The Aortic Valve: A Tale of Three Leaflets :

As you pick up May’s Pediatrics in Review with the articles on bicuspid aortic valve (10.1542/pir.2019-0307) and acute rheumatic fever (10.1542/pir.2019-0288), you will undoubtedly feel thrilled at the chance to brush up on these topics (confession: I may be biased). These articles bring to the forefront the notoriety of aortic valvular disease in children.

There are few things that get a cardiologist as engaged as the aortic valve. The size of the annulus relative to the child’s body surface area; the structure of the three leaflets of the semilunar aortic valve suspended from a fibrous structure above the annulus, meeting perfectly en face; the quest for the origins of the coronary arteries from the sinuses of Valsalva. So many parts make up a perfect aortic valve, and hence, so many things that can go wrong.^1-3A narrowed aortic valve limiting egress from the left ventricle, hence limiting systemic perfusion. The myocardium pumping heavy iron against this fixed obstruction and sometimes failing and becoming weak. Thickened leaflets which don’t allow blood flow smoothly or dysplastic leaflets that allow regurgitation of blood backwards, wasting cardiac output and leading to heart failure if uncorrected.

At birth, the aortic valve may be too small or stenotic; there is not enough blood leaving the left ventricle to perfuse the head or the body—critical aortic stenosis. What does one do? Simplistically, one might think—just stretch the valve open! A valvuloplasty is certainly an option; the question is how is that accomplished? The data tell us that, whether in the operating room or the catheterization laboratory, in experienced hands the survival is equivalent.^{4, 5} The risk is that of making the valve too leaky (aortic insufficiency). Children undergoing balloon valvuloplasty have a higher 5-year re-intervention rate, but the balance of costs between avoiding a sternotomy as a first procedure and the need for a re-intervention in the catheterization laboratory is as yet undetermined.^4,5,6

As the child grows, the valve may become too narrow or too leaky again. By the 10-year mark, nearly 80% of these children need to have their aortic valve replaced, as the native valve cannot be improved upon by more surgery or catherization.⁴ However, the prospect of aortic valve replacement in a child is a complex one. One option is the Ross Procedure. First described in 1967, the child’s pulmonary valve and associated root is used to replace the aortic valve, and a pulmonary homograft is used to replace their pulmonary valve.⁷ This allows the child to remain off major anticoagulation and have an aortic valve that continues to grow with them, yielding an excellent survival of 85% to 90% at 10 years.^7,8

Patients whose pulmonary valves are not normal may be able to get replacement aortic valves, which can be bioprosthetic (tissue-based), made from bovine or porcine pericardium or aortic tissue, or mechanical. This is where the pediatric patient gets the short end of the stick. In general, the smallest replacement aortic valve of either type available currently is 19 mm. To put this in perspective, that is the upper end of normal size for an aortic valve in a 9-year-old boy of average weight and height.^{9, 10,11} There are no replacement options for children younger or smaller than that. Additionally, mechanical aortic valves are artificial materials that trigger blood clots when placed in the body’s milieu, hence these patients need systemic anticoagulation. For a child this means regular blood tests to see if drug levels are therapeutic, tight control on diet (which is hard enough as an adult), and limiting contact sports (which, one may argue, all of middle school is one).

For a child who needs a working aortic valve but can’t get a Ross procedure or an artificial valve, there is the option of replacing the entire aortic root and valve with a homograft. These don’t grow along with the child, however, and not surprisingly have a nearly 5-times higher rate of re-intervention per year compared to the Ross procedure.^{12, 13} Additionally, there is the Ozaki technique: a novel surgical approach of reconstructing the aortic valve leaflets from the patient’s own pericardium. With the first outcomes reported in 2014, this offers children a new realm of possibility, with surgical prowess used to construct a valve that suits their size, is functional, and allows them to avoid systemic anticoagulation.^{14, 15}

All of this to say, pathology of the aortic valve remains a conundrum that the field of pediatric cardiology has been trying to solve for decades. As surgical and catheterization techniques evolve, and pediatric practitioners adapt these to our patient population, things look brighter. Yet we all look forward to the day when more research investment in pediatric congenital heart disease will lead to the development of valve replacement options made specifically for children, not just those that work for small adults.

References:

1. Friedland-Little JM, Zampi JD, Gajarski RJ. Aortic Stenosis. Chapter in Moss and Adams’ Heart Disease in Infants, Children, and Adolescents, Including the Fetus and Young Adult. Allen HD, Shaddy RE, Penny DJ, Feltes TF, Cetta F. Lippincott Williams & Wilkins (LWW). 9^th edition - 2016. ISBN: 978-1-49-630024-9
2. AHA Resources. https://www.heart.org/en/health-topics/heart-valve-problems-and-disease/heart-valve-problems-and-causes/problem-aortic-valve-stenosis
3. AHA Resources. https://www.heart.org/en/health-topics/heart-valve-problems-and-disease/heart-valve-problems-and-causes/problem-aortic-valve-regurgitation
4. Dorobantu DM, Taliotis D, Tulloh RM, Sharabiani MTA, Mohamed Ahmed E, Angelini GD, Stoica SC. Surgical versus balloon valvotomy in neonates and infants: results from the UK National Audit. Open Heart. 2019 Feb 14;6(1):e000938. doi: 10.1136/openhrt-2018-000938. PMID: 30997128; PMCID: PMC6443132
5. Hill GD, Ginde S, Rios R, Frommelt PC, Hill KD. Surgical valvotomy versus balloon valvuloplasty for congenital aortic valve stenosis: a systematic review and meta-analysis. J Am Heart Assoc. 2016 Aug 8;5(8):e003931. doi: 10.1161/JAHA.116.003931. PMID: 27503847; PMCID: PMC5015309
6. Morray BH, McElhinney DB. Semilunar valve interventions for congenital heart disease: jacc state-of-the-art review. J Am Coll Cardiol. 2021 Jan 5;77(1):71–79. doi: 10.1016/j.jacc.2020.10.052. PMID: 33413944
7. Piccardo A, Ghez O, Gariboldi V, Riberi A, Collart F, Kreitmann B, Metras D. Ross and Ross-Konno procedures in infants, children and adolescents: a 13-year experience. J Heart Valve Dis. 2009 Jan;18(1):76–82; discussion 83. PMID: 19301557
8. Brancaccio G, Polito A, Hoxha S, Gandolfo F, Giannico S, Amodeo A, Carotti A. The Ross procedure in patients aged less than 18 years: the midterm results. J Thorac Cardiovasc Surg. 2014 Jan;147(1):383–8. doi: 10.1016/j.jtcvs.2013.02.037. Epub 2013 Mar 13. PMID: 23490251
9. CDC Growth Charts. Children 2–20 years (5^th–95^th percentile) Boys Stature-for-Age and Weight-for-age. https://www.cdc.gov/growthcharts/data/set1clinical/cj41l021.pdf
10. http://www.parameterz.com/sites/valves
11. Cantinotti M, Giordano R, Scalese M, Murzi B, Assanta N, Spadoni I, Maura C, Marco M, Molinaro S, Kutty S, Iervasi G. Nomograms for two-dimensional echocardiography derived valvular and arterial dimensions in Caucasian children. J Cardiol. 2017 Jan;69(1):208–215
12. Etnel JR, Elmont LC, Ertekin E, Mokhles MM, Heuvelman HJ, Roos-Hesselink JW, de Jong PL, Helbing WA, Bogers AJ, Takkenberg JJ. Outcome after aortic valve replacement in children: a systematic review and meta-analysis. J Thorac Cardiovasc Surg. 2016 Jan;151(1):143-52.e1–3. doi: 10.1016/j.jtcvs.2015.09.083. Epub 2015 Sep 28. PMID: 26541831
13. Sharabiani MT, Dorobantu DM, Mahani AS, Turner M, Peter Tometzki AJ, Angelini GD, Parry AJ, Caputo M, Stoica SC. Aortic valve replacement and the ross operation in children and young adults. J Am Coll Cardiol. 2016 Jun 21;67(24):2858–70. doi: 10.1016/j.jacc.2016.04.021. PMID: 27311525
14. Ozaki S, Kawase I, Yamashita H, Uchida S, Nozawa Y, Takatoh M, Hagiwara S. A total of 404 cases of aortic valve reconstruction with glutaraldehyde-treated autologous pericardium. J Thorac Cardiovasc Surg. 2014 Jan;147(1):301–6. doi: 10.1016/j.jtcvs.2012.11.012. Epub 2012 Dec 8. PMID: 23228404
15. Ozaki S, Kawase I, Yamashita H, Uchida S, Takatoh M, Kiyohara N. Midterm outcomes after aortic valve neocuspidization with glutaraldehyde-treated autologous pericardium. J Thorac Cardiovasc Surg. 2018 Jun;155(6):2379–2387. doi: 10.1016/j.jtcvs.2018.01.087. Epub 2018 Feb 15. PMID: 29567131