PROPOSITION OF KNOWN BUT NEW FOR TAVI IMAGING MODALITY Prof. Armine Zarayelyan Endovascular Surgery and Diagnostic Center

THE THEORETICAL PLANE OF THE PROJECT Developed by Professor Armine Zarayelyan

Background I Aortic stenosis (AS) is the most common valvular disorder and its prevalence is going to increase dramatically with the aging of the population Surgical aortic valve replacement is the definitive therapy for patients with severe AS who have symptoms or left ventricular dysfunction TAVI has been developed as an alternative to surgical aortic valve replacement with promising results for patients with severe AS considered to be at high or prohibitive surgical risk Being less invasive than open-chest aortic valve replacement, good outcome and effectiveness of TAVI procedure, it remains associated with the potential for serious complications and still confined to the treatment of elderly and high-risk patients Today there is evidence for the link between annulus size measured by methods currently available and such complications as a paravalvular AR (PVAR) and AV conduction disturbance (AVCD).

Background II Accurate aortic annulus size evaluation is difficult and might require different technique. The knowledge of measuring limitations of the aortic annulus by echocardiography, angiography, or computed tomography and development of new more accurate imaging modalities may decrease the possibility of patient-prosthesis mismatch. There is no any clinical study of dynamic aortic root anatomy with detailed description of the clinical anatomy and dynamic of aortic root, valves and nearby anatomic structures of the heart, which participates in aortic valve movement because of absence such an imaging technology.

AIM The aim of this proposal is theoretically substantiate the possibilities and advantages of use of IVUS imaging modality in evaluation of structures and measurements of aortic root for TAVI and apply for practical application and check of this theoretical proposition

TASKS I (Theoretical plane) To analyze the advantages and limitations of existing today imaging modalities for TAVI. To provide the comparison analyses of the technical specifications of IVUS imaging modality and other imaging modalities using today for TAVI. To theoretically develop the schematics and image models of aortic root that can be obtained by IVUS imaging modality. To investigate the applicability and develop the technique for IVUS imaging modality use in measurement of aortic root structure’s dimensions and diameters and evaluate its changes during cardiac cycle in patients with and without AS.

TASKS II (Practical plane) To develop the guidance and standard for aortic root structure by IVUS visualization in healthy population and in patients with AS. To compare the obtained by IVUS imaging modality results with results obtained by other imaging modalities. To evaluate the value of obtained by IVUS results for TAVI prostheses size proper selection and consequently for TAVI complication rate changes . To use the anatomic and dynamic specifications of aortic root obtained by IVUS for TAVI prostheses further development and elimination of complication rate.

It is important to be familiar not only with the anatomic relationship between aortic root structures but also with its changes during cardiac cycle It is equally important to be familiar with the complex anatomic relationships between the aortic root and its surrounding cardiac structures and their dynamic during cardiac cycle.

SO, WHY THEY ARE CHANGES AND CHANGES IN SO DIFFERENT WAYS??? Different Shapes of TAVI after deployment: Circular (A), triangular (B), and elliptic (C, D). SO, WHY THEY ARE CHANGES AND CHANGES IN SO DIFFERENT WAYS??? Influence of Size or Shape of the Orifice on the TAVI No leaflet distortion is present (A). Distortion occurred after TAVI deployment in an elliptic (B), a triangular (C), or an undersized circular orifice (D).

FOR SUCCESSFUL TAVI IT IS NECESSARY Accurate measurement of the true sagittal and coronal diameters of the aortic annulus at all level Knowledge of degree of sagittal and coronal diameters changes during cardiac cycle. Accurate measurement of aortic root structure’s dimensions and distances such as from basal ring to coronary artery orifice, dimensions of aortic valve leaflets, interleaflet triangles, sinus Valsalva, thickness of aortic wall on different level of aortic root , etc during cardiac cycle. Determination of degree of participation of such aortic structures as interleaflet triangles, sinus Valsava, aortic wall, aortic valve leaflets, LVOT wall in the aortic annulus diameter changes during cardiac cycle.

Coronal / Sagital = 5 - 20 % Sagital & coronal Sagital

SPECIFICATIONS, ADVANTAGES & LIMITATIONS OF IMAGING MODALITY I Adv & Limitation Specifications Imaging modality 2D TTE 2D TEE Angioscopy 3D TEE CT / MRI ICE IVUS Adv Dimension 3D Lim 2D Measurement diameters Sagittal & Coronal Only sagittal Cut plane 0° PA - coronal 90°LAO - sagittal At any plane or level (orthogonal or oblique to them planes At any plane or level (orthogonal or oblique to them planes) From aortic root near-field cardiac structures – SVC, RA Perpendicular to aortic root axis – cross-sectional & longitudinal section from inside of aorta Tangential across the aortic root Not perpendicular to aortic annulus Not perpendicular to aortic annulus. Additive effect of accumulative errors Perpendicular to body axis, not perpendicular to aortic annulus. Standard orthogonal axial & sagittal views need to be reconstructed for obliquely oriented aortic valve. Resolution In-plane <1,0mm In-plane – 0,5 mm Through plane – 50-150μm 3-5mm Through plane 1,25-1,5mm

SPECIFICATIONS, ADVANTAGES & LIMITATIONS OF IMAGING MODALITY II 2D TTE 2D TEE Angioscopy 3D TEE CT / MRI ICE (UltraICE/AcuNav) IVUS Advantages Easy and widely use, repeatability + - +/- - (+) Have confirmed protocol and guide -/+ Standardization of aortic root structures visualization Limitations Limitation caused by aortic valve calcification Limitation caused by aortic motion Radiation exposure Need in general anesthesia Need in contrast medium Under-/over- estimation of aortic annulus High self-cost

How IVUS Works To obtain 360° cross-sectional image,the ultrasound beam must be scaned through a full circle, and the beam direction and deflection on the display must be synchronized. This can be achieved - by mechanically rotating the imaging elements, or - by using electronically switched phased array.

Digital, 64 element (Plag&Play) Company Boston Scientific  Volcano Corporation  Catheter model Atlantis PV Peripheral  Sonicath Ultra 9 Peripheral   Visions PV .018   Visions PV 8.2 - .035”  Visions PV 8.2 French   Imaging method Rotational  Digital, 64 element  (Plag&Play) Grayscale IVUS Yes  Yes+(ChromaFlow) Bloodflow imaging No  Frequency, MHz 15 MHz  9 MHz  20 MHz  10 MHz  Maximum imaging diameter 30 mm  50 mm  24 mm  60 mm  Tip entry profile .105  .118  .030  .055  .058  Tip to transducer 1.5 cm  1 cm  10-13 mm  12 mm  Diameter at transducer (French) 8  9  3.5  8.2  Maximum outer shaft (French) 8.5  3.4  7  Radiopaque markers One  25, 1 cm apart  Wire lumen length 101 cm  NA  31 cm  90 cm  Working length (cm) 95  110  135  90  Maximum guide wire .035  .018  .038  Minimum guide catheter size (Fr) 6 (ID ≥.064)  Minimum sheath size (French) 6  Delivery platform Monorail  Rapid exchange  Over the wire  Catheter list price $725  $980  Available on request 

VISIONS® PV 8.2F INTRAVASCULAR ULTRASOUND IMAGING CATHETER The Visions PV 8.2F catheters may be used only with the In-Vision Imaging System, Volcano s5 or Volcano s5i imaging system, which offers plug and play digital IVUS simplicity for immediate imaging

Following removal of the aortic leaflets, three crescentic ridges mark the hinge lines. The broken line indicates the level of the ventriculo-arterial junction. Two of the three interleaflet fibrous triangles (o) are shown. The irregular shape marks the site of the atrioventricular conduction bundle and left bundle branch. AV conduction bundle R/N ILT L/N ILT VAJ BR 10-12mm below BR 3-5mm below BR STJ SVml

INTENDED IVUS Visions® PV 8.2F USE The IVUS Visions® PV 8.2F catheters are designed for use in the evaluation of vascular morphology in blood vessels of the peripheral vasculature by providing a cross-sectional image of such vessels. The Visions PV 8.2F ultrasound imaging catheters are designed for use as an adjunct to conventional angiographic procedures to provide an image of the vessel lumen and wall structures and dimensional measurements from the image.

At the level of VAJ Rivus = 30mm NCS LCS RCS Diastolic Systolic RA, RV, Conduction system, Septal leaflet of TV N/R ILT RCS LCS NCS LA, RA, TS LA, free pericardium RA, free pericardial space L/N ILT LA, AL MV R/L ILT Space between Ao & PT Diastolic Systolic Dsag(d)=21,7mm Dsag(s)=18,23mm Dcor(d)=27,5mm Dcor(s)=23,1mm Rivus = 30mm D IVUS PV 8.2 =60mm D IVUS Atlantis PV= 30mm Posterior Anterior L R Nadir At the level of VAJ Projection of commissures at STJ

LVOT 10-12 mm below BR Diastole Systole Commissures attachment point Posterior Anterior L R

LVOT 3-5 mm below BR Diastole Systole

BASAL RING LEVEL Diastole Systole

MIDDLE LINE THROUGH SINUS VALSALVA Diastole Systole

COAPTATION LEVEL Diastole Systole

SINOTUBULAR JUNCTION LEVEL Diastole Systole

What can be done with the IVUS imaging modality? Measurement of coronal and sagittal diameters at all level of aortic root Definition of their changes during cardiac cycle Measurement of ILT and definition of their changes during cardiac cycle Measurement of the leaflets dimension and definition of their changes during cardiac cycle Measurement and definition of changes of spatial structures surrounding the aortic root at all levels Measurement of distances to the coronary arteries from different level of aortic root Measurement of CA orifice diameter and its changes during cardiac cycle Evaluation of degree and localization of calcifications

WHAT IT WILL GIVE This direct and accurate measurement results will give possibility to provide the detailed description of aortic root anatomy and develop the definitions of aortic structures specifications, sizes and dynamics. It will facilitate the development of the guidance and standards of aortic root structures IVUS visualization as for healthy population as for patients with AS. The knowledge of exact anatomy and dynamic of aortic root will assist not only in proper TAVI prostheses size selection with consequent minimization of complication rate related to patient-prostheses mismatch but also in further development of TAVI prostheses and extension of its use.

CONCLUSION At this time no single imaging modality is preferred. There is no gold standard and thus it is not possible to define which method is the most accurate. Variation in the reported annulus diameter with various imaging modalities suggests that further study of the factors involved in annulus sizing and development of new more accurate imaging modalities for TAVI are needed The IVUS imaging modality (Vision PV8.2F) has all necessary theoretically demonstrated prerequisites to became the gold standard imaging modality for TAVI and facilitate not only the elimination of complications rate after TAVI but also further development of TAVI technique and prostheses. It is necessary to perform the clinical investigations of the IVUS Vision PV8.2 implementation in the aortic root imaging and measurements with comparison analyses of obtained results with the respective results of other imaging modalities used for TAVI.