Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document.
OBJECTIVE
The aim of the current Valve Academic Research Consortium (VARC)-2 initiative was to revisit the selection and definitions of transcatheter aortic valve implantation (TAVI) clinical endpoints to make them more suitable to the present and future needs of clinical trials. In addition, this document is intended to expand the understanding of patient risk stratification and case selection.


BACKGROUND
A recent study confirmed that VARC definitions have already been incorporated into clinical and research practice and represent a new standard for consistency in reporting clinical outcomes of patients with symptomatic severe aortic stenosis (AS) undergoing TAVI. However, as the clinical experience with this technology has matured and expanded, certain definitions have become unsuitable or ambiguous.


RESULTS
Two in-person meetings (held in September 2011 in Washington, DC, and in February 2012 in Rotterdam, The Netherlands) involving VARC study group members, independent experts (including surgeons, interventional and noninterventional cardiologists, imaging specialists, neurologists, geriatric specialists, and clinical trialists), the US Food and Drug Administration (FDA), and industry representatives, provided much of the substantive discussion from which this VARC-2 consensus manuscript was derived. This document provides an overview of risk assessment and patient stratification that need to be considered for accurate patient inclusion in studies. Working groups were assigned to define the following clinical endpoints: mortality, stroke, myocardial infarction, bleeding complications, acute kidney injury, vascular complications, conduction disturbances and arrhythmias, and a miscellaneous category including relevant complications not previously categorized. Furthermore, comprehensive echocardiographic recommendations are provided for the evaluation of prosthetic valve (dys)function. Definitions for the quality of life assessments are also reported. These endpoints formed the basis for several recommended composite endpoints.


CONCLUSIONS
This VARC-2 document has provided further standardization of endpoint definitions for studies evaluating the use of TAVI, which will lead to improved comparability and interpretability of the study results, supplying an increasingly growing body of evidence with respect to TAVI and/or surgical aortic valve replacement. This initiative and document can furthermore be used as a model during current endeavors of applying definitions to other transcatheter valve therapies (for example, mitral valve repair).
Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. a.kappetein@erasmusmc.nl
A Pieter
AP
Kappetein
Stuart J
SJ
Head
Philippe
P
Généreux
Nicolo
N
Piazza
Nicolas M
NM
van Mieghem
Eugene H
EH
Blackstone
Thomas G
TG
Brott
David J
DJ
Cohen
Donald E
DE
Cutlip
Gerrit-Anne
GA
van Es
Rebecca T
RT
Hahn
Ajay J
AJ
Kirtane
Mitchell W
MW
Krucoff
Susheel
S
Kodali
Michael J
MJ
Mack
Roxana
R
Mehran
Josep
J
Rodés-Cabau
Pascal
P
Vranckx
John G
JG
Webb
Stephan
S
Windecker
Patrick W
PW
Serruys
Martin B
MB
Leon
D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006328:Cardiac Catheterization / Q000009:adverse effects / Q000401:mortality / Q000592:standards*; D015897:Comorbidity; D032882:Comprehension; D032921:Consensus; D023381:Endpoint Determination / Q000592:standards*; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects / Q000379:methods / Q000401:mortality / Q000592:standards*; D006801:Humans; D033181:Information Dissemination; D018579:Patient Selection; D011788:Quality of Life; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D009626:Terminology as Topic; D016896:Treatment Outcome