Definite dilated cardiomyopathy genes.
\r\n\tThe emphasis is on developing or modifying the available oral health diagnosis and preventive and corrective methods for children starting from newborn to pre-schoolers to school going and up to adolescence.
\r\n\tProfessionals involved in providing oral health care to children must keep themselves updated with the available and newer behaviour management and dental procedures and techniques that may begin with the first dental visit of the child write up to providing preventive and comprehensive treatment to the child and develop long-lasting good oral health habits.
\r\n\tThis book will provide an opportunity for various health professionals to share their expertise which may vary from providing various forms of oral health procedures to children at an individual and community level.
The prevalence of heart failure is approximately 1–2% in the adult population and is 10% for those above the age of 70 years [1]. Dilated cardiomyopathy (DCM) is a common form of heart failure defined by dilatation of the left ventricle and reduced ejection fraction [2]. In later phases, dilation of the right ventricle and both atria is often seen, although this is not required for diagnosis. The disease confers a reduction in left ventricular ejection fraction but in early stages dilatation of the left ventricle can be seen with only minimal reduction of systolic function. Definitions vary, sometimes a distinction is made between ischemic and nonischemic DCM; however more often DCM refers to a disease that is not explained by coronary artery disease or abnormal loading conditions due to hypertension or valve defects [2]. With this definition the prevalence is at the least 1 in 2500 in the general population, which is likely an underestimation and some estimates refer the prevalence as high as 1 in 250 [3, 4]. In more than 20% of these patients a known disease causative mutation is found [3, 5]. Mutations in more than 50 different genes have been associated to DCM and some of the most common are the genes encoding for lamin A/C, titin, and desmin [1, 6]. Often the phenotype is the similar regardless of the causative mutation, therefore broad gene panels are used in genetic testing. Some genes however affect the conduction system and have been linked to an increase in sudden cardiac death.
Definitions of cardiomyopathies differ over time and between clinical traditions. While in the future cardiomyopathies might be classified after causative mutations, they have traditionally been classified by phenotype and cardiac morphology, e.g. DCM or hypertrophic cardiomyopathy (HCM). This system of classification has the advantage that the phenotype is most often known prior to the genotype.
Originally, cardiomyopathies were considered distinct primary myocardial disorders of unknown etiology, whereas heart muscle disorders of known etiology or caused by systemic disease were classified as secondary or specific heart muscle disease. In 2006 the American Heart Association proposed a classification that defined cardiomyopathies either as primary or secondary, referring either to a disease were the heart is the sole or primarily affected organ, alternatively where myocardial involvement is part of a systemic disease [7]. However, in 2008, the European Society of Cardiology (ESC) proposed an alternate classification in which a cardiomyopathy is defined as “a myocardial disorder in which the heart muscle is structurally and functionally abnormal in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality”. Furthermore, the ESC subdivides cardiomyopathies depending on morphology and function as well as based upon inheritance pattern; distinguishing between familial or genetic forms versus non-familial or non-genetic forms of cardiomyopathy (Figure 1) [2].
Classification of cardiomyopathies proposed by the European Society of Cardiology [
DCM is a distinct cardiomyopathy and a common cause of heart failure defined by dilatation of the left ventricle and reduced ejection fraction [2]. In later phases dilation of the right ventricle and the atria is often seen, however this is not required for diagnosis. For the diagnosis of DCM, the reduction in global systolic function should not solely be attributable to coronary artery disease or abnormal loading conditions (hypertension, valve disease) [2].
Familial DCM is diagnosed when at least two relatives (first-degree or second-degree) meet the diagnostic criteria for DCM [8].
Diagnostic evaluation for suspected heart failure should be managed in accordance with guidelines, such as those of the ESC [1]. Echocardiography constitutes a cornerstone of the evaluation and is readily available. For the diagnosis of DCM both left ventricular systolic dysfunction, as well as dilatation of the left ventricle, needs to be present and not explained by coronary artery disease or abnormal loading conditions (hypertension, valve disease) [9]. Left ventricular systolic dysfunction is defined as abnormal left ventricular systolic ejection fraction measured with any modality, preferentially echocardiography or cardiac magnet resonance tomography. Left ventricular dilatation (Figure 2) is defined as left ventricular end-diastolic volumes or diameters >2 standard deviations according to nomograms (Z > 2 standard deviations) after correction for body surface area and age, or body surface area and sex [9].
Echocardiography with apical four chamber view showing spherical dilatation of the left ventricle. Image adapted from Jamil et al. [
Cardiac magnetic resonance tomography is valuable as a complement to echocardiography. It allows for a better evaluation of the whole myocardium including the right ventricle and septum which provides aid in ruling out other cardiomyopathies such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and HCM. Myocarditis has been identified as a cause of acquired forms of DCM [10]. Cardiac magnetic resonance can be used to assess the presence of active myocarditis as well as scar tissue that could indicate previous episodes of myocarditis. Cardiac magnetic resonance imaging is, according to the ESC, indicative of active myocarditis if it, in the setting of clinically suspected myocarditis, fulfills 2 out of 3 Lake Louise criteria [11]. These criteria include; high signaling on T2-weighted images (indicative of edema), early gadolinium enhancement (indicative of increased blood flow), and late gadolinium enhancement (indicative of scar tissue) [11].
Of particular importance is a family history of cardiomyopathy, arrhythmia or sudden cardiac death. If another family member also fulfills the criteria for DCM the patient can be said to have familial DCM [8]. A pedigree, a family tree, could be drawn to visualize what family members are affected by the disease or certain symptoms as well as how they are related to each other. By doing this the type of inheritance pattern can often be discerned, see Section 5.1. Inheritance patterns.
Genetic testing requires knowledge about genetics, the disease in question, as well as legal and ethical considerations. It is important that the patient is the one who makes an informed decision about if a gene test should be performed [13]. It is also important to be aware of what the benefits and potential detriments of a genetic test are. The current ESC Heart failure guidelines from 2016 recommend that genetic testing should be performed in accordance with the ESC position statement on genetic counseling and testing in cardiomyopathies from 2010 [1, 13]. Most genotypes cannot be distinguished from each other by evaluation of the phenotype. Due to this broad gene panels are required that incorporate most known definite and putative DCM genes. The ESC states that the main role of genetic testing is in patients with an already confirmed diagnosis of idiopathic DCM (where acquired causes has been ruled out) to enable genetic testing of first degree-relatives and possibly cascade screening, see Section 5.2. Family screening. They caution against the use of genetic testing to establish the diagnosis of a cardiomyopathy in borderline cases except for in the setting of expert teams after detailed clinical and family assessment. In definite DCM most often, the exact gene affected do not change the clinical management of that individual patient. However, in some cases of DCM with red flags such as simultaneous conductions disorders indicative of a specific phenotype, genetic testing can be used to establish a specific genetic diagnosis. In patients with mutations in LMNA that causes DCM, genetic diagnosis might affect the clinical management. It should be noted that negative genetic tests do not rule out that the cardiomyopathy is familial or genetic. The interpretation of genetic tests is time consuming, complicated, and often not conclusive. When the ESC position statement was written in 2010 genetic tests had been mainly used for research purposes and had recently become available for clinicians. Genetic tests have today become more affordable and available. The current trend is towards more genetic evaluations being conducted and it is our opinion that this trend should continue. More patients with DCM receiving a genetic diagnosis will over time improve knowledge of the different genotypes. In order to offer equal health care genetic testing must be conducted even outside the setting of tertiary centers.
Heart failure management should be in accordance with guidelines, such as those of the ESC, which are summarized below [1]. An angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is indicated in left ventricular systolic dysfunction. If symptomatic, i.e. New York Heart Association functional classification (NYHA-class) 2 or above, a beta-blocker should be added to treatment with the ACEi/ARB. In patients who remain symptomatic with systolic ejection fraction ≤35% despite the highest tolerable evidence-based doses of ACEi or ARB as well as a beta-blocker, a mineral receptor antagonist is recommended with maximum tolerated evidence-based dose. If the patient is still symptomatic with systolic ejection fraction ≤35% it is recommended to initiate treatment with an angiotensin receptor neprilysin inhibitor that replaces the ACEi/ARB [1]. Further treatment modalities that should be considered include the addition of ivabradine in patients with sinus rhythm ≥70 beats per minute, or the implantation of a cardiac device to allow for cardiac resynchronization therapy in those with left bundle branch block and QRS ≥130 ms or without left bundle branch block but QRS ≥150 ms. These mentioned treatment modalities have shown increased survival in randomized controlled trials [1]. Digoxin could be considered if symptoms remain, however reduced mortality has not been shown but rather reduced need for hospitalization. The small therapeutic window of digoxin should be kept in mind, most commonly digoxin is used for rate control in atrial fibrillation that is common in heart failure. Loop-diuretics such as furosemide should be considered in patients with heart failure to relieve symptoms and signs of congestion, but this has not been shown to reduce mortality. The dosage of diuretics should be kept as low as possible and cessation of treatment might often be possible. In end-stage heart failure, transplant might be considered or mechanical left ventricular assist devices that can be used as destination therapy, bridge-to-decision, or bridge to transplant [1].
Lately inhibition of sodium-glucose transporter protein 2 (SGLT2i) has proved an interesting treatment modality for heart failure with reduced ejection fraction. In the EMPA-REG trial in 2015, the SGLT2i empagliflozin showed reduced cardiovascular mortality, reduction in all-cause mortality, and reduced need for hospitalization for heart failure in patients with type 2 diabetes mellitus [14]. In 2019 the results of the DAPA-HF trial showed that the SGLT2i dapagliflozin reduced cardiovascular and all-cause mortality as well as risk of worsening heart failure in patients with heart failure with reduced ejection fraction even if they did not have diabetes mellitus [15].
There is an increased risk for both brady- and tachyarrhythmia in DCM, these arrhythmias can also be a contributing factor worsening heart failure. In symptomatic sinus node disease or in high-degree atrioventricular (AV)-block without a reversible cause a pacemaker is indicated in order the relieve symptoms and/or increase survival [3]. Beta-blockers are often indicated for the treatment of symptomatic heart failure but also have antiarrhythmic properties making it useful for both rhythm and rate control. With the exception of beta-blockers currently available antiarrhythmic drugs have not consistently been shown in randomized clinical trials to improve survival in the primary management of arrhythmia. Amiodarone have shown some positive results and is highly useful to control symptoms, to terminate tachyarrhythmia and prevent recurrence [3]. In heart failure with reduced ejection fraction most other antiarrhythmic agents are contraindicated, this includes flecainide and dronedarone otherwise frequently used for rhythm control in atrial fibrillation [3].
An implantable cardioverter defibrillator (ICD) is an effective way to prevent sudden cardiac death in those at risk for developing ventricular tachycardia or ventricular fibrillation [3]. An ICD offers both antitachycardia pacing, rapid ventricular pacing (preferably bursts), that can terminate ventricular tachycardia, as well as cardioversion that effectively terminate ventricular tachycardia and ventricular fibrillation. In addition, an ICD also functions as a bradycardia pacemaker and in combination with a left-ventricular lead it can offer cardiac resynchronization therapy.
The ESC recommends a primary prophylactic ICD for patients with symptomatic heart failure (NYHA-class II-III), left ventricular systolic ejection fraction ≤35% despite at least three months of optimal medical therapy and a life expectancy of at least 1 year [3]. The recommendation is class I (is recommended) for both heart failure due to ischemic heart disease as well as nonischemic cardiomyopathy. The level of evidence is considered stronger for heart failure with ischemic etiology (level A) than for nonischemic etiology (level B) [3]. In the SCD-HeFT trial an ICD reduced all-cause mortality as well as sudden cardiac death in patients with reduced ejection fraction [16]. In the DEFINITE trial, with a study population of patients with heart failure due to nonischemic etiology, sudden cardiac death was reduced by 80%, however reduction in all-cause mortality did not reach statistical significance (hazard ratio 0.65, p = 0.08) [17]. In 2016, the DANISH trial randomized participants with heart failure of nonischemic origin to either an ICD or otherwise optimal medical management (both groups were eligible for cardiac resynchronization therapy), after 5 years there was a significant reduction in sudden cardiac death (HR; 0.50, p = 0.005) [18]. For the whole group no significant reduction was seen in all-cause mortality (HR; 0.87, p = 0.28), however subgroup analysis of patients younger than 68 years showed a reduction all-cause mortality (hazard ratio 0.64; p = 0.01) [18]. This caused uncertainty about whether patients with heart failure of nonischemic etiology should receive ICDs on the same indications as those with ischemic etiology. Since then, a meta-analysis of six trials, that included DANISH, has showed that ICD on primary-prevention indication in patients with heart failure of nonischemic etiology reduced all-cause mortality (hazard ratio 0.76, p = 0.001) [19]. An analysis of the Swedish Heart Failure Registry revealed a 27% relative risk reduction in all-cause mortality after 1 year, this was consistent in both the subgroup with ischemic and with nonischemic etiology [20]. We have previously published a retrospective observational study of our ICD-cohort [21]. In our study 236 patients with primary prevention ICD due to heart failure of ischemic (61.9%) or nonischemic (38.1%) etiology were included, there was no difference in cumulative risk for appropriate therapy between the groups (Mantel-Cox p = 0.985) [21]. The guidelines of the ESC recommending implantation of a primary prevention ICD should therefore be followed in patients with heart failure with both ischemic etiology as well as nonischemic DCM [3].
Most genetic mutations that cause familial DCM have an autosomal dominant inheritance pattern with variable penetrance [22]. However, autosomal recessive, X-linked recessive and mitochondrial inheritance patterns have been described [22]. Sometimes a mutation is found that does not occur in any of the parents, this is called a
Autosomal inheritance is related to a mutation in an autosome, i.e. any chromosome that is not a sex chromosome. Dominant inheritance pattern implies that it is enough with only one mutant allele for the disease to be expressed. This means that the effect of a mutation in a gene masks or overrides the effect of a normal variation of the same gene on the other copy of the same chromosome. Those who have only a mutation in one of their two gene copies are said to be heterozygous. Due to a complex interplay with other genes and with the environment the disease is not always expressed, this is called varying penetrance. Men and women are equally as likely to inherit a mutated gene from a parent that carries it, regardless if it is the father or mother. If one parent carries one copy of the mutated gene, the offspring has a 50% risk of inheriting it. If both parents carry one copy of the gene, the offspring has a 75% risk of inheriting at least one copy.
Autosomal recessive inheritance is caused by mutation in a gene situated on an autosome but requires both the copy inherited from the father and the copy from the mother to be mutaded. For the mutation to cause the disease to be expressed the carrier needs to be homozygous for the mutation. This inheritance pattern requires both parents to carry at least one gene affected by the mutation. Men and women are equally as likely to inherit two affected gene copies from a certain pair of parents. If both parents carry one mutated gene, the offspring has a 25% risk of inheriting two mutated gene copies.
X-linked recessive inheritance pattern is caused by a mutation in a gene situated on the X chromosome. Since the X chromosome is a sex chromosome and females have two copies while males have only one copy, if the inheritance pattern is recessive, males will be affected, while females need to inherit a mutated gene from both their father and mother in order to be affected. Since men never inherit their X-chromosome from their father, the mutated gene can never pass to a son from his father. Daughters have always inherited one of their X-chromosomes from their father, thus an affected father will always have passed the mutated gene on to his daughters. This daughter will only be a carrier and not affected by the disease, unless she also has inherited the mutated gene from her mother. It is therefore common for X-linked recessive diseases to skip generations of daughters. A female that carry one mutated gene copy have a 50% risk of passing this on to both their sons and daughters.
In humans, mitochondria, and also mutations affecting mitochondrial DNA, is inherited from the mother. Both males and female can be affected by mitochondrial disease but only females can pass on the mutation to their offspring.
In many European countries including Sweden, the physician has no legal right to contact or inform first-degree relatives about the results of a genetic test. Instead the patient must be equipped with sufficient knowledge, both verbally and in written form to inform relatives about the genetic aspect of the disease, although usually there is no legal obligation for the patient to do this.
If the proband, the first identified individual with DCM in a family, has a known disease-causing mutation it is possible to screen all first-degree relatives for this single mutation [13]. If the inheritance pattern is autosomal dominant, children each have 50% risk of carrying the mutation. A simple genetic test could with certainty confirm or reject that an individual carries the mutation, this has large implications. If the individual is not a carrier of the mutated gene, no further follow-up is required, no cascade screening is needed of this individual’s children, and the individual have a better chance of living a normal life.
If instead the gene test confirms that an individual carries the mutated gene, so called cascade screening should be considered of this individual’s first-degree relatives. Carrying a known disease-causing mutation implies that cardiologic evaluation should be conducted consisting of at least 12-lead ECG and echocardiography. If this evaluation results in a diagnosis of DCM life-long follow-up is required. If this cardiologic evaluation is inconclusive or finds no signs of DCM continued follow-up is still required. The penetrance of familial DCM is most often age-dependent, age at diagnosis of DCM is most often seen during or after puberty up until 60 years of age [13]. Therefore, renewed assessment with at least ECG and echocardiography should be conducted every year between the ages of 10 and 20 and then every 1–3 years.
In idiopathic DCM, in a setting where genetic testing is not available, negative, or inconclusive, familial DCM can still not be ruled out. All first-degree relatives of the proband should undergo cardiologic evaluation with at least 12-lead ECG and echocardiography [13]. If they are diagnosed with DCM life-long follow-up is required and all their first-degree relatives should undergo cardiologic evaluation as well. If instead the cardiologic evaluation is negative for DCM, the relative should be followed-up with repeat cardiologic evaluations; every 1–3 years for those younger than 10 years of age, every 1–2 years between the age of 10 and 20, and every 2–5 years from 20 years of age up until 50–60 years of age. The reason for this continued evaluation during life is the age-dependent penetrance. For those affected, penetrance is almost complete at 60 years of age, therefore repeated evaluation is not necessary after this [13].
Many genes have been linked to DCM, some with a definite and some with a putative link. For definite DCM genes see Table 1, adapted from McNally et al. [22]. It is often difficult to determine if a mutation in a gene is causative of cardiomyopathy, sometimes mutations are determined to be so called variants of unknown significance. Most genes implicated in the pathogenesis of DCM are highly conserved with few
Gene | Protein | Frequency and overlapping phenotypes |
---|---|---|
MYH7 | Beta-myosin heavy chain | 3–4% of DCM; HCM, LVNC |
TPM1 | Alpha-tropomyosin | 1–2% of DCM; HCM, LVNC |
ACTC1 | Alpha cardiac actin | HCM, LVNC |
TNNT2 | Cardiac troponin T | 3% of DCM; HCM, LVNC |
TNNC1 | Cardiac troponin C | HCM, LVNC |
TNNI3 | Cardiac troponin 1 | HCM |
TTN | Titin | 12–25% of DCM; HCM, tibial muscle dystrophy |
TNNI3K | Troponin 1 interacting kinase | Conduction defect, atrial fibrillation |
ACTN2 | Alpha-actinin 2 | LVNC |
BAG3 | BCL2 Associated Athanogene 3 | Myofibrillar myopathy |
CRYAB | Alpha-B-crystallin | Protein aggregation myopathy |
TCAP | Titin-cap/telethonin | LGMD2G |
CSRP3 | Muscle LIM protein | HCM |
ANKRD1 | Cardiac ankyrin repeat protein | Congenital heart disease |
LDB3 | Cipher/ZASP | LVNC |
NEBL | Nebulette | LVNC, HCM |
DMD | Dystrophin | Duchenne/Becker muscular dystrophy |
SGCA | Alpha-sarcoglycan | LGMD2D |
SGCB | Beta-sarcoglycan | LGMD2E |
SGCD | Delta-sarcoglycan | LGMD2F |
DES | Desmin | <1% of DCM; desminopathies, myofibrillar myopathy |
VCL | Metavinculin | 1% of DCM |
FLNC | Filamin C | 1% of DCM; myofibrillar myopathy, HCM, RCM |
DSP | Desmoplakin | 2% of DCM; ARVC |
PLN | Phospholamban | ARVC, HCM |
LMNA | Lamin A/C | 4–8% of DCM; multiple phenotypes, LGMD1B, EDMD, progeria |
EMD | Emerin | EDMD |
RBM20 | RNA-binding protein 20 | 2% of DCM; RNA-binding protein of spliceosome of TTN and other proteins |
SCN5A | Type V voltage-gated cardiac Na channel | 2–3% of DCM; LQTS, Brugada, atrial fibrillation, conduction defects |
ABCC9 | Component of ATP-sensitive potassium channel | Atrial fibrillation, osteochondrodysplasia |
KCNQ1 | Potassium channel | Atrial fibrillation, LQTS1, short QT1, Jervell and Lange-Nielsen syndrome |
DNAJC19 | HSP40 homolog, C19 | 3-methylglutaconic aciduria type V |
TAZ/G4.5 | Tafazzin | LVNC, Barth syndrome, endocardial fibroelastosis 2 |
Definite dilated cardiomyopathy genes.
ARVC: arrhythmogenic right ventricular cardiomyopathy; DCM: dilated cardiomyopathy; EDMD: Emery Dreifuss muscular dystrophy; HCM: hypertrophic cardiomyopathy; LGMD: limb-girdle muscular dystrophy; LVNC: left ventricular non-compaction cardiomyopathy; LQTS: long QT-syndrome; RCM: restrictive cardiomyopathy. Adapted from McNally et al. [22].
Mutations that have been linked to DCM affect genes related to diverse cell structures such as; ion channels, dystrophin complexes, sarcoplasmic reticulum, nuclear lamina, desmosomes, mitochondria, cytoskeleton, z-disc, and sarcomeres. For an image visualizing different cellular structures related to definite DCM genes see Figure 3.
Cross section of two cardiomyocytes that connect to each other with desmosomes at the intercalated disc. Definite DCM genes and important cellular structures pertaining to them are named. Image by Todd Cooper.
The general consensus is that risk of arrhythmia in DCM scales with the degree of left ventricular systolic dysfunction. Most genotypes cannot be distinguished from each other by evaluation of the phenotype. Due to this broad gene panels are required. However, some genotypes have been shown to be prone to arrhythmia and in some cases sudden cardiac death. Some genes are very rare, or only putative and not definitively linked to DCM. Out of the genes that regularly are found to cause DCM, LMNA and SCN5A stand out for their propensity to cause arrhythmia. Mutations in both of these genes can cause a phenotype with atrial fibrillation, conduction system disease or ventricular tachyarrhythmia as the presenting symptom [22]. Guidelines from the ESC give specific indications for the implantation of an ICD in patients with DCM and LMNA mutation, these are described below [3]. For SCN5A no specific guidelines are given [3]. However, it is reasonable to adapt clinical management for patients with mutation in this gene to account for the known risk for arrhythmia. This also holds true for patients with other or unknown mutations, but with a family history indicative of a high risk of arrhythmia and sudden cardiac death. Such adaptations might include more frequent ambulatory ECG-monitoring or the use of insertable cardiac monitors to screen for potentially life-threatening arrhythmias.
LMNA, the gene encoding the proteins lamin A and C, is one of the most studied DCM genes. Lamin A/C form part of the nuclear lamina and have been implicated in several cellular processes, including regulation of gene expression [22]. DCM associated with mutation in LMNA tend to have age-dependent penetrance but with disease onset early in life, often dysrhythmias mainly conduction disturbances and atrial fibrillation precede the development of heart failure. The risk for sudden cardiac death is also increased, even with only moderately reduced left ventricular ejection fraction [3]. Guidelines of the ESC state that an ICD should be considered (class of recommendation IIa) for patients with DCM and a confirmed disease-causing mutation in LMNA if any of the following clinical risk factors are present; non-sustained ventricular tachycardia, left ventricular ejection fraction ≤45%, male sex, or a non-missense mutation (insertion, deletion, truncation or mutation affecting splicing) [3]. This recommendation is based upon the results of a cohort study of 269 patients with LMNA-mutation and a median follow-up time of 43 months, 48 patients (18%) reached the composite endpoint of sudden cardiac death, appropriate ICD therapy, or aborted cardiac death [23]. In a review of published cohorts of patients with LMNA-associated cardiomyopathy, in total 299 patients, some sort of dysrhythmia was reported in 92% after the age of 30 years [24]. Dysrhythmias included sinus bradycardia, first-degree AV-block, and atrial or ventricular tachyarrhythmias [24]. Notably, almost half died from sudden cardiac death [24]. This high proportion of sudden cardiac death was also noted in those patients who had a pacemaker implanted, which implies that the mode of death in LMNA-associated cardiomyopathy may be caused by ventricular tachyarrhythmias [24].
Mutations in SCN5A, the gene that encodes the sodium voltage-gated channel alpha subunit 5 involved in the main cardiac sodium channel, has been linked to several diseases including Brugada syndrome, long QT-syndrome as well as DCM and ARVC [25]. Different kinds of mutations in SCN5A have been linked to DCM and the mechanism is still uncertain. Interestingly, the phenotype varies in families with the same genotype, indicating that environmental or other confounding factors are at play [25]. Mutations in SCN5A have also been linked to progressive conduction disorder and familial atrial fibrillation. Given this, it is not surprising that DCM due to SCN5A often presents with increased risk of arrhythmia [22].
Currently, familial DCM is likely frequently underdiagnosed, and often genetic testing is not conducted. Increased awareness and availability of genetic evaluation might provide more knowledge and gene-specific therapies and management might become available. Increased identification of affected families will mean that more at-risk individuals will come into contact with health care providers prior to developing the phenotype. This means that future studies should focus on therapies aimed to prevent the development of DCM in these individuals. Further research into the different genotypes and their burden of arrhythmia is also warranted in order to improve risk stratification for sudden cardiac death. This includes the utilization of implantable cardiac monitors in those patients who have certain high-risk genotypes but have been judged not to fulfill criteria for the implantation of an ICD.
Reduced left ventricular systolic ejection fraction is the most common indication for the implantation of an ICD regardless of type of cardiomyopathy. In DCM some genes have been linked to a propensity for arrhythmia, chief among them LMNA and SCN5A. A mutation in LMNA together with other clinical risk factors could warrant implantation of an ICD.
Thanks to Region Gävleborg, our employer, for funding this project. Thanks to Todd Cooper for providing illustrations.
Gustav Mattsson has received speaker’s fee from Alnylam, MSD, and Internetmedicin. Peter Magnusson has received speaker’s fees or grants from Abbott, Alnylam, Amicus Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Internetmedicin, Lilly, MSD, Novo Nordisk, Octopus Medical, Orion Pharma, Pfizer, Vifor Pharma, and Zoll.
The writing of this book chapter was funded by our employer, Region Gävleborg.
ACEi: angiotensin converting enzyme inhibitor; ARVC: arrhythmogenic right ventricular cardiomyopathy; AV: atrioventricular; DCM: dilated cardiomyopathy; ESC: European Society of Cardiology; HCM: hypertrophic cardiomyopathy; ICD: implantable cardioverter defibrillator; NYHA: New York Heart Association; SGLT2i: sodium-glucose transporter protein 2.
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\\n\\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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This chapter deals with the chemistry of cellulose, its extraction and its properties which help various industries to make the most of it.",book:{id:"7363",slug:"cellulose",title:"Cellulose",fullTitle:"Cellulose"},signatures:"Praveen Kumar Gupta, Shreeya Sai Raghunath, Deepali Venkatesh Prasanna, Priyadharsini Venkat, Vidhya Shree, Chandrananthi Chithananthan, Shreya Choudhary, Krithika Surender and Keerthana Geetha",authors:null},{id:"66340",doi:"10.5772/intechopen.85124",title:"Biological Degradation of Polymers in the Environment",slug:"biological-degradation-of-polymers-in-the-environment",totalDownloads:3146,totalCrossrefCites:12,totalDimensionsCites:40,abstract:"Polymers present to modern society remarkable performance characteristics desired by a wide range of consumers but the fate of polymers in the environment has become a massive management problem. Polymer applications offer molecular structures attractive to product engineers desirous of prolonged lifetime properties. These characteristics also figure prominently in the environmental lifetimes of polymers or plastics. Recently, reports of microbial degradation of polymeric materials offer new emerging technological opportunities to modify the enormous pollution threat incurred through use of polymers/plastics. A significant literature exists from which developmental directions for possible biological technologies can be discerned. Each report of microbial mediated degradation of polymers must be characterized in detail to provide the database from which a new technology developed. Part of the development must address the kinetics of the degradation process and find new approaches to enhance the rate of degradation. The understanding of the interaction of biotic and abiotic degradation is implicit to the technology development effort.",book:{id:"7479",slug:"plastics-in-the-environment",title:"Plastics in the Environment",fullTitle:"Plastics in the Environment"},signatures:"John A. 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The emerging of organic coagulants and technology to mitigate the performance and recovery of mineral coagulants from wastewater treatment residual is been proposed.",book:{id:"8357",slug:"organic-polymers",title:"Organic Polymers",fullTitle:"Organic Polymers"},signatures:"Emmanuel Kweinor Tetteh and Sudesh Rathilal",authors:[{id:"199957",title:"Dr.",name:"Sudesh",middleName:null,surname:"Rathilal",slug:"sudesh-rathilal",fullName:"Sudesh Rathilal"},{id:"262983",title:"Dr.",name:"Emmanuel",middleName:null,surname:"Kweinor Tetteh",slug:"emmanuel-kweinor-tetteh",fullName:"Emmanuel Kweinor Tetteh"}]},{id:"58300",doi:"10.5772/intechopen.72589",title:"PET Bottle Recycling for Sustainable Textiles",slug:"pet-bottle-recycling-for-sustainable-textiles",totalDownloads:2672,totalCrossrefCites:12,totalDimensionsCites:20,abstract:"Polyethylene terephthalate (PET), as the most favorable packaging material, is owing to its transparent color, lightweight, strength, food safe, inexpensive price, fully recyclability, etc. In addition to all these advantages, PET as a waste material takes up considerable space in nature and needs to be recycled for the disposal of these wastes. In this regard, recycling enables conserving raw materials, reducing energy use in order to produce virgin PET, and reducing greenhouse gas emissions. Today, PET is the most widely recycled plastic in the world. Eco-friendly products obtained by recycling of PET are mainly used as textile fibers. In addition, both brands and consumers are seen to be enthusiastic in order to minimize the environmental effects of PET wastes. This study is concerned with the use of textile fiber from recycled PET (r-PET) bottles to produce a cotton blended ring and compact yarns. Undoubtedly, the study also includes comparison of cotton blended virgin polyester fiber (v-PET) with r-PET fiber to determine the advantages and disadvantages of r-PET fiber. 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They are made from acrylate monomer, which usually comprises of esters which contains vinyl groups, that is two carbon atoms that are double-bonded to each other, and directly attached to the carbonyl carbon of the ester group. Acrylates possess very diverse characteristic properties ranging from super-absorbency, transparency, flexibility, toughness and hardness, among others. These kinds of materials are used in sundry applications such as diapers, cosmetics, orthopedics, paints and coatings, adhesives, textiles, and many biomedical applications such as contact lenses and bone cements. This book chapter highlights the characteristic properties and applications of acrylates, its derivatives and copolymers.",book:{id:"7750",slug:"acrylate-polymers-for-advanced-applications",title:"Acrylate Polymers for Advanced Applications",fullTitle:"Acrylate Polymers for Advanced Applications"},signatures:"Kingsley Kema Ajekwene",authors:[{id:"296289",title:"Dr.",name:"Kingsley Kema",middleName:null,surname:"Ajekwene",slug:"kingsley-kema-ajekwene",fullName:"Kingsley Kema Ajekwene"}]},{id:"68596",title:"Thermoplastic Recycling: Properties, Modifications, and Applications",slug:"thermoplastic-recycling-properties-modifications-and-applications",totalDownloads:1561,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"The increasing rate of plastic waste generation coupled with undesirable disposal, especially in the urban areas, has resulted to environmental threat in the globe which has been attributed to legislation, poor biodegradability, economic growth, rural to urban migration, increase in consumption, and standard or cost of living. This chapter will focus on overview, properties of virgin and recycled thermoplastics, recycling techniques, and applications of different types of thermoplastic articles such as HDPE, LDPE, PVC, PET, and polypropylene (PP) with improved properties based on modifications using eco-friendly materials for sustainable applications in order to save human existence from the menace of environmental and economic issues.",book:{id:"9319",slug:"thermosoftening-plastics",title:"Thermosoftening Plastics",fullTitle:"Thermosoftening Plastics"},signatures:"Taofik Oladimeji Azeez",authors:null}],onlineFirstChaptersFilter:{topicId:"1415",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"65119",title:"Introductory Chapter: Polyaniline - From Synthesis to Practical Applications",slug:"introductory-chapter-polyaniline-from-synthesis-to-practical-applications",totalDownloads:952,totalDimensionsCites:2,doi:"10.5772/intechopen.83397",abstract:null,book:{id:"7503",title:"Polyaniline - From Synthesis to Practical Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7503.jpg"},signatures:"Florin Nastase"}],onlineFirstChaptersTotal:1},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. 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The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence"},{id:"23",title:"Computational Neuroscience",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. This topic is dedicated to biologically plausible descriptions and computational models - at various abstraction levels - of neurons and neural systems. This includes, but is not limited to: single-neuron modeling, sensory processing, motor control, memory, and synaptic plasticity, attention, identification, categorization, discrimination, learning, development, axonal patterning, guidance, neural architecture, behaviors, and dynamics of networks, cognition and the neuroscientific basis of consciousness. Particularly interesting are models of various types of more compound functions and abilities, various and more general fundamental principles (e.g., regarding architecture, organization, learning, development, etc.) found at various spatial and temporal levels.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness"},{id:"24",title:"Computer Vision",scope:"The scope of this topic is to disseminate the recent advances in the rapidly growing field of computer vision from both the theoretical and practical points of view. Novel computational algorithms for image analysis, scene understanding, biometrics, deep learning and their software or hardware implementations for natural and medical images, robotics, VR/AR, applications are some research directions relevant to this topic.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",keywords:"Image Analysis, Scene Understanding, Biometrics, Deep Learning, Software Implementation, Hardware Implementation, Natural Images, Medical Images, Robotics, VR/AR"},{id:"25",title:"Evolutionary Computation",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. For example, some of the issues of interest could be the following: Advances in evolutionary computation (Genetic algorithms, Genetic programming, Bio-inspired metaheuristics, Hybrid metaheuristics, Parallel ECs); Applications of evolutionary algorithms (Machine learning and Data Mining with EAs, Search-Based Software Engineering, Scheduling, and Planning Applications, Smart Transport Applications, Applications to Games, Image Analysis, Signal Processing and Pattern Recognition, Applications to Sustainability).",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization"},{id:"26",title:"Machine Learning and Data Mining",scope:"The scope of machine learning and data mining is immense and is growing every day. It has become a massive part of our daily lives, making predictions based on experience, making this a fascinating area that solves problems that otherwise would not be possible or easy to solve. This topic aims to encompass algorithms that learn from experience (supervised and unsupervised), improve their performance over time and enable machines to make data-driven decisions. It is not limited to any particular applications, but contributions are encouraged from all disciplines.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence"},{id:"27",title:"Multi-Agent Systems",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Artificial Intelligence",id:"14"},selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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