Early Surgery Versus Conventional Treatment in Very Severe Aortic Stenosis

Study Overview
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Brief Summary
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The optimal timing of surgical intervention remains controversial in asymptomatic patients with very severe aortic stenosis. The investigators therefore try to compare long-term clinical outcomes of early surgery with those of conventional treatment strategy in a prospective randomized trial.

Detailed Description
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Management of asymptomatic patients with severe aortic stenosis (AS) remains controversial, and the combined risks of aortic valve surgery and late complications of aortic valve prosthesis need to be balanced against the possibility of preventing sudden death and lowering cardiac mortality. Considering that sudden cardiac death occurs at a rate of approximately 1% per year and that the average postoperative mortality of isolated AV replacement is 3.0-4.0%, the 2007 European Society of Cardiology guidelines do not recommend aortic valve surgery for asymptomatic patients with severe AS and the 2006 American College of Cardiology/American Heart Association guidelines recommend surgery as a class IIb indication only in patients with extremely severe AS and who are at low operative risk. Clinical outcomes vary widely according to the severity of stenosis in asymptomatic AS, and asymptomatic patients with very severe AS are often referred for aortic valve replacement in clinical practice despite the lack of data supporting early surgery. Rosenhek et al recently reported a worse prognosis with a higher event rate and a risk of rapid deterioration in very severe AS, and the investigators also recently reported that compared with the conventional treatment strategy, early surgery in patients with very severe AS is associated with an improved long-term survival in a prospective, observational study. However, there have been no prospective,randomized studies comparing early surgery with a watchful waiting strategy in very severe AS. We sought to compare long-term clinical outcomes of early surgery with those of conventional management based on current guidelines.

Official Title
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Randomized Comparison of Early Surgery Versus Conventional Treatment in Very Severe Aortic Stenosis

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Procedure: Early surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: asymptomatic patients with very severe aortic stenosis who are potential candidates for early surgery. Very severe aortic stenosis are defined as a critical stenosis in the AV area ≤ 0.75 square centimeter fulfilling one of the following criteria; a peak aortic velocity ≥ 4.5 m/sec or a mean transaortic pressure gradient ≥ 50 mmHg on Doppler echocardiography. According to the revised 2014 AHA/ACC Valvular Heart Disease Guideline that recommends exercise testing to confirm the absence of symptoms in asymptomatic patients with severe AS (Class IIa), eligible patients with a positive exercise test will be excluded from the entry after May, 2014. Exclusion Criteria: Exertional dyspnea Angina Syncope Left ventricular ejection fraction < 50% Significant aortic regurgitation Significant mitral valve disease Pregnancy Age < 20 years or > 80 years Coexisting malignancies Positive exercise test

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: early aortic valve replacement
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Conventional treatment<br>In the conventional treatment group, indications for aortic valve replacement surgery are development of symptoms, reduced left ventricular systolic function and an increase in aortic jet velocity > 0.5 m/sec during follow-up. | |
| Active Comparator: Early Surgery<br>Early surgery is performed within 2 months of randomization. | Procedure: Early surgery<br>* Early surgery is performed within 2 months of randomization.<br>* Other names: Early aortic valve replacement surgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac mortality | defined as death from complications of myocardial infarction, heart failure, shock, complications of cardiac surgery or intervention, other cardiovascular diseases including sudden cardiac death | Entire follow-up ( a minimum of 4 years) | 
| Operative mortality | Operative mortality is defined as death within 30 days of surgery. | up to 30 days after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death |  | Entire follow-up (a minimum of 4 years) | 
| Repeat aortic valve surgery |  | Entire follow-up (a minimum of 4 years) | 
| Clinical thromboembolic events | Diagnosis of thromboembolic events is based on clinical symptoms, signs and imaging studies. | Entire follow-up (a minimum of 4 years) | 
| Hospitalization due to congestive heart failure | A hospitalization due to congestive heart failure is defined as an unplanned, urgent admission for the management of congestive heart failure. | Entire follow-up (a minimum of 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic stenosis, surgery, survival