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- Abdul-Rahim, A. H., et al.
(author)
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Risk of stroke in chronic heart failure patients with preserved ejection fraction, but without atrial fibrillation: analysis of the CHARM-Preserved and I-Preserve trials
- 2017
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:10, s. 742-750
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Journal article (peer-reviewed)abstract
- Aims The incidence and predictors of stroke in patients with heart failure and preserved ejection fraction (HF-PEF), but without atrial fibrillation (AF), are unknown. We described the incidence of stroke in HF-PEF patients with and without AF and predictors of stroke in those without AF. Methods and results We pooled data from the CHARM-Preserved and I-Preserve trials. Using Cox regression, we derived a model for stroke in patients without AF in this cohort and compared its performance with a published model in heart failure patients with reduced ejection fraction (HF-REF)-predictive variables: age, body mass index, New York Heart Association class, history of stroke, and insulin-treated diabetes. The two stroke models were compared and Kaplan-Meier curves for stroke estimated. The risk model was validated in a third HF-PEF trial. Of the 6701 patients, 4676 did not have AF. Stroke occurred in 124 (6.1%) with AF and in 171 (3.7%) without AF (rates 1.80 and 1.00 per 100 patient-years, respectively). There was no difference in performance of the stroke model derived in the HF-PEF cohort and the published HF-REF model (c-index 0.71, 95% confidence interval 0.57-0.84 vs. 0.73, 0.59-0.85, respectively) as the predictive variables overlapped. The model performed well in the validation cohort (0.86, 0.62-0.99). The rate of stroke in patients in the upper third of risk approximated to that in patients with AF (1.60 and 1.80 per 100 patient-years, respectively). Conclusions A small number of clinical variables identify a subset of patients with HF-PEF, but without AF, at elevated risk of stroke.
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- Ambrosy, A. P., et al.
(author)
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Changes in Dyspnea Status During Hospitalization and Postdischarge Health-Related Quality of Life in Patients Hospitalized for Heart Failure: Findings From the EVEREST Trial
- 2016
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In: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 9:5
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Journal article (peer-reviewed)abstract
- Background-Dyspnea is the most common symptom among hospitalized patients with heart failure and represents a therapeutic target. However, the association between short-term dyspnea relief and postdischarge clinical outcomes and health-related quality of life (HRQOL) remains uncertain. Methods and Results-A post hoc analysis was performed of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which enrolled 4133 patients within 48 hours of admission for heart failure with an ejection fraction <= 40%. Physician-assessed dyspnea was recorded on a daily basis from baseline until discharge or day 7 as none, seldom, frequent, or continuous. Patient-reported dyspnea was measured using a 7-point Likert scale, and patients experiencing moderate or marked dyspnea improvement on day 1 were classified as early responders. The Kansas City Cardiomyopathy Questionnaire summary score, which ranges from 0 to 100, was collected postdischarge at week 1. The primary outcome was unfavorable HRQOL, defined a priori as a Kansas City Cardiomyopathy Questionnaire score <45. Secondary outcomes included 30-day all-cause mortality, and all-cause and cause-specific hospitalizations. The final analytic cohort included 1567 patients discharged alive with complete HRQOL data. Patients were 66.0 +/- 12.7 years old and had a mean ejection fraction of 25 +/- 8%. Physician-assessed dyspnea was rated as frequent or continuous in 1399 patients (90%) at baseline, which decreased to 250 patients (16%) by discharge, whereas patient-reported early dyspnea relief was reported by 610 patients (40%). The median Kansas City Cardiomyopathy Questionnaire score at week 1 was 50 (35, 65). All-cause mortality was 3.0%, and all-cause hospitalization was 20.5% within 30 days of discharge. Physician-assessed and patient-reported dyspnea was not independently associated with HRQOL, all-cause mortality, or all-cause or cause-specific hospitalization. Conclusions-In-hospital physician-assessed, and patient-reported dyspnea was not independently associated with postdischarge HRQOL, survival, or readmissions. Although dyspnea relief remains a goal of therapy for hospitalized patients with heart failure with reduced ejection fraction, this measure may not be a reliable surrogate for long-term patient-centered or hard clinical outcomes.
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- Badar, A. A., et al.
(author)
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Clinical characteristics and outcomes of patients with angina and heart failure in the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) Programme
- 2015
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:2, s. 196-204
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Journal article (peer-reviewed)abstract
- AimsTo investigate the relationship between angina pectoris and fatal and non-fatal clinical outcomes in heart failure with reduced and preserved ejection fraction (HF-REF and HF-PEF, respectively). Methods and resultsOf 7599 patients in the CHARM program, 5408 had ischaemic heart disease; 3855 had HF-REF (ejection fraction 45%) and 1553 had HF-PEF. These patients were separated into three groups: no history of angina, previous angina, and current angina. Three coronary outcomes were examined: fatal or non-fatal myocardial infarction (MI); MI or hospitalization for unstable angina (UA); and MI, UA or coronary revascularization. The composite heart failure outcome of cardiovascular death or heart failure hospitalization (HFH) was also analysed, along with its components and all-cause mortality. New York Heart Association functional class was worse in both HF-REF and HF-PEF patients with current angina compared with patients without angina (P<0.001 and P=0.005 respectively), despite similar clinical examination findings and ejection fraction. Patients with current angina had a higher risk of all three coronary outcomes (adjusted hazard ratios ranging from 1.8-3.1) than those without angina but did not have a higher risk of heart failure outcomes or all-cause mortality. ConclusionIn patients with heart failure current angina is associated with significantly more functional limitation and a higher risk of coronary events, across the spectrum of left ventricular ejection fraction.
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- Balmforth, C., et al.
(author)
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Outcomes and Effect of Treatment According to Etiology in HFrEF An Analysis of PARADIGM-HF
- 2019
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In: Jacc-Heart Failure. - : Elsevier BV. - 2213-1779. ; 7:6, s. 457-465
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Journal article (peer-reviewed)abstract
- OBJECTIVES The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor (ARNI) with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial. BACKGROUND Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy. METHODS We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide. RESULTS Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum-related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11). CONCLUSIONS Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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- Bello, Natalie A, et al.
(author)
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Increased risk of stroke with darbepoetin alfa in anaemic heart failure patients with diabetes and chronic kidney disease.
- 2015
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In: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 17:11, s. 1201-1207
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Journal article (peer-reviewed)abstract
- The use of an erythropoesis-stimulating agent, darbepoetin alfa (DA), to treat anaemia in patients with diabetes mellitus and chronic kidney disease was associated with a heightened risk of stroke and neutral efficacy in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), despite epidemiological data suggesting the contrary. However, this association has not been evaluated in another randomized, placebo-controlled trial.
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- Bhatt, A. S., et al.
(author)
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Achieving a Maximally Tolerated beta-Blocker Dose in Heart Failure Patients Is There Room for Improvement?
- 2017
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:20, s. 2542-2550
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Journal article (peer-reviewed)abstract
- Heart failure (HF) is associated with significant morbidity and mortality. Although initially thought to be harmful in HF, beta-adrenergic blockers (beta-blockers) have consistently been shown to reduce mortality and HF hospitalization in chronic HF with reduced ejection fraction. Proposed mechanisms include neurohormonal blockade and heart rate reduction. A new therapeutic agent now exists to target further heart rate lowering in patients who have been stable on a "maximally tolerated b-blocker dose," but this definition and how to achieve it are incompletely understood. In this review, the authors summarize published reports on the mechanisms by which beta-blockers improve clinical outcomes. The authors describe differences in doses achieved in landmark clinical trials and those observed in routine clinical practice. They further discuss reasons for intolerance and the evidence behind using b-blocker dose and heart rate as therapeutic targets. Finally, the authors offer recommendations for clinicians actively initiating and up-titrating b-blockers that may aid in achieving maximally tolerated doses. (C) 2017 by the American College of Cardiology Foundation.
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- Bilchick, K. C., et al.
(author)
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Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators
- 2017
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:21, s. 2606-2618
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Journal article (peer-reviewed)abstract
- BACKGROUND Recent clinical trials highlight the need for better models to identify patients at higher risk of sudden death. OBJECTIVES The authors hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of sudden death, including death from ventricular arrhythmias, would predict the survival benefit with an implantable cardioverter-defibrillator (ICD). METHODS Patients with primary prevention ICDs from the National Cardiovascular Data Registry (NCDR) were compared with control patients with heart failure (HF) without ICDs with respect to 5-year survival using multivariable Cox proportional hazards regression. RESULTS Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p < 0.0001). The ICD-SPRM interaction was significant (p < 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality <= 5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p < 0.0001). CONCLUSIONS The SHFM predicted all-cause mortality in a large cohort with and without ICDs, and the SPRM discriminated and calibrated the potential ICD benefit. Together, the models identified patients less likely to derive a survival benefit from primary prevention ICDs. (J Am Coll Cardiol 2017;69:2606-18) (C) 2017 by the American College of Cardiology Foundation.
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- Bocchi, E. A., et al.
(author)
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Effect of Combining Ivabradine and beta-Blockers: Focus on the Use of Carvedilol in the SHIFT Population
- 2015
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In: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 131:4, s. 218-224
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Journal article (peer-reviewed)abstract
- Objectives: We explored the prescription of beta-blockers with ivabradine in patients with systolic heart failure, focusing on the most frequently coprescribed beta-blocker, carvedilol. Methods: We analyzed outcomes in SHIFT patients with systolic heart failure who were prescribed beta-blockers (carvedilol, bisoprolol, metoprolol, or nebivolol) with ivabradine or placebo. Analysis was by intention to treat in patients prescribed a beta-blocker at the time of the event. Results: Data were available for 2,596 patients receiving carvedilol, 1,483 bisoprolol, 1,424 metoprolol, and 197 nebivolol. Mean treatment duration was 19 months. There was no difference in the effect of ivabradine on the primary composite endpoint of cardiovascular death or heart failure hospitalization between the various beta-blockers [hazard ratios (HR) for risk reduction, 0.75-0.89; p for interaction = 0.86]. Patients prescribed carvedilol with ivabradine had lower rates of primary composite endpoint (HR 0.80, 95% CI: 0.68-0.94), heart failure hospitalization (HR 0.73, 95% CI: 0.61-0.88), and cardiovascular hospitalization (HR 0.80, 95% CI: 0.69-0.92) versus carvedilol with placebo. The dosage of carvedilol had no detectable effect and there were no unexpected safety issues. Conclusions: Whatever beta-blocker was coprescribed with ivabradine, there were improvements in cardiovascular outcomes in patients with systolic heart failure, especially with the most prescribed beta-blocker - carvedilol. (C) 2015 S. Karger AG, Basel
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