Search

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all‐cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all‐cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR‐guided group and 634 in the angiography‐guided group). Median follow‐up was 7 years (interquartile range, 3.22–11.08 years). After 1:1 propensity‐score matching, baseline characteristics between the 2 groups were similar. All‐cause death was significantly lower in the FFR‐guided group compared with the angiography‐guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49–0.85]; P

Background: Hemodynamic assessment of untreated nonculprit lesions was not studied in the PROSPECT study (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). We developed a virtual intravascular ultrasound–derived lesion-specific fractional flow reserve (lesion-specific IVUS-FFR) algorithm to assess individual lesion-level FFR. We sought to investigate the relation between lesion-specific IVUS-FFR and major adverse cardiovascular events (MACE) arising from untreated nonculprit lesions in the PROSPECT study. Methods: In PROSPECT, 697 patients with acute coronary syndromes underwent 3-vessel grayscale and virtual histology–IVUS to correlate untreated nonculprit plaque morphology with 3-year nonculprit related MACE (composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina). Lesion-specific IVUS-FFR was calculated from volumetric IVUS lumen area measurements at 0.4 mm intervals by applying a mathematical circulation model using basic fluid dynamics equations. Results: Lesion-specific IVUS-FFR was analyzable in 3227 nonculprit lesions in 660 patients among whom 54 nonculprit MACE events (3 myocardial infarctions) occurred at median 3.4-year follow-up. By receiver-operating characteristic analysis, the best cutoff value of lesion-specific IVUS-FFR to predict nonculprit MACE was ≤0.95. After adjusting for patient and lesion characteristics, lesion-specific IVUS-FFR (hazard ratio, 4.83 [95% CI, 2.20–10.61]; P <0.001) was an independent predictor of 3-year nonculprit MACE, in addition to minimum lumen area≤4.0 mm2, plaque burden ≥70%, and virtual histology thin-cap fibroatheroma. Conclusions: Minor reductions in lesion-specific IVUS-FFR were independently associated with future nonculprit MACE arising from untreated angiographically mild stenoses along with previously established high-risk lesion morphological characteristics. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00180466. [ABSTRACT FROM AUTHOR]

Background--The predictive value of fractional flow reserve (FFR) measured immediately after percutaneous coronary intervention (PCI) with drug-eluting stent placement has not been prospectively investigated. We investigated the potential of post-PCI FFR measurements to predict clinical outcome in patients from FAME 1 and 2 trials (Fractional Flow Reserve or Angiography for Multivessel Evaluation). Methods and Results--All patients of FAME 1 and FAME 2 who had post-PCI FFR measurement were included. The primary outcome was vessel-oriented composite end point at 2 years, defined as vessel-related cardiovascular death, vessel-related spontaneous myocardial infarction, and ischemia-driven target vessel revascularization. Eight hundred thirty-eight vessels in 639 patients were analyzed. Baseline FFR values did not differ between vessels with versus without vessel-oriented composite end point (0.66±0.11 versus 0.63±0.14, respectively; P=0.207). Post-PCI FFR was significantly lower in vessels with vessel-oriented composite end point (0.88±0.06 versus 0.90±0.06, respectively; P=0.019). Comparing the 2-year outcome of lower and upper tertiles of post-PCI FFR significant difference was found favoring upper tertile in terms of overall vessel-oriented composite end point (9.2% versus 3.8%, respectively; hazard ratio, 1.46; 95% confidence interval, 1.02-2.08; P=0.037) and target vessel revascularization (7.0% versus 2.4%, respectively; hazard ratio, 1.59; 95% confidence interval, 1.03-2.46; P=0.037). When adjusted to sex, hypertension, diabetes mellitus, target vessel, serial stenosis, and baseline percentage diameter stenosis, a strong trend was preserved in terms of target vessel revascularization (harzard ratio, 1.55; 95% confidence interval, 0.97-2.46; P=0.066), favoring the upper tertile. Post-PCI FFR of 0.92 was found to have the highest diagnostic accuracy; however, the positive likelihood ratio remained low (<1.4). Conclusions--A higher post-PCI FFR value is associated with a better vessel-related outcome. However, its predictive value is too low to advocate its use as a surrogate clinical end point. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to evaluate the impact of sex differences on fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Background: The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study demonstrated that FFR-guided PCI improves outcomes compared with an angiography-guided strategy. The role of FFR-guided PCI in women versus men has not been evaluated. Methods: We analyzed 2-year data from the FAME study in the 744 men and 261 women with multivessel coronary disease, who were randomized to angiography- or FFR-guided PCI. Statistical comparisons based on sex were stratified by treatment method. Results: Although women were older and had significantly higher rates of hypertension than men did, there were no differences in the rates of major adverse cardiac events (20.3% vs. 20.2%, p = 0.923) and its individual components at 2 years. FFR values were significantly higher in women than in men (0.75 ± 0.18 vs. 0.71 ± 0.17, p = 0.001). The proportion of functionally significant lesions (FFR ≤ 0.80) was lower in women than in men for lesions with 50% to 70% stenosis (21.1% vs. 39.5%, p < 0.001) and for lesions with 70% to 90% stenosis (71.9% vs. 82.0%, p = 0.019). An FFR-guided strategy resulted in similar relative risk reductions for death, myocardial infarction, and repeat revascularization in men and in women. There were no interactions between sex and treatment method for any outcome variables. Conclusions: In comparison with men, angiographic lesions of similar severity are less likely to be ischemia-producing in women. An FFR-guided PCI strategy is equally beneficial in women as it is in men. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to study whether there is a difference in benefit of fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) in multivessel coronary disease in patients with unstable angina (UA) or non–ST-segment elevation myocardial infarction (NSTEMI), compared with stable angina (SA). Background: The use of FFR to guide PCI has been well established for patients with SA. Its use in patients with UA or NSTEMI has not been investigated prospectively. Methods: In the FAME (Fractional flow reserve versus Angiography for Multivessel Evaluation) study 1,005 patients with multivessel disease amenable to PCI were included and randomized to either angiography-guided PCI of all lesions ≥50% or FFR-guided PCI of lesions with an FFR ≤0.80. Patients admitted for UA or NSTEMI with positive troponin but total creatine kinase <1,000 U/l were eligible for inclusion. We determined 2-year major adverse cardiac event rates of these patients and compared it with stable patients. Results: Of 1,005 patients, 328 had UA or NSTEMI. There was no evidence for heterogeneity among the subgroups for any of the outcome variables (all p values >0.05). Using FFR to guide PCI resulted in similar risk reductions of major adverse cardiac events and its components in patients with UA or NSTEMI, compared with patients with SA (absolute risk reduction of 5.1% vs. 3.7%, respectively, p = 0.92). In patients with UA or NSTEMI, the number of stents was reduced without increase in hospital stay or procedure time and with less contrast use, in similarity to stable patients. Conclusions: The benefit of using FFR to guide PCI in multivessel disease does not differ between patients with UA or NSTEMI, compared with patients with SA. [Copyright &y& Elsevier]

Objectives: We investigated the reliability of fractional flow reserve (FFR) of nonculprit coronary stenoses during percutaneous coronary intervention (PCI) in acute myocardial infarction. Background: Assessing the hemodynamic severity of the nonculprit coronary artery stenoses at the acute phase of a myocardial infarction could improve risk stratification and shorten the diagnostic work-up. Methods: One hundred one patients undergoing PCI for an acute myocardial infarction (n = 75 with ST-segment elevation myocardial infarction [STEMI], and n = 26 with non–ST-segment elevation myocardial infarction) were prospectively recruited. The FFR measurements in 112 nonculprit stenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later. In addition, left ventricular ejection fraction, quantitative coronary angiographic measurements of the nonculprit stenoses, Thrombolysis In Myocardial Infarction (TIMI) flow, corrected TIMI frame count (cTFC), and the index of microcirculatory resistance (n = 14) of the nonculprit vessels were assessed in the acute phase and at control angiogram. Results: The FFR value of the nonculprit stenoses did not change between the acute and follow-up (0.77 ± 0.13 vs. 0.77 ± 0.13, respectively, p = NS). In only 2 patients, the FFR value was higher than 0.8 at the acute phase and lower than 0.75 at follow-up. The TIMI flow, cTFC, percentage diameter stenosis, minimum lumen diameter, and index of microcirculatory resistance did not change. Left ventricular ejection fraction increased significantly in patients with STEMI (from 54 ± 13% to 57 ± 13%, p = 0.03). Conclusions: During the acute phase of acute coronary syndromes, the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR. This allows a decision about the need for additional revascularization and might contribute to a better risk stratification. [ABSTRACT FROM AUTHOR]

Objectives: We tested the hypothesis that residual platelet reactivity after clopidogrel correlates with the extent and severity of coronary atherosclerosis in patients undergoing elective percutaneous coronary intervention (PCI). Background: Platelets are actively involved in vascular atherosclerosis. Methods: We prospectively enrolled 338 patients undergoing PCI for stable angina, loaded with 600-mg clopidogrel. Platelet reactivity was assessed 12 h later by measuring P2Y12 reactivity unit (PRU) with VerifyNow P2Y12 assay (Accumetrics, San Diego, California). High platelet reactivity (HPR) was defined as PRU value ≥240. Presence of multivessel disease (MVD) and total stent length (TSL) were used as surrogate markers of atherosclerosis severity and extension. Results: Patients with MVD showed higher PRU compared with single-vessel disease (SVD) patients (222 ± 85 vs. 191 ± 73; p < 0.001). The PRU increased with the number of stenotic coronaries (1-vessel disease: 191 ± 73; 2-vessel disease: 220 ± 88; 3-vessel disease: 226 ± 80; p = 0.002). The PRU was higher in the third TSL tertile compared with first tertile (217 ± 83 vs. 191 ± 73; p = 0.048). The HPR was most frequently observed among MVD patients (40.5% vs. 21.6% in patients with SVD, respectively; p < 0.001) and those in the third TSL tertile (35.8% vs. 22.2% first tertile; p = 0.028). Higher incidence of periprocedural myocardial infarction was observed in patients with HPR (41.2% vs. 26.7% in patients without HPR; p = 0.008) and in those in the third tertile TSL (37.7% vs. 23.1% first tertile; p = 0.020). By multivariate analysis, HPR was the only independent predictor of periprocedural myocardial infarction (p = 0.034). Conclusions: Patients with more extensive coronary atherosclerosis have a higher rate of HPR, which might partly account for higher risk of periprocedural MI. [Copyright &y& Elsevier]

Supplemental Digital Content is available in the text. Background: During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making. Methods: In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFReng] and disengaged [FFRdis]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFReng–FFRdis was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFReng–FFRdis could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFReng–FFRdis related to the stenosis location, that is, proximal and middle versus distal coronary segments. Results: Overall, FFR significantly changed after GC disengagement: FFReng 0.84±0.08 versus FFRdis 0.80±0.09, P <0.001. Particularly, in 38 stenoses (19%) with FFR values in the 0.81 to 0.85 range, GC disengagement was associated with a shift from above to below the 0.80 clinical cutoff, resulting into a change of the treatment strategy from medical therapy to percutaneous coronary intervention. The impact of GC disengagement was significantly more pronounced with stenoses located in proximal and middle as compared with distal coronary segments (ΔFFReng–FFRdis, proximal and middle 0.04±0.03 versus distal segments 0.03±0.03; P =0.042). Conclusions: GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background—: Fractional flow reserve (FFR)-guided coronary artery bypass graft (CABG) surgery has been associated with lower number of graft anastomoses, lower rate of on-pump surgery, and higher graft patency rate as compared with angiography-guided CABG surgery. However, no clinical benefit has been reported to date. Methods and Results—: Consecutive patients (n=627) treated by CABG between 2006 and 2010 were retrospectively included. In 198 patients, at least 1 stenosis was grafted according to FFR (FFR-guided group), whereas in 429 patients all stenoses were grafted based on angiography (angiography-guided group). The 2 coprimary end points were overall death or myocardial infarction and major adverse cardiovascular events (composite of overall death, myocardial infarction, and target vessel revascularization) up to 6-year follow-up. In the FFR-guided group, patients were significantly younger (66 [57–73] versus 70 [63–76]; P<0.001), more often male (82% versus 72%; P=0.008), and less often diabetic (21% versus 30%; P=0.023). Clinical follow-up (median, 85 [66–104] months) was analyzed in 396 patients after 1:1 propensity-score matching for these 3 variables. The rate of overall death or myocardial infarction was significantly lower in the FFR-guided (n=31 [16%] versus n=49 [25%]; hazard ratio, 0.59 [95% confidence interval, 0.38–0.93]; P=0.020) as compared with the angiography-guided group. Major adverse cardiovascular events rate was also numerically lower in the FFR-guided than in the angiography-guided group (n=42 [21%] versus n=52 [26%]; hazard ratio, 0.77 [95% confidence interval, 0.51–1.16]; P=0.21). Conclusions—: FFR-guided CABG is associated with a significant reduction in the rate of overall death or myocardial infarction at 6-year follow-up as compared with angiography-guided CABG. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to use angiography and grayscale and intravascular ultrasound–virtual histology to assess coronary lesions that caused events during a median follow-up period of 3.4 years. Background: Vulnerable plaque-related events are assumed to be the result of substantial progression of insignificant lesions. Methods: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with acute coronary syndromes underwent treatment of all culprit lesions followed by 3-vessel imaging to assess the natural history of culprit and untreated nonculprit (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were divided into those with versus without substantial lesion progression (SLP) (≥20% angiographic diameter stenosis increase). Results: NC lesion events occurred in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n = 6) occurred only in patients with SLP. Conversely, patients without SLP presented only with unstable or increasing angina requiring rehospitalization. Lesions with versus without SLP occurred later (median time to event 401 vs. 223 days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs. 53.8%, p < 0.0001) but more severe at the time of the event (mean diameter stenosis 73.8% vs. 56%, p < 0.0001); and had comparable baseline median plaque burden (68.7% vs. 70.1%, p = 0.17), minimum luminal area (3.7 vs. 4.0 mm2, p = 0.60), and intravascular ultrasound–virtual histology phenotype (83.3% vs. 90.9%, p = 0.68; classified as fibroatheromas at baseline). Conclusions: NC lesions responsible for future cardiovascular events showed angiographic increase during 3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events due to lesions with SLP were angiographically less severe and presented with a delayed time course but were otherwise indistinguishable from NC events that were not associated with SLP. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Objectives: The goal of this study was to characterize the extent and composition of coronary atherosclerosis in patients with diabetes mellitus or the metabolic syndrome (Met Syn) presenting with acute coronary syndromes (ACS). Background: Diabetes and Met Syn patients have increased rates of major adverse cardiac events (MACE), yet a systematic description of nonculprit lesions for these high-risk groups is incomplete. Methods: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, ACS patients underwent 3-vessel quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention (PCI). Subsequent MACE (cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina) were adjudicated to the originally treated culprit versus untreated nonculprit lesions in 3 patient groups: 1) diabetes; 2) Met Syn; and 3) neither. Median length of follow-up was 3.4 years. Results: Of 673 patients, 119 (17.7%) had diabetes and 239 (35.5%) had Met Syn. The cumulative 3-year MACE rate was 29.4% in patients with diabetes, 21.3% with Met Syn, and 17.4% with neither (p = 0.03). MACE adjudicated to untreated nonculprit lesions occurred in 18.7%, 11.7%, and 9.7% of patients, respectively (p = 0.06). Nonculprit lesions in diabetes and Met Syn patients were longer and had greater plaque burden, smaller lumen areas, with greater necrotic core and calcium content. Diabetes and Met Syn patients with future MACE had greater necrotic core and calcification compared with the normal cardiometabolic group. Conclusions: In this PCI ACS population, patients with diabetes and Met Syn had higher 3-year MACE rates. Lesion length, plaque burden, necrotic core, and calcium content were significantly greater among nonculprit lesions of patients with diabetes and Met Syn, but only necrotic core and calcium were significantly greater in the nonculprit lesions of patients with a future MACE in this exploratory analysis. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to correlate adverse events at long-term follow-up in patients after an acute coronary syndrome with coronary plaque characteristics derived from simultaneous evaluation of their mechanical and compositional properties using virtual histology (intravascular ultrasound virtual histology) and palpography. Background: Fibroatheroma is the plaque morphology with the highest risk of causing adverse cardiac events. Palpography can potentially assess the local mechanical plaque properties with the possibility of identifying fibroatheroma with the highest risk of rupture. Methods: A total of 114 patients with acute coronary syndrome from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) trial underwent a single ultrasound imaging investigation of their 3 coronary vessels with the co-registration of intravascular ultrasound virtual histology and palpography. Major adverse cardiac events (MACE) (cardiac death, cardiac arrest, myocardial infarction, or unstable or progressive angina) were collected up to a median follow-up of 3.4 years and adjudicated to originally treated culprit versus untreated nonculprit lesions. Results: In total, 488 necrotic core–rich plaques were identified and subclassified as thin-cap fibroatheroma (n = 111), calcified thick-cap fibroatheroma (n = 213), and noncalcified thick-cap fibroatheroma (n = 164) and matched to their co-registered palpography data. A total of 16 MACE, adjudicated to untreated nonculprit lesions, were recorded at follow-up. In patients in whom MACE developed, fibroatheroma were larger (plaque area 10.0 mm2 [range: 8.4 to 11.6 mm2] vs. 8.2 mm2 [range: 7.7 to 8.8 mm2] (p = 0.03) compared with patients who were MACE free. By palpography, the maximum and the density strain values did not differ between the varying subtypes of fibroatheroma of patients with or without MACE during follow-up. Conclusions: In acute coronary syndromes, patients treated with stents and contemporary pharmacotherapy, palpography did not provide additional diagnostic information for the identification of fibroatheroma with a high risk of rupture and MACE during long-term follow-up. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466) [Copyright &y& Elsevier]

Objectives: In this substudy of the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, we examined the longitudinal distribution of atherosclerotic plaque burden, virtual histology–intravascular ultrasound (VH-IVUS) characterized necrotic core (NC) content and VH–thin-cap fibroatheroma (TCFA) distribution in nonculprit lesions of patients presenting with acute coronary syndromes. Background: Previous analyses suggested that vulnerable plaques and acute myocardial infarction may occur more frequently in the proximal than the distal coronary tree. Methods: A total of 4,234 proximal, mid, and distal 30-mm-long segments of each epicardial coronary artery were compared with each other and to the left main coronary artery (LMCA). Results: Combining IVUS data from all 3 arteries, there was a gradient in plaque burden from the proximal (42.4%) to mid (37.6%) to distal (32.6%) 30-mm-long segments (p < 0.0001). Overall, 67.4% of proximal, 41.0% of mid, and 29.7% of distal 30-mm-long segments contained at least 1 lesion (plaque burden >40%). Proportion of NC, however, was similar in the proximal and mid 30-mm-long segments of all arteries (10.3% [interquartile range (IQR): 4.8% to 16.7%] vs. 10.6% [IQR: 5.0% to 18.1%], p = 0.25), but less in the distal 30-mm-long segment (9.1% [IQR: 3.7% to 17.8%], p = 0.03 compared with the proximal segment and p = 0.003 compared with the mid segment). Overall, 17.3% of proximal, 11.5% of mid, and 9.1% of distal 30-mm-long segments had at least 1 lesion that was classified as VH-TCFA (p < 0.0001). Comparing the LMCA with the combined cohort of proximal left anterior descending, left circumflex, and right coronary artery 30-mm-long segments: 1) plaque burden was less (35.4% [IQR: 28.8% to 43.5%] vs. 40.9% [IQR: 33.3% to 48.0%], p < 0.0001); 2) fewer LMCAs contained at least 1 lesion (17.5%, p < 0.0001); 3) there was less NC (6.5% [IQR: 2.9% to 12.2%] vs. 9.3% [IQR: 4.3% to 15.9%], p < 0.0001); and 4) LMCAs rarely contained a VH-TCFA (1.8%, p < 0.0001). Conclusions: The current analysis appears to confirm that lesions that are responsible for acute coronary events (large, plaque burden–rich in NC) are somewhat more likely to be present in the proximal than the distal coronary tree, except for the LMCA. [Copyright &y& Elsevier]

Objectives: In a prospective study of the natural history of coronary atherosclerosis using angiography and grayscale and radiofrequency intravascular ultrasound (IVUS)–virtual histology (VH), larger plaque burden, smaller luminal area, and plaque composition thin-cap fibroatheroma emerged as independent predictors of future adverse cardiovascular events. Background: The methodology for IVUS-VH classification for an in vivo natural history study and the prospective image mapping by angiography and grayscale and IVUS-VH have not been established. Methods: All culprit and nonculprit lesions (defined as ≥30% angiographic visual diameter stenoses) were analyzed. Three epicardial vessels as well as all ≥1.5-mm-diameter side branches were divided into 29 CASS (Coronary Artery Surgery Study) segments. Each CASS segment was then subdivided into 1.5-mm-long subsegments, and dimensions were analyzed. All grayscale and IVUS-VH slices from the proximal 6 to 8 cm of the 3 coronary arteries were analyzed, with lesions defined as having more than 3 consecutive slices with ≥40% plaque burden categorized as: 1) VH thin-cap fibroatheroma; 2) thick-cap fibroatheroma; 3) pathological intimal thickening; 4) fibrotic plaque; or 5) fibrocalcific plaque. The locations of angiographic and grayscale and IVUS-VH lesions were recorded in relation to the corresponding coronary artery ostium and nearby side branches. Results: The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. On multivariate analysis, nonculprit lesions associated with recurrent events were characterized by a plaque burden ≥70% (hazard ratio: 5.03; 95% confidence interval: 2.51 to 10.11; p < 0.0001), a minimal luminal area ≤4.0 mm2 (hazard ratio: 3.21; 95% confidence interval: 1.61 to 6.42; p = 0.001), and IVUS-VH phenotype of a thin-cap fibroatheroma (hazard ratio: 3.35; 95% confidence interval: 1.77 to 6.36; p < 0.001). Conclusions: Three-vessel multimodality coronary artery imaging was feasible and allowed the identification of lesion-level predictors for future events in this natural history study. [Copyright &y& Elsevier]