Xiaofan Wu

Incidence, Mechanisms, Predictors, and Clinical Impact of Acute and Late Stent Malapposition After Primary Intervention in Patients With Acute Myocardial Infarction An Intravascular Ultrasound Substudy of the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) Trial

Background— The incidence and mechanisms of acute and late stent malapposition after primary stent implantation in ST-segment elevation myocardial infarction remain unclear. Methods and Results— The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation myocardial infarction patients. The intravascular ultrasound substudy enrolled 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and 13-month follow-up imaging. Postintervention acute stent malapposition (ASM) occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and 40.0% BMS-treated lesions resolved at follow-up, especially within the stent body (66.7%); complete resolution was accompanied by a reduction in external elastic membrane area. An ASM area >1.2 mm2 best separated persistent from resolved ASM. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition area correlated to the decrease of peri-stent plaque in the subset of lesions without positive remodeling and only to change in external elastic membrane in the group with positive remodeling. Independent predictors of late acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60; 95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95% CI, 2.15 to 18.62). Conclusions— The incidence of ASM was similar in PES- and BMS-treated lesions, but late acquired stent malapposition was more common in PES-treated lesions. The reason for resolved ASM was negative remodeling, with larger ASM areas separating persistent from resolved ASM. Late acquired stent malapposition was due mainly to positive remodeling and plaque/thrombus resolution. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Virtual Histology Intravascular Ultrasound Analysis of Non-Culprit Attenuated Plaques Detected by Grayscale Intravascular Ultrasound in Patients With Acute Coronary Syndromes

Noncalcific attenuated plaques identified by grayscale intravascular ultrasound (IVUS) are often seen in patients with acute coronary syndromes and have been associated with no reflow and creatine kinase-MB elevation after percutaneous coronary intervention. Histopathology has shown cholesterol clefts, microcalcification, or organized thrombus. One hundred twenty-four vessels in 64 patients with acute coronary syndromes from the PROSPECT trial were identified for inclusion in the present analysis. After excluding 4 vessels with severe calcification, 9 vessels with <40% plaque burden, and 3 vessels with too few (<3) virtual histology (VH)-IVUS frames for analysis, complete grayscale IVUS and VH-IVUS was available for 108 vessels in 64 patients that contained 39 VH-IVUS thin-capped fibroatheromas (VH-TCFA), 40 thick-capped fibroatheromas (VH-ThFA), and 33 pathologic intimal thickening but no fibrotic or fibrocalcific plaques. Overall, there were 47 grayscale IVUS attenuated plaques in 43 vessels. Compared to the minimum luminal sites of the remaining 65 vessels (controls), attenuated plaques contained larger necrotic core areas (1.5 +/- 0.9 vs 0.9 +/- 0.8 mm(2) in controls, p = 0.001). Fibroatheromas (VH-TCFA or VH-ThFA) were more common at the sites of attenuated plaques than at control sites (VH-TCFA 42.5% vs 29.2%, VH-ThFA 53.2% vs 23.1%, pathologic intimal thickening 4.3% vs 47.7%, p <0.0001). In conclusion, grayscale IVUS attenuated plaques are associated with a large amount of VH-IVUS necrotic core and are markers of the presence of fibroatheromas (VH-TCFA or VH-ThFA). This may explain the biologic instability of these lesions.

The Relationship Between Attenuated Plaque Identified by Intravascular Ultrasound and No-Reflow After Stenting in Acute Myocardial Infarction The HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial

OBJECTIVES The aim of this study was to understand the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infarction (AMI). BACKGROUND Attenuated plaques identified by grayscale intravascular ultrasound (IVUS) might predict transient deterioration in coronary flow and/or no-reflow during percutaneous coronary intervention (PCI). METHODS We analyzed clinical, angiographic, and IVUS data from 364 patients (n = 364 infarct-related arteries) enrolled in the randomized HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. No-reflow was final Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2 in the absence of mechanical obstruction. Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1 mm, scoring the angle as 1 to 4 (corresponding to <90°, 90° to 180°, 180° to 270°, or 270° to 360°, respectively), summing the scores, and normalizing for analysis length. RESULTS Overall, 284 (78.0%) patients had attenuated plaques; no-reflow occurred in 37 (10.2%). Patients with no-reflow had a higher mean attenuation score (median [interquartile range] 2.2 [0.0 to 2.8] vs. 1.3 [0.7 to 1.8], p < 0.001), lower baseline left ventricular ejection fraction (52.8% [43.2% to 61.5%] vs. 61.4% [52.2% to 68.1%], p = 0.002), and more baseline angiographic thrombus (89.2% vs. 74.1%, p = 0.043) with no differences in post-PCI stent expansion versus patients without no-reflow. Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 points (90° to 180°, sensitivity of 81.5%, and specificity of 80.5%). CONCLUSIONS Attenuated plaque was present in three-quarters of patients with AMI. The amount of attenuated plaque strongly correlated with no-reflow; the larger the attenuated plaque, the greater the likelihood of no-reflow. (Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent [TAXUS™] or Uncoated Bare Metal Stent [EXPRESS2™]; NCT00433966).

Dynamic nature of nonculprit coronary artery lesion morphology in STEMI: a serial IVUS analysis from the HORIZONS-AMI trial.

OBJECTIVES The authors sought to report the temporal stability of an untreated, nonculprit lesion phenotype in patients presenting with ST-segment elevation myocardial infarction (STEMI). BACKGROUND The temporal stability of the untreated, nonculprit lesion phenotype has been studied using intravascular ultrasound-virtual histology (IVUS) in patients with stable ischemic heart disease, but not in STEMI patients. METHODS As part of a formal substudy of the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, baseline and 13-month follow-up IVUS was performed in 99 untreated nonculprit lesions in 63 STEMI patients. Lesions were classified as pathological intimal thickening (PIT), IVUS-derived thin-cap fibroatheroma (TCFA), thick-cap fibroatheroma (ThCFA), fibrotic plaque, or fibrocalcific plaque. RESULTS The frequency of TCFA increased from 41% at baseline to 54% at follow-up, whereas ThCFAs decreased from 41% to 34% and PIT decreased from 16% to 8%. Among the 41 lesions classified at baseline as TCFA, at follow-up, 32 (78%) were still classified as TCFA, whereas 9 (22%) were classified as ThCFAs or fibrotic plaques. An additional 21 lesions at follow-up were newly classified as TCFA, developing from either PIT or ThCFA. TCFA at baseline that evolved into non-TCFAs trended toward a more distal location than TCFA that did not change (p = 0.12). In lesions classified as TCFA, the minimum lumen area (MLA) decreased from 8.1 (interquartile range [IQR]: 7.4 to 8.8) mm(2) at baseline to 7.8 (IQR: 7.2 to 8.4) mm(2) at follow-up, p < 0.05; this was associated with an increase in percent necrotic core at the MLA site (14% [IQR: 12 to 16] to 19% [IQR: 17 to 22], p < 0.0001) and over the entire length of the lesion (14% [IQR: 12 to 16] to 18% [IQR: 17 to 20], p < 0.0001). CONCLUSIONS Untreated nonculprit lesions in STEMI patients frequently have TCFA morphology that does not change during 13-month follow-up and is accompanied by a decrease in MLA and an increase in necrotic core. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

Long-Term Follow-Up of Attenuated Plaques in Patients With Acute Myocardial Infarction: An Intravascular Ultrasound Substudy of the HORIZONS-AMI Trial

Background— Intravascular ultrasound (IVUS)-attenuated plaque is characterized by absence of ultrasound signal behind hypoehcoic plaque and is seen almost exclusively in acute coronary syndromes. Methods and Results— We analyzed poststenting and 13-month follow-up IVUS in 186 patients (195 lesions) with acute myocardial infarction who underwent primary percutaneous coronary intervention. The primary prespecified IVUS end point was the in-stent percent net volume obstruction at follow-up. Overall, 70.3% of lesions contained attenuated plaques at baseline. During follow-up, attenuation scores decreased significantly, behind paclitaxel-eluting stents (PES) (14.1 [11.9, 16.3] to 7.7 [5.4, 9.9], P<0.0001), behind bare metal stents (BMS) (18.5 [13.2, 23.8] to 12.0 [6.7, 17.3], P<0.0001), and within distal references (3.1 [1.1, 5.1] to 2.2 [0.2, 4.1], P=0.02). There was a greater calcium increase in attenuated than nonattenuated plaques in both PES (&Dgr;calcium score of 4.4 [3.3, 5.5] versus 1.6 [0.9, 2.3], P<0.0001) and BMS (&Dgr;calcium score of 4.1[2.3, 5.9] versus 1.0 [0.3, 1.7], P=0.001). PES implantation into attenuated plaques was particularly associated with late acquired stent malapposition (36.8% versus 15.4% compared with nonattenuated plaques treated with PES, P=0.03). Changes in attenuation scores correlated with changes in calcium scores both in PES (Pearson correlation coefficient=−0.456, P<0.0001] and BMS sites (Pearson correlation coefficient=−0.450, P=0.0006). In 3 years of follow-up, target lesion revascularization was significantly less in patients with attenuated plaque at baseline (6.0% versus 17.4% in patient without attenuated plaques, P=0.019). Conclusions— Attenuated plaques evolved into calcified plaques after stent implantation. Attenuated plaque is associated with late acquired stent malapposition and related less target lesion revascularization (consistent with less neointimal hyperplasia), especially after PES implantation in patients with acute myocardial infarction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Plaque shift and distal embolism in patients with acute myocardial infarction: a volumetric intravascular ultrasound analysis from the HORIZONS-AMI trial.

Vessel expansion and axial plaque redistribution or distal plaque embolization contribute to the increase in lumen dimensions after stent implantation.

Level of Pregnancy-associated Plasma Protein-A Correlates With Coronary Thin-cap Fibroatheroma Burden in Patients With Coronary Artery Disease: Novel Findings From 3-Vessel Virtual Histology Intravascular Ultrasound Assessment.

Abstract Pregnancy-associated plasma protein-A (PAPP-A) level is an independent predictor of acute cardiovascular event occurrence. To test the hypothesis that increased PAPP-A levels would be associated with a higher burden of coronary thin-cap fibroatheroma (TCFA) thereby underlying the heightened risk for cardiovascular events in patients with coronary artery disease; 154 patients (462 vessels and 975 plaques) with stable angina or non-ST-segment elevation acute coronary syndrome (NSTE-ACS) referred for percutaneous coronary intervention were assessed using 3-vessel virtual histology (VH)-intravascular ultrasound (IVUS). Thin-cap fibroatheroma virtual histology was defined as focal, necrotic core (NC)-rich (≥10% of cross-sectional area) plaques in contact with the lumen, and plaque burden ≥40%. Pregnancy-associated plasma protein-A levels were determined by sandwich enzyme-linked immunosorbent assay, and patients were divided into 3 groups based on PAPP-A level tertiles. Although the highest PAPP-A level tertile was not associated with 3-vessel plaque number, it was associated with 3-vessel VH-TCFA number and necrotic core volume. Patients with ≥3 VH-TCFAs had a higher PAPP-A level than patients with 1 to 3 VH-TCFAs or without any VH-TCFA (13.3 ± 11.8 versus 7.8 ± 4.7 versus 7.4 ± 4.7 mIU/L, P < 0.001, respectively). Moreover, PAPP-A level was an independent predictor of higher total number of VH-TCFAs (OR 1.18; 95% CI 1.07–1.29, P = 0.001). This VH-IVUS study demonstrated, for the first time to our knowledge, that higher PAPP-A levels are associated with higher 3-vessel TCFA burden in patients with coronary artery disease. Pregnancy-associated plasma protein-A, therefore, might be a useful serum biomarker to predict increased coronary TCFA burden and plaque instability.