Sinus Node Dysfunction and Atrial Fibrillation: A Reversible Phenomenon?

BACKGROUND: Symptomatic sinus node dysfunction (SND) consists of a variety of manifestations, including tachycardia-bradycardia syndrome. Atrial fibrillation (AF) is commonly associated with SND, which complicates the management of both conditions. This paper reviews the epidemiology, pathophysiology, and clinical trial data investigating therapeutic approaches for treatment of patients with both SND and AF. METHODS: The authors reviewed articles published in English describing the epidemiology, pathophysiology, and therapeutic approaches for patients with SND and AF. The search was conducted using PubMed. Keywords included: sick sinus syndrome, sinus node dysfunction, atrial fibrillation, pacing, and pulmonary vein isolation. RESULTS: SND affects up to one in five patients with AF. AF can lead to anatomical and electrophysiological remodeling in both atria, including the region of sinoatrial node. Changes including atrial fibrosis, altered calcium channel metabolism, and transformed gene expression have been demonstrated in patients with AF and SND. Nonrandomized clinical trial data have failed to demonstrate whether any pacing strategy can reduce the risk of AF. Pulmonary vein isolation appears to decrease episodes of tachybrady syndrome and sinus pauses. CONCLUSIONS: SND affects up to one in five patients with AF. The pathophysiological derangements in gene expression, ion channel metabolism, and alterations in myocardial architecture associated with AF may lead to anatomic and electrical changes in the region of the sinoatrial node. Ablation may improve symptoms associated with SND in patients with AF. Future randomized trials are needed to clarify the epidemiology and optimal management of patients with SND and AF.

Marked gender differences in progression of mild cognitive impairment over 8 years.

INTRODUCTION: This study examined whether, among subjects with mild cognitive impairment (MCI), women progressed at faster rates than men. METHODS: We examine longitudinal rates of change from baseline in 398 MCI subjects (141 Females, 257 Males) in the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1), followed for up to 8 years (mean 4.1±2.5 years) using mixed effects models incorporating all follow ups (mean 8±4 visits). RESULTS: Women progressed at faster rates than men on ADAS-Cog (p=0.001) and CDR-SB (p=0.003). Quadratic fit for change over time was significant for both ADAS-Cog (p=0.001) and CDR-SB (p=0.004), and the additional acceleration in women was 100% for ADAS-Cog and 143% for CDR-SB. The variability of change was greater in women. The gender effect was greater in ApoE4 carriers. DISCUSSION: Women with MCI have greater longitudinal rates of cognitive and functional progression than men. Studies to confirm and uncover potential mechanisms appear to be warranted.

Brain atrophy rates in first degree relatives at risk for Alzheimer's.

A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p < 0.01), entorhinal cortex (p < 0.01), hippocampus (p < 0.053) and cortical gray matter (p < 0.009). However, when E4 genotype was added as a covariate, none of the FH effects remained significant. Analyses by ApoE genotype showed that the effect of FH on amygdala atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH- subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.