Prospective, randomized, multicenter clinical study comparing a self-expanding covered stent to percutaneous transluminal angioplasty for treatment of upper extremity hemodialysis arteriovenous fistula stenosis.

Use of a covered stent after percutaneous transluminal angioplasty (PTA) was compared to PTA alone for treatment of upper extremity hemodialysis patients with arteriovenous fistula (AVF) stenoses. Patients with AVF stenosis of 50% or more and evidence of AVF dysfunction underwent treatment with PTA followed by randomization of 142 patients to include a covered stent or 138 patients with PTA alone. Primary outcomes were 30-day safety, powered for noninferiority, and six-month target lesion primary patency (TLPP), powered to test whether TLPP after covered-stent placement was superior to PTA alone. Twelve-month TLPP and six-month access circuit primary patency (ACPP) were also hypothesis tested while additional clinical outcomes were observed through two years. Safety was significantly non-inferior while six- and 12-month TLPP were each superior for the covered stent group compared to PTA alone (six months: 78.7% versus 55.8%; 12 months: 47.9% versus 21.2%, respectively). ACPP was not statistically different between groups at six-months. Observed differences at 24 months favored the covered-stent group: 28.4% better TLPP, fewer target-lesion reinterventions (1.6 ± 1.6 versus 2.8 ± 2.0), and a longer mean time between target-lesion reinterventions (380.4 ± 249.5 versus 217.6 ± 158.4 days). Thus, our multicenter, prospective, randomized study of a covered stent used to treat AVF stenosis demonstrated noninferior safety with better TLPP and fewer target-lesion reinterventions than PTA alone through 24 months.

Angiographic Lesion Discordance in Women Presenting With Ischemic Heart Disease: Comparison of Visual Assessment, Quantitative Coronary Angiography, and Quantitative Flow Ratio.

BACKGROUND: Although visual assessment of stenosis severity is routinely used to guide coronary revascularization, there are concerns about its accuracy, especially in women, who present a higher variability in coronary anatomy and ischemic heart disease (IHD). The aim of this study was to assess whether quantitative coronary angiography (QCA) and quantitative flow ratio (QFR) could provide better discrimination of coronary stenosis severity and functional significance than visual assessment alone in women with IHD. METHODS: Coronary angiography was performed in a cohort of women with ischemic symptoms and non-invasive stress perfusion imaging. Visual assessment was done by blinded operators in clinical practice, while QCA and QFR were analyzed in an independent core laboratory. RESULTS: Ninety-nine consecutive patients with 101 lesions were included in the registry, and QFR was successfully measured in 81 lesions (80.2%). Visual assessment provided higher readings of angiographic severity than QCA in 50.5% (n = 51) of lesions. Mean absolute difference between QCA and visual assessment was significantly higher in lesions with >70% diameter stenosis (DS) (25.3 ± 7.3%), compared with both the 40%-55% (9.3 ± 6.8%; P<.001) and the <40% groups (7.0 ± 6.0%; P<.001). QFR was >0.80 in 33.3% of lesions with visually defined >70% DS, while all lesions with QCA-defined >70% DS had QFR ≤0.80. CONCLUSIONS: Interventional cardiologists' visual assessment results in a higher degree of coronary stenosis than QCA. Among women with ischemic symptoms and non-invasive stress perfusion imaging, additional lesion assessment by QCA and QFR may improve operators' ability to determine which patients and lesions will benefit from coronary revascularization.

Long-term serial functional evaluation after implantation of the Fantom sirolimus-eluting bioresorbable coronary scaffold.

BACKGROUND: Quantitative flow ratio (QFR) has been validated as an accurate surrogate of standard wire-based fractional flow reserve. The clinical and angiographic outcomes of the Fantom sirolimus-eluting bioresorbable coronary scaffold (BRS) have been previously studied and reported. We investigate the functional performance of the Fantom BRS. METHODS: The FANTOM II trial prospectively enrolled 240 patients with stable coronary artery disease or unstable angina, of which 235 patients received the Fantom BRS and were included in the present analysis. We performed an independent serial QFR analysis of the target vessel at baseline, post-percutaneous coronary intervention (PCI), and at 6- or 9-month and 24-month follow-up, using a QFR threshold ≤0.80 to define functional ischemia. RESULTS: QFR was analyzable in 178 patients at baseline, 185 post-PCI, 178 at 6- or 9-month follow-up, and 30 at 24-month follow-up. At baseline, 119 patients (66.9%) had a QFR ≤0.80, whereas 12 (6.5%) post-PCI, 13 (7.3%) at 6- or 9-month follow-up, and 3 (10.0%) at 24-month follow-up had a QFR ≤0.80. QFR improved from baseline to post-PCI, and decreased from post-PCI up to 24-month follow-up. During follow-up period, 28 patients (11.9%) had target vessel revascularization, of which 21 had analyzable QFR and 16 patients (76.1%) had QFR ≤0.80 at the time of revascularization. CONCLUSIONS: Off-line serial QFR assessment demonstrated that around 30% patients did not have functionally significant lesions at baseline and the time with target vessel revascularization. PCI with the Fantom BRS improved functional ischemia with a slight decrease in QFR values over 24 months.

The Firehawk Stent: A Review of a Novel Abluminal Groove-Filled Biodegradable Polymer Sirolimus-Eluting Stent.

Despite recent advances in drug-eluting stent (DES) technology, late adverse events remain concerns after percutaneous coronary intervention. The persistence of polymer material on DES has been suggested as a trigger for chronic inflammation. The Firehawk, a novel DES, has a unique design with recessed abluminal grooves, to which sirolimus and biodegradable polymer are applied. The Firehawk stent is designed to minimize polymer volume and antiproliferative drug concentration to reduce inflammation and hypersensitivity reactions. Several recent trials have reported the clinical outcomes of this device. This article provides a review of the current clinical evidence concerning the Firehawk stent.

Prognostic utility of myocardial blush grade after PCI in patients with NSTE-ACS: Analysis from the ACUITY trial.

OBJECTIVE: We evaluated the ability of post-procedural myocardial blush grade (MBG) to stratify outcomes of patients undergoing percutaneous coronary intervention (PCI) for non-ST segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: MBG strongly correlates with survival after reperfusion therapy in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Of 13,819 NSTE-ACS patients randomized in the ACUITY trial, 3,115 patients underwent PCI and had MBG analyzed by an independent angiographic core laboratory. We examined net adverse clinical events (NACE; composite ischemia or bleeding), composite ischemia (death, MI or ischemia-driven revascularization) and non-CABG major bleeding according to final MBG. RESULTS: At 30 days, patients with MBG-0/1 had higher rates of NACE (25.1% vs. 13.9%, P = 0.002) and composite ischemia (19.1% vs. 9.4%, P = 0.002) than patients with MBG-2/3. At 1-year follow-up, MBG-0/1 patients had significantly higher rates of composite ischemia compared to other patients (27.8% vs. 19.8%, P = 0.02). By multivariable analysis, MBG-0/1 was an independent predictor of 30-day ischemia-driven revascularization (OR 5.74 [2.63, 12.54], P < 0.0001) in the total population and among patients with normal post-PCI epicardial TIMI-3 flow (OR 6.39 [2.06, 19.78], P = 0.001). However, 1-year outcomes were similar between patients with and without normal myocardial perfusion. CONCLUSIONS: In conclusion, MBG is a predictor of 30-day revascularization in the overall population and in patients with normal epicardial flow but fails to stratify 1-year outcomes. Thus, unlike in STEMI patients, the prognostic value of MBG in NSTE-ACS patients appears to be limited to the short-term. © 2015 Wiley Periodicals, Inc.

Implications of ventricular arrhythmia "bursts" with normal epicardial flow, myocardial blush, and ST-segment recovery in anterior ST-elevation myocardial infarction reperfusion: a biosignature of direct myocellular injury "downstream of downstream".

AIMS: Establishing epicardial flow with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is necessary but not sufficient to ensure nutritive myocardial reperfusion. We evaluated whether adding myocardial blush grade (MBG) and quantitative reperfusion ventricular arrhythmia "bursts" (VABs) surrogates provide a more informative biosignature of optimal reperfusion in patients with Thrombolysis in Myocardial Infarction (TIMI) 3 flow and ST-segment recovery (STR). METHODS AND RESULTS: Anterior STEMI patients with final TIMI 3 flow had protocol-blinded analyses of simultaneous MBG, continuous 12-lead electrocardiogram (ECG) STR, Holter VABs, and day 5-14 SPECT imaging infarct size (IS) assessments. Over 20 million cardiac cycles from >4500 h of continuous ECG monitoring in subjects with STR were obtained. IS and clinical outcomes were examined in patients stratified by MBG and VABs. VABs occurred in 51% (79/154) of subjects. Microcirculation (MBG 2/3) was restored in 75% (115/154) of subjects, of whom 53% (61/115) had VABs. No VABs were observed in subjects without microvascular flow (MBG of 0). Of 115 patients with TIMI 3 flow, STR, and MBG 2/3, those with VABs had significantly larger IS (median: 23.0% vs 6.0%, p=0.001). Multivariable analysis identified reperfusion VABs as a factor significantly associated with larger IS (p=0.015). CONCLUSIONS: Despite restoration of normal epicardial flow, open microcirculation, and STR, concomitant VABs are associated with larger myocardial IS, possibly reflecting myocellular injury in reperfusion settings. Combining angiographic and ECG parameters of epicardial, microvascular, and cellular response to STEMI intervention provides a more predictive "biosignature" of optimal reperfusion than do single surrogate markers.

Association between intraprocedural thrombotic events and adverse outcomes after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (a Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Substudy).

The present study sought to determine the extent to which adverse angiographic events encountered during percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) are associated with adverse clinical outcomes. Patients with STEMI represent a cohort at particularly high risk of intraprocedural thrombotic events (IPTEs). The overall frequency and implications of IPTEs occurring in patients with STEMI have not been systematically quantified in previous studies. A total of 3,163 patients undergoing primary percutaneous coronary intervention with stent implantation for STEMI in the Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial underwent detailed frame-by-frame core laboratory angiographic analysis to assess IPTEs. The clinical outcomes at 30 days were compared between the patients with and without IPTEs. IPTEs, defined as the development of new or increasing thrombus, abrupt vessel closure, no reflow, slow reflow, and distal embolization at any point during the procedure, occurred in 386 patients (12.2%). The independent predictors of IPTE were thrombus at baseline, lesion length, and randomization to bivalirudin; the patients with IPTEs were also more likely to receive bailout glycoprotein IIb/IIIa inhibitors and unplanned thrombectomy. Compared with patients without IPTEs, the patients with IPTEs had higher 30-day rates of composite major adverse cardiovascular events (death, myocardial infarction, ischemic target vessel revascularization, and stroke; 7.8% vs 4.2%, p = 0.002), major bleeding not related to coronary artery bypass grafting (11.8% vs 6.5%, p <0.001), and all-cause death (4.2% vs 1.8%, p = 0.002). On multivariate analysis, IPTEs were independently associated with 30-day major adverse cardiovascular events, major bleeding, and death. In conclusion, the development of IPTEs in patients undergoing primary percutaneous coronary intervention for STEMI was associated with subsequent adverse outcomes, including major adverse cardiovascular events, major bleeding, and death. Additional studies of strategies to decrease the occurrence of IPTEs are warranted.

The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent.

OBJECTIVES: This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months. BACKGROUND: Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations. METHODS: One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events. RESULTS: The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group. CONCLUSIONS: In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months.

Evaluation of XIENCE V everolimus-eluting and Taxus Express2 paclitaxel-eluting coronary stents in patients with jailed side branches from the SPIRIT IV trial at 2 years.

The aim of this study was to determine whether patients from the Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions (SPIRIT) IV trial who underwent percutaneous coronary intervention, who had target lesions with jailed side branches, had improved clinical outcomes when treated with the XIENCE V versus Taxus Express(2) drug-eluting stent. In the SPIRIT III randomized trial, patients with target lesions with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had lower 2-year rates of major adverse cardiac events. The SPIRIT IV trial represents a larger more diverse patient population compared with SPIRIT III. In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, 3,687 patients who underwent coronary stenting with up to 3 de novo native coronary artery lesions were randomized 2:1 to receive XIENCE V versus Taxus Express(2) stents. Two-year clinical outcomes of patients with or without jailed side branches after stenting were compared. A jailed side branch was defined as any side branch >1.0 mm in diameter within the target segment being stented, excluding bifurcations deemed to require treatment. Of the 3,687 patients in SPIRIT IV, a total of 1,426 had side branches that were jailed during angioplasty of the target lesion. Patients with jailed side branches after XIENCE V compared with Taxus Express(2) implantation had significantly lower 2-year rates of target lesion failure (6.5% vs 11.9%, p = 0.001), major adverse cardiac events (6.6% vs 12.2%, p = 0.0008), ischemia-driven target vessel revascularization (4.1% vs 7.9%, p = 0.004), and stent thrombosis (0.6% vs 2.8%, p = 0.001). In conclusion, patients with jailed side branches after stenting with XIENCE V compared to Taxus Express(2) devices had superior clinical outcomes at 2 years in the large-scale randomized SPIRIT IV trial.

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).

Intra-procedural stent thrombosis: a new risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention for acute coronary syndromes.

OBJECTIVES: The aim of this study was to examine the incidence, correlates, and consequences of intra-procedural stent thrombosis (IPST) in patients with acute coronary syndromes (ACS). BACKGROUND: Stent thrombosis (ST) is a rare but serious complication of percutaneous coronary intervention (PCI). The Academic Research Consortium definition of ST excludes events occurring during PCI. METHODS: Angiograms from the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) and HORIZONS-AMI (Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction) trials were reviewed frame-by-frame at an independent core laboratory for the occurrence of IPST. Patients with versus without IPST were compared to identify baseline characteristics associated with IPST and demonstrate the independent association between IPST and adjudicated events at 30 days and 1 year. RESULTS: Intra-procedural ST occurred in 47 (0.7%) of 6,591 patients. The occurrence of IPST was associated with ST-segment elevation myocardial infarction presentation, high white blood cell count, treatment of thrombotic and bifurcation lesions, bivalirudin monotherapy, bail-out IIb/IIIa inhibitor use, and implantation of bare-metal (rather than drug-eluting) stents. Major adverse ischemic events were markedly higher in patients with versus without IPST, including mortality at 30 days (12.9% vs. 1.4%, p < 0.0001) and 1 year (12.9% vs. 3.1%, p < 0.0001). Out-of-lab Academic Research Consortium definite or probable ST also occurred significantly more often among IPST patients at 30 days (17.4% vs. 1.8%, p < 0.0001) and 1 year (19.9% vs. 2.7%, p < 0.0001). Intra-procedural ST was a significant independent predictor of 1-year mortality (hazard ratio: 3.86, 95% confidence interval: 1.66 to 9.00, p = 0.002). CONCLUSIONS: Intra-procedural ST is a relatively rare complication of PCI in ACS but is strongly associated with subsequent out-of-lab ST and mortality. Intra-procedural ST should be considered as a distinct category of ST and routinely reported, particularly for ACS patients.

Long-term prognosis of patients presenting with ST-segment elevation myocardial infarction with no significant coronary artery disease (from the HORIZONS-AMI trial).

The clinical features and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and no significant coronary artery disease (CAD) have not been well studied. We examined the outcomes of patients with STEMI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial according to the presence or absence of significant CAD. "No-CAD" was defined by the absence of any lesion with a diameter stenosis of ≥30% on quantitative coronary angiography of the baseline coronary angiogram. Of 3,602 patients, 127 (3.5%) had no-CAD. Of these, 86 (67.7%) had angiographically normal coronary arteries, and 41 (32.3%) had mild disease (diameter stenosis <30%). Eight patients had previously been treated with coronary artery bypass grafting. Compared to patients with CAD, patients with no-CAD were younger, had a lower body mass index, were more frequently black, had a lower prevalence of smoking and previous angina, and had a greater left ventricular ejection fraction. Cardiac enzymes were elevated in fewer patients with no-CAD than in those with CAD (63.2% vs 98.7%, p <0.001). At 3 years of follow-up, the patients with no-CAD versus CAD had lower rates of major adverse cardiovascular events (7.7% vs 22.2%, p = 0.002), net adverse clinical events (major adverse cardiovascular events or major bleeding not related to coronary artery bypass grafting, 12.5% vs 26.9%, p = 0.005), and postprocedure coronary revascularization (0% vs 19.5%, p <0.001). The differences in the rates of death or reinfarction, stroke, and major bleeding were not statistically significant. In conclusion, 3.5% of patients with STEMI had no significant CAD. The 3-year prognosis for these patients was favorable compared to that of patients with STEMI and with obstructive CAD.

Implications of pre-procedural TIMI flow in patients with non ST-segment elevation acute coronary syndromes undergoing percutaneous coronary revascularization: insights from the ACUITY trial.

OBJECTIVES: The purpose of this study was to evaluate the prognostic implications of preprocedural TIMI flow in ACS patients undergoing early invasive management. BACKGROUND: Although the negative prognostic impact of reduced Thrombolysis in Myocardial Infarction (TIMI) flow before percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) has been well described, whether this relationship holds in patients with acute coronary syndromes (ACS; unstable angina and non-STEMI) has not been examined. METHODS: We evaluated 3582 moderate and high-risk patients with ACS undergoing PCI enrolled in the ACUITY trial. Patients were divided in 3 groups according to pre-procedural culprit vessel TIMI flow (TIMI 0/1, TIMI 2 and TIMI 3 flows), determined by an independent angiographic core laboratory. RESULTS: Baseline culprit vessel flow was absent (TIMI 0/1) in 453 patients (12.6%), reduced (TIMI 2) in 389 patients (10.9%) and normal (TIMI 3) in 2740 patients (76.5%) patients. Post-PCI TIMI 3 flow was achieved in 87.2%, 86.8% and 98.8% of the 3 groups, respectively (P<0.0001). At 1 year, mortality occurred in 2.7%, 2.4% and 3.0% of patients with baseline TIMI 0/1, 2 and 3 flows, respectively (P=0.82). By multivariable analysis, pre-PCI TIMI flow 0/1 (vs. TIMI 3) was not an independent predictor of 1-year mortality (P=0.61). CONCLUSIONS: Reduced baseline TIMI flow in moderate and high-risk patients with ACS undergoing PCI does not appear to affect survival at 1 year, in contrast to that described in patients with STEMI.

Age- and gender-related changes in plaque composition in patients with acute coronary syndrome: the PROSPECT study.

AIMS: Atherosclerosis accelerates with increasing age; however, young women presenting with acute coronary syndromes (ACS) have adverse outcomes compared to men despite less obstructive coronary artery disease. We sought to evaluate the in vivo plaque characteristics and composition of untreated non-culprit lesions (NCL) at two ages (<65 years old and ≥65 years old) in patients with ACS and examine the effect of sex in both groups. METHODS AND RESULTS: Untreated NCLs from 697 patients with ACS were imaged with greyscale and radiofrequency intravascular ultrasound. NCL plaque morphology, burden, composition, and major adverse cardiac events (MACE) were analysed in both age groups, and a posterior sex-based sub-analysis was performed. Plaques from patients ≥65 (n=974) vs. <65 (n=2,275) years old were longer (median 12.62 mm vs. 10.75 mm, p=0.008) and had greater plaque burden (48.2% vs. 47.5%, p=0.001), necrotic core (12.5% vs. 11.0%, p=0.001) and dense calcium (5.7% vs. 4.0%, p<0.0001). Men <65 years old also had a greater number of fibroatheromas (3.0 vs. 2.0, p=0.007) and NCLs per patient (5.0 vs. 4.0, p=0.004) with larger plaque volumes (47.7% vs. 46.8%, p=0.04), and fewer fibrotic plaques (2.2% vs. 4.4%, p=0.03) than women in the same age group. These sex differences were not observed in patients ≥65 years old. The incidence of MACE during median 3.4 year follow-up did not significantly differ according to age in this study. CONCLUSIONS: The current study confirms in vivo that, with aging, plaque burden, necrotic core and calcium content increase significantly. Moreover, gender-specific differences in the extent and composition of coronary plaque are present in patients <65 years (but not ≥65 years) of age, which suggest differential sex-related effects on atherosclerosis development and progression.

A new score for risk stratification of patients with acute coronary syndromes undergoing percutaneous coronary intervention: the ACUITY-PCI (Acute Catheterization and Urgent Intervention Triage Strategy-Percutaneous Coronary Intervention) risk score.

OBJECTIVES: This study sought to develop a new score specific for patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) (the ACUITY-PCI [Acute Catheterization and Urgent Intervention Triage Strategy-Percutaneous Coronary Intervention] risk score). BACKGROUND: The TIMI (Thrombolysis In Myocardial Infarction) and GRACE (Global Registry for Acute Coronary Events) risk scores are recommended for risk stratification of patients with NSTEACS. However, these scores were not optimized for patients undergoing an early invasive strategy with PCI. METHODS: The ACUITY-PCI risk score was created from data for 1,692 patients enrolled in the formal angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial by integrating clinical, angiographic, laboratory, and electrocardiographic variables selected by multivariable analysis. The score was subsequently validated in a different population of 846 patients and compared with the GRACE and TIMI risk scores, and the SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) and Clinical SYNTAX scores. RESULTS: Six variables (2 clinical, 1 laboratory/electrocardiographic, and 3 angiographic) were included in the ACUITY-PCI score: insulin-treated diabetes; renal insufficiency; baseline cardiac biomarker elevation or ST-segment deviation; bifurcation lesion; small vessel/diffuse coronary artery disease; and the extent of coronary artery disease. Event rates increased significantly across tertiles of ACUITY-PCI score. Compared with the other scores, the ACUITY-PCI score had the best discrimination (C-statistic), calibration (Hosmer-Lemeshow statistic), and index of separation. Moreover, the net reclassification improvement varied from 9% to 38% and the integrated discrimination index from 1.9% to 2.7%. CONCLUSIONS: The ACUITY-PCI risk score is a new tool integrating clinical, angiographic, and laboratory/electrocardiographic variables specifically developed for patients with NSTEACS undergoing PCI. This score displayed better prognostic accuracy in terms of discrimination and calibration than other currently available scores for risk stratification of patients with NSTEACS. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158).

Does clinical presentation affect outcome among patients with acute coronary syndromes undergoing percutaneous coronary intervention? Insights from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study.

BACKGROUND: In some prior studies, patients with ST-elevation myocardial infarction (STEMI) as compared with patients with non-STEMI (NSTEMI) tended to have a higher early mortality but similar long-term outcomes. We compared the angiographic and intravascular ultrasound (IVUS) characteristics of patients with STEMI and NSTEMI in the PROSPECT study to evaluate the independent prognostic value of clinical presentation on long-term outcome. METHODS: After successful revascularization, patients had 3-vessel quantitative coronary angiography, gray scale, and radiofrequency intravascular ultrasound (IVUS) imaging. The primary end point was the occurrence of major adverse cardiac events (MACE) (cardiac death, myocardial infarction, or rehospitalization for unstable or progressive angina). RESULTS: There were 211 patients (31.6%) with STEMI and 457 (68.4%) with NSTEMI. Patients with STEMI and NSTEMI had similar angiographic and IVUS morphologic characteristics. At 3 years, MACE occurred in 22.1% and 19.6%, respectively (hazard ratio [HR] 1.16 [0.81, 1.68], P = .42). There was a higher overall mortality (HR 2.16 [0.94, 4.99], P = .06) and a significantly higher incidence of probable stent thrombosis (HR 4.34 [1.09, 17.36], P = .02) in the STEMI cohort. There were no significant differences between the 2 groups with respect to events related to culprit or to nonculprit lesions. ST-elevation myocardial infarction presentation was not an independent predictor of 3-year MACE (HR 1.14 [0.77, 1.67], P = .52). CONCLUSION: Patients with STEMI and NSTEMI did not differ with respect to residual nonculprit lesion angiographic or IVUS characteristics and had similar rates of MACE at 3 years, without late "catch-up" in NSTEMI. However, probable stent thrombosis and mortality were higher in the STEMI cohort.

Operator versus core laboratory assessment of angiographic reperfusion markers in patients undergoing primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction.

BACKGROUND: Thrombolysis In Myocardial Infarction (TIMI) flow and Myocardial Blush Grade (MBG) are important prognostic indicators before and after primary percutaneous coronary intervention (PCI) in ST-segment-elevation myocardial infarction; however, the concordance and relative prognostic utility of operator (Op) versus angiography core laboratory (ACL) assessed TIMI flow and MBG are unknown. METHODS AND RESULTS: Baseline and final Op and ACL TIMI flow and MBG assessment were compared from the Harmonizing Outcomes with RevascularIZatiON and Stents in AMI trial in 3345 patients undergoing primary PCI using Cohen's κ coefficient. κ Was highest for pre-PCI TIMI flow (0.51, representing moderate agreement) and lowest for post-PCI MBG (0.20, representing fair agreement). Discordance between Op and ACL for final TIMI flow (0 to 2 versus 3) occurred in 12.9% of patients and for final MBG (0 to 1 versus 2 to 3) in 22.4%. Among 415 patients with final TIMI flow 0 to 2 by ACL, Op scoring was TIMI flow 3 in 267 (64.3%). Similarly, among 706 patients with final MBG 0 to 1 by ACL, 563 (79.7%) were classified as MBG 2 to 3 by Op. Post-PCI TIMI 3 flow and MBG 2 to 3 strongly correlated with 3-year survival, as assessed by both Op and ACL (P<0.0001). Mortality was intermediate in patients in whom ACL and Op were discordant, without marked prognostic differences between the discordant groups. CONCLUSIONS: Op and ACL assessment of angiographic markers of reperfusion in ST-segment-elevation myocardial infarction demonstrates fair to moderate agreement. Op tended to favorably grade unfavorable ACL results. Nonetheless, both Op and ACL assessment of reperfusion strongly inform prediction of 3-year mortality.

Intraprocedural thrombotic events during percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndromes are associated with adverse outcomes: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.

OBJECTIVES: The purpose of this study was to assess the prognostic impact of intraprocedural thrombotic events (IPTE) during percutaneous coronary intervention (PCI). BACKGROUND: Ischemic complications of PCI are infrequent but prognostically important. How often these events are a consequence of intraprocedural complications is unknown, with only limited data assessing the occurrence and importance of IPTE. METHODS: A total of 3,428 patients who underwent PCI for non-ST-segment elevation acute coronary syndrome in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial underwent detailed frame-by-frame core laboratory angiographic analysis. An IPTE, defined as the development of new or increasing thrombus, abrupt vessel closure, no reflow, slow reflow, or distal embolization at any time during the procedure, occurred in 121 patients (3.5%). RESULTS: Patients with IPTE had higher in-hospital, 30-day, and 1-year major adverse cardiac event rates than patients without IPTE (25.6% vs. 6.3% in-hospital, 30.6% vs. 9.3% at 30 days, and 37.0% vs. 20.5% at 1 year; p < 0.0001 for each). An IPTE was strongly associated with Q-wave myocardial infarction and out-of-laboratory definite/probable stent thrombosis (in-hospital 3.3% vs. 0.5%, p = 0.006; 30 days 5.8% vs. 1.3%, p < 0.0001; and 1 year 6.7% vs. 2.0%, p = 0.0002). Unplanned revascularization, target vessel revascularization, and major bleeding not associated with coronary artery bypass graft surgery were also increased among patients with IPTE, as was overall 30-day mortality (3.3% vs. 0.7%, p = 0.002). Moreover, IPTE was an independent predictor of 30-day and 1-year composite death/myocardial infarction, stent thrombosis, and major adverse cardiac events. CONCLUSIONS: Although infrequent among patients undergoing early PCI for moderate and high-risk non-ST-segment elevation acute coronary syndrome, IPTE was strongly associated with subsequent adverse outcomes including death, myocardial infarction, and stent thrombosis.

Impact of the presence and extent of incomplete angiographic revascularization after percutaneous coronary intervention in acute coronary syndromes: the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.

BACKGROUND: The clinical significance of incomplete coronary revascularization (ICR) after percutaneous coronary intervention in patients with acute coronary syndromes is unknown. METHODS AND RESULTS: We performed quantitative angiography of the entire coronary tree in 2954 patients with acute coronary syndromes in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. ICR was variably defined if any lesion with diameter stenosis (DS) cutoffs ranging from ≥30% to ≥70% with reference vessel diameter ≥2.0 mm remained after percutaneous coronary intervention. The primary outcome was 1-year composite rate of major adverse cardiac events (death, myocardial infarction, or ischemia-driven unplanned revascularization). With the use of DS cutoffs ≥30%, ≥40%, ≥50%, ≥60%, and ≥70%, the prevalence of ICR after percutaneous coronary intervention was 75%, 55%, 37%, 25%, and 17%, respectively. The 1-year major adverse cardiac event rate was increased among patients with ICR using all of the DS cutoffs. ICR (≥50% DS) was associated with higher 1-year rates of myocardial infarction (12.0% versus 8.2%; hazard ratio, 1.50; 95% confidence interval, 1.18-1.89; P=0.0007) and ischemia-driven unplanned revascularization (15.7% versus 10.2%; hazard ratio, 1.58; 95% confidence interval, 1.28-1.96; P<0.0001), with a trend toward increased mortality (3.1% versus 2.2%; hazard ratio, 1.43; 95% confidence interval, 0.90-2.27; P=0.13). By multivariable analysis, ICR (≥50% DS) was an independent predictor of 1-year major adverse cardiac events (hazard ratio, 1.36; 95% confidence interval, 1.12-1.64; P=0.002). The impact of ICR on major adverse cardiac events was similar regardless of chronic total occlusion presence, but it was more pronounced with a greater number of nonrevascularized lesions. CONCLUSIONS: Depending on the threshold of percent DS, ICR was present in 17% to 75% of patients with acute coronary syndromes after percutaneous coronary intervention. Regardless of the threshold, ICR was strongly associated with 1-year myocardial infarction, ischemia-driven unplanned revascularization, and major adverse cardiac events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00093158.

Comparison of clinical and angiographic prognostic risk scores in patients with acute coronary syndromes: Analysis from the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial.

BACKGROUND: Several prognostic risk scores have been developed for patients with coronary artery disease, but their comparative use in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) undergoing percutaneous coronary intervention (PCI) has not been examined. We therefore investigated the accuracy of the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score, Clinical Synergy Between PCI With Taxus and Cardiac Surgery score (CSS), New Risk Stratification (NERS) score (NERS), Age, Creatinine, Ejection Fraction (ACEF) score, Global Registry for Acute Coronary Events (GRACE) score, and Thrombolysis in Myocardial Infarction (TIMI) score for risk assessment of 1-year mortality, cardiac mortality, myocardial infarction, target vessel revascularization, and stent thrombosis in patients with NSTEACS undergoing PCI. METHODS: The 6 scores were determined in 2,094 patients with NSTEACS treated with PCI enrolled in the angiographic substudy of the ACUITY trial. The prognostic accuracy of the 6 scores was assessed using the c statistic for discrimination and the Hosmer-Lemeshow test for calibration. The index of separation and net reclassification improvement (NRI) were also determined. RESULTS: Scores incorporating clinical and angiographic variables (CSS and NERS) showed the best tradeoff between discrimination and calibration for most end points, with the best discrimination for all end points and good calibration for most of them. The CSS had the best index of separation for most ischemic endpoints and displayed an NRI for cardiac death and myocardial infarction (MI) compared to the other scores, whereas NERS displayed an NRI for all-cause death and target vessel revascularization. The 3 scores-CSS, NERS, and SYNTAX-were the only scores to have both good discrimination and calibration for cardiac mortality. CONCLUSIONS: In patients with NSTEACS undergoing PCI, risk scores incorporating clinical and angiographic variables had the highest predictive accuracy for a broad spectrum of ischemic end points.