Implantable cardioverter defibrillators: do women fare worse than men? Gender comparison in the INTRINSIC RV trial.

INTRODUCTION: Due to limited enrollment of women in previous trials, there is a paucity of data comparing outcome and arrhythmic events in men versus women with implantable cardioverter defibrillators (ICDs). METHODS AND RESULTS: We analyzed outcome of patients in the INTRINSIC RV (Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs) trial based on gender. Women comprised 19% (293/1530) of the INTRINSIC RV population. Compared with men, women were less likely to have coronary disease, ischemic cardiomyopathy, and hyperlipidemia, and were more likely to have congestive heart failure and diabetes. Women were less likely to receive beta blockers and ACE inhibitors, and more likely to receive diuretics. Over 10.8 +/- 3.5 months of follow-up, unadjusted mortality was higher in women than men (6.8% vs 4.1%, P = 0.04). Heart failure hospitalizations occurred in 7.9% of women versus 5.7% of men (P = 0.13). After adjustment for baseline differences and drug therapy, there was no significant difference in mortality between men and women. Adverse events were observed more often in women. There were no gender differences in the percentage of patients receiving appropriate or inappropriate ICD shocks. CONCLUSIONS: In INTRINSIC RV, women receiving ICDs differed from men regarding baseline characteristics and drug therapy. After adjusting for baseline differences and medical therapy, there were no differences in heart failure hospitalization, survival, or ICD shock therapy during follow-up. Apparent undertreatment of heart failure and greater frequency of adverse advents in women receiving ICDs warrant further investigation.

Transforming growth factor-beta isoform expression during bovine ovarian antral follicle development.

Transforming growth factor-beta (TGF-beta) isoforms are important paracrine and autocrine signaling molecules for the regulation of ovarian follicle growth and physiology. Effective communication between the epithelial granulosa cells, the mesenchymal theca cells, and the oocyte is vital for ovarian function and reproductive success. The expression, localization, and regulation of TGF-beta isoforms in the developing bovine follicle was examined using both immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-PCR) procedures. TGF-beta1 protein was found to be present in the granulosa cells of early pre-antral, early antral, and 1-2 mm follicles. Interestingly, there was no visible staining of granulosa cells of 3-5 or 5-10 mm follicles. There was also no TGF-beta1 staining of theca cells. TGF-beta2 and TGF-beta3 staining were present in the granulosa and theca cells of all follicle stages examined. The levels of TGF-beta mRNA expression in granulosa and theca cells from antral follicles was measured using quantitative RT-PCR. For each isoform mRNA expression levels did not change in different sized antral follicles. TGF-beta3 mRNA levels were much higher than those of TGF-beta1 and TGF-beta2 in both granulosa and theca. Expression levels were higher in theca than in granulosa for TGF-beta2 and TGF-beta3. FSH was found to decrease TGF-beta1 mRNA expression in granulosa cells, but had no effect on TGF-beta2 and TGF-beta3. Bovine ovarian follicles were found to have a unique pattern of TGF-beta isoform expression and regulation when compared to other species (i.e., rodent, pig, quail, and human). The similarities and differences between the various species is discussed to help elucidate common functions of TGF-beta in the ovary. In summary, observations demonstrate that as antral follicles develop, TGF-beta3 is the most abundant TGF-beta isoform and TGF-beta1 protein levels decline in large follicles. Granulosa cell TGF-beta1 expression was decreased by FSH and this correlated with reduced levels in large antral follicles. TGF-betas involved in antral follicular growth and development appear to act as paracrine/autocrine signaling molecules having a species-specific pattern of expression.