Circulation February 6, 2018 Issue

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. In today's feature discussion, we are talking about external validation of the DAPT score, a discussion that's going to take us all the way to east Asia, but for now, here are your weekly summaries.

                                                In this week's journal, two studies are presented which compare ductal stenting to surgical shunts in the current era of ductal dependent pulmonary blood flow. As background, infants born with cardiac abnormalities causing dependence on the arterial duct for pulmonary blood flow are often palliated with a shunt between the subclavian artery and either pulmonary arteries. This modified Blalock–Taussig shunt allows progress through early life to an age and weight at which repair or furthermore stable palliation can be safely achieved. However, these modified Blalock–Taussig shunts continue to present concern for post-procedure instability and early mortality.

                                                Duct stenting has emerged as an alternative with potential for greater early stability and improved survival. In the first study, first and corresponding author Dr. Bentham from Yorkshire Heart Centre reviewed data from the National Congenital Heart Audit, comparing the outcomes of 171 neonates who underwent a modified Blalock–Taussig shunt and 83 who underwent attempted ductal stenting, all in the setting of duct dependent pulmonary blood flow between 2012 and 2015. They found that stenting the arterial duct was preferable over the modified Blalock–Taussig shunt in terms of survival to next stage surgery, early post-procedure hemodynamic stability and shorter intensive care and hospital stay. There was a high failure rate both early, with the inability to stent the duct and late, with a greater need for re-intervention on the stented duct compared to the surgical shunt.

                                                The second study originated from four North American pediatric cardiology centers representing the Congenital Catheterization Research Collaborative. First and corresponding author, Dr. Glatz from Children's Hospital of Philadelphia performed a retrospective cohort study reviewing all infants with ductal dependent pulmonary blood flow under a year of age, having either a ductal stent or a modified Blalock–Taussig shunt between 2008 and 2015. Although the observed risks of the primary outcome of death or unplanned re-intervention to treat cyanosis was higher in the surgical shunt group, there was no significant difference between groups after adjusting for patient level factors. Furthermore, after adjusting for patient factors, other outcomes favored the stent group, including fewer procedural complications, shorter intensive care unit length of stay, less frequent need for diuretics and larger and more symmetric pulmonary arteries at last follow up.

                                                These companion papers are discussed in an elegant editorial by Drs. Benson and Van Arsdell from Hospital for Sick Children in Toronto.

                                                The next study tells us that there may be a higher risk of vascular dementia in patient who survive a myocardial infarction. First and corresponding author, Dr. Sundbøll from Aarhus University Hospital in Denmark performed a nationwide, population based study including almost 315,000 patients with myocardial infarction and found that the risk of vascular dementia was higher compared to a matched general population comparison cohort. The risk of vascular dementia was incrementally higher in patients who suffered stroke or developed severe heart failure during the first year after myocardial infarction and in patients who underwent coronary artery bypass grafting. There was no association with all caused dementia, Alzheimer's disease or other dementia sub-types. Take home message is that among one year survivors of myocardial infarction, attention should be placed to persistently higher risk of vascular dementia.

                                                The next study identifies a novel mechanism whereby the RNA binding protein, fragile X mental retardation autosomal homologue one or FXR1, directly regulates gap junction remodeling, leading to dilated cardiomyopathy. Co-first authors Drs. Chu and Novak, corresponding author Dr. Gregorio and colleagues from University of Arizona studied human left ventricle dilated cardiomyopathy biopsy samples as well as mouse models of dilated cardiomyopathy. They found that FXR1 expression was significantly increased in human and mouse dilated cardiomyopathy. Up regulation of FXR1 in the heart altered the location and distribution of gap junctions, subsequently leading to ventricular tachycardia in mice.

                                                Mechanistically, FXR1 associated with intercollated discs and directly interacted with integral gap junction proteins to regulate their expression in cardiomyocytes. Finally, loss of FXR1 in the heart led to dilated cardiomyopathy. Together, these results provide a novel function of FXR1, namely that it directly regulates major gap junction components, contributing to proper cell-cell communication in the heart. Thus, the authors concluded that FXR1 may be a promising target for therapeutic strategies to improve gap junction function in dilated cardiomyopathy.

                                                Well everyone, that wraps it up for our summaries. Now for our feature discussion.

                                                The dual anti-platelet therapy or DAPT score is widely used everywhere to estimate bleeding versus ischemic risk in patients undergoing percutaneous pulmonary intervention. However, very few studies have provided external validation of its utility. Well we have a very important paper in this week's journal that addresses just that in a Japanese population. So pleased to have with us the corresponding author, Dr. Takeshi Kimura from Kyoto University Graduate School of Medicine. Not just him, but also the editorialist for this paper, Dr. Shinya Goto, also an associate editor of Circulation from Tokai University of Japan and last but not least of course, our dear Senior Associate Editor of Circulation, Dr. Laura Mauri from Brigham and Women's Hospital. What an important topic. Takeshi, would you mind to please tell us about your study to start?

Dr Takeshi Kimura:          Actually we thought about the utility of the DAPT score provided from the DAPT study in Japanese patient population. In a full cohort of three studies that are conducted in Japan, we compare the risks for ischemic and bleeding risks from 13 to 36 months after a PCI between patients with DAPT score (high-DS) and DAPT score