Serial Quantitative Coronary Angiography Research Articles

Decrease in LDL-C is associated with decrease in all components of noncalcified plaque on coronary CTA

Background and aimsLDL-C reduction has been associated with a decrease in noncalcified plaque (NCP) by serial quantitative coronary CT angiography (CTA). We evaluated the effect of LDL-C reduction on specific components of noncalcified plaque (NCP). MethodsWe analyzed 154 patients undergoing serial CTAs (118 men, 60 ± 10 years, interval 4 ± 2 years) with baseline LDL-C≥70 mg/dl. Semi-automated software was used for quantifying plaque components based on CT attenuation in Hounsfield units (HU): 30-75, low attenuation plaque (LAP); 76–130, medium-low attenuation plaque (MLAP); 131–350, medium attenuation plaque (MAP); >350, calcified plaque (CP). Decrease in LDL-C was defined as a reduction >10% of baseline LDL-C. Plaque volume changes were compared between patients with (n = 85) and without (n = 69) LDL-C decrease. ResultsThere was interval reduction in total plaque, LAP, MLAP, and MAP volumes in patients with LDL-C decrease vs. patients without LDL-C decrease before and after adjusting for differences between the two groups (all p ≤ 0.001). An increase in CP volume occurred in both groups (p = 0.42). ConclusionsDecrease in LDL-C was associated with reduction in all components of NCP measured by quantitative CTA. Change in total NCP volume may be the optimal measurement for assessing changes over time of coronary plaque on CTA.

The natural course of nonculprit coronary artery lesions; analysis by serial quantitative coronary angiography

BackgroundNonculprit lesions are the major cause of future cardiovascular events. However, the natural course of nonculprit lesions and angiographic predictors of plaque progression are not well-studied. The purpose of our study was to observe the natural course of nonculprit lesions, and to identify predictors of unanticipated future events and angiographic progression in nonculprit lesions.MethodsWe analyzed 640 nonculprit lesions with a length of ≥2 mm and luminal narrowing ≥30% from 320 patients who had two serial angiographic follow-ups; 9 to 13 months post-PCI and 24 months post-PCI. The study endpoints were nonculprit-ischemia driven revascularization (IDR) and the rate of diameter stenosis (DS) progression. Those with progression of DS > 12%/year were defined as ‘rapid progressors’.ResultsDuring the median follow-up period of 737 days, 20 lesions in 20 patients (6.3%) required nonculprit-IDR. Independent predictors of nonculprit-IDR were diabetes (hazard ratio [HR] 2.93, 95% confidence interval [CI] 1.072–8.007, p = 0.036) and lesion type B2/C (HR 4.017, 95% CI 1.614–9.997, p = 0.003). The presence of one or both of the two major risk factors was associated with significant DS progression (3.0 ± 6.8% vs. 3.5 ± 6.1% vs. 6.8 ± 9.9% for lesions with 0, 1 and both risk factors, p < 0.001). Among the 640 lesions, 38 lesions (5.9%) in 33 patients were rapid progressors, while risk factors of rapid progressors included lesion type B2/C as a lesion-related risk factor (HR 1.998, 95% CI 1.006–3.791, p = 0.048) and diabetes mellitus as a patient-related risk factor (HR 3.725, 95% CI 1.937–7.538, p < 0.001). Lesions with both risk factors (type B2/C lesions in diabetic patients) were at the highest risk of rapid progression (odds ratio 3.250, 95% CI 1.451–7.282), compared to type A/B1 lesions in non-diabetic patients.ConclusionNonculprit-IDR was not uncommon during the 2-year follow up period in our population. The major risk factors of nonculprit lesion progression were diabetes and lesion type B2/C.Trial registrationRetrospectively registered and approved by the institutional review board of Seoul National University Hospital (No.: 1801–138-918) on February 2nd, 2018.

Three-Year Clinical and Angiographic Outcomes After Everolimus-Eluting Stent Implantation in Patients With a History of Coronary Artery Bypass Grafting.

The clinical and angiographic outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stent (EES) implantation in patients with a history of coronary artery bypass grafting (CABG) have yet to be fully investigated. The aim of the present study was to investigate 3-year clinical outcomes after EES implantation in patients with a history of CABG.We retrospectively enrolled 176 consecutive patients who had undergone EES implantation. Three-year clinical follow-up data were obtained from all patients. Follow-up angiograms and serial quantitative coronary angiography analysis (QCA) were performed for 139 (79.0%) patients. Patients from the prior CABG (+) group (n = 17; 9.7%) had higher incidences of target lesion revascularization (TLR; 41.2% versus 3.8%, P < 0.001) and major adverse cardiac events (47.1% versus 15.1%, P = 0.004). A landmark analysis conducted 1 year into our study showed a higher incidence of TLR in the prior CABG (+) group (20.0% versus 3.0%, P = 0.017).The reason for EES implantation in the prior CABG (+) group was saphenous vein graft (SVG) failure in 19 (79.2%) lesions, although the target vessel was the SVG in 8 (33.3%) lesions. There were no significant differences in clinical and follow-up QCA data between the native vessel and SVG PCI groups.This study revealed that a history of CABG was a risk factor for TLR after EES implantation. The major reason for PCI after CABG was SVG failure; both native vessel and SVG PCI showed poor outcomes. Further investigations may be warranted to determine which interventions are most effective in this high-risk subset.

The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study

The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments. In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (-0.25 mm, 95% CI -0.36 to -0.17 mm) when compared with patients without NA (-0.13 mm, 95% CI -0.17 to -0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years. In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms.SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT00617084.

TCT-239 Impact Of Overlapping Site On 9 Month Angiographic Results After Multiple Overlapping Everolimus-eluting Stents Implantation: A Serial Quantitative Coronary Angiography Analysis

In the era of drug-eluting stents, multiple overlapping stents was performed more than 10% of patients with diffuse coronary artery diseases. However, correlation between the location of overlapping site and 9 month follow-up (FU) minimum lumen diameter (MLD) site after multiple overlapping

Does “late catch-up” exist in drug-eluting stents: Insights from a serial quantitative coronary angiography analysis of sirolimus versus paclitaxel-eluting stents

Recent studies have suggested the possibility of late catch-up after drug-eluting stent implantation. There are limited data on whether late catch-up exists in sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs). Consecutive patients were routinely recommended 2 serial angiographic follow-ups (at 6-9 and 18-24 months post-percutaneous coronary intervention). A serial quantitative coronary angiographic analysis was performed in lesions not receiving target lesion revascularization at first follow-up. Early luminal loss (LL) was defined as the difference in minimal luminal diameter between the first angiographic follow-up and immediate post-percutaneous coronary intervention, and delayed LL was defined as the difference in minimal luminal diameter between the second and first angiographic follow-up. Four hundred twelve lesions in the main cohort (PES 128, SES 284) and 47 lesions in the secondary hybrid cohort (PES 23, SES 24), which received serial angiographic follow-ups without target lesion revascularization, were included. In the main cohort, early LL was higher in PES compared with SES (0.56 vs 0.20 mm, P < .01), whereas delayed LL occurring after the first angiographic follow-up was higher in SES (0.10 vs 0.28 mm, P < .01), suggesting more prominent late catch-up in SES. Early LL showed better correlation with total LL (correlation coefficient 0.82 vs 0.30) in PES, whereas delayed LL showed better correlation with total LL (correlation coefficient 0.42 vs 0.91) in SES. Such observations were reproducible in the hybrid cohort, where both SES and PES were implanted at index procedure. Late catch-up occurs in both PES and SES with greater delayed late loss in SES. Our data suggest that the process of neointima formation after SES and PES implantation may follow a slightly different timeline.

TCT-398: Does ‘Late Catch-Up’ Exist in Drug Eluting Stents? Insights from a serial quantitative coronary angiography analysis

TCT-398: Does ‘Late Catch-Up’ Exist in Drug Eluting Stents? Insights from a serial quantitative coronary angiography analysis

Stents liberadores de sirolimus com e sem cobertura polimérica: análise seriada com angiografia e ultrassom intracoronariano tridimensional

INTRODUÇÃO: A presença de polímeros sintéticos em contato com a parede vascular tem sido associada a intensa resposta inflamatória local e a eventos adversos tardios. Entretanto, sua ausência pode comprometer a eficácia dos stents farmacológicos em suprimir a hiperplasia intimal. Avaliamos, com angiografia coronariana quantitativa (ACQ) e ultrassom intracoronariano (USIC), a eficácia do stent VestasyncTM (VES), liberador não-polimérico de sirolimus em baixa dose (55 µg), e do stent CypherTM (CYP), liberador de sirolimus polimérico em alta dose (140 µg). MÉTODO: Quinze pacientes com lesões primárias < 14 mm, em artérias coronárias nativas de 2,5 mm a 3,5 mm, foram tratados com VES e comparados a uma coorte histórica de 15 pacientes tratados com CYP. ACQ e USIC foram realizados pós-procedimento, aos 4 e 12 meses. Desfechos primários foram: perda tardia intrastent e porcentual de obstrução volumétrica intrastent. RESULTADOS:As características clínicas eram semelhantes. O grupo VES tinha vasos menores (2,67 ± 0,32 mm vs. 2,98 ± 0,4 mm; P = 0,02). Aos 4 meses, o grupo VES mostrou tendência a maior perda tardia intrastent (0,30 ± 0,25 mm vs. 0,10 ± 0,3 mm; P = 0,06), mas porcentual de obstrução volumétrica intrastent similar ao do grupo CYP (2,8 ± 2,2% vs. 2,2 ± 3,8%; P = 0,60). Aos 12 meses, a perda tardia intrastent foi de 0,37 ± 0,24 mm no grupo submetido a implante de stent VES vs. 0,16 ± 0,36 mm no grupo submetido a implante de stent CYP (P = 0,074), e o porcentual de obstrução volumétrica intrastent foi de 4,0 ± 2,2% no grupo que recebeu stent VES vs. 2,4 ± 3,9% no grupo que recebeu stent CYP (P = 0,17). Não houve casos de reestenose binária. CONCLUSÕES: O stent VES mostrou-se seguro e eficaz em suprimir a hiperplasia intimal até 12 meses. Ausência do polímero e dosagem reduzida da droga não comprometeram sua eficácia. Estudos maiores e com seguimento mais longo são necessários para avaliar se esses achados melhorarão o perfil de segurança dos stents farmacológicos.

Response to Letters Regarding Article, “Effect of Rosuvastatin Therapy on Coronary Artery Stenoses Assessed by Quantitative Coronary Angiography: A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound–Derived Coronary Atheroma Burden”

We thank Dr Kaneda and Drs Sutton, Blumenthal, and Kapur for their interest and commentaries on our analysis.1 In response to Dr Kaneda’s request for sensitivity analyses, we applied the same conservative assumptions employed in the intravascular ultrasound (IVUS) analysis2 to all noncompleters and to those with ischemic events and found that statistically significant regression occurred in both percentage diameter stenosis (%DS) and minimum lumen diameter. With regard to the assessment of disease progression, as in previous quantitative coronary angiography (QCA) studies that we referenced,3 the prespecified outcome variable was the change in baseline stenoses >25%. This is very reasonable because some studies have shown that only progression of stenoses present at baseline was predictive of coronary events.4 In A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound–Derived Coronary Atheroma Burden (ASTEROID), 379 of the 507 randomized patients (75%) had both a baseline and a follow-up QCA study. Sixteen of these patients (4.2%) developed a new lesion of >25% stenosis that represented an increase of at least 20% from baseline. Of those 379 patients, the 292 (77%) with baseline …

Sirolimus-Eluting Stents Suppress Neointimal Formation Irrespective of Metallic Allergy

Metallic allergy is associated with restenosis following bare metal stent implantation, but the impact of metallic allergy on the outcome after implantation of drug-eluting stents (DES) has not been investigated. The present study group consisted of 88 consecutive patients (109 lesions) who underwent percutaneous coronary intervention with sirolimus-eluting stents (SES). Follow-up angiography was obtained at 8 months in all patients. At that time, the patients underwent epicutaneous patch tests for nickel, chromate, molybdenum, manganese, and titanium, which were evaluated after 48 h of contact. The patch test was positive in 14 patients (16%) (5 for manganese, 3 for nickel, 1 for chromate, 1 for Nickel and manganese, and 4 for manganese and chromate). The binary restenosis rate in the patients with a positive patch test was similar to those with negative patch test (6.3% vs 6.5%, p=0.98). Serial quantitative coronary angiography analyses identified no significant differences in late lumen loss of in-stent segments between patients with positive patch test and those with negative patch test (0.19+/-0.49 mm vs 0.12+/-0.48 mm, p=0.55). SES prevent restenosis irrespective of metallic allergy. The classic relationship between metallic allergy and in-stent restenosis, seen with bare metal stents, does not appear to arise with DES, possibly because of the immunosuppressive effect of sirolimus.

Accelerated vascular repair following percutaneous coronary intervention by capture of endothelial progenitor cells promotes regression of neointimal growth at long term follow-up: final results of the Healing II trial using an endothelial progenitor cell capturing stent (Genous R stent)™

The study sought to define the long-term angiographic and clinical outcome of a bio-engineered stent, able to sequester endothelial progenitor cells (EPC) to the stent to promote the post-stenting vascular repair response. The HEALING-II was a multicentre, prospective registry, including 63 patients treated with the implantation of a Genous EPC capture stent. Serial quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) analysis was performed at 6 and 18 month. The 18 month composite MACE rate was 7.9%, whereas 6.3% clinically justified target lesion revascularisations were observed. Although patients received one month of clopidogrel, no (sub)acute or late angiographic stent thrombosis occurred. At 6 month follow-up, in-stent late luminal loss was 0.78+/-0.39 mm and percent in-stent volume obstruction was 22.9+/-13.7% (mean+/-sd). Serial angiographic and IVUS analyses were available in 30 event-free patients at post-procedure, 6 months and 18 months. From 6 months to 18 months follow-up, a significant late regression of neointimal hyperplasia was observed on QCA (late luminal loss 0.59+/-0.31, 24.4% reduction or 16.9% by matched serial analysis) and IVUS (percent in-stent volume obstruction 20.3+/-14.3%, 11.4% reduction or 9.6% by matched serial analysis). The relative increase in circulating EPC titers at long-term follow-up correlated with neointimal compaction in individual patients, suggestive of an EPC-mediated vascular repair response. The HEALING II study suggests that the EPC capture stent, aimed to stimulate the coronary vascular repair response, significantly promotes late regression of neointimal hyperplasia up to 18 months after stent implantation.

Restenosis and Stent Fracture Following Sirolimus-Eluting Stent (SES) Implantation A Serial Quantitative Coronary Angiography (QCA) and Intravascular Ultrasound (IVUS) Study

Restenosis still occurs, even with the sirolimus-eluting stent (SES), and the precise mechanisms and the impact of stent fracture on restensosis have not yet been elucidated. Intravascular ultrasound (IVUS)-guided SES implantation was performed in 184 lesions in 151 patients with stable and unstable angina. Serial (pre-, post- and follow-up) quantitative coronary angiography analysis was obtained in 169 lesions in 138 patients (angiographic follow-up rate: 91%) and 12-month clinical follow-up was done in all patients. Restenosis occurred in 13 (7.7%) of 169 lesions. Stent fracture occurred in 4 (2.4%) of 169 lesions at follow-up. Of the 13 restenotic lesions, 8 had intimal hyperplasia, 4 had stent fracture, and 1 had late stent thrombosis at 7 months. Although multivariate logistic regression analysis revealed that minimal lumen area (min-LA) post (p=0.027), total stent length (p=0.003) and diabetes (p=0.032) were significant independent predictors of restenosis, univariate analysis showed that stent fracture was more common in the restenosis than in the non-restenosis groups (p=0.001). Although min-LA post by IVUS, total stent length by QCA and diabetes are independent predictors for angiographic restenosis, stent fracture occurred in 4 lesions (2.4%) and all of them resulted in restenosis (31% of the restenosis). The impact of stent fracture and its potential role in the development of restenosis deserves further study.

Nocturnal Oxygen Desaturation as a Predictive Risk Factor for Coronary Restenosis After Coronary Intervention Serial Quantitative Coronary Angiography Study

Sleep-disordered breathing may affect coronary artery disease, so patients treated by percutaneous transluminal coronary angioplasty were studied to investigate the relationship between nocturnal oxygen desaturation (NOD) and the loss index. The nocturnal oxygen desaturation index (ODI) was determined by means of a pulse oximeter in 35 patients with coronary artery disease treated by stent placement. The patients were divided into 3 groups according to ODI: <5 events/h (group N, n=6), between 5 and 14 events/h (group A, n=19), and >or=15 events/h (group B, n=10). The relationship between the ODI and loss index was examined in each group. The loss index, 0.27+/-0.23 in group N, 0.30+/-0.27 in group A, and 0.70+/-0.32 in group B, differed significantly between groups N and B (p=0.007). In all patients, the loss index showed a significant positive correlation with the ODI (R=0.585, p=0.002). These findings suggest that NOD may be an important contributor to coronary restenosis in patients treated with stent placement.

Alcohol consumption and coronary atherosclerosis progression—the Stockholm Female Coronary Risk Angiographic Study

Objective: To assess the association of alcohol intake with progression of coronary atherosclerosis. Although moderate drinkers have a lower risk of coronary heart disease than abstainers, the relation of alcohol use and coronary atherosclerosis has not been well studied. Methods and results: In the Stockholm Female Coronary Risk Angiographic Study, we evaluated 103 women, aged 65 years or younger, hospitalized with acute myocardial infarction or unstable angina pectoris who underwent serial quantitative coronary angiography 3–6 months following their index event and repeated an average of 3 years and 3 months (range 2–5 years) later. Individual alcoholic beverage consumption was assessed by a standardized questionnaire. We used mixed model analysis to estimate the effect of alcohol consumption on progression of coronary atherosclerosis, as measured by mean luminal diameter change, controlling for age, smoking, body-mass index, education, physical activity, index cardiac event, menopausal status, diabetes, and history of dyslipidemia. Of the 93 women with complete information on alcohol intake, 14 consumed no alcohol (abstainers), 55 consumed up to 5 g of alcohol per day (light drinkers), and 24 consumed more than 5 g of alcohol per day (moderate drinkers). Coronary atherosclerosis progressed by a multivariate-adjusted average of 0.138 mm (95% confidence interval (CI): 0.027–0.249) among abstainers, 0.137 mm (95% CI: 0.057–0.217) among light drinkers, and −0.054 mm (95% CI: −0.154 to 0.047) among moderate drinkers ( P<0.001). The inverse association persisted in analyses stratified by index event. No beverage type appeared to confer particular benefit. Conclusions: Among middle-aged women with coronary heart disease, moderate alcohol consumption (over 5 g/day) was protective of coronary atherosclerosis progression.

Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study

Background It has been reported that pioglitazone reduces neointimal hyperplasia after balloon-induced vascular injury in an experimental model. Methods To determine whether pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus, we studied 44 stented lesions in 44 patients with diabetes mellitus who underwent successful coronary stent implantation. Study patients were randomized into 2 groups: the pioglitazone group (23 patients with 23 lesions) and the control group (21 patients with 21 lesions). All patients underwent serial quantitative coronary angiography and serial intravascular ultrasound scanning studies. With a motorized pullback system, multiple image slices within the stent were obtained at every 1 mm. The stent area and lumen area were measured, and the neointimal area was calculated. Measurements were averaged over the number of selected image slices. The neointimal index was calculated as the averaged neointimal area divided by the averaged stent area multiplied by 100 (%). Results After 6 months of treatment, angiographic in-stent restenosis (17% vs 43%, respectively, P = .0994) and target lesion revascularization (13% vs 38%, respectively, P = .0835) were less frequent in the pioglitazone group than the control group; however, these differences did not reach significance. The intravascular ultrasound scanning study demonstrated that the neointimal index in the pioglitazone group was significantly smaller than that in the control group (28% ± 9% vs 48% ± 15%, respectively, P <.0001). Conclusion A serial intravascular ultrasound scanning assessment demonstrated that pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus.

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.)

IDL composition and angiographically determined progression of atherosclerotic lesions during simvastatin therapy.

Some patients with coronary artery disease experience continued progression of one or more coronary lesions despite treatment with drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and markedly lower plasma cholesterol levels. We examined relationships between the progression of coronary artery lesions and plasma lipoproteins, in particular intermediate density lipoprotein (IDL) and its composition, in 38 patients with coronary artery disease who had been treated with simvastatin for 2 years. Patients were given lipid-lowering dietary advice; 3 months later they were started on simvastatin therapy (10 mg/d) for 1 month, and after review of their plasma cholesterol levels, the dose was increased to 20 mg/d and later to 40 mg/d if the target level of plasma cholesterol had not been attained. Progression of lesions was determined by serial quantitative coronary angiography (variability of 5.5%) and was defined as an increase in percent diameter stenosis (%S)> or =10%; regression was defined as a decrease in %S > or =10%. The proportions of cholesteryl esters (CEs) and free cholesterol decreased significantly (P<.001), and proportions of protein and triglycerides increased significantly (P<.001) in IDL during simvastatin therapy. The CE content of IDL decreased significantly (-7.2 weight [wt]%, n=20, P<.001) in nonprogressors (patients who did not show progression of any lesions) and did not change significantly (-1.8 wt%, n=14, P=.36) in progressors (patients who showed progression of one or more lesions without regression of any lesion). This decrease in IDL CE content in nonprogressors was significantly (P=.01) different compared with the corresponding change in patients classified as progressors. Mean plasma cholesterol concentration tended to increase in progressors (0.47 mmol/L) and tended to decrease in nonprogressors (-0.39 mmol/L) during the initial 3-month diet period, and these changes were significantly different (P=.02). Furthermore, this change in plasma cholesterol level during the initial diet period was correlated significantly with the change in IDL CE content during the entire study (r=.348, n=38, P=.03). These data suggest that IDL CE content may be a determinant of progression of coronary lesions and may be influenced by compliance with or metabolic response to lipid-lowering dietary advice in patients with coronary artery disease during simvastatin treatment.

Impact of cilostazol on intimal proliferation after directional coronary atherectomy

Cilostazol, a novel platelet aggregation inhibitor, inhibits intimal proliferation in animal models. We randomly assigned 41 patients with lesions suitable for directional coronary atherectomy to the cilostazol group (200 mg/day) or the aspirin (250 mg/day) group. Medication was started before directional coronary atherectomy and was continued to a 6-month follow-up. Serial quantitative coronary angiography and intravascular ultrasound study were performed. Baseline characteristics were not different between the two groups. However, the minimal lumen diameter at follow-up was larger (2.33 ± 0.60 mm vs 1.81 ± 0.68 mm, p = 0.016) and the percent diameter stenosis (24.5% ± 16.6% vs 40.9% ± 21.0%, p = 0.010) was smaller in the cilostazol group. The change in vessel area was not different, but the percent plaque area at follow-up was smaller in the cilostazol group (55.7% ± 11.2% vs 64.5% ± 14.5%, p = 0.044). The restenosis rate was significantly lower in the cilostazol group (0% vs 26%, p = 0.020). We conclude that cilostazol appears to have an inhibitory effect on intimal proliferation after directional coronary atherectomy and may reduce restenosis. (Am Heart J 1998;135:495-502.)

How to standardize vasomotor tone in serial studies based on quantitation of coronary dimensions?

In patients with coronary artery disease including those after coronary bypass graft operation and heart transplantation intervention studies based on serial quantitative coronary angiography, in part combined with intravascular ultrasound, are of increasing relevance. Since vasomotor tone of epicardial coronary arteries is influenced by a variety of factors, angiographic follow-up studies require standardization of coronary tone by induction of maximal dilation. We reviewed the effects of the most potent coronary vasodilatory drug groups, calcium antagonists and nitrocompounds, on coronary diameters. Intravenous or intracoronary injections of verapamil, diltiazem, nifedipine, nicardipine, and nisoldipine can cause profound coronary dilation which has been shown to be maximal with verapamil and nisoldipine. Shortcomings of calcium antagonists include short or unknown duration of action after bolus administration, severe drop in blood pressure, and lack of commercial availability of solutions for injection of many substances. Isosorbide dinitrate induces profound coronary dilation; however, after sublingual administration marked blood pressure decrease can occur, and the duration of action and ideal dose of intracoronary isosorbide dinitrate has not been investigated yet. Injections of molsidomine and its active metabolite, SIN-1, cause longlasting, reproducible, maximal coronary dilation, although only after a waiting period of at least 10 minutes; unfortunately, SIN-1 is only commercially available in France. Nitroglycerin induces reproducible maximal coronary dilation and is easy to administer sublingually or as intracoronary bolus injection with rapid onset of action and no major side effects. The short duration of action may require repeated administrations. To date, repeated intracoronary bolus injections of 0.1 mg nitroglycerin every 10 minutes seem to be the optimal known regimen for standardization of coronary vasomotor tone in serial angiographic studies. Further investigations in this field with old and new vasodilatory drugs are recommendable.

Evolution of coronary atherosclerosis in patients with mild coronary artery disease studied by serial quantitative coronary angiography at 2 and 4 years follow-up. The Multicenter Anti-Atheroma Study (MAAS) Investigators.

Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time. In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosis > or = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors. Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regression was rare.