Studio di coorte sulle apnee centrali ed ostruttive in pazienti affetti dainsufficienza cardiaca cronica su base sistolica:prevalenza e caratteristiche cliniche,evidenza di attivazione neuroendocrina edimplicazioni prognostiche dei disturbi respiratori durante il sonno- Risultati del Verona Congestive Heart Failure Sleep Study -

Background: sleep disordered breathing (obstructive and central sleep apnea)(SDB) may contribute to progression of congestive heart failure (CHF) and may exert pro-arrhythmic effects by eliciting greater sympathetic outflow to the heart, kidney and resistence vessels, by inducing production of proinflammatory mediators and by direct mechanical stimulation of the myocardium; persistent activation of the neuroendocrine system, notably adrenergic and neurohormonal systems, is maladaptative in heart failure and Cromogranin A (CgA) may represent a marker of enhanced neuroendocrine activity in CHF due to comorbid sleep apnea. Hypothesis: to investigate the prevalence of SDB in CHF patients; to determine whether SDB is a risk factor for acute heart failure decompensation and life-threatening ventricular arrhythmia in patients with CHF; to evaluate if CHF patients with SDB have augmented circulating levels of CgA compared to patients without sleep apnea. Methods: 82 consecutive patients with CHF and reduced left ventricular ejection fraction (LVEF<40%) were screened for SDB by unattended nocturnal poligraphy; the Apnea-Hypopnea Index (AHI) was defined as the number of apneas-hypopneas per hour of sleep; patients with an AHI ≥10 events/hour were considered as affected by SDB. 56 patients with stable CHF on optimal medical therapy were included in a prospective study to determine the incidence of acute heart failure decompensation during a median follow-up of 18 months; 46 patients were implanted with a cardiac resinchronization device with cardioverter defibrillator (CRT-ICD) 6 months before inclusion into the cohort and were further studied to collect data on appropriate device interventions and appropriately monitored life-threatening ventricular arrhythmias. Serum CgA was measured in 50 patients throughout the entire course of the study. Results: SDB was diagnosed in 49 out of 82 patients (59,8%). The prevalence of obstructive and central sleep apnea was 37,8% and 22% respectively. Kaplan Meier survival estimates showed a reduced acute heart failure free survival in patients with SDB compared to no SDB patients ( 15 vs 24 months, logrank test p=0,03). On multivariate Cox proportional hazard model SDB was independently associated to a 2,86 fold increased hazard ratio (HR) for acute heart failure (95% CI: 1,09-7,52; p=0,03); atrial fibrillation showed to be a predictor for heart failure decompensation after accounting for the presence of SDB and other confounding factors (HR: 3,14; 95% CI: 1,28-7,70 p=0,01). Malignant ventricular arrhythmia was detected or treated by ICD in 24 out of 46 patients (52%) and SDB was present in 75% of these patients compared to 41% of patients with no detected arrhythmia (p=0,01). Time period to first life threatening arrhythmia was significantly shorter in patients with SDB (logrank test p=0,01); multivariate stepwise cox models revealed an independent correlation for severity of SDB (AHI> 22 vs ≤ 22 events/hour) regarding monitored or treated ventricular arrhythmia (HR 3,53; 95%CI: 1,49-8,64; p=0,006) in primary prevention CHF patients. Serum CgA levels were elevated in patients with AHI>22 ev/h compared to patients with mild or no sleep apnea (165,3 ± 39,6 ng/mL and 72,8 ± 9,4, respectively); on multiple regression analysis AHI was correlated to CgA circulating levels after accounting for LVEF and NYHA class (r=0,377; p<0,01). Conclusions: sleep disordered breathing is an highly prevalent comorbidity in patients with systolic heart failure and is independently associated with an increased risk of heart failure decompensation and malignant ventricular arrhythmia in patients on optimal medical therapy treated with cardiac resinchronization. CgA circulating levels are elevated in CHF patients with AHI>22 ev/h and may represent neuroendocrine activity elicited by sleep apnea.