Project Summary and Abstract: Sleep disordered breathing (SDB), including obstructive sleep apnea (OSA)
and central sleep apnea with Hunter-Cheyne-Stokes respirations is common in patients with heart failure,1,2 is
exaggerated during acute decompensation,3,4 and may potentiate acute cardiac injury in this high-risk setting.5
Mechanisms include large, negative pleural pressure swings (increased left ventricular afterload via increased
transmural pressure),6,7 cyclic hypoventilation (hypoxemia, hypercapnia, acidosis),8 and arousal with
catecholamine surges (arrhythmia).9,10 While in aggregate, the data regarding treatment of SDB with positive
airway pressure have not shown improvement in clinical outcomes in patients with chronic stable heart
failure,11-15 there is a growing body of literature suggesting that acutely decompensated heart failure (ADHF)
may be the preferable time for intervention. Continuous positive airway pressure treatment has been shown to
improve acutely left ventricular ejection fraction in heart failure patients with sleep apnea.16,17 Moreover,
expedited SDB work-up and treatment during (or soon after) hospitalization for heart failure exacerbation
reduces readmission rates. 18,19 Despite these observations, standard treatment of ADHF does not typically
involve sleep assessment. Reasons are multiple but may include lack of clear demonstration of overnight
cardiac injury, as opposed to transient dysfunction during SDB events. New generation troponin assays have
now been developed which now allow a highly sensitive assessment of sub-clinical cardiac injury,20-22 and
these assays have not yet been adequately studied in the context of SDB and acute heart failure. Based on
these concepts the purpose of this project is to determine if sleep disordered breathing results in a
measurable overnight increase in cardiac injury-specific serum biomarker expression in patients
admitted to the hospital with ADHF. Type and burden of SDB events will be assessed using portable
respiratory polygraphy (i.e. a home sleep apnea test), and blood samples will be collected pre and post-sleep.
This protocol will be performed once upon admission, and again in a second phase prior to discharge to
determine if a period of medical heart failure management attenuates cardiac troponin release associated with
sleep apnea. Findings of this research may have important implications for how SDB affects the heart, and for
a multidisciplinary approach to the treatment and prevention of acute heart failure. Results may also be
important for the planning of future interventional studies. This fellowship project will take place at the Sulpizio
Cardiovascular Center, which provides a full spectrum of cardiovascular care, at the University of California
San Diego, a leader in the study of respiratory physiology. The proposal also incorporates formal training for
the PI in clinical research and statistics through the Altman Clinical and Translational Research Institute. The
overall objective of this proposal is for the PI to establish a foundation for an academic career studying
clinically relevant heart-lung-sleep interactions, to which he is firmly committed.
