TY - JOUR
T1 - Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension
AU - Pulmonary Vascular Disease Phenomics (PVDOMICS) Study Group
AU - Lowery, Megan M.
AU - Hill, Nicholas S.
AU - Wang, Lu
AU - Rosenzweig, Erika B.
AU - Bhat, Aparna
AU - Erzurum, Serpil
AU - Finet, J. Emanuel
AU - Jellis, Christine L.
AU - Kaur, Sunjeet
AU - Kwon, Deborah H.
AU - Nawabit, Rawan
AU - Radeva, Milena
AU - Beck, Gerald J.
AU - Frantz, Robert P.
AU - Hassoun, Paul M.
AU - Hemnes, Anna R.
AU - Horn, Evelyn M.
AU - Leopold, Jane A.
AU - Rischard, Franz P.
AU - Mehra, Reena
AU - Hill, N.
AU - Xiao, L.
AU - Fu, Y. P.
AU - Postow, L.
AU - Schmetter, B.
AU - Stanton, K.
AU - Tian, X.
AU - Gray, M.
AU - Wong, B.
AU - Leopold, J.
AU - Waxman, A.
AU - DiCarli, M.
AU - Lawler, L.
AU - Maron, B.
AU - Segrera, S.
AU - Systrom, D.
AU - Yu, P.
AU - Rosenzweig, E. B.
AU - Arcasoy, S.
AU - Brady, D.
AU - Chung, W.
AU - Payne, D.
AU - Grunig, G.
AU - Haythe, J.
AU - Krishnan, U.
AU - Abidov, A.
AU - Garcia, J.
AU - Desai, A.
AU - Knox, K.
AU - Lussier, Y.
N1 - Publisher Copyright:
© 2023 American College of Cardiology Foundation
PY - 2023/11/21
Y1 - 2023/11/21
N2 - Background: Group 1 pulmonary arterial hypertension (PAH) is a progressive fatal condition characterized by right ventricular (RV) failure with worse outcomes in connective tissue disease (CTD). Obstructive sleep apnea and sleep-related hypoxia may contribute to RV dysfunction, though the relationship remains unclear. Objectives: The aim of this study was to prospectively evaluate the association of the apnea-hypopnea index (AHI) and sleep-related hypoxia with RV function and survival. Methods: Pulmonary Vascular Disease Phenomics (National Heart, Lung, and Blood Institute) cohort participants (patients with group 1 PAH, comparators, and healthy control participants) with sleep studies were included. Multimodal RV functional measures were examined in association with AHI and percentage of recording time with oxygen saturation <90% (T90) per 10-unit increment. Linear models, adjusted for demographics, oxygen, diffusing capacity of the lungs for carbon monoxide, pulmonary hypertension medications, assessed AHI and T90, and RV measures. Log-rank test/Cox proportional hazards models adjusted for demographics, oxygen, and positive airway pressure were constructed for transplantation-free survival analyses. Results: Analysis included 186 participants with group 1 PAH with a mean age of 52.6 ± 14.1 years; 71.5% were women, 80.8% were Caucasian, and there were 43 events (transplantation or death). AHI and T90 were associated with decreased RV ejection fraction (on magnetic resonance imaging), by 2.18% (−2.18; 95% CI: −4.00 to −0.36; P = 0.019) and 0.93% (−0.93; 95% CI: −1.47 to −0.40; P < 0.001), respectively. T90 was associated with increased RV systolic pressure (on echocardiography), by 2.52 mm Hg (2.52; 95% CI: 1.61 to 3.43; P < 0.001); increased mean pulmonary artery pressure (on right heart catheterization), by 0.27 mm Hg (0.27; 95% CI: 0.05 to 0.49; P = 0.019); and RV hypertrophy (on electrocardiography), 1.24 mm (1.24; 95% CI: 1.10 to 1.40; P < 0.001). T90, but not AHI, was associated with a 17% increased 5-year risk for transplantation or death (HR: 1.17; 95% CI: 1.07 to 1.28). In non-CTD-associated PAH, T90 was associated with a 21% increased risk for transplantation or death (HR: 1.21; 95% CI: 1.08 to 1.34). In CTD-associated PAH, T90 was associated with RV dysfunction, but not death or transplantation. Conclusions: Sleep-related hypoxia was more strongly associated than AHI with measures of RV dysfunction, death, or transplantation overall and in group 1 non-CTD-associated PAH but only with RV dysfunction in CTD-associated PAH.
AB - Background: Group 1 pulmonary arterial hypertension (PAH) is a progressive fatal condition characterized by right ventricular (RV) failure with worse outcomes in connective tissue disease (CTD). Obstructive sleep apnea and sleep-related hypoxia may contribute to RV dysfunction, though the relationship remains unclear. Objectives: The aim of this study was to prospectively evaluate the association of the apnea-hypopnea index (AHI) and sleep-related hypoxia with RV function and survival. Methods: Pulmonary Vascular Disease Phenomics (National Heart, Lung, and Blood Institute) cohort participants (patients with group 1 PAH, comparators, and healthy control participants) with sleep studies were included. Multimodal RV functional measures were examined in association with AHI and percentage of recording time with oxygen saturation <90% (T90) per 10-unit increment. Linear models, adjusted for demographics, oxygen, diffusing capacity of the lungs for carbon monoxide, pulmonary hypertension medications, assessed AHI and T90, and RV measures. Log-rank test/Cox proportional hazards models adjusted for demographics, oxygen, and positive airway pressure were constructed for transplantation-free survival analyses. Results: Analysis included 186 participants with group 1 PAH with a mean age of 52.6 ± 14.1 years; 71.5% were women, 80.8% were Caucasian, and there were 43 events (transplantation or death). AHI and T90 were associated with decreased RV ejection fraction (on magnetic resonance imaging), by 2.18% (−2.18; 95% CI: −4.00 to −0.36; P = 0.019) and 0.93% (−0.93; 95% CI: −1.47 to −0.40; P < 0.001), respectively. T90 was associated with increased RV systolic pressure (on echocardiography), by 2.52 mm Hg (2.52; 95% CI: 1.61 to 3.43; P < 0.001); increased mean pulmonary artery pressure (on right heart catheterization), by 0.27 mm Hg (0.27; 95% CI: 0.05 to 0.49; P = 0.019); and RV hypertrophy (on electrocardiography), 1.24 mm (1.24; 95% CI: 1.10 to 1.40; P < 0.001). T90, but not AHI, was associated with a 17% increased 5-year risk for transplantation or death (HR: 1.17; 95% CI: 1.07 to 1.28). In non-CTD-associated PAH, T90 was associated with a 21% increased risk for transplantation or death (HR: 1.21; 95% CI: 1.08 to 1.34). In CTD-associated PAH, T90 was associated with RV dysfunction, but not death or transplantation. Conclusions: Sleep-related hypoxia was more strongly associated than AHI with measures of RV dysfunction, death, or transplantation overall and in group 1 non-CTD-associated PAH but only with RV dysfunction in CTD-associated PAH.
KW - connective tissue disease–associated pulmonary arterial hypertension
KW - obstructive sleep apnea
KW - pulmonary arterial hypertension
KW - pulmonary hypertension
KW - right ventricular dysfunction
KW - sleep-related hypoxia
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U2 - 10.1016/j.jacc.2023.09.806
DO - 10.1016/j.jacc.2023.09.806
M3 - Article
C2 - 37968017
AN - SCOPUS:85175482938
SN - 0735-1097
VL - 82
SP - 1989
EP - 2005
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 21
ER -