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Background: Cardiorespiratory fitness (CRF) is closely linked to health status and clinical outcomes in heart failure (HF) patients. We aimed to test whether biomarkers can reflect CRF and its change over time.Methods: This post hoc analysis used data from ambulatory cohorts of heart failure with reduced ejection fraction (HFrEF) (IRONOUT) and heart failure with preserved ejection fraction (HFpEF) (RELAX). Cardiopulmonary exercise testing, 6-minute walk distance (6MWD), and serum biomarkers were measured at baseline and 16- or 24-week follow-up (for IRONOUT and RELAX respectively). Biomarkers included N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2, growth differentiation factor-15, and Galectin-3.Results: Analysis included 225 patients with HFrEF and 216 with HFpEF. Baseline peak VO2, VE/VCO2 slope, and 6MWD showed a mild correlation with the doubling of all 4 tested biomarkers in HFrEF and HFpEF. Following multivariable adjustment (including all biomarkers), the only significant association between change in biomarker and functional parameter in HFrEF was change in NT-proBNP and change in VE/VCO2 slope (3.596% increase per doubling, 95% CI 0.779-6.492, P = .012). In HFpEF, a decrease in peak VO2 was associated with an increase in NT-proBNP (-0.726 mL/min/kg per doubling, 95% CI -1.100 to -0.353, P < .001), and a decrease in 6MWD was associated with an increase in growth differentiation factor-15 (-31.606 m per doubling, 95% CI -61.404 to -1.809, P = .038).Conclusions: In these ambulatory trial cohorts, NT-proBNP was associated with baseline and change in CRF in HFrEF and HFpEF. In contrast, novel biomarkers do not appear suitable as a reliable surrogate for serial assessment of exercise capacity in HF patients given lack of consistent independent association with CRF beyond traditional risk factors and NT-proBNP. [ABSTRACT FROM AUTHOR]

Objective: To identify temporal trends in the use of exercise treadmill testing (ETT) and cardiorespiratory fitness (CRF) estimated by ETT in metabolic equivalents (METs).Patients and Methods: We compiled an ETT database of all available treadmill tests-including those with concomitant stress echocardiography and nuclear perfusion imaging studies-performed at Duke University Hospital from January 1, 1970- December 31, 2012. Six different ramp protocols were used in these combined modalities. CRF at maximal exertion was estimated using established metrics. Eligible patients were required to have no missing data on maximal treadmill speed, grade, and protocol.Results: The most commonly used ETT protocol was the Bruce (n = 28,877), followed by manual test (n = 7390). Since the 1980's, the use of ETT for clinical purposes declined substantially; there was a decreased trend in utilization of 9.4% over the decades 1990-1999 and 2000-2009. When standard protocol (Bruce) was assessed in isolation, trends in CRF decreased progressively from 1970 to 2012 (mean METs (standard deviation): 11.7 (4.3) to 10.5 (3.5)). After adjusting for baseline comorbidities, the trend was reduced to a lesser degree.Conclusions: The use of ETT at our institution has declined over time, perhaps due to changes in clinical practice. In patients undergoing ETT using the standard Bruce protocol, CRF decreased progressively over the last five decades. Future studies are needed to clarify the etiology of the decrease in use of such a powerful predictor of clinical outcomes in our medical care environment. [ABSTRACT FROM AUTHOR]

Background--Daily physical activity assessed by accelerometers represents a novel method to assess the impact of interventions on heart failure (HF) patients' functional status. We hypothesized that daily activity varies by patient characteristics and correlates with established measures of HF severity in HF with preserved ejection fraction. Methods and Results--In this ancillary study of the NEAT-HFpEF trial (Nitrate's Effects on Activity Tolerance in HF With Preserved Ejection Fraction), average daily accelerometer units (ADAU) and hours active per day were assessed during a 14-day period before starting isosorbide mononitrate or placebo (n=110). Baseline ADAU was negatively associated with age, female sex, height, and body mass index, and these variables accounted for 28% of the variability in ADAU (P<0.007 for all). Adjusting for these factors, patients with lower ADAU were more likely to have had an HF hospitalization, orthopnea, diabetes mellitus and anemia, be treated with β-blockers, have higher ejection fraction, relative wall thickness and left atrial volume, and worse New York Heart Association class, HF-specific quality of life scores, 6-minute walk distance, and NT-proBNP (N-terminal pro-B-type natriuretic peptide; P<0.05 for all). Associations between hours active per day and clinical characteristics were similar. Relative to baseline, there were no significant associations between changes in ADAU or hours active per day and changes in standard functional assessments (New York Heart Association, quality of life, 6-minute walk distance, and NT-proBNP) with isosorbide mononitrate. Conclusions--Daily activity is a measure of HF-related and global functional status in HF with preserved ejection fraction. As compared with intermittently assessed standard HF assessments, change in daily activity may provide unique information about the impact of HF interventions on functional status. [ABSTRACT FROM AUTHOR]

Background-In-hospital worsening heart failure (WHF) is an important event that has inconsistent definitions used across trials. We used data from 2 acute heart failure (HF) trials from the National Institutes of Health HF Network, DOSE (Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization Strategies), to understand event rates associated with different WHF definitions. Methods and Results-We pooled data from 668 patients in DOSE and ROSE and assessed the relationship between WHF and the composite end point of rehospitalization, emergency room visits for HF, and mortality through 60 days. We also assessed for a differential relationship between the timing of WHF development and outcomes. The overall incidence of WHF was 14.6% (24.1% in DOSE, 6.3% in ROSE, and 5.0% in DOSE using the ROSE definition). WHF was associated with an increase in the composite end point (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11-2.42; P=0.01). However, the association between WHF and outcomes was significantly stronger in ROSE than in DOSE (HR, 2.67; 95% CI, 1.45-4.91; P<0.01 and HR, 1.28; 95% CI, 0.79-2.08; P=0.31, respectively). Development of WHF between baseline to 24 hours compared with 24 to 48 hours or 48 to 72 hours demonstrated a trend toward improved outcomes (HR, 0.49; 95% CI, 0.21-1.17; P=0.11 and HR, 0.45; 95% CI, 0.20-1.04; P=0.06, respectively). Conclusions-A WHF definition that excluded the intensification of diuretics resulted in a lower event rate but a stronger association with outcomes. These data support the need for continued efforts to standardize WHF definitions in clinical trials. [ABSTRACT FROM AUTHOR]

Background Despite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF. Methods and Results We assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1 symptom or sign of new, persistent, or WHF requiring additional intravenous inotropic/vasodilator or mechanical therapy during index hospitalization. We assessed the relationship between WHF and 30-day mortality, 30-day mortality or HF hospitalization, and 180-day mortality. We also assessed whether there was a differential association between early (days 1-3) vs late (day ≥4) WHF and outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients with WHF were more often male and had a history of atrial fibrillation or diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85-18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25-8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values < .0001). There was no evidence of a difference in outcomes between early and late WHF (all P values for comparison ≥ .2). Conclusions Worsening HF during index hospitalization was associated with worse 30- and 180-day outcomes. Worsening HF may represent an important patient-centered outcome in acute HF and a focus of future treatments. [ABSTRACT FROM AUTHOR]