Call to Action for Cardiovascular Disease in Women: Epidemiology, Awareness, Access, and Delivery of Equitable Health Care: A Presidential Advisory From the American Heart Association.

Addressing the pervasive gaps in knowledge and care delivery to reduce sex-based disparities and achieve equity is fundamental to the American Heart Association's commitment to advancing cardiovascular health for all by 2024. This presidential advisory serves as a call to action for the American Heart Association and other stakeholders around the globe to identify and remove barriers to health care access and quality for women. A concise and current summary of existing data across the areas of risk and prevention, access and delivery of equitable care, and awareness and education provides a framework to consider knowledge gaps and research needs critical toward achieving significant progress for the health and well-being of all women.

Nonprofit Advocacy at the American Heart Association: Creating a Visionary Way Forward at Our 40th Anniversary: An American Heart Association Policy Statement.

In 2021, the American Heart Association celebrates its 40th anniversary in advocacy. This policy statement details the arc of the organization's nonpartisan, evidence-based, equity-focused approach to advocating for public policy change, highlighting key milestones and describing the core components of the association's capacity and activity at all levels of government. This policy statement presents a vision and strategic imperative for future American Heart Association advocacy efforts to inform and influence policy changes that advance equitable, impactful societal solutions that transform and improve cardiovascular health for everyone. The American Heart Association maintains accountability by measuring and evaluating the totality of this work and its impact on equitable health outcomes. The American Heart Association will apply these lessons to constantly refine its own strategic policy focus and advocacy efforts. The association will also serve as a resource and catalyst to other organizations working to engage and educate policy makers, partners, the media, and funders about the important role and contribution of public policy change to achieve shared goals.

Improving Cardiovascular Drug and Device Development and Evidence Through Patient-Centered Research and Clinical Trials: A Call to Action From the Value in Healthcare Initiative's Partnering With Regulators Learning Collaborative.

The pipeline of new cardiovascular drugs is relatively limited compared with many other clinical areas. Challenges causing lagging drug innovation include the duration and expense of cardiovascular clinical trials needed for regulatory evaluation and approvals, which generally must demonstrate noninferiority to existing standards of care and measure longer-term outcomes. By comparison, there has been substantial progress in cardiovascular device innovation. There has also been progress in cardiovascular trial participation equity in recent years, especially among women, due in part to important efforts by Food and Drug Administration, National Institutes of Health, American Heart Association, and others. Yet women and especially racial and ethnic minority populations remain underrepresented in cardiovascular trials, indicating much work ahead to continue recent success. Given these challenges and opportunities, the multistakeholder Partnering with Regulators Learning Collaborative of the Value in Healthcare Initiative, a collaboration of the American Heart Association and the Robert J. Margolis, MD, Center for Health Policy at Duke University, identified how to improve the evidence generation process for cardiovascular drugs and devices. Drawing on a series of meetings, literature reviews, and analyses of regulatory options, the Collaborative makes recommendations across four identified areas for improvement. First, we offer strategies to enhance patient engagement in trial design, convenient participation, and meaningful end points and outcomes to improve patient recruitment and retention (major expenses in clinical trials). Second, new digital technologies expand the potential for real-world evidence to streamline data collection and reduce cost and time of trials. However, technical challenges must be overcome to routinely leverage real-world data, including standardizing data, managing data quality, understanding data comparability, and ensuring real-world evidence does not worsen inequities. Third, as trials are driven by evidence needs of regulators and payers, we recommend ways to improve their collaboration in trial design to streamline and standardize efficient and innovative trials, reducing costs and delays. Finally, we discuss creative ways to expand the minuscule proportion of sites involved in cardiovascular evidence generation and medical product development. These actions, paired with continued policy research into better ways to pay for and equitably develop therapies, will help reduce the cost and complexity of drug and device research, development, and trials.

Advancing Healthcare Reform: The American Heart Association's 2020 Statement of Principles for Adequate, Accessible, and Affordable Health Care: A Presidential Advisory From the American Heart Association.

The mission of the American Heart Association is to be a relentless force for a world of longer, healthier lives. The American Heart Association has consistently prioritized the needs and perspective of the patient in taking positions on healthcare reform while recognizing the importance of biomedical research, providers, and healthcare delivery systems in advancing the care of patients and the prevention of disease. The American Heart Association's vision for healthcare reform describes the foundational changes needed for the health system to serve the best interests of patients and to achieve health care and coverage that are adequate, accessible, and affordable for everyone living in the United States. The American Heart Association is committed to advancing the dialogue around healthcare reform and has prepared this updated statement of our principles, placed in the context of the advances in coverage and care that have occurred after the passage of the Affordable Care Act, the rapidly changing landscape of healthcare delivery systems, and our evolving recognition that efforts to prevent cardiovascular disease can have synergistic benefit in preventing other diseases and improving overall well-being. These updated principles focus on expanding access to affordable health care and coverage; enhancing the availability of evidence-based preventive services; eliminating disparities that limit the availability and equitable delivery of health care; strengthening the public health infrastructure to respond to social determinants of health; prioritizing and accelerating investments in biomedical research; and growing a diverse, culturally competent health and healthcare workforce prepared to meet the challenges of delivering high-value health care.

The American Heart Association 2030 Impact Goal: A Presidential Advisory From the American Heart Association.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

New and Emerging Tobacco Products and the Nicotine Endgame: The Role of Robust Regulation and Comprehensive Tobacco Control and Prevention: A Presidential Advisory From the American Heart Association.

The advent of new tobacco products such as electronic cigarettes and the dramatic rise in their use, especially by adolescents and young adults, are significant public health concerns. Electronic cigarettes have become the most popular tobacco products for youth and adolescents in the United States and are attracting youth to new avenues for nicotine addiction. Although these products may have benefit by helping some smokers quit or to move to a less harmful product, the long-term health effects of these products and the net public health effect associated with their use remain unclear and widely debated. There is increasing concern that the use of newer tobacco products may catalyze transition to the use of other tobacco products or recreational drugs, particularly in young adults. Therefore, there is urgent need for robust US Food and Drug Administration regulation of all tobacco products to avoid the significant economic and population health consequences of continued tobacco use. Although the American Heart Association acknowledges that the ultimate endgame would be an end to all tobacco and nicotine addiction in the United States, it supports first minimizing the use of all combustible tobacco products while ensuring that other products do not addict the next generation of youth and adolescents. The endgame strategy needs to be coordinated with the long-standing, evidence-based tobacco control strategies that have significantly reduced tobacco use and initiation in the United States.

Call to Action: Urgent Challenges in Cardiovascular Disease: A Presidential Advisory From the American Heart Association.

Although advances in care have spurred improvements in cardiovascular outcomes, cardiovascular disease remains the leading cause of death in the United States and around the world. Previous declines in cardiovascular disease mortality have slowed and even reversed for certain demographics. Further concerns exist with regard to cardiovascular drug innovation, quality of care, and healthcare costs. The Value in Healthcare Initiative-Transforming Cardiovascular Care, a collaboration of the American Heart Association and Duke University, Robert J. Margolis, MD, Center for Health Policy, aims to increase access to and affordability of cardiovascular treatment and to decrease barriers to care. The following Call to Action describes trends in cardiovascular care, identifies gaps in areas of cardiovascular disease prevention and treatment, highlights challenges with medical product innovation, and finally, outlines a series of learning collaboratives that will aid in the development of road maps for transforming cardiovascular care.

3D Printable Non-Isocyanate Polyurethanes with Tunable Material Properties.

Green chemistry-based non-isocyanate polyurethanes (NIPU) are synthesized and 3D-printed via rapid, projection photopolymerization into compliant mechanisms of 3D structure with spatially-localized material properties. Trimethylolpropane allyl ether-cyclic carbonate is used to couple the unique properties of two types of reaction chemistry: (1) primary diamine-cyclic carbonate ring-opening conjugation for supplanting conventional isocyanate-polyol reactions in creating urethane groups, with the additional advantage of enabling modular segment interchangeability within the diurethane prepolymers; and (2) thiol-ene (click) conjugation for non-telechelic, low monodispersity, quasi-crystalline-capable, and alternating step-growth co-photopolymerization. Fourier Transform Infrared Spectroscopy is used to monitor the functional group transformation in reactions, and to confirm these process-associated molecular products. The extent of how these processes utilize molecular tunability to affect material properties were investigated through measurement-based comparison of the various polymer compositions: frequency-related dynamic mechanical analysis, tension-related elastic-deformation mechanical analysis, and material swelling analysis. Stained murine myoblasts cultured on NIPU slabs were evaluated via fluorescent microscopy for "green-chemistry" affects on cytocompatibility and cell adhesion to assess potential biofouling resistance. 3D multi-material structures with micro-features were printed, thus demonstrating the capability to spatially pattern different NIPU materials in a controlled manner and build compliant mechanisms.

American Heart Association Principles on the Accessibility and Affordability of Drugs and Biologics: A Presidential Advisory From the American Heart Association.

Net US spending on pharmaceuticals reached $309.5 billion in 2015, an 8.5% increase from the year before, and is expected to reach between $370 and $400 billion by 2020. These current and projected levels have raised serious concerns by policy makers, providers, payers, and patient groups that they are unsustainable and threaten the affordability of and accessibility to much-needed therapies for patients. Two trends related to drugs/biologics and generic drugs/biosimilars underlie this overall increase in spending. First, the market entry prices of innovator pharmaceutical products, or brand drugs and biologics, are at levels that some assessments consider unaffordable to the healthcare system. Second, prices for some established generic drugs such as digoxin and captopril have seen sharp and rapid increases. As an evidence-based patient advocacy organization dedicated to improving the cardiovascular health of all Americans, the American Heart Association has a unique role in advocating for treatments, including medicines that are available, affordable, and accessible to patients. This advisory serves to lay out a set of principles that will guide association engagement in pursuit of this goal.

3D-printed biomaterials with regional auxetic properties.

Tissue engineering is replete with methods for inducing and mediating cell differentiation, which are crucial for ensuring proper regrowth of desired tissues. In this study, we developed a 3D-printed, non-positive Poisson's Ratio (NPPR) scaffold intended for future use in stretch-mediated cell differentiation applications, such as in muscle and tendon regeneration. We utilized dynamic optical projection stereolithography (DOPsL) to fabricate multi-layered, cell-laden NPPR scaffolds - these scaffolds can not only support aggregate cell growth, but can also be printed with locally-tunable force-displacement properties at length scales appropriate for tissue interaction. These NPPR multilayered mesh scaffolds can be embedded into highly elastic hydrogels in order to couple a reduced NPPR behavior to a normally Positive Poisson's Ratio (PPR) solid bulk material. This hybrid structure may potentially enable induced 'auxetic' behavior at the single-cell scale while tuning the Poisson's Ratio to a more isolated value. This would be uniquely suited for providing stretch-mediated effects for various cell-types within the tendon-to-muscle tissue transition.

Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy.

BACKGROUND: Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor approved for cancer treatment by the US Food and Drug Administration, will blunt reperfusion injury. METHODS AND RESULTS: Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before and at surgery), and (3) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (30 minutes coronary ligation, 24 hours reperfusion). In addition, cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated ischemia/reperfusion to probe mechanism. SAHA reduced infarct size and partially rescued systolic function when administered either before surgery (pretreatment) or solely at the time of reperfusion. SAHA plasma concentrations were similar to those achieved in patients with cancer. In the infarct border zone, SAHA increased autophagic flux, assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to simulated ischemia/reperfusion, SAHA pretreatment reduced cell death by 40%. This reduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects. CONCLUSIONS: The US Food and Drug Administration-approved anticancer histone deacetylase inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during ischemia/reperfusion occur, at least in part, through the induction of autophagic flux.

Systems-based improvement in door-to-balloon times at a large urban teaching hospital: a follow-up study from Parkland Health and Hospital System.

BACKGROUND: Timely reperfusion in ST-segment elevation myocardial infarction (STEMI) patients improves clinical outcomes. Implementing strategies to target institutional-specific delays are crucial for improved patient care. METHODS AND RESULTS: Using a novel strategy to analyze specific components of door-to-balloon time (DBT) at our institution, we previously identified several specific interval delays in our prior STEMI protocol. We then implemented 4 strategies to reduce DBT: (1) emergency department physician activation of the STEMI protocol; (2) "single call" broadcast paging of the STEMI team by the page operator; (3) immediate feedback to the emergency and cardiology departments with joint monthly quality improvement meetings; and (4) transfer of the off-hours STEMI patient directly to the laboratory on activation by an in-hospital team. After implementation of the new protocol, we examined each component time interval from the first 59 consecutive STEMI patients treated with the new protocol between March 2007 and June 2008 and compared time intervals with the previous 184 STEMI patients. Compared with the previous 184 STEMI patients, the median DBT of the subsequent 59 STEMI patients significantly improved from 125 to 86 minutes (P<0.0001). This improvement was largely driven by a decrease in the interval from the initial 12-lead ECG to activation of the on-call catheterization team (from 40 to 11 minutes, P<0.0001). CONCLUSIONS: After examining specific component delays in our institution's DBT, we were able to successfully use quality improvement strategies to focus on specific sources of delay in our institution. This dramatically improved our median DBT toward the goal of achieving a guideline-recommended <90 minutes for all patients.

The risk of acute myocardial infarction with etodolac is not increased compared to naproxen: a historical cohort analysis of a generic COX-2 selective inhibitor.

BACKGROUND: This study compares the risk of acute myocardial infarction among patients exposed to etodolac, naproxen, celecoxib, and rofecoxib. METHODS: A retrospective cohort study in 38 258 veteran patients (26 376 patient-years) measured the adjusted odds ratios of acute myocardial infarction during exposure to etodolac, naproxen, celecoxib, or rofecoxib. RESULTS: Diagnosis of acute myocardial infarction was confirmed in 100 patients who were exposed to a study nonsteroidal anti-inflammatory drug. Compared to naproxen, the increased risk of acute myocardial infarction was not significant for etodolac (OR = 1.32, P = .27), whereas celecoxib (OR = 2.18, 95% CI 1.09-4.35, P = .03) and rofecoxib (OR = 2.16, 95 CI 1.04-4.46, P = .04) were significant. A post hoc analysis indicates that patients with a prior history of acute myocardial infarction had a significant, 4.26-fold risk for another acute myocardial infarction if taking celecoxib or rofecoxib. CONCLUSION: Etodolac is not associated with a statistically increased risk of acute myocardial infarction compared to naproxen.

Changes in right ventricular structure and function assessed using cardiac magnetic resonance imaging in bosentan-treated patients with pulmonary arterial hypertension.

Patients with pulmonary arterial hypertension (PAH) usually show improvements in symptoms, exercise capacity, and hemodynamics after treatment with approved medical therapies. This study sought to determine whether improvement in right-sided cardiac function measured using cardiac magnetic resonance imaging would also be seen and whether these changes would correlate with improvement in exercise capacity. Sixteen patients with PAH underwent evaluation at baseline and after 12 months of treatment with bosentan. After treatment, cardiac index, pulmonary vascular resistance, and 6-minute walk distance improved, and there was a trend toward improvement in right ventricular (RV) stroke volume (70 +/- 27 to 81 +/- 30 ml; p = 0.08), but no change in RV ejection fraction (RVEF) or RV end-diastolic volume. Six-minute walk distance improved by 59 m (p <0.05) in the overall cohort and improved more in patients in whom RVEF increased compared with those with stable or decreased RVEF (+98 vs -37 m, respectively; p = 0.01). Three patients died during follow-up, and these patients had significantly lower RVEF and left ventricular end-diastolic volume indexes than surviving patients. In conclusion, these results suggest that cardiac magnetic resonance imaging may have value in determining response to therapy and prognosis in patients with PAH.

Treatment delay in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: a key process analysis of patient and program factors.

BACKGROUND: Most hospitals that perform primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in the United States exceed the recommended door-to-balloon time. There is heightened interest in identifying and eliminating factors that introduce delay. METHODS: We performed a key process analysis of our primary PCI program, assessed the relative contribution of individual time intervals on total ischemic time, and identified predictors of delay. RESULTS: Median times and predictors of delay within each time interval were determined for the entire STEMI cohort ("real world") and after exclusion of patients with atypical symptoms and/or presentations of STEMI that resulted in inherent delay in diagnosis and treatment ("ideal world"). Delays in therapy were symptom onset to presentation (120 minutes [interquartile range, IQR, 60-310 minutes, ideal world] and 150 minutes [IQR 60-360 minutes, real world]; predictors of delay were peripheral vascular disease, self-transportation, daytime and weekend presentation); door-to-balloon time (118.5 minutes [IQR 96-141 minutes, ideal world] and 125 minutes [IQR 100-170 minutes, real world]; predictors of delay were female sex, previous stroke, nighttime and weekend presentation, and cardiogenic shock); and symptom onset to first balloon inflation (272 minutes [IQR 187-465 minutes, ideal world] and 297 minutes [IQR 198-560 minutes, real world]; predictors of delay were peripheral vascular disease, weekend presentation, and self-transportation). CONCLUSIONS: Key process analysis of a primary PCI program identifies treatment delays unique to the hospital and the patient population it serves.