ESC Heart Failure: A New Journal Aims to Broaden Heart Failure Views

ESC Heart Failure, the new daughter journal of the European Journal of Heart Failure, was launched in September 2014 and is published by Wiley on behalf of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). The journal is set up to cover a broad range of articles with the topic of heart failure (HF) in its broadest sense. These articles include original research articles, review articles, editorial comments, case reports, letters to the Editor, and meeting highlights. In addition, the journal aims to cover not only clinical research, but indeed all aspects of HF including basic research reports from subcellular and cellular structures, to animal research, to research on biomarkers, pathophysiology, diagnostic and imaging procedures, to clinical intervention trials. The aim of this Viewpoint is to provide a short overview of what the ESC Heart Failure is publishing and to show a few highlights that have been published in it recently. Ponikowski et al.1 highlighted in an HFA white paper the burden of HF that currently affects ∼6 million people worldwide, stating that the outlook of patients is poor, with survival rates that are several times worse than those for cancer patients.2 Several papers in ESC Heart Failure have highlighted the importance of HF in Asia.3, 4 Lam5 points out the strikingly high prevalence of HF in stage A, with >24% of people in Cambodia and Laos having hypertension as a risk factor for HF development—corresponding numbers in the UK and the USA only reach 13–15%. Similar differences are being reported for tobacco smoking, physical inactivity, and raised blood glucose levels, which prompts the author to state that the prevalence of symptomatic HF is much higher in Southeast Asian countries than in the rest of the world. Two recent reports provide information on the epidemiology of HF in the Middle East. Sulaiman et al. have reported the results of the Gulf acute HF registry showing that these patients are younger and with a higher prevalence of diabetes and of HF with reduced ejection fraction (HFrEF), compared with their Western counterparts.6 Tatari et al.7 have calculated the burden of HF in Lebanon, for which data have not been available so far. They stated that hospitalization care in Lebanon, which is largely delivered by the public sector, yielded direct costs paid by the public and private sector summing up to US$38 million, with an average cost for each HF hospitalization at US$3769. They conclude that the annual total direct cost for HF patients in Lebanon in 2012 was ∼ US$103 million. Hassanein et al.8 report on data from a prospective multicentre observational study of patients presenting to cardiology centres in member countries of the ESC, particularly focusing on 20 centres located all over Egypt. A total of 1475 patients in this registry were hospitalized with acute HF, and the authors concluded that patients in Egypt presented at a much earlier age than those in other regions of the ESC registry. Interesting data have also been published with regard to patients with HF from Japan,9 because Japan has the highest proportion of older people in the world, with 25.9% of the population being 65 years of age or older. The authors report that the number of Japanese outpatients with left ventricular (LV) dysfunction was 979 000 in 2014, and there was a projected gradual increase with the ageing of the population. Interestingly, ischaemic aetiology of HF was less frequently observed in Japan than in the Western population. The prevalence of HF with preserved ejection fraction (HFpEF), however, was similar between Japan and Western countries. The high overall prevalence of HF not only in the Western world but also in developing countries has led to a number of initiatives such as the workshop organized by the Agenzia Italiana del Farmaco with the aim of discussing unmet needs and ways forward in the development of medicines for HF. This workshop is trying to build a template for meetings devoted to debate of unmet needs with all stakeholders towards producing tentative roadmaps for the future.10 Further action is also needed with respect to risk factors for HF. The role of traditional risk factors for coronary artery disease as well as that of nutrition and lifestyles have been shown by recent analyses.11-15 With the overall increasing number of patients with HF worldwide, new diagnostic and therapeutic avenues are urgently required. Olesen et al.16 recently described the electrocardiogram (ECG) as a first step in the detection of LV systolic dysfunction in the elderly. They used data from 260 patients aged 74–92 years who all had echocardiography, a 12-lead ECG, and natriuretic peptide assessment done. The authors suggested that 90% of LV systolic dysfunction may be detected using an ECG approach. In particular, when there is atrial fibrillation (AF), a paced rhythm, left bundle branch block, a QRS duration of ≥120 ms, or an N-terminal pro-B-type natriuretic peptide (NT-proBNP) value >35 pmol/L, a diagnostic echocardiography should be considered. Täger et al.17 studied the cardiac index using data from 50 prospectively included patients with chronic HF and measured cardiac index using both inert gas rebreathing and impedence cardiography at weekly intervals over 3 weeks. The authors concluded than non-invasive measurement of cardiac index was stable over time and in particular that measurement modalities for cardiac index assessment are not interchangeable. The biological variation was less pronounced when inert gas rebreathing techniques were used. In addition to the available prognostic biomarker studies,18-20 prognostic assessments were recently performed in patients with HF using cardiac [123I]metaiodobenzylguanidine imaging and late gadolinium enhancement.21, 22 Kataoka23 investigated the clinical significance of bilateral leg oedema and the added value of monitoring weight gain using data from 1826 outpatient visits of 83 patients with mild to moderate HF. In this study, only 84% of leg oedema events co-existed with weight gain. It was concluded that additional monitoring of weight gain effectively distinguishes clinically significant leg oedema events from insignificant sole leg oedema events. Other studies have shown the prognostic value of the detection of lung congestion through chest X-ray or lung ultrasound in HF patients.24, 25 McDiarmid et al.26 studied the predictive power of late gadolinium enhancement for myocardial recovery in patients with chronic ischaemic HF in 22 patients with severe LV impairment who were randomly assigned to revascularization or not in addition to guideline-indicated pharmacological therapy. They concluded that the duration of the HF syndrome in a given patient is a better predictor of recovery than the transmural extent of late gadolinium enhancement. Acute HF is a life-threatening emergency that requires early diagnosis and treatment.27 Searle et al.28 discussed the differences in the definition of acute HF and the selection criteria for acute HF populations that lead to large differences in the prevalence of acute HF between 1% and 12% of the general population. Cowie et al.29 discussed the variation in the quality of care across hospitals in regions of Europe and the USA. In the call to action paper, they state that in particular in hospital care settings treating patients with acute HF, input from an acute HF expert should be involved to ensure that guidelines and protocols for treatment are implemented for all patients. They also discuss the value of patient education programmes to improve patient outcomes. Access to end-of-life care and support for all patients, family members, and care givers should, in their opinion, form part of a high quality service. Acute HF is a heterogeneous condition with different clinical presentations.30 The variable prevalence of its main clinical manifestation, pulmonary oedema, in clinical trials has been reviewed by Platz et al.31 The role of the different precipitating factors is discussed by Arrigo et al.32 These authors have grouped acute HF patients into the following four groups: acute coronary syndrome, AF, acute pulmonary disease, and other causes. Patients with acute pulmonary disease showed fewer readmission rates but higher 1-year mortality rates, which was especially true in patients 64 years of age or younger. Interesting data were also generated by Sotiropoulos et al.33 who documented—using 402 consecutively hospitalized patients with acute HF—the independent predictive value of an elevated red cell distribution width in patients with HFpEF, but not in those with HFrEF. Konishi et al.34 studied the effects of hypercapnia and hypocapnia among patients with acute HF. Hypercapnia and hypocapnia were observed in 33.7% and 32.6%, respectively, of 193 patients with acute HF. Patients with hypercapnia were more likely to be in New York Heart Association (NYHA) Class IV and to have pulmonary oedema on chest X-ray. The authors of this paper showed that the presence of hypercapnia in acute HF was more frequently associated with immediate airway interventions and possibly involved in the pathophysiology of acute pulmonary oedema. In addition to the effects of gas exchange, Schefold et al.35 showed recently that a single baseline serum creatinine measurement is likewise able to predict death among patients hospitalized for acute HF. Co-morbidities play a major role in disease progression in patients with HF, both among those with HFrEF and among those with HFpEF, however with differences between these two subgroups of HF patients.36, 37 Since no specific treatment is available for HFpEF, the most reasonable approach to symptomatic improvement in patients with HFpEF is treatment of co-morbidities. Skeletal muscle wasting (i.e. sarcopenia) and iron deficiency have recently emerged as important co-morbidities, particularly in patients with HFrEF.38-42 The CONFIRM-HF study aimed to investigate the effects of treating iron deficiency in a double-blind randomized placebo-controlled study using i.v. ferric carboxymaltose to improve 6-min walking distance from baseline to week 24.43 The trial showed good improvement in both quality of life and exercise capacity, and confirmed the overall safety of ferric carboxymaltose in treating iron deficiency in HF.44 A similar randomized and placebo-controlled trial (PRACTICE-ASIA-HF),45 however, conducted as an open-label trial, is aiming to study patients with iron deficiency and a haemoglobin value <14 g/dL. Patients receive either a single dose of 1000 mg of ferric carboxymaltose or i.v. normal saline. Likewise, the primary endpoint of this study is the change in 6-min walk distance within the relatively short time frame of 12 weeks. The results have not been reported so far. The importance of muscle wasting and possible treatment approaches, including exercise training, nutritional support, and medical therapy, were discussed in an overview article by Ebner et al.46 Doehner et al. highlighted the importance of myofibril contractile function of the quadriceps, which is strongly related to insulin sensitivity in patients with chronic HF.47 Frailty, which can be a consequence of muscle wasting, may serve as a new clinical marker for the management of patients with chronic HF, as outlined by Yamada et al.48 Additional insight was provided by Jankowska et al.49 who investigated the prevalence of late-onset hypogonadism in men with systolic HF and its clinical determinants and prognostic consequences. Using data from 201 patients with HFrEF, these authors found that men with HFrEF commonly report sexual complaints and that the combination of sexual dysfunction and testosterone deficiency occurs more frequently than in a general male population. However, the presence of late-onset hypogonadism does not affect long-term mortality when this co-morbidity was adjusted for the severity of HF. Hasin et al. also commented on sexual dysfunction in patients with HF. These authors concluded that sexual dysfunction is prevalent in patients with LV assist device support and that it may be more prominent in these patients than after cardiac transplantation. In addition, they state that ‘problems limiting sexual function related to physiological, psychological, and equipment merit consideration during follow-up’.50 Lastly, Steinbeck et al. have studied a first potential biomarker of skeletal muscle wasting, the C-terminal agrin fragment, in patients with HF.51 Exercise training plays an important part in maintaining patients' quality of life and exercise capacity. However, it is still underused in Europe.52 Nolte et al.53 recently compared the long-term effects of exercise training and exercise capacity, diastolic dysfunction, and quality of life in patients with diastolic dysfunction vs. those with HFpEF using data from 43 patients. These patients performed a combined endurance/resistance training over 6 months on top of usual care. After finishing the study, quality of life as assessed using the Minnesota Living With Heart Failure Questionnaire, general health perception, and the 9-item patient health questionnaire score only improved in the patients with HFpEF, but not in those with asymptomatic diastolic dysfunction. More encouraging results, however, were found with regard to an increase in the patients' peak VO2 value, which improved significantly both in patients with diastolic dysfunction and in patients with HFpEF. This led the authors to conclude that controlled lifestyle modification with physical activity is effective in both cohorts of patients. Kasner et al.54 identified 52 patients with HFpEF based on their E/e' values. In 27 of 52 patients, E/e' increased during exercise training driven by a failure to augment early diastole. This was correlated with a fall in stroke volume and associated with an increase in diastolic index. Stahrenberg et al.55 performed a cross-sectional analysis from the prospective cohort programme Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure (DIAST-CHF) that included 1937 patients with at least one risk factor such as hypertension, atherosclerotic disease, diabetes, or obstructive sleep apnoea. They found that the 6-min walk distance was inversely related to E/e' values. In the multivariable analysis, the 6-min walk distance decreased significantly with age, female gender, increasing body mass index, diabetes, COPD, and peripheral artery disease. The authors therefore concluded that classical risk factors for HF and neuroendocrine activation are independently associated with submaximal exercise capacity, whereas diastolic dysfunction obtained at rest is not. The beneficial effects of combined aerobic exercise and inspiratory muscle training vs. aerobic training alone have been shown in a multicentre randomized tral.56 Inhibition of the renin–angiotensin–aldosterone system remains the mainstay of therapy in patients with chronic HF. He et al.57 performed a randomized trial to assess the efficacy and safety of supramaximal titrated inhibition in patients with idiopathic dilated cardiomyopathy. They concluded that even supramaximal doses of benazepril and valsartan were tolerated and produced extra benefit on top of their low-dose counterparts with regard to clinical outcome and cardiac reverse remodelling.58 PARADIGM-HF is a landmark trial for treatment of HFrEF.59, 60 The success achieved with sacubitril/valsartan vs. enalapril further shows the value of the neurohormonal hypothesis of HF.61 A recent animal model showed that dogs that are randomized to 3 months of oral therapy with ivabradine (compared with no therapy) had a significant decrease of heart rate. The LVEF decreased at 3 months in the control group of HF but increased significantly with ivabradine. Treatment with ivabradine was associated with improved LV diastolic dysfunction, increased sarcoplasmic reticulum calcium uptake and ATPase activity, and decreased plasma levels of vasoactive neurohormones, natriuretic peptides, and pro-inflammatory cytokines.62 Subgroup analyses have confirmed the beneficial effects of ivabradine in patients with low blood pressure and diabetes, respectively, in SHIFT.63, 64 Fraccarollo et al.,65 likewise using an animal model, showed that eplerenone as a mineralocorticoid receptor antagonist had a superior efficacy as compared with spironolactone during the acute myocardial infarction phase, with more beneficial effects on survival, early cardiac dilatation, and functional decline. Among patients with stable advanced chronic HF, a double-blind placebo-controlled trial was performed allocating patients to an i.v. infusion of placebo or levosimendan in a total of 42 patients. Interestingly, levosimendan treatment significantly improved peak oxygen consumption and reduced the VE/CO2 slope and NT-proBNP level in patients with HF.66 Peripartum cardiomyopathy is a major cause of HF in the peripartum period and is considered potentially life threatening.67 Haghikia et al.68 studied 34 patients with this confirmed diagnosis and undertook cardiovascular magnetic resonance imaging at the time of diagnosis and ∼5 months later. About one-third of patients showed LV diastolic dysfunction and right ventricular dysfunction and dilatation, with right ventricular dysfunction being particularly associated with an unfavourable outcome. Most patients with peripartum cardiomyopathy showed a distinct pattern of LV wall motion abnormalities and myocardial scarring. Umazume et al.69 studied changes in blood variables in pregnant women at increased risk of peripartum cardiomyopathy and identified both high sensitive troponin I and NT-proBNP to be highly likely to increase in women with multifoetal pregnancies and/or hypertensive disorders. The authors concluded that the combination of these two biomarkers could contribute to better selection of candidates for echocardiography screening. However, further studies remain necessary.