3-Dimensional personalized planning for transcatheter pulmonary valve implantation in a dysfunctional right ventricular outflow tract

Journal Pre-proof 3-Dimensional personalized planning for transcatheter pulmonary valve implantation in a dysfunctional right ventricular outflow tract

Francesca R. Pluchinotta, Francesco Sturla, Alessandro Caimi, Luca Giugno, Massimo Chessa, Alessandro Giamberti, Emiliano Votta, Alberto Redaelli, Mario Carminati PII:

S0167-5273(19)34925-3

DOI:

https://doi.org/10.1016/j.ijcard.2019.12.006

Reference:

IJCA 28191

To appear in:

International Journal of Cardiology

Received date:

2 October 2019

Revised date:

25 November 2019

Accepted date:

4 December 2019

Please cite this article as: F.R. Pluchinotta, F. Sturla, A. Caimi, et al., 3-Dimensional personalized planning for transcatheter pulmonary valve implantation in a dysfunctional right ventricular outflow tract, International Journal of Cardiology(2019), https://doi.org/ 10.1016/j.ijcard.2019.12.006

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

© 2019 Published by Elsevier.

Journal Pre-proof 3-Dimensional Personalized Planning for Transcatheter Pulmonary Valve Implantation in a Dysfunctional Right Ventricular Outflow Tract

Francesca R Pluchinottaa,b,†,1, MD; Francesco Sturlac,†,1, PhD; Alessandro Caimib,1, MSc; Luca Giugnoa,1, MD; Massimo Chessaa,1, MD, PhD; Alessandro Giambertid,1, MD; Emiliano Vottab,1,

Department of Pediatric and Adult Congenital Heart Disease, IRCCS Policlinico San Donato, San

-p

a

re

Donato Milanese, Italy

Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano,

lP

b

Italy.

3D and Computer Simulation Laboratory, IRCCS Policlinico San Donato, San Donato Milanese,

na

c

ur

Italy

Department of Pediatric and Adult Congenital Cardiac Surgery, IRCCS Policlinico San Donato,

Jo

d

ro

† The two authors equally contributed to the study

of

PhD; Alberto Redaellib,1, PhD; Mario Carminatia,1, MD

San Donato Milanese, Italy 1

All authors take responsibility for all aspects of the reliability and freedom from bias of the

data presented and their discussed interpretation

Short title: 3D CT-based TPVI planning in dilated RVOTs

Address for correspondence:

Journal Pre-proof Francesco Sturla, PhD 3D and Computer Simulation Laboratory, IRCCS Policlinico San Donato Piazza Edmondo Malan 2, 20097 San Donato Milanese, Milan, Italy [email protected]

of

Conflict of interest statement

ro

The authors report no relationships that could be construed as a conflict of interest

-p

Sources of Funding

re

This work was supported by the IRCCS Policlinico San Donato, a Clinical Research Hospital

na

Keywords

lP

partially funded by the Italian Ministry of Health.

ur

Transcatheter pulmonary valve implantation, 3D interventional planning, 3D-printing,

Jo

computed tomography, innovation

Abstract Background. Identification of adequate landing zone for transcatheter pulmonary valve implantation (TPVI) is crucial to successfully treat an aneurysmatic native right ventricle outflow tract (RVOT); three-dimensional (3D) patient-tailored digital and physical printed models are available but their actual strengths and weaknesses still not well documented. The aim of the study was to tackle the planning of transcatheter pulmonary valve implantation (TPVI) in the

Journal Pre-proof dysfunctional and borderline RVOT exploiting both digital and physical printed 3D patientspecific models. Methods. Electrocardiographically gated computed tomography (CT) angiography was segmented and anatomical RVOT geometrical changes dynamically tracked throughout the cardiac cycle using in-house processing. A compliant 3D-printed model was manufactured from

of

the diastolic rest phase to test in vitro the catheter-based procedure feasibility; results were compared against CT-derived in vivo measurements and the actual catheterization outcome.

ro

Results. CT-gated analysis successfully quantified in vivo RVOT dynamic changes corroborating

-p

the feasibility of non-conventional pulmonary jailing percutaneous intervention. Clinicians used

re

the 3D-printed model to test the steps of the jailing procedure; yet, the deformable 3D model

lP

printed at diastole underestimated the final implant dimensions obtained in during cardiac catheterization by the same operators.

na

Conclusions. Multidisciplinary synergy between CT-gated analysis and pre-procedural tests on

ur

3D-printed phantoms can help the interventional team to tackle complex TPVI procedures. To

Jo

fully exploit 3D-printed models, adequate selection of the still frame to print and tuning of printing material properties is crucial and can be aided by 3D dynamic virtual models. Abbreviations 3D: three-dimensional CT: computed tomography DA: diameter from area DP: diameter from perimeter e: eccentricity

Journal Pre-proof PA: pulmonary artery TPVI: percutaneous pulmonary valve implantation RAC: relative area change ROI: region of interest

Jo

ur

na

lP

re

-p

ro

of

RVOT: right ventricular outflow tract

Journal Pre-proof 1. Introduction Surgical repair of many congenital defects (e.g., conotruncal disease) often results in long-term anatomic and functional abnormalities of the right ventricular outflow tract (RVOT) and pulmonary arteries (PAs)[1]. The native RVOT is typically enlarged and frequently exhibits akinesis or dyskinesis and unpredictable aneurysm[2].

of

Transcatheter pulmonary valve implantation (TPVI) in the native patch RVOT has recently proved successful in selected patients with a suitable reconstructed RVOT anatomy[3]; current

ro

commercially available TPVI devices have a diameter span from 16 to 29 mm, this limiting the

-p

suitability of an adequate TPVI landing zone to only 15% of the patients[4].

re

In this scenario, contrast-enhanced ECG-gated computed tomography (CT) has crucially

lP

emerged to dynamically evaluate RVOT/PA three-dimensional (3D) morphology and function, and to identify those patients having a favorable RVOT implantation site able to guarantee TPVI

na

stability throughout the cardiac cycle[5]. Meanwhile, 3D-printed modeling has increasingly

ur

popularized to improve the understanding of various congenital heart conditions and support

Jo

feasibility testing for interventional pre-operative planning in complex or borderline cases[6, 7]. This approach can accurately reproduce the physical shape of the target anatomy; yet, selection of a still-frame from the patient-specific imaging is necessary to print the 3D model. Also, even though sophisticated elastomeric materials are used to reliably mimic the distensibility of the real organs, the features of native tissues may be not fully captured. Herein, we exploited both the strategies to assess TPVI feasibility and plan the intervention in a challenging borderline RVOT/PA anatomy refereed for TPVI. Our main goal was to compare the

Journal Pre-proof two approaches, pinpointing their advantages and limitations, as well as their potential as mutually complementary planning tools for challenging interventional procedures.

2. Methods 2.1 Enrolled patient. A 17-year-old young boy (height=1.87 m, weight=85 Kg, body surface

of

area=2.11 m2) after surgical correction of tetralogy of Fallot with transannular patch during infancy, presented with easy fatigability and dyspnea under effort. Cardiac magnetic resonance

ro

showed severely dilated right ventricle (end-diastolic volume 162 ml/m2, end-systolic volume

-p

69 ml/m2) with severe pulmonary regurgitation and no gradient across the RVOT or PA

re

branches. RVOT was mildly aneurysmatic and magnetic resonance angiography showed a RVOT

lP

pyramidal shape, with proximal and distal diameter of 32 and 27 mm, respectively. Given the

planning.

na

borderline RVOT dimensions, TPVI feasibility was carefully investigated during pre-operative

ur

2.2 CT-gated analysis. The patient underwent CT angiography on a 64-slice multidetector

Jo

system with retrospective ECG-gating (SOMATOM Definition, Siemens, Germany) under injection of contrast medium (Iomeprolo). Multi-phase images of the RVOT/PAs region were acquired at each 10% increment of the cardiac cycle, i.e., from 0% to 100% (acquisition parameters as in Online Table 1). CT data were segmented (Figure 1.A-B) through Mimics Medical Suite (Materialise, Belgium) and all the phases extracted as triangulated 3D surfaces to assess RVOT/PA dynamic changes (Figure 2.A). RVOT/PA centerline was automatically extracted [8] and split in the main PA trunk, right PA and left PA (Figure 2.B).

Journal Pre-proof Through delineation of anatomical landmarks and section planes (Figure 2.C-D) [5], the RVOT/PA surface was clustered into 5 wall regions of interest (ROIs, Figure 2.E, Online Appendix). Accordingly, a nearest neighbour algorithm, able to monitor small surface changes in nodal positions and local shape [9], tracked frame-by-frame RVOT/PA anatomical changes (Online Appendix), automatically computing geometrical area and perimeter on the tracked

of

RVOT/PA cross-sections (Online Figure 1); standardized diameters were calculated from both area (𝐷𝐴 ) and perimeter (𝐷𝑃 ), considering each section as a circle with equivalent area and

ro

perimeter, respectively. Also, eccentricity (e, the grade of the cross-section elliptical shape),

-p

was calculated through direct least square fitting of an ellipse[10]. The analysis was performed

re

through in-house Matlab (The MathWorks Inc., Natick, MA, USA) codes.

lP

CT-derived variables (Online Table 2-4) were assessed over the cardiac cycle and compared between the 5 anatomical ROIs by means of 2-way ANOVA for repeated measures (GraphPad

na

Prism Software, San Diego, CA, USA) with one factor analyzed as a repeated measure factor. A

ur

value of P<0.05 was considered statistically significant.

Jo

2.3 3D printing test-bed. A 3D-printed model of the patient-specific anatomy (Figure 1.C-D) was manufactured from the diastolic rest phase, i.e., 80% of the R-R interval, characterized by the least cardiac motion and, accordingly, by the least expected blurring due to motion artifacts[11]. After segmentation of the blood pool, a hollow model was generated extruding the blood pool surface 2 mm outwards to reproduce the wall thickness. The geometry was printed with the compliant HeartPrint® Flex material (Materialise, Belgium) seeking to take the arterial distensibility into account[12].

Journal Pre-proof The 3D-printed model was exploited to test the personalized catheter-based strategy under fluoroscopy guidance and CT rotational angiography. Results from 3D-testing were compared against both CT-derived in vivo measurements and the actual catheterization outcome.

3. Results

of

3.1 In vivo dynamic RVOT changes. CT-based analysis reported relevant dimensional differences between the analyzed RVOT/PA sectors (P<0.0001) and significant variations within

ro

each sector during the cardiac cycle (P<0.0001, Figure 3). In particular, the proximal and mid

-p

portions of the RVOT trunk proved to be an unfavorable site of implantation for a TPVI

re

procedure with both DP and DA largely above 30 mm in almost all the cardiac phases. The RVOT

lP

trunk dimensions reduced in the distal sector, presenting minimum DP and DA values of 27.0 mm and 26.1 mm at 60% of the R-R interval. However, distal RVOT enlargement was

na

remarkable from diastole to systole with both DP and DA reporting a 27.5% increase up to 34.4

ur

mm and 33.3 mm at 10% of the cardiac cycle, respectively. Hence, RVOT systolic dimensions

Jo

were still adverse for TPVI.

Both right and left PA branches were significantly smaller as compared to the RVOT trunk: D P mean value ranged from 20.0 mm to 24.9 mm in the left PA and from 18.6 mm to 26.1 mm in the right PA. A strong linear correlation (Online Figure 2, r2=0.997) was evident between standardized diameters DA and DP. The RVOT anatomy exhibited an overall elliptical cross-section with e ranging from 0.5 to 0.8. Eccentricity was generally higher in diastole than in systole, especially in the PA branches where

Journal Pre-proof the highest level of circularity was achieved close to peak systole; e was equal to 0.62±0.04 and 0.42±0.05 for the right and the left PA branches, respectively. Dynamic CT-gated assessment highlighted systolic RVOT borderline dimensions for conventional TPVI and supported the feasibility of a branch pulmonary artery jailing technique [13] exploiting the right PA as the initial landing zone for multiple bare metal stents to anchor a

of

transcatheter pulmonary valve. 3.2 In vitro 3D testing. Two guidewires were inserted from both PA branches of the 3D-printed

ro

model (Figure 4.A) and preliminary balloon sizing, performed using the right guidewire,

-p

reported a diameter of 17.6÷17.8 mm (Figure 4.B); jailing stenting was started from the right PA

re

branch all the way down to the main PA with a bare metal CP-stent (Numed, Hopkinton, NY,

lP

USA) 34 mm long initially deployed to a diameter of about 16 mm (15.5÷16.3 mm, Figure 4.C, Online Video 1). Subsequently, a 42 mm long bare metal AndraStent (Andramed, Germany) was

na

deployed in the main PA maintaining a 50% overlap with the CP-stent already expanded in the

ur

right PA (Figure 4.D, Online Video 1), thus jailing the opposite left PA. The final implant (Figure

Jo

4.E-F) reached a maximum diameter equal to 25.1 mm in its proximal portion, as measured under fluoroscopy, while the distal portion reached a final diameter of about 22 mm within the right PA. 3.3 Cardiac catheterization. During cardiac catheterization, the interventional team performed angiographic studies and balloon sizing of the pulmonary trunk following the strategy planned on the 3D-printed phantom (Online Figure 3, Online Video 2). PA systolic and diastolic pressures (sPPA, dPPA) were equal to 30 mmHg and 8 mmHg, respectively, resulting in a pulse pressure (PP=sPPA - dPPA) of 22 mmHg.

Journal Pre-proof Main PA balloon sizing, through a 26x60 mm balloon-in-balloon delivery system (BiB, Numed, Hopkinton, NY, USA), did not provide complete PA occlusion. Therefore, a 28x60 mm BiB sizing was performed, obtaining a complete PA occlusion with an evident notch at the origin of the right PA (Online Figure 3.A). Simultaneous aortography revealed no signs of coronary compression. PA jailing was accomplished in the right PA through successful deployment of an

of

uncovered bare metal AndraStent XXL 57 mm mounted on a 28x60 mm BiB (Online Figure 3.B); angiogram confirmed full stent expansion and the patency of the contralateral left PA. A

ro

subsequent AndraStent XXL 48 mm, mounted on a 30x50 mm BiB balloon, was deployed in the

-p

main PA downward enough to reach the RVOT site of implantation while maintaining a partial

re

50% overlap with the previous stent (Online Figure 3.C-D). 3D rotational angiography showed

lP

normally expanded stents as well as adequate patency of both PA branches (Online Figure 3.E). Finally, a Sapien valve XT 29 mm (Edwards Lifesciences Corp, Irvine, CA, USA) was implanted by

na

standard technique, avoiding the accidental covering of the jailed PA while positioning the

ur

percutaneous valve well below the main PA bifurcation within the pre-stented anchoring region

Jo

(Online Figure 3.F). Angiographic assessment was repeated at the end of the procedure to confirm appropriate valve position and function (Online Figure 3.G), reporting a circular shape with a diameter of 28 mm and no evidence of paraprosthetic leaks (Online Figure 3.H). 3.4 Virtual vs. printed 3D strategies. The same operators reproduced in vivo the jailing procedure, tested on the 3D-printed model, during cardiac catheterization. Though accomplished on a flexible 3D-printed model, in vitro testing underestimated the final in vivo implant dimensions. Indeed, in vitro test revealed that a CP-stent could be adequate to prestent the right PA while an AndraStent, which has a larger nominal diameter, was required

Journal Pre-proof during catheterization. Within the 3D-printed model, the proximal portion of the implant reached a maximum diameter of 25 mm while in vivo a Sapien valve was implanted reporting a final diameter of 28 mm. On the contrary, measurements from CT-gated 3D processing well matched with the final implant dimensions from the catheterization procedure: the largest systolic diameter derived from CT-gated analysis for the right PA (DP=26.1±1.1 mm, DA=25.7±1.1

of

mm, Online Table 3) proved to be consistent with the diameter of 25.9 mm measured during BiB sizing (Online Figure 3.B). CT-gated measurements of percentage relative area change

ro

(RAC), calculated as (maximum area – minimum area)/minimum area [14], were equal to 38.1%

-p

and 50.3% for distal RVOT and right PA, respectively. Pulmonary artery area distensibility, i.e.,

re

the ratio of the RAC and PP, was equal to 17.3·10-3 mmHg-1 and 22.9·10-3 mmHg-1 for distal

lP

RVOT and right PA, respectively. Both values were significantly above the range of distensibility (3.7÷1.9·10-3 mmHg-1) reported for the HeartPrint® Flex material [12], demonstrating the

na

incapability of the 3D model printed at diastole to mimic the in vivo dimensional variation

4. Discussion

Jo

ur

experienced by the RVOT/PA anatomy.

Since its first application in humans, TPVI has emerged as an effective alternative to open heart surgery for the treatment of the dysfunctional RVOT[15]. The PA “jailing” technique, deploying overlapping stents from a PA branch down to the RVOT as an anchor for TPVI, is an already established technique for the percutaneous treatment of large patched RVOTs [13]. Nonetheless, its application in borderline RVOT/PA anatomies can be extremely challenging and requires sound pre-procedural assessment.

Journal Pre-proof For this purpose, technological advances have contributed to novel methods of displaying cardiac imaging, including 3D digital and 3D-printed models, which might help cardiac catheterization procedures[7, 16]. Herein, we employed both digital and physical 3D models, derived from pre-operative CT imaging, to assess TPVI feasibility and plan the intervention in a challenging aneurysmatic RVOT-patched anatomy.

of

On the one hand, electrocardiographically gated CT imaging provides a clear depiction of cardiac anatomy and 3D virtual reconstructions offer a comprehensive overview of complex

ro

congenital defects[17]. Our analysis succeeded in quantifying in vivo RVOT/PA dynamic changes

-p

over the cardiac cycle, providing valuable data to corroborate the jailing technique feasibility

re

prior to the percutaneous treatment thereby avoiding surgery.

lP

On the other hand, though recognizing the clinical relevance of testing TPVI on a 3D-printed model [18], we showed that relevant factors, such as selection of the cardiac frame to 3D-print

na

and the mechanical behavior of the printing material, may have a non-negligible impact on the

ur

results of pre-procedural in vitro tests.

Jo

Hence, pinpointing both strengths and weaknesses of 3D virtual and printed models may help in gaining additional clinical insight into the planning of complex TPVI procedures. 4.1 Pre-procedural 3D dynamic analysis. Dynamic CT-gated assessment proved to be extremely useful to understand the RVOT geometrical complexity and its behavior from diastole to systole. Though RVOT dimensions were at the upper limit of the TPVI admissible range, in vivo CT-gated assessment supported the feasibility of a non-conventional pulmonary jailing intervention; a safe TPVI landing zone was identified and both stents length and their optimal position adequately estimated to overcome possible implant drawbacks.

Journal Pre-proof TPVI is currently limited to pulmonary trunks sized between 16 and 29 mm [4] to guarantee a stable landing zone for the device and avoid post-implant regurgitation. Importantly, these RVOTs are not calcified and tend to be highly distensible, which predisposes to device embolization into the pulmonary circulation or dislodgement into the right ventricle [19], thus requiring interrogation with large and long balloons proved essential.

of

The good accordance between CT-gated 3D measurements and final evidences from catheterization confirms the valuable insight of 3D imaging technology into the planning of

ro

complex percutaneous interventions, focusing on the most clinically relevant region within the

-p

dysfunctional anatomy. Virtual 3D models can provide dynamic rendering, rotations and

re

cutting planes to optimize viewing angles, to visualize overlapping structures and adjust

lP

measurements, e.g., improving the measurements to be taken perpendicular to flow direction. Virtual 3D analysis can also overcome approximations related to the use of fixed

ur

account[5].

na

conventional two-dimensional projections, which cannot take out-of-plane movements into

Jo

As with any modality using ionizing radiation, CT-gated analysis is associated with a higher radiation dose, if compared with a non-gated or ECG-triggered sequential CT acquisition [11, 17]. Though ECG-gated analysis is to be avoided in pediatric age and minimization of radiation exposure is mandatory, pre-procedural CT-gated evaluation was considered acceptable, given the adult biometric body surface area of the patient. In addition, tube potential was reduced from the commonly used 120kV to 100 kV, which remarkably reduces the radiation dose estimates, while maintaining diagnostic image quality[20].

Journal Pre-proof 4.2 Tests on 3D-printed models. In interventional cardiology, conventional two-dimensional visualization on a flat screen may not be enough to fully appreciate the complex relationships of cardiac 3D structures. Under the hypothesis that tissue distensibility can be replicated in a 3Dprinted model by using flexible materials, 3D-printing can transform a 3D digital reconstruction into a physical model, providing tactile perception of the complex 3D morphology[7] and

of

enabling pre-procedural feasibility testing in complex or borderline clinical cases[16]. In this scenario, our analysis clearly showed that selection of the imaging frame to print is

ro

crucial: the 3D model printed at diastole, though deformable, failed to reliably mimic the

-p

large RVOT/PA deformation occurring during systole, inevitably underestimating the final

re

implant dimensions obtained in the catheterization laboratory. Conversely, if printed at

lP

systole, a 3D deformable model might result in unreliable RVOT wall response to the implant; in vivo RVOT systolic configuration is maximally stressed and hence maximally prone to

na

radially shrink owing to elastic recoil, which would be neglected by the 3D-printed phantom.

ur

Though a diastolic configuration is frequently reconstructed to minimize artifacts due to heart

Jo

motion and facilitate inspection of cardiac defects, selection of the optimal cardiac frame to print and adequate tuning of the 3D printing material flexibility still remain a challenge, requiring progressive “trial and error” adjustments before reaching the most suitable patientspecific model configuration. Hence, depending on the anatomical target and the specific function of the model, guidelines to standardize 3D printing technology in surgical and interventional scenarios is desirable to specify compulsory items able to improve both quality and accuracy of pre-procedural analysis [21]. Further efforts are still necessary to tune the printable material properties and effectively

Journal Pre-proof replicate the actual wall extensibility, in particular in native patched RVOTs with highly heterogeneous mechanical properties [22], also taking the accuracy of the 3D printing technique, whose cost still represents a limitation, into account [21]. Despite these limitations, 3D printing has already advanced the education of physicians and the communication with patients [23, 24]; incorporation of medical 3D models is expected to

of

revolutionize undergraduate medical education and reduce the learning curve of inexperienced

ro

trainees [25].

-p

5. Conclusions

re

CT-based 3D digital models can accurately pinpoint RVOT/PA dimensions and dynamic changes

lP

over the cardiac cycle to identify an appropriate TPVI landing zone. To exploit 3D-printed models for feasibility pre-procedural testing, proper selection of the CT still frame to print and

na

tuning of tissue mimicking print material properties is crucial. Given the variability in shape,

ur

size, and dynamic nature of the native RVOT, on-going 3D digital and printed innovations could

Jo

definitively help the interventional team to tackle complex TPVI procedures and deepen off label TPVI techniques, paving the way towards a patient-tailored, effective and safe approach.

Journal Pre-proof Acknowledgments We thank Dr. Francesco Secchi from the Department of Radiology, IRCCS Policlinico San Donato,

Jo

ur

na

lP

re

-p

ro

of

for acquiring the CT dataset.

Journal Pre-proof Figure legends Figure 1. 3D reconstruction. A and B, patient-specific anatomical segmentation from CT data; C, 3D model virtual reconstruction; D, 3D-printed model.

Figure 2. RVOT/PA dynamic reconstruction with CT-derived 3D surfaces reconstructed from 0%

of

to 100% of the cardiac cycle (A). Definition of the anatomical ROIs through identification of the PA bifurcation (B, yellow point) and anatomical cross-sections (C, D); E, schematic of the five

-p

ro

ROIs, i.e., proximal RVOT, mid RVOT, distal RVOT, left PA and right PA.

re

Figure 3. RVOT/PA dynamic anatomical changes over the cardiac cycle with the time-course of

lP

the geometrical variables averaged on the cross-sections of each anatomical ROI: area (A),

na

diameter from A (DA), perimeter (P), diameter from P (DP) and eccentricity (e).

ur

Figure 4. In vitro testing of the jailing technique on the 3D-printed model in the catheterization

Jo

laboratory: A, insertion of guidewires; B, preliminary balloon sizing within the right PA; C, D and E, the target anatomy is tested implanting two overlapping stents to obtain a favorable site of TPVI implantation within the RVOT. F, final result as reconstructed from CT rotational angiography.

Journal Pre-proof References

Jo

ur

na

lP

re

-p

ro

of

[1] Geva T. Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support. J Cardiovasc Magn Reson. 2011;13:9. [2] Martin MH, Meadows J, McElhinney DB, Goldstein BH, Bergersen L, Qureshi AM, et al. Safety and Feasibility of Melody Transcatheter Pulmonary Valve Replacement in the Native Right Ventricular Outflow Tract: A Multicenter Pediatric Heart Network Scholar Study. JACC: Cardiovascular Interventions. 2018;11:1642-50. [3] Schievano S, Coats L, Migliavacca F, Norman W, Frigiola A, Deanfield J, et al. Variations in right ventricular outflow tract morphology following repair of congenital heart disease: implications for percutaneous pulmonary valve implantation. J Cardiovasc Magn Reson. 2007;9:687-95. [4] Ansari MM, Cardoso R, Garcia D, Sandhu S, Horlick E, Brinster D, et al. Percutaneous Pulmonary Valve Implantation: Present Status and Evolving Future. J Am Coll Cardiol. 2015;66:2246-55. [5] Schievano S, Capelli C, Young C, Lurz P, Nordmeyer J, Owens C, et al. Four-dimensional computed tomography: a method of assessing right ventricular outflow tract and pulmonary artery deformations throughout the cardiac cycle. Eur Radiol. 2011;21:36-45. [6] Vukicevic M, Mosadegh B, Min JK, Little SH. Cardiac 3D Printing and its Future Directions. JACC Cardiovasc Imaging. 2017;10:171-84. [7] Anwar S, Singh GK, Miller J, Sharma M, Manning P, Billadello JJ, et al. 3D Printing is a Transformative Technology in Congenital Heart Disease. JACC: Basic to Translational Science. 2018;3:294-312. [8] Verhoelst E SO, Schepers J, Maes J, Sindhwani, N, Lysogor A, Veeckmans B. Mimics® Centerline Extraction: Quantitative Validation (https://www.materialise.com/en/resources/medical/whitepapers/mimics-centerlineextraction-quantitative-validation). [9] Conti CA, Votta E, Corsi C, De Marchi D, Tarroni G, Stevanella M, et al. Left ventricular modelling: a quantitative functional assessment tool based on cardiac magnetic resonance imaging. Interface focus. 2011;1:384-95. [10] Fitzgibbon AW, Pilu M, Fisher RB. Direct least squares fitting of ellipses. Proceedings of 13th International Conference on Pattern Recognition1996. p. 253-7 vol.1. [11] Ohnesorge B, Flohr T. Principles of Multi-slice Cardiac CT Imaging. Multi-slice and Dual-source CT in Cardiac Imaging: Principles — Protocols — Indications — Outlook. Berlin, Heidelberg: Springer Berlin Heidelberg; 2007. p. 71-126. [12] Schickel M TK, Farotto D. Material Characterization of 3D Printed HeartPrint Flex Plus Models and Comparison with Arterial Tissue Properties (https://www.materialise.com/en/resources/medical/whitepapers/materialcharacterization-of-materialise-heartprint-models-and). 2017. [13] Boudjemline Y, Legendre A, Ladouceur M, Boughenou MF, Patel M, Bonnet D, et al. Branch pulmonary artery jailing with a bare metal stent to anchor a transcatheter pulmonary valve in patients with patched large right ventricular outflow tract. Circulation Cardiovascular interventions. 2012;5:e22-5.

Journal Pre-proof

Jo

ur

na

lP

re

-p

ro

of

[14] Gan CT, Lankhaar JW, Westerhof N, Marcus JT, Becker A, Twisk JW, et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest. 2007;132:1906-12. [15] Lurz P, Coats L, Khambadkone S, Nordmeyer J, Boudjemline Y, Schievano S, et al. Percutaneous pulmonary valve implantation: impact of evolving technology and learning curve on clinical outcome. Circulation. 2008;117:1964-72. [16] Grant EK, Olivieri LJ. The Role of 3-D Heart Models in Planning and Executing Interventional Procedures. Canadian Journal of Cardiology. 2017;33:1074-81. [17] Valente AM, Cook S, Festa P, Ko HH, Krishnamurthy R, Taylor AM, et al. Multimodality imaging guidelines for patients with repaired tetralogy of fallot: a report from the AmericanSsociety of Echocardiography: developed in collaboration with the Society for Cardiovascular Magnetic Resonance and the Society for Pediatric Radiology. J Am Soc Echocardiogr. 2014;27:111-41. [18] Valverde I, Sarnago F, Prieto R, Zunzunegui JL. Three-dimensional printing in vitro simulation of percutaneous pulmonary valve implantation in large right ventricular outflow tract. European Heart Journal. 2016;38:1262-3. [19] Hascoet S, Pozza RD, Bentham J, Carere RG, Kanaan M, Ewert P, et al. Early outcomes of percutaneous pulmonary valve implantation using the Edwards SAPIEN 3 transcatheter heart valve system. EuroIntervention. 2019;14:1378-85. [20] Bischoff B, Hein F, Meyer T, Hadamitzky M, Martinoff S, Schomig A, et al. Impact of a reduced tube voltage on CT angiography and radiation dose: results of the PROTECTION I study. JACC Cardiovasc Imaging. 2009;2:940-6. [21] Martelli N, Serrano C, van den Brink H, Pineau J, Prognon P, Borget I, et al. Advantages and disadvantages of 3-dimensional printing in surgery: A systematic review. Surgery. 2016;159:1485-500. [22] Yoo SJ, Thabit O, Kim EK, Ide H, Yim D, Dragulescu A, et al. 3D printing in medicine of congenital heart diseases. 3D printing in medicine. 2015;2:3. [23] Giannopoulos AA, Mitsouras D, Yoo SJ, Liu PP, Chatzizisis YS, Rybicki FJ. Applications of 3D printing in cardiovascular diseases. Nature reviews Cardiology. 2016;13:701-18. [24] Biglino G, Koniordou D, Gasparini M, Capelli C, Leaver LK, Khambadkone S, et al. Piloting the Use of Patient-Specific Cardiac Models as a Novel Tool to Facilitate Communication During Cinical Consultations. Pediatr Cardiol. 2017;38:813-8. [25] Fasel JH, Aguiar D, Kiss-Bodolay D, Montet X, Kalangos A, Stimec BV, et al. Adapting anatomy teaching to surgical trends: a combination of classical dissection, medical imaging, and 3D-printing technologies. Surgical and radiologic anatomy : SRA. 2016;38:361-7.

Journal Pre-proof CReditT author statement

– International Journal of Cardiology

Manuscript Title: 3-Dimensional Personalized Planning for Transcatheter Pulmonary Valve Implantation in a Dysfunctional Right Ventricular Outflow Tract List of all Authors: Francesca R Pluchinottaa,b,†,1, MD; Francesco Sturlac,†,1, PhD; Alessandro Caimib,1, MSc; Luca Giugnoa,1, MD; Massimo Chessaa,1, MD, PhD; Alessandro Giambertid,1, MD; Emiliano Vottab,1, PhD; Alberto Redaellib,1, PhD; Mario Carminatia,1, MD

-p

ro

of

† The two authors equally contributed to the study a Department of Pediatric and Adult Congenital Heart Disease, IRCCS Policlinico San Donato, San Donato Milanese, Italy b Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milano, Italy. c 3D and Computer Simulation Laboratory, IRCCS Policlinico San Donato, San Donato Milanese, Italy d Department of Pediatric and Adult Congenital Cardiac Surgery, IRCCS Policlinico San Donato, San Donato Milanese, Italy 1 All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation

Jo

ur

na

lP

re

CReditT author statement Francesca Pluchinotta: Conceptualization, Writing- Original draft preparation, Writing – review & editing, Project administration. Francesco Sturla: Conceptualization, Methodology, Software, Writing- Original draft preparation, Writing – review & editing. Alessandro Caimi: Methodology, Software, Investigation, Formal Analysis, Writing – review & editing, Validation. Luca Giugno: Data Curation, Validation, Writing – review & editing. Massimo Chessa: Writing – review & editing, Data Curation, Visualization. Alessandro Giamberti: Writing – review & editing, Visualization. Emiliano Votta: Software, Validation, Writing- Reviewing and Editing. Alberto Redaelli: Funding acquisition, Resources, Writing – review & editing. Mario Carminati: Funding acquisition, Supervision, Writing – review & editing.

lP

re

-p

ro

of

Journal Pre-proof

Jo

ur

na

Graphical

abstract

Journal Pre-proof Highlights CT-gated analysis can tackle TPVI feasibility in a borderline RVOT anatomy.



3D patient-tailored digital technologies can improve TPVI planning.



Still frame to print and tuning of 3D-printing material properties are crucial.



Training on 3D-printed phantoms can promote safe interventional skills acquisition.

Jo

ur

na

lP

re

-p

ro

of

