Aortic Root Pressurizing Device: aortic valve evaluation during cardioplegic arrest

Journal Pre-proof Aortic Root Pressurizing Device: aortic valve evaluation during cardioplegic arrest Johannes Steindl, M.D, Michael Kirnbauer, M.D, Johann Fierlbeck, M.E, Michael Krieghofer, LLB.oec, Wolfgang Hitzl, Ph.D, Lynne Hinterbuchner, M.Sc, Rainald Seitelberger, M.D, Christian Dinges, M.D., M.Sc PII:

S0003-4975(19)31900-9

DOI:

https://doi.org/10.1016/j.athoracsur.2019.10.080

Reference:

ATS 33327

To appear in:

The Annals of Thoracic Surgery

Received Date: 17 June 2019 Revised Date:

17 October 2019

Accepted Date: 21 October 2019

Please cite this article as: Steindl J, Kirnbauer M, Fierlbeck J, Krieghofer M, Hitzl W, Hinterbuchner L, Seitelberger R, Dinges C, Aortic Root Pressurizing Device: aortic valve evaluation during cardioplegic arrest, The Annals of Thoracic Surgery (2020), doi: https://doi.org/10.1016/j.athoracsur.2019.10.080. 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 by The Society of Thoracic Surgeons

Aortic Root Pressurizing Device: aortic valve evaluation during cardioplegic arrest Running head: Aortic Root Pressurizing Device Johannes Steindl1, M.D., Michael Kirnbauer2, M.D. Johann Fierlbeck3, M.E., Michael Krieghofer3, LLB.oec., Wolfgang Hitzl4,5, Ph.D. , Lynne Hinterbuchner6, M.Sc. , Rainald Seitelberger1, M.D., Christian Dinges1, M.D., M.Sc.

1

Department of Cardiovascular & Endovascular Surgery, Paracelsus Medical University, Muellner-

Hauptstrasse 48, 5020 Salzburg, Austria 2

Department of Anesthesiology, Perioperative Care and Intensive Care Medicine, Muellner-

Hauptstrasse 48, 5020 Salzburg, Austria 3

PMU Innovations GmbH, Strubergasse 21, 5020 Salzburg, Austria

4

Research Office (biostatistics), Paracelsus Medical University, Strubergasse 21, 5020 Salzburg,

Austria 5

Department of Ophthalmology and Optometry, Paracelsus Medical University, Muellner-

Hauptstrasse 48, 5020 Salzburg, Austria. 6

Department of Internal Medicine, Cardiology and Intensive care, Paracelsus Medical University,

Muellner-Hauptstrasse 48, 5020 Salzburg, Austria

Classifications: adult; cardiac; aortic valve repair; aortic root

Corresponding author Christian Dinges, M.D., MSc., Department of Cardiovascular & Endovascular Surgery, Paracelsus Medical University, Muellner-Hauptstrasse 48, 5020 Salzburg, Austria; e-mail: [email protected]

Word Count: 2500

Abstract Purpose The Aortic Root Pressurizing Device was developed for aortic valve repair surgery. It allows echocardiographic evaluation of the aortic valve during cardioplegic arrest by mimicking diastolic afterload.

Description This polyoxymethylen or polyether-ether-ketone based device consists of a sealing cap nut, a sealing ring, a plug screw and both a filling and a ventilation line. It can be easily connected to any size of aortic Dacron grafts.

Evaluation The device was tested in 15 porcine hearts using a beating heart biosimulator including hemodynamic and echocardiographic monitoring. Valve competence was analyzed both on the beating and resting heart at 60 and 45 mmHg root pressure. Aortic insufficiency was surgically induced by leaflet manipulation. Native aortic valves showed either none or trivial aortic insufficiency. After leaflet manipulation, echocardiographic proof of valve insufficiency was possible in all specimen. Jet direction was identic in all cases at 60 mmHg and 93% at 45 mmHg root pressure.

Conclusions The Aortic Root Pressurizing Device shows highly comparable results of echocardiographic aortic valve evaluation between static and dynamic setting under experimental conditions.

Technology

The Aortic Root Pressurizing Device (ARPD) is a newly developed and patented (Patent number: WO2018206495, AORTIC GRAFT OCCLUDER) polyoxymethylen (POM) or polyether-ether-ketone (PEEK) based surgical device. It consists of a sealing cap nut, a sealing ring, a plug screw and both a filling (inflow-) and a ventilation (outflow-) line. It will be provided for any size of aortic Dacron grafts (Fig. 1A). The ARPD is screwed to the graft´s distal end via its spiral folds. For this purpose, less than 1 cm of graft length is needed. Fixation via the sealing ring and the sealing cap nut provides hemostasis. The installation and removal of the device takes less than one minute. Once in position the device occludes the graft’s distal end. Blood is filled into the aortic root through an inflow-line, mimicking diastolic afterload. Remaining air escapes via the outflow-line (Fig. 1A). After completion of echocardiographic valve evaluation and removal of the device, the graft´s connection zone with the device can be eliminated by length adjustment for the distal aortic anastomosis.

Technique To validate the ARPD’s concept, an experimental test series was performed. The Cardiac Biosimulator™ platform (Life Tec Group, Eindhoven, The Netherlands) (Fig. 2) provides near physiological conditions of aortic valve function and offers the possibility of echocardiographic assessment. It consists of a pulsatile pump system in which a porcine heart is incorporated. In order to facilitate this test series, a specialized version of the ARPD was created (Fig. 1B) by adding a distal connector and a switch. With the switch opened during the dynamic test the device didn’t interfere with the beating heart simulator. However, once the switch was closed, the device provided the exact same function as the original ARPD-version. In this series, fifteen porcine hearts obtained from slaughterhouse pigs were consecutively installed within the Cardiac Biosimulator™ platform (Fig. 3). A 26 mm aortic dacron graft (Vascutek Terumo, Inchinnan, United Kingdom) was anastomosed at a supracommissural level. Both coronary arteries were ligated. 6-0 prolene sutures were stitched to the left and the right coronary leaflets´ free edge, in order to induce leaflet restriction and consecutive

valve insufficiency by tensioning the sutures. An inflow cannula was inserted via the left atrium. Pulsatile flow was created by a pump connected to a left ventricular apex cannula. The modified ARPD-version was connected to the aortic graft and an outflow cannula was installed at the device’s distal opening. A left ventricular venting line was positioned directly through the anterior ventricular wall (Fig. 2). In addition the Cardiac Biosimulator™ platform incorporates sensors for measurement of aortic root pressure, left ventricular pressure and cardiac index. Since the simulator is normally run with water, cornstarch (500 g starch per 12500 ml water; Maizena, Hillegom, The Netherlands) was added in order to enable Doppler ultrasound. Echocardiographic analysis was performed with an Epiq7 system and an X5-1 sonographic probe (Philips, Hamburg, Germany). In order to simulate mid esophageal aortic valve short axis and long axis views in this model, we elaborated a modified view in the caudal region of the left atrium. In this view the sound beam is not exactly in the plane of the aortic annulus but in a slightly angulated view from below. An Octopus tissue stabilizer (Medtronic, Minneapolis, USA) was used to fix the echo transducer to provide identical echocardiographic views. Valve evaluation (Fig. 4) included the detection of an aortic insufficiency (AI) jet (yes / no) and in case of a jet, determination of its direction (central / eccentric; towards anterior mitral leaftlet/ towards ventricular septum). Each porcine heart underwent a test series including two different settings (Fig. 5): The dynamic setting was characterized by pulsatile flow conditions. Therefore, the platform’s pump was activated and the ARPD’s switch was in open position. For induction of the static setting, the pump was stopped and the device’s switch was closed simultaneously, thereby simulating cardioplegic arrest of the heart. Fluid was induced into the aortic root, using a pressure bag to mimic diastolic root pressure, while the left ventricle was vented in a manually controlled fashion. Diastolic root pressure, intraventricular pressure and the difference between them (∆P) were monitored, both in dynamic and static settings. Valve function was evaluated at two different pressure levels. Consequently, the targeted diastolic and static root pressure was 60 and 45 mmHg, while the goal for ventricular pressure was always 10 mmHg, thereby creating a ∆P of 50 and 35 mmHg respectively.

Each test run started with echo evaluation of the unaltered aortic valve (group N). Then aortic insufficiency was created by tensioning the prolene sutures with the left (group L) and right (group R) leaflet. Each group was evaluated both at 60 and 45 mmHg. Mean aortic root pressures were highly comparable between the dynamic and static settings in all groups at both pressure levels (Table 1).

Statistical methods Fisher's Exact test or Pearson's test were used to analyze cross tabulations. Generalized estimation equation models (GEE) with log Gamma distribution were used for continuous or binomial distribution of discrete variables. LSD tests were used for pairwise comparisons. All reported tests were two-sided, and p-values < 0.05 were considered statistically significant. All statistical analyses were performed by use of NCSS (NCSS 10, NCSS, LLC. Kaysville, UT), STATISTICA 13 (Hill, T. & Lewicki, P. Statistics: Methods and Applications. StatSoft, Tulsa, OK) and PASW 24 (IBM SPSS Statistics for Windows, Version 21.0., Armonk, NY).

Results In 12 hearts, a trivial AI jet was echocardiographically proven prior to tensioning of any valve leaflet (group N) in the dynamic setting at 60 mmHg (Table 2). At 45 mmHg those insufficiency jets could be detected in 10 hearts. At 60 mmHg in the static setting, measurements showed the same results as in the dynamic setting in all cases but one, in which a trace and central insufficiency was detectable only in the dynamic setting (14/15; 93.3%; 95% confidence interval [CI]: 68-100%). At 45 mmHg the same finding was detected in two hearts (13/15; 86.6%; 95% CI: 60 -100%). After tensioning of the left leaflet suture (group L), AI was detectable in all hearts both at 60 and 45 mmHg root pressure in the dynamic and static setting (15/15; 100%; 95%CI: 78-100%). The same results were found after tensioning of the right aortic leaflet (group R). Jet direction in group L at 60 mmHg was central in 5 hearts and eccentric in 10 hearts. At this pressure level dynamic and static setting measurements showed exactly the same echocardiographic results regarding jet existence and morphology (15/15; 100%; 95% CI: 78-100%). However, at 45 mmHg, jet direction differed between the dynamic and static setting in one heart, showing an eccentric insufficiency in the dynamic setting and a more central

insufficiency in the static setting (14/15; 93.3%; 95%CI: 68-100%). In group R four central and eleven eccentric insufficiencies, both at 60 and 45 mmHg, with concordant jet directions in all specimen (15/15; 100%; 95% CI: 78-100%; Table 3) were found.

Clinical Experience Currently there is no reliable device for functional aortic valve evaluation during cardioplegic arrest. The results of this study serve as preliminary work for clinical trials to introduce the ARPD into clinical practice.

Comment Aortic valve repair is a complex surgical procedure. A major point of concern is the early intraoperative, post-repair evaluation of valve function already during cardioplegic arrest. So far, due to the lack of a reliable test, such as the water test in mitral valve repair[1], echocardiographic valve analysis on the beating heart remains the gold standard to evaluate procedural success[2]. This requires the completion of the root procedure plus reperfusion. Since all those steps take a considerable amount of time, potential repair failures are only detected at a late timepoint. As a consequence, a further repair attempt requires aortic reclamping, induction of cardioplegic arrest and reopening of the aortic root. This results in longer over all cross clamp times, thereby potentially increasing the patient’s perioperative risk[3]. Therefore the ARPD was developed to allow echocardiographic aortic valve evaluation, while the patient is still on cardiopulmonary bypass and in cardioplegic arrest. The only precondition for using this device is that there is an aortic dacron graft in place – either after valve sparing root replacement or supracoronary aortic replacement with additional aortic valve repair. Summarizing our experiments, the use of the ARPD provides reproducible echocardiographic evaluation of the aortic valve. This might enable surgeons to check the valve during cardioplegic arrest and immediate address further repair improvements, if needed. This also might lead to a higher rate of successful and durable valve repairs. It could reduce reclamping rates and therefore cardiopulmonary bypass- and aortic cross-clamp-times. Besides all technical aspects, an early and valid valve examination tool might increase surgeon’s confidence in mastering this complex procedure. It could

also help to raise the acceptance for valve sparing root surgery in more centers by overcoming the challenging learning curve. The simulator test confirmed the intended function of the ARPD. The ultimate goal of our efforts is to create a surgical tool for regular use in men. Disclosure and Freedom of Investigation This work was supported by the Paracelsus Medical University research support fund [R-17/04/094DIN to Christian Dinges]. Development, Prototyping and Engineering of the ARPD was provided and funded by PMU Innovations GmbH. Travel expenses for in vitro test series were financed by PMU Innovations GmbH. Christian Dinges and Johann Fierlbeck are registered inventors in the pending patent for the ARPD. Christian Dinges is contractual recipient of royalties in case of commercial exploitation. The authors confirm that they had freedom of investigation and full control of the design of the study, methods used, outcome parameters and results, analysis of data, and production of the written report.

Figure legends

Figure 1: Aortic Root Pressurizing Device. A: Drawing of ARPD; B: Drawing of modified ARPD version (only for in vitro testing)

Figure 2: Cardiac Biosimulator™ Platform. A: Scheme of experimental setup; B: Heart incorporated into the Biosimulator™ Platform

Figure 3: Heart prepared for simulator testing

Figure 4: Example of echocardiographic doppler evaluation: static vs. dynamic simulator setting at 60 mmHg showing an eccentric jet after right aortic leaflet restriction. A: short axis view, static setting; B: long axis view, static setting; C: short axis view, dynamic setting; D: long axis view, dynamic setting. All images were taken in the same specimen at 60 mmHg aortic root pressure after right aortic leaflet restriction via prolene suture. AR = aortic root, LV = left ventricle: arrows = colour doppler image of eccentric insufficiency jet.

Figure 5: Study design of echocardiographic valve evaluation ARP = aortic root pressure; ARPD = Aortic Root Pressurizing Device; L = left leaflet restriction; LT = left leaflet prolapse; N = no restriction/prolapse; R = right leaflet restriction; RT = right leaflet prolapse

References [1]

Watanabe T, Arai H. Leakage test during mitral valve repair. Gen Thorac Cardiovasc Surg

2014;62:645-50. [2]

le Polain de Waroux JB, Pouleur AC, Robert A et al. Mechanisms of recurrent aortic

regurgitation after aortic valve repair: predictive value of intraoperative transesophageal echocardiography. JACC Cardiovasc Imaging 2009;2:931-9. [3]

Lansac E, Di Centa I, Sleilaty G et al. Long-term results of external aortic ring annuloplasty

for aortic valve repair. Eur J Cardiothorac Surg 2016;50:350-60.

Disclaimer: The Society of Thoracic Surgeons, The Southern Thoracic Surgical Association, and The Annals of Thoracic Surgery neither endorse nor discourage the use of the new technology described in this article.

Table 1: Mean aortic root pressure, ventricular pressure and ∆P for intended root pressure levels of 60 mmHg and 45 mmHg in dynamic and static simulator

Simulator

Mean

95% Wald Confidence

dynamic

59.6

59.2

60.1

static

61.9

61.5

62.3

dynamic

8.7

8.2

9.9

static

9.4

8.6

10.2

dynamic

51.5

50.4

52.6

static

52.4

51.3

53.5

dynamic

45.2

44.8

45.7

static

45.9

45.5

46.4

dynamic

8.2

7.3

9.0

static

9.0

8.2

9.9

Dynamic

37.5

36.3

38.6

static

36.9

35.8

38.0

ARP = 60 mmHg Aortic root pressure

Ventricular pressure

∆P

ARP = 45 mmHg Aortic root pressure

Ventricular pressure

∆P

ARP = aortic root pressure; ∆P = difference between aortic root pressure and ventricular pressure

Table 2: Detection of aortic insufficiency > 0

Dynamic setting

Static setting

Concordance

95% Confidence Intervals Lower (%)

Upper (%)

ARP = 60 mmHg Group N

12/15

11/15

14/15 (93%)

68

100

Group L

15/15

15/15

15/15 (100%)

78

100

Group R

15/15

15/15

15/15 (100%)

78

100

Group N

10/15

8/15

13/15 (87%)

60

100

Group L

15/15

15/15

15/15 (100%)

78

100

Group R

15/15

15/15

15/15 (100%)

78

100

ARP = 45 mmHg

ARP = aortic root pressure; L = left leaflet restriction; N = no restriction/prolapse; n.a. = not applicable; R = right leaflet restriction;

Table 3: Concordance of jet direction Concordance of jet direction (dynamic vs. static setting)

95% Confidence Intervals Lower (%)

Upper (%)

ARP = 60 mmHg Group N

14/15 (93.3 %)

68

100

Group L

15/15 (100%)

78

100

Group R

15/15 (100%)

78

100

Group N

13/15 (86.7%)

60

100

Group L

15/15 (100%)

78

100

Group R

15/15 (100%)

78

100

ARP = 45 mmHg

ARP = aortic root pressure; L = left leaflet restriction; N = no restriction/prolapse; n.a. = not applicable; R = right leaflet restriction;