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Among the estimated 6.2 million Americans living with heart failure (HF), ≈5%/y may progress to advanced, or stage D, disease. Advanced HF has a high morbidity and mortality, such that early recognition of this condition is important to optimize care. Delayed referral or lack of referral in patients who are likely to derive benefit from an advanced HF evaluation can have important adverse consequences for patients and their families. A 2-step process can be used by practitioners when considering referral of a patient with advanced HF for consideration of advanced therapies, focused on recognizing the clinical clues associated with stage D HF and assessing potential benefits of referral to an advanced HF center. Although patients are often referred to an advanced HF center to undergo evaluation for advanced therapies such as heart transplantation or implantation of a left ventricular assist device, there are other reasons to refer, including access to the infrastructure and multidisciplinary team of the advanced HF center that offers a broad range of expertise. The intent of this statement is to provide a framework for practitioners and health systems to help identify and refer patients with HF who are most likely to derive benefit from referral to an advanced HF center. [ABSTRACT FROM AUTHOR]

Abstract Objective It remains unclear whether left ventricular assist device (LVAD) implantation in non-inotrope dependent patients is of clinical benefit. This study sought to evaluate cause of death in patients listed for heart transplant (HT) to determine the relative risks and benefits of implanting LVAD into patients who are less sick than those included in the original clinical trials. Methods We examined death as the primary outcome in 23,098 patients listed for HT from 2006 to 2014 using proportional subdistribution hazards modeling. Cause of death was examined as a secondary outcome using χ2 tests. Results 1859 (8.1%) patients were removed from the wait list for death, including 229 (2.7%) status 1A, 349 (4.6%) status 1B, 246 (13.2%) status 2, and 1035 (26.0%) status 7 patients (P < 0.0001). Status 2 patients who received LVAD while listed had a higher risk of death compared to those who did not (adjusted HR 1.68; 95% CI 1.09–2.59; P = 0.02), while there was no increased risk of death in status 1A (HR 1.02; 95% CI 0.68–1.51; P = 0.9) and status 1B (HR 0.89; 95% CI 0.65–1.23; P = 0.5) who received LVAD. Status 2 patients who received LVAD were more likely to die cerebrovascular causes (0.6% vs. 0.1%, P = 0.009) and organ failure (70.6% vs. 29.4%, P = 0.003). Conclusions LVAD implantation in status 2 patients listed for HT is associated with a higher risk of death. More research is needed to determine the impact LVAD implantation will have on mortality in patients with ambulatory, non-inotrope dependent HF. [ABSTRACT FROM AUTHOR]

The demographics of patients undergoing heart transplantation in the United States have shifted over the last 10 years, with an increasing number of racial and ethnic minorities undergoing heart transplant. Multiple studies have shown that survival of African American patients after heart transplantation is lower compared with other ethnic groups. We review the data supporting the presence of this outcome disparity and examine the multiple mechanisms that contribute. With an increasingly diverse population in the United States, knowledge of these disparities, their mechanisms, and ways to improve outcomes is essential. [ABSTRACT FROM AUTHOR]

Background There is increasing recognition that the risk of stroke after left ventricular assist device (LVAD) implantation varies based on gender, with a higher risk in female patients. We reviewed our own data to determine gender differences in the risk of stroke. Methods Frequency of stroke, including intracranial hemorrhage and ischemic stroke, was retrospectively evaluated in 110 heart failure patients (mean age 49.6 ± 13.6 years, 32% women) discharged from the hospital after implantation of a HeartMate II ( N = 74) or HeartWare ( N = 36) LVAD. Competing outcomes analysis was used to determine which clinical risk factors were associated with the risk of stroke and death, with the primary end-point being time to first stroke event. Results During a median follow-up of 1.3 years, 26 patients had a stroke (23.6%, 0.14 case per person-year). The median time to first stroke was 0.7 (interquartile range 0.3 to 1.4) years. After adjusting for covariates, risk of stroke was higher for women than for men (hazard ratio 3.1, 95% confidence interval 1.4 to 6.9; p = 0.007). There was no difference in overall survival between men and women. Conclusion The risk of stroke after LVAD varies based on gender, with a higher risk in female patients. More research is needed to fully understand these differences, and whether device management strategies should be tailored based on gender. [ABSTRACT FROM AUTHOR]

Background Contemporary epidemiology of chronic graft failure (GF) after heart transplantation (HT) is not well described. Moreover, differences in the epidemiology of GF based on race/ethnicity remain poorly understood, despite clear evidence of inferior survival of ethnic minorities after HT. Methods The incidence of GF and the population-attributable risk (PAR) of independent risk factors for GF were assessed in 15,255 patients (76% men; mean age 52 ± 12 years) who underwent primary HT from 2004 to 2012. Results During a median follow-up of 4.7 years (interquartile range, 2.3–7.1 years), GF developed in 2,926 patients (19.2%), corresponding to an incidence rate of 39.8/1,000 person-years (95% confidence interval, 38.4–41.3). Blacks were more likely to develop GF than Hispanics or whites, with incidence rates of 55.1, 42.2, and 36.5/1,000 person-years, respectively. After multivariable adjustment, black race was associated with a higher risk of GF (hazard ratio, 1.4; 95% confidence interval, 1.2–1.6; p < 0.001). Blacks and Hispanics were more likely to have risk factors for GF, including low education, public insurance, allosensitization, higher human leukocyte antigen mismatch, non-adherence, and history of rejection requiring hospitalization (all p < 0.001). Rejection requiring hospitalization carried the highest population-attributable risk in all groups, with the highest fraction in blacks (25.8%) compared with whites (18.6%) and Hispanics (15.6%). Socioeconomic and donor risk factors conferred relatively less risk of GF. Conclusions Black HT recipients have the highest risk of GF, with immunologic factors conferring the greatest proportion of that risk. Racial differences in risk factors for GF after HT require further study. [ABSTRACT FROM AUTHOR]

1. To understand racial differences in receipt and timing of palliative care consultations among individuals who died from heart failure. 2. To consider precipitating factors for racial differences in receipt and timing of palliative care consultations among individuals who died from heart failure. Among heart failure (HF) decedents, Black individuals had greater odds of receiving a palliative care consultation (PCC) than whites. Median time from PCC to death was shorter among white than Black individuals. Findings suggest greater recognition of palliative needs among Black HF patients; however, most PCCs in HF occur late. Racially minoritized individuals experience greater heart failure incidence and mortality, yet it is unclear whether there are racial disparities in receipt of palliative care in heart failure. We sought to assess the association between race and receipt and timing of palliative care consultation among adults who died from heart failure. This retrospective cohort study used electronic medical records to identify adults who had a hospitalization at an academic health system in Georgia and died from heart failure between January 1, 2012 and December 31, 2018. Using multivariable logistic regression, we examined associations between decedent characteristics and receipt of palliative care consultation. Of 1,987 individuals who died with heart failure, 45.8% (n=911) received a palliative care consultation. Black individuals had 60% greater odds of receiving a palliative care consultation (OR = 1.60; 95% CI = 1.21-2.11) than white individuals. Median time from palliative care consultation to death was 38.5 days for all patients and was shorter among white than Black individuals (31.2 vs 51.5 days, p=.001). Mean age at death was younger among Black than white individuals (71.3 (14.8) vs. 81.8 (12.3) p<.001) and individuals of "other" race (71.3 (14.8) vs. 80.3 (10.4) p=.001). Relative to white individuals, Black individuals were more likely to receive inotropic therapy (42.3% vs. 54.4%, p<.001), to have a hospital admission in the last month of life (29.7% vs. 39.5%, p<.001), and have an ICU stay in the last month of life (18.3% vs. 30.3%, p<.001). Among adults who died from heart failure, a greater proportion of Black individuals received palliative care consultations compared to white individuals. Black individuals with heart failure died younger and had greater health care utilization near the end of life than whites, perhaps prompting palliative care consultations. Palliative care consultations in heart failure tend to occur late for all patient groups. Efforts to integrate palliative care earlier in the heart failure trajectory are needed. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to investigate post-transplantation outcomes as a function of race and panel reactive antibody (PRA). Background: PRA screening is used to determine the presence of pre-formed antibodies to population-wide human leukocyte antigens (HLAs) in patients being evaluated for heart transplantation (HT). Racial/ethnic differences in long-term survival after HT have been described. However, whether there are significant racial/ethnic differences in PRA among adults awaiting HT is poorly characterized. Methods: We identified patients age ≥18 years in the Organ Procurement and Transplantation database with race/ethnicity of white, black, Hispanic, or Asian and listed for HT between 2000 and 2012 (N = 19,704). A PRA value of ≥10% was used to define clinically meaningful sensitization. Results: Blacks had a higher peak PRA than did all other groups and were more likely to be sensitized. Black HT recipients were more likely to experience graft failure than were Hispanic, white, and Asian recipients (31% vs. 27%, 26%, and 21%, respectively; p < 0.001). The median follow-up was 1,207 days (interquartile range: 373 to 2,364 days), with a trend toward a shorter median time to graft failure in the Asian group than in the black, Hispanic, and white groups (p = 0.065). Sensitized blacks had the lowest rate of allograft survival, whereas nonsensitized Asians had the highest survival. Using Cox proportional regression to adjust for other clinical variables, black race (HR: 1.3; 95% confidence interval [CI]: 1.2 to 1.5), Hispanic ethnicity (HR: 1.2; 95% CI: 1.0 to 1.5), and sensitization (HR: 1.2; 95% CI: 1.1 to 1.4) remained predictors of higher rates of graft failure. Conclusions: Race/ethnicity and level of sensitization are important predictors of graft survival. [Copyright &y& Elsevier]

Little is known about the post heart transplantation management of extra cardiac manifestations in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR‐CM) in the new era of disease modifying treatment for ATTR amyloidosis. This is a retrospective study of all patients with hATTR‐CM associated with the Val142Ile variant who underwent heart transplantation (HT) from January 2014 to February 2022. All 10 patients with the Val142Ile mutation were successfully transplanted, with a 1 year survival post heart transplantation (HT) of 90%, comparable to an age, sex, and race matched cohort of patients transplanted for non‐amyloid indications. However, 4 (40%) of these patients developed progressive extracardiac manifestations requiring initiation of TTR silencer therapy with the small interfering RNA (siRNA) drug patisiran, which was well tolerated with no significant side effects in this population. We recommend formal neurologic evaluation and assessment of extracardiac manifestations annually as part of routine post‐transplant care, and disease modifying therapy, aimed at TTR stabilization or silencing, should be initiated in the context of previously untreated extracardiac manifestations or evidence of subclinical neuropathy to prevent progression. [ABSTRACT FROM AUTHOR]

The article focuses on the clinical case of a 71-year-old woman who has been experiencing abdominal pain and night sweats. It notes that the patient has also complained about maxillary facial pressure and headache, requiring the need to determine whether the pain is associated with another condition. Findings of an examination are said to indicate that a diagnosis of acute sepsis is not likely to be made. A final diagnosis of giant-cell arteritis has been given to the patient.

The article discusses the importance of diverse clinical trial participation, particularly among marginalized populations. Topics include the need to address barriers to access and perceptions of exclusion and the benefits of inclusiveness; the potential for advancing biomedical knowledge through representative sampling; and the importance of building trust among underserved communities and treating potential participants fairly through systemic reforms.

This cohort study assesses differences in donor heart acceptance by transplant center teams for Black and White men and women on the transplant waiting list in the US. Importance: Barriers to heart transplant must be overcome prior to listing. It is unclear why Black men and women remain less likely to receive a heart transplant after listing than White men and women. Objective: To evaluate whether race or gender of a heart transplant candidate (ie, patient on the transplant waiting list) is associated with the probability of a donor heart being accepted by the transplant center team with each offer. Design, Setting, and Participants: This cohort study used the United Network for Organ Sharing datasets to identify organ acceptance with each offer for US non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) adults listed for heart transplant from October 18, 2018, through March 31, 2023. Exposures: Black or White race and gender (men, women) of a heart transplant candidate. Main Outcomes and Measures: The main outcome was heart offer acceptance by the transplant center team. The number of offers to acceptance was assessed using discrete time-to-event analyses, nonparametrically (stratified by race and gender) and parametrically. The hazard probability of offer acceptance for each offer was modeled using generalized linear mixed models adjusted for candidate-, donor-, and offer-level variables. Results: Among 159 177 heart offers with 13 760 donors, there were 14 890 candidates listed for heart transplant; 30.9% were Black, 69.1% were White, 73.6% were men, and 26.4% were women. The cumulative incidence of offer acceptance was highest for White women followed by Black women, White men, and Black men (P <.001). Odds of acceptance were less for Black candidates than for White candidates for the first offer (odds ratio [OR], 0.76; 95% CI, 0.69-0.84) through the 16th offer. Odds of acceptance were higher for women than for men for the first offer (OR, 1.53; 95% CI, 1.39-1.68) through the sixth offer and were lower for the 10th through 31st offers. Conclusions and Relevance: The cumulative incidence of heart offer acceptance by a transplant center team was consistently lower for Black candidates than for White candidates of the same gender and higher for women than for men. These disparities persisted after adjusting for candidate-, donor-, and offer-level variables, possibly suggesting racial and gender bias in the decision-making process. Further investigation of site-level decision-making may reveal strategies for equitable donor heart acceptance. Key Points: Question: Is the race or gender of a patient on the heart transplant waiting list associated with the probability of a donor heart being accepted by the transplant center team with each offer? Findings: In this cohort study of 159 177 heart offers with 13 760 donors and 14 890 candidates, there was a statistically significant difference among the race and gender strata in the cumulative incidence functions, with the cumulative incidence of heart offer acceptance being consistently highest for White women followed by Black women, White men, and Black men. Meaning: The findings suggest that race and gender are significantly associated with the probability of donor heart acceptance and that investigation is needed to change modifiable factors contributing to these disparities. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular conditions that frequently coexist. Among patients with HF, more than one-half also have AF. Both are associated with significant morbidity and mortality. Moreover, the prevalence of each is increasing globally, and this trend is expected to continue owing to an aging population and increased life expectancy. Diagnosis of AF in a patient with HF is associated with greater symptom burden, more frequent hospitalizations, and a worse prognosis. Guideline-directed medical therapy (GDMT) for HF can affect the incidence of AF. Once present, AF can influence the efficacy of some components of GDMT for HF. In this review, we discuss the effect of GDMT for HF across the spectrum of ejection fraction on prevention of AF as well as the benefit of GDMT in patients with vs without AF. [Display omitted] • AF and HF commonly occur concurrently, and the combination is associated with worse prognosis than either condition alone. • GDMT for HF can reduce the incidence of AF. • Further research is needed to clarify the benefit of GDMT for HF in patients with concomitant AF across the range of left ventricular ejection fractions. [ABSTRACT FROM AUTHOR]

Introduction: Central arterial stiffness and wave reflections are important determinants of left ventricular afterload. Given the adverse effect of wave reflections on ventricular-vascular coupling, we sought to determine whether modern guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) influences central aortic parameters. Methods: We assessed central arterial stiffness and wave reflections in 156 subjects (mean age 55 ± 13 yrs, 46% female, 56% black) using arterial tonometry (Sphygmocor, AtCor Medical). GDMT was held for eight hours prior to acquisition of waveforms. Carotid-femoral pulse wave velocity (PWV) was measured. Pulse wave analysis of the radial artery was used to estimate central aortic pressure waveforms. ANOVA was used to compare measurements between groups based on use of GDMT. Results: Mean ejection fraction was 24 ± 9%, with 88% of subjects classified as NYHA II/III. Overall use of GDMT was high: Beta-blockers (97%), ACEi/ARB (65%), mineralocorticoid antagonists (65%), hydralazine-nitrates (19%). Measured SBP (136±31 vs. 110±17 vs. 112±18 vs. 110±18, P<0.001) and PWV (7.2±1.9 vs. 6.8±1.9 vs. 6.9±1.2 vs. 6.4±1.6 m/s, P=0.2) were numerically higher in patients on beta-blockers+ACEiARB+MCA+H-ISDN compared to patients on beta-blockers+ACEi/ARB +MCA, beta-blockers+ACEi/ARB, or beta-blocker only. Pulse wave analysis revealed higher central pressures in patients on beta-blockers+ACEi/ARB+MCA+H-ISDN compared to other groups (Figure). After adjustment for age and sex, higher SBP accounted for the difference in aortic waveforms between groups. Conclusions: HFrEF patients who tolerate more GDMT have a less favorable central aortic waveform, due to higher SBP. Central aortic waveforms could be used for targeted uptitration of GDMT. [ABSTRACT FROM AUTHOR]

Introduction: Leading cardiology organizations have called for initiatives that engage patients with heart failure (HF) in shared decision-making (SDM). In a quality improvement (QI) program conducted in 2 large U.S. health systems, we assessed the impact of QI-focused educational interventions on physicians' documented performance of key SDM practices. Methods: Thirty self-selected physicians participated in the QI program. For baseline and post-intervention periods, the electronic medical records (EMR) of patients with HF were reviewed. Directed content analysis of EMR progress notes was conducted to assess the physicians' documented performance (yes/no) of 5 validated SDM skills: asking patients/caregivers about HF treatment goals, providing patients/caregivers with HF treatment options, explaining pros and cons of HF treatment options, exploring patient/caregiver concerns and fears, and providing opportunities for patients/caregivers to ask questions. Post-baseline, the physicians participated in 4 QI-focused educational webinars that addressed strategies for engaging HF patients in SDM. Results: The 30 physicians reported being in practice for a mean of 15 years and seeing a mean of 24 HF patients per week; 73% were cardiologists and 27% were primary care physicians. The baseline (n = 300) and post-intervention (n = 300) HF patient EMR samples were similar in mean age (74 years), sex (47% female), and race (32% Caucasian, 12% African American, 12% Hispanic, 3% Native American, 41% unknown). From the baseline to post-intervention period, EMR-documented rates of performance for all 5 SDM skills increased significantly (Figure). Conclusions: A QI-focused education program improved SDM physician-patient communication practices for patients with HF. Research is needed to learn if the responses are generalizable. [ABSTRACT FROM AUTHOR]

Introduction: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV‐related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. Methods: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end‐organ disease resulting in the initiation/escalation of anti‐CMV therapy. The secondary outcome was CMV‐related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. Results: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65–5.88, p <.001) and secondary (adjusted HR 3.19, 95% CI: 1.47–6.94, p =.004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p <.001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p =.698). UP was associated with increased incidence of leukopenia within 6 months post‐HT (PET 34.7% vs. UP 43.6%, p =.036). Conclusion: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV‐related hospitalization, and may associate with worse post‐HT graft outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the rare variant genetic architecture of dilated cardiomyopathy differ between patients of African and European ancestry? Findings: In this cross-sectional study of 1198 patients with dilated cardiomyopathy, significantly fewer patients of African ancestry (8.2%) than those European ancestry (25.5%) had variants classified as pathogenic or likely pathogenic, a difference due in part to fewer predicted loss-of-function variants and less case-based evidence to support pathogenicity for variants found only in patients of African ancestry. Meaning: Assumptions regarding dilated cardiomyopathy genetic architecture derived from European ancestry may not be applicable to African ancestry; a current lack of case data limits clinical genetics care for patients of African ancestry with dilated cardiomyopathy. Importance: Black patients with dilated cardiomyopathy (DCM) have increased familial risk and worse outcomes than White patients, but most DCM genetic data are from White patients. Objective: To compare the rare variant genetic architecture of DCM by genomic ancestry within a diverse population of patients with DCM. Design: Cross-sectional study enrolling patients with DCM who self-identified as non-Hispanic Black, Hispanic, or non-Hispanic White from June 7, 2016, to March 15, 2020, at 25 US advanced heart failure programs. Variants in 36 DCM genes were adjudicated as pathogenic, likely pathogenic, or of uncertain significance. Exposure: Presence of DCM. Main Outcomes and Measures: Variants in DCM genes classified as pathogenic/likely pathogenic/uncertain significance and clinically actionable (pathogenic/likely pathogenic). Results: A total of 505, 667, and 26 patients with DCM of predominantly African, European, or Native American genomic ancestry, respectively, were included. Compared with patients of European ancestry, a lower percentage of patients of African ancestry had clinically actionable variants (8.2% [95% CI, 5.2%-11.1%] vs 25.5% [95% CI, 21.3%-29.6%]), reflecting the lower odds of a clinically actionable variant for those with any pathogenic variant/likely pathogenic variant/variant of uncertain significance (odds ratio, 0.25 [95% CI, 0.17-0.37]). On average, patients of African ancestry had fewer clinically actionable variants in TTN (difference, −0.09 [95% CI, −0.14 to −0.05]) and other genes with predicted loss of function as a disease-causing mechanism (difference, −0.06 [95% CI, −0.11 to −0.02]). However, the number of pathogenic variants/likely pathogenic variants/variants of uncertain significance was more comparable between ancestry groups (difference, −0.07 [95% CI, −0.22 to 0.09]) due to a larger number of non-TTN non–predicted loss of function variants of uncertain significance, mostly missense, in patients of African ancestry (difference, 0.15 [95% CI, 0.00-0.30]). Published clinical case-based evidence supporting pathogenicity was less available for variants found only in patients of African ancestry (P <.001). Conclusion and Relevance: Patients of African ancestry with DCM were less likely to have clinically actionable variants in DCM genes than those of European ancestry due to differences in genetic architecture and a lack of representation of African ancestry in clinical data sets. This study compares the rare variant genetic architecture of dilated cardiomyopathy (DCM) among patients with DCM who are of African ancestry compared with European ancestry. [ABSTRACT FROM AUTHOR]

BACKGROUND: The association of historical redlining policies, a marker of structural racism, with contemporary heart failure (HF) risk among White and Black individuals is not well established. METHODS: We aimed to evaluate the association of redlining with the risk of HF among White and Black Medicare beneficiaries. Zip code–level redlining was determined by the proportion of historically redlined areas using the Mapping Inequality Project within each zip code. The association between higher zip code redlining proportion (quartile 4 versus quartiles 1–3) and HF risk were assessed separately among White and Black Medicare beneficiaries using generalized linear mixed models adjusted for potential confounders, including measures of the zip code–level Social Deprivation Index. RESULTS: A total of 2 388 955 Medicare beneficiaries (Black n=801 452; White n=1 587 503; mean age, 71 years; men, 44.6%) were included. Among Black beneficiaries, living in zip codes with higher redlining proportion (quartile 4 versus quartiles 1–3) was associated with increased risk of HF after adjusting for age, sex, and comorbidities (risk ratio, 1.08 [95% CI, 1.04–1.12]; P <0.001). This association remained significant after further adjustment for area-level Social Deprivation Index (risk ratio, 1.04 [95% CI, 1.002–1.08]; P =0.04). A significant interaction was observed between redlining proportion and Social Deprivation Index (P interaction<0.01) such that higher redlining proportion was significantly associated with HF risk only among socioeconomically distressed regions (above the median Social Deprivation Index). Among White beneficiaries, redlining was associated with a lower risk of HF after adjustment for age, sex, and comorbidities (risk ratio, 0.94 [95% CI, 0.89–0.99]; P =0.02). CONCLUSIONS: Historical redlining is associated with an increased risk of HF among Black patients. Contemporary zip code–level social determinants of health modify the relationship between redlining and HF risk, with the strongest relationship between redlining and HF observed in the most socioeconomically disadvantaged communities. [ABSTRACT FROM AUTHOR]

Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Managing disease risk among first-degree relatives of probands diagnosed with a heritable disease is central to precision medicine. A critical component is often clinical screening, which is particularly important for conditions like dilated cardiomyopathy (DCM) that remain asymptomatic until severe disease develops. Nonetheless, probands are frequently ill-equipped to disseminate genetic risk information that motivates at-risk relatives to complete recommended clinical screening. An easily implemented remedy for this key issue has been elusive. Methods: The DCM Precision Medicine Study developed Family Heart Talk , a booklet designed to help probands with DCM communicate genetic risk and the need for cardiovascular screening to their relatives. The effectiveness of the Family Heart Talk booklet in increasing cardiovascular clinical screening uptake among first-degree relatives was assessed in a multicenter, open-label, cluster-randomized, controlled trial. The primary outcome measured in eligible first-degree relatives was completion of screening initiated within 12 months after proband enrollment. Because probands randomized to the intervention received the booklet at the enrollment visit, eligible first-degree relatives were limited to those who were alive the day after proband enrollment and not enrolled on the same day as the proband. Results: Between June 2016 and March 2020, 1241 probands were randomized (1:1) to receive Family Heart Talk (n=621) or not (n=620) within strata defined by site and self-identified race/ethnicity (non-Hispanic Black, non-Hispanic White, or Hispanic). Final analyses included 550 families (n=2230 eligible first-degree relatives) in the Family Heart Talk arm and 561 (n=2416) in the control arm. A higher percentage of eligible first-degree relatives completed screening in the Family Heart Talk arm (19.5% versus 16.0%), and the odds of screening completion among these first-degree relatives were higher in the Family Heart Talk arm after adjustment for proband randomization stratum, sex, and age quartile (odds ratio, 1.30 [1-sided 95% CI, 1.08–∞]). A prespecified subgroup analysis did not find evidence of heterogeneity in the adjusted intervention odds ratio across race/ethnicity strata (P =0.90). Conclusions: Family Heart Talk , a booklet that can be provided to patients with DCM by clinicians with minimal additional time investment, was effective in increasing cardiovascular clinical screening among first-degree relatives of these patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632. [ABSTRACT FROM AUTHOR]

Background: The contemporary measures of hospital performance for heart failure hospitalization and 30-day risk-standardized readmission rate (RSRR) and risk-standardized mortality rate (RSMR) are estimated using the same risk adjustment model and overall event rate for all patients. Thus, these measures are mainly driven by the care quality and outcomes for the majority racial and ethnic group, and may not adequately represent the hospital performance for patients of Black and other races. Methods: Fee-for-service Medicare beneficiaries from January 2014 to December 2019 hospitalized with heart failure were identified. Hospital-level 30-day RSRR and RSMR were estimated using the traditional race-agnostic models and the race-specific approach. The composite race-specific performance metric was calculated as the average of the RSRR/RMSR measures derived separately for each race and ethnicity group. Correlation and concordance in hospital performance for all patients and patients of Black and other races were assessed using the composite race-specific and race-agnostic metrics. Results: The study included 1 903 232 patients (75.7% White [n=1 439 958]; 14.5% Black [n=276 684]; and 9.8% other races [n=186 590]) with heart failure from 1860 hospitals. There was a modest correlation between hospital-level 30-day performance metrics for patients of White versus Black race (Pearson correlation coefficient: RSRR=0.42; RSMR=0.26). Compared with the race-agnostic RSRR and RSMR, composite race-specific metrics for all patients demonstrated stronger correlation with RSRR (correlation coefficient: 0.60 versus 0.74) and RSMR (correlation coefficient: 0.44 versus 0.51) for Black patients. Concordance in hospital performance for all patients and patients of Black race was also higher with race-specific (versus race-agnostic) metrics (RSRR=64% versus 53% concordantly high-performing; 61% versus 51% concordantly low-performing). Race-specific RSRR and RSMR metrics (versus race-agnostic) led to reclassification in performance ranking of 35.8% and 39.2% of hospitals, respectively, with better 30-day and 1-year outcomes for patients of all race groups at hospitals reclassified as high-performing. Conclusions: Among patients hospitalized with heart failure, race-specific 30-day RSMR and RSRR are more equitable in representing hospital performance for patients of Black and other races. [ABSTRACT FROM AUTHOR]

Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice. [Display omitted] • Albuminuria is prevalent in patients with heart failure and confers a strong, consistent and independent association with risk. • The causes of albuminuria in patients with heart failure are incompletely understood, as are the mechanisms linking it to disease progression and adverse outcomes. • Interventions that reduce albuminuria may potentially lower the risk of incident heart failure or prevent progression of existing heart failure. [ABSTRACT FROM AUTHOR]

Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed. [ABSTRACT FROM AUTHOR]

Understanding estimated survival times in discrete groups according to race-ethnicity and age might allow for more accurate patient counseling, to set appropriate expectations for patients who are being considered for HT. Racial disparities in long-term survival after heart transplantation: What should we be telling patients? Black heart transplant (HT) recipients continue to have inferior outcomes compared to other race-ethnic groups, including a higher risk of rejection and allograft failure contributing to lower rates of long-term survival in this population.1-4 It is important for clinicians to understand race-ethnic differences in post-HT survival, so that patients can be counseled accurately. [Extracted from the article]

Importance: Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure-related hospitalization and death.Objective: To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups.Design, Setting, and Participants: A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively.Exposures: The presence of DCM in a proband.Main Outcomes and Measures: Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative.Results: The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, -1.4% [95% CI, -15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]).Conclusions and Relevance: In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives.Trial Registration: ClinicalTrials.gov Identifier: NCT03037632. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic disadvantage is a strong determinant of adverse outcomes in patients with heart failure. However, the contribution of community-level economic distress to adverse outcomes in heart failure may differ across races and ethnicities.Methods: Patients of self-reported Black, White, and Hispanic race and ethnicity hospitalized with heart failure between 2014 and 2019 were identified from the Medicare MedPAR Part A 100% Files. We used patient-level residential ZIP code to quantify community-level economic distress on the basis of the Distressed Community Index (quintile 5: economically distressed versus quintiles 1-4: nondistressed). The association of continuous and categorical measures (distressed versus nondistressed) of Distressed Community Index with 30-day, 6-month, and 1-year risk-adjusted mortality, readmission burden, and home time were assessed separately by race and ethnicity groups.Results: The study included 1 611 586 White (13.2% economically distressed), 205 840 Black (50.6% economically distressed), and 89 199 Hispanic (27.3% economically distressed) patients. Among White patients, living in economically distressed (versus nondistressed) communities was significantly associated with a higher risk of adverse outcomes at 30-day and 1-year follow-up. Among Black and Hispanic patients, the risk of adverse outcomes associated with living in distressed versus nondistressed communities was not meaningfully different at 30 days and became more prominent by 1-year follow-up. Similarly, in the restricted cubic spline analysis, a stronger and more graded association was observed between Distressed Community Index score and risk of adverse outcomes in White patients (versus Black and Hispanic patients). Furthermore, the association between community-level economic distress and risk of adverse outcomes for Black patients differed in rural versus urban areas. Living in economically distressed communities was significantly associated with a higher risk of mortality and lower home time at 1-year follow-up in rural areas but not urban areas.Conclusions: The association between community-level economic distress and risk of adverse outcomes differs across race and ethnic groups, with a stronger association noted in White patients at short- and long-term follow-up. Among Black patients, the association of community-level economic distress with a higher risk of adverse outcomes is less evident in the short term and is more robust and significant in the long-term follow-up and rural areas. [ABSTRACT FROM AUTHOR]

Background: Caregiver support is considered necessary after heart transplant (HT) and left ventricular assist device (LVAD) for patients with end‐stage heart failure (HF). Few studies have demonstrated how caregivers differ by gender and race, and whether that impacts therapy eligibility. Methods: We examined caregiver relationships among 674 patients (32% women, 55% Black) evaluated at Emory University from 2011 to 2017. Therapy readiness was assessed using the Stanford Integrated Assessment for Transplant (SIPAT). Evaluation outcome according to caregiver relationship was compared using χ2 analysis. Multivariable logistic regression determined the association between caregiver and eligibility according to gender and race. Results: Women and Black patients were less likely to have spouses as their support person (P <.001). Women were less likely to be considered eligible for advanced therapies (adjusted odds ratio [aOR].64, 95% confidence interval [CI].46–.89; P =.008), with Black women having lower eligibility than White women (aOR.28, 95% CI.11–.72; P =.008). Social support and SIPAT scores did not significantly influence eligibility by gender or race. Conclusion: Lack of caregiver support is considered a relative contraindication to advanced therapies. Type of caregiver in our cohort varied according to race and gender but did not explain differences in eligibility for advanced therapies. [ABSTRACT FROM AUTHOR]

Heart failure (HF) affects >6 million Americans, with variations in incidence, prevalence, and clinical outcomes by race/ethnicity. Black adults have the highest risk for HF, with earlier age of onset and the highest risk of death and hospitalizations. The risk of hospitalizations for Hispanic patients is higher than White patients. Data on HF in Asian individuals are more limited. However, the higher burden of traditional cardiovascular risk factors, particularly among South Asian adults, is associated with increased risk of HF. The role of environmental, socioeconomic, and other social determinants of health, more likely for Black and Hispanic patients, are increasingly recognized as independent risk factors for HF and worse outcomes. Structural racism and implicit bias are drivers of health care disparities in the United States. This paper will review the clinical, physiological, and social determinants of HF risk, unique for race/ethnic minorities, and offer solutions to address systems of inequality that need to be recognized and dismantled/eradicated. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Arterial stiffening may lead to hypertension, greater left ventricular after-load and adverse clinical outcomes. The underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall. We sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans. Methods and results: We studied 169 subjects (mean age 42.6±14 years, 51.6% male) free of traditional cardiovascular risk factors. Indices of arterial stiffness and wave reflections measured included carotid-femoral Pulse Wave Velocity (PWV), Augmentation Index (Aix) and Pulse Pressure Amplification (PPA). Non-free radical oxidative stress was assessed as plasma oxidized and reduced amino-thiol levels (cysteine/cystine, glutathione/GSSG) and their ratios (redox potentials), and free radical oxidative stress as derivatives of reactive oxygen metabolites (dROMs). Inflammation was assessed as hsCRP and interleukin-6 levels. The non-free radical marker of oxidative stress, cystine was significantly correlated with all arterial indices; PWV (r =0.38, p <0.001), Aix (r =0.35, p <0.001) and PPA (r =−0.30, p <0.001). Its redox potential, was also associated with PWV (r =0.22, p =0.01), while the free radical marker of oxidative stress dROMS was associated with Aix (r =0.25, p <0.01). After multivariate adjustment for age, gender, arterial pressure, height, weight, heart rate and CRP, of these oxidative stress markers, only cystine remained independently associated with PWV (p =0.03), Aix (p =0.01) and PPA (p =0.05). Conclusions: In healthy subjects without confounding risk factors or significant systemic inflammation, a high cystine level, reflecting extracellular oxidant burden, is associated with increased arterial stiffness and wave reflections. This has implications for understanding the role of oxidant burden in pre-clinical vascular dysfunction. [Copyright &y& Elsevier]

[Display omitted] [ABSTRACT FROM AUTHOR]

Cannabis, or marijuana, has potential therapeutic and medicinal properties related to multiple compounds, particularly Δ-9-tetrahydrocannabinol and cannabidiol. Over the past 25 years, attitudes toward cannabis have evolved rapidly, with expanding legalization of medical and recreational use at the state level in the United States and recreational use nationally in Canada and Uruguay. As a result, the consumption of cannabis products is increasing considerably, particularly among youth. Our understanding of the safety and efficacy of cannabis has been limited by decades of worldwide illegality and continues to be limited in the United States by the ongoing classification of cannabis as a Schedule 1 controlled substance. These shifts in cannabis use require clinicians to understand conflicting laws, health implications, and therapeutic possibilities. Cannabis may have therapeutic benefits, but few are cardiovascular in nature. Conversely, many of the concerning health implications of cannabis include cardiovascular diseases, although they may be mediated by mechanisms of delivery. This statement critically reviews the use of medicinal and recreational cannabis from a clinical but also a policy and public health perspective by evaluating its safety and efficacy profile, particularly in relationship to cardiovascular health. [ABSTRACT FROM AUTHOR]