Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure With Preserved Ejection Fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure])

Abstract

Background: In nonrandomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), fewer symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and midrange or preserved ejection fraction (EF ≥40%). We conducted the first randomized sham-controlled trial to evaluate the IASD in HF with EF ≥40%. Methods: REDUCE LAP-HF I (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association class III or ambulatory class IV HF, EF ≥40%, exercise PCWP ≥25 mm Hg, and PCWP-right atrial pressure gradient ≥5 mm Hg. Participants were randomized (1:1) to the IASD versus a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness end point was exercise PCWP at 1 month. The primary safety end point was major adverse cardiac, cerebrovascular, and renal events at 1 month. PCWP during exercise was compared between treatment groups using a mixed-effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results: A total of 94 patients were enrolled, of whom 44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years, and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared with sham control ( P =0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mm Hg in the treatment group versus 0.5±5.0 mm Hg in the control group ( P =0.14). There were no peri-procedural or 1-month major adverse cardiac, cerebrovascular, and renal events in the IASD group and 1 event (worsening renal function) in the control group ( P =1.0). Conclusions: In patients with HF and EF ≥40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT02600234.

Left atrial pressure is associated with iatrogenic atrial septal defect after mitral valve clip

“…Recent studies reported early clinical and haemodynamic benefits of a transcatheter interatrial shunt device designed to reduce left atrial pressure in patients with heart failure, irrespective of LVEF 21 22. The transcatheter interatrial shunt device reduced PCWP during exercise in patients with heart failure with preserved LVEF21 and have shown improvements in NYHA classification, quality of life, 6 min walk test distance and PCWP with no changes in RAP and PAP in patients with heart failure with reduced LVEF 22. In the present study, even though LVEF at 12 months was significantly lower and mean PAP by the catheter after the procedure and the prevalence of MR ≥3+ at 12 months were significantly higher in patients with 12M-iASD than in patients without 12M-iASD, Doppler estimated systolic PAP in patients with 12M-iASD dramatically decreased and became similar to those in patients without 12M-iASD at 12-month follow-up.…”

Advances in the pharmacotherapy of chronic heart failure with preserved ejection fraction: an ideal opportunity for precision medicine

“…93 The Reduce Elevated Left Atrial Pressure in Patients With Heart Failure (REDUCE LAP-HF I) Trial is a prospective, randomized, sham-controlled clinical trial evaluating a novel interatrial shunt device (IASD) in patients with HFpEF and offers a non-pharmacologic approach to unload the left atrium without compromising LV filling or output. 94 This phase II study has recently finished enrollment, and previous unblinded, single-arm studies have demonstrated promising results for safety and efficacy. 95, 96 …”

“…94, 109, 110 These underlying pathogenic factors affect other organs, leading to pulmonary hypertension, skeletal muscle weakness, and sodium retention which serve as distinct clinical features to be targeted by specific therapies. 111 Given the diverse etiologic factors and clinical presentations of HFpEF, we advocate the use of a “matrix approach” to guide individualized therapy in HFpEF (Table 1).…”

Innovative Clinical Trial Designs for Precision Medicine in Heart Failure with Preserved Ejection Fraction

“…In HFpEF, the REDUCE LAP-HF I and II trials (randomized controlled trials of an interatrial shunt device vs. placebo sham procedure) could be viewed as enrichment trials [25]. Patients undergo non-invasive and invasive hemodynamic screening to ensure that only those patients that express the target (elevated left atrial [LA] pressure compared to right atrial [RA] pressure at rest or during exercise) are included into the trial, thereby enriching the trial for those patients who are most likely to respond to a device that creates a shunt between the LA and RA.…”