Internal Thoracic Artery Graft Function During Exercise Assessed by Transthoracic Doppler Echography

nternal Thoracic Artery Graft Function During Exercise Assessed by Transthoracic Doppler Echography Hirofumi Takemura, MD, Michio Kawasuji, MD, Naoki Sakakibara, MD, Takeo Tedoriya, MD, Teruaki Ushijima, MD, and Yoh Watanabe, MD Department of Surgery (), Kanazawa University School of Medicine, Kanazawa, Japan Background. Noninvasive quantitative assessment of internal thoracic artery (TA) graft function at rest and during exercise is important in patients who have undergone coronary artery bypass grafting. Methods. Blood flow in the TA graft was measured using transthoracic color Doppler echography before and after operation in 50 patients who underwent coronary artery grafting using an TA to the left anterior descending artery. The patients were divided into three groups according to the degree of coronary stenosis and previous anterior myocardial infarction: Group 1 included 12 patients with severe (90% or more) coronary stenosis accompanied by anterior infarction. Group 2 included 26 patients with severe coronary stenosis without anterior infarction. Group 3 included 12 patients with moderate (75% or less) coronary stenosis without anterior infarction. Transthoracic echographic images of the TA were obtained through the first intercostal space using a 7.5- MHz probe, and the diameter and cross-sectional area of the TA were measured on B-mode imaging. Systolic, diastolic, and mean blood flow velocity and volume were measured by the Doppler method. Results. nternal thoracic artery diameter increased significantly from 2.2 mm to 2.4 mm after operation. The TA flow patterns in both flow velocity and volume changed from systolic-dominant to diastolic-dominant after operation. Postoperative TA graft flow was 82 +- 24 ml/min, 53 +-- 30 ml/min, and 31 +- 15 ml/min (p < 0.01, group versus 3; p < 0.05, group versus 2) and percent diastolic fraction of TA flow was 72%, 68%, and 62% (not significant) in groups 1, 2, and 3, respectively. Compared with intraoperative TA flow, which was measured using an ultrasound transit-time flowmeter, postoperative TA graft flow was increased in group 1 but not changed in group 2 or 3. The TA graft flow was measured before and after exercise in 19 patients and was compared with TA flow in 10 normal control subjects. The TA graft flow increased significantly with exercise in all patients in the three groups. Percent diastolic fraction of TA flow increased significantly with exercise in patients with severe coronary stenosis (groups 1 and 2), but decreased significantly in patients with moderate stenosis (group 3). Conclusions. Changes in native coronary artery and TA graft may be predicted by assessing TA flow pattern during exercise. Transthoracic color Doppler echography is a clinically useful noninvasive method of assessing TA graft function at rest and during exercise. (Ann Thorac Surg 1996;61:914-9) S urgical results of coronary artery bypass grafting using the internal thoracic artery (TA) have stabilized, and the use of the internal thoracic artery in coronary artery bypass grafting is associated with longterm graft patency and lower late mortality [1-3]. Thus, it is important to be able to characterize the physiologic and anatomic properties of the TA graft. Although this graft has been evaluated angiographically, its physiologic properties cannot be assessed by this technique. Seki and associates [4] described that there is a strong relationship between the TA diameter and the severity of coronary artery stenosis, and Nasu and colleagues [5] reported that the degree of left anterior descending artery stenosis affected distal TA flow using an intravascular Doppler flow guidewire. However, TA graft flow during exercise Accepted for publication Nov 25, 1995. Address reprint requests to Dr Takemura, Department of Surgery (), Kanazawa University School of Medicine, Takara-rnachi 13-1, Kanazawa, 920, Japan. cannot be assessed with these techniques because they are invasive. Noninvasive transthoracic color Doppler echography has been reported to be useful for functional evaluation of the TA graft [6]. The phenomenon that TA graft flow changes from a systolic dominant pattern preoperatively to a diastolic pattern postoperatively was reported using this technique. This study examined the physiologic properties of the TA graft and assessed the relationship of coronary stenosis to actual TA flow at rest and during exercise using transthoracic color Doppler echography. Patients and Methods The study group consisted of 50 patients who underwent elective coronary artery bypass grafting using an TA graft and additional saphenous vein grafts at Kanazawa University Medical Center. The patients ranged in age from 34 to 74 years, with a mean age of 60 years. Twenty-three of these patients had a previous history of 1996 by The Society of Thoracic Surgeons 0003-4975/96/$15.00 Published by Elsevier Science nc SSD 0003-4975(95)01173-0

Ann Thorac Surg TAKEMURA ET AL 915 1996;61:914-9 ECHOGRAPHC TA GRAFT FLOW A Fig 1. Preoperative internal thoracic artery blood flow pattern (A) and postoperative internal thoracic artery graft flow pattern (B) obtained from a 54-year-old man with total occlusion of the left anterior descending coronary artery. (a = peak systolic velocity; b - peak diastolic velocity.) B myocardial infarction; 12 had an anteroseptal myocardial infarction. The TA was anastomosed to the left anterior descending coronary artery in all patients. The average number of grafts per patient was 2.7. Transthoracic color Doppler echography was performed using computed sonography (Toshiba SSH-160A, Tokyo, Japan), with a 7.5-MHz linear array transducer, and two-dimensional images and pulsed Doppler signals were obtained. Patients in whom the TA graft was not visualized postoperatively were excluded from this study. The scanner head was positioned in the first intercostal space. The angle of the ultrasound beam was corrected for the velocity measurements. A left TA graft was used to bypass the left anterior descending artery in 48 patients, whereas a right TA graft was used in 2 patients. Typical flow patterns in the TA graft before and after operation are demonstrated in Figure 1. On B-mode imaging, the diameter and cross-sectional area of the TA were measured. Pulsed Doppler signals were then recorded. The following parameters were determined from the shape of the Doppler signal curve: peak systolic velocity, peak diastolic velocity, and mean velocity. Blood flow was derived from the following formula: blood flow - cross-sectional area (mm2).velocity time integral (cm) heart rate (min 1). 10 2. Velocity time integral is the area between the line traced on the Doppler wave and the base line. These parameters were compared before and after operation. To evaluate the influence of the severity of coronary artery stenosis and previous anterior myocardial infarction on TA graft flow, we divided the patients into three groups. Group 1 consisted of 12 patients with greater than 75% coronary stenosis accompanied by anterior myocardial infarction. Group 2 consisted of 26 patients with greater than 75% coronary stenosis without anterior infarction. Group 3 consisted of 12 patients with 75% or less coronary stenosis without anterior infarction. nternal thoracic artery graft flows and various parameters were compared among the three groups. n 40 of the 50 patients (group 1, 8; group 2, 24; and group 3, 8), intraoperative TA graft flow was also measured after cessation of cardiopulmonary bypass, using an ultrasound transit-time blood flowmeter (model T101; Transonic Systems nc, thaca, NY). Both intraoperative and postoperative TA graft flows were compared among the three groups. Nineteen patients and 10 normal male subjects ranging in age from 24 to 30 years (mean age, 26 years) underwent a treadmill exercise test for 5 minutes on a flat surface at 5 km/h. Blood pressure and heart rate were measured, and double product was calculated before and after exercise. Two-dimensional images and pulsed Doppler signals were also obtained before and after exercise as described above. Graft flow per minute and percent diastolic fraction were determined. Twelve patients were in group 1 or 2, and the other 7 patients were in group 3. Cumulative data were expressed as the mean +_ standard deviation of the mean. Statistical analysis was performed using Student's t test or one-way analysis of variance. ntergroup differences were then compared by Fisher's protected least significant difference test. The criterion for statistical significance was p less than 0.05. Results The TA diameter increased significantly from 2.2 mm to 2.4 mm postoperatively (p < 0.01) (Table 1). Although systolic flow velocity decreased significantly (p < 0.0001),

916 TAKEMURA ET AL Ann Thorac Surg ECHOGRAPHC TA GRAFT FLOW 1996;61:914-9 Table 1. Changes in nternal Thoracic Artery Parameters After Coronary Artery Bypass Grafting ~ Before After p Variable Operation Operation Value TA diameter 2.2 _+ 0.3 2.4 +_ 0.4 <0.01 (mm) Systolic flow velocity 78.5 +_ 19.8 31.8 +_ 16.8 <0.001 (cm/s) Diastolic flow velocity 17.9 + 9.2 31.3 + 18.4 <0.001 (cm/s) Mean flow velocity 24.8 10.0 22.4 _+ 11.6 NS (cm/s) Total flow volume 49.9 _+ 25.2 52.9 _+ 34.6 NS Systolic flow volume 34.0 _+ 16.3 17.1 + 10.6 <0.001 Diastolic flow volume 14.5-10.8 35.7 _+ 26.3 <0.001 Diastolic ratio (%) 30.7 +_ 10.0 65.5 -+ 11.1 <0.001 a The TA flow changed from a systolic-dominant pattern to a diastolicdominant pattern with increases in diastolic velocity, diastolic flow, and diastolic ratio. TA = internal thoracic artery,; NS = not significant. diastolic flow velocity increased significantly (p < 0.001) postoperatively. Although total blood flow in the TA did not change, the systolic flow decreased and the diastolic flow increased significantly postoperatively. Thus postoperatively, the TA flow showed a diastolic dominant pattern. The TA blood flow was compared between the three groups (Fig 2). The TA graft flow in group 1 was higher than those in groups 2 and 3. The TA graft flow in group 2 was higher than that in group 3. Percent diastolic fraction was 72%, 68%, and 62% in groups 1, 2, and 3, respectively (Fig 3). The percentage diastolic fraction increased slightly with the severity of coronary stenosis. The TA graft flow increased postoperatively in comparison with intraoperative TA graft flow except in (%) 90-80 ~ 8 7o-._u 50-40- 30i i 20 ~ c~ 10, O- Group 1 l m Group 2 Group 3 Fig 3. Comparison of diastolic percentage of internal thoracic artery graft flow. group 3 (Fig 4). n group 1, TA graft flow increased significantly from 38 + 30 ml/min to 95 _+ 40 ml/min. n group 2, TA graft flow increased slightly and in group 3, it decreased slightly. n groups 2 and 3, these changes did not reach statistical significance. Hemodynamic changes after exercise in normal subjects, patients with severe stenosis (groups 1 and 2), and patients with moderate stenosis (group 3) are shown in Table 2. Systolic blood pressure, heart rate, and double products increased significantly after exercise in all three groups. There were no significant differences in hemodynamic changes among the three groups. n normal subjects, TA flow increased significantly (p < 0.01), but percent diastolic fraction did not change (Table 3). The TA graft flow increased significantly in all three groups (p < 0.0005 for groups 1 and 2; p < 0.01 for group 3). Percent diastolic fraction of the graft flow increased (ml/rnin) 160 140 120 i p<o.05 p<o.ol i 160 ~ l--lp< s 14 n ~ L a i,! 12 intraoperative postoperative 0 < O0 80 FKO,05 o 10 NS ~- 8 L 40 -~ 20-0 Group 1 T Group 2 Group 3 Fig 2. Comparison of internal thoracic artery (TA) graft flow obtained from transthoracic color pulsed Doppler echography. The TA graft flow in group 1 was the greatest. Group 1 Group 2 Group 3 Fig 4. Changes in internal thoracic artery (TA) graft flow from intraoperative to postoperative. Flow increased significantly in group 1 but decreased slightly in group 3.

Ann Thorac Surg TAKEMURA ET AL 917 1996;61:914-9 ECHOGRAPHC TA GRAFT FLOW Table 2. Changes After Exercise in Systolic Blood Pressure, Heart Rate, and Double Product Normal Control Severe Stenosis Moderate Stenosis Variable Condition (n = 10) (groups 1 and 2; n = 12) (group 3; n = 7) Systolic blood pressure (mm Hg) Heart rate (min -~) Double product (mm Hg rain ~) a-c Significance: "p ~ 0.01, b p < 0.005, c p < 0.001 versus at rest. At rest 131 ± 11 114 ± 13 121 ± 14 After exercise 151 ± 14 c 149 ± 14 c 151-4- 15 ~ At rest 65 _+ 9 71 _+ 9 62 ± 7 After exercise 80 _+ 16 b 91 _+ 13 c 84 ± 11 ~ At rest 86 +_ 15 81 ± 15 74 _+ 10 After exercise 112 ± 50 ~ 134 ± 21 ~ 125 ± 12 ~ significantly in groups 1 and 2 (p ~ 0.01) but decreased significantly in group 3 (p < 0.01). Representative TA graft flow patterns before and after exercise are shown in Figure 5. The TA graft flow pattern in the patients of group 1 and 2 was diastolic-dominant at rest (see Fig 5A). After exercise, diastolic flow increased more than systolic flow (see Fig 5C). n patients in group 3, the graft flow pattern was systolic-dominant in velocity but diastolicdominant in flow volume at rest (see Fig 5B). Both systolic and diastolic velocity increased after exercise, whereas the percent diastolic fraction decreased (see Fig 5D). Comment From this study, we determined that preoperative TA flow is a three-phased pattern composed of high systolic velocity, a small negative wave, and slow diastolic velocity. This triphasic pattern is similar to that in the peripheral artery [7]. The postoperative TA flow pattern became diastolic-dominant with a significant increase in diastolic velocity and diastolic flow [8]. When we discuss the TA graft flow pattern, we must consider the fact that TA graft flows into coronary circulation in confluence with native coronary artery flow. Although some authors have reported the benefits of noninvasive color Doppler echography [6], they did not describe the relationship between the graft flow pattern and the severity of coronary stenosis. Recently, Nasu and associates [5] reported that TA graft flow with proximal coronary low-grade stenosis is lower than that with severe coronary stenosis using an intravaseular Doppler flow guidewire, which is an invasive method. Also in this study, the TA graft flow in patients with moderate coronary artery stenosis was lower than that in patients with severe stenosis, and the percent diastolic fraction in patients with moderate coronary artery stenosis was also lower than that in patients with severe stenosis. These phenomena may demonstrate that TA flow competes with native coronary artery flow in patients with moderate coronary artery stenosis. The TA is one of the branches of the subclavian artery in which mean diastolic pressure is lower than that in the aortic root from which the coronary arteries originate [9]. This may be one of the reasons for the competition between TA graft flow and native coronary artery flow in patients with moderate coronary artery stenosis. Other reasons that the postoperative TA graft does not become diastolic-dominant may include stenosis in the TA graft [10], the presence of a large branch into which most of the TA blood flows, (eg, the first intercostal branch) [11], weakness of contractility in the area affected by myocardial infarction [12], and competition with flow of the saphenous vein graft that was used for bypass near the TA graft. During observation of TA graft flow patterns, changes in flow pattern from diastolic-dominant to systolic-dominant suggest that some event has occurred in the TA graft or in the native coronary artery. Although techniques for measuring intraoperative TA graft flow and postoperative flow differ, both methods are reported to be reliable [12, 13]. This study demonstrated that flow in the TA graft increased postoperatively, especially in group 1. The TA graft flow decreased slightly in group 3 in comparison with intraoperative TA graft flow. There were 4 patients in group 1 in whom the intraoperative TA graft flow into the infarcted area was very low (less than 15 ml/min), indicating the doubtful viability of that area. However, the fact that these very Table 3. Changes After Exercise in nternal Thoracic Artery Flow and Percent Diastolic Fraction in Normal Subjects and Patients With Coronary Stenosis Variable TA flow (ml[min) Percent diastolic fraction (%) Condition Severe Stenosis Moderate Stenosis Normal Subjects (groups 1 and 2; (group 3; (n = 10) n = 12) n = 7) At rest 56 ± 14 59 -+ 34 42 +- 29 After exercise 86 ± 28 a 91 _+ 50 b 66 ± 42 a At rest 31.5 _+ 11.7 70.5 ± 11.4 61.0 ± 10.5 After exercise 31.7 ± 5.7 74.0 + 11.7 a 54.9 12.2 ~' a,b Significance: a p ~ 0.01, b p < 0.0005 versus at rest. TA = internal thoracic artery.

918 TAKEMURA ET AL Ann Thorac Surg ECHOGRAPHC TA GRAFT FLOW 1996;61:914-9 -O.1H A C B D Fig 5. Representative pulsed Doppler images at rest and after exercise. (A, C) A patient with total occlusion of the left anterior descending artery (group 2). (B, D) A patient with 75% coronary stenosis (group 3). (A, B) Before exercise. (C, D) After exercise. low intraoperative TA flows increased postoperatively shows some relation to the improvement in circulation and metabolism in the myocardium, so-called hibernation [141, whereas the fact that TA graft flow decreased in group 3 indicates that competitive flow might result in reduced TA flow and string sign, or in extreme cases a no-flow situation, as reported by Aris and co-workers [15] and Dincer and Barner [16]. Van Citters and Franklin [17] reported that coronary blood flow in the dog increased fourfold with exercise. Hongo and associates [18] demonstrated that coronary blood flow increased from 155 ml/min to 285 ml/min by atrial-pacing-induced tachycardia and that the increase in coronary artery flow with exercise depends on an increase in diastolic flow although diastolic duration is decreased. n this study, TA graft flow increased significantly in all patients with exercise, but the increase in TA graft flow in patients with severe coronary stenosis

Ann Thorac Surg TAKEMURA ET AL 919 1996;61:914-9 ECHOGRAPHC TA GRAFT FLOW was greater than that in patients with moderate stenosis. Although the percent diastolic fraction increased significantly in patients with severe coronary artery stenosis, it decreased significantly in patients with moderate coronary stenosis. As Kajiya and colleagues [19] demonstrated that velocity waveform in a native coronary artery beyond a vein bypass changes to a systolic-predominant pattern in a patient with severe stenosis during transit graft occlusion, coronary flow depends mostly on TA graft flow in such a patient. Otherwise, as described above, the TA graft flow competes with native coronary artery flow in patients with moderate coronary stenosis. Under such conditions, diastolic flow in native coronary artery exceeds that in TA graft after exercise. Because Nasu and associates [5] demonstrated that progression of left anterior descending coronary artery disease changed the TA graft flow pattern measured by intravascular Doppler flow guidewire, when our noninvasive examination revealed a change in TA graft flow pattern during exercise, we were able to predict the progression of the native coronary artery disease. Further follow-up and study are necessary to confirm these findings. Transthoracic color Doppler echography allows accurate assessment of the TA. t can be performed postoperatively for clinical follow-up and for studies of cardiac physiology and pharmacology repeatedly and noninvasively. t provides considerable information concerning the TA graft, which is key to the patient's prognosis. References 1. Boylan MJ, Lytle BW, Loop FD, et al. Surgical treatment of isolated left anterior descending coronary stenosis. Comparison of left internal mammary artery and venous autograft at 18 to 20 years of follow-up. J Thorac Cardiovasc Surg 1994;107:657-62. 2. Loop FD, Lytle BW, Cosgrove DM, et al. nfluence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med 1986;314:1-6. 3. Cameron A, Davis KB, Green GE, Myers WO, Pettinger M. Clinical implications of internal mammary artery bypass grafts. The coronary artery surgery study experience. Circulation 1988;77:815-9. 4. Seki T, Kitamura S, Kawachi K, et al. A quantitative study of postoperative luminal narrowing of the internal thoracic artery graft in coronary artery bypass surgery. J Thorac Cardiovasc Surg 1992;104:1532-8. 5. Nasu M, Akasaka T, Okazaki T, et al. Postoperative flow characteristics of left internal thoracic artery grafts. Ann Thorac Surg 1995;59:154-62. 6. De Bono DP, Samani NJ, Spyt TJ, Hartshorne T, Thrush AJ, Evans DH. Transcutaneous ultrasound measurement of blood-flow in internal mammary artery to coronary artery grafts. Lancet 1992;339:379-81. 7. Jager KA, Phillips DJ, Martin RL, et al. Noninvasive mapping of lower limb arterial lesions. Ultrasound Med Biol 1985;11: 515-21. 8. Fusejima K, Takahara Y, Sudo Y, Murayama H, Masuda Y, nagaki Y. Comparison of coronary hemodynamics in patients with internal mammary artery and saphenous vein coronary artery bypass grafts. A noninvasive approach using combined two-dimensional and Doppler echocardiography. J Am Coil Cardiol 1990;15:131-9. 9. Tedoriya T, Kawasuji M, Ueyama K, Sakakibara N, Takemura H, Watanabe Y. Physiologic characteristics of coronary artery bypass grafts. Ann Thorac Surg 1993;56:951-6. 10. Van Son JAM, Skotnicki SH, Peters MBM, Pijls NH, Noyez L, van Asten WNJC. Noninvasive hemodynamic assessment of the internal mammary artery in myocardial revascularization. Ann Thorac Surg 1993;55:404-9. 11. Singh RN, Magovern GJ. nternal mammary graft. mproved flow resulting from correction of steal phenomenon. J Thorac Cardiovasc Surg 1982;84:146-9. 12. Olinger GN, Mulder DG, Maloney ]V Jr, Buckberg GD. Phasic coronary flow. ntraoperative evaluation of flow distribution, myocardial function, and reactive hyperemic response. Ann Thorac Surg 1976;21:397-404. 13. Barnes RJ, Comline RS, Dobson A, Drost CJ. An implantable transit time ultrasonic blood flow meter. J Physiol 1983;345: 2-3. 14. Braunwald E, Rutherford JD. Reversible ischemic left ventricular dysfunction. Evidence for the "hibernating myocardium." J Am Coil Cardiol 1986;8:1467-70. 15. Aris A, Borrhs X, Rami6 J. Patency of internal mammary artery grafts in no-flow situations. J Thorac Cardiovasc Surg 1987;93:62-4. 16. Dincer B, Barner HB. The "occluded" internal mammary artery graft. Restoration of patency after apparent occlusion associated with progression of coronary disease. J Thorac Cardiovasc Surg 1983;85:318-20. 17. Van Citters RL, Franklin DL. Cardiovascular performance of Alaska sled dogs during exercise. Circ Res 1969;24:33-42. 18. Hongo M, Nakatsuka T, Watanabe N, et al. Effects of heart rate on phasic coronary blood flow pattern and flow reserve in patients with normal coronary arteries. A study with an intravascular Doppler catheter and spectral analysis. Am Heart J 1994;127:545-51. 19. Kajiya F, Tsujioka K, Ogasawara Y, et al. Analysis of flow characteristics in poststenotic region of the human coronary artery during bypass graft surgery. Circulation 1987;76:1092-100.