Table 1.
Overview of trials with atrial shunts in heart failure patients.
| Author/acronym, publication dates | Device | Trial design and patient number (N) | Main inclusion criteria | Endpoints | Main results |
|---|---|---|---|---|---|
| Sondergaard et al.18 Eur J Heart Fail | IASD, Corvia Medical |
Pilot trial/phase I, prospective, single arm, unblinded, multicentre n = 11 | HFpEF (EF >45%), ⩾1 HF hospitalisation or NYHA class III/IV, baseline PCWP at rest ⩾15 mmHg or PCWP exercise ⩾25 mmHg | Primary endpoint: SADEs up to 30 days; secondary endpoints: procedural success and clinical efficacy at 30 days |
No SADEs after 30 days, procedural success rate 100%, PCWP reduced by 28% (19.7 ± 3.4 versus 14.2 ± 2.7; mean ± SD, p = 0.005) |
| Malek et al.19 Int J Cardiol | IASD, Corvia Medical |
1 year follow-up of the phase I trial | All patients survived NYHA class decreased (p = 0.017), 6MWT and QoL improvement ns, no MACE |
||
| REDUCE LAP-HF, Hasenfuss et al.17 Lancet | IASD, Corvia Medical |
Phase I, prospective, single arm, unblinded, multicentre, n = 68 | HFpEF (EF >40%), NYHA class II/III/IV, baseline PCWP at rest ⩾15 mmHg or PCWP exercise ⩾25 mmHg | Primary endpoint: MACCE at 6 months; secondary endpoint: clinical efficacy at 6 months | No MACCRE and sustained device patency at 6 months, mean PCWP reduced at 6 months (baseline p = 0.0124, at exercise p = 0.0255) |
| REDUCE LAP-HF I, Feldman et al.16 Circulation | IASD, Corvia Medical |
Phase II, prospective, 1:1 randomised, parallel group, blinded, sham controlled, n = 44 | HFpEF (EF ⩾40%), NYHA class III/IV, exercise PCWP ⩾25 mmHg, RAP gradient ⩾5 mmHg |
Primary endpoint: ∆PCWP during exercise and MACCRE at 30 days; secondary endpoints: ∆PCWP and ∆workload peak exercise need for explantation, clinical efficacy at 30 days |
Procedural success rate 95.5%, ∆PCWP during exercise significantly decreased (p = 0.028) and no MACCRE at 30 days, no need for explantation |
| Del Trigo et al.20 Lancet | V-Wave | Pilot trial, prospective, single arm, unblinded, single center n = 10 | HFrEF (LVEF ⩽40%), NYHA class III/IV, PCWP at rest ⩾15 mmHg | Endpoints: Safety of the procedure and potential efficacy up to 90 days | Procedural success rate 100%, no procedural related SAE,100% patency at 30 days, PCWP reduced from baseline 23 ± 5 to 17 ± 8 mmHg at 90 days (p = 0.035), early beneficial clinical outcomes at 3 months, one patient died (VT after 2 months) |
| Rodes-Cabau et al.21 JACC CV Interv | V-Wave | Phase I, prospective, single arm, unblinded, multicenter, n = 38 | HFrEF and HFpEF, NYHA class III/IV, HF-hospitalisation prior 12 months or elevated NT-proBNP | Primary endpoint: MACCE, procedural success; secondary endpoints: SAE, SADE, clinical outcomes at 3 and 12 months | Procedural success rate 100%, MACCE rate at 12 months 2.6% (1 periprocedural cardiac tamponade), patency at 3 months 100% but 14% device occlusion and 36% device stenosis at 12 months, patients with preserved shunt patency tended to maintain clinical benefit. |
| Ongoing trials | |||||
| REDUCE LAP HF II, start date: 06/2017 | IASD Corvia Medical |
Phase III, multicenter, prospective, 1:1 randomised, parallel group, blinded, sham controlled, multicenter, n = 605 |
HFpEF, (LVEF ⩾40%), NYHA class II/III/IV, ⩾1 HF hospitalisation or NT-proBNP> 150 pg/ml, exercise PCWP >25 and RAP gradient >5 mmHg |
Primary endpoint: 12-month composite endpoint (1. time to mortality, stroke 2. rate HF hospitalisation/acute HF visits 3. ∆QoL); secondary endpoints: clinical efficacy | NA |
| REDUCE LAP HFrEF, start date: 03/2017 | IASD Corvia Medical |
Phase II, single arm, non-randomised, open label n = 10 |
HFrEF (EF 20–40%), NYHA III/IV, ⩾1 HF hospitalisation or acute HF visit, PCWP ⩾ 18 and RAP gradient ⩾ 5 mmHg | Endpoints: implantation success, MACCE, patency | NA |
| RELIEVE HF, start date 10/2018 | V-Wave | Phase III, 1:1 multicenter, randomised, blinded, n = 500 planned enrolment | HFrEF and HFpEF, ⩾1 HF hospitalisation or NT-proBNP >1500 pg/ml, NYHA class III/IV | Primary endpoint: SADEs up to 30 days, effectiveness hierarchical composite of death, heart transplant or LVAD implantation, HF hospitalizations | NA |
| AFR-PRELIEVE, start date:07/2017, 3-month results: Paitazoglou et al.22 EuroIntervention |
AFR, Occlutech |
Pilot trial/phase II, multicenter, non-randomised, single arm, open label, n = 36 | HFrEF and HFpEF (EF ⩾15%), NYHA class III/IV, PCWP at rest ⩾15 mmHg or PCWP exercise ⩾25 mmHg | Primary endpoint: SADEs at 90 days; secondary endpoint: SADEs up to 360 days, clinical efficacy | 3-month results: 1 SADE (resolved, no sequelae), 100% implantation success rate, 100% device patency, surrogate parameters of HF improved in some patients, 1HFrEF patient died (pneumonia) after 21 days |
6MWT, 6 minute walking test; EF, ejection fraction; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; MACE, major adverse cardiac events; MACCE, major adverse cardiac cerebrovascular events; MACCRE, major adverse cardiac cerebrovascular and renal events; NA, not applicable; ns, not significant; PCWP, pulmonary capillary wedge pressure; QoL, quality of life; RAP, right atrial pressure; SADE, serious adverse device event; SAE, serious adverse events.