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Aims: The role of microvascular complications in the risk conferred by diabetes in heart failure with reduced ejection fraction (HFrEF) is unknown.Methods and Results: We studied 2707 HFrEF patients in the Beta-blocker Evaluation of Survival Trial (BEST), stratified into three groups: no diabetes and diabetes without or with microvascular complications (neuropathy, nephropathy, or retinopathy). The risks of the composite of cardiovascular death or heart failure hospitalization, and all-cause death, were studied using Cox regression analyses adjusted for other prognostic variables. Overall, 964 (36%) patients had diabetes, of which 313 (32%) had microvascular complications. Patients with microvascular complications had more severe symptoms (New York Heart Association class IV 12% vs. 9% diabetes with no complications and 7% no diabetes), and worse quality of life (Minnesota Living with Heart Failure median score 60 vs. 54 and 51 points). In patients with diabetes and complications, the rate of the composite outcome was 50 per 100 person-years of follow-up (compared with 34 and 29 in those with diabetes and no microvascular complications and participants without diabetes, respectively). Compared to patients without diabetes, the adjusted hazard ratio (HR) for the composite outcome was 1.44 [95% confidence interval (CI) 1.22-1.70] and 1.18 (95% CI 1.03-1.35) for patients with diabetes with and without complications, respectively. The risk of all-cause mortality was similarly elevated: adjusted HR 1.42 (95% CI 1.16-1.74) and 1.20 (95% CI 1.01-1.42), respectively.Conclusion: In HFrEF, diabetes with microvascular complications is associated with worse symptoms and outcomes than diabetes without microvascular complications. Prevention of microvascular complications has the potential to improve HFrEF outcomes. [ABSTRACT FROM AUTHOR]

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]

Aims: Information on the effectiveness of beta-blockade in patients with heart failure (HF) and concomitant renal impairment is scarce and beta-blockers are underutilized in these patients. [ABSTRACT FROM PUBLISHER]

Summary Although heart failure is common, disabling, and deadly, there are now many effective treatments, at least for patients with low left-ventricular ejection fraction. For all, angiotensin-converting-enzyme inhibitors and β blockers are the essential disease-modifying treatments, improving symptoms, reducing hospital admissions, and increasing survival. Implantable cardioverter defibrillators also improve survival. For patients with persistent symptoms, angiotensin-receptor blockers and aldosterone antagonists have additional benefits. These treatments are now preferred to digoxin, although this drug can still be useful at an earlier stage in patients with atrial fibrillation. In some patients with persistently severe symptoms and a wide QRS on the electrocardiogram, cardiac resynchronisation therapy also reduces mortality and morbidity. The role of other markers of ventricular dys-synchrony is under investigation. There is growing evidence that left-ventricular assist devices are indicated in some patients with end-stage heart failure. Organised delivery of care also improves outcome. However, there is still no firmly evidence-based treatment for heart failure with preserved ejection fraction. Many new pharmacological, device, and surgical treatments for heart failure are currently under evaluation in clinical trials, and other approaches, including stem-cell treatment, are at an earlier stage of investigation. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI). Background: PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown. Methods: Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT). Results: Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15–1.37; p<0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16–1.33; p<0.001). Conclusions: PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies. [Copyright &y& Elsevier]

The combination of heart failure and chronic obstructive pulmonary disease presents many therapeutic challenges. The cornerstones of therapy are beta-blockers and beta-agonists, respectively. Their pharmacological effects are diametrically opposed, and each is purported to adversely affect the alternative condition. The tolerability of beta-blockade in patients with mild and fixed airflow obstruction likely extends to those with more severe disease. However, the evidence is rudimentary. The long-term influence of beta-blockade on pulmonary function, symptoms, and quality of life is unclear. Low-dose initiation and gradual up-titration of cardioselective beta-blockers is currently recommended. Robust clinical trials are needed to provide the answers that may finally allay physicians'' mistrust of beta-blockers in patients with chronic obstructive pulmonary disease. Beta-agonists are associated with incident heart failure in patients with pulmonary disease and with increased mortality and hospitalization in those with existing heart failure. These purported adverse effects require further investigation. In the meantime, clinicians should consider carefully the etiology of dyspnea and obtain objective evidence of airflow obstruction before prescribing beta-agonists to patients with heart failure. [Copyright &y& Elsevier]

Concern has been raised about combining β blockers with angiotensin-receptor blockers in patients with heart failure. The VALsartan In Acute myocardial infarction (VALIANT) trial enrolled 14,703 patients with myocardial infarction complicated by heart failure or documented left ventricular systolic dysfunction. These patients were randomly allocated to treatment with valsartan, captopril, or both. Physicians were also encouraged to prescribe β blockers because of previous evidence of benefit. The baseline characteristics, treatments, and outcomes were compared among 4 groups: patients taking β blockers at admission only, at discharge only, at both admission and discharge, and neither. Patients treated with β blockers were at lower risk than those not treated at any period. Those treated with β blockers at both intervals had a lower 3-year mortality rate (17.7%) than those treated only at randomization (30.7%) or only at discharge (25.9%). The greatest mortality (35.1%) occurred in patients not treated at either point. No statistically significant interaction with prognosis was observed between β-blocker use and treatment with valsartan or valsartan plus captopril. Patients discharged with a β blocker had a significant survival advantage after adjustment for differences in baseline characteristics and intervening complications (hazard ratio 0.89, 95% confidence interval 0.81 to 0.98, p = 0.02). This association was most pronounced in patients prescribed consistent β blockers at randomization and discharge and was present in both patients with impaired and those with preserved systolic left ventricular function. These results have further confirmed that β blockers reduce the risk of death and nonfatal cardiovascular events in patients with heart failure or systolic left ventricular dysfunction after myocardial infarction. In conclusion, no evidence was found of adverse interactions between the angiotensin-receptor blocker valsartan and β blockers or of a negative effect of the combination of valsartan, captopril, and β blockers. [Copyright &y& Elsevier]