Early Versus Deferred Aortic Valve Replacement in Patients With Moderate Aortic Stenosis and Mitral Regurgitation

Official title

Early Versus Deferred Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation: a Randomized Clinical Trial

Overview

The aim of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with moderate mitral regurgitation.

Detailed description

In more than one-half of all patients with valvular heart disease, more than a single valve is involved. Valvular aortic stenosis coexists with significant mitral valve disease in up to one-third of patients undergoing aortic valve replacement (AVR).

Guidelines for the management of valvular heart disease provide recommendations for isolated valvular lesions; data to guide timing of intervention in patients with multivalvular disease is however scarce. Currently, patients with moderate aortic stenosis (AS) in combination with mitral regurgitation have an indication for aortic valve replacement (AVR) only if the concomitant mitral regurgitation meets an indication for surgery. However, the hemodynamic stress of combined valvular lesions is greater than its individual components, and patients may benefit from early intervention.

Furthermore, the presence of multivalvular heart disease complicates the assessment of individual valvular lesions. In patients with combined AS and mitral regurgitation (MR), increased left ventricular pressure exacerbates the mitral regurgitant volume. Conversely, decreased forward flow across the aortic valve underestimates the severity of aortic stenosis when assessed by a pressure gradient.

Standard cut-off values inadequately reflect the hemodynamic stress in concomitant aortic and mitral valve disease, and recommendations for the timing of valvular replacement fail to account for the complex interplay of multiple valvular lesions.

Timing of intervention in patients with combined AS and MR is therefore challenging and evidence on the optimal timing of intervention is scarce.

Thus, the objective of the present study is to investigate safety and efficacy of early versus deferred aortic valve replacement in patients with moderate aortic stenosis combined with at least moderate mitral regurgitation.

Patients with combined aortic stenosis and mitral regurgitation will be screened for eligibility. If eligible and informed consent is provided, patients will be randomly allocated in a 1:1 ratio to early (within 3 months) or deferred aortic valve replacement (with or without mitral valve intervention).

Interventions

• Procedure Transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement
  Early transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.
• Procedure Deferred treatment, with intervention once AVA is ≤1.0 cm2 or if concomitant mitral regurgitation meets an indication for intervention
  Deferred transcatheter or surgical aortic valve replacement with or without transcatheter or surgical mitral valve repair/replacement.

Primary outcome measures

• The primary outcome will be a composite of all-cause death, stroke, and unplanned hospitalization for heart failure related to valvular heart disease at 2 years. [Time frame: 2 years]

Secondary outcome measures (10)

• All-cause death [Time frame: 5 years]
• Cardiovascular death [Time frame: 5 years]
• Neurologic events [Time frame: 5 years]
• Hospitalization for heart failure [Time frame: 5 years]
• New-onset atrial fibrillation [Time frame: 5 years]
• Implantation of a permanent pacemaker [Time frame: 5 years]
• Aortic or mitral valve re-intervention [Time frame: 5 years]
• NYHA functional class [Time frame: 5 years]
• Days alive out of hospital (DAOH) [Time frame: 5 years]
• The evaluation Health-related quality of life assessment by means of the KCCQ 12 questionnaire [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Age ≥18 years
• Moderate native aortic stenosis defined by an aortic valve area (AVA) ≤1.5 cm2 and >1.0 cm2 and transvalvular mean gradient ≥20 mmHg and <40 mmHg.
• Primary or secondary mitral regurgitation (at least moderate) defined by effective regurgitant orifice area (EROA) ≥20 mm2 or regurgitant volume ≥30 ml
• New York Heart Association (NYHA) functional class ≥2

Exclusion criteria

• Life expectancy <1 year irrespective of valvular heart disease
• Left ventricular ejection fraction <30% or LVESD >70mm
• Echocardiographic evidence of severe right ventricular dysfunction
• Untreated clinically significant CAD requiring revascularisation
• Moderate or severe aortic regurgitation
• Severe tricuspid valve disease requiring intervention
• Symptomatic patients with severe primary MR who are operable and not high risk
• Patients with severe secondary MR who remain symptomatic despite optimal medical therapy and who are judged appropriate for transcatheter edge-to-edge repair or surgery by the Heart Team
• Transcatheter or surgical treatment of valvular and/or coronary artery disease within 90 days prior to randomization
• COPD with home oxygen therapy
• Estimated or measured systolic PAP >70 mmHg
• Stroke within 30 days prior to the randomization
• Inability to provide written informed consent
• Participation in another cardiovascular trial before reaching the primary endpoint.

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

Open label

Primary purpose

Treatment

Study locations

Switzerland · 3 centers

• Insel Gruppe AG, Inselspital Bern — Bern
• University Hospital Geneva (HUG) — Geneva
• Heart Clinic Hirslanden — Zurich

Publications

• Shah AM, Solomon SD. Valvular heart disease in older adults: seeking an ounce of prevention. Eur Heart J. 2016 Dec 14;37(47):3523-3524. doi: 10.1093/eurheartj/ehw354. Epub 2016 Sep 1. No abstract available. PMID 27590452
• Khan F, Okuno T, Malebranche D, Lanz J, Praz F, Stortecky S, Windecker S, Pilgrim T. Transcatheter Aortic Valve Replacement in Patients With Multivalvular Heart Disease. JACC Cardiovasc Interv. 2020 Jul 13;13(13):1503-1514. doi: 10.1016/j.jcin.2020.03.052. PMID 32646692
• Unger P, Pibarot P, Tribouilloy C, Lancellotti P, Maisano F, Iung B, Pierard L; European Society of Cardiology Council on Valvular Heart Disease. Multiple and Mixed Valvular Heart Diseases. Circ Cardiovasc Imaging. 2018 Aug;11(8):e007862. doi: 10.1161/CIRCIMAGING.118.007862. No abstract available. PMID 30354497

Identifiers

NCT: NCT05310461 · TIAMAR

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗