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Dilatation of the Remaining Aorta After Aortic Valve or Aortic Root Replacement in Patients With Bicuspid Aortic Valve: A 5-Year Follow-Up
Dilatation of the Remaining Aorta After Aortic Valve or Aortic Root Replacement in Patients With Bicuspid Aortic Valve: A 5-Year Follow-Up ˇ
Nada Abdulkareem, PhD, Gopal Soppa, MRCS, PhD, Sion Jones, MRCS, Oswaldo Valencia, MD, Jeremy Smelt, MRCS, and Marjan Jahangiri, FRCS (CTh) Department of Cardiothoracic Surgery, St. George’s Hospital, University of London, London, United Kingdom
Background. The natural history and management of ascending aorta (AA) and arch dilatation in patients with bicuspid aortic valve (BAV) after aortic valve replacement (AVR) or aortic root replacement (ARR) remains controversial. Our aim is to identify dilatation of the remaining aorta after AVR or ARR in patients with BAV compared with patients with tricuspid aortic valve (TAV). Methods. Three hundred ninety-five patients who underwent AVR or ARR between 2002 and 2009 were studied. Preoperative computed tomography (CT) and echocardiography were performed in 192 patients with BAV, and the results were compared with those of 203 patients with TAV. An AA diameter 4.5 cm or greater was regarded as aneurysmal. Postoperative echocardiograms, computed tomographic scans, and magnetic resonance images were compared with subsequent imaging at a median follow-up of 4.6 years (2.2–9.8 years). Result. Median ages of patients with BAV and patients with TAV were 57 ± 14 and 65 ± 16 years, respectively
(p < 0.05). Preoperative diameter of AA in the BAV group with no aneurysm (3.5 cm; range, 3.0–4.0 cm; n [ 143) was significantly higher than in the TAV group (3.3 cm; range, 3.1–3.8 cm; n [ 129) (p < 0.001). In both BAV and TAV groups with nonaneurysmal aortas who underwent AVR, there was no significant expansion of the AA and arch at 5 years’ follow-up. In patients with aneurysmal aorta (BAV group, n [ 49; TAV group, n [ 74) who underwent ARR, there was also no significant difference in growth of the remaining aorta at 3 and 5 years’ follow-up. Conclusions. No significant dilatation of the AA or arch was observed after AVR or ARR, respectively, in patients when a cut-off diameter of 4.5 cm or greater was considered for replacement in patients with BAV compared with patients with TAV up to 5 years after operation. The need for aortic replacement at smaller diameters was not found.
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hemodynamic disturbances caused by aortic stenosis or aortic regurgitation [3]. Furthermore, AVR has not been shown to prevent progressive dilatation of the aorta in patients with BAV [4]. In long-term follow-up studies, approximately 10% of patients with BAV after AVR have later undergone ARR for dilatation or dissection [2]. The guidelines for replacing the aortic root in patients with BAV are arbitrarily based on general agreement among expert professionals and data collected from patients with Marfan’s syndrome [5]. It has been noted that complications are higher after AVR in patients with larger aortas and BAV when compared with patients with TAV [6]. Based on the Society for Cardiothoracic Surgery for Great Britain & Ireland database, the overall mortality for elective surgical repair of ascending aortic aneurysms and ARR is 3% to 9% [7]. Therefore, there is a fine balance between trying to avoid reoperation and the unnecessary replacement of the aortic root and AA in patients who might never experience any dilatation. Timing of operation and the extent of aortic replacement continue to be controversial. Some advocate replacing the aorta at an aortic size of 5.5 cm or greater [8]. Others advocate a more aggressive approach when the diameter is 4.5 cm and greater [9]. Furthermore, some propose
icuspid aortic valve (BAV) is the most common cardiac defect, affecting 0.5% to 2% of the general population. It is associated with aortic valve disease and aortic aneurysm. Patients with BAV have a 9-fold risk of aortic dissection, and all these complications can occur a decade earlier than in the normal population [1]. However, the natural history of an unreplaced aortic arch and ascending aorta (AA) and the timely management of dilatation of the aorta in patients with BAV after aortic valve replacement (AVR) or aortic root replacement (ARR) remain controversial. Taking into consideration that complications after AVR in patients with BAV are more frequent than in patients with tricuspid aortic valve (TAV) [2], it is challenging to identify those patients with BAV in whom aortic aneurysm will develop after AVR. Aortic root diameter has been shown to be significantly greater in children and adults with functionally normal BAV compared with those with TAV, independent of the effect of
Accepted for publication March 28, 2013. Address correspondence to Dr Jahangiri, Department of Cardiothoracic Surgery, St. George’s Hospital, Blackshaw Road, London, SW17 0QT, UK; e-mail: [email protected].
Ó 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2013;-:-–-) Ó 2013 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.03.086
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routine elective hemiarch replacement on the basis of the associated aortopathy in patients with BAV [10]. As a result, we set out to examine the fate of the remaining aorta in patients with BAV who underwent AVR or ARR and to compare this group with patients with TAV during the same period. In addition, we aimed to evaluate early and midterm outcomes in these patients.
Patients and Methods Study Design From January 2002 to December 2009, 395 consecutive patients who were operated on under the care of 1 surgeon and underwent AVR or ARR, or both, were studied. Patients with known connective tissue disorders, eg, Marfan’s syndrome, were excluded from the study. Familial screening was not systematically performed when familial aortopathies existed; however, those patients were not excluded from the study. Younger patients with functionally normal BAVs underwent valvepreserving procedures and therefore were excluded from the study. In addition, patients with acute or chronic dissection, patients undergoing a second procedure, and those requiring replacement of the arch and descending thoracic aorta were also excluded. Written informed consent from all patients and approval from the local research ethics committee were obtained.
Data Collection Of the 395 patients, 192 had BAV and 203 had TAV (Fig 1). The diagnosis of BAV was confirmed by direct visualization of the valve phenotype at the time of operation. Patient demographics, imaging data, and follow-up information were collected and evaluated in a prospective manner. Intraoperative data regarding the morphologic characteristics of the aortic valve were
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documented. Transthoracic and transesophageal echocardiograms, computed tomographic scans, and MR images were analyzed, and postoperative complications were documented.
Imaging All patients had initial standard echocardiograms. When the AA or the root was found to be larger than 4.0 cm in diameter by echocardiography in patients with aortic valve disease, CT or magnetic resonance imaging (MRI) was performed. Standard aortic measurements include the diameter (measured perpendicular to both walls) at the aortic annulus, sinuses of Valsalva, sinotubular junction, AA, and the midaortic arch. All measurements were made by 2 cardiac surgeons and 2 cardiologists specializing in echocardiography or cardiac MRI. The technique used to measure depended on the modality used. Patients who underwent only AVR had transthoracic echocardiography to assess the aortic valve, AA, and arch using standard views (parasternal short and long axis, suprasternal). All patients with aortic size greater than 4.0 cm on echocardiography underwent contrast-enhanced CT and in some cases MRI. The definitive plan for intervention on the thoracic aorta was always based on the contrast CT measurement. The size of the thoracic aorta was quantified by 2 linear methods: cross-sectional dimensions in axial and double oblique planes using 3-dimensional volume-rendered images. All these measurements were made by a radiologist specializing in cardiovascular imaging. AA diameter 4.5 cm or more was regarded as aneurysmal. Images were obtained preoperatively and postoperatively at 6 months and 1, 3, and 5 years after operation. All patients who underwent AVR had routine transthoracic echocardiography to assess the aortic valve, AA, and arch using parasternal short- and long-axis
Fig 1. Details of patient classification based on number of valve cusps associated without (BAV, TAV) or with (AA-BAV, AA-TAV) aortic aneurysm. (AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; ARR ¼ aortic root replacement; Asc. Ao. Rep ¼ [supracoronary] ascending aorta replacement; BAV ¼ bicuspid aortic valve; TAV ¼ tricuspid aortic valve.)
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views and suprasternal views. These were obtained either locally or at the referring center, and if the aorta was found to be larger than 4.0 cm, the patients underwent CT. Routine CT or MRI, or both, were performed annually during follow-up in patients who underwent replacement of the AA or ARR.
Surgical Procedure AVR was performed according to American College of Cardiology/American Heart Association guidelines based on patient symptoms and left ventricular changes [11]. If the AA in patients with BAV was larger than 4.5 cm with an enlarged root, ARR was performed [12]. Partial resection of the aorta was not performed. If the dilatation was well above the sinuses, replacement of the AA alone was performed without root replacement. During this period, aortic valve repair was not attempted. Between 2002 and 2005, all operations were performed through a median sternotomy. After 2005, the majority of AVRs were performed through a ministernotomy. All operations were performed using full cardiopulmonary bypass at 35 C . If the aorta was larger than 4.5 cm, it was replaced. ARR with reimplantation of the coronary arteries was performed if the root was dilated (Fig 1). When replacement of the aorta was required, excision was performed as distally as possible without circulatory arrest. Prophylactic hemiarch or arch replacement was not performed. Aortoplasty was also not performed.
Outcomes In-hospital mortality was recorded. Follow-up data included all-cause mortality, imaging as described earlier,
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intervention related to the AA and arch, and whether the patient required reoperation.
Statistical Analysis Continuous variables are reported as mean standard deviation or as medians and ranges when suitable. Percentages and frequencies are used to represent categorical data. Student’s t test was used to analyze continuous variables with normal distribution when comparing 2 groups. A p value of less than or equal to 0.05 was considered the cut-off point of significance. Analysis of variance tables were used when more than 2 groups of variables were compared against each other. For these analyses GraphPad Prism 5 (GraphPad Software Inc, LaJolla, CA) and Microsoft Excel (Microsoft, Redmond, WA) software were used. Event-free and long-term survivals were analyzed using Kaplan-Meier methods.
Results From a total of 395 patients, 203 had TAV and 192 had BAV. In the BAV group, 12 patients had AVR with supracoronary AA replacement and 37 patients had ARR. In the TAV group, 49 patients had AVR with supracoronary AA replacement and 25 had ARR (Fig 1). Concomitant coronary artery bypass grafting (CABG) was performed in 36 (25%) patients with BAV, 4 patients (8.2%) with BAV and aortic aneurysm (AA-BAV), 70 (54.2%) patients with TAV, and 10 (13.5%) patients with TAV and aortic aneurysm (AA-TAV). Preoperative patient demographics are shown in Table 1. Median age of patients with BAV and those with TAV was 58 14 and 65 16 years, respectively (p < 0.05).
Table 1. Preoperative Patient Demographics and Aortic Dimensions Population Variable Age (y) Male sex NYHA III/IV Left ventricular function Good (EF > 45%) Moderate (EF ¼ 30%–45%) Poor (EF < 30%) Aortic valve area, cm2 Peak aortic valve gradient (mm Hg) Mean aortic valve gradient (mm Hg) Aortic stenosis Aortic regurgitation Aortic sinus (cm) Ascending aorta (cm) Aortic arch (cm) Tissue valve, n (%) Mechanical valve, n (%) CABG, n (%)
BAV (n ¼ 143) 57 14 103 (72%) 13 (9%) 74 (51%) 56 (40%) 13 (9%) 0.7 (0.6–0.7) 74 12 43 60 133 (93%) 24 (17%) 3.4 (2.9–3.6) 3.5 (3–4) 3.1 (2.8–3.6) 65 35 25
AA-BAV (n ¼ 49)
TAV (n ¼ 129)
58 12 34 (69%) 5 (10%)
65 16 81 (63%) 11 (9%)
21 (43%) 23 (47%) 5 (10%) 0.8 (0.7–1.2) 69 11 39 60 42 (86%) 13 (27%) 4.65 (4.4–5) 5.05 (4.5–5.8) 3.6 (3–3.8) 34.6 10.2 8.2
59 (46%) 56 (43%) 14 (11%) 0.7 (0.5–0.9) 83 90 46 50 125 (97%) 16 (12%) 3.2 (2.8–3.5) 3.3 (3.1–3.8) 3.2 (2.9–3.4) 65.9 34.1 54.2
AA-TAV (n ¼ 74) 67 15 46 (62%) 4 (5%) 37 (50%) 34 (46%) 3 (4%) 0.9 (0.7–1.3) 79 90 47 50 68 (92%) 17 (19%) 4.2 (3.5–4.9) 5.7 (4.9–6.1) 3.5 (3.1–4.6) 35 13.5 13.5
AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; BAV ¼ bicuspid aortic valve; CABG ¼ coronary artery bypass grafting; EF ¼ ejection fraction; NYHA ¼ New York Heart Association (functional classification of heart failure); TAV ¼ tricuspid aortic valve.
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Preoperative diameters of the sinuses of Valsalva were significantly larger in the BAV group when compared with the TAV group (p < 0.01) in patients without aneurysms. Similarly, preoperative diameters of the sinuses of Valsalva were significantly larger in the AA-BAV group when compared with the AA-TAV group (p < 0.01) (Table 1; Fig 2A). In patients with aortas smaller than 4.5 cm, preoperative diameters at the level of the AA were significantly bigger in the BAV group when compared with the TAV group (p < 0.01), whereas no significant difference was observed in the diameter of the AA-BAV and AA-TAV groups preoperatively (Table 1; Fig 2B). There was no significant difference in the preoperative dimensions of the aortic arch between the 4 groups (Table 1; Fig 2C). In all groups postoperatively, there was no dilatation of the remaining aorta after 5 years of follow-up (Figs 2A, 2B,
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2C). In patients who underwent ARR there will be no expected increase in the dimensions because the AA was replaced. However, there was no significant increase in the diameter of the aortic arch postoperatively at 5 years’ follow-up (Fig 2C). All-cause 5-year mortality was 17 (9.9%) in BAV, 1 (0.6%) in AA-BAV, 21 (12.2%) in TAV, and 8 (4.6%) in AA-TAV. No aortic dissections were recorded at 5 years’ follow-up and no patients underwent reoperation at 5 years after operation.
Operative Characteristics The most common procedure was concomitant CABG. Thirty-six (25%) patients had BAV, 4 (8.2%) patients had AA-BAV, 70 (54.2%) patients had TAV, and 10 (13.5%) patients had AA-TAV. Finally, separate valve and graft procedures were performed in 3 patients.
Fig 2. Serial measurements of thoracic aorta preoperatively and up to 5 years after surgical procedure. Figures in the inset of each panel highlight level at which each measurement was taken. (A) Measurements at level of sinus of Valsalva. (B) Measurement of maximum diameter at level of ascending aorta. (C) Measurements at level of midaortic arch distal to the innominate artery. Differences between groups are highlighted. (AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; BAV ¼ bicuspid aortic valve; TAV ¼ tricuspid aortic valve; ** ¼ p 0.01.)
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Fig 3. Kaplan-Meier survival analysis showing no significant difference in the mortality between the different groups. Numbers at bottom indicate patients at risk for each interval. (AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; BAV ¼ bicuspid aortic valve; TAV ¼ tricuspid aortic valve.)
Hospital Morbidity and Mortality There were 4 hospital deaths (1%). There were 2 deaths in the BAV group with normal-sized aortas and 2 deaths in the TAV group with normal-sized aortas. These 4 patients had concomitant CABG. There were no deaths in the ARR group.
Late Outcomes The median follow-up was 4.6 years (2.2–9.8 years). Complete follow-up was available for 94%. During follow-up, none of the patients required operation to replace any part of the aorta because of aneurysm formation or dissection. One patient with TAV and an associated aneurysm who had undergone ARR presented with type B dissection 9 months after his first operation and was managed conservatively. Also, 1 patient who had aortic stenosis and TAV and had undergone mechanical AVR presented 8 years later with a malfunctioning mechanical prosthesis and required reoperation in which a tissue valve was inserted. She made a very good recovery.
A total of 49 (12%) patients died during follow-up. The cause was cardiac in 6 (11%) patients, noncardiac in 31 (69%) patients, and unknown in 12 (20%) patients. The overall survival was 88.8%, 85.5%, and 83.1% at 3, 5, and 7 years, respectively. The overall mortality was not significantly different between the 4 groups (p ¼ 0.3) as shown in the Kaplan-Meier curve (Fig 3).
Comment In this study, patients with BAV and an AA absolute diameter of 4.5 cm or greater and a dilated root underwent ARR. This was a uniform policy. We have shown that there was no significant difference in morbidity and mortality comparing AVR with ARR in patients with BAV and that no patient with an aortic diameter of less than 4.5 cm required operation for dissection or resection of aneurysm during follow-up. Also, no patient required surgical intervention for the arch. These findings concur with those of Svensson and colleagues [13]. They studied 1,989 patients with BAV at
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a mean follow-up of 6 years, with only 0.2% of complications occurring when the aortic size was 4.5 cm or less. Our study also supports the findings of Park and colleagues [8] stating that progressive dilatation of the arch leading to reoperation after repair of ascending aortic aneurysm in patients with BAV is infrequent. Their study included patients with BAV who underwent AVR or AA repair, or both, without root replacement and aimed to identify the fate of the unreplaced sinuses of Valsalva. At a median follow-up of 3.3 years (range, 0–17 years), only 5% of patients had reoperations, 1 of whom had AA replacement and the other a root replacement. Another study was performed in 1,286 patients with BAV who underwent AVR to evaluate the long-term risk of aortic events after AVR. Median followup was 12 years (range, 0–38 years), which revealed only a 1% risk of dissection, 9.9% progressive aortic dilatation, and 0.9% ARR. In addition, aortic dilatation in their study population did not predict mortality [6]. Conversely, other studies advocate a more aggressive approach to the management of aortic aneurysm in the presence of BAV [11, 14]. Borger and colleagues [14] studied 201 patients who underwent AVR with a followup of 10.3 3.8 years. Their study population included patients with BAV with mild and moderate aortic dilatation (4.0–4.4 cm and 4.5–4.9 cm, respectively). During the follow-up period, 22 patients had long-term complications relating to the AA, with 18 aneurysms and 1 dissection. Patients with moderate aortic dilatation (4.5–4.9 cm) had poor outcomes and patients with mild aortic dilatation (4.0–4.5 cm) had good outcomes that were comparable to nondilated aortas (< 4.0 cm). Patients with BAV have a significantly faster aortic dilatation rate than do patients with TAV [15]. The mechanism of aortic dilatation in BAV includes intrinsic AA pathologic characteristics and abnormality in extracellular matrix remodeling, in addition to the presence of hemodynamic turbulence [16]. In patients with borderline aortic dilatation and in high-risk patients who are unsuitable for major surgical procedures, reduction aortoplasty has been proposed to reduce the rate of aortic dilatation, aorta-related complications, and mortality [17, 18]. However, the results of this technique are controversial, particularly when the resultant postoperative aortic diameter is greater than 3.5 cm. Therefore it is unlikely that reduction aortoplasty alone would reduce wall tension and the rate of aortic dilatation. This would suggest that replacement of the aorta would be associated with a better outcome compared with reduction aortoplasty. Therefore, we did not perform reduction aortoplasty in any of the patients in our study. The exact causative factors contributing to the progression of aortic aneurysm are not entirely clear. The presence of different causes involved in the development of BAV-associated aortopathy makes it difficult to standardize the appropriate time for surgical intervention [19]. Generally, thoracic aneurysms expand slowly by 1 mm per year and patients can live for years after the diagnosis is made without complications. However, when more rapid dilatation is observed ( 0.5 cm/y),
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surgical intervention is sought to prevent catastrophic complications such as aortic rupture and dissection [20]. In our series, none of the patients had arch aneurysm or dissection. Therefore, we do not support the more aggressive approach of prophylactic replacement of the arch with the risks associated with circulatory arrest. The low frequency of these complications in this and other series adds weight to the collective evidence regarding the timing of operation [6, 8].
Conclusions Our study of 395 patients showed no significant dilatation of the aorta after AVR or ARR in patients with BAV compared with patients with TAV up to 5 years after surgical intervention when the cut-off point of 4.5 cm for the AA dimension was used. This supports ARR only with AAs 4.5 cm or larger in patients with BAV with concomitant valvular disease.
Limitations We acknowledge the limitations of this study. In this retrospective study, we did not use z-score or crosssectional area-height ratio. We also acknowledge that it would be ideal to follow patients for longer than 10 years to assess the long-term effects of the surgical procedure. However, our data represent midterm follow-up results and we shall continue to follow our patients to assess the development of any future complications. The use of more than 1 imaging modality was unavoidable because all patients with aneurysms underwent imaging with CT or MRI per guidelines [12]. However, the set of measurements per patient was based on 1 imaging modality to standardize the type of imaging and measurements used throughout the follow-up period. Crossmodality comparisons were not performed.
References 1. Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol 2010;55:2789–800. 2. Yasuda H, Nakatani S, Stugaard M, et al. Failure to prevent progressive dilation of ascending aorta by aortic valve replacement in patients with bicuspid aortic valve: comparison with tricuspid aortic valve. Circulation 2003;108:291–4. 3. Tadros TM, Klein MD, Shapira OM. Ascending aortic dilatation associated with bicuspid aortic valve: pathophysiology, molecular biology, and clinical implications. Circulation 2009;119: 880–90. 4. Karagounis A, Valencia O, Chandrasekaran V, Smith J, Brecker S, Jahangiri M. Management of patients undergoing coronary artery bypass graft surgery with mild to moderate aortic stenosis. J Heart Valve Dis 2004;13:369–73. 5. Bonow RO. Bicuspid aortic valves and dilated aortas: a critical review of the ACC/AHA practice guidelines recommendations. Am J Cardiol 2008;102:111–4. 6. McKellar SH, Michelena HI, Li Z, Schaff HV, Sundt TM 3rd. Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves. Am J Cardiol 2010;106:1626–33. 7. The Society for Cardiothoracic Surgery in Great Britain & Ireland. Sixth National Adult Cardiac Surgical Database Report 2008—Demonstrating quality 2008. Available at: http://www.e-dendrite.com/files/13/file/Pages%20from%20 NACSD%202008.pdf. Accessed May 13, 2013.
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8. Park CB, Greason KL, Suri RM, Michelena HI, Schaff HV, Sundt TM. Fate of nonreplaced sinuses of valsalva in bicuspid aortic valve disease. J Thorac Cardiovasc Surg 2011;142:278–84. 9. Borger MA, David TE. Management of the valve and ascending aorta in adults with bicuspid aortic valve disease. Semin Thorac Cardiovasc Surg 2005;17:143–7. 10. Fazel SS, Mallidi HR, Lee RS, et al. The aortopathy of bicuspid aortic valve disease has distinctive patterns and usually involves the transverse aortic arch. J Thorac Cardiovasc Surg 2008;135:901–7. 11. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): developed in collaboration with the Society of Cardiovascular Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol 2006;48: e1–148. 12. Hiratzka LF, Bakris GL, Beckman JA, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; American College of Radiology; American Stroke Association; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; Society of Thoracic Surgeons; Society for Vascular Medicine. 2010 ACCF/AHA/ AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of
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13. 14.
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Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation 2010;121:e266–396. Svensson LG, Kim KH, Blackstone EH, et al. Bicuspid aortic valve surgery with proactive ascending aorta repair. J Thorac Cardiovasc Surg 2011;142:622–9. Borger MA, Preston M, Ivanov J, et al. Should the ascending aorta be replaced more frequently in patients with bicuspid aortic valve disease? J Thorac Cardiovasc Surg 2004;128: 677–83. Thanassoulis G, Yip JWL, Filion K, et al. 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;5:821–8. Biner S, Rafique AM, Ray I, Cuk O, Siegel RJ, Tolstrup K. Aortopathy is prevalent in relatives of bicuspid aortic valve patients. J Am Coll Cardiol 2009;53:2288–95. Robicsek F, Cook JW, Reames MK, Skipper ER. Size reduction ascending aortoplasty: is it dead or alive? J Thorac Cardiovasc Surg 2004;128:562–70. Niclauss L, Delay D, Ruchat P, von Segesser LK. Reduction aortoplasty: safe and durable treatment for borderline dilatation in selected patients. J Heart Valve Dis 2012;21:584–90. El-Hamamsy I, Yacoub MH. A measured approach to managing the aortic root in patients with bicuspid aortic valve disease. Curr Cardiol Rep 2009;11:94–100. Elefteriades JA. Indications for aortic replacement. J Thorac Cardiovasc Surg 2010;140:45–51.
Nada Abdulkareem, PhD, Gopal Soppa, MRCS, PhD, Sion Jones, MRCS, Oswaldo Valencia, MD, Jeremy Smelt, MRCS, and Marjan Jahangiri, FRCS (CTh) Department of Cardiothoracic Surgery, St. George’s Hospital, University of London, London, United Kingdom
Background. The natural history and management of ascending aorta (AA) and arch dilatation in patients with bicuspid aortic valve (BAV) after aortic valve replacement (AVR) or aortic root replacement (ARR) remains controversial. Our aim is to identify dilatation of the remaining aorta after AVR or ARR in patients with BAV compared with patients with tricuspid aortic valve (TAV). Methods. Three hundred ninety-five patients who underwent AVR or ARR between 2002 and 2009 were studied. Preoperative computed tomography (CT) and echocardiography were performed in 192 patients with BAV, and the results were compared with those of 203 patients with TAV. An AA diameter 4.5 cm or greater was regarded as aneurysmal. Postoperative echocardiograms, computed tomographic scans, and magnetic resonance images were compared with subsequent imaging at a median follow-up of 4.6 years (2.2–9.8 years). Result. Median ages of patients with BAV and patients with TAV were 57 ± 14 and 65 ± 16 years, respectively
(p < 0.05). Preoperative diameter of AA in the BAV group with no aneurysm (3.5 cm; range, 3.0–4.0 cm; n [ 143) was significantly higher than in the TAV group (3.3 cm; range, 3.1–3.8 cm; n [ 129) (p < 0.001). In both BAV and TAV groups with nonaneurysmal aortas who underwent AVR, there was no significant expansion of the AA and arch at 5 years’ follow-up. In patients with aneurysmal aorta (BAV group, n [ 49; TAV group, n [ 74) who underwent ARR, there was also no significant difference in growth of the remaining aorta at 3 and 5 years’ follow-up. Conclusions. No significant dilatation of the AA or arch was observed after AVR or ARR, respectively, in patients when a cut-off diameter of 4.5 cm or greater was considered for replacement in patients with BAV compared with patients with TAV up to 5 years after operation. The need for aortic replacement at smaller diameters was not found.
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hemodynamic disturbances caused by aortic stenosis or aortic regurgitation [3]. Furthermore, AVR has not been shown to prevent progressive dilatation of the aorta in patients with BAV [4]. In long-term follow-up studies, approximately 10% of patients with BAV after AVR have later undergone ARR for dilatation or dissection [2]. The guidelines for replacing the aortic root in patients with BAV are arbitrarily based on general agreement among expert professionals and data collected from patients with Marfan’s syndrome [5]. It has been noted that complications are higher after AVR in patients with larger aortas and BAV when compared with patients with TAV [6]. Based on the Society for Cardiothoracic Surgery for Great Britain & Ireland database, the overall mortality for elective surgical repair of ascending aortic aneurysms and ARR is 3% to 9% [7]. Therefore, there is a fine balance between trying to avoid reoperation and the unnecessary replacement of the aortic root and AA in patients who might never experience any dilatation. Timing of operation and the extent of aortic replacement continue to be controversial. Some advocate replacing the aorta at an aortic size of 5.5 cm or greater [8]. Others advocate a more aggressive approach when the diameter is 4.5 cm and greater [9]. Furthermore, some propose
icuspid aortic valve (BAV) is the most common cardiac defect, affecting 0.5% to 2% of the general population. It is associated with aortic valve disease and aortic aneurysm. Patients with BAV have a 9-fold risk of aortic dissection, and all these complications can occur a decade earlier than in the normal population [1]. However, the natural history of an unreplaced aortic arch and ascending aorta (AA) and the timely management of dilatation of the aorta in patients with BAV after aortic valve replacement (AVR) or aortic root replacement (ARR) remain controversial. Taking into consideration that complications after AVR in patients with BAV are more frequent than in patients with tricuspid aortic valve (TAV) [2], it is challenging to identify those patients with BAV in whom aortic aneurysm will develop after AVR. Aortic root diameter has been shown to be significantly greater in children and adults with functionally normal BAV compared with those with TAV, independent of the effect of
Accepted for publication March 28, 2013. Address correspondence to Dr Jahangiri, Department of Cardiothoracic Surgery, St. George’s Hospital, Blackshaw Road, London, SW17 0QT, UK; e-mail: [email protected].
Ó 2013 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2013;-:-–-) Ó 2013 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.03.086
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routine elective hemiarch replacement on the basis of the associated aortopathy in patients with BAV [10]. As a result, we set out to examine the fate of the remaining aorta in patients with BAV who underwent AVR or ARR and to compare this group with patients with TAV during the same period. In addition, we aimed to evaluate early and midterm outcomes in these patients.
Patients and Methods Study Design From January 2002 to December 2009, 395 consecutive patients who were operated on under the care of 1 surgeon and underwent AVR or ARR, or both, were studied. Patients with known connective tissue disorders, eg, Marfan’s syndrome, were excluded from the study. Familial screening was not systematically performed when familial aortopathies existed; however, those patients were not excluded from the study. Younger patients with functionally normal BAVs underwent valvepreserving procedures and therefore were excluded from the study. In addition, patients with acute or chronic dissection, patients undergoing a second procedure, and those requiring replacement of the arch and descending thoracic aorta were also excluded. Written informed consent from all patients and approval from the local research ethics committee were obtained.
Data Collection Of the 395 patients, 192 had BAV and 203 had TAV (Fig 1). The diagnosis of BAV was confirmed by direct visualization of the valve phenotype at the time of operation. Patient demographics, imaging data, and follow-up information were collected and evaluated in a prospective manner. Intraoperative data regarding the morphologic characteristics of the aortic valve were
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documented. Transthoracic and transesophageal echocardiograms, computed tomographic scans, and MR images were analyzed, and postoperative complications were documented.
Imaging All patients had initial standard echocardiograms. When the AA or the root was found to be larger than 4.0 cm in diameter by echocardiography in patients with aortic valve disease, CT or magnetic resonance imaging (MRI) was performed. Standard aortic measurements include the diameter (measured perpendicular to both walls) at the aortic annulus, sinuses of Valsalva, sinotubular junction, AA, and the midaortic arch. All measurements were made by 2 cardiac surgeons and 2 cardiologists specializing in echocardiography or cardiac MRI. The technique used to measure depended on the modality used. Patients who underwent only AVR had transthoracic echocardiography to assess the aortic valve, AA, and arch using standard views (parasternal short and long axis, suprasternal). All patients with aortic size greater than 4.0 cm on echocardiography underwent contrast-enhanced CT and in some cases MRI. The definitive plan for intervention on the thoracic aorta was always based on the contrast CT measurement. The size of the thoracic aorta was quantified by 2 linear methods: cross-sectional dimensions in axial and double oblique planes using 3-dimensional volume-rendered images. All these measurements were made by a radiologist specializing in cardiovascular imaging. AA diameter 4.5 cm or more was regarded as aneurysmal. Images were obtained preoperatively and postoperatively at 6 months and 1, 3, and 5 years after operation. All patients who underwent AVR had routine transthoracic echocardiography to assess the aortic valve, AA, and arch using parasternal short- and long-axis
Fig 1. Details of patient classification based on number of valve cusps associated without (BAV, TAV) or with (AA-BAV, AA-TAV) aortic aneurysm. (AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; ARR ¼ aortic root replacement; Asc. Ao. Rep ¼ [supracoronary] ascending aorta replacement; BAV ¼ bicuspid aortic valve; TAV ¼ tricuspid aortic valve.)
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views and suprasternal views. These were obtained either locally or at the referring center, and if the aorta was found to be larger than 4.0 cm, the patients underwent CT. Routine CT or MRI, or both, were performed annually during follow-up in patients who underwent replacement of the AA or ARR.
Surgical Procedure AVR was performed according to American College of Cardiology/American Heart Association guidelines based on patient symptoms and left ventricular changes [11]. If the AA in patients with BAV was larger than 4.5 cm with an enlarged root, ARR was performed [12]. Partial resection of the aorta was not performed. If the dilatation was well above the sinuses, replacement of the AA alone was performed without root replacement. During this period, aortic valve repair was not attempted. Between 2002 and 2005, all operations were performed through a median sternotomy. After 2005, the majority of AVRs were performed through a ministernotomy. All operations were performed using full cardiopulmonary bypass at 35 C . If the aorta was larger than 4.5 cm, it was replaced. ARR with reimplantation of the coronary arteries was performed if the root was dilated (Fig 1). When replacement of the aorta was required, excision was performed as distally as possible without circulatory arrest. Prophylactic hemiarch or arch replacement was not performed. Aortoplasty was also not performed.
Outcomes In-hospital mortality was recorded. Follow-up data included all-cause mortality, imaging as described earlier,
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intervention related to the AA and arch, and whether the patient required reoperation.
Statistical Analysis Continuous variables are reported as mean standard deviation or as medians and ranges when suitable. Percentages and frequencies are used to represent categorical data. Student’s t test was used to analyze continuous variables with normal distribution when comparing 2 groups. A p value of less than or equal to 0.05 was considered the cut-off point of significance. Analysis of variance tables were used when more than 2 groups of variables were compared against each other. For these analyses GraphPad Prism 5 (GraphPad Software Inc, LaJolla, CA) and Microsoft Excel (Microsoft, Redmond, WA) software were used. Event-free and long-term survivals were analyzed using Kaplan-Meier methods.
Results From a total of 395 patients, 203 had TAV and 192 had BAV. In the BAV group, 12 patients had AVR with supracoronary AA replacement and 37 patients had ARR. In the TAV group, 49 patients had AVR with supracoronary AA replacement and 25 had ARR (Fig 1). Concomitant coronary artery bypass grafting (CABG) was performed in 36 (25%) patients with BAV, 4 patients (8.2%) with BAV and aortic aneurysm (AA-BAV), 70 (54.2%) patients with TAV, and 10 (13.5%) patients with TAV and aortic aneurysm (AA-TAV). Preoperative patient demographics are shown in Table 1. Median age of patients with BAV and those with TAV was 58 14 and 65 16 years, respectively (p < 0.05).
Table 1. Preoperative Patient Demographics and Aortic Dimensions Population Variable Age (y) Male sex NYHA III/IV Left ventricular function Good (EF > 45%) Moderate (EF ¼ 30%–45%) Poor (EF < 30%) Aortic valve area, cm2 Peak aortic valve gradient (mm Hg) Mean aortic valve gradient (mm Hg) Aortic stenosis Aortic regurgitation Aortic sinus (cm) Ascending aorta (cm) Aortic arch (cm) Tissue valve, n (%) Mechanical valve, n (%) CABG, n (%)
BAV (n ¼ 143) 57 14 103 (72%) 13 (9%) 74 (51%) 56 (40%) 13 (9%) 0.7 (0.6–0.7) 74 12 43 60 133 (93%) 24 (17%) 3.4 (2.9–3.6) 3.5 (3–4) 3.1 (2.8–3.6) 65 35 25
AA-BAV (n ¼ 49)
TAV (n ¼ 129)
58 12 34 (69%) 5 (10%)
65 16 81 (63%) 11 (9%)
21 (43%) 23 (47%) 5 (10%) 0.8 (0.7–1.2) 69 11 39 60 42 (86%) 13 (27%) 4.65 (4.4–5) 5.05 (4.5–5.8) 3.6 (3–3.8) 34.6 10.2 8.2
59 (46%) 56 (43%) 14 (11%) 0.7 (0.5–0.9) 83 90 46 50 125 (97%) 16 (12%) 3.2 (2.8–3.5) 3.3 (3.1–3.8) 3.2 (2.9–3.4) 65.9 34.1 54.2
AA-TAV (n ¼ 74) 67 15 46 (62%) 4 (5%) 37 (50%) 34 (46%) 3 (4%) 0.9 (0.7–1.3) 79 90 47 50 68 (92%) 17 (19%) 4.2 (3.5–4.9) 5.7 (4.9–6.1) 3.5 (3.1–4.6) 35 13.5 13.5
AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; BAV ¼ bicuspid aortic valve; CABG ¼ coronary artery bypass grafting; EF ¼ ejection fraction; NYHA ¼ New York Heart Association (functional classification of heart failure); TAV ¼ tricuspid aortic valve.
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Preoperative diameters of the sinuses of Valsalva were significantly larger in the BAV group when compared with the TAV group (p < 0.01) in patients without aneurysms. Similarly, preoperative diameters of the sinuses of Valsalva were significantly larger in the AA-BAV group when compared with the AA-TAV group (p < 0.01) (Table 1; Fig 2A). In patients with aortas smaller than 4.5 cm, preoperative diameters at the level of the AA were significantly bigger in the BAV group when compared with the TAV group (p < 0.01), whereas no significant difference was observed in the diameter of the AA-BAV and AA-TAV groups preoperatively (Table 1; Fig 2B). There was no significant difference in the preoperative dimensions of the aortic arch between the 4 groups (Table 1; Fig 2C). In all groups postoperatively, there was no dilatation of the remaining aorta after 5 years of follow-up (Figs 2A, 2B,
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2C). In patients who underwent ARR there will be no expected increase in the dimensions because the AA was replaced. However, there was no significant increase in the diameter of the aortic arch postoperatively at 5 years’ follow-up (Fig 2C). All-cause 5-year mortality was 17 (9.9%) in BAV, 1 (0.6%) in AA-BAV, 21 (12.2%) in TAV, and 8 (4.6%) in AA-TAV. No aortic dissections were recorded at 5 years’ follow-up and no patients underwent reoperation at 5 years after operation.
Operative Characteristics The most common procedure was concomitant CABG. Thirty-six (25%) patients had BAV, 4 (8.2%) patients had AA-BAV, 70 (54.2%) patients had TAV, and 10 (13.5%) patients had AA-TAV. Finally, separate valve and graft procedures were performed in 3 patients.
Fig 2. Serial measurements of thoracic aorta preoperatively and up to 5 years after surgical procedure. Figures in the inset of each panel highlight level at which each measurement was taken. (A) Measurements at level of sinus of Valsalva. (B) Measurement of maximum diameter at level of ascending aorta. (C) Measurements at level of midaortic arch distal to the innominate artery. Differences between groups are highlighted. (AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; BAV ¼ bicuspid aortic valve; TAV ¼ tricuspid aortic valve; ** ¼ p 0.01.)
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Fig 3. Kaplan-Meier survival analysis showing no significant difference in the mortality between the different groups. Numbers at bottom indicate patients at risk for each interval. (AA-BAV ¼ bicuspid aortic valve with aortic aneurysm; AA-TAV ¼ tricuspid aortic valve with aortic aneurysm; BAV ¼ bicuspid aortic valve; TAV ¼ tricuspid aortic valve.)
Hospital Morbidity and Mortality There were 4 hospital deaths (1%). There were 2 deaths in the BAV group with normal-sized aortas and 2 deaths in the TAV group with normal-sized aortas. These 4 patients had concomitant CABG. There were no deaths in the ARR group.
Late Outcomes The median follow-up was 4.6 years (2.2–9.8 years). Complete follow-up was available for 94%. During follow-up, none of the patients required operation to replace any part of the aorta because of aneurysm formation or dissection. One patient with TAV and an associated aneurysm who had undergone ARR presented with type B dissection 9 months after his first operation and was managed conservatively. Also, 1 patient who had aortic stenosis and TAV and had undergone mechanical AVR presented 8 years later with a malfunctioning mechanical prosthesis and required reoperation in which a tissue valve was inserted. She made a very good recovery.
A total of 49 (12%) patients died during follow-up. The cause was cardiac in 6 (11%) patients, noncardiac in 31 (69%) patients, and unknown in 12 (20%) patients. The overall survival was 88.8%, 85.5%, and 83.1% at 3, 5, and 7 years, respectively. The overall mortality was not significantly different between the 4 groups (p ¼ 0.3) as shown in the Kaplan-Meier curve (Fig 3).
Comment In this study, patients with BAV and an AA absolute diameter of 4.5 cm or greater and a dilated root underwent ARR. This was a uniform policy. We have shown that there was no significant difference in morbidity and mortality comparing AVR with ARR in patients with BAV and that no patient with an aortic diameter of less than 4.5 cm required operation for dissection or resection of aneurysm during follow-up. Also, no patient required surgical intervention for the arch. These findings concur with those of Svensson and colleagues [13]. They studied 1,989 patients with BAV at
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a mean follow-up of 6 years, with only 0.2% of complications occurring when the aortic size was 4.5 cm or less. Our study also supports the findings of Park and colleagues [8] stating that progressive dilatation of the arch leading to reoperation after repair of ascending aortic aneurysm in patients with BAV is infrequent. Their study included patients with BAV who underwent AVR or AA repair, or both, without root replacement and aimed to identify the fate of the unreplaced sinuses of Valsalva. At a median follow-up of 3.3 years (range, 0–17 years), only 5% of patients had reoperations, 1 of whom had AA replacement and the other a root replacement. Another study was performed in 1,286 patients with BAV who underwent AVR to evaluate the long-term risk of aortic events after AVR. Median followup was 12 years (range, 0–38 years), which revealed only a 1% risk of dissection, 9.9% progressive aortic dilatation, and 0.9% ARR. In addition, aortic dilatation in their study population did not predict mortality [6]. Conversely, other studies advocate a more aggressive approach to the management of aortic aneurysm in the presence of BAV [11, 14]. Borger and colleagues [14] studied 201 patients who underwent AVR with a followup of 10.3 3.8 years. Their study population included patients with BAV with mild and moderate aortic dilatation (4.0–4.4 cm and 4.5–4.9 cm, respectively). During the follow-up period, 22 patients had long-term complications relating to the AA, with 18 aneurysms and 1 dissection. Patients with moderate aortic dilatation (4.5–4.9 cm) had poor outcomes and patients with mild aortic dilatation (4.0–4.5 cm) had good outcomes that were comparable to nondilated aortas (< 4.0 cm). Patients with BAV have a significantly faster aortic dilatation rate than do patients with TAV [15]. The mechanism of aortic dilatation in BAV includes intrinsic AA pathologic characteristics and abnormality in extracellular matrix remodeling, in addition to the presence of hemodynamic turbulence [16]. In patients with borderline aortic dilatation and in high-risk patients who are unsuitable for major surgical procedures, reduction aortoplasty has been proposed to reduce the rate of aortic dilatation, aorta-related complications, and mortality [17, 18]. However, the results of this technique are controversial, particularly when the resultant postoperative aortic diameter is greater than 3.5 cm. Therefore it is unlikely that reduction aortoplasty alone would reduce wall tension and the rate of aortic dilatation. This would suggest that replacement of the aorta would be associated with a better outcome compared with reduction aortoplasty. Therefore, we did not perform reduction aortoplasty in any of the patients in our study. The exact causative factors contributing to the progression of aortic aneurysm are not entirely clear. The presence of different causes involved in the development of BAV-associated aortopathy makes it difficult to standardize the appropriate time for surgical intervention [19]. Generally, thoracic aneurysms expand slowly by 1 mm per year and patients can live for years after the diagnosis is made without complications. However, when more rapid dilatation is observed ( 0.5 cm/y),
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surgical intervention is sought to prevent catastrophic complications such as aortic rupture and dissection [20]. In our series, none of the patients had arch aneurysm or dissection. Therefore, we do not support the more aggressive approach of prophylactic replacement of the arch with the risks associated with circulatory arrest. The low frequency of these complications in this and other series adds weight to the collective evidence regarding the timing of operation [6, 8].
Conclusions Our study of 395 patients showed no significant dilatation of the aorta after AVR or ARR in patients with BAV compared with patients with TAV up to 5 years after surgical intervention when the cut-off point of 4.5 cm for the AA dimension was used. This supports ARR only with AAs 4.5 cm or larger in patients with BAV with concomitant valvular disease.
Limitations We acknowledge the limitations of this study. In this retrospective study, we did not use z-score or crosssectional area-height ratio. We also acknowledge that it would be ideal to follow patients for longer than 10 years to assess the long-term effects of the surgical procedure. However, our data represent midterm follow-up results and we shall continue to follow our patients to assess the development of any future complications. The use of more than 1 imaging modality was unavoidable because all patients with aneurysms underwent imaging with CT or MRI per guidelines [12]. However, the set of measurements per patient was based on 1 imaging modality to standardize the type of imaging and measurements used throughout the follow-up period. Crossmodality comparisons were not performed.
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