41 results on '"McMurray, John J.V."'
Search Results
2. Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multistate model
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Aulin, Julia, Hijazi, Ziad, Lindbäck, Johan, Alexander, John H., Gersh, Bernard J., Granger, Christopher B., Hanna, Michael, Horowitz, John, Lopes, Renato D, McMurray, John J.V., Oldgren, Jonas, Siegbahn, Agneta, and Wallentin, Lars
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Heart Failure ,Inflammation ,Kardiologi ,Growth Differentiation Factor 15 ,Interleukin-6 ,Stroke Volume ,Prognosis ,Peptide Fragments ,Troponin T ,Atrial Fibrillation ,Natriuretic Peptide, Brain ,Humans ,Cardiac and Cardiovascular Systems ,Cystatin C ,Cardiology and Cardiovascular Medicine ,Biomarkers - Abstract
Background: \ud Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.\ud \ud Methods: \ud The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n=2,048), (II) HF with preserved ejection fraction (HFpEF, n=2,520), and (III) No HF (n=7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.\ud \ud Results: \ud Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all p
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- 2022
3. Baseline characteristics of patients with HF with mildly reduced and preserved ejection fraction: DELIVER trial
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Solomon, Scott D., Vaduganathan, Muthiah, Claggett, Brian L., de Boer, Rudolf A., DeMets, David, Hernandez, Adrian F., Inzucchi, Silvio E., Kosiborod, Mikhail N., Lam, Carolyn S.P., Martinez, Felipe, Shah, Sanjiv J., Belohlavek, Jan, Chiang, Chern-En, Willem Borleffs, C. Jan, Comin-Colet, Josep, Dobreanu, Dan, Drozdz, Jaroslaw, Fang, James C., Alcocer Gamba, Marco Antonio, Al Habeeb, Waleed, Han, Yaling, Cabrera Honorio, Jose Walter, Janssens, Stefan P., Katova, Tsvetana, Kitakaze, Masafumi, Merkely, Bela, O'Meara, Eileen, Kerr Saraiva, Jose Francisco, Tereschenko, Sergey N., Thierer, Jorge, Vardeny, Orly, Verma, Subodh, Vinh, Pham Nguyen, Wilderäng, Ulrica, Zaozerska, Natalia, Lindholm, Daniel, Petersson, Magnus, McMurray, John J.V., and Cardiovascular Centre (CVC)
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Aged, 80 and over ,Heart Failure ,Male ,heart failure with preserved ejection fraction ,clinical trials ,heart failure with mildly reduced ejection fraction ,SGLT-2 inhibitors ,Stroke Volume ,Middle Aged ,Peptide Fragments ,Ventricular Function, Left ,Diabetes Mellitus, Type 2 ,Atrial Fibrillation ,Natriuretic Peptide, Brain ,Humans ,Female ,cardiovascular diseases ,Sodium-Glucose Transporter 2 Inhibitors ,Aged - Abstract
Objectives: \ud This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials.\ud \ud Background: \ud The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter–2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF).\ud \ud Methods: \ud Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo.\ud \ud Results: \ud A total of 6,263 patients were randomized (mean age: 72 ± 10 years; 44% women; 45% type 2 diabetes mellitus; 45% with body mass index ≥30 kg/m2; and 57% with history of atrial fibrillation or flutter). Most participants had New York Heart Association functional class II symptoms (75%). Baseline mean LVEF was 54.2 ± 8.8% and median NT-proBNP of 1,399 pg/mL (IQR: 962 to 2,210 pg/mL) for patients in atrial fibrillation/flutter compared with 716 pg/mL (IQR: 469 to 1,281 pg/mL) in those who were not. Patients in both hospitalized and ambulatory settings were enrolled, including 10% enrolled in-hospital or within 30 days of a hospitalization for HF. Eighteen percent of participants had HF with improved LVEF.\ud \ud Conclusions: \ud DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213]).
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- 2022
4. Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N‐terminal pro‐B‐type natriuretic peptide level: insights from the GALACTIC‐HF trial.
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Docherty, Kieran F., McMurray, John J.V., Claggett, Brian L., Miao, Zi Michael, Adams, Kirkwood F., Arias‐Mendoza, Alexandra, Cleland, John G.F., Diaz, Rafael, Echeverria Correa, Luis E, Felker, G. Michael, Fonseca, Candida, Li, Jing, Metra, Marco, Sliwa‐Hahnle, Karen, Solomon, Scott D., Vandekerckhove, Hans J., Vinereanu, Dragos, Voors, Adriaan A., Heitner, Stephen B., and Kupfer, Stuart
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BRAIN natriuretic factor , *IVABRADINE , *HEART failure , *VENTRICULAR ejection fraction , *HEART failure patients , *ATRIAL fibrillation - Abstract
Aim: N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT‐proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC‐HF). Methods and results: The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT‐proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT‐proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1–Q3) NT‐proBNP level was 1675 (812–3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80–1.09), > median 0.81 (0.73–0.90) (p‐interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90–1.15) and > median 0.88 (0.80–0.96) (p‐interaction = 0.035). There was an interaction between treatment and NT‐proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT‐proBNP (p‐interaction = 0.086). Conclusions: In GALACTIC‐HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT‐proBNP levels, especially in patients without AF/AFL. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016‐002299‐28. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Atrial fibrillation in heart failure with preserved ejection fraction - the PARAGON-HF trial
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Cikes, Maja, Planinc, Ivo, Claggett, Brian, Cunningham, Jonathan, Milicic, Davor, Sweitzer, Nancy, Senni, Michele, Gori, Mauro, Linssen, Gerard, Shah, Sanjiv J., Packer, Milton, Pfeffer, Marc, Zile, Michael R., Anand, Inder, Chiang, Lu-May, Lam, Carolyn S.P., Redfield, Margaret, Desai, Akshay S., McMurray, John J.V., and Solomon, Scott D.
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atrial fibrillation ,echocardiography ,heart failure outcomes ,heart failure with preserved ejection fraction ,sacubitril/valsartan - Abstract
Objectives: \ud In this study, we sought to assess the relationship between AFF and outcomes, the treatment response to sacubitril/valsartan and first-detected AFF in patients with HFpEF enrolled in the PARAGON-HF trial.\ud \ud Background: \ud Atrial fibrillation and flutter (AFF) are common in heart failure with preserved ejection fraction (HFpEF) and increase the risk of adverse outcomes.\ud \ud Methods: \ud A total of 4,776 patients formed 3 groups: those with AFF according to electrocardiography (ECG) at enrollment (n = 1,552; 33%), those with history of AFF but without AFF on ECG at enrollment (n = 1,005; 21%), and those without history of AFF or AFF on ECG at enrollment (n = 2,219, 46%). We assessed outcomes, treatment response to sacubitril/valsartan in each group, and the risk associated with first-detected AFF in patients without any known AFF. The primary outcome was a composite of total heart failure hospitalizations and cardiovascular death.\ud \ud Results: \ud History of AFF and AFF at enrollment were associated with higher risk of the primary outcome (risk ratio [RR]: 1.36 [95% CI: 1.12-1.65] and RR 1.31 [1.11-1.54], respectively), than no AFF. Neither history of AFF nor AFF at enrollment modified the treatment effect of sacubitril/valsartan. Post randomization AFF occurred in 12% of patients without previous AFF and was associated with 2.8-fold higher risk of the primary outcome, but it was not influenced by sacubitril/valsartan.\ud \ud Conclusions: \ud History of AFF and AFF on ECG at enrollment were associated with a higher risk of the primary outcome. First-detected AFF was not influenced by sacubitril/valsartan, yet it was associated with increased risk of all subsequent outcomes and may represent a potential target for future HFpEF trials. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
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- 2022
6. Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model.
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Aulin, Julia, Hijazi, Ziad, Lindbäck, Johan, Alexander, John H., Gersh, Bernard J., Granger, Christopher B., Hanna, Michael, Horowitz, John, Lopes, Renato D., McMurray, John J.V., Oldgren, Jonas, Siegbahn, Agneta, Wallentin, Lars, and ARISTOTLE Investigators
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Background: Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.Methods: The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.Results: Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P< .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.Conclusions: In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Effects of apixaban compared with warfarin as gain in event-free time - a novel assessment of the results of the ARISTOTLE trial
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Berglund, Erik, Wallentin, Lars, Oldgren, Jonas, Renlund, Henrik, Alexander, John H., Granger, Christopher B., Hohnloser, Stefan H., Hylek, Elaine M., Lopes, Renato D., McMurray, John J.V., and Lytsy, Per
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Anticoagulation ,Kardiologi ,apixaban ,gains in event-free time ,atrial fibrillation ,Cardiac and Cardiovascular Systems ,stroke prevention ,cardiovascular diseases ,anticoagulation ,bleeding - Abstract
Background:\ud A novel approach to determine the effect of a treatment is to calculate the delay of event, which estimates the gain of event-free time. The aim of this study was to estimate gains in event-free time for stroke or systemic embolism, death, bleeding events, and the composite of these events, in patients with atrial fibrillation randomized to either warfarin or apixaban in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE).\ud \ud Design:\ud The ARISTOTLE study was a randomized double-blind trial comparing apixaban with warfarin.\ud \ud Methods:\ud Laplace regression was used to estimate the delay in time to the outcomes between the apixaban and the warfarin group in 6, 12, 18 and 22 months of follow-up.\ud \ud Results:\ud The gain in event-free time for apixaban versus warfarin was 181 (95% confidence interval 76 to 287) days for stroke or systemic embolism and 55 (–4 to 114) days for death after 22 months of follow-up. The corresponding gains in event-free times for major and intracranial bleeding were 206 (130 to 281) and 392 (249 to 535) days, respectively. The overall gain for the composite of all these events was a gain of 116 (60 to 171) days.\ud \ud Conclusions:\ud In patients with atrial fibrillation, 22 months of treatment with apixaban, as compared with warfarin, provided gains of approximately 6 months in event-free time for stroke or systemic embolism, 7 months for major bleeding and 13 months for intracranial bleeding.
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- 2020
8. Dapagliflozin and atrial fibrillation in heart failure with reduced ejection fraction: insights from DAPA‐HF.
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Butt, Jawad H., Docherty, Kieran F., Jhund, Pardeep S., de Boer, Rudolf A., Böhm, Michael, Desai, Akshay S., Howlett, Jonathan G., Inzucchi, Silvio E., Kosiborod, Mikhail N., Martinez, Felipe A., Nicolau, Jose C., Petrie, Mark C., Ponikowski, Piotr, Bengtsson, Olof, Langkilde, Anna Maria, Schou, Morten, Sjöstrand, Mikaela, Solomon, Scott D., Sabatine, Marc S., and McMurray, John J.V.
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Aims: Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF). We also examined the effect of dapagliflozin on new‐onset AF. Methods and results: The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62–0.92 and 0.74, 95% CI 0.62–0.88, respectively; p for interaction = 0.88]. Consistent benefits were observed for the components of the primary outcome, all‐cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new‐onset AF compared with placebo (HR 0.86, 95% CI 0.60–1.22). However, patients with new‐onset AF had a 5 to 6‐fold higher risk of adverse outcomes when compared to those without incident AF. Conclusions: Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all‐cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new‐onset AF. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Catheter Ablation for Atrial Fibrillation with Heart Failure
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Docherty, Kieran F., Jhund, Pardeep S., and McMurray, John J.V.
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Heart Failure ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Treatment outcome ,MEDLINE ,Atrial fibrillation ,Catheter ablation ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,Treatment Outcome ,0302 clinical medicine ,Text mining ,Internal medicine ,Heart failure ,Atrial Fibrillation ,Catheter Ablation ,medicine ,Cardiology ,Humans ,030212 general & internal medicine ,business - Abstract
No abstract available.
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- 2018
10. Readmission and death in patients admitted with new-onset versus worsening of chronic heart failure: insights from a nationwide cohort.
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Butt, Jawad H., Fosbøl, Emil L., Gerds, Thomas A., Andersson, Charlotte, McMurray, John J.V., Petrie, Mark C., Gustafsson, Finn, Madelaire, Christian, Kristensen, Søren Lund, Gislason, Gunnar H., Torp‐Pedersen, Christian, Køber, Lars, Schou, Morten, and Torp-Pedersen, Christian
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HEART failure ,PATIENT readmissions ,ATRIAL fibrillation ,HOSPITAL admission & discharge ,REGRESSION analysis ,ACQUISITION of data ,HOSPITAL care ,LONGITUDINAL method - Abstract
Aims: To examine the rates of all-cause mortality and heart failure (HF) readmission in patients hospitalized with decompensated HF according to HF duration - new-onset HF and worsening of chronic HF.Methods and Results: In this nationwide observational cohort study, 17 176 patients were included at first hospital admission for HF in the period 2013-2015 using data from Danish nationwide registries. In total, 8860 (51.6%) patients were admitted with new-onset HF and 8316 (48.4%) with worsening of chronic HF. Patients with worsening of chronic HF were characterized by a greater comorbidity burden compared with patients with new-onset HF. The rates of outcomes were examined by multivariable Cox regression models, adjusted for age, sex, and comorbidity. Worsening of chronic HF was associated with a higher rate of the composite endpoint of all-cause mortality or HF readmission [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.31-1.43], all-cause mortality (HR 1.22, 95% CI 1.16-1.28), and HF readmission (HR 1.81, 95% CI 1.69-1.93) compared with new-onset HF. There was an interaction between atrial fibrillation (AF), HF duration, and outcome: in worsening of chronic HF, the rate of the composite endpoint was higher in patients with AF compared with those without (HR 1.12, 95% CI 1.07-1.19), whereas in new-onset HF, the rate of the composite endpoint was lower in patients with AF compared with those without (HR 0.91, 95% CI 0.85-0.96) (P-value for interaction <0.001).Conclusions: Among patients hospitalized with decompensated HF, worsening of chronic HF was associated with poorer outcomes compared with new-onset HF. [ABSTRACT FROM AUTHOR]- Published
- 2020
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11. Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.
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Docherty, Kieran F., Shen, Li, Castagno, Davide, Petrie, Mark C., Abraham, William T., Böhm, Michael, Desai, Akshay S., Dickstein, Kenneth, Køber, Lars V., Packer, Milton, Rouleau, Jean L., Solomon, Scott D., Swedberg, Karl, Vazir, Ali, Zile, Michael R., Jhund, Pardeep S., and McMurray, John J.V.
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HEART beat ,VENTRICULAR fibrillation ,ATRIAL fibrillation ,HEART failure ,CLINICAL trial registries ,RESEARCH ,RESEARCH methodology ,PROGNOSIS ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,QUALITY of life ,HOSPITAL care ,STROKE volume (Cardiac output) ,PEPTIDE hormones ,PEPTIDES - Abstract
Aims: To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator.Methods and Results: Of 13 562 patients from two large HFrEF trials, 10 113 (74.6%) were in SR and 3449 (25.4%) in AF. The primary endpoint was the composite of cardiovascular death or heart failure hospitalization. Heart rate was analysed as a categorical (tertiles, T1-3) and continuous variable (per 10 bpm), separately in patients in SR and AF. Outcomes were adjusted for prognostic variables, including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and also examined using change from baseline heart rate to 1 year (≤ -10 bpm, ≥ +10 bpm, < ±10 bpm). SR patients with a higher heart rate had worse symptoms and quality of life, more often had diabetes and higher NT-proBNP concentrations. They had higher risk of the primary endpoint [T3 vs. T1 adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.35-1.66; P < 0.001; per 10 bpm: 1.12, 95% CI 1.09-1.16; P < 0.001]. In SR, heart rate was associated with a relatively higher risk of pump failure than sudden death (adjusted HR per 10 bpm 1.17, 95% CI 1.09-1.26; P < 0.001 vs. 1.07, 95% CI 1.02-1.13; P = 0.011). Heart rate was not predictive of any outcome in AF.Conclusions: In HFrEF, an elevated heart rate was an independent predictor of adverse cardiovascular outcomes in patients in SR, even after adjustment for NT-proBNP. There was no relationship between heart rate and outcomes in AF.Clinical Trial Registration: ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658. [ABSTRACT FROM AUTHOR]- Published
- 2020
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12. Beta-blockers and outcome in heart failure and atrial fibrillation: A meta-analysis
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Rienstra, Michiel, Damman, Kevin, Mulder, Bart A., van Gelder, Isabelle C., McMurray, John J.V., and van Veldhuisen, Dirk J.
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beta-blocker ,outcome ,heart failure ,atrial fibrillation - Abstract
Objectives The purpose of this study was to analyze the effect of beta blockade on outcome in patients with heart failure (HF) and atrial fibrillation (AF). Background Beta-blockers are widely used in patients with HF and AF. Recommendation in current HF guidelines, however, is based on populations in which the most patients had sinus rhythm. Whether beta-blockers are as useful in AF is uncertain. Methods Studies were included that investigated the effect of placebo-controlled, randomized beta-blocker therapy in patients with AF at baseline and HF with reduced systolic left ventricular ejection fraction (LVEF)
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- 2013
13. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: Insights from the aristotle trial (apixaban for the prevention of stroke in subjects with atrial fibrillation)
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Hijazi, Ziad, Wallentin, Lars, Siegbahn, Agneta, Andersson, Ulrika, Christersson, Christina, Ezekowitz, Justin, Gersh, Bernard J., Hanna, Michael, Hohnloser, Stefan, Horowitz, John, Huber, Kurt, Hylek, Elaine M., Lopes, Renato D., McMurray, John J.V., and Granger, Christopher B.
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NT-proBNP ,risk assessment ,atrial fibrillation ,cardiovascular diseases ,natriuretic peptides - Abstract
Objectives This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Background Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. Methods In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Results Quartiles of NT-proBNP were: Q1, 363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, > 1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p ¼ 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. Conclusions NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984) (J Am Coll Cardiol 2013;61:2274–84) ª 2013 by the American College of Cardiology Foundation
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- 2013
14. Eplerenone and Atrial Fibrillation in Mild Systolic Heart Failure Results From the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) Study
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Sweberg, Karl, Zannad, Faiez, McMurray, John J.V., Krum, Henry, van Veldhuisen, Dirk J., Shi, Harry, Vincent, John, Pitt, Bertram, and Cardiovascular Centre (CVC)
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MODEL ,MYOCARDIAL-INFARCTION ,RECEPTOR ,aldosterone antagonism ,MORTALITY ,ALDOSTERONE ,BLOCKER ,heart failure ,atrial fibrillation ,SPIRONOLACTONE ,PREVENTION ,METAANALYSIS - Abstract
ObjectivesThe purpose of this study was to analyze the incidence of new atrial fibrillation or flutter (AFF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) database.BackgroundAldosterone antagonism in heart failure might influence atrial fibrosis and remodeling and, therefore, risk of developing AFF. The development of new AFF was a pre-specified secondary endpoint in the EMPHASIS-HF study.MethodsPatients in New York Heart Association functional class II and with ejection fraction ≤35% were eligible for EMPHASIS-HF. History of AFF at baseline was reported by investigators using the study case report form. New onset AFF (in those with no history of AFF at baseline) was reported using a specific endpoint form; in a sensitivity analysis we also examined the effect of eplerenone on AFF reported as an adverse event.ResultsNew onset AFF was significantly reduced by eplerenone: 25 of 911 (2.7%) versus 40 of 883 (4.5%) in the placebo group (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.35 to 0.96; p = 0.034). The reduction in the primary endpoint with eplerenone was similar among patients with and without AFF at baseline (HR: 0.60, 95% CI: 0.46 to 0.79 vs. HR: 0.70, 95% CI: 0.57 to 0.85, respectively; p for interaction = 0.41). The risk of cardiovascular (CV) death or hospital admission for worsening heart failure, the primary endpoint, was not significantly different in subjects with and without AFF at baseline (both study groups combined: HR: 1.23, 95% CI: 0.81 to 1.86; p = 0.33).ConclusionsIn patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF. The effects of eplerenone on the reduction of major CV events were similar in patients with and without AFF at baseline.
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- 2012
15. Association of heart rate and outcomes in a broad spectrum of patients with chronic heart failure: Results from the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity) program
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Castagno, Davide, Skali, Hicham, Takeuchi, Madoka, Swedberg, Karl, Yusuf, Salim, Granger, Christopher B., Michelson, Eric L., Pfeffer, Marc A., McMurray, John J.V., and Solomon, Scott D.
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heart rate ,heart failure ,atrial fibrillation ,prognosis ,ejection fraction - Abstract
ObjectivesThe aim of this study was to explore the relationship between baseline resting heart rate and outcomes in patients with chronic heart failure (HF) according to baseline left ventricular ejection fraction (LVEF) and cardiac rhythm.BackgroundElevated resting heart rate is associated with worse outcomes in patients with HF and reduced LVEF. Whether this association is also found in patients with HF and preserved LVEF is uncertain, as is the predictive value of heart rate in patients in atrial fibrillation (AF).MethodsPatients enrolled in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) Program were divided into groups by tertiles of baseline heart rate. Cox proportional hazard models were used to investigate the association between heart rate and pre-specified outcomes in the overall population as well as in subgroups defined according to LVEF (≤40% vs. >40%) and presence (or absence) of AF at baseline.ResultsAfter adjusting for predictors of poor prognosis, patients in the highest heart rate tertile had worse outcomes when compared with those in the lowest heart rate group (e.g., for the composite of cardiovascular death or HF hospital stay hazard ratio: 1.23, 95% confidence interval: 1.11 to 1.36, p < 0.001). The relationship between heart rate and outcomes was similar across LVEF categories and was not influenced by beta-blocker use (p value for interaction >0.10 for both endpoints). However, amongst patients in AF at baseline, heart rate had no predictive value (p value for interaction
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- 2012
16. Severity of renal impairment in patients with heart failure and atrial fibrillation: implications for non-vitamin K antagonist oral anticoagulant dose adjustment.
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Hawkins, Nathaniel M., Jhund, Pardeep S., Pozzi, Andrea, O'Meara, Eileen, Solomon, Scott D., Granger, Christopher B., Yusuf, Salim, Pfeffer, Marc A., Swedberg, Karl, Petrie, Mark C., Virani, Sean, and McMurray, John J.V.
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KIDNEY diseases ,HEART failure patients ,ATRIAL fibrillation ,ANTICOAGULANTS ,GLOMERULAR filtration rate ,DRUG dosage ,CHRONIC kidney failure complications ,STROKE prevention ,CHRONIC kidney failure ,HEART failure ,HETEROCYCLIC compounds ,PROTEINS ,PYRIDINE ,STROKE ,THIAZOLES ,DISEASE complications - Abstract
Aims: The non-vitamin K antagonist oral anticoagulants (NOACs) have varying degrees of renal elimination which may be challenging in patients with heart failure (HF) and atrial fibrillation (AF). We examined the severity and variation in renal impairment, and the proportion of patients requiring NOAC cessation or dose reduction.Methods and Results: A retrospective analysis of patients with HF and AF in the Candesartan in Heart failure Assessment of Reduction in Mortality and Morbidity programme was carried out. Trends in renal impairment over 26 months were defined using Cockcroft-Gault (CG), simplified Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Mean estimated glomerular filtration rate (eGFR) was worse at every time point in patients with AF compared with those without AF, the difference being ∼11 mL/min (CG), 9 mL/min (CKD-EPI), and 7 mL/min (MDRD). As renal function declined, CG classified a greater proportion of patients as having moderate or severe CKD and agreement with MDRD/CKD-EPI declined. At least moderate renal impairment was present in a quarter of patients with AF at baseline, a third by study completion, and approaching a half at least once during follow-up. The projected need for NOAC dose reduction was accordingly high, though it varied between individual NOACs due to different criteria for adjustment.Conclusions: Renal impairment in patients with HF and AF is common, fluctuates, progresses, and frequently mandates NOAC dose reduction, though the need for cessation is rare. Baseline renal function, the method of estimating GFR, and intensity of monitoring should be considered when commencing oral anticoagulation. [ABSTRACT FROM AUTHOR]- Published
- 2016
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17. Is heart rate a risk marker in patients with chronic heart failure and concomitant atrial fibrillation? Results from the MAGGIC meta-analysis.
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Simpson, Joanne, Castagno, Davide, Doughty, Rob N., Poppe, Katrina K., Earle, Nikki, Squire, Iain, Richards, Mark, Andersson, Bert, Ezekowitz, Justin A., Komajda, Michel, Petrie, Mark C., McAlister, Finlay A., Gamble, Greg D., Whalley, Gillian A., and McMurray, John J.V.
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HEART beat ,BIOMARKERS ,HEART failure treatment ,ATRIAL fibrillation ,MORTALITY ,ADRENERGIC beta blockers ,META-analysis ,HEALTH outcome assessment ,ATRIAL fibrillation diagnosis ,COMPARATIVE studies ,CAUSES of death ,HEART failure ,HYPERTENSION ,RESEARCH methodology ,MEDICAL cooperation ,PROGNOSIS ,RESEARCH ,STATISTICS ,EVALUATION research ,PROPORTIONAL hazards models ,STROKE volume (Cardiac output) ,DISEASE complications ,DIAGNOSIS - Abstract
Aim: To investigate the relationship between heart rate and survival in patients with heart failure (HF) and coexisting atrial fibrillation (AF).Methods and Results: Patients with AF included in the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) meta-analysis were the main focus of this analysis (3259 patients from 17 studies). The outcome was all-cause mortality at 3 years. Heart rate was analysed as a categorical (tertiles; T1 ≤77 b.p.m., T2 78-98 b.p.m., T3 ≥98 b.p.m.) and continuous variable. Cox proportional hazard models were used to compare the risk of all-cause death between tertiles of baseline heart rate. Patients in the highest tertile were more often female, less likely to have an ischaemic aetiology or diabetes, had a lower ejection fraction but higher blood pressure and New York Heart Association (NYHA) class. Higher heart rate was associated with higher mortality in patients with sinus rhythm (SR) but not in those in AF. In patients with heart failure and reduced ejection fraction (HF-REF) and AF, death rates per 100 patient years were lowest in the highest heart rate tertile (T1 18.9 vs. T3 15.9) but this difference was not statistically significant (P = 0.10). In patients with heart failure and preserved ejection fraction (HF-PEF), death rates per 100 patient years were highest in the highest heart rate tertile (T1 14.6 vs. T3 16.0, P = 0.014). However, after adjustment for other important prognostic variables, higher heart rate was no longer associated with higher mortality in HF-PEF (or HF-REF).Conclusions: In this meta-analysis of patients with HF, heart rate does not have the same prognostic significance in patients in AF as it does in those in SR, irrespective of ejection fraction or treatment with beta-blocker. [ABSTRACT FROM AUTHOR]- Published
- 2015
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18. History of Atrial Fibrillation as a Risk Factor in Patients With Heart Failure and Preserved Ejection Fraction.
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Oluleye, Oludamilola W., Rector, Thomas S., Win, Sithu, McMurray, John J.V., Zile, Michael R., Komajda, Michel, McKelvie, Robert S., Massie, Barry, Carson, Peter E., and Anand, Inder S.
- Abstract
Atrial fibrillation (AFib) is common in heart failure (HF) with preserved ejection fraction (HFpEF). Current AFib stroke risk prediction models include the presence of HF but do not specifically include HFpEF as a risk factor. Whether a history of AFib should be used to identify patients with HFpEF who are at risk has not been established.Baseline characteristics and outcomes of patients with HFpEF in the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial were analyzed in relation to AFib. At baseline, 1209 (29.3%) had a history of AFib. Of these 557 (13.5%) had history of AFib alone, whereas 670 (16.2%) had both a history and AFib on ECG; 2901 (70.3%) had neither. There were no significant differences in the risk of stroke between the 2 groups with a history of AFib who did or did not have AFib present on baseline ECG. During a median follow-up of 53 months, a fatal or nonfatal stroke occurred in 6.5% (79/1209) patients with history of AFib compared with 3.9% (114/2901) with no AFib. Having a history of AFib was independently associated with higher risk of stroke (hazard ratio, 2.2; 95% confidence interval, 1.6-3.2; P<0.0001) compared with those with no history of AFib.In patients with HFpEF, a history of AFib was common and independently associated with increased risk of stroke, regardless of whether AFib was present on ECG. Patients with HFpEF and a history of AFib should be considered at risk. Further studies are needed to determine whether this risk can be safely reduced.URL: http://www.clinicaltrials.gov. Unique identifier: NCT000095238. [ABSTRACT FROM AUTHOR]
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- 2014
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19. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial.
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Alexander, John H., Lopes, Renato D., Thomas, Laine, Alings, Marco, Atar, Dan, Aylward, Philip, Goto, Shinya, Hanna, Michael, Huber, Kurt, Husted, Steen, Lewis, Basil S., McMurray, John J.V., Pais, Prem, Pouleur, Hubert, Steg, Philippe Gabriel, Verheugt, Freek W.A., Wojdyla, Daniel M., Granger, Christopher B., and Wallentin, Lars
- Abstract
Aims We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). Methods and results In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91%, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39–0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66–1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10% vs. warfarin 3.92%, HR 0.77, 95% CI 0.60–0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78%, HR without aspirin 0.65, 95% CI 0.55–0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Conclusion Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use. [ABSTRACT FROM PUBLISHER]
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- 2014
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20. Left Ventricular Systolic Dysfunction, Heart Failure, and the Risk of Stroke and Systemic Embolism in Patients With Atrial Fibrillation.
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McMurray, John J.V., Ezekowitz, Justin A., Lewis, Basil S., Gersh, Bernard J., van Diepen, Sean, Amerena, John, Bartunek, Jozef, Commerford, Patrick, Oh, Byung-Hee, Harjola, Veli-Pekka, Al-Khatib, Sana M., Hanna, Michael, Alexander, John H., Lopes, Renato D., Wojdyla, Daniel M., Wallentin, Lars, and Granger, Christopher B.
- Abstract
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.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.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.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. [ABSTRACT FROM AUTHOR]
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- 2013
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21. Profile of microvolt T-wave alternans testing in 1003 patients hospitalized with heart failure.
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Jackson, Colette E., Myles, Rachel C., Tsorlalis, Ioannis K., Dalzell, Jonathan R., Spooner, Richard J., Rodgers, John R., Bezlyak, Vladimir, Greenlaw, Nicola, Ford, Ian, Cobbe, Stuart M., Petrie, Mark C., and McMurray, John J.V.
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HEART failure patients ,HOSPITAL patients ,SCIENTIFIC observation ,CARDIAC arrest ,ATRIAL fibrillation ,CARDIAC pacemakers ,CARDIOVASCULAR diseases risk factors - Abstract
Aims Observational studies in selected populations have suggested that microvolt T-wave alternans (MTWA) testing may identify patients with heart failure (HF) at risk of sudden cardiac death. The aims of this study were to investigate the utility of MTWA testing in an unselected population of patients with HF and to evaluate the clinical characteristics associated with the MTWA results. Methods and results A total of 1003 patients hospitalized with decompensated HF were enrolled. MTWA testing was planned 1 month post-discharge; 648 patients returned for MTWA testing. Mean age was 70.8 ± 10.6 years and 58% were male. Of these patients who returned, 318 (49%) were ineligible for MTWA testing due to atrial fibrillation (AF), pacemaker dependency, or physical inability to undertake the test. Of the MTWA tests, 100 (30%) were positive, 78 (24%) were negative, and 152 (46%) were indeterminate; 112/152 indeterminate tests (74%) occurred because of failure to achieve target heart rate (HR) due to chronotropic incompetence or physical limitations. There were differences in patient characteristics according to MTWA result. Independent predictors of a negative result included younger age and higher left ventricular ejection fraction (LVEF). Independent predictors of a positive result included higher HR during MTWA testing and lower LVEF. Independent predictors of an indeterminate result included older age and history of previous/paroxysmal AF. Conclusions Only half of patients with HF are eligible for MTWA testing and the most common result is an indeterminate test. Patients with positive and indeterminate tests have different clinical characteristics. MTWA treadmill testing is not widely applicable in typical HF patients and is unlikely to refine risk stratification for sudden death on a population level. [ABSTRACT FROM PUBLISHER]
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- 2012
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22. Heart failure with preserved ejection fraction: Clinical characteristics of 4133 patients enrolled in the I-PRESERVE trial
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McMurray, John J.V., Carson, Peter E., Komajda, Michel, McKelvie, Robert, Zile, Michael R., Ptaszynska, Agata, Staiger, Christoph, Donovan, J. Mark, and Massie, Barry M.
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HEART failure , *HEART diseases , *THERAPEUTICS , *ETIOLOGY of diseases , *MYOCARDIAL revascularization , *CORONARY disease , *MYOCARDIAL infarction , *ATRIAL fibrillation - Abstract
Abstract: Background: We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction — the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). Methods and results: 4133 patients with a mean age of 72 years (a third were 75 years or older) were randomised and 60% were women. The mean (SD) LVEF was 59 (9)% and almost 80% of patients were in NYHA Class III or IV. Approximately 80% of patients were also overweight or obese. Heart failure was reported by investigators to have a hypertensive aetiology in 64% of patients. Prior myocardial infarction was relatively uncommon (24%), as was coronary revascularisation (13%). Atrial fibrillation and diabetes each occurred in between a quarter and a third of patients. The following treatments were used at baseline: diuretic 83%, beta-blocker 59%, calcium channel blocker 40%, ACE inhibitor 25%, spironolactone 15% and digoxin 14%. Conclusions: Patients in I-PRESERVE are broadly representative of those seen in epidemiological studies and, because of this, the results of this trial should be generally applicable to “real world” patients with heart failure and preserved ejection fraction. [Copyright &y& Elsevier]
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- 2008
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23. Previously known and newly diagnosed atrial fibrillation: A major risk indicator after a myocardial infarction complicated by heart failure or left ventricular dysfunction
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Køber, Lars, Swedberg, Karl, McMurray, John J.V., Pfeffer, Marc A., Velazquez, Eric J., Diaz, Rafael, Maggioni, Aldo P., Mareev, Viatcheslav, Opolski, Grzegorz, Van de Werf, Frans, Zannad, Faiez, Ertl, Georg, Solomon, Scott D., Zelenkofske, Steven, Rouleau, Jean-Lucien, Leimberger, Jeffrey D., and Califf, Robert M.
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MYOCARDIAL infarction ,CORONARY disease ,ATRIAL fibrillation ,ATRIAL arrhythmias ,FIBRINOLYTIC agents - Abstract
Abstract: Aims: To characterize the relationship between known and newly diagnosed atrial fibrillation (AF) and the risk of death and major cardiovascular (CV) events in patients with acute myocardial infarction (MI) complicated by heart failure (HF) and/or left ventricular systolic dysfunction (LVSD). Methods: The VALIANT trial enrolled 14,703 individuals with acute MI complicated by HF and/or LVSD. AF was assessed at presentation and at randomization (median 4.9 days after symptom onset). Primary outcomes were risk of death and major CV events 3 years following acute MI. Results: A total of 1812 with current AF (AF between presentation and randomization), 339 patients with prior AF (history of AF without current AF), and 12,509 without AF were enrolled. Patients with AF were older; had more prior HF, angina, and MI, and received beta-blockers and thrombolytics less often than those without AF. Three-year mortality estimates were 20% in those without AF, 37% with current AF, and 38% with prior AF. Compared with patients without AF, the multivariable adjusted HR of death was 1.25 (1.03–1.52; p =0.03) for prior AF and 1.32 (1.20–1.45; p <0.0001) for current AF. HR for major CV events was 1.15 (0.98–1.35; p =0.08) and 1.21 (1.12–1.31; p <0.0001). Conclusion: AF is associated with greater long-term mortality and adverse CV events with acute MI complicated by HF or LVSD. [Copyright &y& Elsevier]
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- 2006
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24. Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.
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Ducharme, Anique, Swedberg, Karl, Pfeffer, Marc A., Cohen-Solal, Alain, Granger, Christopher B., Maggioni, Aldo P., Michelson, Eric L., McMurray, John J.V., Olsson, Lars, Rouleau, Jean L., Young, James B., Olofsson, Bertil, Puu, Margareta, Yusuf, Salim, and CHARM Investigators
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HEART disease related mortality ,PREVENTION of heart diseases ,CARDIAC arrest ,MORTALITY ,ATRIAL fibrillation prevention ,ATRIAL fibrillation ,CLINICAL trials ,COMPARATIVE studies ,HEART failure ,HETEROCYCLIC compounds ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,COMORBIDITY ,LOGISTIC regression analysis ,EVALUATION research ,RENIN-angiotensin system ,ANGIOTENSIN receptors ,PHYSIOLOGY ,THERAPEUTICS - Abstract
Background: Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population.Methods: 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used.Results: 6379 patients (83.9%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.15%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57).Conclusions: Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF. [ABSTRACT FROM AUTHOR]- Published
- 2006
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25. Cardiac Myosin Activator Omecamtiv Mecarbil Improves Left Ventricular Myocardial Deformation in Chronic Heart Failure: The COSMIC-HF Trial.
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Biering-Sørensen, Tor, Minamisawa, Masatoshi, Claggett, Brian, Liu, Jiankang, Felker, G. Michael, McMurray, John J.V., Malik, Fady I., Abbasi, Siddique, Kurtz, Christopher E., Teerlink, John R., and Solomon, Scott D.
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- 2020
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26. Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction.
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Rørth, Rasmus, Jhund, Pardeep S., Yilmaz, Mehmet B., Kristensen, Søren Lund, Welsh, Paul, Desai, Akshay S., Køber, Lars, Prescott, Margaret F., Rouleau, Jean L., Solomon, Scott D., Swedberg, Karl, Zile, Michael R., Packer, Milton, and McMurray, John J.V.
- Abstract
Supplemental Digital Content is available in the text. Background: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). Methods: Eligibility criteria in PARADIGM-HF included New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and elevated natriuretic peptides: BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (for patients with HF hospitalization within 12 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL). BNP and NT-proBNP were measured simultaneously at screening and only patients who fulfilled entry criteria for both natriuretic peptides were included in the present analysis. The BNP/NT-proBNP criteria were not different for patients in atrial fibrillation. Estimated glomerular filtration rate <30 mL/min per 1.73 m
2 was a key exclusion criterion. Results: The median baseline concentration of NT-proBNP was 2067 (Q1, Q3: 1217–4003) and BNP 318 (Q1, Q3: 207–559), and the ratio, calculated from the raw data, was ≈6.25:1. This ratio varied considerably according to rhythm (atrial fibrillation 8.03:1; no atrial fibrillation 5.75:1) and with age, renal function, and body mass index but not with left ventricular ejection fraction. Each peptide was similarly predictive of death (all-cause, cardiovascular, sudden and pump failure) and heart failure hospitalization, for example, cardiovascular death: BNP hazard ratio, 1.41 (95% CI, 1.33–1.49) per 1 SD increase, P <0.0001; NT-proBNP, 1.45 (1.36–1.54); P <0.0001. Conclusions: The ratio of NT-proBNP to BNP in heart failure and reduced ejection fraction appears to be greater than generally appreciated, differs between patients with and without atrial fibrillation, and increases substantially with increasing age and decreasing renal function. These findings are important for comparison of natriuretic peptide concentrations in heart failure and reduced ejection fraction. [ABSTRACT FROM AUTHOR]- Published
- 2020
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27. IGFBP7 (Insulin-Like Growth Factor–Binding Protein-7) and Neprilysin Inhibition in Patients With Heart Failure.
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Januzzi, James L., Packer, Milton, Claggett, Brian, Liu, Jiankang, Shah, Amil M., Zile, Michael R., Pieske, Burkert, Voors, Adriaan, Gandhi, Parul U., Prescott, Margaret F., Shi, Victor, Lefkowitz, Martin P., McMurray, John J.V., and Solomon, Scott D.
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Supplemental Digital Content is available in the text. Background: Increased activity of IGFBP7 (insulin-like growth factor–binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people. Methods and Results: In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P <0.001); modest association between IGFBP7 and higher early mitral inflow velocity/annular diastolic velocity (P =0.03) and early diastole/peak late diastolic velocity ratio (P =0.04) was also seen. IGFBP7 concentrations were higher in those with LAVi ≥34 mL/m
2 compared with lower LAVi at all time points (all P <0.01). IGFBP7 independently predicted LAVi at baseline even in the presence of NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentrations; highest LAVi was seen in those with elevation in both biomarkers. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations over 36 weeks compared with valsartan (adjusted treatment effect, −7%; P <0.001). Conclusions: Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00887588. [ABSTRACT FROM AUTHOR]- Published
- 2018
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28. Feasibility/eligibility of T-wave alternans testing in patients with heart failure: should we rethink our current modus operandi?: reply.
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Jackson, Colette E., Myles, Rachel C., Tsorlalis, Ioannis K., Dalzell, Jonathan R., Spooner, Richard J., Rodgers, John R., Bezlyak, Vladimir, Greenlaw, Nicola, Ford, Ian, Cobbe, Stuart M., Petrie, Mark C., and McMurray, John J.V.
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LETTERS to the editor ,HEART failure treatment ,POLARIZATION (Electricity) ,FEASIBILITY studies ,ATRIAL fibrillation ,CARDIAC pacemakers ,CARDIOMYOPATHIES - Published
- 2012
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29. Atrial fibrillation: Profile and burden of an evolving epidemic in the 21st century.
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Ball, Jocasta, Carrington, Melinda J., McMurray, John J.V., and Stewart, Simon
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ATRIAL fibrillation , *BURDEN of care , *PUBLIC health , *ECONOMIC impact , *SOCIAL impact , *METABOLIC disorders , *CARDIOVASCULAR diseases ,MEDICAL literature reviews - Abstract
Abstract: Background: Atrial fibrillation (AF) represents an increasing public health challenge with profound social and economic implications. Methods: A comprehensive synthesis and review of the AF literature was performed. Overall, key findings from 182 studies were used to describe the indicative scope and impact of AF from an individual to population perspective. Results: There are many pathways to AF including advancing age, cardiovascular disease and increased levels of obesity/metabolic disorders. The reported population prevalence of AF ranges from 2.3%–3.4% and historical trends reflect increased AF incidence. Estimated life-time risk of AF is around 1 in 4. Primary care contacts reflect whole population trends: AF-related case-presentations increase from less than 0.5% in those aged 40years or less to 6–12% for those aged 85years or more. Globally, AF-related hospitalisations (primary or secondary diagnosis) showed an upward trend (from ~35 to over 100 admissions/10,000 persons) during 1996 to 2006. The estimated cost of AF is greater than 1% of health care expenditure and rising with hospitalisations the largest contributor. For affected individuals, quality of life indices are poor and AF confers an independent 1.5 to 2.0-fold probability of death in the longer-term. AF is also closely linked to ischaemic stroke (3- to 5-fold risk), chronic heart failure (up to 50% develop AF) and acute coronary syndromes (up to 25% develop AF) with consistently worse outcomes reported with concurrent AF. Future projections predict at least a doubling of AF cases by 2050. Summary: AF represents an evolving, global epidemic providing considerable challenges to minimise its impact from an individual to whole society perspective. [Copyright &y& Elsevier]
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- 2013
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30. Eplerenone and Atrial Fibrillation in Mild Systolic Heart Failure: Results From the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) Study
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Swedberg, Karl, Zannad, Faiez, McMurray, John J.V., Krum, Henry, van Veldhuisen, Dirk J., Shi, Harry, Vincent, John, and Pitt, Bertram
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ATRIAL fibrillation , *HEART failure , *ALDOSTERONE antagonists , *HOSPITAL admission & discharge , *ANGIOTENSIN-receptor blockers , *MINERALOCORTICOID receptors , *GLOMERULAR filtration rate , *MEDICAL statistics - Abstract
Objectives: The purpose of this study was to analyze the incidence of new atrial fibrillation or flutter (AFF) in the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure) database. Background: Aldosterone antagonism in heart failure might influence atrial fibrosis and remodeling and, therefore, risk of developing AFF. The development of new AFF was a pre-specified secondary endpoint in the EMPHASIS-HF study. Methods: Patients in New York Heart Association functional class II and with ejection fraction ≤35% were eligible for EMPHASIS-HF. History of AFF at baseline was reported by investigators using the study case report form. New onset AFF (in those with no history of AFF at baseline) was reported using a specific endpoint form; in a sensitivity analysis we also examined the effect of eplerenone on AFF reported as an adverse event. Results: New onset AFF was significantly reduced by eplerenone: 25 of 911 (2.7%) versus 40 of 883 (4.5%) in the placebo group (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.35 to 0.96; p = 0.034). The reduction in the primary endpoint with eplerenone was similar among patients with and without AFF at baseline (HR: 0.60, 95% CI: 0.46 to 0.79 vs. HR: 0.70, 95% CI: 0.57 to 0.85, respectively; p for interaction = 0.41). The risk of cardiovascular (CV) death or hospital admission for worsening heart failure, the primary endpoint, was not significantly different in subjects with and without AFF at baseline (both study groups combined: HR: 1.23, 95% CI: 0.81 to 1.86; p = 0.33). Conclusions: In patients with systolic heart failure and mild symptoms, eplerenone reduced the incidence of new onset AFF. The effects of eplerenone on the reduction of major CV events were similar in patients with and without AFF at baseline. [ABSTRACT FROM AUTHOR]
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- 2012
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31. Apixaban versus Warfarin in Patients with Atrial Fibrillation.
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Granger, Christopher B., Alexander, John H., McMurray, John J.V., Lopes, Renato D., Hylek, Elaine M., Hanna, Michael, Al-Khalidi, Hussein R., Ansell, Jack, Atar, Dan, Avezum, Alvaro, Bahit, M. Cecilia, Diaz, Rafael, Easton, J. Donald, Ezekowitz, Justin A., Flaker, Greg, Garcia, David, Geraldes, Margarida, Gersh, Bernard J., Golitsyn, Sergey, and Goto, Shinya
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VITAMIN K , *CEREBROVASCULAR disease prevention , *ATRIAL fibrillation , *CLINICAL drug trials , *WARFARIN , *PATIENTS - Abstract
Background: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. Methods: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. Results: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). Conclusions: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.) [ABSTRACT FROM PUBLISHER]
- Published
- 2011
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32. Increased Mortality after Dronedarone Therapy for Severe Heart Failure.
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Køber, Lars, Torp-Pedersen, Christian, McMurray, John J.V., Gøtzsche, Ole, Lévy, Samuel, Crijns, Harry, Amlie, Jan, and Carlsen, Jan
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DRUG side effects , *HEART failure treatment , *HEART diseases , *ARRHYTHMIA , *ATRIAL fibrillation - Abstract
Background: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure. Methods: In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure. Results: After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure — 10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group. Conclusions: In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.) N Engl J Med 2008;358:2678-87. [ABSTRACT FROM AUTHOR]
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- 2008
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33. ALBIGLUTIDE AND ATRIAL FIBRILLATION/ATRIAL FLUTTER IN PATIENTS WITH TYPE 2 DIABETES AND ESTABLISHED CARDIOVASCULAR DISEASE - A SECONDARY ANALYSIS OF THE HARMONY OUTCOMES TRIAL.
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Krychtiuk, Konstantin A., Marquis-Gravel, Guillaume, Murphy, Shannon, Chiswell, Karen E., Green, Jennifer, Leiter, Lawrence A., Lopes, Renato D., Del Prato, Stefano, McMurray, John J.V., Hernandez, Adrian F., and Granger, Christopher B.
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ATRIAL flutter , *TYPE 2 diabetes , *ATRIAL fibrillation , *CARDIOVASCULAR diseases , *SECONDARY analysis - Published
- 2024
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34. Long-Term Cardiovascular Outcomes in Systemic Lupus Erythematosus.
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Yafasova, Adelina, Fosbøl, Emil L., Schou, Morten, Baslund, Bo, Faurschou, Mikkel, Docherty, Kieran F., Jhund, Pardeep S., McMurray, John J.V., Sun, Guoli, Kristensen, Søren L., Torp-Pedersen, Christian, Køber, Lars, and Butt, Jawad H.
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CEREBRAL embolism & thrombosis , *SYSTEMIC lupus erythematosus , *ISCHEMIC stroke , *VENTRICULAR arrhythmia , *ATRIAL fibrillation , *STROKE patients , *THROMBOEMBOLISM - Abstract
Background: Data on long-term cardiovascular outcomes in systemic lupus erythematosus (SLE) are sparse.Objectives: This study sought to examine the long-term risk and prognosis associated with cardiovascular outcomes, including heart failure (HF), in patients with SLE.Methods: Using Danish administrative registries, risks of outcomes were compared between SLE patients (diagnosed 1996 to 2018, no history of cardiovascular disease) and age-, sex-, and comorbidity-matched control subjects from the background population (matched 1:4). Furthermore, mortality following HF diagnosis was compared between SLE patients developing HF and age- and sex-matched non-SLE control subjects with HF (matched 1:4).Results: A total of 3,411 SLE patients (median age: 44.6 years [25th to 75th percentile: 31.9 to 57.0 years]; 14.1% men) were matched with 13,644 control subjects. The median follow-up was 8.5 years (25th to 75th percentile: 4.0 to 14.4 years). Absolute 10-year risks of outcomes were: HF, 3.71% (95% confidence interval [CI]: 3.02% to 4.51%) for SLE patients, 1.94% (95% CI: 1.68% to 2.24%) for control subjects; atrial fibrillation, 4.35% (95% CI: 3.61% to 5.18%) for SLE patients, 2.82% (95% CI: 2.50% to 3.16%) for control subjects; ischemic stroke, 3.75% (95% CI: 3.06% to 4.54%) for SLE patients, 1.92% (95% CI: 1.66% to 2.20%) for control subjects; myocardial infarction, 2.17% (95% CI: 1.66% to 2.80%) for SLE patients, 1.49% (95% CI: 1.26% to 1.75%) for control subjects; venous thromboembolism, 6.03% (95% CI: 5.17% to 6.98%) for SLE patients, 1.68% (95% CI: 1.44% to 1.95%) for control subjects; and the composite of implantable cardioverter-defibrillator implantation/ventricular arrhythmias/cardiac arrest, 0.89% (95% CI: 0.58% to 1.31%) for SLE patients, 0.30% (95% CI: 0.20% to 0.43%) for control subjects. SLE with subsequent HF was associated with higher mortality compared with HF without SLE (adjusted hazard ratio: 1.50; 95% CI: 1.08 to 2.08).Conclusions: SLE patients had a higher associated risk of HF and other cardiovascular outcomes compared with matched control subjects. Among patients developing HF, a history of SLE was associated with higher mortality. [ABSTRACT FROM AUTHOR]- Published
- 2021
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35. Reply: Time for an "Atrial-Watchful" Approach for Heart Failure Patients With a Cardiac Implantable Electronic Device.
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Mogensen, Ulrik M., Køber, Lars, and McMurray, John J.V.
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HEART failure treatment , *IMPLANTABLE cardioverter-defibrillators , *ANTICOAGULANTS , *VENTRICULAR ejection fraction , *ATRIAL fibrillation , *COMPARATIVE studies , *HEART atrium , *HEART failure , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *EVALUATION research , *STROKE volume (Cardiac output) ,STROKE risk factors - Published
- 2018
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36. Stroke Risk in Patients With Reduced Ejection Fraction After Myocardial Infarction Without Atrial Fibrillation.
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Ferreira, João Pedro, Girerd, Nicolas, Gregson, John, Latar, Ichraq, Sharma, Abhinav, Pfeffer, Marc A., McMurray, John J.V., Abdul-Rahim, Azmil H., Pitt, Bertram, Dickstein, Kenneth, Rossignol, Patrick, Zannad, Faiez, and High-Risk Myocardial Infarction Database Initiative
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ATRIAL fibrillation , *MYOCARDIAL infarction , *GLOMERULAR filtration rate , *HYPERTENSION ,STROKE risk factors - Abstract
Background: Stroke can occur after myocardial infarction (MI) in the absence of atrial fibrillation (AF).Objectives: This study sought to identify risk factors (excluding AF) for the occurrence of stroke and to develop a calibrated and validated stroke risk score in patients with MI and heart failure (HF) and/or systolic dysfunction.Methods: The datasets included in this pooling initiative were derived from 4 trials: CAPRICORN (Effect of Carvedilol on Outcome After Myocardial Infarction in Patients With Left Ventricular Dysfunction), OPTIMAAL (Optimal Trial in Myocardial Infarction With Angiotensin II Antagonist Losartan), VALIANT (Valsartan in Acute Myocardial Infarction Trial), and EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study); EPHESUS was used for external validation. A total of 22,904 patients without AF or oral anticoagulation were included in this analysis. The primary outcome was stroke, and death was treated as a "competing risk."Results: During a median follow-up of 1.9 years (interquartile range: 1.3 to 2.7 years), 660 (2.9%) patients had a stroke. These patients were older, more often female, smokers, and hypertensive; they had a higher Killip class; a lower estimated glomerular filtration rate; and a higher proportion of MI, HF, diabetes, and stroke histories. The final stroke risk model retained older age, Killip class 3 or 4, estimated glomerular filtration rate ≤45 ml/min/1.73 m2, hypertension history, and previous stroke. The models were well calibrated and showed moderate to good discrimination (C-index = 0.67). The observed 3-year event rates increased steeply for each sextile of the stroke risk score (1.8%, 2.9%, 4.1%, 5.6%, 8.3%, and 10.9%, respectively) and were in agreement with the expected event rates.Conclusions: Readily accessible risk factors associated with the occurrence of stroke were identified and incorporated in an easy-to-use risk score. This score may help in the identification of patients with MI and HF and a high risk for stroke despite their not presenting with AF. [ABSTRACT FROM AUTHOR]- Published
- 2018
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37. Type of Atrial Fibrillation and Outcomes in Patients With Heart Failure and Reduced Ejection Fraction.
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Mogensen, Ulrik M., Jhund, Pardeep S., Abraham, William T., Desai, Akshay S., Dickstein, Kenneth, Packer, Milton, Rouleau, Jean L., Solomon, Scott D., Swedberg, Karl, Zile, Michael R., Køber, Lars, McMurray, John J.V., and PARADIGM-HF and ATMOSPHERE Investigators and Committees
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ATRIAL fibrillation , *HEART failure patients , *MEDICAL statistics , *HOSPITAL care , *HEART disease related mortality , *ATRIAL fibrillation diagnosis , *HEART physiology , *LEFT heart ventricle , *COMPARATIVE studies , *HEART failure , *LONGITUDINAL method , *RESEARCH methodology , *MEDICAL cooperation , *PROGNOSIS , *RESEARCH , *RISK assessment , *SURVIVAL , *WORLD health , *EVALUATION research , *RANDOMIZED controlled trials , *STROKE volume (Cardiac output) , *DISEASE complications - Abstract
Background: Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown.Objectives: This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction.Methods: The study analyzed patients 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. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type.Results: Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; p < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%).Conclusions: Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658). [ABSTRACT FROM AUTHOR]- Published
- 2017
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38. High-Sensitivity Troponin T and Risk Stratification in Patients With Atrial Fibrillation During Treatment With Apixaban or Warfarin.
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Hijazi, Ziad, Wallentin, Lars, Siegbahn, Agneta, Andersson, Ulrika, Alexander, John H., Atar, Dan, Gersh, Bernard J., Hanna, Michael, Harjola, Veli Pekka, Horowitz, John D., Husted, Steen, Hylek, Elaine M., Lopes, Renato D., McMurray, John J.V., and Granger, Christopher B.
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ATRIAL fibrillation treatment , *TROPONIN , *WARFARIN , *ANTICOAGULANTS , *CONGESTIVE heart failure , *HYPERTENSION risk factors , *CONFIDENCE intervals , *DISEASE risk factors - Abstract
Objectives: The aim of this study was to evaluate the prognostic value of high-sensitivity troponin T (hs-TnT) in addition to clinical risk factors and the CHA2DS2VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) risk score in patients with atrial fibrillation (AF). Background: The level of troponin is a powerful predictor of cardiovascular events and mortality. Methods: A total of 14,897 patients with AF were randomized to treatment with apixaban or warfarin in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial. The associations between baseline hs-TnT levels and outcomes were evaluated using adjusted Cox regression models. Results: Levels of hs-TnT were measurable in 93.5% of patients; 75% had levels >7.5 ng/l, 50% had levels >11.0 ng/l, and 25% had levels >16.7 ng/l. During a median 1.9-year period, the annual rates of stroke or systemic embolism ranged from 0.87% in the lowest hs-TnT quartile to 2.13% in the highest hs-TnT quartile (adjusted hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.35 to 2.78; p = 0.0010). The annual rates in the corresponding groups ranged from 0.46% to 4.24% (adjusted HR: 4.31; 95% CI: 2.91 to 6.37; p < 0.0001) for cardiac death and from 1.26% to 4.21% (adjusted HR: 1.91; 95% CI: 1.43 to 2.56; p = 0.0001) for major bleeding. Adding hs-TnT levels to the CHA2DS2VASc score improved the C statistic from 0.620 to 0.635 for stroke or systemic embolism (p = 0.0226), from 0.592 to 0.711 for cardiac death (p < 0.0001), and from 0.591 to 0.629 for major bleeding (p < 0.0001). Apixaban reduced rates of stroke, mortality, and bleeding regardless of the hs-TnT level. Conclusions: Levels of hs-TnT are often elevated in patients with AF. The hs-TnT level is independently associated with an increased risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc risk score. The benefits of apixaban as compared with warfarin are consistent regardless of the hs-TnT level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984) [Copyright &y& Elsevier]
- Published
- 2014
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39. Atrial Fibrillation and Risk of Clinical Events in Chronic Heart Failure With and Without Left Ventricular Systolic Dysfunction: Results From the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) Program
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Olsson, Lars G., Swedberg, Karl, Ducharme, Anique, Granger, Christopher B., Michelson, Eric L., McMurray, John J.V., Puu, Margareta, Yusuf, Salim, and Pfeffer, Marc A.
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ATRIAL fibrillation , *HEART diseases , *DISEASES , *CARDIOVASCULAR system , *MORTALITY - Abstract
Objectives: We assessed the risk of adverse cardiovascular (CV) outcomes associated with atrial fibrillation (AF) in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) program, which enrolled patients with chronic heart failure (CHF) and a broad range of ejection fractions (EFs). Background: Atrial fibrillation is associated with an increased risk of adverse CV outcomes in patients with CHF and reduced EF. The risk of AF in patients with CHF and preserved left ventricular ejection fraction (PEF) is unknown. Methods: A total of 7,599 patients with symptomatic CHF were randomized to candesartan or placebo. Patients were divided by baseline EF (≤40% or >40%) in low or preserved EF groups. Major outcomes were cardiovascular death or hospitalization for worsening heart failure, and all-cause mortality. Median follow-up was 37.7 months. Results: A total of 670 (17%) patients in the low EF group and 478 (19%) in the PEF group had AF at baseline. Atrial fibrillation predicted a high risk of cardiovascular morbidity and mortality regardless of baseline EF. Patients with AF and low EF had the highest absolute risk for adverse CV outcomes. However, AF was associated with greater relative increased risk of the major outcomes in patients with PEF than in patients with low EF: hazard ratio 1.72 (95% confidence interval [CI] 1.45 to 2.06) versus 1.29 (95% CI 1.14 to 1.46), respectively. The same was true for the risk of all-cause mortality. Candesartan was associated with similar treatment effects regardless of baseline rhythm. Conclusions: Atrial fibrillation is associated with an increased risk of CV outcomes in patients with CHF and either reduced EF or PEF. Candesartan improved outcomes similarly regardless of baseline rhythm. [Copyright &y& Elsevier]
- Published
- 2006
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40. Seasonal variation in morbidity and mortality related to atrial fibrillation
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Murphy, Niamh F., Stewart, Simon, MacIntyre, Kate, Capewell, Simon, and McMurray, John J.V.
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ATRIAL fibrillation , *MORTALITY , *SEASONAL variations of diseases , *HOSPITAL patients - Abstract
To determine whether there is seasonal variation in hospitalisations and deaths due to atrial fibrillation (AF) and to examine possible contributors to such variability.We used the linked Scottish Morbidity Record scheme, which provides individualised morbidity and mortality data for the entire Scottish population.Between 1990 and 1996, there were a total of 33,582 male and 34,463 female hospitalisations related to AF. Significantly more admissions occurred in winter compared to summer (P<0.0001). In women, the peak number of admissions (106 per day) occurred in December (12% more than average) and the lowest number (89) in June (6% less than average). The respective figures for men were 10% more (101), 2% less (90). In both sexes, the greatest variation occurred in those aged >85 years—peak winter rates being 35–39% higher than average. A similar phenomenon was evident in relation to mortality in these patients. The average number of men who died during December was 22% higher, and in August 12% lower, than average, P<0.001. In women, the equivalent figures were 28% higher (December) and 14% lower (August), P<0.001. The winter peak of AF admissions did not, however, coincide with the lowest temperatures, and other factors such as seasonal variation in respiratory infection, may account for the monthly variation observed in hospitalisations for AF.There is substantial seasonal variation in AF hospitalisations and deaths, particularly in the elderly. [Copyright &y& Elsevier]
- Published
- 2004
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41. A population-based study of the long-term risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley study
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Stewart, Simon, Hart, Carole L., Hole, David J., and McMurray, John J.V.
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ATRIAL fibrillation ,HEART disease epidemiology - Abstract
: PurposeTo describe the effect of atrial fibrillation on long-term morbidity and mortality.: Subjects and methodsThe Renfrew/Paisley Study surveyed 7052 men and 8354 women aged 45–64 years between 1972 and 1976. All hospitalizations and deaths occurring during the subsequent 20 years were analyzed by the presence or absence of atrial fibrillation at baseline. Lone atrial fibrillation was defined in the absence of other cardiovascular signs or symptoms. Cox proportional hazards models were used to adjust for age and cardiovascular conditions.: ResultsAfter 20 years, 42 (89%) of the 47 women with atrial fibrillation had a cardiovascular event (death or hospitalization), compared with 2276 (27%) of the 8307 women without this arrhythmia. Among men, 35 (66%) of 53 with atrial fibrillation had an event, compared with 3151 (45%) of 6999 without atrial fibrillation. In women, atrial fibrillation was an independent predictor of cardiovascular events (rate ratio [RR] = 3.0; 95% confidence interval [CI]: 2.1–4.2), fatal or nonfatal strokes (RR = 3.2; 95% CI: 1.0–5.0), and heart failure (RR = 3.4; 95% CI: 1.9–6.2). The rate ratios among men were 1.8 (95% CI: 1.3–2.5) for cardiovascular events, 2.5 (95% CI: 1.3–4.8) for strokes, and 3.4 (95% CI: 1.7–6.8) for heart failure. Atrial fibrillation was an independent predictor of all-cause mortality in women (RR = 2.2; 95% CI: 1.5–3.2) and men (RR = 1.5; 95% CI: 1.2–2.2). However, lone atrial fibrillation (which occurred in 15 subjects) was not associated with a statistically significant increase in either cardiovascular events (RR = 1.5; 95% CI: 0.6–3.6) or mortality (RR = 1.8; 95% CI: 0.9–3.8).: ConclusionAtrial fibrillation is associated with an increased long-term risk of stroke, heart failure, and all-cause mortality, especially in women. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
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