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Jacqueline B Palmer,1 Howard S Friedman,2 Katherine Waltman Johnson,1 Prakash Navaratnam,2 Stephen S Gottlieb3 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2DataMed Solutions, LLC, New York, NY, USA; 3Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA Background: Data comparing effects of transient worsening renal function (WRFt) and persistent WRF (WRFp) on outcomes in patients hospitalized with acute heart failure (AHF) are lacking. We determined the characteristics of hospitalized AHF patients who experienced no worsening renal function (non-WRF), WRFt, or WRFp, and the relationship between cohorts and AHF-related outcomes. Methods and results: A patient’s first AHF hospitalization (index) was identified in the Cerner Health Facts® database (January 2008-March 2011). Patients had WRF if serum creatinine (SCr) was ≥0.3 mg/dL and increased ≥25% from baseline, and they were designated as WRFp if present at discharge or WRFt if not present at discharge. A total of 55,436 patients were selected (non-WRF =77%, WRFp =10%, WRFt =13%). WRFp had greater comorbidity burden than WRFt. At index hospitalization, WRFp patients had the highest mortality, whereas WRFt patients had the longest length of stay (LOS) and highest costs. These trends were observed at 30, 180, and 365 days postdischarge and confirmed by multivariable analyses. WRF patients had more AHF-related readmissions than non-WRF patients. In sensitivity analyses of the patient subset with live index hospitalization discharges, postdischarge LOS and costs were highest in WRFt patients, whereas mortality associated with a HF hospitalization was significantly higher for WRF patients vs non-WRF patients, with no difference between WRFp and WRFt. Conclusion: In patients hospitalized for AHF, WRFp was associated with the highest mortality, whereas WRFt was associated with the highest LOS and costs. WRF patients had higher readmissions than non-WRF patients. Transient increases in SCr appear to be associated with detrimental outcomes, especially longer LOS and higher costs. Keywords: renal function, acute heart failure, mortality rate, health outcomes, serum creatinine, cost

BACKGROUND: Worsening renal function (WRF) portends a poor prognosis, and recent deterioration in creatinine might identify patients with elevated intrarenal adenosine in whom adenosine A(1) antagonism may improve renal hemodynamics and function. The purpose of this pilot study was to assess whether rolofylline, an adenosine A(1) antagonist (A(1)RA), would facilitate diuresis while maintaining renal function in patients with acutely decompensated heart failure (ADHF) and recent WRF. METHODS AND RESULTS: Seventy-six patients with ADHF, volume overload, and recent renal deterioration received rolofylline (30 mg, n = 36) or placebo (n = 40) for 3 days. Rolofylline did not demonstrate a beneficial effect on the primary end points of worsening heart failure or renal function after admission or death or readmission within 30 days. Similar proportions of patients receiving rolofylline (33%) and placebo (30%) were treatment failures within 30 days. However, persistent renal impairment (through Day 14) tended to be less common with rolofylline (6%) than placebo (18%). At Day 14, 11 patients receiving placebo and 13 patients receiving rolofylline had a decrease in creatinine > or = 0.3 mg/dL. There were fewer heart failure readmissions with rolofylline (n = 2) than with placebo (n = 7) through Day 60. CONCLUSIONS: The Placebo-Controlled Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects Hospitalized with Worsening Renal Function and Heart Failure Requiring Intravenous Therapy (ie, REACH UP) study did not demonstrate any clear benefit of rolofylline in patients with ADHF and worsening renal function. However, beneficial trends raise the possibility that A(1)RAs might prevent renal dysfunction in these high risk patients. To test this hypothesis, further larger studies need to evaluate the effects of adenosine A(1) antagonists in patients with progressive renal dysfunction in the face of active heart failure therapy. [ABSTRACT FROM AUTHOR]

Depression is common in patients with heart failure (HF), prognostic for adverse outcomes and purportedly related to disease severity. Psychological and physiologic factors relevant to HF were assessed in HF-ACTION, a large randomized study of aerobic exercise training in patients with systolic HF. The relation of objective and subjective parameters was compared with scores on the Beck Depression Inventory (BDI) to examine the hypothesis that depressive symptoms are better associated with perception of disease severity than with objective markers of HF severity. At baseline, 2,322 of 2,331 subjects entered into HF-ACTION completed questionnaires to assess depression (BDI) and quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]). Objective markers of HF severity included ejection fraction, B-type natriuretic peptide, and peak oxygen consumption (using cardiopulmonary exercise testing, with evaluation of duration and respiratory exchange ratio also performed). Measures more likely to be affected by perceived functional status included New York Heart Association (NYHA) classification and the 6-minute walk test. Objective assessments of disease severity were slightly related (peak oxygen consumption) or not related (B-type natriuretic peptide and ejection fraction) to BDI scores. Using multivariate analysis (KCCQ not included), only age, gender, cardiopulmonary exercise testing duration, NYHA class, 6-minute walk distance, and peak respiratory exchange ratio independently correlated with BDI scores. In conclusion, depression was minimally related to objective assessments of severity of disease in patients with HF, but was associated with patient (and clinician) perceptions of disease severity. Addressing depression might improve symptoms in patients with HF. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a major public health problem in the United States. Approximately 5 million Americans are living with HF, and each year, 550,000 more are newly diagnosed. With recent, rapidly advancing technologies, many studies have examined the effects of technology-based HF management programs. Most of these studies focused on telemonitoring devices, lacking an aspect to motivate individuals to manage their own illnesses. This exploratory study was conducted to (1) examine the readiness of patients with HF in using an eHealth program that includes both telemonitoring and motivational components (ie, Web learning modules, eCommunication) and (2) assess the specific needs of patients with HF that can be addressed by a future eHealth program. This was a single group descriptive study using a convenience sample. A total of 44 patients with HF (mean age, 72.8 years; range, 55-85 years) were recruited from the pool of enrollees of the Medicare Coordinated Care Demonstration project for HF management that used only a telemonitoring component. Although only 10 participants were users, among 34 nonusers, 17 reported availability of Web access, and 15 reported that they would use the Internet if access and training were available. Overall, confidence for using telemonitoring devices and Web-based health modules was high, with means of 27 (range, 3-30) and 7.6 (range, 1-10), respectively. Confidence for learning health information using Web modules, however, was lower with a mean of 41.5 (range, 8-80). The 2 most highly rated health information needs were research findings (n = 41, 93.2%) and medication (n = 39, 88.6%). Most participants would like to have e-mail communication with healthcare providers. The findings showed the participants' high readiness to use the proposed eHealth program if access and training were provided. This study used a small convenience sample. Further studies are needed with larger, diverse samples. [ABSTRACT FROM AUTHOR]

Renal function is a very important prognostic indicator in patients with congestive heart failure. While some of the prognostic importance of poor renal function is related to the worse physiology associated with it, there are suggestions that the dysfunction itself is detrimental. Recently, it has been shown that adenosine may mediate much kidney activity. In addition to vasoconstrictive and vasodilatory effects, adenosine is intrinsic to the tubuloglomerular feedback which occurs when an acute increase in sodium levels in the proximal tubule feeds back to decrease glomerular filtration. Adenosine works via both adenosine A1 and A2 receptors. A1-receptor antagonists decrease afferent arteriolar pressure, and increase urine flow and sodium excretion. Studies suggest that A1-receptor antagonists cause a diuretic effect not by a change in the renal haemodynamics, but by the inhibition of water and sodium reabsorption in tubular sites secondary to direct tubuloglomerular feedback. Less consistent has been the occasional finding of increased glomerular filtration rate despite the lack of improved renal plasma flow. Clinically important questions are: what role adenosine plays in causing the poor renal function associated with heart failure and what A1-receptor antagonists do in such situations? If an A1-receptor antagonist could cause diuresis while maintaining or improving glomerular filtration, it would be a useful adjunct in the treatment of severe heart failure. We evaluated the effects of the A1-receptor antagonist CVT-124 (BG-9719) in heart failure patients. CVT-124 increased sodium excretion without decreasing glomerular filtration rate. These data suggest that adenosine might be an important determinant of renal function in patients with heart failure. [ABSTRACT FROM AUTHOR]

Background: Long-term administration of beta-adrenergic blockers to patients after myocardial infarction improves survival. However, physicians are reluctant to administer beta-blockers to many patients, such as older patients and those with chronic pulmonary disease, left ventricular dysfunction, or non-Q-wave myocardial infarction.Methods: The medical records of 201,752 patients with myocardial infarction were abstracted by the Cooperative Cardiovascular Project, which was sponsored by the Health Care Financing Administration. Using a Cox proportional-hazards model that accounted for multiple factors that might influence survival, we compared mortality among patients treated with beta-blockers with mortality among untreated patients during the two years after myocardial infarction.Results: A total of 34 percent of the patients received beta-blockers. The percentage was lower among the very elderly, blacks, and patients with the lowest ejection fractions, heart failure, chronic obstructive pulmonary disease, elevated serum creatinine concentrations, or type 1 diabetes mellitus. Nevertheless, mortality was lower in every subgroup of patients treated with beta-blockade than in untreated patients. In patients with myocardial infarction and no other complications, treatment with beta-blockers was associated with a 40 percent reduction in mortality. Mortality was also reduced by 40 percent in patients with non-Q-wave infarction and those with chronic obstructive pulmonary disease. Blacks, patients 80 years old or older, and those with a left ventricular ejection fraction below 20 percent, serum creatinine concentration greater than 1.4 mg per deciliter (124 micromol per liter), or diabetes mellitus had a lower percentage reduction in mortality. Given, however, the higher mortality rates in these subgroups, the absolute reduction in mortality was similar to or greater than that among patients with no specific risk factors.Conclusions: After myocardial infarction, patients with conditions that are often considered contraindications to beta-blockade (such as heart failure, pulmonary disease, and older age) and those with nontransmural infarction benefit from beta-blocker therapy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the test-retest reliability of intraventricular dyssynchrony (IVD) assessment by tissue Doppler imaging (TDI) echocardiography. Limited response rates to cardiac resynchronization may improve with TDI screening for appropriate recipients. However, the clinical applicability of TDI will depend on the reliability of the test. Repeat TDI was prospectively performed (11 +/- 11 days apart) in 15 patients with QRS intervals >120 ms and left ventricular ejection fractions <35% and 25 normal controls using the same machine, sonographer, and blinded readers for the 2 tests. There was no change in clinical status or treatment between tests. Established and clinically feasible criteria for IVD were evaluated. These were based on differences of TDI-derived activation time between 2, 4, or 12 left ventricular segments. Reliability was assessed by linear correlation and Bland-Altman analysis for quantified measures, along with percentage agreement and kappa statistics for IVD diagnosis. Despite good intrareader (r = 0.98, p <0.0001) and interreader (2 segments: r = 0.96, p <0.0001; 4 segments: r = 0.85, p <0.0001) reliability, test-retest correlations were uniformly modest for the 2-segment (r = 0.26, p = 0.11), 4-segment (r = 0.36, p = 0.021), and 12-segment (r = 0.50, p = 0.0009) measures. Test-retest agreement for IVD diagnosis by either criterion was equally limited (2 segments: 83%, kappa = 0.27; 4 segments: 75%, kappa = 0.47; 12 segments: 68%, kappa = 0.35). Bland-Altman analysis demonstrated wide confidence intervals, exceeding the diagnostic cutoff values for the respective criteria. In conclusion, the accurate assessment of IVD by TDI may be limited by poor test-retest reliability. [ABSTRACT FROM AUTHOR]

Background: Fatigue is a prominent symptom of heart failure (HF). However, underlying mechanisms remain poorly understood. Fluid volume status has been suggested as a physiologic mechanism of HF-related fatigue. Serum osmolality may fluctuate with changes in volume status associated with neurohormonal dysregulation. The relationship of fatigue to serum osmolality has not been assessed in adults with HF., Objectives: Describe the relationship between serum osmolality and fatigue in adults with HF., Methods: We analyzed two waves of cross-sectional data from the National Health and Nutrition Examination Survey (2015-2016 and 2017-2018). Adults who self-reported having HF without select co-morbid conditions known to contribute to fatigue were included. Data were weighted to provide US national estimates, and complex sample design used for analyses. Sequential logistic regression was used to isolate the effect of serum osmolality on the odds of having fatigue., Results: Data from the sample represented 1.4 million Americans with HF (58.5 % male; median age 68 years), of whom 1,001,589 (67.9 %) reported fatigue. Participants with fatigue had lower serum osmolality compared to those without fatigue (t = -3.04, p = .009). Higher serum osmolality was associated with 8.8 % lower odds of experiencing fatigue when controlling for sex and body mass index (OR = 0.912, p = .007, CI 0.857 - 0.972)., Conclusions: HF-related fatigue is associated with lower serum osmolality. Low serum osmolality may indicate excess volume and the presence of a heightened neurohormonal response, both of which may influence fatigue. Alternatively, serum osmolality may directly affect other physiologic changes that may contribute to fatigue., Competing Interests: Declaration of competing interest All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work; and no other relationships or activities that could appear to have influenced the submitted work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., Competing Interests: Funding Support and Author Disclosures Dr O’Meara is supported by the Montreal Heart Institute’s Carolyn & Richard J. Renaud Chair for Research in Heart Failure, with fees paid through her institution for this chair, for a Canadian Heart Function Alliance (CHFA) Team Grant, funded by the CIHR (steering committee member), and for involvement in the following trials as a steering committee member for DAPA-ACT and GARDEN-HF (TIMI group and AstraZeneca), for HEART-FID (steering committee member, American Regent), CARDINAL-HF (steering committee member, Cardurion), and HERMES (national lead investigator, Novo Nordisk); and has received consulting or speaker fees from AstraZeneca, Boehringer Ingelheim, Bayer, and Novartis. Dr Savarese has received grants and personal fees from Vifor, AstraZeneca, Pharmacosmos, and Novartis; has received grants from Boehringer Ingelheim, Boston Scientific, Merck, and Bayer; has received personal fees from Servier, Cytokinetics, Medtronic, Edwards Lifesciences, Teva, and Abbott; and receives funding through the EU Horizon Programme and the Swedish Heart and Lung Foundation. Dr Vardeny has received research support (paid to institution) from the National Institutes of Health, the Food and Drug Administration, AstraZeneca, Bayer, and Cardurion; and has received personal consulting fees from Cardior and Cytokinetics. Dr Allen has received grant funding from the Patient-Centered Outcomes Research Institute and the National Institutes of Health; and has received consulting fees from ACI Clinical, Boston Scientific, Cytokinetics, Novartis, and Quidel. Dr Gottlieb has received consulting fees from Cytokinetics. Dr Zainab serves on the Heart Failure Publication Committee of Cytokinetics. Dr Morris has received consulting fees or honoraria from Abbott, Acorai, BI Lilly, Cytokinetics, Edwards, Ionis, Merck, Novo Nordisk, and Regeneron. Dr Desai works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and has received research grants and consulting for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, SCPharmaceuticals, and Vifor. Dr Teerlink has received consulting fees from Cytokinetics. Dr Saldarriaga-Giraldo has served as a speaker for AstraZeneca, Novartis, Servier, Abbott, Medtronic, Pfizer, Roche, Sanofi, Boehringer Ingelheim, Elly Lilly, Bayer, and Merck; has served as a principal investigator for Amgen, Novartis, Merck, and Bayer; and has served as an advisor for Medtronic, Novartis, Bayer, AstraZeneca, Boehringer Ingelheim, Servier, and Novo Nordisk. Dr Lindenfeld has received grant funding from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and AstraZeneca; and has received consulting fees from Abbott, Alleviant, AstraZeneca, Axon, Bayer, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Merck, Medtronic, VWave, and Vascular Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Correct hospital medication reconciliation is important for continuity of care, but optimal home antihypertensive medication ordering has not been adequately studied. Since excessive hospital blood pressure control is associated with adverse renal and cardiovascular outcomes, we assessed the association of inpatient doses of amlodipine (10mg vs. 5mg) with length of stay and renal failure and fluid and electrolyte disorders (RF/FED). Methods In this retrospective cohort study, clinical and demographic data on patients not initially admitted to the ICU between 2008 and 2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV). Multivariable logistic regression was used to assess the association between amlodipine dose during the first 24 hours of admission and RF/FED. Multivariable linear regression was used to assess the association between amlodipine dose and length of stay when controlling for RF/FED or maximum blood urea nitrogen (BUN) concentration and other confounders. Results There were 5,932 patients included in this study, and 3,038 of whom received 10mg of amlodipine. A 10mg dose of amlodipine was associated with an increased likelihood of RF/FED (OR: 1.248, 95% CI (1.104, 1.412), p<0.001). It was also associated with a longer length of stay (coef.: 0.338, 95% CI (0.067, 0.609), p=0.015). This was not significant when controlling for RF/FED (dose coef.: 0.197, 95% CI (-0.070, 0.464), p=0.147) or maximum BUN (dose coef.: 0.082, 95% CI (-0.147, 0.312), p=0.482). Interpretation Higher amlodipine dose was associated with longer length of stay, and this is likely mediated by RF/FED. Randomized trials are needed to determine which home blood pressure medications should be ordered in the hospital., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gottlieb et al.)

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., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03037632., Competing Interests: Disclosures None.

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.

Background: 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)., Objectives: This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients., Methods: 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., 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., Conclusions: 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., Competing Interests: Funding Support and Author Disclosures Research reported in this publication was supported by a parent award from the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R01HL128857, which included a supplement from the National Human Genome Research Institute. The DCM Precision Medicine Study was supported by computational infrastructure provided by The Ohio State University Division of Human Genetics Data Management Platform and the Ohio Supercomputer Center. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient's life, resulting in a drastic impairment in multiple aspects of daily activities (e.g. physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient's experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient-reported outcomes (PROs) aim to switch traditional care to a more patient-centred approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient's standpoint in HF care., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

What Is This Plain Language Summary About?: This summary presents the results from an ongoing, long-term extension study that followed an earlier study called ATTR-ACT. People who took part in this extension study and ATTR-ACT have a type of heart disease known as transthyretin amyloid cardiomyopathy (ATTR-CM for short), which causes heart failure and death. In ATTR-ACT, people took either a medicine called tafamidis or a placebo (a pill that looks like the study drug but does not contain any active ingredients) for up to 2½ years. So far, in the long-term extension study, people have continued taking tafamidis, or switched from taking a placebo to tafamidis, for another 2½ years. Researchers looked at how many people died in ATTR-ACT and the extension study. The long-term extension study is expected to end in 2027, so these are interim (not final) results., What Did Researchers Find Out?: In the extension study of ATTR-ACT, the risk of dying was lower in people who took tafamidis continuously throughout ATTR-ACT and the extension study than in people who took placebo in ATTR-ACT and switched to tafamidis in the extension study., What Do the Results Mean?: Taking tafamidis increases how long people with ATTR-CM live. People with ATTR-CM who take tafamidis early and continuously are more likely to live longer than those who do not. These results highlight the importance of early detection and treatment in people with ATTR-CM. Clinical Trial Registration : NCT01994889 (ClinicalTrials.gov) Clinical Trial Registration : NCT02791230 (ClinicalTrials.gov).

Importance: Cardiovascular disease contributes outsized mortality in patients from underrepresented racial and ethnic groups. Understanding levels of trust in medical researchers and knowledge of genome sequencing may help identify barriers to research participation and develop strategies to educate patients about the role of genetics in cardiovascular disease., Objective: To assess racial and ethnic differences in trust in medical researchers and genome-sequencing knowledge among patients with idiopathic dilated cardiomyopathy and determine the association between trust in medical researchers and genome-sequencing knowledge., Design, Setting, and Participants: This cross-sectional study conducted by a consortium of 25 US heart failure programs included patients with idiopathic dilated cardiomyopathy defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes. Enrollment occurred from June 7, 2016, to March 15, 2020., Main Outcomes and Measures: Percent distributions, means, and associations of genome-sequencing knowledge scores and research trust scores for Hispanic, non-Hispanic Black (hereafter referred to as Black), and non-Hispanic White participants (hereafter referred to as White)., Results: Among 1121 participants, mean (SD) age was 51.6 (13.6) years with 41.4% Black, 8.5% Hispanic, and 43.4% female. After accounting for site effects, the level of genome-sequencing knowledge was lower in Hispanic and Black participants compared with White participants (mean score difference, -2.6; 95% CI, -3.9 to -1.2 and mean score difference, -2.9; 95% CI, -3.6 to -2.2, respectively). The level of trust in researchers was lowest in Black participants (mean score, 27.7), followed by Hispanic participants (mean score, 29.4) and White participants (mean score, 33.9). Racial and ethnic differences remained after adjusting for education, age at enrollment, duration of dilated cardiomyopathy, and health status. A higher level of trust was associated with a higher level of genome-sequencing knowledge within different racial and ethnic groups., Conclusions and Relevance: In this cross-sectional study, large racial and ethnic differences in levels of genome-sequencing knowledge and trust in medical researchers were observed among patients with dilated cardiomyopathy. Findings from this study can inform future studies that aim to enhance the uptake of genomic knowledge and level of trust in medical researchers.

Cloning of the "Na + pump" (Na + ,K + -ATPase or NKA) and identification of a circulating ligand, endogenous ouabain (EO), a cardiotonic steroid (CTS), triggered seminal discoveries regarding EO and its NKA receptor in cardiovascular function and the pathophysiology of heart failure (HF) and hypertension. Cardiotonic digitalis preparations were a preferred treatment for HF for two centuries, but digoxin was only marginally effective in a large clinical trial (1997). This led to diminished digoxin use. Missing from the trial, however, was any consideration that endogenous CTS might influence digitalis' efficacy. Digoxin, at therapeutic concentrations, acutely inhibits NKA but, remarkably, antagonizes ouabain's action. Prolonged treatment with ouabain, but not digoxin, causes hypertension in rodents; in this model, digoxin lowers blood pressure (BP). Furthermore, NKA-bound ouabain and digoxin modulate different protein kinase signaling pathways and have disparate long-term cardiovascular effects. Reports of "brain ouabain" led to the elucidation of a new, slow neuromodulatory pathway in the brain; locally generated EO and the α2 NKA isoform help regulate sympathetic drive to the heart and vasculature. The roles of EO and α2 NKA have been studied by EO assay, ouabain-resistant mutation of α2 NKA, and immunoneutralization of EO with ouabain-binding Fab fragments. The NKA α2 CTS binding site and its endogenous ligand are required for BP elevation in many common hypertension models and full expression of cardiac remodeling and dysfunction following pressure overload or myocardial infarction. Understanding how endogenous CTS impact hypertension and HF pathophysiology and therapy should foster reconsideration of digoxin's therapeutic utility.

Heart failure with reduced ejection fraction is managed with increasing numbers of guideline-directed medical therapies (GDMT). Benefits tend to be additive. Burdens can also be additive. We propose a heart failure spending function as a conceptual framework for tailored intensification of GDMT that maximizes therapeutic opportunity while limiting adverse events and patient burden. Each patient is conceptualized to have reserve in physiological and psychosocial domains, which can be spent for a future return on investment. Key domains are blood pressure, heart rate, serum creatinine, potassium, and out-of-pocket costs. For each patient, GDMT should be initiated and intensified in a sequence that prioritizes medications with the greatest expected cardiac benefit while drawing on areas where the patient has ample reserves. When reserve is underspent, patients fail to gain the full benefit of GDMT. Conversely, when a reserve is fully spent, addition of new drugs or higher doses that draw upon a domain will lead to patient harm. The benefit of multiple agents drawing upon varied physiological domains should be balanced against cost and complexity. Thresholds for overspending are explored, as are mechanisms for implementing these concepts into routine care, but further health care delivery research is needed to validate and refine clinical use of the spending function. The heart failure spending function also suggests how newer therapies may be considered in terms of relative value, prioritizing agents that draw on different spending domains from existing GDMT.

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.

Background: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial)., Methods: Patients with transthyretin amyloid cardiomyopathy who completed ATTR-ACT could enroll in an LTE, continuing with the same tafamidis dose or, if previously treated with placebo, randomized (2:1) to tafamidis meglumine 80 or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg) following a protocol amendment. In this interim analysis, all-cause mortality was assessed in patients treated with tafamidis meglumine 80 mg in ATTR-ACT continuing in the LTE, compared with those receiving placebo in ATTR-ACT transitioning to tafamidis in the LTE., Results: Median follow-up was 58.5 months in the continuous tafamidis group (n=176) and 57.1 months in the placebo to tafamidis group (n=177). There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44-0.79]; P <0.001). Mortality was also reduced in the continuous tafamidis (versus placebo to tafamidis) subgroups of: variant transthyretin amyloidosis (0.57 [0.33-0.99]; P =0.05) and wild-type transthyretin amyloidosis (0.61 [0.43-0.87]; P =0.006); and baseline New York Heart Association class I and II (0.56 [0.38-0.82]; P =0.003) and class III (0.65 [0.41-1.01]; P =0.06)., Conclusions: In the LTE, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo, highlighting the importance of early diagnosis and treatment in transthyretin amyloid cardiomyopathy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01994889 and NCT02791230.

Agricultural productivity relies on synthetic nitrogen fertilizers, yet half of that reactive nitrogen is lost to the environment. There is an urgent need for alternative nitrogen solutions to reduce the water pollution, ozone depletion, atmospheric particulate formation, and global greenhouse gas emissions associated with synthetic nitrogen fertilizer use. One such solution is biological nitrogen fixation (BNF), a component of the complex natural nitrogen cycle. BNF application to commercial agriculture is currently limited by fertilizer use and plant type. This paper describes the identification, development, and deployment of the first microbial product optimized using synthetic biology tools to enable BNF for corn ( Zea mays ) in fertilized fields, demonstrating the successful, safe commercialization of root-associated diazotrophs and realizing the potential of BNF to replace and reduce synthetic nitrogen fertilizer use in production agriculture. Derived from a wild nitrogen-fixing microbe isolated from agricultural soils, Klebsiella variicola 137-1036 ("Kv137-1036") retains the capacity of the parent strain to colonize corn roots while increasing nitrogen fixation activity 122-fold in nitrogen-rich environments. This technical milestone was then commercialized in less than half of the time of a traditional biological product, with robust biosafety evaluations and product formulations contributing to consumer confidence and ease of use. Tested in multi-year, multi-site field trial experiments throughout the U.S. Corn Belt, fields grown with Kv137-1036 exhibited both higher yields (0.35 ± 0.092 t/ha ± SE or 5.2 ± 1.4 bushels/acre ± SE) and reduced within-field yield variance by 25% in 2018 and 8% in 2019 compared to fields fertilized with synthetic nitrogen fertilizers alone. These results demonstrate the capacity of a broad-acre BNF product to fix nitrogen for corn in field conditions with reliable agronomic benefits.

Background: Outpatient calcitrope infusions-that is, the cardiac inotropes milrinone and dobutamine-are often used for bridge to transplantation and palliation in advanced heart failure, but few data exist about the real-world use of these agents., Methods and Results: We used the Symphony Integrated DataVerse of commercial, managed Medicare, and Medicaid insurance claims of approximately 280 million people (2012-2020) to determine the incidence and characteristics of ambulatory calcitrope use. Demographics were calculated, including geographic densities at the metropolitan statistical area level. A population projection normalized for age, sex, and location was extrapolated to the total US population. Ambulatory dispensing of milrinone was found in 10,533 outpatients, 1867 in 2019. Ambulatory dobutamine use was found in 4967 outpatients, 836 in 2019. The 2019 total US projection was 3411 for milrinone and 1281 for dobutamine. The mean age was 62 years for milrinone and 68 for dobutamine. Males represented 70% of use. There were differences between drugs in geographic distribution, with more milrinone use in the Northeast and South and more dobutamine use in the Midwest. Duration of use was 4.6 ± 7.2 months for milrinone and 1.8 ± 4.0 months for dobutamine. Of the patients receiving milrinone, 30.6% subsequently underwent cardiac transplantation or left ventricular assist device placement, whereas 10% receiving dobutamine went on to advanced therapies. Less than 0.5% of patients received calcitropes while enrolled in hospice care., Conclusions: More than 4000 patients receive outpatient infusion of calcitropes annually in the outpatient setting. Men are much more likely to receive these medications. A minority of the use is as a bridge to advanced therapies. Geographic variability in use suggests better evidence and consistent guidelines may be helpful., (Published by Elsevier Inc.)

Medications with proven benefit in patients with heart failure with reduced ejection fraction are recommended, according to prospective large clinical trials, in the stable patient after careful up-titration in a strict sequential order. Although the relevance of careful clinical up-titration is unproven, there is evidence that after recompensation and shortly after hospital discharge, the rate of cardiovascular death and hospitalization is high. Clinical studies provided evidence that the onset of treatment effects is rapid, occurring within 28 days with most of these drugs used, and in some trials, early treatment after discharge or already started in the hospital has provided benefits. Therefore, early treatment without deferring it to the stable outpatient may be useful to reduce cardiac-related events further. This expert opinion proposes treatment layering according to individual patient phenotypes involving heart rate, blood pressure, impaired renal function, and electrolyte disturbances, as well as dedicated subgroups of patients with specific requirements for treatment initiation. This complements other approaches that suggest starting sequential treatment according to the size of treatment effects of drugs, specific cardiac diseases, and patient wishes. Patient phenotyping may guide personalized drug layering in heart failure with reduced ejection fraction that provides the best outcomes, whereas pragmatic clinical trials are warranted to scrutinize the effectiveness of these approaches., Competing Interests: Funding Support and Author Disclosures Dr Allen has received grants from the American Heart Association, the National Institutes of Health, and the Patient-Centered Outcomes Research Institute; and consulting fees from Abbott, ACI Clinical, Amgen, Boston Scientific, Cytokinetics, and Novartis. Dr Abdin has received speaker honoraria from Novartis; and travel grants from Biotronik, Medtronic, and Novartis. Dr Lindenfeld has received grant funding from AstraZeneca, Sensible Medical, Volumetrix; and personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Impulse Dynamics, and VWave. Dr Lam has received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics; consultancy fees from service on the advisory board, steering committee, or executive committee of Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, Us2.ai, Janssen Research & Development LLC, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, and WebMD Global LLC; and holds a position as cofounder and nonexecutive director of Us2.ai. Dr Savarese has received grants from Boston Scientific (outside the submitted work), Vifor, Boehringer Ingelheim, AstraZeneca, and Novartis; nonfinancial support from Boehringer Ingelheim; and personal fees from Vifor and the Societá Prodotti Antibiotici, AstraZeneca, Roche, Servier, GENESIS, Cytokinetics, and Medtronic. Dr Gottlieb has received grants from Pfizer, Cytokinetics, and Amgen; and consulting for Cytokinetics. Dr Böhm has received support from the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939); and has fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Servier, Medtronic, Vifor, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) constitute a high-risk phenotype with significant morbidity and mortality and poor prognosis. Multiple proinflammatory comorbid conditions influence the pathogenesis of HFpEF and CKD. Renal dysfunction in HFpEF is a consequence of the complex interplay between hemodynamic factors, systemic congestion, inflammation, endothelial dysfunction, and neurohormonal mechanisms. In contrast to heart failure with reduced ejection fraction, there is a dearth of effective targeted therapies for HFpEF. Tailoring study design toward the different phenotypes and delving into their pathophysiology may be fruitful in development of effective phenotype-specific targeted pharmaceutical therapies., Competing Interests: Disclosure Dr M.G. Ananthram has nothing to disclose. Dr S.S. Gottlieb reports consulting to Cytokinetics and Eidos., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated., Methods: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI)., Results: We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27)., Conclusion: We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted., Competing Interests: The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: RB reports funding from ViiV Healthcare and service on scientific advisory boards for Merck & Co, and ViiV Healthcare. SG reports funding from Gilead Sciences, travel support from Gilead Sciences and Bristol-Myers Squibb, and receipt of advisory board fees from Gilead Sciences and GlaxoSmithKline/ViiV Healthcare. MB reports funding from General Electric. AB reports funding from Gilead Sciences. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: Under controlled conditions, mental stress can provoke decrements in ventricular function, yet little is known about the effect of mental stress on diastolic function in patients with heart failure (HF)., Methods and Results: Twenty-four patients with HF with ischemic cardiomyopathy and reduced ejection fraction (n = 23 men; mean left ventricular [LV] ejection fraction 27 ± 9%; n = 13 with baseline elevated E/e') completed daily assessment of perceived stress, anger, and negative emotion for 7 days, followed by a laboratory mental stress protocol. Two-dimensional Doppler echocardiography was performed at rest and during sequential anger recall and mental arithmetic tasks to assess indices of diastolic function (E, e', and E/e'). Fourteen patients (63.6%) experienced stress-induced increases in E/e', with an average baseline to stress change of 6.5 ± 9.3, driven primarily by decreases in early LV relaxation (e'). Age-adjusted linear regression revealed an association between 7-day anger and baseline E/e'; patients reporting greater anger in the week before mental stress exhibited higher resting LV diastolic pressure., Conclusions: In patients with HF with reduced ejection fraction, mental stress can provoke acute worsening of LV diastolic pressure, and recent anger is associated with worse resting LV diastolic pressure. In patients vulnerable to these effects, repeated stress exposures or experiences of anger may have implications for long-term outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes., Objectives: The purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF., Methods: Of the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort., Results: Matched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up., Conclusions: Hospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF., (Published by Elsevier Inc.)

Introduction: Heart failure is associated with increased neurohormonal activation that results in changes in body composition including volume overload and the loss of skeletal muscle, body fat, and bone density. Bioelectrical impedance measures body composition based on the conduction of electrical current through body fluids., Areas Covered: The PubMed and Scopus databases were reviewed up to the third week of June 2020. Cross-sectional studies, retrospective observational studies, prospective observational studies, and randomized controlled trials have examined numerous bioelectrical impedance monitoring strategies to guide the diagnosis, prognosis, and treatment of heart failure. These monitoring strategies include intrathoracic impedance, lung impedance, bioelectrical impedance vector analysis, leg bioelectrical impedance, and thoracic bioreactance., Expert Commentary: Based on the current evidence, more studies are needed to validate bioelectrical impedance in heart failure. Lung impedance appears to be useful for guiding heart failure treatment in patients with ST-elevation myocardial infarction and improving outcomes in outpatients with heart failure. Furthermore, bioelectrical impedance has potential as a noninvasive, quantitative heart failure variable for population-based research.