Progression From Paroxysmal to Persistent Atrial Fibrillation. Clinical Correlates and Prognosis

Objectives: We investigated clinical correlates of atrial fibrillation (AF) progression and evaluated the prognosis of patients demonstrating AF progression in a large population. Background: Progression of paroxysmal AF to more sustained forms is frequently seen. However, not all patients will progress to persistent AF. Methods: We included 1,219 patients with paroxysmal AF who participated in the Euro Heart Survey on AF and had a known rhythm status at follow-up. Patients who experienced AF progression after 1 year of follow-up were identified. Results: Progression of AF occurred in 178 (15%) patients. Multivariate analysis showed that heart failure, age, previous transient ischemic attack or stroke, chronic obstructive pulmonary disease, and hypertension were the only independent predictors of AF progression. Using the regression coefficient as a benchmark, we calculated the HATCH score. Nearly 50% of the patients with a HATCH score >5 progressed to persistent AF compared with only 6% of the patients with a HATCH score of 0. During follow-up, patients with AF progression were more often admitted to the hospital and had more major adverse cardiovascular events. Conclusions: A substantial number of patients progress to sustained AF within 1 year. The clinical outcome of these patients regarding hospital admissions and major adverse cardiovascular events was worse compared with patients demonstrating no AF progression. Factors known to cause atrial structural remodeling (age and underlying heart disease) were independent predictors of AF progression. The HATCH score may help to identify patients who are likely to progress to sustained forms of AF in the near future. \ua9 2010 American College of Cardiology Foundation

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey).

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women

Evidence for the formation of an unusual ternary complex of rabbit liver EF-1α with GDP and deacylated tRNA

AbstractEukaryotic translation elongation factor1α is known to interact in GTP-bound form with aminoacyl-tRNA promoting its binding to the ribosome. In this paper another ternary complex [EF-1α*GDP*deacylated tRNA], never considered in widely accepted elongation schemes, is reported for the first time. The formation of this unusual complex, postulated earlier (FEBS Lett. (1996) 382, 18–20), has been detected by four independent methods. [EF-1α*GDP]-interacting sites are located in the acceptor stem, TψC stem and TψC loop of tRNAPhe and tRNALeu molecules. Both tRNA and EF-1α are found to undergo certain conformational changes during their interaction. The ability of EF-1α to form a complex with deacylated tRNA indicates that the factor may perform an important role in tRNA and aminoacyl-tRNA channeling in higher eukaryotic cells

PTI-1: novel way to oncogenicity

Aim. The prostate tumor-inducing oncogene (PTI-1), presumably encoding a truncated form of eukaryotic translation elongation factor 1A1 (eEF1A1), was discovered as a gene overexpressed in prostate tumor samples and absent in normal tissues. The mechanism of PTI-1 oncogenicity remains obscure. Methods. Several bioinformatics methods were applied to analyze the PTI-1 mRNA structure, translation efficiency and coding potential. Results. In silico analysis of 5'UTR of its mRNA suggest that PTI-1 mRNA most probably belongs to the class of templates with low translation efficiency. Additionally, novel open reading frame (ORF) starting with alternati- ve initiation site situated upstream of the main ORF start codon was found. Finally, the peptide that does not resemble eEF1A1 but is partially homologous to relaxin can be synthesized. Conclusions. We suggest that the alternative upstream start codon may initiate synthesis of a peptide (uPTI-1) homologous to relaxin, the hormone shown to promote the prostate cancer progression. uPTI-1 protein may interact with the respective relaxin-specific receptors, suggesting that the tumorigenic outcome of PTI-1 is possibly realized via the relaxin-dependent pathway

Quaternary organization of the human eEF1B complex reveals unique multi-GEF domain assembly.

Protein synthesis in eukaryotic cell is spatially and structurally compartmentalized that ensures high efficiency of this process. One of the distinctive features of higher eukaryotes is the existence of stable multi-protein complexes of aminoacyl-tRNA synthetases and translation elongation factors. Here, we report a quaternary organization of the human guanine-nucleotide exchange factor (GEF) complex, eEF1B, comprising α, β and γ subunits that specifically associate into a heterotrimeric form eEF1B(αβγ)3. As both the eEF1Bα and eEF1Bβ proteins have structurally conserved GEF domains, their total number within the complex is equal to six. Such, so far, unique structural assembly of the guanine-nucleotide exchange factors within a stable complex may be considered as a 'GEF hub' that ensures efficient maintenance of the translationally active GTP-bound conformation of eEF1A in higher eukaryotes