Underrepresentation of Women in Late-Breaking Cardiovascular Clinical Trials.

Background: Cardiovascular disease is the leading cause of mortality for women and men. Prior studies have demonstrated the underrepresentation of women in published clinical trials, but no study to date has assessed inclusion of women in late-breaking clinical trials (LBCTs) presented at national meetings. The objective is to characterize the inclusion of women participants in LBCT presented at the 2021 American College of Cardiology (ACC), American Heart Association (AHA), and European Society of Cardiology (ESC) annual meetings and identify trial characteristics associated with improved inclusion. Methods: LBCT presented at the 2021 ACC, AHA, and ESC meetings were identified and the inclusion of women as participants was assessed. The inclusion to prevalence ratio (IPR) was calculated by dividing the percentage of women participants by the percentage of women in the disease population. IPRs <1 indicate underenrollment of women. Of the 68 LBCT, 3 trials were excluded due to lack of subject matter relevance. Results: Inclusion of women ranged from 0% to 71%. Only 47.1% of trials reported sex-specific analyses. The average IPR was 0.76 for all trials and did not vary based on conference, trial center, geographic region, or funding source. The average IPR varied based on subspecialty, with a statistical difference between interventional cardiology and heart failure (0.65 vs. 0.88, p = 0.02). The average IPR was significantly lower for procedural studies compared with medication trials (0.61 vs. 0.78, p = 0.008), as well as for studies with mean age <65 and trial size <1500 participants. There was no difference in IPR based on female authorship. Conclusions: LBCT can impact novel drug and device approval, intervention indications, and patient management. Nonetheless, most LBCT underenroll women, particularly, procedural LBCT. In 2021, sex-based enrollment disparities persist, highlighting the need to engage key stakeholders, including funding organizations, national governing bodies, editorial board members, and medical societies, in the creation of a coordinated strategic initiative to advance gender parity. These findings warrant further investigation to increase inclusion of women in trials, including potential enrollment requirements for consideration as LBCT by meeting organizers.

Invasive hemodynamics are equivocal for functional outcomes after MitraClip.

OBJECTIVES: To evaluate invasive hemodynamics in assessing MC therapy success as well as evaluate its effectiveness as a predictor of functional outcomes. BACKGROUND: Mitral regurgitation grade is a poor predictor of functional outcomes after a MitraClip. There is a paucity of data on invasive hemodynamics as a predictor of outcomes. METHODS: Sixty-nine patients underwent MC between 2015 and 2018 at the University of Minnesota Medical Center and were retrospectively analyzed. Invasive hemodynamics were performed before and after device deployment with transesophageal echocardiographic guidance. Statistical analysis was performed using STATA version 16. Student's t test was used for continuous variables and Pearson's chi-squared test for categorical variables. Mann-Whitney test was performed for continuous variables where data were not normally distributed. Logistic and linear regression were used to investigate relationships between variables and outcomes. RESULTS: A total of 69 patients were included in the study. The mean age was 83 (75-87) years and 38 (55%) were male. Eighty-one percentage had >/= NYHA III symptoms. Eighty-seven percentage had severe MR. Pulmonary capillary wedge pressure was 20 (15-24). Overall, there was significant improvement in left atrial pressure including mean left atrial pressure index, MR, and NYHA class after MC (<.001). There was no significant association between invasive hemodynamics (including left atrial mean pressure index or its reduction rate) and functional outcomes (p = NS). MR grade was also not predictive of functional outcomes. CONCLUSION: Left atrial pressure may not be a significant predictor of functional outcomes, and, in isolation, may not be an improvement over MR grade.

The Murmur Online Learning Experience (MOLE) Curriculum Improves Medical Students' Ability to Correctly Identify Cardiac Murmurs.

Introduction: Physical examination skills are receiving less attention in curricula and clinical practice, being supplanted by imaging and other technologies. We developed an online module to introduce auscultation of common cardiac murmurs to second-year medical students. Methods: The Murmur Online Learning Experience (MOLE) curriculum focused on nine common, unique, or highly testable cardiac murmurs, chosen collaboratively by the authors. The curriculum consisted of (1) a nine-item multiple-choice pretest containing a clinical vignette, a photo of stethoscope location, and an auditory clip; (2) nine modules each containing a several-minute-long auditory clip and a written description (location, quality, radiation, change with exam maneuvers); and (3) a nine-item multiple-choice posttest, identical to the pretest but randomly ordered. All second-year medical students at the University of Louisville were given access to MOLE during their cardiovascular curriculum and given an incentive to complete the ungraded activity. Results: One hundred forty-seven (91.8%) students voluntarily completed the pretest and posttest. The mean pretest score was 3.76 out of 9 (SD = 1.77). The mean posttest score was 7.14 out of 9 (SD = 1.78). Paired t-test results demonstrated a p value of <.001. Discussion: An online murmur curriculum consisting of repetitive auditory murmurs and narrative description of murmurs improved second-year medical students' ability to correctly identify common cardiac murmurs. This method of learning murmurs via online curriculum is a practical and effective way to hone students' physical exam skills in the modern era.

Systematic screen of Schizosaccharomyces pombe deletion collection uncovers parallel evolution of the phosphate signal transduction pathway in yeasts.

The phosphate signal transduction (PHO) pathway, which regulates genes in response to phosphate starvation, is well defined in Saccharomyces cerevisiae. We asked whether the PHO pathway was the same in the distantly related fission yeast Schizosaccharomyces pombe. We screened a deletion collection for mutants aberrant in phosphatase activity, which is primarily a consequence of pho1(+) transcription. We identified a novel zinc finger-containing protein (encoded by spbc27b12.11c(+)), which we have named pho7(+), that is essential for pho1(+) transcriptional induction during phosphate starvation. Few of the S. cerevisiae genes involved in the PHO pathway appear to be involved in the regulation of the phosphate starvation response in S. pombe. Only the most upstream genes in the PHO pathway in S. cerevisiae (ADO1, DDP1, and PPN1) share a similar role in both yeasts. Because ADO1 and DDP1 regulate ATP and IP(7) levels, we hypothesize that the ancestor of these yeasts must have sensed similar metabolites in response to phosphate starvation but have evolved distinct mechanisms in parallel to sense these metabolites and induce phosphate starvation genes.