BACKGROUND In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucoseindependent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes. METHODS In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death. RESULTS Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups. CONCLUSIONS Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials .gov number, NCT03036124.

Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

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This study demonstrates the diverse mechanisms and electropharmacological characteristics of AT in adults. Furthermore, radiofrequency ablation of various types of AT could achieve high success and low recurrence rates.

Atrial fibrillation (AF) is the most common sustained arrhythmia, causing a 2-fold increase in mortality and a 5-fold increase in stroke. The Asian population is rapidly aging, and in 2050, the estimated population with AF will reach 72 million, of whom 2.9 million may suffer from AF-associated stroke. Therefore, stroke prevention in AF is an urgent issue in Asia. Many innovative advances in the management of AF-associated stroke have emerged recently, including new scoring systems for predicting stroke and bleeding risks, the development of non-vitamin K antagonist oral anticoagulants (NOACs), knowledge of their special benefits in Asians, and new techniques. The Asia Pacific Heart Rhythm Society (APHRS) aimed to update the available information, and appointed the Practice Guideline sub-committee to write a consensus statement regarding stroke prevention in AF. The Practice Guidelines sub-committee members comprehensively reviewed updated information on stroke prevention in AF, emphasizing data on NOACs from the Asia Pacific region, and summarized them in this 2017 Consensus of the Asia Pacific Heart Rhythm Society on Stroke Prevention in AF. This consensus includes details of the updated recommendations, along with their background and rationale, focusing on data from the Asia Pacific region. We hope this consensus can be a practical tool for cardiologists, neurologists, geriatricians, and general practitioners in this region. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician׳s decision remains the most important factor in the management of AF.

It is becoming clear that mutations in the KVLQT1, human "ether-a-go-go" related gene, cardiac voltage-dependent sodium channel gene, minK and MiRP1 genes, respectively, are responsible for the LQT1, LQT2, LQT3, LQT5 and LQT6 variants of the Romano-Ward syndrome, characterized by autosomal dominant transmission and no deafness. The much rarer Jervell-Lange-Nielsen syndrome (with marked QT prolongation and sensorineural deafness) arises when a child inherits mutant KVLQT1 or minK alleles from both parents. In addition, some families are not linked to the known genetic loci. Cardiac voltage-dependent sodium channel gene encodes the cardiac sodium channel, and long QT syndrome (LQTS) mutations prolong action potentials by increasing inward plateau sodium current. The other mutations cause a decrease in net repolarizing current by reducing potassium currents through "dominant negative" or "loss of function" mechanisms. Polymorphic ventricular tachycardia (torsade de pointes) is thought to be initiated by early after-depolarizations in the Purkinje system and maintained by reentry in the myocardium. Clinical presentations vary with the specific gene affected and the specific mutation. Nevertheless, patients with identical mutations can also present differently, and some patients with LQTS mutations may have no manifest baseline phenotype. The question of whether the latter situation is one of high risk for administration of QT prolonging drugs or during myocardial ischemia is under active investigation. More generally, the identification of LQTS genes has provided tremendous new insights for our understanding of normal cardiac electrophysiology and its perturbation in a wide range of conditions associated with sudden death. It seems likely that the approach of applying information from the genetics of uncommon congenital syndromes to the study of common acquired diseases will be an increasingly important one in the next millennium.

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Non-vitamin K antagonist oral anticoagulants (NOACs) have changed the landscape for stroke prevention in atrial fibrillation (AF). Given the huge burden of AF in Asians, more attention to stroke prevention is clearly needed. Aiming to provide an overview and reappraisal of stroke prevention in Asians with AF, we searched MEDLINE for information on NOACs in Asians. In addition, abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. In the 4 recent Phase 3 trials comparing NOACs to warfarin, a consistent pattern is evident. For efficacy endpoints in the comparison of NOACs vs warfarin, a significant reduction in stroke/systemic embolization was seen for dabigatran 150mg [HR 0.45 (0.28-0.72)], with non-significant trends seen for lower stroke/systemic embolization with other NOACs, except edoxaban 30mg. A similar pattern was seen for ischaemic stroke, with a significant reduction for dabigatran 150mg [HR 0.55 (0.32-0.950]. For haemorrhagic stroke, all NOAC regimes, except rivaroxaban 20mg, had significantly lower hazard ratios. No evidence of increased myocardial infarction was found for NOACs. All-cause mortality was significantly lowered amongst Asian patients on edoxaban 60mg compared to warfarin [HR 0.63 (0.40-0.98)] with non-significant trends to lower mortality with dabigatran 150mg, rivaroxaban and edoxaban 30mg. For safety endpoints, all the NOAC regimes, except rivaroxaban 20mg, significantly reduced major bleeding and 'all bleeding' events. Intracranial haemorrhage was consistently lowered by all NOACs. None of NOACs increased gastrointestinal bleeding. These information suggested that NOACs should be preferentially indicated for stroke prevention in Asians with AF.