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.

Combined treatment with valsartan and spironolactone prevents cardiovascular remodeling in renovascular hypertensive rats.

Treatment with an angiotensin blocker (ARB) and an aldosterone blocker has been shown to have beneficial effects on cardiac remodeling in several cardiac diseases. It is still not clear whether the combination of these drugs is more effective against cardiac remodeling than the use of either agent alone. We examined the effects of combined treatment with valsartan, an ARB, and spironolactone, an aldosterone blocker, on cardiac remodeling in the renovascular hypertensive (RHT) rat. The RHT rats were divided into 4 groups administered valsartan (3 mg/kg/day, ARB group), spironolactone (4 mg/kg/day, SPRL group), both drugs at these doses (combined group), or neither drug (untreated RHT group). After 5 weeks, systolic blood pressure was significantly reduced in the 3 treatment groups, however, there were no significant differences in the extent of blood pressure reduction among the 3 treatment groups. The heart weight/body weight ratio in each of the 3 treatment groups was significantly lower than that in the untreated RHT group. The degree of cardiac and perivascular fibrosis in the SPRL group and the combined group were significantly lower than that in the untreated RHT group. Myocyte remodeling in the ARB group and in the combined group was significantly smaller than that in the untreated RHT group. These results suggest that SPRL treatment prevents cardiac and perivascular fibrosis and ARB treatment suppresses the cellular hypertrophy of myocytes, and that, therefore, combined treatment with both drugs prevents cardiac remodeling by acting against both myocyte hypertrophy and cardiac fibrosis in RHT rats.

Atrial septal pacing to resynchronize atrial contraction and improve atrial transport function.

OBJECTIVES: Atrial septal pacing via a trans-septal breakthrough site within the right atrial septum can shorten global atrial activation time, resulting in significant reduction of recurrence of atrial fibrillation events. This study examined whether this pacing method will lead to resynchronization of atrial contraction and its benefit on hemodynamic function can be maintained for 24 months. METHODS: Thirty patients with atrial fibrillation and delayed atrial conduction were enrolled (17 males, 13 females, mean age 73 +/- 7 years). Trans-septal breakthrough site within the right atrial septum was identified through pacing from the dorsal left atrium. Continuous atrial septal pacing at the trans-septal breakthrough site was performed for 24 months. Time difference (TD) between right and left atrial contractions was measured during atrial septal pacing and sinus rhythm by pulse Doppler echocardiography of the trans-tricuspid (P-At) and mitral (P-Am) blood flows (TD = P-Am - P-At). RESULTS: The atrial lead was screwed near the fossa ovalis in 29 of 30 patients. Atrial septal pacing yielded significantly shorter P wave duration (101.9 +/- 10.4 vs 139.6 +/- 14.7 msec, p < 0.001), leading to significant reduction of TD in atrial contraction (-8.8 +/- 10.0 vs 29.8 +/- 13.6 msec, p < 0.001)as compared to sinus rhythm. Both shorter P wave duration and reduced TD during atrial septal pacing remained statistically significant during the follow-up period as compared to sinus rhythm. Both left atrial diameter and A to E ratio of filling waves at mitral valve were significantly decreased at 12 months and remained decreased at 24 months. CONCLUSIONS: Atrial septal pacing at the trans-septal breakthrough site can resynchronize atrial contraction and results in improved hemodynamic effects during 24 months of follow-up.