- Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation: The Impact of Periprocedural Therapeutic International Normalized Ratio
- Association of Maternal Weight Gain in Pregnancy With Offspring Obesity and Metabolic and Vascular Traits in Childhood
- MG53 Constitutes a Primary Determinant of Cardiac Ischemic Preconditioning
- Bleeding Complications With Dual Antiplatelet Therapy Among Patients With Stable Vascular Disease or Risk Factors for Vascular Disease: Results From the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) Trial
- The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus: Principal Results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) Study: A Randomized Trial
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Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation: The Impact of Periprocedural Therapeutic International Normalized Ratio
Periprocedural thromboembolic and hemorrhagic events are complications of percutaneous radiofrequency catheter ablation of atrial fibrillation. The management of anticoagulation before and after radiofrequency catheter ablation could play an important role in the prevention of these complications. The incidence of thromboembolic events varies from 1% to 5%, depending on the ablation and the anticoagulation strategy used in the periprocedural period. At present, although discontinuation of warfarin 3 to 5 days before ablation with and without bridging with low-weight heparin is the most frequently implemented protocol, the optimal anticoagulation management (minimizing thromboembolism while not increasing hemorrhagic complications) is not well established. We first reported radiofrequency catheter ablation of atrial fibrillation without discontinuation of warfarin. This is the first large series of patients undergoing ablation of atrial fibrillation with different anticoagulation protocols and with different ablation catheters showing that the continuation of therapeutic warfarin during the procedure (radiofrequency catheter ablation) reduces the risk of periprocedural stroke/transient ischemic attack without increasing the risk of hemorrhagic events. Of interest, this anticoagulation protocol eliminates the need for a preprocedural transesophageal echocardiogram. A randomized controlled trial is necessary to confirm the results of our study. See p 2550.
Association of Maternal Weight Gain in Pregnancy With Offspring Obesity and Metabolic and Vascular Traits in Childhood
Variation in gestational weight gain (GWG) is associated with perinatal outcomes, but whether it is importantly associated with longer-term outcomes is unclear. In a prospective cohort of 5154 (for adiposity and blood pressure) and 3457 (for blood assays) mother-offspring pairs, we examined the association of GWG and prepregnancy weight with offspring cardiovascular risk factors at age 9 years. Women who gained more than 2009 Institute of Medicine–recommended amounts of weight during gestation were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, C-reactive protein, and interleukin-6 levels and lower high-density lipoprotein cholesterol and apolipoprotein A levels. Detailed examination demonstrated that greater prepregnancy weight was also independently associated with greater offspring adiposity and adverse cardiovascular risk factors. Furthermore, women who gained weight before 14 weeks of gestation or who gained >500 g/wk from 14 to 36 weeks had offspring with greater adiposity. Greater GWG across the whole distribution between 14 and 36 weeks of gestation was associated with adverse lipid and inflammatory profiles in offspring, largely because of the association of GWG with offspring adiposity. Collectively, our findings support initiatives to maintain healthy weight in women of reproductive age and potentially to prevent excessive GWG, broadly in agreement with current Institute of Medicine recommendations. However, before guidelines on GWG are implemented, long-term follow-up of randomized controlled trials targeting GWG is needed to determine the effects of controlling GWG on a wide range of short- and long-term outcomes for both mother and infant. See p 2557.
MG53 Constitutes a Primary Determinant of Cardiac Ischemic Preconditioning
Cardiac ischemia is the current leading cause of death in the Western world. Because of the limited regenerative capacity of cardiomyocytes, ameliorating ischemia-induced myocardial damage is an important therapeutic target in the treatment of ischemic heart disease. The deleterious effects of cardiac ischemia are ameliorated by ischemic preconditioning (IPC), in which transient ischemia protects against subsequent severe ischemia/reperfusion. In the present study, we have identified MG53, a muscle-specific tripartite motif family protein (TRIM72), as a primary component of cardiac IPC response. MG53-mediated cardioprotection is, at least in part, independent of its known function in membrane repair because IPC profoundly suppresses apoptotic events, which do not involve breakdown of the sarcolemmal membrane, in an MG53-dependent manner. Because IPC is a powerful intrinsic mechanism against ischemia/reperfusion-induced myocardial damage, the identification of MG53 as a primary component of the cardiac IPC response opens a promising therapeutic avenue for the treatment of ischemic heart disease. To translate our bench discoveries from rodents into clinical medicine, many important issues need to be addressed, including determining the potential role MG53 in ischemic postconditioning, in which brief episodes of ischemia/reperfusion applied at the onset of reperfusion confer cardioprotection, in mammalian species including rodents, large animals, and humans. Relative to IPC, ischemic postconditioning is clinically more attractive because of its therapeutic application at the predictable onset of reperfusion. Because MG53 is a muscle-specific TRIM protein, an intriguing question is whether other members of the TRIM family contribute to organ protection, particularly in organs in which an IPC response can be observed. See p 2565.
Bleeding Complications With Dual Antiplatelet Therapy Among Patients With Stable Vascular Disease or Risk Factors for Vascular Disease: Results From the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) Trial
Choosing the optimal antiplatelet regimen for a patient requires a thorough understanding of not only the benefits of therapy but the risks as well. This is especially important now that several different antiplatelet agents are available. The Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial is the largest and longest study of the risks of dual antiplatelet therapy, and this analysis of CHARISMA data provides insights into the frequency of bleeding, risk factors for bleeding, and consequences of bleeding. Clinicians will find the data useful when they try to balance the risks and benefits of dual antiplatelet therapy with aspirin and clopidogrel in stable patients with vascular disease or with risk factors for vascular disease, like those enrolled in the CHARISMA trial. See p 2575.
The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus: Principal Results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) Study: A Randomized Trial
Antiplatelet agents are widely reported to be effective in preventing the recurrence of cardiovascular events. Clinical guidelines have recommended that individuals with risk factors for coronary heart disease (eg, diabetes mellitus) take aspirin for both primary and secondary prevention. Cilostazol, a phosphodiesterase III inhibitor with antiplatelet, antithrombotic, vasodilatory, and antiproliferative effects, is currently indicated for the treatment of intermittent claudication and/or ischemic signs and symptoms associated with chronic arterial occlusion around the world and secondary prevention of cerebral infarction in Asian countries. However, there was no report comparing the efficacy and usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the prevention of occurrence or progression of atherosclerosis in diabetic patients. This is the first study to directly compare the effect of cilostazol and aspirin on the progression of atherosclerosis in diabetic patients. In this international, prospective, randomized, open, blinded end point study involving a total of 329 Asian type 2 diabetic patients suspected of peripheral artery disease, we found that cilostazol treatment (100 to 200 mg/d) potently and safely inhibited the progression of carotid intima-media thickness, an established surrogate marker of cardiovascular events, compared with aspirin treatment (81 to 100 mg/d) during a 2-year observation period. Our findings suggest that cilostazol is a more effective antiatherosclerotic agent than aspirin in patients with type 2 diabetes mellitus. A large-scale prospective trial is needed to establish the usefulness of cilostazol for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus. See p 2584.
- MG53 Constitutes a Primary Determinant of Cardiac Ischemic Preconditioning
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