Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Access to durable LVAD therapy for patients with limited social support: Surveying program-specific approaches.

Racial and ethnic disparities in provision of left ventricular assist device (LVAD) therapy have been identified. These disparities may be at least partially related to socioeconomic factors, including social support networks and financial constraints. This study aimed to identify specific barriers, and variations in institutional approaches, to the provision of equitable care to underserved populations. A survey was administered to 237 LVAD program personnel, including physicians, LVAD coordinators, and social workers, at more than 100 LVAD centers across 7 countries. Three fourths of respondents reported that their program required a support person to live with the LVAD patient for some period of time following implantation. In addition, 31% of respondents reported that patients with the inability to pay for medications are turned down at their program. The most significant barriers to successful LVAD implantation were lack of social support, lack of insurance, and lack of timely referral. The most consistently identified supports needed from the hospital system for success in underserved populations were the provision of a solution for patient transportation to and from hospital visits and the provision of financial support. This survey highlights the challenges facing LVAD programs that care for underserved patient populations and sets the stage for specific interventions aimed at reducing disparities in access to care.

Carotid Intima-Media Thickness and Improved Stroke Risk Assessment in Hypertensive Black Adults.

BACKGROUND: We aim to determine the added value of carotid intima-media thickness (cIMT) in stroke risk assessment for hypertensive Black adults. METHODS: We examined 1,647 participants with hypertension without a history of cardiovascular (CV) disease, from the Jackson Heart Study. Cox regression analysis estimated hazard ratios (HRs) for incident stroke per standard deviation increase in cIMT and quartiles while adjusting for baseline variables. We then evaluated the predictive capacity of cIMT when added to the pool cohort equations (PCEs). RESULTS: The mean age at baseline was 57 ± 10 years. Each standard deviation increase in cIMT (0.17 mm) was associated with approximately 30% higher risk of stroke (HR 1.27, 95% confidence interval: 1.08-1.49). Notably, cIMT proved valuable in identifying residual stroke risk among participants with well-controlled blood pressure, showing up to a 56% increase in the odds of stroke for each 0.17 mm increase in cIMT among those with systolic blood pressure <120 mm Hg. Additionally, the addition of cIMT to the PCE resulted in the reclassification of 58% of low to borderline risk participants with stroke to a higher-risk category and 28% without stroke to a lower-risk category, leading to a significant net reclassification improvement of 0.22 (0.10-0.30). CONCLUSIONS: In this community-based cohort of middle-aged Black adults with hypertension and no history of CV disease at baseline, cIMT is significantly associated with incident stroke and enhances stroke risk stratification.

Opportunities to Increase Science of Diversity and Inclusion in Clinical Trials: Equity and a Lack of a Control.

The United States witnessed a nearly 4-fold increase in personal health care expenditures between 1980 and 2010. Despite innovations and obvious benefits to health, participants enrolled in clinical trials still do not accurately represent the racial and ethnic composition of patients nationally or globally. This lack of diversity in cohorts limits the generalizability and significance of results among all populations and has deep repercussions for patient equity. To advance diversity in clinical trials, robust evidence for the most effective strategies for recruitment of diverse participants is needed. A major limitation of previous literature on clinical trial diversity is the lack of control or comparator groups for different strategies. To date, interventions have focused primarily on (1) community-based interventions, (2) institutional practices, and (3) digital health systems. This review article outlines prior intervention strategies across these 3 categories and considers health policy and ethical incentives for substantiation before US Food and Drug Administration approval. There are no current studies that comprehensively compare these interventions against one another. The American Heart Association Strategically Focused Research Network on the Science of Diversity in Clinical Trials represents a multicenter, collaborative network between Stanford School of Medicine and Morehouse School of Medicine created to understand the barriers to diversity in clinical trials by contemporaneous head-to-head interventional strategies accessing digital, institutional, and community-based recruitment strategies to produce informed recruitment strategies targeted to improve underrepresented patient representation in clinical trials.

Efficacy and Adherence Rates of a Novel Community-Informed Virtual World-Based Cardiac Rehabilitation Program: Protocol for the Destination Cardiac Rehab Randomized Controlled Trial.

BACKGROUND: Innovative restructuring of cardiac rehabilitation (CR) delivery remains critical to reduce barriers and improve access to diverse populations. Destination Cardiac Rehab is a novel virtual world technology-based CR program delivered through the virtual world platform, Second Life, which previously demonstrated high acceptability as an extension of traditional center-based CR. This study aims to evaluate efficacy and adherence of the virtual world-based CR program compared with center-based CR within a community-informed, implementation science framework. METHODS: Using a noninferiority, hybrid type 1 effectiveness-implementation, randomized controlled trial, 150 patients with an eligible cardiovascular event will be recruited from 6 geographically diverse CR centers across the United States. Participants will be randomized 1:1 to either the 12-week Destination Cardiac Rehab or the center-based CR control groups. The primary efficacy outcome is a composite cardiovascular health score based on the American Heart Association Life's Essential 8 at 3 and 6 months. Adherence outcomes include CR session attendance and participation in exercise sessions. A diverse patient/caregiver/stakeholder advisory board was assembled to guide recruitment, implementation, and dissemination plans and to contextualize study findings. The institutional review board-approved randomized controlled trial will enroll and randomize patients to the intervention (or control group) in 3 consecutive waves/year over 3 years. The results will be published at data collection and analyses completion. CONCLUSIONS: The Destination Cardiac Rehab randomized controlled trial tests an innovative and potentially scalable model to enhance CR participation and advance health equity. Our findings will inform the use of effective virtual CR programs to expand equitable access to diverse patient populations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05897710.

Mild antecedent COVID-19 associated with symptom-specific post-acute sequelae.

BACKGROUND: The impact of COVID-19 severity on development of long-term sequelae remains unclear, and symptom courses are not well defined. METHODS: This ambidirectional cohort study recruited adults with new or worsening symptoms lasting ≥3 weeks from confirmed SARS-CoV-2 infection between August 2020-December 2021. COVID-19 severity was defined as severe for those requiring hospitalization and mild for those not. Symptoms were collected using standardized questionnaires. Multivariable logistical regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between clinical variables and symptoms. RESULTS: Of 332 participants enrolled, median age was 52 years (IQR 42-62), 233 (70%) were female, and 172 (52%) were African American. Antecedent COVID-19 was mild in 171 (52%) and severe in 161 (48%). In adjusted models relative to severe cases, mild COVID-19 was associated with greater odds of fatigue (OR:1.83, CI:1.01-3.31), subjective cognitive impairment (OR:2.76, CI:1.53-5.00), headaches (OR:2.15, CI:1.05-4.44), and dizziness (OR:2.41, CI:1.18-4.92). Remdesivir treatment was associated with less fatigue (OR:0.47, CI:0.26-0.86) and fewer participants scoring >1.5 SD on PROMIS Cognitive scales (OR:0.43, CI:0.20-0.92). Fatigue and subjective cognitive impairment prevalence was higher 3-6 months after COVID-19 and persisted (fatigue OR:3.29, CI:2.08-5.20; cognitive OR:2.62, CI:1.67-4.11). Headache was highest at 9-12 months (OR:5.80, CI:1.94-17.3). CONCLUSIONS: Mild antecedent COVID-19 was associated with highly prevalent symptoms, and those treated with remdesivir developed less fatigue and cognitive impairment. Sequelae had a delayed peak, ranging 3-12 months post infection, and many did not improve over time, underscoring the importance of targeted preventative measures.

Racial and Ethnic Disparities in the Trends and Outcomes of Cardiogenic Shock Complicating Peripartum Cardiomyopathy.

Importance: Cardiogenic shock (CS) is a recognized complication of peripartum cardiomyopathy (PPCM) associated with poor prognosis. Although racial and ethnic disparities have been described in the occurrence and outcomes of PPCM, it is unclear if these disparities persist among patients with PPCM and CS. Objectives: To evaluate the temporal trends in CS incidence among hospitalized patients with PPCM stratified by race and ethnicity and to investigate the racial and ethnic differences in hospital mortality, mechanical circulatory support (MCS) use, and heart transplantation (HT). Design, Setting, and Participants: This multicenter retrospective cohort study included hospitalized patients with PPCM complicated by CS in the US from 2005 to 2019 identified from the National Inpatient Sample (NIS). Data analysis was conducted in November 2021. Exposure: PPCM complicated by CS. Main Outcomes and Measures: The main outcome was incidence of CS in PPCM stratified by race and ethnicity. The secondary outcome was racial and ethnic differences in hospital mortality, MCS use, and HT. Results: Of 55 804 hospitalized patients with PPCM, 1945 patients had CS, including 947 Black patients, 236 Hispanic patients, and 702 White patients, translating to an incidence rate of 35 CS events per 1000 patients with PPCM. The mean (SD) age was 31 (9) years. Black and Hispanic patients had higher CS incidence rates (39 events per 1000 patients with PPCM) compared with White patients (33 events per 1000 patients with PPCM). CS incidence rates significantly increased across all races and ethnicities over the study period. Overall, the odds of developing CS were higher in Black patients (aOR, 1.17 [95% CI, 1.15-1.57]; P < .001) and Hispanic patients (aOR, 1.37 [95% CI, 1.17-1.59]; P < 001) compared with White patients during the study period. Compared with White patients, the odds of in-hospital mortality were higher in Black (adjusted odds ratio [aOR], 1.67 [95% CI, 1.21-2.32]; P = .002) and Hispanic (aOR, 2.20 [95% CI, 1.45-3.33]; P < .001) patients. Hispanic patients were more likely to receive any type of MCS device (aOR, 2.23 [95% CI, 1.60-3.09]; P < .001), intraaortic balloon pump (aOR, 1.65 [95% CI, 1.11-2.44]; P < .001), and ventricular assisted device (aOR, 4.45 [95% CI, 2.45-8.08]; P < .001), compared with White patients. Black patients were more likely to receive VAD (aOR, 2.69 [95% CI, 1.63-4.42]; P < .001) compared with White patients. Black and Hispanic patients were significantly less likely to receive HT compared with White patients (Black patients: aOR, 0.51 [95% CI, 0.33-0.78]; P = .02; Hispanic patients: aOR, 0.15 [95% CI, 0.06-0.42]; P < .001). Conclusions and Relevance: These findings highlight significant racial disparities in mortality and HT among hospitalized patients with PPCM complicated by CS in the US. More research to identify factors of racial and ethnic disparities is needed to guide interventions to improve outcomes of patients with PPCM.

Improving Enrollment of Underrepresented Racial and Ethnic Populations in Heart Failure Trials: A Call to Action From the Heart Failure Collaboratory.

Importance: Despite bearing a disproportionate burden of heart failure (HF), Black and Hispanic individuals have been poorly represented in HF clinical trials. Underrepresentation in clinical trials limits the generalizability of the findings to these populations and may even introduce uncertainties and hesitancy when translating trial data to the care of people from underrepresented groups. The Heart Failure Collaboratory, a consortium of stakeholders convened to enhance HF therapeutic development, has been dedicated to improving recruitment strategies for patients from diverse and historically underrepresented groups. Observations: Despite federal policies from the US Food and Drug Administration and National Institutes of Health aimed at improving trial representation, gaps in trial enrollment proportionate to the racial and ethnic composition of the HF population have persisted. Increasing trial globalization with limited US enrollment is a major driver of these patterns. Additional barriers to representative enrollment include inequities in care access, logistical issues in participation, restrictive enrollment criteria, and English language requirements. Conclusions and Relevance: Strategies for improving diverse trial enrollment include methodical study design and site selection, diversification of research leadership and staff, broadening of eligibility criteria, community and patient engagement, and broad stakeholder commitment. In contemporary HF trials, diverse trial enrollment is not only feasible but can be efficiently achieved to improve the generalizability and translation of trial knowledge to clinical practice.

Utilizing Artificial Intelligence to Enhance Health Equity Among Patients with Heart Failure.

Patients with heart failure (HF) are heterogeneous with various intrapersonal and interpersonal characteristics contributing to clinical outcomes. Bias, structural racism, and social determinants of health have been implicated in unequal treatment of patients with HF. Through several methodologies, artificial intelligence (AI) can provide models in HF prediction, prognostication, and provision of care, which may help prevent unequal outcomes. This review highlights AI as a strategy to address racial inequalities in HF; discusses key AI definitions within a health equity context; describes the current uses of AI in HF, strengths and harms in using AI; and offers recommendations for future directions.

Racial differences in cardiopulmonary outcomes of hospitalized COVID-19 patients with acute kidney injury.

In-hospital acute kidney injury (IH-AKI) has been reported in a significant proportion of patients with COVID-19 and is associated with increased disease burden and poor outcomes. However, the mechanisms of injury are not fully understood. We sought to determine the significance of race on cardiopulmonary outcomes and in-hospital mortality of hospitalized COVID-19 patients with AKI. We conducted a retrospective cohort study of consecutive patients hospitalized in Grady Health System in Atlanta, Georgia between February and July 2020, who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on qualitative polymerase-chain-reaction assay. We evaluated the primary composite outcome of in-hospital cardiac events, and mortality in blacks with AKI versus non-blacks with AKI. In a subgroup analysis, we evaluated the impact of AKI in all blacks and in all non-blacks. Of 293 patients, effective sample size was 267 after all exclusion criteria were applied. The mean age was 61.4 ± 16.7, 39% were female, and 75 (28.1%) had IH-AKI. In multivariable analyses, blacks with IH-AKI were not more likely to have in-hospital cardiac events (aOR 0.3, 95% Confidence interval (CI) 0.04-1.86, p = 0.18), require ICU stay (aOR 0.80, 95% CI 0.20-3.25, p = 0.75), acute respiratory distress syndrome (aOR 0.77, 95% CI 0.16-3.65, p = 0.74), require mechanical ventilation (aOR 0.51, 95% CI 0.12-2.10, p = 0.35), and in-hospital mortality (aOR 1.40, 95% CI 0.26-7.50, p = 0.70) when compared to non-blacks with IH-AKI. Regardless of race, the presence of AKI was associated with worse outcomes. Black race is not associated with higher risk of in-hospital cardiac events and mortality in hospitalized COVID-19 patients who develop AKI. However, blacks with IH-AKI are more likely to have ARDS or die from any cause when compared to blacks without IH-AKI.

Improving the enrollment of women and racially/ethnically diverse populations in cardiovascular clinical trials: An ASPC practice statement.

Cardiovascular disease (CVD) remains the leading cause of death for both women and men worldwide. In the United States (U.S.), there are significant disparities in cardiovascular risk factors and CVD outcomes among racial and ethnic minority populations, some of whom have the highest U.S. CVD incidence and mortality. Despite this, women and racial/ethnic minority populations remain underrepresented in cardiovascular clinical trials, relative to their disease burden and population percentage. The lack of diverse participants in trials is not only a moral and ethical issue, but a scientific concern, as it can limit application of future therapies. Providing comprehensive demographic data by sex and race/ethnicity and increasing representation of diverse participants into clinical trials are essential in assessing accurate drug response, safety and efficacy information. Additionally, diversifying investigators and clinical trial staff may assist with connecting to the language, customs, and beliefs of study populations and increase recruitment of participants from diverse backgrounds. In this review, a working group for the American Society for Preventive Cardiology (ASPC) reviewed the literature regarding the inclusion of women and individuals of diverse backgrounds into cardiovascular clinical trials, focusing on prevention, and provided recommendations of best practices for improving enrollment to be more representative of the U.S. society into trials.

Ten things to know about ten cardiovascular disease risk factors.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Acute on chronic severe aortic insufficiency due to rheumatoid arthritis-associated valvulitis.

Rheumatoid Arthritis associated valvular heart disease (RA-VHD) may occur in patients in varying degrees of severity. Aortic valve involvement leading to severe symptomatic aortic insufficiency is a rare complication of rheumatoid arthritis. This entity has not been well characterized and its clinical predictors are undefined. The pathology of RA-VHD can extend from benign nodular development to acute valvulitis with late-stage leaflet fibrosis and severe valvular regurgitation. In this report, we describe a rare case of acute heart failure (AHF) resulting from severe aortic valve destruction and insufficiency due to persistent chronic inflammation in a patient with long-standing RA. Persistent systemic inflammation of RA involved the aortic valve causing nodular thickening and leaflet destruction. Our patient had compensated chronic heart failure due to progressive aortic insufficiency resulting from gradual leaflet destruction. However, she suddenly developed AHF requiring valve replacement. Her clinical presentation, gross and histological images suggest an acute/subacute disruption of the friable aortic leaflets that resulted in AHF.

Pre-existing cardiovascular disease, acute kidney injury, and cardiovascular outcomes in hospitalized blacks with COVID-19 infection.

BACKGROUND: The Corona Virus 19 (COVID-19) infection is associated with worse outcomes in blacks, although the mechanisms are unclear. We sought to determine the significance of black race, pre-existing cardiovascular disease (pCVD), and acute kidney injury (AKI) on cardiopulmonary outcomes and in-hospital mortality of COVID-19 patients. METHODS: We conducted a retrospective cohort study of blacks with/without pCVD and with/without in-hospital AKI, hospitalized within Grady Memorial Hospital in Georgia between February and July 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on qualitative polymerase-chain-reaction assay. The primary outcome was a composite of in-hospital cardiac events. RESULTS: Of the 293 patients hospitalized with COVID-19 in this study, 71 were excluded from the primary analysis (for race/ethnicity other than black non-Hispanic). Of the 222 hospitalized COVID-19 patients included in our analyses, 41.4% were female, 78.8% had pCVD, and 30.6% developed AKI during the admission. In multivariable analyses, pCVD (OR 4.7, 95% CI 1.5-14.8, P=0.008) and AKI (OR 2.7, 95% CI 1.3-5.5, P=0.006) were associated with increased odds of in-hospital cardiac events. AKI was associated with increased odds of in-hospital mortality (OR 8.9, 95% CI 3.3-23.9, P<0.0001). The presence of AKI was associated with increased odds of ICU stay, mechanical ventilation, and acute respiratory distress syndrome (ARDS). CONCLUSION: pCVD and AKI were associated with higher risk of in-hospital cardiac events, and AKI was associated with a higher risk of in-hospital mortality in blacks.

State-of-the-Art review: Hypertension practice guidelines in the era of COVID-19.

The global burden of hypertension (HTN) is immense and increasing. In fact, HTN is the leading risk factor for adverse cardiovascular disease outcomes. Due to the critical significance and increasing prevalence of the disease, several national and international societies have recently updated their guidelines for the diagnosis and treatment of HTN. In consideration of the COVID-19 pandemic, this report provides clinicians with the best strategies to prevent HTN, manage the acute and long-term cardiac complications of HTN, and provide the best evidence-based care to patients in an ever-changing healthcare environment. The overarching goal of the various HTN guidelines is to provide easily accessible information to healthcare providers and public health officials, which is key for optimal clinical practice. However, the COVID-19 pandemic has challenged the ability to provide safe care to the most vulnerable hypertensive populations throughout the world. Therefore, this review compares the most recent guidelines of the 2017 American College of Cardiology/American Heart Association and multiple U.S. societies, the 2018 European Society of Cardiology/European Society of Hypertension, the 2019 National Institute for Care and Health Excellence, and the 2020 International Society of Hypertension. While a partial emphasis is placed on the management of HTN in the midst of COVID-19, this review will summarize current concepts and emerging data from the listed HTN guidelines on the diagnosis, monitoring, management, and evidence-based treatments in adults.

Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure.

BACKGROUND: The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overload, potentially facilitating decongestion and improving the clinical course of patients with acute heart failure (AHF). OBJECTIVES: The TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conducted to address the acute use of tolvaptan to improve congestion in AHF. METHODS: The TACTICS-HF study randomized patients (n = 257) within 24 h of AHF presentation in a prospective, double blind, placebo-controlled trial. Patients were eligible regardless of ejection fraction, and were randomized to either 30 mg of tolvaptan or placebo given at 0, 24, and 48 h, with a fixed-dose furosemide regimen as background therapy. The primary endpoint was the proportion of patients considered responders at 24 h. Secondary endpoints included symptom improvement, changes in renal function, and clinical events. RESULTS: Dyspnea relief by Likert scale was similar between groups at 8 h (25% moderately or markedly improved with tolvaptan vs. 28% placebo; p = 0.59) and at 24 h (50% tolvaptan vs. 47% placebo; p = 0.80). Need for rescue therapy was also similar at 24 h (21% tolvaptan, 18% placebo; p = 0.57). The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32). Tolvaptan resulted in greater weight loss and net fluid loss compared with placebo, but tolvaptan-treated patients were more likely to experience worsening renal function during treatment. There were no differences in in-hospital or post-discharge clinical outcomes. CONCLUSIONS: In patients hospitalized with AHF, dyspnea, and congestion, the addition of tolvaptan to a standardized furosemide regimen did not improve the number of responders at 24 h, despite greater weight loss and fluid loss. (Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure [TACTICS-HF]; NCT01644331).