Breast Arterial Calcifications on Mammography: Awareness and Reporting Preferences Amongst Referring Physicians in Canada.

Purpose: Breast arterial calcifications (BAC) on mammography have been correlated with increased cardiovascular risk. The Canadian Society of Breast Imaging released a position statement on BAC reporting in January 2023. This study evaluates the awareness of the clinical significance of BAC and reporting preferences of referring physicians in Canada. Methods: A 15-question survey was distributed to Canadian physicians who may review mammography results via regional and subspecialty associations and on social media following local institutional ethical approval. Responses were collected over 10 weeks from February to April 2023. Results: Seventy-two complete responses were obtained. We are unable to determine the response rate, given the means of distribution. Only 17% (12/72) of responding physicians were previously aware of the association between BAC and increased cardiovascular risk, and 51% (37/72) preferred the inclusion of BAC in the mammography report. Fifty-six percent (40/72) indicated that BAC reporting would prompt further investigation, and 63% (45/72) would inform patients that their mammogram showed evidence of BAC. Sixty-nine percent (50/72) would find grading of BAC beneficial and 71% (51/72) agreed that there is a need for national guidelines. Conclusion: Less than a quarter of responding Canadian referring physicians were previously aware of the association between BAC and cardiovascular risk, although half of respondents indicated a preference for BAC reporting on mammography. Most participating physicians would inform their patients of the presence of BAC and consider further cardiovascular risk management. There was consensus that a national BAC grading system and clinical management guidelines would be beneficial.

Shared Lifestyle-Related Risk Factors of Cardiovascular Disease and Cancer: Evidence for Joint Prevention.

Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide and are the major focus of the World Health Organization's joint prevention programs. While, diverse diseases, CVD and cancer, have many similarities. These include common lifestyle-related risk factors and shared environmental, metabolic, cellular, inflammatory, and genetic pathways. In this review, we will discuss the shared lifestyle-related and environmental risk factors central to both diseases and how the strategies commonly used to prevent atherosclerotic vascular disease can be applied to cancer prevention.

Low Serum Testosterone in Men with Newly Diagnosed Androgen-Deprivation Therapy-Naïve Prostate Cancer and Its Relationship to Cardiovascular Risk Factors: A RADICAL-PC Substudy.

PURPOSE: Cardiovascular disease is a common cause of death in prostate cancer patients. Low testosterone is associated with increased cardiovascular risk in the general male population. We investigated the relationship between serum testosterone, cardiovascular disease and risk factors in androgen-deprivation therapy-naïve prostate cancer patients. MATERIALS AND METHODS: We performed a cross-sectional analysis of a subgroup of 1,326 androgen-deprivation therapy-naïve men from RADICAL-PC (Role of Androgen-Deprivation Therapy In CArdiovascular Disease-A Longitudinal Prostate Cancer study) in whom serum testosterone was measured at baseline. RADICAL-PC is a prospective multicenter cohort study of men (2,565) enrolled within 1 year of prostate cancer diagnosis, or within 6 months of commencing androgen-deprivation therapy for the first time. Cardiovascular risk factors, cancer characteristics and total serum testosterone were collected at baseline. Low testosterone was defined as total serum testosterone <11 nmol/L (<320 ng/dL). A Framingham cardiovascular risk score ≥15 was considered high risk for future cardiovascular events. We performed logistic regression to calculate odds ratios for the association between testosterone and cardiovascular risk. RESULTS: Among 1,326 participants (median age 67 years, range 45-93), 553 (42%) had low testosterone. Low testosterone was associated with existing cardiovascular disease, diabetes, elevated hemoglobin A1c, obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension and Framingham score >15. Among patients with low testosterone, the odds ratio for high cardiovascular risk was 1.33 (1.02-1.73) after adjusting for ethnicity, education, alcohol use, cancer characteristics, physical activity and body mass index. CONCLUSIONS: Among androgen-deprivation therapy-naïve prostate cancer patients, low testosterone is common and associated with increased cardiovascular risk factors.

Cardiovascular Risk in Men with Prostate Cancer: Insights from the RADICAL PC Study.

PURPOSE: We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy. MATERIALS AND METHODS: We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores. RESULTS: Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/m2 or greater, 24% low levels of physical activity, mean handgrip strength was 37.3 kg and 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom androgen deprivation therapy was planned had higher Framingham risk scores than those not intending to receive androgen deprivation therapy, and this risk was abolished after adjustment for confounders. CONCLUSIONS: Two-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

Exercise Training for Cancer Survivors.

OPINION STATEMENT: Cardiovascular diseases are a common cause of morbidity and mortality in cancer survivors. Furthermore, some cancer therapies are now being increasingly recognized to have negative cardiovascular effects, or cardiotoxicity. Exercise therapy has been found to improve cardiorespiratory fitness in patients with cancer as well as attenuate the cardiotoxic effects of cancer therapy. It is the centerpiece for cardiac and pulmonary rehabilitation programs. It is also an important component in cardio-oncology rehabilitation. Exercise is generally safe, and its benefit is observed when started as soon as the diagnosis of cancer and throughout cancer survivorship.

Parenting a 6-Year Old Is Not What I Planned in Retirement: Trauma and Stress among Grandparents Due to the Opioid Crisis.

There is little research about trauma, financial stress, and social service needs emanating from the experience of parenting grandchildren caused by the opioid crisis in the United States. We conducted a qualitative study with 15 grandparents who currently or in the past had custodial care of their grandchildren. We also interviewed nine issue-related stakeholders in Eastern Massachusetts. Specific inquiries centered on events leading up to a change in guardianship, stressors related to legal, financial, and family issues, and system-wide response to the grandparents' needs. Results indicate that the opioid crisis presents distinct challenges for the grandparent-led families and for the systems that serve the new family arrangement. Crisis triggers a change in guardianship and continues throughout the years. The continued crises stem from events related to the parent's opioid use disorder (OUD) and from expenses related to raising a young family, especially when the grandchild has adverse childhood experiences. Our analysis shows that systems break down on a number of levels, and the fluidity of custodial arrangements due to parents' OUD status does not map onto existing support or benefit systems. Policy responses must focus on the immediate and long-term needs of grandparent caretakers, especially since the opioid crisis is likely to continue.

Clinically Relevant Physical Benefits of Exercise Interventions in Breast Cancer Survivors.

Evidence is currently limited for the effect of exercise on breast cancer clinical outcomes. However, several of the reported physical benefits of exercise, including peak oxygen consumption, functional capacity, muscle strength and lean mass, cardiovascular risk factors, and bone health, have established associations with disability, cardiovascular disease risk, morbidity, and mortality. This review will summarize the clinically relevant physical benefits of exercise interventions in breast cancer survivors and discuss recommendations for achieving these benefits. It will also describe potential differences in intervention delivery that may impact outcomes and, lastly, describe current physical activity guidelines for cancer survivors.

Complementary and alternative medicine among veterans and military personnel: a synthesis of population surveys.

BACKGROUND: Recent reports reinforce the widespread interest in complementary and alternative medicine (CAM), not only among military personnel with combat-related disorders, but also among providers who are pressed to respond to patient demand for these therapies. However, an understanding of utilization of CAM therapies in this population is lacking. OBJECTIVE: The goals of this study are to synthesize the content of self-report population surveys with information on use of CAM in military and veteran populations, assess gaps in knowledge, and suggest ways to address current limitations. RESEARCH DESIGN: The research team conducted a literature review of population surveys to identify CAM definitions, whether military status was queried, the medical and psychological conditions queried, and each specific CAM question. Utilization estimates specific to military/veterans were summarized and limitations to knowledge was classified. RESULTS: Seven surveys of CAM utilization were conducted with military/veteran groups. In addition, 7 household surveys queried military status, although there was no military/veteran subgroup analysis. Definition of CAM varied widely limiting cross-survey analysis. Among active duty and Reserve military, CAM use ranged between 37% and 46%. Survey estimates do not specify CAM use that is associated with a medical or behavioral health condition. CONCLUSIONS: Comparisons between surveys are hampered due to variation in methodologies. Too little is known about reasons for using CAM and conditions for which it is used. Additional information could be drawn from current surveys with additional subgroup analysis, and future surveys of CAM should include military status variable.

Payment-related barriers to medications for opioid use disorder: A critical review of the literature and real-world application.

BACKGROUND: The national opioid crisis continues to intensify, despite the fact that opioid use disorder (OUD) is treatable and opioid overdose deaths are preventable through first-line treatment with medications for opioid use disorder (MOUD). This study identifies and categorizes payment-related barriers that impact MOUD access and retention from both the provider and patient perspectives and provides insight into how these barriers can be addressed. METHODS: We performed a critical review of the literature (peer-reviewed studies and relevant documents from the gray literature) to identify payment-related access and retention barriers to MOUD. We used the results of this review to develop an analytic framework to understand how payment impacts MOUD access and retention for both providers and patients. In addition, we reviewed action plans developed by Massachusetts communities that participated in the Healing Communities Study (HCS) to analyze which payment-related barriers were addressed through the study. RESULTS: We identified 18 payment-related barriers that patients or providers face when initiating or continuing MOUD with either methadone or buprenorphine in Opioid Treatment Programs (OTP) and non-OTP settings. Patient-related barriers mainly relate to health insurance coverage or the design of health plans (e.g., cost sharing, covered benefits) resulting in direct (medical and non-medical) and indirect costs that can affect both access and retention, especially as they relate to services provided in OTPs. Provider-related barriers include low reimbursement and administrative burden and are most likely to impact access to MOUD. Evidence-based strategies to expand MOUD as part of the HCS in Massachusetts targeted about half of the patient and provider payment-related barriers identified. CONCLUSION: Patients and providers face an array of payment-related barriers that impact access to and retention on MOUD, most of which relate to inadequate health insurance coverage, features of health plans, and key federal and state policies. As new regulatory policies are enacted that expand access to MOUD, such as greater flexibility in OTPs and MOUD delivered via telehealth, it will be important to align these delivery changes with payment reform involving payers, providers, and policymakers.

Mobile clinics for opioid use disorders: What they do and how they do it. A qualitative analysis.

INTRODUCTION: People with substance use disorders (SUD) face many barriers to receiving evidence-based treatments including access to and cost of treatment. People who use drugs face stigma that limits access to traditional office-based clinics. With the goal of reducing morbidity and mortality, mobile clinics reduce many of these barriers by providing harm reduction and on-demand low-threshold medical care. METHODS: In 2020 Massachusetts Department of Public Health (DPH) Mobile Addiction Services Program expanded a program called Community Care in Reach building on its success in reducing barriers to care and increasing patient encounters. In the current evaluation we conducted site visits to the four new mobile clinics and conducted one individual semi-structured provider interview at each of the four clinics. In addition, we supported a monthly learning collaborative of staff in four agencies involved with this initiative. The current evaluation used the RE-AIM framework to analyze the implementation of the mobile clinics. RESULTS: Clinicians described many challenges and opportunities. The typical patient is unhoused, having a substance use disorder, and disconnected from traditional pathways to care. Clinicians are able to initiate people on buprenorphine largely due to the trust they establish with patients. Referral networks are facilitated by established community linkages. The philosophy of care is patient-centered. Mobile clinics provide a wide range of healthcare services including harm reduction, although finding a location to park and relations with police can be challenging. The workflow is uneven due to the model that is built on unscheduled visits. CONCLUSION: This study provides insight into how mobile clinics address the gaps in care for persons with OUD and fatal opioid overdoses. Harm reduction services are a critical intervention and financial sustainability of mobile clinics has to be tested.

Effect of long-term tafamidis treatment on health-related quality of life in patients with transthyretin amyloid cardiomyopathy.

AIMS: To evaluate the effect of long-term tafamidis treatment on health-related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension (LTE) study. METHODS AND RESULTS: We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) and clinical summary (KCCQ-CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR-ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR-ACT and tafamidis for 30 months in the LTE study. In ATTR-ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6- to 7-point reduction in least squares (LS) mean (standard error) KCCQ-OS and KCCQ-CS scores at month 30 (-6.25 [1.53] and -7.48 [1.39]), with little or no further decline over the next 30 months (-5.92 [1.77] and -9.21 [1.88] at month 60). Patients who received placebo in ATTR-ACT had a 20-point reduction in LS mean KCCQ-OS and KCCQ-CS scores at month 30 (-19.60 [1.94] and -19.90 [2.01]), but the decline slowed after initiating tafamidis (-24.70 [3.04] and -25.30 [3.36] at month 60). CONCLUSION: Tafamidis reduced HRQoL decline in patients with ATTR-CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR-ACT, tafamidis reduced the decline in HRQoL during the LTE study.

The effect of long-term tafamidis treatment on quality of life in people with transthyretin amyloid cardiomyopathy (ATTR-CM): A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This summary explains some results of a study called ATTR-ACT and its ongoing long-term extension study that were published in the European Journal of Heart Failure. The purpose of ATTR-ACT was to find out if a drug called tafamidis is an effective treatment for people with a heart condition called transthyretin amyloid cardiomyopathy (ATTR-CM). People took tafamidis or placebo for up to 2.5 years in ATTR-ACT (the initial study). A placebo looks like the study medicine but does not contain any active ingredients. After people completed the initial study, they could take part in the extension study. An extension study allows people to continue receiving treatment after the original clinical study ends and helps researchers understand how well a treatment works over a longer time period. This extension study allows people to receive tafamidis for up to an additional 5 years. People who took placebo in the initial study now receive tafamidis. People who took tafamidis in the initial study continue tafamidis treatment. Researchers looked at changes in peoples' ability to enjoy life ('quality of life') and heart failure symptoms since they started ATTR-ACT. Results are available for the first 2.5 years of the extension study. WHAT ARE THE KEY TAKEAWAYS?: During the initial study, there was less worsening of quality of life and heart failure symptoms in people who took tafamidis compared to people who took placebo. In the extension study, quality of life and heart failure symptoms were maintained or nearly maintained in people who took tafamidis in the initial study. In people who started tafamidis in the extension study, quality of life and heart failure symptoms continued to worsen, but the worsening slowed down. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Tafamidis slows the worsening of quality of life and heart failure symptoms in people with ATTR-CM. People with ATTR-CM should start treatment early to receive the most benefit.Clinical Trial Registration: NCT01994889 (ATTR-ACT) (ClinicalTrials.gov).

Atrial Fibrillation as a Prognostic Factor for All-Cause Mortality in Patients With Transthyretin Amyloid Cardiomyopathy.

Background: Atrial fibrillation/atrial flutter (AF/AFL) are common manifestations of transthyretin amyloid cardiomyopathy (ATTR-CM) but have not been found to be predictive of mortality. Objectives: This analysis aimed to examine whether baseline or historical AF/AFL at enrollment was prognostic for all-cause mortality. Methods: In the ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), a 30-month study of tafamidis vs placebo for ATTR-CM, AF/AFL was evaluated as an independent prognostic factor for all-cause mortality using Cox proportional hazards modelling. The impact of AF/AFL on tafamidis efficacy was explored by adding an interaction term for AF/AFL status and treatment. Results: ATTR-ACT enrolled 441 patients with ATTR-CM (median age 75 years; 90% male); 314 (71.2%) had baseline or historical AF/AFL at enrollment. AF/AFL was an independent prognostic factor for all-cause mortality after adjusting for covariates prespecified in the ATTR-ACT model (treatment, genotype, New York Heart Association functional class; HR: 0.550; 95% CI: 0.368-0.821) but not in an expanded stepwise model selection analysis including 23 covariates (blood urea nitrogen and N-terminal pro-B-type natriuretic peptide concentration, 6-minute walk test distance, genotype, treatment, and global longitudinal strain were prognostic [P < 0.01]). The interactions between tafamidis treatment and AF/AFL for all-cause mortality (P = 0.33) and changes in Kansas City Cardiomyopathy Questionnaire Overall Summary score (P = 0.83) and 6-minute walk test distance (P = 0.82) were not significant. Conclusions: In ATTR-ACT, baseline or historical AF/AFL was prognostic for all-cause mortality in analyses with limited adjustment but not after accounting for additional indicators of disease severity. Baseline or historical AF/AFL did not impact the efficacy of tafamidis treatment. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).

Moving towards establishing centres of excellence in cardiac amyloidosis: an International Cardio-Oncology Society statement.

The prevalence of amyloidosis has been increasing, driven by a combination of improved awareness, evolution of diagnostic pathways, and effective treatment options for both transthyretin and light chain amyloidosis. Due to the complexity of amyloidosis, centralised expert providers with experience in delineating the nuances of confirmatory diagnosis and management may be beneficial. There are many potential benefits of a centre of excellence designation for the treatment of amyloidosis including recognition of institutions that have been leading the way for the optimal treatment of this condition, establishing the expectations for any centre who is engaging in the treatment of amyloidosis and developing cooperative groups to allow more effective research in this disease space. Standardising the expectations and criteria for these centres is essential for ensuring the highest quality of clinical care and community education. In order to define what components are necessary for an effective centre of excellence for the treatment of amyloidosis, we prepared a survey in cooperation with a multidisciplinary panel of amyloidosis experts representing an international consortium. The purpose of this position statement is to identify the essential elements necessary for highly effective clinical care and to develop a general standard with which practices or institutions could be recognised as a centre of excellence.

The role of health plans in addressing the opioid crisis: A qualitative study.

INTRODUCTION: Health plans are key players in substance use treatment in the United States, and the opioid crisis presents new challenges for them. This article is part of the HEALing Communities Study (HCS) funded by NIH, which seeks to facilitate communities' adoption of activities that might reduce overdose deaths, including overdose prevention education and naloxone distribution, medication for opioid use disorder, and safer opioid prescribing. We examine how health plans in one state (Massachusetts) are adapting to encourage and sustain activities that help communities to address opioid use disorder (OUD). METHODS: We conducted semi-structured interviews with managers of behavioral health services at eight health plans in Massachusetts that that have Medicare, Medicaid, and commercial lines of business. Two plans in this sample contract with a specialized behavioral health organization ("carve-out"). The interviewees also completed a survey on policies regarding access to treatment and opioid prescribing. Interviews were recorded and transcribed and analyzed using thematic analysis. Analysis of the data included intended influence of the policies at three levels: member level (micro), group or community level (meso), and system or institutional level (macro). RESULTS: All health plans developed strategies to increase access to treatment for OUD, primarily through eliminating or decreasing cost-sharing, eliminating pre-authorization for MOUD, and increasing supply of providers. Health plans encourage qualified practitioners to offer MOUD, but most do not provide incentives or training. Identifying high risk populations is a focus of health plans in this sample. Naloxone is a covered benefit in all health plans, although with variation in monthly limits and cost-sharing. Most health plans take measures to influence opioid prescribing. Health plans' activities are predominately aimed at the micro (member) level with little ability to influence at the macro (wider system-level changes). CONCLUSION: This study provides insight into how health plans develop strategies to address the rise in OUD and fatal opioid overdoses, many of which are key in the HCS initiative. How active a role health plans play in addressing the opioid crisis varies, even within the insurance industry in one state (Massachusetts).

A Comprehensive Multidisciplinary Diagnostic Algorithm for the Early and Efficient Detection of Amyloidosis.

Amyloidosis is a rare protein misfolding disease caused by the accumulation of amyloid fibrils in various tissues and organs. There are different subtypes of amyloidosis, with light chain (AL) amyloidosis being the most common. Amyloidosis is notoriously difficult to diagnose because it is clinically heterogeneous, no single test is diagnostic for the disease, and diagnosis typically involves multiple specialists. Here, we propose an integrated, multidisciplinary algorithm for efficiently diagnosing amyloidosis. Drawing on research from several medical disciplines, we have combined clinical decisions and best practices into a comprehensive algorithm to facilitate the early detection of amyloidosis. Currently, many patients are diagnosed more than 6 months after symptom onset, yet early diagnosis is the major predictor of survival. Our algorithm aims to shorten the time to diagnosis with efficient sequencing of tests and minimizing uninformative investigations. We also recommend typing and staging of confirmed amyloidosis to guide treatment. By reducing time to diagnosis, our algorithm could lead to earlier and more targeted treatment, ultimately improving prognosis and survival.

Protocol for the implementation of a statewide mobile addiction program.

With overdose deaths increasing, improving access to harm reduction and low barrier substance use disorder treatment is more important than ever. The Community Care in Reach® model uses a mobile unit to bring both harm reduction and clinical care for addiction to people experiencing barriers to office-based care. These mobile units provide many resources and services to people who use drugs, including safer consumption supplies, naloxone, medication for substance use disorder treatment, and a wide range of primary and preventative care. This protocol outlines the evaluation plan for the Community in Care® model in MA, USA. Using the RE-AIM framework, this evaluation will assess how mobile services engage new and underserved communities in addiction services and primary and preventative care.

The Burden of Uncontrolled Cardiovascular Risk Factors in Men With Prostate Cancer: A RADICAL-PC Analysis.

Background: Cardiovascular disease (CVD) incidence is higher in men with prostate cancer (PC) than without. Objectives: We describe the rate and correlates of poor cardiovascular risk factor control among men with PC. Methods: We prospectively characterized 2,811 consecutive men (mean age 68 ± 8 years) with PC from 24 sites in Canada, Israel, Brazil, and Australia. We defined poor overall risk factor control as ≥3 of the following: suboptimal low-density lipoprotein cholesterol (>2 mmol/L if Framingham Risk Score [FRS] ≥15 and ≥3.5 mmol/L if FRS <15), current smoker, physical inactivity (<600 MET min/wk), suboptimal blood pressure (BP) (≥140/90 mm Hg if no other risk factors, systolic BP ≥120 mm Hg if known CVD or FRS ≥15, and ≥130/80 mm Hg if diabetic), and waist:hip ratio >0.9. Results: Among participants (9% with metastatic PC and 23% with pre-existing CVD), 99% had ≥1 uncontrolled cardiovascular risk factor, and 51% had poor overall risk factor control. Not taking a statin (odds ratio [OR]: 2.55; 95% CI: 2.00-3.26), physical frailty (OR: 2.37; 95% CI: 1.51-3.71), need for BP drugs (OR: 2.36; 95% CI: 1.84-3.03), and age (OR per 10-year increase: 1.34; 95% CI: 1.14-1.59) were associated with poor overall risk factor control after adjustment for education, PC characteristics, androgen deprivation therapy, depression, and Eastern Cooperative Oncology Group functional status. Conclusions: Poor control of modifiable cardiovascular risk factors is common in men with PC, highlighting the large gap in care and the need for improved interventions to optimize cardiovascular risk management in this population.

A case of Starr-Edwards valve thrombosis in pregnancy.

Starr-Edwards ball-in-cage prosthetic heart valves, although durable, are associated with a particularly high rate of thromboembolic complications. This valve is seldom used in North America, and is certainly not the valve of choice in a woman of childbearing age. Few reports exist from the 1970s of thrombotic complications in pregnant women with Starr-Edwards prostheses, and the optimal management strategy for such valves is unclear. Here, the case is reported of a 31-year-old woman with a Starr-Edwards prosthesis in the mitral position who was transferred to the authors' center at six weeks' gestation with pulmonary edema. Transthoracic echocardiography demonstrated thrombosis of the prosthetic valve, with a mean gradient of 23 mmHg. When treated initially with intravenous heparin and furosemide the patient improved significantly; however, the optimal management going forward was unclear. Here, the options for anticoagulation during pregnancy and for management in the event of valve thrombosis are reviewed. In the absence of any clear guidelines, a thorough discussion of the various risks and benefits with the patient is necessary, but ultimately any consideration of the risk to the mother is paramount.

RARG S427L attenuates the DNA repair response to doxorubicin in induced pluripotent stem cell-derived cardiomyocytes.

Doxorubicin is a commonly used chemotherapeutic drug, but its use is limited by doxorubicin-induced cardiotoxicity (DIC), which can lead to irreversible heart failure and death. A missense variant rs2229774 (p.S427L) in the retinoic acid receptor gamma (RARG) gene is associated with increased susceptibility to DIC, but the precise mechanism underlying this association is incompletely understood. We performed molecular dynamic simulations to determine the effect of this variant on RARG structure and then validated these predictions using CRISPR-Cas9-genome-edited, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). We found that this variant leads to reduced activation of its target genes in response to doxorubicin, including gene pathways involved in DNA repair and consequently an inability to mediate DNA repair after exposure to doxorubicin. Our findings establish a role of RARG p.S427L in attenuating DNA repair in DIC and provide insight into the pathogenesis of this cardiotoxic effect.