Change In Minimal Lumen Diameter Research Articles

Exaggeration of nonculprit stenosis severity during acute myocardial infarction: implications for immediate multivessel revascularization

ObjectivesThis study was designed to assess the prevalence and clinical significance of exaggerated nonculprit lesion stenosis in the setting of acute (<12 h) myocardial infarction (AMI). BackgroundAlthough microvascular spasm may reduce nonculprit artery flow during AMI, it is unknown whether increased tone may exaggerate nonculprit lesion severity. MethodsIn patients with additional angiography within nine months of AMI, and significant nonculprit lesions imaged in matching views, stenosis severity was compared between studies in a random blinded fashion using validated quantitative coronary angiography software. Baseline demographics, medications, hemodynamics at each study, and clinical status at follow-up (infarct/unstable angina/stable angina) were used to determine the independent influence of the infarct presentation on stenosis exaggeration. ResultsFrom 548 patients with AMI (1/99 to 6/01, 321 with multivessel disease), 112 had additional angiography; of these 48 had 59 lesions suitable for analysis. Between infarct and noninfarct angiograms there was a significant change in minimal lumen diameter (1.53 ± 0.51 mm vs. 1.78 ± 0.65 mm, p < 0.001) and percentage stenosis (49.3 ± 14.5% vs. 40.4 ± 16.6%, p < 0.0001) of the nonculprit lesion without significant change in reference segment diameter, which was not predicted by changes in medication or hemodynamics. Twenty-one percent of patients had lesions >50% at AMI that were <50% at non-AMI angiography. Infarct versus noninfarct setting was the only significant independent predictor of change in nonculprit stenosis. ConclusionsSignificant exaggeration of nonculprit lesion stenosis severity occurs at infarct angiography, which may affect revascularization decision making in an appreciable number of patients.

Coronary restenosis elimination with a sirolimus eluting stent; First European human experience with 6-month angiographic and intravascular ultrasonic follow-up

Coronary stenting is limited by a 10%-60% restenosis rate due to neointimal hyperplasia. Sirolimus is a macrocyclic lactone agent that interacts with cell-cycle regulating proteins and inhibits cell division between phases G1 and S1. The hypothesis tested in this study is that local delivery of sirolimus with an eluting stent can prevent restenosis. Fifteen patients were treated with 18 mm sirolimus eluting BX VELOCITY stents. Quantitative angiography and three-dimensional quantitative intravascular ultrasound were performed at implantation and at the 6 months follow-up. All stent implantations were successful. One patient died on day 2, of cerebral haemorrhage and one patient suffered a subacute stent occlusion due to edge dissection (re-PTCA, CKMB 42). At 9 months no further adverse events had occurred and all patients were angina free. Quantitative coronary angiography revealed no change in minimal lumen diameter and percent diameter stenosis and hence no in-lesion or in-stent restenosis. Quantitative intravascular ultrasound showed that intimal hyperplasia volume and percent obstruction volume at follow-up were negligible at 5.3 mm(3)and 1.8%, respectively. No edge effect was observed in the segments proximal and distal to the stents. Implantation of a sirolimus-eluting stent seems to effectively prevent intimal hyperplasia.

Serial quantitative coronary angiography and coronary events

Background Although assessment of progression of atherosclerosis by quantitative coronary angiography (QCA) is used as a surrogate for coronary events, no validation study has compared the several QCA measures used. Methods and Results The Cholesterol Lowering Atherosclerosis Study was a clinical trial testing the efficacy of colestipol-niacin on the progression of coronary atherosclerosis. Baseline/2-year coronary angiograms were obtained on 156 men with prior coronary artery bypass graft surgery. Changes in percent diameter stenosis and minimum lumen diameter (both measured in coronary lesions and segments) and coronary segment measures of average diameter, percent involvement, and vessel edge roughness were measured by QCA. Coronary events ascertained over 12 years of follow-up included myocardial infarction (MI), coronary death, and coronary artery revascularizations. Proportional hazards models evaluated the relation between QCA change measures and coronary events. Changes in percent diameter stenosis and minimum lumen diameter of coronary artery lesions were significantly related to the risk of MI/coronary death. All QCA measures were significantly related to the risk of any coronary event. Relative risks for each QCA measure were of similar magnitude when estimated separately within each treatment group. Change in minimum lumen diameter of lesions was the only measure independently associated with the risk of coronary events. Conclusions All QCA measures of progression of coronary artery disease were related to all coronary events (including revascularizations). Only QCA measures of lesion progression were related to MI/coronary death. QCA measures of lesion change may be better surrogate end points for “hard” coronary events than measures of change in coronary segments. (Am Heart J 2000;139:993-9.)

Use of nitric-oxide-eluting polymer-coated coronary stents for prevention of restenosis in pigs

Restenosis after angioplasty remains an unresolved problem despite an increase in use of coronary stents. It has been theorized that nitric oxide (NO) exerts several actions that can prevent restenosis. These include inhibition of proliferation of smooth muscle cells, prevention of arterial spasms, and decreasing aggregation of platelets in response to exposure to collagen. To determine whether NO coated stents decrease restenosis in a pig balloon injury model. We used coronary stents impregnated with a slow-release precursor of NO in the porcine model of restenosis. Tantalum coil coronary stents (Cordis) were coated with a polymer impregnated with a slow-release precursor of NO. Polymer-coated stents without active precursors were used as controls. Oversized stents were mounted on a delivery balloon and subsequently deployed in the right coronary and left anterior descending arteries of each animal. Repeated recording of angiograms demonstrated that changes in minimum lumen diameter on going from immediately after stenting to 28-day follow-up for the control and NO-eluting-stent groups were similar, namely decreases of 1.89 +/- 0.33 and 2.08 +/- 0.28 mm, respectively. The morphometric results, showing that severe luminal narrowing occurred for both groups, were similar. The percentage area stenoses were 85 +/- 5% for the control group and 84 +/- 6% for the NO-eluting group. Histology demonstrated that profuse formation of neointima and an inflammatory cell infiltrate occurred. Severe diameter stenosis occurred both for control and for treatment groups. The degree of angiographic stenosis was markedly worse than that previously reported for this model. Sustained release of a precursor of NO did not prevent restenosis in this model. This might have been due to a lack of efficacy of nitric oxide or to a profuse and overwhelming stimulatory effect of the polymer in the coated stents.

The Effect of Intracoronary β‐Radiation on Neointimal Formation and Vascular Remodeling in Balloon‐Injured Porcine Coronary Arteries: Effect of Dose Rate

Background: Neointimal formation and vascular remodeling are major mechanisms contributing to coronary restenosis after percutaneous transluminal coronary angioplasty. Intracoronary γ‐ and β‐radiation have been shown to inhibit neointimal formation in balloon‐injured porcine coronary arteries. However, the effects of Intracoronary radiation (ICR) dose and dose rate on vascular remodeling versus inhibition of neointimal formation have not been evaluated. Methods and Results: Forty‐one Hanford Miniature swine were subjected to oversized balloon injury in the left anterior descending and right coronary artery. A spiral centering catheter with perfusion capabilities was placed in the injured segment for circumferentially uniform radiation dose delivery to the vessel wall. Each artery was randomly afterloaded with a dummy wire or an active wire with the 32P source encapsulated in either a short (3 mm) or long (27 mm) segment at the distal end of the wire. The 3‐mm source wire was used to deliver 650, 1,300, and 1,900 cGy while the 27‐mm source wire was used to deliver 1,200 and 3,500 cGy of β‐radiation to the adventitia (∼ 0.5 mm into the vessel wall). The dose rate for ICR varied from 2.5 to 140 cGylsec, depending on the mCi strength of the 32P source at the time of endovascular radiation. One month later, repeat coronary angiography and intravascular ultrasound (IVUS) to measure the external elastic lamina (EEL) area were done. The animals were sacrificed and the coronary vasculature was perfusion fixed. Morphometric, quantitative coronary angiographic, and IVUS analyses were carried out in a blinded fashion. A significant reduction in percent area stenosis (PAS) and neointimal area (NA) was observed on morphometry in coronary arteries treated with 3,500 cGy of β‐radiation. The PAS and NA was 44%± 13% and 0.96 ± 0.25 mm2 in the control groups versus 19%± 14% and 0.30 ± 0.23 mm2 in the 3,500‐cGy group (P &lt; 0.02). There was no significant difference on morphometry between the control and the other four β‐radiationtreated groups. There was no significant improvement in the change in minimum lumen diameter (ΔMLD) between the control and the five radiation‐treated groups. Further analysis of angiographic data revealed that the apparent lack of beneficial effect on angiography was due to significant reductions in lumen diameter in the subgroups of arteries subjected to ICR at a dose rate &gt; 50 cGylsec with the 3‐mm source wire only. The ΔMLD was ‐1.39 ± 0.49, –1.79 ± 0.64, and ‐1.79 ± 0.39 mm in the 650‐, 1,300‐, and 1,900‐cGy groups treated with a dose rate &gt; 50 cGylsec versus ‐0.56 ± 0.95 in control (P &lt; 0.05). This reduction in lumen diameter on angiography was associated with a significant reduction in vessel (EEL) area especially in the groups treated with the 3 mm source at a dose rate &gt; 50 cGylsec. The EEL area was 8.8 ± 1.7, 9.9 ± 1.7, and 8.9 ± 0.6 mm2 in the 650, 1,300, and 1,900 cGy groups treated at a dose rate &gt; 50 cGylsec compared to 11.7 ± 1.6 mm2 in control arteries (P &lt; 0.001). Conclusions: Endovascular β‐radiation at high doses (3,500 cGy to adventitia) and dose rate &lt; 50 cGylsec inhibits restenosis after balloon injury in the porcine model of coronary restenosis. This dose and dose rate is associated with a neutral effect on vascular remodeling. While lower doses of ICR did not worsen the PAS, a reduction in MLD and EEL area were observed. However, this adverse effect on angiographic restenosis and vascular remodeling appears to be largely limited to the subgroups treated at dose rates &gt; 50 cGylsec.

Prospective randomized trial of corticosteroids for the prevention of restenosis after intracoronary stent implantation

Background Inflammatory responses have been implicated as one of the major contributors to neointimal hyperplasia after coronary stenting. The aim of this study was to evaluate the effect of pretreatment with single-dose intravenous methylprednisolone on preventing in-stent restenosis. Methods One hundred and forty consecutive patients for elective coronary stenting (focal, de novo lesion and reference diameter ≥3 mm) were randomly assigned to either a methylprednisolone or a placebo group. Either 1 g methylprednisolone or placebo was intravenously infused 6 to 12 hours before stenting with one of two types of stents. Follow-up angiography was performed at 6 months and clinical evaluation made at regular intervals. Results Baseline characteristics were similar between both groups. Stenting was successful in all patients, and in-hospital events did not occur in any patients. Follow-up angiography was performed in 127 patients (follow-up rate of 91.4%). The minimal lumen diameter increased from 0.86 ± 0.50 mm before intervention to 3.34 ± 0.42 mm after intervention ( P = .02). At follow-up, minimal lumen diameter decreased to 2.14 ± 0.78 mm ( P < .01). Angiographic restenosis rate was 17.5% in the steroid group and 18.8% in the placebo group ( P = .85), with no differences between the 2 types of stent. Clinical follow-up was available in all patients (10.3 ± 2.5 months) and clinical events during the follow-up period were similar in both groups. Conclusions Single-dose pretreatment with intravenous methylprednisolone before coronary stenting had no effect on the change in minimal lumen diameter at a mean follow-up time. (Am Heart J 1999;138:60-3.)

Aggressive cholesterol lowering delays saphenous vein graft atherosclerosis in women, the elderly, and patients with associated risk factors. NHLBI post coronary artery bypass graft clinical trial. Post CABG Trial Investigators.

The NHLBI Post Coronary Artery Bypass Graft trial (Post CABG) showed that aggressive compared with moderate lowering of low-density lipoprotein-cholesterol (LDL-C) decreased obstructive changes in saphenous vein grafts (SVGs) by 31%.1 Using lovastatin and cholestyramine when necessary, the annually determined mean LDL-C level ranged from 93 to 97 mg/dL in aggressively treated patients and from 132 to 136 mg/dL in the others (P<0.001). The present study evaluated the treatment effect in subgroups defined by age, gender, and selected coronary heart disease (CHD) risk factors, ie, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C) <35 mg/dL, and triglyceride serum levels >/=200 mg/dL at baseline. As evidenced by similar odds ratio estimates of progression (lumen diameter decrease >/=0.6 mm) and lack of interactions with treatment, a similar beneficial effect of aggressive lowering was observed in elderly and young patients, in women and men, in patients with and without smoking, hypertension, or diabetes mellitus, and those with and without borderline high-risk triglyceride serum levels. The change in minimum lumen diameter was in the same direction for all subgroup categories, without significant interactions with treatment. Aggressive LDL-C lowering delays progression of atherosclerosis in SVGs irrespective of gender, age, and certain risk factors for CHD.

Effects of intensive lipid lowering by low-density lipoprotein apheresis on regression of coronary atherosclerosis in patients with familial hypercholesterolemia: Japan Low-density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS)

Twenty-five heterozygous familial hypercholesterolemic patients treated with LDL-apheresis and drugs and 11 patients treated with drugs underwent follow-up angiography 2.3 years later. One-hundred thirteen lesions were measured by quantitative angiography. Mean LDL-cholesterol levels during the trial were 140±34 mg/dl in the apheresis group and 170±58 mg/dl ( P<0.05) in the control group. The mean changes in minimal lumen diameter of lesions were +0.19±0.30 mm (improved) in the apheresis group ( n=76) and −0.44±0.40 mm (worsened) in the control group ( n=37) ( P<0.0001). When progression and regression were defined as a change in minimal lumen diameter of ±0.67 mm, in the apheresis group, two (8%) patients had progression, 19 (76%) stayed unchanged and four (16%) had regression, but in the control group seven (64%) patients had progression and four (36%) stayed unchanged. The frequency of regression or no change was significantly higher in the apheresis group than in the control group ( P<0.004). Intensive cholesterol lowering therapy with LDL-apheresis and lipid lowering drugs can achieve a substantial decrease in LDL-cholesterol levels to induce regression of coronary lesions in familial hypercholesterolemic patients with advanced coronary artery disease.

Histopathological Correlates of Early Arterial Recoil following Directional Coronary Atherectomy

Elastic recoil has been implicated in the pathophysiology of restenosis after conventional balloon angioplasty alone. Directional atherectomy may attenuate arterial recoil by removing the internal elastic lamina and medial smooth muscle cells and altering the vessel wall architecture. This study sought to evaluate early recoil after directional atherectomy and its relation with excision of deep arterial wall structures. We prospectively evaluated the correlation of the histopathologic evidence of media or adventitia as assessed in the atheroma retrieved during the procedure with the early changes in minimal lumen diameter after directional atherectomy followed by adjunct balloon dilatation in 50 consecutive cases. Recoil was assessed by routinely performed 1- and 15-min postprocedure angiograms, and patients were divided into two groups according to the absence (group I, n = 26) or presence (group II, n = 24) of recoil. The mean changes in minimal luminal diameter between 1 and 15 min was +0.22 mm in group I and –0.14 mm in group II. The absence of recoil was strongly associated with evidence of media tissue in the pathologic analysis as compared with cases with recoil (42 vs. 18%, respectively; p = 0.02). Similarly, retrieval of adventitia was seen exclusively in the group without recoil (15 vs. 0%; p = 0.06). Vessels that underwent recoil had significantly larger reference and immediate postprocedure minimal luminal diameters (3.62 ± 0.57 and 3.02 ± 0.45 mm, respectively) as compared with arteries with no recoil (3.28 ± 0.35 and 2.75 ± 0.43 mm, respectively; p < 0.05 for both). Therefore, early luminal changes, likely related to elastic recoil, correlated with excision of deep wall structures during directional atherectomy. Arteries that showed recoil were larger, possibly due to thicker muscular layer and/or larger plaque burden as compared with arteries that did not recoil. Thus, optimal tissue debulking during directional atherectomy appears to attenuate recoil, providing an additional insight into the mechanism of action of this percutaneous revascularization device.

Effects of Fluvastatin on Coronary Atherosclerosis in Patients With Mild to Moderate Cholesterol Elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained ≥160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (± cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, ΔMLD −0.028 versus −0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, ΔMLD −0.024 versus −0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

Retardation of coronary atherosclerosis: the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and other angiographic trials.

A large number of both primary and secondary preventive trials suggest that treatment of elevated plasma lipids may reduce the frequency of coronary heart disease (CHD) events. Meta-analyses indicate that for every 10% reduction of cholesterol, CHD mortality is lowered by 13% and all-cause mortality by 10%. Experience from several angiographic trials also suggests that coronary atherosclerosis can be retarded, and in some instances limited regression induced, by low-density lipoprotein (LDL)-cholesterol reduction and/or high-density lipoprotein (HDL)-cholesterol elevation. Coronary angiographic studies have shown that although the effects on retardation/regression of altherogenic lesions have been small, with luminal diameter changes of around 0.10 mm, the effects on clinical events were more substantial, with reductions of the order of 50%. There is also evidence that it is the mild and moderate lesions that are of particular concern with respect to the occurrence of clinical coronary events. The progression of atherosclerosis and the occurrence of coronary events are probably not exclusively dependent on a lowering of LDL-cholesterol concentrations. Analyses from the Monitored Atherosclerosis Regression Study (MARS), the Cholesterol Lowering Atherosclerotic Study (CLAS), and the Programs on the Surgical Control of the Hyperlipidaemias (POSCH) indicate that triglyceride-rich lipoproteins may also be of importance for the progression of mild/moderate lesions in subjects treated with cholesterol-lowering regimens. Recently, the results of the 5-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) demonstrated that bezafibrate significantly retarded the progression of coronary atheroma and coronary events in young male survivors of myocardial infarction, as assessed by changes in minimum lumen diameter. This positive outcome is most likely due to the beneficial treatment effects on the levels of serum triglycerides (-31%), plasma fibrinogen (-12%), and HDL cholesterol (+9%). The results of the BECAIT on progression of coronary atherosclerosis are comparable with those of two recent angiographic trials with HMG-CoA reductase inhibitors, the Multicenter Anti-Atheroma Study (MAAS), and the Regression Growth Evaluation Statin Study (REGRESS), despite different lipid and metabolic effects. BECAIT is the first controlled angiographic study to show that a fibrate can significantly retard the progression of coronary atherosclerosis. The exact mechanisms by which this occurs remain to be elucidated. However, the results of BECAIT illustrate the importance of factors other than LDL cholesterol in the progression of coronary atherosclerosis.

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): Design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35–75 years of age with low-density lipoprotein (LDL) cholesterol of 115–190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30–75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8 mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.

High dose rate intracoronary radiation for inhibition of neointimal formation in the stented and balloon-injured porcine models of restenosis: Angiographic, morphometric, and histopathologic analyses

Purpose : We examined the effects of intracoronary irradiation delivered at a high dose rate on neointimal hyperplasia after injury induced by tow methods: balloon overstretch injury, and stent implantation in a porcine model of coronary restenosis. Methods and Materials : In 34 Hanford maniature swine, a segment of each coronary artery was targeted for injury and treatment. Teh artery segments were treated with 192Ir at doses of 10 Gy over 4 min (eight animals), 15 Gy over 6 min (nine animals), 25 Gy over 10 min (nine animals) or control (siulation wire only; eight animals). The treated segments were subjected to stent implantation (left anterior descending and right coronary artery) or balloon overstretch (circumflex) injury. Twenty-eight days later, repeat coronary angiography and sacrifice were done. Quantitative coronary angiography, morphometry, and extensive histopathologic analyses were carried out in a blinded fashion. Results : The change in minimal lumen diameter from postinjury to presacrifice in the stent-injured left anterior descending was -0.79 ± 0.34 (mean: ± SD) mm in the control group, compared to -0.43 ± 0.35 mm in the 15 Gy ( p = 0.04) and -0.21 ± 0.50 mm in the 25 Gy ( p = 0.01) groups; and in the balloon-injured circumflex was -0.31 ± 0.22 mm in the control group compared to -0.03 ± 0.18 mm in the 10 Gy ( p = 0.05) and 0.00 ± 0.33 in the 15 Gy ( p = 0.01) groups. Percent area stenosis in the left anterior descending was 36 ± 9% in the control group compared to 18 ± 12% in the 15 Gy ( p = 0.003) and 11 ± 11% in the 25 Gy ( p < 0.001) groups; and in the circumflex was 16 ± 10% in the control groups, compared to 5 ± 5% in the 15 Gy ( p = 0.02) and 2 ± 2% in the 25 Gy ( p = 0.009) groups. Histopathology showed a striking reduction in the amount of neointima in the irradiated arteries compared with control vessels. other radiation effects were stromal fibrin exudate, thinning of the media, and adventitial fibrosis and leukocyte infiltration in the radiated arterial segments. Conclusions : High dose rate intracoronary irradiation with 192Ir effectively inhibits intimal proliferation after stent-induced as well as balloon-overstretch injury. This shorter treatment time (4 to 10 min) may provide a clinically practical approach to the prevention of restenosis after angioplasty.

TIMI Frame Count

Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7 +/- 3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2 +/- 2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4 +/- 3.0) and circumflex counts (22.2 +/- 4.1, P < .001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90 minutes after thrombolytic administration followed a continuous unimodal distribution (there were not subpopulations of slow and fast flow) with a mean value of 39.2 +/- 20.0 frames, which improved to 31.7 +/- 12.9 frames by 18 to 36 hours (P < .001). No correlation existed between improvements in CTFCs and changes in minimum lumen diameter (r=-.05, P=.59). The mean 90-minute CTFC among nonculprit arteries (25.5 +/- 9.8) was significantly higher (flow was slower) compared with arteries with normal flow in the absence of acute MI (21.0 +/- 3.1, P < .001) but improved to that of normal arteries by 1 day after thrombolysis (21.7 +/- 7.1, P=NS). The CTFC is a simple, reproducible, objective and quantitative index of coronary flow that allows standardization of TIMI flow grades and facilitates comparisons of angiographic end points between trials. Disordered resistance vessel function may account in part for reductions in flow in the early hours after thrombolysis.

Contributions of frequency distribution analysis to the understanding of coronary restenosis. A reappraisal of the gaussian curve.

Clinical restenosis after balloon angioplasty can be categorized by use of dichotomous terms based on the presence or absence of recurrent myocardial ischemia. In contrast, recent investigations have concluded that late luminal renarrowing, documented through angiographic imaging, occurs to a variable extent in nearly all stenoses. This process has been characterized by a gaussian or normal frequency distribution, with restenosis simply representing an extreme form of this delayed remodeling. In the current study, frequency distribution analysis was used to examine the process of coronary restenosis in a large cohort of patients at risk. Quantitative coronary angiographic analysis was applied to 9279 cineangiograms obtained in 3093 patients before and immediately after angioplasty and after 6-month follow-up. Late loss, defined as the change in minimum lumen diameter of the target stenosis from postdilation to follow-up, did not statistically conform to a normal distribution (P<.0001 by both chi2 statistic and Kolmogorov-Smirnov test), even after the exclusion of the 236 stenoses that displayed total occlusions at follow-up angiography. Examination of deviation from a normal curve revealed an excessively high frequency of stenoses that experienced either little change (0.0+/-0.3 mm) or marked change (1.0 to 2.0 mm) in late loss, with a low frequency of stenoses with intermediate values (0.3 to 1.0 mm). Similarly, although the distribution of percent diameter stenosis of the target lesion was statistically normal immediately after dilation, this gaussian distribution disappeared during the follow-up period. Other angiographic indexes of restenosis also failed to approximate a normal curve. In an attempt to improve the goodness of fit, a probabilistic model of late loss was created on the basis of deconvolution of the observed data distribution. Two theoretical, discrete populations of stenoses were identified, one with and one without overall late luminal narrowing. Unlike the gaussian distribution, this model provided a good representation of the observed data (P=NS for lack of fit). The frequency distributions of angiographic indexes of restenosis often superficially resemble a gaussian curve, an appearance that is artifactually enhanced by the measurement imprecision of current quantitative techniques. Nevertheless, standard indexes of coronary restenosis fail to conform statistically to a normal distribution. The pattern of deviations observed supports the possible existence of discrete subpopulations of lesions, each with a different propensity toward the development of restenosis after coronary intervention.

Familial Hypercholesterolaemia Regression Study: a randomised trial of low-density-lipoprotein apheresis

Low-density-lipoprotein (LDL) apheresis has the theoretical advantage over anion-exchange resins and hydroxy-methylglutaryl coenzyme A inhibitors of decreasing lipoprotein(a) as well as LDL. To confirm this advantage, patients with heterozygous familial hypercholesterolaemia and coronary artery disease were randomised to receive LDL apheresis fortnightly (with disposable dextran sulphate/cellulose columns) plus simvastatin 40 mg daily, or colestipol 20 g plus simvastatin 40 mg daily. Quantitative coronary angiography was repeated after a mean of 2·1 years in 20 patients undergoing apheresis and in 19 on combination drug therapy. Changes in serum lipoproteins were similar in both groups apart from greater lowering by apheresis of LDL cholesterol (3·2 vs 3·4 mmol/L in drug group, p=0·03) and lipoprotein(a) (geometric means 14 vs 21 mg/dL, p=0·03). There were no significant differences in primary angiographic endpoints per patient but lesion-based and segment-based secondary endpoints were biased in favour of the drug group (change in minimum lumen diameter of lesions 0·07 vs -0·004 mm, p=0·046; change in mean lumen diameter of segments 0·02 vs -0·06 mm, p=0·01). None of the angiographic changes correlated with lipoprotein(a) concentrations. Per patient changes in % diameter stenosis and minimum lumen diameter in the two groups were as or more favourable than those observed in five published trials that assessed lipid-lowering drug therapy by quantitative coronary angiography. Although LDL apheresis combined with simvastatin was more effective than colestipol plus simvastatin in reducing LDL cholesterol and lipoprotein(a), it was less beneficial in influencing coronary atherosclerosis and should be reserved for patients unresponsive to drugs. Decreasing lipoprotein(a) seems to be unnecessary if LDL cholesterol is reduced to 3·4 mmol/L or less.

951-70 Absence of Bleeding and Subacute Occlusion After Palmaz-Schatz Coronary Stenting Using a New Antithrombotic Regimen

Subacute thrombotic occlusion and bleeding complications related to antithrombotic therapy are the major limitations of elective coronary stenting. The effectiveness of a new antithrombotic regimen without full early anticoagulation to prevent these complications has been evaluated in 52 consecutive pts (62 ± 11 years, 82% male) who underwent elective Palmaz-Schatz stenting in 58 lesions. Four lesions were restenotic and 3 lesions were located in venous graft. The mean reference diameter was 3.3 ± 0.6 mm, with a mean diameter stenosis of 71 ± 9%. Intravenous heparin was given only during the procedure. After stenting, the pts were treated with aspirin, dipyridamole, dextran, warfarin and subcutaneous low molecular weight heparin (LMWH) [enoxaparine, 40 mg/day]. LMWH was started 6 h after stenting and stopped when an INR of 2–3 was achieved, The aPTI and the INR were determined daily before discharge. In all pts, serial quantitative angiographic follow-up (FU) study was performed at 24 hours, 30 days and 6 months after stenting. Optimal angiographic stent result was achieved in 98% of the lesions, and minimal lumen diameter (MLD) increased from 1.2 ± 0.4 to 3.6 ± 0.5 mm (p &lt; 0.001). The aPTI remained normal (mean: 32 ± 5.6 sec, range: 24 to 48 sec) during LMWH administration; and an INR &gt;2 was achieved 3 days after intervention in 94% of stented pts. Neither an event (myocardial infarction. coronary surgery or death) nor major bleeding occurred during the first month. At 24 hand 1 month angiographic FU, all stented lesions remained patent, with no significant changes in MLD. At 6 months FU, all stented arteries remained patent, MLD decreased significantly to 2.5 ± 0.8 mm (p &lt; 0.001), and a restenosis rate of 23% (95% CI: 13–36%) of stented lesions (stenosis ≥50% criteria) was observed. These data suggest that, after elective stenting with optimal angiographic result, the initial combination of LMWH (with no significant effect on aPTT) plus anti platelet therapy, followed by anticoagulation with coumadin, prevent subacute occlusion and bleeding complications, without detrimental effect on previous reported restenosis rate.

Morphologic changes during follow-up after successful percutaneous transluminal coronary balloon angioplasty: Quantitative angiographic analysis in 778 lesions—further evidence for the restenosis paradox

The purpose of this study was to determine if there are any morphologic characteristics of lesions that renarrow (that is, restenotic lesions) following successful coronary balloon angioplasty that are different from their appearance pretreatment or from the appearance of nonrestenotic lesions that might provide some new insight into the restenosis phenomenon. The study population consisted of 653 patients (778 lesions) with 6 months of angiographic follow-up (94% angiographic follow-up rate) who were participating in the Multicenter European Research trial with Cilazapril after Angioplasty to prevent Transluminal coronary Obstruction and Restenosis (MERCATOR) study. Detailed quantitative angiographic measurements, including the mean diameter of the vessel segment (in millimeters) that was subjected to balloon dilation, were performed preangioplasty, postangioplasty, and at follow-up using the cardiovascular angiographic analysis system to provide some objective measurement of the actual extent of luminal changes in the months following coronary balloon angioplasty. Two different approaches for restenosis were used: (1) static criterion of >50% diameter stenosis at follow-up and (2) dynamic criteria of ≥0.40 or ≥0.72 mm change in minimal lumen diameter between postangioplasty and follow-up. Both approaches identified more severe stenosis to be a typical feature for restenotic lesions before angioplasty compared with nonrestenotic lesions. No differences were observed in lesion length, balloon-inflated vessel segment, or roughness index before angioplasty between the groups. Conflicting data were found for the amount of atherosclerotic plaque, symmetry index, and curvature index. The restenotic lesion at follow-up compared with its initial appearance gave conflicting results depending on which approach was used. The dynamic criteria illustrate that the reference diameter and the mean diameter of the entire segment dilated are reduced during follow-up. Two messages emerge from the study: (1) the restenosis process clearly involves the apparent normal vessel wall adjacent to the actual lesion, probably in response to the unavoidable injury caused by balloon dilatation and (2) the use of percentage diameter stenosis measurements depending on the assumptions of normality for a reference segment will therefore underestimate the true extent of the restenosis process and should be replaced in clinical angiographic studies by absolute luminal measurements.

Restenosis after directional coronary atherectomy and balloon angioplasty: Comparative analysis based on matched lesions

Objectives. Late lumen narrowing after directional coronary atherectomy was assessed by quantitative coronary angiography and compared with that after balloon angioplasty.Background. Directional coronary atherectomy has been introduced as an alternative technique for balloon angioplasty and may reduce the incidence of restenosis.Methods. A prospectively collected consecutive series of 87 native coronary artery lesions successfully treated with atherectomy were matched with 87 coronary artery lesions selected from a consecutive series of lesions that had been successfully dilated by balloon angioplasty. Late angiographic analysis was performed in 158 lesions. The net gain index represents the ultimate gain in minimal lumen diameter at follow-up study, normalized for the vessel size. This index is the result of the relative gain attained during the procedure (the ratio of the change in minimal lumen diameter and reference diameter) and the relative loss observed during the follow-up period (the ratio of the change in minimal lumen diameter during the follow-up period and the reference diameter).Results. Matching for clinical and angiographic variables resulted in two comparable groups with similar baseline stenosis characteristics. Atherectomy resulted in a more pronounced increase in minimal lumen diameter than did balloon angioplasty (mean ± SD 1.17 ± 0.29 to 2.44 ± 0.42 mm vs. 1.21 ± 0.38 to 2.00 ± 0.36 mm, p < 0.001). However, this favorable immediate result was subsequently lost during late angiographic follow-up, so that the minimal lumen diameter at follow-up and the net gain index did not differ significantly between the two groups (1.76 ± 0.62 vs. 1.77 ± 0.59 nun, p = 0.93, and 0.18 ± 0.19 vs. 0.17 ± 0.17, p = 0.70). Consequently, ths relative gain and relative loss were higher in the atherectomy group. For both techniques, the relative gain was linearly related to the relative loss but the slope of the regression line was steeper for atherectomy, suggesting that the relative loss in the atherectomy group is proportionally even larger for a given relative gain compared with that in the angioplasty group.Conclusions. In matched groups of patients, atherectomy induces a greater initial gain in minimal lumen diameter than does balloon angioplasty. However, the vascular wall injury induced by the device is of a different nature (debulking vs. dilating) that leads to more relative loss over the follow-up period in the atherectomy group.

Enalapril in the prevention of restenosis following intracoronary intervention in a swine model.

Restenosis following percutaneous transluminal coronary angioplasty continues to be a major limitation of the procedure. To test whether an angiotensin-converting enzyme inhibitor may reduce restenosis, this study utilized an atherosclerotic, stented, Hanford miniature swine model of restenosis. Each animal first was started on an atherogenic diet and had balloon abrasion of the left anterior descending and right coronary arteries. Four months later, balloon-mounted coil stents were placed into the abraded coronary arteries of each animal. Twenty-four animals then were randomly assigned to one of two groups: enalapril, and control. The enalapril group received 50 mg orally twice daily starting 1 week before intracoronary stenting. Follow-up 2 months later revealed angiographic stenosis in the control group of 30% +/- 13%/25% +/- 10% (left anterior descending/right coronary artery) versus 37% +/- 9%/20% +/- 11% in the enalapril group (P = not significant). The change in minimal lumen diameter from immediately after stenting to follow-up was not significantly different between control and enalapril groups. Area stenosis and maximal intimal thickness obtained by morphometric analysis were also compared, and the mean percentage area stenosis for the control group was 39 +/- 12%/31% +/- 16% and for enalapril 36% +/- 14%/35% +/- 19%. The maximal intimal thickness in the control group was 573 microns +/- 204 microns/605 microns +/- 266 microns and in the enalapril group 530 microns +/- 220 microns/424 microns +/- 237 microns. There was no statistical difference. Enalapril fails to reduce restenosis in this animal model.