Understanding the Complexity of Heart Failure Risk and Treatment in Black Patients

Traditional and Unique Determinants of Hf Risk in BlackS

Racial Differences in Traditional Cardiovascular Risk Factors and Incidence of HF

Traditional cardiovascular risk factors including hypertension, diabetes mellitus, obesity, and chronic kidney disease are known risk factors for incident HF. The prevalence of each of those risk factors is substantially higher in Blacks compared with other race-ethnic groups, except for diabetes mellitus which has a slightly higher prevalence in Hispanics (Table 1).^1,7 The lower prevalence of healthy lifestyle behaviors in Blacks contributes to the higher prevalence of cardiovascular risk factors in this subgroup. Only 1 in 10 Blacks have at least 5 cardiovascular health metrics at ideal levels, compared with 1.3 in 10 Hispanics, and ≈1.8 in 10 non-Hispanic Whites.¹ Importantly, these disparities may be more prominent among women than men. When examining Life’s Simple 7 scores among National Health and Nutritional Examination Survey (NHANES) participants, Black women had significantly lower scores as compared with White women, while differences between Black and White men were relatively small.⁸ Despite higher body mass index and atherosclerotic CVD risk, Black women are less likely than White women to attempt weight loss or to report a healthy diet.⁹ Importantly, self-perception as overweight is a strong contributor to healthy lifestyle behaviors,⁹ but desired weight and weight self-perceptions vary by race/ethnicity and sex due to important cultural differences in ideal body image. Hair care and maintenance may be a unique barrier to physical activity for Black women, in particular, however, many clinicians may not feel comfortable addressing this issue with Black patients.¹⁰ The higher prevalence of modifiable cardiovascular risk factors contributes to the higher prevalence of HF in Blacks. An analysis of the Health, Aging, and Body Composition Study estimated that the preventable fraction of incident HF due to modifiable risk factors was 67.8% (95% CI, 55.1%–76.8%) in Black participants, compared with 48.9% (95% CI, 35.1%–59.8%) in White participants.¹¹ Similarly, an analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) study demonstrates that modifiable cardiometabolic risk factors were the strongest predictors of incident HF in Blacks, including higher diastolic blood pressure (BP) and body mass index, lower HDL (high-density lipoprotein) cholesterol, and kidney disease.¹²

Hypertension as a Risk Factor for Incident HF in Blacks

Hypertension is the strongest modifiable population risk factor for HF, and appropriate management of hypertension prevents the onset of HF.^13,14 For example, three-quarters of those who developed HF in the CARDIA study had a diagnosis of hypertension by the age of 40.¹² Despite higher levels of awareness and treatment of hypertension in Blacks compared with other race-ethnic groups, however, they are less likely to have their BP controlled to target.^1,15 An analysis of 8796 hypertensive adults identified from the NHANES suggests that the difficulty achieving recommended BP targets is not due to inferior treatment (Table 2).¹⁵ Compared with Whites and Hispanics, Black patients were the most likely to receive combination antihypertensive therapy (including diuretics and calcium channel blockers) and had the highest average number of antihypertensive medications (1.91 [95% CI, 1.84–1.97]). Despite this, only 31% of Black patients had their BP controlled to Joint National Committee recommended targets, as compared with 43% of Whites.

The difficulty achieving BP targets in Blacks may be related to underlying racial differences in vascular function. Multiple prior studies have demonstrated that Blacks have impaired endothelium-dependent and–independent vasodilation compared with Whites.^16–18 Endothelial cells of Blacks appear to generate more oxidant stress, leading to enhanced inactivation of the potent vasodilator nitric oxide (NO).¹⁹ This diminished response to endogenous and exogenous NO in Blacks likely contributes to the more severe hypertension, and hypertensive HF, in the Black population. Moreover, Blacks display more adverse changes in cardiac structure and function in response to arterial stiffness compared with Whites, indicating a greater vulnerability of the myocardium to the effects of arterial stiffness and vascular dysfunction. An analysis of 5727 subjects in the ARIC (Atherosclerosis Risk in Communities) study demonstrated greater arterial afterload in Blacks compared with Whites, measured as higher systemic vascular resistance and reduced arterial compliance.²⁰ Arterial afterload was more strongly associated with increased left ventricular (LV) end-diastolic volumes, LV mass, and worse diastolic function in Blacks. Moreover, the association of arterial afterload with adverse changes in cardiac structure were stronger in Blacks with a greater proportion of African genetic ancestry. Epidemiologically, multiple studies have documented an increased prevalence of LV hypertrophy (LVH) in Blacks even after adjusting for other cardiovascular risk factors.^21,22 Moreover, the population attributable risk of incident HF is higher in Black men and women than in Whites due to a markedly higher prevalence of malignant LVH (LVH associated with abnormal levels of cardiac troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]).²²

Racial Differences in Prevalence of Rare Genetic Variants Associated With Incident HF

Increasing use of population-based genome-sequencing studies has identified variation in alleles and their frequency that may be associated with racial differences in incident HF.

Compared with Whites, Blacks have ≈3-fold increased risk for developing dilated cardiomyopathy (DCM), and ≈2-fold increased risk of death after diagnosis that is not explained by socioeconomic status and hypertension.² A recent genome wide association study performed in a Black cohort estimated the heritability of DCM to be 33% (compared with 18% for HF in Framingham offspring²³), and identified a novel intronic locus in the CACNB4 gene which encodes a calcium channel subunit essential to cardiac muscle contraction.²⁴ Another analysis of subjects with DCM identified 4 unique genetic variants in Bcl2-associated anthanogene 3 (BAG3) found almost exclusively in Black participants and were associated with an ≈2-fold higher risk of death or HFH.²⁵ Importantly, the 4 variants identified in this analysis were annotated as benign, likely benign, or of indeterminate pathogenicity in a widely used public database of genomic information, which may be due in part to the overall lack of data on subjects of African ancestry in genetic studies.

Studies of women with peripartum cardiomyopathy demonstrate that Black women have a more severe disease profile, including younger age at onset, more severe LV dysfunction at initial presentation, and lower rates of LV recovery.^26,27 In a multinational cohort of women with peripartum cardiomyopathy, the prevalence of truncating variants (including TTNtv [titin truncating variants]) was similar to that observed in a cohort of patients with DCM, suggesting a potential genetic cause for peripartum cardiomyopathy.²⁸ Moreover, the prevalence of TTNtv was higher in women of African ancestry compared with those of European ancestry.²⁸ In a series of 220 women with peripartum cardiomyopathy from a single center, Black women were less likely than non-Black women to recover their EF to >50%.²⁷ Even among those women with LVEF recovery, the rate of recovery was twice as slow for Black women despite equivalent prescription of angiotensin-converting enzyme inhibitors (ACEi) and β-blockers between racial groups.

The hereditary form of TTR (transthyretin)-related cardiac amyloidosis disproportionately affects Blacks, as the valine-to-isoleucine substitution at position 122 on chromosome 18 is carried by 3% to 5% of Black Americans.^29,30 Despite widespread recognition that the valine-to-isoleucine substitution variant is strongly associated with the risk of HF, few Black patients are recognized as having TTR-related cardiomyopathy or undergo genetic testing for TTR in routine clinical practice.^30,31 Underrecognition of TTR-related disease in Blacks may be, in part, due to the high prevalence of co-occuring disorders associated with LVH, including hypertension, obesity, and diabetes mellitus. Nonetheless, the increasing number of novel therapies being studied for treatment of TTR cardiac amyloidosis raises the imperative to ensure that Blacks receive appropriate diagnostic testing to identify this condition.

The high prevalence of LVH in Blacks may also be associated with difficulty diagnosing hypertrophic cardiomyopathy. In one series of 1900 patients referred to a specialty hypertrophic cardiomyopathy program, Black patients more commonly had an uncertain diagnosis, were less likely to be referred for risk stratification of sudden death, and were less likely to have implanted cardioverter-defibrillators.³² Another multicenter series of 2467 patients with hypertrophic cardiomyopathy demonstrated that Black patients were less likely than Whites to undergo genetic testing.³³ Moreover, Blacks were less likely to have a pathogenic or likely pathogenic sarcomeric mutation identified and were more likely to have a variant of unknown significance.

Although many of the aforementioned studies also showed a higher prevalence of traditional cardiovascular risk factors including hypertension and diabetes mellitus in the enrolled Black subjects, the presence of traditional cardiovascular risk factors should not preclude the use of genetic testing, as the concomitant presence of underlying genetic variants with traditional risk factors may explain the earlier onset of disease in many Black patients. Wider adoption of genetic testing in diverse populations is necessary, as a thorough understanding of the contribution of genomic variation to disease is particularly relevant for conditions in which the disease burden is disproportionately high.

Relative Deficiency of Natriuretic Peptides in Blacks

NPs (natriuretic peptides) are produced in response to increased cardiac wall tension and stress and have various protective cardiometabolic effects, including vasodilation and promotion of natriuresis and diuresis.³⁴ Animal studies have documented impaired production of NPs promotes salt-sensitive hypertension and cardiac hypertrophy.^35,36 Thus, a relative deficiency of NPs may be associated with multiple adverse phenotypes, including LVH, salt and fluid retention, and hypertension.³⁷ Multiple analyses have documented lower levels of NPs in Black subjects without HF. Black subjects enrolled in the Dallas Heart Study and the Multi-Ethnic Study of Atherosclerosis (MESA), who were free of CVD at the time of enrollment, demonstrated lower NT-proBNP levels compared with Whites.^37,38 Moreover, genetic ancestry informed the lower NT-proBNP levels, such that a 20% increase in African ancestry was associated with a ≈10% decrease in NT-proBNP levels among self-reported Black and Hispanic participants in MESA.³⁸ Thus, there appear to be genetic underpinnings contributing to the lower NP levels in Blacks.

Blacks Have a High Prevalence of Salt Sensitivity That Is Known to Contribute to Adverse Cardiovascular Outcomes

Strictly speaking, salt sensitivity is a physiological trait whereby BP exhibits changes parallel to changes in salt intake.³⁹ Although the mechanisms are poorly understood, it is thought that the elevation in BP exhibited by salt-sensitive individuals after a sodium load is required to induce a pressure natriuresis. Salt sensitivity is thought to be present in up to 75% of hypertensive Blacks and some normotensive Blacks.^40–42 Moreover, the salt-sensitive phenotype is characterized by low renin and aldosterone levels, suggesting that the associated hemodynamic alterations are not directly secondary to increased renin-angiotensin-aldosterone system (RAAS) activity.⁴³ Alternate mechanisms for sodium retention in Blacks have not been well defined, but may include reduced potassium intake, decreased urinary kallikrein excretion, upregulation of epithelial sodium channel activity, deficiencies in NP production, and APOL1 gene nephropathy risk variants.^37,38 Racial differences in activity of the RAAS may also be relevant in patients with HF. In a small sample of Black patients with chronic ambulatory HF, higher proportion of African ancestry was associated with lower aldosterone levels, while higher proportion of European ancestry was associated with higher levels.⁴⁴ A recent post hoc analysis of data from 3 acute HF clinical trials demonstrated that Black patients with acute HF have lower levels of plasma renin activity and aldosterone than non-Black patients.⁴⁵ Moreover, plasma renin activity was related to racial differences in diuretic efficiency and the risk for rehospitalization. Additional studies are needed to examine racial differences in sodium and fluid homeostasis in subjects with acute and chronic HF.

Social Determinants of HF Susceptibility and Outcomes

Neighborhood and Residential Environment

The economic and racial segregation created by redlining, a practice implemented by US federal agencies in the 1930s that continued until the 1970s, has resulted in persistent economic inequality that can be documented even today.⁴⁶ In addition to the economic inequalities, it is also clear that persons living in more impoverished and racially segregated neighborhoods are more likely to develop incident CVD and HF even after adjusting for the burden of traditional cardiovascular risk factors, suggesting that neighborhood-related risks for poor cardiovascular outcomes are not fully explained by the higher burden of cardiovascular risk factors.^47–49 An analysis of 27 078 Black and White participants in the Southern Community Cohort Study showed that each interquartile increase in neighborhood deprivation was associated with a 12% increase in incident HF.⁴⁸ Similarly, living in a food desert, defined as low-income areas with low access to healthful foods, was associated with an increased risk of repeat all-cause and HFHs.⁵⁰ The association between neighborhood deprivation and CVD risk may be mediated in part through environmental factors that negatively impact on patients’ ability to engage in healthy lifestyle behaviors and self-care. For example, commercial facilities for physical activity are less likely to exist in neighborhoods with lower-income or higher proportions of race/ethnic minorities.⁵¹ A lack of neighborhood walkability and green space can increase sedentary lifestyle and physical inactivity.^52–54 Multiple studies have demonstrated that low-income and predominantly Black neighborhoods have fewer supermarkets or specialty food stores than high-income or predominantly White neighborhoods, such that there is a lower availability of fresh, healthy foods.⁵⁵ Thus, the cumulative effects of neighborhood deprivation may be particularly deleterious for race-ethnic minorities.

Implicit Bias as a Determinant of Quality of Healthcare

Implicit bias refers to unconscious attitudes or stereotypes that involuntarily affect our understanding and actions. Prior studies have documented that implicit bias can affect the clinical decision-making of health care providers, including the acute care of Black patients with HF from the emergency department to the intensive care unit (ICU). Lo et al⁵⁶ examined >12 million adult visits to US emergency departments from 2001 to 2010 with a chief complaint related to HF symptoms. Among all non-ICU admissions, Blacks were less likely to be hospitalized than Whites, even among older patients with higher levels of acuity. Another analysis of admissions for HF at a single, quarternary care academic center noted that Black and Latinx HF patients were 9% and 17% less likely to be admitted to a cardiology service from the ED than White patients.⁵⁷ Unfortunately, disparate access to a cardiologist appears to persist for Black patients with HF even when managed in an ICU setting. In an examination of 104 835 patients who required ICU admission for a primary diagnosis of acute HF, Blacks were less likely to be seen by a cardiologist during their ICU stay.⁵⁸ Of note, patients who receive care from a cardiologist have better clinical outcomes, including increased in-hospital survival and decreased likelihood of 30-day readmission.^57,58 Even for patients with access to advanced HF care, there may be subtle differences in the choice of advanced HF therapy. A recent study presented clinical vignettes describing an end-stage HF patient to 422 advanced HF clinicians, of whom 42 were probed about their decision making strategy during an intensive think-aloud interview.⁵⁹ The interviews revealed a number of themes that influenced disparate decision making, including greater concern for trust and adherence for the Black patient, and a sense that the Black patient was sicker, ultimately resulting in the Black patient being less likely to be offered heart transplant (HT), and more likely to be offered left ventricular assist device (LVAD). These findings are notable, particularly providers’ greater concerns for nonadherence among the Black patient, a finding that has been documented in multiple other studies where case vignettes were presented to clinicians with every detail about the patient being identical (medical history, description of symptoms, etc) except for the race of the patient.^60,61

Challenges for Improving Treatment of Black PATIENTS With HF

Prevention of HF

The onset of HF can be substantially postponed or prevented altogether with targeted prevention of cardiovascular risk factors. Incident HF in Blacks in the CARDIA cohort occurred at an average age of 39 years and was predicted by the presence of hypertension, obesity, chronic kidney disease, and depressed systolic function 10 to 15 years before HF onset.¹² Similarly, a prior analysis of 2934 participants in the Health, Aging, and Body Composition Study suggested that the preventable fraction of incident HF in this elderly cohort was 67.8% in Blacks and 48.9% in Whites.¹¹ For Blacks in this cohort, the preventable fraction of incident HF associated with systolic BP >140 mm Hg was 30.1% and was 19.5% for LVH. Interestingly, the association of LVH with incident HF (which was present even in 8.6% of Black subjects with systolic BP <140 mm Hg) was additive to and independent of the risk due to uncontrolled hypertension, which may be an indicator of the presence of undiagnosed cardiac amyloidosis in this elderly cohort. Due to the greater morbidity and mortality associated with hypertension in Blacks, current guidelines for treatment of hypertension in adults incorporate race-specific recommendations including the initial use of thiazide-type diuretics or calcium channel blockers, as well as the use of 2 or more antihypertensive medications.⁶²

Improved Utilization of Guideline-Directed Medical Therapy

The landscape of guideline-directed medical therapy (GDMT) for HF is rapidly changing, with novel therapies including ARNI (angiotensin receptor-neprilysin inhibitors), SGLT2 (sodium-glucose co-transporter-2) inhibitors, and other drugs showing substantial improvements in morbidity and mortality. Current guidelines for the treatment of stage C HF with reduced ejection fraction also include the use of combination therapy with hydralazine and isosorbide dinitrate (H-ISDN) as a class I recommendation for Blacks with HF.⁶³ It has been postulated that the improvement in outcomes in Blacks treated with H-ISDN is due to the theory that this drug combination improves the biologic underpinnings of reduced NO bioavailability in Black patients. ISDN is an organic nitrate that stimulates NO signaling and bioavailability, and H is a vasodilator and antioxidant that inhibits the enzymatic formation of reactive oxygen species and ameliorates excess oxidative stress. Despite this, H-ISDN is widely underutilized in eligible Blacks with HF.^64–66 There has been widespread concern related to adherence, as use may be limited by 3× a day dosing as well as the side effect profile.⁶⁷ However, Callier et al⁶⁸ conducted semistructured interviews with 81 cardiologists attending an annual scientific meeting to explore their attitudes towards race-based guidelines. Nearly half of participants expressed skepticism or strongly disapproved of race-based drug labels and the use of race in drug prescribing. Participants expressed concern about the impact of admixture, and that race-based labeling may prohibit the drug from being prescribed to non-Black patients who may also benefit. Increased use of precision medicine may help determine which patients derive the most benefit from H-ISDN, irrespective of race/ethnicity. The Genetic Risk Assessment of HF substudy of A-HeFT has demonstrated polymorphisms in the guanine nucleotide-binding proteins β-3 subunit, endothelial NO synthase, and aldosterone synthase that are associated with greater therapeutic effect of fixed-dose H-ISDN.^69–71 For example, although the −344T>C polymorphism in the promoter region of the aldosterone synthase gene may be associated with higher aldosterone levels, as well as increased risk of atrial fibrillation and HFH, the CC genotype is less prevalent in Blacks and may correlate with greater percent European ancestry.^44,71

Although data on race-based utilization of novel therapies is somewhat limited, many registries show that prescription of standard GDMT including ACEI/angiotensin II receptor blockers, β-blockers, and mineralocorticoid receptor antagonists (MRA) is comparable among Blacks and Whites with HF.^65,72,73 In the Change the Management of Patients With Heart Failure (CHAMP-HF) registry, dosing and titration of GDMT is suboptimal regardless of race/ethnicity.^72,74 Blacks were equally as likely to be treated with ARNI as Whites; however, few Black patients received both ARNI and H-ISDN.^65,72 Currently, there is little data on real-world use of SLGT2 inhibitors for HF. Future research should monitor race-based differences in patterns of utilization; despite the high burden of diabetes mellitus in Black patients, a recent retrospective analysis of claims data on >1 000 000 US adults with diabetes mellitus showed that Blacks were less likely than Whites to be started on SGLT2i.⁷⁵

Improved Utilization of Advanced Therapies for HF

Although the number of Black patients receiving advanced HF therapies appears to be growing,^76,77 it is unclear whether the growth is proportional to the number of Black patients affected by HF. A recent analysis of the Interagency Registry of Mechanically Assisted Circulatory Support indicates per capita LVAD implantation rates for Blacks did not increase proportionally with increases in HF incidence, suggesting continued racial disparities.⁷⁷ There are a number of reasons why Blacks may be underrepresented as recipients of advanced HF therapies, including underinsurance, lack of social support, and other factors. Moreover, Blacks hospitalized with acute HF are less likely to be treated by a cardiologist than non-Black patients, which may have a direct impact on the likelihood of recognition of stage D HF and need for advanced therapies.^57,58

Lack of Inclusion of Minorities in Clinical Trials

While Blacks are overrepresented in the incidence and prevalence of HF, they are underrepresented in the clinical trials used to determine treatment.⁷⁸ Recent data demonstrate that trial-eligible patients in real-world clinical settings have worse clinical outcomes than patients enrolled in clinical trials.⁷³ The worse outcomes are driven in part by differences among Blacks and women, suggesting that more research is needed to understand the complex social and behavioral factors that are not measured in most contemporary cardiovascular trials. Although the National Institutes of Health requires investigators to explicitly address their approach for prospective enrollment of women and minorities in all human subjects research, no such requirement exists for the pharmaceutical industry. Moreover, large and costly trials are often performed without adequate numbers of minority patients, such that conclusions regarding the effectiveness of new medications in the populations who have the greatest potential to benefit are based on post hoc analyses. The low participation of Blacks in clinical trials may in part be patient-driven due to mistrust of the healthcare system, and may, in part, be provider-driven as prior studies have documented that Blacks are more likely to be perceived as nonadherent, and that physicians are less likely to discuss new and alternative therapies with Black patients.^59,79 Future studies should continue to prioritize adequate representation of race-ethnic minorities as trial participants to ensure generalizability of findings to the most vulnerable populations.

Financial Toxicity of Novel Medical and Device Therapies

Recent Food and Drug Administration approval of novel therapeutic agents for the treatment of HF has thrust drug costs to the forefront of conversations about shared decision-making. The out-of-pocket costs and financial toxicity of novel HF drugs limit access to effective therapies and may negatively impact medication adherence. Although most analyses have determined that novel drugs are cost-effective for the healthcare system, few studies have analyzed patients’ actual out-of-pocket drug costs. An analysis of projected out-of-pocket costs for Medicare part D plans estimates expenditures as high as $1685 annually for ARNI (nearly $1400 more than those prescribed an ARB), with monthly costs exceeding $160 during the coverage gap.⁸⁰ This magnitude of monthly cost for one therapy may be quite meaningful to patients, particularly when polypharmacy for multiple comorbid conditions is taken into account. Smith et al⁸¹ conducted structured interviews with 49 patients with HF with reduced ejection fraction and determined that only 43% would want to switch to sacubitril-valsartan if their out-of-pocket cost was $100 more per month than their current costs, compared with 92% who said that they would definitely or probably switch if their out-of-pocket cost was $5 more per month. Importantly, only 20% of participants in this study said their physician had initiated a conversation about cost with them in the past year. Currently, there are limited data on whether cost differentially impacts utilization of novel HF therapies according to race/ethnicity. Given the widespread socioeconomic differences that exist according to race/ethnicity, future research should capture how patient access to GDMT varies based on drug cost, socioeconomic status, and race.

Key Areas for Improvement

Although this list is not all-encompassing, the multitude of factors influencing racial disparities in HF incidence and outcomes are summarized in Figure 3. Since the causes for the existence of health disparities are multifactorial, the solutions for the elimination of health disparities will need to be multifactorial as well. Each factor can be viewed as an opportunity for intervention to improve the treatment of HF in Blacks to reduce disparities. Disparities can only be eliminated through concerted efforts to increase knowledge of determinants of differences in disease burden, differences in response to treatment of disease, and to improve contextual factors that influence clinical outcomes. The social-ecological model is a framework that emphasizes the multiple levels of influence that impact patients’ behaviors and clinical outcomes.⁸² The social-ecological model acknowledges the relevance of biological and genetic aspects of an individual’s risk for disease but puts those risks into the context of interpersonal, community, and societal factors to allow clinicians and researchers to understand the range of factors that influence an individual’s outcomes. This type of framework allows the visualization of key areas that must be targeted to improve race-ethnic disparities in HF, so that collecting data on the multiple levels of risk will improve understanding and facilitate implementation of multi-level prevention strategies (Figure 4).

Traditional clinical trials and treatment guidelines focus primarily on the individual patient. Focusing on the management of individual cardiovascular risk factors, particularly hypertension, obesity and physical inactivity, continues to be one of the most important strategies to control the incidence of HF in Blacks. Clinicians need to be aware of and provide culturally sensitive recommendations for barriers to implementing therapeutic lifestyle changes that may be uniquely present for Black patients (eg, haircare and lack of available neighborhood resources as barriers to exercise).^10,51 Increasing clinician awareness that Black patients with significant LVH, particularly if LVH is present in the setting of relatively well controlled BP, warrant a clinical investigation to rule out cardiac amyloidosis.³⁰ Given the rapid growth of novel medical and device therapies becoming available for HF, encouraging minority patients to participate in clinical trials should be a high priority for all clinicians, as patients may be more likely to participate in research studies at the urging of their primary clinician. Improving academic-community partnerships could also help attract patients and family members who are primarily followed in community settings to consider referral for inclusion in clinical trials. Identifying methods to improve shared decision-making and discussions about the potential financial costs of novel therapies should also be a priority for clinicians during clinic encounters. Clinicians can also help to assist patients with building strong bonds at the interpersonal level, by encouraging family based genetic counseling for HF risk.⁸³ In addition, educating patients to discuss the medical severity of their HF with loved ones may give families time to openly discuss care plans and social support options for advanced HF therapies before the patient is in critical cardiogenic shock.

Although changes at the community level may be outside of the control of the healthcare providers, clinicians must be aware of the unique challenges present for patients who live in socioeconomically deprived neighborhoods. Voucher programs have been successfully used to improved patients’ access to healthy foods, recreational exercise facilities, and even higher quality housing.^84–87 For example, Trapl et al⁸⁵ used a produce prescription program to increase fruit and vegetable consumption among 224 patients (mean age 62 years, 97% Black) with hypertension at a safety-net clinic. Patients had 3 clinic visits at monthly intervals, where they received a BP check, targeted nutrition counselling, and were given vouchers to purchase fresh produce at farmers markets. Eighty-six percent visited a farmers market to purchase produce using their vouchers; at the end of the follow-up period, significant improvement in fruit and vegetable consumption and decline in fast food consumption was observed. To fully understand the impact of community-level and neighborhood deprivation on health behaviors and outcomes, many have advocated for integrating social determinants of health including neighborhood composition and characteristics, food and housing insecurity, behavior and lifestyle patterns, and other factors into the electronic medical record as well as prospective research activities.^49,88

At the organizational level, there are ample opportunities for improving coordinated care of Black patients with HF. Algorithms embedded into the electronic medical record could be useful for implementation of various quality metrics, including screening for genetic causes of cardiomyopathy based on clinical criteria (ie, severity of LVH to screen for amyloidosis), automatic inpatient cardiology consultations and referrals to specialty HF clinics based on the number of prior hospitalizations and 30-day readmissions, or medication adjustments to ensure that evidence-based GDMT is being prescribed and appropriately titrated for all patients.^74,89 Similarly, organizational policies requiring implicit bias training for clinicians may be an effective method to educate providers on how implicit bias impacts clinical decision-making. Diversification of the workforce and increasing community outreach can help reduce disparities, as prior research has shown that increasing the number of doctors who are race/ethnic minorities can improve adherence and the quality of communication experienced by patients, while administering care in nontraditional settings in the community (ie, barbershops) can also improve clinical outcomes.^90–92

At the policy level, there are multiple examples of legislation that have resulted in tangible health consequences for Black patients. Inadequate access to healthcare has long been recognized as having a disproportionate impact on the health of Blacks. The Patient Protection and Affordable Care Act increased the proportion of Americans with health insurance, with proportionally greater gains for race/ethnic minorities.⁹³ Since adoption of the Affordable Care Act, rates of HT listing and LVAD implantation increased for Black patients in states that were early adopters of Medicaid expansion, confirming policies that improve access also improve clinical outcomes.^94,95 The Hospital Readmissions Reduction Program was intended to reduce 30-day hospital readmissions by increasing accountability of patient care organizations, improving the quality of care, and enhancing care coordination particularly at the time of discharge. However, there is evidence that the Hospital Readmissions Reduction Program disproportionately penalizes safety-net hospitals that serve greater proportions of race-ethnic minorities and socioeconomically disadvantaged patients, which has the potential to actually worsen existing disparities.⁹⁶ Ongoing efforts seek to improve the risk adjustment algorithms by taking socioeconomic and societal factors into account, to ensure that minority-serving and safety-net hospitals do not incur excessive payment penalties, as excess readmissions for these hospitals may also be influenced by aspects of the postdischarge environment that are beyond the control of the hospital or its providers.^96,97

Novel policies should also be employed to improve the state of funding for healthcare disparities research. Recent data shows that Black applicants for National Institutes of Health research funding are less likely to be funded even after controlling for educational background, previous research awards, publication record, and other factors.^98,99 A follow-up analysis demonstrates that topic choice may be the largest driver of that funding gap, since Black investigators are more likely to propose research on health disparities, and to use study designs that include humans, communities, and behavioral interventions.⁹⁹ The authors of this pivotal study speculated that disparities research may be “less likely to excite the enthusiasm” of study sections and reviewers compared with other topics. In a recent editorial, Carnethon et al¹⁰⁰ proposed several methods that could be used by the National Institutes of Health to improve funding rates for health disparities research including (1) involve health disparities experts on every study section, (2) continue to improve the race/ethnic diversity of the pool of peer reviewers, (3) designate a proportion of funding within each National Institutes of Health institute research portfolio that must address health disparities topics, and (4) expand efforts to support diversity-focused science by creating programs that target funding toward investigators who are studying health disparities.

Conclusions

Despite the ever-growing portfolio of scientific literature describing the existence of health disparities, the healthcare community continues to struggle to find viable methods to effectively eliminate disparities. The exquisite complexity of factors that impact the persistence of health disparities, ranging from genetics, to cardiovascular risk factor burden, to social determinants of health that affect lifestyle and health behaviors, to implicit bias that may affect treatment recommendations, present a challenge of epic proportion for the medical community to tackle. Still, we must meet that challenge head on, by continuing to encourage research initiatives, quality metrics, clinical trial enrolment, reporting of results, as well as patient education and engagement that are sensitive to race and ethnic differences in the manifestations of CVD. Preventing adverse clinical outcomes in HF is not only crucial for patients’ well-being and quality of life, but has become an increasing priority for clinicians, hospitals, and payers in the post-Hospital Readmissions Reduction Program era. Prioritizing culturally sensitive healthcare and health equity with a goal of eliminating health disparities is one obvious way to satisfy all of the relevant stakeholders, particularly our minority patients who stand to gain the most.

Nonstandard Abbreviation and Acronyms

ARIC	Atherosclerosis Risk in Communities
ARNI	angiotensin receptor-neprilysin inhibitor
BP	blood pressure
GDMT	guideline-directed medical therapy
HF	heart failure
HFH	heart failure hospitalization
ICU	intensive care unit
LV	left ventricular
LVH	LV hypertrophy
MESA	Multi-Ethnic Study of Atherosclerosis
NO	nitric oxide
NP	natriuretic peptide
NT-proBNP	N-terminal pro-B-type natriuretic peptide
SGLT2	sodium-glucose co-transporter-2
TTNtv	titin truncating variant
TTR	transthyretin
H-ISDN	combination therapy with hydralazine and isosorbide dinitrate

Acknowledgments

The authors would like to thank Khadijah Breathett, MD, MSc for helping to conceive of this project.

Sources of Funding

Dr Morris has received research grants from National Heart, Lung, and Blood Institute (National Institutes of Health [NIH] K23 HL124287 and R03 HL146874), the Robert Wood Johnson Foundation (Harold Amos Medical Faculty Development Program), and the Woodruff Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Footnotes

For Sources of Funding and Disclosures, see page 311.

Correspondence to: Alanna A. Morris, MD, MSc, Division of Cardiology, Emory University School of Medicine, 1462 Clifton Rd Suite 504, Atlanta GA 30322. Email [email protected]edu

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