Abstract Background Classification of chronic heart failure (HF) is on the basis of criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and ...therapeutic strategies. Objectives This study used cluster analysis to explore clinical phenotypes in chronic HF patients. Methods A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) study, which evaluated exercise training versus usual care in chronic systolic HF. An association between identified clusters and clinical outcomes was assessed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing. Results Four clusters were identified (ranging from 248 to 773 patients in each), in which patients varied considerably among measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. Compared with cluster 1, risk of all-cause mortality and/or all-cause hospitalization ranged from 0.65 (95% confidence interval 95% CI: 0.54 to 0.78) for cluster 4 to 1.02 (95% CI: 0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had a disproportionately lower risk of 0.61 (95% CI: 0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak oxygen consumption and clinical outcomes between clusters (p for interaction <0.04). Conclusions Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and the need for improved phenotyping of the syndrome. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437 )
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Prognosis in heart failure (HF) patients is commonly assessed based on clinical characteristics. The association between partner status and socioeconomic status (SES) and outcomes ...in chronic HF requires further study. Methods We performed a post-hoc analysis of HF-ACTION, which randomized 2331 HF patients with ejection fraction ≤35% to usual care +/− aerobic exercise training. We examined baseline quality of life and functional capacity and outcomes (all-cause mortality/hospitalization) by partner status and SES using adjusted Cox models and explored an interaction with exercise training. Outcomes were examined based on partner status, education level, annual income, and employment. Results Having a partner, education beyond high school, an income >$25,000, and being employed were associated with better baseline functional capacity and quality of life. Over a median follow-up of 2.5 years, higher education, higher income, being employed, and having a partner were associated with lower all-cause mortality/hospitalization. After multivariable adjustment, lower mortality was seen associated with having a partner (Hazard Ratio HR 0.91, 95% Confidence Interval CI: 0.81–1.03, P = .15) and more than a high school education (HR 0.91, CI: 0.80–1.02, P = .12), although these associations were not statistically significant. There was no interaction between any of these variables and exercise training on outcomes (all P > .5). Conclusions Having a partner and higher SES were associated with greater functional capacity and quality of life at baseline but were not independent predictors of long-term clinical outcomes in chronic HF patients. These findings provide information that may be considered as potential variables impacting outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Furosemide is the most commonly used loop diuretic in patients with heart failure (HF) despite data suggesting potential pharmacologic and antifibrotic benefits with torsemide. We investigated ...patients with HF in Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure who were discharged on either torsemide or furosemide. Using inverse probability weighting to account for the nonrandom selection of diuretic, we assessed the relation between choice of diuretic at discharge with 30-day mortality or HF hospitalization and 180-day mortality. Of 7,141 patients in the trial, 4,177 patients were included in this analysis, of which 87% (n = 3,620) received furosemide and 13% (n = 557) received torsemide. Torsemide-treated patients had lower ejection fraction and blood pressure and higher creatinine and natriuretic peptide level compared with furosemide. Torsemide was associated with similar outcomes on unadjusted analysis and nominally lower events on adjusted analysis (30-day mortality/HF hospitalization odds ratio 0.89, 95% CI 0.62 to 1.29, p = 0.55 and 180-day mortality hazard ratio 0.86, 95% CI 0.63 to 1.19, p = 0.37). In conclusion, these data are hypothesis-generating and randomized comparative effectiveness trials are needed to investigate the optimal diuretic choice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Highlights • DM was associated with lower adherence to exercise and reduced peak VO2 and 6MWD at baseline. • DM patients have an attenuated response to exercise, independent of reduced adherence. • ...DM patients have cardiac and peripheral dysfunction that result in attenuated exercise tolerance. • DM was associated with increased hospitalization, driven by non-HF hospitalizations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background The aim of this study was to investigate the clinical characteristics, exercise training response, β-blocker selectivity, and outcomes in patients with heart failure (HF) and chronic ...obstructive pulmonary disease (COPD). Methods We performed an analysis of HF-ACTION, which randomized 2,331 patients with HF having an ejection fraction of ≤35% to usual care with or without aerobic exercise training. We examined clinical characteristics and outcomes (mortality/hospitalization, mortality, cardiovascular CV mortality/CV hospitalization, and CV mortality/HF hospitalization) by physician-reported COPD status using adjusted Cox models and explored an interaction with exercise training. The interaction between β-blocker cardioselectivity and outcomes was investigated. Results Of patients with COPD status documented (n = 2311), 11% (n = 249) had COPD. Patients with COPD were older, had more comorbidities, and had lower use of β-blockers compared with those without COPD. At baseline, patients with COPD had lower peak oxygen consumption and higher V e /V co2 slope. During a median follow-up of 2.5 years, COPD was associated with increased mortality/hospitalization, mortality, and CV mortality/HF hospitalization. After multivariable adjustment, the risk of CV mortality/HF hospitalization remained increased (hazard ratio HR 1.46, 95% CI 1.14-1.87), whereas mortality/hospitalization (HR 1.15, 95% CI 0.96-1.37) and mortality (HR 1.33, 95% CI 0.99-1.76) were not significantly increased. There was no interaction between COPD and exercise training on outcomes or between COPD and β-blocker selectivity on mortality/hospitalization (all P > .1). Conclusions Chronic obstructive pulmonary disease in patients with HF was associated with older age, more comorbidities, reduced exercise capacity, and increased CV mortality/HF hospitalization, but not a differential response to exercise training. β-Blocker selectivity was not associated with differences in outcome for patients with vs without COPD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background The strength of race as an independent predictor of long-term outcomes in a contemporary chronic heart failure (HF) population and its association with exercise training response have not ...been well established. We aimed to investigate the association between race and outcomes and to explore interactions with exercise training in patients with ambulatory HF. Methods We performed an analysis of HF-ACTION, which randomized 2331 patients with HF having an ejection fraction ≤35% to usual care with or without exercise training. We examined characteristics and outcomes (mortality/hospitalization, mortality, and cardiovascular mortality/HF hospitalization) by race using adjusted Cox models and explored an interaction with exercise training. Results There were 749 self-identified black patients (33%). Blacks were younger with significantly more hypertension and diabetes, less ischemic etiology, and lower socioeconomic status versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at baseline. Over a median follow-up of 2.5 years, black race was associated with increased risk for all outcomes except mortality. After multivariable adjustment, black race was associated with increased mortality/hospitalization (hazard ratio HR 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR 1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar cardiovascular mortality. There was no interaction between race and exercise training on outcomes ( P > .5). Conclusions Black race in patients with chronic HF was associated with increased prevalence of modifiable risk factors, lower exercise performance, and increased HF hospitalization, but not increased mortality or a differential response to exercise training.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Angina pectoris (AP) is associated with worse outcomes in heart failure (HF). We investigated the association of AP with health-related quality of life (HRQoL), exercise capacity, and ...clinical outcomes, and its interaction with exercise training in a HF population. We grouped 2,331 HF patients with reduced ejection fraction (EF) in the HF-ACTION trial of usual care +/- exercise training according to whether they had self-reported AP by Canadian classification score (CCS). HRQoL and clinical outcomes were assessed by AP status. In HF-ACTION, 406 (17%) patients had AP at baseline (44% with CCS ≥ II) with HF severity similar to those without AP. Patients with AP had similar baseline exercise capacity but worse depressive symptoms and HRQoL. AP was associated with 22% greater adjusted risk for all-cause mortality/hospitalizations, driven by hospitalizations. There was significant interaction between baseline AP and exercise training peak VO2 change (P=0.019), but not other endpoints. Exercise training was associated with greater peak VO2 improvement after 3 months in patients with AP (treatment effect=1.25 mL/kg/min, 95% CI=0.6–1.9). In conclusion, AP was associated with worse HRQoL and depressive symptoms. Despite greater peak VO2 improvement with exercise training, patients with AP experienced more adverse outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary Background The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain. We investigated whether ...baseline and change in objectively-assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance. Methods We assessed prospective data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January, 2002, and January, 2004. Participants also either had existing cardiovascular disease (if age ≥50 years) or at least one additional cardiovascular risk factor (if age ≥55 years). Participants were followed-up for cardiovascular events (defined as cardiovascular mortality, non-fatal stroke, or myocardial infarction) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months. Adjusted Cox proportional hazard models quantified the association of baseline and change in ambulatory activity (from baseline to 12 months) with the risk of a subsequent cardiovascular event, after adjustment for each other and potential confounding variables. This study is registered with ClinicalTrials.gov NCT00097786. Findings During 45 211 person-years follow-up, 531 cardiovascular events occurred. Baseline ambulatory activity (hazard ratio HR per 2000 steps per day 0·90, 95% CI 0·84–0·96) and change in ambulatory activity (0·92, 0·86–0·99) were inversely associated with the risk of a cardiovascular event. Results for change in ambulatory activity were unaffected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months. Interpretation In individuals at high cardiovascular risk with impaired glucose tolerance, both baseline levels of daily ambulatory activity and change in ambulatory activity display a graded inverse association with the subsequent risk of a cardiovascular event. Funding Novartis Pharmaceuticals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Diuretic unresponsiveness often occurs during hospital admission for acute heart failure (AHF) and is associated with adverse outcome. This study aims to investigate determinants, clinical ...outcome, and the effects of nesiritide on diuretic response early after admission for AHF. Methods Diuretic response , defined as weight loss per 40 mg of furosemide or equivalent, was examined from hospital admission to 48 hours in 4,379 patients from the ASCEND-HF trial. As an additional analysis, a urinary diuretic response metric was investigated in 5,268 patients using urine volume from hospital admission to 24 hours per 40 mg of furosemide or equivalent. Results Mean diuretic response was −0.42 kg/40 mg of furosemide (interquartile range −1.0, −0.05). Poor responders had lower blood pressure, more frequent diabetes, long-term use of loop diuretics, poorer baseline renal function, and lower urine output (all P < .01). Randomized nesiritide treatment was not associated with diuretic response ( P = .987). Good diuretic response was independently associated with a significantly decreased risk of 30-day all-cause mortality or heart failure rehospitalization (odds ratio 0.44, 95% CI 0.29-0.65, highest vs lowest quintile, P < .001). Diuretic response based on urine output per 40 mg of furosemide showed similar results in terms of clinical predictors, association with outcome, and the absence of an effect of nesiritide. Conclusions Poor diuretic response early after hospital admission for AHF is associated with low blood pressure, renal impairment, low urine output, and an increased risk of death or rehospitalization early after discharge. Nesiritide had a neutral effect on diuretic response.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background The contribution of diabetes to the burden of heart failure (HF) remains largely undescribed. Assessing diabetes temporal trends among US patients hospitalized with HF, and their ...relation with quality measures, in real-world practice can help to define this burden. Methods Using data from the Get With the Guidelines–Heart Failure registry, we assessed temporal trends in diabetes prevalence among patients with HF, and in subgroups with reduced ejection fraction (HFrEF - EF <40%), borderline EF (HFbEF - 40% ≤ EF< 50%), or preserved EF (HFpEF - EF ≥50%), hospitalized between 2005 and 2015. Logistic regression was used to assess whether in-hospital outcomes and HF quality of care were related to trends. Results Among 364,480 HF hospitalizations, 160,171 had diabetes (44.0% overall, 41.8% in HFrEF, 46.7% in HFbEF, 45.5% in HFpEF). There was a temporal increase in diabetes frequency in HF patients (43.2% to 45.8%; Ptrend < 0.0001), including among those with HFrEF (42.0% to 43.6%; Ptrend < 0.0001), HFbEF (46.0% to 49.2%; Ptrend < 0.0001), or HFpEF (43.6% to 46.8%, Ptrend < 0.0001). Diabetic patients had a longer hospital stay (adjusted odds ratio aOR: 1.14, 95%CI: 1.12–1.16), but lower in-hospital mortality (aOR: 0.93 0.89–0.97) compared to those without diabetes, with limited differences in quality measures. Temporal trends in diabetes were not associated with in-hospital mortality or length of stay. There were no temporal interactions of most HF quality measures with diabetes status. Conclusions Approximately 44% of hospitalized HF patients have diabetes, and this proportion has been increasing over the past 10 years, particularly among those patients with new onset HFpEF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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