Joanna J. Wykrzykowska

Value of the SYNTAX score for risk assessment in the all-comers population of the randomized multicenter LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial

OBJECTIVES We aimed to assess the predictive value of the SYNTAX score (SXscore) for major adverse cardiac events in the all-comers population of the LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial. BACKGROUND The SXscore has been shown to be an effective predictor of clinical outcomes in patients with multivessel disease undergoing percutaneous coronary intervention. METHODS The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the LEADERS trial (patients after surgical revascularization were excluded). Post hoc analysis was performed by stratifying clinical outcomes at 1-year follow-up, according to 1 of 3 SXscore tertiles. RESULTS The 1,397 patients were divided into tertiles based on the SXscore in the following fashion: SXscore<or=8 (SXlow) (n=464), SXscore>8 and <or=16 (SXmid) (n=472), and SXscore>16 (SXhigh) (n=461). At 1-year follow-up, there was a significantly lower number of patients with major cardiac event-free survival in the highest tertile of SXscore (SXlow=92.2%, SXmid=91.1%, and SXhigh=84.6%; p<0.001). Death occurred in 1.5% of SXlow patients, 2.1% of SXmid patients, and 5.6% of SXhigh patients (hazard ratio [HR]: 1.97, 95% confidence interval [CI]: 1.29 to 3.01; p=0.002). The myocardial infarction rate tended to be higher in the SXhigh group. Target vessel revascularization was 11.3% in the SXhigh group compared with 6.3% and 7.8% in the SXlow and SXmid groups, respectively (HR: 1.38, 95% CI: 1.1 to 1.75; p=0.006). Composite of cardiac death, myocardial infarction, and clinically indicated target vessel revascularization was 7.8%, 8.9%, and 15.4% in the SXlow, SXmid, and SXhigh groups, respectively (HR: 1.47, 95% CI: 1.19 to 1.81; p<0.001). CONCLUSIONS The SXscore, when applied to an all-comers patient population treated with drug-eluting stents, may allow prospective risk stratification of patients undergoing percutaneous coronary intervention. (LEADERS Trial Limus Eluted From A Durable Versus ERodable Stent Coating; NCT00389220).

A New Tool for the Risk Stratification of Patients With Complex Coronary Artery Disease The Clinical SYNTAX Score

Background—Presently, no effective risk model exists to predict long-term mortality or other major adverse cardiovascular and cerebrovascular events (MACCE) in those patients undergoing percutaneous coronary intervention (PCI). This study aimed to assess whether the Clinical SYNTAX Score (CSS) calculated by multiplying the SYNTAX Score to a modified ACEF score (age/ejection fraction +1 for each 10 mL the creatinine clearance <60 mL/min per 1.73 m2) would improve the ability of either score to predict mortality and MACCE. Methods and Results—The CSS was calculated in 512 patients enrolled in the ARTS-II study who had serum creatinine levels, ejection fraction, and body weight recorded at baseline. Clinical outcomes in terms of MACCE and mortality at 1- and 5-year follow-up were stratified according to CSS tertiles: CSSLOW⩽15.6 (n=170), 15.627.5 (n=171). At 1-year follow-up, rates of repeat revascularization and MACCE were significantly higher in the highest tertile group. At 5-year follow-up, CSSHIGH had a comparable rate of myocardial infarction, a trend toward a significantly higher rate of death, and significantly higher rates of repeat revascularization and overall MACCE compared with patients in the lower 2 tertiles. The respective C-statistics for the CSS, SYNTAX Score, and ACEF score for 5-year mortality were 0.69, 0.62, and 0.65 and for 5-year MACCE were 0.62, 0.59, and 0.57. Conclusions—An improvement in the ability of the SYNTAX Score to predict MACCE and mortality can be achieved by combining the SYNTAX Score with a simple clinical risk score incorporating age, ejection fraction, and creatinine clearance to produce the Clinical SYNTAX score. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235170.

Bioresorbable Scaffolds versus Metallic Stents in Routine PCI

BACKGROUND Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug‐eluting stents in percutaneous coronary intervention (PCI). We performed an investigator‐initiated, randomized trial to compare an everolimus‐eluting bioresorbable scaffold with an everolimus‐eluting metallic stent in the context of routine clinical practice. METHODS We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target‐vessel failure (a composite of cardiac death, target‐vessel myocardial infarction, or target‐vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end‐point events. RESULTS The median follow‐up was 707 days. Target‐vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2‐year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan–Meier estimates in time‐to‐event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2‐year cumulative event rates, 2.0% and 2.7%, respectively), target‐vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2‐year cumulative event rates, 5.5% and 3.2%), and target‐vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2‐year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2‐year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target‐vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow‐up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077.)

A New Tool for the Risk Stratification of Patients With Complex Coronary Artery DiseaseClinical Perspective

Background—Presently, no effective risk model exists to predict long-term mortality or other major adverse cardiovascular and cerebrovascular events (MACCE) in those patients undergoing percutaneous coronary intervention (PCI). This study aimed to assess whether the Clinical SYNTAX Score (CSS) calculated by multiplying the SYNTAX Score to a modified ACEF score (age/ejection fraction +1 for each 10 mL the creatinine clearance <60 mL/min per 1.73 m2) would improve the ability of either score to predict mortality and MACCE. Methods and Results—The CSS was calculated in 512 patients enrolled in the ARTS-II study who had serum creatinine levels, ejection fraction, and body weight recorded at baseline. Clinical outcomes in terms of MACCE and mortality at 1- and 5-year follow-up were stratified according to CSS tertiles: CSSLOW⩽15.6 (n=170), 15.627.5 (n=171). At 1-year follow-up, rates of repeat revascularization and MACCE were significantly higher in the highest tertile group. At 5-year follow-up, CSSHIGH had a comparable rate of myocardial infarction, a trend toward a significantly higher rate of death, and significantly higher rates of repeat revascularization and overall MACCE compared with patients in the lower 2 tertiles. The respective C-statistics for the CSS, SYNTAX Score, and ACEF score for 5-year mortality were 0.69, 0.62, and 0.65 and for 5-year MACCE were 0.62, 0.59, and 0.57. Conclusions—An improvement in the ability of the SYNTAX Score to predict MACCE and mortality can be achieved by combining the SYNTAX Score with a simple clinical risk score incorporating age, ejection fraction, and creatinine clearance to produce the Clinical SYNTAX score. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00235170.

Molecular Imaging of Factor XIIIa Activity in Thrombosis Using a Novel, Near-Infrared Fluorescent Contrast Agent That Covalently Links to Thrombi

Background—Activated factor XIII (FXIIIa) mediates fibrinolytic resistance and is a hallmark of newly formed thrombi. In vivo imaging of FXIIIa activity could further elucidate the role of this molecule in thrombosis and other biological processes and aid in the clinical detection of acute thrombi. Methods and Results—An FXIIIa-sensitive near-infrared fluorescence imaging agent (A15) was engineered by conjugating a near-infrared fluorochrome to a peptide ligand derived from the amino terminus of &agr;2-antiplasmin. To evaluate the molecular specificity of A15 for FXIIIa, a control agent (C15) was also synthesized by modifying a single key glutamine residue in A15. Fluorescence imaging experiments with A15 demonstrated stronger thrombosis enhancement in human plasma clots in vitro (P < 0.001 versus C15 clots and other controls). A15 was found to be highly specific for the active site of FXIIIa and was covalently bound to fibrin. In vivo murine experiments with A15 demonstrated significant signal enhancement in acute intravascular thrombi (P <0.05 versus C15 group). Minimal A15 enhancement was seen in older aged thrombi (>24 hours), consistent with an expected decline of FXIIIa activity over time. Imaging results were confirmed on correlative histopathology and fluorescence microscopy. Conclusions—A15 is a novel optical imaging agent that is specifically crosslinked to fibrin by FXIIIa, permitting detection of FXIIIa activity in experimental thrombi in vivo. This agent should permit assessment of FXIIIa activity in a broad range of biological processes and could aid in the clinical diagnosis of acute thrombi.

Initial experience and clinical evaluation of the Absorb bioresorbable vascular scaffold (BVS) in real-world practice: the AMC Single Centre Real World PCI Registry.

AIMS To report procedural and midterm clinical outcomes after the use of the second-generation Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) in a real-world percutaneous coronary intervention (PCI) registry. METHODS AND RESULTS All patients assigned to treatment with the Absorb BVS in the Academic Medical Center, Amsterdam, between August 2012 and August 2013 were included in a prospective registry. A total of 135 patients were included in the study, including 53 (39%) acute coronary syndrome (ACS) patients (13% ST-segment elevation myocardial infarction [STEMI]). In total 159 lesions were treated, including 102 (62%) with a type B2 or C classification. Pre- and post-procedural quantitative coronary angiography (QCA) analyses showed an acute gain of 1.37±0.53 mm. An angiographic success rate was achieved in 152 (96%) of the lesions. Six-month follow-up was available in 97% of the patients. Six-month cumulative target vessel failure (composite of all-cause mortality, any myocardial infarction [MI] and target vessel revascularisation [TVR]) rate was 8.5%, including a 3.0% MI, 3.0% definite scaffold thrombosis, 6.3% target lesion revascularisation, and an 8.5% TVR rate. CONCLUSIONS The use of the Absorb BVS in a cohort reflecting daily clinical practice is feasible and associated with good procedural safety and angiographic success rate. In addition, six-month follow-up is associated with acceptable clinical outcomes.

Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents In Vivo Assessment With Optical Coherence Tomography

BACKGROUND Pathology studies on fatal cases of very late stent thrombosis have described incomplete neointimal coverage as common substrate, in some cases appearing at side-branch struts. Intravascular ultrasound studies have described the association between incomplete stent apposition (ISA) and stent thrombosis, but the mechanism explaining this association remains unclear. Whether the neointimal coverage of nonapposed side-branch and ISA struts is delayed with respect to well-apposed struts is unknown. METHODS AND RESULTS Optical coherence tomography studies from 178 stents implanted in 99 patients from 2 randomized trials were analyzed at 9 to 13 months of follow-up. The sample included 38 sirolimus-eluting, 33 biolimus-eluting, 57 everolimus-eluting, and 50 zotarolimus-eluting stents. Optical coherence tomography coverage of nonapposed side-branch and ISA struts was compared with well-apposed struts of the same stent by statistical pooled analysis with a random-effects model. A total of 34 120 struts were analyzed. The risk ratio of delayed coverage was 9.00 (95% confidence interval, 6.58 to 12.32) for nonapposed side-branch versus well-apposed struts, 9.10 (95% confidence interval, 7.34 to 11.28) for ISA versus well-apposed struts, and 1.73 (95% confidence interval, 1.34 to 2.23) for ISA versus nonapposed side-branch struts. Heterogeneity of the effect was observed in the comparison of ISA versus well-apposed struts (H=1.27; I(2)=38.40) but not in the other comparisons. CONCLUSIONS Coverage of ISA and nonapposed side-branch struts is delayed with respect to well-apposed struts in drug-eluting stents, as assessed by optical coherence tomography. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00389220, NCT00617084.

Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents

BACKGROUND Pathology studies on fatal cases of very late stent thrombosis have described incomplete neointimal coverage as common substrate, in some cases appearing at side-branch struts. Intravascular ultrasound studies have described the association between incomplete stent apposition (ISA) and stent thrombosis, but the mechanism explaining this association remains unclear. Whether the neointimal coverage of nonapposed side-branch and ISA struts is delayed with respect to well-apposed struts is unknown. METHODS AND RESULTS Optical coherence tomography studies from 178 stents implanted in 99 patients from 2 randomized trials were analyzed at 9 to 13 months of follow-up. The sample included 38 sirolimus-eluting, 33 biolimus-eluting, 57 everolimus-eluting, and 50 zotarolimus-eluting stents. Optical coherence tomography coverage of nonapposed side-branch and ISA struts was compared with well-apposed struts of the same stent by statistical pooled analysis with a random-effects model. A total of 34 120 struts were analyzed. The risk ratio of delayed coverage was 9.00 (95% confidence interval, 6.58 to 12.32) for nonapposed side-branch versus well-apposed struts, 9.10 (95% confidence interval, 7.34 to 11.28) for ISA versus well-apposed struts, and 1.73 (95% confidence interval, 1.34 to 2.23) for ISA versus nonapposed side-branch struts. Heterogeneity of the effect was observed in the comparison of ISA versus well-apposed struts (H=1.27; I(2)=38.40) but not in the other comparisons. CONCLUSIONS Coverage of ISA and nonapposed side-branch struts is delayed with respect to well-apposed struts in drug-eluting stents, as assessed by optical coherence tomography. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00389220, NCT00617084.

3-Dimensional optical coherence tomography assessment of jailed side branches by bioresorbable vascular scaffolds: a proposal for classification.

OBJECTIVES The purpose of this study is to assess jailing of side branches (SB) by the everolimus-eluting, bioresorbable vascular scaffold (BVS) with 3-dimensional (3D) optical coherence tomography (OCT) reconstruction. BACKGROUND Because BVS struts at the SB orifice are suspected of being bioresorbed and/or forming a neointimal bridge, OCT has been used to evaluate the struts in detail at that particular site. Our understanding of the 3D relationship of the strut and the SB orifice is limited by the use of 2-dimensional OCT images. Fourier-domain OCT enables reliable 3D reconstruction of coronary vessels. METHODS The ABSORB Cohort B (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trial is a multicenter single-arm trial to assess the safety and performance of the BVS. Fourier-domain OCT pullbacks (C7-XR system, LightLab Imaging Inc., Westford, Massachusetts) are obtained at pullback speed of 20 mm/s and 3D renderings are performed. The orifices of the SB are assessed visually. The area of SB orifice and the number of strut-free compartments delineated by the BVS struts are evaluated. RESULTS Fifty-one OCT pullbacks were acquired: 33 pullbacks were imaged with Fourier-domain OCT and 27 treated segments had 46 side branches. Three-dimensional assessment was feasible in 87% (40 of 46) of pullbacks. The mean area of the SB orifice was 1.16 +/- 1.02 mm(2). The mean number of strut-free compartments was 2.0 +/- 1.1. The classification of the overhanging struts is proposed. CONCLUSIONS This study demonstrates that 3D OCT reconstruction is feasible to evaluate the orifices of SB jailed with BVS. (ABSORB Clinical Investigation, Cohort B; NCT00856856).

Vascular Tissue Reaction to Acute Malapposition in Human Coronary Arteries Sequential Assessment With Optical Coherence Tomography

Background— The vascular tissue reaction to acute incomplete stent apposition (ISA) is not well known. The aim of this study was to characterize the vascular response to acute ISA in vivo and to look for predictors of incomplete healing. Methods and Results— Optical coherence tomography studies of 66 stents of different designs, implanted in 43 patients enrolled in 3 randomized trials, were analyzed sequentially after implantation and at 6 to 13 months. Seventy-eight segments with acute ISA were identified in 36 of the patients and matched with the follow-up study by use of fiduciary landmarks. The morphological pattern of healing in the ISA segments was categorized as homogeneous, layered, crenellated, bridged, partially bridged, or bare, depending on the persistence of ISA and on the coverage. After 6 months, acute ISA volume decreased significantly, and 71.5% of the ISA segments were completely integrated into the vessel wall. Segments with acute ISA had higher risk of delayed coverage than well-apposed segments (relative risk 2.37, 95% confidence interval 2.01–2.78). Acute ISA size (estimated as ISA volume or maximum ISA distance per strut) was an independent predictor of ISA persistence and of delayed healing at follow-up. Conclusions— Neointimal healing tends to reduce ISA, with the malapposed stent struts often integrated completely into the vessel wall, resulting in characteristic morphological patterns. Coverage of ISA segments is delayed with respect to well-apposed segments. The larger the acute ISA, the greater the likelihood of persistent malapposition at follow-up and delayed healing. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00617084 and NCT00934752.