The Journal of Thoracic and Cardiovascular Surgery

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Accepted Manuscript The Ross procedure: time to re-evaluate the guidelines Martin Misfeld, MD PhD, Michael A. Borger, MD PhD PII: S0022-5223(18)31853-1 DOI: 10.1016/j.jtcvs.2018.07.014 Reference: YMTC 13226 To appear in: The Journal of Thoracic and Cardiovascular Surgery Received Date: 9 July 2018 Accepted Date: 10 July 2018 Please cite this article as: Misfeld M, Borger MA, The Ross procedure: time to re-evaluate the guidelines, The Journal of Thoracic and Cardiovascular Surgery (2018), doi: 10.1016/ j.jtcvs.2018.07.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. 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.

The Ross procedure: time to re-evaluate the guidelines Martin Misfeld, MD PhD, and Michael A. Borger, MD PhD University Clinic of Cardiac Surgery, Heart Center, University of Leipzig, Leipzig, Germany Words: 550 Corresponding address: Michael A. Borger, MD, PhD Director of Cardiac Surgery Leipzig Heart Center, University of Leipzig Struempellstrasse 39 04289 Leipzig, Germany Phone: +49-341-865-0 Fax: +49-341-865-1452 Email: michael.borger@helios-kliniken.de

Central message: The Ross procedure is associated with excellent long-term results in centers of expertise. Future versions of valve guidelines should more strongly recommend this option.

In this issue of the Journal, David et al. provide another piece of convincing evidence that the Ross procedure is an excellent therapeutic option in select patients requiring aortic valve replacement (AVR) surgery. In their series of 212 patients with a median age of 34 years, the cumulative probability of freedom from Ross-related reoperation at 20 years was a superb 85.9%. The probability of autograft regurgitation at 20 years was 13.0% and homograft dysfunction was 19.7%. The independent predictors of autograft failure were older age at operation, male gender, preoperative aortic valve regurgitation, and time since operation. Furthermore, no operative deaths or serious adverse events were observed in the 14% of patients who required valve reoperation during follow up. Such data plays a large role in the observation that Ross patients from experienced centers have the same life expectancy as age- and gender-matched controls from the general population 2,3. Recent evidence suggest that Ross patients may even have better long-term survival than those undergoing mechanical AVR 4. Several important studies have been published in the last few years demonstrating very good to excellent long-term results of the Ross procedure in large series of young adult AVR patients 2-5. Despite these findings, the Ross operation has not gained widespread acceptance and published valve guidelines have generally not been supportive of the procedure. The latest American guidelines gave a class IIb, level of evidence C recommendation for the Ross procedure in young patients when vitamin K anticoagulation is contraindicated or undesirable 6, and the most recent European guidelines 7 does not even mention the Ross operation whatsoever. Both sets of guidelines recommend a mechanical prosthesis in young adults requiring AVR. However, it is specifically this patient population that may benefit the most from a Ross procedure, if performed by experienced hands.

One argument against wider adoption the Ross procedure is the fact that only a few centers have published extensively on this subject. However, the same argument can be applied to minimally-invasive and robotic mitral valve repair, aortic valve sparing procedures, and thoraco-abdominal aortic repair. Single center series from a small number of expert surgeons represent the gold standard by which others should be comparing their results. Whether that means that such procedures should be diminished and / or neglected by the guidelines writing committees is open to discussion. The recently published low rates of Ross-related reoperations during very long follow up are summarized in Table 1. This table supplies strong support that the Ross procedure should be offered to young patients requiring AVR. With the exception of the study from Martin et al, 4 long-term freedom from valve-related reoperation rates are comparable to those achieved with a mechanical prosthesis, without any of the risks involved with lifelong anticoagulation. It should be noted that the abovementioned results include early experience with the Ross operation in each of the study centers. Further improvements may be expected when knowledge that has been attained over time is applied. For example, there is now sufficient evidence that reoperation rates post-ross are higher in patients with connective tissue disorders, isolated aortic regurgitation, and those that do not undergo some form of aortic root stabilization.

In conclusion, the paper by David et al supplies further evidence that the Ross procedure is an excellent alternative in young adults requiring AVR in centers of expertise. It is time for the guidelines to reflect the ever growing body of evidence supporting this operation.

Table 1: Late results of the Ross operation. n Age (years) 20-year freedom from Ross-related reoperation Autograft (95% CI) Homograft (95% CI) David et al. 1 212 34 (median, IQR 28 41) 88.5% (82.0 92.8) 91.8% (85.3 95.4) Sievers et al. 2 630 44.7 ± 11.9 (mean +/- SD) 89.8 % (84.3 95.7) 91.0 % (86.3 96.0) Skillington et al. 3 322 39.5 96 % _ (mean, range 15 63) (92 98)* Martin et al. 5 310 40.8 ± 10.6 (mean +/- SD) 60.8 % (50.2 69.8) 61.8 % (52.0 70.2) *results are at 18 years SD = standard deviation, IQR = interquartile range

References 1. David TE, Ouzounian M, David CM, Lafreniere-Roula M, Manlhiot C. Late results of the Ross procedure. J Thorac Cardiovasc Surg 2018:XXX. 2. Sievers HH, Stierle U, Petersen M, Klotz S, Richardt D, Diwoky M, et al. Valve performance classification in 630 subcoronary Ross patients over 22 years. J Thorac Cardiovasc Surg 2018;156:79-86. 3. Skillington PD, Mohkles MM, Takkenberg JJM, Larobina M, O`Keefe M, Wynne R, et al. The Ross procedure using autologous support of the pulmonary autograft: techniques and late results. J THorac Cardiovasc Surg 2015;149:S46-52. 4. Buratto E, Shi WY, Wynne R, Poh CL, Larobina M, O'Keefe M, et al. Improved survival after the Ross procedure compared with mechanical aortic valve replacement. J Am Coll Cardiol. 2018;71:1337-44. 5. Martin E, Mohammadi S, Jacques F, Kalavrouziotis D, Voisine P, Doyle D, et al. Clinical outcomes following the Ross procedure in adults: A 25-year longitudinal study. J Am Coll Cardiol 2017;70: 1890-9. 6. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin III JP, Fleisher LA, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guidelines for the management of patients with valvular heart disease. J Am Coll Cardiol 2017;70:252-89. 7. Falk V, Baumgartner H, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur J Cardiothorac Surg 2017;52:616-64. 8. Hanke T, Charitos EL, Paarmann H, Stierle U, Sievers HH. Haemodynamic performance of a new pericardial aortic bioprosthesis during exercise and recovery:

comparison with pulmonary autograft, stentless aortic bioprosthesis and healthy control groups. Eur J Cardiothorac Surg 2013;44:e295-301. 9. Aicher D, Holz A, Feldner S, Köllner V, Schäfers HJ. Quality of life after aortic valve surgery: replacement versus reconstruction. J Thorac Cardiovasc Surg 2011;142:e19-24.