title: A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial.
abstract: BACKGROUND
  Heart failure with preserved ejection fraction (HFPEF) is a common, globally recognised, form of heart failure for which no treatment has yet been shown to improve symptoms or prognosis. The pathophysiology of HFPEF is complex but characterised by increased left atrial pressure, especially during exertion, which might be a key therapeutic target. The rationale for the present study was that a mechanical approach to reducing left atrial pressure might be effective in HFPEF.
  
  
  METHODS
  The REDUCe Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF) study was an open-label, single-arm, phase 1 study designed to assess the performance and safety of a transcatheter interatrial shunt device (IASD, Corvia Medical, Tewkesbury, MA, USA) in patients older than 40 years of age with symptoms of HFPEF despite pharmacological therapy, left ventricular ejection fraction higher than 40%, and a raised pulmonary capillary wedge pressure at rest (>15 mm Hg) or during exercise (>25 mm Hg). The study was done at 21 centres (all departments of cardiology in the UK, Netherlands, Belgium, France, Germany, Austria, Denmark, Australia, and New Zealand). The co-primary endpoints were the safety and performance of the IASD at 6 months, together with measures of clinical efficacy, including functional capacity and clinical status, analysed per protocol. This study is registered with ClinicalTrials.gov, number NCT01913613.
  
  
  RESULTS
  Between Feb 8, 2014, and June 10, 2015, 68 eligible patients were entered into the study. IASD placement was successful in 64 patients and seemed to be safe and well tolerated; no patient had a peri-procedural or major adverse cardiac or cerebrovascular event or need for cardiac surgical intervention for device-related complications during 6 months of follow-up. At 6 months, 31 (52%) of 60 patients had a reduction in pulmonary capillary wedge pressure at rest, 34 (58%) of 59 had a lower pulmonary capillary wedge pressure during exertion, and 23 (39%) of 59 fulfilled both these criteria. Mean exercise pulmonary capillary wedge pressure was lower at 6 months than at baseline, both at 20 watts workload (mean 32 mm Hg [SD 8] at baseline vs 29 mm Hg [9] at 6 months, p=0·0124) and at peak exercise (34 mm Hg [8] vs 32 [8], p=0·0255), despite increased mean exercise duration (baseline vs 6 months: 7·3 min [SD 3·1] vs 8·2 min [3·4], p=0·03). Sustained device patency at 6 months was confirmed by left-to-right shunting (pulmonary/systemic flow ratio: 1·06 [SD 0·32] at baseline vs 1·27 [0·20] at 6 months, p=0·0004).
  
  
  CONCLUSIONS
  Implantation of an interatrial shunt device is feasible, seems to be safe, reduces left atrial pressure during exercise, and could be a new strategy for the management of HFPEF. The effectiveness of IASD compared with existing treatment for patients with HFPEF requires validation in a randomised controlled trial.
  
  
  BACKGROUND
  Corvia Medical Inc.
authors.affiliation: Heart Centre, Georg-August Universität, Gottingen, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuß
authors.affiliation: St Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Chris
authors.initials: C
authors.lastname: Hayward
authors.affiliation: Cardiology Department, Columbia University, New York, NY, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Burkhoff
authors.affiliation: Hospital of the University of Pennsylvania, Philadelphia PA, USA.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Silvestry
authors.affiliation: The Prince Charles Hospital, Brisbane, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: McKenzie
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Gustafsson
authors.affiliation: Na Homolce Hospital, Prague, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Malek
authors.affiliation: St Antonius Ziekenhuis, Nieuwegein, Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Van der Heyden
authors.affiliation: Allgemeines Krankenhaus Universitätskliniken, Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Lang
authors.affiliation: Golden Jubilee National Hospital, Glasgow, Scotland, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Petrie
authors.affiliation: National Heart & Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK.
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Leon
authors.affiliation: Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia. Electronic address: david.kaye@bakeridi.edu.au.
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000368:Aged; D006328:Cardiac Catheterization; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D019919:Prosthesis Implantation; D013318:Stroke Volume