bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diuretics
Authors: Dauw Jeroen , Gottlieb Stephen , Mullens Wilfried 
Published: December 2023

Abstract
Diuretics are one of the most frequently used therapies in heart failure management of a large proportion of patients. Although all diuretic classes have been around since the late 1960s, there has been little evidence and guidance for their use. As a consequence, diuretic therapy is currently variably implemented and depends largely on physicians’ experiences and local habits. In this chapter, the pharmacological properties of the different diuretic classes are discussed and the most important trials cited. An integrated approach to diuretic therapy is proposed, based on the recently published position paper on diuretic use by the Heart Failure Association. This protocol emphasizes rapid initiation of loop diuretics, adequate dosing, and a stepped pharmacological approach based upon early diuretic response evaluation. The goal is to quickly and thoroughly optimize fluid status and decrease decongestion. In chronic heart failure, diuretics should be tailored to each patient specifically
New and emerging therapies in heart failure
Authors: Rosano Giuseppe , Filippatos Gerasimos , Starling Randall 
Published: December 2023

Abstract
The treatment of heart failure (HF) has substantially changed over the last decades, owing to the introduction of new drug classes. Improved understanding of HF as a disorder of circulatory haemodynamics, neurohormonal imbalance, pathological cardiac remodelling, and increased arrhythmogenic instability led to the development of novel treatments with efficacy in reducing morbidity and mortality, particularly in patients with reduced ejection fraction. These treatments included vasodilator therapy with hydralazine/isosorbide dinitrate combination and the ushering of drugs correcting the neurohormonal imbalance (angiotensin-converting enzyme inhibitors, beta-blockers, angiotensin T1 receptor blockers, mineralocorticoid receptor antagonists, ivabradine, and sacubitril/valsartan). Current regulatory agencies’ requirements request evidence for the efficacy of new treatments on mortality and morbidity endpoints. This chapter provides an overview of the novel pharmacotherapeutic targets and emerging treatment options in HF, including omecamtiv mecarbil, vericiguat, adenosine A1 agonists, beta-3 agonists, and finerenone.
Cardiac resynchronization therapy for heart failure
Authors: Martens Pieter , Goncalvesova Eva , Mullens Wilfried 
Published: December 2023

Abstract
Cardiac resynchronization therapy (CRT) is one of the most successful heart failure therapies demonstrating improved quality of life and reduction in heart failure hospitalization, as well as in all-cause mortality, in a cost-efficient manner in selected patients with symptomatic heart failure with reduced ejection fraction with dyssynchrony. CRT alleviates electromechanical dyssynchrony, thereby resulting in short- and long-term beneficial myocardial changes in macroscopic reverse remodelling and microscopic cellular adaptations. Despite the well-established role of CRT in the management of patients with heart failure with reduced ejection fraction, a sizeable proportion of eligible patients (up to two-thirds) do not receive a CRT device. Better knowledge with regard to indications for CRT, understanding the elements in patient selection for CRT, choosing between a CRT-pacemaker and a CRT-defibrillator, and using a systematic approach to post-implantation follow-up targeted at global heart failure disease modification will allow for better familiarization with CRT and improved global uptake.
Acute heart failure: diagnostic and prognostic assessment
Authors: Chioncel Ovidiu , Filippatos Gerasimos , Mebazaa Alexandre , Harjola Veli-Pekka , Masip Josep 
Published: December 2023

Abstract
Acute heart failure (AHF) refers to rapid or gradual onset or worsening of symptoms and/or signs of HF, reflecting diverse abnormalities of congestion and/or hypoperfusion status, leading to unplanned hospital admission, ED visit, or outpatient visit. AHF requires urgent evaluation with subsequent initiation of the treatment. The diagnostic workup must start at the time of the first medical contact and be continued throughout the initial patient pathway. Initial diagnosis should be based on clinical judgment to integrate patient history with physical examination. Since the sensitivity and specificity of symptoms and signs are only modest, diagnosis of AHF should be further confirmed by appropriate additional investigations, such as biomarkers, ECG, chest X-ray, lung ultrasound, laboratory assessment, and echocardiography. During the diagnostic process, coexisting life-threatening clinical conditions or precipitants that require urgent correction need to be immediately identified and managed. The diagnostic workup should continue with the identification of clinical phenotypes, acutely decompensated HF, acute pulmonary oedema, acute right failure, and cardiogenic shock, that would support the initiation of the early individualized treatments.
Acute heart failure: pharmacological and non-pharmacological management
Authors: Fountoulaki Katerina , Parissis John , Collins Sean , Yilmaz Mehmet Birhan , Mebazaa Alexandre 
Published: December 2023

Abstract
Acute heart failure (AHF) is a life-threatening medical condition requiring timely and tailored treatment. Much like acute coronary syndromes, AHF management is ‘time sensitive’. However, most of the treatment methods are symptomatic and largely based on expert consensus rather than robust evidence. Diagnostic workup and appropriate pharmacological and non-pharmacological treatment must be started promptly and in parallel. The cornerstone of AHF management is identifying precipitating factors and specific clinical phenotypes. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion present with peripheral hypoperfusion or cardiogenic shock. Disposition decisions and triage to the appropriate level of care are important components of AHF management affecting the quality of care and outcome. Intravenous diuretics and vasoactive agents remain the mainstay of therapy for AHF. Oxygen therapy and/or ventilatory support may be also indicated to correct hypoxaemia and progressive respiratory failure. Despite symptomatic and haemodynamic improvement provided by acute treatment, none of the recommended therapies are effective in improving prognosis of AHF patients.
Advanced heart failure: assessment
Authors: Gal Tuvia Ben , Jessup Mariell , Costanzo Maria-Rosa 
Published: December 2023

Abstract
Many gaps exist in the correct and timely recognition of when patients with heart failure (HF) have reached the advanced stages of their disease and require referral to a tertiary HF programme. Patients believed to have advanced HF are often those who are not receiving optimal guidelines-directed medical therapy; heart transplant or device-based therapy may be avoided by the application of the appropriate medical therapy. There has been progress in the recognition of key clinical features during the assessment of advanced HF syndrome, in the utilization of various imaging techniques, and in the development of scores for the risk stratification of potential candidates for advanced HF therapies. The optimal evaluation of advanced HF patients requires simultaneous consideration of multiple diagnostic modalities and the participation of multidisciplinary teams. Likewise, a thorough psychosocial evaluation must be undertaken, acknowledging the social determinants of health that may impact the outcome of each advanced HF procedure.
Heart transplantation
Authors: Miličić Davor , Mehra Mandeep , Starling Randall C 
Published: December 2023

Abstract
Heart transplantation (HTx), represents the golden standard of treatment for patients with refractory advanced heart failure. The aim of HTx is to improve survival, symptoms and quality of life. In general, HTx rates are by far too low with respect to the growing numbers of potential allograft recipients, even in countries with highest transplant rates. At least 50% of patients on transplant lists have to be bridged with the use of ventricular assist devices. Current guidelines offer detailed instructions for pretransplant work-up, and define indications and contraindications for HTx. Age 70+, severe pulmonary hypertension and other significant comorbidities should be considered as prohibiting factors for HTx. Organ allocation, explantation and allograft implantation should be performed by experienced teams. Posttransplant management requires dedicated multidisciplinary team approach, and in appropriately selected pateints, provides a median survival of 12.5 years, with good functional capacity and quality of life.
Chronic lung disease
Authors: Masip Josep , Portillo Karina , Arrigo Mattia 
Published: December 2023

Abstract
Heart failure (HF) and chronic lung diseases (CLD) are very prevalent entities, with a close relationship. CLD may affect the heart, predominantly the right ventricle, through pulmonary hypertension, which may aggravate or precipitate HF. Conversely acute left-sided HF often causes lung congestion, with varying degrees of acute respiratory failure, often inducing a remodelling of the alveolar–capillary units of the lungs. Parenchymal changes induced by chronic HF finally alter lung function, causing a restrictive pattern, with gas diffusion impairment and an abnormal ventilatory pattern, especially during exercise. One third of the patients with HF have concomitant CLD, mainly chronic obstructive or interstitial pulmonary diseases. The identification of HF and CLD is often challenging because they share common signs and symptoms. Previous clinical data, together with a careful physical examination, lung function tests, echocardiography, and other imaging techniques, as well as blood gases biomarkers and on occasion cardiopulmonary exercise testing are essential for the diagnosis and management of these patients.
Pulmonary hypertension associated with left heart disease
Authors: Lang Irene M , Rosenkranz Stephan 
Published: December 2023

Abstract
Although pulmonary hypertension (PH) is most commonly due to left heart disease (LHD), we have the least information on this condition regarding pathology, pathophysiology, genetics, and treatments. New guidelines are labelling the condition as PH associated with LHD, although PH is in a majority of cases due to LHD (PH-LHD). Apart fromthe difficulty of finding adequate models and identifying molecular mechanisms of disease, the precise nomenclature of PH-LHD remains controversial, with two proposed sub-categories of PH-LHD, isolated post-capillary (iPC-PH) and combined pre- and post-capillary pulmonary hypertension (CPC-PH) that carry different prognoses. With regards to treatments, current recommendations do not differentiate between PH-LHD subtypes, and suggest a primary focus on the underlying left heart disease condition. Additional difficulties in this group of PH arise from: (1) heterogeneity of clinical presentation, (2) dependence of haemodynamics and on hydration status, (3) uncertainties as to whether PH in PH-LHD is to be classified as a comorbidity of LHD or whether LHD is to be classified as the comorbidity of PH, thus resulting in uncertainty whether the heart or the lung are the primary treatment target, and (4) irreversibility of the condition. The field has been helped by a rigorous scientific approach to patients’ characteristics by a ‘molecular’ dissection of associated conditions with phenomapping, modern imaging, randomized controlled clinical treatment trials, in-depth understanding, and arising treatments of a few specific conditions that lead to PH-LHD, such as cardiac amyloidosis or hypertrophic cardiomyopathy.
Iron deficiency in heart failure
Authors: Jankowska Ewa A , Anker Stefan D , Ponikowski Piotr 
Published: December 2023

Abstract
Abstract: Iron deficiency (ID) is an ominous non-cardiovascular co-morbidity highly prevalent in patients with heart failure (HF). The presence of ID in patients with HF, regardless of concomitant anaemia, translates into exaggerated HF symptoms, impaired exercise capacity, poor quality of life, frequent recurrent HF hospitalizations, high mortality and increased healthcare costs. ID is diagnosed in patients with HF when serum ferritin is &lt; 100 ng/mL (ng/mL = μg/L), or when serum ferritin is between 100 and 299 ng/mL combined with a transferrin saturation (TSAT) of &lt; 20% (TSAT = (iron/TIBC) × 100%). According to the ESC guidelines on HF (2016, 2021), all patients with HF are recommended to be screened for ID using serum ferritin and TSAT, regardless of left ventricular ejection fraction (LVEF), haemoglobin level and kidney function. The results of the FAIR-HF, CONFIRM-HF, and AFFIRM-AHF trials along with meta-analyses have established the basis for the ESC recommendation that intravenous iron supplementation with ferric carboxymaltose (FCM) should be considered in symptomatic patients with LVEF &lt;45% and ID (defined as above) in order to alleviate HF symptoms, improve exercise capacity and quality of life. The major results of the AFFIRM-AHF trial have led the foundations for the recommendation that intravenous iron supplementation with FCM should be considered in symptomatic HF patients recently hospitalized for HF and with LVEF &lt; 50% and ID (defined as above) in order to reduce the risk of HF hospitalization. Therapy with FCM has been demonstrated to be effective and safe. Cost-effectiveness analysis has confirmed that intravenous iron supplementation with FCM in iron deficient patients after an episode of acute HF is dominant in the UK, USA, and Switzerland, and is highly cost-effective in Italy. Ongoing clinical trials are expected to provide further evidence on the effect of this therapy on long-term cardiovascular mortality in iron deficient patients with HF (FAIR-HF2, IRONMAN, HEART-FID) and on exercise capacity and quality of life in iron deficient patients with HF with preserved ejection fraction (FAIR-HFpEF).
Cognitive impairment and depression
Authors: Doehner Wolfram , Vitale Cristiana , Yilmaz Mehmet Birhan 
Published: December 2023

Abstract
Heart failure (HF) and functional brain disorders frequently co-exist because of common risk factors and a high degree of interaction affecting particularly elderly people. HF is a risk factor for cognitive impairment and depression leading to a difficult pattern of comorbidity with mutual aggravation and overall disease progression with aggravation of symptomatic status and poor prognosis. Cognitive decline and depression pose a particular challenge for clinical management of HF patients and for maintaining appropriate treatment regimens. The combination of HF with the loss of cognitive capability and of motivation for self-care and treatment compliance can lead to a very poor quality of life, increased risk of hospitalization, and a dramatic increase in health care expenditure. Therapeutic options for cognitive and depressive disorders in patients with HF remain a challenge and require comprehensive and multi-modal care strategies. The most important step for such comprehensive treatment concepts is the systematic awareness of cognitive decline and depression as common complications of HF. Early recognition and thorough assessment of cognitive impairment and depressive disorder are recommended in patients with HF.
Cancer and heart failure
Authors: Farmakis Dimitrios , Lyon Alexander , Boer Rudolf de , Belenkov Yuri 
Published: December 2023

Abstract
Cancer as a comorbidity in heart failure patients is increasing in prevalence as result of the increasing survival in both conditions and the ageing of populations around the world. A new cancer diagnosis in a patient with HF has a double impact upon the indications for and selection of both HF therapies and cancer treatments. This chapter reviews the impact of a cancer diagnosis and cancer treatments upon HF treatment including pharmacological, therapies, cardiac implantable electronic devices (CIED), advanced surgical interventions, and exercise rehabilitation. The impact of HF and its therapy on cancer treatment is further discussed, including how to monitor HF patients during systemic anticancer therapy, and the management of CIEDs in the context of radiation therapy to a field including the heart.
Frailty in heart failure
Authors: Jankowska Ewa A , Vitale Cristiana , Choi Dong-Ju 
Published: December 2023

Abstract
Frailty constitutes a clinically relevant and prevalent pathology in patients with heart failure (HF). It is of a particular importance in the context of ageing in contemporary societies. According to the Heart Failure Association experts, frailty is defined as a multidimensional dynamic state, independent of age, that makes the individual with HF more vulnerable to the effect of stressors. Frailty is particularly prevalent in elderly subjects, those with numerous comorbidities, and sarcopenia. Importantly, the prevalence of frailty in patients with HF is independent of age because it is not just a reflection of the ageing process, but rather the consequence of an exaggerated decline in functional reserves of multiple systems and organs. Frailty in patients with HF translates into worse functional status, poorer quality of life, the presence of disability, and dependence on the others, along with an increased risk of recurrent cardiovascular and non- cardiovascular hospitalizations, and high mortality.
Self-care and patient education
Authors: Jaarsma Tiny , Hill Loreena , Lambrinou Ekaterini , Strömberg Anna , Hansen Tina 
Published: December 2023

Abstract
Self-care is a vital part of the comprehensive management of heart failure. Self-care includes behaviours of patients and caregivers that aim to maintain stability, monitor changes in signs and symptoms, and respond to changes. Optimal self-care improves patient outcomes and can prevent deterioration and exacerbation. With a greater emphasis on self-care, the ability to participate in daily life requires knowledge as well as interpretation, skills, and action. All health-care providers have a responsibility to educate and support patients with heart failure and their caregivers. This chapter will explore a number of approaches to educating patients and caregivers, as well as the special considerations associated with health literacy. We also present a range of tools and resources that can be used in patient education. Furthermore, we describe the importance of including family members or other informal caregivers.
Digital health in heart failure
Authors: Singhal Arvind , Cowie Martin R 
Published: December 2023

Abstract
This chapter discusses digital technologies used in the diagnosis, monitoring, and management of heart failure (HF). Remote monitoring for decompensation of HF can be in the form of telephone support, or by telemonitoring systems which collect and send physiological data to the HF team. The evidence for remote monitoring is mixed, but remote pulmonary artery pressure monitoring is consistently effective at reducing HF hospitalization in patients at higher risk. Wearable devices are increasingly accurate at measuring physiological variables and show promise for HF monitoring and prognostication, rehabilitation, and for arrhythmia detection. Electronic health records are likely to become central to the connectivity and usability of multiple data streams, but challenges remain in integrating and summarizing these data for clinical decision making. Improving digital literacy and accessibility of digital technologies is essential to ensure equitable implementation of the advantages digital health can bring.
Big data in heart failure
Authors: Mamas Mamas A , Kotecha Dipak 
Published: December 2023

Abstract
Big data describes large volume of data, both structured and unstructured, that can be mined for information using machine learning approaches. Such data are recorded routinely as part of medical care and frequently form an essential part of care delivery. These data can be acquired from healthcare systems in which the treatment, risk stratification or identification of patients with heart failure (HF), and includes electronic healthcare records, imaging data, and/or information derived from wearable devices or apps. Data derived from real world patients with HF provides important information around trajectories, clinical outcomes and response to treatment of patient groups often excluded from randomized trials, and often form the basis of national audits and public benchmarking. They help inform the impact of national policies on HF patient outcomes and should be considered as complementary to data derived from randomized controlled trials. Machine learning approaches have been leveraged in such disparate data sources to allow for the identification of novel HF phenogroups, identify patients that will respond/do not respond to treatment and have contributed to the development of prognosis models that will promote a personalized approach to patients with HF.
Metabolic modulation of histone acetylation mediated by HMGCL activates the FOXM1/β-catenin pathway in glioblastoma
Authors: Sun Yanfei , Mu Guangjing , Zhang Xuehai , Wu Yibo , Wang Shuai , Wang Xu , Xue Zhiwei , Wang Chuanwei , Liu Jilong , Li Wenbo , Zhang Lin , Guo Yunyun , Zhao Feihu , Liu Xuemeng , Xue Zhiyi , Zhang Yan , Ni Shilei , Wang Jian , Li Xingang , Han Mingzhi , Huang Bin 
Published: December 2023

Abstract

Background
Altered branched-chain amino acid (BCAA) metabolism modulates epigenetic modification, such as H3K27ac in cancer, thus providing a link between metabolic reprogramming and epigenetic change, which are prominent hallmarks of glioblastoma multiforme (GBM). Here, we identified mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase (HMGCL), an enzyme involved in leucine degradation, promoting GBM progression and glioma stem cell (GSC) maintenance.

Methods
In silico analysis was performed to identify specific molecules involved in multiple processes. Glioblastoma multiforme cells were infected with knockdown/overexpression lentiviral constructs of HMGCL to assess malignant performance in vitro and in an orthotopic xenograft model. RNA sequencing was used to identify potential downstream molecular targets.

Results
HMGCL, as a gene, increased in GBM and was associated with poor survival in patients. Knockdown of HMGCL suppressed proliferation and invasion in vitro and in vivo. Acetyl-CoA was decreased with HMGCL knockdown, which led to reduced NFAT1 nuclear accumulation and H3K27ac level. RNA sequencing-based transcriptomic profiling revealed FOXM1 as a candidate downstream target, and HMGCL-mediated H3K27ac modification in the FOXM1 promoter induced transcription of the gene. Loss of FOXM1 protein with HMGCL knockdown led to decreased nuclear translocation and thus activity of β-catenin, a known oncogene. Finally, JIB-04, a small molecule confirmed to bind to HMGCL, suppressed GBM tumorigenesis in vitro and in vivo.

Conclusions
Changes in acetyl-CoA levels induced by HMGCL altered H3K27ac modification, which triggers transcription of FOXM1 and β-catenin nuclear translocation. Targeting HMGCL by JIB-04 inhibited tumor growth, indicating that mediators of BCAA metabolism may serve as molecular targets for effective GBM treatment.