Giora Weisz

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation.

OBJECTIVES The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. BACKGROUND Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ~10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. METHODS The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. RESULTS Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. CONCLUSIONS This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data.

Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study

BACKGROUND The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation. METHODS ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10-15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov, number NCT00638794. FINDINGS Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8583 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 [95% CI 1·43-4·31], p=0·001) and myocardial infarction (adjusted HR 1·42 [1·09-1·86], p=0·01), was inversely related to bleeding (adjusted HR 0·73 [0·61-0·89], p=0·002), but was not related to mortality (adjusted HR 1·20 [0·85-1·70], p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 [0·58-3·64], p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 [0·43-0·99], p=0·04). INTERPRETATION The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised. FUNDING Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics.

Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study

BACKGROUND Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI. METHODS The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127. FINDINGS We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation. INTERPRETATION In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. FUNDING Bristol-Myers Squibb and Sanofi-Aventis.

Five-Year Follow-Up After Sirolimus-Eluting Stent Implantation : Results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial

OBJECTIVES The aim of this study was to examine the 5-year clinical safety and efficacy outcomes in patients enrolled in the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) trial. BACKGROUND The SIRIUS trial was a double-blinded randomized study that demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS). METHODS Patients (n = 1,058) with de novo native coronary artery lesions were randomized to either SES (n = 533) or control BMS (n = 525) and were followed for 5 years. RESULTS Between 1 and 5 years, additional clinical events were similarly distributed among the sirolimus and control groups. At 5 years, in sirolimus versus control patients, target lesion revascularization was 9.4% versus 24.2% (p < 0.001) and major adverse cardiovascular events and target vessel failure rates were 20.3% versus 33.5% and 22.5% versus 33.5%, respectively (p < 0.0001 for both). There were no significant differences in death, myocardial infarction, and nontarget lesion revascularization. No significant differences were observed in the cumulative incidence of stent thrombosis for sirolimus versus control patients with either protocol-derived (1.0% vs. 0.8%) or Academic Research Consortium definitions (3.9% vs. 4.2%). CONCLUSIONS In patients with noncomplex coronary artery disease, clinical outcomes 5 years after implantation of SES continue to demonstrate significant reduction in the need for repeat revascularization, with similar safety (death and myocardial infarction) compared with BMS, without evidence for either disproportionate late restenosis or late stent thrombosis.

Relationship Between Intravascular Ultrasound Guidance and Clinical Outcomes After Drug-Eluting Stents The Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Study

Background— Prior small to modest-sized studies suggest a benefit of intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent (DES) implantation in an unrestricted patient population is unknown. Methods and Results— Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter, nonrandomized “all-comers” study of 8583 consecutive patients at 11 international centers designed to determine the frequency, timing, and correlates of stent thrombosis and adverse clinical events after DES. Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in 3349 patients (39%), and larger-diameter devices, longer stents, and/or higher inflation pressures were used in 74% of IVUS-guided cases. IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis (0.6% [18 events] versus 1.0% [53 events]; adjusted hazard radio, 0.40; 95% confidence interval, 0.21–0.73; P=0.003), myocardial infarction (2.5% versus 3.7%; adjusted hazard radio, 0.66; 95% confidence interval, 0.49–0.88; P=0.004), and composite adjudicated major adverse cardiac events (ie, cardiac death, myocardial infarction, or stent thrombosis) (3.1% versus 4.7%; adjusted hazard radio, 0.70; 95% confidence interval, 0.55–0.88; P=0.002). The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions, although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease. Conclusions— In ADAPT-DES, the largest study of IVUS use to date, IVUS guidance was associated with a reduction in stent thrombosis, myocardial infarction, and major adverse cardiac events within 1 year after DES implantation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Relationship Between Intravascular Ultrasound Guidance and Clinical Outcomes After Drug-Eluting Stents: The ADAPT-DES Study

Background— Prior small to modest-sized studies suggest a benefit of intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent (DES) implantation in an unrestricted patient population is unknown. Methods and Results— Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter, nonrandomized “all-comers” study of 8583 consecutive patients at 11 international centers designed to determine the frequency, timing, and correlates of stent thrombosis and adverse clinical events after DES. Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in 3349 patients (39%), and larger-diameter devices, longer stents, and/or higher inflation pressures were used in 74% of IVUS-guided cases. IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis (0.6% [18 events] versus 1.0% [53 events]; adjusted hazard radio, 0.40; 95% confidence interval, 0.21–0.73; P=0.003), myocardial infarction (2.5% versus 3.7%; adjusted hazard radio, 0.66; 95% confidence interval, 0.49–0.88; P=0.004), and composite adjudicated major adverse cardiac events (ie, cardiac death, myocardial infarction, or stent thrombosis) (3.1% versus 4.7%; adjusted hazard radio, 0.70; 95% confidence interval, 0.55–0.88; P=0.002). The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions, although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease. Conclusions— In ADAPT-DES, the largest study of IVUS use to date, IVUS guidance was associated with a reduction in stent thrombosis, myocardial infarction, and major adverse cardiac events within 1 year after DES implantation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Clinical ResearchInterventional CardiologyFive-Year Follow-Up After Sirolimus-Eluting Stent Implantation: Results of the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) Trial

OBJECTIVES The aim of this study was to examine the 5-year clinical safety and efficacy outcomes in patients enrolled in the SIRIUS (Sirolimus-Eluting Stent in De-Novo Native Coronary Lesions) trial. BACKGROUND The SIRIUS trial was a double-blinded randomized study that demonstrated that sirolimus-eluting stents (SES) significantly improved angiographic results (at 8 months) and clinical outcomes (at 9 and 12 months) compared with bare-metal stents (BMS). METHODS Patients (n = 1,058) with de novo native coronary artery lesions were randomized to either SES (n = 533) or control BMS (n = 525) and were followed for 5 years. RESULTS Between 1 and 5 years, additional clinical events were similarly distributed among the sirolimus and control groups. At 5 years, in sirolimus versus control patients, target lesion revascularization was 9.4% versus 24.2% (p < 0.001) and major adverse cardiovascular events and target vessel failure rates were 20.3% versus 33.5% and 22.5% versus 33.5%, respectively (p < 0.0001 for both). There were no significant differences in death, myocardial infarction, and nontarget lesion revascularization. No significant differences were observed in the cumulative incidence of stent thrombosis for sirolimus versus control patients with either protocol-derived (1.0% vs. 0.8%) or Academic Research Consortium definitions (3.9% vs. 4.2%). CONCLUSIONS In patients with noncomplex coronary artery disease, clinical outcomes 5 years after implantation of SES continue to demonstrate significant reduction in the need for repeat revascularization, with similar safety (death and myocardial infarction) compared with BMS, without evidence for either disproportionate late restenosis or late stent thrombosis.

Gender and the Extent of Coronary Atherosclerosis, Plaque Composition, and Clinical Outcomes in Acute Coronary Syndromes

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 mm(2), 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.

Detection of Lipid-Core Plaques by Intracoronary Near-Infrared Spectroscopy Identifies High Risk of Periprocedural Myocardial Infarction

Background— Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures. Methods and Results— The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3× upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI4 mm ≥500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI4 mm ≥500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI4 mm (P=0.0002). Conclusions— NIRS provides rapid, automated detection of extensive LCPs that are associated with a high risk of periprocedural MI, presumably due to embolization of plaque contents during coronary intervention.

Prognostic impact of a chronic total occlusion in a non-infarct-related artery in patients with ST-segment elevation myocardial infarction: 3-year results from the HORIZONS-AMI trial

AIMS We sought to investigate the impact of multivessel disease (MVD) with and without a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) on mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS In the HORIZONS-AMI trial, of 3283 patients undergoing primary PCI, 1524 patients (46.4%) had single-vessel disease (SVD), 1477 (45.0%) had MVD without a CTO, and 283 (8.6%) had MVD with a CTO in a non-IRA. Compared with SVD patients and MVD patients without a CTO, patients with a non-IRA CTO were significantly less likely to achieve post-procedural TIMI 3 flow (P = 0.0003), more often had absent myocardial blush (P = 0.0002), and less frequently achieved complete ST-segment resolution (P = 0.0001). By multivariable analysis, MVD with CTO in a non-IRA was an independent predictor of both 0- to 30-day mortality [hazard ratio (HR) 2.88, 95% confidence interval (CI) 1.41-5.88, P = 0.004] and 30-day to 3-year mortality (HR 1.98, 95% CI 1.19-3.29, P= 0.009), while MVD without a CTO was a significant predictor for 0- to 30-day mortality (HR 2.20, 95% CI 1.00-3.06, P = 0.049) but not late mortality. CONCLUSION In patients with STEMI undergoing primary PCI in the HORIZONS-AMI trial, MVD with or without a CTO in a non-IRA was an independent predictor of early mortality. The presence of a CTO in a non-IRA was also an independent predictor of increased late mortality to 3 years.