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A study was conducted to evaluate the capacity of patient-specific induced pluripotent stem-cell models from a family affected by long-QT syndrome to give rise to functional cardiomyocytes that recapitulate the electrophysiological characteristics of the disorder. Results indicated that in such cases the patient-derived cells recapitulated the electrophysiological characteristics of the disorder.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2010.06.039 Byline: Klaus A. Tiroch, Dirk Sibbing, Werner Koch, Tobias Roosen-Runge, Julinda Mehilli, Albert Schomig, Adnan Kastrati Abstract: The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. The genes encoding enzymes for clopidogrel activation are polymorphic, leading to reduced or increased function, depending on the respective genotype. Reduced-function alleles have been associated with an increase in cardiovascular events. Article History: Received 9 January 2010; Accepted 24 June 2010

Results of a study to evaluate and compare the efficacy of ticagrelor as against clopidogrel in the treatment of acute coronary syndrome have revealed that ticagrelor was more effective and beneficial. However, certain adverse effects of ticagrelor do occur, which are highlighted.

The study aims to evaluate the correct radiation dose of cardiac computed tomography (CT) angiography (CCTA) in normal, routine clinical practice and to identify the factors contributing to radiation dose. The results indicate a vast difference in CT doses between different studies and confirm the presence of effective strategies to reduce radiation, though not often used.

The study examines if bivalirudin is superior to unfractionated heparin in patients with stable or unstable angina who undergo percutaneous coronary intervention (PCI) after pretreatment with clopidogrel. Bivalirudin did not provide net clinical benefit in comparison with unfractionated heparin, but it did markedly reduce the incidence of major bleeding.

The long-term outcome of treatment with sirolimus-eluting stents, as compared with bare-metal stents is evaluated by analyzing the data obtained from randomized trials. The results have shown that the use of sirolimus-eluting stents have no significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents, but the risk of stent thrombosis is at least as great as that observed with bare-metal stents.

A test was conducted to assess whether abciximab is associated with clinical benefit in high risk patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600mg of clopidogrel. Results reveal that abciximab reduces the risk of adverse events in patients with non-ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel.

A study is designed to show noninferiority of the paclitaxel stent as compared with the sirolimus stent, defined as a difference in the extent of in-segment late luminal loss of no more than 0.16 mm. The results reveal that in patients with diabetes mellitus and coronary artery disease, use of the sirolimus-eluting stent is associated with a decrease in the extent of late luminal loss, as compared with use of the paclitaxel-eluting stent, suggesting a reduced risk of restenosis.

An attempt is made to compare outcomes of sirolimus-eluting and paclitaxel-eluting coronary stents on the basis of data generated by randomized head-to-head clinical trials. It is concluded that patients receiving sirolimus-eluting stents had a significantly lower risk of restenosis and target vessel revascularization compared with those receiving paclitaxel-eluting stents.

A study aims to assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute St-segment elevation myocardial infarction (STEMI), presenting between 12 and 48 hours after symptom onset, vs. a conventional conservative strategy. An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.

An attempt is made to assess whether drug-eluting stents are more effective treatment of in-stent restenosis as compared to conventional balloon angioplasty and to examine the relative merits of a sirolimus-eluting stent and a paclitaxel-eluting stent. The findings indicate that a strategy based on sirolimus or paclitaxel-eluting stents is superior to conventional balloon angioplasty for the prevention of recurrent restenosis.

The optimal pharmacological strategy for bridging the delay between admission and performance of percutaneous coronary intervention (PCI) in patients with acute myocardial infraction (MI) is not known. Various studies show that early administration of reteplase plus abciximab does not lead to a reduction of infarct size compared with abciximab alone in patients with acute MI referred for PCI.

The drug abciximab does not appear to benefit patients who have angioplasty to treat coronary artery disease, according to a study of 2,159 patients. Angioplasty is a procedure that opens blocked arteries. In this study, those who took abciximab had the same outcome as those who took a placebo, or inactive substance.

Giving patients with unstable angina or a heart attack anticoagulant drugs three to five days before angioplasty may not reduce their risk of complications from the procedure, according to a study of 410 patients. Unstable angina and heart attacks are both caused by blood clots that prevent blood flow to the heart. Angioplasty is a procedure used to break up blood clots and other obstructions in the coronary arteries.

Programmed cell death involves the activation of caspase proteases that can mediate the cleavage of vital cytoskeletal proteins. We have recently reported that, in failing cardiac myocytes, caspase-3 activation is associated with a reduction in contractile performance. In this study we used a modified yeast two-hybrid system to screen for caspase-3 interacting proteins of the cardiac cytoskeleton. We identified ventricular essential myosin light chain (vMLC1) as a target for caspase-3. By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFV[E.sup.135]G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance. Adenoviral gene transfer of the caspase inhibitor p35 in vivo prevented caspase-3 activation and vMLC1 cleavage, with positive impact on contractility. These data suggest that direct cleavage of vMLC1 by activated caspase-3 may contribute to depression of myocyte function by altering cross-bridge interaction between myosin and actin molecules. Therefore, activation of apoptotic pathways in the heart may lead to contractile dysfunction before cell death.

Women who have had a heart attack can have a similar outcome as men provided they are treated as aggressively as men are. This treatment should include angioplasty if necessary, to open up blocked coronary arteries. In a study of 1,937 patients, women had the same death rate as men even though they were older on average and more likely to have diabetes or hypertension., Context: A higher mortality risk for women with acute myocardial infarction (AMI) is a common finding in studies that compare the postinfarction outcome of women vs men. It is not clear, however, whether sex is an independent predictor of death among patients systematically treated with aggressive reperfusion and medical strategies. Objective: To assess the impact of patient's sex on outcome in a consecutive series of patients with AMI treated with a reperfusion strategy largely based on percutaneous coronary interventions. Design, Setting, and Patients: Inception cohort of 1937 patients (502 women and 1435 men) who were admitted with a diagnosis of AMI to a tertiary referral institution between January 1995 and December 2000. Main Outcome Measures: Mortality at 1 year after AMI. Results: Compared with men, women were older (70 vs 61 years; P Conclusion: Despite their more advanced age and greater prevalence of diabetes or hypertension, women with AMI who were treated with a reperfusion strategy largely based on percutaneous coronary interventions show a similar outcome as men.

A coronary stent plus the drug abciximab appears to be more effective for heart attack patients than tissue plasminogen activator (tPA), according to a study of 140 patients. A stent is a small cylinder that keeps an artery open, abciximab is an anticoagulant, and tPA breaks up the blood clots that cause most heart attacks.

Byline: Eckhard Alt, Richard Ammer, Gunter Lehmann, Katja Putter, Gregory M. Ayers, Jay Pasquantonio, Albert Schomig Abstract: The aim of this study was to identify predictors for recurrent atrial fibrillation after internal and external cardioversion in 157 patients. After cardioversion, patients were treated orally with sotalol (174 [+ or -] 54 mg/day). Univariate predictors for recurrence included coronary artery disease (p < 0.05) and advanced age (p < 0.05). Multivariate adjusted risk for relapse increased with the presence of coronary artery disease (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.6 to 8.0), presence of atrial fibrillation >2 months before cardioversion (OR 2.3; 95% CI 1.4 to 4.5), left atrial diameter >60 mm (OR 2.1; 95% CI 1.2 to 3.1), and age >65 years (OR 1.6; 95% CI 1.3 to 3.3). In 26% of patients with lone atrial fibrillation, recurrence was observed compared with 51% of patients with underlying structural heart disease (p < 0.05). The mode of conversion, internal or external, had no impact on the recurrence rate. These findings might be useful for selection of the most appropriate therapy for the individual patient. (Am Heart J 1997;134:419-25). Author Affiliation: Munich, Germany, and Redmond, Wash From the Medizinische Klinik, Klinikum rechts der Isar der Technischen, Universitat Munchen and InControl, Inc Article History: Received 21 August 1996; Accepted 24 April 1997 Article Note: (footnote) [star] Reprint requests: Eckhard Alt, MD, 1. Medizinische Klinik, Klinikum rechts der Isar, Ismaninger Str. 22, D-81675 Munchen, Germany. E-mail:alt@medl.med.tu-muenchen.de, [star][star] 0002-8703/97/$5.00 + 0 4/1/83034

Antiplatelet therapy may be more effective than standard anticoagulant therapy in preventing complications after the stent placement following coronary angioplasty. Antiplatelet therapy blocks the formation of platelets, which activate the clotting procedure. Researchers compared the number of complications after stent placement in 257 patients receiving antiplatelet therapy and 260 patients receiving traditional anticoagulant therapy. The antiplatelet combination to ticlopidine and aspirin was superior to the anticoagulant combination of intravenous heparin, phenprocoumon, and aspirin. Anti-platelet patients had a much lower risk of heart attack and less need for repeated procedures. Stent occlusion occurred in 0.8% of the antiplatelet patients compared to 5.4% in the patients receiving anticoagulants. A small number of patients in the anticoagulant group, but none of the antiplatelet patients, had bleeding episodes.