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The electrocardiographic (ECG) manifestation of ventricular repolarization includes J (Osborn), T, and U waves. On the basis of biophysical principles of ECG recording, any wave on the body surface ECG represents a coincident voltage gradient generated by cellular electrical activity within the heart. The J wave is a deflection with a dome that appears on the ECG after the QRS complex. A transmural voltage gradient during initial ventricular repolarization, which results from the presence of a prominent action potential notch mediated by the transient outward potassium current (I to ) in epicardium but not endocardium, is responsible for the registration of the J wave on the ECG. Clinical entities that are associated with J waves (the J-wave syndrome) include the early repolarization syndrome, the Brugada syndrome and idiopathic ventricular fibrillation related to a prominent J wave in the inferior leads. The T wave marks the final phase of ventricular repolarization and is a symbol of transmural dispersion of repolarization (TDR) in the ventricles. An excessively prolonged QT interval with enhanced TDR predisposes people to develop torsade de pointes. The malignant "Ron-T" phenomenon, i.e., an extrasystole that originates on the preceding T wave, is due to transmural propagation of phase 2 reentry or phase 2 early afterdepolarization. A pathological "U" wave as seen with hypokalemia is the consequence of electrical interaction among ventricular myocardial layers at action potential phase 3 of which repolarization slows. A physiological U wave is thought to be due to delayed repolarization of the Purkinje system. A.N.E. 2005;10(2):211-223electrocardiography; J wave; T wave; U wave

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Background and objectivesDaprodustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) being investigated for the treatment of anemia of CKD. In this noninferiority trial, we compared daprodustat administered three times weekly with epoetin alfa (epoetin) in patients on prevalent hemodialysis switching from a prior erythropoiesis-stimulating agent (ESA).Design, setting, participants, & measurementsPatients on hemodialysis with a baseline hemoglobin of 8–11.5 g/dl receiving an ESA were randomized 2:1 to daprodustat three times weekly (n=270) or conventional epoetin (n=137) for 52 weeks. Dosing algorithms aimed to maintain hemoglobin between 10 and 11 g/dl. The primary end point was mean change in hemoglobin from baseline to the average during the evaluation period (weeks 28–52). The principal secondary end point was average monthly intravenous iron dose. Other secondary end points included BP and hemoglobin variability.ResultsDaprodustat three times weekly was noninferior to epoetin for mean change in hemoglobin (model-adjusted mean treatment difference [daprodustat-epoetin], −0.05; 95% confidence interval, −0.21 to 0.10). During the evaluation period, mean (SD) hemoglobin values were 10.45 (0.55) and 10.51 (0.85) g/dl for daprodustat and epoetin groups, respectively. Responders (defined as mean hemoglobin during the evaluation period in the analysis range of 10 to 11.5 g/dl) were 80% in the daprodustat group versus 64% in the epoetin group. Proportionately fewer participants in the daprodustat group versus the epoetin group had hemoglobin values either below 10 g/dl or above 11.5 g/dl during the evaluation period. Mean monthly intravenous iron use was not significantly lower with daprodustat versus epoetin. The effect on BP was similar between groups. The percentage of treatment-emergent adverse events was similar between daprodustat (75%) and epoetin (79%).ConclusionsDaprodustat was noninferior to epoetin in hemoglobin response and was generally well tolerated.Clinical Trial registry name and registration number:Anemia Studies in Chronic Kidney Disease: Erythropoiesis via a Novel Prolyl Hydroxylase Inhibitor Daprodustat–Three Times Weekly Dosing in Dialysis (ASCEND-TD), NCT03400033

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Plasma migalastat clearance decreased as degree of renal impairment increased. Data from the migalastat HCl clinical program will guide dosing and intervals for patients with Fabry disease with renal impairment.

Management of Atrial Fibrillation. There are three fundamental approaches to the management of atrial fibrillation (AF): rate control, rhythm control, and anticoagulation. Selecting a course of treatment requires a thorough knowledge of these therapeutic alternatives. This article explores treatment options, including the relative benefits of rate control versus rhythm control, which are complicated by the lack of highly effective and safe antiarrhythmic drugs. Anticoagulation is also an important issue in AF management, and warfarin effectively reduces the incidence of thromboembolic events in AF patients. The use of warfarin, however, presents its own complications. We conclude that individualization of therapy is paramount when treating AF.