Cancer Treatment-Related Cardiovascular Toxicity in Gynecologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Improvements in early detection and treatment of gynecologic malignancies have led to an increasing number of survivors who are at risk of long-term cardiac complications from cancer treatment. Multimodality therapies for gynecologic malignancies, including conventional chemotherapy, targeted therapeutics, and hormonal agents, place patients at risk of cancer therapy-related cardiovascular toxicity during and following treatment. Although the cardiotoxicity associated with some female predominant cancers (eg, breast cancer) have been well recognized, there has been less recognition of the potential adverse cardiovascular effects of anticancer therapies used to treat gynecologic malignancies. In this review, the authors provide a comprehensive overview of the cancer therapeutic agents used in gynecologic malignancies, associated cardiovascular toxicities, risk factors for cardiotoxicity, cardiac imaging, and prevention strategies.

Diagnostic Cardiovascular Imaging and Therapeutic Strategies in Pregnancy: JACC Focus Seminar 4/5.

The prevalence of cardiovascular disease (CVD) in pregnancy, both diagnosed and previously unknown, is rising, and CVD is a leading cause of maternal morbidity and mortality. Historically, women of child-bearing potential have been underrepresented in research, leading to lasting knowledge gaps in the cardiovascular care of pregnant and lactating women. Despite these limitations, clinicians should be familiar with the safety of frequently used diagnostic and therapeutic interventions to adequately care for this at-risk population. This review, the fourth of a 5-part series, provides evidence-based recommendations regarding the use of common cardiovascular diagnostic tests and medications in pregnant and lactating women.

Sex Differences in COVID-19 Hospitalization and Mortality.

Background: To investigate sex differences in coronavirus disease 2019 (COVID-19) outcomes in a large Illinois-based cohort. Methods: A multicenter retrospective cohort study compared males versus females with COVID-19 infections from March 1, 2020, to June 21, 2020, in the Rush University System. We analyzed sex differences in rates of hospitalization, intensive care unit (ICU) admission, vasopressor use, endotracheal intubation, and death in this cohort. A multivariable model correcting for age and sum of comorbidities was used to explore associations between sex and COVID-19-related outcomes. Results: There were 8108 positive COVID-19 patients-4300 (53.0%) females and 3808 (47.0%) males. Males had higher rates of hospitalization (19% vs. 13%; p < 0.001), ICU transfer (8% vs. 4%; p < 0.001), vasopressor support (4% vs. 2%; p < 0.001), and endotracheal intubation (5% vs. 2%; p < 0.001). Of those who died, 92 were males and 64 were females (2% vs. 1%; p = 0.003). A multivariable model correcting for age and sum of comorbidities showed a significant association between male sex and mortality in the total cohort (odds ratio, 1.96; 95% confidence interval, 1.34-2.90; p = 0.001). Conclusion: Male sex was independently associated with death, hospitalization, ICU admissions, and need for vasopressors or endotracheal intubation, after correction for important covariates.

Sex-Based Considerations in the Evaluation of Chest Pain and Management of Obstructive Coronary Artery Disease.

PURPOSE OF REVIEW: Coronary artery disease (CAD) is a major cause of morbidity and mortality globally and poses a threat to both men and women across their lifespans. There is accumulating evidence to support that CAD may present differently in women and men, ranging from the clinical presentation, diagnosis, and management of the disease to underlying differences in the biological and pathophysiological mechanisms. This has called for an expansion of our conventional tools used in the diagnosis and management of obstructive CAD. Understanding these key sex differences will potentially help tailor our diagnostic and treatment strategies and provide equitable and optimal care to both men and women. RECENT FINDINGS: Numerous studies have consistently shown that women with CAD tend to be older, have a higher burden of co-morbidities, and experience worse outcomes compared to their male counterparts. Women tend to wait longer to seek medical care for cardiovascular symptoms and when they do, they are usually referred late in the disease process and treated less aggressively. Women are significantly underrepresented in most cardiovascular clinical trials, thereby creating an important limitation in the evidence base used for treating cardiovascular disease in women. In this review, we sought to describe the sex-based considerations in evaluation and management of obstructive CAD, underscore the mechanisms behind these considerations, and help develop a more personalized approach according to current paradigms.

Microvascular Disease and Small-Vessel Disease: The Nexus of Multiple Diseases of Women.

Microvascular disease, or small-vessel disease, is a multisystem disorder with a common pathophysiological basis that differentially affects various organs in some patients. The prevalence of small-vessel disease in the heart has been found to be higher in women compared with men. Additionally, other diseases prominently affecting women, including heart failure with preserved ejection fraction, Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension (PAH), endothelial dysfunction in diabetes, diabetic cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, may have a common etiologic linkage related to microvascular disease. To the best of our knowledge this is the first article to investigate this potential linkage. We sought to identify various diseases with a shared pathophysiology involving microvascular/endothelial dysfunction that primarily affect women, and their potential implications for disease management. Advanced imaging technologies, such as magnetic resonance imaging and positron-emission tomography, enable the detection and increased understanding of microvascular dysfunction in various diseases. Therapies that improve endothelial function, such as those used in PAH, may also be associated with benefits across the full spectrum of microvascular dysfunction. A shared pathology across multiple organ systems highlights the need for a collaborative, multidisciplinary approach among medical subspecialty practitioners who care for women with small-vessel disease. Such an approach may lead to accelerated research in diseases that affect women and their quality of life.

Review of Cardiovascular Drugs in Pregnancy.

Cardiovascular disease is now the leading cause of pregnancy-related deaths in the United States. Increasing maternal mortality in the United States underscores the importance of proper cardiovascular management. Significant physiological changes during pregnancy affect the heart's ability to respond to pathological processes such as hypertension and heart failure. These physiological changes further affect the pharmacokinetic and pharmacodynamic properties of cardiac medications. During pregnancy, these changes can significantly alter medication efficacy and metabolism. This article systematically reviews the literature on safety, efficacy, pharmacokinetics, and pharmacodynamics of cardiovascular drugs used for hypertension and heart failure during pregnancy and lactation. The 2017 American College of Cardiology/American Heart Association hypertension guidelines recommend transitioning pregnant patients to methyldopa, nifedipine, or labetalol. Heart failure medications, including beta-blockers, furosemide, and digoxin, are relatively safe and can be used effectively. Medications that block the renin angiotensin-aldosterone system have been shown to be beneficial in the general population; however, they are teratogenic and, therefore, contraindicated in pregnancy. Cardiovascular medications can also enter breast milk and, therefore, care must be taken when selecting drugs during the lactation period. A summary of the safety of drugs during pregnancy and lactation from an online resource, LactMed by the National Library of Medicine's TOXNET database, is included. High-risk pregnant patients with cardiovascular disease require a multispecialty team of doctors, including health care providers from obstetrics and gynecology, maternal fetal medicine, internal medicine, cardiovascular disease specialists, and specialized pharmacology expertise.

Heart Centers for Women: Historical Perspective on Formation and Future Strategies to Reduce Cardiovascular Disease.

Heart Centers for Women (HCW) developed as a response to the need for improved outcomes for women with cardiovascular disease (CVD). From 1984 until 2012, more women died of CVD every single year in comparison with men. Initially, there was limited awareness and sex-specific research regarding mortality or outcomes in women. HCW played an active role in addressing these disparities, provided focused care for women, and contributed to improvements in these gaps. In 2014 and 2015, death from CVD in women had declined below the level of death from CVD in comparison with men. Even though awareness of CVD in women has increased among the public and healthcare providers and both sex- and gender-specific research is currently required in all research trials, not all women have benefitted equally in mortality reduction. New strategies for HCW need to be developed to address these disparities and expand the current HCW model. The HCW care team needs to direct academic curricula on sex- and gender-specific research and care; expand to include other healthcare professionals and other subspecialties; provide new care models; address diversity; and include more male providers.

Sex Differences in Ischemic Heart Disease: Advances, Obstacles, and Next Steps.

Evolving knowledge of sex-specific presentations, improved recognition of conventional and novel risk factors, and expanded understanding of the sex-specific pathophysiology of ischemic heart disease have resulted in improved clinical outcomes in women. Yet, ischemic heart disease continues to be the leading cause of morbidity and mortality in women in the United States. The important publication by the Institute of Medicine titled "Women's Health Research-Progress, Pitfalls, and Promise," highlights the persistent disparities in cardiovascular disease burden among subgroups of women, particularly women who are socially disadvantaged because of race, ethnicity, income level, and educational attainment. These important health disparities reflect underrepresentation of women in research, with the resultant unfavorable impact on diagnosis, prevention, and treatment strategies in women at risk for cardiovascular disease. Causes of disparities are multifactorial and related to differences in risk factor prevalence, access to care, use of evidence-based guidelines, and social and environmental factors. Lack of awareness in both the public and medical community, as well as existing knowledge gap regarding sex-specific differences in presentation, risk factors, pathophysiology, and response to treatment for ischemic heart disease, further contribute to outcome disparities. There is a critical need for implementation of sex- and gender-specific strategies to improve cardiovascular outcomes. This review is tailored to meet the needs of a busy clinician and summarizes the contemporary trends, characterizes current sex-specific outcome disparities, delineates challenges, and proposes transformative solutions for improvement of the full spectrum of ischemic heart disease clinical care and research in women.