrid decremental accessory pathways. Atrial ventricular pathways, atrial physicular pathways, and nodoventricular pathways.

                                                Adenosine can elicit dormant conduction defined as a restoration of excitability by adenosine in tissue rendered inexcitable by partial cellular damage secondary to ablation. There are three discrete clinical scenarios in which adenosine reveals dormant conduction - after pulmonary vein isolation, after achieving bi-directional cavo-tricuspid isthmus block, and following successful ablation of antegrade and retrograde accessory potential. Adenosine, through activation of IKADO hyperpolarizing these cells so that the sodium channels are reactivated, restoring excitability. Adenosine, though its inhibition of cyclic ANP mediated increases in the slow inward calcium current and its downstream inhibitory effects on SR-calcium release, INCX and ITI, terminates focal arrhythmias caused by triggered activity. The response to adenosine may indicate triggered activity where termination occurs versus insensitivity of localized re-entry to adenosine.

                                                That's it for this month, we hope that you will find The Journal to be the go-to place for everyone interested in the field. See you next time.