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The
long-term goal of this program is to develop quantitative tools for dynamic
assessment of autonomic nervous system activity (ANSA), specifically its
cardiovascular effects. Although various indices of heart rate
variability (HRV) have long been used for general assessment of ANSA, methods
for dynamic analysis are lacking. At present, no method has been
developed for tracking instabilities or extreme fluctuations of ANSA that
may lead to life-threatening cardiac arrhythmias and sudden death.
The project will focus on the validation of recently developed quantitative
technique for tracking the changes in ANSA, referred to as Modified Karhunen-Loeve
transform (MKLT). Using MKLT, the PI and colleagues showed that multidimensional
disturbances of cardiac rhythm (MDCR) predicted spontaneous initiation
of ventricular tachyarrhythmias (VTA) and atrial fibrillation (AF).
Because ANSA is known to play a major role in the modulation of cardiac
rhythm and because changes in ANSA are known to participate in arrhythmogenesis,
we hypothesized that MDCR indicates pronounced instabilities of ANSA that
predispose to the initiation of spontaneous arrhythmias. As a model
of spontaneous arrhythmias, we will focus on paroxysmal AF whose initiation
is known to have a strong relationship to the changes in ANSA. We
will examine MDCR that arise during pharmacological maneuvers that affect
ANSA. These will include stimulation of beta1-adrenergic receptors of the
heart with dobutamine, beta-adrenergic blockage with propranolol and parasympathetic
blockage with atropine. At the next step, we will compare MDCR that
arise during pharmacological tests with spontaneous MDCR that precede initiation
of paroxysmal AF in the same patient population. The patients will
undergo 72-hour ambulatory (Holter) ECG monitoring in the antiarrhythmic
drug-free state. In addition, we will examine the effects of clinical
data, including age, sex, LVEF and presence of structural heart disease
on the manifestations of MDCR. We will also compare MDCR, as detected
by MKLT, with the traditional time and frequency domain HRV-indices.
The results will yield a critical examination of the utility of MDCR for
signaling pronounced instabilities in ANSA which might predispose to the
initiation of spontaneous cardiac arrhythmias. (PDF
VERSION)(MS
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