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