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Background - In patients who develop in-stent restenosis, successful revascularization can be difficult to achieve using percutaneous methods. This study was designed to verify the surgical results in this setting and to evaluate the potential beneficial role of arterial bypass conduits. Methods and Results - Sixty consecutive coronary artery bypass patients with previous in-stent restenosis and 60 control cases were randomly assigned to receive an arterial conduit (either right internal thoracic or radial artery; study group) or a great saphenous vein graft (control group) on the first obtuse marginal artery to complete the surgical revascularization procedure. At a mean follow-up of 52±11 months, patients were reassessed clinically and by angiography. Freedom from clinical and instrumental evidence of ischemia recurrence was found in 19 of 60 subjects in the study group versus 45 of 60 in the control series (P=0.01). The results of the arterial grafts were excellent in both the study and control groups (right internal thoracic artery patency rate, 19 of 20 for both, and radial artery patency rate, 20 of 20 versus 19 of 20; P=0.99). Saphenous vein grafts showed lower patency rate than arterial grafts in both series and had extremely high failure rate in the study group (patency rate, 10 of 20 in the study group versus 18 of 20 in the control group; P=0.001). Use of venous graft was an independent predictor of failure in the study group, whereas hypercholesterolemia was associated with graft failure in both series. Conclusions - Venous grafts have an high incidence of failure among cases who previously developed in-stent restenosis, whereas the use of arterial conduits can improve the angiographic and clinical results. Arterial grafts should probably be the first surgical choice in this patient population. © 2005 American Heart Association, Inc.

Background: The angiographic patency of composite Y internal thoracic artery-saphenous vein grafts has not been investigated in detail. Methods: Twenty-five patients who received composite Y internal thoracic artery-saphenous vein grafts had control angiography and vasoactive challenges with serotonin, acetylcholine, and isosorbide dinitrate at a mean of 2.5 ± 1.2 years after surgery. Results: The perfect patency rate of composite Y internal thoracic artery-saphenous vein grafts was 72% (18/25). The distal portion of the internal thoracic artery was stringed in 4 patients and occluded in 2. The saphenous branch of the composite Y internal thoracic artery-saphenous vein grafts was found patent in all patients except 1. No failures were reported in the proximal tract of the intemal thoracic artery. The distal tract of the internal thoracic artery showed reduced capacity of endothelium-mediated relaxation. Conclusion: The short-term patency of composite Y internal thoracic artery-saphenous vein grafts is suboptimal and markedly influenced by distal runoff and native flow competition.

Background - No information is available on the long-term results of radial artery (RA) grafts used as coronary artery bypass conduits. Methods and Results - In this report, we describe the long-term (105±9 months) angiographic results of a series of 90 consecutive patients in whom the RA was used as a coronary artery bypass conduit directly anastomosed to the ascending aorta. The long-term patency and perfect patency rates of the RA were 91.6% and 88%, respectively, versus 97.5% and 96.3% for internal thoracic artery grafts. The severity of stenosis of the target vessel clearly influenced long-term RA patency, whereas location of the target vessel and long-term use of calcium channel blockers did not influence angiographic results. Preserved endothelial function and absence of flow-limiting, fibrous, intimal hyperplasia were also documented. Conclusions - Ten years after surgery, RA grafts have excellent patency and perfect patency rates. Appropriate surgical technique and correct indication are the key factors for long-term RA patency.

Background and objective: The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery. Methods: In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels. Results: PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively (P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1. Conclusions: Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations. © 2004 Kluwer Academic Publishers.

Background: No data are available on the early vasoreactive profile of skeletonized internal thoracic artery grafts. Methods: Fifteen patients undergoing primary isolated coronary artery bypass grafting were randomly assigned to receive a skeletonized or pedicled internal thoracic artery graft. On the second postoperative day all patients were subjected to follow-up angiography and endovascular infusion of serotonin, acetylcholine, and isosorbide dinitrate. Results: Internal thoracic artery grafts were widely patent in all cases. Mean diameters of the internal thoracic artery were 1.95 ± 0.17 mm in the pedicled group and 2.26 ± 0.40 mm in the skeletonized group. After serotonin challenge, mean internal thoracic artery diameters were reduced to 1.44 ± 0.34 mm and 1.64 ± 0.14 mm, respectively; acetylcholine challenge lead to a moderate degree of vasoconstriction (1.55 ± 0.59 mm in the pedicled group and 1.84 ± 0.15 mm in the skeletonized group). No statistically significant difference was evident between the two groups at any step. Conclusion: Skeletonization does not affect the early vasoreactive profile of internal thoracic artery grafts used for surgical myocardial revascularization.

Background: Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date. Methods and Results: The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P < .0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 ± 0.34, 0.99 ± 0.44, and 10.1 ± 7.8 mg/dL versus 0.18 ± 0.14, 0.15 ± 0.48, and 2.6 ± 4.1 mg/dL for GG versus non-GG carriers (P < .0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 ± 0.8 and 2.8 ± 0.3 versus 2.1 ± 0.5 and 1.3 ± 0.1, respectively (P < .0001). The mean duration of mechanical ventilation was 22.5 ± 2.1 versus 12.7 ± 6.7 hours (P < .01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. Conclusion: The interleukin 6 - 174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

Background: Despite its common acceptance in clinical practice, the effective benefits of normothermic systemic perfusion during coronary artery bypass operations are far from established. Methods: A total of 113 patients undergoing primary isolated coronary artery bypass were randomly assigned to normothermic (37°C) or hypothermic (26°C) systemic perfusion. The clinical course of the patients was prospectively recorded, and several inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin 6, plasminogen activator inhibitor 1, prothrombin time, activated partial thromboplastin time, platelets, and white blood cell counts) were determined before surgical intervention; 24, 48, and 72 hours thereafter; and at hospital discharge. Results: Postoperatively, 2 in-hospital deaths occurred in the normothermic series and none in the hypothermic series. Four patients had a myocardial infarction, 1 had respiratory insufficiency, 1 had to be reoperated on for graft malfunction, and none had renal insufficiency in the hypothermic group versus 1 patient with each of these complications in the normothermic series. Mean blood loss in the first 24 hours was 766 ± 223 mL in the normothermic group and 740 ± 220 mL in the hypothermic group. None of these differences was statistically significant. Similarly, no significant difference in the postoperative level of any of the measured variables at any time point was evident between the patients in the normothermic and hypothermic groups. Conclusion: Normothermic systemic perfusion does not influence the clinical course or the extent of inflammatory and hemostatic activation in patients undergoing primary isolated coronary artery bypass.

Background. This study was conceived to explore the correspondence between scintigraphic imaging of the sympathetic innervation of human postischemic left ventricular aneurysms and direct immunohistochemical localization of the nerve fibers in the same area. Methods and Results. In 7 patients undergoing left ventricular aneurysmectomy for postischemic ventricular aneurysm, the findings of thallium 201 and metaiodobenzylguanidine myocardial scintigraphy were compared with direct immunohistochemical localization of the nerve fibers in the same area. This comparison showed good correspondence between scintigraphic and immunohistochemical data, although scintigraphy failed to detect areas of minimal sympathetic innervation. Moreover, microscopic analysis showed sympathetic nerve fibers with peculiar morphology and distribution in the aneurysmal zone. Conclusions. There is a good correspondence between immunohistochemical and scintigraphic imaging in the detection of sympathetic cardiac nerves in human left ventricular aneurysms; a morphologically abnormal sympathetic reinnervation can be found in the aneurysmal area (although denervation can persist in some zones).

Background. The aim of this study was to determine the course of the main inflammatory and fibrinolytic markers in patients undergoing primary elective coronary artery bypass graft with extracorporeal circulation. Methods. One hundred and thirteen patients (105 males, 8 females) undergoing primary isolated coronary artery bypass with normo- (37°C) or hypothermic (26°C) systemic perfusion were prospectively studied. The clinical course of the patients was recorded and inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin-6, plasminogen activator inhibitor-1, prothrombin time, activated partial thromboplastin time, platelets and white blood cell counts) were determined before surgery, 24, 48 and 72 hours thereafter, and at hospital discharge. Results. Two patients died (mortality 1.7%) and 6 had a major complication (event free survival > 94%). Interleukin-6, lymphocyte, neutrophil and monocyte levels increased after surgery but returned to normal at hospital discharge. C-reactive protein levels increased after 24 hours and remained high at hospital discharge. Plasminogen activator inhibitor-1, prothrombin time, and activated partial thromboplastin time increased from few hours postoperatively and returned to normal before discharge. Platelets decreased immediately after surgery and normalized only at hospital discharge. Fibrinogen decreased in the first 24 postoperative hours, raised later and remained elevated at hospital discharge. Conclusions. Cardiopulmonary bypass activates inflammatory response and hemostatic/fibrinolytic balance in patients undergoing primary isolated coronary artery bypass.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels - measured daily up to 72 hours before surgery, after surgery, and at discharge - showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 ± 3.4 vs 1.4 ± 0.9 days, p = 0.02) and in the hospital (6.7 ± 4.0 vs 5.3 ± 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization. © 2001 by Excerpta Medica, Inc.

Background: The purpose of this study was to elucidate the midterm endothelium-dependent vasodilatory capacity of radial artery grafts anastomosed to the aorta, as well as their morphometric evolution with the time. Methods: Five years after surgery we evaluated the response of aorta-anastomosed radial artery grafts to the endovascular infusion of acetylcholine in 11 of the first 61 patients operated on at our institution, and we compared it to the response with that of internal thoracic artery grafts. Moreover, the first 20 patients who had a perfect radial artery graft on angiography at 1 year were restudied at 5 years and subjected to a comparative analysis of the diameters of the radial artery graft and the grafted coronary arteries. Results: At midterm angiography, dilation of the 2 types of grafts was similar in response to acetylcholine administration (radial artery, from 2.61 ± 0.39 to 2.90 ± 0.34 mm; internal thoracic artery, from 2.68 ± 0.21 to 2.93 ± 0.27 mm; P = .01 for both). The diameters of aorta-anastomosed radial artery grafts and grafted coronary arteries increased between both 1 and 5 years according to angiographic studies (radial artery grafts, from 2.08 ± 0.45 to 2.54 ± 0.53 mm; grafted coronary arteries, from 1.92 ± 0.47 to 2.18 ± 0.41 mm; P < .001 for both), but the increase was greater for the radial artery grafts (P < .001). Conclusions: Aorta-anastomosed radial artery grafts maintain an appreciable capacity for endothelium-dependent vasodilatation 5 years after implantation and undergo a progressive increase in luminal diameter with time. These observations contradict the presumed tendency for progressive fibrous intimal hyperplasia to develop in radial artery grafts.

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Objective: To evaluate the midterm angiographic results of the use of radial artery grafts for myocardial revascularization. Methods: The first 68 consecutive surviving patients who received a radial artery graft proximally anastomosed to the aorta at our institution were studied again at 5 years (mean 59 ± 6.5 months) of follow-up; 48 of these patients had previously undergone an early angiographic examination. The response of the radial artery to the endovascular infusion of serotonin was evaluated 1 and 5 years after the operation, and the midterm status of the radial artery graft was correlated with the degree of preoperative stenosis of the target vessel and with calcium-channel blocker therapy. Results: The patency and perfect patency rates of the radial artery grafts 5 years after the operation were 91.9% and 87.0%, respectively. All radial artery grafts that were patent early after the operation remained patent at midterm follow-up, and early parietal irregularities in 7 patients were seen to have disappeared after 5 years. The early propensity toward graft spasm after serotonin challenge was markedly decreased at midterm follow-up. The continued use of calcium- channel antagonists after the first postoperative year did not influence the radial artery graft status, whereas the preoperative severity of the target- vessel stenosis markedly influenced the angiographic results. Conclusions: The midterm angiographic results of radial artery grafts used for myocardial revascularization are excellent. The correct surgical indication is essential. Continued therapy with calcium-channel antagonists after the first year does not influence the midterm angiographic results.

Objective: To evaluate the flow reserve and adequacy to meet myocardial requests in stress conditions of mammary artery-left anterior descending (IMA-LAD) grafts using a non-invasive method. Methods: Patients (20) with angiographic evidence of normofunctioning left IMA-LAD grafts were submitted to dypiridamole Tl201 myocardial scintigraphy and concomitant transthoracic echo-doppler evaluation of the IMA flow at a mean interval of 32.5 months after surgery. Results: Under basal conditions, the mean peak and end flow velocities in systole were 0.39 and 0.06 m/s, respectively In diastole, the mean peak and end flow velocities were 0.27 and 0.02 m/s and mean tele-diastolic flow velocity was 0.14 m/s, with a mean systolic/diastolic ratio of 1.51. After dypiridamole infusion, mean systolic velocities were 0.47 (peak) and 0.23 (end) m/s, respectively +20 and +283%, whereas mean diastolic velocities were 0.56 (peak) and 0.06 (end) m/s, +107 and +200%, respectively. Mean tele-diastolic flow velocity increased to 0.32 m/s (+ 128%) and the systolic-diastolic index changed to 0.85. In all cases no significant scintigraphic evidence of induced ischemia was demonstrated in the LAD region. Conclusions: Transthoracic echo-doppler evaluation combined with Tl201 myocardial scintigraphy is a useful tool for the assessment of IMA flow reserve and adequacy to stress conditions. In the late postoperative period, the IMA shows the possibility of increasing the flow velocity, almost 2-fold; the increase in flow is prevalently diastolic and leads to a complete reversal of the physiological systolic/diastolic flow ratio. The flow reserve of IMA is always able to meet the augmented myocardial oxygen demand after dypiridamole infusion.

Background. The hemodynamic significance of patent mammary graft side branches is still controversial. This study was designed to evaluate the potential for flow steal of patent mammary side branches in different hemodynamic conditions. Methods. Echo-Doppler measurement of mammary graft flow was performed at rest and after dipyridamole-induced coronary vasodilatation in 10 patients with angiographic demonstration of evident mammary graft side branches (study group) and in 10 matched control patients (control group). Concomitant thallium-201 myocardial scintigraphy was performed to assess the adequacy of mammary flow to the myocardial oxygen demand. Patients of the study group were also submitted to flow evaluation in condition of selective muscular or combined systemic and coronary relaxation. Results. No difference in mammary flow and adequacy to myocardial oxygen demand was detected between patients of the study and control groups both at rest and after dipyridamole infusion. In patients with patent side branches the systolic-to-diastolic flow ratio was maintained in case of combined coronary and peripheral vasodilatation, whereas selective muscular relaxation led to an increase in the systolic and a reduction in the diastolic flow. Conclusions. Flow steal from patent mammary graft side branches is possible only in case of selective muscular vasodilatation. As this situation is unlikely to occur in the clinical setting, the potential for flow steal of mammary side branches in cardiac surgery patients seems to be minimal.

Background. Here we report our experience with the incidence and the surgical treatment of the internal mammary artery (IMA) malperfusion syndrome, evaluate the predictive role of previously described risk factors for the syndrome, and assess the late patency of IMA grafts in patients in whom an IMA malperfusion syndrome was diagnosed and treated by additional saphenous vein grafting of the left anterior descending coronary artery. Methods. From June 1992 to November 1995, 969 IMAs were anastomosed to the left anterior descending coronary artery system. In 11 patients, IMA malperfusion syndrome was diagnosed and treated by additional saphenous vein grafting of the LAD. There were 8 men and 3 women with a mean age of 58.9 years. The angiographic and clinical data for each patient were reviewed, and all but 1 surviving patient underwent late angiographic control (mean follow- up, 18 months; range, 4 to 46 months). Results. One patient died in the hospital. No previously described risk factor was strongly associated with the occurrence of IMA malperfusion syndrome. Late angiography revealed a malfunctioning IMA graft in 7 of the 9 patients. A string sign was observed in 1 patient and a normally functioning IMA anastomosed to a diagonal branch not connected to the LAD, in another. In no patient was a widely patent and normally functioning IMA graft observed. Conclusions. In our series, a high proportion of IMA grafts were found to be malfunctioning at late angiography. This observation, in contrast to previous reports, suggests that IMA malperfusion syndrome can often be attributable to technical problems in harvesting the IMA or in performing the IMA anastomosis. Functional IMA insufficiency seems to play only a marginal role in determining the IMA malperfusion syndrome.

Objectives. We sought to investigate the effects of revascularization on the contractile reserve of dysfunctional myocardium. Background. The improvement in dysfunctional but viable myocardium after revascularization is frequently less than expected from the amount of contractile reserve detected on dobutamine stress echocardiography. The fate of the contractile reserve, when it does not result in an adequate contractile recovery, is unknown. Methods. Basal contraction and contractile reserve of infarct zones were assessed by dobutamine stress echocardiography in 21 postinfarction male patients before and >3 months after revascularization (30 infarct zones; mean ± SD left ventricular ejection fraction 35 ± 8%). An infarct zone wall motion score index (WMSI) was calculated. Results. Before revascularization, contractile reserve was present in 14 infarct zones (12 patients) and absent in 16 (9 patients). After revascularization, ejection fraction increased by 5 ± 4% (p < 0.01) in patients classified as positive for contractile reserve and remained unchanged in those classified as negative. New York Heart Association classification improved in 58.3% and 22.2% of patients, respectively. Basal contraction improved in eight zones with previous contractile reserve (57.1%) and in one zone without (6.3%) (p < 0.01). Contractile reserve was still evident in 13 zones with previous contractile reserve (93%; 8 with contractile recovery), and it developed in 6 zones without (38%; none with contractile recovery). WMSI values after revascularization were decreased from values before revascularization during low dose dobutamine in zones with and without previous contractile reserve (p < 0.01 and < 0.05, respectively). Conclusions. After revascularization, contractile reserve is maintained or even increases in viable infarct zones that do not recover as expected. It may also develop in some infarct zones judged not to be viable before revascularization. This increased