Reduction Aortoplasty for the Ascending Aortic Aneurysm With Aortic Valve Disease

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1 Circulation Journal Official Journal of the Japanese Circulation Society ORIGINAL ARTICLE Cardiovascular Surgery Reduction Aortoplasty for the Ascending Aortic Aneurysm With Aortic Valve Disease Does Bicuspid Valve Matter? Ho Young Hwang, MD; Mi-Suk Shim, MD; Eun-Ah Park, MD; Hyuk Ahn, MD, PhD Background: The outcomes of reduction ascending aortoplasty (RAA) performed with aortic valve surgery were evaluated and the results of RAA in patients with bicuspid aortic valve (BAV) were compared with those in patients with tricuspid valve. Methods and Results: From October 1994 to April 2009, 88 patients underwent RAA. Aortic valve was bicuspid in 45 patients (BAV group) and tricuspid in 43 patients (TAV group). Total circulatory arrest was required in 45 patients. Preoperative ascending aortic diameter was 45.5±4.7 mm. Early mortality rate was 1.1%. Ten-year survival rate and freedom from cardiac death were 91.1% and 96.2%, respectively. No differences in clinical outcomes were found between the 2 groups. No aorta-related complications including aortic rupture, dissection and reoperation were observed. Aortic diameter at the last follow-up (61±43 months) was 37.8±4.3 mm. The interval between surgery and follow-up CTA was associated with aneurysmal recurrence (P=0.022). Average rate of dilatation was 0.42±0.49 mm/year (n=37). A need for total circulatory arrest was associated with an increase of the aortic diameter (P=0.009). BAV was associated with neither aneurysmal recurrence nor increase of aortic diameter. Conclusions: RAA in patients with an ascending aortic aneurysm combined with aortic valve disease could be performed with acceptable early and long-term outcomes, even in patients with BAV. Long-term follow-up evaluation might be necessary due to the risk of redilatation especially in patients with an extended aneurysm, which required total circulatory arrest for RAA. (Circ J 2011; 75: ) Key Words: Aneurysm; Aorta; Computed tomography Surgeons are frequently required to deal with an ascending aortic aneurysm during aortic valve surgery. Although extremely large aneurysms should be replaced with synthetic grafts, this extensive procedure might be avoided by a simpler procedure known as reduction ascending aortoplasty (RAA), especially in patients with a moderately dilated ascending aorta. 1,2 RAA is a feasible technique that presents various advantages, such as being less radical than graft replacement, decreased incidence of bleeding, shorter cross clamp time and lower rates of mortality and morbidity. 3,4 However, controversies still exist with regard to indications, techniques and long-term results of RAA. 5 8 Bicuspid aortic valve (BAV) is a congenital anomaly that shares common histopathological findings with connective tissue disorders. 9 In patients with BAV, current guidelines recommend replacement of the ascending aorta during aortic valve surgery when the aortic diameter is greater than 45 mm. 10 The aims of this study were to: (1) evaluate the long-term results of RAA performed with aortic valve surgery and (2) compare the results in patients with BAV with those in patients with tricuspid valve. Methods Patient Characteristics Between October 1994 and April 2009, an ascending aortic aneurysm combined with aortic valve disease was identified in 165 patients. Among these, 88 patients (male/female = 48/40) underwent RAA in combination with aortic valve surgery based on the surgeon s discretion. The study protocol was reviewed by the Institutional Review Board and approved as a minimal risk retrospective study that did not require individual consent based on the institutional guide- Received August 9, 2010; revised manuscript received September 1, 2010; accepted September 27, 2010; released online December 9, 2010 Time for primary review: 22 days Department of Thoracic and Cardiovascular Surgery (H.Y.H., H.A.), Department of Radiology (M.-S.S., E.-A.P.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea Mailing address: Hyuk Ahn, MD, PhD, Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 28 Yeongeon-dong, Chongno-gu, Seoul , Korea. ahnhyuk@snu.ac.kr ISSN doi: /circj.CJ All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 Reduction Ascending Aortoplasty 323 Table 1. Patient Characteristics Total BAV group TAV group Age (years) 59.0± ± ± Male/female 48/40 27/18 21/ BSA (m 2 ) 1.64± ± ± Risk factors, n (%) Smoking 16 (18.2%) 12 (26.7%) 4 (9.3%) Hypertension 30 (34.1%) 20 (44.4%) 10 (23.3%) Diabetes mellitus 7 (8.0%) 3 (6.6%) 4 (9.3%) Overweight (BMI > 25 kg/m 2 ) 26 (29.6%) 17 (37.8%) 9 (20.9%) Dyslipidemia 2 (2.3%) 1 (2.2%) 1 (2.3%) >0.999 History of stroke 1 (1.2%) 0 (0.0%) 1 (2.3%) Atrial fibrillation 17 (19.3%) 5 (11.1%) 12 (27.9%) LV dysfunction (EF <35%) 8 (9.1%) 4 (8.9%) 4 (9.3%) >0.999 PVOD 1 (1.2%) 0 (0.0%) 1 (2.3%) BAV, bicuspid aortic valve; TAV, tricuspid aortic valve; BSA, body surface area; BMI, body mass index; LV, left ventricle; EF, ejection fraction; PVOD, peripheral vascular obstructive disease. Table 2. Characteristics of Aortic Valve Disease Total BAV group TAV group Aortic valve disease, n (%) <0.001 Aortic stenosis 48 (54.5%) 35 (77.8%) 13 (30.2%) Aortic regurgitation 30 (34.1%) 8 (17.8%) 22 (51.2%) Aortic stenoinsufficiency 10 (11.4%) 2 (4.4%) 8 (18.6%) Aortic diameter (mm) 45.5± ± ± Abbreviations see in Table 1. lines for waiver of consent. Age at time of surgery was 59.0±11.6 years. Aortic valve morphology was bicuspid in 45 patients (BAV group) and tricuspid in 43 patients (tricuspid aortic valve (TAV) group; degenerative disease in 18 patients and rheumatic pathology in 25 patients). Smoking and hypertension were more frequent in the BAV group and atrial fibrillation was more common in the TAV group (Table 1). Associated aortic valve diseases included aortic stenosis in 48 patients (54.5%), aortic regurgitation in 30 patients (34.1%) and mixed lesion in 10 patients (11.4%). Stenotic lesions were more frequent in the BAV group than in the TAV group (35 of 45, 77.8% vs. 13 of 43, 30.2%; P<0.001). Preoperative diameter of the ascending aorta was 45.5±4.7 mm (Table 2). No difference in aortic diameter was observed in patients with BAV and those with tricuspid morphology (BAV group vs. TAV group, 46.0±5.0 mm vs. 45.0±4.5 mm; P=0.310). Indications of RAA RAA is usually performed in patients with a moderately dilated ascending aorta regardless of aortic valve morphology (40 50 mm in diameter; n=79). Nine patients with an aortic diameter greater than 50 mm underwent RAA during the study period; 6 patients with poor left ventricular function underwent RAA to reduce myocardial ischemic time. In our early study period, we performed RAA even in patients with an aortic diameter between 50 mm and 60 mm (n=3). When patients had combined aortic root dilatation (diameter of the sinus of Valsalva greater than 5 cm and/or displaced coronary os distal to the sino-tubular junction), ascending aorta was concomitantly replaced rather than reduced. We did not perform RAA in patients with systemic connective tissue disease such as Marfan and Loey-Dietz syndromes. Surgical Procedures An arterial inflow cannula was usually inserted on the proximal aortic arch (n=58; 65.9%). During the early study period, however, the femoral artery was the preferred site for arterial cannulation (n=27; 30.7%). Three patients underwent axillary cannulation for repair of a dilated proximal aortic arch. The mid-portion of the ascending aorta was opened longitudinally and extended proximally into the non-coronary sinus. Following completion of the aortic valve procedure, the incision was extended distally, up to the distal ascending aorta. Reduction was performed by closing the aorta with pledgeted double layer 4-0 polypropylene sutures without resecting the aortic wall; first layer by continuous mattress suture and second layer by continuous over and over sutures (Figure 1). A brief period (9.6±3.0 min) of total circulatory arrest (TCA) with retrograde cerebral perfusion was required in 45 patients for completion of the reduction procedure. No external wrapping procedure was performed. Operative Data The aortic valve was replaced with a mechanical valve (n=47; 53.4%) or bioprosthesis (n=32; 36.4%) in the majority of the patients. Nine patients underwent aortic valve repair. Cardiopulmonary bypass time and aortic cross clamp time were 154±51 min and 95±42 min, respectively. Twentyfour patients underwent concomitant cardiac procedures

3 324 HWANG HY et al. Figure 1. 3-D Computed tomographic angiograms before reduction ascending aortoplasty (A) and 5 years after surgery (B). including mitral valve procedures (n=21) and arrhythmia surgery (n=4). More patients in the TAV group underwent concomitant procedures than in the BAV group (P<0.001). As a result, cardiopulmonary bypass time and aortic cross clamp time were longer in the TAV group than in the BAV group (P=0.032 and P=0.046, respectively; Table 3). Evaluation of Long-Term Outcomes Patients underwent regular postoperative follow up through the outpatient clinic at 3- or 4-month intervals, and were contacted by telephone for confirmation of their condition if the last clinic visit was not conducted at the scheduled time. Clinical and angiographic follow up was closed on 31 July Follow-up was complete in 94.3% (n=82) of survivors, with a follow-up duration of 74 (1 190) months. Operative mortality was defined as death within 30 days. Cardiac death was defined as any death related to cardiac events, including sudden death during follow up. Major adverse cardiovascular or cerebral events (MACCE) included death from any cause, cardiac events, aorta-related complications including aortic rupture, dissection and reoperation for aortic aneurysm and cerebrovascular accident. Evaluation of the Ascending Aorta At least 1 follow-up computed tomographic angiogram (CTA) was performed in 74 patients. Latest CTA was performed at 61±43 months after surgery. A radiologist blinded to the patients data reviewed all of the CTAs. A recurrence

4 Reduction Ascending Aortoplasty 325 Table 3. Operative Data Total BAV group TAV group Valve replacement, n (%) Mechanical valve 47 (53.4%) 21 (46.7%) 26 (60.5%) Bioprosthesis 32 (36.4%) 18 (40.0%) 14 (32.6%) Valve repair, n (%) 9 (10.2%) 6 (13.3%) 3 (7.0%) Concomitant procedures, n (%) 24 (27.3%) 4 (8.9%) 20 (46.5%) <0.001 Mitral valve surgery 21 (23.9%) 4 (8.9%) 17 (39.5%) Tricuspid valve surgery 2 (2.3%) 0 (0.0%) 2 (4.7%) Arrhythmia surgery 4 (4.5%) 1 (2.2%) 3 (7.0%) Others 4 (4.5%) 0 (0.0%) 4 (9.3%) Brief TCA, n (%) 45 (51.1%) 26 (6.6%) 19 (9.3%) CPB time (min) 153.9± ± ± ACC time (min) 95.4± ± ± TCA, total circulatory arrest; CPB, cardiopulmonary bypass; ACC, aortic cross clamp. Other abbreviations see in Table 1. Table 4. Early Mortality and Morbidities Total BAV group TAV group Mortality 1 (1.1%) 0 (0.0%) 1 (2.3%) Morbidities Atrial fibrillation 21 (23.9%) 12 (26.7%) 9 (20.9%) Complete atrioventricular block 3 (3.4%) 1 (2.2%) 2 (4.7%) Low cardiac output syndrome 3 (3.4%) 3 (6.7%) 0 (0.0%) Stroke 3 (3.4%) 1 (2.2%) 2 (4.7%) Acute renal failure 2 (2.3%) 0 (2.4%) 2 (4.7%) Bleeding reoperation 1 (1.1%) 0 (0.0%) 1 (2.3%) Abbreviations see in Table 1. Figure 2. Kaplan-Meier analysis revealed that 10-year freedom from cardiac death was 96.2% (A) without intergroup difference (B). BAV, bicuspid aortic valve; TAV, tricuspid aortic valve.

5 326 HWANG HY et al. Table 5. Independent Predictors for Redilatation of the Ascending Aorta (>45 mm) Univariate Multivariate Relative risk (95%CI) Age NS Sex >0.999 Smoking Body surface area Overweight (BMI > 25 kg/m 2 ) Diabetes mellitus >0.999 Hypertension Dyslipidemia NS PVOD >0.999 Atrial fibrillation Left ventricular EF NS Aortic stenosis Bicuspid aortic valve >0.999 Preoperative aortic diameter CPB time NS ACC time NS A need of TCA >0.999 Duration of CTA (months) ( ) CI, confidence interval; NS, not significant; BMI, body mass index; CTA, computed tomographic angiogram. Other abbreviations see in Tables 1,3. Table 6. Risk Factors for Increase of the Aortic Diameter Univariate Multivariate Relative risk (95%CI) Age Sex Smoking NS Body surface area Overweight (BMI > 25 kg/m 2 ) >0.999 Diabetes mellitus Hypertension Dyslipidemia >0.999 PVOD >0.999 Atrial fibrillation Left ventricular EF NS Aortic stenosis NS Bicuspid aortic valve NS Preoperative aortic diameter CPB time 0094 NS ACC time A need of TCA ( ) Abbreviations see in Tables 1,3,5. of aneurysm was defined as an aortic diameter greater than 45 mm on the follow-up CTA. Two or more CTA were performed in 37 patients. The mean interval between the earliest and latest CTA was 53±29 months. The rate of dilatation was calculated as millimeter per year. Statistical Analysis Statistical analysis was performed using the SPSS software package (version 12.0, SPSS Inc, Chicago, IL, USA). Data are expressed as mean ± standard deviation, proportions or median and range. Comparison between the 2 groups was performed using the chi-square test or Fisher s exact test for categorical variables and Student s t-test for continuous variables. Risk factors for recurrence of an aneurysm and increase of aortic diameter were analyzed. Multivariate stepwise logistic regression analysis was performed using variables with a less than 0.2 in univariate analysis. Survival rates were estimated using the Kaplan-Meier method and comparisons between groups were performed with the logrank test. Survival curves were drawn using Prism software (version 5.0, GraphPad Software Inc, CA, USA). A

6 Reduction Ascending Aortoplasty 327 of less than 0.05 was considered statistically significant. Results Early Clinical Results Operative mortality was 1.1% (1 of 88). The patient died of acute respiratory distress syndrome on the 28th postoperative day. Postoperative complications including atrial fibrillation (n=21; 23.9%) and third degree conduction block (n=3; 3.4%) were not different between the 2 groups (Table 4). One patient in the TAV group underwent reoperation due to bleeding. However, it was not associated with aortic reduction suture. Long-Term Outcomes Among 87 survivors, late death occurred in 5 (5.7%) patients, including 3 cardiac deaths. The overall 10-year survival rate was 91.1%. There was no significant difference in overall survival between the 2 groups (BAV group vs. TAV group, 97.8% vs. 85.7% at 10 years; P=0.193). Ten-year freedom from cardiac death was 96.2%. No difference was found in freedom from cardiac death between the 2 groups (BAV group vs. TAV group, 97.8% vs. 94.7%; P=0.518; Figure 2). No patients suffered from aorta-related complications such as aortic dissection, rupture and aortic reoperation. MACCEfree survival at 10 years was 82.6%. MACCE-free survival was higher in the BAV group, although it did not reach statistical significance (BAV group vs. TAV group, 95.6% vs. 72.6%; P=0.105). Changes in Repaired Ascending Aorta The mean diameter of repaired aorta was 37.8±4.3 mm at the last follow-up. None of the patients had an ascending aorta greater than 50 mm. Multivariate analysis revealed that the interval between surgery and last follow-up CTA was the only significant risk factor for aneurysmal recurrence (P=0.022; Table 5). Among 41 patients who underwent 2 or more follow-up CTA, the ascending aortic diameter increased in 23 patients during follow-up. The average dilatation rate of the ascending aorta was 0.42±0.49 mm/year. Multivariate analysis demonstrated that a need for TCA during reduction plasty was an independent predictor for later increase of the aortic diameter (Table 6). The presence of BAV influenced neither aneurysmal recurrence nor increase of aortic diameter (P>0.999 and P=0.183, respectively). Discussion The present study demonstrated 4 main findings. First, RAA for a moderate ascending aortic aneurysm combined with aortic valve disease could be performed with low periprocedural risks and good long-term results. Second, there were no aorta-related complications, including aortic dissection, rupture and reoperation up to 15 years after ascending aorta reduction procedure. Third, a need for TCA was an independent predictor for an increase in the repaired ascending aorta. Fourth, the presence of a BAV did not influence early and late clinical outcomes and redilatation of the ascending aorta after reduction aortoplasty. A need to address the dilated ascending aorta encountered in 5 15% of the patients who underwent aortic valve surgery. 3 There are several techniques for dealing with an ascending aortic aneurysm combined with aortic valve disease, such as supported and unsupported aortoplasty, separate replacement of the aortic valve and ascending aorta, composite replacement as described by Bentall and aortic root replacement with pulmonary autograft. 4,11 13 Although extremely large aneurysms should be treated with graft replacement of the aneurysmal segment, this extensive procedure may be avoided by a simple, conservative procedure such as RAA, especially in cases of moderately dilated ascending aorta. 1,2 RAA is a feasible technique that presents various advantages, including being less radical than graft replacement with less bleeding, shorter cross clamp time and lower rates of mortality and morbidity. 3,4 Several characteristics of the ascending aortic aneurysm make it suitable for RAA. Most of the ascending aortic aneurysms are less than 6 cm in diameter, are absent of mural clots with thin or normal wall thickness and have smooth intima without atheroma. 1,8 However, controversies still exist with regard to indications, techniques and long-term results of RAA. 5 8 Previous studies have demonstrated that in-hospital mortality associated with RAA and aortic valve replacement ranged from 1.5 to 11.8% and bleeding complications related to reduction suture were rare. 5 7,14 The present study also demonstrated low operative mortality and acceptable morbidities after RAA. There were no reoperations related to bleeding from aortic suture lines. Long-term results were also acceptable with a 10-year overall survival rate and freedom from cardiac death of 91.1% and 96.2%, respectively. Previous studies have demonstrated some drawbacks of simple RAA for an aneurysm of the ascending aorta. In 1997, Mueller et al. reported a high rate of recurrence of aneurysms among long-term survivors. 7 Among 13 survivors, 2 patients underwent ascending aorta prosthetic replacement due to a recurrent aneurysm and another 2 patients underwent the Bentall operation due to aortic dissection with an average interval of 63 months after RAA. Other authors have reported similar results of late recurrence. 15,16 On the contrary, recent studies have demonstrated low rates of recurrence after RAA. 6,14 Due to a concern about late redilatation, some authors have recommended external reinforcement using synthetic grafts or mesh. 2,5,8 However, serious complications might occur with external reinforcement such as migration of the wrap and atrophy of the native aortic wall. 17,18 It has also been suggested that the elasticity of the ascending aorta, known as the Windkessel function, which enables the ascending aorta to store energy and volume during systole and release it during diastole, is diminished after external wrapping. 6 In the present study, we performed RAA without external support in all patients. However, no patient experienced aortic dissection, which frequently occurred in patients with aortic aneurysm, 19,20 and rupture and aorta-related reoperation during a period of 74 (1 190) months after surgery. Although none of the patients underwent aortic reoperation, some patients had an aortic diameter greater than 45 mm. Multivariate analysis showed that the only significant risk factor for recurrence of an aneurysm was duration of CTA follow-up. Accordingly, longterm evaluation of the repaired aorta using CTA or other imaging modalities might be necessary to detect aneurysmal recurrence. Previous reports have demonstrated that preoperative diameter of the ascending aorta and regurgitant aortic valve are associated with recurrence of the aneurysm. 7,9,14 However, we did not find these factors to be associated with aneurysmal recurrence. In the present study, use of TCA was a significant risk factor for an increase in the ascending aorta. The need of TCA to complete RAA might be due to the aneurysmal segment extending up to the distal ascending aorta or proximal

7 328 HWANG HY et al. aortic arch. Dilatation of the distal ascending aorta also suggests that not only hemodynamic stress on the proximal ascending aorta due to the aortic valve disease, but also aortic wall pathology, might play an etiologic role. BAV, which is a heritable disorder, shares common histopathological findings with connective tissue disorders such as medial degeneration, increased matrix metalloproteinase activity and decreased fibrillin-1 in the aortic wall without genetic abnormalities, such as mutation in the FBN1 and TGFBR genes seen frequently in patients with Marfan syndrome. 9,21,22 For this reason, some authors avoided performing RAA in patients with BAV, although others reported excellent outcomes. 4,6,23 Current guidelines indicate that the ascending aorta should be replaced when the aortic diameter is greater than 4.5 cm in patients who undergo aortic valve surgery due to BAV disease. 10 In the present study, RAA was performed when the aortic diameter was less than 50 mm even in patients with BAV. The average preoperative diameter of the ascending aorta was similar in the 2 groups. Although there were some differences between the 2 groups in preoperative risk factors and concomitant cardiac procedure performed, early and late clinical outcomes were similar between the 2 groups. BAV was associated with neither recurrence of an aneurysm nor later increase in diameter in multivariate analyses. Study Limitations First, the present study was not performed in a prospective manner, although all consecutive patients who underwent RAA in combination with aortic valve surgery were enrolled. Second, there were differences in the baseline characteristics between the 2 groups. Although we performed multivariate analysis, this might affect our results. Third, we did not routinely evaluate the ascending aortic diameter during the early postoperative period. In addition, follow-up CTA was not performed on a regular basis and less than half of the patients underwent 2 or more CTA during follow up. Fourth, although no patients underwent aortic reoperation including aortic root replacement and arch replacement during follow-up, we did not analyze any changes in the size of the sinus of Valsalva or aortic arch because these were beyond our scope. Finally, because the number of enrolled patients is relatively small, it is insufficient to reach a definite conclusion. References 1. Barnett MG, Fiore AC, Vaca KJ, Milligan TW, Barner HB. Tailoring aortoplasty for repair of fusiform ascending aortic aneurysms. Ann Thorac Surg 1995; 59: Arsan S, Akgun S, Kurtoglu N, Yildirim T, Tekinsoy B. Reduction aortoplasty and external wrapping for moderately sized tubular ascending aortic aneurysm with concomitant operations. Ann Thorac Surg 2004; 78: Carrel T, von Segesser L, Jenni R, Gallino A, Egloff L, Bauer E, et al. Dealing with dilated ascending aorta during aortic valve replacement: Advantages of conservative surgical approach. Eur J Cardiothorac Surg 1991; 5: Bauer M, Pasic M, Schaffarzyk R, Siniawski H, Knollmann F, Meyer R, et al. Reduction aortoplasty for dilatation of the ascenidng aorta in patients with bicuspid aortic valve. Ann Thorac Surg 2002; 73: Feindt P, Litmathe J, Borgens A, Böeken U, Kurt M, Gams E. Is size-reducing ascending aortoplasty with external reinforcement an option in modern aortic surgery. Eur J Cardiothorac Surg 2007; 31: Walker T, Bail DHL, Gruler M, Vonthein R, Steger V, Ziemer G. Unsupported reduction ascending aortoplasty: Fate of diameter and of Windkessel function. Ann Thorac Surg 2007; 83: Muller XM, Tevaearai HT, Genton CY, Hurni M, Ruchat P, Fischer AP, et al. Drawback of aortoplasty for aneurysm of the ascending aorta asscociated with aortic valve disease. Ann Thorac Surg 1997; 43: Robiscek F, Cook JW, Reames MK, Skipper ER. Size reduction ascenidng aortoplasty: Is it dead or alive? 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