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Circulation: Arrhythmia and Electrophysiology On the Beat


Jun 19, 2018

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.

Dr Paul Wang:                   In our first paper, Farhad Pashakhanloo and associates examine the three-dimensional structure of the healed infarct and the ventricular tachycardia reentrant pathways in high-resolution models of infarcted porcine hearts. The authors used ex vivo late gadolinium enhancement in diffusion tensor MRI data of eight chronically infarcted porcine hearts at sub-millimeter resolution in a novel scar map thickness metric to reveal the heterogeneous organization of infarct. The authors use simulation to model ventricular tachycardia pathways. They found that a surviving sub-endocardial tissue later of varying thickness less than or equal to 2.2 millimeters surrounding the scar participated in the majority of ventricular tachycardias. The authors concluded that these analyses provided a better understanding of infarc-related ventricular tachycardia.

Dr Paul Wang:                   In our next paper, Thomas Hadberg Lynge and associates studied the incidence of sudden cardiac death in a population of congenital heart disease in Denmark. Among 24.4 million person years over a nine-year period, there were 11,451 deaths that were examined. Of 809 cases of sudden cardiac death, 90, or 11% of the cases, were from congenital heart disease. Of these cases, 53, or 59% had the diagnosis of congenital heart disease prior to death. The incidence of sudden cardiac death was 9.6 times higher among patients with congenital heart disease compared to patients without congenital heart disease, p<0.01. The annual incidence of sudden cardiac death in congenital heart disease in infants declined after implementation of a nationwide fetal ultrasound screening.

Dr Paul Wang:                   In our next paper, Qifeng Zhou and Carole Maleck and associates examine the relationship between circulating microRNA-21 in low-voltage left atrial areas and outcomes of atrial fibrillation ablation. In 102 patients, average age 62.1 years, CHADS2-VASc score 2.3, LA size 41.5 millimeters, undergoing ablation for persistent atrial fibrillation, the authors performed three-dimensional voltage mapping and determined the extent of left atrial low-voltage as bipolar electrograms less than 0.5 millivolts during sinus rhythm. Prior to ablation, 69 microRNAs were identified in all samples, with an average of 123 microRNAs detected per sample. The authors found that the serum concentration of microRNA-21, a microRNA that has been previously linked to cardiac fibrosis and development, was strongly associated with the extent of low-voltage left atrial areas and were associated with atrial fibrillation-free survival after catheter ablation. The authors also found that low-voltage left atrial areas were negatively correlated with ablation success in one-year follow-up.

Dr Paul Wang:                   In our next paper, Uma Srivatsa and associates examine the discharge and surgical records from California non-federal hospitals and identified patients who had the principle diagnosis of atrial fibrillation, catheter ablation, and had at least one prior hospitalization for atrial fibrillation. The authors compared 4,169 ablation cases to a similar number of weighted match controls. 39% of the ablation group was greater than 65 years, 72% male, 84% Caucasian. The mean follow-up was 3.6 years. In adjusted models, ablation was associated with a significantly lower mortality per patient years, 0.9% versus 1.9%, a hazard ratio of 0.59 with a p-value of less than 0.0001. Similarly, a lower ischemic stroke rate, 0.3% versus 0.59%, with a hazard ratio of 0.68 and a decreased rate of hemorrhagic stroke, 0.11% versus 0.35%.

Dr Paul Wang:                   In our next paper, Mahmood Alhusseini and associates studied 55 patients with persistent atrial fibrillation in whom ablation terminated atrial fibrillation prior to pulmonary vein isolation in a multicenter registry. The authors mapped atrial fibrillation from global electrograms for 365 atrial fibrillation cycles using either a published phase method or a commercial activation phase method. The sites of atrial fibrillation termination showed rotational or focal patterns that were spatially conserved but fluctuated in time, in 51 out of 55 patients, or 55 out of 55 patients, for the first or the second method. Organized readings were detected for 61.6% or 70.6% of one minute for each method, and were confirmed by automatic phase tracking. The authors concluded that sites at which persistent atrial fibrillation terminated by ablation showed organized activation that fluctuate over time due to fusion from concurrent organized zones or fibrillatory waves, yet recur in conserved spatial regions.

Dr Paul Wang:                   In our next paper, Niyada Naksuk and associates examine the risk of sudden cardiac death in patients with right ventricular dysfunction. The authors examined the Mayo Clinic Cardiac Care Unit Database, including 5,463 consecutive patients with complete echocardiographic evaluation to assess with right ventricular systolic function and with right ventricular dysfunction severity. Patients with right ventricular dysfunction were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and a lower baseline left ventricular ejection fraction compared to those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of sudden cardiac death was highest with moderate severe right ventricular dysfunction 7.4% versus 4.4% in mild right ventricular dysfunction versus 1.6% in normal right ventricular function, p<0.001. After adjustment for baseline characteristics, mild right ventricular dysfunction had an adjusted hazard ratio of 1.56, and moderate severe right ventricular dysfunction, a hazard ratio of 1.91. Moderate severe right ventricular dysfunction remained an independent predictor of sudden cardiac death for patients with left ventricular ejection fraction greater than 35%, with or without a preexisting implantable defibrillator.

Dr Paul Wang:                   In our next paper, Ruben Casado Arroyo and Decebal Gabriel Laţcu and associates examined the electrocardiographic and intracardiac activation features of left atrial roof-dependent macro reentrant flutter. The authors found that roof-dependent left atrial flutter circled the right ventricular pulmonary veins in 32 out of 33 cases. The left atrial roof flutters were classified as ascendant on the posterior wall and descendant on the anterior wall in 24 cases, termed posterior to anterior, or ascendant on the anterior wall and descendant on the posterior wall, termed anterior to posterior, in nine cases. Both forms had positive large-amplitude p-waves in leads V1 to V2, with decreasing amplitude in leads V3 to V6. Posterior to anterior roof flutters had a positive p-wave in the inferior and a negative p-wave in leads 1 in AVL, similar to counterclockwise mitral annular flutter, but coronary sinus activation was simultaneous. Anterior to posterior roof flutters were similar to clockwise mitral annular flutter, with negative p-wave in the inferior leads, and transitioned to flatter negative p-wave in leads V3 to V6. Coronary sinus activation time of less than 39 milliseconds identified roof versus mitral annular flutter, with a sensitivity of 100% and a specificity of 97%.

Dr Paul Wang:                   In our next paper, Masateru Takigawa and associates examined the common isthmus in post-atrial fibrillation flutter multi-loop atrial tachycardia. They studied 193 consecutive post-atrial fibrillation atrial tachycardia patients. The authors classified multi-loop atrial tachycardias into three categories. The combination of two anatomic, macro reentrant, atrial tachycardias in 43.2%. One anatomical macro reentrant atrial tachycardia, and one non-anatomical reentrant atrial tachycardia in 27.3%, and two non-anatomical reentrant atrial tachycardias in 25%. Anatomical obstacles such as cavo-tricuspid isthmus, left atrial roof and mitral isthmus, and pulmonary vein and/or pulmonary vein carina are frequently included in the circuit in dual-loop atrial tachycardias. The common isthmus was smaller, shorter, and narrower, with electrograms of lower voltage, longer duration, and time to the diastolic phase when one of the two loops were non-anatomical.

Dr Paul Wang:                   In our next paper, Nicholas Child and associates examine the pattern of activation in patients with persistent atrial fibrillation in order to better understand its mechanism. They examined 14 patients with persistent atrial fibrillation with a mean age 61 years, left ventricular ejection fraction 59%, using simultaneous bi-atrial contact mapping with 64 electrode catheters. The atrial electrograms were transformed into phase and subsequent spatial-temporal mapping to identify phase singularities. They observed more phase singularities in the left atrium compared to the right atrium. Although some phase singularities of duration sufficient to complete more than one rotation were detected, the maximum phase singularity duration was only 1,150 milliseconds, and 97% of phase singularities persisted for too short a period to complete a full rotation. The authors concluded that, because no sustained rotors or localized drivers were detected, the mechanism of arrhythmia maintenance was consistent with the multiple-wavelet hypothesis with passive activation of short-lived rotational activity.

Dr. Paul Wang:                  In our next paper, Bum-Rak Choi and associates used optical mapping, cellular patch clamping, and computer modeling in a transgenic rabbit model of LQT1 to examine the mechanisms of early after depolarization formation and polymorphic ventricular tachycardia initiation. The authors found that the transient outward potassium current, ITO, is both significantly larger and inactivates more slowly in the right ventricle than the left ventricle, and links mechanistically this regional variation of ITO properties to the observed regional variation of early after depolarization frequency abundant in the right ventricle and absent in the left ventricle. It shows that larger ITO in the right ventricle causes a Vmax to traverse the critical window range for reactivation of the L-calcium channel earlier during the action potential plateau, before sufficient activation of IKR, promoting early after depolarization formation in the short action potential region. These early after depolarization propagate unidirectionally to form reentrant and polymorphic ventricular tachycardia.

Dr Paul Wang:                   In our final paper, Tatiana Vinogradova and associates examine the regulation of basal spontaneous beating of rabbit sinoatrial nodal cells, which are regulated by ionic currents in local subsarcolemmal calcium releases from ryanodine receptors. These cells have elevated basal level of cyclic AMP and cyclic AMP-mediated PKA-dependent phosphorylation, regulated by phosphodiesterase 3 and 4 activation. The authors found that the major phosphodiesterase subtypes expressed in rabbit sinoatrial node cells were phosphodiesterase 3A, 4B, and 4D. Phosphodiesterase 3A colocalized with alpha-actin. Phosphodiesterase 4D, circa and phospholamban in z-lines. Phosphodiesterase 3 and 4B colocalized beneath the sarcolemma. The authors found that basal cardiac pacemaker function is regulated by dual phosphodiesterase 3 and 4 activation, which operates in a synergistic manner to limit cyclic AMP-dependent PKA-dependent phosphorylation and to suppress local subsarcolemmal calcium releases, decreasing the spontaneous sinoatrial node cells' beating rate.

Dr Paul Wang:                   That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.