Expansive remodeling in venous bypass grafts: novel implications for vein graft disease

ObjectiveTo date, intimal hyperplasia has been regarded as the principle mechanism responsible for subsequent vein graft disease. Lumen remodeling has not been previously considered as an additional mechanism. The objectives of this study were to determine changes in lumen remodeling in arterialized vein grafts, the accompanying cellular and extracellular matrix events contributing to remodeling, and the effects of a high cholesterol diet.Methods and resultsReversed jugular vein-to-common carotid artery interposition grafts were constructed in 70 normocholesterolemic and 11 hypercholesterolemic male New Zealand white rabbits. The lumen area initially remained unchanged between 1 and 4 weeks but significantly increased by 40% at 12 weeks. This phase of expansive positive remodeling was accompanied by significantly increased cell apoptosis, collagen synthesis (1.7-fold), collagen content (3.7-fold), gelatinase (MMP-2 and MMP-9) levels and decreased tissue inhibitor of metalloproteinase (TIMP) levels. Expansive remodeling temporally corresponded to high macrophage infiltration and increased low density lipoprotein (LDL) retention (fourfold) in the vein grafts. A high cholesterol diet stimulated early macrophage infiltration and increased MMP-12 (metalloelastase) levels, which was associated with earlier onset of expansive remodeling.ConclusionExpansive lumenal remodeling is a novel mechanism of vein graft response to the arterial circulation, which is accelerated by a high cholesterol diet.     

Intravascular stenting for stenosis of aortocoronary venous bypass grafts

To test the ability of endoluminal stents to prevent saphenous vein graft restenosis after balloon angioplasty, 13 patients with angina and previous coronary bypass surgery underwent implantation of one or more stents into 14 stenosed grafts. Implantation was technically successful in all cases and there were no major in-hospital complications. During a median follow-up interval of 7 months (range 2 to 26), 10 patients (77%) underwent follow-up angiography. Seven patients remained asymptomatic or in improved condition without further intervention; three patients had further angioplasty with stent implantation for a new stenosis in the same graft. Two patients (20%) developed within-stent restenosis. There was one death from progressive congestive heart failure 7 months after implantation. No patient had a myocardial infarction or needed surgical revascularization during the follow-up period. In selected cases, stent implantation appears to be a promising new technique that may decrease the incidence of restenosis after balloon angioplasty in venous bypass grafts. The rate of complications is low. Further experience and longer follow-up will be needed before definite recommendations can be made about its use.     

Intravascular ultrasound to assess aortocoronary venous bypass grafts in vivo.

In 20 consecutive patients (18 men and 2 women, aged 42 to 72 years) undergoing repeat coronary angiography because of new onset of angina pectoris 4 months to 11 years (mean 53 months) after aortocoronary saphenous venous bypass operation, the graft to the left anterior descending (n = 12), left circumflex (n = 4) or right coronary (n = 2) artery, or a diagonal branch (n = 2) was studied by both intravascular ultrasound and angiography. Sonographic images were obtained using a 4.8Fr catheter with a crystal mechanically rotated at 900 rpm; quantitative coronary angiograms were recorded in biplane projections. In 18 patients, qualitatively as well as quantitatively evaluable images could be recorded; no complications occurred. The venous wall in general appeared to be homogenous; there were no separate layers identifiable. Simultaneous ultrasound and angiographic measurements were performed at a total of 75 sites (2 to 6 per bypass). In 4 of these patients (10 of 75 sites), neither intravascular ultrasound nor angiography revealed any pathologic changes; these bypasses were classified as normal. At the remaining 65 sites, arteriosclerotic lesions were detected in each case by ultrasound, but at only 33 sites by angiography. Median wall thickness was 0.59 mm (95% confidence interval 0.54 to 0.63) in normal grafts and 1.02 mm (0.99 to 1.07; p less than 0.001) in diseased grafts. The cross-sectional luminal area determined by ultrasound correlated well with the angiographic assessment (r = 0.90; p less than 0.001), but the measured values were significantly higher (17 +/- 4 vs 14 +/- 4 mm2; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Restenosis predictors after stent implantation of venous aortocoronary bypass grafts

Follow-up studies after stent implantation of native coronary arteries have reported reduced rates of angiographic restenosis. In contrast, stent implantation in the treatment of obstructive disease of coronary artery bypass grafts is complicated by higher restenosis rates. We sought to determine, if different predictors contribute to the high restenosis rate following stent implantation of coronary artery bypass grafts. We investigated long-term angiographic outcome of 205 stent implantations performed in 177 patients. Multivariate analysis correlated clinical, procedural and angiographic variables with the incidence of angiographic restenosis defined as diameter stenosis > 50% at follow-up. Angiographic restenosis was observed in 34% of lesions treated. Multiple logistic regression analysis defined diabetes mellitus (OR 6.89, CI 2.41-9.69), graft recanalization (OR 2.69, CI 1.08-6.63), lesion at the aortic anastomosis (OR 6.98, CI 2.76-19.25), lesion at the coronary anastomosis (OR 2.95, CI 1.18-7.49), high diameter stenosis after stent placement (OR 7.01, CI 2.64-15.71), placement of long stents (OR 2.78, CI 1.11-7.36) and implantation of more than one stent (OR 7.34, CI 2.08-20.15) as independent predictors of graft in-stent restenosis. Critical consideration of these variables may help to identify patients who are poor candidates for stent implantation and who may benefit from different interventional approaches.     

Frequency of deep venous thrombosis in asymptomatic patients with coronary artery bypass grafts.

The frequency of deep vein thrombosis (DVT) in patients undergoing coronary artery bypass graft (CABG) surgery has not been established. Therefore to estimate the frequency of clinically silent DVT, we performed ultrasound examinations of the leg veins in 29 asymptomatic CABG patients before hospital discharge. We used high-resolution B-mode ultrasonography with color Doppler imaging. Fourteen (48.3%, 95% confidence interval 30.1 to 66.4%) had 20 documented leg vein thromboses, and all but one patient had DVT limited to the calf veins. Of the 20 thrombi 10 (50.0%) were present in the leg ipsilateral and 10 (50.0%) in the leg contralateral to the saphenous vein harvest site. None of the DVTs were suspected clinically. DVT was not associated with any local sign attributed to saphenous vein harvest such as pitting edema, incisional drainage, or local tenderness or with any putative risk factor for DVT such as cigarette use, distant history of malignancy, or varicose veins. Follow-up of these patients 5 to 11 months after CABG surgery showed no clinical evidence of DVT or pulmonary embolism. Our findings indicate that asymptomatic DVT of the calf occurs with surprisingly high frequency, 44.8% after CABG surgery. Future studies in patients undergoing CABG surgery should address the natural history of asymptomatic DVT, determine its clinical importance, and develop optimal strategies for prophylaxis and treatment.     

Intravascular ultrasound assessment of the presence of vascular remodeling in diseased human saphenous vein bypass grafts

Remodeling occurs in diseased human coronary arteries; however, reports of remodeling in diseased autologous saphenous vein bypass graft (SVG) stenoses are inconsistent. Preintervention intravascular ultrasound and quantitative coronary angiography were used to study 104 SVG stenoses in 93 consecutive patients. Lesion site and proximal and distal reference segment measurements included vein graft, external elastic membrane, lumen, wall (vein graft minus lumen), and plaque (external elastic membrane minus lumen) areas. Three indexes of remodeling were assessed: (1) lesion site SVG (or external elastic membrane) area was compared with the average reference segment, (2) SVG area was correlated with the wall area and external elastic membrane area was correlated with the plaque area, and (3) the impact of excess plaque accumulation (at the stenosis compared with the reference segment) on lumen compromise was calculated. Overall, the ratio of lesion/reference vein graft area was 1.07 +/- 0.25; however, 23 lesions were classified as negative remodeling (ratio <0.9), 37 as intermediate remodeling (ratio between 0.9 and 1.1), and 44 as positive remodeling (ratio >1.1). Reference segment vein graft area correlated with wall area (r = 0.906, p <0.0001), and external elastic membrane area correlated with plaque area (r = 0.703, p <0.0001). Similarly, lesion site vein graft area correlated with wall area (r = 0.978, p <0.0001), and external elastic membrane area correlated with plaque area (r = 0.961, p <0.0001). The regression line relating delta lumen area to delta wall area was y = -0.22 x - 6.2 (r = 0.451, p <0.0001) and the regression line relating delta lumen to delta plaque area was y = -0.47 x - 4.5 (r = 0.572, p <0.0001). (A slope of 0 would indicate perfect positive remodeling and a slope of 1.0 no positive remodeling.) Diseased SVGs undergo positive and negative remodeling similar to native coronary arteries.     

Statin therapy in the primary prevention of early atrial fibrillation after coronary artery bypass grafting

ObjectiveAssessment of the role of statin therapy in the prevention of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) in patients without prior atrial fibrillation.MethodsA retrospective analysis of 206 patients, aged 57.2 ± 7.9 years (mean ± SD), who underwent isolated CABG is carried out. All patients are divided into two groups. The first group (nSt-patients) includes the patients who did not receive statin therapy prior to CABG (n = 82). The second group (St-patients) includes the patients who received statin therapy prior to CABG (n = 124). Both groups received the statin therapy from the first day after CABG. The risk of occurrence of POAF is evaluated using the Cox-regression model.ResultsThe rate of POAF was 25.6% in nSt-patients and 6.5% in St-patients (P = 0.020). On the 4th day after CABG, white blood cells (WBC) count was 11.0 (9.0, 13.0) × 10⁹/mL (medians with inter-quartile ranges) in nSt-patients and 9.0 (7.6, 10.2) × 10⁹/mL in St-patients (P < 0.001). The peak WBC numbers occurred on the day of POAF onset. The Cox-regression analysis shows that only two factors (statin therapy and number of grafts) had significant influence on the POAF onset. Odds ratio of POAF event prediction by statin therapy was 0.20 (95%CI: 0.08–0.51), P < 0.001. Each subsequent graft increased the risk of POAF in 2.1 times.ConclusionStatin therapy carried out prior to the CABG is an effective approach to primary prevention of POAF in early postoperative period. Statin therapy after CABG in nSt-patients does not give prophylactic effect observed in St-patients.     

Adaptive mechanisms of arterial and venous coronary bypass grafts to an increase in flow demand

OBJECTIVE—To compare the mechanisms by which arterial and venous grafts increase their flow during pacing induced tachycardia, early and later after coronary bypass surgery.
DESIGN—43 grafts (13 epigastric artery, 15 mammary artery, 15 saphenous vein) evaluated early (9 (3) days (mean (SD)) after bypass surgery were compared with 41 other grafts (15 epigastric, 11 mammary, 15 saphenous vein) evaluated later after surgery (mean 23 months, range 6 to 168 months) by quantitative angiography and intravascular Doppler velocity analysis during atrial pacing. Controls were 17 normal coronary arteries.
RESULTS—Baseline graft flow tended to be lower later after surgery than early (41 (16) v 45 (21) ml/min, NS). Blood flow increased during pacing by 30 (16)% early after surgery, less than later after surgery (+46 (18)%, p < 0.001) and less than in normal coronary arteries (+54 (27)%, p < 0.001 v early grafts; NS v late grafts). There was no difference between venous and arterial grafts. No significant vasodilatation was observed during pacing early after surgery in arterial and venous grafts. Later after surgery, significant vasodilatation was observed only in arterial grafts (mammary and epigastric grafts), from 2.41 (0.37) to 2.53 (0.41) mm (+5.1% v basal, p < 0.001). Early after surgery and in venous grafts later after surgery, the increase in flow was entirely due to an increase in velocity. In later arterial grafts, the relative contribution of the increase in velocity to the increase in flow during pacing was lower in arterial grafts (70 (22)%) than in venous grafts (102 (11)%, p < 0.001) and similar to normal coronary arteries (68 (28)%).
CONCLUSIONS—Early and later after surgery, arterial grafts and venous grafts both increase their flow similarly during pacing. Early arterial grafts and venous grafts increase their flow only through an increase in velocity. Later after surgery, arterial grafts act as more physiological conduits and increase their flow in the same way as normal coronary arteries, through an increase in velocity and calibre mediated by the endothelium.


Keywords: coronary artery bypass graft; endothelial function     

Ultrastructural changes of venous autologous bypass grafts in rabbits: Correlation of patency and development

Summary Electron microscopic techniques were used to correlate the patency of venous autografts in rabbits with ultrastructural changes within a time range from 5 days to 6 months p.o. Early degenerative changes of the grafts include endothelial desquamation followed by fibrin deposition or platelet adhesion, mural edema and extensive medial and adventitial degeneration. The regeneration of the grafts is due to an early adventitial vascularization (10 days p.o.), which enables the surviving smooth muscle cells and fibrocytes to proliferate and to develop an arterial-like vessel. The organization of the 6-month-old graft is comparable to the carotid artery of the animal, but shows, in contrast, many features of a muscular artery.

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Zusammenfassung Mit Hilfe elektronenmikroskopischer Methoden wurde versucht, die Funktionsfähigkeit autologer Venentransplantate mit ultrastrukturellen Veränderungen in einem Zeitraum von 5 Tagen bis 6 Monaten p. o. zu korrelieren. Frühe degenerative Veränderungen der Transplantate umfassen Endothelabschilferungen mit anschließender Fibrin- bzw. Plättchenauflagerung, murale Ödeme und ausgedehnte mediale und adventitielle Degenerationen. Die Regeneration der Transplantate wird ermöglicht durch eine frühe adventitielle Kapillarisierung (10 Tage p. o.), die die überlebenden glatten Muskelzellen und Fibrozyten in die Lage versetzt, zu proliferieren und ein arterienähnliches Gefäß zu entwickeln. Der Aufbau der 6 Monate alten Vene ist vergleichbar mit der Arteria carotis communis der Tiere, zeigt aber im Gegensatz dazu überwiegend Merkmale einer Arterie vom muskulären Typ.

     

A chymase gene variant is associated with atherosclerosis in venous coronary artery bypass grafts.

BACKGROUND: Angiotensin II is known to stimulate proliferation of fibroblasts and smooth muscle cells and enhance the atherosclerotic process in native coronary arteries. The impact of genetic polymorphisms of the renin-angiotensin-aldosterone system on coronary bypass graft degeneration is unknown. METHODS: We examined polymorphisms of four genes (AGTR1, CYP11B2, ACE, CMA) in 101 patients who had follow-up coronary angiography due to symptoms 88 +/- 52 months after coronary artery bypass graft surgery. Bypass degeneration was determined with quantitative coronary angiography and an adjusted Gensini score. RESULTS: Homozygosity for the G allele of the CMA-1905 polymorphism was associated with a higher degree of bypass degeneration (Bypass Gensini score CMA AA 21.4 +/- 39; AG 24.2 +/- 39.8; GG 27.8 +/- 42.3; NS-time adjusted Gensini bypass scores CMA AA 0.25 +/- 0.68; AG 0.57 +/- 1.82; GG 3.25 +/- 13.2; P = 0.005). No association could be detected for the AGTR1, CYP11B2 or ACE polymorphism. CONCLUSION: The CMA allele G is a genetic risk factor for atherosclerosis in venous coronary artery bypass grafts. Its importance has to be shown in further studies. Other polymorphisms of the renin-angiotensin-aldosterone system do not seem to play a role in bypass degeneration.     

Abnormal venous valves: a cause of early obstruction of saphenous vein bypass grafts

Factors other than technical error and poor run-off may account for occlusion or obstruction of aortocoronary vein bypass grafts in the early postoperative period. Four cases are presented in which graft obstruction was caused by venous valves. Discussion of the etiology of this problem and recommendations for its prevention are included.     

Risk factors for the development of restenosis following stent implantation of venous bypass grafts

OBJECTIVE—To analyse the variables involved in the high restenosis rate following stent implantation in coronary artery bypass grafts.
DESIGN—A retrospective analysis of a consecutive group of patients attending a tertiary centre.
PATIENTS—The long term angiographic outcome of 219 stent implantations for individual lesions performed in 191 patients was investigated. Multivariate analysis correlated clinical, procedural, and angiographic variables with the incidence of angiographic restenosis, defined as diameter stenosis > 50% at follow up.
RESULTS—Angiographic restenosis was observed in 34% of lesions treated. Multiple logistic regression analysis defined diabetes mellitus (odds ratio 6.91, 95% confidence interval (CI) 2.43 to 9.69), graft recanalisation (2.89, 95% CI 1.18 to 6.63), lesion at the aortic anastomosis (6.98, 95% CI 2.77 to 21.31), lesion at the coronary anastomosis (3.01, 95% CI 1.19 to 7.69), high diameter stenosis after stent placement (7.21, 95% CI 2.66 to 16.81), placement of long stents (2.73, 95% CI 1.09 to 7.39), and implantation of more than one stent (7.31, 95% CI 2.08 to 19.96) as independent predictors of graft in-stent restenosis.
CONCLUSIONS—There appears to be a specific risk factor constellation contributing to the high restenosis rate following stent implantation in venous bypass grafts. Critical consideration of these variables may help identify patients who are poor candidates for stent implantation and who may benefit from a different approach.


Keywords: coronary artery bypass graft; stent; restenosis