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

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Процедура 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.
• Процедура 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.

Первичные конечные точки

• 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. [Срок оценки: 2 years]

Вторичные конечные точки (10)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Швейцария · 3 центра

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

Публикации

• 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

Идентификаторы

NCT: NCT05310461 · TIAMAR

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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