Luis Manzano

Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis

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).

Predictors of clinical outcomes in elderly patients with heart failure

Heart failure (HF) in the elderly carries a poor prognosis. We used the SENIORS dataset of elderly HF patients aged ≥70 years in order to develop a risk model for this population.

Disseminated-to-Skin Kala-azar and the Acquired Immunodeficiency Syndrome

Excerpt To the editor: The worldwide spread of infection with the human immunodeficiency virus (HIV) may modify the usual expression of regional endemic diseases. Conversely, those atypical forms m...

Anaemia among patients with heart failure and preserved or reduced ejection fraction: results from the SENIORS study

Anaemia is a co‐morbidity frequently seen in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Its presence carries adverse prognostic effects. The effects of anaemia have not been extensively investigated in patients with preserved or only mildly reduced LVEF. We sought to investigate prevalence and incidence of anaemia in patients with HF irrespective of whether reduced or preserved ejection fraction are present. In addition, we sought to study the effects of nebivolol on the development of anaemia.

Erythropoietin as a treatment of anemia in heart failure: Systematic review of randomized trials

BACKGROUND Anemia in heart failure is both common and associated with worse symptoms and increased mortality. Several small randomized controlled trials (RCTs) have assessed erythropoiesis-stimulating agents (ESAs), but definitive evaluation and clinical guidance are required. We sought to systematically review the effects of ESAs in chronic heart failure. METHODS An extensive search strategy identified 11 RCTs with 794 participants comparing any ESA with control over 2 to 12 months of follow-up. Published and additionally requested data were incorporated into a Cochrane systematic review (CD007613). RESULTS Nine studies were placebo controlled, and 5, double blinded. Erythropoiesis-stimulating agent treatment significantly improved exercise duration by 96.8 seconds (95% CI 5.2-188.4, P = .04) and 6-minute walk distance by 69.3 m (95% CI 17.0-121.7, P = .009) compared with control. Benefit was also noted for peak oxygen consumption (+2.29 mL/kg per minute, P = .007), New York Heart Association class (-0.73, P < .001), ejection fraction (+5.8%, P < .001), B-type natriuretic peptide (-226.99 pg/mL, P < .001), and quality-of-life indicators with a mean increase in hemoglobin level of 2 g/dL. There was a significantly lower rate of heart failure-related hospitalizations with ESA therapy (odds ratio 0.56, 95% CI 0.37-0.84, P = .005). No associated increase in adverse events or mortality (odds ratio 0.58, 95% CI 0.34-0.99, P = .047) was observed, although the number of events was limited. CONCLUSION Meta-analysis of small RCTs suggests that ESA treatment can improve exercise tolerance, reduce symptoms, and have benefits on clinical outcomes in anemic patients with heart failure. Confirmation requires larger, well-designed studies with careful attention to dose, attained hemoglobin level, and long-term outcomes.

Active Crohn's disease patients show a distinctive expansion of circulating memory CD4+CD45RO+CD28null T cells.

In a previous study we found an expansion of circulating memory (CD45RO+) CD4+ T cells in patients with Crohns disease (CD). The aim of this work was to investigate the phenotypic and functional characteristics of this T-cell subset in CD. We analyzed in peripheral blood CD4+CD45RO+ T cells from CD patients the expression of surface markers associated to immune activation, costimulation, and apoptosis. In sorted CD4+CD45RO+ T cells apoptosis was quantified by fluorescent annexin V binding. Healthy subjects and patients with ulcerative colitis and acute bacterial enterocolitis served as control groups. An increased percentage of memory CD4+CD45RO+ T cells lacking the expression of costimulatory receptor CD28 was detected in patients with active CD when compared to the other groups evaluated. This expanded CD4+CD45RO+CD28null T-cell subset expressed mostly the effector-cell marker CD57+. Both CD28 downregulation and CD57 expression correlated to CDAI and surrogate markers of disease activity. These phenotypic changes observed on CD4+CD45RO+ T cells from active CD returned to values similar to healthy controls after clinical remission. Moreover, this memory CD28νll T-cell subset might express more intracytoplasmic TNF and IFN-γ than their CD28+ counterpart. Significantly lower frequencies of memory CD4+CD45RO+ T cells expressing CD95 apoptosis receptor were found in patients with active CD. Moreover, sorted CD4+CD45RO+and CD4+CD45RO+ CD28null T cells from patients with active CD exhibited a lower apoptotic rate than that found in healthy controls and inactive CD patients. According to our data, circulating T lymphocytes from active CD patients show distinctive phenotypic and functional changes, characterized by an expansion of memory CD4+CD45RO+CD28null T cells expressing effector-associated cell surface molecules and displaying enhanced resistance to apoptosis.

Diagnosis of elderly patients with heart failure

The prevalence and mortality of heart failure (HF) increase with age. As a result, the early diagnosis of HF in this population is useful to reduce cardiovascular morbidity and probably mortality. However, the diagnosis of HF in the elderly is a challenge. These challenges arise from the under‐representation of elderly patients in diagnostic studies and clinical trials, the increasing prevalence of HF with relatively normal ejection fraction, the difficulty in accurate diagnosis, the underuse of diagnostic tests, and the presence of co‐morbidities. Particularly in the elderly, symptoms and signs of HF may be atypical and can be simulated or disguised by co‐morbidities such as respiratory disease, obesity, and venous insufficiency. This review aims to provide a practical clinical approach for the diagnosis of older patients with HF based on the scarce available evidence and our clinical experience. Therefore, it should be interpreted in many aspects as an opinion paper with practical implications. The most useful clinical symptoms are orthopnoea and paroxysmal nocturnal dyspnoea. However, confirmation of the diagnosis always requires further tests. Although natriuretic peptides accurately exclude cardiac dysfunction as a cause of symptoms, the optimal cut‐off level for ruling out HF in elderly patients with other co‐morbidities is still not clear. In our opinion, echocardiography should be performed in all elderly patients to confirm the diagnosis of HF, except in those cases with low clinical probability and a concentration of brain natriuretic peptide (BNP) or N‐terminal proBNP (NT‐proBNP) lower than 100 or 400 pg/mL, respectively.

Prevalence and clinical profile and management of peripheral arterial disease in elderly patients with diabetes

INTRODUCTION Peripheral arterial disease (PAD) increases with age and diabetes. The aim of this study was to assess the prevalence of PAD in an elderly population with diabetes. METHODS This multicenter and cross-sectional study included patients >70 years, with an established diagnosis of diabetes. PAD was defined as those patients with a history of revascularization or amputation due to ischemia, or a pathological ankle-brachial index (ABI). Adequate blood pressure (BP), LDL cholesterol and HbA1c control were considered as <130/80 mm Hg, <100 mg⁄dL and <7.0%, respectively. RESULTS A total of 1462 patients were included. The most frequent cardiovascular risk factor and cardiovascular disease were hypertension (80.37%) and PAD (60.60% overall; 83.2% of those assisted by vascular surgeons vs 31.9% of those attended by other medical specialists; p<0.001), respectively. However, when ABI was measured, 70.99% of the study population had PAD (80.2% of those assisted by vascular surgeons vs 59.6% of those attended by other medical specialists; p<0.001). The predictors for a pathological ABI included male gender, smoking, dyslipidemia, family history of premature cardiovascular disease, sedentary lifestyle, diabetic-related complications, heart and cerebrovascular diseases. Although risk factors control was very poor, it was even lower in patients with PAD. CONCLUSIONS The prevalence of PAD is high in diabetic elderly patients. The concomitance with other risk factors and cardiovascular diseases was very high. The ABI allowed increasing the diagnosis of PAD.

Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis

Objectives To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. Design Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction <0.45. Participants 13 833 patients from 11 trials; median age 64; 24% women. Main outcome measures The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. Results Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo). Conclusion Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital. Registration PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.

Relationship between Ankle-Brachial Index and Chronic Kidney Disease in Hypertensive Patients with No Known Cardiovascular Disease

Both decreased GFR and albuminuria are associated with an elevated prevalence of peripheral artery disease. However, the combined effects of these alterations previously were not evaluated. Patients with hypertension and with no known vascular disease (n = 955; mean age 66 yr; 56% male) were selected from internal medicine outpatient clinics throughout Spain. Cardiovascular risk factors, urinary albumin excretion, and the ankle-brachial index (ABI) were assessed in all participants. GFR was estimated according to the Cockroft-Gault equation. Of the study population, 62% had diabetes, 23.8% had a GFR <60 ml/min per 1.73 m2, and 43.8% had albuminuria. The prevalence of ABI <0.9 was greater in patients with a GFR <60 ml/min per 1.73 m2 (37.4 versus 24.3%; P < 0.0001) and in those who had albuminuria (32.2 versus 23.3%; P = 0.001). In patients with both alterations, the prevalence of ABI <0.9 was 45.7%. Multivariate analysis indicated that the factors that were associated independently with low ABI were age (odds ratio [OR] 1.06; 95% confidence interval [CI] 1.03 to 1.08; P < 0.0001), triglyceride concentration (OR 1.003; 95% CI 1.001 to 1.005; P = 0.001), presence of albuminuria (OR 1.61; 95% CI 1.18 to 2.20; P = 0.003), smoking habit (OR 1.72; 95% CI 1.13 to 2.63; P = 0.012), and a GFR <60 ml/min per 1.73 m2 (OR 1.47; 95% CI 1.01 to 2.17; P = 0.049). In patients with hypertension and without known vascular disease, reduced GFR and albuminuria are associated independently with an ABI <0.9. Their combined presence characterizes a subgroup of the population who have an elevated prevalence of peripheral artery disease and could benefit from early diagnosis and treatment.