Optimization of Commissural Alignment During Transcatheter Aortic Valve Implantation With Evolut FX+. A Randomized, Prospective Study.
Phase: NA
Conditions: Aortic Stenosis, Trans-catheter Aortic Valve Implantation, Commissural Alignment
Sponsor: Oslo University Hospital

 
 
Official title of the study: Optimization of Commissural Alignment During 
Transcatheter Aortic Valve Implantation with Evolut FX+: A randomized, 
prospective study 
 
NCT number: Not yet assigned. 
 
Regional ethics committee approval number: 904586. 
 
Date of the document final version: 14th of October 2025 
 
 

 
 
Study Protocol: Optimization of Commissural Alignment During Transcatheter 
Aortic Valve Implantation with Evolut FX+: A randomized, prospective study 
 
Project leader: Trygve Sundby Hall 
Primary investigator and PhD-candidate: Ahmed Al-Ani 
Study coordinator: Cecilie Egeland 
Other members of the study group: Tonje Amb Aksnes and Jørgen Gravning 
PhD group: Trygve Sundby Hall, Anders Opdahl, Jørgen Gravning and Thor 
Edvardsen 
 
Versjon 1.2 
 
1. Background and rationale 
Transcatheter Aortic Valve Implantation (TAVI) has become a preferred treatment for patients 
with severe aortic stenosis who are at high or intermediate surgical risk (1). However, when 
compared to surgical aortic valve replacement, TAVI less often results in commissural 
alignment (2). Optimizing commissural alignment between the transcatheter valve and the 
native aortic valve is critical in preserving future coronary access, especially for younger 
patients and patients with known coronary artery disease that may require percutaneous 
coronary intervention (PCI) after TAVI (3, 4). In addition, an increasing number of patients are 
considered for redo-TAVI if failure of their first TAVI-valve occurs. Commissural misalignment 
impacts the feasibility of a redo-TAVI procedure, because of risk of sinus sequestration and 
coronary obstruction as well as the possibility for leaflet modification techniques of their 
prior TAVI valve (3). It may also have effects on valve functionality and durability (5, 6). 
Current implantation techniques vary in their ability to obtain commissural alignment, which 
impact coronary artery access and PCI after TAVI as well as redo-TAVI procedures (7, 8). 
 
The latest-generation self-expandable Evolut FX+ TAVI valve offers potential benefits 
in achieving commissural alignment or later better coronary access compared to older 
generations of the Evolut family (3, 4). Khera et al. compared Evolut FX and Evolut PRO+ in a 
non-randomized trial. They concluded that the new design features of the Evolut FX system 
appeared to significantly improve the ability to achieve commissural alignment (4). Later, the 
FX+ valve has been released, which incorporates a modified frame with larger coronary 

 
 
access windows to improve catheter maneuverability and access to coronary arteries. Recent 
work has indicated that the position of the delivery system in the descending aorta is 
important for commissural alignment and avoidance of coronary overlap (7). Furthermore, 
Konami et al recently demonstrated that rotation of the fluoroscopic “Hat” marker in the 
descending aorta is useful for improving commissural alignment in TAVI with Evolut devices 
(8). Currently, it is common that the operator rotates the delivery system in a left anterior 
oblique (LAO) projection to achieve that the "Hat" marker is facing the great curvature of the 
descending aorta before crossing the aortic arch, but at which LAO degree this should be 
performed has not been established.  
 
On this background, we believe that the optimal implantation technique to obtain the 
best possible commissural alignment and subsequent coronary access with the Evolut FX+ for 
each specific patient remains unclear and warrants further investigation. This is underpinned 
by recent data supporting that patient-specific rotation with the self-expanding "ACURATE 
neo" TAVI-valve, based on computed tomography (CT)-analysis obtained before implantation, 
may improve the success rate of commissural alignment (9). Also, another study by 
Bieliauskas et al. based a patient- and valve-specific implantation technique on each 
patient´s pre-operative CT (three types of valves; Evolut R/PRO, ACURATE neo2, Portico), 
which allowed for safe and reproducible implantation (10). The purpose of the present study 
is to prospectively evaluate the efficacy and safety of a novel patient-specific rotation of the 
Evolut FX+ TAVI valve and the delivering system during the transfemoral (TF) procedure. 
Specifically, it aims to evaluate and compare the commonly used fluoroscopic (X-ray) LAO 
degree for rotation of the delivery system and more patient-specific LAO degree achieved by 
CT analysis prior to the procedure. The degree of alignment and coronary overlap will be 
measured with ECG-gated CT after the procedure. Thus, it will prospectively explore if these 
two techniques differ in obtaining commissural alignment, coronary overlap and safety 
outcomes following implantation of latest-generation Evolut FX+ valve. 
 
2. Study objectives 
In patients with severe aortic stenosis indicated for TF-TAVI with the Evolut FX+ valve after 
multidisciplinary heart team meeting: 
Primary Objective: 
• 
To investigate and compare commissural alignment of two rotational positioning 
methods based on the positioning of the fluoroscopic “Hat” marker at the descending 
aorta with the Evolut FX+ valve. 
Secondary Objective: 

 
 
• 
To evaluate and compare the likelihood of successful post-TAVI coronary access 
assessed by CT after TAVI with the Evolut FX+ valve. 
 
3. Study hypotheses 
In patients with severe aortic stenosis indicated for TF-TAVI with the Evolut FX+ valve after 
heart team meeting: 
 
1. A strategy of patient-specific rotation will be superior to a generalized approach in 
obtaining commissural alignment. 
 
2. A strategy of patient-specific rotation will increase the likelihood of successful post-
TAVI coronary access assessed by CT after TAVI with the Evolut FX+ valve. 
 
4. Overview of study design 
• 
Randomized, prospective, single-center observational study. 
 
 

 
 
5. Study sample 
5.1. Target enrollment: 40 patients. 
5.2 Inclusion criteria:  
• 
Patients with severe aortic stenosis indicated for TAVI after heart team 
meeting. 
• 
Age ≥65 years. 
• 
Patients planned by the TAVI team to receive a self-expandable valve (Evolut 
FX+ valve). 
• 
Patients providing informed consent. 
5.3 Exclusion criteria:  
• 
Severe peripheral vascular disease preventing transfemoral access. 
• 
Prior aortic valve replacement or bicuspid valve. 
• 
Severely reduced kidney function (estimated glomerular filtration rate <30). 
 
6. Randomized treatments 
Subjects will be randomized to a patient-specific rotational method or a conventional 
generalized rotational method before the procedure. 
 
7. Study procedures 
7.1 Overview of study procedures 
Pre-procedural (standard) assessment 
• 
Baseline CT scan to evaluate aortic root anatomy by using 3mensio analysis software. 
• 
Clinical and echocardiographic assessment (left ventricular function, aortic valve area, 
mean gradient). 
• 
Coronary angiography to assess native coronary anatomy. 
• 
Blood tests. 
Procedural steps 

 
 
• 
Valve implantation: The Evolut FX+ valve will be implanted using standard 
transfemoral access under fluoroscopic guidance. 
• 
Rotational positioning methods:  
• 
Method 1 (generalized approach): The “Hat” marker positioned in the 
descending aorta with fluoroscopy at 25 degrees left anterior oblique. 
• 
Method 2 (patient-specific approach): The “Hat” marker positioned in the 
descending aorta with fluoroscopy at the pre-procedural identified degree at 
which the right and non-coronary cusp overlap (from CT analysis). 
Post-procedural assessment 
• 
CT imaging:  
o Assessment of commissural alignment post-TAVI. 
o Coronary ostial relationship with the implanted valve. 
• 
Clinical and echocardiographic assessment (left ventricular function, aortic valve area, 
mean gradient). 
• 
Blood tests. 
• 
Hospital chart review for safety endpoints. 
 
 
 

 
 
7.2. Screening and recruitment 
All patients with severe aortic stenosis indicated for TAVI with the Evolut FX+ valve after 
heart team meeting at Oslo University Hospital (OUS) Ullevål will be screened for eligibility 
and screening logs will be registered during the whole study period. Potential participants 
will be identified after the heart and TAVI meetings have been completed, as only those who 
receive a decision for Evolut FX+ will be asked to participate in the study (there are always 
two operators from the intervention group present and all operators at the section (5 
operators) will be involved in the recruitment by notifying the study group if patients have 
been approved for TAVI with Evolut FX+. The participants will then receive written and verbal 
information from one of the individuals in the study group or one of the treating physicians 
at the department (either in-hospital during their pre-operative evaluation so that they will 
have time to evaluate over days/weeks before they possibly consent to inclusion, or 
alternatively early during admission for surgery so that patients will have sufficient time to 
evaluate if they want to participate (at least the day before)). All participants will meet and 
receive information from a study group member (Cecilie Egeland, Ahmed Al-Ani, Trygve 
Sundby Hall, Tonje Amb Aksnes, Jørgen Gravning) before giving consent, and this study group 
member will not be in a "treatment relationship" with the patient (ref. 7.3 and paragraph 13 
of the Health Research Act) . 
7.3. Informed consent 
Written informed consent after oral information and reading relevant documents will be 
obtained before the procedure. A copy of the signed consent document will be given to the 
patient and the original will be retained by the study personnel. The informed consent will be 
obtained in accordance with paragraph 13 of the Health Research Act. This means that the 
informed consent and signature will be obtained by a "neutral" person that is not involved in 
the treatment of the patient. 
7.4. Randomization 
Randomization will be performed using sealed envelopes, each containing a pre-determined 
treatment assignment, that are opened sequentially as participants are enrolled. This 
process helps to maintain allocation concealment and reducing the potential for selection 
bias. 
7.5. Follow-up 
Following the operation routine clinical follow-up will be performed as part of the standard 
procedure for all patients that are operated in our hospital. Standard clinical assessment, 
blood tests and safety endpoints will be reviewed and registered from the hospital chart. An 
ECG-gated CT scan of the heart after the TF-TAVI procedure will be performed during or a 
few days after the hospital stay. 

 
 
7.6 Variable list 
A detailed variable list is attached as supplementary information to the present protocol. 
 
8. Study outcomes 
8.1 Primary efficacy outcomes 
• 
Proportion of patients achieving commissural alignment post-TAVI (measured by CT-
analysis after TAVI). 
• 
The relationship between alignment and rotational positioning method after TAVI. 
8.2 Secondary efficacy outcome 
• 
The likelihood of successful coronary access assessed by CT after TAVI. 
8.3 Safety outcomes 
• Pacemaker, vascular complications, pericardial effusion, open surgery, valve 
embolization, stroke, peri-procedural MI, kidney failure and death. 
 
9. Data management 
• 
All data will be de-identified and registered in “Medinsight”. Data will be obtained 
from hospital records reporting investigations that are performed in their usual 
clinical pathway. The only additional investigation that will be performed will be an 
additional CT-scan after the TAVI. 
 
10. Withdrawal of participants 
Participants may withdraw consent to participate at any stage of the study and for any reason. 
 
11. Statistical considerations 
• 
Commissural alignment will be reported and statistically compared by use of the 
proportion of patients achieving alignment (defined as 0 degrees to 15 degrees being 
commissural alignment, 15.1 degrees to 30.0 degrees being mild commissural 
misalignment, 30.1 degrees to 45.0 degrees being moderate commissural 
misalignment and 45.1 to 60.0 degrees being severe commissural misalignment) (3). 

 
 
• 
Coronary access feasibility will be reported and statistically compared by use of 
proportion of patients achieving coronary access feasibility (defined as severe 
coronary overlap (within 0 degrees to 15 degrees) and less severe coronary overlap 
(>15 degrees)) (4). 
• 
Safety outcomes will be reported and statistically compared by use of the proportion 
of patients with occurrence of each safety outcome. 
• 
Categorical variables will be presented as numbers and/or percentages, and 
continuous variables will be presented as means (standard deviation) or medians 
(quartiles 1 to 3). Continuous variables will be compared with the t-test (if normally 
distributed) or the Mann-Whitney U test (if skewed). Categorical variables will be 
compared by using the Pearson chi square test or Fischer’s exact test (if any field 
included <6). A p-value of < 0.05 will be regarded statistically significant, and all 
hypothesis testing will be two tailed. 
• 
The potential difference in proportion of commissural alignment between the two 
techniques is unknown and thus no power calculation has been done. Comparisons 
between groups will therefore be descriptive and mainly hypothesis-generating. 
 
12. Study organization 
The study organization will be comprised of study coordinator Cecilie Egeland, primary 
investigator MD Ahmed Al-Ani and project leader MD PhD Trygve Sundby Hall. The study 
group will also include MD PhD and section leader of cardiac intervention at OUS, Ullevål 
Tonje Amb Aksnes and Professor and section leader of the echocardiography department at 
OUS, Ullevål Jørgen Gravning. The TAVI-team at the section of cardiac intervention at OUS, 
Ullevål supports the study and will assist in recruiting patients. The study will be part of an 
ongoing PhD-project at the University of Oslo that is supervised by MD PhD Trygve Sundby 
Hall, MD PhD Anders Opdahl, Professor Jørgen Gravning and Professor Thor Edvardsen. 
 
13. Ethical considerations 
• 
The study will be conducted according to the principles of the Declaration of Helsinki 
and the Uniform Requirements for Manuscripts Submitted to Biomedical Journals by 
the International Committee of Medical Journal Editors.  
• 
We will seek approval in our hospital’s local ethics committee and the privacy 
protection act supervisor. 

 
 
• 
We will seek approval from the Norwegian Regional Committees for Medical and 
Health Research Ethics (REK). 
• 
Informed consent will be obtained from all participants. 
• 
Data confidentiality will be maintained according to Good Clinical Practice (GCP) 
guidelines. 
• 
We consider the study to be a pilot study as this specific approach to patient-specific 
rotation has not been investigated previously. However, similar studies have been 
conducted on different rotation methods that have improved commissural alignment 
of current and previous generations of TAVI valves. Based on the findings found in 
these studies, we believe that a further patient-specific approach to the degree of 
rotation in the descending aorta could improve commissural alignment and 
potentially facilitate subsequent access to the coronary arteries by angiography/PCI, 
as well as improve the results of “redo TAVI” and valve functionality/durability. 
However, we believe it is ethically sound practice to initially evaluate whether 
differences in commissural alignment will be observed and, if so, how large this is, as 
well as to conduct CT-based analysis for the likelihood of coronary access after 
implantation. We have opted not to test coronary access after surgery with selective 
coronary angiography as this procedure does not have sufficient benefit and only 
imposes additional risk to the patients included. As various rotation techniques are 
currently performed based on the operator's own judgment, we believe it is 
appropriate to initially investigate the approach scientifically, prospectively and 
systematically in a study. Based on the observations from the study, it will be easier to 
assess whether it is appropriate to conduct a larger study to evaluate whether the 
method will actually improve coronary access in future clinical events and the results 
of "redo TAVI" in those patients who need this in the years after the first 
implantation. 
• 
The study will assess and compare two techniques that in daily clinical practice may 
be used according to operator preference. Thus, the consequences of participating in 
the study are minimal for each patient, since the only additional investigation will be 
a post-TAVI CT-scan. However, this CT-scan may also be an advantage for the included 
patients as information obtained from this CT will be informative for future 
investigations and if PCI is needed during follow-up. Therefore, we believe that both 
the potential benefit and the potential risk for each study participant is limited. The 
observations from the study may inform and better define if there should be a 
preferred implantation technique in the future. 
 
14. Estimated timeline 

 
 
OUS Ullevål hospital performs about 200 TAVIs per year, of which approximately 60% (n = 
120) are performed with the Evolut FX+ valve. We aim to continuously include patients from 
September 2025 until the target inclusion of 40 patients is reached (estimated to be around 
January-May 2026). After final inclusion, the data will be analysed and used for research until 
May 2031 (project period end). After May 2031, the data will be stored for five years until 
May 2036 (for control purposes and no active research will be done after project period end 
May 2031). 
 
15. Purpose and implications 
We anticipate that the patient-specific implantation techniques may: 
• 
Improve commissural alignment, leading to better coronary access and a higher 
degree of success in redo TAVI-procedures. 
• 
Reduce procedural complexity for future diagnostic angiography/PCI/redo TAVI-
procedures. 
• 
Contribute to refining best practices for Evolut FX+ valve implantation in TAVI 
patients. 
 
16. Financial aspects and disclosures 
• 
The study will be financed in full by Oslo University Hospital. Dr. Al-Ani disclose that 
he serves as a proctor (interventional cardiologist) for Medtronic, which has 
manufactured the Evolut FX+ valve. Medtronic will have no involvement in the study. 
The other study personnel have no disclosures to report.  
 
17. Publication plan 
• 
The observations from this study will be reported in peer-reviewed medical journals 
and at national/international conferences. 
 
18. References 
1. Vahanian A., Beyersdorf F., Praz F. et al. 2021 ESC/EACTS guidelines for the management of 
valvular heart disease. Eur Heart J . 2022;43:561-632. 

 
 
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Native Aortic Valve Following Surgical and Transcatheter Aortic Valve Replacement and its 
Impact on Valvular Function and Coronary Filling. JACC Cardiovasc Interv. 2018 Sep 
10;11(17):1733-1743. 
3.  Tang GHL, Amat-Santos IJ, De Backer O et al. Rationale, Definitions, Techniques, and 
Outcomes of Commissural Alignment in TAVR: From the ALIGN-TAVR Consortium. JACC 
Cardiovasc Interv. 2022 Aug 8;15(15):1497-1518. 
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Alignment in TAVR With the Newest Evolut FX Self-Expanding Supra-Annular Valve: First-in-
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2020;13(9):1043– 1045. 
7. Tang GHL, Sengupta A, Alexis SL et al. Conventional versus modified delivery system 
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Cardiovasc Interv. 2022 Feb;99(3):924-931. 
8. Konami Y, Sakamoto T, Suzuyama H et al. Commissural alignment in the Evolut TAVR 
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2023;9(2):156-165. 
9. Redondo A, Valencia-Serrano F, Santos-Martínez S et al. Accurate commissural alignment 
during ACURATE neo TAVI procedure. Proof of concept. Rev Esp Cardiol (Engl Ed). 2022 
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