Complementary and Alternative Medicines in the Management of Heart Failure: A Scientific Statement From the American Heart Association.

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

Biomass smoke inhalation promotes neuroinflammatory and metabolomic temporal changes in the hippocampus of female mice.

Smoke from wildland fires has been shown to produce neuroinflammation in preclinical models, characterized by neural infiltrations of neutrophils and monocytes, as well as altered neurovascular endothelial phenotypes. To address the longevity of such outcomes, the present study examined the temporal dynamics of neuroinflammation and metabolomics after inhalation exposures from biomass-derived smoke. 2-month-old female C57BL/6 J mice were exposed to wood smoke every other day for 2 weeks at an average exposure concentration of 0.5 mg/m3. Subsequent serial euthanasia occurred at 1-, 3-, 7-, 14-, and 28-day post-exposure. Flow cytometry of right hemispheres revealed two endothelial populations of CD31Hi and CD31Med expressors, with wood smoke inhalation causing an increased proportion of CD31Hi. These populations of CD31Hi and CD31Med were associated with an anti-inflammatory and pro-inflammatory response, respectively, and their inflammatory profiles were largely resolved by the 28-day mark. However, activated microglial populations (CD11b+/CD45low) remained higher in wood smoke-exposed mice than controls at day 28. Infiltrating neutrophil populations decreased to levels below controls by day 28. However, the MHC-II expression of the peripheral immune infiltrate remained high, and the population of neutrophils retained an increased expression of CD45, Ly6C, and MHC-II. Utilizing an unbiased approach examining the metabolomic alterations, we observed notable hippocampal perturbations in neurotransmitter and signaling molecules, such as glutamate, quinolinic acid, and 5-α-dihydroprogesterone. Utilizing a targeted panel designed to explore the aging-associated NAD+ metabolic pathway, wood smoke exposure drove fluctuations and compensations across the 28-day time course, ending with decreased hippocampal NAD+ abundance on day 28. Summarily, these results indicate a highly dynamic neuroinflammatory environment, with potential resolution extending past 28 days, the implications of which may include long-term behavioral changes, systemic and neurological sequalae directly associated with wildfire smoke exposure.

Curricular-driven screening for atrial fibrillation at community pharmacies.

BACKGROUND: Atrial fibrillation (AF) increases the risk of stroke. It can be asymptomatic and patients may be unaware they have AF. Therefore, there is a need to develop a sustainable community model to screen for unrecognized AF. OBJECTIVE: The objective is to assess a curriculum driven model developed by the University of New Mexico College of Pharmacy (UNM-CoP) to evaluate AF screening at 3 community pharmacy sites. METHODS: Screenings and education for AF were performed by fourth year pharmacy students during their advanced pharmacy practice experience (APPE) community rotation at pre-selected independent pharmacies. Patients were screened using the KardiaMobile device (AliveCor®, Mountain View, CA), an FDA-cleared device that interprets a medical-grade ECG in 30 seconds. All screening materials and devices were provided by UNM-CoP. Semi-structured interviews with each targeted pharmacy were conducted to assess the logistics, value, and sustainability of the program (N=5 pharmacists). RESULTS: AF assessment was performed over a 7-month period by 8 students at three pharmacies. Students screened a total of 63 patients (62% female, 56 ± 14 years of age) with 92% of the encounters taking less than 10 minutes to complete. Three patients (4.7%) were found to have possible AF. Positive scores were noted when assessing value to the pharmacy (8.8 ± 0.8, scale 1-10 with 10 being high value) and professionally (9.7 ± 0.6). DISCUSSION: Student-pharmacists provides a likely pathway for sustainability for this clinical initiative and provides for a novel and measurable APPE patient interaction. CONCLUSION: Curricular driven AF assessment in community pharmacies was shown to be a feasible model. Additional studies are needed to assess whether population-based real-time assessment and detection of AF can reduce the risk of stroke in previously undetected AF. If stroke reduction is realized, reimbursement for service is likely and can contribute to further sustainability.

Effect of CES1 genetic variation on enalapril steady-state pharmacokinetics and pharmacodynamics in healthy subjects.

AIMS: Enalapril is a prodrug and needs to be activated by carboxylesterase 1 (CES1). A previous in vitro study demonstrated the CES1 genetic variant, G143E (rs71647871), significantly impaired enalapril activation. Two previous clinical studies examined the impact of G143E on single-dose enalapril PK (10 mg); however, the results were inconclusive. A prospective, multi-dose, pharmacokinetics and pharmacodynamics (PK/PD) study was conducted to determine the impact of the CES1 G143E variant on enalapril steady-state PK and PD in healthy volunteers. METHODS: Study participants were stratified to G143E non-carriers (n = 15) and G143E carriers (n = 6). All the carriers were G143E heterozygotes. Study subjects received enalapril 10 mg daily for seven consecutive days prior to a 72 hour PK/PD study. Plasma concentrations of enalapril and its active metabolite enalaprilat were quantified by an established liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: The CES1 G143E carriers had 30.9% lower enalaprilat Cmax (P = 0.03) compared to the non-carriers (38.01 vs. 55.01 ng/mL). The carrier group had 27.5% lower AUC0-∞ (P = 0.02) of plasma enalaprilat compared to the non-carriers (374.29 vs. 515.91 ng*h/mL). The carriers also had a 32.3% lower enalaprilat-to-enalapril AUC0-∞ ratio (P = 0.003) relative to the non-carriers. The average maximum reduction of systolic blood pressure in the non-carrier group was approximately 12.4% at the end of the study compared to the baseline (P = 0.001). No statistically significant blood pressure reduction was observed in the G143E carriers. CONCLUSIONS: The CES1 loss-of-function G143E variant significantly impaired enalapril activation and its systolic blood pressure-lowering effect in healthy volunteers.

Assessment of particulate matter toxicity and physicochemistry at the Claim 28 uranium mine site in Blue Gap, AZ.

Thousands of abandoned uranium mines (AUMs) exist in the western United States. Due to improper remediation, windblown dusts generated from AUMs are of significant community concern. A mobile inhalation lab was sited near an AUM of high community concern ("Claim 28") with three primary objectives: to (1) determine the composition of the regional ambient particulate matter (PM), (2) assess meteorological characteristics (wind speed and direction), and (3) assess immunological and physiological responses of mice after exposures to concentrated ambient PM (or CAPs). C57BL/6 and apolipoprotein E-null (ApoE-/-) mice were exposed to CAPs in AirCARE1 located approximately 1 km to the SW of Claim 28, for 1 or 28 days for 4 hr/day at approximately 80 µg/m3 CAPs. Bronchoalveolar lavage fluid (BALF) analysis revealed a significant influx of neutrophils after a single-day exposure in C57BL/6 mice (average PM2.5 concentration = 68 µg/m3). Lungs from mice exposed for 1 day exhibited modest increases in Tnfa and Tgfb mRNA levels in the CAPs exposure group compared to filtered air (FA). Lungs from mice exposed for 28 days exhibited reduced Tgfb (C57BL/6) and Tnfa (ApoE-/-) mRNA levels. Wind direction was typically moving from SW to NE (away from the community) and, while detectable in all samples, uranium concentrations in the PM2.5 fraction were not markedly different from published-reported values. Overall, exposure to CAPs in the region of the Blue GAP Tachee's Claim-28 uranium mine demonstrated little evidence of overt pulmonary injury or inflammation or ambient air contamination attributed to uranium or vanadium.

Population screening for atrial fibrillation by student pharmacists at health fairs.

BACKGROUND: Individuals with unrecognized atrial fibrillation (AF) may be at an increased risk of stroke. There is a need to develop a sustainable and reproducible population-based screening model to identify unrecognized AF. OBJECTIVE: The objective of this study is to evaluate AF screening and education at student pharmacist-driven health fairs. METHODS: Screening for AF was performed by student members of the American Pharmacist Association Academy of Student Pharmacists with preceptor oversight. Participants were screened using the KardiaMobile device (AliveCor, Mountain View, CA), a Food and Drug Administration-cleared device that interprets a medical-grade electrocardiogram in 30 seconds. Student pharmacists also calculated a CHA2DS2-VASc score. Participant education was provided using an American Heart Association AF patient information sheet. Learning assessment was evaluated with 3 multiple choice questions. RESULTS: Students screened a total of 697 participants over a 6-month period at 13 health fairs. Overall, 71% of the participants were women aged 56 ± 15 years (mean ± SD). Sixteen of the participants (2.3%) who were screened received results indicating possible AF. None of the participants with a possible positive finding had symptoms suggestive of AF. Of these 16 participants, 11 (69%) had a CHA2DS2-VASc score greater than or equal to 2 (2.7 ± 0.7). Most participants answered each learning assessment question correctly. More than 95% of participants believed that screening for AF at health fairs was important or very important. CONCLUSION: Student pharmacist-driven health fairs were shown to be feasible models to screen for AF and were effective in providing AF education to the public. Student pharmacists also cultivated a clinical skill that is transferable to their future practice setting, including the community pharmacy setting. Additional studies are needed to assess whether population-based real-time assessment and detection of AF can reduce the risk of stroke in individuals with previously undetected AF.

Single dose oral ranolazine pharmacokinetics in patients receiving maintenance hemodialysis.

PURPOSE: Ranolazine is a novel anti-angina treatment approved in the United States for chronic stable angina. Ranolazine pharmacokinetics have not been studied previously in patients who receive maintenance hemodialysis. This study describes the pharmacokinetics of ranolazine and three major metabolites (CVT-2738, CVT-2512, CVT-2514) in patients receiving thrice weekly hemodialysis. METHODS: Eight participants receiving maintenance hemodialysis completed this prospective, open-label study (study identifier NCT01435174 at Clinicaltrials.gov). Three participants received a single tablet of ranolazine 500 mg (followed by an interim analysis), and five received 2 tablets of ranolazine 500 mg. Blood samples were collected over 65 h to determine the pharmacokinetic characteristics during and between hemodialysis sessions. Non-compartmental analysis was used to determine the individual pharmacokinetic parameters. RESULTS: Ranolazine off-hemodialysis elimination phase half-lives were 3.6 and 3.9 h for 500 mg and 1000 mg doses, respectively. The time to maximum concentration ranged from 2 to 18 hours and the average maximum concentration was 0.65 ± 0.27 mcg/mL and 1.18 ± 0.48 mcg/mL for ranolazine 500 mg and 1000 mg dose, respectively. The mean hemodialysis percent reduction ratio for the ranolazine 500 mg dose was 52.3 ± 8.1% and for the ranolazine 1000 mg dose was 69.2 ± 37.6%. CONCLUSIONS: Data on ranolazine dosing in patients receiving maintenance hemodialysis is almost non-existent. Given the extent of pharmacokinetic variability observed with the 500 mg and 1000 mg oral doses of ranolazine, neither can be recommended as a starting dose in patients receiving maintenance hemodialysis. Guided by the information gained form this study about the extent of hemodialytic drug clearance, further multi-dose clinical trials of ranolazine are needed to optimize therapeutic outcomes in this patient population.

Crataegus Special Extract WS 1442 Effects on eNOS and microRNA 155.

Increased expression of microRNA 155 (miR-155) results in a decrease in endothelial nitric oxide synthase (eNOS) expression and impaired endothelial function. Factors that have been shown to increase expression of miR-155 may be mitigated by WS 1442, an extract of hawthorn leaves and flowers (Crataegus special extract) that contains a range of pharmacologically active substances including oligomeric proanthocyanidins and flavonoids. The purpose of this study is to determine the effect of WS 1442 on the expression of miR-155 and eNOS in the presence of tumor necrosis factor (TNF-α). Human umbilical vein endothelial cells (HUVECs) were studied after the exposure to TNF-α, with or without simvastatin (positive control) and WS 1442. The expression levels of eNOS, phosphorylated eNOS, and miR-155 in the different HUVEC treatment groups were determined by western blot and quantitative real-time polymerase chain reaction, respectively. To evaluate the effect of WS 1442 on the eNOS activity, the medium and intracellular nitrate/nitrite (NO) concentrations were also analyzed using a colorimetric Griess assay kit. The results demonstrated that TNF-α upregulated miR-155 expression and decreased eNOS expression and NO concentrations. WS 1442 also increased miR-155 expression and decreased eNOS expression but, unlike TNF-α, increased phosphorylated eNOS expression and NO concentrations. Surprisingly, WS 1442 increased miR-155 expression; however, WS 1442 mitigated the overall negative effect of miR-155 on decreasing eNOS expression by increasing expression of phosphorylated eNOS and resulting in an increase in NO concentrations. In the setting where miR-155 may be expressed, WS 1442 may offer vascular protection by increasing the expression of phosphorylated eNOS.

A Comprehensive Functional Assessment of Carboxylesterase 1 Nonsynonymous Polymorphisms.

Carboxylesterase 1 (CES1) is the predominant human hepatic hydrolase responsible for the metabolism of many clinically important medications. CES1 expression and activity vary markedly among individuals; and genetic variation is a major contributing factor to CES1 interindividual variability. In this study, we comprehensively examined the functions of CES1 nonsynonymous single nucleotide polymorphisms (nsSNPs) and haplotypes using transfected cell lines and individual human liver tissues. The 20 candidate variants include CES1 nsSNPs with a minor allele frequency >0.5% in a given population or located in close proximity to the CES1 active site. Five nsSNPs, including L40Ter (rs151291296), G142E (rs121912777), G147C (rs146456965), Y170D (rs148947808), and R171C (rs201065375), were loss-of-function variants for metabolizing the CES1 substrates clopidogrel, enalapril, and sacubitril. In addition, A158V (rs202121317), R199H (rs2307243), E220G (rs200707504), and T290M (rs202001817) decreased CES1 activity to a lesser extent in a substrate-dependent manner. Several nsSNPs, includingL40Ter (rs151291296), G147C (rs146456965), Y170D (rs148947808), and R171C (rs201065375), significantly reduced CES1 protein and/or mRNA expression levels in the transfected cells. Functions of the common nonsynonymous haplotypes D203E-A269S and S75N-D203E-A269S were evaluated using cells stably expressing the haplotypes and a large set of the human liver. Neither CES1 expression nor activity was affected by the two haplotypes. In summary, this study revealed several functional nsSNPs with impaired activity on the metabolism of CES1 substrate drugs. Clinical investigations are warranted to determine whether these nsSNPs can serve as biomarkers for the prediction of therapeutic outcomes of drugs metabolized by CES1.

In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions.

In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m2. Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC0-24 and Cmax were lower in fed subjects vs fasted subjects, and Tmax was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic levels but increased gastric levels of ibuprofen, which suggest that slow gastric emptying and transit dominate the effect for plasma drug concentration. The finding of high levels of ibuprofen in stomach and small intestine 7 h post dosing was unexpected. Future work is needed to better understand the role of various GI parameters, such as motility and gastric emptying, on systemic ibuprofen levels in order to improve in vitro predictive models.

Opioid overdose prevention through pharmacy-based naloxone prescription program: Innovations in health care delivery.

BACKGROUND: Given that opioid misuse/abuse and opioid overdose have reached epidemic proportions in the United States, expansion of naloxone access programs are desperately needed. The objective of this study was to describe emerging trends in naloxone rescue kit (NRK) prescription patterns by pharmacists in New Mexico as an example of a unique health care delivery system. METHODS: The study presents cross-sectional analysis of the data on NRK prescriptions by pharmacists who received naloxone pharmacist prescriptive authority certification since 2013. Data were obtained from the Prevention of Opioid Overdose by New Mexico Pharmacists (POINt-Rx) Registry, maintained by the University of New Mexico and the New Mexico Pharmacists Association. RESULTS: Since 2013, 133 NRKs prescribed by pharmacists have been reported to the POINt-Rx Registry. The mean age of the patients was 41.5 ± 12.0 years (range: 19-67 years), and 60.2% were female participants. Only 11.3% of the prescriptions were from pharmacists practicing in rural/mixed urban-rural areas. The majority of NRKs (89.5%) were first-time prescriptions. The most common reason for a NRK prescription was patient's request (56.4%), followed by a pharmacist's prescription of NRK due to high dose of prescription opioids (28.6%) and history of opioid misuse/abuse (15.0%). In addition to opioids, other frequently reported substances included alcohol (9.2%) and benzodiazepines (10.8%). More than a third of patients (38.5%) reported polysubstance use in the previous 72 hours. CONCLUSIONS: These results indicate that patients at risk of opioid overdose might feel comfortable soliciting NRKs from a pharmacist. Participation of pharmacists in rural areas in the naloxone prescriptive authority highlight the opportunity for this novel health care delivery model in underserved areas; however, the program is clearly underutilized in these areas. Such a model can provide expanded patient access in community practices, whereas systematic efforts for uptake of the program by policy makers, communities, and pharmacists continue to be needed nationwide.

Incorporation of a community pharmacy-based heart failure assessment tool by advanced pharmacy practice experience students.

OBJECTIVES: To incorporate a published clinical tool related to heart failure (HF) assessment into advanced pharmacy practice experiences in the community pharmacy setting to provide a meaningful and innovative learning experience for students. SETTING: Sixteen independent and chain community pharmacies that served as advanced pharmacy practice experience locations. PRACTICE DESCRIPTION: Sixteen community pharmacy locations served as rotation sites and participated in data collection (8 chain and 8 independent). PRACTICE INNOVATION: This was the first study in which pharmacy students used The One-Minute Clinic for Heart Failure (TOM-C HF) tool to assess HF within the community pharmacy setting. INTERVENTIONS: Trained student pharmacists identified patients who may have heart failure by evaluating medication dispensing records, interviewed the patient using the TOM-C HF tool, and made interventions as clinically appropriate. EVALUATION: The number of students using the TOM-C HF tool, the number and types of interventions made, and student perceptions about the educational and professional value of the patient interaction. RESULTS: Thirty-three of 83 (40%) students completed 63 patient assessments. Thirty-five percent of patients (22/63) were candidates for an intervention. Interventions were performed in 9 of 22 patients (41%). More than 65% of students found the patient interaction to have educational and professional value. CONCLUSION: Students were able to assess HF patients and make interventions in a community pharmacy setting. The majority of students also perceived some value in these assessments. The incorporation of a clinical tool in the community setting driven by fourth-year pharmacy students has been shown to be feasible and to provide both a novel advanced practice experience. In addition, it may be expandable to the services offered at community pharmacies.

Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation.

Sacubitril was recently approved by the Food and Drug Administration for use in combination with valsartan for the treatment of patients with heart failure with reduced ejection fraction. As a prodrug, sacubitril must be metabolized (hydrolyzed) to its active metabolite sacubitrilat (LBQ657) to exert its intended therapeutic effects. Thus, understanding the determinants of sacubitril activation will lead to the improvement of sacubitril pharmacotherapy. The objective of this study was to identify the enzyme(s) responsible for the activation of sacubitril, and determine the impact of genetic variation on sacubitril activation. First, an incubation study of sacubitril with human plasma and the S9 fractions of human liver, intestine, and kidney was conducted. Sacubitril was found to be activated by human liver S9 fractions only. Moreover, sacubitril activation was significantly inhibited by the carboxylesterase 1 (CES1) inhibitor bis-(p-nitrophenyl) phosphate in human liver S9. Further incubation studies with recombinant human CES1 and carboxylesterase 2 confirmed that sacubitril is a selective CES1 substrate. The in vitro study of cell lines transfected with wild-type CES1 and the CES1 variant G143E (rs71647871) demonstrated that G143E is a loss-of-function variant for sacubitril activation. Importantly, sacubitril activation was significantly impaired in human livers carrying the G143E variant. In conclusion, sacubitril is selectively activated by CES1 in human liver. The CES1 genetic variant G143E can significantly impair sacubitril activation. Therefore, CES1 genetic variants appear to be an important contributing factor to interindividual variability in sacubitril activation, and have the potential to serve as biomarkers to optimize sacubitril pharmacotherapy.

Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes.

BACKGROUND: Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE-/-) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, generated as ultrafine (UFP) and fine (FP) sizes, with additional exposures using UFP or FP combined with gaseous copollutants derived from fresh gasoline and diesel emissions, labeled as UFP + G and FP + G. RESULTS: The UFP and UFP + G exposure groups resulted in the most profound pulmonary and neuroinflammatory effects. Phagocytosis of UFP + G particles via resident alveolar macrophages was substantial in both mouse strains, particularly after chronic exposure, with concurrent increased proinflammatory cytokine expression of CXCL1 and TNFα in the bronchial lavage fluid. In the acute exposure paradigm, only UFP and UFP + G induced significant changes in pulmonary inflammation and only in the ApoE-/- animals. Similarly, acute exposure to UFP and UFP + G increased the expression of several cytokines in the hippocampus of ApoE-/- mice including Il-1ß, IL-6, Tgf-ß and Tnf-α and in the hippocampus of C57BL/6 mice including Ccl5, Cxcl1, Il-1ß, and Tnf-α. Interestingly, Il-6 and Tgf-ß expression were decreased in the C57BL/6 hippocampus after acute exposure. Chronic exposure to UFP + G increased expression of Ccl5, Cxcl1, Il-6, and Tgf-ß in the ApoE-/- hippocampus, but this effect was minimal in the C57BL/6 mice, suggesting compensatory mechanisms to manage neuroinflammation in this strain. CONCLUSIONS: Inflammatory responses the lung and brain were most substantial in ApoE-/- animals exposed to UFP + G, suggesting that the surface area-dependent interaction of gases and particles is an important determinant of toxic responses. As such, freshly generated UFP, in the presence of combustion-derived gas phase pollutants, may be a greater health hazard than would be predicted from PM concentration, alone, lending support for epidemiological findings of adverse neurological outcomes associated with roadway proximity.

Hyponatremia, Cognitive Function, and Mobility in an Outpatient Heart Failure Population.

BACKGROUND The association of hyponatremia with cognitive impairment and mobility in heart failure (HF) patients is unknown. The purpose of this study was to determine if hyponatremia is associated with cognitive and mobility impairment as measured by simple, validated, and time-sensitive tests. MATERIAL AND METHODS This was a prospective study in patients with reduced and preserved ejection fraction (HFrEF, HFpEF) seen in outpatient HF clinics. Hyponatremia was defined as sodium level ≤136 mEq/L. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) tool, and mobility was measured with the Timed Up and Go test (TUG-t). RESULTS A total of 121 patients were evaluated; 30% were hyponatremic (134±1.9 mEq/l, range 128-136 mEq/l). Overall, 92% of hyponatremic patients had cognitive impairment (MoCA <26) compared to 76% of the non-hyponatremic patients [relative risk 1.2 (confidence interval: 1.02-1.4, p=0.02)]. In regard to mobility, 72% of hyponatremic patients and 62% of non-hyponatremic patients (p=0.4) had TUG-t times that were considered to be worse than average. A total of 84% (N=76) of HFrEF and 71% (N=22) of HFpEF patients had cognitive impairment (p=0.86). HFrEF patients had significantly lower overall MoCA scores (21.2±3.7 vs. 23.3±3.6, p=0.006) and similar TUG-t times compared to HFpEF patients. CONCLUSIONS Most heart failure patients (HFrEF and HFpEF) seen in an ambulatory setting had impairment of cognitive function and mobility, with a higher prevalence among those with hyponatremia. Screening can be done using tests that can be administered in a clinical setting.

Nurse-Enhanced Computerized Cognitive Training Increases Serum Brain-Derived Neurotropic Factor Levels and Improves Working Memory in Heart Failure.

BACKGROUND: Memory loss is common in heart failure (HF) patients, but few interventions have been tested to treat it. The objective of this study was to evaluate efficacy of a cognitive training intervention, Brain Fitness, to improve memory, serum brain-derived neurotropic factor (BDNF) levels, working memory, processing speed, executive function, instrumental activities of daily living, mobility, depressive symptoms, and health-related quality of life. METHODS AND RESULTS: Twenty-seven HF patients were randomly assigned to Brain Fitness and health education active control interventions. Data were collected at baseline and 8 and 12 weeks. Linear mixed models analyses were completed. Patients in the Brain Fitness group were older with lower ejection fraction. At 12 weeks, a group by time interaction effect was found for serum BDNF levels (P = .011): serum BDNF levels increased among patients who completed Brain Fitness and decreased among patients who completed health education. No differences were found in memory, but a group by time interaction (P = .046) effect was found for working memory. CONCLUSIONS: Findings support efficacy of Brain Fitness in improving working memory and serum BDNF levels as a biomarker of intervention response. A randomized controlled study is needed among a larger more diverse group of HF patients.

A web application for self-monitoring improves symptoms in chronic systolic heart failure.

OBJECTIVE: The objective of this study was to determine if a Web application that promoted mindfulness of the progress of the chronic disease through self-monitoring improved quality of life in heart failure. MATERIALS AND METHODS: This was a prospective single-center single-group study. Participants were instructed how to use the Web application and to perform self-monitoring daily for 12 weeks. A comprehensive physical exam, assessment of New York Heart Association (NYHA) class, the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and an evaluation of self-management were performed in person at baseline and at 12 weeks. RESULTS: Participants consisted of older (mean, 59 years), predominantly female (63%) adults with NYHA class II or III symptoms. NYHA classification (preintervention versus postintervention, 2.5±0.13 versus 2.0±0.13; p=0.0032) and MLHFQ score (55.7±4.6 versus 42.6±5.1, respectively; p=0.0078) improved over 12 weeks of self-monitoring. A trend toward improvement was also demonstrated in weight (preintervention versus postintervention, 209±9.6 pounds versus 207±9.4 pounds; by paired t test, p=0.389), number of times exercised per week (1.29±0.5 versus 2.5±0.6, respectively; p=0.3), and walk distance (572±147 yards versus 845±187 yards, respectively; p=0.119). Jugular venous distention (preintervention versus postintervention, 8.1±0.6 cm versus 6.7±0.3 cm; p=0.083) and peripheral edema (29.2% versus 16.7%, respectively; p=0.375) decreased after 12 weeks of self-monitoring via the Web application. CONCLUSIONS: A Web application for self-monitoring heart failure over 12 weeks improved both NYHA classification and MLHFQ score. The trend in improved physical activity and physical exam support these outcomes. The number of patients reporting a sodium-restricted diet increased over the 12 weeks, which may have led to the positive findings.

Heart failure assessment at the community pharmacy level: a feasibility pilot study.

BACKGROUND: A key element missing in disease-management programs for heart failure (HF) is participation of the community pharmacist. The purpose of this study is to determine if a simple and efficient clinical tool will allow community pharmacists to identify patients at risk for worsening HF. DESIGN: The One Minute Clinic for Heart Failure (TOM-C HF) was developed as a simple six-item symptom screening tool to be used during routine patient/customer interactions. SETTING: Ten community pharmacies located in the upper Midwest. PATIENTS: Self-identified HF patients. RESULTS: 121 unique patients were evaluated over a 12-month period. The application of this clinical tool took between 1 and 5 minutes in over 80% of the interactions. Seventy-five patients (62%) had one or more signs or symptoms of worsening HF. The most common symptoms detected included edema (39%) and increased shortness of breath (17%). Self-reported weight gain of more than 5 pounds was seen in 19% of patients. CONCLUSION: The TOM-C HF tool was used to identify patients in a time-efficient manner in the community pharmacy setting who appear to be developing worsening HF. Inclusion of the community pharmacists as an early screen for HF decompensation may be an important link in disease-management programs to help reduce hospital readmission rates.

Characterization of Mild Delayed Gestational Hypertension in Rats Following Ozone Exposure.

The contribution of air pollution induced cardio-pulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continues to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remains sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model. The exposure resulted in acute depression of heart rate and core body temperature as compared to control animals. Ozone exposed animals also presented with a slight but significant increase in arterial blood pressure which was perpetuated until term. The data presented here illustrates the feasibility of murine models to assess cardiovascular complications caused by inhaled toxicants during the window of pregnancy.

Characterization of Mild Delayed Gestational Hypertension in Rats Following Ozone Exposure.

The contribution of air pollution-induced cardiopulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continue to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remain sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model. The exposure resulted in acute depression of heart rate and core body temperature as compared to control animals. Ozone-exposed animals also presented with a slight but significant increase in arterial blood pressure which was perpetuated until term. The data presented here illustrates the feasibility of murine models to assess cardiovascular complications caused by inhaled toxicants during the window of pregnancy.