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1.	Agarwal, Anubha, et al. (författare) Toward a Universal Definition of Etiologies in Heart Failure : Categorizing Causes and Advancing Registry Science 2024 Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 17:4 Forskningsöversikt (refereegranskat)abstract Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.
2.	Alehagen, Urban, et al. (författare) Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50% 2015 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS and WILKINS. - 1941-3289 .- 1941-3297. ; 8:5, s. 862-870 Tidskriftsartikel (refereegranskat)abstract Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.
3.	Alehagen, Urban, et al. (författare) Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry 2015 Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 8:2, s. 252-260 Tidskriftsartikel (refereegranskat)abstract Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.
4.	Ambrosy, A. P., et al. (författare) 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 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 9:5 Tidskriftsartikel (refereegranskat)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.
5.	Andersen, Kasper, 1974-, et al. (författare) Dose–Response Relationship of Total and Leisure Time Physical Activity to Risk of Heart Failure : a prospective cohort study 2014 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 7:5, s. 701-708 Tidskriftsartikel (refereegranskat)abstract Background—The nature of the association between levels of physical activity and risk of heart failure is little known. We investigated nonlinear associations of total and leisure time physical activity with risk of heart failure.Methods and Results—In 1997, 39 805 persons without heart failure completed a questionnaire of lifestyle factors and medical history. We used Cox regression models to investigate total (adjusting for education and previous myocardial infarction) and direct (multivariable-adjusted) effects of self-reported total and leisure time physical activity on risk of heart failure of any cause and heart failure of nonischemic origin. Heart failure diagnoses were obtained until December 31, 2010. Higher leisure time physical activity was associated with lower risk of heart failure of any cause; hazard ratio of the total effect of leisure time physical activity was for fifth versus first quintile 0.54; 95% confidence interval was 0.44 to 0.66. The direct effect was similar. High total daily physical activity level was associated with lower risk of heart failure, although the effect was less pronounced than for leisure time physical activity (total effect hazard ratio, 0.81; 95% confidence interval, 0.69–0.95; fifth versus first quintile). A similar direct effect observed.Conclusions—Leisure time physical activity was inversely related to risk of developing heart failure in a dose–response fashion. This was reflected in a similar but less pronounced association of total physical activity with risk of heart failure. Only part of the effects appeared to be mediated by traditional risk factors.
6.	Bello, N. A., et al. (författare) Influence of Previous Heart Failure Hospitalization on Cardiovascular Events in Patients With Reduced and Preserved Ejection Fraction 2014 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 7:4, s. 590-595 Tidskriftsartikel (refereegranskat)abstract Background-Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between previous HF hospitalization and randomization in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) trials on clinical outcomes in patients with both reduced and preserved ejection fraction. Methods and Results-CHARM enrolled 7599 patients with New York Heart Association class II to IV HF, of whom 5426 had a history of previous HF hospitalization. Cox proportional hazards regression models were used to assess the association between time from previous HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF during a median of 36.6 months. For patients with HF and reduced or preserved ejection fraction, rates of cardiovascular mortality and HF hospitalization were higher among patients with previous HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for patients with HF and reduced ejection fraction within each category. Event rates for those with HF with preserved ejection fraction and a HF hospitalization in the 6 months before randomization were comparable with the rate in patients with HF and reduced ejection fraction with no previous HF hospitalization. Conclusions-Rates of cardiovascular death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high-risk population for future clinical trials in HF and reduced ejection fraction and HF with preserved ejection fraction.
7.	Bello, N. A., et al. (författare) Influence of Prior Heart Failure Hospitalization on Cardiovascular Events in Patients with Reduced and Preserved Ejection Fraction 2014 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 7, s. 590-595 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: -Hospitalization for acute heart failure (HF) is associated with high rates of subsequent mortality and readmission. We assessed the influence of the time interval between prior HF hospitalization and randomization in the CHARM trials on clinical outcomes in patients with both reduced and preserved ejection fraction. METHODS AND RESULTS: -CHARM enrolled 7,599 patients with NYHA class II-IV heart failure, of whom 5,426 had a history of prior HF hospitalization. Cox proportional hazards regression models were utilized to assess the association between time from prior HF hospitalization and randomization and the primary outcome of cardiovascular death or unplanned admission to hospital for the management of worsening HF over a median of 36.6 months. For patients with HF and reduced (HFrEF) or preserved (HFpEF) ejection fraction, rates of CV mortality and HF hospitalization were higher among patients with prior HF hospitalization than those without. The risk for mortality and hospitalization varied inversely with the time interval between hospitalization and randomization. Rates were higher for HFrEF patients within each category. Event rates for those with HFpEF and a HF hospitalization in the 6 months prior to randomization were comparable to the rate in HFrEF patients with no prior HF hospitalization. CONCLUSIONS: -Rates of CV death or HF hospitalization are greatest in those who have been previously hospitalized for HF. Independent of EF, rates of death and readmission decline as time from HF hospitalization to trial enrollment increased. Recent HF hospitalization identifies a high risk population for future clinical trials in HFrEF and HFpEF. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00634400.
8.	Das, D., et al. (författare) Ivabradine in Heart Failure: The Representativeness of SHIFT (Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial) in a Broad Population of Patients With Chronic Heart Failure 2017 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 10:9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry. METHODS AND RESULTS: We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction <40%, New York Heart Association class II-IV, sinus rhythm, and heart rate >/=70 beats per minute) and non-SHIFT type. Baseline characteristics and medication use were compared and change in eligibility over time was reported at 6 months and 1 year in a subset of patients. Overall, 14.2% (n=3741) of patients were SHIFT type. These patients were more likely to be younger, men, have diabetes mellitus, ischemic heart disease, lower left ventricular ejection fraction, and more recent onset HF (<6 months; all, P<0.001). Although 88.9% of SHIFT type and 88.5% of non-SHIFT type (P=0.421) were receiving selected beta-blockers, only 58.8% and 67.3% (P<0.001) were on >50% of target dose. From those patients who had repeated visits within 6 months (n=5420) and 1 year (n=6840), respectively, 10.2% (n=555) and 10.6% (n=724) of SHIFT-type patients became ineligible, 77.3% (n=4188) and 77.3% (n=5287) remained ineligible, and 4.6% (n=252) and 4.9% (n=335) of non-SHIFT-type patients became eligible for initiation of ivabradine. CONCLUSIONS: From the Swedish Heart Failure Registry, 14.2% of patients with HF were eligible for ivabradine. These patients more commonly were not receiving target beta-blocker dose. Over time, a minority of patients became ineligible and an even smaller minority became eligible.
9.	Desai, A. S., et al. (författare) Factors Associated With Noncompletion During the Run-In Period Before Randomization and Influence on the Estimated Benefit of LCZ696 in the PARADIGM-HF Trial 2016 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 9:6 Tidskriftsartikel (refereegranskat)abstract Background-The 8442 patients randomized in the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, in which sacubitril/valsartan (LCZ696) reduced both death and HF hospitalization more than enalapril, were a subset of 10 521 patients entering sequential, single-blind run-in periods (enalapril 10 mg twice daily for 2 weeks followed by LCZ696 200 mg twice daily for 4 to 6 weeks) to ensure short-term tolerability of the 2 study medications. We identified the predictors of run-in noncompletion and estimated the implications of noncompletion for the overall study result. Methods and Results-Patient factors associated with run-in noncompletion were defined in multivariable logistic regression models. The effectiveness of LCZ696 in a broader cohort approximating the full run-in population was estimated by weighting randomized patients according to the inverse probability of run-in completion; 2079 (19.8%) subjects discontinued the study during the run-in period, including 1102 (10.5%) during the enalapril phase and 977 (9.3%) during the LCZ696 phase. In multivariable models, lower systolic blood pressure, lower estimated glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide, and ischemic cause of heart failure were associated with higher risk for run-in noncompletion. Repeat analysis of the effect of randomized treatment giving greater weight to randomized patients resembling those who did not complete the run-in did not alter the hazard ratio favoring LCZ696 over enalapril for the primary end point of cardiovascular death or heart failure hospitalization, or the additional key end points of cardiovascular death and all-cause mortality. Conclusions-Patients with lower blood pressure, lower glomerular filtration rate, and more severe heart failure were at higher risk for noncompletion during the run-in period of PARADIGM-HF. Weighted analysis of key study outcomes accounting for the effect of run-in noncompletion did not alter the benefit of LCZ696 over enalapril.
10.	Dorans, Kirsten S., et al. (författare) Alcohol and Incident Heart Failure Among Middle-Aged and Elderly Men Cohort of Swedish Men 2015 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 8:3, s. 422-427 Tidskriftsartikel (refereegranskat)abstract Background Compared with no alcohol consumption, heavy alcohol intake is associated with a higher rate of heart failure (HF) whereas light-to-moderate intake may be associated with a lower rate. However, several prior studies did not exclude former drinkers, who may have changed alcohol consumption in response to diagnosis. This study aimed to investigate the association between alcohol intake and incident HF. Methods and Results We conducted a prospective cohort study of 33 760 men aged 45 to 79 years with no HF, diabetes mellitus, or myocardial infarction at baseline participating in the Cohort of Swedish Men Study. We excluded former drinkers. At baseline, participants completed a food frequency questionnaire and reported other characteristics. HF was defined as hospitalization for or death from HF, ascertained by Swedish inpatient and cause-of-death records from January 1, 1998, through December 31, 2011. We constructed Cox proportional hazards models to estimate multivariable-adjusted incidence rate ratios. During follow-up, 2916 men were hospitalized for (n=2139) or died (n=777) of incident HF. There was a U-shaped relationship between total alcohol intake and incident HF (P=0.0004). There was a nadir at light-to-moderate alcohol intake: consuming 7 to <14 standard drinks per week was associated with a 19% lower multivariable-adjusted rate of HF compared with never drinking (incidence rate ratio, 0.81; 95% confidence interval, 0.69-0.96). Conclusions In this cohort of Swedish men, there was a U-shaped relationship between alcohol consumption and HF incidence, with a nadir at light-to-moderate intake. Heavy intake did not seem protective.
11.	Eapen, Z. J., et al. (författare) Do Countries or Hospitals With Longer Hospital Stays for Acute Heart Failure Have Lower Readmission Rates?: Findings From ASCEND-HF 2013 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. 727-32 Tidskriftsartikel (refereegranskat)abstract Background- Hospital readmission is an important clinical outcome of patients with heart failure. Its relation to length of stay for the initial hospitalization is not clear. Methods and Results- We used hierarchical modeling of data from a clinical trial to examine variations in length of stay across countries and across hospitals in the United States and its association with readmission within 30 days of randomization. Main outcomes included associations between country-level length of stay and readmission rates, after adjustment for patient-level case mix; and associations between length of stay and readmission rates across sites in the United States. Across 27 countries with 389 sites and 6848 patients, mean length of stay ranged from 4.9 to 14.6 days (6.1 days in the United States). Rates of all-cause readmission ranged from 2.5% to 25.0% (17.8% in the United States). There was an inverse correlation between country-level mean length of stay and readmission (r=-0.52; P<0.01). After multivariable adjustment, each additional inpatient day across countries was associated with significantly lower risk of all-cause readmission (odds ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.02) and heart failure readmission (odds ratio, 0.79; 95% confidence interval, 0.69-0.99; P=0.03). Similar trends were observed across US study sites concerning readmission for any cause (odds ratio, 0.92; 95% confidence interval, 0.85-1.00; P=0.06) and readmission for heart failure (odds ratio, 0.90; 95% confidence interval, 0.80-1.01; P=0.07). Across countries and across US sites, longer median length of stay was independently associated with lower risk of readmission. Conclusions- Countries with longer length of stay for heart failure hospitalizations had significantly lower rates of readmission within 30 days of randomization. These findings may have implications for developing strategies to prevent readmission, defining quality measures, and designing clinical trials in acute heart failure. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852.
12.	Ferreira, J. P., et al. (författare) Impact of Insulin Treatment on the Effect of Eplerenone: Insights From the EMPHASIS-HF Trial 2021 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 14:6 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). METHODS: The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. RESULTS: The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulintreated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.500.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3-4) in patients with insulin-treated diabetes, 16 (13-19) in patients with diabetes not receiving insulin, and 26 (24-28) in patients without diabetes. CONCLUSIONS: Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes.
13.	Gravning, J., et al. (författare) Prognostic Effect of High-Sensitive Troponin T Assessment in Elderly Patients With Chronic Heart Failure Results From the CORONA Trial 2014 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 7:1, s. 96-103 Tidskriftsartikel (refereegranskat)abstract Background The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study. Methods and Results Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality. Conclusions Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
14.	Kalantarian, Shadi, et al. (författare) Long-Term Electrocardiographic and Echocardiographic Progression of Arrhythmogenic Right Ventricular Cardiomyopathy and Their Correlation With Ventricular Tachyarrhythmias. 2021 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 14:9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Prior studies of structural and electrocardiographic changes in arrhythmogenic right ventricular (RV) cardiomyopathy and their role in predicting ventricular arrhythmias (ventricular tachycardia) have shown conflicting results.METHODS: We reviewed 405 ECGs, 315 transthoracic echocardiographies, and 441 implantable cardioverter defibrillator interrogations in 64 arrhythmogenic RV cardiomyopathy patients (56% men, mean age [SD], 44.2 [14.6] years) over a mean follow-up of 10 (range, 2.3-19) years. Generalized estimating equations were used to identify the association between ECG abnormalities, clinical variables, and transthoracic echocardiographic measurements (>mild degree of tricuspid regurgitation, RV outflow tract diameter in parasternal long axis and short axis, RV end-diastolic area, fractional area change).RESULTS: There was a 4.65 (95% CI, 0.51%-8.8%) increase in RV end-diastolic area, a 3.75 (95% CI, 1.17%-6.34%) decrease in fractional area change, and 1.9 (95% CI, 1.3-2.8) higher odds (odds ratio) of RV wall motion abnormality with every 5-year increase in age after patients' first transthoracic echocardiography. >Mild tricuspid regurgitation was an independent predictor of RV enlargement and dysfunction (hazard ratio of >10% drop in fractional area change from baseline [95% CI], 3.51 [1.77-6.95] and hazard ratio of >10% increase in RV end-diastolic area from baseline [95% CI], 4.90 [2.52-9.52]). Patients with implantable cardioverter defibrillator were more likely to develop >mild tricuspid regurgitation and larger structural and functional disease progression. More pronounced increase in RV end-diastolic area was translated into higher rates of any ventricular tachycardia. Inferior T-wave inversions and sum of R waves (mm) in V1 to V3 were predictors of RV enlargement and dysfunction with the former also predicting risk of any ventricular tachycardia.CONCLUSIONS: Arrhythmogenic RV cardiomyopathy is a progressive disease. Tricuspid regurgitation is an independent predictor of structural disease progression, which may be exacerbated by use of a transvenous implantable cardioverter defibrillator lead.
15.	Kaluza, Joanna, et al. (författare) Processed and Unprocessed Red Meat Consumption and Risk of Heart Failure Prospective Study of Men 2014 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 7:4, s. 552-U27 Tidskriftsartikel (refereegranskat)abstract Background-Epidemiological studies of red meat consumption in relation to risk of heart failure (HF) are scarce. We examined the associations of unprocessed and processed red meat consumption with HF incidence and mortality in men. Methods and Results-The population-based prospective Cohort of Swedish Men included 37 035 men, aged 45 to 79 years, with no history of HF, ischemic heart disease, or cancer at baseline. Meat consumption was assessed with a self-administered questionnaire in 1997. During a mean follow-up of 11.8 years, 2891 incidences and 266 deaths from HF were ascertained. Consumption of processed meat was statistically significant positively associated with risk of HF in both age-and multivariable-adjusted models. Men who consumed > 75 g/d processed meat compared with those who consumed <25 g/d had a 1.28 (95% confidence interval, 1.10-1.48, P trend=0.01) higher risk of HF incidence and 2.43 (95% confidence interval, 1.52-3.88, P trend<0.001) higher risk of HF mortality. The consumption of unprocessed meat was not associated with increased risk of incidence of HF or mortality from HF. Conclusions-Findings from this prospective study of men with low to moderate red meat consumption indicate that processed red meat consumption, but not unprocessed red meat, is associated with an increased risk of HF.
16.	Kristensen, S. L., et al. (författare) Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation 2017 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 10:10 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Patients with heart failure (HF) and atrial fibrillation (AF) have higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) than HF patients without AF. There is uncertainty about the prognostic importance of a given concentration of NT-proBNP in HF patients with and without AF. We investigated this question in a large cohort of patients with HF and reduced ejection fraction. METHODS AND RESULTS: We studied 14 737 patients with HF and reduced ejection fraction and a measurement of NT-proBNP at time of screening, enrolled in either the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) or the ATMOSPHERE trial (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure), of whom 3575 (24%) had AF on their baseline ECG. Median (Q1, Q3) levels of NT-proBNP were 1817 pg/mL (1095-3266 pg/mL) in those with AF and 1271 pg/mL (703-2569 pg/mL) in those without (P<0.0001). Patients with AF were older (67 versus 62 years), had worse New York Heart Association class (III/IV; 36% versus 24%), and experienced fewer previous HF hospitalizations (52% versus 61%) or myocardial infarction (30% versus 46%); all P<0.001. We categorized patients with and without AF into 5 NT-proBNP bands: <400, 400 to 999 (reference), 1000 to 1999, 2000 to 2999, and >/=3000 pg/mL. For the primary composite outcome of cardiovascular death or HF hospitalization, event rates differed for patients with and without AF in the lowest band (<400 pg/mL; 8.2 versus 5.0 per 100 patient-years), but not for the higher bands (400-999 pg/mL, 7.4 versus 7.7 per 100 patient-years; 1000-1999 pg/mL, 9.8 versus 11.4 per 100 patient-year; 2000-2999 pg/mL, 13.5 versus 13.4 per 100 patient-years; >/=3000 pg/mL, 22.7 versus 23.0 per 100 patient-years). These findings were consistent whether NT-proBNP was examined as a categorical or continuous variable and before and after adjustment for other prognostic variables. We found similar results for the components of the composite outcome and all-cause mortality. CONCLUSIONS: HF and reduced ejection fraction patients with AF had higher NT-proBNP than those without AF. However, above a concentration of 400 pg/mL (representing most patients in each group), NT-proBNP had similar predictive value for adverse cardiovascular outcomes, irrespective of AF status. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier NCT00853658 (ATMOSPHERE) and NCT01035255 (PARADIGM-HF).
17.	Krum, H., et al. (författare) Clinical Benefit of Eplerenone in Patients With Mild Symptoms of Systolic Heart Failure Already Receiving Optimal Best Practice Background Drug Therapy: Analysis of the EMPHASIS-HF Study 2013 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. 711-8 Tidskriftsartikel (refereegranskat)abstract Background- In EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), eplerenone significantly reduced major cardiovascular events versus placebo in 2737 patients with mild symptoms of heart failure and an ejection fraction of <35%, in addition to recommended therapy. However, it is not known whether such benefits were preserved in patients receiving optimal background drug therapy, that is, high doses of angiotensin-converting enzyme inhibitor (ACEi, or angiotensin receptor blocker), beta-blocker, or both drug classes. Methods and Results- We further analyzed EMPHASIS-HF according to the use and dose of these BACKGROUND: value for interaction 0.80, 0.15, and 0.53, respectively), as well as for all-cause mortality. There were no major safety issues, except a borderline increased risk of hypotension with eplerenone in those on high-dose ACEi or ACEi/beta-blocker. Conclusions- Eplerenone provides substantial benefit on major events (with an acceptable safety profile) in patients with mild symptoms of systolic heart failure, even in those already receiving high doses of standard background therapies. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.
18.	Lanfear, D. E., et al. (författare) Association of arginine vasopressin levels with outcomes and the effect of V2 blockade in patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial 2013 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:1, s. 47-52 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Arginine vasopressin (AVP) levels are elevated in proportion to heart failure severity and are associated with higher cardiovascular mortality in ambulatory patients. However, the relationship between baseline and trends in AVP with outcomes in patients hospitalized for worsening heart failure with reduced ejection fraction is unclear. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial investigated the effects of tolvaptan in patients with worsening heart failure and ejection fraction
19.	Larsson, Susanna C., et al. (författare) Healthy Lifestyle and Risk of Heart Failure : Results From 2 Prospective Cohort Studies 2016 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 9:4 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The joint impact of multiple healthy lifestyle factors on heart failure (HF) risk is unclear. We investigated the separate and collective associations of healthy lifestyle factors with HF incidence in 2 population-based prospective cohort studies.METHODS AND RESULTS: This study consisted of 33,966 men (Cohort of Swedish Men) and 30,713 women (Swedish Mammography Cohort) who were 45 to 83 years of age and free of HF and ischemic heart disease at baseline. A healthy lifestyle was defined as being a nonsmoker and physically active (≥150 min/wk), and having body mass index between 18.5 and 25 kg/m(2) and a healthy diet (defined as adherence to a modified Mediterranean diet). Incident HF cases were ascertained by linkage with the Swedish National Patient Register and the Swedish Cause of Death Register. Cox proportional hazards regression was used to analyze the data. During 13 years of follow-up, HF was diagnosed in 1488 men and 1096 women. Each healthy lifestyle factor was associated with a statistically significant lower risk of HF in both men and women, and the risk decreased with increasing number of healthy behaviors. The greatest reduction in HF risk was observed for combinations that included nonsmoking. Compared with men and women with none of the healthy lifestyle factors, the multivariable relative risks (95% confidence interval) of HF for those with all 4 healthy behaviors were 0.38 (0.28-0.53) in men and 0.28 (0.19-0.41) in women.CONCLUSIONS: Adhering to a healthy lifestyle is associated with a substantially lower HF risk.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01127698 and NCT01127711.
20.	Lauten, Alexander, et al. (författare) Percutaneous Left-Ventricular Support With the Impella-2.5-Assist Device in Acute Cardiogenic Shock Results of the Impella-EUROSHOCK-Registry 2013 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:1, s. 23-30 Tidskriftsartikel (refereegranskat)abstract Background-Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. Methods and Results-This multicenter registry retrospectively included 120 patients (63.6 +/- 12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8 +/- 5.0 mmol/L to 4.7 +/- 5.4 mmol/L (P=0.28) and 2.5 +/- 2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317 +/- 526 days of follow-up, survival was 28.3%. Conclusions-In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.
21.	Lauten, Alexander, et al. (författare) Response to Letter Regarding Article, "Percutaneous Left-Ventricular Support With the Impella-2.5-Assist Device in Acute Cardiogenic Shock Results of the Impella-EUROSHOCKRegistry" 2013 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:4, s. E56-E56 Tidskriftsartikel (refereegranskat)
22.	Levitan, Emily B., et al. (författare) Adiposity and Incidence of Heart Failure Hospitalization and Mortality A Population-Based Prospective Study 2009 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 2:3, s. 202-208 Tidskriftsartikel (refereegranskat)abstract Background-Obesity is associated with heart failure (HF) incidence. We examined the strength of the association of body mass index (BMI) with HF by age and joint associations of BMI and waist circumference (WC). Methods and Results-Women aged 48 to 83 (n=36 873) and men aged 45 to 79 (n=43 487) self-reported height, weight, and WC. HF hospitalization or death (n=382 women, 718 men) between January 1, 1998, and December 31, 2004, was determined through administrative registers. Hazard ratios, from Cox proportional-hazards models, for an interquartile range higher BMI were 1.39 (95% CI, 1.15 to 1.68) at age 60 and 1.13 (95% CI, 1.02 to 1.27) at 75 in women. In men, hazard ratios were 1.54 (95% CI, 1.37 to 1.73) at 60 and 1.25 (95% CI, 1.16 to 1.35) at 75. A 10-cm higher WC was associated with 15% (95% CI, 2% to 31%) and 18% (95% CI, 4% to 33%) higher HF rates among women with BMI 25 and 30 kg/m(2), respectively; hazard ratios for 1 kg/m(2) higher BMI were 1.00 (95% CI, 0.96 to 1.04) and 1.01 (95% CI, 0.98 to 1.04) for WC 70 and 100 cm, respectively. In men, a 10-cm higher WC was associated with 16% and 18% higher rates for BMI 25 and 30 kg/m(2), respectively; a 1 kg/m(2) higher BMI was associated with 4% higher HF rates regardless of WC. Conclusions-Strength of the association between BMI and HF events declined with age. In women, higher WC was associated with HF at all levels of BMI. Both BMI and WC were predictors among men. (Circ Heart Fail. 2009;2:202-208.)
23.	Levitan, Emily B., et al. (författare) Coffee Consumption and Incidence of Heart Failure in Women 2011 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 4:4, s. 414- Tidskriftsartikel (refereegranskat)abstract Background-Previous studies of the relationship between coffee consumption and incidence of heart failure (HF) have not been consistent, with both potential benefit and potential harm reported. We therefore examined the association between coffee consumption and HF hospitalization or mortality in women. Methods and Results-We conducted a prospective, observational study of 34 551 participants of the Swedish Mammography Cohort who were 48 to 83 years old and did not have HF, diabetes, or myocardial infarction at baseline. Diet was measured using food-frequency questionnaires. Cox models were used to calculate hazard ratios of HF hospitalization or death from HF as the primary cause, as determined through the Swedish inpatient and cause-of-death registers between January 1, 1998, and December 31, 2006. Over 9 years of follow-up, 602 HF events occurred. Women who consumed >= 5 cups of coffee per day did not have higher rates of HF events than those who consumed <5 cups per day (multivariable-adjusted hazard ratio, 0.93; 95% confidence interval, 0.72 to 1.20). Compared with women who consumed <= 1 cup of coffee per day, hazard ratios were 1.01, 0.82, 0.94, and 0.87 for women who consumed 2, 3, 4, and >= 5 cups per day, respectively (P for trend =0.23). Further adjustment for self-reported hypertension did not change the results. Conclusions-In this population of middle-aged and older women, we did not find an association between coffee consumption and incidence of HF events. (Circ Heart Fail. 2011; 4: 414-418.)
24.	Lewis, Eldrin F., et al. (författare) Health-Related Quality of Life Outcomes in PARADIGM-HF 2017 Ingår i: Circulation: Heart Failure. - 1941-3289 .- 1941-3297. ; 10 Tidskriftsartikel (refereegranskat)abstract © 2017 American Heart Association, Inc. Background Patients with heart failure and reduced ejection fraction have impaired health-related quality of life (HRQL) with variable responses to therapies that target mortality and heart failure hospitalizations. In PARADIGM-HF trial (Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] With ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure), sacubitril/valsartan reduced morbidity and mortality compared with enalapril. Another major treatment goal is to improve HRQL. Given improvements in mortality with sacubitril/valsartan, this analysis provides comprehensive assessment of impact of therapy on HRQL in survivors only. Methods and Results Patients (after run-in phase) completed disease-specific HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) at randomization, 4 month, 8 month, and annual visits. Changes in KCCQ scores were calculated using repeated measures analysis of covariance model that adjusted for treatment and baseline values (principal efficacy prespecified at 8 months). Among the 8399 patients enrolled in PARADIGM-HF, 7623 (91%) completed KCCQ scores at randomization with complete data at 8 months for 6881 patients (90% of baseline). At 8 months, sacubitril/valsartan group noted improvements in both KCCQ clinical summary score (+0.64 versus -0.29; P=0.008) and KCCQ overall summary score (+1.13 versus -0.14; P < 0.001) in comparison to enalapril group and significantly less proportion of patients with deterioration (≥5 points decrease) of both KCCQ scores (27% versus 31%; P=0.01). Adjusted change scores demonstrated consistent improvements in sacubitril/valsartan compared with enalapril through 36 months. Conclusions Change scores in KCCQ clinical summary scores and KCCQ overall summary scores were better in patients treated with sacubitril/valsartan compared with those treated with enalapril, with consistency in most domains, and persist during follow-up beyond 8 months. These findings demonstrate that sacubitril/valsartan leads to better HRQL in surviving patients with heart failure. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.
25.	Li, S. J., et al. (författare) Prognostic Significance of Resting Heart Rate and Use of beta-Blockers in Atrial Fibrillation and Sinus Rhythm in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Swedish Heart Failure Registry 2015 Ingår i: Circulation. Heart failure. - : LIPPINCOTT WILLIAMS and WILKINS. - 1941-3289 .- 1941-3297. ; 8:5, s. 871-9 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In heart failure and reduced ejection fraction, the prognostic role of heart rate (HR) in atrial fibrillation (AF) is unknown and the effectiveness of beta-blockers has recently been questioned in AF. METHODS AND RESULTS: A total of 18 858 patients with heart failure and reduced ejection fraction registered with Swedish Heart Failure Registry were included in this study: patients with sinus rhythm (SR; n=11 466) and patients with AF (n=7392). The outcome measure was all-cause mortality. Compared with HR 100 beats per minute. However, in AF, the hazard ratio increased only for HR >100 beats per minute (1.30; P=0.001). beta-blocker use was associated with reduced mortality in SR (hazard ratio, 0.77; P=0.011) and in AF (hazard ratio, 0.71; P<0.001). For beta-blocker use in SR, the hazard ratio gradually increased with HR increment, whereas in AF, the hazard ratio significantly increased only for HR >100 beats per minute (1.29; P=0.003) compared with HR 100 beats per minute. beta-blocker use was associated with reduced mortality both in SR and in AF.
26.	Liem, David A, et al. (författare) Molecular- and organelle-based predictive paradigm underlying recovery by left ventricular assist device support 2014 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 7:2, s. 359-366 Tidskriftsartikel (refereegranskat)
27.	Lim, Shir Lynn, et al. (författare) Association Between Use of Long-Acting Nitrates and Outcomes in Heart Failure With Preserved Ejection Fraction 2017 Ingår i: Circulation Heart Failure. - : Lippincott Williams & Wilkins. - 1941-3289 .- 1941-3297. ; 10:4 Tidskriftsartikel (refereegranskat)abstract Nitrates may be beneficial in heart failure with preserved ejection fraction (HFpEF) by enhancing cGMP signaling and improving hemodynamics, but real-world data on potential efficacy are lacking.
28.	Lund, Lars H., et al. (författare) Association of Spironolactone Use With All-Cause Mortality in Heart Failure A Propensity Scored Cohort Study 2013 Ingår i: Circulation Heart Failure. - : Lippincott Williams & Wilkins. - 1941-3289 .- 1941-3297. ; 6:2, s. 174-183 Tidskriftsartikel (refereegranskat)abstract Background-In 3 randomized controlled trials in heart failure (HF), mineralocorticoid receptor antagonists reduced mortality. The net benefit from randomized controlled trials may not be generalizable, and eplerenone was, but spironolactone was not, studied in mild HF. We tested the hypothesis that spironolactone is associated with reduced mortality also in a broad unselected contemporary population with HF and reduced ejection fraction, in particular New York Heart Association (NYHA) I-II. Methods and Results-We prospectively studied 18 852 patients (age 71+/-12 years; 28% women) with NYHA I-IV and ejection fraction <40% who were registered in the Swedish Heart Failure Registry between 2000 and 2012 and who were (n=6551) or were not (n=12 301) treated with spironolactone. We derived propensity scores for spironolactone treatment based on 41 covariates. We assessed survival by Cox regression with adjustment for propensity scores and with matching based on propensity score. We performed sensitivity and residual confounding analyses and analyzed the NYHA I-II and III-IV subgroups separately. One-year survival was 83% versus 84% in treated versus untreated patients (log rank P<0.001). After adjustment for propensity scores, the hazard ratio for spironolactone was 1.05 (95% confidence interval, 1.00-1.11; P=0.054). Spironolactone interacted with NYHA (P<0.001). In the NYHA I-II subgroup, after adjustment for propensity scores, the hazard ratio for spironolactone was 1.11 (95% confidence interval, 1.02-1.21; P=0.019). Conclusions-In an unselected contemporary population of HF with reduced ejection fraction, spironolactone was not associated with reduced mortality. The net benefits of spironolactone may be lower outside the clinical trial setting and in milder HF.
29.	McMurray, John J. V., et al. (författare) Left Ventricular Systolic Dysfunction, Heart Failure, and the Risk of Stroke and Systemic Embolism in Patients With Atrial Fibrillation Insights From the ARISTOTLE Trial 2013 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 6:3, s. 451-460 Tidskriftsartikel (refereegranskat)abstract Background-We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin. Methods and Results-The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups. Conclusions-Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups.
30.	Mentz, R. J., et al. (författare) Clinical Profile and Prognostic Value of Anemia at the Time of Admission and Discharge Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction: Findings From the EVEREST Trial 2014 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 7:3, s. 401-8 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Anemia has been associated with worse outcomes in patients with chronic heart failure (HF). We aimed to characterize the clinical profile and postdischarge outcomes of hospitalized HF patients with anemia at admission or discharge. METHODS AND RESULTS: An analysis was performed on 3731 (90%) of 4133 hospitalized HF patients with ejection fraction 100 days) on adjusted analysis (both P>0.1). CONCLUSIONS: Among hospitalized HF patients with reduced ejection fraction, modest anemia at discharge but not baseline was associated with increased all-cause mortality and short-term cardiovascular mortality plus HF hospitalization. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00071331.
31.	Mostofsky, Elizabeth, et al. (författare) Chocolate Intake and Incidence of Heart Failure A Population-Based Prospective Study of Middle-Aged and Elderly Women 2010 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 3:5, s. 612-616 Tidskriftsartikel (refereegranskat)abstract Background-Randomized clinical trials have shown that chocolate intake reduces systolic and diastolic blood pressure, and observational studies have found an inverse association between chocolate intake and cardiovascular disease. The aim of this study was to investigate the association between chocolate intake and incidence of heart failure (HF). Methods and Results-We conducted a prospective cohort study of 31 823 women aged 48 to 83 years without baseline diabetes or a history of HF or myocardial infarction who were participants in the Swedish Mammography Cohort. In addition to answering health and lifestyle questions, participants completed a food-frequency questionnaire. Women were followed from January 1, 1998, through December 31, 2006, for HF hospitalization or death through the Swedish inpatient and cause-of-death registers. Over 9 years of follow-up, 419 women were hospitalized for incident HF (n=379) or died of HF (n=40). Compared with no regular chocolate intake, the multivariable-adjusted rate ratio of HF was 0.74 (95% CI, 0.58 to 0.95) for women consuming 1 to 3 servings of chocolate per month, 0.68 (95% CI, 0.50 to 0.93) for those consuming 1 to 2 servings per week, 1.09 (95% CI, 0.74 to 1.62) for those consuming 3 to 6 servings per week, and 1.23 (95% CI, 0.73 to 2.08) for those consuming >= 1 servings per day (P=0.0005 for quadratic trend). Conclusions-In this population, moderate habitual chocolate intake was associated with a lower rate of HF hospitalization or death, but the protective association was not observed with intake of >= 1 servings per day. (Circ Heart Fail. 2010;3:612-616.)
32.	Nowak, Christoph, et al. (författare) Kidney Disease Biomarkers Improve Heart Failure Risk Prediction in the General Population. 2020 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 13:8 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The kidneys play an important role in heart failure (HF), but it is unclear if renal biomarkers improve HF risk prediction beyond established risk factors. We aimed to assess whether adding biomarkers of kidney disease to conventional risk factors improved 10-year risk prediction for incident HF in a contemporary community sample.METHODS: We included 450 212 participants in the UK Biobank aged 39 to 70 years without HF who had been assessed in 2006 to 2010 with the urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. There were 1701 incident cases of HF during up to 10.3 years of follow-up (mean 8.2±0.7 years). We used the Atherosclerosis Risk in Communities study heart failure risk score excluding natriuretic peptides as the base model to which we added eGFR and urine albumin-to-creatinine ratio. Harrell's C-statistic of ARIC-HF was 0.845 (95% CI, 0.831-0.859).RESULTS: Each combination of added kidney measures (creat-eGFR, cysC-eGFR, and urine albumin-to-creatinine ratio) led to significant improvement in risk discrimination, calibration, and reclassification. The optimal pair of added kidney measures was cysC-eGFR and urine albumin-to-creatinine ratio (ΔC=0.019 [95% CI, 0.015-0.022]). Addition of cysC-eGFR made the largest contribution to reclassification improvement (continuous net reclassification improvement 0.323 [95% CI, 0.278-0.360]).CONCLUSIONS: In a large community sample, the addition of kidney disease markers to conventional risk factors improved prediction of 10-year HF risk. Our results support including kidney disease markers in the identification of persons at highest risk of HF and demonstrate a possible role of impaired kidney function in HF development in asymptomatic persons.
33.	Okumura, N., et al. (författare) Effects of sacubitril/valsartan in the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) according to background therapy 2016 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 9:9 Tidskriftsartikel (refereegranskat)abstract Background - In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitor enalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. Methods and Results - We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no), and defibrillating device (implanted defibrillating device, yes/no). We also examined the effect of study drug according to β-blocker dose (≥50% and <50% of target dose) and according to whether patients had undergone previous coronary revascularization. We analyzed the primary composite end point of cardiovascular death or heart failure hospitalization, as well as cardiovascular death. Most randomized patients (n=8399) were treated with a diuretic (80%) and β-blocker (93%); 47% of those taking a β-blocker were treated with ≥50% of the recommended dose. In addition, 4671 (56%) were treated with a mineralocorticoid receptor antagonist, 2539 (30%) with digoxin, and 1243 (15%) had a defibrillating device; 2640 (31%) had undergone coronary revascularization. Overall, the sacubitril/valsartan versus enalapril hazard ratio for the primary composite end point was 0.80 (95% confidence interval, 0.73-0.87; P<0.001) and for cardiovascular death was 0.80 (0.71-0.89; P<0.001). The effect of sacubitril/valsartan was consistent across all subgroups examined. The hazard ratio for primary end point ranged from 0.74 to 0.85 and for cardiovascular death ranged from 0.75 to 0.89, with no treatment-by-subgroup interaction. Conclusions - The benefit of sacubitril/valsartan, over an angiotensin-converting enzyme inhibitor, was consistent regardless of background therapy and irrespective of previous coronary revascularization or β-blocker dose. © 2016 American Heart Association, Inc.
34.	Ottesen, Anett Hellebø, et al. (författare) Glycosylated Chromogranin A in Heart Failure : Implications for Processing and Cardiomyocyte Calcium Homeostasis 2017 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 10:2 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Chromogranin A (CgA) levels have previously been found to predict mortality in heart failure (HF), but currently no information is available regarding CgA processing in HF and whether the CgA fragment catestatin (CST) may directly influence cardiomyocyte function.METHODS AND RESULTS: CgA processing was characterized in postinfarction HF mice and in patients with acute HF, and the functional role of CST was explored in experimental models. Myocardial biopsies from HF, but not sham-operated mice, demonstrated high molecular weight CgA bands. Deglycosylation treatment attenuated high molecular weight bands, induced a mobility shift, and increased shorter CgA fragments. Adjusting for established risk indices and biomarkers, circulating CgA levels were found to be associated with mortality in patients with acute HF, but not in patients with acute exacerbation of chronic obstructive pulmonary disease. Low CgA-to-CST conversion was also associated with increased mortality in acute HF, thus, supporting functional relevance of impaired CgA processing in cardiovascular disease. CST was identified as a direct inhibitor of CaMKIIδ (Ca(2+)/calmodulin-dependent protein kinase IIδ) activity, and CST reduced CaMKIIδ-dependent phosphorylation of phospholamban and the ryanodine receptor 2. In line with CaMKIIδ inhibition, CST reduced Ca(2+) spark and wave frequency, reduced Ca(2+) spark dimensions, increased sarcoplasmic reticulum Ca(2+) content, and augmented the magnitude and kinetics of cardiomyocyte Ca(2+) transients and contractions.CONCLUSIONS: CgA-to-CST conversion in HF is impaired because of hyperglycosylation, which is associated with clinical outcomes in acute HF. The mechanism for increased mortality may be dysregulated cardiomyocyte Ca(2+) handling because of reduced CaMKIIδ inhibition.
35.	Rahman, Iffat, et al. (författare) Relationship Between Physical Activity and Heart Failure Risk in Women 2014 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 7:6, s. 877-881 Tidskriftsartikel (refereegranskat)abstract Background-Physical activity is a modifiable health-related behavior shown to be associated with reduced risk of coronary heart disease and stroke. There is some evidence that this could also be the case for heart failure. We investigated whether total physical activity, as well as different domains of physical activity, was associated with heart failure risk. Methods and Results-The Swedish Mammography Cohort was used in which 27 895 women were followed up from 1997 to 2011. First event of heart failure was ascertained through the Swedish National Patient Register and Cause of Death Register. Cox proportional hazards regression analyses were conducted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals. We also analyzed survival percentiles by applying Laplace regression. During an average follow-up time of 13 years (369 207 person-years), we ascertained 2402 first events of heart failure hospitalizations and deaths. We found that moderate to high levels of total physical activity were associated with a reduced risk of future heart failure. When looking into different domains of physical activity, walking/bicycling >20 minutes/d was associated with 29% lower risk of heart failure (95% confidence interval, -36% to -21%), when investigating survival percentiles this could be translated into 18 months longer heart failure-free survival. Conclusions-Our study shows that physical activity could protect against heart failure in women. When looking closer into different domains of physical activity, walking or biking >= 20 minutes every day was associated with the largest risk reduction of heart failure.
36.	Rohde, L. E., et al. (författare) Cardiac and Noncardiac Disease Burden and Treatment Effect of Sacubitril/Valsartan Insights From a Combined PARAGON-HF and PARADIGM-HF Analysis 2021 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 14:3, s. 361-371 Tidskriftsartikel (refereegranskat)abstract Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction. Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed the previously validated Meta-Analysis Global Group in Chronic Heart Failure risk score into cardiac (left ventricular ejection fraction, New York Heart Association class, blood pressure, time since HF diagnosis, HF medications), noncardiac comorbid (body mass index, creatinine, diabetes, chronic obstructive pulmonary disease, smoking), and demographic (age, gender) categories. Based on these domains, an index representing the balance of cardiac to noncardiac comorbid burden was created (cardiac-comorbid index). Clinical outcomes were time to first HF hospitalization or cardiovascular deaths and all-cause mortality. Results: Higher scores of the cardiac domain were observed in PARADIGM-HF (10 [7-13] versus 5 [3-6], P<0.001) and higher scores of the demographic domain in PARAGON-HF (10 [8-13] versus 5 [2-9], P<0.001). In PARADIGM-HF, the contribution of the cardiac domain to clinical outcomes was greater than the noncardiac domain (P<0.001), while in PARAGON-HF the attributable risk of the comorbid and demographic categories predominated. Individual scores from each sub-domain were linearly associated with the risk of clinical outcomes (P<0.001). Beneficial effects of sacubitril/valsartan were observed in patients with preponderance of cardiac over noncardiac comorbid burden (cardiac-comorbid index >5 points), suggesting a significant treatment effect modification (interaction P<0.05 for both outcomes). Conclusions: Domains of disease burden are clinically relevant features that influence the prognosis and treatment of patients with HF. The therapeutic benefits of sacubitril/valsartan vary according to the balance of components of disease burden, across different ranges of left ventricular ejection fraction.
37.	Romano, K. A., et al. (författare) Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure 2023 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 16:1 Tidskriftsartikel (refereegranskat)abstract Background: The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling.Methods: Here we examined both clinical and mechanistic relationships between PAGln and heart failure (HF). First, we examined associations among plasma levels of PAGln and HF, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 2 independent clinical cohorts of subjects undergoing coronary angiography in tertiary referral centers (an initial discovery US Cohort, n=3256; and a validation European Cohort, n=829). Then, the impact of PAGln on cardiovascular phenotypes relevant to HF in cultured cardiomyoblasts, and in vivo were also examined.Results: Circulating PAGln levels were dose-dependently associated with HF presence and indices of severity (reduced ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide) independent of traditional risk factors and renal function in both cohorts. Beyond these clinical associations, mechanistic studies showed both PAGln and its murine counterpart, phenylacetylglycine, directly fostered HF-relevant phenotypes, including decreased cardiomyocyte sarcomere contraction, and B-type natriuretic peptide gene expression in both cultured cardiomyoblasts and murine atrial tissue.Conclusions: The present study reveals the gut microbial metabolite PAGln is clinically and mechanistically linked to HF presence and severity. Modulating the gut microbiome, in general, and PAGln production, in particular, may represent a potential therapeutic target for modulating HF.Registration: URL: ; Unique identifier: NCT00590200 and URL: ; Unique identifier: DRKS00020915.
38.	Rossignol, P., et al. (författare) Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients with Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo Additional to Optimal Medical Therapy: Results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) 2014 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 7:1, s. 51-58 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: -Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with systolic heart failure (HF), but may induce a worsening of renal function (WRF) and/or hyperkalemia (HK). We assessed the risk factors for MRA-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) METHODS AND RESULTS: -Serial changes in estimated glomerular filtration rate (eGFR) and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K>4.5, 5 or 5.5 mmol/L occurred in 74.7 %, 32.5 %, and 8.9 % of EMPHASIS-HF patients, respectively. WRF defined as a decrease in eGFR > 20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent i) rise in serum potassium, and ii) reduction in eGFR compared with placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (e.g. age >/=75 years, hypertension, diabetes, non-white race, ejection fraction <30%, and treatment with an antiarrythmics drug or loop diuretic). Eplerenone retained its survival benefits, without any significant interaction with the association between HK >5.5 mmol/l only and WRF and worse outcomes. CONCLUSIONS: -In HF patients receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurence did not eliminate the survival benefit of eplerenone. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov number. Unique identifier: NCT00232180.
39.	Røsjø, Helge, et al. (författare) Chromogranin B in Heart Failure : a Putative Cardiac Biomarker Expressed in the Failing Myocardium 2010 Ingår i: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 3:4, s. 503-511 Tidskriftsartikel (refereegranskat)abstract BackgroundChromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development.Methods and ResultsCgB regulation was investigated in patients with chronic HF and in a post–myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5.2-fold increased in the noninfarcted part of the left ventricle of HF animals compared with sham-operated animals (P<0.001). CgB mRNA level in HF animals correlated closely with animal lung weight (r=0.74, P=0.04) but not with CgA mRNA levels (r=0.20, P=0.61). CgB protein levels were markedly increased in both the noninfarcted (110%) and the infarcted part of the left ventricle (70%) but unaltered in other tissues investigated. Myocardial CgB immunoreactivity was confined to cardiomyocytes. Norepinephrine, angiotensin II, and transforming growth factor-β increased CgB gene expression in cardiomyocytes. Circulating CgB levels were increased in HF animals (median levels in HF animals versus sham, 1.23 [interquartile range, 1.03 to 1.93] versus 0.98 [0.90 to 1.04] nmol/L; P=0.003) and in HF patients (HF patients versus control, 1.66 [1.48 to 1.85] versus 1.47 [1.39 to 1.58] nmol/L; P=0.007), with levels increasing in proportion to New York Heart Association functional class (P=0.03 for trend). Circulating CgB levels were only modestly correlated with CgA (r=0.31, P=0.009) and B-type natriuretic peptide levels (r=0.27, P=0.014).ConclusionsCgB production is increased and regulated in proportion to disease severity in the left ventricle and circulation during HF development.
40.	Savarese, Gianluigi, et al. (författare) Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction 2016 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 9:11 Tidskriftsartikel (refereegranskat)abstract Background-In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients. Methods and Results-In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF=50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median followup of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately. Conclusions-In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.
41.	Shen, L., et al. (författare) Contemporary Characteristics and Outcomes in Chagasic Heart Failure Compared With Other Nonischemic and Ischemic Cardiomyopathy 2017 Ingår i: Circulation. Heart failure. - 1941-3289 .- 1941-3297. ; 10:11 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Chagas' disease is an important cause of cardiomyopathy in Latin America. We aimed to compare clinical characteristics and outcomes in patients with heart failure (HF) with reduced ejection fraction caused by Chagas' disease, with other etiologies, in the era of modern HF therapies. METHODS AND RESULTS: This study included 2552 Latin American patients randomized in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure) trials. The investigator-reported etiology was categorized as Chagasic, other nonischemic, or ischemic cardiomyopathy. The outcomes of interest included the composite of cardiovascular death or HF hospitalization and its components and death from any cause. Unadjusted and adjusted Cox proportional hazards models were performed to compare outcomes by pathogenesis. There were 195 patients with Chagasic HF with reduced ejection fraction, 1300 with other nonischemic cardiomyopathy, and 1057 with ischemic cardiomyopathy. Compared with other etiologies, Chagasic patients were more often female, younger, and had lower prevalence of hypertension, diabetes mellitus, and renal impairment (but had higher prevalence of stroke and pacemaker implantation) and had worse health-related quality of life. The rates of the composite outcome were 17.2, 12.5, and 11.4 per 100 person-years for Chagasic, other nonischemic, and ischemic patients, respectively-adjusted hazard ratio for Chagasic versus other nonischemic: 1.49 (95% confidence interval, 1.15-1.94; P=0.003) and Chagasic versus ischemic: 1.55 (1.18-2.04; P=0.002). The rates of all-cause mortality were also higher. CONCLUSIONS: Despite younger age, less comorbidity, and comprehensive use of conventional HF therapies, patients with Chagasic HF with reduced ejection fraction continue to have worse quality of life and higher hospitalization and mortality rates compared with other etiologies. CLINICAL TRIAL REGISTRATION: PARADIGM-HF: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255; ATMOSPHERE: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658.
42.	Solomon, S. D., et al. (författare) Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction: The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) Trial 2016 Ingår i: Circ Heart Fail. - 1941-3289 .- 1941-3297. ; 9:3 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696) reduced cardiovascular morbidity and mortality compared with enalapril in patients with heart failure (HF) and reduced ejection fraction (EF) in the Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. We evaluated the influence of EF on clinical outcomes and on the effectiveness of sacubitril/valsartan compared with enalapril. METHODS AND RESULTS: Eight thousand three hundred ninety-nine patients with New York Heart Association class II to IV HF with reduced EF [left ventricular EF (LVEF)
43.	Thompson, Jessica Harman, et al. (författare) Shared Decision-Making About End-of-Life Care Scenarios Compared Among Implantable Cardioverter Defibrillator Patients A National Cohort Study 2019 Ingår i: Circulation Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 12:10 Tidskriftsartikel (refereegranskat)abstract Background: Authors of expert guidelines and consensus statements recommend that decisions at the end-of-life (EOL) be discussed before and after implantation of an implantable cardioverter defibrillator (ICD) and include promotion of shared decision-making. The purpose of this study was to describe experiences, attitudes, and knowledge about the ICD at EOL in ICD recipients and to compare experiences, attitudes, and knowledge in ICD recipients with and without heart failure (HF). We further sought to determine factors associated with having discussions about EOL. Methods and Results: Using a national registry in Sweden of all ICD recipients (n=5355) in 2012, an EOL questionnaire, along with other ICD-related measures, was completed by 2403 ICD recipients. Of the participants, 1275 (n=53%) had HF. Their responses in the knowledge, experience, and attitude domains were almost identical to those without HF. Forty percent of patients with and without HF did not want to discuss their illness trajectory or deactivation of their ICD ever. In logistic regression analyses, we found that having had an ICD shock (OR, 2.05; CI, 1.64-2.56), having high levels of anxiety (OR, 1.41; CI, 1.04-1.92), and having high levels of ICD concerns (OR, 1.53; CI, 1.22-1.92) were the only significant predictors of having discussions with providers about EOL scenarios (Pamp;lt;0.001 for full model). Conclusions: HF was not a predictor of having an EOL conversation. Further research is needed to determine if attitudes related to not wanting to discuss EOL interfere with good quality of life and of death, or if shared decision-making should be encouraged in these individuals.
44.	Tomczyk, Mateusz M., et al. (författare) Mitochondrial Sirtuin-3 (SIRT3) Prevents Doxorubicin-Induced Dilated Cardiomyopathy by Modulating Protein Acetylation and Oxidative Stress 2022 Ingår i: Circulation Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 15:5 Tidskriftsartikel (refereegranskat)abstract Background: High doses of doxorubicin put cancer patients at risk for developing dilated cardiomyopathy. Previously, we showed that doxorubicin treatment decreases SIRT3 (sirtuin 3), the main mitochondrial deacetylase and increases protein acetylation in rat cardiomyocytes. Here, we hypothesize that SIRT3 expression can attenuate doxorubicin induced dilated cardiomyopathy in vivo by preventing the acetylation of mitochondrial proteins. Methods: Nontransgenic, M3-SIRT3 (truncated SIRT3; short isoform), and M1-SIRT3 (full-length SIRT3; mitochondrial localized) transgenic mice were treated with doxorubicin for 4 weeks (8 mg/kg body weight per week). Echocardiography was performed to assess cardiac structure and function and validated by immunohistochemistry and immunofluorescence (n=4-10). Mass spectrometry was performed on cardiac mitochondrial peptides in saline (n=6) and doxorubicin (n=5) treated hearts. Validation was performed in doxorubicin treated primary rat and human induced stem cell derived cardiomyocytes transduced with adenoviruses for M3-SIRT3 and M1-SIRT3 and deacetylase deficient mutants (n=4-10). Results: Echocardiography revealed that M3-SIRT3 transgenic mice were partially resistant to doxorubicin induced changes to cardiac structure and function whereas M1-SIRT3 expression prevented cardiac remodeling and dysfunction. In doxorubicin hearts, 37 unique acetylation sites on mitochondrial proteins were altered. Pathway analysis revealed these proteins are involved in energy production, fatty acid metabolism, and oxidative stress resistance. Increased M1-SIRT3 expression in primary rat and human cardiomyocytes attenuated doxorubicin-induced superoxide formation, whereas deacetylase deficient mutants were unable to prevent oxidative stress. Conclusions: Doxorubicin reduced SIRT3 expression and markedly affected the cardiac mitochondrial acetylome. Increased M1-SIRT3 expression in vivo prevented doxorubicin-induced cardiac dysfunction, suggesting that SIRT3 could be a potential therapeutic target for mitigating doxorubicin-induced dilated cardiomyopathy.
45.	Tromp, Jasper, et al. (författare) Fibrosis Marker Syndecan-1 and Outcome in Patients With Heart Failure With Reduced and Preserved Ejection Fraction 2014 Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 7:3, s. 457-U119 Tidskriftsartikel (refereegranskat)abstract Background-Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF). Methods and Results-We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0 +/- 11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5 +/- 14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors. Conclusions-In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
46.	Vaduganathan, M., et al. (författare) Predictive Value of Low Relative Lymphocyte Count in Patients Hospitalized for Heart Failure With Reduced Ejection Fraction Insights from the EVEREST Trial 2012 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 5:6, s. 750-758 Tidskriftsartikel (refereegranskat)abstract Background—Low lymphocyte count has been shown to be an independent prognostic marker in heart failure (HF) in the outpatient setting. Limited data exist regarding whether relative lymphocyte count correlates with postdischarge outcomes in patients hospitalized for HF. Methods and Results—We performed a post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, which randomized 4133 patients hospitalized for worsening HF with an ejection fraction ≤40% within 48 hours of admission to tolvaptan or placebo for a median follow-up of 9.9 months. The primary end points of all-cause mortality and cardiovascular mortality or HF hospitalization were analyzed in patients with available baseline complete blood counts (n=3717). Lymphocyte percentage was analyzed as a continuous variable. Times to events were compared using log-rank tests and multivariable Cox regression models. Patients with low lymphocyte percentage tended to be older and had higher rates of comorbid disease (diabetes mellitus, atrial fibrillation, and renal insufficiency). Low lymphocyte counts were associated with wide QRS duration, high natriuretic peptides, and low ejection fraction, blood pressure, and serum sodium. These patients were less likely to receive evidence-based HF medications. After adjusting for 22 known clinical risk factors, a 10% decrease in lymphocytes was associated with an increased hazard of all-cause mortality (adjusted hazard ratio 1.31 [95% CI: 1.14–1.150], P<0.001) and cardiovascular mortality or HF hospitalization (adjusted hazard ratio 1.14 [95% CI: 1.04–1.25], P=0.007) in the first 100 days postdischarge. Lymphopenia during hospitalization normalizes in majority of patients in the early postdischarge period. Conclusions—Low relative lymphocyte count during hospitalization for HF is an independent predictor of poor outcomes in the early postdischarge period, beyond traditional prognostic indicators.
47.	van der Meer, P., et al. (författare) Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure) Clinical and Prognostic Associations 2018 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 11:2 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. METHODS AND RESULTS: We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was -0.25 g/dL and + 1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders. CONCLUSIONS: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers.
48.	van Deursen, Vincent M., et al. (författare) Prognostic Value of Plasma Neutrophil Gelatinase-Associated Lipocalin for Mortality in Patients With Heart Failure 2014 Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 7:1, s. 35-42 Tidskriftsartikel (refereegranskat)abstract Background In patients with heart failure, renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel marker of renal tubular damage, in patients with heart failure with or without renal dysfunction, and compare it with 2 frequently used biomarkers of chronic kidney disease. Methods and Results Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were assessed in 562 patients with heart failure. Chronic kidney disease was defined as eGFRless than60 mL/min per 1.73 m(2). Outcome was all-cause mortality at 36 months. Mean age was 7111 years, 61% were men, and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54 +/- 20 mL/min per 1.73 m(2), mean cystatin C was 11.2 (7.7-16.2) mg/L, and median plasma NGAL was 85 (60-123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality, in patients with and without chronic kidney disease (hazard ratio [per SD increase in log NGAL]=1.45 [1.22-1.72]; Pless than0.001 and hazard ratio=1.51 [1.06-2.16]; P=0.023, respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions Plasma NGAL predicts mortality in patients with heart failure, both in patients with and without chronic kidney disease and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.
49.	Vardeny, O., et al. (författare) Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) 2018 Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 11:4 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients. METHODS AND RESULTS: We characterized patients in PARADIGM-HF by whether they reported hypotension during study run-in periods (enalapril, followed by sacubitril/valsartan) and after randomization and assessed whether hypotension modified the efficacy of sacubitril/valsartan. Of the 10513 patients entering the enalapril run-in, 136 (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228 (2.4%) patients experienced hypotension and 51% were unable to successfully complete the run-in. After randomization, 388 (9.2%) participants had 501 hypotensive events with enalapril, and 588 (14.0%) participants had 803 hypotensive events with sacubitril/valsartan (P<0.001). There was no difference between randomized treatment groups in the number of participants who discontinued therapy because of hypotension. Individuals with a hypotensive event in either group were older, had lower blood pressure at randomization, and were more likely to have an implantable cardioverter defibrillator. Participants with hypotensive events during run-in who were ultimately randomized derived similar efficacy from sacubitril/valsartan compared with enalapril as those without hypotensive events (P interaction>0.90). CONCLUSIONS: Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived similar benefit from sacubitril/valsartan compared with enalapril as those who did not experience hypotension.
50.	Vedin, Ola, et al. (författare) Significance of Ischemic Heart Disease in Patients with Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction : A Nationwide Cohort Study 2017 Ingår i: Circulation: Heart Failure. - : LIPPINCOTT WILLIAMS & WILKINS. - 1941-3289 .- 1941-3297. ; 10:6 Tidskriftsartikel (refereegranskat)abstract Background - The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF <40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%-50%) and preserved EF (HFpEF; EF ≥50%) has been much less explored. Methods and Results - We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89-0.93] versus HFmrEF and risk ratio, 0.90 [0.88-0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84-0.95] versus HFmrEF and hazard ratio, 0.84 [0.80-0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time. Conclusions - HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types.

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