Heart failure (HF) and atrial fibrillation (AF) are two conditions that are likely to dominate the next 50 years of cardiovascular (CV) care. Both are increasingly prevalent and associated with high ...morbidity, mortality, and healthcare cost. They are closely inter-related with similar risk factors and shared pathophysiology. Patients with concomitant HF and AF suffer from even worse symptoms and poorer prognosis, yet evidence-based evaluation and management of this group of patients is lacking. In this review, we evaluate the common mechanisms for the development of AF in HF patients and vice versa, focusing on the evidence for potential treatment strategies. Recent data have suggested that these patients may respond differently than those with HF or AF alone. These results highlight the clear clinical need to identify and treat according to best evidence, in order to prevent adverse outcomes and reduce the huge burden that HF and AF are expected to have on global healthcare systems in the future. We propose an easy-to-use clinical mnemonic to aid the initial management of newly discovered concomitant HF and AF, the CAN-TREAT HFrEF + AF algorithm (Cardioversion if compromised; Anticoagulation unless contraindication; Normalize fluid balance; Target initial heart rate <110 b.p.m.; Renin-angiotensin-aldosterone modification; Early consideration of rhythm control; Advanced HF therapies; Treatment of other CV disease).
Digoxin: the Good and the Bad Ziff, Oliver J., MBChB, BSc; Kotecha, Dipak, MBChB, PhD, MRCP, FESC, FHEA
Trends in cardiovascular medicine,
10/2016, Volume:
26, Issue:
7
Journal Article
Peer reviewed
Open access
After 230 years of use, digitalis remains an important and useful therapy for patients with atrial fibrillation, heart failure and the 30-50 % of patients with both conditions. Although the ...combination of positive inotropic activity with negative chronotropic effects have been shown to reduce hospital admissions in heart failure, there is a distinct lack of robust trial data, particularly in patients with atrial fibrillation. We recently performed a comprehensive meta-analysis of all digoxin studies and demonstrated a neutral effect on mortality. This contradicts prior observational data that overlook the fact that digitalis is usually given as second-line therapy to the sickest patients. Use of these agents in clinical practice should take account of appropriate dose, serum concentration, drug interactions and potential side effects. The aim of this review is to evaluate the evidence base for cardiac glycosides and provide a pragmatic guide to their advantages and disadvantages.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Objective To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods.Data sources and study ...selection Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (PROSPERO: CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment).Data extraction and synthesis Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias.Main outcome measures Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling.Results 52 studies were systematically reviewed, comprising 621 845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4 006 210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29 525).Conclusions Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.
Full text
Available for:
BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Background Atrial fibrillation (AF) and heart failure frequently coexist, commonly resulting in serious adverse events. With both conditions increasing in prevalence and justified concerns ...about treatment efficacy, it is vital to understand how the type of heart failure impacts on prognosis. Methods We performed a systematic review of studies examining cardiovascular outcomes in AF patients with heart failure and reduced ejection fraction (AF-HFrEF) compared to those with preserved ejection fraction (AF-HFpEF). The primary outcome was all-cause mortality, meta-analyzed using a random-effects model. Prospective registration: PROSPERO-CRD42014007305. Results Thirteen studies were included in the systematic review (n = 54,587) with 10 suitable for meta-analysis, including retrospective/prospective cohorts and sub-group analyses of randomized trials. AF-HFrEF was present in 49% and these patients were younger, more often male and with higher NYHA class than AF-HFpEF. Oral anticoagulation use was 55% versus 50% respectively (p < 0.001). All-cause mortality was significantly higher in AF-HFrEF; risk ratio (RR) 1.24, 95% CI 1.12–1.36, p < 0.001 (n = 45,100), with absolute death rates of 24% compared to 18% in AF-HFpEF over 2 years. There were no significant differences in incident stroke (RR 0.85, 95% CI 0.70–1.03, p = 0.094; n = 33,773) or heart failure hospitalization (RR 1.21, 95% CI 0.96–1.53, p = 0.115; n = 31,583). The risk of bias was generally low, but heterogeneity was substantial. Conclusions All-cause mortality is significantly higher in AF patients with HFrEF compared to HFpEF, although stroke risk and heart failure hospitalization are similar. Further studies are needed to address the prevention of adverse outcomes in all AF patients with heart failure, regardless of ejection fraction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Echocardiography plays an essential role in the diagnosis and assessment of cardiovascular disease. Measurements derived from echocardiography are also used to determine the severity of disease, its ...progression over time, and to aid in the choice of optimal therapy. It is therefore clinically important that echocardiographic measurements be reproducible, repeatable, and reliable. There are a variety of statistical tests available to assess these parameters, and in this article the authors summarize those available for use by echocardiographers to improve their clinical practice. Correlation coefficients, linear regression, Bland-Altman plots, and the coefficient of variation are explored, along with their limitations. The authors also provide an online tool for the easy calculation of these statistics in the clinical environment (www.birmingham.ac.uk/echo). Quantifying and enhancing the reproducibility of echocardiography has important potential to improve the value of echocardiography as the basis for good clinical decision-making.
•Good reproducibility, repeatability, and reliability are essential for echo studies.•Straightforward statistical evaluation can improve echocardiography practice.•A free online tool is available at www.birmingham.ac.uk/echo.
Summary Background Atrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. β blockers are indicated in patients with symptomatic heart failure ...with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of β blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation. Methods We extracted individual-patient data from ten randomised controlled trials of the comparison of β blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. Analysis was by intention to treat. Outcome data were meta-analysed with an adjusted Cox proportional hazards regression. The study is registered with Clinicaltrials.gov , number NCT0083244 , and PROSPERO, number CRD42014010012. Findings 18 254 patients were assessed, and of these 13 946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1·5 years (SD 1·1) were 16% (2237 of 13 945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. β-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio 0·73, 0·67–0·80; p<0·001), but not in patients with atrial fibrillation (0·97, 0·83–1·14; p=0·73), with a significant p value for interaction of baseline rhythm (p=0·002). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, New York Heart Association class, heart rate, and baseline medical therapy. Interpretation Based on our findings, β blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation. Funding Menarini Farmaceutica Internazionale (administrative support grant).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Incidence and prevalence of atrial fibrillation (AF) are expected to increase dramatically; however, we currently lack comprehensive data on temporal trends in unselected clinical populations.
...Analysis of the UK Clinical Practice Research Datalink (CPRD) from 1998 to 2010 of patients with incident AF, excluding major valvular disease, linked to hospital admission data and national statistics. Fifty-seven thousand eight hundred eighteen adults were identified with mean age 74.2 (SD, 11.7) years and 48.3% women. Overall age-adjusted incidence of AF per 1000 person years was 1.11 (95% CI, 1.09-1.13) in 1998-2001, 1.33 (1.31-1.34) in 2002-2006, and 1.33 (1.31-1.35) in 2007-2010. Ongoing increases in incidence were noted for patients aged ≥75 years, with similar temporal patterns in women and men. Associated comorbidities varied over time, with a constant prevalence of previous stroke, increases in hypertension and diabetes mellitus, and decreases in ischemic heart disease. Among patients aged 55 to 74 years, there was a significant reduction in mortality over time (
<0.001), but mortality rates in patients aged ≥75 years remained static at 14% to 15% per year (
=0.84). Projections of AF prevalence demonstrated a constant yearly rise, increasing from 700 000 patients in 2010 to between 1.3 and 1.8 million patients with AF in the United Kingdom by 2060.
In a large general practice population, incident AF increased and then plateaued overall, with a continued increase in patients aged ≥75 years. The large projected increase in AF prevalence associated with temporal changes in AF-related comorbidities suggests the need for comprehensive implementation of AF prevention and management strategies.
Our objective was to examine gender differences in clinical presentation, management and prognosis of atrial fibrillation (AF) in a contemporary cohort.
In 6412 patients, 39.7% women, of the ...PREvention oF thromboembolic events - European Registry in Atrial Fibrillation, we examined gender differences in symptoms, risk factors, therapies and 1-year incidence of adverse outcomes.
Men with AF were on average younger than women (mean±SD: 70.1±10.7 vs 74.1±9.7 years, p<0.0001). Women more frequently had at least one AF-related symptom at least occasionally compared with men (95.4% in women, 89.8% in men, p<0.0001). Prescription of oral anticoagulation was similar, with an increase of non-vitamin K antagonist oral anticoagulants from 5.9% to 12.6% in women and from 6.2% to 12.6% in men, p<0.0001 for both.Men were more frequently treated with electrical cardioversion and ablation (20.6% and 6.3%, respectively) than women (14.9% and 3.3%, respectively), p<0.0001. Women had 65% (OR: 0.35; 95% CI (0.22 to 0.56)) lower age-adjusted and country-adjusted odds of coronary revascularisation, 40% (OR: 0.60; (0.38 to 0.93)) lower odds of acute coronary syndrome and 20% (OR: 0.80; (0.68 to 0.96)) lower odds of heart failure at 1 year. There were no statistically significant gender differences in 1-year stroke/transient ischaemic attack/arterial thromboembolism and major bleeding events.
In a 'real-world' European AF registry, women were more symptomatic but less likely to receive invasive rhythm control therapy such as electrical cardioversion or ablation. Further study is needed to confirm that these differences do not disadvantage women with AF.
Abstract
Aims
We assessed the performance of modelsf (risk scores) for predicting recurrence of atrial fibrillation (AF) in patients who have undergone catheter ablation.
Methods and results
...Systematic searches of bibliographic databases were conducted (November 2018). Studies were eligible for inclusion if they reported the development, validation, or impact assessment of a model for predicting AF recurrence after ablation. Model performance (discrimination and calibration) measures were extracted. The Prediction Study Risk of Bias Assessment Tool (PROBAST) was used to assess risk of bias. Meta-analysis was not feasible due to clinical and methodological differences between studies, but c-statistics were presented in forest plots. Thirty-three studies developing or validating 13 models were included; eight studies compared two or more models. Common model variables were left atrial parameters, type of AF, and age. Model discriminatory ability was highly variable and no model had consistently poor or good performance. Most studies did not assess model calibration. The main risk of bias concern was the lack of internal validation which may have resulted in overly optimistic and/or biased model performance estimates. No model impact studies were identified.
Conclusion
Our systematic review suggests that clinical risk prediction of AF after ablation has potential, but there remains a need for robust evaluation of risk factors and development of risk scores.
Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain.
We performed a prospectively designed, umbrella review ...of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence.
We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke.
Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
