Identification of an aromatase haplotype that is associated with gene expression and postmenopausal osteoporosis.

CONTEXT: Osteoporosis has a significant genetic component. The aromatase-dependent conversion of androgenic precursors is the main source of estrogens in postmenopausal women. OBJECTIVE: The objective of the investigation was to study the relationship of a set of single nucleotide polymorphisms (SNPs) of the aromatase gene with osteoporosis and determine their functional influence on gene transcription. DESIGN, PARTICIPANTS, AND METHODS: This was a case-control study including 135 women with vertebral fractures due to postmenopausal osteoporosis and 312 controls. Alleles at four SNPs situated between exons I.2 and 3 were determined by Taqman assays. Total aromatase RNA and differential allelic-specific expression were studied by RT-real time PCR in adipose tissue samples taken from 50 individuals. RESULTS: The SNPs studied were in strong linkage disequilibrium. A common haplotype, present in about half of the population, was identified as being associated with an increased risk of fractures (odds ratio 1.8, 95% confidence interval 1.2-2.8, P = 0.006). There was evidence of differential allelic expression. In heterozygous individuals, transcripts bearing T alleles at rs700518 SNP (which were included in the risk haplotype) were less abundant than those with the alternative C alleles (P < 0.001). Total aromatase expression was four times lower in fat samples from individuals who were homozygotes for the unfavorable alleles than in the opposite homozygotes (P = 0.007). CONCLUSIONS: A common haplotype of aromatase associated with gene expression is also associated with the risk of osteoporotic vertebral fractures in postmenopausal women. These data are in line with the hypothesis that the aromatase-dependent synthesis of estrogens plays an important role in bone homeostasis in postmenopausal women.

The 'Valve Racket': a new and different concept of atrioventricular valve repair.

OBJECTIVE: Mitral regurgitation due to prolapse of the mitral leaflets frequently compromises annuloplasty repair procedures. We present a new annuloplasty ring that overcomes this difficulty, preventing displacement of the leaflets into the atrium. METHODS: The 'Valve Racket' is a prosthetic ring transformed into a racket by means of handmade mesh using expanded polytetrafluoroethylene (ePTFE Gore-Tex). After transection of the marginal chordae tendineae, five sheep had the new racket implanted in the mitral (n = 3) and in the tricuspid position (n = 2). The surviving sheep underwent postoperative evaluation. RESULTS: After six months of operation, a standard transthoracic study showed competent valves without significant gradients and without residual valve regurgitation. The ring appeared encapsulated by a uniform fibrous tissue but the threads showed a completely denuded surface except in the zone proximal to the ring. Thrombi or calcification deposits in the ring, racket's mesh, or cardiac chamber were not observed. CONCLUSION: This initial experience confirmed the efficacy and simplicity of the technique.

Reoperations after tricuspid valve repair.

OBJECTIVE: The objective was to analyze the short- and long-term results of patients with previous tricuspid valve repair who had valve dysfunction and required cardiac reoperations. METHODS: Between 1976 and 2002, 74 patients with a mean age of 53.8 +/- 12.2 years underwent valve reoperations for dysfunction of previous tricuspid valve repair. Mitral and tricuspid lesions were diagnosed in 40 patients (54%), triple valve disease (mitral, aortic, tricuspid) was diagnosed in 26 patients (35.1%), isolated tricuspid disease was diagnosed in 6 patients (8.1%), and aortic and tricuspid lesions were diagnosed in 2 patients (2.7%). Reoperations included tricuspid valve replacement in 43 patients (58.1%) and a new tricuspid valve repair procedure in the remaining 31 patients (41.9%). RESULTS: Hospital mortality (30-day or within first admission) was 35.1% (n = 26). In the multivariate analysis, risk factors for hospital mortality included body mass index less than 20 kg/m2 and greater than 24 kg/m2 , triple valve disease, use of intra-aortic balloon counterpulsation, and presence of postoperative complications. The follow-up was complete in 100% of patients, with a mean follow-up of 14.2 years (range 4 months to 26 years). The late mortality was 40.5% (n = 30). Predictors of late mortality were body mass index less than 20 kg/m2 , cardiac surgery before 1991, and development of dysfunction early after tricuspid valve repair. At the follow-up closing date, 19 patients are alive (25.7%). The actuarial survival was 11.8% +/- 4.9% at 26 years. CONCLUSIONS: Patients with failure of a tricuspid valve repair procedure requiring reoperation have a poor prognosis with a high mortality rate both in-hospital and in the long-term.

Tricuspid valve repair: an old disease, a modern experience.

BACKGROUND: We review our experience in patients who required surgical correction of tricuspid valve disease with concomitant disease of the mitral or aortic valve, or both, operated on between 1987 and 1999. METHODS: We studied 232 consecutive patients (mean age, 59.8 years) followed for a mean of 6.8 years (range, 2 to 12 years). All patients were investigated by means of Doppler echocardiography, with hemodynamic studies in 135. Median tricuspid insufficiency was 3+. The cause was rheumatic heart disease in 186 patients and degenerative in 46. All patients underwent suture annuloplasty (De Vega or segmental) at the time of mitral or aortic valve surgery. Tricuspid lesions were functional in 128 patients and organic in 104. RESULTS: The hospital and late mortality rates were 8.1% and 23.3%, respectively. These figures were independent of the type of annuloplasty performed. Predictors of hospital mortality were biologic prosthesis, renal insufficiency, time of cardiopulmonary bypass, and use of inotropic drugs. Predictors of late mortality were age older than 60 years, left ventricular ejection fraction less than 0.50, and New York Heart Association functional class IV. At 12 years, the actuarial survival rate was 50.5% +/- 6.1%, and the actuarial curve free from reoperation 75.7% +/- 7.3%. The actuarial curve for freedom from valve-related complication was 39.0% +/- 6.3% at 11 years. CONCLUSIONS: Despite the use of modern technologic advances in the diagnosis and treatment of valvular hear disease, tricuspid insufficiency continues to be a poor prognostic factor in patients with concomitant disease of the mitral or aortic valve, or both.