Background-Mutations in multiple genes have been implicated in familial atrial fibrillation (AF), but the underlying mechanisms, and thus implications for therapy, remain ill-defined.

Introduction Cardiac implantable electronic device (CIED) infections are potentially preventable complications associated with high morbidity, mortality, and cost. A recently developed bio-absorbable antibacterial envelope (TYRX™-A) might prevent CIED infections in high-risk subjects. However, data regarding safety and efficacy have not been published. Methods and results In a single-center retrospective cohort study, we compared the prevalence of CIED infections among subjects with ≥2 risk factors treated with the TYRX™-A envelope (N=135), the non-absorbable TYRX™ envelope (N=353), and controls who did not receive an envelope (N=636). Infection was ascertained by individual chart review. The mean (95% confidence interval) number of risk factors was 3.08 (2.84 to 3.32) for TYRX™-A, 3.20 (3.07 to 3.34) for TYRX™, and 3.09 (2.99 to 3.20) for controls, P=0.3. After a minimum 300 days follow-up, the prevalence of CIED infection was 0 (0%) for TYRX™-A, 1 (0.3%) for TYRX™, and 20 (3.1%) for controls (P=1 for TYRX™-A versus TYRX™, P=0.03 for TYRX™-A versus controls, and P=0.002 for TYRX™ versus controls). In a propensity score-matched cohort of 316 recipients of either envelope and 316 controls, the prevalence of infection was 0 (0%) and 9 (2.8%), respectively, P=0.004. When limited to 122 TYRX™-A recipients and 122 propensity-matched controls, the prevalence of CIED infections was 0 (0%) and 5 (4.1%), respectively, P=0.024. Conclusions Among high-risk subjects, the TYRX™-A bio-absorbable envelope was associated with a very low prevalence of CIED related infections that was comparable to that seen with the non-absorbable envelope.

Background Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. While its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging (ECGI) to map the cardiac electrophysiologic substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate which promotes arrhythmogenesis. Methods and Results 25 subjects (9 LQT1, 9 LQT2, 5 LQT3 and 2 LQT5) with genotype and phenotype positive LQTS underwent ECGI. Seven normal subjects provided control. Epicardial maps of activation, recovery times (RT), Activation-recovery intervals (ARI) and repolarization dispersion were constructed. Activation was normal in all patients. However, RT and ARI were prolonged relative to control, indicating delayed repolarization and abnormally long APD (312 ± 30 ms vs. 235 ± 21 ms in control). ARI prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119 ± 19 ms/cm vs. 2.0 ± 2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130 ± 27 ms/cm in 12 symptomatic patients vs. 98 ± 19 ms/cm in 13 asymptomatic patients; P < 0.05). Conclusions LQTS patients display regions with steep repolarization dispersion caused by localized APD prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECGI in risk stratification.

Abstract-Patients with autonomic failure are disabled by orthostatic hypotension, which can be worsened by the nighttime pressure natriuresis induced by associated supine hypertension. Several pharmacological agents are available that effectively reduce nighttime hypertension, but none of them prevent pressure natriuresis. Because hypertension of autonomic failure can be driven by residual sympathetic tone, we hypothesized that clonidine would be effective in reducing blood pressure (BP) and nocturnal natriuresis. Therefore, we determined the effect of placebo, 0.1 mg clonidine, and 0.1-mg/h nitroglycerin transdermal patch on supine BP, orthostatic hypotension, and pressure natriuresis in 23 patients with primary autonomic failure and supine hypertension. Medications were given at 8:00 PM, and BP was recorded every 2 hours for 12 hours. The maximal decrease in BP was seen 6 to 8 hours after drug administration and was similar to clonidine and nitroglycerin (Ϫ29Ϯ9 and Ϫ30Ϯ10 mm Hg, respectively), as was the average fall in BP throughout the night. However, only clonidine effectively reduced nocturnal natriuresis (Ϫ0.09 mmol/mg Cr; 95% CI, Ϫ0.13 to Ϫ0.04; Pϭ0.004), but this was not associated with improvement in morning orthostatic hypotension because of a residual hypotensive effect. The decrease in BP induced by clonidine was modestly but significantly correlated with the magnitude of residual sympathetic tone determined in 10 subjects by the fall in BP induced by ganglionic blockade (rϭ0.66; Pϭ0.043). These results are consistent with residual sympathetic tone contributing to supine hypertension in autonomic failure, which can be targeted with clonidine to decrease BP and nocturnal natriuresis. Key Words: drugs Ⅲ hypertension Ⅲ autonomic nervous system Ⅲ natriuresis P rimary autonomic failure is characterized by severe orthostatic hypotension defined by a fall in systolic blood pressure (BP) of Ն20 mm Hg or diastolic BP of Ն10 mm Hg 1 and accompanied by disabling symptoms of cerebral hypoperfusion. Paradoxically, patients may also experience high BP when supine. 2 Supine hypertension worsens orthostatic hypotension because it induces pressure natriuresis during the night causing volume depletion, 3 can complicate the treatment of orthostatic hypotension because it limits the use of pressor agents during the day, and increases the risk of cardiovascular events and end-organ damage. 4,5 Several vasodilators are effective in decreasing BP at night, but none of them decrease nighttime pressure natriuresis or improve orthostatic hypotension the next morning. In many autonomic failure patients, supine hypertension is driven by residual sympathetic tone acting on hypersensitive receptors and unrestrained by the impairment of baroreflex buffering. 6 Therefore, we hypothesized that clonidine, a selective ␣ 2 -adrenergic agonist that acts centrally to reduce sympathetic outflow, would be effective in reducing supine hypertension and nocturnal natriuresis, resulting in improved orthostatic hypotension the next morning. Th...