A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronary artery disease.

Familial HDL deficiency (FHD) is a rare autosomal dominant lipoprotein disorder. We describe a novel genetic variant of the apolipoprotein A-I (apoA-I) gene resulting in FHD. The proband is a 51-year-old woman who was hospitalized due to severe heart failure. Her plasma HDL-cholesterol (C) and apoA-I concentrations were 0.08mmol/l and 1mg/dl, respectively. She exhibited corneal opacities and planar xanthomas on eyelids and elbows. Coronary angiography demonstrated extensive obstructions in two major vessels. Genomic DNA sequencing of the patient's apoA-I gene revealed a homozygosity for a GC deletion between 5 GC repeats in exon 4, creating a frameshift and a stop codon at residue 178. We designated this mutation as apoA-I Shinbashi. The proband's father, son, and daughter were found to be heterozygous for this mutation and their HDL-C and apoA-I levels were about half of normal levels, demonstrating a gene dosage effect. The father underwent coronary bypass surgery at age of 70 years. Lecithin-cholesterol acyltransferase (LCAT) activity was decreased by 63% in the homozygote and 31% in heterozygotes, respectively. This new case of apoA-I deficiency, apoA-I Shinbashi, is the first case involving a single gene defect of the apoA-I gene to develop all the characteristics for apoA-I deficiency, including premature coronary heart disease.

Various routes of septal propagation in common atrial flutter.

INTRODUCTION: Although in the treatment of common atrial flutter, the isthmus between the tricuspid valve annulus and the eustachian ridge is often chosen as the site for conduction block by radiofrequency ablation, the precise path of the flutter circuit remains unknown. We therefore investigated the propagation of the atrial flutter wave front around the coronary sinus ostium and how its path is altered by application of radiofrequency current. METHODS AND RESULTS: To assess activation pattern, activation in the region surrounding the coronary sinus ostium was mapped using a deflectable decapolar catheter under basal conditions and while applying radiofrequency current to the septal isthmus, between the tricuspid valve annulus and the eustachian ridge. In five of eleven patients studied, the eustachian ridge side, below the coronary sinus ostium, was activated earlier, and the flutter wave exited from either the tricuspid valve annulus side or the eustachian ridge side, above the coronary sinus ostium. In four patients, a partial line of block created by applying radiofrequency current between the tricuspid valve annulus and the coronary sinus ostium or between the coronary sinus ostium and the eustachian ridge led to a shift in the direction of propagation of the flutter wave front from anterior to posterior or from posterior to anterior of the coronary sinus ostium, and prolongation of the cycle length. CONCLUSION: Application of radiofrequency current to the septal isthmus, between the tricuspid valve annulus and the eustachian ridge, can shift both the anterior and posterior propagation of flutter around the coronary sinus ostium.

Effect of continuous ATP injection on human hemodynamics.

Continuous ATP injection is used clinically for Tl imaging or coronary flow measurement and because the effect on human hemodynamics is unknown, the present study investigated it in 14 patients undergoing heart catheter examination. Continuous ATP injection induced chest symptoms in 13 of the patients and second-degree atrioventricular block in one, but these complications disappeared immediately after the end of ATP infusion. Continuous ATP injection decreased aortic pressure, but increased pulmonary artery pressure, right atrial pressure and pulmonary capillary wedge pressure. ATP increased heart rate, stroke volume and cardiac output, the latter the result of an increase in preload, a decrease in afterload, and the increase in heart rate.