MD Conference Express AHA 2013 - (Page 22)
SPOTLIGHT ON
Presentations
from the
Atrial Fibrillation
1
Elaine M. Hylek, MD, MPH,
Boston University School of
Medicine, Boston, Massachusetts,
USA, discussed the advantages and
disadvantages of anticoagulant use for
patients at risk for atrial fibrillation (AF).
On the negative side, warfarin use is at the
top of the list as it is the primary reason
for emergency department visits and
subsequent hospitalization in the United
States [Budnitz DS et al. N Engl J Med
2011]. The management of warfarin is
complex and because of individual patient
characteristics, a "one dose fits all strategy"
would never apply. Newer anticoagulants
such as dabigatran, rivaroxaban, and
apixaban are as effective as warfarin in
preventing AF, with the added benefit
of lower rates of critical organ bleeding,
bleeding
death,
and
intracranial
hemorrhage [Granger CB et al. N Engl J
Med 2011; Patel MR et al. N Engl J Med
2011; Connolly SJ et al. N Engl J Med 2009].
For the effective use of target specific oral
anticoagulants in clinical practice, Dr.
Hylek recommends better patient and
dose selection, better blood pressure
control, the avoidance of concomitant
antiplatelet therapy, better determination
of interval follow-up, paying close
attention to package insert directions, and
the periodic assessment of the patient's
renal function. She also recommends that
rivaroxaban be taken with food.
2
John Camm, MD, St. George's
University of London, London,
United Kingdom, presented new
insights into the use of personalized
medicine
in
the
management
of AF. Protemics is the study of
protein dynamics during disease
modifications of the body [Lam L et al.
Int J Cardiol 2006]. During AF, plasma
proteins mediate thrombogenesis,
inflammation,
endocardial
injury,
and structural remodeling [De Sousa
Al et al. J Mol Cell Cardiol 2010].
In an ethnically homogeneous AF
population, plasma proteomics can
be used to identify distinct functional
patterns of protein expression that
report on known stroke and bleeding
risk phenotypes. AF biomarkers, such
C-reactive protein (CRP; inflammation),
pro-brain natriuretic peptides and
troponin (myocardial injury/stress),
marix metalloproteinases (MMPs),
tissue inhibitors of MMPs and
D-dimer (prothombotic state) can be
used to make predictions of incident
and prevalent AF, outcome in AF
populations, treatment successes, and
AF mechanism and treatment choices
[Kornej J et al. Hamostaseologie 2013].
Many biomarkers have been evaluated
in AF association studies, but none is yet
clinically valuable.
3
According to Dobromir Dobrev,
MD, University Duisburg-Essen,
Essen, Germany, a focus on the
fundamental molecular mechanisms
of AF could lead to new antiarrhythmic
drugs and nontraditional approaches
such as upstream therapy. Progression
of AF (paroxysmal and chronic) has
been linked to electrical, structural,
and
Ca(2+)-handling
remodeling,
particularly disruptions in sarcoplasmic
reticulum (SR) Ca(2+) homeostasis
including ryanodine receptor (RyR2)
channel dysfunction and diastolic SR
Ca(2+) leaks [Dobrev D et al. Cardiovasc
Res 2011]. These dysfunctions might
decrease contractile function and
increase the propensity for atrial
arrhythmias. Increased sarcoplasmic
reticulum (SR) Ca(2+) leaks cause
AF-promoting atrial delayed after
depolarizations (DAD) and triggered
activity in chronic AF patients probably
though Ca(2+)/calmodulin-dependent
protein kinase-II -hyperphosphorylated
RyR2, in combination with larger Na(+)Ca(2+)-exchange current for a given SR
Ca(2+) release and increased diastolic
[Ca(2+)](i)-voltage coupling gain [Voigt
N et al. Circulation 2012]. It is hoped
that a better understanding of the
molecular mechanics of AF will lead to
the development of novel mechanismbased therapeutic approaches.
4
Other novel approaches to treat
AF are low-level vagus nerve
stimulation (LL-VNS), cryoblation
of extrinsic sympathovagal nerves,
and renal sympathetic denervation
to modify hypertension as upstream
therapy. Peng-Sheng Chen, MD,
School of Medicine, Indiana University,
Bloomington, Indiana, USA, discussed
the modulating autonomics in AF.
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