Aortic Valve Replacement Versus Conservative Treatment in Asymptomatic Severe Aortic Stenosis

Not Applicable

Completed

• Conditions: Aortic Stenosis
• Interventions: Procedure: surgical aortic valve replacement

• Registration Number: NCT02436655
• Lead Sponsor: Clinical Centre of Serbia

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 Timeline

• Study First Submitted: 2015-04-30
• Study First Submitted QC: 2015-05-04
• Study First Posted: 2015-05-07
• Study Start: 2015-06
• Primary Completion: 2021-05
• Study Completion: 2021-05
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-23
• Last Update Posted: 2022-01-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 157

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
elective aortic valve replacement	surgical aortic valve replacement	elective aortic valve surgery (replacement) within 4 weeks after randomization

Primary Outcome Measures

Name	Time	Method
all cause death, Major Adverse Cardiac Event (MACE) including: ( Acute Myocardial Infarction - AMI, Stroke - CVI, unplanned hospitalization for Heart failure (HF) needing intravenous treatment	5 years

Secondary Outcome Measures

Name	Time	Method
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
thromboembolic complications based on clinical symptoms, signs and imaging studies	5 years
repeated major adverse cardiovascular events	5 years
all-cause death + heart failure hospitalization	5 years

Trial Locations

Locations (14)

Vilnius University Hospital Santariskiu klinikos; 🇱🇹 Vilnius, Lithuania

University Clinical Centre Zvezdara; 🇷🇸 Belgrade, Serbia

Cardiovascular Center 'Dedinje"; 🇷🇸 Belgrade, Serbia

University Clinical Center ''Sestre milosrdnice''; 🇭🇷 Zagreb, Croatia

CCSerbia; 🇷🇸 Belgrade, Serbia

Institute for Clinical and Experimental Medicine (IKEM); 🇨🇿 Prague, Czechia

University Hospital Galway; 🇮🇪 Galway, Ireland

Medical University of Silesia; 🇵🇱 Katowice, Poland

Insitute for Cardiovascular Diseases "Sremska Kamenica"; 🇷🇸 Novi Sad, Serbia

University Hospital Brno; 🇨🇿 Brno, Czechia

Cardiovascular Center Aalst; 🇧🇪 Aalst, Belgium

University Clinical Center "Rebro"; 🇭🇷 Zagreb, Croatia

Hôpital Cardiologique de Haut Lévèque; 🇫🇷 Pessac, France

Città della Salute e della Scienza di Torino; 🇮🇹 Turin, Piedmont, Italy