Aortic Diameter Growth in Children With a Bicuspid Aortic Valve
2017; Elsevier BV; Volume: 120; Issue: 1 Linguagem: Inglês
10.1016/j.amjcard.2017.03.245
ISSN1879-1913
AutoresRemy Merkx, Anthonie L. Duijnhouwer, Evelien Vink, Jolien W. Roos‐Hesselink, Michiel Schokking,
Tópico(s)Cardiac Valve Diseases and Treatments
ResumoKnowledge of aortic growth in patients with bicuspid aortic valve (BAV) is essential to identify patients at risk for dissection, but data on children remain unclear. We retrospectively evaluated the aortic diameters of all pediatric BAV patients, identified through an echocardiographic database (2005 to 2013). Medical records were reviewed and aortic diameters re-measured on echocardiographic images at diagnosis and if available on variable mid- and endpoints follow-up. Dilatation (z-score >2) was based on 2 different z-score equation methods (Gautier/Campens). In 234 of the total 250 BAV patients, aortic diameters were analyzed; median age was 6.1 years (interquartile range 1.7 to 10), of which 63% were male. Aortic coarctation was present in 81 (36%) patients, 23% had a ventricular septal defect. BAV morphology according to Sievers was as follows: type 0 in 128 patients (55%), type 1 in 96 (41%), and type 2 in 10 (4%). Ascending aortic (AA) dilatation was present in 24% (Gautier) and 36% (Campens) at inclusion. Median follow-up was 4.7 years. The AA was the only location where mean z-scores progressed significantly with age: 0.06 (Gautier) and 0.09 (Campens) units per year between ages 5 and 15 years. Associations for higher AA z-scores at older age were an initial z-score >2 (p <0.001) and aortic valve stenosis (p 2) was based on 2 different z-score equation methods (Gautier/Campens). In 234 of the total 250 BAV patients, aortic diameters were analyzed; median age was 6.1 years (interquartile range 1.7 to 10), of which 63% were male. Aortic coarctation was present in 81 (36%) patients, 23% had a ventricular septal defect. BAV morphology according to Sievers was as follows: type 0 in 128 patients (55%), type 1 in 96 (41%), and type 2 in 10 (4%). Ascending aortic (AA) dilatation was present in 24% (Gautier) and 36% (Campens) at inclusion. Median follow-up was 4.7 years. The AA was the only location where mean z-scores progressed significantly with age: 0.06 (Gautier) and 0.09 (Campens) units per year between ages 5 and 15 years. Associations for higher AA z-scores at older age were an initial z-score >2 (p <0.001) and aortic valve stenosis (p <0.05). Neither dissection nor preventive aortic surgery occurred. In conclusion, only the AA seems at risk for complication, although no aortic complications occurred in this pediatric BAV cohort. BAV morphology seems associated with larger AA z-scores and valvular dysfunction. Bicuspid aortic valve (BAV) is the most common congenital heart defect and has considerable morbidity and mortality.1Ward C. Clinical significance of the bicuspid aortic valve.Heart. 2000; 83: 81-85Crossref PubMed Scopus (597) Google Scholar, 2Basso C. Boschello M. Perrone C. Mecenero A. Cera A. Bicego D. Thiene G. De Dominicis E. An echocardiographic survey of primary school children for bicuspid aortic valve.Am J Cardiol. 2004; 93: 661-663Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 3Mordi I. Tzemos N. Bicuspid aortic valve disease: a comprehensive review.Cardiol Res Pract. 2012; 2012: 196037Crossref PubMed Scopus (69) Google Scholar It occurs isolated or in combination with additional heart defects and may occur in the context of a syndrome.1Ward C. Clinical significance of the bicuspid aortic valve.Heart. 2000; 83: 81-85Crossref PubMed Scopus (597) Google Scholar, 4Braverman A.C. Guven H. Beardslee M.A. Makan M. Kates A.M. Moon M.R. The bicuspid aortic valve.Curr Probl Cardiol. 2005; 30: 470-522Abstract Full Text Full Text PDF PubMed Google Scholar, 5Fernandes S.M. Sanders S.P. Khairy P. Jenkins K.J. Gauvreau K. Lang P. Simonds H. Colan S.D. Morphology of bicuspid aortic valve in children and adolescents.J Am Coll Cardiol. 2004; 44: 1648-1651Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 6Ciotti G.R. Vlahos A.P. Silverman N.H. Morphology and function of the bicuspid aortic valve with and without coarctation of the aorta in the young.Am J Cardiol. 2006; 98: 1096-1102Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 7Yuan S.M. Jing H. Lavee J. The bicuspid aortic valve and its relation to aortic dilation.Clinics (Sao Paulo). 2010; 65: 497-505Crossref PubMed Scopus (23) Google Scholar In young adults, valve dysfunction requiring an intervention occurs frequently and valve dysfunction degree seems associated to BAV morphologic phenotype.1Ward C. Clinical significance of the bicuspid aortic valve.Heart. 2000; 83: 81-85Crossref PubMed Scopus (597) Google Scholar, 4Braverman A.C. Guven H. Beardslee M.A. Makan M. Kates A.M. Moon M.R. 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Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve.Am J Cardiol. 2007; 99: 978-983Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 11Mahle W.T. Sutherland J.L. Frias P.A. Outcome of isolated bicuspid aortic valve in childhood.J Pediatr. 2010; 157: 445-449Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Aortic dilatation, predisposing for life-threatening rupture and dissection, is found in half of adult patients.1Ward C. Clinical significance of the bicuspid aortic valve.Heart. 2000; 83: 81-85Crossref PubMed Scopus (597) Google Scholar, 12Della Corte A. Bancone C. Quarto C. Dialetto G. Covino F.E. Scardone M. Caianiello G. Cotrufo M. Predictors of ascending aortic dilatation with bicuspid aortic valve: a wide spectrum of disease expression.Eur J Cardiothorac Surg. 2007; 31: 397-404Crossref PubMed Scopus (265) Google Scholar, 13Verma S. Siu S.C. Aortic dilatation in patients with bicuspid aortic valve.N Engl J Med. 2014; 370: 1920-1929Crossref PubMed Scopus (354) Google Scholar, 14Michelena H.I. Khanna A.D. Mahoney D. Margaryan E. Topilsky Y. Suri R.M. Eidem B. Edwards W.D. Sundt 3rd, T.M. Enriquez-Sarano M. Incidence of aortic complications in patients with bicuspid aortic valves.JAMA. 2011; 306: 1104-1112Crossref PubMed Scopus (580) Google Scholar Dilatation rates and its associations are well studied in adults,12Della Corte A. Bancone C. Quarto C. Dialetto G. Covino F.E. Scardone M. Caianiello G. Cotrufo M. Predictors of ascending aortic dilatation with bicuspid aortic valve: a wide spectrum of disease expression.Eur J Cardiothorac Surg. 2007; 31: 397-404Crossref PubMed Scopus (265) Google Scholar, 13Verma S. Siu S.C. Aortic dilatation in patients with bicuspid aortic valve.N Engl J Med. 2014; 370: 1920-1929Crossref PubMed Scopus (354) Google Scholar, 15Thanassoulis G. Yip J.W. Filion K. Jamorski M. Webb G. Siu S.C. Therrien J. Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves.Nat Clin Pract Cardiovasc Med. 2008; 5: 821-828Crossref PubMed Scopus (119) Google Scholar, 16Detaint D. Michelena H.I. Nkomo V.T. Vahanian A. Jondeau G. Sarano M.E. Aortic dilatation patterns and rates in adults with bicuspid aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy.Heart. 2014; 100: 126-134Crossref PubMed Scopus (153) Google Scholar but for children these data are largely unclear.8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar, 10Holmes K.W. Lehmann C.U. Dalal D. Nasir K. Dietz H.C. Ravekes W.J. Thompson W.R. Spevak P.J. Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve.Am J Cardiol. 2007; 99: 978-983Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 17Beroukhim R.S. Kruzick T.L. Taylor A.L. Gao D. Yetman A.T. Progression of aortic dilation in children with a functionally normal bicuspid aortic valve.Am J Cardiol. 2006; 98: 828-830Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 18Warren A.E. Boyd M.L. O'Connell C. Dodds L. Dilatation of the ascending aorta in paediatric patients with bicuspid aortic valve: frequency, rate of progression and risk factors.Heart. 2006; 92: 1496-1500Crossref PubMed Scopus (103) Google Scholar, 19Gurvitz M. Chang R.K. Drant S. Allada V. Frequency of aortic root dilation in children with a bicuspid aortic valve.Am J Cardiol. 2004; 94: 1337-1340Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar In children, the aortic diameter is typically corrected, mostly for body size area, age, and gender. The advised method is to use z-scores (the number of standard deviations above or below the expected diameter). Different regression equations for expected aortic diameter and corresponding z-scores are currently in use, none of which having emerged as optimal. In the present study, we retrospectively investigated aortic diameter (z-score) change during follow-up and its possible associations in a pediatric cohort with BAV. We included all children 2.5 m/s, as jet velocity is the strongest predictor for clinical outcome.21Baumgartner H. Hung J. Bermejo J. Chambers J.B. Evangelista A. Griffin B.P. Iung B. Otto C.M. Pellikka P.A. Quinones M. American Society of EchocardiographyEuropean Association of EchocardiographyEchocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice.Eur J Echocardiogr. 2009; 10: 1-25Crossref PubMed Scopus (808) Google Scholar Aortic valve regurgitation was present when reported mild or more, based on jet evaluation and descending aortic backflow on color Doppler, left ventricular dimensions, and pressure half-time.22Zoghbi W.A. Enriquez-Sarano M. Foster E. Grayburn P.A. Kraft C.D. Levine R.A. Nihoyannopoulos P. Otto C.M. Quinones M.A. Rakowski H. Stewart W.J. Waggoner A. Weissman N.J. American Society of EchocardiographyRecommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography.J Am Soc Echocardiogr. 2003; 16: 777-802Abstract Full Text Full Text PDF PubMed Scopus (3389) Google Scholar Patients were scored as having hypertension when they were medically treated for high blood pressure. One researcher (RM) measured aortic diameters at the sinus of valsalva (SOV), STJ, and AA, defined as maximal diameter between STJ and aortic arch. Up to 3 studies were included (oldest, latest, and middlemost; ≥6 months apart). Measurements were performed in parasternal long-axis view at end-diastole, leading edge to leading edge, and perpendicular to the long axis of the aorta (Supplementary Figure 1).23Goldstein S.A. Evangelista A. Abbara S. Arai A. Asch F.M. Badano L.P. Bolen M.A. Connolly H.M. Cuellar-Calabria H. Czerny M. Devereux R.B. Erbel R.A. Fattori R. Isselbacher E.M. Lindsay J.M. McCulloch M. Michelena H.I. Nienaber C.A. Oh J.K. Pepi M. Taylor A.J. Weinsaft J.W. Zamorano J.L. Dietz H. Eagle K. Elefteriades J. Jondeau G. Rousseau H. Schepens M. Multimodality imaging of diseases of the thoracic aorta in adults: from the American Society of Echocardiography and the European Association of Cardiovascular Imaging: endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance.J Am Soc Echocardiogr. 2015; 28: 119-182Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar Averages of 3 measurements, preferably in various cardiac cycles, were used. Missing height and weight data were interpolated if growth curves looked stable and had at least 4 points within 9 months. Continuous variables are presented as mean (±SD) or median (interquartile range [IQR]) where appropriate, and categorical variables as frequencies. Differences were detected with Student's t, one-way analysis of variance, Pearson chi-square, Fisher's exact, or McNemar tests. Intraclass correlation and Bland-Altman plots assessed interobserver agreement on aortic measurements between 2 observers in 20 random patients. Aortic diameters were converted to z-scores using 2 different methods: by Gautier et al and by Campens et al. Both used the body surface area formula by Du Bois and both did not include neonates and toddlers,24Gautier M. Detaint D. Fermanian C. Aegerter P. Delorme G. Arnoult F. Milleron O. Raoux F. Stheneur C. Boileau C. Vahanian A. Jondeau G. Nomograms for aortic root diameters in children using two-dimensional echocardiography.Am J Cardiol. 2010; 105: 888-894Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar, 25Campens L. Demulier L. De Groote K. Vandekerckhove K. De Wolf D. Roman M.J. Devereux R.B. De Paepe A. De Backer J. Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories.Am J Cardiol. 2014; 114: 914-920Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar although, as representative data on these very young children are lacking, we nevertheless chose to apply these methods. For this reason, we also performed additional regression analysis on absolute diameters at first examination. A z-score >2 was considered abnormal. Only Gautier's method was used for analysis of aortic growth in various subgroups. To account for dependency of serial measurements, the mean z-score over time was described with 5th order polynomials (quintics) constructed from a linear mixed-effects model, allowing single and serial measurements, unequal intervals, and a random intercept per subject. A likelihood ratio test assessed differences between subgroups. This model only allowed a univariate approach. p-values <0.05 were considered statistically significant. Analyses were performed in SPSS 20 (IBM Corp.). Of 11,792 children who underwent echocardiography, BAV was reported in 286. A total of 36 patients were excluded from the study because of incorrect diagnosis (n = 32), missing images (n = 1) or cardiac surgery distorting original valve anatomy before 2005 (n = 3). Of the 250 (2.1%) remaining patients, aortic diameters could be assessed in 234 (Ross procedure after 2005, n = 1; image storage errors, n = 4; inadequate images, n = 7; no height or weight data, n = 4), providing 580 studies. Table 1 describes their baseline characteristics, categorized by valve morphology. Median age at first valve intervention was 0.4 years (IQR 0 to 2.3). Patients with aortic coarctation had significantly lower rates of valve interventions compared with those without (7% vs 19%, p <0.05).Table 1Demographics, categorized by Sievers' valve morphologyCharacteristicsTotaln = 234Type 0Type 1Type 2APLATRLRNLR:RNn = 97 (42%)n = 31 (13%)n = 53 (23%)n = 43 (18%)n = 10 (4%)Growth parameters (mean ± SD) Age (years)6.4 ± 5.06.2 ± 5.56.9 ± 5.46.4 ± 4.96.2 ± 4.26.8 ± 3.1 Body Surface Area (m2)0.8 ± 0.40.8 ± 0.50.9 ± 0.50.8 ± 0.40.8 ± 0.40.9 ± 0.2 Body Mass Index (kg/m2)16 ± 316 ± 316 ± 316 ± 316 ± 215 ± 2Male sex63%59%52%70%65%100%Syndrome11%14%7%13%7%0% Turner5% †13% of female subjects.5%7%8%2%0% 22q11 deletion3%5%0%2%0%0% Other ‡Specification in Supplementary Table 1.3%4%0%4%5%0%Cardiac malformations §One patient can have several malformations. Any∗∗57%78%35%49%35%60% Coarctation of the aorta∗∗36%52%16%34%14%40% Ventricular septal defect∗23%33%19%19%7%30% Patent ductus arteriosus15%23%7%9%9%10% Atrial septal defect9%12%7%8%9%0% Hypoplastic aortic arch9%12%10%4%2%20% Other∗ ‡Specification in Supplementary Table 1.33%44%19%26%23%30%Systemic hypertension ‖Considered present if seen in at least one of the echocardiographic studies.5%5%7%8%0%0%Aortic valve dysfunction ‖Considered present if seen in at least one of the echocardiographic studies. Any∗∗57%37%74%55%81%100% Aortic valve stenosis∗∗40%15%61%34%72%100% Aortic valve regurgitation∗∗48%30%61%47%74%70%Aortic valve intervention∗∗16%6%23%15%35%10% 2nd5%..... 3rd, 4th, 5th0.4%.....Ascending aortic intervention0%.....Aortic arch intervention∗∗33%50%13%30%14%40%Significance of association between presented characteristic and BAV morphologic phenotype: ∗p <0.05, ∗∗p <0.001.AP = anterior-posterior orientation; LAT = lateral orientation; RL = right-left coronary cusp fusion; RN = right-noncoronary cusp fusion; LR:RN = left-right and right-noncoronary cusp fusion.† 13% of female subjects.‡ Specification in Supplementary Table 1.§ One patient can have several malformations.‖ Considered present if seen in at least one of the echocardiographic studies. Open table in a new tab Significance of association between presented characteristic and BAV morphologic phenotype: ∗p <0.05, ∗∗p <0.001. AP = anterior-posterior orientation; LAT = lateral orientation; RL = right-left coronary cusp fusion; RN = right-noncoronary cusp fusion; LR:RN = left-right and right-noncoronary cusp fusion. Interobserver agreement coefficients on aortic measurements were 0.98 (SOV), 0.87 (STJ), and 0.96 (AA). Overall difference between observers was −0.39 mm (p 2 at first examination were highest for the AA (Table 2), irrespective of the used z-score equation.24Gautier M. Detaint D. Fermanian C. Aegerter P. Delorme G. Arnoult F. Milleron O. Raoux F. Stheneur C. Boileau C. Vahanian A. Jondeau G. Nomograms for aortic root diameters in children using two-dimensional echocardiography.Am J Cardiol. 2010; 105: 888-894Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar, 25Campens L. Demulier L. De Groote K. Vandekerckhove K. De Wolf D. Roman M.J. Devereux R.B. De Paepe A. De Backer J. Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories.Am J Cardiol. 2014; 114: 914-920Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar Figure 2 presents the 5th order polynomials best estimating the mean course of z-scores, with 95% confidence intervals of the estimate. The AA showed highest z-scores and was the only location demonstrating significant growth between ages 5 and 15 years, for both z-score equations: 0.67 to 1.24 (Gautier) and 0.45 to 1.29 (Campens), resulting in mean growth rates of 0.06 and 0.09 z-score units per year, respectively. Both methods showed no z-score progression for the SOV. The STJ was significantly greater than normal, but also nonprogressive. Significant differences are observed between both methods of z-score equation, particularly in the neonatal and toddler ages, with exceedingly high z-scores for Campens' equation.Table 2Mean z-scores and prevalence of a z-score >2 at first echocardiography (n = 234, median age = 6.1 years)Gautier'sequationCampens'equationp-valueZ-score (mean ±SD) Sinus of Valsalva-0.2 ± 1.50.6 ± 1.5 ‡<0.001 Sinotubular junction0.3 ± 1.8 †-- Ascending aorta0.8 ± 1.7 ‡1.4 ± 2.2 ‡ 2 (% ±SE) Sinus of Valsalva8 ± 215 ± 2<0.001∗McNemar test. Sinotubular junction15 ± 2-- Ascending aorta24 ± 336 ± 3<0.001∗McNemar test.Significance compared with normal population (mean z-score = 0): †p <0.01; ‡p <0.001.Campens did not provide an equation for the sinotubular junction.∗ McNemar test. Open table in a new tab Significance compared with normal population (mean z-score = 0): †p <0.01; ‡p 2 at inclusion was associated with a higher AA z-score at older age, compared with patients with an initial z-score <2 (p <0.001). However, the z-score progression rate (Δz/Δt) was only minimally different between both groups and thus larger AA diameter was not associated with "faster" AA growth. Presence of AS also resulted in significantly higher AA z-scores (p 2 was not associated to the presence of AS. Comparing patients with versus without aortic regurgitation, aortic arch and valve interventions, and specifically a history of coarctation did not result in significant differences in estimated z-score course. For the SOV, a z-score >2 at inclusion (p <0.001), male gender (p <0.01), Sievers' type 2 (p <0.01), syndromes (p <0.001), and absence of AS (p 2 (23% vs 6%, p <0.05) and less often had AS (28% vs 60%, p 2 (4% vs 13%, p <0.05). Higher STJ z-scores were observed in syndromes (p 2 (p <0.001), and right-non coronary cusp fusion subtype within Sievers' type 1 valve morphology (p 2 and presence of AS were clinical markers for higher z-scores in early adulthood, but z-score progression was not faster. Indeed, aortic pathology in the context of BAV seems not a clinical problem in childhood. Previous studies compared contributing factors using numerical growth rates. This is the first study providing a visualized comparison of aortic diameter growth in children with a BAV.8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar, 10Holmes K.W. Lehmann C.U. Dalal D. Nasir K. Dietz H.C. Ravekes W.J. Thompson W.R. Spevak P.J. Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve.Am J Cardiol. 2007; 99: 978-983Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 17Beroukhim R.S. Kruzick T.L. Taylor A.L. Gao D. Yetman A.T. Progression of aortic dilation in children with a functionally normal bicuspid aortic valve.Am J Cardiol. 2006; 98: 828-830Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 18Warren A.E. Boyd M.L. O'Connell C. Dodds L. Dilatation of the ascending aorta in paediatric patients with bicuspid aortic valve: frequency, rate of progression and risk factors.Heart. 2006; 92: 1496-1500Crossref PubMed Scopus (103) Google Scholar, 19Gurvitz M. Chang R.K. Drant S. Allada V. Frequency of aortic root dilation in children with a bicuspid aortic valve.Am J Cardiol. 2004; 94: 1337-1340Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar As expected, BAV was common in our pediatric cardiology department and clearly associated with valve- and non–valve-related morbidity such as coarctation of the aorta,2Basso C. Boschello M. Perrone C. Mecenero A. Cera A. Bicego D. Thiene G. De Dominicis E. An echocardiographic survey of primary school children for bicuspid aortic valve.Am J Cardiol. 2004; 93: 661-663Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 26Roos-Hesselink J.W. Scholzel B.E. Heijdra R.J. Spitaels S.E. Meijboom F.J. Boersma E. Bogers A.J. Simoons M.L. Aortic valve and aortic arch pathology after coarctation repair.Heart. 2003; 89: 1074-1077Crossref PubMed Scopus (112) Google Scholar but also with other anomalies such as ventricular septal defects and patent ductus arteriosus, for which only putative associations were mentioned.5Fernandes S.M. Sanders S.P. Khairy P. Jenkins K.J. Gauvreau K. Lang P. Simonds H. Colan S.D. Morphology of bicuspid aortic valve in children and adolescents.J Am Coll Cardiol. 2004; 44: 1648-1651Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 6Ciotti G.R. Vlahos A.P. Silverman N.H. Morphology and function of the bicuspid aortic valve with and without coarctation of the aorta in the young.Am J Cardiol. 2006; 98: 1096-1102Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 7Yuan S.M. Jing H. Lavee J. The bicuspid aortic valve and its relation to aortic dilation.Clinics (Sao Paulo). 2010; 65: 497-505Crossref PubMed Scopus (23) Google Scholar, 27Duran A.C. Frescura C. Sans-Coma V. Angelini A. Basso C. Thiene G. Bicuspid aortic valves in hearts with other congenital heart disease.J Heart Valve Dis. 1995; 4: 581-590PubMed Google Scholar, 28Yuan S.M. Jing H. The bicuspid aortic valve and related disorders.Sao Paulo Med J. 2010; 128: 296-301Crossref PubMed Google Scholar, 29Cripe L. Andelfinger G. Martin L.J. Shooner K. Benson D.W. Bicuspid aortic valve is heritable.J Am Coll Cardiol. 2004; 44: 138-143Abstract Full Text Full Text PDF PubMed Scopus (474) Google Scholar Awareness and echocardiographic screening for other anomalies in clinical practice is mandatory. Similar to Fernandes et al,9Fernandes S.M. Khairy P. Sanders S.P. Colan S.D. Bicuspid aortic valve morphology and interventions in the young.J Am Coll Cardiol. 2007; 49: 2211-2214Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar valve interventions occurred in a minority and mainly early in life, typically for aortic stenosis. Most importantly, no intervention for aortic dilatation was needed and no complications of aortic dilatation occurred. However, some follow-up seems warranted as we do not want to miss the individual patient with rapid increase in diameter. For the patient with isolated, normally functioning BAV, we suggest to perform echocardiography every 5–10 years. The AA shows the largest relative diameter and clearly grows faster than can be expected based on body growth and/or age. No significant differences in absolute AA diameter were observed between patients with isolated BAV and BAV patients with associated lesions or valve dysfunction. However, the isolated BAV group was only small. Although patients with an initial z-score >2 and patients with AS had a higher initial z-score, they all had similar AA growth, which makes AA diameter growth predictable. The progression of 0.06 to 0.09 z-score units per year was notably similar to literature that likewise used z-scores,8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar, 10Holmes K.W. Lehmann C.U. Dalal D. Nasir K. Dietz H.C. Ravekes W.J. Thompson W.R. Spevak P.J. Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve.Am J Cardiol. 2007; 99: 978-983Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar as was absolute aortic diameter growth.17Beroukhim R.S. Kruzick T.L. Taylor A.L. Gao D. Yetman A.T. Progression of aortic dilation in children with a functionally normal bicuspid aortic valve.Am J Cardiol. 2006; 98: 828-830Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar Fernandes et al8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar earlier concluded that young patients initially presenting with higher z-scores seem to be at highest risk for aortic dilatation at later age, and this seems valid for all locations. It seems logical that only the AA is at risk for dilatation-related complications, as it is the only location showing z-score progression, but whether these patients indeed have an elevated need to undergo (preventive) aortic surgery at later age is not well studied. We propose regular follow-up for patients entering young adulthood to overcome this gap in knowledge. Earlier studies suggested protective effects of a coarctation history on AA z-score progression, but we could not confirm this finding.8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar, 13Verma S. Siu S.C. Aortic dilatation in patients with bicuspid aortic valve.N Engl J Med. 2014; 370: 1920-1929Crossref PubMed Scopus (354) Google Scholar, 15Thanassoulis G. Yip J.W. Filion K. Jamorski M. Webb G. Siu S.C. Therrien J. Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves.Nat Clin Pract Cardiovasc Med. 2008; 5: 821-828Crossref PubMed Scopus (119) Google Scholar Also, aortic regurgitation and aortic or valvular interventions were not associated with aortic size. Previous studies reported conflicting data on the increase of aortic dimensions at the level of the SOV.8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar, 10Holmes K.W. Lehmann C.U. Dalal D. Nasir K. Dietz H.C. Ravekes W.J. Thompson W.R. Spevak P.J. Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve.Am J Cardiol. 2007; 99: 978-983Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 17Beroukhim R.S. Kruzick T.L. Taylor A.L. Gao D. Yetman A.T. Progression of aortic dilation in children with a functionally normal bicuspid aortic valve.Am J Cardiol. 2006; 98: 828-830Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 18Warren A.E. Boyd M.L. O'Connell C. Dodds L. Dilatation of the ascending aorta in paediatric patients with bicuspid aortic valve: frequency, rate of progression and risk factors.Heart. 2006; 92: 1496-1500Crossref PubMed Scopus (103) Google Scholar, 19Gurvitz M. Chang R.K. Drant S. Allada V. Frequency of aortic root dilation in children with a bicuspid aortic valve.Am J Cardiol. 2004; 94: 1337-1340Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar We found no z-score progression at this level. The clinical relevance of having an underlying syndrome on STJ diameters remains unclear, mainly because of the heterogeneity of this group. It is suggested that in adult cohorts, BAV morphology is associated with valve dysfunction and complications.3Mordi I. Tzemos N. Bicuspid aortic valve disease: a comprehensive review.Cardiol Res Pract. 2012; 2012: 196037Crossref PubMed Scopus (69) Google Scholar, 4Braverman A.C. Guven H. Beardslee M.A. Makan M. Kates A.M. Moon M.R. The bicuspid aortic valve.Curr Probl Cardiol. 2005; 30: 470-522Abstract Full Text Full Text PDF PubMed Google Scholar, 5Fernandes S.M. Sanders S.P. Khairy P. Jenkins K.J. Gauvreau K. Lang P. Simonds H. Colan S.D. Morphology of bicuspid aortic valve in children and adolescents.J Am Coll Cardiol. 2004; 44: 1648-1651Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 6Ciotti G.R. Vlahos A.P. Silverman N.H. Morphology and function of the bicuspid aortic valve with and without coarctation of the aorta in the young.Am J Cardiol. 2006; 98: 1096-1102Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Our study confirms this in a pediatric cohort. Valve morphology should be determined at young age, for which in our opinion Sievers' classification is applicable. Distribution of BAV morphology differed from Sievers' original study, possibly because of differences in age category.20Sievers H.H. Schmidtke C. A classification system for the bicuspid aortic valve from 304 surgical specimens.J Thorac Cardiovasc Surg. 2007; 133: 1226-1233Abstract Full Text Full Text PDF PubMed Scopus (764) Google Scholar Comparing studies that included BAV morphology is challenging because of a large variety in classifications. Many studies applied morphologic classification named after localization of 1 supposed fusion line (right-left, right-non and left-non coronary cusp fusion), whereas Sievers' classification also allows 0 and 2 fusion lines.5Fernandes S.M. Sanders S.P. Khairy P. Jenkins K.J. Gauvreau K. Lang P. Simonds H. Colan S.D. Morphology of bicuspid aortic valve in children and adolescents.J Am Coll Cardiol. 2004; 44: 1648-1651Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 8Fernandes S. Khairy P. Graham D.A. Colan S.D. Galvin T.C. Sanders S.P. Singh M.N. Bhatt A. Lacro R.V. Bicuspid aortic valve and associated aortic dilation in the young.Heart. 2012; 98: 1014-1019Crossref PubMed Scopus (66) Google Scholar, 9Fernandes S.M. Khairy P. Sanders S.P. Colan S.D. Bicuspid aortic valve morphology and interventions in the young.J Am Coll Cardiol. 2007; 49: 2211-2214Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar Given the visual similarities between type 0 anteroposterior orientation and type 1 right-left coronary cusp fusion and between type 0 lateral orientation and type 1 right-left or left-non coronary cusp fusion (Figure 1), distribution of morphology, valve dysfunction, and interventions were notably similar to the literature.5Fernandes S.M. Sanders S.P. Khairy P. Jenkins K.J. Gauvreau K. Lang P. Simonds H. Colan S.D. Morphology of bicuspid aortic valve in children and adolescents.J Am Coll Cardiol. 2004; 44: 1648-1651Abstract Full Text Full Text PDF PubMed Scopus (192) Google Scholar, 9Fernandes S.M. Khairy P. Sanders S.P. Colan S.D. Bicuspid aortic valve morphology and interventions in the young.J Am Coll Cardiol. 2007; 49: 2211-2214Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar z-score equation methods by Gautier et al and Campens et al regrettably are not designed for use in patients below 2 years, causing z-scores in these subjects to be only based on extrapolated data and difficult to interpret.24Gautier M. Detaint D. Fermanian C. Aegerter P. Delorme G. Arnoult F. Milleron O. Raoux F. Stheneur C. Boileau C. Vahanian A. Jondeau G. Nomograms for aortic root diameters in children using two-dimensional echocardiography.Am J Cardiol. 2010; 105: 888-894Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar, 25Campens L. Demulier L. De Groote K. Vandekerckhove K. De Wolf D. Roman M.J. Devereux R.B. De Paepe A. De Backer J. Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories.Am J Cardiol. 2014; 114: 914-920Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar Both methods provide clearly different results in this age group, with Campens' method appearing the least accurate. For this reason, we calculated the annual z-score progression in children between 5 and 15 years. As we clinically found children presenting with AA z-scores >2 to have larger AAs in adolescence, we urge the need for z-score validation in cohorts with sufficient representation of neonates and toddlers, for the clinician to be aware of the expected growth. Instead of using the z-score, we propose to use Figure 3 to evaluate whether a specific AA diameter is abnormal for a child with a BAV and possibly associated with complications later in life. This could be of benefit especially in patients younger than 5 years of age as the z-score has clear limitations here. Patients with an AA diameter above the 95% prediction interval of our BAV cohort should therefore probably be controlled more frequently. All limitations of a retrospective study apply. We studied subjects in our tertiary center, introducing a selection bias. Two-dimensional echocardiography might not represent the 3-dimensional aortic shape and might have been subject to technical improvement during the study. We nonetheless believe in the reproducibility of this study with high interobserver agreement and observed differences within reported measurement variability.23Goldstein S.A. Evangelista A. Abbara S. Arai A. Asch F.M. Badano L.P. Bolen M.A. Connolly H.M. Cuellar-Calabria H. Czerny M. Devereux R.B. Erbel R.A. Fattori R. Isselbacher E.M. Lindsay J.M. McCulloch M. Michelena H.I. Nienaber C.A. Oh J.K. Pepi M. Taylor A.J. Weinsaft J.W. Zamorano J.L. Dietz H. Eagle K. Elefteriades J. Jondeau G. Rousseau H. Schepens M. Multimodality imaging of diseases of the thoracic aorta in adults: from the American Society of Echocardiography and the European Association of Cardiovascular Imaging: endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance.J Am Soc Echocardiogr. 2015; 28: 119-182Abstract Full Text Full Text PDF PubMed Scopus (384) Google Scholar Echocardiography is still the primary investigation of choice for diagnosis and follow-up of children with a BAV, making our results applicable to most clinical situations. Our predictions lack external validation and we hope other research groups will provide this in the near future. The elementary shape of a 5th order polynomial might influence results in the extreme ages, although accuracy is suggested by the population size. We sincerely thank T. de Haan (statistics) and C. de Korte and G. Weijers (data acquisition). The authors have no conflicts of interest to disclose. Download .pdf (.54 MB) Help with pdf files Supplementary Figures 1-6 and Supplementary Tables 1 and 2 Corrigendum to: Merkx R, Duijnhouwer AL, Vink E, Roos-Hesselink JW, Schokking M. Aortic Diameter Growth in Children with a Bicuspid Aortic Valve. Am J Cardiol 2017;120(1):131–136.American Journal of CardiologyVol. 122Issue 3PreviewStatement: Full-Text PDF
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