\r\n\t2. Animal and vegetal protein hydrolysates \r\n\t3. Macroalgae seaweeds extracts \r\n\t4. Beneficial microorganisms, etc.
\r\n
\r\n\tThe elucidation of the agricultural function (i.e. improving nutrient use efficiency, quality, and tolerance to abiotic stresses) and action mechanisms of PBs will permit to develop a second generation of PBs where synergies and complementary mechanisms can be functionally designed to feed the future.
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N.E. Brown and Its Viability as a Traditional African Medicinal Plant",doi:"10.5772/intechopen.96473",slug:"the-importance-of-em-sceletium-tortuosum-em-l-n-e-brown-and-its-viability-as-a-traditional-african-m",body:'
1. Introduction
Sceletium tortuosum (L.) N.E. Br. and Sceletium expansum L. Bolus (formerly known as Mesembryanthemum tortuosum L. and Mesembryanthemum expansum L.) forms part of the succulent group of plants within the Mesembryanthemaceae family (Figure 1). The common names given to Sceletium are kanna and kougoed. However, some may argue that the name kougoed refers to the finished traditional preparation made by drying and fermenting the harvested plant material, which increases its stimulating effect. The plant is native to South Africa, where it is well known by the indigenous people, especially in Namaqualand, where the plant is utilized regularly for its medicinal and anti-depressant properties [2].
Figure 1.
Sceletium plant and its “skeletonised appearance” of the dried leaves [1].
According to Schultes [3] and Harvey et al. [4] the main substances responsible for these properties are the alkaloids mesembrine, mesembrenine (mesembrenone), and mesembrenol. Interest in S. tortuosum has been growing for its potential to be an alternative supplement in the promotion of health and treating a variety of psychological and psychiatric disorders such as depression and anxiety [5]. Studies on the chemistry and biological activity on Traditional African Medicinal Plants (TAMP) have only recently (1997–2008) been published, despite TAMP having been reported as one of the oldest medicinal systems in various ethnobotanical reports [6, 7].
Soilless culture systems (SCS’s) in controlled greenhouse environments have proven to be the most effective strategy for agricultural production by providing flexibility as well as control. Crops can be produced in and out of season, while water and soilless media can easily be monitored for its total nutrient status. For these reasons SCS’s within a greenhouse environment provide for high quality products and high yields, even in places where environmental conditions would not usually permit [8].
Relevant natural compounds, mainly secondary metabolite concentration and composition, determine the quality of medicinal plants. However, water availability, light intensity and temperature are examples of various environmental conditions which affect the quality and quantity of such secondary metabolites [9]. Hence, investigating the effect of different soilless growing media and fertigation regimes on the vegetative growth and alkaloid concentration of S. tortuosum will contribute to developing optimal growing protocols for cultivating high quality medicinal plants in hydroponics for the ethno-pharmaceutical industry. The aim of this chapter was therefore, to highlight pharmaceutical and economic viability of S. tortuosum and relate the medicinal value of the plant with respect to the bioactive compound found in it and suggest ways of cultivating the plant in a soilless systems.
2. Mesembryanthemaceae FENZL: a sub family of Aizoaceae
Within the family Aizoaceae Martinov. there are currently four sub-families, namely Sesuvioideae, Aizooideae, Ruschioideae, and Mesembryanthemoideae [10, 11]. Succulent plants within the Aizoaceae family are popularly termed “Mesembs”, and sometimes placed in their own family, the Mesembryanthemaceae [2]. Common terms used to describe this group of succulent plants are vygies, fig-marigolds, flowering-stones, ice plants and, midday flowers, among others. These plants fascinate many plant enthusiasts and have become popular collector’s items due to their remarkable variation in leaf architecture, flower color and form, and fruit structure (Figure 2). Different genera within the family grow in various habitats, and examples can thus be found growing in rocky crevices, silty flats and in saline wastelands. Mesembs occur mainly in south-western Africa, including Angola, South Africa, Zimbabwe, Botswana and Namibia [2, 12] (Figure 3).
Figure 2.
Sceletium tortuosum plant surrounded by its white flowers [13].
Figure 3.
Geographical map indicating the distribution of Sceletium in South Africa (redrawn by Gerike & Viljoen [1]).
This family has received a large amount of attention in the present century both in herbaria collections and in the field. There are several reasons why the family is important in the ecosystems where they occur: they stabilize soil, which prevents erosion; various insects are catered for year-round by their blossoms, while some leaves serve as fodder for livestock. Apart from its ecological importance, this group of plants also has ethnobotanical value, and is used in making soap, poultices, preserves and also in some cases can serve as a type of psycho-active stimulant [2] (Figure 2).
3. The genus Sceletium (L.) N.E. BR.
S. tortuosum (L.) N.E. Br. and S. expansum L. Bolus (formerly known as Mesembryanthemum tortuosum L. and Mesembryanthemum expansum L.) forms part of the succulent group of plants within the Mesembryanthemaceae family. The name Sceletium is derived from the Latin word sceletus, or skeleton in English, due to the noticeable leaf veins resembling skeleton-like structures within dried leaves of the plants. Sceletium spp. are easily identified by this skeletonised structure of the leaves [2, 10]. The common names given to Sceletium are kanna and kougoed. However some may argue that the name kougoed refers to the finished traditional preparation made by drying and fermenting the harvested plant material, which increases its psychoactive effect [2, 14] (Figure 4).
Figure 4.
A commercial product by medico herbs containing dried S. tortuosum in capsules (https://medicoherbs.com/products/kanna-capsules-60).
Strong evidence suggest that the indigenous people of southern Africa used one or both Sceletium species as a vision-inducing narcotic. However, the hallucinogenic effect of kanna/kougoed could have been confused with other intoxicating plants such as Cannabis spp. or Sclerocarya spp. as the narcotic use of the plant was never observed directly. Despite this, alkaloids possessing sedative, cocaine-like effects have been found within both of these species of Sceletium [3]. Other known species of Sceletium include the following: S. crassicaule L. Bolus, S. exalatum Gerbaulet, S. expansum L. Bolus, S. rigidum L. Bolus, S. strictum L. Bolus, and S. varians (Haw.) Gerbaulet [2, 10].
S. tortuosum is now considered a medicinal crop plant and is classified as mind-altering, sedative, euphoric, and not hallucinogenic [14, 15]. The alkaloids responsible for these psychoactive properties are mesembrine and mesembrenone. However, the concentration of alkaloids within individual plants may vary depending on their chemotype. Uses of the plant include the treatment of anxiety, stress, nervous tension, alcohol addiction, colic in infants and for suppressing hunger and thirst (Figure 5). With clear ethno-pharmaceutical value it is also worthy to mention that the use of S. tortuosum develops no physical or psychological dependency [15].
Figure 5.
A commercial product by Phyto force containing tinctured S. tortuousm (https://www.phyto-force.co.za/product/Sceletium/).
4. Relevance of traditional African medicinal plants
Interest in the knowledge and use of Traditional African Medicinal Plants (TAMP) as well as an ever-increasing human population has led to the commercialization of traditional African medicines at a fast rate [16]. As stated in Keirungi and Fabricius [17], the economic value of indigenous medicinal plants in South Africa is approximately US$60 000 000 or R4 000 000 000 annually. The number of people in South Africa that depend on TAMP to aid their medical needs is estimated at 27 million [18]. The majority of plants used for traditional medicine are harvested from the wild except for some which are selected and cultivated by traditional healers [19].
In 1998 it was estimated that 20 000 tonnes of plant material were being traded in South African markets [20]. Seven hundred thousand tonnes of plant material have been extracted from the wild for this market which mostly consist of people with disadvantaged socio-economic situations or backgrounds [21]. As stated in Makunga et al. [21], US$ 50–100 million in the form of approximately 1000 plant species are being exchanged in this informal sector.
5. Secondary metabolites and alkaloids
Plant secondary metabolites are divided into three categories, namely terpenoids, flavonoids, and alkaloids. Consisting of multiple chemical structures and biological activities, secondary metabolites are an extremely wealthy source of compounds and are utilized in pharmaceutical, nutraceutical, cosmetic and fine chemical industries. Examples of familiar natural plant products that are used as drugs and/or dietary supplements are: artemisinin, paclitaxel, ginsenoside, lycopene, and resveratrol [22]. Secondary metabolites play a major role in plants’ adaptation to their environment and are thought to be responsible for antimicrobial and anti-viral activities exhibited by plants [23, 24]. Apart from protecting plants against leaf damage instigated by the incident light intensity via ultra-violet trapping mechanisms, they cause allelopathy, antipathogens and antifeeding mechanisms in plants [25, 26, 27].
Alkaloids are potent secondary metabolites that consist of one or several nitrogen (N) atoms in their molecular structure. There are approximately 20 000 alkaloid structures that have been described and are classified according to their molecular ring (heterocyclic) structure. There are different types of mesembrine alkaloids in Sceletium species. Among these are; (3aS,7aS)-3a-(3,4-dimethoxyphenyl)-1-methylhexahydro-1H-indol-6(2H)-one; (3aR,7aS)-3a-(3,4-dimethoxyphenyl)-1-methyl-3,3a,7,7a-tetrahydro-1H-indol-6(2H)-one; (3aS,6 R,7aS) − 3a-(3,4-dimethoxyphenyl) − 1-methyloctahydro-1H-indol-6-ol; and (3aR,6S,7aS)-3a-(3,4-dimethoxyphenyl)-1-methyl-2,3,3a,6,7,7a-hexahydro-1H-indol-6-ol [28, 29]. These groups are indole, isoquinoline, quinolone, tropane, pyrrolizidine and quinolizidine alkaloids. Some alkaloids are neurotoxins and/or mind-altering substances. Most have pharmacological or toxicological relevance, and many isolated alkaloids serve as therapeutic agents in medicine [16]. Alkaloids confer several biological effects on plants such as stimulants (caffeine and ephedrine), antitussive (codeine), pain killer (morphine), anti-malarial (quinine), aphrodisiac (yohimbine), phosphodiesterase inhibitor (papaverine), antiarrhythmic (ajmaline), anti-gouty arthritis (colchicines), anti-rheumatic pains (capsaicin), antiglaucoma (pilocarpine) and anti-psoriasis berberine [30, 31, 32].
Like section Ganymedes (Narcissus pallidulus and Narcissus triandrus) within Amaryllidaceae family, Sceletium is one of the few plant genera containing mesembrine alkaloids [33, 34]. According to Krstenansky [29], not all Sceletium species have been reported to contain mesembrine alkaloids. While species like S. tortuosum, S. anatomicum, S. crassicaule, S. expansum, S. namaquense and S. strictum have been reported to contain mesembrinated, the status of S. archeri, S. emarcidum, S. exalatum, S. joubertii, S. rigidum, S. varians and S. subvelutinum in terms of mesembrine alkaloids is not yet confirmed [29, 35].
6. Soilless culture
Soilless culture, also known as hydroponics and/or hydroculture is the term that is used when methods of growing plants without soil is utilized. Artificial or soilless substrate may or may not be used to provide structural support for the plants depending on the grower and method used [36].
Ecological imbalances such as extreme temperatures, chemical toxicity and oxidative stress are threatening conventional agricultural practices. With an annual rise in population and consumers becoming more aware of the quality, quantity and nutritious value of products consumed, challenges within agricultural systems to keep up with demands and standards are becoming more complex. The need for more efficient and controlled cultivation methods have risen dramatically. Soilless culture systems have been proved to be one of the most efficient and effective cultivation method in the agriculture industry of today [8].
7. Electrical conductivity and nutrients
Serving as indicators for soil fertility, nutrient concentrations within soil have been of interest for decades. Nutrients can be organic or inorganic. Availability, utilization, translocation and absorption of nutrients by crop plants for growth and development are referred to as mineral nutrition. Plants require a variety of nutrients in order to successfully grow and develop to their full potential. The most important mineral nutrients are the macro nutrients, namely nitrogen, phosphorous and potassium, although plants also require micro-nutrients in smaller amounts which can be argued to be equally important [37].
Plants require nitrogen (N) in the largest quantities compared to other elements. N serves as a constituent for many plant cell components such as, amino acids, proteins and nucleic acids. When there is a lack of N availability to a plant, the plants growth will be inhibited rapidly, followed by the common characteristic symptom, chlorosis in older leaves [38, 39]. Phosphorous (P) serves as an integral component of valuable compounds found in plant cells. These include phospholipids as well as sugar-phosphate intermediates of respiration and photosynthesis. Necrotic spots, dark-green colouration of leaves, which could also become malformed, as well as rapid malfunctioning of photosynthetic apparatus and stunted growth are common characteristic symptoms of P deficiency [39, 40].
Furthermore, various enzymes that are important in respiration and photosynthesis are activated by potassium (K). The osmotic potential of plant cells are also partly regulated by K. Marginal chlorosis of leaves, which further develops into necrosis of leaf tips or margins and in between veins is the most common symptom of K deficiency in plants [39, 41]. Likewise, cell wall synthesis and mitotic cell division depend on the availability of calcium (Ca) ions. Normal functioning of plant membranes and various plant responses to environmental and hormonal signals require Ca. Necrosis of young meristematic regions where cell division and cell wall formation is most prominent is a characteristic symptom of Ca deficiency [39, 42]. Also, cystine, cysteine, and methionine are amino acids in which sulfur (S) is found. Sulfur is also a constituent of a number of co-enzymes and vitamins, namely coenzyme A, S-adenosylmethionine, biotin, Vitamin B1 and pantothenic acid, which are all essential for optimal metabolism in plant cells [39, 43].
Electrical conductivity (EC) is the measurement used to indicate the total concentration of nutrients within an aqueous solution. High EC indicates a high concentration of nutrients within the solution, while a low EC indicates a low concentration of nutrients [44]. When plants are supplied with a high EC nutrient solution, the nutrient concentration within the leaves will not necessarily be higher than in plants supplied with a low EC nutrient solution [45], suggesting that the nutrient uptake in plants is not necessarily based on the amount of nutrients available.
8. Water amounts
Production of plants in the modern sense requires advancements in technology that will allow the optimization of cultivating high quality plant material while minimizing the use of natural resources, such as water [46]. This is also true for the growing of medicinal and aromatic plants, as well as plant production in general [47].
South African agriculture faces increasing pressure to use water more efficiently, as the industry must oblige to demonstrate efficient and effective water use due to limited valuable natural resources [48]. The role of irrigated farming in the livelihood of a nation cannot be underscored. In South Africa in particular, agricultural sector uses the highest volume of water compared to other sectors. To increase the amount of water needed in other critical sector of the economy, there is the need to improve on water use efficiency during irrigation through reduced water consumption without compromising yield. Regrettably, the concept of irrigation efficiency is often misinterpreted leading to the general belief that water just evaporates with minimal irrigation efficiencies and re-emerges with significant progress in agricultural productivity [49]. This necessitated the emergence of the South African water management framework which oversees holistically, the water source, the irrigation farm, bulk conveyance system and the irrigation scheme to ensure water balance across all sectors [49].
It has been observed that a considerably higher concentration of secondary metabolites are produced in medicinal or spice plants grown under water deficient conditions, compared to identical plants of the same species grown with ample amounts of water [50]. Although changes in the synthesis of desired natural compounds is clear when drought stress is applied to plants, the overall effect of applying drought stress for optimizing specific secondary metabolites in plants remains complex. The amount of water also influences other relevant factors such as plant biomass yield and rate of growth. Depending on the plant and the growers’ desired outcome with regards to quality, quantity, and rate of growth, the amount of water applied should be carefully considered as there is no prevalent recommendation that can be made for all plants. By deliberately applying drought-stress without first thoroughly investigating how different plants react to different amounts of water and the method of applying it could yield undesirable results [51].
9. Conclusion
Sceletium tortuosum is indigenous to South Africa. It is one of the very few plants known to contain highly sought after mesembrine alkaloids. Its potential as an alternative supplement in the promotion of health and treating a variety of psychological and psychiatric disorders such as depression and anxiety has stimulated interest in its pharmacological property and possibility of its commercialization. Therefore, meeting pharmacological and economic needs of ever-increasing human population necessitates the use of efficient systems such as hydroponics which require minimum use of land and environmental factors can be maximally controlled to cultivate the plant for optimal yield.
\n',keywords:"African medicine, Aizoaceae, alkaloids, hydroponics, mesembrine, mesembrenine, mesembrenol, mesembryanthemaceae",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/75402.pdf",chapterXML:"https://mts.intechopen.com/source/xml/75402.xml",downloadPdfUrl:"/chapter/pdf-download/75402",previewPdfUrl:"/chapter/pdf-preview/75402",totalDownloads:227,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:3,totalAltmetricsMentions:0,introChapter:null,impactScore:2,impactScorePercentile:76,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"December 26th 2020",dateReviewed:"February 7th 2021",datePrePublished:"April 14th 2021",datePublished:"May 11th 2022",dateFinished:"February 24th 2021",readingETA:"0",abstract:"Sceletium tortuosum is a succulent plant that belongs to the family Mesembryanthemaceae (Aizoaceae). It is indigenous to South Africa, where it is well known by the indigenous people, especially in Namaqualand where the plant is utilized regularly for its medicinal and psycho-active properties. The main alkaloids responsible for these properties are mesembrine, mesembrenine (mesembrenone), and mesembrenol. The potential of the plant to be an alternative supplement in the promotion of health and treating a variety of psychological and psychiatric disorders such as depression and anxiety has stimulated interest in its pharmacological property and possibility of its commercialization. The economic value of indigenous medicinal plants in South Africa is approximately US$60 000 000 or R4 000 000 000 annually. Thus, interest in the knowledge and use of Traditional African Medicinal Plants (TAMP) as well as meeting pharmacological and economic needs of ever-increasing human population has led to the commercialization of traditional African medicines at a fast rate. It was found that S. tortuosum has clear pharmaceutical and economical importance and is one of the only known plants to contain the alkaloids mesembrenone and mesembrine which can be utilized for the promotion of health and/or treating a variety of psychological disorders such as anxiety and depression.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/75402",risUrl:"/chapter/ris/75402",book:{id:"11752",slug:"natural-drugs-from-plants"},signatures:"Richard James Faber, Charles Petrus Laubscher and Muhali Olaide Jimoh",authors:[{id:"200819",title:"Prof.",name:"Charles",middleName:"Petrus",surname:"Petrus Laubscher",fullName:"Charles Petrus Laubscher",slug:"charles-petrus-laubscher",email:"laubscherc@cput.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Cape Peninsula University of Technology",institutionURL:null,country:{name:"South Africa"}}},{id:"344558",title:"Dr.",name:"Muhali",middleName:"Olaide",surname:"Olaide Jimoh",fullName:"Muhali Olaide Jimoh",slug:"muhali-olaide-jimoh",email:"jimohm@cput.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Cape Peninsula University of Technology",institutionURL:null,country:{name:"South Africa"}}},{id:"344562",title:"MSc.",name:"Richard",middleName:null,surname:"James Faber",fullName:"Richard James Faber",slug:"richard-james-faber",email:"richardjf@live.co.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Cape Peninsula University of Technology",institutionURL:null,country:{name:"South Africa"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Mesembryanthemaceae FENZL: a sub family of Aizoaceae",level:"1"},{id:"sec_3",title:"3. The genus Sceletium (L.) N.E. BR.",level:"1"},{id:"sec_4",title:"4. Relevance of traditional African medicinal plants",level:"1"},{id:"sec_5",title:"5. Secondary metabolites and alkaloids",level:"1"},{id:"sec_6",title:"6. Soilless culture",level:"1"},{id:"sec_7",title:"7. Electrical conductivity and nutrients",level:"1"},{id:"sec_8",title:"8. Water amounts",level:"1"},{id:"sec_9",title:"9. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Gericke, N. and Viljoen, A.M., 2008. Sceletium—a review update. Journal of Ethnopharmacology, 119(3), pp.653-663.'},{id:"B2",body:'Smith, G.F., Chesselet, P., van Jaarsveld, E.J., Hartmann, H., Hammer, S., van Wyk, B.-E., Burgoyne, P., Klak, C., Kurzweil, H., 1998. Mesembs of the World, 1st ed. Briza Publications, Pretoria, South Africa.'},{id:"B3",body:'Schultes, R.E., 1976. Hallucinogenic Plants. 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Prod. 42, 558-566. https://doi.org/10.1007/978-1-4614-8591-9_3'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Richard James Faber",address:null,affiliation:'
Department of Horticultural Sciences, Faculty of Applied Sciences, Cape Peninsula University of Technology, City of Cape Town, South Africa
'},{corresp:"yes",contributorFullName:"Charles Petrus Laubscher",address:"laubscherc@cput.ac.za",affiliation:'
Department of Horticultural Sciences, Faculty of Applied Sciences, Cape Peninsula University of Technology, City of Cape Town, South Africa
Department of Horticultural Sciences, Faculty of Applied Sciences, Cape Peninsula University of Technology, City of Cape Town, South Africa
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1. Introduction
Alongside the progressive aging of the general population, aortic valve disease is currently one of the most common heart valve diseases worldwide, and its management is going to have a central role in public health, with an expected doubling of the cases in the next 50 years [1, 2]. This topic is particularly significant in developed countries, as in the United States, 4.2 to 5.6 million (approximately 2.5% of the population) are estimated to have a clinically relevant form of heart valve disease in which aortic valve diseases account for 35% of cases [3]. Notwithstanding worldwide primary etiology of aortic stenosis is rheumatic fever. In western countries, regular access to antibiotic therapy and the aging of the population made calcific aortic valve disease, its most common cause, giving account to the rise of aortic stenosis as the most significant heart valve disease in the elderly population [4].
Transcatheter aortic valve implantation (TAVI) has progressively emerged as a valid alternative and choice since 16 April 2002, the date of the world’s first TAVI, performed by Alain Cribier in Lyon (France). In the European Society of Cardiology (ESC) 2012 Guidelines TAVI was limited to surgical high/prohibitive risk patients [5], mainly based on the results of the Placement of Aortic Transcatheter Valves I (PARTNER I; NCT005308944) trial. This trial investigated patients with severe aortic stenosis who were not suitable candidates for surgery; TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause (71.8% vs. 93.6%, Hazard Ratio 0.50; 95% CI 0.39–0·65; p < 0.0001), cardiovascular death (57.3% vs. 85.9%; p < 0.0001), repeat hospitalizations (47.6% vs. 87.3%; p < 0.0001), and cardiac symptoms in terms of New York Heart Association (NYHA) class improvement (NYHA III-IV 14.3% vs. 40%; p = 0.531) [6]. In 2016 PARTNER II trial (NCT01314313), comparing SAVR and TAVI in a randomized trial considering intermediate-risk, patients concluded that TAVI had a similar rate of the primary endpoint (death and disabling stroke) at 2 years follow-up in the overall cohort (Hazard Ratio 0.87; 95% CI 0.71–1.07; p = 0.18) and lower in the transfemoral-access cohort (Hazard Ratio 0.78; 95% CI 0.61–0.99; p = 0.04). On the other hand, surgery demonstrated fewer major vascular complications and less paravalvular aortic regurgitation compared to transcatheter approach [7]. In 2019 results from PARTNER III trial (NCT02675114), comparing SAVR and TAVI in surgical low-risk, patients confirmed that the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVI than with conventional surgery (8.5% vs. 15.1%) [8]. In parallel to PARTNER trials, based on a balloon-expandable prosthesis (Edwards Sapien valve), surgical replacement and transcatheter aortic valve implantation (SURTAVI - intermediate-risk; NCT01586910) and Evolut (low-risk; NCT02701283) trials were conducted, comparing standard surgical therapy to transcatheter implantation of a self-expandable aortic prosthesis (Medtronic Evolut valve). In both studies, TAVI was not inferior to surgery in reducing the primary endpoint of death from any cause or disabling stroke at 24 months [9, 10]. In 2019, based on the evidence generated by these clinical trials, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved TAVI for the treatment of symptomatic severe aortic stenosis in surgical low-risk patients (Figure 1) [11, 12].
Figure 1.
Overview of the most important clinical trials, stratified according to surgical risk scores.
2021 ESC/EACTS Guidelines (Figure 2) for the management of valvular heart disease have a more balanced approach, currently recommending TAVI for elderly (≥ 75 anni, STS-PROM/EuroSCORE II >8%) or patients unsuitable for surgery and SAVR for younger patients who are low risk for surgery (<75 years and STS-PROM/EuroSCORE II <4%) or in patients who are operable and unsuitable for transfemoral TAVI, leaving gray-zone context to the comprehensive evaluation of individual clinical, anatomical, and procedural factors by the Heart Team, which discussion is however recommended in every scenario [13].
Figure 2.
Management of patients with aortic stenosis [13].
2. Patients selection
Aortic stenosis is frequently associated with advanced age and numerous cardiovascular non-cardiovascular diseases. Because of that, the treatment choice is based on a careful and 360° patient evaluation.
2.1 General screening: symptoms and prognostic impact
A typical benign course characterizes aortic valve stenosis during most of its natural history. At the same time, a drastic prognostic worsening occurs after symptoms onset, with an event-free survival of only 30–50% at two years and with an average survival of just 2–3 years without aortic valve replacement [14, 15, 16, 17]. For that reason, looking for even vague symptoms and closer follow-up have a central role during the medical visit. Aortic stenosis typically manifests itself with effort angina, dyspnea, progressively evolving to congestive heart failure, pre-syncopal, and syncopal events. However, symptoms may be atypical, like fatigue or tiredness, especially in the elderly who, for concomitant reasons, are not able to perform relevant efforts. Usually, in western countries, the onset of the symptoms occurs between 7th and 9th decade of life as a consequence of progressive calcification of valvular cusps [18]. In elderly/complex patients, a critical effort should be to recognize the most likely cause of symptoms, especially in mild or moderate aortic stenosis, as symptoms normally occur in severe stenosis. Moreover, aortic stenosis shares the same risk factors and symptoms as other cardiac and noncardiac diseases. Dyspnea can be present in asthma, chronic obstructive pulmonary disease (COPD), anemia, renal failure, deconditioning, and coronary artery disease (CAD), which could also be manifest with angina and arrhythmias-related presyncope or syncope. In particular, CAD in aortic valve stenosis patients is highly-prevalent; it was found in 69.7% of patients addressed to TAVR in the PARTNER II trial and in 69.2% of patients assigned to SAVR in the SURTAVI trial [7, 9]. Coronary angiography is recommended in assessing each patient with severe aortic stenosis to identify patients that could benefit from contemporary coronary revascularization [13].
In general, aortic valve stenosis progression is constant, with an average annual reduction in the valvular aortic area of 0.03 ± 0.01 cm2/year and about 2.7 ± 0.1 mmHg in the mean transaortic pressure gradient [19]. To improve proper follow-up and identify the most suitable time to proceed to aortic valve replacement, In 2020, American Heart Association (AHA)/American College of Cardiology (ACC) guidelines classify patients into 4 stages according to the natural history phase of aortic valve stenosis: from those at risk of development aortic stenosis (Stage A), to progressive aortic stenosis with mild or moderate calcifications (Stage B), to asymptomatic severe aortic stenosis with normal or reduced left ventricular ejection fraction (LVEF) (Stage C), and to symptomatic aortic stenosis with normal or reduced LVEF (Stage D). This classification is useful in the management of patients because each stage is associated with a proper diagnostic-therapeutic iter; in particular, aortic valve replacement is recommended in all Stage D patients and in Stage C with reduced LVEF (< 50%) [20]. In fact, despite improving symptoms in the short term, medical therapy is not capable of changing the natural history of severe aortic stenosis; therefore, aortic valve replacement is the only effective therapy.
2.2 Risk stratification
According to 2021 ESC/EACTS guidelines for the management of valvular heart disease, aortic valve replacement is recommended for every symptomatic severe aortic stenosis (IB) and asymptomatic severe aortic stenosis with systolic left ventricular dysfunction (LVEF <50% IB; < 55% IIa B) without another cause, undergoing coronary artery bypass graft (CABG) or surgical intervention on the ascending aorta or another heart valve, demonstrable symptoms or sustained fall in blood pressure (> 20 mmHg) on exercise testing (IIa B-C), and/or procedural low-risk plus a risk parameter (very severe aortic stenosis, severe valve calcification and peak aortic valve velocity progression ≥0.3 m/sec/year, markedly elevated brain natriuretic peptide levels) [13].
Once indication to valve replacement is defined, the choice between surgical and transcatheter intervention lies on age, surgical hazard, previous cardiac surgery, a concomitant cardiac condition requiring intervention, technical parameters, comorbidities, and frailty. These parameters should be evaluated by a multidisciplinary heart team, whose role is predominant, especially in moderate-risk patients, in which cases guidelines provide less indications [13]. Aspects favoring SAVR are younger age (typically <75 years), low surgical risk, no previous thoracic surgery, coronary or heart valve disease requiring intervention, and nonrelevant comorbidities, while older age (≥ 75 years), high surgical risk, previous thoracic surgery, and comorbidities favor TAVR. The scores that are commonly used in the definition of the surgical risk are Society of Thoracic Surgeons Mortality (STS) score and EuroSCORE II. Although, these scores were born and developed for stratifying risk in patients undergoing cardiac surgery and not for those who are scheduled for transcatheter therapy. Moreover, they provide just only low correlation with 30-day mortality [21]. In a recent multicenter study performed on patients assigned to TAVI, STS score and EuroSCORE II demonstrated just a moderate correlation and a low accuracy for inhospital adverse events and for 30-day and medium-term mortality, pointing out the necessity of dedicated scores [22].
Technical aspects will be discussed in a separate section (see Anatomical assessment).
2.3 Futility
Transcatheter aortic valve implantation was developed to improve prognosis and has revolutionized the treatment of elderly patients affected by severe aortic stenosis. The expansion in indication and the spread among centers determined the increase of its demand. Consequently, adequate patients selection has become fundamental to avoid wasted resources. Currently, TAVI represents a highly expensive intervention and a relevant issue in a health system where economic resources are limited. However, cost/efficacy analysis had demonstrated a non-inferiority of TAVI respective to SAVR in the long run; in particular, Cohen et al. [23] demonstrated how, despite a higher procedural cost, TAVI allows significantly reduced follow-up costs, compared to SAVR. According to the 2017 American College of Cardiology (ACC) consensus, avoiding intervention on patients who are not going to benefit in survival or quality of life is appropriate. In particular, futility is defined for patients with a life expectancy inferior to 1 year and for those with expected survival with benefit of <25% at 2 years, as evaluated with NYHA class and/or Canadian Cardiovascular Society (CCS) angina grade improvement [24].
In the recent frailty in older adults undergoing aortic valve replacement (FRAILTY-AVR; NCT01845207) study, 646 TAVI patients have been stratified with several frailty scores. The one that had the major correlation with prognosis was the essential frailty toolset (ETF) score. This score is composed of 4 items: mobility (assessed by the time necessary to get up from a chair), cognitive function, hemoglobin value, and serum albumin value. It is interesting to notice that the highest (i.e. the worst) score (5) was associated with a mortality rate of 63% and a major disability rate of 16%. The persistence of a high ETF score value after interventions focused on its reduction could be a futility marker in this kind of patient [25].
In addition to the futility issue, the TAVI’s outcome still has several possibilities of improvement; after implantation, there is a 30-days mortality rate of 7.8% and 2.2%, with old and new devices, respectively [26]. Moreover, considering 5 years of follow-up derived from major trials, the mortality rates exponentially increase. In the Core Valve US pivotal extreme and High-Risk trial (NCT01240902), a prospective, multicenter, and single-arm clinical trial of TAVI enrolling 639 patients with severe aortic stenosis at extreme surgical risk, with a mean age of 82.8 ± 8.4 years, a 5-year mortality rate of 71.6% was observed (with futility of 50.8%) [27]. The same behavior was confirmed in the PARTNER I and II trials, enrolling, respectively, inoperable and surgical intermediate-risk patients randomly assigned to TAVI or SAVR, reporting a 5-year mortality of 71.8% vs. 93.6% (p < 0.0001; PARTNER I) and of 47.9% and 43.4% (p = 0.21; PARTNER II) [6, 7]. It is interesting to notice that a rapid increase in mortality is observed after about 30 days from intervention [28]. Several studies have demonstrated that in patients undergoing TAVI, after an early phase of high cardiovascular risk, this drastically reduces but, in elderly, non-valvular heart failure and noncardiac diseases represent the main causes of death. According to Chen et al. metanalysis, main etiologies are: infections/sepsis (14%), cancer (7%), renal insufficiency (4%), multi-organ failure (3%), and other causes (23%) [29]. This scenario is easily understandable considering that TAVI patients are generally older and have more comorbidities, compared to patients addressed to conventional surgery, and despite valvular disease correction, advanced age and comorbidities still represent a heavy frailty burden [30, 31]. Although, age is not automatically a synonymous of frailty, the latter has demonstrated to significantly affect the outcome of patients undergoing TAVI even in the 90-years-old population [32].
Several factors are associated with increased morbidity and mortality at 1 year after aortic valve replacement among cardiac conditions, atrial fibrillation (AF), left ventricular systolic dysfunction, mitral regurgitation, pre-capillary pulmonary hypertension, and right ventricular dysfunction. Among extracardiac conditions, COPD and restrictive lung diseases, chronic kidney disease, cancer, advanced age, and frailty are the most impacting from a prognostic point of view [33]. In this context, a fundamental question concerns if aortic valve replacement may improve or resolve symptoms and associated conditions affecting prognosis. Indeed, left ventricular systolic dysfunction, when other potential causes are excluded, improves in about two-thirds of the patients from 48 hours to 1-year post aortic valve replacement [34], and mitral regurgitation, especially if functional, may be positively affected after TAVI [35]. Conversely, COPD (with poor exercise tolerance, oxygen-dependency or use of noninvasive ventilation), precapillary pulmonary hypertension (especially with systolic pulmonary artery pressure > 60 mmHg), primary mitral valve regurgitation, active cancer, and cognitive impairment are unlikely to get better after aortic valve replacement and are thus associated with a worse prognosis [36, 37, 38].
Considering the multidimensional phenotype and the discordance among the various tests and scores used in clinical practice, quantifying the impact of frailty could be challenging. Its assessment is however essential in patients’ selection in order to improve extracardiac diseases and avoid vain invasive procedures.
2.3.1 Balloon aortic valvuloplasty (BAV)
Widely used in high surgical risk patients since it was first introduced by Cribier et al. in 1985, BAV is progressively gaining significance in patients’ stratification, clinical stabilization, and forecasting the results of a definitive correction of the valve disease, as a “bridge to decision (medical therapy/TAVI/SAVR)” therapy. In particular, the evaluation of BAV’s results provides prognostic information and is capable of identifying patients who are going to take advantage of aortic valve disease correction [39, 40]. In addition, performing BAV could improve mobility and general status of frailty patients, helping them to bear intensive rehabilitation courses that could be fundamental to face up to aortic valve intervention with the lowest frailty degree. In the end, in frailty patients, in which a judgment of futility has been made (especially for poor life expectancy), BAV may be used as a temporary palliative treatment, as a “destination therapy” [24]. A major limitation of BAV has always been the risk of vascular complications, as the most widespread vascular access site is the femoral venous and arterial access. This site is associated with a rate of major and minor vascular complications of, respectively, 2.7% and 6.6%, even with the use of advanced hemostasis systems (Angio-Seal and ProGlide) [41]. In recent years, there was an important effort in researching techniques to minimize periprocedural complications and, in this context, the Safety and Feasibility of Transradial Mini-invasive Balloon Aortic Valvuloplasty (SOFTLY; NCT03087552) study showed the feasibility and safety of a mini-invasive approach combining radial artery access and LV pacing through the wire (without implantation of a temporary pacemaker through venous access) [42]. The possibility of a mini-invasive approach able to significantly reduce access-related complications could be a great incentive for the use of BAV in order to improve frailty situations before an aortic valve disease definitive correction is performed.
3. Anatomical assessment
3.1 Echocardiography
Echocardiography is fundamental to diagnosis and to assess aortic stenosis severity, valve calcifications, LV systolic and diastolic function, and other cardiac pathologies. Current ESC guidelines underline the importance of echocardiographic evaluation when blood pressure is well controlled to reduce confounding flow effects of increased afterload [13].
Aortic stenosis severity assessment lies on the measurement of mean pressure transvalvular gradient, peak transvalvular velocity (Vmax), and aortic valve area (AVA). Based on these parameters, three categories of severe aortic stenosis may be identified and could benefit from aortic valve replacement [13]:
High-gradient AS: characterized by mean gradient ≥40 mmHg, Vmax ≥4 m/s, AVA ≤ 1 cm2 (or AVAi ≤0.6 cm2/m2);
“Classical” low-flow, low-gradient AS (LF-LG AS): characterized by mean gradient <40 mmHg, AVA ≤ 1 cm2 (or AVAi ≤0.6 cm2/m2), LVEF <50%, and as an additional variable, indexed stroke volume (SVi) ≤ 35 ml/m2; in these cases, dobutamine stress echocardiogram is recommended to identify true classical LF-LG AS, which presents increasing mean pressure (≥ 40 mmHg) and could benefit from AVR, form pseudo-severe AS. In particular, patients with true classical LF-LG AS have developed functional improvement one year after TAVI, but no significant LV function improvement [43].
“Paradoxical” low-flow, low-gradient AS: characterized by mean gradient <40 mmHg, AVA ≤ 1 cm2 (or AVAi ≤0.6 cm2/m2), LVEF ≥50% and SVi ≤ 35 ml/m2. This condition is typical of patients with profound concentric LV hypertrophy with small cavities that are not able to generate enough SV to effectively open the aortic valve [44]. In this context, a computerized tomography (CT) assessment of valve calcification’s degree helps to define the probability of true severe AS (highly likely with Agatston units >3000 for men and > 1600 for women).
In peculiar cases, especially with patients with poor echocardiographic transthoracic windows, transesophageal echocardiography could be a valid alternative (Figure 3).
Figure 3.
Integrated assessment of patients with aortic valve stenosis [13].
3.2 Cardiac catheterization
Despite the evaluation of aortic valve stenosis is mainly based on echocardiography, there is a not negligible discrepancy between effective aortic valve area (AVA) derived from Doppler and from cardiac catheterization. According to Minners et al., there are inconsistencies in grading aortic valve stenosis in patients with normal LV function, in particular with respect to AVA, while mean pressure gradient seems to be a more robust parameter [45]. In a prospective study on assessment of aortic stenosis severity between echocardiography and cardiac catheterization, AVA correlated poorly between the two techniques, with an average AVA difference of 0.25 cm2 (range 0–1.59) [46]. That is due to the fact transvalvular pressure gradient is maximal at the level of the vena contracta, the point in a fluid stream where the diameter of the stream is the least and fluid velocity is at its maximum, which occurs where all the layers of the stream converge, slightly downstream of anatomic aortic valve area. After the vena contracta, part of the jet kinetic energy is recovered in pressure but, during this process, there is some energetic dispersion as a result of flow separation and vortex formation. Echocardiography, measuring transvalvular pressure gradient at the vena contracta (where it is maximal), tends to overestimate pressure gradient and, therefore, underestimate aortic orifice area. Cardiac catheterization, instead, tends to measure a lower transvalvular pressure gradient because it samples it at some distance downstream to vena contracta, where conversely catheter would have trouble maintaining the position of the pressure sensor due to the instabilities secondary to flow-jet turbulence [46]. As assessed by Garcia et al., effective orifice area calculated by catheterism (EOAcath) may therefore be larger than the one calculated by echocardiography (EOAecho). This overestimation becomes relevant as the ascending aorta diameter decreases, mostly when sino-tubular junction diameter is ≤30 mm [47]. Moreover, echocardiography could also overestimate EOA because of poor alignment of the ultrasound beam with the stenotic jet [48]. In the end, cardiac catheterization provides data about pulmonary pressures and resistances that, if elevated, could identify an advanced pathology grade that may not benefit from valve correction [37]. Nevertheless, current ESC/EACTS Guidelines for the management of valvular heart disease recommend LV catheterization only when there is a severe aortic stenosis clinic and noninvasive assessment is inconclusive [13]. Criteria for defining aortic valve stenosis severity and its prognosis are derived from catheter measurements, and nowadays the invasive assessment could be a valid ally in an accurate definition of aortic stenosis severity, although a proper selection is mandatory to limit unavoidable complications related to its invasiveness.
3.3 Computerized tomography scan
Electrocardiogram-gated CT scan has a central role in the pre-procedural planning for TAVI. First of all, it is fundamental to evaluate annular valvular area and perimeter (essential to guide the choice of prosthesis’ size), extent and distribution of calcifications, aortic root anatomy, and height of coronary ostia from aortic annulus and LV outflow tract dimension (Figure 4). All this information is pivotal to define prosthesis implantation. For example, an overestimation of the aortic annulus dimensions poses a significant risk for aortic root lesions or disruption during prosthesis release. On the other hand, underestimation increases the risk of paravalvular aortic regurgitation [49, 50]. Considering that aortic annulus dimensions vary throughout the cardiac cycle, they should be measured during systole, i.e., when they are larger.
Figure 4.
Computed tomography evaluation for TAVI procedural planning. Aortic annulus measure (A) and calcium distribution (B). Coronary distance from virtual basal ring (C, D). Aorta and peripheral artery evaluation for a transfemoral access (E-G).
Another main scope of CT scan concerns the planning of vascular access through imaging of aorta and iliofemoral vasculature. This assessment has become increasingly important and has led to a significant decrease of pre- and post-procedural major and minor vascular complications in TAVR patients [51].
4. Device
Transcatheter therapies for the treatment of aortic stenosis have seen a fast and progressive development in technology. Many platforms are nowadays available; it is possible to categorize the devices according to the deployment mechanism: balloon-expandable valves (BEV) and self-expandable valves (SEV). The third category of devices, mechanically expandable, is less widespread. They also differ in the leaflets’ position and their relationship with the annular plane (Figure 5).
Figure 5.
Principal TAVI platforms and technical characteristics.
4.1 Balloon-expandable valves
The SAPIEN platform (Edwards Lifesciences, Irvine, USA) is one of the most diffuse BEVs. It is an intra-annular device, with bovine pericardial leaflets mounted on a cobalt-chromium balloon-expandable frame. SAPIEN valves have a flexible delivery system that allows adapting the implantation in angulated aorta; the balloon expansion allows volumetric modification according to annular sizes, although it is not recapturable during the implantation. The fourth-generation SAPIEN 3 Ultra features an increased outer seal cuff to reduce paravalvular leak (PVL). There are 4 currently available sizes: 20, 23, 26, and 29 mm. The SAPIEN family valves have a lower stent frame profile, which makes easier the coronary catheterization after TAVI [52].
4.2 Self-expanding valves
The Evolut PRO+ (Medtronic, Minneapolis, USA) is the last generation prosthesis of the Evolut family of SEV. They have a supra-annular design and consists of three porcine pericardial leaflets attached to a self-expanding nitinol stent. The stent is a diamond-shaped cell and the valve has an hourglass shape, with a larger circumference at the proximal and distal anchoring points. The delivery system allows the device to recapture after partial deployment and repositioning. Four valve sizes are available (23, 26, 29 and 34 mm) [52].
The ACURATE Neo 2 valve (Boston Scientific, MA, USA) is a SEV with supra-annular design and porcine pericardial leaflets. Its design includes stabilizing arches to facilitate correct positioning. Its top-down deployment, with or without the need for ventricular pacing, does not allow any recapture. It has less radial force, so pre-dilatation is mandatory. The open-cell design and the short-stent body should ease coronary access after implantation. Furthermore, it has a superior crown designed to keep the native cusps away from the coronary ostia [53].
The Portico valve (Abbott Vascular, Santa Clara, CA, USA) comprises a bioprosthetic bovine pericardial aortic valve mounted upon a self-expandable nonflared nitinol frame. The leaflets are located at the annular level, ensuring valve function immediately upon deployment.
Allegra (Biosensors International, Morges, Switzerland) and HYDRA (SMT, Wakhariawadi, India) are two self-expanding nitinol frame valves with bovine pericardial leaflets. Their use is limited to high surgical risk patients and the evidence of safety and efficacy are quietly poor.
4.3 Device choice
So far, there is insufficient evidence to claim the superiority of a prosthesis or another. Each TAVI device has a unique design, and certain elements may slightly favor one or another prosthesis. Among the factors to consider when choosing a valve for TAVI, those that may favor BEV are short or narrow sinus of Valsalva, the presence of conduction disturbances (right bundle branch block or 1st degree AV block), and the anticipated need for future coronary re-access and a horizontal aorta. In small annuli and in case of severe LV outflow tract calcification, SEV may be preferred [52, 54].
The intra-annular design is associated with higher trans-prosthetic gradients and more frequent patient-prosthesis mismatch (an effective orifice area too small in comparison to patient’s body surface area) [55]. Patient-prosthesis mismatch is associated with a worse prognosis in surgical prosthesis; however, the clinical relevance of TAVI remains uncertain [56].
Only few randomized trials directly compared different TAVI devices. Direct comparisons are difficult because the small number of events makes necessary the use of composite endpoints. Furthermore, data from early generations TAVI devices cannot be automatically extrapolated to current-generation prosthesis. The Comparison of Transcatheter Heart Valves in High-Risk Patients With Severe Aortic Stenosis (CHOICE; NCT01645202) trial, which randomized high-risk patients to receive a BEV (Sapien XT) or a SEV (Core Valve), showed a greater rate of device success with early generation BEV. The greater device success of BEV in comparison to SEV (95.9% vs. 77.5%; relative risk, 1.24; 95% CI, 1.12–1-37; p < 0.001) was driven by a significantly lower frequency of significant aortic regurgitation and less frequent need for the implant of a second valve. Placement of a new permanent pacemaker was less frequent in the BEV group (17.3% vs. 37.6%, P = 0.001). A randomized trial compared the SAPIEN 3 valve with the ACURATE Neo valve (Safety and efficacy of the Symetis ACURATE Neo/TF Compared to the Edwards SAPIEN 3 Bioprosthesis - SCOPE 1; NCT03011346) [57]. The non-inferiority of the ACURATE Neo was not met in a composite endpoint. In the SCOPE 2 trial (NCT03192813), the ACURATE Neo valve did not meet the non-inferiority criteria in comparison with Core Valve Evolut prosthesis. Nevertheless, the ACURATE neo showed a significative reduction in permanent pacemaker implantation (PPI) (10.5% vs. 18%) [58]. Data from observational analysis seem to favor BEV [59, 60], but should be interpreted with caution.
5. Minimizing complications
5.1 Paravalvular leaks
Paravalvular leak (PVL) consists of a residual gap between the native calcified aortic valve, aortic annulus, and the prosthesis. PVL can be identified during the TAVI procedure using invasive hemodynamics and cine-angiography, while echocardiography is the most diffusely used technique to detect, grade, and follow PVL [61].
The hemodynamic effects of a significant residual regurgitation have a negative clinical impact. Moderate to severe PVL are independent predictors of short-term and long-term mortality, while the impact of mild PVL is unclear [62].
Calcification of the aortic valve, leaflet asymmetry, prosthesis malposition and under-sizing, and the use of SEV is associated with the development of PVL [63]. SEV is more influenced by the calcium burden, as they exert less radial force than BEV, therefore they are more often under-expended or eccentrically shaped. On the other side, the higher radial force exerted by BEV could lead to annular rupture [63, 64].
The first-generation devices had a 30-day incidence of moderate to severe PVL of 9.0% and 11.8% (respectively for SEV and BEV) in high-risk patients [65, 66]. Newer-generation devices were designed with features aimed to reduce PVL, such as external skirt of the SAPIEN 3 Valve and the external sealing system of the Evolut PRO Valve. In the more recent PARTNER III trial, the SAPIEN 3 valve had a decreased incidence of moderate to severe PVL in low-risk patients (0.6%) and of note that was similar to residual PVL of SAVR (0.5%) [8]. In the Evolut Low-Risk Trial, there was a greater incidence of moderate to severe PVL: 3,5% in TAVI vs. 0,5% in SAVR [10]. This discrepancy is consistent with the different designs of prosthesis.
A significant PVL may benefit from several treatment options, which includes balloon post-dilatation of the prosthesis, percutaneous closure with plugs, and TAVI-in-TAVI to exert a superior radial force against the PVL, and surgical intervention.
5.2 Coronary obstruction and coronary re-access
Almost half of the patients undergoing TAVI have coronary artery disease, and about a third of the patients are in a low-risk population [8, 67]. TAVI may influence coronary in two ways: the prosthetic valve struts may prevent the selective catheterization of coronaries during PCI and the prosthesis or the dislodged native leaflets may cause acute coronary obstruction.
The coronary re-access following TAVI is influenced by several anatomical factors (sino-tubular junction dimensions, sinus height, leaflet length and bulkiness, sinus of Valsalva width, and coronary ostial height) and device-related and procedural factors (commissural tab orientation, sealing skirt height, and valve implantation depth) [68]. Prosthesis with higher frame design hinders coronary re-access more than those with a lower frame due to the barrier of the stent frame in allowing coronary catheters to directly engage the coronary ostia (Figure 6). Therefore, selective coronary angiography after TAVI with some SEV could be more challenging than with BEV [68].
Figure 6.
Difference between TAVI device profile in coronary re-engagement. Device with low profile could theoretically guarantee a easier coronary cannulation.
Otherwise, some SEVs, such as ACURATE NEO (Boston Scientific, MA, USA), are characterized by lower stent frame, which could allow for easy coronary engagement.
The alignment of the TAVI valve commissures with the native aortic valve commissures is a promising modifiable factor to facilitate coronary re-access. TAVI differs from aortic valve replacement in the fact that the orientation of commissural posts relative to the coronary ostia is random. It has been shown that specific orientations of the Evolut and ACURATE neo at initial deployment could improve commissural alignment [69]. Of note, a commissural alignment is particularly helpful in high-frame SEV in avoiding coronary artery overlap; this may be fundamental in coronary artery access and redo TAVR.
Acute or delayed coronary obstruction after TAVI is a rare but life-threatening complication, with an incidence inferior to 1% [70, 71]. Coronary obstruction is usually caused by the displacement of the calcified native valve leaflet over the coronary ostium or by the direct occlusion of the coronary ostium by the covered skirt of the transcatheter aortic prosthesis. Anatomical factors associated with coronary obstruction are low coronary ostia height and shallow sinuses of Valsalva. Procedural-related elements include BEV and valve-in-valve (VIV) for surgical bioprosthesis [70]. To prevent this complication some coronary protection techniques may be used, such as preventive coronary wiring or positioning of an undeployed stent in high-risk patients. If the coronary blood flow is compromised during or after TAVI release, the stent is retracted and deployed to create a channel for coronary perfusion between the displaced leaflets and the aortic wall (chimney technique) [72, 73].
5.3 Pacemaker implantation
High-grade atrioventricular block requiring permanent pacemaker implantation (PPI) is one of the most common complications following TAVI, with an incidence ranging from 2 to 36%, depending on the patient population in exam and the prosthesis design [74]. Notably, the rate of PPI remains high even in recent trials with newer generation devices compared with previous trials [74, 75]. SEV is associated with higher risk of PPI than BEV, probably because of the increased radial force exerted on the left ventricle outflow tract (Figure 7). In the Core Valve High-Risk trial, PPI was significantly more frequent in the TAVI group than in the SAVR group (19.8% vs. 7.1%, p < 0.001) [65]. A more frequent occurrence of PPI in TAVI patients was also observed in the Evolut Low-Risk trial [10]. In the PARTNER III trial, the rate of PPI-associated TAVI was similar to that of surgical patients (6.6% vs. 4.1%, hazard ratio 1.65; 95% CI, 0.92 to 2.95), although the onset of a new left bundle block was more common after TAVI (22.0% vs. 8.0%; hazard ratio 3.17; 95% CI 2.13 to 4.72) [8].
Figure 7.
Relationship between transcatheter heart valve and conduction system.
The link between the occurrence of conduction disturbances and the TAVI procedure is explained by the proximity between the aortic valve and the structures of the cardiac conduction system. The atrioventricular node is situated in the right atrium, continues as the Bundle of His, and then splits into the left and the right bundle branches. The Bundle of His emerges at the level of the interventricular membranous septum, caudally to the commissure between the right and noncoronary cusp. The course of the Bundle of His may be within the right half of the membranous sept, within the left half, or under the endocardium; conduction disorders during TAVI are lower with the first anatomic variant [76, 77]. During TAVI, the conduction system can be injured by the insertion of guidewires, balloon pre-dilation, and valve deployment.
The conduction disturbances after TAVI range from new-onset complete atrioventricular blockade to left bundle branch block and transient complete atrioventricular block. The presence of baseline right bundle branch block (RBBB) is the strongest predictor of need for PPI. Other predictors for PPI after TAVI are PR-interval prolongation, left anterior hemiblock, older age, presence of left ventricle outflow tract calcifications, severe mitral annular calcification, and the length of the membranous septum. Procedural predictors are the use of SEV, deeper valve implantation, balloon pre- and post-dilation, and prosthesis oversizing (Figure 8) [74, 78, 79, 80].
Figure 8.
Major factors associated with permanent pacemaker implantation after TAVI.
As per standard of care, PPI is recommended when the patient develops a persistent complete or high-grade atrioventricular block after TAVI. It is also recommended in case of new-onset alternating bundle branch block, while it may be considered in patients with pre-existing right bundle branch block who develop new post-procedure conduction disturbance. There is not yet consensus about the optimal strategy for patients with other conduction abnormalities [78].
PPI after TAVI has been associated with increased mortality and rehospitalization, as the need for RV pacing may lead to decreased LV function and heart failure, yet there is still conflicting evidence [78, 81]. Risk factors that should be assessed in the preoperative TAVI evaluation are preexisting conduction disturbances and LVOT calcification. There may be a trade-off between the reduction of PVL and the risk of PPI, as a greater radial force may reduce the regurgitation, but it may damage the conduction system [52]. A BEV may be preferred in patients with baseline conduction disorders. A higher implantation strategy may minimize the contact between the valve and membranous septum, reducing conduction defects after the implantation [82]. In this context, an angiographic view providing an accurate visualization of the implantation depth (the cusp overlap view, as the right coronary cusp and the noncoronary cusp appear overlapping) demonstrates to reduce the rate of PPI [83].
6. Particular cases
6.1 Pure aortic regurgitation
Moderate to severe aortic regurgitation has a prevalence of 0.5%. The course of chronic aortic regurgitation leads to left ventricular dilation and heart failure. Primary aortic regurgitation may be caused by infective endocarditis, rheumatic disease, or degenerative/calcific valve disease. Bicuspid aortic valve, while more commonly associated with stenosis, may cause pure aortic regurgitation or a mixed disease. Aortic regurgitation may also be secondary to marked dilation of the ascending aorta [84].
The gold standard treatment is surgery, with both aortic valve replacement or aortic valve-sparing root replacement. Currently, the role of TAVI is limited to selected patients with aortic regurgitation deemed ineligible for SAVR [13, 85].
The commercially available TAVI devices have been designed for the treatment of degenerative calcific aortic stenosis. The presence of a rigid frame of calcium in the annulus provides an anchoring point for device deployment. The lack of calcium poses thus a significant challenge, as there is increased risk of device malposition, dislodgment, and embolization. The lack of calcification may also lead to higher rates of PVL. Another issue is the risk of implanting undersized devices, as regurgitant aortic valves are more elastic than calcific stenotic valves and can expand to a greater degree during valve deployment. Furthermore, the concomitant presence of a certain degree of aortic disease with dilation and friable tissues poses a further degree of risk for the procedure [85, 86].
Registry data show that TAVI in pure aortic regurgitation has worse outcome than TAVI in aortic stenosis. A 331 patients registry showed a 3% rate of procedure-related death, a 3.6% conversion to open surgery, a 1.2% rate of coronary obstruction, a 1.5% of aortic root injury, and a 16.6% need for second valve implantation. Newer generations valves scored better, as device success went from 61.3% to 81.1% (p < 0.001) and moderate to severe aortic regurgitation decreased from 18.8 to 4.2% (p < 0.001). [85] In another registry, also including patients with failing bioprosthesis, device success was achieved in 85% of patients with new-generation devices [87].
New prosthesis specifically designed for aortic regurgitation are currently being investigated, such as the Trilogy Heart Valve (Trilogy; Jena Valve Technology), which features anchor rings to clasp the native aortic leaflets [88]. While TAVI may be an alternative for selected patients deemed at high risk for surgical aortic valve replacement, it is currently an off-label indication; randomized control trials and long-term data are still needed.
6.2 Bicuspid aortic valve stenosis
The bicuspid aortic valve is the most common congenital heart defect, with an incidence of around 1% [89]. Almost half of the patients undergoing isolated aortic valve replacement have a bicuspid aortic valve, with a higher incidence in younger patients [90]. In the contemporary practice, up to 10% of patients with bicuspid aortic valve stenosis are referred to TAVI [91].
Echocardiography often underestimates the prevalence of bicuspid valves in calcified aortic stenosis [91]. CT scan provides a more accurate diagnosis and visualization of the bicuspid morphology [92]. Bicuspid aortic valve encompasses a wide range of morphologies; the most common classification categorizes it according to the number of raphes [93].
Aortic annuli in patients with bicuspid valve tends to be larger than in patients with a tricuspid valve. The annulus size may be outside of the range for the currently available devices. Furthermore, the aortic valve complex may have a non-tubular geometry, such as tapered or funnel anatomy. This adds complexity to the selection of a compatible prosthesis [94].
Bicuspid valves have a higher calcific burden than tricuspid stenotic valves. The calcium involves the leaflets in an asymmetrical way and often extends to the LV outflow tract. The majority of the bicuspid valves have a fibrotic and calcified raphe. These anatomic elements hinder the optimal expansion of the valve during TAVI. The asymmetric expansion of the prosthesis increases the risk of PVL. The presence of a highly calcified raphe, if localized between right coronary cusp and non-coronary cusp, increases the risk of conduction disturbances. Calcified raphe and excess leaflet calcification have been found to predict all-cause mortality in TAVI, and when both were present patients had higher rates of aortic root injury and PVL [94, 95].
In addition, coronary anomalies are more frequent in patients with bicuspid aortic valve, and 20 to 30% of them have concomitant aortic disease [89, 94]. Many patients may need aortic root surgery in addition to the valve replacement.
Data about the outcome of TAVI in bicuspid valve anatomy are limited to observational studies, as it was an exclusion criterion in all the randomized trials confronting TAVI with SAVR. In patients at increased surgical risk included in the STS/ACC transcatheter valve therapy registry (STS/ACC TVT Registry; NCT01737528), TAVI for bicuspid aortic valve stenosis showed acceptable safety outcomes with low complications rates [96]. When current-generation devices were used, device success was higher (96.3 vs. 93.5; P = 0.001) and the incidence of moderate to severe PVL was lower (2.7% vs. 14.0%; P < 0.001) in comparison with older-generation devices. With current-generation devices, device success was slightly lower in the bicuspid valve group (96.3% vs. 97.4%; P = 0.07) in comparison with tricuspid stenosis, with a slightly higher incidence of residual moderate or severe PVL. A comparable 1-year mortality was observed, with no increase in the risk of stroke [97]. Results of TAVI in low-risk patients with bicuspid valve anatomy seem similar to those patients with tricuspid aortic valve. In the PARTNER 3 bicuspid registry, with a population of 169 patients, a propensity score matching with TAVI patients showed no difference in the primary endpoint and in the individual components (death, strokes, cardiovascular rehospitalization). Of note, almost half of the patients submitted (47%) were not treated, being excluded because of anatomic or clinical criteria [98]. Another small prospective trial showed good short-term outcomes in low-risk patients with bicuspid aortic valve [99]. Despite the good outcomes in selected patients with favorable anatomies those results cannot be inferred for all the patients with bicuspid aortic valve.
Technical recommendations for TAVI include more frequent balloon valvuloplasty and post-dilation, a low degree of oversizing, and the use of repositioning prosthesis. In tapered anatomies, a supra-annular positioning of the prosthesis has been suggested [94].
7. Conclusions
In recent years the treatment of severe aortic stenosis has been deeply transformed by the introduction of the transcatheter approach. We have reported an overview of the more relevant clinical and technical aspects of the TAVI procedure. As the indications extend to younger patients and with lower surgical risk, it is even more crucial to optimize the results and reduce the complication rate. Further improvements in both technologies and techniques are needed before expanding indications in aortic stenosis in bicuspid valve and in aortic regurgitation.
\n',keywords:"aortic valve stenosis, aortic valve disease, Transcatheter aortic valve implantation, Transcatheter aortic valve replacement, interventional cardiology",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/82685.pdf",chapterXML:"https://mts.intechopen.com/source/xml/82685.xml",downloadPdfUrl:"/chapter/pdf-download/82685",previewPdfUrl:"/chapter/pdf-preview/82685",totalDownloads:14,totalViews:0,totalCrossrefCites:0,dateSubmitted:"May 8th 2022",dateReviewed:"June 14th 2022",datePrePublished:"July 21st 2022",datePublished:null,dateFinished:"July 14th 2022",readingETA:"0",abstract:"Degenerative aortic valve disease is the most common heart valve disease in western countries. After the onset of symptoms, the prognosis of aortic stenosis is poor, despite optimal medical therapy. In recent years transcatheter aortic valve implantation has been affirmed as a viable treatment for patients with high to low surgical risk. Patient screening and procedural planning are crucial for minimizing complications and achieving procedural success. In the last decade, we have seen a progressive technological development in the percutaneous approach, allowing for expanding indications even in low-risk populations. Here we report a brief review summarizing patient screening and procedural planning in patients with aortic valve disease undergoing a transcatheter approach.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/82685",risUrl:"/chapter/ris/82685",signatures:"Francesco Gallo, Alberto Barolo, Enrico Forlin and Marco Barbierato",book:{id:"11739",type:"book",title:"Cardiovascular Diseases",subtitle:null,fullTitle:"Cardiovascular Diseases",slug:null,publishedDate:null,bookSignature:"Dr. David C. Gaze",coverURL:"https://cdn.intechopen.com/books/images_new/11739.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80356-117-2",printIsbn:"978-1-80356-116-5",pdfIsbn:"978-1-80356-118-9",isAvailableForWebshopOrdering:!0,editors:[{id:"71983",title:"Dr.",name:"David C.",middleName:null,surname:"Gaze",slug:"david-c.-gaze",fullName:"David C. Gaze"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Patients selection",level:"1"},{id:"sec_2_2",title:"2.1 General screening: symptoms and prognostic impact",level:"2"},{id:"sec_3_2",title:"2.2 Risk stratification",level:"2"},{id:"sec_4_2",title:"2.3 Futility",level:"2"},{id:"sec_4_3",title:"2.3.1 Balloon aortic valvuloplasty (BAV)",level:"3"},{id:"sec_7",title:"3. Anatomical assessment",level:"1"},{id:"sec_7_2",title:"3.1 Echocardiography",level:"2"},{id:"sec_8_2",title:"3.2 Cardiac catheterization",level:"2"},{id:"sec_9_2",title:"3.3 Computerized tomography scan",level:"2"},{id:"sec_11",title:"4. Device",level:"1"},{id:"sec_11_2",title:"4.1 Balloon-expandable valves",level:"2"},{id:"sec_12_2",title:"4.2 Self-expanding valves",level:"2"},{id:"sec_13_2",title:"4.3 Device choice",level:"2"},{id:"sec_15",title:"5. Minimizing complications",level:"1"},{id:"sec_15_2",title:"5.1 Paravalvular leaks",level:"2"},{id:"sec_16_2",title:"5.2 Coronary obstruction and coronary re-access",level:"2"},{id:"sec_17_2",title:"5.3 Pacemaker implantation",level:"2"},{id:"sec_19",title:"6. Particular cases",level:"1"},{id:"sec_19_2",title:"6.1 Pure aortic regurgitation",level:"2"},{id:"sec_20_2",title:"6.2 Bicuspid aortic valve stenosis",level:"2"},{id:"sec_22",title:"7. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Iung B, Arangalage D. 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Journal of Thoracic and Cardiovascular Surgery. 2007;133(5):1226-1233'},{id:"B94",body:'Vincent F, Ternacle J, Denimal T, Shen M, Redfors B, Delhaye C, et al. Transcatheter aortic valve replacement in bicuspid aortic valve stenosis. Circulation. Lippincott Williams and Wilkins. 2021;143(10):1043-1061'},{id:"B95",body:'Yoon SH, Kim WK, Dhoble A, Milhorini Pio S, Babaliaros V, Jilaihawi H, et al. Bicuspid aortic valve morphology and outcomes after Transcatheter aortic valve replacement. Journal of the American College of Cardiology. 2020;76(9):1018-1030'},{id:"B96",body:'Forrest JK, Kaple RK, Ramlawi B, Gleason TG, Meduri CU, Yakubov SJ, et al. Transcatheter aortic valve replacement in bicuspid versus tricuspid aortic valves from the STS/ACC TVT registry. JACC: Cardiovascular Interventions. 2020;13(15):1749-1759'},{id:"B97",body:'Halim SA, Edwards FH, Dai D, Li Z, Mack MJ, Holmes DR, et al. Outcomes of transcatheter aortic valve replacement in patients with bicuspid aortic valve disease: A report from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter valve therapy registry. Circulation. 2020;141(13):1071-1079'},{id:"B98",body:'Williams MR, Jilaihawi H, Makkar R, O’Neill WW, Guyton R, Malaisrie SC, et al. The PARTNER 3 bicuspid registry for Transcatheter aortic valve replacement in low-surgical-risk patients. JACC: Cardiovascular Interventions. 2022;15(5):523-532'},{id:"B99",body:'Waksman R, Craig PE, Torguson R, Asch FM, Weissman G, Ruiz D, et al. Transcatheter aortic valve replacement in low-risk patients with symptomatic severe bicuspid aortic valve stenosis. JACC: Cardiovascular Interventions. 2020;13(9):1019-1027'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Francesco Gallo",address:"galfra87@gmail.com",affiliation:'
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IntechOpen’s Academic Editors and Authors have received funding for their work through many well-known funders, including: the European Commission, Bill and Melinda Gates Foundation, Wellcome Trust, Chinese Academy of Sciences, Natural Science Foundation of China (NSFC), CGIAR Consortium of International Agricultural Research Centers, National Institute of Health (NIH), National Science Foundation (NSF), National Aeronautics and Space Administration (NASA), National Institute of Standards and Technology (NIST), German Research Foundation (DFG), Research Councils United Kingdom (RCUK), Oswaldo Cruz Foundation, Austrian Science Fund (FWF), Foundation for Science and Technology (FCT), Australian Research Council (ARC).
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\\n\\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\\n\\n
\\n\\t
Does your institution already have a budget for covering Open Access publication costs?
\\n\\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\\n
\\n\\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\\n\\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\\n\\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
\n\n
In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
If you are associated with any of the institutions in our list below, you can apply to receive OA publication funds by following the instructions provided in the links. Please consult the Open Access policies or grant Terms and Conditions of any institution with which you are linked to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
Please note that this list is not a definitive one and is updated regularly. To suggest possible modifications or the inclusion of your institution/funder, please contact us at funders@intechopen.com
\n\n
Please be aware that you must be a member, or grantee, of the institutions/funders listed in order to apply for their Open Access publication funds.
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Academic reflection on the matter led to the development of the international business ethics field, which seeks to answer a key question: how should a company behave when the standards followed in the host country are lower than those followed in the home country? This chapter will fulfill three goals. Firstly, it will present the new moral dilemmas that economic globalization and technological change are posing to multinational corporations. Secondly, it will introduce a number of answers developed by practitioners in civil society, government and business. Finally, it will review a number of theoretical answers developed by normative researchers by adapting traditional moral theories such as utilitarianism, kantian deontology and virtue ethics. 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He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. Ray",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Statistical Institute",country:{name:"India"}}},{id:"415409",title:"Prof.",name:"Maghsoud",middleName:null,surname:"Amiri",slug:"maghsoud-amiri",fullName:"Maghsoud Amiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Allameh Tabataba'i University",country:{name:"Iran"}}},{id:"357085",title:"Mr.",name:"P. Mohan",middleName:null,surname:"Anand",slug:"p.-mohan-anand",fullName:"P. Mohan Anand",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"356696",title:"Ph.D. Student",name:"P.V.",middleName:null,surname:"Sai Charan",slug:"p.v.-sai-charan",fullName:"P.V. Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"7",type:"subseries",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. 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\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
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\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
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\r\n\tThe success of dental implant treatment is not solely dependent on the osseointegration around the implant. Aside from the criteria used to describe the hard tissue response at the implant level, the success criteria in implant dentistry include three additional aspects: peri-implant soft tissue, prosthesis, and patient’s satisfaction.
\r\n
\r\n\tThe Prosthodontics and Implant Dentistry topic will provide readers with up-to-date resources on the prosthodontics factors such as aesthetics, restorative materials, the design of prosthesis, case selection, occlusion, oral rehabilitation, among others, all of which play an important role in determining the success of a well osseointegrated implant. With the help of digital dental technology, these can now be accomplished more predictably.
\r\n
\r\n\tThe end goal of prosthesis is always considered when planning successful implant placement. The readers in this field will be able to learn more about taking a holistic approach when treating their dental implant cases.
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