Engaging Patients to Improve Medical Decision Making and Optimize Health Outcomes
Larry A. Allen, MD, MHS
University of Colorado
An increasing number of therapies have been developed for the treatment of heart failure with reduced ejection fraction (HFrEF). When used in combination, patients often experience significant improvements in cardiac function, quality of life, and survival. However, busy clinicians treating stable patients with chronic diseases are often incentivized to “leave well enough alone”. Meanwhile, multimorbidity has become the norm, such that patients and their families often face treatment hypercomplexity, polypharmacy, and financial toxicity. As progressive diseases near end-stage, uncertainty increases and treatments become increasingly high-risk/high-reward, compounding the difficulty of medical decision making. Within this context, scalable strategies that promote patient-centered, value-based care are needed. Shared decision making—between the clinician who is expert in the medical issues and the patient who is expert in their own values, goals, and preferences—provides a framework from which to address the growing challenge of optimizing care for each individual patient from an increasing number of treatment options. Decision aids are tools that can facilitate shared decision making so that patients can work with clinicians to choose their care wisely. Unfortunately, most tools are not used because the context in which they are developed and tested are not reflective of the “real-world”. Within the HFrEF setting, our group has developed and tested multiple, varied, pragmatic decision aids that help patients, their families, and their clinicians with high-quality decision making throughout the trajectory of illness. In the DECIDE-LVAD program, patients being evaluated for left ventricular assist device placement who were given a 26-minute video and 8-page pamphlet knew more about LVADs than patients who received usual LVAD education and were more likely to decide on treatment that matched their goals. Based on these positive results, all 175 LVAD programs in the United States were contacted, and 71% started using the I-DECIDE-LVAD PtDA, with 83% of their eligible patients receiving the tool as part of their decision-making process, and 46% of programs making it their programmatic standard of care for all patients. The EPIC-HF trial—Electronically delivered, Patient-activation tool for Intensification of medications for Chronic Heart Failure with reduced ejection fraction—tested a 3-minute video and 1-page checklist sent to patients just prior to a clinic visit encouraging them to work with their clinicians to make at least 1 positive change to their guideline-directed medical therapies, overcoming clinical inertia to produce a 20% increase in intensification of high-value therapies. In the future, processes for rapid and rigorous development of decision support tools that are broadly available and easy to implement are needed to realize the potential of medical discoveries.
Developing a Precision Medicine Approach to Vascular Inflammation and Pulmonary Hypertension
Stephen Chan, MD, PhD
University of Pittsburgh Medical Center
Vascular inflammation critically regulates endothelial cell (EC) pathophenotypes, yet causative mechanisms remain incompletely defined, particularly in pulmonary arterial hypertension (PAH). Both lysosomal activity and cholesterol metabolism have been linked to cellular inflammation in other contexts, but the relevance to PAH is unclear. Supported by genomic and metabolomic association analyses of mortality in PAH across >3,000 patients in total, we have established a paradigm whereby allele-specific SNP regulation of endosomal lysosomal acidification controls sterol and bile acid metabolism, downstream inflammation, and PAH severity. Using computational algorithms to predict protein target druggability, we have identified and experimentally validated a small molecule that targets lysosomal acidification and reduces inflammation in PAH as well as other conditions of viral and bacterial infections of the lung. This paradigm defines a specific genetic and metabolic predisposition to PAH and carries implications for diagnostic and therapeutic development in PAH as well as in other conditions dependent upon acquired and innate immune regulation.
Sex Differences in Cardiovascular Risk
Susan Cheng, MD, MPH, MMSc
Cedars-Sinai Medical Center
Background. Sex differences in the presentation of cardiovascular diseases (CVD) are well recognized in clinical practice. Prominent examples include manifestations of coronary microvascular disease and heart failure with preserved ejection fraction, among many others. We hypothesize that sex differences in cardiovascular pathophysiology arise from not only genetic and hormonal factors but from under-appreciated sex differences in ‘normal’ physiology and sex-based variation in the response to exposures and stressors over the life course; it would then follow that these differences should, in some cases, motivate consideration of sex-specific interventions. To test this main hypothesis, we have conducted a series of studies centered on sex differences in commonly measured cardiovascular traits and outcomes, beginning with a focus on blood pressure and related end-organ disease.
Methods. Our primary approaches involve integrating phenotype and outcomes data generated from clinical and population studies. In the initial stage of analyses, we examined blood pressure measures obtained from individuals assessed repeatedly over several decades of serial standardized exams run through four large U.S. community-based cohort studies. We conducted both sex-pooled and sex-specific analyses of the longitudinal blood pressure data with attention to baseline levels, rates of change, and life course trajectories. Next, we examined the extent to which there may be discernible sex differences in how blood pressure trajectories are related cross-sectionally with cardiometabolic risk exposures or prospectively with incident cardiovascular disease. Finally, we investigated in community-based, clinical trial, and population scale cohorts whether there may be sex differences in response to interventions targeting cardiometabolic risk traits, including but not limited to elevated blood pressure.
Results. In the first stage of analyses, we observed that blood pressure levels in adulthood are not only lower in females than males in the healthy state but that women compared with men exhibit a steeper blood pressure increase with aging that begins as early as in the third decade and continues throughout the life course. In the next stage of analyses, we found that trajectories of rising blood pressure are steeper in women than men in the setting of equivalent burden of cardiometabolic risk factor exposure. Further, we found that increased risk for incident cardiovascular disease is significant starting at a lower systolic blood pressure threshold for women (110 mmHg) than for men (120 mmHg). Finally, in analyses of cohort, trial, and population data, we observed sex-dependent effects on cardiovascular outcomes for certain interventions, including intensive versus standard blood pressure lowering treatment and varying doses of aerobic and muscle-strengthening physical activity.
Conclusions. Our results to date suggest that sex differences in cardiovascular risk and disease manifestations may arise in part from under-recognized sex divergence in primordial cardiometabolic traits and their response to stressors over time. Our blood pressure findings, in particular, are concordant with accumulating evidence of sex-specific vascular physiology predisposing to sex differences in pathophysiology, likely all emanating from sexual dimorphism in gene expression in addition to autonomic, neurohormonal, and stochastic factors influencing blood pressure regulation. In the context of prior and ongoing work by our group and others, our study results suggest the possible need for more sex-specific definitions of cardiometabolic health and disease as well as more tailored approaches to risk and disease management.
The Role of Risk Factor Modification in the Treatment of Atrial Fibrillation
Jeffrey J. Goldberger, MD, MBA
University of Miami
Introduction: Obesity and epicardial adipose tissue (EAT) are associated with atrial fibrillation (AF) and AF outcomes. Weight loss improves outcomes in AF. Liraglutide is a GLP-1 agonist approved for weight loss. We assessed whether pre-ablation treatment with Liraglutide in addition to standard risk factor modification (RFM) improves AF ablation outcomes compared to RFM in obese patients with AF.
Methods: In the Liraglutide Effect in Atrial Fibrillation (LEAF) study, 65 patients with BMI≥27 kg/m2 who opted for catheter ablation to treat AF were enrolled and randomized to a 3 month pre-ablation period of RFM or RFM plus Liraglutide (RFM+L, titrated to 1.8 mg daily). There were 6 withdrawals; 4 patients opted not to proceed with ablation and 1 patient no longer had AF after RFM+L. Ablation procedures targeted pulmonary vein isolation (PVI). Echocardiograms were used to assess epicardial adipose tissue (EAT) from the parasternal long axis view at enrollment and prior to ablation. Long-term monitoring was used to assess freedom from AF.
Results: There were 28 patients in RFM (age 61.8±10.3 years, 29% female) weighing 102.8±17.0 kg (BMI 34.7±4.7 kg/m2) and 31 in RFM+L (age 62.2±8.6 years, 26% female) weighing 109.6±19.5 kg (BMI 37.4±6.4 kg/m2); 80% had persistent AF and 20% had paroxysmal AF with 85% having hypertension, 27% diabetes, and 44% obstructive sleep apnea. CHA2DS2-VASc score was 2.4±1.6 and left ventricular ejection fraction was 56.3±10.4%.
Median time from enrollment to ablation was 4.5 and 4.0 months in RFM and RFM+L, respectively (p=0.14). For all patients, there was significant pre-ablation reduction in weight (2.8±3.7%, p<0.001) and EAT (0.8±1.6 mm, p<0.001), with no significant difference between RFM and RFM+L (2.1±3.0% vs 3.4±4.1%, and 1.1±1.7 mm vs 0.6±1.5 mm, respectively). Complete PVI was achieved in all but one patient undergoing ablation with only one complication (post-procedure pericarditis). The figure shows Kaplan-Meier freedom from AF off antiarrhythmic drugs after a 3 month blanking period for the two groups.
Conclusion: In a group of obese patients with primarily persistent AF, pre-ablation treatment with RFM and/or RFM+Liraglutide results in weight loss and reduction in EAT. Treatment with RFM+Liraglutide results in better outcomes from PVI ablation than RFM alone, particularly those with persistent AF. Treatment with GLP-1 agonists may be useful adjunctive therapy for obese patients with AF.
Racial and Ethnic Differences in Awareness and Prevalence of Unidentified Cardiovascular Risk Factors Among Health System Employees.
Jennifer H Mieres, MD
Hofstra University/ Northwell Health
Introduction: Workplace wellness programs have become increasingly common as employers search for strategies to lessen the economic burden of chronic illness especially cardiovascular disease (CVD). Employer-sponsored health promotion activities have become a central focus of creating a healthier workforce, enhancing employee productivity, and generating substantive cost savings for health care. Although many of the performance metrics used to guide the effectiveness and benefit of workplace wellness programs have emphasized undetected risk and health status, minimal emphasis has been placed on employee knowledge, detection gaps, and issues in health literacy which hinder appropriate health seeking behaviors. We sought to evaluate general knowledge of CVD risk, self-reported prevalence of common CVD risk factors and willingness to undergo in-depth CVD screening amongst a cohort of employees within a large integrated health care system and to identify any racial and ethnic differences.
Purpose: To evaluate awareness about cardiovascular (CVD) risk among a racially and ethnically diverse cohort of health system employees.
Setting : Voluntary survey of health system employees during an annual CVD awareness and screening event.
Methods: We performed initial CVD screening measurements (blood pressure, body mass index) in 759 health system employees and collected patient- reported answers to questions about their own CVD risk factors (hypertension, high cholesterol, diabetes, overweight, smoking, physical inactivity and family history of CVD) and whether or not they believed that CVD is preventable. Subjects were offered in-depth follow-up CVD screening (lipid panel, hs-CRP, hemoglobin A1c), if interested. Analysis: Continuous measures were compared across sex and racial/ethnic subsets using a t test and analysis of variance technique. Univariable and multivariable logistic regression models were used to estimate the employee’s willingness to undergo further comprehensive screening.
Results: African American, Hispanic, and Asian employees were younger than white employees (P < .0001). More than one- quarter of African Americans reported a history of hypertension, a higher rate than for other subgroups (P = .001). The rate of self-reported diabetes was highest in African American and Asian employees (P = .001). African Americans had a 54% reduced odds of electing to pursue follow-up CVD screening (odds ratio: .46, 95% confidence interval = .24.91, P = .025).
Conclusion: Presence of CVD risk factors and knowledge of their importance differ among racial and ethnic groups of health system employees in our cohort. Additionally, there are differences in interest in pursuing follow-up screening once risk factors are identified. Development of evidence-based customization strategies by racial and ethnic group may improve understanding of and interest in CVD risk factors and advance prevention. The data from this study will inform future research and strategies for employee health promotion.
Co-Authors: Amgad N Makaryus, MD Stacey E Rosen, MD, Leslie Kang, MPH,
Leslee J. Shaw, PhD, Beth Nash, MD, Reva Gajer, NP, Whitney Coppolino, MD
Impact of COVID-19 on Cardiovascular Disease Outcomes, Care, and Prevention
Laurence S. Sperling, MD
Background: Prior to the COVID-19 Public Health Emergency (PHE) cardiovascular disease (CVD) had been the leading cause of mortality since 1910 (with exception of 1918-1920 during the Spanish influenza pandemic). Racial and ethnic disparities have persisted. Trends in adverse outcomes have been of concern both nationally and globally. Since March of 2020 converging syndemics of poor population health and disparities, in addition to the challenges and consequences of COVID-19 have had a significant impact on CVD outcomes, care, and prevention.
Methods: Several publications highlighting the intersection between high level public health questions during the PHE and the imperative to focus on CVD prevention initiatives will be discussed: Acute Cardiac Events during COVID-Associated Hospitalizations from COVID-NET dataset (JACC 2023;81(6), Impact of the COVID-19 Pandemic on Cardiac Rehabilitation Participation (Circ CV Qual Outcomes 2022;15), and Myocarditis Cases Reported after mRNA-COVID vaccination in the U.S. from 12/20-8/21 (JAMA 2022;327). In addition, an overview of the CDC-CMS Million Hearts Initiative will be shared.
Results: Eleven percent of 8460 adults hospitalized with COVID-19 from January-November 2021 had an acute cardiovascular event which was most prevalent among patients with underlying cardiac disease (23%). Acute ischemic heart disease (5.5%) and acute heart failure (5.4%) were the most frequent CVD events. Acute myocarditis or pericarditis was noted in 0.3%. Cardiac events were associated with a doubling in the risk of ICU admission and in-hospital death. Importantly, a rapid decline in the participation of cardiac rehabilitation (CR) was noted with incomplete recovery during the PHE; 220 CR facilities were closed. A novel finding was that rates of myocarditis were highest after the second dose of mRNA vaccine. This was most notable among young males (50-106 cases/ million). Of these cases 96% were hospitalized and 87% had symptom resolution by discharge.
Conclusion: Collaboration between academic medical centers, public health efforts, and community-focused health equity are needed to optimize CVD prevention. Strategies to prevent COVID-19 infection remain essential, especially in vulnerable populations. The PHE has had a notable and persistent impact on CV care. New care models for the delivery of CR are needed. There is a favorable net clinical benefit of mRNA COVID vaccination in all populations. Vaccination may be a component of comprehensive CVD prevention. The CDC-CMS Million Hearts Initiative’s 3 pillars- Building Healthy Communities, Optimizing Care, and a Core Focus on Health Equity provide an opportunity to prevent 1 million heart attacks, strokes, and CV events in our nation by 2027 through the implementation of proven and effective strategies.
Single Cell Multi-omic Approaches to Understanding Cardiac Development and Disease
Sean M. Wu, MD PhD
Recent advances in single cell multi-omic technologies have transformed our ability to understand how individual cells contribute to whole organ responses in development and disease. By leveraging these technologies, we have gained new insights in the biology of congenital heart diseases and in fetal and neonatal cardiomyocyte proliferation. We have also utilized single cell transcriptomic technology to identify new surface markers in the cardiac conduction system and have engineered monoclonal antibodies that target this structure for real-time intraoperative imaging to avoid iatrogenic heart block. In addition, the ability to simultaneously profile immune cell populations and their T cell receptor repertoire has enabled us to gain mechanistic insights into myocarditis induced by immune checkpoint inhibitor treatments of cancers. More recently, we made advances in the use of single cell multi-omic tools to address the transcriptional and epigenetic landscape of progenitors and differentiated cells during cardiac development and their implications in the pathogenesis of cardiovascular diseases. We anticipate that with the increasing use of machine learning and artificial intelligence tools to annotating large-scale multi-omic datasets we will identify novel targets of cardiac diseases for the development of therapeutic and preventive strategies in the future.