Predicting future left anterior descending artery events from non-culprit lesions: insights from the Lipid-Rich Plaque study.

AIMS: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. METHODS AND RESULTS: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001). CONCLUSION: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.

Feasibility and Safety of Low-Dose Intra-Coronary Tenecteplase During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction (ICE T-TIMI 49).

Following primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction, microvascular perfusion is often impaired secondary to thrombotic embolization. Intracoronary (IC) fibrinolytic administration may reduce thrombotic burden and distal embolization. The ICE-T-TIMI-49 study evaluated the feasibility and safety of low-dose IC tenecteplase (TNK) during PPCI. The study randomized 40 PPCI patients to a volume matched bolus of IC TNK (4 mg) (n = 20) or IC saline placebo (n = 20) before and following PPCI. The primary end point was percent diameter stenosis of the culprit lesion following first bolus. The primary end point did not differ between IC placebo (median 100%, interquartile range [IQR] 83.0,100.0) and IC TNK (median 100% stenosis, IQR 91.0,100.0; p = 0.522). However, the proportion of patients with reduction in thrombus following first bolus tended to be greater with IC TNK (placebo: 12.5% vs IC TNK: 40.0%, p = 0.133). Following PPCI, the corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC) was lower (faster) with placebo (16.0 frames [IQR 12.0,24.0] vs 24.0 frames [22.0,32.0], p = 0.045) due to a trend towards greater frequency of hyperemia (cTFC <14), a marker of distal embolization (50.0% vs 8.3%, p = 0.056). There was no difference in TIMI major bleeds and no intracranial hemorrhage. In conclusion, treatment with low-dose IC TNK appears safe and well tolerated during PPCI. Although IC TNK administration did not improve percent stenosis, a trend towards reduced thrombus burden was demonstrated with less hyperemia (a marker of distal embolization). Our findings provide support for a large randomized study.

Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: a prospective, cohort study.

BACKGROUND: Near-infrared spectroscopy (NIRS) intravascular ultrasound imaging can detect lipid-rich plaques (LRPs). LRPs are associated with acute coronary syndromes or myocardial infarction, which can result in revascularisation or cardiac death. In this study, we aimed to establish the relationship between LRPs detected by NIRS-intravascular ultrasound imaging at unstented sites and subsequent coronary events from new culprit lesions. METHODS: In this prospective, cohort study (LRP), patients from 44 medical centres were enrolled in Italy, Latvia, Netherlands, Slovakia, UK, and the USA. Patients with suspected coronary artery disease who underwent cardiac catheterisation with possible ad hoc percutaneous coronary intervention were eligible to be enrolled. Enrolled patients underwent scanning of non-culprit segments using NIRS-intravascular ultrasound imaging. The study had two hierarchal primary hypotheses, patient and plaque, each testing the association between maximum 4 mm Lipid Core Burden Index (maxLCBI4mm) and non-culprit major adverse cardiovascular events (NC-MACE). Enrolled patients with large LRPs (≥250 maxLCBI4mm) and a randomly selected half of patients with small LRPs (<250 maxLCBI4mm) were followed up for 24 months. This study is registered with ClinicalTrials.gov, NCT02033694. FINDINGS: Between Feb 21, 2014, and March 30, 2016, 1563 patients were enrolled. NIRS-intravascular ultrasound device-related events were seen in six (0·4%) patients. 1271 patients (mean age 64 years, SD 10, 883 [69%] men, 388 [31%]women) with analysable maxLCBI4mm were allocated to follow-up. The 2-year cumulative incidence of NC-MACE was 9% (n=103). Both hierarchical primary hypotheses were met. On a patient level, the unadjusted hazard ratio (HR) for NC-MACE was 1·21 (95% CI 1·09-1·35; p=0·0004) for each 100-unit increase maxLCBI4mm) and adjusted HR 1·18 (1·05-1·32; p=0·0043). In patients with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 2·18 (1·48-3·22; p<0·0001) and adjusted HR was 1·89 (1·26-2·83; p=0·0021). At the plaque level, the unadjusted HR was 1·45 (1·30-1·60; p<0·0001) for each 100-unit increase in maxLCBI4mm. For segments with a maxLCBI4mm more than 400, the unadjusted HR for NC-MACE was 4·22 (2·39-7·45; p<0·0001) and adjusted HR was 3·39 (1·85-6·20; p<0·0001). INTERPRETATION: NIRS imaging of non-obstructive territories in patients undergoing cardiac catheterisation and possible percutaneous coronary intervention was safe and can aid in identifying patients and segments at higher risk for subsequent NC-MACE. NIRS-intravascular ultrasound imaging adds to the armamentarium as the first diagnostic tool able to detect vulnerable patients and plaques in clinical practice. FUNDING: Infraredx.

Impact of institutional culture on rates of transfusions during cardiovascular procedures: The Michigan experience.

BACKGROUND: Red blood cell (RBC) transfusions have been associated with morbidity and mortality in both coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI). As a mechanism for identifying determinants of RBC practice, we quantified the relationship between a center's PCI and CABG transfusion rate. METHODS: We identified all patients undergoing CABG (n = 16,568) or PCI (n = 94,634) at each of 33 centers from 2010 through 2012 in the state of Michigan and compared perioperative RBC transfusion rates for CABG and PCI at each center. Crude and adjusted transfusion rates were modeled separately. We adjusted for common preprocedural risk factors (12 for CABG and 23 for PCI) and reported Pearson correlation coefficients based on the crude and risk-adjusted rates. RESULTS: As expected, RBC transfusion was more common after CABG (mean 46.5%) than PCI (mean 3.3%), with wide variation across centers for both (CABG min:max 26.5:71.3, PCI min:max 1.6:6.0). However, RBC transfusion rates were significantly correlated between CABG and PCI in both crude, 0.48 (P = .005), and adjusted, 0.53 (P = .001), analyses. These findings were consistent when restricting to nonemergent cases (radj = 0.44, P = .001). CONCLUSIONS: Red blood cell transfusion rates were significantly correlated between the CABG and PCI at individual hospitals in Michigan, independent of patient case mix. Future work should explore institutional practice patterns, philosophies, and guidelines for RBC transfusions.

Impact of gender and age on in vivo virtual histology-intravascular ultrasound imaging plaque characterization (from the global Virtual Histology Intravascular Ultrasound [VH-IVUS] registry).

Virtual histology intravascular ultrasound (VH-IVUS) analyses were performed in the first 990 patients enrolled in the 3,000+ patient global VH-IVUS Registry to assess the impact of gender and age on in vivo VH-IVUS plaque characterization. The 990 patients were divided into 3 age group terciles (<58, 58 to 68, and >68 years) and again divided according to gender. In conclusion, (1) both women and men had an increase in plaque with increasing age; (2) at any age, men had more plaque than women; (3) percentages of dense calcium and necrotic core increased with increasing patient age in both men and women; and (4) gender differences were lowest in the oldest tercile (>68 years).

Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial.

BACKGROUND: Early restoration of epicardial flow before primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been associated with improved clinical outcomes. METHODS: We hypothesized that early administration of the glycoprotein IIb/IIIa inhibitor eptifibatide in the emergency department (ED) would yield superior epicardial flow and myocardial perfusion before primary PCI compared with initiating eptifibatide after diagnostic angiography in the cardiac catheterization laboratory (CCL). Three hundred forty-three patients with STEMI were randomized to either early ED eptifibatide (n = 180) or CCL eptifibatide (n = 163). RESULTS: The primary end point (pre-PCI corrected TIMI frame count) was significantly lower (faster flow) with early eptifibatide (77.5 +/- 32.2 vs 84.3 +/- 30.7, P = .049). The incidence of normal pre-PCI TIMI myocardial perfusion was increased among patients treated in the ED versus CCL (24% vs 14%, P = .026). There was no excess of TIMI major or minor bleeding among patients treated in the ED versus CCL (6.9% [12/174] vs 7.8% [11/142], P = NS). CONCLUSION: A strategy of early initiation of eptifibatide in the ED before primary PCI for STEMI yields superior pre-PCI TIMI frame counts, reflecting epicardial flow, and superior TIMI myocardial perfusion compared with a strategy of initiating eptifibatide in the CCL without an increase in bleeding risk.