Enchanced ventilatory and heart rate response to central chemoreflex activation in patients with heart failure and central sleep apnea

Abstract

Central chemoreflex activation by carbon dioxide (CO2) is an important mechanism regulating sympathetic drive as well as ventilation in health and disease. Patients with congestive heart failure (CHF) have potentiated ventilatory and hemodynamic responses to CO2 compared to normals. Patients with CHF and central sleep apnea (CSA) have more adverse outcomes than patients with CHF and no CSA. Hypothesis: Patients with CHF and CSA have greater potentiation of ventilatory and heart rate responses to central chemoreceptor activation by hypercapnia than normals and CHF patients without CSA. Methods: 14 subjects with optimally treated CHF and LVEF 40% and 14 normal controls underwent assessment of central chemoreceptor sensitivity by CO2 re-breathing with hyperoxic background with continuous monitoring for four minutes on a MedGraphics metabolic gas cart; 3 separate runs were performed and results averaged. CO2 sensitivity was measured by plotting the slope of the change in VE and heart rate (HR) versus the change in end-tidal CO2 (PetCO2). All subjects underwent overnight polysomnography (PSG) within 12 hours of CO2 sensitivity testing. CSA was defined as central apnea-hypopnea index 15/hr; individuals with obstructive sleep apnea were excluded. For CO2 sensitivity, CHF subjects with CSA by PSG were compared to CHF subjects with no CSA as well as to normals (ANOVA). Results: Clinical characteristics of the CHF study group included mean age 63 13, LVEF 30 16, NYHA class 21 16. All subjects with CHF were treated with beta-blockers. Ventilatory and heart rate data are summarized in the table. Conclusion: CHF with CSA is characterized by potentiation of ventilatory response to central chemoreceptor activation by hypercapnia compared to subjects with CHF with no CSA and normals. CHF/CSA did not have an increased HR response compared to CHF nonCSA but both groups have a higher HR response than normals. Increased central chemoreceptor sensitivity to CO2 may contribute to worse outcomes for patients with CHF and CSA compared to those with no CSA despite optimal medical therapy.