Towards a More Standardized Bicuspid Aortic Valve Repair: Rationale and Design of CONTOUR Trial - a Randomized Trial

Official title

Towards a More Standardized Bicuspid Aortic Valve Repair: Rationale and Design of CONTOUR Trial

Overview

Background: Between one-third and one-half of patients with bicuspid aortic valve (BAV) disease develop significant aortic regurgitation (AR) at a young age, leading to cardiomyopathy and heart failure. Aortic valve repair is an evolving and still underused strategy in BAV patients with AR. The lack of sufficient standardization remains the main limitation of current repair techniques, resulting in an increased risk of AR recurrence and reoperation. The most controversial issue is the stabilization of the BAV annulus. The CONTOUR trial aims to compare two different BAV annuloplasty concepts in a prospective randomized study. Methods: CONTOUR is a multicenter, randomized controlled trial designed to enroll 100 consecutive BAV patients with AR across four sites in Germany. BAV AR patients with an asymmetric configuration and without concomitant root aneurysm will be randomized 1:1 to undergo aortic valve repair using an internal HAART 200 annuloplasty device (i.e., INTERNAL group) (n=50) or external annuloplasty (i.e., double external ring annuloplasty) in the EXTERNAL group (n=50). 4D flow MRI will be performed preoperatively (t1), postoperatively at discharge (t2), and at 1-year follow-up (t3) for rater-blinded assessment of hemodynamic profiles (i.e., flow eccentricity) and regurgitation fraction at the MRI core-lab. Two hierarchically ordered primary endpoints will be considered: (1) postoperative reduction of flow eccentricity at hospital discharge and (2) regurgitation fraction (%) at 1-year follow-up. Discussion: The CONTOUR trial is designed to test the hypothesis that an internal annuloplasty device, creating a completely symmetric post-repair BAV geometry, achieves superior aortic valve repair outcomes compared to external annuloplasty. If our hypothesis is confirmed, our study will significantly influence aortic valve repair practice and contribute to the refinement of guideline recommendations in the management of BAV patients with AR.

Interventions

• Device Internal HAART 200 annuloplasty device
  For the INTERNAL group, the HAART 200 internal annuloplasty ring (CorCym, London, UK), specifically designed for BAV morphology, will be used for all patients. Intraoperative sizing for the internal ring is based on the geometric orientation and size of the non-fused cusp. A standard ball sizer is used for the measurement of the non-fused cusp to assess commissural orientation and surface area of the non-fused cusp. Sizing typically results in values of 23mm or 25mm, with other sizes being very
• Device double external ring annuloplasty
  For the EXTERNAL group, all study patients will undergo double external Dacron ring annuloplasty by simultaneous stabilization of the basal virtual ring and the STJ \[22\]. The surgical technique of double external annuloplasty, detailed by the Lansac group \[22\], involves aortic annulus sizing with a Hegar dilator to select the sizes of the external subannular annuloplasty ring and STJ ring (same size). After deep dissection of the aortic root, 6-7 2-0 pledgeted U sutures are placed circumfere

Primary outcome measures

• Post-repair reduction of flow eccentricity in percent assessed via cardiac magnetic resonance imaging (MRI) [Time frame: Between the preoperative baseline (max. 30 days preoperative) (t1) and postoperative (pre-discharge) (t2) periods]
• Regurgitation fraction in percent assessed via cardiac magnetic resonance imaging (CMR) [Time frame: Measurements will be taken at baseline (t1), an early post-operative time point (t2), and at 1-year follow-up (t3). The primary analysis will assess changes from baseline (t1) to both post-operative time points (t2 and t3).]

Secondary outcome measures (10)

• Severity of aortic regurgitation (mild/moderate/severe)* [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• Transvalvular gradient (mmHg) [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• All-cause mortality (yes/no) [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• Adverse cardiac events (MACCE) (yes/no) [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• Aortic valve re-intervention (yes/no) [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• Re-hospitalization due to cardiac reasons (yes/no) [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• Device-related complications (safety endpoint) (yes/no) [Time frame: Assessment at month 6 (t2) and month 12 (t3) in both study groups]
• Assessment of valvular cardiomyopathy: LV diameters (LVESD, LVEDD) [Time frame: Assessment at post-procedural baseline (Day 0 = t1), month 6 (t2), and month 12 (t3) in both study groups.]
• Assessment of valvular cardiomyopathy LV volumes (LVESV, LVEDV) [Time frame: Assessment at post-procedural baseline (t1), month 6 (t2), and month 12 (t3) in both study groups.]
• Assessment of valvular cardiomyopathy LV strain (GLS) [Time frame: Assessment at post-procedural baseline (t1), month 6 (t2), and month 12 (t3) in both study groups.]

Eligibility criteria

Inclusion criteria

• Presence of fused BAV phenotype with an asymmetric configuration (commissural orientation < 170 degree) \[14\]
• Severe aortic regurgitation (vena contracta (vc) > 6mm and/or pressure half-time (PHT) < 200 ms and/or effective regurgitant orifice area (EROA) > 30 mm2 and/or regurgitant volume (RV) > 60 ml/beat and/or left ventricular end-systolic diameter (LVESD) > 50mm (or indexed LVESD > 20mm/m2 BSA) and/or regurgitation fraction (RF) in cardiothoracic MRI > 40%) (at least one parameter is required) \[15\]
• Isolated aortic valve surgery or concomitant procedure (including CABG and/or mitral/tricuspid valve surgery and/or ascending aortic surgery)
• Willingness to participate and written informed consent
• Age at surgery > 18 years

Exclusion criteria

• Moderate/severe BAV stenosis (pmean > 20mmHg)
• Moderate/severe BAV cusp calcifications extending beyond the raphe region and/or necessitating patch implantation (deemed irreparable based on preoperative TOE (as by decision of the operating surgeon)
• Concomitant aortic root aneurysm > 45mm requiring simultaneous aortic root surgery \[16\]
• Acute/subacute BAV endocarditis
• Contraindication to MRI

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Germany · 4 centers

• University Hospital Augsburg — Augsburg
• University Heart and Vascular Center Frankfurt — Frankfurt am Main
• Heart Center Leipzig — Leipzig
• Medical Center Hamburg-Eppendorf — Hamburg

Publications

• Girdauskas E, Stock S, Hofbauer D, Petersen J, Reichenspurner H, Holubec T, Walther T, Vogl T, Borger M, Gutberlet M, Kroncke T, Decker J, Zapf A, Lezius S, Lenz A, Lansac E, Bannas P. Towards a More Standardized Bicuspid Aortic Valve Repair: Rationale and Design of the CONTOUR Trial. Eur J Cardiothorac Surg. 2025 Dec 1;67(12):ezaf360. doi: 10.1093/ejcts/ezaf360. PMID 41124604

Identifiers

NCT: NCT06869954 · 23-0625

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗