Effect of compliance mismatch on vascular graft patency

The hypothesis that a mismatch in compliance between a vascular graft and its host artery is detrimental to graft patency was tested by implanting paired arterial autografts, prepared with differential glutaraldehyde fixation of carotid arteries in the femoral arteries of dogs. These grafts differed only in circumferential compliance: they were 100% (compliant) vs. 40% (stiff) as compliant as the host artery. Their flow surfaces were equivalent, as determined by physicochemical measurements and scanning electron microscopy; both lacked viable cells, as determined by in vitro cell culture. In 14 dogs, eight stiff and two compliant grafts became occluded within 3 months, the latter doing so within 24 hours after their contralateral counterparts. Cumulative patencies were 85% and 37% for compliant and stiff grafts, respectively (p less than 0.05) and 100% and 43%, excluding the two dogs with bilateral graft failures (p less than 0.01). We conclude that even with near optimal flow surfaces, compliance mismatch is deleterious to graft patency.     

Decellularized native and engineered arterial scaffolds for transplantation

More than 570,000 coronary artery bypass grafts are implanted each year, creating an important demand for small-diameter vascular grafts. For patients who lack adequate internal mammary artery or saphenous vein, tissue-engineered arteries may prove useful. However, the time needed to tissue engineer arteries (7 weeks or more) is too long for many patients. Decellularized cadaveric human arteries are another possible source of vascular conduit, but limited availability and the potential for disease transmission limit their widespread use. In contrast, decellularized tissue-engineered arteries could serve as grafts for immediate implantation, as scaffolds onto which patients' cells could be seeded, or as carriers for genetically engineered cells to aid cell transplantation. The goal of this study was to quantify the effects of decellularization on vascular matrix and mechanical properties. Specifically, we compared cellular elimination, extracellular matrix retention, and mechanical characteristics of porcine carotid arteries before and after treatment with three decellularization methods. In addition, for the first time, tissue-engineered arteries were decellularized. Decellularized native arteries were also used as a scaffold onto which vascular cells were seeded. These studies identified a decellularization method for native and engineered arteries that maximized cellular elimination, without greatly compromising mechanical integrity. We showed that engineered tissues could be decellularized, and demonstrated the feasibility of reseeding decellularized vessels with vascular cells.     

Effect of coronary artery bypass grafting on native coronary artery stenosis. Comparison of internal thoracic artery and saphenous vein grafts

BACKGROUND: The purpose of this study was to investigate the influence of coronary artery bypass grafting on the degree of stenosis of the native coronary artery. METHODS: Experimental design: retrospective data analysis. Setting: University hospital. Patients: consecutive patients undergoing coronary artery bypass grafting (n=52). Bypasses using internal thoracic artery grafts (n=26) and saphenous vein grafts (n=37) to incompletely occluded coronary arteries were studied. Interventions: coronary artery bypass grafting using internal thoracic artery or saphenous vein grafts. Measures: stenosis of the native coronary artery on angiography. RESULTS: Three recipient coronary arteries bypassed with internal thoracic artery grafts (12%) and 14 recipient coronary arteries bypassed with saphenous vein grafts (38%) showed progression of narrowing (p=0.024). Two recipient coronary arteries bypassed with internal thoracic artery grafts (8%) and 13 recipient coronary arteries bypassed with saphenous vein grafts (35%) showed total occlusion (p=0.016). Hypertension, hyperlipidemia, diabetes mellitus, and smoking history did not correlate with progression of stenosis of the native coronary arteries. Graft flow measured during surgery in the saphenous vein grafts was not significantly different between the group that exhibited progression of the native stenosis and the group that did not. CONCLUSIONS: Coronary artery bypass grafting with saphenous vein grafts may result in progression of stenosis of the recipient coronary artery. This is less likely after coronary artery bypass grafting with internal thoracic artery grafts. This difference may be due to the ability of the pedicled internal thoracic artery graft to regulate flow. Thus competitive flow in the native coronary artery is minimized. This has significant clinical implications.     

Standard coronary artery bypass grafting and beating heart bypass. Indications and long-term results.

OBJECTIVES AND METHOD: We have performed 225 cases of coronary artery bypass grafting (CABG), between October 15 1995 and September 8 1999. We have evaluated the operative results of 121 cases (53.8%) of conventional CABG and 104 cases (46.2%) of minimally invasive coronary artery bypass grafting performed during this period. The average numbers of bypassed grafts was 3.45 for conventional CABG, and 1.41 for minimally invasive coronary artery bypass grafting. Sixty-seven right internal thoracic arteries, 145 left internal thoracic arteries, 71 gastroepiploic arteries, 38 radial arteries and 12 saphenous veins were used for conventional CABG, and 29 right internal thoracic arteries, 81 left internal thoracic arteries, 18 gastroepiploic arteries, 3 radial arteries, 10 saphenous veins and 2 inferior epigastric arteries were used for minimally invasive coronary artery bypass grafting. The total number of 303 grafts were anastomosed to 417 coronary arteries for conventional CABG, and 143 grafts were anastomosed to 147 coronary arteries for minimally invasive coronary artery bypass grafting. RESULTS: Although two saphenous veins were occluded, the early postoperative patency rate was 100% for conventional CABG using right internal thoracic arteries, left internal thoracic arteries, gastroepiploic arteries and radial arteries. Three site of stenosis in 18 left internal thoracic arteries and 2 in 16 right internal thoracic arteries were recognized in minimally invasive coronary artery bypass grafting without the use of stabilizers. One site of stenosis in 63 left internal thoracic arteries was recognized in minimally invasive coronary artery bypass grafting with the use of stabilizers. CONCLUSION: The use of stabilizers enables adaptation of the minimally invasive coronary artery bypass grafting procedure to a wider range of coronary artery bypass procedures, and a higher graft patency can be expected.     

Neo-intimal hyperplasia in vascular grafts and its implications for autologous arterial grafting.

With the advent of modern microsurgical procedures and an improved understanding of the cellular dynamics of vascular graft adaptation, arterial grafts are being used more frequently in surgical practice. In this article the structure and development of neointimal hyperplasia in vascular grafts, both venous and arterial, are reviewed briefly. The underlying biology of venous graft adaptation is now well understood. However, in addition to venous grafts, many different arterial conduits are now being used; these include the radial artery, internal mammary (thoracic) and gastroepiploic arteries. The different clinical outcomes of these arterial grafts and the underlying cell biology of their adaptation to the grafted environment are also reviewed.     

Skeletonization does not influence internal thoracic artery innervation

BACKGROUND: This study was designed to compare the effect of surgical harvesting on internal thoracic artery innervation and to assess the eventual presence of denervation supersensitivity in skeletonized grafts. METHODS: Nineteen patients who underwent primary isolated coronary artery bypass grafting were randomly assigned to receive a skeletonized (n = 9) or pedicled (n = 10) internal thoracic artery graft. Immunohistochemical nerve localization using anti-S-100 protein, anti-160-kd neurofilament polypeptide and anti-tyrosine hydroxylase antibodies was performed on distal specimens of arteries to study vascular innervation. Moreover, endovascular vasoactive challenges using serotonin and methylergometrine were performed at early angiographic control to evaluate the eventual presence of denervation supersensitivity. RESULTS: Quantitative analysis of immunohistochemical specimens revealed lack of difference in the number of positive cells between skeletonized and pedicled arteries for all the antibodies used. No difference in the reaction to serotonin and methylergometrine was found between skeletonized and pedicled arteries. CONCLUSIONS: Skeletonization does not influence internal thoracic artery innervation.     

Experience of coronary artery bypass grafting with internal thoracic artery]

Between March 1990 and May 1991, twenty-nine patients underwent coronary artery bypass grafting. The mean number of grafts was 2.7 +/- 0.9 grafts per patient. 28 patients (96.6% of all cases) underwent CABG with the internal thoracic arteries. The perioperative mortality was 3.4% (1/29 cases). The postoperative coronary angiography at one month revealed that the early patency of total grafts, of internal thoracic artery grafts and of saphenous vein grafts were 96.7% (58/60 grafts), 100% (29/29 grafts), 93.5% (29/31 grafts) respectively. The early patency of internal thoracic artery graft was better than of saphenous vein graft.     

Failure of internal thoracic artery grafts: conclusions from coronary angiography mid-term follow-up

BACKGROUND: The objective of this study was to identify causes of the failures of internal thoracic artery bypass grafts according to operative technique, the internal thoracic artery used, and the coronary artery grafted. METHODS: This retrospective study concerns 302 follow-up angiographies performed in patients treated with 512 internal thoracic artery bypass grafts: 115 single grafts, 78 sequential grafts, and 109 grafts with two internal thoracic arteries (61 Y grafts). Postoperative angiography was performed after a mean period of 17.3 +/- 4.1 months. RESULTS: Failures consisted of 11 (2%) occluded grafts and 19 (4%) nonfunctioning grafts (threadlike internal thoracic artery). There was no difference in patency among the various types of left anterior descending artery bypass grafts anastomosed with the left internal thoracic artery. The failure rate was higher with the right internal thoracic artery (13%) than with the left internal thoracic artery (4%; p < 0.05). The failure rate of the left anterior descending artery bypass grafts (3%) was lower than that for the branches of circumflex artery bypass grafts (13%; p < 0.05). The 19 cases of nonfunctioning grafts did not include significant anastomotic stenosis: 14 were related to competitive blood flow, 4 to a poor recipient coronary arterial bed, and 1 to significant distal coronary stenosis. CONCLUSIONS: At least two thirds of failures of bypass grafts could have been avoided by more objective analysis of the coronary stenosis on preoperative coronary angiography and better mastery of the surgical technique.     

A case of simultaneous operation of coronary artery bypass and ascending aorta to bifemoral bypass for ischemic heart disease combined with bilateral leg ischemia]

A 58-year-old man was admitted to our hospital because of angina pectoris with severe intermittent claudication. Angiography showed triple-vessel disease of the coronary artery and complete obstruction of the bilateral common iliac arteries from their origins. Both femoral arteries were patent by collateral supplies. Combined revascularization of coronary and femoral arteries was performed. Coronary arteries were bypassed with in situ left internal thoracic artery, gastroepiploic artery and saphenous vein graft. Bilateral femoral arteries were bypassed with externally supported Dacron graft from ascending aorta through the preperitoneal space. The patient recovered well and postoperative angiography revealed all bypass grafts patent.     

Pressure characteristics in arterial grafts for coronary bypass surgery

The haemodynamic properties of arterial grafts were studied by measuring the pressure waveform at the tip of the grafts in 28 patients who underwent coronary artery bypass surgery (CABG). The internal thoracic and gastroepiploic arteries were harvested as pedicles for CABG. Pressure wave of the ascending aorta and arterial grafts were simultaneously recorded with an electrocardiogram under stable haemodynamic conditions before cardiopulmonary bypass. Systolic, diastotic and mean pressures were measured, and mean systolic and diastolic pressures calculated for systolic and diastolic areas divided by time. The ascending aorta showed high sustained diastolic pressure that decreased gradually. Pressures in the internal thoracic and gastroepiploic artery grafts had narrow contours and decreased rapidly. Pressure waveforms in the internal thoracic and gastroepiploic artery grafts had a notch between the systolic and diastolic contours. There was no difference in systolic pressure between the ascending aorta and internal thoracic and gastroepiploic artery grafts. Diastolic pressures were 64(9), 55(7), and 51(6) mmHg in the ascending aorta and internal thoracic and gastroepiploic artery, respectively. Mean(s.d.) pressures were 75(9), 65(9) and 59(7) mmHg in the ascending aorta and internal thoracic and gastroepiploic artery grafts, respectively. Diastolic and mean pressures in the internal thoracic artery grafts were significantly lower than in the ascending aorta but significantly higher than in the gastroepiploic artery grafts. The mean(s.d.) calculated diastolic pressure in the internal thoracic artery grafts was significantly lower than in the ascending aorta but significantly higher than in the gastroepiploic artery grafts. The inferior capacity of flow through the arterial grafts may be mainly attributable to reduced diastolic pressure, which is caused by anatomical characteristics. Arterial grafts originating from a systolic-dominant circulation far away from the heart have a limited ability to supply blood to the diastolic-dominant coronary circulation.     

Midterm endothelial function and remodeling of radial artery grafts anastomosed to the aorta

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.     

Skeletonization of bilateral internal thoracic artery grafts lowers the risk of sternal infection in patients with diabetes

OBJECTIVE: Deep sternal wound infection is a dreaded complication of coronary artery bypass surgery, particularly in patients with diabetes. This study determines whether skeletonization of internal thoracic artery conduits compared with pedicled harvesting reduces the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting. METHODS: We reviewed prospectively gathered data on all patients who have undergone coronary artery bypass grafting and received bilateral internal thoracic artery grafts at our institution since 1990. We compared patients with diabetes who received skeletonized (n = 79) versus conventional pedicled (n = 36) internal thoracic artery conduits. RESULTS: The proportion of patients taking insulin (19.0% vs 14.0% for skeletonized vs conventional grafts, respectively, P =.6) or oral hypoglycemic agents (68.4% vs 69.4%, P =.9), as well as the prevalence of type I diabetes (2.5% vs 8.3%, P =.18), were similar in both groups. Patients who received skeletonized grafts were more likely to receive a free rather than an in situ right internal thoracic artery graft (93.7% vs 30.6%, P <.001). The prevalence of deep sternal wound infection was significantly lower in patients who received skeletonized grafts compared with patients who received conventional grafts (1.3% vs 11.1%, P =.03). Patients in the skeletonized group were also less likely to develop any (superficial or deep) sternal wound infection postoperatively (5.1% vs 22.2%, P =.03). There was no significant difference in the prevalence of deep sternal wound infection between patients with diabetes who received skeletonized internal thoracic arteries and patients without diabetes who underwent conventional internal thoracic artery grafting (n = 578) (1.2% vs 1.6%, respectively, P =.8). CONCLUSIONS: Skeletonization of internal thoracic artery conduits lowers the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting. We no longer consider diabetes a contraindication to bilateral internal thoracic artery grafting, provided the internal thoracic arteries are skeletonized.     

Coronary revascularization using only arterial grafts in patients with left main coronary artery stenosis]

Although increasing use is being made of arterial grafts (internal thoracic arteries and right gastroepiploic artery) for coronary revascularization, application to left main coronary artery (LMT) patients is frequently not possible. During the period from December 1989 to July 1991, coronary revascularization was conducted on 9 LMT patients using only arterial grafts and no venous grafts. The bypass grafts were 6 left internal thoracic artery grafts, 9 right internal thoracic artery grafts and 9 right gastroepiploic artery grafts, a total of 24 grafts and an average of 2.7 bypasses per patient. There were no operated deaths, but five patients required IABP support after cardiopulmonary bypass. They had more than 90% stenotic lesions of left main coronary artery. In contrast, four patients with less than 90% stenotic lesion were uneventful. The cause of these catastrophic hemodynamics was considered reduced blood flow by graft spasm. All patients could be functionally placed in New York Heart Association Class I or II. Postoperative stress tests were made on eight patients and the results were normal in seven. Eight patients have had postoperative angiograms. Twenty-one of 22 grafts were patent. The present results demonstrate that an arterial bypass is possible even on LMT patients by IABP support.     

Minimally invasive coronary artery bypass grafting with bilateral internal thoracic arteries: Will this be the future?

Objective

The aim was to show that total arterial revascularization via a left minithoracotomy using bilateral internal thoracic arteries was not only feasible but also a safe and reproducible procedure with excellent midterm outcomes.

Use of arterial grafts for coronary revascularization. Experience of 2987 anastomoses.

OBJECTIVES: The aim of this study was to evaluate the performance and the quality of arterial grafts for coronary artery bypass grafting at The Heart Institute of Japan, Tokyo Women's Medical University. PATIENTS AND METHODS: From January 1970 to March 1998, 2987 arterial grafts, including left and right internal thoracic arteries, gastroepiploic artery, radial artery and inferior epigastric artery, were used in 1673 patients. In the same period, 1225 saphenous vein grafts were used. Early graft patency was angiographically determined. Also, histological evaluation of operative specimens and preoperative angiographic evaluation of arterial grafts were performed. RESULTS: The total number of hospital deaths was 38 (2.3%). Of 4212 grafts, 3919 grafts (93%) were evaluated angiographically and 3714 of 3919 grafts were patent (94.8%). The patency rate of internal thoracic artery was better than that of gastroepiploic artery (p < 0.0001), radial artery (p = 0.0005) and saphenous vein grafts (p < 0.0001). However, the patency rate of gastroepiploic artery was better than that of saphenous vein grafts (p = 0.04), while no significant difference was detected between gastroepiploic artery and rdial artery. Only one internal thoracic artery specimen obtained at surgery showed atherosclerotic change, but all gastroepiploic artery specimens had moderate to severe atherosclerotic changes with CD68-positive cell infiltration. Only one patient's left internal thoracic artery out of 200 was not angiographically useable as a conduit, while multiple stenotic lesions in gastroepiploic artery were observed. CONCLUSIONS: In the graft selection for CABG, the primary choice is internal thoracic artery and the secondary choice is right internal thoracic artery, from the standpoint of histological and angiographic evaluation, gastroepiploic artery and/or radial artery, depending on the target anastomotic site, degree of stenosis, and in situ or free use is the third choice.     

The fate of the radial artery conduit in coronary artery bypass grafting surgery.

Coronary artery bypass grafting (CABG) is the standard surgical procedure for the treatment of advanced coronary artery disease. CABG surgery has been demonstrated to improve symptoms and, in specific subgroups of patients, to prolong life. Despite its success, the long-term outcome of coronary bypass surgery is strongly influenced by the fate of the vascular conduits used. Impressive long-term disease-free patency rate of the left internal thoracic artery-left anterior descending coronary artery (LITA-LAD) graft, coupled with proven long-term survival benefits, has led to its becoming a 'golden standard' of CABG. Previous long-term studies have also shown unsatisfactory patency of saphenous vein grafts used for myocardial revascularization, compared with internal thoracic artery grafts. Thus, the use of arterial conduits has expanded beyond the internal thoracic arteries (ITAs) to include the right gastroepiploic artery, the inferior epigastric artery, and the radial artery. The assumption is that although the performance of one or two arterial ITA graft is superb, more arterial grafts should perform better in the long-term follow-up. Several studies concerning the use of the radial artery bypass grafts have documented excellent clinical results and satisfactory short-term as well as mid-term patency rates at restudy angiography, supporting its continued use as a bypass conduit. However, a note of caution concerning radial artery conduit patency rate have appeared in few recent reports. Thus, in this paper, we summarize the current evidence about the radial artery as a conduit in CABG surgery, with special emphasis on the clinical results.     

Training of deep microsurgical skill: Establishment of a high-volume intracranial carotid bypass model

ObjectiveTo establish a model for a high-volume intracranial carotid bypass operation.MethodsHigh-volume internal carotid-middle cerebral artery bypass was performed on 9 cadaver heads with arteries of porcine forearms as grafts by 6 residents with no previous experience in vascular anastomosis on cadavers. The intima was dissected immediately after the anastomoses were completed to observe the patency of anastomosis.ResultsAfter different duration periods of training using this model, 36 vascular anastomoses on 18 sides were successfully performed by the 6 residents with a self-made difficulty regulation device. As the difficulty level increased, the time needed for anastomosis lengthened and patency rate showed a decreasing trend. As the amount of training increased, the residents were able to decrease the amount of time to complete the operation with increasing patency rates.ConclusionsThe model of high-volume internal carotid-middle cerebral artery bypass with arteries of porcine forearms has the advantages of material similarity, easy access of grafts, better simulation of intraoperative conditions, and adjustable difficulties. Our results suggest that this new procedure has a better simulation-training platform which is closer to the real surgical procedure for surgeons willing to master the technique of a high-volume bypass operation.     

Use of arterial grafts for coronary revascularization

Objectives: The aim of this study was to evaluate the performance and the quality of arterial grafts for coronary artery bypass grafting at The Heart Institute of Japan, Tokyo Women’s Medical University.Patients and Methods: From January 1970 to March 1998, 2987 arterial grafts, including left and right internal thoracic arteries, gastroepiploic artery, radial artery and inferior epigastric artery, were used in 1673 patients. In the same period, 1225 saphenous vein grafts were used. Early graft patency was angiographically determined. Also, histological evaluation of operative specimens and preoperative angiographic evaluation of arterial grafts were performed.Results: The total number of hospital deaths was 38 (2.3%). Of 4212 grafts, 3919 grafts (93%) were evaluated angiographically and 3714 of 3919 grafts were patent (94.8%). The patency rate of internal thoracic artery was better than that of gastroepiploic artery (p < 0.0001), radial artery (p = 0.0005) and saphenous vein grafts (p < 0.0001). However, the patency rate of gastroepiploic artery was better than that of saphenous vein grafts (p = 0.04), while no significant difference was detected between gastroepiploic artery and rdial artery. Only one internal thoracic artery specimen obtained at surgery showed atherosclerotic change, but all gastroepiploic artery specimens had moderate to severe atherosclerotic changes with CD68-positive cell infiltration. Only one patient’s left internal thoracic artery out of 200 was not angiographically useable as a conduit, while multiple stenotic lesions in gastroepiploic artery were observed.Conclusions: In the graft selection for CABG, the primary choice is internal thoracic artery and the secondary choice is right internal thoracic artery, from the standpoint of histological and angiographic evaluation, gastroepiploic artery and/or radial artery, depending on the target anastomotic site, degree of stenosis, and in situ or free use is the third choice.     

Decellularized Porcine Saphenous Artery for Small‐Diameter Tissue‐Engineered Conduit Graft

Decellularized xenografts have been identified as potential scaffolds for small‐diameter vascular substitutes. This study aimed to develop and investigate a biomechanically functional and biocompatible acellular conduit using decellularized porcine saphenous arteries (DPSAs), through a modified decellularization process using Triton X‐100/NH₄OH solution and serum‐containing medium. Histological and biochemical analysis indicated a high degree of cellular removal and preservation of the extracellular matrix. Bursting pressure tests showed that the DPSAs could withstand a pressure of 1854 ± 164 mm Hg. Assessment of in vitro cell adhesion and biocompatibility showed that porcine pulmonary artery endothelial cells were able to adhere and proliferate on DPSAs in static and rotational culture. After interposition into rabbit carotid arteries in vivo, DPSAs showed patency rates of 60% at 1 month and 50% at 3 months. No aneurysm and intimal hyperplasia were observed in any DPSAs. All patent grafts showed regeneration of vascular elements, and thrombotic occlusion was found to be the main cause of graft failure, probably due to remaining xenoantigens. In conclusion, this study showed the development and evaluation of a decellularization process with the potential to be used as small‐diameter grafts.     

Vineberg graft: flow reserve of bilateral implantation after 27 years

We report a patient who underwent bilateral internal thoracic artery implantation into the myocardium known as a Vineberg procedure 27 years ago. Coronary angiography and Doppler echocardiography revealed patent grafts with total occlusion of all native coronary arteries. We measured flow velocities at rest and under stress conditions with noninvasive ultrasonic Doppler echocardiography. The flow patterns in both grafts were biphasic as in native coronary arteries. Under stress conditions no increase in flow was detectable as a marker of end-stage coronary artery disease with refractory angina pectoris.