The prognostic value of sleep disordered breathing and the hypoxemic burden in HFpEF patients

Abstract

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is an important health care problem, responsible for a decreased quality of life, high health care costs, and a poor prognosis. Sleep disordered breathing (SDB) is suggested to be an important comorbidity in HFpEF, but its prevalence is probably underestimated due to limited SDB screening in clinical practice. Currently, no parameter reflects the full complexity and prognostic effect of SDB in HFpEF. Time spent with an oxygen saturation below 90% (T90), representing the hypoxemic burden, is an independent predictor of mortality and is superior compared to the widely accepted apnoea hypopnea index (AHI) in patients with HF with reduced ejection fraction (HFrEF). However, this association has not been explored in HFpEF patients. Purpose This study investigates the prevalence of SDB, comprising the diagnoses obstructive sleep apnoea and central sleep apnoea, in a HFpEF cohort. Moreover, the prognostic association of hypoxemic burden in SDB, expressed as T90, with more frequent HF hospitalizations or all-cause mortality is assessed in HFpEF patients. Methods Patients were prospectively included from our specialised HFpEF outpatient clinic from August 2017 until July 2021. All patients underwent a detailed diagnostic workup. An at home sleep monitoring device was used to obtain oximetry data, including T90, and information on respiratory effort, nasal flow and snoring. The patients were divided into tertiles based on T90 or AHI. In these tertiles pairwise Kaplan-Meier analysis was conducted to compare the probability of the composite endpoint of HF hospitalization or all-cause mortality. A Bonferroni correction was made with a statistical significance of p<0.0167. Results This analysis comprises 126 HFpEF patients, with a median age of 75 [70–80] years, 86 (68.3%) patients were female. In total 60 (47.6%) patients were diagnosed with SDB. The median T90 value was 13.7 minutes, with tertiles low (<2.8 min), middle (2.8–31.2 min), and high (>31.2 minutes). The mean follow up time was 40 months (95% CI 37 to 42) and in total 22 patients (17.5%) reached the composite endpoint. Kaplan-Meier analysis showed a gradual higher probability of HF hospitalization or death with higher T90 tertiles, with a significant difference in the highest compared to the lowest T90 tertile (χ2=7.4, p=0.006) (figure 1). Kaplan Meier analysis comparing tertiles based on the AHI (AHI <5.8; 5.8–12.2; >12.2) showed no different probability of the composite endpoint (χ2=3.1 p=0.208). Conclusion SDB is highly prevalent in HFpEF and the hypoxemic burden (expressed as T90) is an important prognostic factor. T90 may be a superior prognostic marker in HFpEF compared to the widely accepted AHI. Future research should evaluate whether targeting the hypoxemic burden in HFpEF treatment is effective in improving the prognosis. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Heart Foundation