Background-Genetic studies have identified ion channel gene variants in families segregating atrial fibrillation (AF), the most common arrhythmia in clinical practice. Here, we tested the hypothesis that vulnerability to AF is associated with variation in SCN5A, the gene encoding the cardiac sodium channel. Methods and Results-We resequenced the entire SCN5A coding region in 375 subjects with either lone AF (nϭ118) or AF associated with heart disease (nϭ257). Controls (nϭ360) from the same population were then genotyped for the presence of mutations or rare variants identified in the AF cases. In 10 probands (2.7%), 8 novel variants not found in the control population (0%; Pϭ0.001) were identified. All variants affect highly conserved residues in the SCN5A protein. In 6 families with Ͼ1 affected member, the novel variant cosegregated with AF. We also identified 11 rare missense variants in 12 probands (3.2%) that have previously been associated with inherited arrhythmia syndromes (eg, congenital long-QT syndrome and Brugada syndrome). Conclusions-Mutations or rare variants in SCN5A may predispose patients with or without underlying heart disease to AF. The findings of the present study expand the clinical spectrum of disorders of the cardiac sodium channel to include AF and represent important progress toward molecular phenotyping and directed rather than empirical therapy for this common arrhythmia.

Background-We and others have reported mutations in the cardiac predominant sodium channel gene SCN5A in patients with atrial fibrillation (AF). We also have reported that SCN1B is associated with Brugada syndrome and isolated cardiac conduction disease. We tested the hypothesis that mutations in the 4 sodium channel ␤-subunit genes SCN1B-SCN4B contribute to AF susceptibility. Methods and Results-Screening for mutations in the 4 ␤-subunit genes was performed in 480 patients with AF (118 patients with lone AF and 362 patients with AF and cardiovascular disease) and 548 control subjects (188 ethnically defined anonymized subjects and 360 subjects without AF). The effects of mutant ␤-subunits on SCN5A mediated currents were studied using electrophysiological studies. We identified 2 nonsynonymous variants in SCN1B (resulting in R85H, D153N) and 2 in SCN2B (R28Q, R28W) in patients with AF. These occur at residues highly conserved across mammals and were absent in control subjects. In 3 of 4 mutation carriers, the ECGs showed saddleback-type ST-segment elevation in the right precordial leads. Transcripts encoding both SCN1B and SCN2B were detected in human atrium and ventricle. In heterologous expression studies using Chinese hamster ovary cells, the mutant ␤1-or ␤2-subunits reduced SCN5A-mediated current and altered channel gating compared with coexpression of wild-type subunits. Conclusions-Loss of function mutations in sodium channel ␤-subunits were identified in patients with AF and were associated with a distinctive ECG phenotype. These findings further support the hypothesis that decreased sodium current enhances AF susceptibility. (Circ Arrhythmia Electrophysiol. 2009;2:268-275.)

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In this study of bioabsorbable screw fixation of free tendon grafts used in anterior cruciate ligament reconstruction, we performed load-to-failure and cyclic loading of tendon fixation in porcine bone. Bone density measurements from dual photon absorptometry scans were obtained to correlate bone density with fixation failure. The average density of porcine bone (1.42 g/cm2) was similar to that of young human bone (1.30 g/cm2) and significantly higher than that of elderly human cadaveric bone specimens (0.30 g/cm2). Cyclic loading was performed on free tendon grafts fixed with a bioabsorbable screw alone and on grafts fixed with a bioabsorbable screw and an anchor (polylactic acid ball or cortical bone disk). Stiffness of fixation increased substantially with the addition of a cortical bone disk anchor or polylactic acid ball compared with the interference screw alone. Tensile fixation strength of central quadriceps free tendon and hamstring tendon grafts were significantly superior in porcine bone of density similar to young human bone than in elderly human cadaveric bone. The bioabsorbable interference screw yielded loads at failure comparable with traditional bone-tendon-bone and hamstring tendon fixation when controlled for bone density. The addition of a cortical bone disk anchor provided the most optimal fixation of free tendon with the bioabsorbable screw and reduced slippage with cyclic loading to a very low level.

In this setting, a standardized handover tool is associated with a decrease in the loss of patient information, an improvement in the quality of communication during postoperative transfer, a decrease in postoperative complications, and an improvement in 24-hr patient outcomes.