Noninvasive assessment of coronary flow reserve in the right gastroepiploic artery graft

Noninvasive Assessment of Coronary Flow Reserve in the Right Gastroepiploic Artery Graft Giuseppe Tavilla, MD, Nico H. J. Pijls, MD, PhD, Kathinka H. Peels, MD, and Eric Berreklouw, MD, PhD Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, and Departments of Cardiothoracic Surgery and Cardiology, Catharina Hospital, Eindhoven, The Netherlands

Background. To investigate the functional capacity of the right gastroepiploic artery graft (GEA) and its ability to adapt to provide adequate flow at peak myocardial demand, we investigated the feasibility of determining coronary flow reserve (CFR) provided by this vessel using transabdominal color Doppler echocardiography and the correlation between this noninvasive determination of flow reserve and nuclear stress scintigraphy. Methods. In 40 selected patients, who underwent complete arterial myocardial revascularization using the GEA and the internal thoracic arteries (ITAs), CFR of the GEA was measured at maximum coronary hyperemia induced by intravenous adenosine infusion, 7 months (range 3 to 20) after surgery. In the same period, in 31 of this group of patients, exercise thallium scintigraphy was performed. Results. We succeeded in measuring CFR in 37 of 40 patients with values ranging from 1.1 to 3.6 with an average of 2.1 ⴞ 0.7. During adenosine infusion, mean velocity in the GEA significantly increased from 48 ⴞ 20 to 89 ⴞ 41 cm/sec (p < 0.001), mean arterial blood

pressure significantly decreased from 96 ⴞ 11 to 87 ⴞ 11 mm Hg (p < 0.001), and heart rate significantly increased from 74 ⴞ 11 to 87 ⴞ 15 beats/min (p < 0.001). In 8 of these 37 patients, the nuclear exercise test was positive (compatible with reversible ischemia in the distribution area of the GEA). Average CFR in these 8 patients with positive nuclear stress test was 1.46 ⴞ 0.28 versus 2.27 ⴞ 0.70 in those patients with a negative test (p < 0.001). Conclusions. Noninvasive determination of CFR of GEAs is feasible, using transabdominal Doppler echocardiography. The present study shows that coronary vasodilator reserve and autoregulation is maintained in myocardium supplied by the GEA and that the CFR has a significant correlation with the results of noninvasive nuclear exercise testing. Therefore, noninvasive determination of CFR by transabdominal Doppler echocardiography might be a valuable contribution to functional assessment of GEAs. (Ann Thorac Surg 2000;70:2040 – 4) © 2000 by The Society of Thoracic Surgeons

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easy, it would be useful if a method would be available to evaluate the functional capacity of this graft noninvasively. Therefore, the aim of this study was to investigate the usefulness of noninvasive transabdominal echoDoppler measurement to visualize the GEA and, more specifically, if it is possible to determine CFR noninvasively in these patients. Because no data are known about the coronary flow reserve (CFR) in GEAs, this study was primarily intended as a feasibility study; the second aim was to investigate if a correlation exists between the measured value of CFR and the result of nuclear stress scintigraphy that was performed in most of the patients shortly before the CFR measurement.

he superiority of pedicled internal thoracic artery (ITA) grafts in comparison with venous grafts in terms of long-term patency is beyond any doubt [1, 2]. Moreover, patients who received two pedicled ITAs have over a 15-year period diminished risks of death, reoperation, and angioplasty [3]. In the last few years, other arterial conduits have been used to perform complete arterial revascularization, particularly in young patients with multivessel disease, who need more grafts than can be provided by both pedicled ITAs. One of these alternative arterial grafts is the gastroepiploic artery (GEA), which has become the arterial conduit of preference after both ITAs [4 – 8]. Data about the mid-term and long-term patency of this graft are not as abundant as for the ITAs and little is known about the functional capacity of the GEA and the ability of this vessel to adapt to provide adequate flow at peak myocardial demand, an adaptation which is known from the ITAs [9]. Because selective catheterization of the GEA is not Accepted for publication May 25, 2000. Address reprint requests to Dr Tavilla, Department of Cardiothoracic Surgery, Leiden University Medical Center, K6-S, PO Box 9600, 2300 RC Leiden, The Netherlands; e-mail: [email protected].

© 2000 by The Society of Thoracic Surgeons Published by Elsevier Science Inc

Material and Methods Patient Population Between April 1994 and October 1995, 77 patients underwent coronary bypass surgery with complete arterial revascularization, using the GEA graft in combination with both ITAs in 69 patients and in combination with only the left ITA in 8 patients. No saphenous vein grafts were used. 0003-4975/00/$20.00 PII S0003-4975(00)02130-5

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In 71 of these patients, noninvasive echo-Doppler examination of the GEA graft was performed between 3 and 20 months after surgery. In 65 of these 71 patients the GEA graft could be detected and a reasonable flow signal was obtained [10]. From these 65 patients, the best 40 patients were selected in whom the Doppler signals were considered sufficiently well by the investigators to expect that also after induction of hyperemia a good signal could be obtained and, therefore, in whom it was justified to perform the protocol as will be described below. These 40 patients, therefore, were selected on the basis of a good visualization of the GEA graft and good Doppler and color-Doppler signals. These 40 patients consisted of 36 men and 4 women with a mean age of 53 ⫾ 9 years (range 42 to 67). In these patients the GEA was transposed to the heart antegastrically and ventrally to the liver [11]. The GEA was anastomosized on the posterior descending artery in 34 patients and on the distal main right coronary artery in 6 patients. After having obtained written informed consent, exercise thalliumscintigraphy was performed, followed by the echo-Doppler examination at baseline conditions and at maximum coronary hyperemia induced by intravenous adenosine infusion as described below. At time of the study all patients were in New York Heart Association class 1.

Echodoppler Studies and Measurement of Coronary Flow Reserve The GEA graft evaluation was performed 7 months (range 3 to 20) after coronary bypass surgery. Echocardiography was performed using a HP Sonos 1000 ultrasound system (Hewlett Packard, Andover, MA) with a 2.5 and 3.5 Mhz transducer by a transabdominal approach. The patient was examined in supine position, breathing normally. With the transducer positioned below the right chondral margin lateral to midline, the GEA graft flow was detected by color Doppler echocardiography. Although many smaller veins and arteries can be seen below the ventral abdominal wall, the GEA graft was identified based upon the following three criteria: (1) a vessel with a diameter of 1.5 to 3 mm containing high speed blood flow velocities indicating an arterial signal, with a general flow pattern in a caudocranial direction; (2) a collar of abnormal echo-intensive perivascular tissue, as is not observed around normal native arteries in that area; (3) A typical tortuous and unpredictable course, in some sections perpendicular to the transducer and in other sections almost tangentially imaged. Because the systolic-diastolic flow pattern in a GEA graft is not expected to be typical and is strongly dependent on both the relative distance to its origin and on the size of the distribution area of the recipient coronary artery, the systolic-diastolic flow pattern was not used as a characteristic to recognize the GEA graft. The three criteria mentioned above were never observed in patients not operated on and if present in operated on patients, were considered as specific for the GEA graft [10]. Guided by color Doppler imaging, a pulsed Doppler

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flow signal was acquired with the sample positioned in the GEA graft as parallel as possible to the visualized color Doppler flow signals. From the pulsed Doppler flow velocity spectrum, maximal and mean velocity (Vmax and Vmean, respectively) were measured on line. The echocardiographic images and Doppler signals were registered on super VHS videotape for off-line analysis and archiving. After the GEA graft was visualized, and baseline studies were performed, an intravenous infusion of adenosine was given at a rate of 140 ␮g 䡠 kg⫺1 䡠 min⫺1 during 4 minutes. It has been documented previously that maximum myocardial hyperemia can be obtained in this way [12]. During the adenosine infusion, the blood pressure and mean arterial pressure (MAP) was measured every minute and heart rate was monitored continuously. After steady state maximum hyperemia had been obtained, the echo-Doppler examination was performed again and Vmax and Vmean were calculated again. Coronary flow reserve of the GEA graft was calculated by the equation:

CFR ⫽

Vmean, hyperemic MAPbaseline ⫻ Vmean, baseline MAPhyperemic

The correction for changes in mean blood pressure is necessary because at maximum vasodilatation, blood flow velocity is proportional to arterial pressure, which has been documented to decrease by 10% to 15% at intravenous adenosine infusion [12].

Exercise Nuclear Scintigraphy Bicycle exercise testing was performed in 31 patients at an initial workload of 20 W, which was increased by 20 W every minute. A 12-lead electrocardiogram was recorded continuously. The test was considered positive when horizontal or downsloping ST depression of at least 0.1 mV was recorded 80 msec after the J-point by two adjacent leads. At peak exercise, 14 mCi (500 MBq) of Tc99m-Sestamibi was administered in a large anticubital vein. Exercise was maintained for 1 more minute, and single photon emission computed tomography (SPECT) imaging was performed. Transaxial slices were reconstructed by filtered backprojection. No attenuation or scatter correction was applied. Transaxial slices were reoriented to obtain oblique angle tomograms parallel to the long and short axes of the left ventricle. After 24 hours, 14 mCi (500 MBq) of Tc99m-Sestamibi was injected again, and rest images were obtained. All SPECT images were evaluated by two experienced reviewers unaware of the other study data. The scintigram was considered positive if reversible filling defects in the posterior wall were visible between the stress and resting images.

Statistical Analysis Results are expressed as mean ⫾ the standard deviation. A paired Student’s t test was used for comparison between two sets. A p value less than 0.05 was considered significant.

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Table 1. Measurements at Baseline and After Infusion of Adenosine

V mean MAP Heart rate

Baseline

Adenosine

P

48 ⫾ 20 91 ⫾ 11 75 ⫾ 11

89 ⫾ 41 85 ⫾ 11 91 ⫾ 15

⬍0.001 ⬍0.001 ⬍0.001

V mean ⫽ mean velocity of GEA graft;

MAP ⫽ mean arterial pressure.

Results Procedural Results and Hemodynamic Observations In this selected group of 40 patients, we succeeded to measure coronary flow reserve reliably in 37. In 2 patients adequate signals were obtained at resting conditions but not at hyperemia, and in 1 patient no GEA was detected at all anymore. This patient experienced severe chest pain for several hours 1 week earlier and at invasive catheterization, the GEA, which was present at the echoDoppler examinations 1 month earlier, was now occluded. No complication occurred in any of our patients due to the investigation protocol and none of these patients experienced any complaint due to the examination except a burning angina-like sensation on the chest or in the throat that occurred in 29 of them, and which is a well-known but harmless side effect of adenosine infusion [12]. This unpleasant sensation was scaled on a scale of 0 to 10 and the average scaling indicated by the patients was 3. During the adenosine infusion, mean velocity in the GEA graft significantly increased from 48 ⫾ 20 to 89 ⫾ 41 cm/sec ( p ⬍ 0.001), mean arterial blood pressure significantly decreased from 96 ⫾ 11 to 87 ⫾ 11 mmHg ( p ⬍ 0.001), and heart rate significantly increased from 74 ⫾ 11 to 87 ⫾ 15 beats/min ( p ⬍ 0.001; Table 1), which is in accordance with earlier studies [12]. Examples of the echocardiographic, Doppler, and color-Doppler images at rest and at hyperemia made in one of the patients are shown in Figure 1 and Figure 2, respectively.

Fig 1. Transcutaneous Doppler echocardiography imaging of the right gastroepiploic artery (GEA) graft at rest, before infusion of adenosine. Notice the typical collar of abnormal echo-intensive perivascular tissue around the artery (small arrows).

Fig 2. Transcutaneous Doppler echocardiography imaging of the right gastroepiploic artery (GEA) graft at hyperemia after infusion of adenosine. Notice the typical collar of abnormal echo-intensive perivascular tissue around the artery (small arrows).

Coronary Flow Reserve and Relation to Nuclear Scintigrams The values of coronary flow reserve in the individual patients are tabulated in Table 2 and ranged from 1.1 to 3.6 with an average of 2.1 ⫾ 0.7. There was no significant ( p ⫽ 0.225) difference between the mean CFR value for vessels bypassed to the right coronary artery (mean CFR 2.42) or the right posterior descending artery (mean CFR 2.03). The results of the exercise nuclear testing are also shown in Table 2. In 8 patients, the nuclear exercise test was positive, ie, compatible with reversible ischemia in the distribution area of the GEA graft. In 7 of these 8 patients, CFR was below 1.5. Average CFR in these 8 patients with a positive nuclear stress test was 1.46 ⫾ 0.28 versus 2.27 ⫾ 0.70 in those 23 patients with a negative test ( p ⬍ 0.001; Fig 3). In the group of 8 patients with positive nuclear exercise test there were no complaints of angina pectoris.

Comment The results of this study demonstrate that in selected patients it is feasible to determine CFR in the right GEA noninvasively by means of echo-Doppler echocardiography and thereby to perform a functional assessment of the graft, associating this method with nuclear stress scintigraphy, which was performed shortly before the CFR measurement. The capacity of the ITA to adapt its flow in response to increased myocardial oxygen demand after exercise test [9] or after pharmacological stimulation [13, 14] has been reported. We [15] first reported the intraoperative use of pulsed Doppler echocardiography to evaluate the patency of the GEA as a pedicled coronary artery bypass graft. Subsequently using transabdominal color Doppler echocardiography, we were able to measure the postoperative flow of the GEA graft up to 17 months after surgery [10]. Takayama and collegues [16], reported the use of an implantable ultrasonic Doppler miniprobe to evaluate the response of the GEA graft after various stimuli 2 weeks postoperatively in 10 patients. GEA graft flow

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Table 2. Results of CFR After Adenosine and Nuclear Exercise Test Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40

Age Mean Nuclear Target Coronary Sex (Years) CFR Exercise Test Artery M M M M M M M M M M M M M F M M F M M M M M M M M M M M M M M M M M M M F M F M

56 52 48 46 65 46 58 48 47 53 50 66 45 61 64 47 66 57 62 50 50 56 59 42 54 46 54 46 56 51 55 52 59 53 54 43 52 51 54 59

1.70 1.41 1.59 1.46 1.40 1.86

⫺ ⫹ ⫺ ⫹ ⫹ ⫺

1.41 3.10 2.14 3.58 1.26 2.08 2.71 2.20 1.96 2.31 2.60 3.20 1.31

⫹ ⫺ ⫺ ⫺ ⫺ ⫹

1.06 1.20 2.04 2.89 2.28 2.69 3.30 2.31 2.02 1.43 1.68 3.40 1.46 1.21 3.05

⫹ ⫺ ⫺

1.43 2.78 2.00

⫺

⫺ ⫺ ⫺

⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹ ⫺

RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RCA RDP RDP RDP RCA RCA RDP RDP RCA RDP RDP RDP RCA RCA RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP RDP

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CFR of approximately 2 discriminates patients with or without ischemia during classical diagnostic coronary angiography [17, 18]. Our results suggest that measurement of the CFR of the GEA graft using a Doppler echography is a valid technique, as already reported for the ITA [14]. Moreover, the sensitivity of thallium-201 SPECT in detecting myocardial ischemia is much higher than that of the exercise electrocardiogram [19]. In our patients, presenting with a positive thallium scintigraphy, all of them but 1 had a CFR less than 2 (only 1 patient had 2.08). This means that the sensitivity of noninvasive determination of CFR in the GEA graft compared with thallium scintigraphy has a sensitivity of 88%. On the other hand, 8 patients with a negative thallium scintigraphy also had a CFR less than 2, which means that the specificity of CFR compared with nuclear scintigraphy is approximately 75%. In our study, there were a number of patients who had a low CFR in spite of a negative thallium test. This can be explained in part by the fact that, due to a different extent of the myocardium to be supplied, baseline flow may have been high in a number of these patients. It is well known that CFR is dependent on baseline flow [20]. Because the extent of the myocardial territory supplied by the GEA may be quite variable, large in some patients and smaller in others, it is likely that baseline flow in the different GEAs may be quite different, and therefore more scatter is expected in the CFR values in vessels associated with negative thallium testing than would be the case in native coronary arteries, where the vessel size is matched by nature to the amount of tissue to be supplied. Therefore a high baseline flow may be responsible for the low values of CFR associated with negative thallium in our study. This variability also indicates a limitation of such measurement in clinical practice. Another explanation for low CFR values could be microvascular disease [20]. These data are in accordance with the relation between CFR and presence of reversible ischemia as found in earlier invasive studies comparing CFR determined by the Doppler wire and nuclear testing [20]. In our study, maximum coronary vasodilation was achieved by intra-

M ⫽ male; F ⫽ female; CFR ⫽ coronary flow reserve; RDP ⫽ right descending posterior artery; RCA ⫽ right coronary artery.

velocity increased after dobutamine infusion, during walking exercise, but no significant effect was seen after oral intake of coronary vasodilating drugs. However, they demonstrated an increase of flow velocity in 3 GEA grafts by direct infusion of 2.5 mg isosorbide dinitrate at the time of the postoperative angiography. However, the number of grafts studied in Takayama’s report is too small to draw conclusions about the adaptability of the GEA graft to increase its flow in response to an augmented oxygen demand of the myocardium. Previous studies using a Doppler guide wire demonstrated that a

Fig 3. Correlation between coronary flow reserve of the right gastroepiploic artery graft and nuclear scintigrams.

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venous infusion of adenosine at a rate of 140 ␮g 䡠 kg⫺1 䡠 min⫺1. It has been documented that such infusion of adenosine creates an steady state maximum vasodilation of the myocardial vascular bed comparable with the rate of hyperemia achieved by intracoronary papaverin injection, which is considered as the gold standard of hyperemia [21]. Our study also has some limitations. First of all, the method described is not possible to apply in all patients. The 40 patients (out of 71 patients) were selected on the basis of a good visualization of the GEA graft and good Doppler and color-Doppler signals during the first routine Doppler follow-up. Probably with increasing experience of the investigators, this group of patients will be larger. Furthermore, our results are not validated by invasive determination of CFR using a Doppler guide wire, which is presently the gold standard for evaluating CFR in conscious humans. In conclusion, despite some limitations inherent to this feasibility study, our study shows that it is possible to assess the functional status of the right GEA graft noninvasively by echo-Doppler examinations performed through the abdominal wall. Moreover, our study shows that coronary vasodilator reserve and autoregulation is maintained in myocardial distributions supplied by the GEA graft and that the values of CFR have a significant correlation with the results of noninvasive nuclear exercise testing. Therefore, noninvasive determinations of CFR by transabdominal Doppler echocardiography might be a valuable contribution to the functional assessment of GEA grafts.

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