Anticoagulation and restenosis after percutaneous transluminal coronary angioplasty

Restenosis after angioplasty is probably related to 2 processes: thrombosis and recurrence of atherosclerosis. Many approaches to altering these processes are available, but to date none has shown a high rate of success. Heparin has properties relevant to both processes; this makes it an attractive compound for further study. The anticoagulant action of heparin is well known. It is mediated primarily though complex formation with antithrombin III, which leads to a conformational change and an increased rate of thrombin inactivation. Heparin has additional antithrombotic actions, largely mediated through the formation of the same complex, but involving precursor elements such as factor Xa. These actions of heparin can be localized to different portions of the large, complex molecule. Additionally, experimental studies have demonstrated an antiproliferative action of heparin, a property that may be relevant to smooth muscle cell proliferation after angioplasty. This is mediated by a fairly small, functionally distinct nonanticoagulant portion of the heparin molecule. Fragments of heparin possessing particular actions are being investigated experimentally and clinically. Continued investigations of the structure and function of heparin promise to lead to a decreased rate of restenosis and a better understanding of the mechanisms of angioplasty.     

Use of QT dispersion measured on treadmill exercise electrocardiograms for detecting restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: Treadmill exercise electrocardiography (ECG) has been used to detect restenosis in patients following percutaneous transluminal coronary angioplasty (PTCA). However, the level of sensitivity achieved using conventional criteria of ST-segment depression is too low to be clinically useful in this population. HYPOTHESIS: QT dispersion is a sensitive method for detecting myocardial ischemia and may improve the accuracy of treadmill exercise ECG testing for detecting restenosis after PTCA. METHODS: We evaluated 104 patients who underwent PTCA for the treatment of single-vessel coronary artery disease and who had no history of myocardial infarction. Treadmill exercise ECG and coronary angiograms were performed 3 months after PTCA to determine the accuracy of diagnosis restenosis based on standard ST-segment depression and QT dispersion criteria. RESULTS: Restenosis was observed in 37 of the 104 patients (36%) 3 months after PTCA. QT dispersion immediately after exercise was significantly greater in patients with than in those without restenosis, as was the difference in QT dispersion before and immediately after exercise. The sensitivity, specificity, and accuracy of ST-segment depression criteria were 59, 64, and 63%, respectively. Measurements of QT dispersion immediately after exercise (> or = 50 ms: positive, < 50 ms: negative) improved the sensitivity, specificity, and accuracy of treadmill ECG for predicting restenosis to 81, 87, and 85%, respectively. CONCLUSIONS: This novel diagnostic method using QT dispersion-based criteria significantly improves the clinical usefulness of treadmill exercise ECG for detecting the presence of restenosis after PTCA.     

Angiographic morphology of restenosis after percutaneous transluminal coronary angioplasty

Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) occurs frequently. To better define the restenosis process, a quantitative analysis was performed of coronary angiographic morphologic characteristics at restenosis, before and immediately after PTCA. In 22 patients cine frames showing stenosis at its most severe narrowing were traced and quantitatively analyzed. Immediately after PTCA, stenosis diameter (0.7 +/- 0.3 to 1.9 +/- 0.6 mm, mean +/- standard deviation, p less than 0.05) was increased; percent stenosis (77 +/- 11 to 34 +/- 16%, p less than 0.05), neck index (1.2 +/- 1.4 to 0.5 +/- 0.6, p less than 0.05) and irregularity (9 of 22 patients) were decreased. At follow-up, quantitative coronary morphologic values in most cases were similar to those before PTCA. There were individual changes, which occurred in an unpredictable and highly variable fashion, so that average values were not changed. The eccentricity ratio was not significantly changed by angioplasty or at restenosis. Thus, although successful PTCA results in specific changes in angiographic coronary stenotic morphology, these are reversed by the restenosis process.     

Importance of stenosis morphology in the estimation of restenosis risk after elective percutaneous transluminal coronary angioplasty

To determine the importance of predilatation stenosis morphology on the risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA), 500 procedures were randomly chosen for analysis from 3,839 consecutive successful PTCA procedures. Angiographic follow-up was available for 308 patients (62%) at a mean of 7.3 +/- 3.4 months after PTCA. One dilated site was randomly chosen per procedure. One hundred and one sites had documented restenosis (greater than or equal to 50% mean diameter stenosis from multiple projections) by quantitative angiography (33% of all sites restudied and 20% of all sites dilated). Twenty-eight morphologic variables and 20 other angiographic, clinical and procedural variables were analyzed by an observer blinded to clinical outcome. Univariate analysis found post-PTCA percent stenosis greater than 30% (p = 0.005), bend point location (p = 0.01), post-PTCA gradient greater than 15 mm Hg (p = 0.02), angina class III to IV (p = 0.03), age (p = 0.04) and the absence of dissection (p = 0.04) to predict restenosis. Multivariate analysis found only 2 significant (p less than 0.05) independent predictors of restenosis: post-PTCA percent stenosis greater than 30% and bend point location. Restenosis occurred in 41% of lesions located at an end-diastolic vessel angle greater than or equal to 45 degrees compared with 28% in lesions on lesser bends. Thus, only 1 predilatation morphologic characteristic, stenosis location at a bend point, was an important independent predictor of restenosis, and should be considered when assessing patients for PTCA.     

Results of a routine exercise treadmill testing strategy early after percutaneous transluminal coronary angioplasty

BACKGROUND: Some physicians use routine exercise treadmill testing early after percutaneous transluminal coronary angioplasty (PTCA), yet there have been few prospective studies examining the results of such a functional testing strategy. OBJECTIVES: To examine the results of a routine post-PTCA exercise treadmill testing strategy, and to explore the impact of such a strategy on follow-up functional tests and cardiac procedures. PATIENTS AND METHODS: Functional test results were examined from a cohort of 226 patients who underwent PTCA at a single institution in which a routine functional testing strategy is used. Tests were defined as 'routine' if they were performed solely because the patient had a prior PTCA. Tests were defined as 'selective' if they were done for a clinical indication or if there was no functional testing during the six-month follow-up. RESULTS: A total of 183 patients (81%) underwent at least one functional test during the six-month period after PTCA. Of these patients, 150 (82%) underwent routine functional testing, the majority (73%) of which were exercise treadmill tests. Sixty-seven per cent of patients who had routine functional testing had their first functional test less than seven weeks after their PTCA. Most routine exercise treadmill tests were found to be electrically or clinically indeterminate (46%), but a substantial number were either electrically or clinically positive (28%), or electrically and clinically negative (39%). Of patients who had electrically or clinically positive routine tests, 57% had repeat functional testing and 23% had repeat revascularization. Of patients who had electrically and clinically negative tests, 53% had repeat functional testing and 10% had repeat revascularization. Of the patients who had electrically or clinically indeterminate tests, 53% had repeat functional testing and 14% had repeat revascularization. The rate of clinical events was less than 4%, irrespective of the results of the exercise treadmill tests. CONCLUSIONS: Routine exercise treadmill testing early after PTCA is associated with a low clinical yield. Most routine exercise treadmill testing results in indeterminate and negative tests, which often lead to more functional tests with little difference in clinical outcome. These results call into question the use of a routine post-PTCA functional testing strategy.     

Factors predicting recurrent restenosis after percutaneous transluminal coronary balloon angioplasty

To identify factors that predict a second restenosis after repeat percutaneous transluminal coronary balloon angioplasty (PTCA), the records of 196 consecutive patients undergoing redilation for treatment of a first restenosis were reviewed. Repeat PTCA was successful in 181 (92%) of these patients. After a successful second PTCA, 47 patients (26%) developed a second restenosis (recurrent restenosis group, group 1) and 134 (single restenosis group, group 2) did not. The 2 patient groups were compared with respect to clinical, angiographic and procedural factors at second PTCA. Univariate correlates of a second restenosis were younger age (54 +/- 10 vs 57 +/- 9 years, p less than 0.05), interval less than 60 days between initial PTCA and recurrence of anginal symptoms (55% of patients in group 1 vs 25% in group 2, p = 0.001), a greater number of inflations (6.3 +/- 4.2 vs 4.4 +/- 2.5, p less than 0.005) and a shorter maximal balloon inflation time (49 +/- 26 vs 69 +/- 36 seconds, p = 0.0006). With multivariate analysis, the 2 factors that emerged as independent predictors of recurrent restenosis were recurrence of symptoms less than 60 days after initial PTCA (p less than 0.004) and a greater number of inflations (p less than 0.04). These data suggest that younger age and rapid recurrence of anginal symptoms after first PTCA predict an increased likelihood that a second restenosis will occur after repeat PTCA and that certain procedural factors, in particular the greater number of balloon inflations and a shorter maximal balloon inflation time, may play an important role in the development of recurrent restenosis.     

Serum lipids and restenosis after successful percutaneous transluminal coronary angioplasty

The effects of plasma lipids on the clinical and angiographic parameters of 134 patients, in whom coronary angioplasty was performed in 157 vessels, were prospectively examined. During a 6-month follow-up, restenosis was detected angiographically in 39 patients (29%; 45 vessels). None of the clinical, biochemical, or angiographic variables examined was predictive of stenosis and the tendency of a vessel to restenose was not patient-dependent but rather lesion-related. However, restenosis developed in 31 of 102 vessels (30%) in patients with high-density lipoprotein (HDL) cholesterol 40 mg/dl, compared with restenosis in 10 of 55 vessels (19%) in patients with HDL cholesterol >40 mg/dl (p = 0.092). No significant differences were observed when restenosis rates were compared in patients with total cholesterol levels >250 mg/dl or < 250 mg/dl; no differences were seen in low-density lipoprotein (LDL) cholesterol levels when comparing patients with >160 mg/dl and < 160 mg/dl. In 117 patients (132 vessels), complete serial blood specimens were obtained until the concluding angiography at 6 months. During follow-up, both groups (those with and without restenosis) had almost similar findings. Triglycerides decreased equally in both groups, and total cholesterol increased mildly in those who had restenosis; HDL and LDL cholesterol levels increased significantly in each group. No significant differences were observed with respect to extent of these changes between the groups. Thus, although lipid levels at the time of angioplasty and at 6 months follow-up were not found to predict the occurrence of restenosis, the association of low high-density lipoprotein levels and the tendency for restenosis should not be overlooked.     

Detection of coronary restenosis by exercise electrocardiography thallium-201 perfusion imaging and coronary angiography in asymptomatic patients after percutaneous transluminal coronary angioplasty

Noninvasive detection of restenosis in patients remaining asymptomatic after percutaneous transluminal coronary angioplasty (PTCA) remains a major clinical problem. The value of exercise electrocardiography (ECG) and exercise-redistribution thallium-201 single-photon emission computed tomography (SPECT) in detecting restenosis in such patients remains uncertain. Discordances between these tests and coronary angiography is a common situation. We studied 179 consecutive patients remaining asymptomatic after successful PTCA (208 vessels), who underwent 6 +/- 2 months of exercise ECG, SPECT, and coronary angiography. We sought to assess the diagnostic value of the noninvasive tests compared with coronary angiography, and identify the determinants of discordances between the tests. Restenosis (diameter stenosis >50%) was detected in 39% of patients and in 37% of vessels. The overall sensitivity, specificity, and accuracy for exercise ECG and SPECT in detecting restenosis in individual vessels were, respectively, 53% versus 63% (p = 0.06), 59% versus 77% (p = 0.0001), and 57% versus 72% (p = 0. 0001). On multivariate analysis, positive exercise ECG was associated with higher heart rate response (p = 0.02), incomplete revascularization (p = 0.004), and angiographic restenosis (p = 0. 03), whereas positive SPECT was associated with incomplete revascularization (p = 0.02), infarct-related artery PTCA (p = 0.01), and angiographic restenosis (p = 0.0001). Accuracies of the 2 tests were not significantly different in patients with incomplete revascularization or PTCA of an infarct-related vessel. Overall, SPECT is more accurate than exercise ECG in detecting asymptomatic restenosis. Nevertheless, incomplete revascularization and PTCA of an infarct-related artery could cause reversible perfusion defects regardless of restenosis, reducing the diagnostic value of SPECT in such patients.     

Repeat percutaneous transluminal angioplasty in coronary artery restenosis

Early experience with repeat transcutaneous transluminal coronary angioplasty (TTCA) in 9 coronary patients is reviewed. The interval between the first and the repeat TTCA varied between 1 and 12 months averaging 4.9 +/- 4.7 months. Repeat dilatation of the anterior interventricular branch was performed in 7 patients, that of the right coronary artery, in 1, and that of the circumflex artery, in 1. All repeat operations were successful. Changes in the degree of stenosis and the mean arterial blood pressure gradient were actually similar in both dilatations.     

Design considerations in the study of restenosis after percutaneous transluminal coronary angioplasty

Restenosis after percutaneous transluminal coronary angioplasty is a critical factor limiting the overall usefulness of this procedure in the treatment of patients with coronary artery disease. Difficult problems must be overcome in the design of studies to investigate restenosis. Some of these patients problems wil be discussed.     

粘附分子与冠脉成形术后再狭窄

冠心病的介入治疗 ,尤其是经皮腔内冠脉成形术 (ｐｅｒｃｕｔａｎｅｏｕｓｔｒａｎｓｌｕｍｉｎａｌｃｏｒｏ ｎａｒｙａｎｇｉｏｐｌａｓｔｙ ,ＰＴＣＡ)及冠脉内支架术(ｉｎｔｒａｃｏｒｏｎａｒｙｓｔｅｎｔｉｎｇ ,ＩＣＳ)已成为冠心病治疗的主要手段之一 ,但 30 %～ 5 0 %的ＰＴＣＡ术后及 10 %～ 15 %的ＩＣＳ术后的再狭窄 (ｒｅｓｔｅｎｏｓｉｓ ,ＲＳ)率已成为影响冠脉成形术远期疗效的重要因素。冠脉成形术所致的内皮损伤、血栓形成、炎症反应、细胞迁移增殖和血管重塑等与ＲＳ关系密切。随着对ＲＳ研究的不断深入 ,发现细胞粘附分…     

Efficacy of repeat percutaneous transluminal coronary angioplasty for coronary restenosis

The short- and long-term outcome of patients within the NHLBI PTCA Registry who underwent repeat PTCA for coronary restenosis were analyzed. Of 1,880 patients in whom an initial PTCA was successful, 203 had a repeat PTCA attempted after restenosis developed. Repeat PTCA was usually performed within 6 months of the first procedure. The success rate of repeat PTCA was 85.2%. As a direct result of repeat PTCA, 1.5% of patients had an MI and 2% required emergency CABG. No patien died as a result of the attempted second procedure. One to 3 years of follow-up information was available in 94% of eligible patients. Most patients (75,9%) did not have a subsequent (third) PTCA, CABG or an MI. The late mortality rate was 0.8%. Angiographic follow-up information was available in 62 patients. Sustained enhancement of the diameter of the redilated lesion was observed in 66%. Thus, repeat PTCA has a high success and a low complication rate. Most patients did not have subsequent restenosis and are free of angina. Hence, repeat PTCA should be recommended for patients who have restenosis and should be considered as an integral component of PTCA therapy.     

Transoesophageal pacing echocardiography for detection of restenosis after percutaneous transluminal coronary angioplasty

Non-invasive documentation of restenosis after successful percutaneoustransluminal coronary angioplasty (PTCA) remains a problem.Thus, transoesophageal pacing echocardiography (TPE) with simultaneousrapid atrial pacing via the same probe, a recently validatedmethod for detection of coronary artery disease, was used in60 patients for detection of restenosis after successful PTCA(54 patients with one and six patients with multivessel PTCA).The patients came for routine follow-up angiography 5.4 ±3.7 months after PTCA regardless of clinical status. Restenosis(diameter stenosis 50%) was demonstrated in 22 patients. Diseaseprogression in previously normal vessels was noted in threeadditional patients. Results for detection of restenosis anddisease progression were compared to exercise ECG and in 40patients to Tc-99m methoxy-isobutyl-isonitrile (MIBI)-radionuclideperfusion imaging. Diagnostic standard exercise ECG could beperformed in only 38 patients, due to peripheral vascular disease,joint disease or premature exhaustion in the rest of patients.TPE was non-diagnostic in two patients due to ineffective pacingor patient discomfort. Sensitivity of TPE for detection of restenosisand disease progression after PTCA was 84% compared with 50%and 86% for exercise ECG and Tc-99m MIBI-SPECT (P<0.03 andns), respectively. Specificity of TPE (85%) was also higherthan that of exercise ECG (59%, P<0.03) and comparable tothe specificity of MIBI-SPECT (84%). Overall accuracy of TPEwas far superior to exercise ECG and similar to MIBI-SPECT (84%)vs 54% and 85%) (P=0.0007 and ns, respectively). We conclude that TPE is useful and accurate for patient follow-upafter PTCA and is especially valuable in patients unable toperform a conventional exercise test.     

Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele.     

Role of cytokines in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty

BACKGROUND: Inflammatory cytokines play an important role in mediating inflammatory/proliferative responses including atherosclerosis. However, their role in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains to be clarified. OBJECTIVE: To determine plasma levels of inflammatory cytokines as well as cytokine-generation capacities of monocytes before PTCA and after the follow-up period. METHODS: Plasma levels of cytokines in 34 consecutive patients before and 3-6 months after PTCA were measured by enzyme-linked immunosorbent assay. We measured the plasma levels of macrophage-colony-stimulating factor (MCSF) and transforming growth factor-beta. Cytokine-generation capacities of monocytes were also measured by a whole-blood induction method with lipopolysaccharide. The levels of cytokines measured for assessment of the capacities included those of interleukin-1alpha, interleukin-1beta, interleukin-6, granulocyte-colony-stimulating factor, tumor necrosis factor-alpha and interferon-gamma. RESULTS: Plasma levels of MCSF in patients without restenosis (n = 20) decreased significantly (from 1460+/-138 microg/ml before PTCA to 1039+/-125 microg/ml after the follow-up period, P < 0.01), whereas those in patients with restenosis (n = 14) increased significantly (from 1107+/-105 microg/ml before PTCA to 1039+/-125 microg/ml after the follow-up period, P < 0.05). We noted a positive correlation between the increase in plasma levels of MCSF and the extent of loss of lumen by restenosis. Cytokine-generation capacities of monocytes for interleukin-1alpha and interleukin-1beta of patients with restenosis significantly increased but those of patients without restenosis did not. Furthermore, plasma levels of C-reactive protein decreased significantly only in patients without restenosis after the follow-up period. CONCLUSIONS: These results suggest that inflammatory changes mediated by cytokines may be involved in the pathogenesis of restenosis after PTCA.     

Evaluation of restenosis after percutaneous transluminal coronary angioplasty using a Doppler index, the Tei index

Cardiac function and restenosis were evaluated after percutaneous transluminal coronary angioplasty (PTCA) using a Doppler index (the Tei index). Thirty-eight patients, 31 men and 7 women (mean age 57 years) with ischemic heart disease were studied. The underlying heart diseases were angina pectoris without left ventricular asynergy in 16 patients and old myocardial infarction (OMI) with left ventricular asynergy in 22 . Ejection fraction was measured by M-mode echocardiography and deceleration time, and the interval between cessation and onset of the mitral inflow velocity (a), ejection time at aortic valve (b), and the Tei index [(a-b)/b] were measured by M-mode echocardiography performed before and 6 months after PTCA. The ejection fraction, deceleration time and Tei index showed no changes after PTCA in patients with angina pectoris with or without restenosis. In patients with OMI with restenosis, the Tei index increased slightly after PTCA, from 0.56 +/- 0.15 to 0.61 +/- 0.13. The deceleration time changed from 0.23 +/- 0.03 to 0.24 +/- 0.02 msec, and the ejection fraction from 0.46 +/- 0.11 to 0.51 +/- 0.17, neither significantly. However, in patients with OMI without restenosis (15 out of 22 patients), the Tei index significantly improved after PTCA, from 0.55 +/- 0.13 to 0.48 +/- 0.12 (p < 0.05). In patients with left ventricular asynergy due to old myocardial infarction, without restenosis, the Tei index significantly improved after PTCA. The Tei index is useful for evaluating restenosis after PTCA in patients with OMI.