Development of an Effective Treatment for Cheyne-Stokes Respiration

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As many as half of all patients with heart failure exhibit Cheyne-Stokes respiration (CSR), a form of disordered breathing in which short periods (approx 30 sec) of regular breathing alternate with periods during which breathing stops (apnea). Patients with heart failure and CSR have a markedly poorer outcome compared to heart failure patients whose breathing is normal during sleep. While the reasons for the differential outcome are not fully known, it is likely that the direct consequences of CSR, which include increased sympathetic activity and frequent declines in blood oxygen level, contribute to impairment of cardiac function. When effective treatment causes CSR to revert to a continuous breathing pattern, the available evidence shows that patient condition and survival improve. However, the current front-line therapy, continuous positive airway pressure (CPAP) ameliorates CSR in only 50% of heart failure patients. We plan to use a novel loop gain theory developed in our laboratory that enables us to calculate a precise level of inspired CO2 for each patient that will convert CSR into a continuous pattern. The work planned in this program will employ a manual method to deliver an optimised CO2 treatment for each patient during the night whenever the patient begins to exhibit CSR. In order to carry out our study, we will recruit patients with heart failure and suspected CSR for overnight sleep studies which involve measurement of respiratory, cardiovascular and sleep variables. Based upon our studies over the past two years in such patients, carried out at the Alfred and Monash Medical Centre, CO2 treatment will restore continuous breathing in all patients. In the current study we will determine how termination of CSR affects patients in terms of respiratory and cardiovascular function, as well as sleep architecture and quality (duration of sleep and time in its various stages). We anticipate that our proposed study will show that restricting the time a patient spends breathing with a periodic pattern while asleep will provide an acute benefit and justify a major program of device development to translate our technique into a home-based device for overnight patient use. Success in our program has the potential to benefit many of the approximately 25 million people world-wide with congestive heart failure, a condition that remains one of the leading causes of morbidity and mortality in the western world and now constitutes the leading cause of hospitalisation in developed countries.

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