TABLE VIII.B. 4.d2.

Evidence for PAP and clinical outcomes in HFpEF

Study	Year	LOE	Study design	Study groups	Clinical endpoints	Conclusion
Arias et al.750	2005	1b	RCT	Patients with OSA (AHI ≥ 10/h and excessive daytime sleepiness with ESS ≥ 10) and healthy control subjects OSA patients were randomized to 12 weeks of sham CPAP vs. effective CPAP and crossed-over to alternate therapy n = 32	Recording at baseline, after effective nasal CPAP therapy for 12 weeks, and sham CPAP therapy for 12 weeks TTE Blood pressures Urine catecholamines	1. Diastolic function improved in the OSA patients after 12 weeks ofeffective CPAP therapy. 2. There was also significant increase in ratio of peak early filling velocity (E) to peak late filling velocity (A) of diastolic transmitral flow (E/A) and reduction in mitral deceleration time and isovolumic relaxation.
Alchanatis et al.1243	2000	2b	Prospective CS	Patients with OSA (AHI > 15/h) n = 15	Blood pressure and TTE at baseline and after 12–14 weeks of nasal CPAP therapy	1. At baseline, there was diastolic dysfunction present in OSA patients and was improved (increased E/A ratio, decreased IVRT) after 12 weeks of CPAP therapy.
Cloward et al.1241	2003	2b	Prospective CS	Patient with desaturation index >40/h and ≥20% cumulative time spent with arterial oxygen saturation (SaO2) < 90% n = 25	TTE at baseline, 1 and 6 months following initiation of PAP therapy	1. Severe OSA was associated with left ventricular hypertrophy (LVH), left atrial enlargement (LAE), right atrial enlargement (RAE), and right ventricular hypertrophy (RVH). 2. Those compliant with CPAP therapy, there significant reductions in LVH after 6 months of CPAP therapy as measured by interventricular septal distance. 3. RAE and LAE were unchanged after CPAP therapy.
Dursunoglu et al.1244	2007	2b	Prospective CS	Patients with severe OSA (AHI > 33/h) n = 25	TTE and blood pressure in patients with severe OSA at baseline and 6 months of CPAP therapy	1. There was significant reduction in LV wall thickness (interventricular septum and LV posterior wall) in the CPAP treated group. 2. There was significant improvement in LV global dysfunction after 6 months of PAP therapy.
Shivalkar et al.1246	2006	2b	Prospective CS	Patients with severe, symptomatic OSA, and age- and gender-matched controls n = 40	TTE and blood pressure at baseline and after 6 months of PAP	1. PAP therapy significantly improved heart rate and blood pressure. 2. PAP resulted in improved pulmonary artery pressures, interventricular septum thickness, right ventricle dimensions, mitral annular systolic tissue doppler velocity (Sm), tricuspid annular Sm, and right ventricle free wall Sm.
Akar Bayram et al.1242	2009	2b	Prospective CS	Newly diagnosed OSA patients with AHI ≥ 15 and control patients without OSA n = 46	TTE at baseline and after 6 months of PAP therapy in the study group compared to control patients	1. Patients who were on CPAP therapy had improved systolic and diastolic function after 6 months of CPAP therapy.
Glantz et al.1245	2017	1b	RCT	Revascularized CAD patients with non-sleepy OSA (AHI ≥ 15, ESS < 10) were assigned to CPAP or no-CPAP Group n = 171	Echocardiographic measurements were obtained at baseline, 3 and 12 months	1. There was no improvement in diastolic dysfunction in non-sleepy CAD patients with OSA on CPAP therapy. 2. CPAP use of >4 h/night resulted in improved diastolic dysfunction in post hoc analysis.
Craig et al1247	2015	1b	RCT	2 centers randomized 238 patients to 6 months of CPAP or standard care n = 238	Echocardiograms were done for 168 patients and cardiac magnetic resonance scans were done for 68 patients. Baseline ODI was 13.5/h and ESS was 8.4. Baseline LV ejection fraction was well preserved (60.4%)	1. CPAP had no significant effect on ECHO-derived LA area or early to late left ventricular filling velocity (E/A). 2. Small change in echo-derived LV end diastolic volume (EDV) with CPAP was noted (−5.9 mL with 95% CI −10.6 to −1.2; p = 0.015). 3. No significant changes were detected by CMR or LV mass index or LVEF.