Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction.

BACKGROUND: Despite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking. METHODS: A survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4-5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest. RESULTS: Cardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07-3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18-4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01-3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48-4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine. CONCLUSIONS: Our results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

The Effects of the ManageHF4Life Mobile App on Patients With Chronic Heart Failure: Randomized Controlled Trial.

BACKGROUND: The successful management of heart failure (HF) involves guideline-based medical therapy as well as self-management behavior. As a result, the management of HF is moving toward a proactive real-time technological model of assisting patients with monitoring and self-management. OBJECTIVE: The aim of this paper was to evaluate the efficacy of enhanced self-management via a mobile app intervention on health-related quality of life, self-management, and HF readmissions. METHODS: A single-center randomized controlled trial was performed. Participants older than 45 years and admitted for acute decompensated HF or recently discharged in the past 4 weeks were included. The intervention group ("app group") used a mobile app, and the intervention prompted daily self-monitoring and promoted self-management. The control group ("no-app group") received usual care. The primary outcome was the change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score from baseline to 6 and 12 weeks. Secondary outcomes were the Self-Care Heart Failure Index (SCHFI) questionnaire score and recurrent HF admissions. RESULTS: A total of 83 participants were enrolled and completed all baseline assessments. Baseline characteristics were similar between the groups except for the prevalence of ischemic HF. The app group had a reduced MLHFQ at 6 weeks (mean 37.5, SD 3.5 vs mean 48.2, SD 3.7; P=.04) but not at 12 weeks (mean 44.2, SD 4 vs mean 45.9, SD 4; P=.78), compared to the no-app group. There was no effect of the app on the SCHFI at 6 or 12 weeks. The time to first HF readmission was not statistically different between the app group and the no-app group (app group 11/42, 26% vs no-app group 12/41, 29%; hazard ratio 0.89, 95% CI 0.39-2.02; P=.78) over 12 weeks. CONCLUSIONS: The adaptive mobile app intervention, which focused on promoting self-monitoring and self-management, improved the MLHFQ at 6 weeks but did not sustain its effects at 12 weeks. No effect was seen on HF self-management measured by self-report. Further research is needed to enhance engagement in the app for a longer period and to determine if the app can reduce HF readmissions in a larger study. TRIAL REGISTRATION: ClinicalTrials.gov NCT03149510; https://clinicaltrials.gov/ct2/show/NCT03149510.

Measured Versus Estimated Resting Metabolic Rate in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Obesity is common in heart failure with preserved ejection fraction (HFpEF), and a hypocaloric diet can improve functional capacity. Malnutrition, sarcopenia, and frailty are also frequently present, and calorie restriction could harm some patients. Resting metabolic rate (RMR) is an essential determinant of caloric needs; however, it is rarely measured in clinical practice. The accuracy of commonly used predictive equations in HFpEF is unknown. METHODS: RMR was measured with indirect calorimetry in 43 patients with HFpEF undergoing right heart catheterization at the University of Michigan, and among 49 participants in the SECRET trial (Study of the Effects of Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction); SECRET patients also had dual-energy X-ray absorptiometry body composition measures. Measured RMR was compared with RMR estimated using the Harris Benedict, Mifflin-St Jeor, World Health Organization, and Academy for Nutrition and Dietetics equations. RESULTS: All predictive equations overestimated RMR (by >10%, P<0.001 for all), with mean (95% CI) differences Harris Benedict equation +250 (186-313), Mifflin-St. Jeor equation +169 (110-229), World Health Organization equation +300 (239-361), and Academy for Nutrition and Dietetics equation +794 (890-697) kcal/day. Results were similar across both patient groups, and the discrepancy between measured and estimated RMR tended to increase with body mass index. In SECRET, measured RMR was closely associated with lean body mass (ρ=0.74; by linear regression adjusted for age and sex: ß=27 [95% CI, 18-36] kcal/day per kg, P<0.001; r2=0.56). CONCLUSIONS: Commonly used predictive equations systematically overestimate measured RMR in patients with HFpEF. Direct measurement of RMR may be needed to effectively tailor dietary guidance in this population. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT00959660.

Resting Oxygen Consumption and Heart Failure: Importance of Measurement for Determination of Cardiac Output With the Use of the Fick Principle.

BACKGROUND: Resting oxygen consumption (VO2) is often estimated and frequently used to guide therapeutic decisions in symptomatic heart failure (HF) patients. The relationship between resting VO2 and symptomatic HF and the accuracy of estimations of VO2 in this population are unknown. METHODS AND RESULTS: We performed a cross-sectional study of HF patients (n = 691) and healthy control subjects (n = 77). VO2 was measured with the use of a metabolic cart, and estimated VO2 was calculated with the use of the Dehmer, LaFarge, and Bergstra formulas and the thermodilution method. The measured and estimated VO2 were compared and the potential impact of estimations determined. In the multivariable model, resting VO2 decreased with increasing New York Heart Association (NYHA) functional class in a stepwise fashion (ß NYHA functional class IV vs control = -36 mL O2/min; P < .001). Estimations of VO2 with the use of derived equations diverged from measured values, particularly for patients with NYHA functional class IV limitations. The percentage difference of measured VO2 versus estimated VO2 was >25% in 39% (n = 271), 25% (n = 170), 82% (n = 566), and 39% (n = 271) of HF patients when using the Dehmer, LaFarge, Bergstra, and thermodilution-derived estimations of VO2 respectively. CONCLUSIONS: Resting VO2 decreases with increasing NYHA functional class and is lower than in control subjects. Using estimations of VO2 to calculate CO may introduce clinically important error.

Construct Validity of the Multi-Source Interference Task to Examine Attention in Heart Failure.

BACKGROUND: Patients with heart failure (HF) are at risk of cognitive dysfunction, including decreased directed attention. Directed attention is critical for performing daily activities including HF self-care by facilitating one to follow instructions or train-of-thought when there are interferences in which presented stimuli are in conflict with one another. The Multi-Source Interference Task (MSIT) is a computerized neuropsychological test that examines the function of the dorsal anterior cingulate cortex, the neurological substrate for directed attention. However, the MSIT has not been used in past HF studies. OBJECTIVE: The purpose of the study was to examine construct validity of the MSIT in HF. METHODS: Baseline data were obtained from a cognitive intervention study among patients with HF (n = 22) and age- and education-matched healthy adults (n = 20). Construct validity was evaluated using t tests to examine differences between patients with HF and healthy adults and congruent and incongruent MSIT trials. Pearson's correlations were computed to examine relationships between the MSIT and Trail-Making Test, Stroop Test, and Attentional Function Index. RESULTS: Compared with healthy adults, patients with HF demonstrated worse performance (i.e., slower response times and higher error rates) on MSIT. Patients with HF had worse performance on MSIT incongruent trials than congruent trials. Interference z scores of MSIT did not correlate with Trail-Making Tests A and B and Stroop Test interference z scores, but the MSIT interference z scores correlated with perceived attention function measured by Attentional Function Index. DISCUSSION: Construct validity of the MSIT was supported, in part, among patients with HF. The MSIT is a sensitive measure of detecting worse directed attention among patients with HF compared with healthy adults. The preliminary findings support the use of the MSIT as a measure of directed attention in HF. Confirmation is warranted for current findings in larger samples.

Reduced Myocardial Flow Reserve by Positron Emission Tomography Predicts Cardiovascular Events After Cardiac Transplantation.

BACKGROUND: We evaluated the diagnostic and prognostic value of quantification of myocardial flow reserve (MFR) with positron emission tomography (PET) in orthotopic heart transplant patients. METHODS AND RESULTS: We retrospectively identified orthotopic heart transplant patients who underwent rubidium-82 cardiac PET imaging. The primary outcome was the composite of cardiovascular death, acute coronary syndrome, coronary revascularization, and heart failure hospitalization. Cox regression was used to evaluate the association of MFR with the primary outcome. The relationship of MFR and cardiac allograft vasculopathy severity in patients with angiography within 1 year of PET imaging was assessed using Spearman rank correlation and logistic regression. A total of 117 patients (median age, 60 years; 71% men) were identified. Twenty-one of 62 patients (34%) who underwent angiography before PET had cardiac allograft vasculopathy. The median time from orthotopic heart transplant to PET imaging was 6.4 years (median global MFR, 2.31). After a median of 1.4 years, 22 patients (19%) experienced the primary outcome. On an unadjusted basis, global MFR (hazard ratio, 0.22 per unit increase; 95% confidence interval, 0.09-0.50; P<0.001) and stress myocardial blood flow (hazard ratio, 0.48 per unit increase; 95% confidence interval, 0.29-0.79; P=0.004) were associated with the primary outcome. Decreased MFR independently predicted the primary outcome after adjustment for other variables. In 42 patients who underwent angiography within 12 months of PET, MFR and stress myocardial blood flow were associated with moderate-severe cardiac allograft vasculopathy (International Society of Heart and Lung Transplantation grade 2-3). CONCLUSIONS: MFR assessed by cardiac rubidium-82 PET imaging is a predictor of cardiovascular events after orthotopic heart transplant and is associated with cardiac allograft vasculopathy severity.

Ischemic Cardiac Events Following Treatment of the Internal Mammary Nodal Region Using Contemporary Radiation Planning Techniques.

PURPOSE: Regional nodal irradiation, including radiation therapy (RT) to the internal mammary node (IMN) region, improves oncologic outcomes in patients with node-positive breast cancer. Concern remains, however, given the proximity of the IMNs to the heart and the association between cardiac RT exposure and toxicity. The objective of the study was to evaluate rates of ischemic cardiac events (ICEs) and associated risk with treatment of the IMN region. METHODS AND MATERIALS: The cardiac outcomes of 2126 patients treated with adjuvant breast RT or breast and nodal RT from 1984 to 2007 at a single institution were reviewed. The primary endpoint was an ICE following RT initiation. The association between IMN RT and ICEs was assessed using Cox proportional hazards models. Treatment with both IMN RT and 3-dimensional (3D) conformal radiation therapy (CRT) began in 1997; therefore, subset analyses of patients with only 3D CRT were performed to minimize bias associated with improved treatment technique. RESULTS: The median follow-up period was 9.3 years. An ICE occurred in 87 patients (4.1%). No increased 10-year rate of ICEs was observed with IMN RT compared with no IMN RT in the total cohort (3.2% [95% confidence interval (CI), 2.4%-4.3%] vs 3.4% [95% CI, 1.5%-7.5%]; hazard ratio [HR], 0.88; P=.73). Similarly, no statistically significant difference was noted in the 3D CRT-planned, left-sided disease subset (5.1% [95% CI, 1.8%-14.1%] vs 4.0% [95% CI, 2.0%-8.0%]; HR, 1.18, P=.76). On multivariate analysis, adjusting for cardiac risk factor imbalances, no significantly increased hazard was noted with IMN RT (HR, 1.84; P=.28) in the 3D CRT-planned, left-sided disease subset. CONCLUSIONS: No statistically significant association between IMN RT and ICEs was demonstrated in a review of patients treated at a single institution from 1984 to 2007. Given the long natural history and low overall rate of ICEs, continued follow-up of this study, as well as additional studies in the 3D CRT era, is warranted to confirm these results. Minimizing cardiac exposure, when treating a limited IMN field, is critical to limit excess risk of ICEs.

APOE ε4 and Memory Among Patients With Heart Failure.

Twenty-three percent to 50% of heart failure (HF) patients have memory loss. Objectives were to (a) characterize major allelic frequency of 2 variants in apolipoprotein ( APOE) gene in HF patients, (b) evaluate differences in memory and serum brain-derived neurotrophic factor (BDNF) levels based on APOE ε4 allele(s), and (c) estimate effect sizes (ESs) and confidence intervals (CIs). In this pilot, 29 HF patients were enrolled and 26 completed. Recall and delayed recall memory were measured at baseline and 12 weeks. Serum was collected at baseline and 8 weeks. Seven (24.1%) patients had APOE ε4 allele. No significant differences were found in recall and delayed recall memory or serum BDNF levels based on APOE ε4 allele. ESs were small to medium; CIs indicated ES precision was small. Future studies are needed to fully understand how genotypic and neuropsychological phenotypic variables influence response to computerized cognitive training.

Randomized Crossover Study of the Natural Restorative Environment Intervention to Improve Attention and Mood in Heart Failure.

BACKGROUND: In heart failure (HF), attention may be decreased because of lowered cerebral blood flow and increased attentional demands needed for self-care. OBJECTIVE: Guided by the Attention Restoration Theory, the objective was to test the efficacy of the natural restorative environment (NRE) intervention on improving attention and mood among HF patients and healthy adults. METHODS: A randomized crossover pilot study was conducted among 20 HF patients and an age- and education-matched comparison group of 20 healthy adults to test the efficacy of the NRE intervention compared with an active control intervention. Neuropsychological tests were administered to examine attention, particularly attention span, sustained attention, directed attention, and attention switching, at before and after the intervention. Mood was measured with the Positive and Negative Affect Schedule. RESULTS: No significant differences were found in attention and mood after the NRE intervention compared with the control intervention among the HF patients and the healthy adults. In analyses with HF patients and healthy adults combined (n = 40), significant differences were found. Compared with the control intervention, sustained attention improved after the NRE intervention (P = .001) regardless of the presence of HF. Compared with the healthy adults, HF patients performed significantly worse on attention switching after the control intervention (P = .045). CONCLUSIONS: The NRE intervention may be efficacious in improving sustained attention in HF patients. Future studies are needed to enhance the NRE intervention to be more efficacious and tailored for HF patients and test the efficacy in a larger sample of HF patients.

Comparing the Effectiveness of an Axial and a Centrifugal Left Ventricular Assist Device in Ventricular Unloading.

Centrifugal (CFG) and axial flow (AX) left ventricular assist devices have different hydrodynamic properties that may impact the effectiveness of left ventricular unloading. We sought to determine whether patients implanted with the HeartWare HVAD (CFG) and HeartMate II (AX) had a similar degree of hemodynamic support by comparing parameters measured using echocardiography and right heart catheterization. Using our prospectively collected database, we identified 268 patients implanted with the AX and 93 with the CFG. Demographic characteristics were similar between groups. AX patients had a significantly lower INTERMACS score. Baseline ventricular dimension, mitral regurgitation, right ventricular systolic pressure, right atrial pressure, mean pulmonary artery pressure, cardiac output, and pulmonary vascular resistance were similar. Wedge pressure was higher, and left ventricular ejection fraction was lower at baseline in the AX. After implantation, there was a greater reduction of right atrial pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, and left ventricular internal diameter during diastole in the AX cohort. After implantation, cardiac output by Fick calculation showed a greater improvement in the AX group. These results demonstrate that both AX and CFG devices resulted in left ventricular unloading; however, AX devices may offer advantages in the magnitude of left ventricular unloading, which could have implications in myocardial recovery or reduction in pulmonary vascular resistance before transplantation.

Effects of Total Dose Infusion of Iron Intravenously in Patients With Acute Heart Failure and Anemia (Hemoglobin < 13 g/dl).

Iron deficiency is common in heart failure (HF), and intravenous (IV) iron therapy has been associated with improved clinical status in ambulatory patients with HF. There are limited data to support the safety and efficacy of IV iron administration in patients with acute HF. This was a retrospective cohort study of patients admitted to the University of Michigan Health System for HF with low iron studies during admission. Patients were grouped based on the receipt of IV iron therapy. Study outcomes included change in hemoglobin, 30-day readmission, and adverse events. Forty-four patients who received IV iron and 128 control patients were identified. The mean dose of IV iron received was 1,057 (±336) mg. IV iron resulted in a significantly greater increase in hemoglobin over time (p = 0.0001). The mean change in hemoglobin in the iron and control groups was 0.74 g/dl and 0.01 g/dl at day 7 and 2.61 g/dl and 0.23 g/dl at day 28, respectively. Thirty-day readmission rates were 30% and 22% for patients in the iron and control groups, respectively (p = 0.2787). In conclusion, total dose infusion IV iron is well tolerated and associated with significant improvement in hemoglobin in acute HF.

Refusal to participate in heart failure studies: do age and gender matter?

AIMS AND OBJECTIVES: The objective of this retrospective study was to evaluate reasons heart failure patients decline study participation, to inform interventions to improve enrollment. BACKGROUND: Failure to enrol older heart failure patients (age > 65) and women in studies may lead to sampling bias, threatening study validity. DESIGN: This study was a retrospective analysis of refusal data from four heart failure studies that enrolled 788 patients in four states. METHODS: Chi-Square and a pooled t-test were computed to analyse refusal data (n = 300) obtained from heart failure patients who were invited to participate in one of the four studies but declined. RESULTS: Refusal reasons from 300 patients (66% men, mean age 65·33) included: not interested (n = 163), too busy (n = 64), travel burden (n = 50), too sick (n = 38), family problems (n = 14), too much commitment (n = 13) and privacy concerns (n = 4). Chi-Square analyses showed no differences in frequency of reasons (p > 0·05) between men and women. Patients who refused were older, on average, than study participants. CONCLUSIONS: Some reasons were patient-dependent; others were study-dependent. With 'not interested' as the most common reason, cited by over 50% of patients who declined, recruitment measures should be targeted at stimulating patients' interest. Additional efforts may be needed to recruit older participants. However, reasons for refusal were consistent regardless of gender. RELEVANCE TO CLINICAL PRACTICE: Heart failure researchers should proactively approach a greater proportion of women and patients over age 65. With no gender differences in type of reasons for refusal, similar recruitment strategies can be used for men and women. However, enrolment of a representative proportion of women in heart failure studies has proven elusive and may require significant effort from researchers. Employing strategies to stimulate interest in studies is essential for recruiting heart failure patients, who overwhelmingly cited lack of interest as the top reason for refusal.

Nutritional Risk Index predicts mortality in hospitalized advanced heart failure patients.

BACKGROUND: Hospitalized advanced heart failure (HF) patients are at high risk for malnutrition and death. The Nutritional Risk Index (NRI) is a simple, well-validated tool for identifying patients at risk for nutrition-related complications. We hypothesized that, in advanced HF patients from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial, the NRI would improve risk discrimination for 6-month all-cause mortality. METHODS: We analyzed the 160 ESCAPE index admission survivors with complete follow-up and NRI data, calculated as follows: NRI = (1.519 × discharge serum albumin [in g/dl]) + (41.7 × discharge weight [in kg] / ideal body weight [in kg]); as in previous studies, if discharge weight is greater than ideal body weight (IBW), this ratio was set to 1. The previously developed ESCAPE mortality model includes: age; 6-minute walk distance; cardiopulmonary resuscitation/mechanical ventilation; discharge ß-blocker prescription and diuretic dose; and discharge serum sodium, blood urea nitrogen and brain natriuretic peptide levels. We used Cox proportional hazards modeling for the outcome of 6-month all-cause mortality. RESULTS: Thirty of 160 patients died within 6 months of hospital discharge. The median NRI was 96 (IQR 91 to 102), reflecting mild-to-moderate nutritional risk. The NRI independently predicted 6-month mortality, with adjusted HR 0.60 (95% CI 0.39 to 0.93, p = 0.02) per 10 units, and increased Harrell's c-index from 0.74 to 0.76 when added to the ESCAPE model. Body mass index and NRI at hospital admission did not predict 6-month mortality. The discharge NRI was most helpful in patients with high (≥ 20%) predicted mortality by the ESCAPE model, where observed 6-month mortality was 38% in patients with NRI < 100 and 14% in those with NRI > 100 (p = 0.04). CONCLUSIONS: The NRI is a simple tool that can improve mortality risk stratification at hospital discharge in hospitalized patients with advanced HF.

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.

Impact of prior admissions on 30-day readmissions in medicare heart failure inpatients.

OBJECTIVE: To determine how all-cause hospitalizations within 12 months preceding an index heart failure (HF) hospitalization affect risk stratification for 30-day all-cause readmission. PATIENTS AND METHODS: Early readmission of inpatients with HF is challenging to predict, yet this outcome is used to compare hospital performance and guide reimbursement. Most risk models do not consider the potentially important variable of prior admissions. We analyzed Medicare inpatients with HF aged 66 years or older admitted to 14 Michigan community hospitals from October 1, 2002, to March 31, 2003, and from January 1 to June 30, 2004. Clinical data were obtained from admission charts, hospitalization dates from Centers for Medicare & Medicaid Services (CMS) claims, and mortality dates from the Social Security Death Index. We used mixed-effects logistic regression and reclassification indices to evaluate the ability of a CMS chart-based readmission risk model, prior admissions, and their combination to predict 30-day readmission in survivors of the index HF hospitalization. RESULTS: Of 1807 patients, 43 (2.4%) died during the index admission; 476 of 1764 survivors (27%) were readmitted 30 or fewer days after discharge. Adjusted for the CMS readmission model, prior admissions significantly increased the odds of 30-day readmission (1 vs 0: odds ratio, 4.67; 95% CI, 3.37-6.46; ≥2 vs 0: odds ratio, 6.49; 95% CI, 4.93-8.55; both P<.001), improved model discrimination (c statistic, 0.61-0.74, P<.001), and reclassified many patients (net reclassification index, 0.40; integrated discrimination index, 0.12). CONCLUSION: In Medicare inpatients with HF, prior all-cause admissions strongly increase all-cause readmission risk and markedly improve risk stratification for 30-day readmission.

Vitamin D receptor genetics on extracellular matrix biomarkers and hemodynamics in systolic heart failure.

INTRODUCTION: Vitamin D deficiency has been associated with the development of myocardial hypertrophy and inflammation. These findings suggest that vitamin D status and vitamin D receptor (VDR) genomics may play a role in myocardial fibrosis. The aim of this pilot study was to determine the association between vitamin D levels, VDR polymorphisms, and biomarkers of left ventricular remodeling and hemodynamics. METHODS: In a cross-sectional pilot study, patients with ejection fraction (EF) <40% (and New York Heart Association ≥ II) undergoing right heart catheterization were included in the study. Blood was collected for determination of 25-hydroxyvitamin D level (antibody competitive immunoassay), VDR genotypes (BsmI, ApaI, TaqI, and FokI), and biomarkers (N-terminal propeptide of collagen type III [PIIINP], matrix metalloproteinase 2, and galectin 3). The vitamin D genotypes were determined through the use of pyrosequencing. RESULTS: A total of 30 patients with a mean EF of 17% ± 8% were enrolled. There was a significant association between the BsmI C allele, ApaI G allele, and TaqI A allele, which formed a haplotype block (CGA) for analysis. There were no differences in baseline parameters between patients with the VDR haplotype block (n = 20) and those without (n = 10). Individual genotypes were not associated with any biomarker or hemodynamics. Patients with the CGA haplotype demonstrated significantly higher log PIIINP values (1.74 ± 0.32 mcg/mL vs 1.36 ± 0.31 mcg/mL, P = .0041). When evaluating vitamin D levels below and above the median level (19 ng/mL), there was no significant difference between these 2 groups in regard to biomarker levels for left ventricular remodeling. CONCLUSION: This study has shown that a biomarker for collagen type III synthesis, PIIINP, was associated with the CGA haplotype of BsmI, ApaI, and TaqI single nucleotide polymorphisms on the VDR. These findings suggest that VDR genetics may play a role in myocardial fibrosis in patients with systolic heart failure.

Risk stratification for death and all-cause hospitalization in heart failure clinic outpatients.

BACKGROUND: Most heart failure (HF) risk stratification models were developed for inpatient use, and available outpatient models use a complex set of variables. We hypothesized that routinely collected clinical data could predict the 6-month risk of death and all-cause medical hospitalization in HF clinic outpatients. METHODS AND RESULTS: Using a quality improvement database and multivariable Cox modeling, we derived the Heart Failure Patient Severity Index (HFPSI) in the University of Michigan HF clinic (UM cohort, n = 1,536; 314 reached primary outcome). We externally validated the HFPSI in the Ann Arbor Veterans' Affairs HF clinic (VA cohort, n = 445; 106 outcomes) and explored "real-time" HFPSI use (VA-RT cohort, n = 486; 141 outcomes) by tracking VA patients for 6 months from their most recently calculated HFPSI, rather than using an arbitrary start date for the cohort. The HFPSI model included blood urea nitrogen, B-type natriuretic peptide, New York Heart Association class, diabetes status, history of atrial fibrillation/flutter, and all-cause hospitalization within the prior 1 and 2 to 6 months. The concordance c statistics in the UM/VA/VA-RT cohorts were 0.71/0.68/0.74. Kaplan-Meier curves and log-rank testing demonstrated excellent risk stratification, particularly between a large, low-risk group (40% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 8%/12%/12%) and a small, high-risk group (10% of patients, 6-month event rates in the UM/VA/VA-RT cohorts 57%/58%/79%). CONCLUSIONS: The HFPSI uses readily available data to predict the 6-month risk of death and/or all-cause medical hospitalization in HF clinic outpatients and could potentially help allocate specialized HF resources within health systems.

Healthcare resource use among heart failure patients in a randomized pilot study of a cognitive training intervention.

OBJECTIVES: To compare healthcare resource use of patients with heart failure (HF) randomized to the cognitive training intervention and to the health education active control intervention in a randomized controlled pilot study. BACKGROUND: Cognitive training interventions may be efficacious and improve patients' memory and abilities to perform instrumental activities of daily living and self-care behaviors that may, in turn, lower healthcare resource use, but the influence of these interventions on healthcare resource use is unknown. METHODS: Thirty-four HF patients were randomized to the computerized plasticity-based cognitive training intervention called Brain Fitness and to the health education active control intervention and completed the study. The primary outcome variable for the study was memory (recall and delayed recall). The secondary purpose of the study that is the focus of this paper was to compare healthcare resource use between the two groups using the third-party payer perspective. Data were collected at baseline and at 8 and 12 weeks after baseline. Healthcare resources were priced at Medicare payment levels for services and average wholesale price for medications. RESULTS: Average costs of visits, procedures, and medications were similar between groups. Average costs of hospitalizations and tests, and therefore total costs, were half as much in the Brain Fitness group as compared to the active control group, but this difference was not significantly different from zero (p = 0.24). CONCLUSIONS: Larger randomized controlled trials are needed that include analyses of program costs and costs associated with medical and non-medical services in order to fully evaluate efficacy of this intervention.