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Abstract Background Cardiovascular disease (CVD) is the leading cause of death globally for both men and women, yet women remain historically underrepresented in cardiovascular clinical trials (CV trials), despite facing a disproportionately high burden of morbidity and mortality in many forms of CVD. Purpose We aim to determine the representation of women across a broad range of CV trials. Methods The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data was extracted to identify the country of study, disease type, trial size, clinical intervention and age of the participants. We calculated the proportion of women and the ratio of number of females to male participants (F:M ratio) for each trial. The female participation to prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Results We identified 1,079 registered CV trials, which included 1,396,104 participants, of whom 571,641 (41.0%) were women. The median F:M ratio was significantly lower for studies on arrhythmia (0.5), coronary heart disease (CHD) (0.39), acute coronary syndrome (ACS) (0.32) and heart failure (HF) (0.51), but was higher for obesity (1.44) and pulmonary hypertension (PH) (2.86) CV trials. F:M ratio was higher for trials on lifestyle intervention (1.51) than for drug trials. PPRs were low for clinical trials on CHD (0.66), ACS (0.79), and stroke (0.74). There was a trend to increasing PPR from 2017 to 2023, p=0.056. Conclusion Representation of women in CV trials varies by disease state, region, intervention, and sponsor type. Better understanding of reasons for these differences may enable more tailored interventions to improve representation of women globally and across therapeutic areas.Figure 1 Figure 2

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome, predominantly affecting women. Psychological distress is common pre- and post-SCAD, yet sex-specific patterns remain understudied. This cross-sectional study aimed to examine sex differences in the psychological distress of patients with SCAD. METHODS: Adult patients diagnosed with SCAD within the past 3 years, confirmed by coronary angiography, were recruited from 6 Canadian hospitals between April 2022 and January 2025. Participants completed questionnaires assessing sociodemographics and validated measures of psychological distress: Patient Health Questionnaire-9 for depression, Generalized Anxiety Disorder-7 for generalized anxiety, Cardiac Anxiety Questionnaire for cardiac-related anxiety, and PTSD Checklist-5 for posttraumatic stress symptoms. Sex differences were analyzed using t tests for continuous variables and χ 2 tests for categorical variables. Multivariable linear regression models assessed the association between sex and psychological distress, adjusting for age, pre-SCAD mental health diagnosis, and employment status. RESULTS: Among 326 patients (92.9% women; mean age=53.3±11.1 years), women reported higher rates of preexisting mental health conditions (29.2% versus 8.7%; P =0.035). Post-SCAD women reported higher mean scores than men on the Patient-Health-Questionnaire-9, Cardiac-Anxiety-Questionnaire, and PTSD Checklist-5 (all P <0.05). Female sex was associated with greater depressive (B=2.94; P =0.010), cardiac anxiety (B=7.09; P =0.008), and posttraumatic stress symptoms (B=5.94; P =0.048) after adjustment. Clinically significant symptoms were more common in women versus men: 25.1% versus 0% (depression), 21.5% versus 4.4% (anxiety), 54.8% versus 26.1% (cardiac anxiety), and 15.5% versus 0% (posttraumatic stress). CONCLUSIONS: Both women and men experience clinically significant cardiac anxiety following SCAD, but women report a greater psychological burden, including more preexisting mental health conditions and twice the distress after SCAD. These results underscore the importance of routine psychological screening and timely intervention to support mental health and recovery outcomes, particularly among women.

Background: Spontaneous Coronary Artery Dissection (SCAD) is a cause of acute coronary syndrome, particularly among women, and is associated with psychological distress, including depression, anxiety, and post-traumatic stress (PTSD) symptoms. Fibromuscular dysplasia (FMD), a vascular condition that alters the arteries, is often found in patients with SCAD, adding complexity and uncertainty with a second serious diagnosis. This study examined the differences in mental health symptoms between SCAD survivors with and without FMD to better understand their unique psychosocial needs and inform interventions to enhance patient outcomes. Methods: Patients diagnosed with SCAD within the past 3 years were recruited from 6 Canadian cardiac hospitals. Participants completed questionnaires assessing socio-demographics, comorbidities, and validated psychological measures, including Patient Health Questionnaire-9 (PHQ-9) for depression, Generalized Anxiety Disorder-7 (GAD-7) for generalized anxiety, Cardiac Anxiety Questionnaire (CAQ) for cardiac-related anxiety, and PTSD Checklist (PCL-5) for PTSD symptoms. Differences in mental health outcomes between SCAD survivors with and without FMD were analyzed using t-tests for continuous variables and chi-square tests for categorical variables. Results: The study included 326 participants (92.9% female; mean age 53.3 years), with 67 participants (20.6%) having a confirmed diagnosis of FMD at the time of questionnaire completion (39.3% FMD at study completion). Post-SCAD, patients with FMD reported significantly higher scores than patients without FMD on the GAD-7 (6.4±5.9 vs. 4.7±4.9, p = .028), CAQ (29.9±13.1 vs. 26.0±12.3, p = .023), and PCL-5 (17.2±15.4 vs. 13.3± 14.0, p = .048). The proportion of SCAD survivors with FMD scoring in the clinically diagnostic range was significantly higher than those in patients without FMD: 32.8% vs. 20.8% for depression, 31.3% vs. 17.4% for anxiety, 64.2% vs. 49.2% for cardiac anxiety, and 25.4% vs. 11.6% for PTSD (all p < .05). Conclusions: Our findings suggest that SCAD survivors with comorbid FMD experience significantly higher distress —depression, generalized anxiety, cardiac-related anxiety, and PTSD symptoms—compared to those without FMD. Longitudinal research is needed to explore the role of these mental health concerns in long-term mental health and cardiac outcomes. Enhanced psychological interventions for those with FMD may be required.

Importance Cardiovascular (CV) disease is the leading cause of death globally for both men and women, yet women remain historically underrepresented in CV clinical trials, despite facing a disproportionately high burden of morbidity and mortality in many forms of CV disease. Objective To determine the representation of women across a broad range of CV trials. Evidence Review The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data were extracted to identify the country of study, disease type, trial size, clinical intervention, and age of the participants. The proportion of women and the ratio of number of female to male participants (F:M ratio) were calculated for each trial. The women’s participation:prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Findings A total of 1079 registered CV trials were identified, including 1 396 104 participants, of whom 571 641 (41.0%) were women. The F:M ratio was significantly lower for studies on arrhythmia (median [IQR], 0.5), coronary heart disease (median [IQR], 0.39 [0.33-0.70]), acute coronary syndrome (median [IQR], 0.32 [0.24-0.51]), and heart failure (median [IQR], 0.51 [0.32-0.87]) but higher for obesity (median [IQR], 1.44 [1.08-4.50]) and pulmonary hypertension (median [IQR], 2.86 [1.50-3.97]) trials. The F:M ratio was higher for trials on lifestyle interventions (median [IQR], 1.51 [0.77-3.24]) than for drug trials. PPRs were low for clinical trials on coronary heart disease (median [IQR], 0.66 [0.50-0.86]), acute coronary syndrome (median [IQR], 0.79 [0.51-0.87]), and stroke (median [IQR], 0.74 [0.61-0.95]). Representation of women in CV trials varied by disease state, region, intervention, and sponsor type. Conclusions and Relevance These findings highlight both progress and persistent challenges in representation of women within CV trials. These gaps not only limit the generalizability of trial outcomes but also perpetuate inequities in evidence-based care for women with CV conditions.

Background: Regadenoson is a selective A2A receptor agonist that is administered as a fixed dose bolus with rapid onset (∼30 sec), and short duration (∼2-4 min) of action. The aim of this study was to evaluate the feasibility of real-time myocardial contrast echocardiography (MCE) for quantification of coronary flow reserve (CFR) in healthy humans during regadenoson vasodilator stress. Methods: Fifteen subjects [3 males, age: 45.8±5.2 years, BMI 23.8±2.3 kg/m2] with normal LV wall motion and no CAD underwent real-time MCE. Three standard apical LV views were acquired during a continuous intravenous (IV) infusion of Definity (1.3 ml in 60 cc 0.9% saline at 200 ml/hr) at rest and during vasodilator stress (regadenoson 400 ug IV bolus). Following transient microbubble destruction, microbubble velocity (β, sec -1 ), myocardial blood volume (A, dB) and myocardial blood flow (MBF, dB/sec) were determined. Videodensitometric quantification using a 16-segment model at end-systole was performed off-line. Results: Quantification of reserve parameters was feasible in all (15/15) patients, 188/240 segments (78%)[82%, 80% and 70% of 4-, 2-, 3-chambers apical views] and 43/45 (95%) coronary territories [one each of Cx and RCA territories were not feasible]. Augmentation from baseline to vasodilator stress was observed for both ß (s -1 ) [0.65± 0.25 vs 0.79± 0.21, P=0.031] and MBF (dB/sec) [2.85± 1.43 vs 4.65± 2.06, P= 0.002], however A (dB) did not change [06.62± 2.57 vs 6.79±2.1, P=0.463]. CFR measurements from all views were similar (Fig 1). There was no significant difference between CFR measured in the 3 coronary territories, although some heterogeneity was noted in the posterior circulation CFR (Fig 2). Conclusion: Real-time MCE during Regadenoson vasodilator stress is feasible, and is a useful technique for the rapid noninvasive quantification of CFR in healthy humans.

Cardiovascular disease remains the leading cause of death in women. Given accumulating evidence on sex- and gender-based differences in cardiovascular disease development and outcomes, the need for more effective approaches to screening for risk factors and phenotypes in women is ever urgent. Public health surveillance and health care delivery systems now continuously generate massive amounts of data that could be leveraged to enable both screening of cardiovascular risk and implementation of tailored preventive interventions across a woman’s life span. However, health care providers, clinical guidelines committees, and health policy experts are not yet sufficiently equipped to optimize the collection of data on women, use or interpret these data, or develop approaches to targeting interventions. Therefore, we provide a broad overview of the key opportunities for cardiovascular screening in women while highlighting the potential applications of artificial intelligence along with digital technologies and tools.

Although cardiovascular disease (CVD) is the leading cause of mortality in women globally, cardiovascular care for women remains suboptimal, with poorer outcomes than for men. During the past two decades, there has been an incremental increase in research and publications on CVD in women, addressing sex-specific risk factors, symptoms, pathophysiology, treatment, prevention and identification of inequities in care. Nonetheless, once women have manifested CVD, they continue to have increasingly worse outcomes than men. An approach to addressing these global disparities has been the worldwide establishment of specialised centres providing cardiovascular care for women. These women’s heart centres (WHCs) allow a comprehensive approach to the cardiovascular care of women across the lifespan. The purpose of this article is to define the need for and role of these specialised centres by outlining sex-specific gaps in CVD care, and to provide guidance on components within WHCs that may be considered when establishing such programmes.

OBJECTIVES: To describe the development and initial results of an examination and certification process assessing competence in critical care echocardiography. DESIGN: A test writing committee of content experts from eight professional societies invested in critical care echocardiography was convened, with the Executive Director representing the National Board of Echocardiography. Using an examination content outline, the writing committee was assigned topics relevant to their areas of expertise. The examination items underwent extensive review, editing, and discussion in several face-to-face meetings supervised by National Board of Medical Examiners editors and psychometricians. A separate certification committee was tasked with establishing criteria required to achieve National Board of Echocardiography certification in critical care echocardiography through detailed review of required supporting material submitted by candidates seeking to fulfill these criteria. SETTING: The writing committee met twice a year in person at the National Board of Medical Examiner office in Philadelphia, PA. SUBJECTS: Physicians enrolled in the examination of Special Competence in Critical Care Electrocardiography (CCEeXAM). MEASUREMENTS AND MAIN RESULTS: A total of 524 physicians sat for the examination, and 426 (81.3%) achieved a passing score. Of the examinees, 41% were anesthesiology trained, 33.2% had pulmonary/critical care background, and the majority had graduated training within the 10 years (91.6%). Most candidates work full-time at an academic hospital (46.9%). CONCLUSIONS: The CCEeXAM is designed to assess a knowledge base that is shared with echocardiologists in addition to that which is unique to critical care. The National Board of Echocardiography certification establishes that the physician has achieved the ability to independently perform and interpret critical care echocardiography at a standard recognized by critical care professional societies encompassing a wide spectrum of backgrounds. The interest shown and the success achieved on the CCEeXAM by practitioners of critical care echocardiography support the standards set by the National Board of Echocardiography for testamur status and certification in this imaging specialty area.

Biological sex is increasingly recognized as a critical determinant of health and disease, particularly relevant to the topical COVID-19 pandemic caused by the SARS-CoV-2 coronavirus. Epidemiological data and observational reports from both the original SARS epidemic and the most recent COVID-19 pandemic have a common feature: males are more likely to exhibit enhanced disease severity and mortality than females. Sex differences in cardiovascular disease and COVID-19 share mechanistic foundations, namely, the involvement of both the innate immune system and the canonical renin-angiotensin system (RAS). Immunological differences suggest that females mount a rapid and aggressive innate immune response, and the attenuated antiviral response in males may confer enhanced susceptibility to severe disease. Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19, either to serve as a protective mechanism by deactivating the RAS or as the receptor for viral entry, respectively. Loss of membrane ACE2 and a corresponding increase in plasma ACE2 are associated with worsened cardiovascular disease outcomes, a mechanism attributed to a disintegrin and metalloproteinase (ADAM17). SARS-CoV-2 infection also leads to ADAM17 activation, a positive feedback cycle that exacerbates ACE2 loss. Therefore, the relationship between cardiovascular disease and COVID-19 is critically dependent on the loss of membrane ACE2 by ADAM17-mediated proteolytic cleavage. This article explores potential mechanisms involved in COVID-19 that may contribute to sex-specific susceptibility focusing on the innate immune system and the RAS, namely, genetics and sex hormones. Finally, we highlight here the added challenges of gender in the COVID-19 pandemic.