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.     

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.     

Effect of angiotensin converting enzyme inhibition on the incidence of restenosis after percutaneous transluminal coronary angioplasty.

To determine whether angiotensin converting enzyme (ACE) inhibition may reduce the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we retrospectively identified 322 consecutive patients who underwent a successful procedure from June 1988 to December 1989. No patients developed chest pain, ST segment elevation, positive cardiac enzymes, or other evidence of abrupt vessel closure following the PTCA. All patients received intravenous heparin after PTCA and aspirin was begun on the day prior to PTCA. Patients were separated into two groups: those at hospital discharge incidentally treated for hypertension or heart failure with ACE inhibitors (n = 36), and those treated with a drug regimen which did not include ACE inhibitors (n = 286). The two groups were similar with respect to age (61 +/- 13.5 vs. 60 +/- 12.5, p = NS) and other demographic characteristics. Restenosis, defined as the presentation to a physician with symptoms of angina within 6 months of the PTCA and the finding on repeat catheterization of a significant restenosis at the site of the PTCA, occurred in 30% of the patients who were discharged on a drug regimen which did not include ACE inhibitors vs. 3% (p less than .05) in those treated with an ACE inhibitor. Thus, it appears that the use of ACE inhibitors may significantly reduce the incidence of restenosis after successful PTCA.     

Effect of angiotensin converting enzyme inhibition on the incidence of restenosis after percutaneous transluminal coronary angioplasty

To determine whether angiotensin converting enzyme (ACE) inhibition may reduce the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we retrospectively identified 322 consecutive patients who underwent a successful procedure from June 1988 to December 1989. No patients developed chest pain, ST segment elevation, positive cardiac enzymes, or other evidence of abrupt vessel closure following the PTCA. All patients received intravenous heparin after PTCA and aspirin was begun on the day prior to PTCA. Patients were separated into two groups: those at hospital discharge incidentally treated for hypertension or heart failure with ACE inhibitors (n=36), and those treated with a drug regimen which did not include ACE inhibitors (n=286). The two groups were similar with respect to age (61 ± 13.5 vs. 60 ± 12.5, p=NS) and other demographic characteristics. Restenosis, defined as the presentation to a physician with symptoms of angina within 6 months of the PTCA and the finding on repeat catheterization of a significant restenosis at the site of the PTCA, occurred in 30% of the patients who were discharged on a drug regimen which did not include ACE inhibitors vs. 3% (p <.05) in those treated with an ACE inhibitor. Thus, it appears that the use of ACE inhibitors may significantly reduce the incidence of restenosis after successful PTCA.     

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.     

Controlled balloon inflation reduces long-term restenosis after percutaneous transluminal coronary angioplasty.

PURPOSE: The trauma induced by balloon angioplasty has an impact on the outcome of coronary interventions, such as stent procedures. However, balloon inflation for PTCA is not yet standardized even though procedural and long-term outcomes might be affected. METHODS: During routine PTCA, a total of 454 patients [mean age, 60.9 +/- 9.0 years; 162 (35.7%) with 1-vessel disease; 159 (35%) with 2-vessel disease; 133 (29.3%) with 3-vessel disease] were allotted to computer-assisted dilatation (CAPS) with a pressure slope of 0.2 bar/s (CAPS 0.2; n = 149 patients), 1.0 bar/s (CAPS 1.0; n = 154 patients) or to standard inflation with a hand-driven pump (n = 151 patients). Angiographic follow-up rates after 4.1 +/- 3.2 months were 88.1% for the hand-driven pump, 94% for CAPS 0.2 and 87.7% for CAPS 1.0. RESULTS: Flow reducing (1.3-2.0%) and non-flow reducing (12.6-14.9%) dissections were equally distributed among all groups as were major adverse cardiac events (2.6-4.0%). The stent rate was 1.3% with the hand-driven pump, 0.7% with CAPS 0.2 and 1.3% with CAPS 1.0. Angiographic restenosis rate was 48.9% with the hand-driven pump, 44.3% with CAPS 0.2 and 32.6% with CAPS 1.0. (hand-driven pump versus CAPS 1.0, p < 0.007; CAPS 0.2 versus CAPS 1.0, p < 0.049). CONCLUSIONS: The pressure slope during balloon inflation in PTCA has a significant impact on restenosis. The impact on stent procedures has yet to be determined.     

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.     

放射治疗预防血管成形术后再狭窄的研究现状

经皮冠状动脉球囊成形术(FICA)后有30％～40％的患者在半年内发生再狭窄,严重限制了其远期疗效。血管成形术后再狭窄的发生主要是由于内膜的增生和血管的重塑。冠状动脉支架植入的应用抵消了血管的病理性重塑,使再狭窄率下降了10％,但是支架内的内膜增生程度反而加重。目前国内外对预防再狭窄的研究包括药物治疗、基因治疗、新的成形术和放射疗法等。前三者均未得满意的效果,而放射线辐射具有特定的生物学效应,致再狭窄的防治获得良好的效果。本文对放射治疗预防再狭窄的现状和进展进行归纳和分     

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…     

Tissue characteristics of restenosis after percutaneous transluminal coronary angioplasty in diabetic patients.

OBJECTIVES: The purposes of this study were to analyze coronary specimens from patients with diabetes mellitus (DM) and to compare them with specimens from patients without DM. BACKGROUND: Diabetes mellitus is associated with an increased incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Increased hypercellular smooth muscle cell proliferation with exaggerated intimal hyperplasia formation may be responsible for this predisposition. METHODS: Eighteen coronary atherectomy specimens with restenosis after PTCA from patients with DM were compared with 18 coronary atherectomy specimens with restenosis after PTCA from patients without DM. Total and segmental areas were quantified on trichrome-stained tissue of hypercellular tissue, collagen-rich sclerotic tissue, atheroma and thrombus. Demographic and angiographic data were similar in both groups. RESULTS: The percentage of total plaque area composed of hypercellular tissue was lower in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (19 +/- 6% vs. 44 +/- 5%; p = 0.003). The percentage of collagen-rich sclerotic tissue area was larger in restenotic specimens from patients with DM than in restenotic specimens from patients without DM (77 +/- 9% vs. 53 +/- 4%; p = 0.004). The percentages of atheroma and thrombus were similar in both groups. CONCLUSIONS: Intimal hypercellular tissue content is reduced in restenotic tissue from patients with DM. Collagen-rich sclerotic content is increased in restenotic lesions from patients with DM. These results suggest an accelerated fibrotic rather than a proliferative response in diabetic lesions from patients with restenosis after PTCA.     

Influence of the methodology of percutaneous transluminal coronary angioplasty on restenosis

Restenosis after percutaneous transluminal coronary angioplasty (PTCA) remains the principal factor preventing broader application of this form of myocardial revascularization. Several methodologic variables contribute to the quality of the angioplasty result and may directly or indirectly influence restenosis rates after the procedure. PTCA operators attempt to minimize thrombotic activity at the angioplasty site by delaying PTCA when thrombus is present, with heparin and antiplatelet agents and with thrombolytic agents if thrombus is identified during the procedure. Therapy directed at preventing coronary artery spasm with nitrates and calcium antagonists has no proven efficacy in preventing restenosis. Residual stenosis and pressure gradient have been shown to be predictors of restenosis. Retrospective studies have indicated that a balloon to artery diameter ratio greater than 1 favors long-term patency; however, preliminary results of a prospective randomized study suggested that acute complications were more frequent with larger balloons. The interplay of other balloon-related variables (maximal inflation pressure, number of inflations, duration of inflations, balloon material and length of balloon) and the potential influence on restenosis are discussed. Recommendations for patient management after PTCA are also offered. A number of prospective randomized trials using antiplatelet agents and modification of risk factors are underway to test ability of these strategies to influence restenosis.     

Increased IgM-anticardiolipin antibodies in patients with restenosis after percutaneous transluminal coronary angioplasty.

Increased anticardiolipin antibodies (acL) are often associated with arterial thrombosis in patients with autoimmune diseases. A mural thrombus at the site of percutaneous transluminal coronary angioplasty (PTCA) has been suggested as the initial cause for restenosis after primarily successful PTCA. In this study, IgM- and IgG-acL were determined in 65 men with coronary artery disease treated by PTCA; patients with infectious and autoimmune diseases were excluded from the study. Follow-up coronary angiography was performed 12 months after PTCA; restenosis was defined as greater than or equal to 50% reduction in diameter of the coronary vessel. The series comprised 2 groups: 34 patients (mean age 56 +/- 8 years) with (group A) and 31 (mean age 55 +/- 9 years) without (group B) restenosis. Medical history and laboratory findings were comparable in both groups. In patients with restenosis, IgM-acL were more often increased (9 of 34) than were those in patients without restenosis (2 of 31; p less than 0.05); IgG-acL values did not differ in both groups. Furthermore, there was no correlation between any vascular risk factors or laboratory findings, or both, with both IgM- and IgG-acL levels. Thus, IgM-acL appear to be independent indicators for an increased risk for restenosis after PTCA. Our observations suggest that an autoimmune mechanism may have a role in restenosis.     

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.