IMPACT OF PROLONGED NOCTURNAL HYPOXEMIA ON LONG-TERM CLINICAL OUTCOMES IN PATIENTS WITH PRE-CAPILLARY PULMONARY HYPERTENSION

Abstract

Objective: Obstructive sleep apnea (OSA) and/or nocturnal hypoxemia is prevalent in patients with pulmonary hypertension (PH). However, the pathophysiological determinants of adverse outcomes remain ambiguous. We aimed to investigate the prognostic significance of various sleep parameters for long-term prognosis in patients with pre-capillary PH. Design and method: Consecutive patients diagnosed with precapillary pulmonary hypertension (PH) by right heart catheterization who underwent overnight cardiorespiratory polygraphy for the assessment of OSA were enrolled. Time-to-event analysis was performed investigating cardiorespiratory indices (apnea-hypopnea index [AHI] and percentage total recording time <90% [T90]) and clinical worsening using the log-rank test and multivariable Cox proportional hazard models adjusted for multiple confounders. Results: Of 440 eligible Chinese patients with PH, 134 (30.5%) had OSA and 147 (33.4%) had nocturnal hypoxemia (T90 greater than 10%). Over a median follow-up of 12.1 months, 72 (16.4%) patients experienced clinical worsening. AHI did not predict a higher risk of incident CW (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.932-1.001, P = 0.225), whereas T90 was associated with an increased risk of CW (HR: 1.01, 95% CI 1.00-1.01, P = 0.018). The likelihood of CW increased by 8% per 10-unit increase in T90 (HR: 1.08, 95% CI 1.020-1.14, P = 0.018). Patients with nocturnal hypoxemia carried an HR of 1.89 for CW events (HR: 1.89, 95% CI 1.19-3.00, P = 0.007) and these associations persisted after covariates adjustments. Clinical worsening-free survival probability over two-year follow-up periods for patients with nocturnal normoxemia and hypoxemia were 87% and 76.9%, respectively (Log-rank P = 0.006), while the trend towards a non-statistical significance of patients with and without OSA. The association of nocturnal hypoxemia reflected by T90 and CW remained robust across different subgroups and did not potentially interact with potential effect modifiers including age, gender, BMI, and pulmonary hemodynamic parameters (P for interaction >0.05). Conclusions: In patients with precapillary PH, nocturnal hypoxemia defined by T90 was a robust risk predictor of long-term clinical worsening. Investigation of nocturnal hypoxemic burden in PH may aid in the early risk-stratification in patients with precapillary PH.