1992, The British Journal of Radiology, 65, 1086-1092
Myocardial damage following coronary bypass surgery: assessment with antimyosin antibody uptake By A. Jimenez-Heffernan, MD, J. M. Latre, MD, *M. Concha, MD, M. Torres, MD, M. Martinez-Paredes, MD, J. M. Llamas-Elvira, MD, F. M. Gonzalez, MD, A. Valverde, MD and A. Mateo, MD Nuclear Medicine and 'Cardiovascular Surgery Services, Hospital Reina Sofia, Cordoba, Spain {Received 14 January 1992 and in final form 8 July 1992, accepted 10 August 1992) Keywords: Antimyosin antibody uptake, Myocardial damage, Coronary bypass surgery
Abstract. To assess the role of '"In antimyosin antibody (AbAm) in the delineation of myocardial damage following coronary bypass surgery, we studied 51 consecutive patients who underwent coronary surgery, 27 of whom had a history of prior myocardial infarction. All patients underwent a diagnostic protocol comprising: (1) "Tc m pyrophosphate (PYP) and AbAm injection 48 h after surgery (AbAm imaging 24 and 48 h post-injection) (myocardial/background and myocardial/lung ratios were obtained respectively from the computer image); (2) Radioimmunoassay (RIA) serum CK-B levels from samples obtained immediately before surgery, and 24 and 48 h later; (3) clinical and ECG follow-up. Twenty-five patients showed positive AbAm studies, 10 had positive PYP images, and 21 had CK-B levels above normal limits at 24 h. One patient with abnormal AbAm, PYP and CK-B studies had new Q waves on the ECG after surgery. This patient was considered to have sustained a peri-operative myocardial infarction. The large number of positive AbAm studies probably reflects myocardial damage frequently associated with coronary bypass surgery.
Antimyosin antibody (AbAm) imaging has been gaining popularity due to its specificity for myocardial necrosis (Khaw et al, 1986, 1987a,b). Myocyte necrosis associated with acute myocardial infarction (Antunes et al, 1989), acute myocarditis (Yasuda et al, 1987) and heart transplant rejection (Carrio et al, 1988; Latre et al, 1992) have been successfully delineated by AbAm uptake. Loss of sarcolemmal integrity permits exposure of intracellular myosin to circulating fab fragments of antibody (Khaw et al, 1979) with subsequent antigen-antibody reaction and binding. Coronary bypass surgery is widely used as treatment for coronary disease in a number of situations. A serious complication of bypass surgery is peri-operative myocardial infarction (PMI), frequently subendocardial and small (Roberts, 1983), which may represent the end of a spectrum beginning with minimal myocardial damage due to non-specific surgical trauma, with various intermediate degrees of severity. PMIs may occur at the time of anaesthesia induction, during cardiopulmonary bypass or post-operatively (Schaff et al, 1984). Several factors may play a role in the development of perioperative damage, including reperfusion injury of previously ischaemic myocardium (Miyazaki et al, 1987) following a period of operative non-perfusion (Bulkley & Hutchins, 1977). Our purpose was to assess the role of AbAm scintigraphy in the delineation of myocardial damage in patients following coronary bypass surgery, comparing Address correspondence to: Amelia Jimenez-Heffernan, MD, Apartado de Correos n 3041, 14004 Cordoba, Spain. 1086
it with "Tc m pyrophosphate (PYP), and serum CK-B radioimmunoassay (RIA) measurements. Patients and methods
Fifty-one consecutive patients who underwent aortocoronary bypass surgery were studied in a prospective protocol comprising the following procedures: "Tc m PYP and '"In AbAm injection on the same day, 48 h after surgery, obtaining PYP images 3-4 h after injection and AbAm images 24 and 48 h later (AbAm injection immediately following PYP scintigraphy). CK-B serum levels were measured from samples obtained immediately before, 24 h and 48 h after surgery. All patients were followed up clinically and electrocardiographically. The protocol was approved by the hospital's research committee and patients provided informed consent in all cases. The effective dose equivalent from both radionuclide procedures was estimated to be 10.5 mSv. Twenty-four patients had no history of myocardial infarction (MI) but 27 did, nine of whom received thrombolytic therapy. The age of the infarct ranged from 10 days to 2.7 years (Table I). Patients underwent bypass surgery because of unstable angina in 19 cases and stable angina in 25; seven patients were asymptomatic early affter i.v. thrombolysis for acute myocardial infarction (and underwent surgery within a protocol of early surgical revascularization after thrombolysis). Localization of necrosis was assessed by electrocardiography, with additional data obtained from the preoperative coronary angiography, and from PYP scintigraphy in four cases. Forty-eight patients had signifiThe British Journal of Radiology, December 1992
Antimyosin assessment of myocardial damage in coronary bypass surgery
lar ROIs on the anterior view image. The cut-off level used for M/L uptake ratio was 1.86, and was obtained Age of MI No. of patients Thrombolysis from the mean value plus 2 SDs (1.62 + 0.12) of a control group of 18 heart transplant patients with no 1 10 days biopsy evidence of rejection and normal resting left 7 21-30 days ventricular function as assessed by MUGA ventriculo6 1.5-3 months graphy (Latre et al, 1992). Only patients with elevated 2 4-6 months M/L ratios at 24 and 48 h were considered to have a 11 > 2 years positive antimyosin study. The estimated effective dose Total 27 equivalent from AbAm imaging is 8.1 mSv. CK-B measurements were performed by RIA (NMS cant disease of the left anterior descending artery. The Pharmaceuticals). Venous blood samples were obtained number of diseased vessels and the coronary arteries immediately before surgery and at 24 and 48 h after the bypassed are shown in Tables II and III. The coronary operation. The normal upper limit of serum CK-B was arteries were grafted with saphenous vein in 30 patients, set at 12.5 ng/ml as recommended by the manufacturer. Quantitative and visual analysis of imaging prowith internal mammary artery in four patients, and with cedures was carried out by two independent experienced both in 17 patients. An average of 2.7 vessels were grafted. The mean cardiopulmonary bypass time was observers. Quantitative results were expressed in terms of 107 ±35.9 min; the mean aortic cross-clamp time was 48 ±19.6 min. Cardiopulmonary bypass was prolonged mean±SD. Kolmogorov-Smirnov's test was used to verify that numerical parameters followed a normal in two patients because of bleeding. distribution. Student's /-test and one-factor variance analysis, followed by Newman Keul's test, were used to Protocol 99Tcm p Y p scanning was performed with 700 MBq compare the means of quantitative parameters in injected intravenously. Four-view planar images were different situations. The relations between quantitative obtained 3-4 h after injection and registered on a parameters were assessed obtaining Pearson's correla256 x 256 resolution computer matrix (450 Kcts/view). tion coefficient and qualitative parameters were assessed The ratio of myocardial to background (M/B) uptake by the chi-squared test. was obtained from an irregular region of interest (ROI) over the myocardial area, in counts per pixel, from the anterior view. A computer-generated mirror image in Results the right hemithorax was used as the background Twenty-five patients presented positive AbAm uptake region. The upper normal limit for M/B ratio was set at (M/L > 1.86) at 24 and 48 h post-injection, with means 1.21. This limit was obtained from the mean plus 2 of 2.09 ±0.1 and 2.10 ±0.1 respectively; their M/L ratios standard deviations (SDs) (0.99 + 0.11) of a control ranged from 1.91 to 2.43 at 24 h and from 1.87 to 2.43 group of 17 patients with non-coronary chest pain who at 48 h. Myocardial uptake was diffuse (Fig. 1) in 17 underwent PYP scanning as part of a protocol for the cases and segmental in seven (Fig. 2), with three patients differential diagnosis of thoracic pain, and who were showing uptake in more than one myocardial segment. found to have oesophageal (11 patients) or thoracic soft Table IV summarizes these results and shows myotissue (6 patients) lesions. PYP images were negative in cardial localization of uptake. Figure 3 represents a all cases. The estimated effective dose equivalent from negative antimyosin image in a patient with 24 and 48 h PYP imaging is 2.4 mSv. M/L ratios of 1.69 and 1.67 respectively. Ten patients had positive PYP M/B uptake ratios Following the PYP scintigraphy, a 70 MBq dose of 11 'In-labelled AbAm (MYOSCINT, Centocor) was ( > 1.21), with a mean of 1.33 + 0.1 (range 1.25-1.73). injected intravenously. Four-view planar images Table IV shows the myocardial segments involved. (450 Kcts/view) were obtained 24 and 48 h after injec- Seven of these patients had positive antimyosin M/L tion and registered on a 256 x 256 computer matrix. ratios. Serum CK-B levels were elevated ( > 12.5 ng/ml) in Myocardial/lung (M/L) activity ratios, in counts per pixel, were calculated from myocardial and lung irregu- 21 patients at 24 h (mean 22.6 ±11.2 ng/ml), and the Table I. Patients with prior myocardial infarction (MI).
Table II. Patients: number of significantly diseased and bypassed vessels No. of vessels
Artery
No. of patients
Left anterior descending Right coronary Circumflex Obtuse marginal Posterolateral left ventricular branch First diagonal
48 28 17 16 11 11
No. of patients 7 19 12 12 1
Vol. 65, No. 780
Table III. Coronary arteries bypassed
1087
A. Jimenez-Heffernan et al
Figure 1. Diffuse myocardial uptake of '"In antimyosin antibody 48 h after injection. This patient had M/L AbAm ratios of 2.29 and 2.39 at 24 and 48 h post-injection, respectively.
elevation persisted at 48 h in six of these patients (mean 17 + 3.9 ng/ml). Baseline measurements were negative in all patients. Figure 4 shows the distribution of CK-B levels in all patients. Five of the seven patients with positive AbAm and PYP studies had elevated CK-B serum levels at 24 h. Positive CK-B levels at 24 h were found in 11/25 (44%) patients with a positive AbAm study and in 6/10 (60%) patients with a positive PYP study.
Figure 3. Negative antimyosin image in a patient with M/L ratios of 1.69 and 1.67 at 24 and 48 h respectively. Note prominent non-specific hepatic activity and some degree of bone marrow uptake.
No good correlation was found between PYP M/B and AbAm M/L ratios. There was some correlation, although low, between AbAm M/L ratios at 24 and 48 h
•
fxOOOl
A
p
Myocardial damage following coronary bypass surgery: assessment with antimyosin antibody uptake By A. Jimenez-Heffernan, MD, J. M. Latre, MD, *M. Concha, MD, M. Torres, MD, M. Martinez-Paredes, MD, J. M. Llamas-Elvira, MD, F. M. Gonzalez, MD, A. Valverde, MD and A. Mateo, MD Nuclear Medicine and 'Cardiovascular Surgery Services, Hospital Reina Sofia, Cordoba, Spain {Received 14 January 1992 and in final form 8 July 1992, accepted 10 August 1992) Keywords: Antimyosin antibody uptake, Myocardial damage, Coronary bypass surgery
Abstract. To assess the role of '"In antimyosin antibody (AbAm) in the delineation of myocardial damage following coronary bypass surgery, we studied 51 consecutive patients who underwent coronary surgery, 27 of whom had a history of prior myocardial infarction. All patients underwent a diagnostic protocol comprising: (1) "Tc m pyrophosphate (PYP) and AbAm injection 48 h after surgery (AbAm imaging 24 and 48 h post-injection) (myocardial/background and myocardial/lung ratios were obtained respectively from the computer image); (2) Radioimmunoassay (RIA) serum CK-B levels from samples obtained immediately before surgery, and 24 and 48 h later; (3) clinical and ECG follow-up. Twenty-five patients showed positive AbAm studies, 10 had positive PYP images, and 21 had CK-B levels above normal limits at 24 h. One patient with abnormal AbAm, PYP and CK-B studies had new Q waves on the ECG after surgery. This patient was considered to have sustained a peri-operative myocardial infarction. The large number of positive AbAm studies probably reflects myocardial damage frequently associated with coronary bypass surgery.
Antimyosin antibody (AbAm) imaging has been gaining popularity due to its specificity for myocardial necrosis (Khaw et al, 1986, 1987a,b). Myocyte necrosis associated with acute myocardial infarction (Antunes et al, 1989), acute myocarditis (Yasuda et al, 1987) and heart transplant rejection (Carrio et al, 1988; Latre et al, 1992) have been successfully delineated by AbAm uptake. Loss of sarcolemmal integrity permits exposure of intracellular myosin to circulating fab fragments of antibody (Khaw et al, 1979) with subsequent antigen-antibody reaction and binding. Coronary bypass surgery is widely used as treatment for coronary disease in a number of situations. A serious complication of bypass surgery is peri-operative myocardial infarction (PMI), frequently subendocardial and small (Roberts, 1983), which may represent the end of a spectrum beginning with minimal myocardial damage due to non-specific surgical trauma, with various intermediate degrees of severity. PMIs may occur at the time of anaesthesia induction, during cardiopulmonary bypass or post-operatively (Schaff et al, 1984). Several factors may play a role in the development of perioperative damage, including reperfusion injury of previously ischaemic myocardium (Miyazaki et al, 1987) following a period of operative non-perfusion (Bulkley & Hutchins, 1977). Our purpose was to assess the role of AbAm scintigraphy in the delineation of myocardial damage in patients following coronary bypass surgery, comparing Address correspondence to: Amelia Jimenez-Heffernan, MD, Apartado de Correos n 3041, 14004 Cordoba, Spain. 1086
it with "Tc m pyrophosphate (PYP), and serum CK-B radioimmunoassay (RIA) measurements. Patients and methods
Fifty-one consecutive patients who underwent aortocoronary bypass surgery were studied in a prospective protocol comprising the following procedures: "Tc m PYP and '"In AbAm injection on the same day, 48 h after surgery, obtaining PYP images 3-4 h after injection and AbAm images 24 and 48 h later (AbAm injection immediately following PYP scintigraphy). CK-B serum levels were measured from samples obtained immediately before, 24 h and 48 h after surgery. All patients were followed up clinically and electrocardiographically. The protocol was approved by the hospital's research committee and patients provided informed consent in all cases. The effective dose equivalent from both radionuclide procedures was estimated to be 10.5 mSv. Twenty-four patients had no history of myocardial infarction (MI) but 27 did, nine of whom received thrombolytic therapy. The age of the infarct ranged from 10 days to 2.7 years (Table I). Patients underwent bypass surgery because of unstable angina in 19 cases and stable angina in 25; seven patients were asymptomatic early affter i.v. thrombolysis for acute myocardial infarction (and underwent surgery within a protocol of early surgical revascularization after thrombolysis). Localization of necrosis was assessed by electrocardiography, with additional data obtained from the preoperative coronary angiography, and from PYP scintigraphy in four cases. Forty-eight patients had signifiThe British Journal of Radiology, December 1992
Antimyosin assessment of myocardial damage in coronary bypass surgery
lar ROIs on the anterior view image. The cut-off level used for M/L uptake ratio was 1.86, and was obtained Age of MI No. of patients Thrombolysis from the mean value plus 2 SDs (1.62 + 0.12) of a control group of 18 heart transplant patients with no 1 10 days biopsy evidence of rejection and normal resting left 7 21-30 days ventricular function as assessed by MUGA ventriculo6 1.5-3 months graphy (Latre et al, 1992). Only patients with elevated 2 4-6 months M/L ratios at 24 and 48 h were considered to have a 11 > 2 years positive antimyosin study. The estimated effective dose Total 27 equivalent from AbAm imaging is 8.1 mSv. CK-B measurements were performed by RIA (NMS cant disease of the left anterior descending artery. The Pharmaceuticals). Venous blood samples were obtained number of diseased vessels and the coronary arteries immediately before surgery and at 24 and 48 h after the bypassed are shown in Tables II and III. The coronary operation. The normal upper limit of serum CK-B was arteries were grafted with saphenous vein in 30 patients, set at 12.5 ng/ml as recommended by the manufacturer. Quantitative and visual analysis of imaging prowith internal mammary artery in four patients, and with cedures was carried out by two independent experienced both in 17 patients. An average of 2.7 vessels were grafted. The mean cardiopulmonary bypass time was observers. Quantitative results were expressed in terms of 107 ±35.9 min; the mean aortic cross-clamp time was 48 ±19.6 min. Cardiopulmonary bypass was prolonged mean±SD. Kolmogorov-Smirnov's test was used to verify that numerical parameters followed a normal in two patients because of bleeding. distribution. Student's /-test and one-factor variance analysis, followed by Newman Keul's test, were used to Protocol 99Tcm p Y p scanning was performed with 700 MBq compare the means of quantitative parameters in injected intravenously. Four-view planar images were different situations. The relations between quantitative obtained 3-4 h after injection and registered on a parameters were assessed obtaining Pearson's correla256 x 256 resolution computer matrix (450 Kcts/view). tion coefficient and qualitative parameters were assessed The ratio of myocardial to background (M/B) uptake by the chi-squared test. was obtained from an irregular region of interest (ROI) over the myocardial area, in counts per pixel, from the anterior view. A computer-generated mirror image in Results the right hemithorax was used as the background Twenty-five patients presented positive AbAm uptake region. The upper normal limit for M/B ratio was set at (M/L > 1.86) at 24 and 48 h post-injection, with means 1.21. This limit was obtained from the mean plus 2 of 2.09 ±0.1 and 2.10 ±0.1 respectively; their M/L ratios standard deviations (SDs) (0.99 + 0.11) of a control ranged from 1.91 to 2.43 at 24 h and from 1.87 to 2.43 group of 17 patients with non-coronary chest pain who at 48 h. Myocardial uptake was diffuse (Fig. 1) in 17 underwent PYP scanning as part of a protocol for the cases and segmental in seven (Fig. 2), with three patients differential diagnosis of thoracic pain, and who were showing uptake in more than one myocardial segment. found to have oesophageal (11 patients) or thoracic soft Table IV summarizes these results and shows myotissue (6 patients) lesions. PYP images were negative in cardial localization of uptake. Figure 3 represents a all cases. The estimated effective dose equivalent from negative antimyosin image in a patient with 24 and 48 h PYP imaging is 2.4 mSv. M/L ratios of 1.69 and 1.67 respectively. Ten patients had positive PYP M/B uptake ratios Following the PYP scintigraphy, a 70 MBq dose of 11 'In-labelled AbAm (MYOSCINT, Centocor) was ( > 1.21), with a mean of 1.33 + 0.1 (range 1.25-1.73). injected intravenously. Four-view planar images Table IV shows the myocardial segments involved. (450 Kcts/view) were obtained 24 and 48 h after injec- Seven of these patients had positive antimyosin M/L tion and registered on a 256 x 256 computer matrix. ratios. Serum CK-B levels were elevated ( > 12.5 ng/ml) in Myocardial/lung (M/L) activity ratios, in counts per pixel, were calculated from myocardial and lung irregu- 21 patients at 24 h (mean 22.6 ±11.2 ng/ml), and the Table I. Patients with prior myocardial infarction (MI).
Table II. Patients: number of significantly diseased and bypassed vessels No. of vessels
Artery
No. of patients
Left anterior descending Right coronary Circumflex Obtuse marginal Posterolateral left ventricular branch First diagonal
48 28 17 16 11 11
No. of patients 7 19 12 12 1
Vol. 65, No. 780
Table III. Coronary arteries bypassed
1087
A. Jimenez-Heffernan et al
Figure 1. Diffuse myocardial uptake of '"In antimyosin antibody 48 h after injection. This patient had M/L AbAm ratios of 2.29 and 2.39 at 24 and 48 h post-injection, respectively.
elevation persisted at 48 h in six of these patients (mean 17 + 3.9 ng/ml). Baseline measurements were negative in all patients. Figure 4 shows the distribution of CK-B levels in all patients. Five of the seven patients with positive AbAm and PYP studies had elevated CK-B serum levels at 24 h. Positive CK-B levels at 24 h were found in 11/25 (44%) patients with a positive AbAm study and in 6/10 (60%) patients with a positive PYP study.
Figure 3. Negative antimyosin image in a patient with M/L ratios of 1.69 and 1.67 at 24 and 48 h respectively. Note prominent non-specific hepatic activity and some degree of bone marrow uptake.
No good correlation was found between PYP M/B and AbAm M/L ratios. There was some correlation, although low, between AbAm M/L ratios at 24 and 48 h
•
fxOOOl
A
p
