Combined anatomical and clinical factors for the long-term risk stratification of patients undergoing percutaneous coronary intervention: the Logistic Clinical SYNTAX score

Background The SYNTAX score (SXscore), an anatomical-based scoring tool reflecting the complexity of coronary anatomy, has established itself as an important long-term prognostic factor in patients undergoing percutaneous coronary intervention (PCI). The incorporation of clinical factors may further augment the utility of the SXscore to longer-term risk stratify the individual patient for clinical outcomes. Methods and results Patient-level merged data from >6000 patients in seven contemporary coronary stent trials was used to develop a logistic regression model—the Logistic Clinical SXscore—to predict 1-year risk for all-cause death and major adverse cardiac events (MACE). A core model (composed of the SXscore, age, creatinine clearance, and left ventricular ejection fraction) and an extended model [incorporating the core model and six additional (best performing) clinical variables] were developed and validated in a cross-validation procedure. The core model demonstrated a substantial improvement in predictive ability for 1-year all-cause death compared with the SXscore in isolation [area under the receiver operator curve (AUC): core model: 0.753, SXscore: 0.660]. A minor incremental benefit of the extended model was shown (AUC: 0.791). Consequently the core model alone was retained in the final the Logistic Clinical SXscore model. Validation plots confirmed the model predictions to be well calibrated. For 1-year MACE, the addition of clinical variables did not improve the predictive ability of the SXscore, secondary to the SXscore being the predominant determinant of all-cause revascularization. Conclusion The Logistic Clinical SXscore substantially enhances the prediction of 1-year mortality after PCI compared with the SXscore, and allows for an accurate personalized assessment of patient ris

Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

BackgroundTo test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES) ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST) is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases.MethodsFrom 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a) short Thrombelastogram PlateletMapping™ (TEG) and (b) VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15) as previously described.ResultsThere were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02) and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07). 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group.ConclusionThis study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk

CMR Native T1 Mapping Allows Differentiation of Reversible Versus Irreversible Myocardial Damage in ST-Segment–Elevation Myocardial Infarction

Background—CMR T1 mapping is a quantitative imaging technique allowing the assessment of myocardial injury early after ST-segment–elevation myocardial infarction. We sought to investigate the ability of acute native T1 mapping to differentiate reversible and irreversible myocardial injury and its predictive value for left ventricular remodeling. Methods and Results—Sixty ST-segment–elevation myocardial infarction patients underwent acute and 6-month 3T CMR, including cine, T2-weighted (T2W) imaging, native shortened modified look-locker inversion recovery T1 mapping, rest first pass perfusion, and late gadolinium enhancement. T1 cutoff values for oedematous versus necrotic myocardium were identified as 1251 ms and 1400 ms, respectively, with prediction accuracy of 96.7% (95% confidence interval, 82.8% to 99.9%). Using the proposed threshold of 1400 ms, the volume of irreversibly damaged tissue was in good agreement with the 6-month late gadolinium enhancement volume (r=0.99) and correlated strongly with the log area under the curve troponin (r=0.80) and strongly with 6-month ejection fraction (r=−0.73). Acute T1 values were a strong predictor of 6-month wall thickening compared with late gadolinium enhancement. Conclusions—Acute native shortened modified look-locker inversion recovery T1 mapping differentiates reversible and irreversible myocardial injury, and it is a strong predictor of left ventricular remodeling in ST-segment–elevation myocardial infarction. A single CMR acquisition of native T1 mapping could potentially represent a fast, safe, and accurate method for early stratification of acute patients in need of more aggressive treatment. Further confirmatory studies will be needed

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Clinical Efficacy of Polymer-Based Paclitaxel-Eluting Stents in the Treatment of Complex, Long Coronary Artery Lesions From a Multicenter, Randomized Trial

Background— Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking. Methods and Results— TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express 2 and an uncoated Express 2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group ( P =0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively ( P =0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively ( P =0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients ( P <0.0001). Conclusions— The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice

How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction?

Aims Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation. Methods and results In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2-95.8] to 36.7 (IQR: 22.7-59.5), P 40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: −0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: −0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR − pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm3 of stent), P: 0.01] were associated with a potentially deleterious increase in IMR. Conclusion Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burde

The influence of coronary plaque morphology assessed by optical coherence tomography on final microvascular function after stenting in patients with ST-elevation myocardial infarction

Objectives The index of microcirculatory resistance (IMR) provides a reproducible assessment of the status of coronary microvasculature in patients with ST-elevation myocardial infarction (STEMI). Frequency-domain optical coherence tomography (FD-OCT) enables detailed assessment of the morphology of coronary plaque. We sought to determine the influence of the initial culprit coronary plaque anatomy within the infarct-related artery on IMR after stenting in STEMI. Patients and methods In 25 STEMI patients IMR was measured immediately before and after stent implantation. FD-OCT imaging was performed at the same time points and atherothrombotic volume (ATV) before stenting, prolapsed+floating ATV after stenting and ΔATV was measured using three different strategies. Results There were no relationships between preprocedural IMR and FD-OCT parameters. Prestenting IMR was related only to pain to wire time (P: 0.02). Irrespective of the method adopted, the final IMR was related to prestenting ATV (ρ: 0.44, P: 0.03 for method I, ρ: 0.48, P: 0.02 for method II and ρ: 0.30, P: 0.06 for method III) and ΔATV (ρ: 0.41, P: 0.04 for method II and ρ: 0.44, P: 0.03 for method III). Conclusion IMR measured before stenting is independent of the appearances of the culprit coronary plaque within the infarct-related artery. IMR after stenting, and more importantly, the change in IMR after stenting, reflect the degree of distal embolization during stent implantation

A prospective evaluation of the safety and efficacy of the TAXUS Element paclitaxel-eluting coronary stent system for the treatment of de novo coronary artery lesions: Design and statistical methods of the PERSEUS clinical program

<p>Abstract</p> <p>Background</p> <p>Paclitaxel-eluting stents decrease angiographic and clinical restenosis following percutaneous coronary intervention compared to bare metal stents. TAXUS Element is a third-generation paclitaxel-eluting stent which incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The stent is intended to have enhanced radiopacity and improved deliverability compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS Element stent are being evaluated in the pivotal PERSEUS clinical trials.</p> <p>Methods/Design</p> <p>The PERSEUS trials include two parallel studies of the TAXUS Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority trial in subjects with lesion length ≤28 mm and vessel diameter ≥2.75 mm to ≤4.0 mm which compares TAXUS Element to the TAXUS Express²paclitaxel-eluting stent system. The Workhorse study employs a novel Bayesian statistical approach that uses prior information to limit the number of study subjects exposed to the investigational device and thus provide a safer and more efficient analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective, single-arm, superiority trial in subjects with lesion length ≤20 mm and vessel diameter ≥2.25 mm to <2.75 mm that compares TAXUS Element with a matched historical bare metal Express stent control.</p> <p>Discussion</p> <p>The TAXUS PERSEUS clinical trial program uses a novel statistical approach to evaluate whether design and metal alloy iterations in the TAXUS Element stent platform provide comparable safety and improved procedural performance compared to the previous generation Express stent. PERSEUS trial enrollment is complete and primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel are registered at <url>http://www.clinicaltrials.gov</url>, identification numbers NCT00484315 and NCT00489541.</p

Predictors of Paravalvular Regurgitation Following Implantation of the Fully Repositionable and Retrievable Lotus Transcatheter Aortic Valve (From the REPRISE II Trial Extended Cohort)

Paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR) is associated with worse long-term outcomes. The Lotus Valve incorporates an innovative adaptive seal designed to minimize PVL. This analysis evaluated the incidence and predictors of PVL following implantation of the Lotus transcatheter aortic valve. The REPRISE II study with Extended Cohort enrolled 250 high-surgical risk patients with severe symptomatic aortic stenosis. Aortic regurgitation was assessed by echocardiography pre-procedure, at discharge and 30 days by an independent core lab. Baseline and procedural predictors of mild or greater PVL at 30 days (or at discharge if 30-day data were not available) were determined using a multivariate regression model (N=229). Among 229 patients, 197 (86%) had no/trace PVL, 30 had mild, and 2 had moderate PVL; no patient had severe PVL. Significant predictors of mild/moderate PVL included device:annulus area ratio (odds ratio [OR]: 0.87 (95% CI: 0.83-0.92); P&lt;0.001), LVOT calcium volume (OR:2.85;(1.44-5.63); P=0.003), and annulus area (OR:0.89(0.82-0.96); P=0.002). When the device:annulus area ratio was &lt;1, the rate of mild/moderate PVL was 53.1% (17/32). The rates of mild/moderate PVL with 0-5%, 5-10%, and &gt;10% annular oversizing by area were 17.5% (11/63), 2.9% (2/70), and 3.2% (2/63), respectively. Significant independent predictors of PVL included device:annulus area ratio and LVOT calcium volume. When the prosthetic valve was oversized by ≥5%, the rate of mild or greater PVL was only 3%. In conclusion, the overall rates of PVL with the Lotus Valve are low and predominantly related to device/annulus areas and calcium; these findings have implications for optimal device sizing