We carried out a genome-wide association study (GWAS) of congenital heart disease (CHD). Our discovery cohort comprised 1,995 CHD cases and 5,159 controls, and included patients from each of the three major clinical CHD categories (septal, obstructive and cyanotic defects). When all CHD phenotypes were considered together, no regions achieved genome-wide significant association. However, a region on chromosome 4p16, adjacent to the MSX1 and STX18 genes, was associated (P=9.5×10−7) with the risk of ostium secundum atrial septal defect (ASD) in the discovery cohort (N=340 cases), and this was replicated in a further 417 ASD cases and 2520 controls (replication P=5.0×10−5; OR in replication cohort 1.40 [95% CI 1.19-1.65]; combined P=2.6×10−10). Genotype accounted for ~9% of the population attributable risk of ASD.

This novel catheter gives reproducible recordings of local impedance, which are dependent on scar level. Absolute LI drop, and also percentage drop, on ablation may give an indication of tissue contact and subsequent effective lesion formation.

Objective: To investigate the detailed anatomy of the terminal crest (crista terminalis) and its junctional regions with the pectinate muscles and intercaval area to provide the yardstick for structural normality. Design: 97 human necropsy hearts were studied from patients who were not known to have medical histories of atrial arrhythmias. The dimensions of the terminal crest were measured in width and thickness from epicardium to endocardium, at the four points known to be chosen as sites of ablation. Results: The pectinate muscles originating from the crest and extending along the wall of the appendage towards the vestibule of the tricuspid valve had a non-uniform trabecular pattern in 80% of hearts. Fine structure of the terminal crest studied using light and scanning electron microscopy consisted of much thicker and more numerous fibrous sheaths of endomysium with increasing age of the patient. 36 specimens of 45 (80%) specimens studied by electron microscopy had a predominantly uniform longitudinal arrangement of myocardial fibres within the terminal crest. In contrast, in all specimens, the junctional areas of the terminal crest with the pectinate muscles and with the intercaval area had crossing and non-uniform architecture of myofibres. Conclusions: The normal anatomy of the muscle fibres and connective tissue in the junctional area of the terminal crest/pectinate muscles and terminal crest/intercaval bundle favours non-uniform anisotropic properties.T he terminal crest is a significant structure in several forms of atrial tachyarrhyhmias and, occasionally, it is the target for radiofrequency catheter procedures. In common atrial flutter, the terminal crest acts as a natural barrier to conduction.1 Such block in conduction across the crest in patients with common atrial flutter 2 seems to be determined functionally rather than anatomically, since transverse conduction is known to be preserved in some patients. Studies using intracardiac echocardiography have shown that two thirds of focal right atrial tachycardias seen in the absence of structural heart disease arise along the terminal crest. Ablation targeting the crest has also been used in patients with inappropriate sinus tachycardia. 4 Despite its relevance to clinical and experimental studies, the architecture of the terminal crest in the human heart has not been studied in detail. Using an extensive collection of human hearts, we have determined the width and thickness of the terminal crest at four points and charted the variations in the trabecular arrangement of the pectinate muscles that originate from the terminal crest. In addition, in selected cases, we analysed the fine structure of the crest at these four points, elucidating the changes in the orientation of the bundles of fibres and the arrangement of the connective tissue. The latter structural features may explain why the crest can function as a functional barrier in patients with isthmic atrial flutter. METHODSWe examined 97 randomly selected hearts from patients with unknown medical h...

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