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Objective Assess impact of Medicare Part D benefit phases on adherence with evidence-based medications after hospitalization for an acute myocardial infarction. Data Source Random 5 percent sample of Medicare beneficiaries. Study Design Difference-in-difference analysis of drug adherence by AMI patients stratified by low-income subsidy ( LIS) status and benefit phase. Data Collection/Extraction Methods Subjects were identified with an AMI diagnosis in Medicare Part A files between April 2006 and December 2007 and followed until December 2008 or death ( N = 8,900). Adherence was measured as percent of days covered ( PDC) per month with four drug classes used in AMI treatment: angiotensin-converting enzyme ( ACE) inhibitors/angiotensin II receptor blockers ( ARBs), beta-blockers, statins, and clopidogrel. Monthly exposure to Part D benefit phases was calculated from flags on each Part D claim. Principal Findings For non- LIS enrollees, transitioning from the initial coverage phase into the Part D coverage gap was associated with statistically significant reductions in mean PDC for all four drug classes: statins (−7.8 percent), clopidogrel (−7.0 percent), beta-blockers (−5.9 percent), and ACE inhibitor/ ARBs (−5.1 percent). There were no significant changes in adherence associated with transitioning from the gap to the catastrophic coverage phase. Conclusions As the Part D doughnut hole is gradually filled in by 2020, Medicare Part D enrollees with critical diseases such as AMI who rely heavily on brand name drugs are likely to exhibit modest increases in adherence. Those reliant on generic drugs are less likely to be affected. [ABSTRACT FROM AUTHOR]

Previous studies suggest that adenosine A1 receptor antagonists may promote natriuresis without deleterious effects on renal function. This study evaluated renal and hemodynamic effects as well as safety, pharmacokinetics, and tolerability of BG9928, a selective adenosine A1-receptor antagonist, in patients with heart failure. In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation study, 33 patients received a single dose of BG9928 (0.03, 0.3, 1.0, or 3.0 mg/kg) or placebo intravenously. Change from baseline in urinary sodium excretion for the 8-hour postdose interval was greater for all dosing groups versus placebo. The 0.03-mg/kg and 0.3-mg/kg groups had significant reductions in body weight versus placebo (−0.8 kg, −1.1 kg, 0.3 kg, respectively; P < 005). No changes in creatinine clearance or hemodynamic parameters were observed among any of the BG9928 groups versus placebo. However, pulmonary capillary wedge pressure tended to decrease and correlated with weight loss. Across the range of doses studied, pharmacokinetic parameters were linear and predictable. One patient who received the highest dose (3.0 mg/kg) developed seizures, and no further patients received that dose. Single intravenous BG9928 doses of up to 1.0 mg/kg were well tolerated and increased sodium excretion without worsening renal function. Further studies are needed to determine the clinical benefit of adenosine A1 receptor antagonism. [ABSTRACT FROM PUBLISHER]

Background: Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis.Objectives: The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry.Methods: Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189).Results: U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival.Conclusions: In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745). [ABSTRACT FROM AUTHOR]

Background: Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF.Methods and Results: Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99).Conclusions: Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD. [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.)

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: 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: 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.)

Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown., Methods: Using the Veterans Aging Cohort Study Survey Cohort, insomnia symptoms were measured and dummy coded with the item, "Difficulty falling or staying asleep?" (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with the Department of Veterans Affairs (VA) and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded., Results: HIV-infected (N = 3108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics [hazard ratio (HR) = 1.64, 95% confidence interval (CI): 1.16 to 2.31, P = 0.005], CVD risk factors (HR = 1.62, 95% CI: 1.14 to 2.30, P = 0.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, and cocaine use; HR = 1.70, 95% CI: 1.19 to 2.43, P = 0.003), and HIV-specific factors (HIV-1 RNA, CD4 T-cell count, and antiretroviral therapy; HR = 1.66, 95% CI: 1.16 to 2.37, P = 0.005). Additional adjustment for nonbenzodiazepine sleep medication (HR = 1.62, 95% CI: 1.13 to 2.32, P = 0.009) did not attenuate the association; however, it fell short of significance at P < 0.01 after adjustment for depressive symptoms (HR = 1.51, 95% CI: 0.98 to 2.32, P = 0.060) or antidepressant medication (HR = 1.51, 95% CI: 1.04 to 2.19, P = 0.031)., Conclusions: Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV.

Background: Alzheimer's disease and related disorders (ADRD) are prevalent in older adults, increase the costs of chronic heart failure (CHF) management, and may be associated with undertreatment of cardiovascular disease., Objective: The purpose of our study was to determine the relationship between comorbid ADRD and CHF medication use and adherence among Medicare beneficiaries with CHF., Methods: This 2-year (1/1/2006-12/31/2007) cross-sectional study used data from the Chronic Condition Data Warehouse of the Centers for Medicare and Medicaid Services. Medicare beneficiaries with evidence of CHF who had systolic dysfunction and Medicare Parts A, B, and D coverage during the entire study period were included. ADRD was identified based on diagnostic codes using the Chronic Condition Data Warehouse algorithm. CHF evidence-based medications (EBMs) were selected based on published guidelines: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selected β-blockers, aldosterone antagonists, and selected vasodilators. Measures of EBMs included a binary indicator of EBM use and medication possession ratio among users., Results: Of 9827 beneficiaries with CHF and systolic dysfunction, 24.2% had a diagnosis of ADRD. Beneficiaries with ADRD were older (80.8 vs 73.6 years; P < 0.0001) and more likely to be female (69.3% vs 58.1%; P < 0.0001). Overall EBM use was lower in patients with CHF and ADRD compared with patients with CHF but no ADRD (85.3% vs 91.2%; P < 0.0001). Lower use among those with ADRD was consistent across all EBM classes except vasodilators. Among beneficiaries receiving EBM, those with ADRD had a slightly higher mean medication possession ratio for EBM compared with those without ADRD (0.86 vs 0.84; P = 0.0001)., Conclusions: EBM medication adherence was high in this population, regardless of ADRD status. However, patients with ADRD had lower EBM use compared with those without ADRD. Low use of specific EBM medications such as β-blockers was found in both groups. Therefore, interventions targeting increased treatment with specific EBMs for CHF, even among patients with ADRD, may be of benefit and could help reduce CHF-related hospitalizations., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

The etiology, predictive value, and biobehavioral aspects of depression in heart failure (HF) are described in this article. Clinically elevated levels of depressive symptoms are present in approximately 1 out of 5 patients with HF. Depression is associated with poor quality of life and a greater than 2-fold risk of clinical HF progression and mortality. The biobehavioral mechanisms accounting for these adverse outcomes include biological processes (elevated neurohormones, autonomic nervous system dysregulation, and inflammation) and adverse health behaviors (physical inactivity, medication nonadherence, poor dietary control, and smoking). Depression often remains undetected because of its partial overlap with HF-related symptoms and lack of systematic screening. Behavioral and pharmacologic antidepressive interventions commonly result in statistically significant but clinically modest improvements in depression and quality of life in HF, but not consistently better clinical HF or cardiovascular disease outcomes. Documentation of the biobehavioral pathways by which depression affects HF progression will be important to identify potential targets for novel integrative behavioral and pharmacologic interventions., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To delineate clinician opinion on the efficacy, safety, and logistics of perioperative beta-adrenergic blockade for patients undergoing noncardiac surgery., Design: Survey of opinions and clinical practices., Setting: Internet-based survey form., Participants: Members of the Associations of Veterans Affairs Anesthesiologists and Surgeons and chiefs of cardiology in centers with surgical programs., Interventions: None., Measurements and Main Results: One hundred twenty-seven responses from 62 Veterans Affairs Medical Centers in 35 states (57 anesthesiologists, 45 surgeons, 25 cardiologists) were analyzed. Ninety-two percent agreed that it is effective in reducing short-term adverse outcomes, declining to 60% for long-term outcome. There was greater enthusiasm for its use in patients with known coronary artery disease (87%) than in patients with risk factors only (72%). Although 66% considered it efficacious in vascular surgery, only 30% were convinced it was for nonvascular surgery (with a similar distribution for safety in these settings). Preoperative use was favored (94%), with most physicians favoring use within 1 week of surgery (52%). Most favored 1 to 2 weeks of postoperative therapy (43%), with the remainder favoring shorter (19%) or longer (35%) durations. Although 71% of clinicians reported frequent use in their practice, most believed its use was largely informal by their colleagues (83%) and rarely based on a formal clinical pathway (13%)., Conclusion: A wide range of opinions by clinicians regarding the efficacy, safety, and logistics of perioperative beta-adrenergic blockade was encountered, suggesting need for additional clinical research and centralized efforts at increasing compliance with existing guidelines.