Heart failure in women

Heart failure (HF) has steadily increased in prevalence and affects both males and females equally. Despite this, there has been a significant underrepresentation of women in large scale HF trials. This disparity has lead to a deficit in understanding important gender-based differences in pathophysiology, diagnosis and treatment strategies. We review these gaps and explore a biological basis for varying outcomes. Endogenous estrogen plays an important role in epidemiology and outcome. The administration of exogenous estrogen has had varied success in treatment and is outlined extensively below. Additionally, we highlight unique HF syndromes through pregnancy and important sex-specific issues concerning transplant and mechanical circulatory support. A central theme remains: there is a clear need for increased female recruitment in clinical trials, and more studies exploring the role of gender-based biology in HF treatment.     

Risk of Colorectal Adenomas in Women with Prior Breast Cancer

Background and Aims

Longer life expectancy in patients with prior breast cancer may increase their risk of developing other primary cancers, including colorectal cancer (CRC). Whether the risk of developing CRC in this patient population is higher in comparison to those with no prior cancer remains unclear. The purpose of this study was to compare the prevalence of colorectal adenomas and any CRC in breast cancer survivors with those who have no history of prior cancer and assess any difference with use of antiestrogen therapy.

Methods

We compared the prevalence of colorectal cancer and adenomas in breast cancer survivors with that of a group of matched controls. Eligible survivors were ??85?years of age; had initially been diagnosed with stage 0, I, II, or III breast cancer; had completed all cancer treatments with the exception of adjuvant antiestrogen therapy; and had no evidence of recurrence on follow-up. We used the screening colonoscopy database at our institution to identify age-, sex-, and race-matched controls with no history of cancer.

Results

We identified 302 study-eligible breast cancer survivors and 302 matched controls. No colorectal cancers were found in either group. Forty-one breast cancer survivors and 30 controls had tubular adenomas; four survivors and three controls had villous adenoma; and eight survivors and ten controls had advanced adenoma. Multivariate regression analysis revealed that adjuvant antiestrogen therapy was not significantly associated with an increased risk of advanced adenoma.

Conclusions

The prevalence of colorectal adenomas in breast cancer survivors and controls was similar. Breast cancer survivors, including those receiving adjuvant antiestrogen therapies may follow the colorectal screening guidelines used for average-risk population.     

Not all obstructive cardiac lesions are created equal: double-chamber right ventricle in pregnancy

Double-chambered right ventricle (DCRV) is a rare form of right ventricular outflow tract (RVOT) obstruction accounting for approximately 1% of patients with congenital heart disease. It consists of an anomalous muscle bundle that divides the right ventricle usually between the sinus (inlet) and the infundibulum (outlet). This division creates a proximal chamber with high pressure and a distal chamber with low pressure. The hemodynamic obstruction of the RVOT is usually an acquired phenomenon, however the substrate for the anomalous muscle bundle is likely congenital. The diagnosis of DCRV should be considered in the young patient with an elevated right ventricular systolic pressure and intracavitary gradient. Echocardiography and cardiac MRI are the principal diagnostic tools for the assessment of DCRV. This entity is often misdiagnosed as pulmonary hypertension in the young patient, and can often go overlooked and untreated for many years. Definitive therapy involves surgical resection of the muscle bundle. This can often be curative and if done in a timely fashion, may prevent right ventricular remodeling. We describe the unique diagnostic dilemma, the course and management of a young adult with DCRV during pregnancy.     

Contribution of GPR30 for 1,25 dihydroxyvitamin D3 protection in EAE

Previous studies have demonstrated that vitamin D3-mediated protection in EAE occurs only in females and is dependent on the presence of diestrus levels of 17β-estradiol (E2). To evaluate the role of estrogen receptors in vitamin D3 treatment of EAE, we compared disease severity, CNS histopathology and immunological responses in vehicle and calcitrol (1,25 dihydroxyvitamin D₃) treated WT C57BL/6 mice vs. GPR30 membrane estrogen receptor (MER) knockout mice with MOG-35-55 peptide-induced EAE. Our results demonstrated that vitamin D₃-mediated prevention of clinical signs, CNS cellular lesions and demyelination observed in WT mice was abrogated in GPR30-KO mice with EAE. Regulatory effects of vitamin D₃ treatment that were MER dependent included increased levels of IL-10 and IL-6 secreted by MOG peptide-reactive splenocytes and increased expression of CCL5, CCR1 & CCR3 in spleen tissue. These results demonstrate for the first time that the MER is a key contributor to the E2-dependent effects of vitamin D₃-mediated protection in EAE.