Characteristics of frequency content of atrial signal-averaged electrocardiograms during sinus rhythm in patients with paroxysmal atrial fibrillation

To clarify the characteristics of the frequency content of atrial signal-averaged electrocardiograms (ECGs) during sinus rhythm in patients with paroxysmal atrial fibrillation, P wave-triggered signal-averaged ECGs were recorded in 28 patients with and 34 control patients without paroxysmal atrial fibrillation. Fast Fourier transform analysis was performed on the 100-ms segment starting 75 ms before the end of the P wave. An area ratio (AR50) was calculated by dividing the area under the spectrum curve between 20 and 50 Hz, multiplied by 100, by the area between 0 and 20 Hz. Magnitude ratios (MR20, MR30, MR40and MR50) were calculated by dividing the magnitude at 20, 30, 40 and 50 Hz, respectively, multiplied by 100, by the maximal magnitude of the entire signal.AR50was significantly greater in patients with than without paroxysmal atrial fibrillation (62.3 ± 34.2 vs. 42.4 ± 18.4). MRM and MR30were also significantly greater in patients with than without paroxysmal atrial fibrillation (MR2076.1 ± 15.2 vs. 60 ± 20.2; MR3041 ± 18.8 vs. 26.6 ± 14.4), although no significant differences in MR40or MR50were observed between the two patient groups. The difference in MR30between groups remained significant even after taking into account the presence of organic heart disease.It is concluded that, irrespective of the presence of organic heart disease, the terminal portion of the P wave contained significantly more components in the 20- to 50-Hz range, especially around 30 Hz, in patients with than in patients without paroxysmal atrial fibrillation. These results suggest that frequency analysis could characterize atrial signal-averaged ECGs of patients at risk for paroxysmal atrial fibrillation

α-Selective glycosidation of d-tagatofuranose with a 3,4-O-isopropylidene protection

An α-selective glycosidation reaction of D-tagatofuranose was successfully achieved using 3,4-O-isopropylidene-protected D-tagatofuranose as a glycosyl donor. A variety of glycosyl acceptors, including primary, secondary, and β-amino alcohols, and carbohydrates, can be used for this D-tagatofuranosidation reaction with complete α-selectivities and good yields (57-83%). The stereochemistries at the anomeric positions were determined by nuclear Overhauser effect spectroscopic correlations, as well as comparison of the chemical shifts in the 13C NMR spectra

Phenotypic homozygous familial hypercholesterolemia successfully treated with proprotein convertase subtilisin/kexin type 9 inhibitors

Key Clinical Message Recent data reveal phenotypic HoFH patients may be responsive to PCSK9 inhibitors, challenging prior assumptions. Genetic testing advancements now more accurately forecast patient responses to these therapies, improving treatment strategies

MEKK1 is essential for cardiac hypertrophy and dysfunction induced by Gq

Signaling via mitogen-activated protein kinases is implicated in heart failure induced by agonists for G protein-coupled receptors that act via the G protein Gαq. However, this assertion relies heavily on pharmacological inhibitors and dominant-interfering proteins and not on gene deletion. Here, we show that endogenous cardiac MAPK/ERK kinase kinase-1 (MEKK1)/(MAP3K1), a mitogen-activated protein kinase kinase kinase, is activated by heart-restricted overexpression of Gαq in mice. In cardiac myocytes derived from embryonic stem cells in culture, homozygous disruption of MEKK1 selectively impaired c-Jun N-terminal kinase activity in the absence or presence of phenlyephrine, a Gαq-dependent agonist. Other terminal mitogen-activated protein kinases were unaffected. In mice, the absence of MEKK1 abolished the increase in cardiac mass, myocyte size, hypertrophy-associated atrial natriuretic factor induction, and c-Jun N-terminal kinase activation by Gαq, and improved ventricular mechanical function. Thus, MEKK1 mediates cardiac hypertrophy induced by Gαq in vivo and is a logical target for drug development in heart disease involving this pathway