Sex-based differences in candidacy for transcatheter tricuspid valve intervention.

BACKGROUND: Women have a higher prevalence of tricuspid regurgitation (TR) and present at more advanced stages as compared with men. Given the high operative mortality associated with tricuspid valve (TV) surgery, transcatheter tricuspid valve interventions (TTVI) have emerged as a promising treatment option. We explored sex-based differences among patients with significant TR who would be expected to be eligible for TTVI. METHODS: Between March 2021-2022, 12,677 unique adult patients underwent a transthoracic echocardiogram at our tertiary care institution. Clinical and echocardiographic data were collected for patients with more than moderate TR. The 2021 European Society of Cardiology valve guidelines were used to retrospectively define sub-populations who would have been eligible for TTVI, TV surgery, or medical therapy. Patients were grouped by sex and compared using t-tests, Wilcoxon rank-sum, Pearson chi-square, and Cox regression for survival analysis. RESULTS: Of 569 patients, 52% (296/569) were female. Men had a higher prevalence of left ventricular dysfunction (p < 0.001), mitral regurgitation (p = 0.023), and signs of heart failure (New York Heart Association stage III (p = 0.031)). Women had more isolated TR (p = 0.020) and TR due to severe pulmonary hypertension (p < 0.001). Most patients (74.6% of women, 76.9% of men) were precluded from both transcatheter and surgical intervention due to advanced disease. 10.8% of women and 9.2% of men would have qualified for TTVI (p = 0.511). CONCLUSION: The majority of patients with significant TR presenting to a tertiary care center are not eligible for TTVI. Sex is not a predictor of eligibility for TTVI among patients with significant TR.

Spontaneous Coronary Artery Dissection in a 19-Year-Old Male Athlete.

We present a 19-year-old male athlete, without cardiovascular risk factors, with anterior ST-segment elevation myocardial infarction caused by left anterior descending artery spontaneous coronary artery dissection. Symptoms began during a swim practice, and patient endorsed using C4 Ripped (Cellucor), a preworkout supplement to enhance athletic performance. We hypothesize that this was the major contributor to presentation. The patient showed improvement after 4 days.

DISC1 and reelin interact to alter cognition, inhibition, and neurogenesis in a novel mouse model of schizophrenia.

The etiology of schizophrenia (SCZ) is multifactorial, and depending on a host of genetic and environmental factors. Two putative SCZ susceptibility genes, Disrupted-in-Schizophrenia-1 (DISC1) and reelin (RELN), interact at a molecular level, suggesting that combined disruption of both may lead to an intensified SCZ phenotype. To examine this gene-gene interaction, we produced a double mutant mouse line. Mice with heterozygous RELN haploinsufficiency were crossed with mice expressing dominant-negative c-terminal truncated human DISC1 to produce offspring with both mutations (HRM/DISC1 mice). We used an array of behavioral tests to generate a behavioral phenotype for these mice, then examined the prefrontal cortex and hippocampus using western blotting and immunohistochemistry to probe for SCZ-relevant molecular and cellular alterations. Compared to wild-type controls, HRM/DISC1 mice demonstrated impaired pre-pulse inhibition, altered cognition, and decreased activity. Diazepam failed to rescue anxiety-like behaviors, paradoxically increasing activity in HRM/DISC1 mice. At a cellular level, we found increased α1-subunit containing GABA receptors in the prefrontal cortex, and a reduction in fast-spiking parvalbumin positive neurons. Maturation of adult-born neurons in the hippocampus was also altered in HRM/DISC1 mice. While there was no difference in the total number proliferating cells, more of these cells were in immature stages of development. Homozygous DISC1 mutation combined with RELN haploinsufficiency produces a complex phenotype with neuropsychiatric characteristics relevant to SCZ and related disorders, expanding our understanding of how multiple genetic susceptibility factors might interact to influence the variable presentation of these disorders.