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Background: Residual and significant post-infarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models low dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodelling effects. We studied the safety and efficacy of immediate post PCI low dose intracoronary IGF1 infusion in STEMI patients. Methods: Using a double-blind, placebo controlled, multi-dose study design, we randomized 47 STEMI patients with significantly reduced (≤ 40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n=15), 1.5ng IGF1 (n=16) or 15ng IGF1 (n=16). All received optimal medical therapy. Safety endpoints were freedom from hypoglycaemia, hypotension or significant arrhythmias within 1 hour of therapy. The primary efficacy endpoint was LVEF and secondary endpoints were LV volumes, mass, stroke volume, and infarct size at 2 months follow up, all assessed by MRI. Treatment effects were estimated by analysis of covariance adjusted for baseline (24hrs) outcome. Results: No significant differences in safety endpoints occurred between treatment groups out to 30 days (chi squared test, p-value = 0.77).There were no statistically significant differences in baseline (24 hrs post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5ng IGF1, treatment with 15ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (p=0.018), LV mass (p=0.004) and stroke volume (p=0.016). Late gadolinium enhancement (±SD) at 2 months was lower in 15ng IGF1 (34.5±29.6g) compared to placebo (49.1±19.3g) or 1.5ng IGF1 (47.4±22.4g) treated patients, though the result was not statistically significant (p = 0.095). Conclusion: In this pilot trial, low dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose dependent benefit on post MI remodeling that may warrant further study. Despite timely reperfusion by primary PCI (PPCI) a significant cohort of patients develop adverse left ventricular remodelling with clinical sequelae such as arrhythmia and heart failure[1].Therapeutic approaches to avert such remodeling, including a variety of cell therapy and ischemia- reperfusion-injury mitigation trials have achieved modest success 2.;3. Thus, there remains a significant opportunity for novel therapies in this field.

OBJECTIVES This study sought to explore the association between biomarker elevation, with creatine kinase-myocardial band (CK-MB) or cardiac troponin (cTn), following percutaneous coronary intervention (PCI) and mortality in patients undergoing PCI for stable angina with normal baseline values. BACKGROUND Several studies have shown a strong association between post-PCI CK-MB elevation and subsequent mortality. However, the prognostic significance of troponin elevation following coronary intervention is still debated. METHODS Patient-level data from 5 contemporary coronary stent trials and 1 large registry were pooled. Mortality of patients with stable angina, with normal baseline biomarkers, was compared between patients with and those without different cutoff values of cTn and CK-MB. RESULTS A total of 13,452 patients were included in this pooled analysis. The overall percentage of patients with elevated biomarkers following PCI was 23.9% for CK-MB and 68.4% for cTn. In the patient cohort for whom both assays were available (n = 8,859), 2.4% had both CK-MB ≥5 × the upper limit of normal (ULN) and cTn ≥35 × ULN, while 92% had both CK-MB

Background: The GLOBAL LEADERS (GLOBAL LEADERS: A Clinical Study Comparing Two Forms of Anti-platelet Therapy After Stent Implantation) study randomly assigned 15,991 patients undergoing percutaneous coronary intervention to 1-month dual antiplatelet therapy (DAPT) followed by 23-month ticagrelor monotherapy or conventional 12-month DAPT followed by 12-month aspirin. Apart from Q-wave myocardial infarction (MI), all study endpoints were analyzed as investigator reported. Objectives: This was a pre-specified ancillary study assessing whether experimental therapy is noninferior, and if met, superior, to conventional treatment for the coprimary efficacy endpoint of all-cause death, nonfatal MI, nonfatal stroke, or urgent target vessel revascularization and superior in preventing BARC 3 (Bleeding Academic Research Consortium) or 5 bleeding (coprimary safety endpoint) at 2 years with a 0.025 significance level to preserve nominal 5% alpha error. Methods: An independent clinical event committee adjudicated investigator-reported and eventually unreported events of 7,585 patients from the 20 top-enrolling participating sites. Results: The 2-year coprimary efficacy endpoint occurred in 271 (7.14%) and in 319 (8.41%) patients in the experimental and conventional groups, respectively (rate ratio [RR]: 0.85; 95% confidence interval [CI]: 0.72 to 0.99), fulfilling noninferiority (p noninferiority

AIMS The purpose of this study was to assess the incidence and predictors of graft failure prior to discharge. Multi-slice computed tomography has the ability to evaluate graft patency in a non-invasive way. METHODS AND RESULTS Of 145 consecutive patients who were screened, 73 were included in the study (78% male, mean age 65 years). A total of 206 grafts were analysed (2.8±0.9 grafts/patient). Of the 206 grafts, 126 were venous, 72 were left internal mammary, five were right internal mammary and three were radial grafts. We evaluated 100% of proximal anastomoses sites and 92% (190/206) of the distal anastomoses. We identified five patients (6.8%) who had at least one occluded graft. A total of seven out of 206 (3.4%) grafts were occluded. Independent predictors of successful graft outcome were left anterior descending artery as a recipient artery, good distal run-off as assessed by a surgeon and vessel size larger than 2 mm. CONCLUSIONS The results demonstrate that the in-hospital acute graft failure rate is 3.4% (6.8% of patients). Multi-slice computed tomography is a robust technique to assess novel therapies to reduce the rate of graft attrition further, and might be clinically useful in patients with persistent or early recurrence of symptoms after CABG.

BACKGROUND The use of drug-eluting stents (DES) in patients at high risk of bleeding or thrombosis has not been prospectively studied; limited data are available in patients who have a low restenosis risk. OBJECTIVES This study sought to compare a hydrophilic polymer-based, second-generation zotarolimus-eluting stent (ZES) with a unique drug fast-release profile versus bare-metal stents (BMS) under similar durations of dual-antiplatelet therapy (DAPT). METHODS We randomly assigned 1,606 patients with stable or unstable symptoms, and who on the basis of thrombotic bleeding or restenosis risk criteria, qualified as uncertain candidates for DES, to receive ZES or BMS. DAPT duration was on the basis of patient characteristics, rather than stent characteristics, and allowed for a personalized 1-month dual antiplatelet regimen. The primary endpoint was the risk of 1-year major adverse cardiovascular events (MACE), which included death, myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS Median DAPT duration was 32 days (interquartile range [IQR]: 30 to 180 days) and did not differ between the groups. In the ZES group, 140 patients (17.5%) reached the primary endpoint, compared with 178 patients (22.1%) in the BMS group (hazard ratio: 0.76; 95% confidence interval: 0.61 to 0.95; p = 0.011) as a result of lower MI (2.9% vs. 8.1%; p < 0.001) and TVR rates (5.9% vs. 10.7%; p = 0.001) in the ZES group. Definite or probable stent thrombosis was also significantly reduced in ZES recipients (2.0% vs. 4.1%; p = 0.019). CONCLUSIONS Compared with BMS, DES implantation using a stent with a biocompatible polymer and fast drug-eluting characteristics, combined with an abbreviated, tailored DAPT regimen, resulted in a lower risk of 1-year MACE in uncertain candidates for DES implantation. (Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS] Study; NCT01385319) (C) 2015 by the American College of Cardiology Foundation.

textabstractAims: Although large clinical trials have shown that everolimus-eluting stents (EES) significantly reduce target vessel revascularisation (TVR), myocardial infarction (MI) and stent thrombosis (ST) compared to paclitaxel-eluting stents (PES) in diverse populations, there is a paucity of data comparing EES and PES in patients presenting with MI. Methods and results: We performed a post hoc subgroup analysis on COMPARE, an all-comer trial comparing EES to PES. We identified 863 patients (EES=434, PES=429 treated for MI: 452 ST-elevation MI (STEMI) and 411 non ST-elevation MI (NSTEMI). EES was associated with a significant reduction in the primary endpoint, a composite of all-cause mortality, MI, and TVR, at two years (RR=0.57; 95% CI: 0.40-0.83, p=0.002). While the effect was more marked in the STEMI (RR=0.51; 95% CI: 0.30-0.87, p=0.01) than the NSTEMI subgroup (RR=0.65; 95% CI: 0.39-1.08, p=0.09), the interaction p-value (0.5) suggests that a difference in treatment effect between presentations is unlikely. ST rates were significantly lower with EES (RR=0.30; 95% CI: 0.12-0.73, p=0.005). Conclusions: At two years, EES results are superior to PES in terms of safety and efficacy endpoints in treatment of MI.

Background Hypoenhanced regions on multidetector CT (MDCT) coronary angiography correlate with myocardial hyperperfusion. In addition to a limited capillary density, chronic myocardial infarction (MI) commonly contains a considerable amount of adipose tissue. Objective We explored whether regional myocardial hypoenhancement on contrast-enhanced MDCT could be identified with standard coronary artery calcium (CAC) scoring acquisitions with noncontrast CT. Methods Consecutive patients with a history of MI who were referred for contrast-enhanced MDCT from November 2006 until March 2009 were studied. Noncontrast CT for CAC scoring was also performed. The correlation between regional myocardial hypoenhancement on contrast-enhanced CT and regional myocardial hypoattenuated areas on noncontrast CT was defined. Results Eighty-three patients (mean age, 61.5 ± 12.5 years; n = 67; 81% male) with previous MI were studied. A total of 1411 myocardial segments were evaluated. Two hundred thirty-nine segments (17%) showed myocardial hypoenhancement by MDCT and 140 segments (9.6%) by CAC. On a patient level, noncontrast CT showed a sensitivity, specificity, positive predictive value, (PPV) and negative predictive value (NPV) of 66% (95% CI, 0.53–0.77), 100% (95% CI, 0.76–1.00), 100% (95% CI, 0.90–1.00), and 41% (95% CI, 0.26–0.58), respectively, to detect myocardial hypoenhancement. On a per segment level, noncontrast CT showed a sensitivity, specificity, PPV, and NPV of 58% (95% CI, 0.51–0.64), 100% (95% CI, 0.99–1.00), 99% (95% CI, 0.94–1.00), and 92% (95% CI, 0.90–0.93), respectively, to detect myocardial hypoenhancement. Conclusions Our findings suggest that chronic MI can be detected with standard CAC scoring acquisitions.

Acute coronary syndrome is associated with intracoronary thrombosis secondary to platelet activation. Previous groups have investigated platelet activation in both stable and unstable vascular disease. Most measures of platelet activation are not routinely available or easily adaptable to large scale clinical use. Recently, measurement of the mean platelet component (MPC) has become part of the routine data provided by an automated full blood count analyser, the Advia 120. MPC measures platelet density which changes on platelet activation. Our objectives were to determine if platelet activation, as measured by MPC, is increased in patients with stable coronary artery disease (CAD) and to determine if MPC could be useful in differentiating people with stable CAD from controls on an everyday clinical basis. Three hundred and forty-five consecutive patients attending for elective coronary angiography had full blood count analysis and MPC measurement performed using an ADVIA-120 analyser. Three hundred and twenty-four were analysed in our final dataset. Two hundred and fifty-three (78%) had CAD. Patients with CAD were significantly (p

To determine the adjunctive value of CT coronary angiography (CTCA) in the diagnostic work-up of patients with typical angina pectoris.CTCA was performed in 62 consecutive patients (45 male, mean age 58.8 +/- 7.7 years) with typical angina undergoing diagnostic work-up including exercise-ECG and conventional coronary angiography. Only patients with sinus heart rhythm and ability to breath hold for 20 s were included. Patients with initial heart rates/=70 beats/min received beta-blockers. We determined the post-test likelihood ratios, to detect or exclude patients with significant (/=50% lumen diameter reduction) stenoses, of exercise-ECG and CTCA separately, and of CT performed after exercise-ECG testing. The prevalence of patients with significant coronary artery disease (CAD) was 74%. Positive and negative likelihood ratios for exercise-ECG were 2.3 [95% confidence interval (CI): 1.0-5.3] and 0.3 (95% CI: 0.2-0.7) and for CTCA 7.5 (95% CI: 2.1-27.1) and 0.0 (95% CI: 0.0-8), respectively. CTCA increased the post-test probability of significant CAD after a negative exercise-ECG from 58 to 91%, and after a positive exercise-ECG from 89 to 99%, while CT correctly identified patients without CAD (probability 0%).Non-invasive CTCA is a potentially useful tool, in the diagnostic work-up of patients with typical angina pectoris, both to detect and to exclude significant CAD.

Studies have indicated varying mortality risks with timing of stent thrombosis (ST), but few have been adequately powered with prospective late follow-up. PROTECT randomized 8,709 subjects to either Endeavor zotarolimus-eluting or Cypher sirolimus-eluting stents. PROTECT Continued Access enrolled 1,018 patients treated with Endeavor zotarolimus-eluting stents. Subjects completed at least 4 and 3 years of follow-up, respectively. ARC-defined definite and probable ST events were stratified by time from index procedure: early (≤30 days), late (30 and ≤360 days), and very late (360 days). Rates of death and myocardial infarction were analyzed by ST timing. Median follow-up was 4.1 years. There were 184 ST events (1.9%): 61 early, 27 late, and 96 very late. Patient and procedural characteristics were similar between timing groups. There was no difference in dual-antiplatelet therapy use at discharge (97%) or 1 year (84%). Cardiac death in patients with ST at 4 years occurred in 32.1% compared with 2.5% in patients without ST (p0.001). Combined rates of cardiac death and myocardial infarction did not differ according to ST timing, yet early ST was more commonly associated with cardiac death at 4 years than later ST (50.8% for early vs 18.5% for late vs 24.0% for very late; p0.001). The relation between ST timing and outcomes did not differ between stent types. In conclusion, in prospective data, cardiac death was more common after early ST than later ST. Although ST remains infrequent, continued efforts to determine how to reduce ST, particularly within the first 30 days, are warranted. (The PROTECT trial is registered with ClinicalTrials.gov, number NCT00476957.).

Background— Surveillance conventional coronary angiography (CCA) is recommended 2 to 6 months after stent-supported left main coronary artery (LMCA) percutaneous coronary intervention due to the unpredictable occurrence of in-stent restenosis (ISR), with its attendant risks. Multislice computed tomography (MSCT) is a promising technique for noninvasive coronary evaluation. We evaluated the diagnostic performance of high-resolution MSCT to detect ISR after stenting of the LMCA. Methods and Results— Seventy-four patients were prospectively identified from a consecutive patient population scheduled for follow-up CCA after LMCA stenting and underwent MSCT before CCA. Until August 2004, a 16-slice scanner was used (n=27), but we switched to the 64-slice scanner after that period (n=43). Patients with initial heart rates >65 bpm received β-blockers, which resulted in a mean periscan heart rate of 57±7 bpm. Among patients with technically adequate scans (n=70), MSCT correctly identified all patients with ISR (10 of 70) but misclassified 5 patients without ISR (false-positives). Overall, the accuracy of MSCT for detection of angiographic ISR was 93%. The sensitivity, specificity, and positive and negative predictive values were 100%, 91%, 67%, and 100%, respectively. When analysis was restricted to patients with stenting of the LMCA with or without extension into a single major side branch, accuracy was 98%. When both branches of the LMCA bifurcation were stented, accuracy was 83%. For the assessment of stent diameter and area, MSCT showed good correlation with intravascular ultrasound ( r =0.78 and 0.73, respectively). An intravascular ultrasound threshold value ≥1 mm was identified to reliably detect in-stent neointima hyperplasia with MSCT. Conclusions— Current MSCT technology, in combination with optimal heart rate control, allows reliable noninvasive evaluation of selected patients after LMCA stenting. MSCT is safe to exclude left main ISR and may therefore be an acceptable first-line alternative to CCA.

The most effective strategy for bifurcation stenting is currently undefined. The Culotte technique was developed as a method that ensures complete bifurcation lesion coverage. However, it went out of favour due to a high rate of restenosis when utilizing bare metal stents. Drug-eluting stents reduce the rate of restenosis and need for repeat lesion revascularization compared with bare metal stents; we re-evaluated this technique with drug-eluting stent implantation.Between April 2002 and October 2003, 207 patients were treated for at least one bifurcation lesion with drug-eluting stent implantation to both the main vessel and side branch. Of these, 23 were treated with the Culotte technique (11.1%) for 24 lesions. Sirolimus-eluting stents were used in 8.3%, and paclitaxel-eluting stents in the remaining 92.7%.Clinical follow-up was obtained in 100%. One patient had a myocardial infarction at 14 days (maximum rise in creatine kinase 872 IU/L) related to thrombosis occurring in another lesion, and underwent repeat revascularization. There were no episodes of stent thrombosis in the Culotte lesions. At eight months follow-up, there were no deaths and no further myocardial infarction. One patient required target lesion revascularization (TLR), and a second underwent target vessel revascularization. The cumulative rates of survival-free of TLR and major adverse cardiac events were 94.7% and 84.6% respectively. Angiographic follow-up was obtained in 16 patients (69.6%) at a mean period of 8.3+/-4.3 months. The late lumen loss for the main vessel and side branch were 0.48+/-0.56 mm and 0.53+/-0.33 mm respectively, with binary restenosis rates of 18.8% and 12.5%.In this small study of bifurcation stenting utilizing the Culotte technique with drug-eluting stent implantation, there was a low rate of major adverse events and need for target lesion revascularization at eight months, when compared with historical data of bifurcation stenting with bare metal stents. Further re-evaluation of this technique utilizing drug-eluting stents, is warranted in the setting of larger randomized studies.

Background— The impact of drug-eluting stent (DES) implantation on the incidence of major adverse cardiovascular events in patients undergoing percutaneous intervention for left main (LM) coronary disease is largely unknown. Methods and Results— From April 2001 to December 2003, 181 patients underwent percutaneous coronary intervention for LM stenosis at our institution. The first cohort consisted of 86 patients (19 protected LM) treated with bare metal stents (pre-DES group); the second cohort comprised 95 patients (15 protected LM) treated exclusively with DES. The 2 cohorts were well balanced for all baseline characteristics. At a median follow-up of 503 days (range, 331 to 873 days), the cumulative incidence of major adverse cardiovascular events was lower in the DES cohort than in patients in the pre-DES group (24% versus 45%, respectively; hazard ratio [HR], 0.52 [95% CI, 0.31 to 0.88]; P =0.01). Total mortality did not differ between cohorts; however, there were significantly lower rates of both myocardial infarction (4% versus 12%, respectively; HR, 0.22 [95% CI, 0.07 to 0.65]; P =0.006) and target vessel revascularization (6% versus 23%, respectively; HR, 0.26 [95% CI, 0.10 to 0.65]; P =0.004) in the DES group. On multivariate analysis, use of DES, Parsonnet classification, troponin elevation at entry, distal LM location, and reference vessel diameter were independent predictors of major adverse cardiovascular events. Conclusions— When percutaneous coronary intervention is undertaken at LM lesions, routine DES implantation, which reduces the cumulative incidence of myocardial infarction and the need for target vessel revascularization compared with bare metal stents, should currently be the preferred strategy.

The aim of this study was to assess the short- and mid-term clinical impact of intravascular ultrasound guidance in 58 patients referred for elective percutaneous treatment of unprotected left main coronary artery disease with drug-eluting stents. The use of intravascular ultrasound, used in 41% of the procedures, was not associated with additional clinical benefit with respect to angiographic-assisted stent deployment.

We performed coronary plaque imaging with 16-row multislice computed tomography in 85 patients who had stable angina pectoris and a high pretest likelihood of having coronary plaque to evaluate plaque burden, i.e., extent (number of diseased coronary segments) and size (small vs large) of plaque. We also assessed type of plaque (calcified, noncalcified, or mixed) and its anatomic distribution. Of 85 patients included, 78 (92%) had fully evaluable multislice computed tomograms that allowed assessment of coronary plaque burden, including major and side branches (or=2 mm), yielding a total of 855 segments. These 78 patients (92% men; mean age +/- SD 58 +/- 11.5 years) were in sinus rhythm, with heart rates of70 beats/min (spontaneous or induced by beta blocker). Plaque was detected in 57% of all segments (487 of 855). The mean number of segments with plaque per patient +/- SD was 6.2 +/- 3.9. Plaque was classified as large in 33% of segments and small in 67%. Overall, 65% of plaques were calcified, 24% were noncalcified, and 11% were mixed. Plaques were predominantly located in the proximal and middle segments of the main coronary vessels.

We performed multislice computed tomographic coronary angiography in 45 patients who had chronic total occlusions and were scheduled for percutaneous recanalization. Multivariate analysis identified a blunt stump (by conventional angiography), occlusion length >15 mm, and severe calcification (by multislice computed tomographic coronary angiography) as independent predictors of procedural failure.

Fifty-one patients (42 men; 60 +/- 12 years of age) who had previous stent implantation underwent multislice computed tomographic coronary angiography. All coronary branchesor = 2.0 mm were independently evaluated by 2 observers and screened for in-stent restenosis (or = 50%) and occlusion. The consensus reading was compared with the quantitative coronary angiogram. Six of the 74 (8.1%) evaluated stents (3 restenoses and 3 occlusions) were significantly diseased. The sensitivity, specificity, and positive and negative predictive values to identify restenosis were 83.3% (95% confidence interval [CI] 35.9 to 99.6), 98.5% (95% CI 92.1 to 100), 83.3% (95% CI 35.9 to 99.6), and 97.3% (95% CI 92.1 to 100), respectively. One in-stent restenosis remained undetected.

Background— The diagnostic performance of the latest 64-slice CT scanner, with increased temporal (165 ms) and spatial (0.4 mm 3 ) resolution, to detect significant stenoses in the clinically relevant coronary tree is unknown. Methods and Results— We studied 52 patients (34 men; mean age, 59.6±12.1 years) with atypical chest pain, stable or unstable angina pectoris, or non–ST-segment elevation myocardial infarction scheduled for diagnostic conventional coronary angiography. All patients had stable sinus rhythm. Patients with initial heart rates ≥70 bpm received β-blockers. Mean scan time was 13.3±0.9 seconds. The CT scans were analyzed by 2 observers unaware of the results of invasive coronary angiography, which was used as the standard of reference. All available coronary segments, regardless of size, were included in the evaluation. Lesions with ≥50 luminal narrowing were considered significant stenoses. Invasive coronary angiography demonstrated the absence of significant disease in 25% (13 of 52), single-vessel disease in 31% (16 of 52), and multivessel disease in 45% (23 of 52) of patients. One unsuccessful CT scan was classified as inconclusive. Ninety-four significant stenoses were present in the remaining 51 patients. Sensitivity, specificity, and positive and negative predictive values of CT for detecting significant stenoses on a segment-by-segment analysis were 99% (93 of 94; 95% CI, 94 to 99), 95% (601 of 631; 95% CI, 93 to 96), 76% (93 of 123; 95% CI, 67 to 89), and 99% (601 of 602; 95% CI, 99 to 100), respectively. Conclusions— Noninvasive 64-slice CT coronary angiography accurately detects coronary stenoses in patients in sinus rhythm and presenting with atypical chest pain, stable or unstable angina, or non–ST-segment elevation myocardial infarction.

Objective: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. Design and patients: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. Setting: Academic tertiary referral centre. Results: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16). Conclusions: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

The percutaneous treatment of coronary bifurcation stenoses is hampered by an increased rate of subsequent restenosis. The present study reports on the outcomes of a consecutive series of 58 patients with 65 de novo bifurcation stenoses treated with sirolimus-eluting stent implantation in both the main vessel and side branch. At 6 months, the incidence of major adverse cardiac events was 10.3% (1 death and 5 target lesion revascularizations) with no episodes of acute myocardial infarction or stent thrombosis.

Objectives This study was designed to prospectively evaluate the diagnostic performance of multislice spiral computed tomography (MSCT) coronary angiography for the detection of significant lesions in all segments of the coronary tree potentially suitable for revascularization. Background Noninvasive MSCT coronary angiography is a promising coronary imaging technique. Methods Sixteen-row MSCT coronary angiography was performed in 128 patients (89% men, mean age 58.9 ± 11.7 years) in sinus rhythm with stable angina pectoris scheduled for conventional coronary angiography. Sixty percent (77 of 128) of patients received pre-scan oral beta-blockers, resulting in a mean heart rate of 57.7 ± 7.7 beats/min. The diagnostic performance of MSCT for detection of significant lesions (≥50% diameter reduction) was compared with that of quantitative coronary angiography (QCA). Results The sensitivity of MSCT for detection of significant lesions was 92% (216 of 234, 95% confidence interval [CI]: 88 to 95). Specificity was 95% (1,092 of 1,150, 95% CI: 93 to 96), positive predictive value 79% (216 of 274, 95% CI: 73 to 88), and negative predictive value 98% (1,092 of 1,110, 95% CI: 97 to 99). Two ≥50% lesions were missed because of motion artifacts and two because of severe coronary calcifications. The rest (78%, 14 of 18) were detected but incorrectly classified as

Aims To test the hypothesis that diabetic status may be used as a prognostic indicator in heart failure (HF) patients. Methods and results We studied 1246 consecutive patients with left ventricular dysfunction. All patients had a cardiopulmonary exercise test and an echocardiogram. Cardiac catheterisation was systematically performed to define HF aetiology. Twenty-two percent of the patients were diabetic (hypoglycaemic drugs or fasting blood glucose \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(>\) \end{document}126 mg/dL); in diabetic patients, HF aetiology was ischaemic in 58% vs. 40% in non-diabetic patients (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{

The purpose of this study was to assess the safety and effectiveness of sirolimus-eluting stent (SES) postdilatation with largely oversized balloons. We evaluated the clinical outcome of 68 consecutive patients enrolled in the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry who underwent percutaneous coronary intervention with SES implantation and further postdilatation with balloons > 1 mm larger than the stent nominal size. Angiographic follow-up was either scheduled for selected subgroups or clinically driven. Overall, 75 lesions were treated. The procedure was successful in 98.5% of the cases. One patient (1.5%) underwent emergency coronary bypass surgery for acute vessel occlusion. During 10.1 +/- 1.7 months of follow-up, three patients (4.5%) died, one (1.5%) had acute myocardial infarction, and four (6%) had target vessel revascularization. At angiographic follow-up, loss index was 0.13 +/- 0.34 and restenosis rate was 7.7%. Although not routinely recommended in every patient, SES postdilatation with largely oversized balloons appears a safe and effective strategy for selected patients.

The aim of this study was to evaluate the effectiveness of sirolimus-eluting stent (SES) implantation for patients with multivessel disease, which included left anterior descending artery (LAD) treatment. Since April 2002, SES has been utilized as the device of choice for all interventions in our institution as part of the Rapamycin-Eluting Stent Evaluated at Rotterdam Hospital (RESEARCH) registry. In the first 6 months of enrolment, 99 consecutive patients (17.6% of the total population) were treated for multivessel disease involving the LAD. The impact of SES implantation on major adverse cardiac events (MACE) was evaluated. All the patients received SES in the LAD. Additional stent implantation in the right coronary artery, the left circumflex, or in all three major vessels was attempted successfully in 32 (32%), 51 (52%), and 16 (16%) of the treated patients respectively. During a mean follow-up of 360 ± 59 days (range, 297–472 days), we had one death, one non-Q-wave myocardial infarction, and eight patients required subsequent intervention. The event-free survival of MACE at 1 year was 85.6%. SES implantation for multivessel disease in a consecutive series of patients is associated with low incidence of adverse events. The reported results are related predominantly to the reduction in repeat revascularization. Catheter Cardiovasc Interv 2004;63:57–60. © 2004 Wiley-Liss, Inc.

The effectiveness of sirolimus-eluting stent (SES) implantation in patients treated electively for left main (LM) stenoses has not been yet ascertained. The present study reports on the clinical and angiographic outcome of 16 consecutive patients treated electively for de novo stenoses in the LM. The impact of SES implantation on major adverse cardiac events was evaluated. Mean age was 65 ± 11 years. Unprotected LM was present in nine (56%), and eight patients (50%) received stents extending into both the left anterior descending and circumflex arteries for stenoses of the distal left main bifurcation. In-house mortality and reintervention rate was zero. One patient developed a non-Q-wave myocardial infarction related to the index procedure. At 1-year clinical follow-up, there were no deaths or further myocardial infarctions; one (6%) patient required target lesion revascularization. A total of 12 patients (75%) underwent 6-month angiographic follow-up with a late lumen loss of 0.04 ± 0.65 mm and one focal restenosis (8% of patients). Elective SES implantation for LM disease was associated with zero mortality and a very low incidence of additional major adverse events at 1 year. Catheter Cardiovasc Interv 2004; 62:292–296. 2004 Wiley-Liss, Inc.

A total of 91 patients with 112 lesions received 2.25-mm sirolimus-eluting stents (SESs), and these lesions were compared with those treated with SESs ofor =2.5-mm diameter in the same procedure (n = 109). The reference diameters were 1.88 +/- 0.34 and 2.52 +/- 0.57 mm, respectively (p0.01). At follow-up, the late lumen loss was 0.07 +/- 0.48 mm for the 2.25-mm SES versus 0.03 +/- 0.38 mm for the larger SES (p = 0.5), and the binary restenosis rate was 10.7% versus 3.9%, respectively (p = 0.1). The 12-month target lesion revascularization rate was 5.5%. In conclusion, 2.25-mm SESs were associated with low rates of clinical and angiographic late complications.

textabstractObjective: Percutaneous coronary intervention in patients with a history of previous coronary artery bypass grafting (CABG) is associated with an increased rate of subsequent adverse events compared to those without prior CABG. We evaluated the impact of utilizing the sirolimus-eluting stent (SES) in this high-risk population. Methods: Since April 2002, SES implantation was utilized as the default strategy for all percutaneous procedures in our hospital. Consecutive patients with a history of previous CABG and de novo lesions (n=47) treated exclusively with SES, were compared to 66 patients who received bare stents in the 6-month period just before SES introduction. Results: There were no significant differences between the groups (SES and bare stent) with respect to baseline clinical or lesion characteristics. The only difference between the groups related to the nominal diameter of stent utilized, which was smaller in the SES group than the bare stent group. (The maximum diameter of SES available was 3.0 mm). At 1 year, the cumulative incidence of major adverse events (defined as death, myocardial infarction, or target vessel revascularization) was significantly lower in the SES group than the bare stent group [8.5 versus 30.3%, hazard ratio 0.37 (95% confidence interval 0.15-0.91); P=0.03]. Conclusions: The utilization of the sirolimus-eluting stent for percutaneous intervention in a high-risk population with a history of previous CABG surgery is associated with a significant reduction in the rate of major adverse cardiac events at 1 year.

Background— We describe the clinical and morphological patterns of restenosis after sirolimus-eluting stent (SES) implantation. Methods and Results— From 121 patients with coronary angiography obtained >30 days after SES implantation, restenosis (diameter stenosis >50%) was identified in 19 patients and 20 lesions (located at the proximal 5-mm segment in 30% or within the stent in 70%). Residual dissection after the procedure or balloon trauma outside the stent was identified in 83% of the proximal edge lesions. Lesions within the stent were focal, and stent discontinuity was identified in some lesions evaluated by intravascular ultrasound. Conclusions— Sirolimus-eluting stent edge restenosis is frequently associated with local trauma outside the stent. In-stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Local conditions instead of intrinsic drug-resistance to sirolimus are likely to play a major role in post-SES restenosis.

ObjectivesWe sought to compare coronary stent implantation with balloon angioplasty (BA), in a diabetic population, in terms of the six-month angiographic outcome and four-year clinical events.BackgroundDiabetic patients have a poor angiographic and clinical outcome after standard coronary BA. To date, it is still unclear whether stent implantation may improve this outcome.MethodsWe investigated this issue by individual matching of 314 diabetic patients treated with either coronary stenting or standard BA. These two groups were derived from a population of consecutive diabetic patients (1993 to 1996). Matching criteria were gender, anti-diabetic regimen, stenosis location, reference diameter, and minimal luminal diameter (±0.4 mm). One lesion per patient was considered for matching.ResultsBaseline characteristics were similar between the two groups of 157 patients. At six months, the rates of restenosis (27% vs. 62%; p < 0.0001) and occlusion (4% vs. 13%; p < 0.005) were lower in the stent group than in the BA group. This was associated with a significant decrease in ejection fraction at six months in the BA group (p = 0.02) while, during the same period, no change was observed in the stent group (p = NS). Subgroup analysis demonstrated that angiographic benefit was consistent among the subgroups. At four years, the combined clinical end point of cardiac death and non-fatal myocardial infarction was lower in the stent group (14.8% vs. 26.0%; p = 0.02), as was the need for repeat revascularization (35.4% vs. 52.1%; p = 0.001).ConclusionsIn a population of diabetic patients, coronary stent implantation was associated with a highly beneficial effect on the six-month angiographic outcome and four-year clinical events compared with standard BA.

AIMS Abnormal coronary vasomotion plays a role in the clinical expression of coronary artery disease. We hypothesized that the functional C825T polymorphism located in the ubiquitous G-protein beta3 subunit, implicated in the cellular signal transduction of many receptors, could modify artery coronary vasomotion. We assessed the potential association of the pertussis toxin-sensitive G protein beta3 subunit (GNB3) gene C825T polymorphism on coronary vasomotion in humans. METHODS AND RESULTS We examined the response of angiographically normal human coronary arteries (n=131) after intravenous injection of methylergonovine maleate, a vasoconstrictor, followed by injection of isosorbide dinitrate, a vasodilator, according to GNB3 genotypes. Coronary vasomotion was assessed with quantitative coronary angiography. Subjects bearing at least one T allele had greater susceptibility to vasoconstriction in response to methylergonovine maleate than CC subjects, whereas vasodilation in response to isosorbide dinitrate did not differ among the different genotypes. CONCLUSION The C825T polymorphism of the G-protein beta3 subunit may be a genetic determinant of coronary artery vasomotion in humans.

Background —Several reports have demonstrated a high mortality rate in diabetic patients treated by standard coronary balloon angioplasty. No clear explanation has been provided for this finding. Methods and Results —Consecutive diabetic patients successfully treated by standard coronary balloon angioplasty (n=604) were enrolled in a follow-up program including repeated angiography at 6 months and long-term clinical follow-up. Clinical follow-up was available in 603 patients (99.8%). Twelve patients died, 2 underwent bypass surgery before scheduled repeated angiography, and 76 declined angiography. Determinants of long-term mortality were analyzed in the 513 patients with angiography at 6 months and long-term clinical follow-up (mean follow-up, 6.5±2.4 years). On the basis of the results of repeated angiography, 3 groups of patients were defined: group 1, 162 patients without restenosis (32%); group 2, 257 patients with nonocclusive restenosis (50%); and group 3, 94 patients with coronary occlusion (18%). Overall actuarial 10-year mortality rate was 36%. Actuarial 10-year mortality was 24% in group 1, 35% in group 2, and 59% in group 3 ( P P =0.0003) and cardiac mortality (hazard ratio, 2.38; 95% CI, 1.48 to 3.85; P =0.0004). Conclusions —This study demonstrates that restenosis, especially in its occlusive form, is a major determinant of long-term mortality in diabetic patients after coronary balloon angioplasty.

Background —Limited angioscopic information is available on the natural history of infarct-related plaque after myocardial infarction (MI), in particular the effect of thrombolysis. Methods and Results —We studied with angioscopy the morphological characteristics of the infarct-related lesion in 56 patients between 24 hours and 4 weeks after MI. Forty of these patients were initially treated with a thrombolytic agent. Most lesions were complex (complex+ulcerated shape=54%). The predominant color of the plaque was yellow in 79% of cases; only 6% were uniformly white. Angioscopically visible thrombus was found in 77% of cases. Despite angioscopic evidence of instability, only 7% of the patients had post-MI angina. During the 1-month time window since the occurrence of MI, there was no significant difference in the angioscopic appearance of the plaque except for a slight increase in uniformly white plaques ( P =.07). The use of a thrombolytic agent at the onset of MI was associated with a reduction in thrombus size and less protruding thrombi ( P =.02) but not with a decreased frequency of plaque containing thrombi. Furthermore, a trend for more frequently ulcerated plaques (45% versus 16%, P =.06) was associated with the use of a thrombolytic agent. Conclusions —These results suggest that healing of the infarct-related lesion requires more than 1 month and that an “unstable” yellow plaque with adherent thrombus is common during that period. This finding may partly explain the unique behavior of recent infarct-related lesions, which are more prone to occlude than other lesions.

Balloon coronary angioplasty is a revascularization procedure which increases the luminal diameter at a site of arterial stenosis, leading to mechanical disruption of the atherosclerotic plaque and to stretching of the vascular wall (1). This procedure can be complicated by thrombosis or restenosis, which occur in 5% and 30% of the cases respectively (2).These complications probably result from exposure of blood to components of atherosclerotic plaque, subendothelium and components of vascular wall, leading to activation of coagulation (thrombin generation) and platelets (3,4). Recent data point to simultaneous increase of leukocyte adhesive receptors, indicating an additional process of leukocyte activation, which could play a key role in the vascular healing process after angioplasty (5). These elements could also play a role in the thrombotic and stenotic complications. Among leukocytes, monocytes play a unique role in the pathogenesis of atherosclerosis and they are potent activators of blood coagulation through ability to express tissue factor (TF) upon activation (6,7). TF is a cell membrane-associated glycoprotein that initiates the coagulation cascade, and induces thrombin formation and therefore platelet activation (8). Several reports indicate that circulating monocytes can overexpress TF during acute coronary syndroms, specially during unstable angina, but the underlying stimulus is unknown (9,10). TF gene transcription can be induced by endotoxin, tumour necrosis factor and a variety of immune or inflammatory stimulus (7,8). As some of these components are present at the site of plaque rupture (11), we hypothesized that exposure of blood to components of atherosclerotic plaque could upregulate TF expression in circulating monocytes. Accordingly, we designed a study to determine whether elective single-vessel angioplasty could increase monocyte TF response, under clinical conditions, in patients with coronary disease. For this purpose, we compared the levels of TF content in monocytes after short culture, before and after balloon angioplasty in patients with stable angina. A small group of patients with unstable angina who underwent angioplasty during the same period were also studied. Additionally, plasma levels of prothrombin fragment 1+2, a sensitive marker of thrombin formation, were determined.

Background Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients. Methods and Results We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%; P =.0002) owing to both a greater late loss (0.79±0.70 versus 0.41±0.61 mm, respectively; P P Conclusions Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.

Background Although intracoronary stent implantation significantly reduces restenosis compared with balloon angioplasty, a minority of patients still develop restenosis predominantly due to neointimal hyperplasia. Experimental studies suggest that the renin-angiotensin system is involved in neointimal hyperplasia after arterial injury. In humans, the plasma and cellular levels of ACE are associated with an I/D genetic polymorphism in the ACE gene, DD patients having higher levels. Methods and Results We investigated a possible relation between the ACE I/D polymorphism and restenosis in 146 patients who underwent successful implantation of a Palmaz-Schatz stent and had 6-month follow-up angiography. The minimal lumen diameter (MLD) before and after the procedure did not differ significantly among the three groups of genotypes ( DD , ID , and II ). At follow-up, MLD had a significant inverse relationship to the number of D alleles present ( DD , 1.65±0.71 mm; ID , 1.84±0.60 mm; II , 2.05±0.61 mm; P D alleles ( DD , 0.89±0.61 mm; ID , 0.60±0.52 mm; II , 0.40±0.53 mm; P 50% diameter stenosis at follow-up) approximated by the adjusted odds ratio was 2.00 per number of D alleles (95% confidence interval, 1.03 to 3.88, P Conclusions The ACE I/D polymorphism influences the level of late luminal loss after coronary stent implantation. These results suggest that the renin-angiotensin system may be implicated in the pathogenesis of restenosis after coronary stenting.

Recent in vitro studies suggest that angiotensin converting enzyme (ACE) inhibitors stimulate endothelial cell proliferation and migration. The present study was designed to test the hypothesis that an ACE inhibitor may accelerate endothelial regrowth in vivo. Twenty eight New Zealand White rabbits were randomized to receive placebo or the ACE inhibitor perindopril and underwent iliac balloon denudation. Endothelial regrowth, quantified 28 days after injury using Evans blue, was significantly greater in perindopril-treated animals than in controls (131 +/- 9 mm2 vs 69 +/- 8 mm2; P < .001). These results were confirmed by scanning electron microscopy and by specific immunostaining for endothelial cells. These data provide the first in vivo demonstration that ACE inhibitors accelerate endothelial regrowth after arterial injury. This effect may contribute to the benefit observed with ACE inhibition following arterial injury.

Background Globalisation in coronary stent research calls for harmonization of clinical endpoint definitions and event adjudication. Little has been published about the various processes used for event adjudication or their impact on outcome reporting. Methods and results We performed a validation of the clinical event committee (CEC) adjudication process on 100 suspected events in the RESOLUTE All-comers trial (Resolute-AC). Two experienced Clinical Research Organisations (CRO) that had already extensive internal validation processes in place, participated in the study. After initial adjudication by the primary-CEC, events were cross-adjudicated by an external-CEC using the same definitions. Major discrepancies affecting the primary end point of target-lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), or clinically-indicated target-lesion revascularization (CI-TLR), were analysed by an independent oversight committee who provided recommendations for harmonization. Discordant adjudications were reconsidered by the primary CEC. Subsequently, the RAC database was interrogated for cases that based on these recommendations merited re-adjudication and these cases were also re-adjudicated by the primary CEC. Final discrepancies in adjudication of individual components of TLF occurred in 7 out of 100 events in 5 patients. Discrepancies for the (hierarchical) primary endpoint occurred in 5 events (2 cardiac deaths and 3 TV-MI). After application of harmonization recommendations to the overall RAC population (n = 2292), the primary CEC adjudicated 3 additional clinical-TLRs and considered 1 TV-MI as no event. Conclusions A harmonization process provided a high level of concordance for event adjudication and improved accuracy for final event reporting. These findings suggest it is feasible to pool clinical event outcome data across clinical trials even when different CECs are responsible for event adjudication.

Objectives We hypothesized that percutaneous transluminal coronary angioplasty performed on coronary stenoses that have demonstrated rapid angiographic progression would be associated with a high risk of restenosis. Background High rates of restenosis have been documented after percutaneous transluminal coronary angioplasty of unstable lesions and of lesions that recurrapidly after a successful initial angioplasty. This suggests that the ‘activity’ of the plaque at the time of angioplasty may be an important factor determining the risk of restenosis. Methods In our institution we recommend angiographic follow-up for all patients with successful percutaneous transluminal coronary angioplasty. In this way we identified 86 consecutive patients who, at the time of angiographic follow-up had not developed restenosis at the dilated site, butrequired a further percutaneous transluminal coronary angioplasty at a different site (which was successful). Based on quantitative angiographic measurements, 45 of these lesions (rapidly progressive lesions) had significantly increased in severity in the interval between the two angiograms (7.7 ± 3.3 months) while 41 (stable lesions) had not. Rapid progression was defined as a >0.4 mm decrease in minimal lumen diameter between initial angiography and percutaneous transluminal coronary angioplasty. All 86 patients had further angiographic follow-up 6 months later. Results Baseline clinical and angiographic variables were similar in both groups except that a higher proportion of patients in the rapid progression group had unstable angina (20% vs 5% P

Intravascular metallic stents are increasingly used in the non-surgical management of coronary atherosclerosis. Despite intensive anticoagulation, subacute stent thrombosis, which usually has serious clinical consequences, and major haemorrhagic complications remain major problems after stent implantation. In addition, conventional management with anticoagulant therapy requires prolonged hospitalization. In a prospective multicentre study, we investigated the efficacy of a combination of two antiplatelet agents, ticlopidine 500 mg daily and aspirin 200 mg daily, without oral anticoagulation after stent implantation. Since November 1993, 529 consecutive patients, in whom 545 vessels were successfully stented with conventional (non-heparin coated) stents have been enrolled. Stenting was performed as a bailout procedure for failed angioplasty in 112 patients, for a suboptimal result after angioplasty in 314 patients, and electively in the remaining 103 patients. Coronary events related, or possibly related, to stent thrombosis occurred in 5.4% of patients stented as a bailout procedure and in 1.8% of patients stented for a suboptimal result. Serious bleeding complications occurred in 5.4% of patients stented as a bailout procedure and 1.5% of patients stented for a suboptimal result. Neither stent thrombosis nor serious bleeding complications were seen in patients stented electively. Ticlopidine therapy was discontinued in 1.9% of patients due to neutropenia (0.6%) or rash (1.3%). Mean hospital stay decreased from 6.16 +/- 2.14 days to 4.2 +/- 2.15 days during the study period. A combination of two antiplatelet agents can be employed in the vast majority of patients after coronary stent implantation. Subacute stent thrombosis rates and bleeding complications compare favourably with those reported using conventional therapy and the duration of hospitalization is reduced.

The long-term efficacy of percutaneous coronary intervention for mildly obstructive coronary narrowings is limited by the occurrence of restenosis, limiting the applicability of this therapy for these lesions. The present study reports on a consecutive series of 20 patients treated with sirolimus-eluting stent implantation for 23 angiographically mild de novo lesions (defined as a diameter stenosis50% by quantitative coronary angiography). At a mean follow-up of 399 +/- 120 days, the survival-free of major adverse events was 95%, with no patient requiring target lesion revascularization.

Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialisation of the stent struts. We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimus-eluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.

Background Discordant results have been reported regarding morphological predictors of restenosis after percutaneous transluminal coronary angioplasty (PTCA). These discrepancies may be related to the limitations of angiography in the study of plaque morphology. Methods and Results We studied 117 consecutive patients who underwent successful PTCA and who underwent coronary angioscopy before and immediately after the procedure. Angiographic follow-up was performed in 99 (85%) patients. We analyzed the relationship between angioscopic variables at the time of PTCA and the occurrence of restenosis assessed by quantitative coronary angiography. Plaque shape and color had no effect on late loss in luminal diameter (late loss: smooth lesions, 0.55±0.68 mm; complex lesions, 0.76±0.60 mm; white plaques, 0.51±0.56 mm; yellow plaques, 0.65±0.72 mm; P =NS). An angioscopic protruding thrombus at the PTCA site was associated with significantly greater loss in luminal diameter (late loss: no thrombus, 0.47±0.54 mm; lining thrombus, 0.59±0.67 mm; protruding thrombus, 1.07±0.77 mm; P P =NS). Conclusions These results show that coronary angioscopy may be helpful in predicting the risk of restenosis after PTCA. The high rate of angiographic recurrence observed when PTCA is performed at thrombus-containing lesions supports a role for thrombus in the process of luminal renarrowing after PTCA.

The present study reports on the clinical outcome of 31 consecutive patients with left main coronary artery disease treated with a sirolimus-eluting stent. The implantation of this stent was associated with abolition of post-discharge fatal events and percutaneous reintervention.

BACKGROUND Nitric oxide (NO), in addition to its potent vasorelaxant properties, may participate in growth regulation of cultured smooth muscle cells. It was recently demonstrated that in vivo endothelial injury induces the production of NO from L-arginine in the arterial wall. METHODS AND RESULTS We studied the effects of long-term administration of L-arginine, the precursor of NO, on neointimal thickening and on neoendothelium-dependent vasorelaxation 4 weeks after balloon denudation of normocholesterolemic rabbit iliac arteries. Rabbits were fed with either a standard diet or a diet supplemented with L-arginine (2.25%) in their drinking water 3 days before and during 4 weeks after balloon denudation. The effectiveness of L-arginine supplementation was confirmed by measurement of plasma arginine levels. L-Arginine had no effect on hemodynamic parameters. All animals were killed 4 weeks after balloon denudation, and a digital histomorphometric analysis of three serial nonconsecutive histological cross sections per iliac artery was performed. Intimal thickening was reduced (P < .05) from 0.43 +/- 0.08 (SE) mm2 in controls (n = 8) to 0.24 +/- 0.02 mm2 in treated animals (n = 8). Ten animals (n = 5 in each group) were used for in vitro vasoreactivity assessment 4 weeks after balloon denudation. Neoendothelium-dependent acetylcholine-induced relaxation (10(-8) mol/L to 3.10(-5) mol/L) in treated animals (Emax = -24.1 +/- 5.5%) was significantly greater than in controls (Emax = -8.9 +/- 2.2%). Endothelium-independent relaxation did not differ between groups (Emax = -58.1 +/- 6.5% in L-arginine-supplemented animals versus -52.9 +/- 6.8% in controls). CONCLUSIONS Our results demonstrate that L-arginine, a precursor of NO, reduces neointimal thickening after balloon denudation and improves neoendothelial-dependent acetylcholine-induced relaxation.

BACKGROUND ST-segment depression during exercise testing is frequently observed in the absence of restenosis after coronary angioplasty. METHODS AND RESULTS We studied the determinants of this phenomenon in 70 consecutive patients with unstable angina related to a single left anterior descending coronary artery lesion who had successful angioplasty without restenosis (< 50% stenosis by quantitative angiography). We compared preangioplasty clinical, angiographic, and hemodynamic variables in the group with positive (ExT Pos, n = 35; ST depression, 2.3 +/- 0.9 mm) and negative (ExT Neg, n = 35; ST depression, 0.3 +/- 0.5 mm) results on exercise testing at follow-up angiography. At this time, minimal lumen diameter (1.7 +/- 0.4 mm) and mean residual stenosis (34 +/- 11%) in the ExT Pos group were not significantly different from the values (1.9 +/- 0.5 mm, 38 +/- 10%) in the ExT Neg group. Before angioplasty, the ExT Pos group had a lower ejection fraction (63 +/- 8% versus 68 +/- 9%, P < .05), more marked anterior hypokinesis estimated by the extent of anterior wall contraction on quantitative ventriculography (P < .05), and a greater end-systolic volume (30 +/- 11 versus 25 +/- 9 mL/m2, P < .05) than the ExT Neg group. At follow-up angiography, regional anterior wall motion was normal in 68 patients (97%). Anterior hypokinesis before angioplasty was strongly associated (P < .01) with a positive exercise test at control (71% compared with 31% in patients with normal wall motion before angioplasty). CONCLUSIONS In the absence of significant epicardial stenosis after angioplasty, ST-segment depression is strongly associated with the presence of preprocedural regional ventricular dysfunction that has recovered at follow-up angiography.

BACKGROUND: Studies examining the relative value of clinical, exercise test, and angiographic data in the prediction of further clinical events after a first acute myocardial infarction (AMI) have produced conflicting results. METHODS: We examined the relative value of clinical, exercise test, and angiographic data as predictors of death, recurrent infarction, and the subsequent development of angina or dyspnea in 303 consecutive patients who underwent exercise testing and coronary angiography within 2 months of an uncomplicated first acute myocardial infarction (AMI), and who were followed for 48 (+/- 22) months. RESULTS: A combination of two clinical and two exercise variables correctly identified 79% of subsequent deaths. No variables had a predictive value for re-infarction. A combination of two exercise variables correctly identified 75% of patients who developed angina during follow up. A combination of two clinical variables and one exercise variable correctly identified 76% of patients who developed dyspnea during follow up. CONCLUSIONS: Exercise testing provided useful prognostic information independent of clinical data. Combining clinical and exercise data identified a group of patients at low risk of future events. In this low-risk group of patients, the addition of angiographic data did not provide additional prognostic information.

Aim The purpose of this study was to define the in-vitro and in-vivo effects of intracoronary enhancement on the absolute density values of coronary plaques during multislice computed tomography. Methods We studied seven ex-vivo left coronary artery specimens surrounded by olive oil and filled with isotonic saline and four solutions with decreasing dilutions of contrast material: control (isotonic saline), 1/200, 1/80, 1/50, and 1/20. The multislice computed tomography protocol was: slice/collimation 32 x 2 x 0.6 mm and rotation time 330 ms. The attenuation (Hounsfield units) value of atherosclerotic plaques was measured for each dilution in lumen, plaque (noncalcified coronary wall thickening), calcium, and surrounding oil. In-vivo assessment was performed in 12 patients (nine men; mean age 58.7 +/- 9.9 years) who underwent two subsequent multislice computed tomography scans (arterial and delayed) after intravenous administration of a single bolus of contrast material. The attenuation values of lumen and plaques during arterial and delayed computed tomography were compared. The results were compared with one-way analysis of variance and correlated with Pearson's test. Results Mean lumen (45 +/- 38 -669 +/- 151 HU) and plaque (11 +/- 35-101 +/- 72 HU) attenuation differed significantly (P

Summary Background Everolimus-eluting and paclitaxel-eluting stents, compared with bare metal stents, reduced the risk of restenosis in clinical trials with strict inclusion and exclusion criteria. We compared the safety and efficacy of the second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice. Methods We randomly assigned 1800 consecutive patients (aged 18–85 years) undergoing percutaneous coronary intervention at one centre to treatment with everolimus-eluting or paclitaxel-eluting stents. The primary endpoint was a composite of safety and efficacy (all-cause mortality, myocardial infarction, and target vessel revascularisation) within 12 months. Patients were not told which stent they had been allocated. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01016041. Findings Follow-up was completed in 1797 patients. The primary endpoint occurred in 56 (6%) of 897 patients in the everolimus-eluting stent group versus 82 (9%) of 903 in the paclitaxel-eluting stent group (relative risk 0·69 [95% CI 0·50–0·95], p value for superiority=0·02). The difference was attributable to a lower rate of stent thrombosis (6 [ vs 23 [3%], 0·26 [0·11–0–64], p=0·002), myocardial infarction (25 [3%] vs 48 [5%], 0·52 [0·33–0·84], p=0·007), and target vessel revascularisation (21 [2%] vs 54 [6%], 0·39 [0·24–0·64], p=0·0001). Cardiac death, non-fatal myocardial infarction, or target lesion revascularisation occurred in 44 [5%] patients in the everolimus-eluting stent group versus 74 [8%] patients in the paclitaxel-eluting stent group, p value for superiority was 0·005. Interpretation The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice. Funding Unrestricted grants from Abbott Vascular and Boston Scientific.

BACKGROUND Serotonin, released by aggregating platelets, may contribute to or cause myocardial ischemia by constricting epicardial vessels. Experimental studies suggest that this constriction is mediated by two distinct serotonin receptor subtypes: 5-hydroxytryptamine1-like (S1-like) and 5-hydroxytryptamine2 (S2). METHODS AND RESULTS To determine the relative contribution of S1-like and S2 receptors to the vasoconstrictor effects of serotonin, we studied the effect of ketanserin (0.75 mg, intracoronary), a selective S2 receptor antagonist, on the constrictor response of human coronary vessels to intracoronary infusions of serotonin. In control patients (n = 7), serotonin (10(-4) mol/l) caused significant (p less than 0.05) constriction only in distal segments, which was significantly (p less than 0.05) inhibited by ketanserin. In stable angina patients (n = 8), serotonin (10(-4) mol/l) caused significant constriction in proximal (p less than 0.01) and distal (p less than 0.01) segments, which was significantly inhibited by ketanserin in proximal (p less than 0.05) but not distal (p = 0.30) segments. In patients with variant angina (n = 3), epicardial occlusion at the site of preexisting stenoses in proximal locations occurred at infused concentrations of 10(-6) (one patient) or 10(-5) (two patients) mol/l. The infusion of the same concentration of serotonin after ketanserin again caused epicardial occlusion. CONCLUSIONS Our results suggest that functionally important S1-like receptors that mediate vasoconstriction exist in the epicardial vessels of patients with stable or variant angina. Their activation, either at hyperreactive sites in patients with variant angina or in the distal epicardial vessels of patients with chronic stable angina, may contribute to or cause myocardial ischemia when serotonin is released after the intracoronary activation of platelets.

BACKGROUND It has been suggested that recurring coronary artery spasm may lead to the development of fixed atherosclerotic coronary obstructions. METHODS AND RESULTS We studied 10 patients with typical Prinzmetal's variant angina in whom the disease remained active for years and in whom occlusive coronary spasm occurred reproducibly at the same arterial site during repeat coronary arteriography (25 +/- 12 months after initial angiography). At initial evaluation, four patients had significant (greater than or equal to 50% fixed coronary diameter reduction) one-vessel coronary artery disease, and six had nonsignificant disease. Spasm developed at stenotic sites (20-65% diameter reduction) in nine patients and at an angiographically normal site in one patient. Progression of coronary disease was assessed in 62 segments: 10 spastic (of which nine were stenotic) and 52 nonspastic (eight stenotic and 44 angiographically normal), using computerized arteriography. Mean diameters (millimeters) of spastic segments, nonspastic stenoses, and angiographically normal nonspastic segments were not significantly different at first and second arteriograms (1.52 +/- 0.14 versus 1.43 +/- 0.21, 1.32 +/- 0.17 versus 1.12 +/- 0.23, and 2.40 +/- 0.12 versus 2.42 +/- 0.12, respectively). Stenosis progression (from 65% diameter reduction to total occlusion) occurred in one patient at a spastic site and in two at nonspastic sites (from 34% to 65% and from 84% to 100%). Complicated stenoses suggestive of plaque fissuring were not observed during the study. CONCLUSIONS In patients with chronic Prinzmetal's variant angina without myocardial infarction, stenosis progression was not frequently observed at spastic sites despite the recurrence of focal coronary spasm over relatively long periods of time.