Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage passes to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Greg Hundley, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature article really starts to look at micro-circulatory dysfunction and abnormal coronary perfusion during exercise that can be associated with myocardial ischemia. I hear you're anxious to hear about it, but why don't we go to your article first. Dr Carolyn Lam: Here we go. This first paper I'd like to tell you about reports a novel cardiac kinase as a potential regulator in heart failure. Dr Greg Hundley: Now remind me, Carolyn, I got to take me back a little bit. What are cardiac kinases? Dr Carolyn Lam: Ah, I thought you would ask. Cardiac kinases are known to play a critical role in the development of heart failure and represent potential trackable therapeutic targets. Now to identify novel cardiac kinases involved in heart failure, the corresponding authors, Dr Hind Lal from University of Alabama at Birmingham and colleagues, employed an integrated transcriptomics and bioinformatics analysis and identified homeodomain-interacting protein kinase 2 or HIP kinase 2, as a novel candidate kinase. Now this is the first study to define the role of HIP kinase 2 in cardiac biology. In essence, they performed a series of mouse experiments that showed that cardiac HIP kinase 2 expression is elevated in adults compared to embryonal and neonatal stage of mouse experiments, but down regulated in failing hearts. Deletion of HIP kinase 2 in the cardiomyocytes led to decreased cardiac function in adulthood. The cardiac effect of HIP kinase 2 correlated to its gene expression level and impaired ERK signaling was discovered as the main driver of HIP kinase 2 deficient phenotype by enhancing apoptosis. Taken together these findings really suggest that cardiomyocyte HIP kinase 2 is required to maintain novel cardiac function via ERK signaling. Dr Greg Hundley: All right, Carolyn, my favorite question, what does this mean for us clinically? Dr Carolyn Lam: Two points, first since HIP kinase 2 is protective in cardiomyocytes, gene therapy using HIP kinase 2 could be a potential therapeutic method of heart failure treatment in future. Secondly, because inhibition of HIP kinase 2 has been proposed as a therapeutic approach for certain cancers and for renal fibrosis, these results suggest that caution needs to be taken for the potential cardiotoxicity of HIP kinase 2 inhibition in the adult heart. Interesting. Dr Greg Hundley: Yeah. Very nice. Well, I'm going to switch gears a little bit Carolyn and talk about ablation for atrial fibrillation. And the corresponding author of this paper is Jason Andrade from Vancouver General Hospital. In his study, they randomly assigned 346 patients with drug-refractory paroxysmal atrial fibrillation to A, contact force guided RF ablation, B, four-minute cryoballoon ablation or C, two-minute cryoballoon ablation and they followed the patients for 12 months. Now the primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmias, whether that be AFib, aflutter, atrial tachycardia, between days 91 and 365 after the ablation or a repeat ablation procedure at any time. And the secondary endpoints included freedom from symptomatic arrhythmia and AF burden. Dr Carolyn Lam: Interesting clinical question. What did the results show? Dr Greg Hundley: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring, was 54, 52 and 52% with each of those therapies respectively. One-year freedom from symptomatic tachyarrhythmia defined by continuous monitoring was 79, 78 and 73% with those therapies respectively. No difference statistically in either. Dr Carolyn Lam: Right. No sign