bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosome-Level Genome Assembly of the Blacktail Brush Lizard,Urosaurus nigricaudus, Reveals Dosage Compensation in an Endemic Lizard
Authors: Davalos-Dehullu Elizabeth , Baty Sarah M , Fisher Robert N , Scott Peter A , Dolby Greer A , Munguia-Vega Adrian , Cortez Diego
Published: December 2023

Urosaurus nigricaudus is a phrynosomatid lizard endemic to the Baja California Peninsula in Mexico. This work presents a chromosome-level genome assembly and annotation from a male individual. We used PacBio long reads and HiRise scaffolding to generate a high-quality genomic assembly of 1.87 Gb distributed in 327 scaffolds, with an N50 of 279 Mb and an L50 of 3. Approximately 98.4% of the genome is contained in 14 scaffolds, with 6 large scaffolds (334–127 Mb) representing macrochromosomes and 8 small scaffolds (63–22 Mb) representing microchromosomes. Using standard gene modeling and transcriptomic data, we predicted 17,902 protein-coding genes on the genome. The repeat content is characterized by a large proportion of long interspersed nuclear elements that are relatively old. Synteny analysis revealed some microchromosomes with high repeat content are more prone to rearrangements but that both macro- and microchromosomes are well conserved across reptiles. We identified scaffold 14 as the X chromosome. This microchromosome presents perfect dosage compensation where the single X of males has the same expression levels as two X chromosomes in females. Finally, we estimated the effective population size for U. nigricaudus was extremely low, which may reflect a reduction in polymorphism related to it becoming a peninsular endemic.
Barriers primary care clinic leaders face to improving value in a consumer choice health plan design
Authors: McDonald Tim , Debbarma Arindam , Whaley Christopher , Reid Rachel , Dowd Bryan
Published: December 2023

Primary care clinics are a frequent focus of policy initiatives to improve the value of health care; yet, it is unclear whether they have the ability or incentive to take on the additional tasks that these initiatives ask of them. This paper reports on a qualitative study assessing barriers that clinic leaders face to reducing cost within a tiered cost-sharing commercial health insurance benefit design that gives both consumers and clinics a strong incentive to reduce cost. We conducted semi-structured interviews of clinical and operational leaders at a diverse set of 12 Minnesota primary care clinics and identified 6 barriers: insufficient information on drivers of cost; clinics controlling a portion of spending; patient preference for higher cost specialists; administrative challenges; limited resources; and misalignment of incentives. We discuss approaches to reducing these barriers and opportunities to implement them.
How policymakers innovate around behavioral health: adoption of the New Mexico “No Behavioral Health Cost-Sharing” law
Authors: Harris Samantha J , Golberstein Ezra , Maclean Johanna Catherine , Stein Bradley D , Ettner Susan L , Saloner Brendan
Published: December 2023

State policymakers have long sought to improve access to mental health and substance use disorder (MH/SUD) treatment through insurance market reforms. Examining decisions made by innovative policymakers (“policy entrepreneurs”) can inform the potential scope and limits of legislative reform. Beginning in 2022, New Mexico became the first state to eliminate cost-sharing for MH/SUD treatment in private insurance plans subject to state regulation. Based on key informant interviews (n = 30), this study recounts the law's passage and intended impact. Key facilitators to the law's passage included receptive leadership, legislative champions with medical and insurance backgrounds, the use of local research evidence, advocate testimony, support from health industry figures, the severity of MH/SUD, and increased attention to MH/SUD during the COVID-19 pandemic. Findings have important implications for states considering similar laws to improve access to MH/SUD treatment.
Application of plant fibers in subgrade engineering: current situation and challenges
Authors: Guo Jiayi , Yi Junyan , Pei Zhongshi , Feng Decheng
Published: December 2023

The application of plant fibers in subgrade engineering is increasingly receiving attention. As a sustainable material, plant fibers possess characteristics such as lightweight, renewability, and biodegradability. The morphology, chemical composition, mechanical properties, and hydraulic properties of plant fibers determine their application scenarios in subgrade engineering. Degradation is also an important factor affecting the long-term performance of plant fibers. In order to overcome their limitations in subgrade engineering, physical and chemical modifications have become necessary. Through physical or chemical modification, the compatibility between plant fibers and the matrix can be enhanced, improving dispersibility and adhesiveness. Plant fibers can be applied in subgrade engineering through methods, such as soil improvement, incorporation into geosynthetic materials, and the use of prefabricated components. Among these, soil improvement with plant fiber can enhance soil crack resistance and stability, adding fibers to geosynthetic materials can strengthen the mechanical properties of the soil, and prefabricated components can effectively reinforce slopes. This article reviews the current application status of plant fibers in subgrade engineering. In comparison to other soil stabilization materials, plant fibers offer clear economic and environmental advantages. Nevertheless, they come with two drawbacks, namely restricted mechanical properties and excessive water absorption. Challenges such as technical standards, fiber dispersibility, and durability still exist in their application. In the future, the application of plant fibers in subgrade engineering will continue to expand. Through technological innovation and standard development, it will provide environmentally friendly and efficient solutions for sustainable subgrade construction.
British Columbia beekeeping revenues and costs: survey data and profit modeling
Authors: Bixby Miriam , Cunningham Morgan , Foster Leonard , Higo Heather , Morfin Nuria
Published: December 2023

British Columbia beekeepers, like many beekeepers around the world, are currently facing declines in honey bee health and high overwinter colony losses. To better understand the economics and the cycle of yearly colony loss and replacement of this critical agricultural industry, we collected and analyzed survey data on beekeeping costs and returns. Forty British Columbia beekeepers provided details about revenue sources, variable costs, capital costs, and investments. Ten surveyed beekeepers managed between 1 and 9 colonies, 10 managed between 10 and 39 colonies, 9 managed between 40 and 100 colonies, 5 managed between 101 and 299 colonies, 3 managed between 300 and 699 colonies, and 3 managed 700 colonies or more. The data was used to calculate beekeeping profit and to parameterize a model that explores the economic impact of colony loss rates and replacement strategies. Survey results show that when the data is aggregated, revenues exceed costs for beekeeping operations in British Columbia with a per colony profit of $56.92 or $0.87 per pound of honey produced. Surveyed operations with fewer than 100 colonies have negative profits, while operations with 100–299 colonies have positive profits. Surveyed operations in the Cariboo, North Coast, and Okanagan regions have the highest profits while surveyed operations in the Peace region have the lowest profits. Profit modeling shows that replacing losses with packages generates lower profit than replacing losses with split colonies. Our modeling shows that operations that diversify their revenue to include bee sales and commercial pollination accrue higher profits and can withstand higher winter loss rates.
The impact of COVID-19 and long COVID on sexual function in cisgender women
Authors: Seehuus Martin , Fertig Madison , Handy Ariel B , Clifton Jessica , Stanton Amelia M
Published: December 2023

Background

Research suggests that COVID-19 impairs sexual function in men, but little is known about the impact of COVID-19 (or long COVID) on sexual function in women.

Aim

We sought to compare the sexual function of cisgender women who had never had COVID-19, who had COVID-19 but not long COVID, and who had long COVID, and assessed whether long COVID symptoms and/or emotional distress mediate the relationship between COVID-19 history and sexual function.

Methods

In total, 2329 adult cisgender women were recruited online as study participants. Half of these women reported having had COVID-19, and the other half reported never having had COVID-19. Of those who had COVID-19, 25% (n = 170) reported having long COVID. We compared the mean Female Sexual Function Index (FSFI) scores by using t-tests for each of the primary comparison categories (never COVID vs COVID and only COVID vs long COVID). Four path models were used to test the hypotheses that (1) long COVID symptoms or (2) depression, anxiety, and/or stress assessed with the subscales of the 21-item Depression, Anxiety, and Stress Scale (DASS-21) mediated the relationship between COVID-19 and sexual function.

Outcomes

Sexual function was measured with the FSFI, long COVID symptoms were assessed using the Centers for Disease Control working symptom set, and emotional distress was measured with the DASS-21.

Results

In total, 1313 participants provided data suitable for analysis. The never-COVID group (n = 645, 49.1%) had higher scores on the Desire, Arousal, Lubrication, and Satisfaction subscales of the FSFI (mean [M] [SD] FSFI total Mnever COVID = 27.98 [4.84] vs MCOVID = 27.05 [5.21]) than the combined only-COVID (n = 498, 37.9%) and long-COVID (n = 170, 12.9%) groups. The FSFI subscale scores were significantly higher in the only-COVID group than in the long-COVID group for the Arousal, Lubrication, and Orgasm and lower for the Pain subscales and higher for overall sexual function (FSFI total Monly COVID = 27.49 [5.00] vs Mlong COVID = 25.77 [5.61]. None of the proposed mediation models had adequate model fit.

Clinical Implications

Clinicians treating cisgender women who have COVID-19 should consider proactively discussing sexual function with their patients and offering available resources.

Strengths and Limitations

In this study we used a large and diverse sample, but this sample did not include transgender or gender-diverse persons. This study was also correlational; as such, causal conclusions cannot be drawn. Further, the mechanism of action remains unexplained.

Conclusions

The study findings suggest the following: (1) COVID-19 infection is associated with impaired sexual function in cisgender women, and (2) that women with long COVID experienced incrementally more impaired sexual function than women with COVID-19 who did not develop long COVID.
Dilated and hypokinetic non-dilated cardiomyopathy
Authors: Seferović Petar M , Bozkurt Biykem , Polovina Marija
Published: December 2023

Dilated cardiomyopathy (DCM) refers to a variety of heterogeneous myocardial disorders that result in ventricular dilatation accompanied by contractile dysfunction. Aetiologies include genetic, metabolic, infectious, inflammatory, toxin-induced, autoimmune, and endocrine causes, peripartum cardiomyopathy, tachycardia-induced cardiomyopathy, and progression of hypertrophic/infiltrative cardiomyopathies to a dilated phenotype in advanced stages. DCM is an important cause of heart failure with reduced ejection fraction (HFrEF), and the leading indication for heart transplantation. Besides the risk of progressive heart failure, DCM is associated with a high risk of arrhythmias and sudden cardiac death. Patients with DCM should undergo thorough diagnostic evaluation, including diagnostic strategies appropriate for all patients with heart failure, and a dedicated search for a specific aetiology. Those with HFrEF should also receive guideline-directed therapies (GDT) for their management. Additionally, when a specific treatment strategy is available for a specific aetiology, it should be considered, in addition to GDTs for HFrEF.
Hypertrophic cardiomyopathy
Authors: Elliott Perry , Noutsias Michel , Anastasakis Aris
Published: December 2023

Hypertrophic cardiomyopathy is an inherited myocardial disease defined by cardiac hypertrophy that is unexplained by abnormal loading conditions. Typical symptoms include dyspnoea, chest pain, palpitations, and syncope, often caused by dynamic obstruction to the left ventricular outflow tract. Some patients are at increased risk of sudden cardiac death, heart failure, and atrial fibrillation. Treatment focuses on the relief of symptoms with drugs and septal reduction therapies for left ventricular outflow obstruction, prevention of sudden cardiac death with implantable cardioverter–defibrillators, and prevention of stroke with anticoagulation.
Myocarditis and pericarditis
Authors: Heymans Stephane , Ristić Arsen D , Adler Yehuda , Imazio Massimo
Published: December 2023

Myocarditis can cause atrial and ventricular arrhythmias, and transient or chronic and progressive heart failure. Viruses are the most frequent infectious triggers. Systemic diseases and toxic agents are important non-infectious causes of myocarditis. As viral triggers in peri- and myocarditis are common cough viruses, with only a minority of infected persons developing peri- or myocarditis, a certain immune–genetic susceptibility—including coding and non-coding genes—of the affected person is key. Endomyocardial biopsies are indicated in acute myocarditis if progressive or persistent severe cardiac dysfunction and/or life-threatening ventricular arrhythmias with a lack of short-term response to usual medical treatment are present. Cardiac magnetic resonance is essential in all patients with a high suspicion of myocarditis, after significant coronary artery disease has been excluded or considered to be unlikely. This chapter will discuss the pathophysiology of (peri-)myocarditis and its heterogeneous disease presentation, as well as its diagnosis and treatment in more detail.
Congenital heart disease
Authors: Budts Werner , Roos-Hesselink Jolien
Published: December 2023

In addition to arrhythmia, heart failure (HF) is one of the major late complications in adult congenital heart disease (ACHD). Residual lesions and sequelae of previous interventions might cause circulatory failure, with or without progressive ventricular dysfunction, leading to reduced functional capacity, signs and symptoms of HF, and finally premature death. Structural optimization is the first step to counter this disease progression, but in many cases, medical treatment is needed to stabilize against further deterioration. In contrast to HF in acquired heart disease, evidence of clinical benefit of drug therapy in ACHD is limited to lacking. As a last resort, resynchronization, ventricular assist device, and transplantation are options to consider. However, venous access, anatomical complexity, and associated comorbidity strongly influence the decision-making process.
Endocrine and metabolic abnormalities
Authors: Huelsmann Martin , Seferović Jelena P , Cosentino Francesco
Published: December 2023

Endocrine and metabolic diseases can affect the structure and/or function of the heart. The most common endocrine diseases that could lead to heart failure (HF) are thyroid disorders, phaeochromocytoma, and primary hyperaldosteronism. Other endocrine diseases related to HF are rare and include parathyroid, pituitary, as well as adrenal gland, abnormalities. Endocrine diseases may also worsen pre-existing HF. Treatment of underlying disorders usually improves HF. Although HF in endocrine diseases is rare, it may have an adverse prognostic impact. Therefore, careful screening with natriuretic peptides and/or echocardiographic assessment is mandatory. In the setting of HF, endocrine causes are often reversible. Therefore, the differential diagnosis of causes of congestive heart failure should always include an endocrinological pattern of laboratory tests.
Cancer and cancer therapy
Authors: Farmakis Dimitrios , Lyon Alexander , Lopez Fernandez Teresa , Cardinale Daniela
Published: December 2023

Heart failure can be caused by a range of cardiotoxic cancer therapies. The most common are anthracycline chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, with the development of targeted molecular cancer therapies, the number of cancer treatments causing heart failure are increasing with new culprits identified every year. Some cardiotoxic cancer treatments cause myocyte necrosis or apoptosis and permanent cardiac injury, whereas others can cause temporary impairment of ventricular function, which recovers after withdrawal of the culprit cancer drug. Immune checkpoint inhibitors can cause heart failure by activating acute fulminant myocarditis or via a non-inflammatory heart failure syndrome during prolonged treatment. In addition, other forms of cancer therapy-induced cardiotoxicity, such as arterial hypertension, myocardial ischaemia, rhythm disturbances, and thromboembolism, may also contribute to the development or exacerbation of heart failure. High-dose irradiation to a volume, including the heart, is also a cause of heart failure that occurs many years later, either directly via myocardial damage or indirectly via radiation-induced coronary, valvular, or pericardial disease. Cancer itself may further affect the cardiovascular system through metabolic derangement, autonomic dysfunction, and other mechanisms, while there is increasing recognition of myocardial atrophy and dysfunction as a result of cachexia in patients with advanced malignancies.
Neurohormonal activation in heart failure
Authors: Bayes-Genis Antoni , Zannad Faiez
Published: December 2023

Heart failure (HF) with reduced ejection fraction (HFrEF) has evolved over the past three decades from a mainly cardiac structural derangement to the result of deleterious effects of sustained neurohormonal activation on the heart and circulation. Some of the neurohormonal axes activated in HF have vasoconstrictor and antidiuretic effects (with growth-promoting properties), and include the sympathetic nervous system, the renin–angiotensin–aldosterone system, and the vasopressin–arginine system. In the acute setting, these adaptive responses may be beneficial, but long-term overactivation, such as that seen in patients with chronic HF, results in maladaptive processes such as left ventricular remodelling and disease progression. Other systems, including the natriuretic peptide system (with natriuretic and antimitogenic effects), exert opposing counter-regulatory vasodilatory pathways. The neurohormonal hypothesis of HF has been validated in multiple landmark clinical trials, which construe current evidence-based treatment for patients with HFrEF.
Inflammation, oxidative stress, and endothelial dysfunction
Authors: Heymans Stephane
Published: December 2023

The capillary bed is essential to provide sufficient oxygen and nutrients to cardiomyocytes, and controls inflammation and fibrosis under pathological conditions. Microvascular rarefaction and dysfunction are central in causing cardiac dysfunction and structural remodelling. Regulation of oxidative stress, control of the influx of inflammatory cells, and sensing of mechanical stress and metabolic load (lipids and glucose) are the main functions of these endothelial cells. Therefore, diabetes, hyperlipidaemia, hypertension, and immune dysregulation strongly impact endothelial function, causing cardiac hypertrophy and resulting in cardiac dysfunction, mainly heart failure with preserved ejection fraction.
Heart failure with mildly reduced ejection fraction
Authors: Voors Adriaan A , Moura Benda , Lund Lars , Lam Carolyn SP
Published: December 2023

The 2016 European Society of Cardiology (ESC) Heart Failure Guidelines introduced heart failure with mildly reduced ejection fraction (HFmrEF) as a separate category of patients. These patients have a left ventricular ejection fraction (LVEF) of between 40% and 50%. Patients in this mildly reduced category were already acknowledged as an unidentified ‘grey area’, and the main purpose of providing this category of patients with a name was to gain knowledge on their prevalence, characteristics, clinical outcome, and treatment responses. Four years later, a large number of studies have increased our knowledge on patients with HFmrEF. Firstly, the most important lessons are that with regard to an ischaemic aetiology, HFmrEF more closely resembles heart failure with reduced ejection fraction (HFrEF) than heart failure with preserved ejection fraction (HFpEF). Secondly, the ejection fraction often changes over time and these changes seem to be prognostically more important than the baseline ejection fraction alone. Lastly, retrospective analyses from prospective randomized clinical trials, including the full spectrum of LVEF, suggest that patients with HFmrEF might benefit from therapies that have been shown to improve outcome in HFrEF, whereas no such benefit was seen in patients with HFpEF. This resulted in the renaming of ‘heart failure with mid-range ejection fraction’ to ‘heart failure with mildly reduced ejection fraction’, and in new recommendations for therapies for patients with HFmrEF in the 2021 ESC Heart Failure Guidelines.
Right heart failure
Authors: Lüscher Thomas F , Gorter Thomas M , Price Susanna , Riele Anneline , Gatzoulis Michael A
Published: December 2023

The right ventricle (RV) is crucial to maintaining the circulation but differs from the left ventricle (LV) in shape, myocardial mass, pressure, and blood supply. It is affected by a number of diseases that differ from those impacting the LV. The RV is a low-pressure chamber and, as such, suffers particularly from increasing afterload that originates from dysfunction of the LV (i.e. heart failure with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) ejection fraction) and pulmonary arterial hypertension. Furthermore, there are cardiac conditions that primarily or mainly affect the RV. Arrhythmogenic cardiomyopathy is a fibrofatty restructuring of the free right ventricular wall (in some involving the LV), leading to right ventricular pump failure, arrhythmias, and sudden cardiac death. Right ventricular infarction, often overlooked in the acute setting, can cause similar complications. Finally, congenital heart diseases, such as atrial and ventricular septal defects, Ebstein disease, and complex malformations, particularly affect right ventricular function, either directly or indirectly, which importantly determines their outcome.
Echocardiography
Authors: Debonnaire Philippe , Delgado Victoria , Edvardsen Thor , Popescu Bogdan A , Bax Jeroen J
Published: December 2023

Non-invasive cardiac imaging determines heart failure diagnosis, risk stratification, prognosis, and stepwise clinical patient approach. Echocardiography is the preferred first-line imaging tool. Cardiovascular magnetic resonance, computed tomography, and nuclear imaging further refine management strategy, depending on local expertise, availability, risk/benefit, and economic considerations. Imaging of functional and structural cardiac abnormalities initiates heart failure diagnosis, subtyping, and aetiology. The presence of significant coronary artery disease is subsequently ruled out by functional (ischaemia) or anatomical (stenosis) cardiac imaging tests. Myocardial viability detection justifies and predicts the effect of myocardial revascularization. The extent of ventricular remodelling (geometry), defined by size and shape, is additionally assessed to identify the need, timing, and type of additional heart failure therapy (drugs, devices, and/or interventions). Finally, non-invasive cardiac imaging aids to select heart failure patients who might benefit from percutaneous or surgical valve repair or replacement.
Angiotensin-converting enzyme inhibitors
Authors: Ferrari Roberto , Guardigli Gabriele , Bozkurt Biykem
Published: December 2023

Few stories in the history of medical research can generate interest and inspire as much as the mythical journey from ‘Poison to Panacea’. When Ferreira travelled from Santiago to London to work in the laboratory of Sir John Vane, he could not have imagined that a bite from Bothrops jararaca, a Brazilian viper, could give rise to angiotensin-converting enzyme (ACE) inhibitors, which to date have arguably the strongest portfolio of placebo-controlled trials in medicine. After the discovery of these drugs, the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) I was conducted and proved pivotal in the practice of cardiology. CONSENSUS I gave both hope and belief—hope that breathless patients with advanced congestive heart failure (CHF) could be treated with a drug that can impact significantly the natural history of the disease, and belief that a new class of medicine had finally arrived as a result of this study and of many subsequent others that have shown that ACE inhibitors have a demonstrable efficacy in patients with left ventricular dysfunction with or without CHF symptoms, in those after an acute myocardial infarction, and even in the prevention of myocardial infarction and its associated sequelae in the context of primary or secondary prevention. Treatment of all these patients is supported by both American and European guidelines, expert opinion, and convincing clinical trials. It is a practical first-line recommendation to all clinicians, healthcare providers, and policymakers to mirror the details of the main trials as much as possible with regard to the drug, dosage, and frequency of administration. This chapter describes the journey of the ACE inhibitor drug class from its origins—the poisonous venom of the Brazilian pit viper Bothrops Jararaca to its use (rather than non-use) during the actual Covid-19 pandemic.
Beta-blocker therapy
Authors: Tomasoni Daniela , Adamo Marianna , Tsutsui Hiroyuki , Metra Marco
Published: December 2023

Beta-blockers are the mainstay of current treatment of patients with chronic heart failure with reduced ejection fraction (HFrEF). Randomized clinical trials have consistently shown their beneficial effects on mortality and morbidity, including hospitalization, in patients with HFrEF. These favourable effects are associated with left ventricular reverse remodelling and improved ejection fraction. Current heart failure guidelines recommend treatment with bisoprolol, carvedilol, metoprolol succinate, or nebivolol to reduce the risk of heart failure hospitalization and death. However, their use in clinical practice remains low and needs further implementation. Further data are also needed in specific subgroups where lack of efficacy was shown in retrospective analyses such as in patients with concomitant atrial fibrillation and those with heart failure with preserved ejection fraction. Also an individualized approach seems reasonable, with women probably requiring lower doses.
Diuretics
Authors: Dauw Jeroen , Gottlieb Stephen , Mullens Wilfried
Published: December 2023

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

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

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

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

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

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

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

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

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: 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 < 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 < 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 <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 < 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

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

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

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

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

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

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.