Profile of Patients Hospitalized for Heart Failure Who Leave Against Medical Advice.

BACKGROUND: There is a paucity of information on patients hospitalized with heart failure (HF) who leave against medical advice (AMA). We sought to identify patient and hospital characteristics and outcomes of patients with HF who left AMA compared with those conventionally discharged to home. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure registry, data were analyzed from January 2010 to June 2019. In addition, outcomes were examined from a subset of hospitalizations with Medicare-linked claims between January 2010 and November 2015. The fully eligible population included 561,823 patients and the Medicare-linked subset included 74,502 patients. In total, 8747 patients (1.56%) left AMA. The proportion of patients leaving AMA increased from 1.1% to 2.1% over the years of study. Patients leaving a HF hospitalization AMA, compared with patients conventionally discharged to home, were more likely younger, minorities, Medicaid covered, or uninsured. The Medicare-linked subset of patients who left AMA had substantially higher 30-day and 12-month readmission rates and higher mortality at each assessment point over 12 months compared with patients who were conventionally discharged to home. After risk adjustments, the hazard ratio of mortality in the Medicare-linked subset AMA group compared with the conventionally discharged to home group was 1.25 (95% confidence interval, 1.03-1.51; P = .005). CONCLUSIONS: One in 64 hospitalized patients with HF left AMA. An AMA discharge status was associated with higher risk for adverse 30-day and 12-month outcomes compared with being conventionally discharged home. Strategies that identify patients at risk of leaving AMA and policies to direct interventional strategies are warranted.

Obstructive sleep apnea and cardiovascular disease in blacks: a call to action from the Association of Black Cardiologists.

Obstructive sleep apnea (OSA) has emerged as a new and important risk factor for cardiovascular disease (CVD). Over the last decade, epidemiologic and clinical research has consistently supported the association of OSA with increased cardiovascular (CV) morbidity and mortality. Such evidence prompted the American Heart Association to issue a scientific statement describing the need to recognize OSA as an important target for therapy in reducing CV risk. Emerging facts suggest that marked racial differences exist in the association of OSA with CVD. Although both conditions are more prevalent in blacks, almost all National Institutes of Health-funded research projects evaluating the relationship between OSA and CV risk have been conducted in predominantly white populations. There is an urgent need for research studies investigating the CV impact of OSA among high-risk minorities, especially blacks. This article first examines the evidence supporting the association between OSA and CVD and reviews the influence of ethnic/racial differences on this association. Public health implications of OSA and future directions, especially regarding minority populations, are discussed.

Virtual terminator nucleotides for next-generation DNA sequencing.

We synthesized reversible terminators with tethered inhibitors for next-generation sequencing. These were efficiently incorporated with high fidelity while preventing incorporation of additional nucleotides, and we used them to sequence canine bacterial artificial chromosomes in a single-molecule system that provided even coverage for over 99% of the region sequenced. This single-molecule approach generated high-quality sequence data without the need for target amplification and thus avoided concomitant biases.

Atrial fibrillation and mortality in African American patients with heart failure: results from the African American Heart Failure Trial (A-HeFT).

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and portends a worsened prognosis. Because of the low enrollment of African American subjects (AAs) in randomized HF trials, there are little data on AF in AAs with HF. This post hoc analysis reviews characteristics and outcomes of AA patients with AF in A-HeFT. METHODS AND RESULTS: A total of 1,050 AA patients with New York Heart Association class III/IV systolic HF, well treated with neurohormonal blockade (87% ß-blockers, 93% angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker), were randomized to an added fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo. Atrial fibrillation was confirmed in 174 (16.6%) patients at baseline and in an additional 9 patients who developed AF during the study, for a final cohort of 183 (17.4%). Comparison of patients with AF versus no AF revealed the following: mean age 61 ± 12 versus 56 ± 13 years (P < .001), systolic blood pressure (BP) 124 ± 18 versus 127 ± 18 mm Hg (P = .044), diastolic BP 74 ± 11 versus 77 ± 10 mm Hg (P = .002), creatinine level 1.4 ± 0.5 versus 1.2 ± 0.5 mg/dL (P < .001), and brain natriuretic peptide 431 ± 443 versus 283 ± 396 pg/mL (P < .001). No significant difference was observed in ejection fraction, left ventricular end-diastolic diameter, or quality-of-life scores. However, AF increased the risk of mortality significantly among AA patients (P = .018), and the use of FDC I/H reduced the risk of mortality in patients with AF (HR 0.21, P = .002). CONCLUSION: African Americans with HF and AF (vs no AF) were older, had lower BP, and had higher creatinine and brain natriuretic peptide levels. Mortality and morbidity were worse when AF was present, and these data suggest that there may be an enhanced survival benefit with the use of FDC I/H in AA patients with HF and AF.

Treatment of heart failure in African Americans--a call to action.

Advances in heart failure treatment have not necessarily translated into equity in improved outcomes for African Americans. Heart failure in African Americans is characterized by a higher prevalence, especially at younger ages; more-adverse course with more frequent hospitalizations; and higher mortality rates compared to the general population. Despite this distinct disease profile, African Americans are remarkably underrepresented in large heart failure trials. This paper reviews the unique course of heart failure in African Americans and discusses treatment in the context of clinical trial evidence. African Americans with heart failure may respond differently to some standard therapies compared to whites, but low levels of enrollment of AAs in large clinical trials preclude valid conclusions in certain cases. An important exception is the African American Heart Failure Trial (AHeFT), a well-designed, prospective, randomized, placebo-controlled, double-blind study, that added a combination of fixed-dose isosorbide dinitrate/hydralazine (ISDN/ HYD) to standard therapy and showed a 43% improvement in survival and a 33% reduction in first hospitalizations. Despite compelling evidence from AHeFT, post hoc secondary analyses, and recommendations from current practice guidelines, ISDN/HYD remains underutilized in African Americans with heart failure. In this paper, we put forth a call to action for racial equity in clinical research and treatment in African Americans with heart failure.

Role of nicotinic acetylcholine receptor subunits in the mode of action of neonicotinoid, sulfoximine and spinosyn insecticides in Drosophila melanogaster.

Insecticides remain valuable tools for the control of insect pests that significantly impact human health and agriculture. A deeper understanding of insecticide targets is important in maintaining this control over pests. Our study systematically investigates the nicotinic acetylcholine receptor (nAChR) gene family, in order to identify the receptor subunits critical to the insect response to insecticides from three distinct chemical classes (neonicotinoids, spinosyns and sulfoximines). Applying the CRISPR/Cas9 gene editing technology in D. melanogaster, we were able to generate and maintain homozygous mutants for eight nAChR subunit genes. A ninth gene (Dß1) was investigated using somatic CRISPR in neural cells to overcome the low viability of the homozygous germline knockout mutant. These findings highlight the specificity of the spinosyn class insecticide, spinosad, to receptors containing the Dα6 subunit. By way of contrast, neonicotinoids are likely to target multiple receptor subtypes, beyond those receptor subunit combinations previously identified. Significant differences in the impacts of specific nAChR subunit deletions on the resistance level of flies to neonicotinoids imidacloprid and nitenpyram indicate that the receptor subtypes they target do not completely overlap. While an R81T mutation in ß1 subunits has revealed residues co-ordinating binding of sulfoximines and neonicotinoids differ, the resistance profiles of a deletion of Dß1 examined here provide new insights into the mode of action of sulfoxaflor (sulfoximine) and identify Dß1 as a key component of nAChRs targeted by both these insecticide classes. A comparison of resistance phenotypes found in this study to resistance reported in insect pests reveals a strong conservation of subunit targets across many different insect species and that mutations have been identified in most of the receptor subunits that our findings would predict to have the potential to confer resistance.

Mitral valve annular bacterial vegetative mass masquerading as a left atrial myxoma.

A 49-year-old male with chronic kidney disease and history of renal transplantation in 2006 on chronic immunosuppressant therapy presented with a 1-week history of chills and generalized myalgia. He had a temperature of 101 degrees F. One set of blood cultures grew methicillin-sensitive Staphylococcus aureus. Transesophageal echo (TEE) revealed a mobile mass that was 2 cm in length attached by a thin stalk to the base of the anterior leaflet of the mitral valve. The surgical diagnosis was a left atrial myxoma. The echocardiographic as well as the surgical findings were consistent with an atrial myxoma. However, the histopathology of the specimen showed no evidence of myxoma as the characteristic stellate mesenchymal cells were absent. Instead the milieu of inflammatory cells, fibrin and multimicrobial colonization of both Gram-positive and Gram-negative cocci suggested a super infected vegetative mass. It is interesting that the mitral valve was intact as de novo vegetation being formed on a structurally normal native valve is rare. In some instances, the echocardiographic distinction between atrial masses such as vegetation, thrombus or an atrial myxoma may be ambiguous. Not only does surgical removal allow histological determination of the diagnosis that is critical for treatment, but in cases where an infected mass is mobile and greater than 15 mm, as in this case, there is high potential for embolization. Surgical removal significantly decreases the risk of an embolic event.

Effects of assistive technology on functional decline in people aging with a disability.

This study used a randomized control group design to investigate the impact of an assistive technology and home modification intervention on function for individuals who are aging with a disability. There were 91 participants with polio, rheumatoid arthritis, cerebral palsy, spinal cord injury, stroke, and other impairments. Outcome data were collected at 12 and 24 months through in-home interviews using the Older Americans Resources and Services Instrument (OARS) and the Functional Independence Measure (FIM), and through monthly telephone contact on the hours of in-home care, hospitalizations, and acquisition of AT. The treatment group received an in-home evaluation of their equipment and home modification needs. All recommended AT and home modifications were provided and paid for in full or in part by the study. The control group received the standard community-available health care. A significant "group by time" interaction for the FIM suggested a slower decline in function for the treatment group over 2 years. Further analyses found that the treatment group was more likely to use equipment to maintain independence vs. personal assistance. This study supports the value of assistive technology for adults aging with a disability and suggests that it be provided earlier in the aging process.

Outcome in African Americans and other minorities in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: The SCD-HeFT demonstrated that implantable cardioverter/defibrillator (ICD) therapy significantly improved survival compared to medical therapy alone in stable moderately symptomatic heart failure patients with an ejection fraction < or = 35%. The purpose of this report is to describe the outcomes in African Americans (AAs) and other minorities. METHODS: Of 2521 patients enrolled, 23% were minorities and 17% were AAs. Baseline demographic, clinical variables, socioeconomic status, and long-term outcomes were compared according to race. Two major prespecified subgroups were examined: heart failure cause (ischemic vs nonischemic) and New York Heart Association class (II vs III). RESULTS: At baseline, compared to whites, AAs were younger and had more nonischemic heart failure, lower ejection fractions, worse New York Heart Association functional class, and higher prevalence of a history of nonsustained ventricular tachycardia. Comparable percentages of whites and AAs held paid jobs, but whites had a significantly higher educational level and household income (P = .001). Compliance with ICD implantation and medical therapy was comparable in both subgroups. No significant difference was observed in the rate of ICD discharge among whites and AAs. Adjusted mortality risk was significantly higher in AAs compared to whites (hazard ratio 1.27, P = .038). Mortality was equally reduced in both race groups receiving ICD therapy compared to placebo (hazard ratio 0.65 in AAs and 0.73 in whites). CONCLUSIONS: Survival benefits from ICD therapy in SCD-HeFT were not dependent on race. In addition, in this clinical trial setting, there was no evidence that AAs were less willing to accept ICD therapy than whites.

Emerging role of anemia in heart failure.

Current medical therapy of heart failure (HF) focuses primarily on blockade of the neurohormonal pathways. This approach appears to have reached a benefit plateau, despite the introduction of new and improved drugs. Therefore, new targets for pharmacologic intervention are now being actively sought, and anemia has emerged as a potential candidate. Anemia is a frequently occurring comorbidity in patients with HF. However, its true prevalence is difficult to determine because no uniform definition of anemia associated with HF currently exists. Therefore, reported prevalence data can vary significantly, ranging from 4% to 55%, depending on the study population and the applied definition of anemia. Data from recent observational studies and clinical trials suggest that a low hemoglobin concentration in patients with HF is associated with, and is an independent risk factor for, increased morbidity and mortality. In light of these findings, anemia is being discussed as a possible new treatment target in patients with HF. So far, however, only a few small studies have explored this possibility using erythropoiesis-stimulating proteins, which for many years have been successfully used in the treatment of anemia secondary to chronic kidney disease or cancer chemotherapy. Preliminary data from these initial HF studies have shown that increased hemoglobin concentrations in patients with anemia were associated with improvements in cardiac and renal function as well as exercise capacity and a reduced need for hospitalizations. Larger, controlled clinical trials are needed to clearly establish the benefits and safety aspects of anemia treatment on morbidity and possibly mortality in HF patients.

Synthesis and stereochemical assignment of brasilibactin A.

[structure: see text] Brasilibactin A, a naturally occurring siderophore related to the mycobactins, has been synthesized in six steps. Use of asymmetric titanium-mediated aldol reactions allowed the preparation of both diastereomers from a common synthetic intermediate, thus allowing the relative stereochemistry of the natural product to be assigned. Brasilibactin A exhibits no inhibition of histone deacetylases (HDACs) in spite of the N-formyl-N-hydroxy lysine moiety that is expected to affect the activity of these metal-dependent lysine-modifying enzymes.

Pleiotropic Effects of Loss of the Dα1 Subunit in Drosophila melanogaster: Implications for Insecticide Resistance.

Nicotinic acetylcholine receptors (nAChRs) are a highly conserved gene family that form pentameric receptors involved in fast excitatory synaptic neurotransmission. The specific roles individual nAChR subunits perform in Drosophila melanogaster and other insects are relatively uncharacterized. Of the 10 D. melanogaster nAChR subunits, only three have described roles in behavioral pathways; Dα3 and Dα4 in sleep, and Dα7 in the escape response. Other subunits have been associated with resistance to several classes of insecticides. In particular, our previous work has demonstrated that an allele of the Dα1 subunit is associated with resistance to neonicotinoid insecticides. We used ends-out gene targeting to create a knockout of the Dα1 gene to facilitate phenotypic analysis in a controlled genetic background. To our knowledge, this is the first report of a native function for any nAChR subunits known to be targeted by insecticides. Loss of Dα1 function was associated with changes in courtship, sleep, longevity, and insecticide resistance. While acetylcholine signaling had previously been linked with mating behavior and reproduction in D. melanogaster, no specific nAChR subunit had been directly implicated. The role of Dα1 in a number of behavioral phenotypes highlights the importance of understanding the biological roles of nAChRs and points to the fitness cost that may be associated with neonicotinoid resistance.

Self-Care for the Prevention and Management of Cardiovascular Disease and Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association.

Self-care is defined as a naturalistic decision-making process addressing both the prevention and management of chronic illness, with core elements of self-care maintenance, self-care monitoring, and self-care management. In this scientific statement, we describe the importance of self-care in the American Heart Association mission and vision of building healthier lives, free of cardiovascular diseases and stroke. The evidence supporting specific self-care behaviors such as diet and exercise, barriers to self-care, and the effectiveness of self-care in improving outcomes is reviewed, as is the evidence supporting various individual, family-based, and community-based approaches to improving self-care. Although there are many nuances to the relationships between self-care and outcomes, there is strong evidence that self-care is effective in achieving the goals of the treatment plan and cannot be ignored. As such, greater emphasis should be placed on self-care in evidence-based guidelines.

Hospitalization for heart failure in the presence of a normal left ventricular ejection fraction: results of the New York Heart Failure Registry.

OBJECTIVES: We conducted a prospective multicenter registry in a large metropolitan area to define the clinical characteristics, hospital course, treatment, and factors precipitating decompensation in patients hospitalized for heart failure with a normal ejection fraction (HFNEF). BACKGROUND: The clinical profile of patients hospitalized for HFNEF has been characterized by retrospective analyses of hospital records and state data banks, with few prospective single-center studies. METHODS: Patients hospitalized for heart failure (HF) at 24 medical centers in the New York metropolitan area and found to have a left ventricular (LV) ejection fraction of > or 50% within seven days of admission were included in this registry. Patient demographics, signs and symptoms of HF, coexisting and exacerbating cardiovascular and medical conditions, treatment, laboratory tests, procedures, and hospital outcomes data were collected. Analysis by gender and race was prespecified. RESULTS: Of 619 patients, 73% were women, who were on average four years older than men (72.8 +/- 14.1 years vs. 68.6 +/- 13.8 years, p < 0.001). Black non-Hispanic patients comprised 30% of the study population. They were eight years younger than other patients (66.0 +/- 14.2 years vs. 74 +/- 13.5 years p < 0.001). Co-morbid conditions and their prevalence were: hypertension, 78%; increased LV mass, 82%; diabetes, 46%; and obesity, 46%. Before clinical decompensation that precipitated hospitalization, 86% of patients had chronic symptoms compatible with New York Heart Association functional classes II to IV. Factors precipitating clinical decompensation were identified in 53% of patients. In-hospital mortality was 4.2%. CONCLUSIONS: Patients hospitalized for HFNEF are most often chronically incapacitated elderly women with a history of hypertension and increased LV mass. Reasons for clinical decompensation are identified in only one-half of patients.

Clinical characteristics and echocardiographic features of black men vs. black women with systolic heart failure.

PURPOSE: We sought to determine whether significant differences exist in clinical characteristics and echocardiographic features between black men and black women who presented to an outpatient heart failure clinic. METHODS: A retrospective review of the charts of 114 consecutive patients with systolic dysfunction who presented to a heart failure clinic in Brooklyn from 1999--2003 was performed. The first echocardiogram within six months of presentation to the clinic was used for analysis. The clinical characteristics included are: age, sex, body mass index (BMI) and diabetes status. A significance level of <0.05 was used throughout. SUMMARY: Based on the analysis of 108 black men and women, overall, men have a significantly larger left ventricular end-diastolic diameter (LVEDD) compared to women (p<0.006). Younger men (7.17 cm) had a larger LVEDD compared to older men (6.37 cm) and both younger and older women (6.22 cm and 6.40 cm, respectively). This difference in LVEDD between the sexes decreased with aging. Men (22.17) had a lower ejection fraction (EF) than women (25.37). No significant differences were noted in the BMI (30.45 for men and 28.60 for women) and the albumin level (3.59 for men and 3.44 for women) between the sexes. However, the younger age group (particularly younger men) had a higher BMI than the older age group (p=0.008).