Machine Learning Identifies New Predictors on Restenosis Risk after Coronary Artery Stenting in 10,004 Patients with Surveillance Angiography.

OBJECTIVE: Machine learning (ML) approaches have the potential to uncover regular patterns in multi-layered data. Here we applied self-organizing maps (SOMs) to detect such patterns with the aim to better predict in-stent restenosis (ISR) at surveillance angiography 6 to 8 months after percutaneous coronary intervention with stenting. METHODS: In prospectively collected data from 10,004 patients receiving percutaneous coronary intervention (PCI) for 15,004 lesions, we applied SOMs to predict ISR angiographically 6-8 months after index procedure. SOM findings were compared with results of conventional uni- and multivariate analyses. The predictive value of both approaches was assessed after random splitting of patients into training and test sets (50:50). RESULTS: Conventional multivariate analyses revealed 10, mostly known, predictors for restenosis after coronary stenting: balloon-to-vessel ratio, complex lesion morphology, diabetes mellitus, left main stenting, stent type (bare metal vs. first vs. second generation drug eluting stent), stent length, stenosis severity, vessel size reduction, and prior bypass surgery. The SOM approach identified all these and nine further predictors, including chronic vessel occlusion, lesion length, and prior PCI. Moreover, the SOM-based model performed well in predicting ISR (AUC under ROC: 0.728); however, there was no meaningful advantage in predicting ISR at surveillance angiography in comparison with the conventional multivariable model (0.726, p = 0.3). CONCLUSIONS: The agnostic SOM-based approach identified-without clinical knowledge-even more contributors to restenosis risk. In fact, SOMs applied to a large prospectively sampled cohort identified several novel predictors of restenosis after PCI. However, as compared with established covariates, ML technologies did not improve identification of patients at high risk for restenosis after PCI in a clinically relevant fashion.

Acute and Midterm Outcome After MitraClip Therapy in Patients With Severe Mitral Regurgitation and Left Ventricular Dysfunction.

The clinical outcome of patients with severe primary and secondary mitral regurgitation (MR) and heart failure or significantly reduced left ventricular ejection fraction (LVEF) who underwent percutaneous mitral valve repair (pMVR) is yet not well known. This study compares midterm outcome of patients with severe left ventricular dysfunction (EF ≤30%) versus patients with slightly or moderately reduced or normal LVEF (EF >30%) after pMVR. One hundred thirty-six consecutive patients were enrolled: 42 patients displayed severe left ventricular dysfunction, group 1 (logistic EuroSCORE I 27.7 ± 21.8%; secondary MR in 37 patients), and 94 patients displayed slightly or moderately reduced or normal LVEF, group 2 (logistic EuroSCORE I 17 ± 18.2%; secondary MR in 21 patients). The primary efficacy endpoint was death of any cause, repeat mitral valve intervention, and/or New York Heart Association class ≥III, which was reached in 31% of patients in group 1 versus 40% in group 2 (p = 0.719) at a median follow-up of 371 days. MR, graded by transthoracic echocardiography, was reduced in both groups (p <0.001) and New York Heart Association class improved in each group (p <0.001), with no differences between groups (p >0.05). In conclusion, at midterm follow-up, the pMVR provided significant clinical benefits with comparable results achieved both in patients with significantly reduced and in patients with moderately reduced to normal LVEF. Thus, pMVR represents a feasible and effective treatment in high-risk patients who otherwise have limited therapeutic options and no safe option to reduce MR.

ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting.

BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS: Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Randomized comparison of biolimus-eluting stents with biodegradable polymer versus everolimus-eluting stents with permanent polymer coatings assessed by optical coherence tomography.

We sought to compare the healing patterns of biolimus-eluting stents with biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with permanent polymer (PP-EES, Xience) using intravascular optical coherence tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19). Stent tissue coverage and apposition as well as the incidence of peri-strut low intensity area (PLIA) were assessed by OCT at 6-8 months. Generalized linear mixed models were used to account for clustered data. OCT imaging was available for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890 struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63-3.79), P = 0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21-12.5], P = 0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %) had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43-2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar stent coverage and apposition as assessed by OCT at 6-8 months. In addition, PLIA-possible markers of delayed arterial healing-were observed with similar frequency in both groups.

Dangerous liaison: successful percutaneous edge-to-edge mitral valve repair in patients with end-stage systolic heart failure can cause left ventricular thrombus formation.

AIMS: To evaluate the characteristics and clinical outcome of patients with new formation of left ventricular (LV) thrombus after percutaneous edge-to-edge mitral valve repair. METHODS AND RESULTS: Between 2009 and 2012 we intended to treat 150 patients with severe mitral regurgitation (MR) with percutaneous edge-to-edge mitral valve repair in our centre. Post-procedural transthoracic echocardiographic examinations scheduled during the hospital stay revealed the new formation of LV thrombi in three out of 150 patients. All three patients suffered from end-stage systolic heart failure with a LV ejection fraction (LVEF) below 20% and were successfully treated in terms of MR reduction (reduction of at least two MR grades). No thrombus formation was observed in patients with a LVEF >20% treated in our centre (a total of 136 patients). The frequency of new LV thrombus formation in the cohort of patients with a LVEF ≤20% treated in our centre was 21% (three out of 14 patients). CONCLUSIONS: New formation of LV thrombus was detected in patients with severely depressed LVEF (≤20%) after successful reduction of MR following percutaneous edge-to-edge mitral valve repair. This phenomenon could be a play of chance, but percutaneous edge-to-edge mitral valve repair using the MitraClip¨ system is a new procedure. Special care is needed when performing new procedures, and the unexpected post-procedural finding of LV thrombus formation in approximately 20% in this cohort is worth reporting.

Three-dimensional echocardiographic optimization improves outcome in cardiac resynchronization therapy compared to ECG optimization: a randomized comparison.

AIMS: There is little consensus on optimal atrioventricular (AV) and ventricular-to-ventricular (VV) intervals in cardiac resynchronization therapy (CRT). The aim of this study was to examine a novel combination of Doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized AV- and VV-interval optimization compared to conventional electrocardiogram (ECG) optimization. METHODS: In this double-blind, randomized controlled trial, 77 patients (male: 57, age: 68 ± 10 years) with severely reduced ejection fraction (EF), New York Heart Association (NYHA) class III or IV, and wide QRS complex (>120 ms) have been included. Patients were randomized to either AV- and VV-interval optimization using DE and 3DE (group 1, n = 39) or ECG (group 2, n = 38). 3DE was performed in all patients for the evaluation of left ventricular (LV) dimensions, EF and systolic dyssynchrony index (SDI), and NYHA class obtained before CRT and after 3 months. Primary endpoint of the study was clinical response to CRT, defined as a reduction of NYHA class by ≥1 score. Secondary endpoints were change of EF, LV volumes, and SDI. RESULTS: There were significantly more responders in group 1 (82%) than in group 2 (58%, P = 0.021). Similarly, group 1 showed a larger increase in EF (7.0 ± 6.0% vs 3.4 ± 5.6%, P = 0.015) and a more pronounced reduction of SDI (-4.5 ± 5.9% vs -1.5 ± 5.6%, P = 0.039) than group 2. CONCLUSION: Compared with conventional ECG optimization, this novel echocardiographic optimization protocol resulted in a significantly higher response rate, improved LV systolic function, and may be used to select the optimal AV and VV intervals in CRT.

Prognostic value of late gadolinium enhancement in cardiovascular magnetic resonance imaging after acute ST-elevation myocardial infarction in comparison with single-photon emission tomography using Tc99m-Sestamibi.

BACKGROUND: Infarct size is an important predictor of cardiac risk after acute myocardial infarction. The established modality for its assessment is Tc99m-Sestamibi Single-photon emission computed tomography (SPECT). In recent years, data are emerging demonstrating that scar size as assessed by late gadolinium enhancement in cardiovascular magnetic resonance imaging (CMR) as well as the presence of microvascular obstruction (MO) may also provide prognostic information, however, so far no direct comparisons of both modalities have been reported. METHODS: We retrospectively analysed patients (n = 281) with acute ST-elevation myocardial infarction and primary angioplasty who underwent Tc99m-Sestamibi-SPECT and CMR on a 1.5 T scanner at a median of 4.3 (IQR: 3.7-5.1) and 4.9 (IQR: 4.1-5.9) days after the acute event, respectively. The primary endpoint of the study was a composite of all-cause mortality, recurrent myocardial infarction and congestive heart failure requiring hospitalization. RESULTS: During a median follow-up of 3.0 (IQR: 2.0-4.5) years, 24 events occurred. The best predictor was MO (P < 0.0001), followed by infarct size by CMR (P = 0.0043) and infarct size by SPECT (P = 0.012) (all P-values corrected for clinical risk). In a multivariate model including clinical and periprocedural parameters, MO remained the only significant predictor in addition to clinical risk. CONCLUSIONS: The extent of MO as determined by CMR has an excellent prognostic value in predicting cardiac events following acute myocardial infarction and may be used as an alternative to infarct size assessment by Tc99m-Sestamibi-SPECT.

Prognostic value of coronary computed tomography angiography during 5 years of follow-up in patients with suspected coronary artery disease.

AIMS: Coronary computed tomography angiography (CCTA) has a high accuracy for detection of obstructive coronary artery disease (CAD). Several studies also showed a good predictive value for subsequent cardiac events. However, the follow-up period of these studies was limited to ~2 years and long-term follow-up data on prognosis out to 5 years are very limited. METHODS AND RESULTS: This study is based on 1584 patients with suspected CAD undergoing CCTA between December 2003 and November 2006. Among other CCTA parameters, the total plaque score defined as number of abnormal segments (having either a non-obstructive plaque or a stenosis) and the most severe stenosis were recorded. The primary endpoint was a composite of death and non-fatal myocardial infarction. Revascularization procedures later than 90 days after the CT study were assessed as secondary endpoints. During a median follow-up of 5.6 years (IQR: 5.1-6.3 years) 61 patients suffered death or myocardial infarction and 52 underwent late revascularization. The severity of CAD and the total plaque score were the best predictors of death and non-fatal myocardial infarction, both significantly improving prediction over standard clinical risk scores (multivariate c-index 0.60 and 0.66, respectively, P = 0.002 and <0.0001, respectively). The annual event rate ranged from 0.24% for patients with no CAD to 1.1% for patients with obstructive CAD and 1.5% for patients with CAD and extensive plaque load (>5 segments). Both parameters also improved prediction of need for subsequent revascularization (c-index 0.72 and 0.63, respectively, P < 0.0001 and P = 0.0013, respectively). CONCLUSION: Data from CCTA predict both death and myocardial infarction as well as need for subsequent revascularizations out to 5 years. CCTA imaging may be a valuable tool in the assessment of long-term prognosis in patients with suspected CAD.

Second-versus first-generation "Limus"-eluting stents in diabetic patients with coronary artery disease: a randomized comparison in setting of ISAR-TEST-4 trial.

BACKGROUND: Patients with diabetes mellitus remain at higher risk for adverse events following percutaneous coronary intervention and the identification of the optimum drug eluting stents (DES) in these patients is of high clinical relevance. We compared effectiveness of everolimus-eluting stents (EES; Xience) versus sirolimus-eluting stents (SES; Cypher) in patients with diabetes mellitus enrolled in the Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents (ISAR-TEST-4) trial. METHODS: In the setting of the ISAR-TEST-4 trial, 1304 patients with broad inclusion criteria were randomized to treatment with EES or SES. The focus of the present analysis is on a cohort of 377 patients with diabetes mellitus assigned to receive EES (n = 184) or SES (n = 193). The primary endpoint was the composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target lesion revascularization (TLR) at 3-year follow-up. Secondary endpoints were parameters of angiographic and clinical restenosis (in-stent late lumen loss, binary restenosis, and TLR), all-cause mortality and definite/probable stent thrombosis. RESULTS: EES was comparable to SES concerning the incidence of the primary endpoint (21% vs. 24%, respectively; relative risk = 0.87; 95% CI, 0.57-1.34; P = 0.53). Concerning the secondary endpoint, TLR at 3 years with EES versus SES stents was not statistically different (14.7% vs. 16.6%, respectively; relative risk = 0.85; 95% CI, 0.51-1.43; P = 0.55). In terms of angiographic outcomes patients treated with EES as compared to SES had significantly lower late lumen loss (0.22 ± 0.46 mm vs. 0.44 ± 0.66 mm, respectively; P < 0.001) and binary restenosis (8.4% vs. 17%, respectively; P = 0.02) at 6- to 8-month angiographic follow-up. EES was comparable to SES concerning the incidence of all-cause death (10% vs. 16%, respectively; relative risk = 0.66; 95% CI, 0.37-1.18; P = 0.16) and stent thrombosis (1.1% vs. 3.1%, respectively; P = 0.19). CONCLUSIONS: In patients with diabetes mellitus enrolled in a real-world randomized control trial, EES is comparable to SES in terms of clinical efficacy and safety out to 3 years; angiographic markers of antirestenotic efficacy favored EES.

Statin pretreatment and presentation patterns in patients with coronary artery disease.

BACKGROUND: Knowledge on the impact of pretreatment statin therapy on presentation of patients with coronary artery disease (CAD) is incomplete. The aim of this study was to investigate the impact of statin pretreatment on presentation patterns of patients with CAD. METHODS: The study included 12,989 consecutive patients with CAD who underwent coronary angiography. The primary outcome was presentation as stable angina or acute coronary syndrome (ACS) according to statin pretreatment. RESULTS: At the time of presentation, 8147 (62.7%) patients were receiving statins and 4842 (37.3%) patients were not receiving statins. Presentation pattern in patients receiving statins vs. those not receiving statins was: stable angina in 5939 (72.9%) vs. 2102 (43.4%) patients; odds ratio (OR) = 3.50, 95% confidence interval (CI) 3.25-3.78; p < 0.001; unstable angina in 1435 (17.6%) vs. 1011 (20.9%) patients; OR = 0.81, 95% CI 0.74-0.89; p < 0.001; non- -ST-segment elevation myocardial infarction (NSTEMI) in 463 (5.7%) vs. 505 (10.4%) patients; OR = 0.52, 95% CI 0.45-0.59; p < 0.001; and ST-segment elevation myocardial infarction (STEMI) in 310 (3.8%) vs. 1224 (25.3%) patients; OR = 0.11, 95% CI 0.10-0.13; p < 0.001. Gensini score (median [25th to 75th percentiles]) was significantly higher in patients on statins presenting with stable angina (26.5 [13.0-59.5] vs. 21.0 [10.5-47.4]; p < 0.001) or ACS (39.3 [17.5-77.0] vs. 37.0 [18.0-64.0]; p = 0.001). In multivariable analysis, statin therapy was an independent correlate of reduced presentation with ACS (adjusted OR = 0.35 [0.32-0.39]; p < 0.001) or STEMI (adjusted OR = 0.18 [0.16-0.22]; p < 0.001). CONCLUSIONS: Despite having a higher coronary atherosclerotic burden, patients with CAD on statin therapy have reduced odds for presentation with ACS and STEMI compared to patients not receiving statins.

The assessment of area at risk and myocardial salvage after coronary revascularization in acute myocardial infarction: comparison between CMR and SPECT.

OBJECTIVES: This study sought to compare cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) for assessment of area at risk, scar size, and salvage area after coronary reperfusion in acute myocardial infarction. BACKGROUND: Myocardial salvage is an important surrogate endpoint assessing the success of coronary reperfusion in acute myocardial infarction. SPECT, the established modality for assessment of myocardial salvage, requires radiopharmaceutical injection before revascularization and 2 examinations. The combination of T2 and late enhancement imaging in CMR can assess myocardial salvage in 1 examination, but up to now, data comparing both modalities are very limited. METHODS: We analyzed 207 patients who were treated by primary revascularization in acute myocardial infarction and who underwent both SPECT and CMR for assessment of myocardial salvage. In CMR, T2-weighted turbo spin echo sequences for area at risk and contrast-enhanced inversion recovery gradient echo sequences were performed. RESULTS: Image quality was insufficient in 27 patients (13%). In the remaining 180 patients, mean area at risk was 29.4 ± 18.7% of the left ventricle (LV), and infarct size was 14.7 ± 16.9% LV, resulting in a mean salvage area of 14.9 ± 15.1% LV in SPECT, whereas in CMR, mean area at risk was 28.0 ± 14.5% LV, and infarct size was 16.0 ± 13.5% LV, resulting in a mean salvage area of 11.9 ± 12.3%. Results of both modalities correlated well for area at risk (r = 0.80), scar size (r = 0.87), and salvage area (r = 0.66, all p < 0.0001). CONCLUSIONS: Assessment of the salvage area by CMR using T2 and late enhancement imaging correlates well with the established modality of SPECT. CMR therefore may be an alternative to paired SPECT imaging for myocardial salvage assessment, but the contraindications of the modality and limitations in the established T2 imaging sequences currently cause a considerable rate of data loss.

One-year outcomes with abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary interventions in patients with non-ST-segment elevation myocardial infarction: updated results from the ISAR-REACT 4 trial.

AIMS: Thirty-day results of the double-blind, randomised Intracoronary Stenting and Antithrombotic Regimen -Rapid Early Action for Coronary Treatment (ISAR-REACT) 4 trial showed no difference in ischaemic complications and a reduction in bleeding by bivalirudin versus abciximab and heparin in 1,721 patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing percutaneous coronary intervention (PCI). A longer follow-up may be required to assess the whole potential benefit of a periprocedural antithrombotic therapy. METHODS AND RESULTS: The primary outcome for this analysis was the composite of death, myocardial infarction or target vessel revascularisation one year after randomisation. Secondary outcome was the composite of death or myocardial infarction. At one year, the primary outcome occurred in 21.3% of patients assigned to abciximab and heparin versus 21.5% assigned to bivalirudin (hazard ratio [HR] 0.99; 95% confidence interval [CI]: 0.80-1.21; p=0.94). The combined incidence of death or myocardial infarction was 15.7% in the abciximab and heparin group versus 16.0% in the bivalirudin group (HR 0.99; 95% CI: 0.78-1.26; p=0.94). The mortality rates were 4.0% and 4.7%, respectively (HR 0.85; 95% CI: 0.54-1.34; p=0.48). At one year, no significant differences in the primary outcome were observed with abciximab and heparin versus bivalirudin in any of the subgroups analysed. CONCLUSIONS: In patients with NSTEMI undergoing PCI, abciximab with heparin and bivalirudin provide comparable outcomes at one year, although bivalirudin reduced the rate of bleeding at 30 days. CLINICAL TRIAL REGISTRATION INFORMATION: URL www.clinicaltrials.gov; Unique identifier NCT00373451.

Association of ST-elevation and non-ST-elevation presentation on ECG with transmurality and size of myocardial infarction as assessed by contrast-enhanced magnetic resonance imaging.

BACKGROUND: It is the general perception, that ST-elevation myocardial infarction is associated with transmural ischemia while Non-ST elevation myocardial infarction is found in non-transmural subendocardial ischemia. This association, however, derives primarily from post mortem studies. METHODS: A total of 220 patients with acute myocardial infarction (MI) who had PCI on admission and contrast-enhanced cardiac magnetic resonance imaging (CMR) within one week were included into the study. Size and transmural extent of MI was quantified by CMR and correlated with the ECG on admission. RESULTS: Based on the ECG findings, 57% were classified as STEMI and 43% as NSTEMI. CMR infarct size was significantly larger in STEMI than NSTEMI (23.2 vs. 14.2 LV%, p<0.001). As assessed by CMR, STEMI patients were transmural in 63% as compared to 27% of patients with NSTEMI (p<0.001). In a multivariable logistic regression model, total infarct size was significantly associated with presence of STEMI (OR: 1.045, 95% CI [1.014-1.077], p=0.004) whereas the number of transmural segments did not significantly add further information for a STEMI/NSTEMI classification (p=0.054, change of c-index from 0.69 to 0.70). CONCLUSIONS: The electrocardiographic STEMI/NSTEMI classification does rather characterize the total size of MI than the transmural extent as assessed by CMR.

Relation of fibrinogen level with cardiovascular events in patients with coronary artery disease.

Evidence on the usefulness of fibrinogen for the risk stratification of patients with coronary artery disease remains inconclusive. The aims of this study were to investigate the association of fibrinogen with cardiovascular events and to assess whether this biomarker provides additional prognostic information on top of that provided by traditional cardiovascular risk factors. This study included 13,195 patients with angiography-proved coronary artery disease and fibrinogen measurements available. Receiver-operating characteristic curve analysis showed that the best fibrinogen cutoff for mortality prediction was 402.0 mg/dl. On the basis of this cutoff, patients were divided into 2 groups: the group with fibrinogen >402.0 mg/dl (n = 5,198) and the group with fibrinogen ≤402.0 mg/dl (n = 7,997). The primary outcome was 1-year mortality. All-cause deaths occurred in 393 patients with fibrinogen >402.0 mg/dl and in 246 patients with fibrinogen ≤402.0 mg/dl (Kaplan-Meier estimates of mortality 7.7% and 3.1%, log-rank test p <0.001). The relation between fibrinogen and mortality followed a J-shaped pattern, with lowest mortality in patients with fibrinogen concentrations of 295 to 369 mg/dl. After adjustment for cardiovascular risk factors and relevant clinical variables, fibrinogen remained an independent correlate of all-cause mortality (adjusted hazard ratio 1.07, 95% confidence interval 1.04 to 1.10, p <0.001, for each 50 mg/dl increase in fibrinogen level), but it did not improve the discriminatory power of the model for mortality prediction (integrated discrimination improvement 0.002, p = 0.32). In conclusion, in patients with coronary artery disease, fibrinogen is an independent correlate of mortality, but it does not provide additional prognostic information on top of that provided by traditional cardiovascular risk factors.

Two rare variants explain association with acute myocardial infarction in an extended genomic region including the apolipoprotein(A) gene.

Relatively low numbers of kringle 4 type 2 repeats in apolipoprotein(a) and specific haplotypes of the SLC22A3-LPAL2-LPA region on chromosome 6 are associated with an increased risk of coronary disease. We examined the possibility that rs3798220 and rs10455872, short variations located in LPA [the apolipoprotein(a) gene], and related to the number of kringle 4 type 2 repeats, may serve as markers for the association between haplotypes and acute myocardial infarction. Genotypes were determined with TaqMan assays in a sample of 2136 cases and 1211 controls. The minor alleles of rs3798220 and rs10455872 were associated with increased risks (rs3798220-C: adjusted OR 2.14, 95% CI, 1.37-3.33, P = 0.00080; rs10455872-G: adjusted OR 1.74, 95% CI 1.36-2.24, P < 0.00001). After adjustments were made for potential confounders, none of nine polymorphisms included in a haplotype analysis were singly related to disease. Two risk haplotypes were identified; one (CCTTGTGTG; OR 1.25, 95% CI 1.08-1.45, P = 0.0022) was correlated with rs3798220-C and the other (CCCTGGATC; OR 1.65, 95% CI 1.14-2.38, P = 0.0074) with rs10455872-G. Thus, the findings allowed for a more precise definition of risk-associated markers: specific nucleotides in LPA instead of standard haplotypes defined by noneffective variants from the extensive SLC22A3-LPAL2-LPA region.

Uric acid and prognosis in angiography-proven coronary artery disease.

BACKGROUND: The optimal uric acid (UA) level associated with the lowest mortality and the strength of association between UA and mortality in various subgroups of patients with coronary artery disease (CAD) are unknown. MATERIALS AND METHODS: This study included 13 273 patients with angiographic confirmation of CAD and UA measurements available. The primary outcome analysis was 1-year mortality. RESULTS: Based on the receiver operating characteristic curve analysis, the best cut-off of UA for mortality prediction was 7·11 mg/dL. Using this cut-off, patients were divided into two groups: the group with UA ≤ 7·11 mg/dL (n = 9075) and the group with UA > 7·11 mg/dL (n = 4198). Cardiac mortality was 6·3% (256 deaths) in patients with UA > 7·11 mg/dL and 2·3% (201 deaths) in patients with UA ≤ 7·11 mg/dL [hazard ratio (HR) = 2·82, 95% confidence interval (CI) 2·36-3·36; P < 0·001]. After adjustment for cardiovascular risk factors, UA remained an independent correlate of cardiac mortality (HR = 1·20, 95% CI 1·08-1·34; P = 0·001, for each standard deviation increase in the logarithmic scale of UA). The relationship between cardiac or all-cause mortality and UA showed a J-shaped pattern with lowest mortality in patients with UA between 5·17 and 6·76 mg/dL. UA predicted mortality across all subgroups of patients, with strongest association in women and patients without arterial hypertension. CONCLUSIONS: UA predicted an increased risk of cardiac mortality across all subgroups of patients with CAD. The association between UA and cardiac or all-cause mortality had a 'J-shaped' pattern with lowest risk of death in patients with UA levels between 5·17 and < 6·76 mg/dL.

Antiplatelet efficacy of prasugrel in patients with high on-clopidogrel treatment platelet reactivity and a history of coronary stenting.

Little is known about the antiplatelet action of the 3 rd generation thienopyridine prasugrel in patients showing high platelet reactivity (PR) levels on clopidogrel. Thus, we aimed to determine the antiplatelet efficacy of prasugrel loading (LD) and maintenance dose (MD) treatment in a registry of patients with high PR levels on clopidogrel and a consecutive switch over to prasugrel in a setting of routine platelet function testing. In our registry of patients treated by percutaneous coronary intervention (n=73) with high levels of PR on clopidogrel, the ADP-induced platelet aggregation (PA, in AU x min) was assessed on a Multiplate analyser 1) after clopidogrel LD, 2) after prasugrel LD and 3) on prasugrel MD (5 vs. 10 mg/day). In patients with high PR levels on clopidogrel, prasugrel LD resulted in significantly lower PA values (574 [462-698] vs. 156 [89-234] AU x min; p<0.0001). Only 2.7% of patients showed high PR (HPR, ≥468 AU x min) following prasugrel LD. On prasugrel MD, PA was significantly higher as compared to prasugrel LD (248 [145-406] vs. 156 [89-234] AU x min; p<0.0001) with more patients showing HPR on MD vs. LD (16.4% vs. 2.7%; p=0.009). For prasugrel MD, HPR rates were higher in 5 vs. 10 mg/day treated patients (46.2% vs. 10.0%; p=0.006). In conclusion, for patients with high PR levels on clopidogrel, prasugrel LD abolished this status in the majority of patients. However, prasugrel response variability was detected, being more pronounced on prasugrel MD vs. LD treatment. The clinical impact of these findings warrants further investigation.

Early vascular healing with rapid breakdown biodegradable polymer sirolimus-eluting versus durable polymer everolimus-eluting stents assessed by optical coherence tomography.

BACKGROUND: Differences in early arterial healing patterns after stent implantation between biodegradable and durable polymer based new generation drug-eluting stents are not well understood. The aim of this study was to compare the healing patterns of a novel rapid breakdown (≤8 weeks) biodegradable polymer sirolimus-eluting stent (BP-SES) with a durable polymer everolimus-eluting stent (EES) using intravascular optical coherence tomography (OCT) at 4 months. METHODS: A total of 20 patients were randomly assigned to stenting with BP-SES (n=11) or EES (n=9). Overall intravascular imaging was available for 15 (75%) patients. The primary endpoint was the difference in rate of uncovered struts between BP-SES and EES. To account for strut-level clustering, the results in both treatment groups were compared using a generalized linear mixed model approach. RESULTS: Regarding the primary endpoint, BP-SES as compared to EES showed similar rates of uncovered struts (37 [6.8%] versus 167 [17.5%], odds ratio (OR) 0.45 (95% CI 0.09-2.24), p=0.33). There were no malapposed struts in BP-SES group and 14 malapposed struts in EES group (p=0.97). No difference in percent neointimal volume (14.1±8.2% vs. 11.4±6.4%, p=0.56) was observed. CONCLUSIONS: Although rapid-breakdown BP-SES as compared to EES showed signs of improved early tissue coverage, after adjustment for strut-level clustering these differences were not statistically significant. No differences in ability to suppress neointimal hyperplasia after stent implantation between 2 stents were observed.

Polymer-free sirolimus-eluting versus polymer-based paclitaxel-eluting stents: an individual patient data analysis of randomized trials.

INTRODUCTION AND OBJECTIVES: The angiographic and clinical efficacy of polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents remain a matter of debate. We sought to investigate angiographic and clinical measures of efficacy of polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents. METHODS: Patient data from the randomized intracoronary stenting and angiographic restenosis-test equivalence between the 2 drug-eluting stents (ISAR-TEST) clinical trial and the LIPSIA Yukon clinical trial (randomized comparison of a polymer-free sirolimus-eluting stent vs a polymer-based paclitaxel-eluting stent in patients with diabetes mellitus) were pooled. The angiographic (primary) endpoint was in-stent late lumen loss at 6 months to 9 months. The clinical (secondary) endpoints were death or myocardial infarction, cardiac death or myocardial infarction, target lesion revascularization, and myocardial infarction. RESULTS: A total of 686 patients (polymer-free sirolimus-eluting stents, n=345 vs polymer-based paclitaxel-eluting stents, n=341) and 751 lesions (polymer-free sirolimus-eluting stents, n=383 vs polymer-based paclitaxel-eluting stents, n=368) were included in the study. Control angiography (606 lesions, 80.6%) showed comparable in-stent late lumen loss for polymer-free sirolimus-eluting stents vs polymer-based paclitaxel-eluting stents (0.53 [0.59] mm vs 0.46 [0.57] mm; P=.15). Median follow-up was 34.8 months. Polymer-free sirolimus-eluting stents and polymer-based paclitaxel-eluting stents were associated with comparable risk of death or myocardial infarction (relative risk=1.17; 95% confidence interval, 0.49-2.80; P=.71), cardiac death or myocardial infarction (relative risk=1.17; 95% confidence interval, 0.72-1.89; P=.50), target lesion revascularization (relative risk=0.98; 95% confidence interval, 0.65-1.47; P=.93), and myocardial infarction (relative risk=1.79; 95% confidence interval, 0.85-3.76; P=.12). CONCLUSIONS: In this pooled analysis, polymer-free sirolimus-eluting stents were comparable to polymer-based paclitaxel-eluting stents with respect to both angiographic and clinical efficacy.

Prognostic value of uric acid in patients with Type 2 diabetes mellitus and coronary artery disease.

Studies investigating the prognostic role of UA (uric acid) in patients with Type 2 diabetes mellitus have given conflicting findings. We undertook the present study to assess the association between UA and outcome in patients with Type 2 diabetes mellitus and CAD (coronary artery disease). The study included 3705 patients with diabetes mellitus and angiography-proven CAD. UA was measured before coronary angiography. The primary outcome was 1-year all-cause mortality. The UA concentration [median (25th-75th quartiles)] was 6.44 mg/dl (5.40-7.70 mg/dl). There were 264 deaths (7.1%) during follow-up: 45 deaths in patients of the first UA quartile, 43 deaths in patients of the second UA quartile, 51 deaths in patients of the third UA quartile and 125 deaths in patients of the fourth UA quartile {Kaplan-Meier estimates of mortality, 5.1, 4.8, 5.6 and 14.0% respectively; unadjusted HR (hazard ratio), 2.81 [95% CI (confidence interval), 2.21-3.58]; P<0.001 for fourth quartile compared with first-third quartiles combined}. In the multivariable analysis, UA predicted all-cause mortality with an adjusted HR of 1.29 (95% CI, 1.12-1.48; P<0.001), for each S.D. increase in the logarithmic scale of UA level. The inclusion of UA in the multivariable model alongside known cardiovascular risk factors and other relevant variables increased the discriminatory power of the model regarding prediction of all-cause mortality [absolute and relative IDI (integrated discrimination improvement) 0.034 and 20.5% respectively; P<0.001]. In conclusion, in patients with Type 2 diabetes mellitus and confirmed CAD, elevated levels of UA predict mortality independently of known cardiovascular risk factors.