In a prospective study, 697 patients with acute coronary syndromes underwent three-vessel coronary angiography and imaging after PCI. Of 132 subsequent major adverse cardiovascular events, ...approximately half occurred at the site of the previous culprit lesion.
Approximately 1,350,000 Americans annually have an acute coronary syndrome (unstable angina or myocardial infarction with or without ST-segment elevation).
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Although percutaneous coronary intervention and pharmacologic therapies have improved the prognosis for such patients,
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recurrent major adverse cardiovascular events occur in a substantial proportion of cases.
Recurrent cardiac ischemic events can be due to recurrence at the original treatment site, the presence of untreated lesions elsewhere, or progressive lesions. However, prospective, systematic data on the origin of recurrent events are lacking. Moreover, retrospective studies have shown that most atherosclerotic plaques responsible for future acute coronary syndromes are angiographically mild,
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Objectives This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men. Background Pathological studies suggest ...that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques. Methods A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound IVUS) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis. Results Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (>70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p < 0.0001). The frequency of other plaque phenotypes was similar for men and women including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not significantly different between men and women, although women were rehospitalized more frequently due to culprit lesion–related angina. For men, nonculprit lesion minimal lumen area ≤4.0 mm2 , PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive. Conclusions The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.
We investigated the relation between overall atheroma burden and clinical events in the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study. In ...PROSPECT, 660 patients (3,229 nonculprit lesions with a plaque burden ≥40% and complete intravascular ultrasound data) were divided into tertiles according to baseline percent atheroma volume (PAV: total plaque/vessel volume). Patients were followed for 3.4 years (median); major adverse cardiac events (MACE: death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization because of unstable or progressive angina) were adjudicated to either culprit or nonculprit lesions. Compared with patients in low or intermediate PAV tertiles, patients in the high PAV tertile had the greatest prevalence of plaque rupture and radiofrequency thin-cap fibroatheroma (VH-TCFA) and the highest percentage of necrotic core volume; they were also more likely to have high-risk lesion characteristics: ≥1 lesion with minimal luminal area ≤4 mm2 , plaque burden >70%, and/or VH-TCFA. Three-year cumulative nonculprit lesion-related MACE was greater in the intermediate and high tertiles than in the low tertile (6.3% vs 14.7% vs 15.1%, low vs intermediate vs high tertiles, p = 0.009). On Cox multivariable analysis, insulin-dependent diabetes (hazard ratio HR 3.98, p = 0.002), PAV (HR 1.06, p = 0.03), and the presence of ≥1 VH-TCFA (HR 1.80, p = 0.02) were independent predictors of nonculprit MACE. In conclusion, increasing baseline overall atheroma burden was associated with more advanced, complex, and vulnerable intravascular ultrasound lesion morphology and independently predicted nonculprit lesion-related MACE in patients with acute coronary syndromes after successful culprit lesion intervention.
Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the ...grayscale and virtual histology (VH)–intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤4 mm2 , IVUS plaque burden ≥70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥70%, minimum luminal area ≤4 mm2 , and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.
Objectives The purpose of this study was to determine the clinical impact of non-fibroatheroma lesion phenotype in patients presenting with an acute coronary syndrome (ACS). Background Although ...fibroatheromas (FAs) are known to be clinically unstable, the impact of non-FA lesion phenotype on clinical outcomes has not been studied. Methods In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with an ACS underwent 3-vessel grayscale and virtual histology intravascular ultrasound (VH-IVUS) after successful percutaneous intervention for all culprit lesions and were followed for 3 years. Patients were divided into those who had only the non-FA phenotype (pathological intimal thickening or fibrotic and/or fibrocalcific lesions) versus those who had at least 1 nonculprit FA. Results Among 2,880 nonculprit lesions identified by VH-IVUS, 39.8% were non-FAs (1,042 pathological intimal thickening, 72 fibrotic, and 33 fibrocalcific). Nonculprit major adverse cardiac events (MACE) (death, myocardial infarction, or urgent rehospitalization for progressive or unstable angina) were attributed to only 7 non-FA lesions (0.7%) versus 43 FA lesions (2.7%, p < 0.001) during 3 years follow-up. Of 609 patients, 67 (11.0%) patients had only non-FA lesion phenotypes. Patients with only non-FAs tended to be younger and more often female, have fewer nonculprit lesions and less overall plaque burden and necrotic core, and fewer nonculprit lesion MACE compared with patients with at least 1 FA. In the adjusted Cox proportional hazards model, absence of a FA was a significant predictive of a lower 3-year nonculprit MACE rate (hazard ratio: 0.23; 95% confidence interval: 0.06 to 0.95). Conclusions Non-FA lesions were clinically stable and were rarely associated with clinical events during 3 years of follow-up. The intermediate-term prognosis in patients presenting with ACS in whom all nonculprit lesions are non-FAs is favorable. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466 )
Objectives This study investigated coronary artery remodeling patterns associated with clinical outcomes. Background In the prospective, multicenter PROSPECT (Providing Regional Observations to Study ...Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm2 , a plaque burden ≥70%, and a IVUS–virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. Methods Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). Results Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. Conclusions The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions PROSPECT; NCT00180466 )
This study investigated coronary artery remodeling patterns associated with clinical outcomes.
In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events ...in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling.
Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort).
Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions.
The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. (
An Imaging Study in Patients With Unstable Atherosclerotic Lesions PROSPECT; NCT00180466).
The study sought to examine the relative importance of lesion location versus vessel area and plaque burden in predicting plaque rupture within nonculprit fibroatheromas (FAs) in patients with acute ...coronary syndromes.
Previous studies have demonstrated that plaque rupture is associated with larger vessel area and greater plaque burden clustering in the proximal segments of coronary arteries.
In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study 3-vessel grayscale and radiofrequency-intravascular ultrasound was performed after successful percutaneous coronary intervention in 697 patients with acute coronary syndromes. Untreated nonculprit lesion FAs were classified as proximal (<20 mm), mid (20 to 40 mm), and distal (>40 mm) according to the distance from the ostium to the maximum necrotic core site.
Overall, 74 ruptured FAs and 2,396 nonruptured FAs were identified in nonculprit vessels. The majority of FAs (73.6%) were located within 40 mm of the ostium, and the vessel area and plaque burden progressively decreased from proximal to distal FA location (both p < 0.001). In a multivariate logistic regression model, independent predictors for plaque rupture included the distance from the ostium to the maximum necrotic core site per millimeter (odds ratio OR: 0.86; 95% confidence interval CI: 0.76 to 0.98; p = 0.02), plaque burden per 10% (OR: 2.05; 95% CI: 1.63 to 2.58; p < 0.0001), vessel area per mm(2) (OR: 1.14; 95% CI: 1.11 to 1.17; p < 0.0001), calcium (OR: 0.09; 95% CI: 0.05 to 0.18; p < 0.0001), and right coronary artery location (OR: 2.16; 95% CI: 1.25 to 3.27; p = 0.006). By receiver-operating characteristic analysis, vessel area correlated with plaque rupture stronger than either plaque burden (p < 0.001) or location (p < 0.001).
Large vessel area, plaque burden, proximal location, right coronary artery location, and lack of calcium were associated with FA plaque rupture. The present study suggests that among these variables, vessel area may be the strongest predictor of plaque rupture among non-left main coronary arteries. (
An Imaging Study in Patients With Unstable Atherosclerotic Lesions PROSPECT; NCT00180466).
The safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the Taxus Express paclitaxel-eluting stent (PES) has been demonstrated through 2 years in the SPIRIT II and III ...randomized clinical trials, but limited longer-term data have been reported. In the SPIRIT III trial, 1,002 patients with up to 2 lesions in 2 coronary arteries were randomized 2:1 to EESs versus PESs at 65 United States sites. At completion of 3-year follow-up, treatment with EES compared to PES resulted in a significant 30% decrease in the primary clinical end point of target vessel failure (cardiac death, myocardial infarction, or ischemic-driven target vessel revascularization, 13.5% vs 19.2%, hazard ratio 0.70, 95% confidence interval 0.50 to 0.96, p = 0.03) and a 43% decrease in major adverse cardiovascular events, cardiac death, myocardial infarction, or ischemic-driven target lesion revascularization (9.1% vs 15.7%, hazard ratio 0.57, 95% confidence interval 0.39 to 0.83, p = 0.003). In a landmark analysis, major adverse cardiovascular events were decreased to a similar extent with EES compared to PES 0 through 1 year and 1 year through 3 years (hazard ratio 0.56, 95% confidence interval 0.35 to 0.90; hazard ratio 0.59, 95% confidence interval 0.31 to 1.11, respectively). In conclusion, patients treated with EES rather than PES in the SPIRIT III trial had significantly improved event-free survival at 3 years. From 1 year to 3 years hazard curves continued to diverge in favor of EES, consistent with an improving long-term safety and efficacy profile of EES compared to PES, with no evidence of late catchup.
The purpose of this study was to determine the clinical impact of non-fibroatheroma lesion phenotype in patients presenting with an acute coronary syndrome (ACS).
Although fibroatheromas (FAs) are ...known to be clinically unstable, the impact of non-FA lesion phenotype on clinical outcomes has not been studied.
In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with an ACS underwent 3-vessel grayscale and virtual histology intravascular ultrasound (VH-IVUS) after successful percutaneous intervention for all culprit lesions and were followed for 3 years. Patients were divided into those who had only the non-FA phenotype (pathological intimal thickening or fibrotic and/or fibrocalcific lesions) versus those who had at least 1 nonculprit FA.
Among 2,880 nonculprit lesions identified by VH-IVUS, 39.8% were non-FAs (1,042 pathological intimal thickening, 72 fibrotic, and 33 fibrocalcific). Nonculprit major adverse cardiac events (MACE) (death, myocardial infarction, or urgent rehospitalization for progressive or unstable angina) were attributed to only 7 non-FA lesions (0.7%) versus 43 FA lesions (2.7%, p < 0.001) during 3 years follow-up. Of 609 patients, 67 (11.0%) patients had only non-FA lesion phenotypes. Patients with only non-FAs tended to be younger and more often female, have fewer nonculprit lesions and less overall plaque burden and necrotic core, and fewer nonculprit lesion MACE compared with patients with at least 1 FA. In the adjusted Cox proportional hazards model, absence of a FA was a significant predictive of a lower 3-year nonculprit MACE rate (hazard ratio: 0.23; 95% confidence interval: 0.06 to 0.95).
Non-FA lesions were clinically stable and were rarely associated with clinical events during 3 years of follow-up. The intermediate-term prognosis in patients presenting with ACS in whom all nonculprit lesions are non-FAs is favorable. (
An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466).
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