Table 1.

Summary of Completed Clinical Trials Performed With IASDs

Device	Study	Study Design (Key Inclusion Criteria)	No.	Author	Year Published	Time Frame	Main Efficacy Findings*
Corvia Atrial Shunt	Feasibility	Single arm (EF >45%, NYHA class II–IV, PCWP >15 mm Hg at rest or >25 mm Hg during exercise)	11	Søndergaard et al 32	2014	1 mo	PCWP at rest† ↓5 mm Hg
				Malek et al 33	2015	12 mo	NYHA class ↓0.5; MLWHF ↓29; 6MWT ↑32 m
	REDUCE LAP‐HF 34	Single arm (EF >40%, NYHA II–IV, PCWP >15 mm Hg at rest or >25 mm Hg during exercise)	64	Hasenfuß et al 35	2016	6 mo	Exercise PCWP*, † ↓3 mm Hg Qp:Qs 1.27 Peak exercise PCWP/W per kg 15 mm Hg/W per kg
				Kaye et al 36	2016	12 mo	NYHA median by 1 class; 6MWT ↑32 m; MLWHF questionnaire ↓15; patency confirmed in 98.5%
				Kaye et al 40	2018	36 mo	Observed mortality was 3.4/100 pt‐y; lower than 10.2/100 pt‐y predicted by baseline MAGGIC score (P=0.02)
	REDUCE LAP‐HF I mechanistic study 38	Randomized, sham‐controlled, double‐blinded (NYHA III/IV, EF ≥40%, exercise PCWP ≥15 mm Hg)	44	Feldman et al 37	2018	1 mo	PCWP at peak exercise † ↓3 mm Hg Peak exercise PCWP/W per kg 16 mm Hg/W per kg
				Shah et al 39	2018	12 mo	Yearly HFH rate ↓67% (P=0.06); NYHA median by 1 class; 6MWT no difference; KCCQ no difference. 100% shunt patency
V‐Wave Gen1	Special access pilot (Canada)	Single arm (NYHA III/IV, EF ≤40%, PCWP ≥15 mm Hg)	10	Del Trigo et al 47	2016	3 mo	N=8/9 showed improved NYHA; Duke activity status 11; KCCQ 35; 6MWT 74 m; PCWP ↓6 mm Hg
	Pilot	Single arm (NYHA III/IV; EF >15%; ≥1 HFHs within 1 y)	38	Rodes‐Cabau et al 48	2018	12 mo	NYHA class I or II in 62%; KCCQ 73% improved ≥5‐point improvement; 6MWT ↑28 m; no significant change in PCWP, RAP, or PAP; Qp:Qs 1.1; 14% of valves occluded and 36% stenotic by 12 mo; better hemodynamic responses in patients with patent shunt
V‐Wave Gen2	Pilot	Single arm (NYHA III or IV)	6	Guimaraes et al 49	2020	12 mo	NYHA class I or II in 83%; Duke activity status ↑15; KCCQ ↑32; 6MWT ↑64 m; Qp:Qs 1.16.
Occlutech AFR	AFR‐PRELIEVE	Single arm (NYHA III or IV; EF ≥15%)	36	Paitazoglou et al 51	2019	3 mo	In HFrEF/HFpEF: NYHA class ‐1.4/‐1.1; KCCQ ↑16/↑20; 6MWT 30/↑26 m; PCWP ↓2/↓5 mm Hg; Qp:Qs 1.3/1.1
NoYa	Pilot	Single arm (EF >35%)	10	Lotan 53	2019	1–3 mo	Shunt diameter 3‐4 mm; 6MWT 56 m; BNP 1878 pg/mL

6MWT indicates 6‐minute walk test; AFR, atrial flow regulator; BNP, B‐type natriuretic peptide; EF, ejection fraction; HFH, heart failure hospitalization; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; IASD, interatrial shunt device; KCCQ, Kansas City Cardiomyopathy Questionnaire; MAGGIC, Meta‐Analysis Global Group in Chronic Heart Failure; MLWHF, Minnesota Living With Heart Failure; NYHA, New York Heart Association; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PRELIEVE, Pilot Study to Assess Safety and Efficacy of a Novel Atrial Flow Regulator (AFR) in Heart Failure Patients; REDUCE LAP‐HF, Reduce Elevated Left Atrial Pressure in Patients With Heart Failure; Qp:Qs, ratio of pulmonary to systemic blood flow; RAP, right atrial pressure; and W, watts.

^*For single‐arm studies, values are changes relative to patients’ baseline values; for randomized studies, changes are relative to the control group.

^†Indicates primary end point when one was declared prospectively.