Clinical trial NCT05310461: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Valve Replacement in Patients With Moderate Aortic Stenosis Combined With Mitral Regurgitation
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2022-04-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: All-cause death
timeFrame: 5 years
measure: Cardiovascular death
timeFrame: 5 years
measure: Neurologic events
timeFrame: 5 years
measure: Hospitalization for heart failure
timeFrame: 5 years
measure: New-onset atrial fibrillation
timeFrame: 5 years
measure: Implantation of a permanent pacemaker
timeFrame: 5 years
measure: Aortic or mitral valve re-intervention
timeFrame: 5 years
measure: NYHA functional class
timeFrame: 5 years
measure: Days alive out of hospital (DAOH)
timeFrame: 5 years
measure: The evaluation Health-related quality of life assessment by means of the KCCQ 12 questionnaire
timeFrame: 5 years
Other outcomes:
measure: Major vascular complications (VARC-3)
timeFrame: 5 years
measure: Cardiac structural complications (major, minor) (VARC-3)
timeFrame: 5 years
measure: Cerebrovascular events (disabling and non-disabling stroke, and TIA) (VARC-3)
timeFrame: 5 years
measure: Myocardial infarction
timeFrame: 5 years
measure: Acute kidney injury (VARC-3)
timeFrame: 5 years
measure: Access-related non-vascular major complications (VARC-3)
timeFrame: 5 years
measure: Bleeding type 3-5 (VARC-3)
timeFrame: 5 years
measure: Prosthetic valve endocarditis
timeFrame: 5 years
measure: Prosthetic valve thrombosis
timeFrame: 5 years
measure: Valve-related dysfunction requiring reintervention
timeFrame: 5 years
Locations:
city: Bern
country: Switzerland
facility: Insel Gruppe AG, Inselspital Bern
city: Geneva
country: Switzerland
facility: University Hospital Geneva (HUG)
city: Zürich
country: Switzerland
facility: Heart Clinic Hirslanden
Study officials:
affiliation: Insel Gruppe AG
name: Thomas Pilgrim, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.