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Intraoperative transesophageal echocardiographic diagnosis of prosthetic conduit compression after valved conduit replacement of the ascending aorta
CASE REPORTS
Intraoperative Transesophageal Echocardiographic Diagnosis of Prosthetic Conduit Compression After Valved Conduit Replacement of the Ascending Aorta Mathias Bruefach III, MD, and Gregg S. Hartman, MD OMBINED replacement of the aortic valve and ascending aorta remains a procedure associated with an increased incidence of postoperative bleeding. 1 This can be atmbuted to a variety of causes, including prolonged bypass times, permeabihty of prosthetic conduit materials, fragility of ectanc tissues, and the technical difficulty of the reanastomosis of the native coronary arteries. Attempts to control postoperative bleeding by wrapping the prosthetic conduit with residual native aorta may be effective but can predispose the patient to other comphcations because of accumulation of blood within the aneurysm sac. A fistula, or "Cabrol" shunt, can be created between the aneurysm sac and the right atrial appendage to prevent such accumulation. 2 Today's modern conduit materials, such as collagenImpregnated woven Dacron (Hemashleld Meadox Medical, Oakland, NJ), are more hemostatic in nature. With newer surgical techniques and use of products such as topical fibrin and glue, routine creation of an aneurysm-right atrial fistula is no longer a necessity. 1 Intraoperatlve transesophageal echocardlography (TEE) allows immediate and continual assessment of the aortic repair. This gives the anesthesiologist the ability to identify coronary kinking and/or conduit compression as possible causes of postbypass hemodynamlc instability and to help direct prompt intervention before irreversible sequelae occur. This case report details one instance in which TEE was used to identify compression of the aortic conduit as the cause of postbypass cardiovascular collapse after valved conduit replacement of the ascending aorta in a 26-year-old patient with Marfan's syndrome. Prompt recognition of compression of the aortic conduit within the aneurysm sac allowed easy surgical decompression of the sac, rapid resuscitation, and phcation with a modified Cabrol shunt to the right atrium.
C
CASE REPORT A 26-year-old man with Marfan's syndrome and an enlarging aneurysm of the ascending aorta presented for replacement of the aortic valve and ascending aorta. The
From the Department of Anesthesiology, The New York Hosp~talCornell MedwaI Center, New York, N Y Address lepnnt requests to Mathtas Bruefach III, MD, Department of Anesthestology, The New York Hospttal-CorneIl Medical Center, 1300 York Ave, New York, N Y IO021 Copyright © 1996 by W B Saunders Company 1053-0770/96/1006-001453 00/0 Key words aorttc aneurysm, TEE, eondult, compresston 778
patient's functional status was NYHA class I. Past medical history was significant for uncomplicated repair of a descendlng thoracic aortic aneurysm 18 months before admission. Preoperative medications included atenolol and enalapril; there were no known drug allergies. Preoperative transthoraclc echocardiogram showed normal left ventricular size and function, an aortic root diameter of 5.5 cm, moderate aortic insufficiency, and late systolic mitral prolapse without regurgitation. Cardiac catheterization was remarkable for a dilated aortic root, moderate aortic insufficiency, mild mitral insufficiency, and normal coronary arteries. On the day of surgery, the patient was premedicated with oral diazepam, 5.0 rag, and arrived at the operating room calm but alert While the patient breathed 100% 02 wa face mask, hemodynamic monitors were applied, including right radial arterial catheter, 5-lead electrocardiogram, and pulse oximeter. Anesthesia was induced with sodium thlopental and fentanyl, and lntubaUon of the trachea was facilitated with pancuronium. Anesthesia was then maintained with additional fentanyl, mldazolam, isoflurane, and pancuronium. A 9.0F right internal jugular sheath was inserted through which a 8.0F 4-lumen thermodilutlon pulmonary artery catheter was placed. After orogastric suctioning, an Acuson(Mountain View, CA) 5.0-MHz monoplane TEE probe was inserted without difficulty. Initial TEE twodimensional (2-D) examination confirmed preoperative findings of a dilated left ventricle with normal systolic function (EF [ejection fraction] = 56%) and aneurysmal dilatation of the proximal ascending aorta to a dmmeter of 6.2 cm. The aortic valve was trileaflet, and when interrogated with color-flow Doppler, mild aortic insufficiency was noted. The aortic valve and ascending aorta were replaced with a 25-ram St. Jude valved conduit(St. Jude Medical, St. Paul, MN). The native coronaries were anastomosed to the conduit with "buttons" of native aorta, and the residual aneurysm wall was then "wrapped" over the conduit for improved hemostasis After a cross-clamp time of 110 minutes and a total bypass time of 140 minutes, the patient was easily weaned from cardiopulmonary bypass with only a bolus injection of 1 g of calcium chloride. Immediately postbypass, transgastric short-axis views of the left ventricle showed excellent global systolic function. Long-axis views of the left ventricular outflow tract were unsuccessful at imaging the prosthesis well but showed only minimal regurgitation The prosthetic aortic conduit was imaged and was noted to have an irregular, although patent, lumen (Fig 1), and a moderate amount of echolucent blood was imaged within the aneurysm sac surrounding the conduit.
Journal of Cardlothoractc and Vascular Anesthesia, Vol 10, No 6 (October), 1996: pp 778-780
TEE DIAGNOSIS OF AORTIC CONDUIT COMPRESSION
Fig 1. Short-axis view of the proximal ascending aorta in the early postbypass period(diastole) Note the irregular contour of the conduit lumen(C), which measures 20 mm in diameter. Moderate hematoma(H) is present within the aneurysm sac and is noted to be the same echodensity as the blood within the conduit lumen. Note the normal arterial pressure tracing at the bottom of the screen. LA, left atrium.
779
fled Cabrol shunt was fashioned between the aneurysm sac and the right atrmm using a 10-mm Goretex (S.L. Gore, Flagstaff, AZ) tube graft to ensure decompression of the aneurysm sac and to allow full reexpansion of the conduit (Fig 3). Closure of the chest continued uneventfully, and the patient was transferred to the intensive care unit in relatively stable condition, using a low-dose norepinephrine infusion to counteract peripheral vasodilation. The patient's postoperative course was unremarkable. He was weaned from mechanical ventilation 20 hours postoperatively, required no homologous blood products, and was discharged home on postoperative day 8 in good condition. Transthoracic echocardiogram 5 days postoperatively was notable for normal left ventricular size and function (EF 55%). The aortic conduit was fully expanded, and the hematoma within the aneurysm sac was opacified, with no indications of persistent flow within the sac or the Goretex shunt. Follow-up echocardiogram 6 months postoperatively showed improved left ventricular function (EF 60%), normal prosthetic valvular function, a fully expanded aortic conduit, and a small echo-free space between the aortic wrap and the conduit most likely consistent with liquefied hematoma. The aneurysm-to-right atrial shunt could not be imaged.
Protamine was then administered to reverse the heparin anticoagulation. An arterial blood sample for blood gas analysis and activated coagulation time was withdrawn. Immediately on return of the blood pressure display, hypotension was noted that was refractory to volume admimstration and repeated 100-1xg doses of phenylephrine. TEE imaging at this time showed global left ventrlcular depression, expansion of the aneurysm cavity, and compression of the aortic conduit with near-total diastolic obliteration of the lumen (Fig 2). The surgical team was notified, and the aneurysm sac was promptly incised, with Immediate improvement in the systemic blood pressure and prompt return of normal left ventricular function. A modi-
The utility of intraoperatwe TEE as a diagnostic aid and as a tool to grade therapy has grown rapidly. Much has been written on the ability of TEE to assess ventrlcular function, native and prosthetic valvular function, and native aortic pathology. 3 TEE has now become an accepted method to evaluate the entire thoracic aorta for dissection and/or rupture. Although it does not offer the ability to image the coronaries adequately, it is portable, faster, and less invaswe than aortography or computed tomography, does not require intravascular contrast, and provides diagnostic
Fig 2. Short-axis view of the proximal ascending aorta 13 minutes later Note the increased amount of hematoma within the aneurysm sac and near-complete diastolic collapse of the conduit(diameter 5,1 mm). The arterial pressure tracing is flattened, and the left atrium is dilated.
Fig 3 Short-axis view of the proximal ascending aorta after surgical decompression The conduit is fully reexpanded The arterial pressure tracing has regained its normal contour, and the hematoma within the aneurysm has begun to opacify. The left coronary ostium(L) is clearly patent. LAP,, left atrial appendage
DISCUSSION
780
BRUEFACH AND HARTMAN
accuracy that equals or surpasses that of those modaliUes. 4 However, there are not many reports on the use of intraoperative TEE to assess the functional integrity of a prosthetic aortic conduit after replacement of the ascending aorta. The incidence of conduit compression or kinking of the coronaries when the ascending aorta is replaced using a native aortic "wrap" is unknown, and mention of such cases usually occurs within the context of larger series of aortic replacements. 1,2,5The deformation of the conduit that was noted in the immediate postbypass period might have been caused by size mismatch, or suturing technique, and may have predisposed the conduit to compression by uneven distribution of mtra-aneurysmal pressures. Thus, a small leak at any of the anastamotic sites or just generalized oozing could have resulted m enough pressure to compress the conduit further and probably cause kinking of the coronary arteries as well. The operation described initially by Bentall and De Bono m 1968 involved replacement of the ascending aorta with a valved conduit and closure of the aneurysm with an aortic "wrap. ''6 Cabrol modified this with the inclusion of a right atrial appendage-to-aortic aneurysm anastomosis in order to control hemorrhage. This method presented the development of tension within the aneurysm sac, which might weaken the coronary anastomoses. It also protected against kinking of the coronaries and conduit compression. Westaby et al, I in 1992, showed that with newer more impervious conduit materials and liberal use of products such as topical fibrin "glue" and clotting factors, replacement of the ascending aorta could be performed with complete excision of the diseased native aorta. Although this "open" method eliminates the ability to use a native aortic wrap and requires more meticulous attention to suture lines to achieve adequate primary hemostasis, it eliminates the danger of conduit compression or coronary tension or kinking and allows the direct visual inspection of the
prosthesis and all anastomoses during chest closure. 1 This may also serve to shorten overall surgical time. Regardless of the method used (open or closed), intraoperatlve TEE can be a vital part of the initial assessment of the prosthetic valve and conduit in the immediate postbypass period. Careful evaluation of the prosthetic valve, and, if possible, the distal anastomosis should be performed before protamine administration; 2-D imaging will reveal information concerning the contour of the conduit and the presence of significant quantities of hematoma within the aneurysm sac. Color-flow Doppler can be used to assess the valve for the presence of regurgitation (either intravalvular or perivalvular) and to look for anastomotic leaks. Lastly, continuous-wave Doppler may be used to perform a baseline evaluation of transvalvular gradients. In cases where abnormalities are found, such as irregularities in the lumen of the conduit, large amounts of hematoma within the aneurysm sac, perivalvular regurgitation, or leakage at the distal anastomosis, the surgical team should be notified. Frequent reevaluation is warranted to monitor for progression. Measurement of the diameters of the conduit and aneurysm sac on weaning from bypass, and again after protamine admimstration, will help to quantify any changes that do occur. Ideally, the diameter of the aneurysm sac should remain the same, or should decrease, and any hematoma that is present in the aneurysm sae should soon begin to opacify in the absence of flow within the cavity. Sudden changes in hemodynamic parameters, as occurred in this case, should also prompt reevaluation. TEE in this case proved to be a valuable diagnostic tool. This patient's intraoperative complication required prompt surgical intervention in order to avoid undesirable sequelae. TEE was able to facilitate the diagnosis and direct the appropriate intervention allowing an otherwise uneventful postoperative course.
REFERENCES
1 Westaby S, Parry A, Pxllal R Aortic root replacement Modifications of techmque with improvements in technology Eur J Cardiothorac Surg 6:$44-$49, 1992 2. Cabrol C, Pavie A, Gandlbakhch I, et al' Complete replacement of the ascending aorta with re~mplantatlon of the coronary arteries J Thorac Cardlovasc Surg 81.309-315, 1981 3. Khanderia BK, Seward JB, Tajlk AJ' Transesophageal echocardiography. Mayo Chn Proc 69:856-863, 1994
4. Blanchard DG, Kamura BJ, Dlttnch HC, et al: Transesophageal echocard~ography of the aorta, lAMA 272:546-551, 1994 5 Cabrol C, Pavle A, Mesmldrey P, et al: Long-term results with total replacement of the ascending aorta and relmplantat~on of the coronary arteries. 1 Thorac Cardlovasc Surg 91:17-25, 1986 6 Bentall H, De Bono A. A techmque for complete replacement of the ascending aorta Thorax 23:338-339, 1968
Intraoperative Transesophageal Echocardiographic Diagnosis of Prosthetic Conduit Compression After Valved Conduit Replacement of the Ascending Aorta Mathias Bruefach III, MD, and Gregg S. Hartman, MD OMBINED replacement of the aortic valve and ascending aorta remains a procedure associated with an increased incidence of postoperative bleeding. 1 This can be atmbuted to a variety of causes, including prolonged bypass times, permeabihty of prosthetic conduit materials, fragility of ectanc tissues, and the technical difficulty of the reanastomosis of the native coronary arteries. Attempts to control postoperative bleeding by wrapping the prosthetic conduit with residual native aorta may be effective but can predispose the patient to other comphcations because of accumulation of blood within the aneurysm sac. A fistula, or "Cabrol" shunt, can be created between the aneurysm sac and the right atrial appendage to prevent such accumulation. 2 Today's modern conduit materials, such as collagenImpregnated woven Dacron (Hemashleld Meadox Medical, Oakland, NJ), are more hemostatic in nature. With newer surgical techniques and use of products such as topical fibrin and glue, routine creation of an aneurysm-right atrial fistula is no longer a necessity. 1 Intraoperatlve transesophageal echocardlography (TEE) allows immediate and continual assessment of the aortic repair. This gives the anesthesiologist the ability to identify coronary kinking and/or conduit compression as possible causes of postbypass hemodynamlc instability and to help direct prompt intervention before irreversible sequelae occur. This case report details one instance in which TEE was used to identify compression of the aortic conduit as the cause of postbypass cardiovascular collapse after valved conduit replacement of the ascending aorta in a 26-year-old patient with Marfan's syndrome. Prompt recognition of compression of the aortic conduit within the aneurysm sac allowed easy surgical decompression of the sac, rapid resuscitation, and phcation with a modified Cabrol shunt to the right atrium.
C
CASE REPORT A 26-year-old man with Marfan's syndrome and an enlarging aneurysm of the ascending aorta presented for replacement of the aortic valve and ascending aorta. The
From the Department of Anesthesiology, The New York Hosp~talCornell MedwaI Center, New York, N Y Address lepnnt requests to Mathtas Bruefach III, MD, Department of Anesthestology, The New York Hospttal-CorneIl Medical Center, 1300 York Ave, New York, N Y IO021 Copyright © 1996 by W B Saunders Company 1053-0770/96/1006-001453 00/0 Key words aorttc aneurysm, TEE, eondult, compresston 778
patient's functional status was NYHA class I. Past medical history was significant for uncomplicated repair of a descendlng thoracic aortic aneurysm 18 months before admission. Preoperative medications included atenolol and enalapril; there were no known drug allergies. Preoperative transthoraclc echocardiogram showed normal left ventricular size and function, an aortic root diameter of 5.5 cm, moderate aortic insufficiency, and late systolic mitral prolapse without regurgitation. Cardiac catheterization was remarkable for a dilated aortic root, moderate aortic insufficiency, mild mitral insufficiency, and normal coronary arteries. On the day of surgery, the patient was premedicated with oral diazepam, 5.0 rag, and arrived at the operating room calm but alert While the patient breathed 100% 02 wa face mask, hemodynamic monitors were applied, including right radial arterial catheter, 5-lead electrocardiogram, and pulse oximeter. Anesthesia was induced with sodium thlopental and fentanyl, and lntubaUon of the trachea was facilitated with pancuronium. Anesthesia was then maintained with additional fentanyl, mldazolam, isoflurane, and pancuronium. A 9.0F right internal jugular sheath was inserted through which a 8.0F 4-lumen thermodilutlon pulmonary artery catheter was placed. After orogastric suctioning, an Acuson(Mountain View, CA) 5.0-MHz monoplane TEE probe was inserted without difficulty. Initial TEE twodimensional (2-D) examination confirmed preoperative findings of a dilated left ventricle with normal systolic function (EF [ejection fraction] = 56%) and aneurysmal dilatation of the proximal ascending aorta to a dmmeter of 6.2 cm. The aortic valve was trileaflet, and when interrogated with color-flow Doppler, mild aortic insufficiency was noted. The aortic valve and ascending aorta were replaced with a 25-ram St. Jude valved conduit(St. Jude Medical, St. Paul, MN). The native coronaries were anastomosed to the conduit with "buttons" of native aorta, and the residual aneurysm wall was then "wrapped" over the conduit for improved hemostasis After a cross-clamp time of 110 minutes and a total bypass time of 140 minutes, the patient was easily weaned from cardiopulmonary bypass with only a bolus injection of 1 g of calcium chloride. Immediately postbypass, transgastric short-axis views of the left ventricle showed excellent global systolic function. Long-axis views of the left ventricular outflow tract were unsuccessful at imaging the prosthesis well but showed only minimal regurgitation The prosthetic aortic conduit was imaged and was noted to have an irregular, although patent, lumen (Fig 1), and a moderate amount of echolucent blood was imaged within the aneurysm sac surrounding the conduit.
Journal of Cardlothoractc and Vascular Anesthesia, Vol 10, No 6 (October), 1996: pp 778-780
TEE DIAGNOSIS OF AORTIC CONDUIT COMPRESSION
Fig 1. Short-axis view of the proximal ascending aorta in the early postbypass period(diastole) Note the irregular contour of the conduit lumen(C), which measures 20 mm in diameter. Moderate hematoma(H) is present within the aneurysm sac and is noted to be the same echodensity as the blood within the conduit lumen. Note the normal arterial pressure tracing at the bottom of the screen. LA, left atrium.
779
fled Cabrol shunt was fashioned between the aneurysm sac and the right atrmm using a 10-mm Goretex (S.L. Gore, Flagstaff, AZ) tube graft to ensure decompression of the aneurysm sac and to allow full reexpansion of the conduit (Fig 3). Closure of the chest continued uneventfully, and the patient was transferred to the intensive care unit in relatively stable condition, using a low-dose norepinephrine infusion to counteract peripheral vasodilation. The patient's postoperative course was unremarkable. He was weaned from mechanical ventilation 20 hours postoperatively, required no homologous blood products, and was discharged home on postoperative day 8 in good condition. Transthoracic echocardiogram 5 days postoperatively was notable for normal left ventricular size and function (EF 55%). The aortic conduit was fully expanded, and the hematoma within the aneurysm sac was opacified, with no indications of persistent flow within the sac or the Goretex shunt. Follow-up echocardiogram 6 months postoperatively showed improved left ventricular function (EF 60%), normal prosthetic valvular function, a fully expanded aortic conduit, and a small echo-free space between the aortic wrap and the conduit most likely consistent with liquefied hematoma. The aneurysm-to-right atrial shunt could not be imaged.
Protamine was then administered to reverse the heparin anticoagulation. An arterial blood sample for blood gas analysis and activated coagulation time was withdrawn. Immediately on return of the blood pressure display, hypotension was noted that was refractory to volume admimstration and repeated 100-1xg doses of phenylephrine. TEE imaging at this time showed global left ventrlcular depression, expansion of the aneurysm cavity, and compression of the aortic conduit with near-total diastolic obliteration of the lumen (Fig 2). The surgical team was notified, and the aneurysm sac was promptly incised, with Immediate improvement in the systemic blood pressure and prompt return of normal left ventricular function. A modi-
The utility of intraoperatwe TEE as a diagnostic aid and as a tool to grade therapy has grown rapidly. Much has been written on the ability of TEE to assess ventrlcular function, native and prosthetic valvular function, and native aortic pathology. 3 TEE has now become an accepted method to evaluate the entire thoracic aorta for dissection and/or rupture. Although it does not offer the ability to image the coronaries adequately, it is portable, faster, and less invaswe than aortography or computed tomography, does not require intravascular contrast, and provides diagnostic
Fig 2. Short-axis view of the proximal ascending aorta 13 minutes later Note the increased amount of hematoma within the aneurysm sac and near-complete diastolic collapse of the conduit(diameter 5,1 mm). The arterial pressure tracing is flattened, and the left atrium is dilated.
Fig 3 Short-axis view of the proximal ascending aorta after surgical decompression The conduit is fully reexpanded The arterial pressure tracing has regained its normal contour, and the hematoma within the aneurysm has begun to opacify. The left coronary ostium(L) is clearly patent. LAP,, left atrial appendage
DISCUSSION
780
BRUEFACH AND HARTMAN
accuracy that equals or surpasses that of those modaliUes. 4 However, there are not many reports on the use of intraoperative TEE to assess the functional integrity of a prosthetic aortic conduit after replacement of the ascending aorta. The incidence of conduit compression or kinking of the coronaries when the ascending aorta is replaced using a native aortic "wrap" is unknown, and mention of such cases usually occurs within the context of larger series of aortic replacements. 1,2,5The deformation of the conduit that was noted in the immediate postbypass period might have been caused by size mismatch, or suturing technique, and may have predisposed the conduit to compression by uneven distribution of mtra-aneurysmal pressures. Thus, a small leak at any of the anastamotic sites or just generalized oozing could have resulted m enough pressure to compress the conduit further and probably cause kinking of the coronary arteries as well. The operation described initially by Bentall and De Bono m 1968 involved replacement of the ascending aorta with a valved conduit and closure of the aneurysm with an aortic "wrap. ''6 Cabrol modified this with the inclusion of a right atrial appendage-to-aortic aneurysm anastomosis in order to control hemorrhage. This method presented the development of tension within the aneurysm sac, which might weaken the coronary anastomoses. It also protected against kinking of the coronaries and conduit compression. Westaby et al, I in 1992, showed that with newer more impervious conduit materials and liberal use of products such as topical fibrin "glue" and clotting factors, replacement of the ascending aorta could be performed with complete excision of the diseased native aorta. Although this "open" method eliminates the ability to use a native aortic wrap and requires more meticulous attention to suture lines to achieve adequate primary hemostasis, it eliminates the danger of conduit compression or coronary tension or kinking and allows the direct visual inspection of the
prosthesis and all anastomoses during chest closure. 1 This may also serve to shorten overall surgical time. Regardless of the method used (open or closed), intraoperatlve TEE can be a vital part of the initial assessment of the prosthetic valve and conduit in the immediate postbypass period. Careful evaluation of the prosthetic valve, and, if possible, the distal anastomosis should be performed before protamine administration; 2-D imaging will reveal information concerning the contour of the conduit and the presence of significant quantities of hematoma within the aneurysm sac. Color-flow Doppler can be used to assess the valve for the presence of regurgitation (either intravalvular or perivalvular) and to look for anastomotic leaks. Lastly, continuous-wave Doppler may be used to perform a baseline evaluation of transvalvular gradients. In cases where abnormalities are found, such as irregularities in the lumen of the conduit, large amounts of hematoma within the aneurysm sac, perivalvular regurgitation, or leakage at the distal anastomosis, the surgical team should be notified. Frequent reevaluation is warranted to monitor for progression. Measurement of the diameters of the conduit and aneurysm sac on weaning from bypass, and again after protamine admimstration, will help to quantify any changes that do occur. Ideally, the diameter of the aneurysm sac should remain the same, or should decrease, and any hematoma that is present in the aneurysm sae should soon begin to opacify in the absence of flow within the cavity. Sudden changes in hemodynamic parameters, as occurred in this case, should also prompt reevaluation. TEE in this case proved to be a valuable diagnostic tool. This patient's intraoperative complication required prompt surgical intervention in order to avoid undesirable sequelae. TEE was able to facilitate the diagnosis and direct the appropriate intervention allowing an otherwise uneventful postoperative course.
REFERENCES
1 Westaby S, Parry A, Pxllal R Aortic root replacement Modifications of techmque with improvements in technology Eur J Cardiothorac Surg 6:$44-$49, 1992 2. Cabrol C, Pavie A, Gandlbakhch I, et al' Complete replacement of the ascending aorta with re~mplantatlon of the coronary arteries J Thorac Cardlovasc Surg 81.309-315, 1981 3. Khanderia BK, Seward JB, Tajlk AJ' Transesophageal echocardiography. Mayo Chn Proc 69:856-863, 1994
4. Blanchard DG, Kamura BJ, Dlttnch HC, et al: Transesophageal echocard~ography of the aorta, lAMA 272:546-551, 1994 5 Cabrol C, Pavle A, Mesmldrey P, et al: Long-term results with total replacement of the ascending aorta and relmplantat~on of the coronary arteries. 1 Thorac Cardlovasc Surg 91:17-25, 1986 6 Bentall H, De Bono A. A techmque for complete replacement of the ascending aorta Thorax 23:338-339, 1968