Brief Title
Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis
Official Title
Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis: (AVATAR Trial): A Multicentre Randomized Controlled Trial
Brief Summary
Whether to intervene in asymptomatic patients with severe aortic stenosis and normal left
ventricular ejection fraction remains controversial. The investigators therefore try to
compare clinical outcomes of elective aortic valve replacement to conventional treatment and
watchful waiting strategy in a prospective randomized trial.
Detailed Description
Aortic valve replacement (AVR) therapy is obvious choice in symptomatic severe aortic
stenosis (AS) patients, because it improves symptoms, LV function and survival. Therefore,
the accurate diagnosis of the disease, determination of its severity and precise evaluation
of patients' clinical status is essential. However, the treatment decisions and indication
for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction
(LV EF) are vague and the subject of ongoing debate. The most recent European and American
guidelines have class I indication for AVR in asymptomatic severe AS patients with normal LV
EF only in patients already scheduled for other cardiac surgery (for example by-pass
surgery). In the case of symptom positive stress test American and European guideline
differs, with European guidelines having class I indication and American guidelines only IIb
indication. In all those cases of asymptomatic severe AS patients with normal LV EF the level
of evidence is C, in other words there are no randomized trials. The consequence is that the
decisions are made individually, patient by patient, and for this reason a patient with
identical echocardiographic/clinical characteristics might be operated in USA but not in
Europe (or any other part in the world), and vice-versa.
With the experience that has accumulated so far, there are retrospective and observational
data that elective AVR might lead to favorable outcome compared to late (after symptom onset)
surgery. This may especially come to attention with the understanding that annual risk of
sudden cardiac death in asymptomatic severe AS patients with normal LV EF might be very
similar or even a bit higher than operative mortality in experienced cardiac surgery centers.
Nevertheless, the majority of cardiologist worldwide are reluctant to send their asymptomatic
patient with isolated severe AS and normal LV EF to AVR, and it will probably stay like that
till randomized trials give us an answer whether elective AVR is beneficial.
Study Type
Interventional
Primary Outcome
all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment
Secondary Outcome
in-hospital and 30 days operative mortality in operated patients in both groups
Condition
Aortic Stenosis
Intervention
surgical aortic valve replacement
Study Arms / Comparison Groups
conventional drug treatment
Description: conservative treatment and watchful waiting till symptom onset (then aortic valve replacement). Other indications for aortic valve replacement include reduced left ventricular systolic function
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
157
Start Date
June 2015
Completion Date
May 2021
Primary Completion Date
May 2021
Eligibility Criteria
Inclusion Criteria:
- men and women of any ethnic origin aged ≥18 years
- Written informed consent
- V max across the aortic valve > 4m/s or Pmean ≥ 40mmHg and AVA ≤ 1cm2 or AVAi ≤
0.6cm2/m2 at rest
- Without reported symptoms
- Society of Thoracic Surgeons (STS) score < 8%
Exclusion Criteria:
- Participation in another clinical trial within 30 days prior randomization
- Pregnant or nursing women
- Mental condition rendering the patient unable to understand the nature, scope and
possible consequences of the study or to follow the protocol
- Positive stress-test defined as:
1. Anginal chest pain during testing
2. Syncope, dizziness during testing
3. Decrease in systolic blood pressure during exercise ≥ 20mmHg
4. Malignant arrhythmia during exercise testing (VT or VF)
- Left ventricular ejection fraction < 50% at rest
- Very severe AS (defined as Vmax > 5.5 m/s at rest)
- Significant disease of other valves (Mitral stenosis with Pmean > 5mg, or any
significant regurgitation ≥ 3+
- Recent AMI (< 1 year)
- Need for additional by-pass surgery or for aortic root replacement (i.e Bentall) or
ascending aorta in asymptomatic patients undergoing AVR
- Previous by-pass surgery
- Previous any heart valve surgery
- Impaired renal function, i.e. creatinine >200 µmol/L or glomerular filtration rate <
30 mL/min/1.73 m2
- Significant pulmonary hypertension at rest (PASP > 50mmHg)
- Uncontrolled hypertension at rest (systolic >180 mmHg and diastolic >100 mmHg)
- Significant co-morbidity with reduced life expectance (< 3 years)
- Uncontrolled Diabetes Mellitus (HbA1C > 9 %)
- Significant COPD (FEV1 < 70% of predicted value)
- Permanent or paroxysmal atrial fibrillation
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Marko Banovic, MD, PhD, FESC, FACC, ,
Location Countries
Belgium
Location Countries
Belgium
Administrative Informations
NCT ID
NCT02436655
Organization ID
FWA00011929
Responsible Party
Principal Investigator
Study Sponsor
Clinical Centre of Serbia
Study Sponsor
Marko Banovic, MD, PhD, FESC, FACC, Principal Investigator, Cardiology Department, University Clinical Centre of Serbia
Verification Date
May 2021