Natural History of a Dilated Ascending Aorta After Aortic Valve Replacement

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1 Circ J 2005; 69: Natural History of a Dilated Ascending Aorta After Aortic Valve Replacement Katsuhiko Matsuyama, MD; Akihiko Usui, MD; Toshiaki Akita, MD; Masaharu Yoshikawa, MD; Masaomi Murayama, MD; Takashi Yano, MD; Hiroharu Takenaka, MD; Wataru Katou, MD; Masashi Toyama, MD; Masaho Okada, MD; Motonari Sawaki, MD; Yuichi Ueda, MD Background Little information is available regarding the incidence of aortic dissection or rupture in patients with a dilated ascending aorta after aortic valve replacement (AVR). The present clinical study aimed to demonstrate the incidence of aortic complications after AVR in patients with a dilated ascending aorta and to clarify those risk factors associated with the progression of a dilated ascending aorta or late aortic events. Methods and Results A total of 35 patients with a dilated ascending aorta at the time of AVR were enrolled. A dilated ascending aorta was defined as 40 mm or greater in diameter by preoperative computed tomography or operative findings. The baseline ascending aorta diameter ranged from 40 to 55mm with a mean of 44.8±4.4mm. There was a high frequency of bicuspid valve disease in patients with a dilated ascending aorta (57%). The mean follow-up interval was 8.1±3.5 years (range: ). Aortic events occurred in 5 patients (aortic dissection in 1, rupture in 2, reoperation in 2) during the follow-up. One aortic dissection developed at a baseline aortic size of 42 mm, whereas 2 aortic ruptures occurred at baseline aortic sizes of 47 mm and 50 mm. There was no statistically significant univariate association between any of the patient clinical characteristics and late aortic events or ascending aortic progression. Conclusion Although the clinical course of patients with a dilated ascending aorta is unpredictable, aortic events may occur even in patients with a baseline aortic diameter of <50 mm. Therefore, preventive aortic surgery at the time of AVR should be considered to prevent aortic dissection or rupture in patients with an even slightly dilated ascending aorta with a diameter of 40 to 50 mm, unless the patient has a high operative risk or older age. (Circ J 2005; 69: ) Key Words: Aneurysm; Aortic valve replacement; Ascending aorta Wall stress is directly proportional to the aortic diameter, but inversely proportional to the wall thickness and strength according to Laplace s law. Therefore, increasing size is more strongly associated with an increasing risk of rupture. 1 A recent report demonstrated that the mean rate of occurrence of aortic events is only 2% per year for small aneurysms of 5.0 cm in diameter or less, rises to 3% for aneurysms measuring 5.0 to 5.9 cm, and this figure increases up to 6.9% for aneurysms of 6.0cm or greater. 1 The current recommendation is that 60mm is the appropriate size criterion for elective resection of an ascending aortic aneurysm. 1,2 Aortic valve disease is frequently associated with ascending aortic dilatation because of hemodynamic burdens caused by forceful jets from the aortic stenosis or increased stroke volume caused by aortic regurgitation. The growth rate of an ascending aorta dilation associated with aortic valve disease may be different from that of an aorta dilated spontaneously with a normal aortic valve. Aortic valve replacement (AVR), which reduces the hemodynamic (Received October 1, 2004; revised manuscript received December 24, 2004; accepted January 17, 2005) Nagoya University Graduate School of Medicine, Department of Cardio-Thoracic Surgery, Nagoya, Japan Mailing address: Katsuhiko Matsuyama, MD, Nagoya University Graduate School of Medicine, Department of Cardio-Thoracic Surgery, 65 Tsurumai-cho, Showa-ku, Nagoya , Japan. k-matsuy@f3.dion.ne.jp burdens to the aortic wall, may prevent the further dilatation of the aorta. However, it still remains controversial how to treat a dilated aorta at the time of AVR. 3,4 Additional operations for a dilated ascending aorta during the initial aortic valve surgery also increase the operative risk. Little information is available regarding the incidence of aortic dissection or rupture in patients with a dilated ascending aorta after AVR. At our institution, AVR alone has often been performed in patients with a dilated ascending aorta greater than 40 or 50 mm in diameter. The current clinical study reports the incidence of aortic complications after AVR in patients with a dilated ascending aorta, and clarifies those risk factors associated with the progression of a dilated ascending aorta or late aortic events. Methods Out of a total of 227 patients who underwent AVR without aortic root replacement or replacement of the ascending aorta at our institution between April 1990 and December 2000, we retrospectively assessed 35 patients with a dilated ascending aorta at the time of AVR. A dilated ascending aorta was defined as 40mm or greater in diameter by preoperative computed tomography (CT) or operative findings. Patients with a dilated sinus of Valsalva, annuloaortic ectasia or Marfan syndrome were excluded. Concomitant coronary bypass grafting or mitral operation was also excluded. Postoperative changes in the size of the ascend-

2 Ascending Aorta After AVR 393 Table 1 Characteristics of Patients Dilated aorta No dilated aorta (n=35) (n=192) p-value Age at operation (years) 57±14 (18 76) 58±13 (18 82) NS Gender (female) 14 (40%) 84 (44%) Hypertension 11 (31%) 50 (26%) NS Aortic valve disease NS Stenosis 14 (40%) 104 (54%) Regurgitation 21 (60%) 88 (46%) Valve pathology < Bicuspid 20 (57%) 39 (20%) Tricuspid 15 (43%) 153 (80%) Aortic valve prosthesis NS Mechanical 29 (83%) 157 (87%) Biological 6 (17%) 25 (13%) Ascending aortic diameter (mm) 44.8±4.4 (range: 40 55) NS, not significant. Fig 1. Frequency distribution of baseline ascending aortic diameter. The shadow bars represent patients with late aortic events. ing aorta were identified by plain CT. Annular dilatation was calculated by dividing the changes in the diameter during the follow-up period over the original diameter. Continuous variables were presented as the means ± SD, and statistical analyses were performed using Student s t-test. The baseline characteristics were compared by use of a chi-squared test for dichotomous variables. Survival and event-free rates were calculated using the Kaplan-Meier method. Univariate analysis was performed for risk factors of the following aortic events or aortic dilatation. A p-value less than 0.05 was considered to be statistically significant. Results The characteristics of the study population are presented in Table 1. In patients with no dilated aorta, preoperative aortic diameter was not measured if the ascending aorta was obviously small. There was a high frequency of bicuspid valve disease in patients with a dilated ascending aorta (57%). The majority of patients (83%) received mechanical valve prostheses. The frequency distribution of the ascending aortic diameter at baseline is shown in Fig 1. There were no operative deaths. The follow-up was complete (100%), and the mean follow-up interval was 8.1±3.5 years (range: ). One tricuspid valve patient with a baseline aortic diameter of 43mm and 1 bicuspid valve patient with a baseline aortic diameter of 41 mm underwent reoperation 3.7 years and 13 years after AVR for postoperative aortic enlargement with diameters of 60 mm and 55 mm, respectively. There were 5 late deaths during the follow-up. The causes of deaths were aortic rupture in 2 patients, myocardial infarction in 1 patient, brain infarction in 1 patient, and cancer in 1 patient. The cumulative survival rate after AVR was 87.2% at 10 years (Fig 2). Aortic events occurred in 5 patients (aortic dissection in 1 patient, rupture in 2 patients, reoperation in 2 patients). Freedom from aortic events was 87.2% at 10 years (Fig 3). One aortic dissection developed at a baseline aortic size of 42 mm, whereas 2 aortic ruptures occurred at baseline aortic sizes of 47 mm and 50 mm. A univariate analysis of those risk factors predictive of aortic events is shown in Table 2. There was no statistically significant univariate association between aortic events and clinical characteristics, including the baseline aortic diameter. In all 192 patients with no dilated aorta, there was neither aortic event nor significant aortic enlargement requiring reoperation during the follow-up. A radiologic follow-up was available in 32 patients, ranging from 3 to 14.1 years with a median of 7.8 years. Another 3 patients died of an aortic rupture, myocardial infarction,

3 394 MATSUYAMA K et al. Fig 2. Survival after aortic valve replacement. Fig 3. Freedom from aortic events. Table 2 Comparison Characteristics of Patients With or Without Aortic Events Aortic events No aortic events (n=5) (n=30) Baseline aortic diameter (mm) 44.6± ±4.4 (range: 41 50) (range: 40 55) Hypertension 2 (40%) 9 (30%) Age at operation (years) 59±18 56±14 Gender (female) 2 (40%) 12 (40%) Aortic valve disease Stenosis 2 (40%) 12 (40%) Regurgitation 3 (60%) 18 (60%) Valve pathology Bicuspid 3 (60%) 15 (50%) Tricuspid 2 (40%) 12 (40%) Aortic valve prosthesis Mechanical 4 (80%) 25 (83%) Biological 1 (20%) 4 (13%) Left ventricular ejection fraction 65±5 62±10 Aortic valve gradient (mmhg) 23.8± ±11.9 Postoperative systolic BP (mmhg) 125±20 122±16 Postoperative diastolic BP (mmhg) 72±19 68±18 BP, blood pressure.

4 Ascending Aorta After AVR 395 and brain infarction before radiologic measurements of ascending aorta could take place. The expansion rates of the ascending aorta ranged from 0.5 mm to 2.6 mm/year, with a mean of 0.58 mm/year (Fig 4). Progressive aortic dilatation, defined as an increase in diameter >5 mm, occurred in 19% (6/32) patients, whereas the remaining 81% patients had no increase or a minimal increase. Moreover, 88% (7/8) of the patients with a baseline aortic size of 50mm or greater had no progression of their ascending aorta during follow-up. There was no correlation between the baseline diameter and aortic events (Fig 1). Moreover, no statistically significant univariate association was found between aortic growth (>5 mm) and any of the patient characteristics, including gender, age, bicuspid valve, aortic valve gradient, postoperative blood pressure, and baseline aortic diameter. Discussion In most reports, the aortic diameter was measured by echocardiography, which cannot visualize the entire ascending aorta. 1,4,5,8 To assess the size of the ascending aorta precisely, a CT scan was performed during the follow-up period in the present study. Treatment decisions for an ascending aorta dilated secondary to aortic valve disease have not been clearly reported, because the natural history of patients after AVR with a dilated ascending aorta is unknown. Previous reports showed that patients with a baseline ascending aorta diameter of 40 mm or 50 mm after AVR were likely to suffer aortic complications. 4,5 Natsuaki et al reported that postoperative dissections developed in 12% of the patients (3/26) with preoperative ascending diameters of 40 mm. 6 However, a recent report demonstrated the stability of a dilated ascending aorta following AVR. 4 In that report, only 9.3% (10/107) in the population of patients with baseline ascending aortic diameters of 35 mm displayed an increase in diameter exceeding 3 mm. Aortic valve replacement alone, as mentioned above, may be reasonable in patients with mild aortic dilatation (<40 mm). Therefore, in the present study, only those patients with an initial aortic size of 40 mm or greater were studied. As a result, 19% of the patients had progressive aortic dilatation ( 5mm), and 14% of the patients had late aortic events. One patient who developed an aortic dissection had a baseline aortic size of 42 mm, and 2 aortic ruptures occurred at baseline aortic sizes of 47 mm and 50 mm. The baseline aortic size was not associated with late aortic events in patients with a dilated ascending aorta with a diameter of 40 mm. Therefore, patients with an even slightly dilated ascending aorta with a diameter of <50 mm may be at risk for aortic events to a certain degree. The rate of expansion after surgery has also been shown to be an important predictor of rupture. In the present study, the expansion rates of the ascending aorta ranged from 0.5 mm to 2.4 mm/year, with a mean of 0.45 mm/year. Most of the patients (82%) had no changes in their aortic size. No statistically significant univariate association was found between ascending aortic expansion and any of the clinical variables. Andrus et al reported an ascending aortic expansion rate of 0.1 mm/year after AVR. 4 Therefore, AVR is likely to modify the natural history of ascending aorta disease. Yasuda et al reported that aortic dilatation after AVR in bicuspid valve patients tended to be faster than that in tricuspid valve patients, although no baseline aortic diameter Fig 4. Changes of ascending aortic diameter after aortic valve replacement. was shown. 5 A recent report showed that 30% (8/27) of bicuspid valve patients had an ascending aorta aneurysm after isolated AVR. 8 The prevalence of congenital bicuspid valve disease has been reported to be 1 to 2%. 9 The present study had a high frequency of bicuspid valve disease in patients with a dilated ascending aorta. It has been reported that patients with bicuspid aortic valve are at increased risk of aneurysms of the ascending aorta, aortic dissections, and rupture. 10 However, in the current study, 2 out of 5 aortic events occurred in tricuspid valve patients, and bicuspid valve disease failed to be a risk factor for aortic enlargement or the occurrence of aortic events. This may be due to the small number of patients. However, it is notable that even tricuspid valve patients with a slightly dilated aorta are at risk of late aortic events. Natsuaki et al recommended the use of tissue valves, because patients with a mechanical valve are more likely to develop a postoperative aortic dissection than are those with a tissue valve. 6 In the present study, there was only 1 aortic event in a patient with a tissue valve, although the number of tissue valves was quite small. Various types of surgery for a dilated ascending aorta have been reported, such as wrapping of the aorta, Shaw- Lapel and tailoring aortoplasty with or without external wall support, and graft replacement. 3 Of those procedures, the most simple and conservative method is wrapping of the aorta. However, the problem with wrapping the ascending aorta is bulging or herniation of the aortic wall at the lips of the wrap. Graft replacement is the best reliable treatment. A recent report showed that operative mortality was 5% for patients undergoing AVR and graft replacement of the ascending aorta. 11 The operative risk for AVR and graft replacement of ascending aorta may be lower than the occurrence of late aortic events in patients with isolated AVR. Graft replacement should be considered unless the patient has a high operative risk or older age. There are several limitations in the present study. First, we evaluated only a small number of patients. If the current

5 396 MATSUYAMA K et al. study had a larger number of patients, some risk factors concerning aortic enlargement or events may have been detected. Second, the risk of hypertension was not fully assessed in the study. It has been reported that hypertension itself is a possible cause of dilatation of the aortic root or ascending aorta, 8,12 and that the increase in the ascending aorta diameter was 1.25 mm/year in normotensive and 2.8 mm/year in hypertensive patients with a bicuspid aortic valve. 8 However, the blood pressure of all 5 patients with late aortic events had been well-controlled. Finally, the ascending aortic size measured in patients with aortic events does not necessarily represent the size immediately before the occurrence of the aortic events. In conclusion, although the clinical course of patients with a dilated ascending aorta is unpredictable, aortic events may occur even in patients with a baseline aortic diameter of <50 mm. Therefore, preventive aortic surgery at the time of AVR should be considered to prevent aortic dissection or rupture in patients with an even slightly dilated ascending aorta with a diameter of 40 to 50 mm unless the patient has a high operative risk or older age. If a dilated ascending aorta was not treated, careful radiologic follow-up is warranted, and the timing of the reoperation should be determined. References 1. Davies RR, Goldstein LJ, Coady MA, Tittle SL, Rizzo JA, Kopf GS, et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: Simple prediction based on size. Ann Thorac Surg 2002; 73: 17 27; Discussion Kawachi Y, Nakashima A, Kosuga T, Tomoeda H, Toshima Y, Nishimura Y. Comparative study of the natural history and operative outcome in patients 75 years and older with thoracic aortic aneurysm. Circ J 2003; 67: Sutsch G, Jenni R, von Segesser L, Turina M. Predictability of aortic dissection as a function of aortic diameter. Eur Heart J 1991; 12: Andrus BW, O Rourke DJ, Dacey LJ, Palac RT. Stability of ascending aortic dilatation following aortic valve replacement. Circulation 2003; 108(Suppl 1): II-295 II Yasuda H, Nakatani S, Stugaard M, Tsujita-Kuroda Y, Bando K, Kobayashi J, 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(Suppl 1): II-291 II Natsuaki M, Itoh T, Rikitake K, Okazaki Y, Naitoh K. Aortic complications after aortic valve replacement in patients with dilated ascending aorta and aortic regurgitation. J Heart Valve Dis 1998; 7: Pieters FA, Widdershoven JW, Gerardy AC, Geskes G, Cheriex EC, Wellens HJ. Risk of aortic dissection after aortic valve replacement. Am J Cardiol 1993; 72: Kuralay E, Demirkilic U, Ozal E, Oz BS, Cingoz F, Gunay C, et al. Surgical approach to ascending aorta in bicuspid aortic valve. J Card Surg 2003; 18: Roberts WC. The structure of the aortic valve in clinically isolated aortic stenosis: An autopsy study of 162 patients over 15 years of age. Circulation 1970; 42: Roberts CS, Roberts WC. Dissection of the aorta associated with congenital malformation of the aortic valve. J Am Coll Cardiol 1991; 17: Sioris T, David TE, Ivanov J, Armstrong S, Feindel CM. Clinical outcomes after separate and composite replacement of the aortic valve and ascending aorta. J Thorac Cardiovasc Surg 2004; 128: Kim M, Roman MJ, Cavallini MC, Schwartz JE, Pickering TG, Devereux RB. Effect of hypertension on aortic root size and prevalence of aortic regurgitation. Hypertension 1996; 28:

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