Publications by authors named "Kjekshus J"
Importance: Sequencing studies have identified causal genetic variants for distinct subtypes of heart failure (HF) such as hypertrophic or dilated cardiomyopathy. However, the role of rare, high-impact variants in HF, for which ischemic heart disease is the leading cause, has not been systematically investigated.
Objective: To assess the contribution of rare variants to all-cause HF with and without reduced left ventricular ejection fraction.
Background: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy.
Objectives: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR).
Methods: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed.
Objective: To assess the relationship between heart rate (HR), pulse pressure (PP), and their association with mortality in a population of high-risk patients following acute myocardial infarction (MI).
Methods: We performed an analysis in 22,398 patients included in "The High-Risk Myocardial Infarction Database Initiative", a database of clinical trials evaluating pharmacologic interventions in patients with MI complicated by signs of heart failure (HF) or left ventricular dysfunction. We found an interaction between HR and PP.
Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes.
Methods And Results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF.
Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials.
Methods And Results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.
Background: Heart rate has been reported to be associated with adverse outcome in heart failure (HF) and myocardial infarction (MI), but conflicting evidence exists regarding its impact in patients with associated atrial fibrillation (AF).
Objectives: We investigated the differential impact of heart rate on clinical outcomes according to the presence or absence of AF in patients with reduced systolic function and/or HF after MI.
Methods: We studied the association of heart rate with outcome using Cox-models in a merged dataset (n=28,771) of four randomized trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT).
Background: The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail.
Methods: We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014.
Aims: To examine the impact of diabetes mellitus on long-term clinical outcomes in patients with myocardial infarction (MI) complicated by clinical signs of heart failure (HF) or left ventricular dysfunction (LVD).
Methods And Results: The High-Risk MI Database consists of individual data from 28 771 patients and was created by merging four large recent randomized clinical trials (VALIANT, EPHESUS, OPTIMAAL, and CAPRICORN) that each examined the impact of pharmacological interventions following MI in patients with evidence of HF or LVD. The mean age of patients was 65 years, 70% were male, and almost 94% Caucasian.
Background: The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF).
Objectives: This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo.
Methods: The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials.
Objectives: This study sought to evaluate whether a panel of biomarkers improved prognostication in patients with heart failure (HF) and reduced ejection fraction of ischemic origin using a systematized approach according to suggested requirements for validation of new biomarkers.
Background: Modeling combinations of multiple circulating markers could potentially identify patients with HF at particularly high risk and aid in the selection of individualized therapy.
Methods: From a panel of 20 inflammatory and extracellular matrix biomarkers, 2 different biomarker panels were created and added to the Seattle HF score and the prognostic model from the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study (n = 1,497), which included conventional clinical characteristics and C-reactive protein and N-terminal pro-B-type natriuretic peptide.
Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE).
Methods: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE.
Context And Objective: To evaluate if YKL-40 can provide prognostic information in patients with ischemic heart failure (HF) and identify patients who may benefit from statin therapy.
Materials And Methods: The association between serum YKL-40 and predefined outcome was evaluated in 1344 HF patients assigned to rosuvastatin or placebo.
Results: YKL-40 was not associated with outcome in adjusted analysis.
Aim: We aimed to study the relationships of loop diuretic dose with renal function and clinical outcomes in patients with chronic heart failure (HF).
Methods And Results: Loop diuretic dose at baseline was recorded in patients included in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). The relationship to change in estimated glomerular filtration rate (eGFR) over time and to the first occurrence of the composite outcome of cardiovascular (CV) death or hospitalization owing to HF was examined in propensity score matched cohorts.
Background: We have previously demonstrated an association between increased sFRP3 expression and adverse outcome in a population of HF irrespective of cause and left ventricular ejection fraction. In this study we evaluated the prognostic value of sFRP3 in older patients with chronic systolic HF of ischemic origin.
Methods: We evaluated sFRP3, by tertiles, as a risk factor for the primary endpoint (cardiovascular [CV] mortality, nonfatal myocardial infarction, nonfatal stroke), all-cause mortality, CV mortality, death from worsening HF (WHF), any coronary event, including sudden death, as well as hospitalizations for CV causes and WHF in 1444 patients from the CORONA population, randomly assigned to 10 mg rosuvastatin or placebo.
Background: Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF).
Methods And Results: We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF.
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponins (cTns) measured with sensitive assays provide strong prognostic information in patients with stable coronary artery disease. However, the relationship between these biomarkers and myocardial contractile function, as well as infarct size, in this patient group, remains to be defined. The study population consisted of 160 patients referred to a follow-up echocardiography scheduled 1 year after coronary revascularization.
View Article and Find Full Text PDFAims: To investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure (HF).
Methods And Results: We studied 5011 patients with HF and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for death were estimated for 0-30 days and ≥31 days after first post-randomization WHF, MI, or stroke used as a time-dependent variable, compared with patients with none of these events.
Objectives: Reduced arterial vasodilatatory capacity is a marker of coronary heart disease. The aim was to investigate if the difference between the vasodilatory response before and after exercise, as assessed by non-invasive methodology, is related to endothelial and inflammatory biomarkers.
Design: Post-ischemic hyperemia after 5 min of arterial occlusion was examined before and after a bicycle test with strain-gauge plethysmography (measuring peak reactive hyperemia in the forearm) and peripheral arterial tonometry (PAT hyperemia ratio: measuring pulse waves in the index finger relative to the contra-lateral index finger) in 30 healthy males.
Aims: Current guidelines do not explicitly recommend statin use in heart failure (HF). Relatively low numbers of atherothrombotic events among HF patients, in the context of their elevated competing risks for non-atherothrombotic causes of death, may have prevented previous analyses of clinical trials from detecting a benefit for statins. We pooled data from two landmark trials of HF patients not on statin therapy randomized to rosuvastatin 10 mg daily vs.
View Article and Find Full Text PDFAims: Leucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth.
Methods And Results: We measured leucocyte telomere length in 3275 patients with chronic ischaemic systolic heart failure participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) study.
Background: Recent genome-wide association studies have identified multiple loci that are associated with an increased risk of developing coronary artery disease (CAD). The impact of these loci on the disease severity and prognosis of ischemic heart failure due to CAD is currently unknown.
Methods: We undertook association analysis of 7 single nucleotide polymorphism (rs599839, rs17465637, rs2972147, rs6922269, rs1333049, rs501120, and rs17228212) at 7 well established CAD risk loci (1p13.
Background: The extracellular matrix (ECM) plays an important role in left ventricular remodeling and progression of heart failure (HF). Biglycan and mimecan are ECM proteins that are abundantly expressed in cardiac tissue but have not been evaluated as prognostic markers in HF. We investigated their interaction with statin treatment and association with adverse outcome in chronic HF.
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