Rationale and design of the randomized, controlled Early Valve Replacement Guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis (EVOLVED) trial

Am Heart J. 2019 Jun:212:91-100. doi: 10.1016/j.ahj.2019.02.018. Epub 2019 Mar 15.

Abstract

Background: The optimal timing of aortic valve replacement in asymptomatic patients with aortic stenosis is uncertain. Replacement fibrosis, as assessed by midwall (nonischemic) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging, is an irreversible marker of left ventricular decompensation in aortic stenosis. Once established, it progresses rapidly and is associated with poor long-term prognosis in a dose-dependent manner.

Trial design: The objective of this multicenter prospective randomized controlled trial is to determine whether early aortic valve replacement in asymptomatic patients with severe aortic stenosis can improve the adverse prognosis associated with midwall LGE. Patients will be screened for likelihood of having LGE with electrocardiography or high-sensitivity troponin I. Those at high risk will proceed to CMR imaging. Approximately 400 patients with midwall LGE will be randomized 1:1 to early valve replacement or routine care. Those who do not exhibit midwall LGE will continue with routine care and be randomized to a study registry or no further follow-up. Follow-up will be annual for approximately 3 years until the number of required outcome events is achieved. The primary endpoint is a composite of all-cause mortality and unplanned aortic stenosis-related hospitalization. The expected event rate is 25.0% in the routine care arm and 13.4% in the early intervention arm over the first 2 years; 88 observed primary outcome events will give 90% power at 5% significance level. Key secondary endpoints include all-cause mortality, sudden cardiac death, stroke, and symptomatic status.

Conclusion: The EVOLVED trial is the first multicenter randomized controlled trial to compare early aortic valve replacement to routine care in asymptomatic patients with severe aortic stenosis and midwall LGE.

Trial registration: ClinicalTrials.gov NCT03094143.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aortic Valve / diagnostic imaging*
  • Aortic Valve / surgery
  • Aortic Valve Stenosis / complications
  • Aortic Valve Stenosis / diagnosis*
  • Aortic Valve Stenosis / surgery
  • Asymptomatic Diseases
  • Echocardiography
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Heart Valve Prosthesis Implantation / methods*
  • Humans
  • Hypertrophy, Left Ventricular / diagnosis*
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / physiopathology
  • Magnetic Resonance Imaging, Cine / methods*
  • Male
  • Middle Aged
  • Myocardium / pathology*
  • Prognosis
  • Prospective Studies
  • Severity of Illness Index
  • Ventricular Function, Left / physiology*

Associated data

  • ClinicalTrials.gov/NCT03094143