Microclimate evaluation of strap-based wheelchair seating systems for persons with spinal cord injury: A pilot study.

STUDY PURPOSE: The purpose of this pilot study was to assess microclimate characteristics of two versions of a strap-based wheelchair seating system (perforated and solid straps) and to conduct preliminary microclimate comparisons of subjects' current wheelchair seating systems. MATERIALS AND METHODS: In this pilot study, the microclimate properties of two variations (solid and perforated) of a strap-based seating system were compared with two commonly used seating systems. Six subjects sat on three different seating systems each for 100-min test periods, while temperature and relative humidity were measured with a single sensor adjacent to the skin-seat interface. Additionally, thermal images of the seat interface were collected before and after each test period. RESULTS: The thermal images revealed that the maximum surface temperature of the solid-strap-based seating system was significantly lower than the other seating systems, -1.21 °C. (95% CI -2.11 to -0.30, p = 0.02), immediately following transfer out of the seat. Five minutes after transferring out of the seat, the perforated-strap seat was significantly cooler than the other seats -0.94 °C. (95% CI -1.59 to -0.30), p = 0.01, as was the solid-strap-based seat, -1.66 °C. (95% CI -2.69 to -0.63), p = 0.01. There were no significant differences in interface temperature or relative humidity measured with the single sensor near the skin-seat interface. CONCLUSION: This pilot study offers preliminary evidence regarding the microclimate of the strap-based seating systems compared with other common seating systems. Clinically, the strap-based seating system may offer another option for those who struggle with microclimate management.

Prognostic Value of Insulin-Like Growth Factor-Binding Protein 7 in Patients with Heart Failure and Preserved Ejection Fraction.

BACKGROUND: The prognostic merit of insulin-like growth factor-binding protein 7 (IGFBP7) is unknown in heart failure and preserved ejection fraction (HFpEF). METHODS AND RESULTS: Baseline IGFBP7 (BL-IGFBP7; n = 302) and 6-month change (Δ; n = 293) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years; secondary outcomes included HF events. Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age (R2 = 0.13; P < .0001), amino-terminal pro-B-type NP (R2 = 0.22; P < .0001), and estimated glomerular filtration rate (eGFR; R2 = 0.14; P < .0001), but not with signs/symptoms of HFpEF. BL-IGFBP7 was significantly associated with the primary outcome (hazard ratio [HR] = 1.007 per ng/mL; P < .001), all-cause mortality (HR = 1.008 per ng/mL; P < .001), and HF events (HR = 1.007 per ng/mL; P < .001). IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro-B-type NP and eGFR but not all variables in the I-PRESERVE prediction model. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was significantly associated with decrease in eGFR in patients randomized to irbesartan (R2 = 0.09; P = .002). ΔIGFBP7 was not independently associated with outcome. CONCLUSIONS: Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events, but after multivariable adjustment this association was no longer present. Further studies of IGFBP7 are needed to elucidate its mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00095238.

Longer Withdrawal Time Is Associated With a Reduced Incidence of Interval Cancer After Screening Colonoscopy.

BACKGROUND & AIMS: Withdrawal times and adenoma detection rates are widely used quality indicators for screening colonoscopy. More rapid withdrawal times have been associated with undetected adenomas, which can increase risk for interval colorectal cancer. METHODS: We analyzed records of 76,810 screening colonoscopies performed between 2004 and 2009, by 51 gastroenterologists practicing in Minneapolis and St Paul, MN. Colonoscopy records were linked electronically to the state cancer registry (Minnesota Cancer Surveillance System) to identify incident interval cancers that were diagnosed within 5.5 years after the screening examination. RESULTS: The physicians' mean ± SD withdrawal time was 8.6 ± 1.7 minutes and adenoma detection rates were 25% ± 9%. Longer mean withdrawal times were associated with higher adenoma detection rates (3.6% per minute; 95% confidence interval: 2.4% to 4.8%; P < .0001). We identified 78 cancers during 410,687 person-years of follow-up, for an annual rate of 0.19/1000 person-years. Physicians' mean annual withdrawal times were inversely associated with cancer incidence (P < .0001). Compared with withdrawal times ≥6 minutes, the adjusted incidence rate ratio for withdrawal times of <6 minutes was 2.3 (95% confidence interval: 1.5-3.4; P < .0001). CONCLUSIONS: Shorter mean annual withdrawal times during screening colonoscopies were independently associated with lower adenoma detection rates and increased risk of interval colorectal cancer.

Extended Follow-Up of Patients With Heart Failure Receiving Autonomic Regulation Therapy in the ANTHEM-HF Study.

OBJECTIVE: Evaluate the effects of a novel autonomic regulation therapy (ART) via vagus nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced left ventricular ejection fraction during a 12-month follow-up period. METHODS: The Autonomic Regulation Therapy for the Improvement of Left Ventricular Function and Heart Failure Symptoms (ANTHEM-HF) study enrolled 60 subjects with New York Heart Association class II-III HF and low left ventricular ejection fraction (≤40%), who received open-loop ART using VNS randomized to left or right cervical vagus nerve placement and followed for 6 months after titration to a therapeutic output current (2.0 ± 0.6 mA). Patients received chronic stimulation at a frequency of 10 Hz and pulse duration of 250 µsec. Forty-nine subjects consented to participate in an extended follow-up study for an additional 6 months (12 months total posttitration) to determine whether the effects of therapy were maintained. RESULTS: During the 6-month extended follow-up period, there were no device malfunctions or device-related serious adverse effects. There were 7 serious adverse effects unrelated to the device, including 3 deaths (2 sudden cardiac deaths, 1 worsening HF death). There were 5 nonserious adverse events that were adjudicated to be device-related. Safety and tolerability were similar, and there were no significant differences in efficacy between left- and right-sided ART. Overall, mean efficacy measure values at 12 months were not significantly different from mean values at 6 months. CONCLUSIONS: Chronic open-loop ART via left- or right-sided VNS continued to be feasible and well-tolerated in patients with HF with reduced EF. Improvements in cardiac function and HF symptoms seen after 6 months of ART were maintained at 12 months.

Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues.

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin.

OBJECTIVE: New regimens to treat hepatitis C virus infection have expanded the eligible patient population to include more patients receiving concurrent warfarin. The primary objective of this study was to assess whether a drug interaction occurs when these regimens are added to warfarin therapy. METHODS: This was a retrospective cohort design using a nationwide database of the Veterans Affairs Health System. Patients on warfarin therapy treated with sofosbuvir or ombitasvir, paritaprevir-ritonavir, and dasabuvir (OBV-PTV/r-DSV) from March 2014 through October 2015 were identified. The warfarin dose response was calculated using a warfarin sensitivity index (WSI) defined as the steady-state INR divided by the mean daily warfarin dose. The primary outcome was the change in WSI from hepatitis C treatment initiation to completion. RESULTS: The final sample consisted of 271 patients. The WSI decreased 23% from a mean baseline value of 0.53 to 0.39 (decrease of 0.14; 95% CI = 0.11 to 0.16; P < 0.001). OBV-PTV/r-DSV produced a significantly greater decrease than any sofosbuvir regimen. Concurrent ribavirin accounted for an additional decrease in warfarin sensitivity of -0.09 (95% CI = -0.06 to -0.12; P < 0.001). The percentage of subtherapeutic INR results increased from 26% prior to hepatitis C treatment to 58% during treatment. CONCLUSIONS: Results indicate a clinically significant reduction in warfarin dose-response when hepatitis C treatment regimens were added to warfarin. They were most profound with OBV-PTV/r-DSV. Ribavirin was associated with an additive effect. Clinicians should be aware of this potential drug interaction to closely monitor and minimize subtherapeutic levels of anticoagulation.

High-resolution wrist-worn overnight oximetry has high positive predictive value for obstructive sleep apnea in a sleep study referral population.

BACKGROUND: Reducing the need for diagnostic sleep studies for obstructive sleep apnea (OSA) would reduce direct and opportunity costs while expediting time to treatment for this common and morbid disorder. We sought to determine if an established sleep apnea screening questionnaire (STOP-BANG) and wrist-worn overnight oximetry data could provide high positive predictive value for the presence of OSA. METHODS: We conducted a prospective observational study of consecutive unattended sleep study patients at a single facility. Patients were referred for sleep testing after chart review by a sleep physician. We assessed area under the receiver-operating characteristic curve (ROC AUC) and positive predictive value (PPV) of STOP-BANG score and oxygen desaturation index (ODI) for a respiratory disturbance index (RDI) ≥15/h. RESULTS: Among 234 test patients, 65 % had an RDI ≥15/h. STOP-BANG had poor ability to discriminate these patients (ROC AUC 0.62). ODI added significant diagnostic information to the STOP-BANG score, increasing the ROC AUC to 0.86. Having the ODI, the STOP-BANG score no longer contributed significant diagnostic information, and the ODI alone discriminated as well as the combination (ROC AUC 0.86). Forty nine percent had an ODI ≥7/h, which had PPV of 92 % (95 % confidence interval (CI), 86 to 96 %). In the validation sample of 1,196 consecutive patients, ODI ≥ 7/h had a PPV of 97 % (95 % CI, 95 to 97 %). CONCLUSIONS: Among patients with a high prevalence of OSA, high ODI is common and its presence has high PPV for OSA. These data suggest that overnight oximetry prior to sleep testing could significantly reduce the number of patients requiring sleep studies, thereby reducing costs and time to treatment.

Mortality prediction using a modified Seattle Heart Failure Model may improve patient selection for ventricular tachycardia ablation.

BACKGROUND: Catheter ablation is frequently used as a palliative option to reduce shock burden in patients with ventricular tachycardia (VT). A risk prediction tool that accurately predicts short-term survival could improve patient selection for VT ablation. OBJECTIVE: The objective of the study is to assess utility of the Seattle Heart Failure Model (SHFM) to predict 6-month mortality in patients undergoing VT ablation. METHODS: Data on patients who underwent VT ablation at 2 tertiary institutions were retrospectively compiled. The SHFM score at the time of ablation, including 2 added VT variables, was used to predict 6-month mortality. The predicted number of deaths was compared to the observed number to assess model calibration. Model discrimination of those who died within 6 months was assessed by both K- and C-statistics. RESULTS: Mean age of the 243 patients was 63 ± 12 years; 89% were male. Mean SHFM score for the cohort was 1.3 ± 1.3. The Kaplan-Meier probability of death within 6 months was 14% (34 patients). The number of deaths estimated by the SHFM at 6 months was 31 (13%) giving a predicted to observed ratio of 0.91 (95% CI 0.64-1.30). The K-statistic for 6-month mortality predictions was 0.77 (95% CI 0.73-0.81), whereas the C-statistic was 0.84 (95% CI 0.78-0.92). Patients with an SHFM score ≥4.0 had an estimated positive predictive value of 80% (95% CI 28%-99%) for dying within 6 months of VT ablation. CONCLUSION: The SHFM was well calibrated to a sample of patients who underwent VT ablation and provided good discrimination of short-term deaths. This model could be useful as a prognostic tool to improve patient selection for VT ablation.

Autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure: results of the ANTHEM-HF trial.

OBJECTIVE: ANTHEM-HF evaluated a novel autonomic regulation therapy (ART) via either left or right vagus nerve stimulation (VNS) in patients with heart failure (HF) and reduced ejection fraction (HFrEF). METHODS AND RESULTS: Sixty subjects (New York Heart Association [NYHA] functional class II-III, left ventricular ejection fraction (LVEF) ≤ 40%, left ventricular end-diastolic diameter ≥ 50 mm to < 80 mm) receiving optimal pharmacologic therapy were randomized at 10 sites. VNS systems were randomly implanted on the left (n = 31) or right (n = 29) side. All patients were successfully implanted and 59 were titrated over 10 weeks to a well tolerated stimulation intensity. One patient died 3 days after an embolic stroke that occurred during implantation. Common device-related adverse events after VNS titration were transient mild dysphonia, cough, and oropharyngeal pain, which were similar for left- and right-side VNS. After 6 months of ART, the adjusted left-right differences in LVEF, left ventricular end-systolic volume (LVESV), and left ventricular end-systolic diameter (LVESD) were 0.2% (95% CI -4.4 to 4.7), 3.7 mL (95% CI -7.0 to 14.4), and 1.3 mm (95% CI -0.9 to 3.6), respectively. In the combined population, absolute LVEF improved by 4.5% (95% CI 2.4-6.6), LVESV improved by -4.1 mL (95% CI -9.0 to 0.8), and LVESD improved by -1.7 mm (95% CI -2.8 to -0.7). Heart rate variability improved by 17 ms (95% CI 6.5-28) with minimal left-right difference. Six-minute walk distance improved an average of 56 m (95% CI 37-75); however, improvement was greater for right-side ART (77 m [95% CI 49-105]). NYHA functional class improved in 77% of patients (baseline to 6 months). CONCLUSIONS: Chronic open-loop ART via left- or right-side VNS is feasible and well tolerated in HFrEF patients. Safety and efficacy measures are encouraging and warrant further study.

Differential effects of professional leaders on health care teams in chronic disease management groups.

BACKGROUND: Leadership by health care professionals is likely to vary because of differences in the social contexts within which they are situated, socialization processes and societal expectations, education and training, and the way their professions define and operationalize key concepts such as teamwork, collaboration, and partnership. This research examines the effect of the nurse and physician leaders on interdependence and encounter preparedness in chronic disease management practice groups. PURPOSE: The aim of this study was to examine the effect of complementary leadership by nurses and physicians involved in jointly producing a health care service on care team functioning. METHODOLOGY: The design is a retrospective observational study based on survey data. The unit of analysis is heart failure care groups in U.S. Veterans Health Administration medical centers. Survey and administrative data were collected in 2009 from 68 Veterans Health Administration medical centers. Key variables include nurse and physician leadership, interdependence, psychological safety, coordination, and encounter preparedness. Reliability and validity of survey measures were assessed with exploratory factor analysis and Cronbach alphas. Multivariate analyses tested hypotheses. FINDINGS: Professional leadership by nurses and physicians is related to encounter preparedness by different paths. Nurse leadership is associated with greater team interdependence, and interdependence is positively associated with respect. Physician leadership is positively associated with greater psychological safety, respect, and shared goals but is not associated with interdependence. Respect is associated with involvement in learning activities, and shared goals are associated with coordination. Coordination and involvement in learning activities are positively associated with encounter preparedness. PRACTICE IMPLICATIONS: By focusing on increasing interdependence and a constructive climate, nurse and physician leaders have the opportunity to increase care coordination and involvement in learning activities.

Chapter 12: systematic review of prognostic tests.

A number of new biological markers are being studied as predictors of disease or adverse medical events among those who already have a disease. Systematic reviews of this growing literature can help determine whether the available evidence supports use of a new biomarker as a prognostic test that can more accurately place patients into different prognostic groups to improve treatment decisions and the accuracy of outcome predictions. Exemplary reviews of prognostic tests are not widely available, and the methods used to review diagnostic tests do not necessarily address the most important questions about prognostic tests that are used to predict the time-dependent likelihood of future patient outcomes. We provide suggestions for those interested in conducting systematic reviews of a prognostic test. The proposed use of the prognostic test should serve as the framework for a systematic review and to help define the key questions. The outcome probabilities or level of risk and other characteristics of prognostic groups are the most salient statistics for review and perhaps meta-analysis. Reclassification tables can help determine how a prognostic test affects the classification of patients into different prognostic groups, hence their treatment. Review of studies of the association between a potential prognostic test and patient outcomes would have little impact other than to determine whether further development as a prognostic test might be warranted.

Comparative effectiveness of Clostridium difficile treatments: a systematic review.

BACKGROUND: Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown. PURPOSE: To determine whether, among adults with C. difficile infection, treatment with certain antibiotics compared with others results in differences in initial cure, recurrence, and harms. DATA SOURCES: MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review. STUDY SELECTION: Randomized, controlled trials of adults with C. difficile infection, independent of outcomes, who were treated with medications available in the United States. Observational studies reporting strain were included. DATA EXTRACTION: Study design, inclusion and exclusion criteria, quality and strength of evidence as assessed by 2 reviewers, study definitions, and duration of treatment and follow-up. Outcomes included initial cure, recurrence, and treatment harms. DATA SYNTHESIS: 11 trials that included 1463 participants were identified. Three trials compared metronidazole with vancomycin; 8 compared metronidazole or vancomycin with another agent, combined agents, or placebo. Strain was analyzed in 1 trial and 2 cohort studies. No study comparing 2 antimicrobial agents demonstrated a statistically significant difference for initial cure; all comparisons were of low to moderate strength of evidence. Moderate-strength evidence from 1 study demonstrated that recurrence was decreased with fidaxomicin versus vancomycin (15% vs. 25%; difference, -10 percentage points [95% CI, -17 to -3 percentage points]; P=0.005). Subgroup analysis of a single study comparing metronidazole with vancomycin for patients who have severe C. difficile infection showed no difference by intention-to-treat analysis; this was rated as insufficient-strength evidence. Harms, when reported, did not differ between treatments in any study. LIMITATIONS: Definitions of diarrhea, C. difficile infection, initial cure, and relapse varied. Some studies reported insufficient detail to allow assessment of all randomly assigned participants or of harms. CONCLUSION: No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin. PRIMARY FUNDING SOURCE: U.S. Department of Health and Human Services.

Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial.

BACKGROUND: Growth-differentiation factor-15 (GDF-15) is emerging as a prognostic biomarker in patients with coronary artery disease. Little is known about GDF-15 as a biomarker in patients with heart failure. METHODS AND RESULTS: The circulating concentration of GDF-15 was measured at baseline (n=1734) and at 12 months (n=1517) in patients randomized in the Valsartan Heart Failure Trial (Val-HeFT). GDF-15 levels at baseline ranged from 259 to 25 637 ng/L and were abnormally high (>1200 ng/L) in 85% of patients. Higher levels were associated with features of worse heart failure and biomarkers of neurohormonal activation, inflammation, myocyte injury, and renal dysfunction. Baseline GDF-15 levels (per 100 ng/L) were associated with the risks of mortality (hazard ratio, 1.017; 95% confidence interval, 1.014 to 1.019; P<0.001) and first morbid event (hazard ratio, 1.020; 95% confidence interval, 1.017 to 1.023; P<0.001). In a comprehensive multiple-variable Cox regression model that included clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T, GDF-15 remained independently associated with mortality (hazard ratio, 1.007; 95% confidence interval, 1.001 to 1.014; P=0.02) but not first morbid event. At 12 months, the GDF-15 levels had increased by a similar amount in the placebo and valsartan groups (P=0.94). Increases in GDF-15 over 12 months were independently associated with the risks of future mortality and first morbid event also after adjustment for clinical prognostic variables, B-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity troponin T and their changes. CONCLUSIONS: GDF-15 reflects information from several pathological pathways and provides independent prognostic information in heart failure. GDF-15 levels increase over time, suggesting that GDF-15 reflects a pathophysiological axis that is not completely addressed by the therapies prescribed in Val-HeFT.

Proteinuria, chronic kidney disease, and the effect of an angiotensin receptor blocker in addition to an angiotensin-converting enzyme inhibitor in patients with moderate to severe heart failure.

BACKGROUND: Chronic kidney disease (CKD) is an established risk factor for poor outcomes in heart failure (HF). Whether proteinuria provides additional prognostic information is not known. Renin-angiotensin blockade medications improve outcomes in HF but are underutilized in HF patients with renal dysfunction because of safety concerns and a lack of evidence of their effectiveness. METHODS AND RESULTS: In the Valsartan in Heart Failure Trial (Val-HeFT), 5010 patients with class II, III, or IV heart failure were randomly assigned to receive valsartan or placebo. The 2 primary outcomes were death and first morbid event, defined as death, sudden death with resuscitation, hospitalization for HF, or administration of intravenous inotropic or vasodilator drugs for 4 hours or more without hospitalization. The study cohort was divided into subgroups according to the presence of CKD (estimated glomerular filtration rate <60 mL x min(-1) x 1.73 m(-2)) and proteinuria (positive dipstick). Multivariable Cox proportional hazards regression models were used to examine the relationships between study outcomes and proteinuria, including its interaction with CKD. The interaction between valsartan and CKD was also tested. The effect of valsartan on estimated glomerular filtration rate was estimated by generalized linear models, including tests of interactions between treatment and CKD. At baseline, CKD was found in 58% and dipstick-positive proteinuria in 8% of patients. Dipstick-positive proteinuria was independently associated with mortality (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.01 to 1.62, P=0.05) and first morbid event (HR 1.28, 95% CI 1.06 to 1.55, P=0.01). The increased risk of death associated with dipstick-positive proteinuria was similar for those with and without CKD (HR 1.26, 95% CI 0.96 to 1.66 versus HR 1.37, 95% CI 0.83 to 2.26; P=0.94), as was the hazard for first morbid event (HR 1.26, 95% CI 1.01 to 1.57 versus HR 1.42, 95% CI 0.98 to 2.07; P=0.71). Valsartan reduced estimated glomerular filtration rate compared with placebo to a similar extent (P=0.52) in the subgroups with CKD (mean reduction -3.6 mL x min(-1) x 1.73 m(-2)) and without CKD (mean reduction -4.0 mL x min(-1) x 1.73 m(-2)) and by -3.8 mL x min(-1) x 1.73 m(-2) in both groups combined. The beneficial effect of valsartan on first morbid events was similar in those with and without CKD (HR 0.86, 95% CI 0.74 to 0.99 versus HR 0.91, 95% CI 0.73 to 1.12; P=0.23) and was significant in the subgroup with CKD. The effect of valsartan on mortality did not differ in patients with and without CKD (HR 1.01, 95% CI 0.85 to 1.20 versus HR 0.91, 95% CI 0.69 to 1.25; P=0.08). CONCLUSIONS: CKD was common and dipstick-positive proteinuria was infrequent in this sample of patients with HF. After controlling for other risk factors, including CKD, the relatively small subgroup with dipstick-positive proteinuria did have worse outcomes. Valsartan reduced the estimated glomerular filtration rate by the same amount in patients with and without CKD and reduced the risk of the first morbid event in patients with CKD, which suggests its beneficial effects in patients with HF and CKD.

Quality of Chronic Obstructive Pulmonary Disease-Related Health Care in Rural and Urban Veterans Affairs Clinics.

Only minor disparities were found between patients at rural and urban clinics in this examination of the differences in the quality of health care for patients with COPD.

Association of Implantable Cardioverter Defibrillators With Survival in Patients With and Without Improved Ejection Fraction: Secondary Analysis of the Sudden Cardiac Death in Heart Failure Trial.

Importance: Improvement in left ventricular ejection fraction (EF) to >35% occurs in many patients with reduced EF at baseline. To our knowledge, whether implantable cardioverter defibrillator (ICD) therapy improves survival for these patients is unknown. Objective: To examine the efficacy of ICD therapy in reducing risk of all-cause mortality and sudden cardiac death among patients with an EF ≤35% at baseline, with or without an improvement in EF to >35% during follow-up. Design, Setting, and Participants: This retrospective analysis examined data collected in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which randomly assigned 2521 patients to placebo, amiodarone, or ICD between 1997 and 2001. A subset of 1902 participants (75.4%) of the SCD-HeFT had a repeated assessment of EF a mean (SD) of 13.5 (6) months after randomization. We stratified these patients by EF ≤35% and >35% based on the first repeated EF measurement after randomization and compared all-cause mortality in 649 patients randomized to placebo vs 624 patients randomized to ICD. Follow-up started with the repeated EF assessment. Analysis was performed between January 2016 and July 2016. Exposures: Implantable cardioverter-defibrillator therapy. Main Outcomes and Measures: All-cause mortality and sudden cardiac death. Results: Of the included 1273 patients, the mean (SD) age was 59 (12) years, and 977 (76.7%) were male and 1009 (79.3%) were white. Repeated EF was >35% in 186 participants (29.8%) randomized to ICD and 185 participants (28.5%) randomized to placebo. During a median follow-up of 30 months, the all-cause mortality rate was lower in the ICD vs placebo group, both in patients whose EF remained ≤35% (7.7 vs 10.7 per 100 person-year follow-up) and in those whose EF improved to >35% (2.6 vs 4.5 per 100 person-year follow-up). Compared with placebo, the adjusted hazard ratio for the effect of ICD on mortality was 0.64 (95% CI, 0.48-0.85) in patients with a repeated EF of ≤35% and 0.62 (95% CI, 0.29-1.30) in those with a repeated EF >35%. There was no interaction between treatment assignment and repeated EF for predicting mortality. Conclusions and Relevance: Among participants in the SCD-HeFT who had a repeated EF assessment during the course of follow-up, those who had an improvement in EF to >35% accrued a similar relative reduction in mortality with ICD therapy as those whose EF remained ≤35%. Prospective randomized clinical trials are needed to test ICD efficacy in patients with an EF >35%. Trial Registration: clinicaltrials.gov Identifier: NCT01114269.

Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial.

OBJECTIVES: The aims of this study were to explore the relationship of baseline levels of natriuretic peptides (NPs) with outcomes and to test for an interaction between baseline levels of NPs and the effects spironolactone. BACKGROUND: Plasma NPs are considered to be helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF), and elevated levels are associated with adverse outcomes. Levels of NPs higher than certain cutoffs are often used as inclusion criteria in clinical trials of HFpEF to increase the likelihood that patients have HF and to select patients at higher risk for events. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. METHODS: The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) trial randomized patients with HFpEF and either prior hospitalization for HF or elevated natriuretic peptide levels (B-type NP [BNP] ≥100 pg/ml or N-terminal proBNP ≥360 pg/ml) to spironolactone or placebo. Baseline BNP (n = 430) or N-terminal proBNP (n = 257) levels were available in 687 patients enrolled from the Americas in the elevated-NP stratum of TOPCAT. RESULTS: Higher levels of NPs were independently associated with an increased risk for TOPCAT's primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for HF when analyzed either continuously or grouped by terciles, adjusting for region of enrollment, age, sex, atrial fibrillation, diabetes, renal function, body mass index, and heart rate. There was a significant interaction between the effect of spironolactone and baseline NP terciles for the primary outcome (p = 0.017), with greater benefit of the drug in the lower compared with higher NP terciles. CONCLUSIONS: Similar to the effects of irbesartan in the I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction) trial, a greater benefit of spironolactone was observed in the group with lower levels of NPs and overall risk in TOPCAT. Elevated NPs in HFpEF identify patients at higher risk for events but who may be less responsive to treatment. The mechanism of this apparent interaction between disease severity and response to therapy requires further exploration. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).

Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT.

BACKGROUND: Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia. METHODS AND RESULTS: Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (P< or =0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein. Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions. CONCLUSIONS: Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them.

Quality of life in advanced heart failure: role of mitral regurgitation.

BACKGROUND: Quality of life is increasingly used as an important end point in clinical trials of treatments for heart failure; thus, relationships between traditional clinical variables and quality of life need to be understood. Baseline data from an ongoing multi-institutional study of a surgically implanted cardiac support device (CorCap, Acorn Cardiovascular, Inc, St Paul, MN) positioned around the heart to halt progression of remodeling in patients with cardiomyopathy provide an opportunity to study the relationship between mitral regurgitation (MR) and quality of life in a group of relatively young patients. OBJECTIVE: The objective of this study was to determine whether the degree of MR correlates with quality of life in patients presenting with significant symptoms of heart failure. METHODS: Baseline MR was assessed by echocardiography and patients were stratified according to whether there was a clinical indication for mitral valve surgery. The effect of heart failure on quality of life was measured by the Minnesota Living with Heart Failure questionnaire (MLHF). The New York Heart Association class, exercise performance measured by peak oxygen consumption and the 6-minute walk test, and the SF-36 physical function measure were analyzed as potential mediating variables. RESULTS: Mean MR grade was 2 +/- 1.5 on a 0-to-4 (worst) scale (n = 260) and ejection fraction averaged 27% +/- 9%. Most patients (82%) had New York Heart Association class III symptoms. Peak oxygen consumption averaged 14.7 +/- 4.3 mL/kg per minute and average walking distance was 348 +/- 83 m. Median (quartile range) SF-36 physical function was 35 (20-50) on a 0-to-100 (best) scale. Median MLHF score was 61 (47.5-77) on a 0-to-105 (worst) scale. The degree of MR and having an indication for mitral valve repair were not associated with the patients' quality of life. Controlling for symptoms and functional measures, older age was independently associated with better quality of life. CONCLUSIONS: The degree of MR was not related to MLHF scores, suggesting that surgery to reduce MR might not have predictable effects on quality of life. Further studies are needed to understand why younger patients reported worse quality of life and how this observation could impact therapy.

Relationships between clinical assessments and patients' perceptions of the effects of heart failure on their quality of life.

BACKGROUND: Hypothetically, most of the effects of heart failure on quality of life might be attributed to symptoms produced by the pathology. Relationships between measures of these concepts need to be quantified to test this conceptual model. METHODS AND RESULTS: Measurements of heart failure pathology and symptoms and quality of life as measured by the Minnesota Living with Heart Failure (MLHF) questionnaire at the 4-month visit in the Valsartan Heart Failure Trial were analyzed. Correlation and regression analyses corrected for estimated reliability of measurements were used to quantify relationships. The percentage of variance in dependent variables that was related to explanatory variables was summarized by the coefficient of determination (100 xR(2)) from regression models. Dyspnea at rest, dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, fatigue, and New York Heart Association class were significantly related to MLHF scores. Combined, these symptoms explained 41% of the variation in MLHF scores. Controlling for symptoms, age explained an additional 4.5% of the variation in MLHF scores, whereas race, gender, and available comorbidities each explained <1%. Pathologic measures including ejection fraction, B-type natriuretic peptide, jugular venous distension, rales, peripheral edema, systolic blood pressure, creatinine, and hemoglobin were not strongly related to symptom assessments (combined R(2) = 17%) or MLHF scores (combined R(2) = 7%). CONCLUSION: Symptoms of heart failure explain a substantial proportion of the variation in the effects of heart failure on patients' quality of life as measured by the MLHF score. The effects of heart failure on quality of life can vary with age independently of symptoms. Pathologic measures of heart failure including some well-known correlates of the risk of hospitalization and death are not strongly related to symptoms or quality of life. Further studies are needed to understand the relationships between heart failure pathology and symptoms and to identify determinants of the effects of heart failure on patients' quality of life that were not related to symptoms.