Transcatheter Aortic Valve Implantation Without Predilation

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that the avoidance of balloon valvuloplasty for predilation of the native aortic valve is associated with a reduction of the composite primary endpoint in TAVI patients with severely impaired left-ventricular ejection fraction (LVEF ≤35%).

Detailed Description
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Transcatheter aortic valve implantation (TAVI) has evolved as an alternative to surgical aortic valve replacement (SAVR) with now more than 50,000 implantations in patients with symptomatic severe aortic stenosis, who were considered to be at very high or prohibitive operative risk. Before deployment of transcatheter heart valves (THV), current medical practice requires right-ventricular rapid burst pacing (>180 bpm) with induction of a functional cardiac arrest for up to 30 seconds for balloon aortic valvuloplasty (BAV). This step is thought to be necessary to predilate the native aortic valve and to facilitate an accurate positioning of the THV. However, BAV has been shown to have numerous detrimental effects: i) the functional cardiac arrest induced by rapid pacing for BAV leads to transient coronary, cerebral, and renal ischemia. ii) In patients with impaired left ventricular ejection fraction, prolonged cardiac depression after rapid pacing is observed and may result in hemodynamic failure and systemic inflammatory response syndrome (SIRS), which are both associated with a high peri-procedural mortality. iii) BAV has been identified as a major source of embolization of thrombotic and valvular material and increases the risk for coronary obstruction with subsequent myocardial infarction and stroke. iv) the local trauma in the left-ventricular outflow tract caused by BAV contributes to conduction disturbances with the need for permanent pacemaker implantation after TAVI. A non-randomized pilot study by Grube et al. (JACC Interventions 2011) has recently shown that TAVI without BAV is feasible and safe, since self-expanding THV are able to dilate the stenosed aortic valve through the radial forces of the self-expanding nitinol frame, in which the prosthesis is mounted. According to the mentioned study, omitting BAV allows the delivery of the THV in a controlled fashion without hemodynamic compromise of the patient. Patients with LVEF≤35% will be randomized (like the flip of a coin) to TAVI without BAV (experimental group) or TAVI with BAV for predilation (control group).

Official Title
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Use of the Self-Expanding Medtronic CoreValve Prosthesis Without Predilation in Patients With Severely IMPaired Left-VentrIcular Ejection Fraction for TAVI Trial - The SIMPLIFy TAVI Trial

Conditions
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Aortic Stenosis, Left Ventricular Function Systolic Dysfunction, High-risk Patients, Transcatheter Aortic Valve Implantation

Intervention / Treatment
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* Procedure: TAVI without BAV
* Procedure: TAVI standard procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LVEF ≤35% Aortic valve stenosis with an aortic valve area <1 cm2 (<0,6 cm3/m2) Males or females at least 18 years of age Logistic EuroSCORE ≥15% and age ≥75 years or if age <75 years: logistic EuroSCORE ≥20% and/or a significant contraindication for open heart surgery (e.g., porcelain aorta or severe COPD) Signed informed consent Exclusion Criteria: Patients with a device regulating the heart rhythm by pacing (e.g. pacemaker, resynchronization device, implanted defibrillator) Patients with a pre-existing class I or class II indication for new pacemaker implantation according to the 2007 ESC guidelines Lack of written informed consent, severe mental disorder, drug/alcohol addiction Life expectancy < 1 year Hypersensitivity or contraindication to acetyl salicyl acid, heparin, ticlopidine, clopidogrel, nitinol or sensitivity to contrast media that cannot be adequately premedicated Recent myocardial infarction (STEMI within the last 3 months) Left ventricular or atrial thrombus by echocardiography Uncontrolled atrial fibrillation Mitral or tricuspidal valvular insufficiency (> grade II) Previous aortic valve replacement with mechanical valve Evolutive or recent cerebrovascular event (within the last 3 months) Vascular conditions that make insertion and endovascular access to the aortic valve impossible Symptomatic carotid or vertebral arterial narrowing (>70%) disease Abdominal or thoracic aortic aneurysm in the path of the delivery system Bleeding diathesis or coagulopathy or patient refusing blood transfusion Active gastritis or peptic ulcer disease Severely impaired renal function, GFR < 30 ml/min Participation in another drug or device study that would jeopardize the appropriate analysis of end-points of this study. High probability of non-adherence to the follow-up requirements (due to social, psychological or medical reasons) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAVI without predilation<br> | Procedure: TAVI without BAV<br>* Avoidance of balloon valvuloplasty (BAV) of the native aortic valve before valve deployment<br>|
| Active Comparator: Standard TAVI procedure<br> | Procedure: TAVI standard procedure<br>* TAVI standard procedure including BAV before valve deployment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary composite efficacy endpoint | Occurrence of all-cause mortality, stroke, non-fatal myocardial infarction, acute kidney injury, or pacemaker implantation at 30 days after TAVI. | 30 days after TAVI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular & all-cause mortality |  | 6 months, 12 months after TAVI | 
| Major/minor stroke |  | 6 months, 12 months after TAVI | 
| Myocardial infarction |  | 6 months, 12 months after TAVI | 
| conduction disturbances and pacemaker implantation rate |  | 6 months, 12 months after TAVI | 
| Acute kidney injury |  | 6 months, 12 months after TAVI | 
| Rate of postdilation |  | 30 days, 6 months, 12 months after TAVI | 
| Transvalvular mean gradient as assessed by echocardiography |  | 30 days, 6 months, 12 months after TAVI | 
| Re-hospitalization for symptoms of cardiac/valve-related decompensation |  | 30 days, 6 months, 12 months after TAVI | 
| Severity of periprosthetic aortic regurgitation (AR) as assessed by echocardiography, angiography, and hemodynamic measurements (AR index) |  | 30 days, 6 months, 12 months after TAVI | 
| Life-threatening/major/minor bleeding |  | 30 days, 6 months, 12 months after TAVI | 
| Vascular access complications |  | 30 days, 6 months, 12 months after TAVI | 
| Repeat procedure for valve-related dysfunction (surgical or interventional therapy) |  | 30 days, 6 months, 12 months after TAVI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic stenosis, Transcatheter aortic valve implantation, TAVI, Predilation, Balloon valvuloplasty, BAV, CoreValve