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[14] Etz CD, Misfeld M, Borger MA, Luehr M, Strotdrees E, Mohr FW. Current indications for surgical repair in patients with bicuspid aortic valve and ascending aortic ectasia. Cardiol Res Pract 2012;2012:313879. [15] Etz CD, Homann TM, Silovitz D, Spielvogel D, Bodian CA, Luehr M et al. Long-term survival after the Bentall procedure in 206 patients with bicuspid aortic valve. Ann Thorac Surg 2007;84:1186–93. [16] Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382:1329–40. [17] Badiu CC, Eichinger W, Bleiziffer S, Hermes G, Hettich I, Krane M et al. Should root replacement with aortic valve-sparing be offered to patients

with bicuspid valves or severe aortic regurgitation? Eur J Cardiothorac Surg 2010;38:515–22. [18] Girdauskas E, Disha K, Raisin HH, Secknus MA, Borger MA, Kuntze T. Risk of late aortic events after an isolated aortic valve replacement for bicuspid aortic valve stenosis with concomitant ascending aortic dilation. Eur J Cardiothorac Surg 2012;42:832–7. [19] Wang Y, Wu B, Dong L, Wang C, Shu X. Type A aortic dissection in patients with bicuspid or tricuspid aortic valves: a retrospective comparative study in 288 Chinese patients. Eur J Cardiothorac Surg 2013;44:172–7. [20] Sievers HH, Schmidtke C. A classification system for the bicuspid aortic valve from 304 surgical specimens. J Thorac Cardiovasc Surg 2007;133: 1226–33.

EDITORIAL COMMENT

European Journal of Cardio-Thoracic Surgery 48 (2015) 150–151 doi:10.1093/ejcts/ezu418 Advance Access publication 28 October 2014

Cite this article as: Della Corte A. The conundrum of aortic dissection in patients with bicuspid aortic valve: the tissue, the mechanics and the mathematics. Eur J Cardiothorac Surg 2015;48:150–1.

The conundrum of aortic dissection in patients with bicuspid aortic valve: the tissue, the mechanics and the mathematics Alessandro Della Corte* Department of Cardiothoracic Sciences, Second University of Naples, V Monaldi Hospital, Naples, Italy * Corresponding author. Department of Cardiothoracic Sciences, Second University of Naples, Cardiovascular Surgery and Transplant, V. Monaldi Hospital, via L Bianchi, 80131 Naples, Italy. Tel: +39-081-7064020; fax: +39-081-5464594; e-mail: [email protected] (A. Della Corte).

Keywords: Acute aortic dissection • Stanford type A • Bicuspid aortic valve

Studies addressing the features and outcomes of type A aortic dissection (TAAD) in the bicuspid aortic valve (BAV) patient population can importantly feed into our knowledge of BAV aortopathy, increasing the level of evidence underpinning official recommendations [1]. Etz et al. presented a retrospective comparison between tricuspid aortic valve (TAV) and BAV patients operated on for acute TAAD [2]. Two findings were particularly striking, although not statistically significant: (i) the mean ascending aortic diameter at the time of dissection was greater with BAV than with TAV (by more than 7 mm); (ii) notwithstanding the significantly younger patient age at dissection, BAV implied a higher hospital mortality. Both findings confirm previous independent observations [3–5] and call for in-depth reflections. Regarding the greater aortic diameter at dissection, this might seem unexpected, given the common notion that BAV patients’ aorta is prone to ‘earlier’ failure. Of note, in a recent study, the same difference in mean diameters was found [4], reaching statistical significance there, probably due to the greater numbers. What is the possible explanation for this evidence? Firstly, the fact that ‘post-dissection’ diameters were reported in both studies [2, 4] could allow the hypothesis that when TAAD occurs, the BAV aorta undergoes a greater acute enlargement than the TAV aorta, possibly due to intrinsically worse aortic wall cohesion. In a recent

investigation, a mean diameter increment of 30% was calculated; unfortunately, BAV patients were excluded from such analysis [6]. However, in another report [3] predissection diameters (when available) were also significantly greater in the BAV group, which disproves that hypothesis. So, if the BAV aorta really dissects at a greater diameter than the TAV one, then why has prophylactic elective surgery of BAV aortopathy been traditionally indicated for smaller diameters? Indeed, the latest version of the guidelines recommend surgery for the same cut-off of 55 mm for both nonsyndromic TAV- and BAV-associated aortopathies, in the absence of risk factors [1]. Secondly, considering this matter also in mathematical terms as previously suggested [7], the a priori risk of TAAD at a given aortic diameter is a ratio between the number of events occurring (numerator) and the number of patients at risk (denominator), i.e. those presenting with the given diameter. Studies having TAAD as their referral [2–5] can only estimate the numerator; thus, the absolute number of TAADs occurring in dilated aortas could be high with BAV because in the general BAV population aortic dilatation is frequent. The denominator question also relates to why indexing methods are not a solution: as Etz et al. correctly argued, a policy of pre-emptive operation on all patients with a Svensson index >9–10 could have led to a number of unnecessary operations [2]. None of the proposed indexing methods has been

C.D. Etz et al. / European Journal of Cardio-Thoracic Surgery

in BAV-associated dissection. Therefore, even though late survival was excellent with an aggressive approach with regard to the BAV root (94% composite root replacements vs 46% with TAV) [2], we do not know whether a more individualized management, including selective indication to root replacement (with its higher inherent operative risk) in BAV patients with the root phenotype and/or entry tear at the sinus level, would have entailed a better early outcome too. The general perspective on BAV aortopathy pathogenesis should change from the dichotomy between haemodynamic and genetic theories to a new unifying vision whereby variable combinations of flow disturbance and genetic defects produce diverse phenotypes with different risks of TAAD [9]. This new vision calls for the development of risk stratification criteria and personalized methods of surveillance and treatment: the disease is multiform; any generalization would be misleading.

REFERENCES [1] Erbel R, Aboyans V, Boileau C, Bossone E, Di Bartolomeo R, Eggebrecht H et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult * The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2873–926. [2] Etz CD, von Aspern K, Hoyer A, Girrbach FF, Leontyev S, Bakhtiary F et al. Acute type A aortic dissection: characteristics and outcomes comparing patients with bicuspid versus tricuspid aortic valve. Eur J Cardiothorac Surg 2015;48:142–50. [3] Eleid MF, Forde I, Edwards WD, Maleszewski JJ, Suri RM, Schaff HV et al. Type A aortic dissection in patients with bicuspid aortic valves: clinical and pathological comparison with tricuspid aortic valves. Heart 2013;99: 1668–74. [4] Rylski B, Desai ND, Bavaria JE, Vallabhajosyula P, Moser W, Pochettino A et al. Aortic valve morphology determines the presentation and surgical approach to acute type A aortic dissection. Ann Thorac Surg 2014;97: 1991–6. [5] Januzzi JL, Isselbacher EM, Fattori R, Cooper JV, Smith DE, Fang J et al. Characterizing the young patient with aortic dissection: results from the International Registry of Aortic Dissection (IRAD). J Am Coll Cardiol 2004; 43:665–9. [6] Rylski B, Blanke P, Beyersdorf F, Desai ND, Milewski RK, Siepe M et al. How does the ascending aorta geometry change when it dissects? J Am Coll Cardiol 2014;63:1311–9. [7] Sundt TM III. Replacement of the ascending aorta in bicuspid aortic valve disease: where do we draw the line? J Thorac Cardiovasc Surg 2010;140: S41–4. [8] Bissell MM, Hess AT, Biasiolli L, Glaze SJ, Loudon M, Pitcher A et al. Aortic dilation in bicuspid aortic valve disease: flow pattern is a major contributor and differs with valve fusion type. Circ Cardiovasc Imaging 2013;6: 499–507. [9] Della Corte A, Body SC, Booher AM, Schaefers HJ, Milewski RK, Michelena HI et al. Surgical treatment of bicuspid aortic valve disease: knowledge gaps and research perspectives. J Thorac Cardiovasc Surg 2014;147: 1749–57. [10] Della Corte A, Bancone C, Dialetto G, Covino FE, Manduca S, Montibello MV et al. The ascending aorta with bicuspid aortic valve: a phenotypic classification with potential prognostic significance. Eur J Cardiothorac Surg 2014;46:240–7.

AORTIC SURGERY

adequately tested so far, in terms of sensitivity and, equally important, specificity [1]. Thirdly, the mechanics: both hypertension and aortic enlargement increase wall tension, but the mechanical failure of the diseased intimal and medial layers, prompting TAAD development, can be demonstrably reached even without dilatation. The mechanical stimulus that is currently believed to be causative in intimal tear formation is abnormal shear stress: normally, wall shear stress decreases exponentially with increasing aortic diameter; however, this does not happen in the BAV aorta [8], owing to the altered flow patterns prompted by the eccentricity of valve opening. Thus, with TAV, local haemodynamics would favour TAAD onset more likely when the diameter is not aneurismal, whereas, in the BAV aorta, the triggering biomechanical cue would stand even with dilatation, a hypothesis that fits with the observation by Etz et al. [2]. There is a clear need for further improvement of our knowledge of the mechanisms and risk factors for TAAD: they might be only in part shared with aortic dilatation and at least in part different between BAV and TAV patients. Rather than searching for a cut-off diameter for universal surgical indication, future efforts should be aimed at discovering which are the measurable factors determining TAAD risk, along with (or instead of ) aortic diameter [9]. Unfortunately, Etz’s study failed to report on the ‘pattern’ of proximal aortic dimensions [2], i.e. distinguishing dilatations prevailing at the sinuses of Valsalva (root phenotype) from the more common phenotype with maximal dilatation at the supracoronary tract [10]. Notably, the site of intimal tear was more frequently at the root level in BAV than TAV patients [2], and the rate of >grade II aortic regurgitation (typically associated with root phenotype [10]) was particularly high [2]. Compared with the usually reported proportions—20–30% of the BAV-associated dilatations [10]—the root phenotype seems consistently over-represented in BAV-TAAD series [2–4], thus confirming our suggestion that it might represent a higher risk phenotype [10]. The comparable hospital mortality in BAV- and TAV-TAAD patients [2, 4], mirroring the report from the International Registry of Aortic Dissection of similar mortality in young and older TAAD patients [5], shows that the catastrophic nature of the disease implies a high perioperative risk quite independent of the patient’s age. In the BAV group [2], the higher prevalence of entry tear location at the sinuses ( possible coronary ostial involvement), the more frequent need for resuscitation at presentation ( possible rupture, tamponade, shock or infarction) is, and the higher postoperative rates of both assist device implant and cardiac deaths may all indicate that aortic wall fragility increases the severity of TAAD in some BAV patients. In addition, the most complicated anatomoclinical forms of TAAD may exert an ‘age-selection’, in that the older patients (more frequently TAV) may die even before hospital admission, whereas the younger, otherwise healthier ones (more often BAVs) may reach the operative room even in the most compromised conditions, implying worse outcomes. No study has ever compared long-term outcomes of supracoronary replacement versus composite root replacement specifically

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The conundrum of aortic dissection in patients with bicuspid aortic valve: the tissue, the mechanics and the mathematics.

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