Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

Rapid Ventricular Pacing Facilitates Transarterial Embolization in Vein of Galen Malformations.

Background: Mural type vein of Galen malformation (mVOGM) is a congenital high flow arteriovenous shunt between choroidal arteries and the prosencephalic vein of Markowski leading to heart failure and hydrovenous disorder in children. Embolizing fistulous connections can be challenging and typically requires adjunctive techniques such as induced hypotension, balloon-assisted flow control, and creation of a coil basket. These maneuvers add time, complexity, and unpredictability. Rapid ventricular pacing (RVP) has been proposed as an alternative strategy with fewer drawbacks, but has not been well studied. The approach involves catheterizing the right ventricle with a pacing catheter connected to a temporary external pacemaker. Prior to embolization, RVP is initiated to lower cardiac output. Following embolization, pacing is discontinued, and the heart returns to sinus rhythm. Methods: We performed RVP in five mVOGM patients from 4/2020 through 7/2021. Accounting for multiple procedures, RVP was utilized in ten cases and twenty-six pedicles. Results: Ventricular capture was achieved in all instances and was well tolerated, without arrhythmia. Casting the arterial pedicle with liquid embolic immediately adjacent to, or traversing, the fistulous point was achieved in 9/10 cases. There were no procedural complications. In 1 case, creation of a coil basket in the venous pouch was required to achieve a stable arterial cast Conclusions: This report describes the largest case series utilizing RVP in mVOGM. The technique appears safe and well tolerated.

Capacity of management plans for aquatic invasive species to integrate climate change.

The consequences of climate change will affect aquatic ecosystems, including aquatic invasive species (AIS) that are already affecting these ecosystems. Effects on AIS include range shifts and more frequent overwintering of species. These effects may create new challenges for AIS management. We examined available U.S. state AIS management plans to assess each program's capacity to adapt to climate-change effects. We scored the adaptive capacity of AIS management plans on the basis of whether they addressed potential impacts resulting from climate change; demonstrated a capacity to adapt to changing conditions; provided for monitoring strategies; provided for plan revisions; and described funding for implementation. Most plans did not mention climate change specifically, but some did acknowledge climatic boundaries of species and ecosystem sensitivities to changing conditions. Just under half the plans mentioned changing environmental conditions as a factor, most frequently as part of research activities. Activities associated with monitoring showed the highest capacity to include information on changing conditions, and future revisions to management plans are likely to be the easiest avenue through which to address climate-change effects on AIS management activities. Our results show that programs have the capacity to incorporate information about climate-change effects and that the adaptive-management framework may be an appropriate approach.

Mass spectrometry assisted assignment of NMR resonances in reductively 13C-methylated proteins.

Reductive 13C-methylation of proteins has been used as an isotope labeling strategy to study protein structure, function, and dynamics by nuclear magnetic resonance (NMR) spectroscopy. However, assigning the resulting 13C-dimethylamine peaks in a 1H-13C NMR spectrum has proved to be difficult, but it is important to expand the scope of the method. The assignment strategy presented here utilizes mass spectrometry (MS) for sequence identification and varying 13C/12C isotope ratios to correlate with NMR data. The site-specific reactivity of the lysines and N-terminal amine of a protein is exploited to produce a sample with varying 13C/12C ratios at each dimethylamine. MS and NMR are used to quantitate and correlate these ratios in order to assign peaks in the 1H-13C NMR spectrum. Hen egg white lysozyme was used as a model protein to demonstrate this assignment strategy.