Ferric carboxymaltose for the treatment of iron-deficient heart failure patients: a systematic review and meta-analysis.

AIMS: Intravenous ferric carboxymaltose (FCM) has been shown to improve functional capacity and quality of life in iron deficient heart failure patients. However, FCM's effect on hospitalizations and mortality remains unclear as previous randomized controlled trials (RCTs) and their meta-analyses have been underpowered to detect significant differences. We sought to conduct an updated meta-analysis using recently published RCT data. METHODS AND RESULTS: Online databases were searched from inception until November 2020 for RCTs evaluating the effects of FCM on clinical outcomes in iron-deficient heart failure patients. Outcomes of interest included heart failure hospitalizations, all-cause mortality, and cardiovascular mortality. Meta-analysis was performed using a fixed-effect model and estimates were reported as odds ratios (ORs), hazard ratios, or rate ratios (RRs) along with corresponding 95% confidence intervals (CIs). A total of 1947 patients (n = 1062 in the FCM group; n = 885 in the placebo group) were included. FCM, compared with placebo, significantly reduced the risk of the composite endpoint of time to first heart failure hospitalization or cardiovascular death (hazard ratio = 0.76; 95% CI = 0.63-0.90; I2 = 55%). FCM also significantly reduced the risk of recurrent heart failure hospitalizations (RR = 0.68; 95% CI = 0.54-0.85; I2 = 71%) and recurrent cardiovascular hospitalizations (RR = 0.71; 95% CI = 0.59-0.86; I2 = 56%). However, FCM had no significant effect on the risk of all-cause (OR = 0.97; 95% CI = 0.73-1.28; I2 = 0%) or cardiovascular mortality (OR = 0.93; 95% CI = 0.69-1.27; I2 = 0%). CONCLUSIONS: Ferric carboxymaltose reduces heart failure hospitalizations and cardiovascular hospitalizations with no beneficial effect on all-cause and cardiovascular mortality in iron-deficient heart failure patients. These findings reinforce the role of FCM as a therapeutic option in heart failure patients.

Common Co-Morbidities in Heart Failure - Diabetes, Functional Mitral Regurgitation and Sleep Apnoea.

Heart failure (HF) is a condition that carries a considerable burden of disability many now related to co-existing co-morbidities. The drive to find newer effective therapies targeting novel mechanisms has led to a recent emphasis on treating common co-morbidities that are clustered around contemporary HF patients. Here is renewed contemporary co-morbidities that until recently have received little attention but which are now subject of considerable interest and potential therapeutic advance. These include, diabetes, functional mitral regurgitation and sleep disordered breathing. These three contemporary co-morbidities that have recently been subject to major trial evaluation will be reviewed in this paper.

Estado nutricional en insuficiencia cardiaca avanzada y receptores de trasplante cardiaco / Nutritional status in advanced heart failure and heart transplant patients

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A comparison of research into cachexia, wasting and related skeletal muscle syndromes in three chronic disease areas.

INTRODUCTION: We compared the frequency of cancer, heart and lung related cachexia and cachexia-related research articles in the specialist journal, Journal of Cachexia, Sarcopenia and Muscle (JCSM) to those seen in a leading European journal in each specialist area during 2015 and 2016 to assess whether work on cachexia and related fields is relatively over or under represented in each specialist area. RESULTS: In the dedicated journal, Journal of Cachexia, Sarcopenia and Muscle, there were 44 references related to cancer, 5 related to respiratory disease, 5 related to heart failure, and 21 related to more than one of these chronic diseases. Despite this cancer preponderance, in the European Journal of Cancer in the two publication years, there were only 5 relevant publications (0.67% of the journal output), compared to 16 (1.41%) in the European Respiratory Journal and 10 (2.19%) in the European Journal of Heart Failure. CONCLUSIONS: There is considerable under-representation of cancer cachexia-related papers in the major European Cancer journal despite a high proportion in the dedicated cachexia journal. The under-representation is even more marked when expressed as a percentage, 0.67%, compared to 1.41% and 2.19% of the lung and heart journals respectively. These results are consistent with a worrying lack of interest in, or publication of, cachexia and related syndromes research in the cancer literature in Europe compared to its importance as a clinical syndrome. Greater interest is shown in lung and cardiology journals.

Heart failure 2016: still more questions than answers.

Heart failure has reached epidemic proportions given the ageing of populations and is associated with high mortality and re-hospitalization rates. This article reviews and summarizes recent advances in the diagnosis, assessment and treatment of the patients with heart failure. Data are discussed based also on the most recent guidelines indications. Open issues and unmet needs are highlighted.

Espindolol for the treatment and prevention of cachexia in patients with stage III/IV non-small cell lung cancer or colorectal cancer: a randomized, double-blind, placebo-controlled, international multicentre phase II study (the ACT-ONE trial).

BACKGROUND: Cancer cachexia is a major cause of morbidity and mortality with no widely approved treatment. METHODS: The ACT-ONE trial is a randomized, double-blind, parallel group, placebo-controlled, phase II multicentre trial in patients (25-80 years) with stages III or IV colorectal cancer or non-small cell lung cancer-related cachexia that tested two doses of espindolol (a novel non-selective ß blocker with central 5-HT1a and partial ß2 receptor agonist effects). The primary endpoint was the difference in the rate of weight change over 16 weeks (linear mixed-effect model for repeated measures) between high-dose espindolol and placebo. RESULTS: Eighty-seven patients were randomized centrally in blocks in a ratio 3:2:1 [42 high dose, 10 mg twice daily (bd):31 placebo:14 low dose, 2.5 mg bd]. High-dose espindolol produced a statistically and clinically significant weight gain (+0.54 kg/4 weeks, 95% CI 0.38-0.70) compared with a weight loss on placebo (-0.21 kg/4 weeks, 95% CI -0.37-0.05); P < 0.0001. High-dose espindolol produced a statistically significant increase in lean body mass, whilst changes in fat mass were neutral. Hand grip strength significantly (high dose -1.15 ± 0.7 kg, placebo -3.51 ± 0.8 kg change per 4 weeks; P = 0.0134), stair climbing power, and 6-min walk test non-significantly were all directionally in favour of high-dose espindolol. There were no clinically significant differences in safety signals or survival between treatment groups, although a numerical excess of dyspnoea was seen with high-dose espindolol (19.1%) compared with placebo (3.2%). CONCLUSIONS: This positive trial showed that espindolol 10 mg bd significantly reversed weight loss, improved fat free mass, and maintained fat mass in advanced colorectal cancer and non-small cell lung cancer-related cachexia. This was associated with a significant improvement in handgrip strength, supporting the further investigation of 10 mg bd espindolol for the treatment of cancer cachexia. Although not powered to look at dose response, most treatment effects for low dose lay between high dose and placebo, suggesting that there may be a dose response in the effects of espindolol.

Consensus Meeting on "Uric Acid and Cardiovascular Risk" held at University Magna Graecia, Catanzaro, Italy, May 2014. Publication of the Proceedings as a special issue in the International Journal of Cardiology.

Introduction to a special supplement issue on the importance of uric acid in cardiovascular disorders.

Eplerenone's role in the management of complex cardiovascular disorders.

The accompanying special issue reviews the role of eplerenone and spironolactone in the management of various cardiovascular and renal conditions.

New strategies for heart failure with preserved ejection fraction: the importance of targeted therapies for heart failure phenotypes.

The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes, suboptimal study designs, or inadequate statistical power. Many novel agents are in various stages of research and development for potential use in patients with HF-PEF. To maximize the likelihood of identifying effective therapeutics for HF-PEF, lessons learned from the past decade of research should be applied to the design, conduct, and interpretation of future trials. This paper represents a synthesis of a workshop held in Bergamo, Italy, and it examines new and emerging therapies in the context of specific, targeted HF-PEF phenotypes where positive clinical benefit may be detected in clinical trials. Specific considerations related to patient and endpoint selection for future clinical trials design are also discussed.

Effects of cardiac contractility modulation by non-excitatory electrical stimulation on exercise capacity and quality of life: an individual patient's data meta-analysis of randomized controlled trials.

BACKGROUND: Although cardiac contractility modulation (CCM) has emerged as a promising device treatment for heart failure (HF), the effect of CCM on functional capacity and quality of life has not been the subject of an individual patient data meta-analysis to determine its effect on measures of functional capacity and life quality. This meta-analysis is aimed at systematically reviewing the latest available randomized evidence on the effectiveness of CCM on functional capacity and quality of life indexes in patients with HF. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in May 2013 to identify eligible randomized controlled trials comparing CCM with sham treatment or usual care. Primary outcomes of interest were peak oxygen consumption, 6-minute walk test distance and quality of life measured by Minnesota Living With Heart Failure Questionnaire. There was no sufficient information to address safety. Mean difference and 95% confidence intervals (C.I.s) were calculated for continuous data using a fixed-effects model. RESULTS: Three studies enrolling 641 participants were identified and included. Pooled analysis showed that, compared to control, CCM significantly improved peak oxygen consumption (mean difference +0.71, 95% C.I. 0.20 to 1.21 mL/kg/min, p=0.006), 6-minute walk test distance (mean difference +13.92, 95% C.I. -0.08 to 27.91 m, p=0.05) and quality of life measured by Minnesota Living With Heart Failure Questionnaire (mean difference -7.17, 95% C.I. -10.38 to -3.96, p<0.0001). CONCLUSIONS: Meta-analysis of individual patient data from randomized trials suggests that CCM has significant if somewhat modest benefits in improving measures of functional capacity and quality of life.