Is amiodarone still a reasonable therapeutic option for rhythm control in atrial fibrillation?

Amiodarone is the most potent antiarrhythmic drug available and is commonly prescribed to treat and prevent not only life-threatening ventricular arrhythmias but also atrial fibrillation (AF). The latest European Society of Cardiology AF guidelines state that amiodarone is recommended for long-term rhythm control in all AF patients but that other antiarrhythmic drugs should be considered first whenever possible, due to its extracardiac toxicity. In patients without significant or with only minimal structural heart disease, amiodarone is not listed as a possibility in their therapeutic scheme. Still, amiodarone is widely and liberally used, and is the most prescribed antiarrhythmic drug for patients with AF despite its high toxicity profile. Non-cardiovascular death was more frequent with amiodarone treatment than with a rate control strategy in AFFIRM, while meta-analyses suggest an association between amiodarone use in patients without structural heart disease and increased non-cardiovascular mortality. Severe or even fatal outcomes due to amiodarone may occur years after treatment initiation and are often not acknowledged by the prescribing physician, who may no longer be following the patient. The lack of widely accepted diagnostic criteria and symptom definitions may lead to underestimation of the incidence of severe side effects and of its toxicity. Unlike the underestimated risk of toxicity with amiodarone, severe complications associated with catheter ablation are usually directly ascribed to the treatment even by non-medical personnel, possibly resulting in overestimation of risks. This brief review will address the issue of amiodarone overuse and the frequent underestimation of its toxicity, while suggesting scenarios in which its use is entirely reasonable, and compare it with catheter ablation.     

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe role of change in fractional flow reserve derived from CT (FFR_CT) across coronary stenoses (ΔFFR_CT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown.ObjectivesTo investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization.MaterialsPatients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR_CT was measured 2 ?cm distal to stenosis. ΔFFR_CT was manually measured as the difference of FFR_CT across visible stenosis.ResultsOf 4730 patients (66 ?± ?10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR_CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ?< ?0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR_CT. Among the 3 models (model 1: risk factors ?+ ?stenosis type and location ?+ ?CAD-RADS; model 2: model 1 ?+ ?FFR_CT; model 3: model 2 ?+ ?ΔFFR_CT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ?< ?0.001), with the greatest incremental value for FFR_CT 0.71–0.80. ΔFFR_CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR_CT ≤0.8, a diagnostic strategy incorporating ΔFFR_CT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ?< ?0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%.ConclusionsΔFFR_CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR_CT, particularly for those with FFR_CT 0.71–0.80. ΔFFR_CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.     

顺行指掌侧固有动脉推进皮瓣修复指端组织缺损的临床疗效观察

目的探讨顺行指掌侧固有动脉推进皮瓣应用于指端组织缺损患者的疗效。方法77例指端组织缺损患者随机分为两组,对照组行指动脉逆行岛状皮瓣修复术,实验组行顺行指掌侧固有动脉推进皮瓣修复术,比较两组的疗效、术后患指功能以及并发症。结果实验组的治疗优良率和术后患指功能评分均显著高于对照组(P<0.05);两组的术后并发症发生率无统计学差异(P>0.05)。结论顺行指掌侧固有动脉推进皮瓣在指端组织缺损患者中应用效果显著,可促进术后患指功能恢复,安全性高。     

Eulerian Algorithms for Computing the Forward Finite Time Lyapunov Exponent Without Finite Difference upon the Flow Map

In this paper, effective Eulerian algorithms are introduced for the computation of the forward finite time Lyapunov exponent (FTLE) of smooth flow fields. The advantages of the proposed algorithms mainly manifest in two aspects. First, previous Eulerian approaches for computing the FTLE field are improved so that the Jacobian of the flow map can be obtained by directly solving a corresponding system of partial differential equations, rather than by implementing certain finite difference upon the flow map, which can significantly improve the accuracy of the numerical solution especially near the FTLE ridges. Second, in the proposed algorithms, all computations are done on the fly, that is, all required partial differential equations are solved forward in time, which is practically more natural. The new algorithms still maintain the optimal computational complexity as well as the second order accuracy. Numerical examples demonstrate the effectiveness of the proposed algorithms.     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

Genetically predicted childhood obesity and adult atrial fibrillation: A mendelian randomization study

Background and aimsIt is unclear whether the association of childhood obesity with adult atrial fibrillation observed in observational studies reflects causal effects. The aim of this study was to evaluate the association of childhood obesity with adult atrial fibrillation using genetic instruments.Methods and resultsWe used a two-sample Mendelian randomization (MR) design to evaluate the association between childhood obesity and adult atrial fibrillation. Two sets of genetic variants (15 single nucleotide polymorphisms [SNPs] for childhood body mass index [BMI] and 12 SNPs for dichotomous childhood obesity) were selected as instruments. Summary data on SNP-childhood obesity and SNP-atrial fibrillation associations were obtained from recently published genome-wide association studies. Effect estimates were evaluated using inverse-variance weighted (IVW) methods. Other MR analyses, including MR-Egger, simple and weighted median, weighted MBE and MR-PRESSO methods were performed in sensitivity analyses.The IVW models showed that both a genetically predicted one-standard deviation increase in childhood BMI (kg/m²) and higher log-odds of childhood obesity were associated with a substantial increase in the risk of atrial fibrillation (OR = 1.22, 95% CI: 1.11–1.34, P < 0.001; OR = 1.09, 95% CI: 1.04–1.14, P < 0.001). MR-Egger regression showed no evidence of genetic pleiotropy for childhood BMI (intercept = 0.000, 95% CI: ?0.024 to 0.023), but for childhood obesity (intercept = ?0.036, 95% CI: ?0.057 to ?0.015). Similar results were observed using leave-one-out and other MR methods in sensitivity analyses.ConclusionsThis MR analysis found a consistent association between genetically predicted childhood obesity and an increased risk of adult atrial fibrillation. Further research is warranted to validate our findings.