| 1. |
- Castagno, D., et al.
(författare)
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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
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 59:20, s. 1785-1795
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The 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. BACKGROUND: Elevated 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). METHODS: Patients 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%) and presence (or absence) of AF at baseline. RESULTS: After 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 <0.001). CONCLUSIONS: Resting heart rate is an important predictor of outcome in patients with stable chronic HF without AF, regardless of LVEF or beta-blocker use.
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| 2. |
- Curtain, J. P., et al.
(författare)
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Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF
- 2022
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:3, s. 551-561
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Tidskriftsartikel (refereegranskat)abstract
- Aims Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods and results Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.
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| 3. |
- Kristensen, S. L., et al.
(författare)
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Prevalence and incidence of intraventricular conduction delays and outcomes in patients with heart failure and reduced ejection fraction: Insights from PARADIGM-HF and ATMOSPHERE
- 2020
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:12, s. 2370-9
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The importance of intraventricular conduction delay (IVCD), incidence of new IVCD and its relationship to outcomes in heart failure and reduced ejection fraction (HFrEF) is not well studied. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. METHODS AND RESULTS: Risk of the primary composite outcome of cardiovascular death or HF hospitalization and all-cause mortality were estimated by use of Cox regression according to baseline QRS duration and morphology in 11,861 patients without an intracardiac device. At baseline, 1,789 (15.1%) patients had left bundle branch block (LBBB), 524 (4.4%) RBBB, 454 (3.8%) non-specific IVCD, 2588 (21.8%) "mildly abnormal" QRS (110-129 milliseconds [ms]) and 6506 (54.9%) QRS <110 ms. During a median follow-up of 2.5 years, the risk of the primary composite endpoint was higher among those with a wide QRS, irrespective of morphology: hazard ratios (95% CI) LBBB 1.36 (1.23, 1.50), RBBB 1.54 (1.31, 1.79), nonspecific IVCD 1.65 (1.40, 1.94) and QRS 110-129 ms 1.35 (95% CI 1.23, 1.47), compared with QRS duration <110 ms. A total of 1,234 (15.6%) patients developed new-onset QRS-widening >/=130 ms (6.1 per 100 py). Incident LBBB occurred in 495 (6.3%) patients (2.4 per 100 py) and was associated with a higher risk of the primary composite outcome; HR 1.42 (1.12, 1.82). CONCLUSION: In patients with HFrEF, a wide QRS was associated with worse clinical outcomes irrespective of morphology. The annual incidence of new-onset LBBB was around 2.5%, and associated with a higher risk of adverse outcomes, highlighting the importance of repeat ECG review.
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| 4. |
- Vazir, A., et al.
(författare)
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Prognostic importance of temporal changes in resting heart rate in heart failure patients: an analysis of the CHARM program
- 2015
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 36:11, s. 669-675
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Resting heart rate (HR) is a predictor of adverse outcome in patients with heart failure (HF). Whether changes in HR over time in patients with chronic HF are also associated with adverse outcome is unknown. We explored the relationship between changes in HR from a preceding visit, time-updated HR (i.e. most recent available HR value from a clinic visit) and subsequent outcomes in patients with chronic HF. METHODS AND RESULTS: We studied 7599 patients enrolled in the candesartan in heart failure: assessment of reduction in mortality and morbidity program. We calculated change in HR from the preceding visit and explored its association with outcomes in Cox proportional hazards models, as well the association between time-updated HR and outcome. An increase in HR from preceding visit was associated with a higher risk of all-cause mortality and the composite endpoint of cardiovascular death or hospitalization for HF (adjusted hazard ratio 1.06, 95% confidence intervals, CI: 1.05-1.08, P < 0.001, per 5 b.p.m. higher HR), with lowering of HR being associated with lower risk, adjusting for covariates, including time-updated beta-blocker dose and baseline HR. Time-updated resting HR at each visit was also associated with risk (adjusted hazard ratio 1.07, 95% CI: 1.06-1.09; P < 0.001, per 5 b.p.m. higher HR). CONCLUSIONS: Change in HR over time predicts outcome in patients with chronic HF, as does time-updated HR during follow-up. These data suggest that frequent outpatient monitoring of HR, and identification of changes over time, possibly with remote technologies, may identify patients with HF who may be at increased risk of rehospitalization or death.
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| 5. |
- Docherty, Kieran F, et al.
(författare)
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Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.
- 2020
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 22:3, s. 528-538
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Tidskriftsartikel (refereegranskat)abstract
- 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.Of 13562 patients from two large HFrEF trials, 10113 (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 10bpm), 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 1year (≤-10bpm, ≥+10bpm, <±10bpm). 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 10bpm: 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 10bpm 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.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.ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658.
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| 6. |
- Silvano, Alessandro, et al.
(författare)
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Observing Antarctic Bottom Water in the Southern Ocean
- 2023
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Ingår i: Frontiers in Marine Science. - 2296-7745. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Dense, cold waters formed on Antarctic continental shelves descend along the Antarctic continental margin, where they mix with other Southern Ocean waters to form Antarctic Bottom Water (AABW). AABW then spreads into the deepest parts of all major ocean basins, isolating heat and carbon from the atmosphere for centuries. Despite AABW's key role in regulating Earth's climate on long time scales and in recording Southern Ocean conditions, AABW remains poorly observed. This lack of observational data is mostly due to two factors. First, AABW originates on the Antarctic continental shelf and slope where in situ measurements are limited and ocean observations by satellites are hampered by persistent sea ice cover and long periods of darkness in winter. Second, north of the Antarctic continental slope, AABW is found below approximately 2 km depth, where in situ observations are also scarce and satellites cannot provide direct measurements. Here, we review progress made during the past decades in observing AABW. We describe 1) long-term monitoring obtained by moorings, by ship-based surveys, and beneath ice shelves through bore holes; 2) the recent development of autonomous observing tools in coastal Antarctic and deep ocean systems; and 3) alternative approaches including data assimilation models and satellite-derived proxies. The variety of approaches is beginning to transform our understanding of AABW, including its formation processes, temporal variability, and contribution to the lower limb of the global ocean meridional overturning circulation. In particular, these observations highlight the key role played by winds, sea ice, and the Antarctic Ice Sheet in AABW-related processes. We conclude by discussing future avenues for observing and understanding AABW, impressing the need for a sustained and coordinated observing system.
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| 7. |
- Wikstrand, John, 1938, et al.
(författare)
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The large-scale placebo-controlled beta-blocker studies in systolic heart failure revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with stratified subsets from MERIT-HF
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 275:2, s. 134-143
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment. MethodsWe compared stratified ((s)) subsets in MERIT-HF with patients in CIBIS-II [New York Heart Association (NYHA) class III/IV and ejection fraction (EF) 35%] and COPERNICUS (NYHA III/IV and EF <25%) and in patients with systolic HF in SENIORS-SHF (age 70years and EF 35%). ResultsThe annual mortality rates in the placebo and beta-blocker arms were: (i) CIBIS-II (n=2647), 13.2% vs. 8.8% (relative risk reduction 34%, 95% CI: 19-46, P<0.0001) and MERIT-HFs (n=2002), 14.8% vs. 8.6% (relative risk reduction 42%, 95% CI: 24-56, P<0.0001); (ii) COPERNICUS (n=2289), 19.7% vs. 12.8% (relative risk reduction 35%, 95% CI: 19-48, P=0.0014) and MERIT-HFs (n=795), 19.1% vs. 11.7% (relative risk reduction 39%; 95% CI: 11-58, P=0.0086); (iii) SENIORS-SHF (n= 1359), 11.3% vs. 9.7% (relative risk reduction 16%, NS) and MERIT-HFs (n=985), 14.8% vs. 10.1% (relative risk reduction 32%, 95% CI: 2-53, P=0.038). The effects on the other outcomes assessed were similar. Analyses indicated fewer discontinuations from randomized treatment on beta-blockers compared with placebo in COPERNICUS and the MERIT-HFs subsets. ConclusionThe efficacy and tolerability of bisoprolol, carvedilol and metoprolol CR/XL are similar in patients with systolic HF, irrespective of NYHA class or ejection fraction. Nebivolol is less effective and not better tolerated.
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