Contemporary outcomes of optimally treated heart failure patients with sleep apnea. Case for urgency in evaluation of newer interventions? From The Atlanta Cardiomyopathy Consortium

The incidence and prevalence of heart failure (HF) continues to rise in the United States. Over fivemillion Americans carry the diagnosis of HF that leads to 12–15 million office visits and 6.5 million hospital days per year; 550,000 new cases are diagnosed annually [1]. Besides morbidity andmortality, the economic burden of HF is substantial, the direct and indirect cost of HF in 2008 was $34.8 billion and is on pace to triple by 2030 [2]. Sleep disorder breathing, or sleep apnea (SA), is a highly prevalent co-morbid condition occurring in 40–75% of HF patients [3–6]. Evenwith the current advances in medical therapy, the prevalence of SA has remained unchanged [7]. SA is known to induce hypoxia, increase sympathetic stimulation, inflammatory and oxidative stress, and has been associated with adverse outcomes in HF [8–11]. When diagnosed early, effective treatment of SA improves left ventricular ejection fraction, sympathetic activity, quality of life, and yet reports on improvement of clinical outcomes have been conflicting [12–19]. In this study, we assessed the outcomes in a contemporary cohort of HF patients with clinically diagnosed SA on optimal medical therapy followed in a tertiary care specialty clinic. We examined the association of history of SAwith outcomes in 313 ambulatory HF patients enrolled in the Atlanta Cardiomyopathy Consortium, a prospective cohort study enrolling HF patients from three university-affiliated teaching hospitals from July 2007. Inclusion criteria included age N18 years and a diagnosis of HF with either reduced or preserved ejection fraction. Exclusion criteria included congenital heart disease, previous heart transplantation or currently awaiting transplant, known cardiac infiltrative disease (e.g., amyloidosis), previous other solid organ transplantation, and endstage HF requiring outpatient continuous inotrope infusion. All patients underwent past history surveys, physical examination, electrocardiogram, 6-minute walk test, psychosocial questionnaires, and collection of blood and urine samples at baseline. Every six months, the patients are contacted to assess medication changes, procedures, new diagnoses, and hospitalizations. Mortality data are collected through medical record review, information obtained from family members, and Social Security Death Index query. Hospitalization data are obtained from regular electronic health record review, all outpatient notes from any specialty encounter for any reported admission to an outside hospital, and direct patient inquiry during follow-up. Primary outcome was defined as the composite of death, cardiac transplantation, left ventricular assist device (LVAD) use, or HF related hospitalization. The secondary outcome incorporated the primary outcome and all-cause admissions. Values are expressed as mean±standard deviation (SD) for continuous and count (%) for categorical variables. Outcomes were described with Kaplan–Meier estimates and compared with the logrank statistic between groups. Categorical variables were compared using the chi-square test, and other continuous, non-time dependent variables in these groups were compared with t-test. Multivariable Cox proportional hazards analysis was then performed adjusting for known predictors of outcomes. Statistical analysis was done with SAS 9.2 (SAS Institute Inc., Cary, NC, USA). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology. Mean age of patients was 57±12 years, 65% were male and 50% were white. Sixty seven (22%) patients had history of SA. Other comorbidities included diabetes (34%), coronary artery disease (40%), hypertension (67%), dyslipidemia (52%) and active tobacco abuse (13%). Beta-blocker use was 93% and ACE inhibitors or angiotensin II receptor blocker was 79%, respectively. Mean ejection fraction was 30±15%. Table 1 compares the baseline characteristics of patients with and without SA. Prevalence of chronic kidney disease, diabetes, and depressionwas significantly higher in patients with SA. Therewas