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Dermal fibroblasts were obtained from members of a family with the long-QT syndrome and from controls and were used to generate pluripotent stem cells, which were then directed to differentiate into cardiac myocytes. The cells recapitulated characteristics of the long-QT syndrome. The long-QT syndrome is a familial, usually autosomal dominant disease characterized by an abnormally prolonged ventricular repolarization phase and a propensity toward polymorphic ventricular tachycardia (often termed torsades de pointes) and sudden cardiac death. 1 – 3 At least 10 different forms of the long-QT syndrome have been described, but in approximately 45% of genotyped patients, the underlying causes are mutations in the KCNQ1 (also known as KVLQT1 or Kv7.1 ) gene, which encodes the pore-forming alpha subunits of the channels generating I Ks , an adrenergic-sensitive, slow outward potassium current. 2 , 4 , 5 This form of the long-QT syndrome is designated as . . .

This trial compared the combination of abciximab and unfractionated heparin with bivalirudin in patients with non–ST-segment elevation MI who were undergoing coronary stenting. The two regimens had similar efficacy, but there was more bleeding with abciximab and heparin. An invasive strategy of coronary angiography, with revascularization when appropriate, is recommended for high-risk patients who have an acute coronary syndrome. 1 , 2 Owing to the key role that the rupture of an atherosclerotic plaque, which is highly prothrombotic, plays in the pathogenesis of these syndromes, 3 identifying the most appropriate adjunctive antithrombotic therapy before, during, and after percutaneous coronary intervention (PCI) has been the target of extensive research for the past three decades. Abciximab is a glycoprotein IIb/IIIa inhibitor with potent platelet-antiaggregative effects. 4 Although the administration of abciximab during PCI was not associated with a clinical benefit in patients in stable . . .

Bivalirudin is a new direct thrombin inhibitor. In patients undergoing PCI for stable coronary disease, bivalirudin and unfractionated heparin resulted in similar overall outcomes, but there was less major bleeding with bivalirudin. Bivalirudin is a new direct thrombin inhibitor. In patients undergoing PCI for stable coronary disease, bivalirudin and unfractionated heparin resulted in similar overall outcomes, but there was less major bleeding with bivalirudin. Percutaneous coronary intervention (PCI) is commonly used to treat patients with coronary artery disease. To minimize the risk of thrombotic complications during and shortly after the procedure, many different antithrombotic regimens have been investigated and are currently in use. Increasing evidence of the adverse consequences of periprocedural bleeding suggests that protection from thrombotic complications should not be the sole measure by which antithrombotic therapies are evaluated. 1 Aspirin, clopidogrel, and heparin are established antithrombotic drugs that are widely recommended according to current guidelines on PCI. 2 Pretreatment with 300 to 600 mg of clopidogrel increasingly is used before PCI because of mounting . . .

Decreased vagal activity after myocardial infarction results in reduced heart-rate variability and increased risk of death. To distinguish between vagal and sympathetic factors that affect heart-rate variability, we used a signal-processing algorithm to separately characterise deceleration and acceleration of heart rate. We postulated that diminished deceleration-related modulation of heart rate is an important prognostic marker. Our prospective hypotheses were that deceleration capacity is a better predictor of risk than left-ventricular ejection fraction (LVEF) and standard deviation of normal-to-normal intervals (SDNN). We quantified heart rate deceleration capacity by assessing 24-h Holter recordings from a post-infarction cohort in Munich (n=1455). We blindly validated the prognostic power of deceleration capacity in post-infarction populations in London, UK (n=656), and Oulu, Finland (n=600). We tested our hypotheses by assessment of the area under the receiver-operator characteristics curve (AUC). During a median follow-up of 24 months, 70 people died in the Munich cohort and 66 in the London cohort. The Oulu cohort was followed-up for 38 months and 77 people died. In the London cohort, mean AUC of deceleration capacity was 0·80 (SD 0·03) compared with 0·67 (0·04) for LVEF and 0·69 (0·04) for SDNN. In the Oulu cohort, mean AUC of deceleration capacity was 0·74 (0·03) compared with 0·60 (0·04) for LVEF and 0·64 (0·03) for SDNN (p<0·0001 for all comparisons). Stratification by dichotomised deceleration capacity was especially powerful in patients with preserved LVEF (p<0·0001 in all cohorts). Impaired heart rate deceleration capacity is a powerful predictor of mortality after myocardial infarction and is more accurate than LVEF and the conventional measures of heart-rate variability.

Comparative assessment of clinical outcomes after use of drug-eluting stents versus bare-metal stents for treatment of aortocoronary saphenous vein graft lesions has not been undertaken in large randomised trials. We aimed to undertake a comparison in a randomised trial powered for clinical endpoints. In this randomised superiority trial, patients with de-novo saphenous vein graft lesions were assigned by computer-generated sequence (1:1:1:3) to receive either drug-eluting stents (one of three types: permanent-polymer paclitaxel-eluting stents, permanent-polymer sirolimus-eluting stents, or biodegradable-polymer sirolimus-eluting stents) or bare-metal stents. Randomisation took place immediately after crossing of the lesion with a guidewire, and was stratified for each participating centre. Investigators assessing data were masked to treatment allocation; patients were not masked to allocation. The primary endpoint was the combined incidence of death, myocardial infarction, and target lesion revascularisation at 1 year. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00611910. 610 patients were allocated to treatment groups (303 drug-eluting stent, 307 bare-metal stent). Drug-eluting stents reduced the incidence of the primary endpoint compared with bare-metal stents (44 [15%] vs 66 [22%] patients; hazard ratio [HR] 0·64, 95% CI 0·44–0·94; p=0·02). Target lesion revascularisation rate was reduced by drug-eluting stents (19 [7%] vs 37 [13%] patients; HR 0·49, 95% CI 0·28–0·86; p=0·01). No significant differences were seen between drug-eluting stents and bare-metal stents regarding all-cause mortality (15 [5%] vs 14 [5%] patients; HR 1·08, 95% CI 0·52–2·24; p=0·83), myocardial infarction (12 [4%] vs 18 [6%]; HR 0·66, 95% CI 0·32–1·37; p=0·27), or definite or probable stent thrombosis (2 [1%] in both groups; HR 1·00, 95% CI 0·14–7·10; p=0·99). In patients undergoing percutaneous coronary intervention for de-novo saphenous vein graft lesions, drug-eluting stents are the preferred treatment option because they reduce the risk of adverse events compared with bare-metal stents. Deutsches Herzzentrum.

High-sensitivity cardiac troponin assays enable the measurement of cardiac troponin concentrations in the majority of patients with coronary artery disease. The objective of this study was to investigate the prognostic value of sensitive cardiac troponin in patients with stable and unstable angina presenting with undetectable levels of conventional troponin. This study included 1,057 patients with stable (808 patients) or unstable (249 patients) angina who presented with undetectable conventional cardiac troponin T and underwent coronary artery revascularization. The cardiac troponin T was measured with conventional and high-sensitivity assays, in parallel, using the same plasma sample. The primary end point was 4-year mortality. The total sensitive troponin T level (median [interquartile range]) was 0.008 (0.005-0.014) μg/L. Variables independently associated with an elevated level of sensitive troponin T were elderly age, male sex, higher body mass index, presence of diabetes, unstable angina, increased New York Heart Association class, reduced left ventricular ejection fraction, elevated level of N-terminal pro-brain natriuretic peptide, reduced glomerular filtration rate, and elevated level of C-reactive protein. During the follow-up period, there were 83 deaths. The sensitive troponin T level was an independent predictor of 4-year mortality (adjusted hazard ratio = 1.47 with 95% CI 1.17-1.84, P < .001 for each unit increase in the natural logarithm of the sensitive troponin T). The elevated levels of sensitive cardiac troponin T in patients with stable or unstable angina presenting with undetectable conventional cardiac troponin T are significantly associated with reduced survival.

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.

Diabetes mellitus is associated with an increased risk of restenosis, stent thrombosis, and death after percutaneous coronary interventions. Little is known about the late outcome of patients with diabetes mellitus who receive drug-eluting stents (DES). This study includes a prospective database of 2557 consecutive patients with coronary artery disease who underwent DES implantation in native coronary arteries in 2 German hospitals. The primary end points of the study were mortality and clinical restenosis (target lesion revascularization). Secondary end points were binary angiographic restenosis, stent thrombosis, and the composite of death or myocardial infarction. Within a median follow-up period of 2.3 years, stent thrombosis occurred in 14 patients with diabetes versus 17 patients without diabetes: 3-year Kaplan-Meier estimates of stent thrombosis were 2.2% versus 1.0%, with a relative risk of 2.17 (95% CI 1.09-4.33, P = .027). Binary angiographic restenosis was observed in 87 patients with diabetes and 208 patients without diabetes (15.2% vs 13.5%, P = .32). Target lesion revascularization was needed in 93 patients with diabetes and 219 patients without diabetes (12.8% vs 12.0%, P = .56). There were 93 deaths among diabetic patients versus 118 deaths among nondiabetic patients: 3-year Kaplan-Meier estimates of mortality were 17.3% versus 7.8%, with a relative risk of 2.10 (95% CI 1.61-2.74, P < .001). After adjustment in the multivariable analyses, diabetes remained an independent predictor of 3-year mortality with a hazard ratio of 1.63 (95% CI 1.23-2.17, P < .001), but not of angiographic ( P = .92) or clinical restenosis ( P = .97). Although DES attenuate diabetes-associated excess risk of restenosis, risk of death and thrombotic complications remains higher in patients with diabetes than in nondiabetic patients in the DES era.

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.

Intracoronary stenting is an accepted treatment for vessel closure after percutaneous transluminal coronary angioplasty (PTCA). 1 – 3 Moreover, as compared with balloon angioplasty, elective stent placement reduces the rate of restenosis. 4 , 5 However, thrombotic occlusion of the stent, as well as hemorrhagic and peripheral vascular complications due to the intensive anticoagulation recommended for the first few weeks after the procedure, seriously limits the benefits of intracoronary stenting. 6 , 7 Recent studies with intravascular ultrasonography or coated stents suggest that anticoagulant therapy may be dispensable. 8 , 9 We recently identified a high level of surface expression of the inducible fibrinogen receptor on platelets as . . .