Implementation Science to Achieve Equity in Heart Failure Care: A Scientific Statement From the American Heart Association.

Guideline-directed medical therapies and guideline-directed nonpharmacological therapies improve quality of life and survival in patients with heart failure (HF), but eligible patients, particularly women and individuals from underrepresented racial and ethnic groups, are often not treated with these therapies. Implementation science uses evidence-based theories and frameworks to identify strategies that facilitate uptake of evidence to improve health. In this scientific statement, we provide an overview of implementation trials in HF, assess their use of conceptual frameworks and health equity principles, and provide pragmatic guidance for equity in HF. Overall, behavioral nudges, multidisciplinary care, and digital health strategies increased uptake of therapies in HF effectively but did not include equity goals. Few HF studies focused on achieving equity in HF by engaging stakeholders, quantifying barriers and facilitators to HF therapies, developing strategies for equity informed by theory or frameworks, evaluating implementation measures for equity, and titrating strategies for equity. Among these HF equity studies, feasibility was established in using various educational strategies to promote organizational change and equitable care. A couple include ongoing randomized controlled pragmatic trials for HF equity. There is great need for additional HF implementation trials designed to promote delivery of equitable guideline-directed therapy.

Examining Heart Failure Outcomes Amidst Housing Insecurity.

BACKGROUND: How housing insecurity might affect patients with heart failure (HF) is not well characterized. Housing insecurity increases risks related to both communicable and non-communicable diseases. For patients with HF, housing insecurity likely increases the risk for worse outcomes and rehospitalizations. METHODS AND RESULTS: We analyzed U.S. HF hospitalizations using the 2020 National Inpatient Sample (NIS) and Nationwide Readmissions Database (NRD) to evaluate the impacts of housing insecurity on HF outcomes and hospital utilization. Individuals were identified as having housing insecurity using diagnostic ICD-10 codes. Demographics and comorbidities were compared between HF patients with and without housing insecurity. An adjusted logistic regression was performed to evaluate the relationships between housing insecurity and socioeconomic status on in-hospital mortality. Using a Cox proportional hazards model, HF patients with and without housing insecurity were evaluated for the risk of all-cause and HF-specific readmissions over time. Of the 1,003,270 hospitalizations for HF in the U.S. in 2020, 16,150 were identified as having housing insecurity (1.6%) and 987,120 were identified as having no housing insecurity (98.4%). The median age of patients with housing insecurity hospitalized for HF was 57, as compared to 73 in the population with no housing insecurity. A higher proportion of patients in the housing insecurity group were Black (35% vs 20.1%) or Hispanic (11.1% vs 7.3%). Patients with housing insecurity were more likely to carry a diagnosis of alcohol use disorder (15.2% vs 3.3%) or substance use disorder (70.2% vs 17.8%), but were less likely to use tobacco (18.3% vs 28.7%). Patients with housing insecurity were over 4.5 times more likely to have Medicaid (52.4% vs 11.3%). Median length of stay did not differ between patients with housing insecurity versus those without. Patients with housing insecurity were more likely to discharge Against Medical Advice (11.4% vs 2.03%). After adjusting for patient characteristics, housing insecurity was associated with lower in-hospital mortality (OR 0.60, 95% CI 0.39 - 0.92). Housing insecurity was associated with a higher risk of all-cause readmissions at 180 days (HR 1.13, 95% CI 1.12 - 1.14). However, there was no significant difference in the risk of HF-specific readmissions at 180 days (HR 1.07, 95% CI 0.998 - 1.14) CONCLUSIONS: Patients with HF and housing insecurity have distinct demographic characteristics. They are also more likely to be readmitted after their initial hospitalization when compared to those without housing insecurity. Identifying and addressing specific comorbid conditions for patients with housing insecurity who are hospitalized for HF may allow clinicians to provide more focused care, with the goal of preventing morbidity, mortality, and unnecessary readmissions.

Development and Optimization of the Veterans Affairs' National Heart Failure Dashboard for Population Health Management.

BACKGROUND: In 2020, the Veterans Affairs (VA) health care system deployed a heart failure (HF) dashboard for use nationally. The initial version was notably imprecise and unreliable for the identification of HF subtypes. We describe the development and subsequent optimization of the VA national HF dashboard. MATERIALS AND METHODS: This study describes the stepwise process for improving the accuracy of the VA national HF dashboard, including defining the initial dashboard, improving case definitions, using natural language processing for patient identification, and incorporating an imaging-quality hierarchy model. Optimization further included evaluating whether to require concurrent ICD-codes for inclusion in the dashboard and assessing various imaging modalities for patient characterization. RESULTS: Through multiple rounds of optimization, the dashboard accuracy (defined as the proportion of true results to the total population) was improved from 54.1% to 89.2% for the identification of HF with reduced ejection fraction (HFrEF) and from 53.9% to 88.0% for the identification of HF with preserved ejection fraction (HFpEF). To align with current guidelines, HF with mildly reduced ejection fraction (HFmrEF) was added to the dashboard output with 88.0% accuracy. CONCLUSIONS: The inclusion of an imaging-quality hierarchy model and natural-language processing algorithm improved the accuracy of the VA national HF dashboard. The revised dashboard informatics algorithm has higher use rates and improved reliability for the health management of the population.

Modulating cholesterol efflux capacity to improve cardiovascular disease.

PURPOSE OF REVIEW: Low HDL-cholesterol (HDL-C) levels are predictive of incident atherosclerotic cardiovascular disease events. However, the use of medication to raise HDL-C levels has not consistently shown clinical benefit. As a result, studies have shifted toward HDL function, specifically cholesterol efflux, which has been inversely associated with prevalent subclinical atherosclerosis as well as subsequent atherosclerotic cardiovascular disease events. The purpose of this review is to summarize the effects of current medications and interventions on cholesterol efflux capacity. RECENT FINDINGS: Medications for cardiovascular health, including statins, fibrates, niacin, and novel therapeutics, are reviewed for their effect on cholesterol efflux. Differences in population studied and assay used are addressed appropriately. Lifestyle interventions, including diet and exercise, are also included in the review. SUMMARY: The modification of cholesterol efflux capacity (CEC) by current medications and interventions has been investigated in both large randomized control trials and smaller observational cohorts. This review serves to compile the results of these studies and evaluate CEC modulation by commonly used medications. Altering CEC could be a novel therapeutic approach to improving cardiovascular risk profiles.

New models for heart failure care delivery.

Heart failure (HF) is a common disease with increasing prevalence around the world. There is high morbidity and mortality associated with poorly controlled HF along with increasing costs and strain on healthcare systems due to a high rate of rehospitalization and resource utilization. Despite the establishment of clear evidence-based guideline directed medical therapies (GDMT) proven to improve HF morbidity and mortality, there remains significant clinical inertia to optimizing HF patients on GDMT. Only a minority of HF patients are prescribed on all four classes of GDMT. To bridge the gap between the vulnerable population of HF patients and lifesaving GDMT, HF implementation is of increasing importance. HF implementation involves strategies and techniques to improve GDMT optimization along with other modalities to improve HF management. HF implementation meets patients where they are, including at the time of acute decompensation in the inpatient setting, at the vulnerable discharge stage, and at the chronic management stage in the outpatient setting. Inpatient HF implementation strategies include protocolized rapid titration of GDMT, site-level audit-and-feedback, virtual GDMT optimization teams, and electronic health record notifications and alerts. Discharge HF implementation strategies include education at patient and provider levels, discharge summaries, and HF transitional programs. Outpatient HF implementation strategies include digital innovations such as electronic health record utilization and mobile applications, population level strategies such as registries and clinical dashboards), changes in HF team structure and member roles, remote monitoring with implanted devices and telemonitoring, and hospital at home care model. With a growing population of HF patients, there is an increasing need for novel and creative HF implementation and monitoring methods.

Trends in Income Inequities in Cardiovascular Health Among US Adults, 1988-2018.

BACKGROUND: Mean cardiovascular health has improved over the past several decades in the United States, but it is unclear whether the benefit is shared equitably. This study examined 30-year trends in cardiovascular health using a suite of income equity metrics to provide a comprehensive picture of cardiovascular income equity. METHODS: The study evaluated data from the 1988-2018 National Health and Nutrition Examination Survey. Survey groupings were stratified by poverty-to-income ratio (PIR) category, and the mean predicted 10-year risk of a major cardiovascular event or death based on the pooled cohort equations (PCE) was calculated (10-year PCE risk). Equity metrics including the relative and absolute concentration indices and the achievement index-metrics that assess both the prevalence and the distribution of a health measure across different socioeconomic categories-were calculated. RESULTS: A total of 26 633 participants aged 40 to 75 years were included (mean age, 53.0-55.5 years; women, 51.9%-53.0%). From 1988-1994 to 2015-2018, the mean 10-year PCE risk improved from 7.8% to 6.4% (P<0.05). The improvement was limited to the 2 highest income categories (10-year PCE risk for PIR 5: 7.7%-5.1%, P<0.05; PIR 3-4.99: 7.6%-6.1%, P<0.05). The 10-year PCE risk for the lowest income category (PIR <1) did not significantly change (8.1%-8.7%). In 1988-1994, the 10-year PCE risk for PIR <1 was 6% higher than PIR 5; by 2015-2018, this relative inequity increased to 70% (P<0.05). When using metrics that account for all income categories, the achievement index improved (8.0%-7.1%, P<0.05); however, the achievement index was consistently higher than the mean 10-year PCE risk, indicating the poor persistently had a greater share of adverse health. CONCLUSIONS: In this serial cross-sectional survey of US adults spanning 30 years, the population's mean 10-year PCE risk improved, but the improvement was not felt equally across the income spectrum.

Interventions for Optimization of Guideline-Directed Medical Therapy: A Systematic Review.

Importance: Implementation of guideline-directed medical therapy (GDMT) in real-world practice remains suboptimal. It is unclear which interventions are most effective at addressing current barriers to GDMT in patients with heart failure with reduced ejection fraction (HFrEF). Objective: To perform a systematic review to identify which types of system-level initiatives are most effective at improving GDMT use among patients with HFrEF. Evidence Review: PubMed, Embase, Cochrane, CINAHL, and Web of Science databases were queried from January 2010 to November 2023 for randomized clinical trials that implemented a quality improvement intervention with GDMT use as a primary or secondary outcome. References from related review articles were also included for screening. Quality of studies and bias assessment were graded based on the Cochrane Risk of Bias tool and Oxford Centre for Evidence-Based Medicine. Findings: Twenty-eight randomized clinical trials were included with an aggregate sample size of 19 840 patients. Studies were broadly categorized as interdisciplinary interventions (n = 15), clinician education (n = 5), electronic health record initiatives (n = 6), or patient education (n = 2). Overall, interdisciplinary titration clinics were associated with significant increases in the proportion of patients on target doses of GDMT with a 10% to 60% and 2% to 53% greater proportion of patients on target doses of ß-blockers and renin-angiotensin-aldosterone system inhibitors, respectively, in intervention groups compared with usual care. Other interventions, such as audits, clinician and patient education, or electronic health record alerts, were also associated with some improvements in GDMT utilization, though these findings were inconsistent across studies. Conclusions and Relevance: This review summarizes interventions aimed at optimization of GDMT in clinical practice. Initiatives that used interdisciplinary teams, largely comprised of nurses and pharmacists, most consistently led to improvements in GDMT. Additional large, randomized studies are necessary to better understand other types of interventions, as well as their long-term efficacy and sustainability.

Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients With Coronavirus Disease-19.

Introduction: The impact of colchicine on hospitalized patients with Coronavirus disease-19 (COVID-19) related cardiac injury is unknown. Materials and Methods: In this multicenter randomized controlled open-label clinical trial, we randomized hospitalized adult patients with documented COVID-19 and evidence of cardiac injury in a 1:1 ratio to either colchicine 0.6 mg po twice daily for 30 days plus standard of care or standard of care alone. Cardiac injury was defined as elevated cardiac biomarkers, new arrhythmia, new/worsened left ventricular dysfunction, or new pericardial effusion. The primary endpoint was the composite of all-cause mortality, need for mechanical ventilation, or need for mechanical circulatory support (MCS) at 90 days. Key secondary endpoints included the individual components of the primary endpoint and change in and at least 2-grade reduction in the World Health Organization (WHO) Ordinal Scale at 30 days. The trial is registered with clinicaltrials.gov (NCT04355143). Results: We enrolled 93 patients, 48 patients in the colchicine arm and 45 in the control arm. There was no significant difference in the primary outcome between the colchicine and control arms (19 vs. 15%, p = 0.78), nor in the individual components of all-cause mortality (17 vs. 15%, p = 1.0) and need for mechanical ventilation (8 vs. 5%, p = 0.68); no patients in either group required MCS. The change in (-1.8 ± 2.4 vs. -1.2 ± 2.0, p = 0.12) and at least 2-grade reduction (75 vs. 75%, p = 1.0) in the WHO ordinal scale was also similar between groups. Conclusion: Patients hospitalized with COVID-19 and evidence of cardiac injury did not benefit from colchicine therapy.

DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes.

The total contribution of the acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes, DGAT1 and DGAT2, to mammalian triacylglycerol (TG) synthesis has not been determined. Similarly, whether DGAT enzymes are required for lipid droplet (LD) formation is unknown. In this study, we examined the requirement for DGAT enzymes in TG synthesis and LDs in differentiated adipocytes with genetic deletions of DGAT1 and DGAT2. Adipocytes with a single deletion of either enzyme were capable of TG synthesis and LD formation. In contrast, adipocytes with deletions of both DGATs were severely lacking in TG and did not have LDs, indicating that DGAT1 and DGAT2 account for nearly all TG synthesis in adipocytes and appear to be required for LD formation during adipogenesis. DGAT enzymes were not absolutely required for LD formation in mammalian cells, however; macrophages deficient in both DGAT enzymes were able to form LDs when incubated with cholesterol-rich lipoproteins. Although adipocytes lacking both DGATs had no TG or LDs, they were fully differentiated by multiple criteria. Our findings show that DGAT1 and DGAT2 account for the vast majority of TG synthesis in mice, and DGAT function is required for LDs in adipocytes, but not in all cell types.

The Gap to Fill: Rationale for Rapid Initiation and Optimal Titration of Comprehensive Disease-modifying Medical Therapy for Heart Failure with Reduced Ejection Fraction.

There are gaps in the use of therapies that save lives and improve quality of life for patients with heart failure with reduced ejection fraction, both in the US and abroad. The evidence is clear that initiation and titration of guideline-directed medical therapy (GDMT) and comprehensive disease-modifying medical therapy (CDMMT) to maximally tolerated doses improves patient-focused outcomes, yet observational data suggest this does not happen. The purpose of this review is to describe the gap in the use of optimal treatment worldwide and discuss the benefits of newer heart failure therapies including angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors. It will also cover the efficacy and safety of such treatments and provide potential pathways for the initiation and rapid titration of GDMT/CDMMT.

Impact of Body Mass Index >50 on Cardiac Structural and Functional Characteristics and Surgical Outcomes After Bariatric Surgery.

BACKGROUND: Body mass index (BMI) ≥50.0 kg/m2 has been associated with increased surgical complications and mortality. We assessed echocardiographic characteristics and bariatric surgery complications of patients with BMI ≥50.0 kg/m2 vs. those in less severe obesity. METHODS AND RESULTS: A retrospective analysis in patients who underwent gastric bypass was performed. Pre-surgery structural characteristics analyzed included left atrial dimension (LA), left ventricle mass (LVM), LVM indexed for height2.7 (LVMI), and LV hypertrophy (LVH). Functional characteristics included LV diastolic and systolic function. Degree of obesity was correlated with cardiac parameters, comorbidities, and surgical complications. Data on 312 patients (75.3 % women, age 39.3 ± 0.6 years, BMI 50.2 ± 0.5 kg/m2) were analyzed. Cardiac parameters on the basis of BMI (<50 kg/m2 vs. ≥50 kg/m2) were LA 39.6 ± 4.8 vs. 41.9 ± 5.2 mm, LVM 161 ± 46 vs. 194 ± 56 g, LVMI 43.6 ± 0.9 vs. 51.8 ± 1.3 g/ht2.7, and systolic pulmonary pressure 43.7 ± 10.1 vs. 50.5 ± 11.3 mmHg, respectively (all p < 0.001). LVMI was correlated with BMI (p < 0.001), 2-h glucose on a glucose tolerance test (p = 0.01), and ejection fraction (p = 0.01). Surgical complications were not different among groups. Presence of LVH was independently associated with BMI ≥50 kg/m2 and female sex, after adjusting for age, diabetes, hypertension, and pulmonary hypertension. CONCLUSION: Body mass index ≥50 kg/m2 was independently associated with female sex and LVH but not with hypertension, diabetes, or a higher rate of surgical complications.

Modulation of HDL metabolism by the niacin receptor GPR109A in mouse hepatocytes.

The niacin receptor GPR109A is a G(i)-protein-coupled receptor which mediates the effects of niacin on inhibiting intracellular triglyceride lipolysis in adipocytes. However, the role of GPR109A in mediating the effects of niacin on high density lipoprotein (HDL) metabolism is unclear. We found niacin has no effect on HDL-C in GPR109A knockout mice. Furthermore, niacin lowered intracellular cAMP in primary hepatocytes mediated by GPR109A. We used an adeno-associated viral (AAV) serotype 8 vector encoding GPR109A under the control of the hepatic-specific thyroxine-binding globulin promoter to specifically overexpress GPR109A in mouse liver. Plasma HDL-C, hepatic ABCA1 and the HDL cholesterol production rate were significantly reduced in mice overexpressing GPR109A. Overexpression of GPR109A reduced primary hepatocyte free cholesterol efflux to apoA-I; conversely, GPR109A deficient hepatocytes had increased ABCA1-mediated cholesterol efflux. These data support the concept that the HDL-C lowering effect of niacin in wild-type mice is mediated through stimulation of GPR109A in hepatocytes; such an effect then leads to reduced hepatocyte ABCA1 expression and activity, decreased cholesterol efflux to nascent apoA-I, and reduced HDL-C levels. These results indicate that niacin-mediated activation of GP109A in liver lowers ABCA1 expression leading to reduced hepatic cholesterol efflux to HDL.