Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis

Carlos E. Ruiz; Rebecca T. Hahn; Alain Berrebi; Jeffrey S. Borer; Donald E. Cutlip; Greg Fontana; Gino Gerosa; Reda Ibrahim; Vladimir Jelnin; Hasan Jilaihawi; E. Marc Jolicoeur; Chad Kliger; Itzhak Kronzon; Jonathon Leipsic; Francesco Maisano; Xavier Millan; Patrick Nataf; Patrick T. O'Gara; Philippe Pibarot; Stephen R. Ramee; Charanjit S. Rihal; Josep Rodes-Cabau; Paul Sorajja; Rakesh Suri; Julie A. Swain; Zoltan G. Turi; E. Murat Tuzcu; Neil J. Weissman; Jose L. Zamorano; Patrick W. Serruys; Martin B. Leon

doi:10.1093/eurheartj/ehx211

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis

Carlos E. Ruiz, Rebecca T. Hahn, Alain Berrebi, Jeffrey S. Borer, Donald E. Cutlip, Greg Fontana, Gino Gerosa, Reda Ibrahim, Vladimir Jelnin, Hasan Jilaihawi, E. Marc Jolicoeur, Chad Kliger, Itzhak Kronzon, Jonathon Leipsic, Francesco Maisano, Xavier Millan, Patrick Nataf, Patrick T. O'Gara, Philippe Pibarot, Stephen R. RameeCharanjit S. Rihal, Josep Rodes-Cabau, Paul Sorajja, Rakesh Suri, Julie A. Swain, Zoltan G. Turi, E. Murat Tuzcu, Neil J. Weissman, Jose L. Zamorano, Patrick W. Serruys, Martin B. Leon

Cardiovascular Medicine

Research output: Contribution to journal › Review article › peer-review

14 Scopus citations

Abstract

The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

Original language	English (US)
Pages (from-to)	1224-1245
Number of pages	22
Journal	European heart journal
Volume	39
Issue number	15
DOIs	https://doi.org/10.1093/eurheartj/ehx211
State	Published - Apr 14 2018

Keywords

closure devices
regurgitation
transcatheter

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1093/eurheartj/ehx211

Cite this

Ruiz, C. E., Hahn, R. T., Berrebi, A., Borer, J. S., Cutlip, D. E., Fontana, G., Gerosa, G., Ibrahim, R., Jelnin, V., Jilaihawi, H., Jolicoeur, E. M., Kliger, C., Kronzon, I., Leipsic, J., Maisano, F., Millan, X., Nataf, P., O'Gara, P. T., Pibarot, P., ... Leon, M. B. (2018). Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis. European heart journal, 39(15), 1224-1245. https://doi.org/10.1093/eurheartj/ehx211

Ruiz, CE, Hahn, RT, Berrebi, A, Borer, JS, Cutlip, DE, Fontana, G, Gerosa, G, Ibrahim, R, Jelnin, V, Jilaihawi, H, Jolicoeur, EM, Kliger, C, Kronzon, I, Leipsic, J, Maisano, F, Millan, X, Nataf, P, O'Gara, PT, Pibarot, P, Ramee, SR, Rihal, CS, Rodes-Cabau, J, Sorajja, P, Suri, R, Swain, JA, Turi, ZG, Tuzcu, EM, Weissman, NJ, Zamorano, JL, Serruys, PW & Leon, MB 2018, 'Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis', European heart journal, vol. 39, no. 15, pp. 1224-1245. https://doi.org/10.1093/eurheartj/ehx211

@article{b404e2030d064f509118f795ee596575,

title = "Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis",

abstract = "The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.",

keywords = "closure devices, regurgitation, transcatheter",

author = "Ruiz, {Carlos E.} and Hahn, {Rebecca T.} and Alain Berrebi and Borer, {Jeffrey S.} and Cutlip, {Donald E.} and Greg Fontana and Gino Gerosa and Reda Ibrahim and Vladimir Jelnin and Hasan Jilaihawi and Jolicoeur, {E. Marc} and Chad Kliger and Itzhak Kronzon and Jonathon Leipsic and Francesco Maisano and Xavier Millan and Patrick Nataf and O'Gara, {Patrick T.} and Philippe Pibarot and Ramee, {Stephen R.} and Rihal, {Charanjit S.} and Josep Rodes-Cabau and Paul Sorajja and Rakesh Suri and Swain, {Julie A.} and Turi, {Zoltan G.} and Tuzcu, {E. Murat} and Weissman, {Neil J.} and Zamorano, {Jose L.} and Serruys, {Patrick W.} and Leon, {Martin B.}",

note = "Funding Information: 1Hackensack University Medical Center, Structural and Congenital Heart Center, Hackensack, New Jersey; 2Columbia University Medical Center and Cardiovascular Research Foundation, New York, New York; 3H{\^o}pital Europ{\'e}en Georges Pompidou, Paris, France; 4State University of New York Downstate Medical Center and College of Medicine, New York, New York; 5Baim Institute for Clinical Research, Boston, Massachusetts; 6Cedars Sinai Medical Center, Los Angeles, California; 7Padua University Hospital, Padua, Italy; 8Montreal Heart Institute, Montreal, Quebec, Canada; 9NYU Langone Medical Center, New York, New York; 10Lenox Hill Heart and Vascular Institute-North Shore LIJ Health System, New York, New York; 11St. Paul{\textquoteright}s Hospital, University of British Columbia, Vancouver, British Columbia, Canada; 12University Hospital Zurich, Zurch, Switzerland; 13Hospital Santa Creu i Sant Pau, Barcelona, Spain; 14AP-HP H{\^o}pital Bichat Service de Cardiologie, Paris, France; 15Brigham & Women{\textquoteright}s Hospital, Boston, Massachusetts; 16Qu{\'e}bec Heart & Lung Institute, Quebec City, Quebec, Canada; 17Ochsner Clinic, New Orleans, Louisiana; 18Mayo Clinic, Rochester, Minnesota; 19Minneapolis Heart Institute and Abbott Northwestern Hospital, Minneapolis, Minnesota; 20Clevelend Clinic, Cleveland, Ohio; 21Mount Sinai School of Medicine, New York, New York; * Corresponding author. Dr. Carlos E. Ruiz, Hackensack University Medical Center, Structural and Congenital Heart Center, 30 Prospect Avenue, 5 Main, Room 5640, Hackensack, New Jersey 07601. E-mail: Carlos.Ruiz@hackensackmeridian.org Dr. Ruiz has received institutional educational grants from Medtronic, St. Jude Medical, and Philips Healthcare; and is a consultant for St. Jude Medical. Dr. Hahn is a consultant for St. Jude Medical; and is a speaker for GE Medical, Abbott Vascular, and Boston Scientific. Dr. Berrebi is a speaker for Philips Healthcare. Dr. Borer is on the data safety monitoring board for Cardiorentis, Novartis, Celladon, GlaxoSmithKline, and Pfizer; is a consultant for Boehringer Ingelheim, Abbott, Sarepa, Amgen, and Gilead; serves on the events adjudication committee for AstraZeneca, Takeda USA, and Biotronik; serves on the advisory board of ARMGO; and owns stock in Biomarin. Dr. Cutlip receives institutional research support from Medtronic and Boston Scientific. Dr. Fontana is national principal investigator (PI) for Abbott; is a consultant for Medtronic; is a consultant and PI for LivaNova; is on the speakers bureau for Peerbridge Health; and has equity in Entourage Medical. Dr. Gersa receives meeting attendance sponsorship from Edwards Lifesciences, Medtronic, Sorin, Neochord, Artech, St. Jude Medical, and Aptiva Medica; receives speakers bureau fees from St. Jude Medical; and receives research grants sponsorship from Gada Group. Dr. Ibrahim is a consultant and proctor for St. Jude Medical, Gore, and Boston Scientific; and has received honoraria from AstraZeneca, Bayer, Boston Scientific, and St. Jude Medical. Dr. Jelnin is a consultant for Cardiac Implants; has received an institutional grant from Philips Healthcare; and has received educational grants from St. Jude Medical and Medtronic. Dr. Jilaihawi is a consultant to Edwards Lifesciences and St. Jude Medical; and his institution receives a research grant from Medtronic. Dr. Kliger has received speaking honoraria from St. Jude Medical and Philips Healthcare. Dr. Kronzon is a consultant for Philips Healthcare, CRF Clinical Trials Center, Cardiovascular Research Foundation, and Cardiac Implants, LLC. Dr. Leipsic has institutional core laboratory contracts for Edwards, Medtronic, Neovasc, Tendyne, and Ancora; and serves as a consultant for Edwards, Valcare, Valtech, Heartflow, and Circle Cardiovascular Imaging. Dr. Maisano is a consultant for St. Jude Medical; and has received grants from St. Jude Medical and Philips. Dr. Pibarot has core laboratory contracts with Edwards Lifesciences, for which he receives no direct compensation. Dr. Sorajja has served as a speaker, consultant, and on the advisory board for Abbott Vascular, Medtronic, and Boston Scientific; and has served as a consultant for Intervalve and Lake Regions Medical. Dr. Suri is co-PI of the COAPT trial; is on the Steering Committee for PORTICO valve St. Jude Medical; is national PI for Perceval–LivaNova; and receives research grants from Edwards, Abbott, St. Jude Medical, and LivaNova. Dr. Turi is on the clinical events committee for Mitralign; and receives educational grants from Medtronic and St. Jude Medical. Dr. Tuzcu is on the clinical events committee for Mitralign; has received 2 grants from Medtronic and St. Jude; and taught in the St. Jude Interventional Fellows Course, but waived the honoraria. Dr. Weissman{\textquoteright}s organization has received research grant support from Abbott, Boston Scientific, Direct Flow, Edwards, Medtronic, and St. Jude Medical. Dr. Serruys has received personal fees from Abbott Vascular, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, SinoMedical Sciences Technology, Soci{\'e}t{\'e} Europa Digital Publishing, Stentys France, Svelte Medical Systems, Volcano, St. Jude Medical, and Xeltis. Dr. Leon serves on the PARTNER executive committee for Edwards (unpaid) and on the scientific advisory boards of Medtronic, Abbott, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper. Thomas Luescer, MD, served as Guest Editor for this paper. VC 2017 American College of Cardiology Foundation and European Society of Cardiology. This article is being published concurrently in Journal of the American College of Cardiology, 10.1016/j.jacc.2017.02.038. The articles are identical except for minor stylistic and spelling differences in keeping with each journal{\textquoteright}s style. Either citation can be used when citing this article. Publisher Copyright: {\textcopyright} The Author 2017.",

year = "2018",

month = apr,

day = "14",

doi = "10.1093/eurheartj/ehx211",

language = "English (US)",

volume = "39",

pages = "1224--1245",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "15",

}

TY - JOUR

T1 - Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis

AU - Ruiz, Carlos E.

AU - Hahn, Rebecca T.

AU - Berrebi, Alain

AU - Borer, Jeffrey S.

AU - Cutlip, Donald E.

AU - Fontana, Greg

AU - Gerosa, Gino

AU - Ibrahim, Reda

AU - Jelnin, Vladimir

AU - Jilaihawi, Hasan

AU - Jolicoeur, E. Marc

AU - Kliger, Chad

AU - Kronzon, Itzhak

AU - Leipsic, Jonathon

AU - Maisano, Francesco

AU - Millan, Xavier

AU - Nataf, Patrick

AU - O'Gara, Patrick T.

AU - Pibarot, Philippe

AU - Ramee, Stephen R.

AU - Rihal, Charanjit S.

AU - Rodes-Cabau, Josep

AU - Sorajja, Paul

AU - Suri, Rakesh

AU - Swain, Julie A.

AU - Turi, Zoltan G.

AU - Tuzcu, E. Murat

AU - Weissman, Neil J.

AU - Zamorano, Jose L.

AU - Serruys, Patrick W.

AU - Leon, Martin B.

N1 - Funding Information: 1Hackensack University Medical Center, Structural and Congenital Heart Center, Hackensack, New Jersey; 2Columbia University Medical Center and Cardiovascular Research Foundation, New York, New York; 3Hôpital Européen Georges Pompidou, Paris, France; 4State University of New York Downstate Medical Center and College of Medicine, New York, New York; 5Baim Institute for Clinical Research, Boston, Massachusetts; 6Cedars Sinai Medical Center, Los Angeles, California; 7Padua University Hospital, Padua, Italy; 8Montreal Heart Institute, Montreal, Quebec, Canada; 9NYU Langone Medical Center, New York, New York; 10Lenox Hill Heart and Vascular Institute-North Shore LIJ Health System, New York, New York; 11St. Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada; 12University Hospital Zurich, Zurch, Switzerland; 13Hospital Santa Creu i Sant Pau, Barcelona, Spain; 14AP-HP Hôpital Bichat Service de Cardiologie, Paris, France; 15Brigham & Women’s Hospital, Boston, Massachusetts; 16Québec Heart & Lung Institute, Quebec City, Quebec, Canada; 17Ochsner Clinic, New Orleans, Louisiana; 18Mayo Clinic, Rochester, Minnesota; 19Minneapolis Heart Institute and Abbott Northwestern Hospital, Minneapolis, Minnesota; 20Clevelend Clinic, Cleveland, Ohio; 21Mount Sinai School of Medicine, New York, New York; * Corresponding author. Dr. Carlos E. Ruiz, Hackensack University Medical Center, Structural and Congenital Heart Center, 30 Prospect Avenue, 5 Main, Room 5640, Hackensack, New Jersey 07601. E-mail: Carlos.Ruiz@hackensackmeridian.org Dr. Ruiz has received institutional educational grants from Medtronic, St. Jude Medical, and Philips Healthcare; and is a consultant for St. Jude Medical. Dr. Hahn is a consultant for St. Jude Medical; and is a speaker for GE Medical, Abbott Vascular, and Boston Scientific. Dr. Berrebi is a speaker for Philips Healthcare. Dr. Borer is on the data safety monitoring board for Cardiorentis, Novartis, Celladon, GlaxoSmithKline, and Pfizer; is a consultant for Boehringer Ingelheim, Abbott, Sarepa, Amgen, and Gilead; serves on the events adjudication committee for AstraZeneca, Takeda USA, and Biotronik; serves on the advisory board of ARMGO; and owns stock in Biomarin. Dr. Cutlip receives institutional research support from Medtronic and Boston Scientific. Dr. Fontana is national principal investigator (PI) for Abbott; is a consultant for Medtronic; is a consultant and PI for LivaNova; is on the speakers bureau for Peerbridge Health; and has equity in Entourage Medical. Dr. Gersa receives meeting attendance sponsorship from Edwards Lifesciences, Medtronic, Sorin, Neochord, Artech, St. Jude Medical, and Aptiva Medica; receives speakers bureau fees from St. Jude Medical; and receives research grants sponsorship from Gada Group. Dr. Ibrahim is a consultant and proctor for St. Jude Medical, Gore, and Boston Scientific; and has received honoraria from AstraZeneca, Bayer, Boston Scientific, and St. Jude Medical. Dr. Jelnin is a consultant for Cardiac Implants; has received an institutional grant from Philips Healthcare; and has received educational grants from St. Jude Medical and Medtronic. Dr. Jilaihawi is a consultant to Edwards Lifesciences and St. Jude Medical; and his institution receives a research grant from Medtronic. Dr. Kliger has received speaking honoraria from St. Jude Medical and Philips Healthcare. Dr. Kronzon is a consultant for Philips Healthcare, CRF Clinical Trials Center, Cardiovascular Research Foundation, and Cardiac Implants, LLC. Dr. Leipsic has institutional core laboratory contracts for Edwards, Medtronic, Neovasc, Tendyne, and Ancora; and serves as a consultant for Edwards, Valcare, Valtech, Heartflow, and Circle Cardiovascular Imaging. Dr. Maisano is a consultant for St. Jude Medical; and has received grants from St. Jude Medical and Philips. Dr. Pibarot has core laboratory contracts with Edwards Lifesciences, for which he receives no direct compensation. Dr. Sorajja has served as a speaker, consultant, and on the advisory board for Abbott Vascular, Medtronic, and Boston Scientific; and has served as a consultant for Intervalve and Lake Regions Medical. Dr. Suri is co-PI of the COAPT trial; is on the Steering Committee for PORTICO valve St. Jude Medical; is national PI for Perceval–LivaNova; and receives research grants from Edwards, Abbott, St. Jude Medical, and LivaNova. Dr. Turi is on the clinical events committee for Mitralign; and receives educational grants from Medtronic and St. Jude Medical. Dr. Tuzcu is on the clinical events committee for Mitralign; has received 2 grants from Medtronic and St. Jude; and taught in the St. Jude Interventional Fellows Course, but waived the honoraria. Dr. Weissman’s organization has received research grant support from Abbott, Boston Scientific, Direct Flow, Edwards, Medtronic, and St. Jude Medical. Dr. Serruys has received personal fees from Abbott Vascular, AstraZeneca, Biotronik, Cardialysis, GLG Research, Medtronic, SinoMedical Sciences Technology, Société Europa Digital Publishing, Stentys France, Svelte Medical Systems, Volcano, St. Jude Medical, and Xeltis. Dr. Leon serves on the PARTNER executive committee for Edwards (unpaid) and on the scientific advisory boards of Medtronic, Abbott, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper. Thomas Luescer, MD, served as Guest Editor for this paper. VC 2017 American College of Cardiology Foundation and European Society of Cardiology. This article is being published concurrently in Journal of the American College of Cardiology, 10.1016/j.jacc.2017.02.038. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article. Publisher Copyright: © The Author 2017.

PY - 2018/4/14

Y1 - 2018/4/14

N2 - The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

AB - The VARC (Valve Academic Research Consortium) for transcatheter aortic valve replacement set the standard for selecting appropriate clinical endpoints reflecting safety and effectiveness of transcatheter devices, and defining single and composite clinical endpoints for clinical trials. No such standardization exists for circumferentially sutured surgical valve paravalvular leak (PVL) closure. This document seeks to provide core principles, appropriate clinical endpoints, and endpoint definitions to be used in clinical trials of PVL closure devices. The PVL Academic Research Consortium met to review evidence and make recommendations for assessment of disease severity, data collection, and updated endpoint definitions. A 5-class grading scheme to evaluate PVL was developed in concordance with VARC recommendations. Unresolved issues in the field are outlined. The current PVL Academic Research Consortium provides recommendations for assessment of disease severity, data collection, and endpoint definitions. Future research in the field is warranted.

KW - closure devices

KW - regurgitation

KW - transcatheter

UR - http://www.scopus.com/inward/record.url?scp=85046282898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046282898&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehx211

DO - 10.1093/eurheartj/ehx211

M3 - Review article

C2 - 28430909

AN - SCOPUS:85046282898

SN - 0195-668X

VL - 39

SP - 1224

EP - 1245

JO - European Heart Journal

JF - European Heart Journal

IS - 15

ER -

Clinical Trial Principles and Endpoint Definitions for Paravalvular Leaks in Surgical Prosthesis

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this