| 1. |
- Mentz, R. J., et al.
(författare)
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Atrial fibrillation or flutter on initial electrocardiogram is associated with worse outcomes in patients admitted for worsening heart failure with reduced ejection fraction: Findings from the EVEREST Trial
- 2012
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703. ; 164:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Heart failure (HF) complicated by atrial fibrillation/flutter (AF/AFL) is associated with worse outcomes. However, the clinical profile and outcomes of patients following hospitalization for HF with AF/AFL on initial electrocardiogram (ECG) has not been well studied. Methods EVEREST was a randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with HF with ejection fraction <= 40%. A post hoc analysis was performed comparing the clinical characteristics and outcomes [all-cause mortality and cardiovascular mortality/HF hospitalization] of patients with AF/AFL versus sinus rhythm (SR) on baseline ECG, which were centrally analyzed. Times to events were compared using log-rank tests and Cox regression models. Results Of the 4133 patients, 1195 (29%) were classified with AF/AFL and 2071(50%) with SR. The remaining patients (21%) were excluded because ECGs were unavailable (n = 106), rhythm was paced (n = 727), or junctional/other supraventricular (n = 34). AF/AFL patients were older, with increased weight, faster heart rate, higher blood urea nitrogen, and natriuretic peptide levels compared to SR patients. Anticoagulation was prescribed in 67% of AF/AFL patients on discharge. AF/AFL patients were less likely to receive beta-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (all P < .05). After risk adjustment, AF/AFL was associated with increased mortality (hazard ratio 1.23; 95% CI, 1.04-1.46) and cardiovascular mortality/HF hospitalization (hazard ratio 1.26; 95% CI, 1.07-1.47). Conclusion AF/AFL on initial ECG in patients hospitalized with HF with reduced ejection fraction is associated with lower use of evidence-based therapies and increased mortality and rehospitalization compared to patients in SR. (Am Heart J 2012;164:884-892.e2.)
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| 2. |
- Vaduganathan, M., et al.
(författare)
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Relation of Serum Uric Acid Levels and Outcomes Among Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction (from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan Trial)
- 2014
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 114:11, s. 1713-21
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the clinical profiles associated with serum uric acid (sUA) levels in a large cohort of patients hospitalized for worsening chronic heart failure with ejection fraction (EF) /=30 ml/min/1.73 m(2), sUA was strongly associated with increased all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.22 to 1.69, p <0.001) and the composite end point (hazard ratio 1.44, 95% confidence interval 1.26 to 1.64, p <0.001). However, in patients with estimated glomerular filtration rate <30 ml/min/1.73 m(2), sUA was not related with either end point (both p >0.4). Adjusted interaction analyses for gender, race, and admission allopurinol use were not significant. In conclusion, sUA is commonly elevated in patients hospitalized for worsening chronic heart failure and reduced EF, especially in men and blacks. The prognostic use of sUA differs by baseline renal function, suggesting different biologic and pathophysiologic significance of sUA among those with and without significant renal dysfunction.
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| 3. |
- Zannad, F., et al.
(författare)
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Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:10, s. 1082-1094
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Tidskriftsartikel (refereegranskat)abstract
- Endpoint selection is a critically important step in clinical trial design. It poses major challenges for investigators, regulators, and study sponsors, and it also has important clinical and practical implications for physicians and patients. Clinical outcomes of interest in heart failure trials include all-cause mortality, cause-specific mortality, relevant non-fatal morbidity (e.g. all-cause and cause-specific hospitalization), composites capturing both morbidity and mortality, safety, symptoms, functional capacity, and patient-reported outcomes. Each of these endpoints has strengths and weaknesses that create controversies regarding which is most appropriate in terms of clinical importance, sensitivity, reliability, and consistency. Not surprisingly, a lack of consensus exists within the scientific community regarding the optimal endpoint(s) for both acute and chronic heart failure trials. In an effort to address these issues, the Heart Failure Association of the European Society of Cardiology (HFA-ESC) convened a group of expert heart failure clinical investigators, biostatisticians, regulators, and pharmaceutical industry scientists (Nice, France, 12-13 February 2012) to evaluate the challenges of defining heart failure endpoints in clinical trials and to develop a consensus framework. This report summarizes the group's recommendations for achieving common views on heart failure endpoints in clinical trials.
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| 4. |
- Ambrosy, A. P., et al.
(författare)
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Clinical course and predictive value of liver function tests in patients hospitalized for worsening heart failure with reduced ejection fraction: an analysis of the EVEREST trial
- 2012
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 14:3, s. 302-311
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Abnormal liver function tests (LFTs) are common in ambulatory heart failure (HF). The aim of this study was to characterize abnormal LFTs during index hospitalization. METHODS AND RESULTS: A post-hoc analysis was carried out of the placebo group of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) trial, which enrolled patients hospitalized for HF with an ejection fraction (EF) 34 IU/L), alanine transaminase (ALT, >34 IU/L), alkaline phosphatase (AP, >123 IU/L),gamma-glutamyl transferase (GGT, >50 IU/L), and total bilirubin (T Bili, >1.2 mg/dL) were measured at baseline, discharge/day 7, and post-discharge. Co-primary endpoints were all-cause mortality (ACM) and cardiovascular mortality or first HF hospitalization (CVM + HFH). Study participants had a mean age of 65.6 +/-12.0 years, were mostly male, reported high prevalences of medical co-morbidities, and were well treated with evidence-based therapies. Baseline LFT abnormalities were common (ALB 17%, AST 21%, ALT 21%, AP 23%, GGT 62%, and T Bili 26%). Abnormal T Bili was the only marker to decrease substantially from baseline (26%) to discharge/day 7 (19%). All LFTs, except AP, improved post-discharge. Lower baseline ALB and elevated T Bili were associated with higher rates of ACM, and in-hospital decreases in ALB and increases in T Bili were associated with higher rates of both ACM and CVM + HFH. CONCLUSION: LFT abnormalities are common during hospitalization for HF in patients with reduced EF and were persistent at discharge. Baseline and in-hospital changes in ALB and T Bili provide additional prognostic value.
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| 5. |
- Mentz, R. J., et al.
(författare)
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Influence of documented history of coronary artery disease on outcomes in patients admitted for worsening heart failure with reduced ejection fraction in the EVEREST trial
- 2013
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 15:1, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Data on the prognosis of heart failure (HF) patients with coronary artery disease (CAD) have been conflicting. We describe the clinical characteristics and mode-specific outcomes of HF patients with reduced ejection fraction (EF) and documented CAD in a large randomized trial. METHODS AND RESULTS: EVEREST was a prospective, randomized trial of vasopressin-2 receptor blockade, in addition to standard therapy, in 4133 patients hospitalized with worsening HF and reduced EF. Patients were classified as having CAD based on patient-reported myocardial infarction (MI) or coronary revascularization. We analysed the characteristics and outcomes [all-cause mortality and cardiovascular (CV) mortality/HF hospitalization] of patients with and without documented CAD. All events were centrally adjudicated. Documented CAD was present in 2353 patients (57%). Patients with CAD were older and had more co-morbidities compared with those without CAD. Patients with CAD were more likely to receive a beta-blocker, but less likely to receive an angiotensin-converting enzyme (ACE) inhibitor or aldosterone antagonist (P < 0.01). After risk adjustment, patients with documented CAD had similar mortality [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.97-1.30], but were at an increased risk for CV mortality/HF hospitalization (HR 1.25, 95% CI 1.12-1.41) due to an increased risk for HF hospitalization (HR 1.26, 95% CI 1.10-1.44). Patients with CAD had increased HF- and MI-related events, but similar rates of sudden cardiac death. CONCLUSION: Documented CAD in patients hospitalized for worsening HF with reduced EF was associated with a higher burden of co-morbidities, lower use of HF therapies (except beta-blockers), and increased HF hospitalization, while all-cause mortality was similar.
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| 6. |
- Greene, S. J., et al.
(författare)
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Prognostic Value of Monocyte Count in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction (from the EVEREST Trial)
- 2012
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 110:11
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Tidskriftsartikel (refereegranskat)abstract
- Monocytes play a critical role in the pathophysiology of heart failure (HF), but few studies have evaluated the prognostic implications of an increased monocyte count in patients with HF and reduced ejection fraction (EF). The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) examined the effects of tolvaptan in patients with worsening HF and EF /=800/mul. Patients with increased monocyte count tended to have an increased EF and were less likely to have a history of diabetes mellitus, hypercholesterolemia, or coronary revascularization but were more likely to have higher HF functional class and to be taking HF therapies such as diuretics, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and digoxin (p <0.05 for all comparisons). At median follow-up of 9.9 months, increased monocyte count was predictive of all-cause mortality (hazard ratio 1.27, 95% confidence interval 1.003 to 1.60, p = 0.047) but was not associated with cardiovascular mortality or HF hospitalization (hazard ratio 1.06, 95% confidence interval 0.87 to 1.30, p = 0.55). Similar results were seen when monocyte count was analyzed as a continuous variable. However, after adjustment for baseline clinical risk factors, monocyte count was not predictive of either primary end point. In conclusion, increased monocyte count occurs in a minority of patients hospitalized with HF and is associated with poor postdischarge prognosis. However, it does not contribute prognostic value above other more traditional risk factors.
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| 7. |
- Greene, S. J., et al.
(författare)
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The Prognostic Significance of Heart Rate in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction in Sinus Rhythm. Insights From the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) Trial
- 2013
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Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 1:6, s. 488-496
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to characterize the relationship between heart rate and post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction (EF) in sinus rhythm. Background: A reduction in heart rate improves clinical outcomes in patients with chronic heart failure and in sinus rhythm, but the association between heart rate and post-discharge outcomes in patients with HHF is presently unclear. Methods: This post-hoc analysis of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) trial examined 1,947 patients with HHF and EF≤40% not in atrial fibrillation/flutter or pacemaker dependent. Results: The median follow-up period was 9.9 months. At baseline, patients with a higher heart rate tended to be younger with lower EF and were more likely to have worse New York Heart Association functional class and higher natriuretic peptide levels. After adjustment for clinical risk factors, baseline heart rate was not predictive of all-cause mortality (p≥ 0.066). However, at≥70 beats/min, every 5-beat increase in 1-week post-discharge heart rate was independently associated with increased all-cause mortality (hazard ratio: 1.13 [95% confidence interval: 1.05 to 1.22]; p= 0.002). Similarly, every 5-beat increase≥70 beats/min in 4-week post-discharge heart rate was predictive of all-cause mortality (hazard ratio: 1.12 [95% confidence interval: 1.05 to 1.19]; p= 0.001). Conclusions: In this large cohort of patients with HHF with reduced EF and in sinus rhythm, baseline heart rate did not correlate with all-cause mortality. In contrast, at≥70 beats/min, higher heart rate in the early post-discharge period was independently predictive of death during subsequent follow-up. Further study of post-discharge heart rate as a potential therapeutic target in this high-risk population is encouraged. © 2013 American College of Cardiology Foundation.
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| 8. |
- Khan, S. S., et al.
(författare)
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Changes in Serum Potassium Levels During Hospitalization in Patients With Worsening Heart Failure and Reduced Ejection Fraction (from the EVEREST Trial)
- 2015
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 115:6, s. 790-796
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Tidskriftsartikel (refereegranskat)abstract
- Both hyperkalemia and hypokalemia may be related to heart failure (HF) therapy and are associated with adverse outcomes. Abnormalities in serum potassium levels in hospitalized patients with HF and reduced ejection fraction (EF) have not been previously investigated. A post hoc analysis was performed in 1,907 hospitalized patients with worsening HF and reduced EF in the placebo arm of the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan (EVEREST) trial. Serum potassium was measured at randomization and at discharge or day 7. The co-primary end points were all-cause mortality (ACM) and cardiovascular mortality or the first HF hospitalization (CVM + HFH). The association between inhospital change in potassium levels and time to outcomes was evaluated using multivariate Cox regression models. Study participants had a mean age of 65.6 +/- 12.0 years and were on optimal guideline-directed medical therapies, including beta blockers (77%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (85%), and aldosterone antagonists (55%). Baseline potassium concentration was 4.3 +/- 0.6 mEq/l, and hyperkalemia or hypokalemia was seen in 6.5% of the participants. On average, serum potassium level increased by 0.21 +/- 0.66 mEq/l, p < 0.0001, during hospitalization. Inhospital potassium change was not associated with either the primary or the secondary end point over a median follow-up of 9.9 months. In conclusion, in patients with reduced EF hospitalized for worsening HF, serum potassium abnormalities are common at baseline (within 48 hours of admission) and potassium levels increase during hospitalization, despite aggressive diuretic therapy. However, they are not associated with all-cause or CVM or HFH. Inhospital changes in potassium may limit the implementation of evidence-based therapies such as mineralocorticoid receptor antagonists. (C) 2015 Elsevier Inc. All rights reserved.
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| 9. |
- Mentz, R. J., et al.
(författare)
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The Impact of Chronic Obstructive Pulmonary Disease in Patients Hospitalized for Worsening Heart Failure With Reduced Ejection Fraction: An Analysis of the EVEREST Trial
- 2012
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164. ; 18:7, s. 515-523
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is prevalent in heart failure (HF) patients, yet these patients are poorly characterized. We aimed to describe the characteristics and outcomes of patients with systolic dysfunction and COPD in a contemporary HF randomized trial. Methods and Results: EVEREST investigated 4,133 patients hospitalized with worsening HF and an ejection fraction (EF) <= 40%. We analyzed the characteristics and outcomes (all-cause mortality and cardiovascular mortality/HF hospitalization) of patients according to baseline COPD status. COPD was present in 10% (n = 416) of patients. Patients with COPD had a higher prevalence of comorbidities and were less likely to receive a beta-blocker, angiotensin-converting enzyme inhibitor, or aldosterone antagonist. On univariate analysis, COPD was associated with increased all-cause mortality (HR 1.41, 95% CI 1.18-1.67) and cardiovascular mortality/HF hospitalization (HR 1.29, 95% CI 1.11-1.49). After adjusting for potential confounders, the risk associated with COPD remained increased, but was not statistically significant. Conclusion: The presence of COPD in HF patients is associated with an increased burden of comorbidities, lower use of HF therapies, and a trend toward worse outcomes. These findings provide a starting point for prospective investigations of the treatment of HF comorbidities to reduce the high postdischarge event rates. CI Cardiac Fail 2012;18:515-523)
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| 10. |
- Sarma, S., et al.
(författare)
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Association between diabetes mellitus and post-discharge outcomes in patients hospitalized with heart failure: findings from the EVEREST trial
- 2013
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 15:2, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We evaluated the impact of diabetes mellitus (DM) and diabetic therapy on outcomes in patients with reduced ejection fraction (EF) after hospitalization for heart failure (HF). DM is prevalent in patients hospitalized with HF, yet inconclusive data exist on the post-discharge outcomes of this patient population. METHODS AND RESULTS: Post-hoc analysis was performed on the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) study, a randomized trial of patients hospitalized with HF (n = 4133) with median follow-up of 9.9 months. DM status was determined from intake questionnaires and cross-verified by medication history. Univariate relationships were examined using chi(2) test, t-test, and Wilcoxon tests. The two primary outcomes of (i) all-cause mortality (ACM) and (ii) cardiovascular mortality or HF hospitalization (CVM + HFH) were assessed for those with and without DM and by diabetic treatment strategy using log rank tests and multivariable Cox regression models. DM was present in 40% of participants. Patients with DM were more likely to have hypertension, coronary artery disease, and chronic kidney disease. Diabetes was associated with ACM and CVM + HFH (both P < 0.001). Following multivariate risk adjustment, DM was associated with ACM, but this estimate was imprecise [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.00-1.34] and remained associated with CVM or HFH (HR 1.17; 95% CI 1.04-1.31). Diabetic control strategy did not independently affect outcomes. CONCLUSION: Diabetes is common in patients hospitalized for heart failure with a reduced EF. These patients have a higher post-discharge CVM and higher HF hospitalizations compared with patients with no diabetes. Different diabetic treatment regimens did not appear to influence post-discharge outcomes.
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