Insertable cardiac monitors after cryptogenic stroke--a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation.

BACKGROUND AND PURPOSE: Recently, the CRYSTAL AF trial detected paroxysmal atrial fibrillation (AF) in 12.4% of patients after cryptogenic ischaemic stroke (IS) or cryptogenic transient ischaemic attack (TIA) by an insertable cardiac monitor (ICM) within 1 year of monitoring. Our aim was (i) to assess if an AF risk factor based pre-selection of ICM candidates would enhance the rate of AF detection and (ii) to determine AF risk factors with significant predictive value for AF detection. METHODS: Seventy-five patients with cryptogenic IS/TIA were consecutively enrolled if at least one of the following AF risk factors was present: a CHA2DS2-VASc score ≥4, atrial runs, left atrium (LA) size >45 mm, left atrial appendage (LAA) flow ≤0.2 m/s, or spontaneous echo contrast in the LAA. The electrocardiographic and echocardiographic criteria were chosen as they have been repeatedly reported to predict AF; the same applies for four of the six items of the CHA2DS2-VASc score. The study end-point was the detection of one or more episodes of AF (≥2 min). RESULTS: Seventy-four patients underwent implantation of an ICM; one patient had AF at the date of implantation. After 6 months, AF was detected in 21/75 patients (28%), after 12 months in 25/75 patients (33.3%). 92% of AF episodes were asymptomatic. LA size >45 mm and the presence of atrial runs were independently associated with AF detection [hazard ratio 3.6 (95% confidence interval 1.6-8.4), P = 0.002, and 2.7 (1.2-6.7), P = 0.023, respectively]. CONCLUSIONS: The detection rate of AF is one-third after 1 year if candidates for an ICM after cryptogenic IS/TIA are selected by AF risk factors. LA dilation and atrial runs independently predict AF.

[Lipomatous hypertrophy of the interatrial septum]. / Lipomatöse Hypertrophie des interatrialen Septums.

The echocardiographic examination of a female, overweight patient, 71 years of age, with left-sided breast cancer, performed in another hospital, revealed a tumor of the interatrial septum of 3.2 x 4.0 cm. The patient was transferred to our clinic and the finding was identified as a lipomatous hypertrophy of the interatrial septum by echocardiography, computer tomography and nuclear magnetic resonance imaging. It was confirmed by biopsy and histological examination. The lipomatous hypertrophy of the interatrial septum is a rare, benign disease, which usually does not cause a hemodynamic significant obstruction of the blood flow. An increased incidence of atrial arrhythmias is known to occur in this condition and seems to be the only functional restriction.

[Effect of extent and distribution of left ventricular hypertrophy on clinical aspects and hemodynamics of patients with hypertrophic obstructive cardiomyopathy]. / Einfluss von Ausmass und Verteilung der linksventrikulären Hypertrophie auf die Klinik und die Hämodynamik von Patienten mit hypertroph obstruktiver Kardiomyopathie.

UNLABELLED: The influence of the extent and distribution of the echocardiographically determined left-ventricular hypertrophy was evaluated in respect to clinical symptoms and hemodynamics at rest and under bicycle-exercise. 49 patients with hypertrophic obstructive cardiomyopathy [HOCM] (34 men, 15 women, mean age 43 years, subvalvular gradient after provocation 10-270 mm Hg, ejection fraction greater than 55%) and 10 controls (seven men, three women, mean age 44 years) were investigated. Enddiastolic left-ventricular diameter and basal thickness of the anterior and posterior septum, and the lateral and posterior wall of the left ventricle were echocardiographically measured. The distribution of basal hypertrophy (for the anterior septum and the posterior wall greater than or equal to 15 mm, for the posterior septum and the lateral wall greater than or equal to 17 mm) was classified as type I (1 segment, n = 17), II (2, n = 14) and III (greater than or equal to 3 segments, n = 18), according to Maron et al. (1981). At rest and during symptom-limited bicycle exercise, cardiac index (CI), stroke volume index (SVI), and mean pulmonary capillary wedge pressure (PCWP) were determined at sinus rhythm by a Swan-Ganz-catheter and by the thermodilution method. RESULTS: With increasing hypertrophy, there was a reduction of the left-ventricular enddiastolic diameter. A NYHA-class greater than II was observed in 18% of patients with type-I hypertrophy, in 29% with type II, but in 61% with type III (p less than or equal to 0.05). Of patients with type III, 44% (p less than or equal to 0.05). In type-III hypertrophy the with type I 6% had suffered syncopes; with type II, 14%, and with type III, 44% (p less than or equal to 0.05). In type-III hypertrophy the maximum exercise level (72 +/- 24 Watt) was significantly (p less than 0.05) lower compared with controls (110 +/- 42 W), in type I (99 +/- 35 W), and in type II (100 +/- 45 W). At maximum stress PCWP was significantly increased in types I, II, and III (type I = 22 +/- 8 mm Hg, II = 24 +/- 12 mm Hg, III = 29 +/- 8 mm Hg) compared with controls (8 +/- 4 mm Hg); SVI was significantly lower in type III (49 +/- 13 ml/m2) than in controls (65 +/- 12 ml/m2) and in type I (60 +/- 11 ml/m2); SVI was 60 +/- 17 ml/m2 in type II. At maximum stress, cardiac index was significantly lower in type III (6.2 +/- 2.1 l/min/m2) than in controls (8.9 +/- 2.1 l/min/m2) and in type I (8.4 +/- 1.7 l/min/m2). CONCLUSIONS: In patients with HOCM, severe left-ventricular hypertrophy type III accompanied by a reduced ventricular cavum is associated with more pronounced clinical symptoms, a reduced working capacity and the occurrence of syncopes. In these patients, despite increased filling pressures, the increase in stroke volume and cardiac index are insufficient at stress. Therefore, echocardiographically evaluated left-ventricular hypertrophy and geometry are helpful to estimate the severity of functional disorder in HOCM.

Mutational analysis of the pseudoknot in the tRNA-like structure of turnip yellow mosaic virus RNA. Aminoacylation efficiency and RNA pseudoknot stability.

Site-directed mutations were introduced in the connecting loops and one of the two stem regions of the RNA pseudoknot in the tRNA-like structure of turnip yellow mosaic virus RNA. The kinetic parameters of valylation for each mutated RNA were determined in a cell-free extract from wheat germ. Structure mapping was performed on most mutants with enzymic probes, like RNase T1, nuclease S1 and cobra venom ribonuclease. An insertion of four A residues in the four-membered connecting loop L1 that crosses the deep groove of the pseudoknot reduces aminoacylation efficiency. Deletions up to three nucleotides do not affect aminoacylation or RNA pseudoknot formation. Deletion of the entire loop abolishes aminoacylation. Although elimination of the pseudoknot is presumed, this could not be demonstrated. Unlike the mutations in loop L1, all mutations in the three-membered connecting loop L2 that crosses the shallow groove of the RNA pseudoknot decrease the aminoacylation efficiency considerably. Nonetheless, the RNA pseudoknot is still present in most mutated RNAs. These results indicate that a number of mutations can be introduced in both loops without abolishing aminoacylation. Results obtained with the introduction of mismatches and A.U base-pairs in stem S1 of the pseudoknot, containing three G.C base-pairs in wild-type RNA, indicate that the pseudoknot is only marginally stable. Our estimation of the gain of free energy due to the pseudoknot formation is at most 2.0 kcal/mol. The pseudoknot structure can, however, be stabilized upon binding the valyl-tRNA synthetase.

Quantitative HPLC analysis of the level of fecapentaenes and their precursors in human feces by a chemical conversion method.

A fast and reliable hplc method for the quantitative analysis of total fecapentaene-12 (FP-12 and its precursors) and total fecapentaene-14 (FP-14 and its precursors) in human feces is described. The analysis is based on the rapid chemical conversion of fecapentaenes and their precursors to more stable methoxytetraenols and the use of synthetic, not naturally occurring, fecapentaene-13 (FP-13) as an internal standard. The synthesis and physical properties of this internal standard are described. The convenience and reproducibility of the method were illustrated by applying the procedure to stool samples obtained from twelve individuals on 3 consecutive days. Levels of total FP's were in the range of 0.1-25.4 micrograms for total FP-12 and 0.1-8.5 micrograms for total FP-14 per g of wet feces. Appreciable fluctuations were observed between levels in samples from the same individual on different days. Reproducibility and recovery were shown to be good.

Synthesis and biological activity of analogs of fecapentaene-12.

Analogs of the potent fecal mutagen fecapentaene-12 have been prepared and tested both for mutagenicity and for their ability to serve as biological precursors of 1. It was found that mutagenicity in three different Salmonella tester strains TA96, TA100, and TA104, decreased rapidly as the number of conjugated double bonds was reduced. The aldehyde 8, analogous to the hydrolysis product of 1, showed only low mutagenicity, even in the aldehyde-sensitive strain TA104. None of the polyenes prepared was able to function as a direct biological precursor of 1 under the conditions employed.