Aortic Stenosis
Conditions
Keywords
aortic stenosis, normal ejection fraction, asymptomatic
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.
Interventions
PROCEDUREsurgical aortic valve replacement
open heart aortic valve replacement
Sponsors
Clinical Centre of Serbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment | 36 months |
Secondary
| Measure | Time frame |
|---|---|
| repeat aortic valve surgery in operated patients in both groups | 5 years |
| major bleeding according to consensus report from the Bleeding Academic Research Consortium | 5 years |
| in-hospital and 30 days operative mortality in operated patients in both groups | 30 days |
| repeated major adverse cardiovascular events | 5 years |
| all-cause death + heart failure hospitalization | 5 years |
| thromboembolic complications based on clinical symptoms, signs and imaging studies | 5 years |
Countries
Belgium, Croatia, Czechia, France, Ireland, Italy, Lithuania, Poland, Serbia
Outcome results
None listed