In patients with advanced heart failure and LBBB, baseline SPWMD is a strong predictor of the occurrence of reverse remodeling after CRT, thus suggesting its usefulness in identifying patients likely to benefit from biventricular pacing.

Background-Depressed baroreflex sensitivity obtained by means of a phenylephrine test plays a prognostic role in patients with a previous myocardial infarction. Our purpose was to evaluate the correlation and agreement between the baroreflex sensitivity obtained with phenylephrine and that obtained by two noninvasive methods: the ␣-index and sequence analysis. Methods and Results-The ␣-index was measured by means of the spectral analysis of RR and systolic blood pressure variabilities in both the high-and low-frequency bands; sequences were identified from simultaneously recorded time series in which the RR and systolic blood pressure concurrently increased or decreased. Noninvasive baroreflex sensitivity tests were performed during both spontaneous and controlled respiration. Fifty-two consecutive patients with recent myocardial infarction underwent the analyses. Although the correlations between phenylephrine and either of the noninvasive methods were always significant, those found during controlled respiration had the highest r values (rϭ.70). However, the limits of agreement calculated by means of the Bland and Altman method were wide for both noninvasive methods. Conclusions-The

Background-Brugada syndrome is associated with a high risk of sudden cardiac death and is caused by mutations in the cardiac voltage-gated sodium channel gene. Previously, the R282H-SCN5A mutation in the sodium channel gene was identified in patients with Brugada syndrome. In a family carrying the R282H-SCN5A mutation, an asymptomatic individual had a common H558R-SCN5A polymorphism and the mutation on separate chromosomes. Therefore, we hypothesized that the polymorphism could rescue the mutation. Methods and Results-In heterologous cells, expression of the mutation alone did not produce sodium current. However, coexpressing the mutation with the polymorphism produced significantly greater current than coexpressing the mutant with the wild-type gene, demonstrating that the polymorphism rescues the mutation. Using immunocytochemistry, we demonstrated that the R282H-SCN5A construct can traffic to the cell membrane only in the presence of the H558R-SCN5A polymorphism. Using fluorescence resonance energy transfer and protein fragments centered on H558R-SCN5A, we demonstrated that cardiac sodium channels preferentially interact when the polymorphism is expressed on one protein but not the other. Conclusions-This study suggests a mechanism whereby the Brugada syndrome has incomplete penetrance. More importantly, this study suggests that genetic polymorphisms may be a potential target for future therapies aimed at rescuing specific dysfunctional protein channels. (Circulation. 2006;114:368-376.)

The reproducibility of frequency domain parameters depends on the analysed condition. These results are of primary importance when the effects of drugs or other interventions on heart rate variability are under investigation.