title: Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: A consensus document from the Mitral Valve Academic Research Consortium.
abstract: Mitral regurgitation (MR) is one of the most prevalent valve disorders and has numerous aetiologies, including primary (organic) MR, due to underlying degenerative/structural mitral valve (MV) pathology, and secondary (functional) MR, which is principally caused by global or regional left ventricular remodelling and/or severe left atrial dilation. Diagnosis and optimal management of MR requires integration of valve disease and heart failure specialists, MV cardiac surgeons, interventional cardiologists with expertise in structural heart disease, and imaging experts. The introduction of trans- catheter MV therapies has highlighted the need for a consensus approach to pragmatic clinical trial design and uniform endpoint definitions to evaluate outcomes in patients with MR. The Mitral Valve Academic Research Consortium is a collaboration between leading academic research organizations and physician-scientists specializing in MV disease from the United States and Europe. Three in-person meetings were held in Virginia and New York during which 44 heart failure, valve, and imaging experts, MV surgeons and interventional cardiologists, clinical trial specialists and statisticians, and representatives from the U.S. Food and Drug Administration considered all aspects of MV pathophysiology, prognosis, and therapies, culminating in a 2-part document describing consensus recommendations for clinical trial design (Part 1) and endpoint definitions (Part 2) to guide evaluation of transcatheter and surgical therapies for MR. The adoption of these recommendations will afford robustness and consistency in the comparative effectiveness evaluation of new devices and approaches to treat MR. These principles may be useful for regulatory assessment of new transcatheter MV devices, as well as for monitoring local and regional outcomes to guide quality improvement initiatives.
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York Cardiovascular Research Foundation, New York, New York gs2184@columbia.edu.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: Mount Sinai Health System, New York, New York.
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.affiliation: The Ohio State University, Columbus, Ohio.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Arie Pieter
authors.initials: AP
authors.lastname: Kappetein
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York Cardiovascular Research Foundation, New York, New York Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Généreux
authors.affiliation: Hartcentrum Hasselt, Hasselt, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Vranckx
authors.affiliation: Cardiovascular Research Foundation, New York, New York Mount Sinai Health System, New York, New York.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mehran
authors.affiliation: Asklepios Hospital St. Georg, Hamburg, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kuck
authors.affiliation: Columbia University Medical Center/New York-Presbyterian Hospital, New York, New York Cardiovascular Research Foundation, New York, New York.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.affiliation: McGill University Health Center, Montreal, Quebec, Canada.
authors.forename: Nicolo
authors.initials: N
authors.lastname: Piazza
authors.affiliation: Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Head
authors.affiliation: Athens University Hospital Attikon, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: the Hôpital Bichat, Paris, France. For complete information on the MVARC members and participants, please see the Online Appendix. The MVARC initiative was funded by unrestricted grant support from Abbott Vascular, Boston Scientific, Cardiac Dimensions, Cordis, Edwards Lifesciences, Guided Delivery Systems Inc., Mitralign, Medtronic, Valtech. Dr. Stone has served as a consultant for AGA Medical, AstraZeneca, Atrium, Boston Scientific, Cardiovascular Systems, Inc., Eli Lilly/Daiichi Sankyo partnership, InfraReDx, InspireMD, Miracor, Osprey, Reva, TherOx, Thoratec, Velomedix, and Volcano; and has equity in the Biostar and MedFocus family of funds, Caliber, Guided Delivery Systems, MiCardia, and Vascular Nanotransfer Technologies. Dr. Adams has received royalties for intellectual property paid to his medical institution from Edwards Lifesciences and Medtronic.
authors.forename: Alec S
authors.initials: AS
authors.lastname: Vahanian
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000401:mortality; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000401:mortality; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D002986:Clinical Trials as Topic / Q000379:methods*; D023381:Endpoint Determination; D006333:Heart Failure / Q000209:etiology / Q000401:mortality; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D008944:Mitral Valve Insufficiency / Q000401:mortality / Q000601:surgery*; D061330:Multidetector Computed Tomography / Q000379:methods; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D019106:Postoperative Hemorrhage / Q000209:etiology / Q000401:mortality; D011475:Prosthesis Failure; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000401:mortality; D016896:Treatment Outcome
keywords: Heart failure; Mitral regurgitation; Mitral valve; Valve intervention; Valve surgery (or cardiac surgery)