\r\n\tThe application of these complex statistical models provides a greater understanding of the complex processes and mechanisms. Complex statistical models are a powerful tool that enables researchers in the health and medical sciences to increase their knowledge and understanding of complex systems and thus advance knowledge.
\r\n
\r\n\tThis book is devoted to applying complex models to health and medical sciences, both the classical and Bayesian approaches, and this book contain documentation of the contributions with the codes or script of the data analysis, that is relevant because it will help readers apply the models to new contexts.
",isbn:"978-1-80356-078-6",printIsbn:"978-1-80356-077-9",pdfIsbn:"978-1-80356-079-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"c5034363e1754265689dea0988fd89f8",bookSignature:"Prof. Cruz Vargas-De-León",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10678.jpg",keywords:"Generalized Estimating Equation, Longitudinal Model, Path Analysis, Structural Equation Models, Modelling Recurrent Events, Multiple Survival Outcomes, Spatial Models, Temporal Models, Meta-Regressions, Clinical Trials, Structural Equation Modelling, Bayesian Statistics",numberOfDownloads:41,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 3rd 2021",dateEndSecondStepPublish:"December 24th 2021",dateEndThirdStepPublish:"March 1st 2022",dateEndFourthStepPublish:"May 20th 2022",dateEndFifthStepPublish:"July 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"6 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:'Cruz Vargas-De-León received a certificate for highly cited research in "Mathematical Biosciences". He has been biographed by Marquis Who\'s Who in the World. Two of his articles have been awarded "Excellent papers" by National Program for Research Evaluation in Italy.',coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"421022",title:"Prof.",name:"Cruz",middleName:null,surname:"Vargas-De-León",slug:"cruz-vargas-de-leon",fullName:"Cruz Vargas-De-León",profilePictureURL:"https://mts.intechopen.com/storage/users/421022/images/system/421022.png",biography:'Cruz Vargas-De-León is a Professor of Biostatistics and Applied Mathematics. He has a bachelor\'s degree in mathematics (Statistics), a master\'s degree in health sciences, a master\'s degree in complexity sciences, and is currently a Student Ph.D. in Health Sciences. He is interested in Biostatistical and Biomathematical Modelling for Health. He has published more than 50 scientific articles, 35 of them in high-impact journals and indexed in JCR. He is also an Academic Editor of “International Journal of Hypertension”. \nHe has participated in the validation of surveys, randomized controlled trials, systematic reviews and meta-analyses, the construction of indices in medicine, and the identification of immunological biomarkers in cancer and epidemiological studies (Syphilis, Dengue, SARS-CoV-2, among others), and estimation of parameters of differential equation models.\nHe has received a certificate for the highly cited research in "Mathematical Biosciences" (2016, Elsevier), and the Guerrero State Award for Merit in Science and Technology "Guillermo Soberón" (2016). He has been biographed by Marquis Who\'s Who in the World in Issue 30 (2013). Two of his articles have been awarded "Excellent papers" by National Program for Research Evaluation (2011-2014) in Italy. Since 2015 he is a member of the National System of Researchers (SNI, in Spanish) from the National Council of Science and Technology (CONACYT, in Spanish).',institutionString:"Universidad Autónoma de Guerrero",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Universidad Autónoma de Guerrero",institutionURL:null,country:{name:"Mexico"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"15",title:"Mathematics",slug:"mathematics"}],chapters:[{id:"81784",title:"Practical and Optimal Crossover Designs for Clinical Trials",slug:"practical-and-optimal-crossover-designs-for-clinical-trials",totalDownloads:3,totalCrossrefCites:0,authors:[null]},{id:"82011",title:"Spatial Statistics in Vector-Borne Diseases",slug:"spatial-statistics-in-vector-borne-diseases",totalDownloads:13,totalCrossrefCites:0,authors:[null]},{id:"81944",title:"The Basics of Structural Equations in Medicine and Health Sciences",slug:"the-basics-of-structural-equations-in-medicine-and-health-sciences",totalDownloads:11,totalCrossrefCites:0,authors:[null]},{id:"81710",title:"Spatial Modeling in Epidemiology",slug:"spatial-modeling-in-epidemiology",totalDownloads:15,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444315",firstName:"Karla",lastName:"Skuliber",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/444315/images/20013_n.jpg",email:"karla@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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\n
1. Introduction
\n
Aortic root dilation (AoD) is frequently an incidentally discovered, asymptomatic finding in that is seen on various imaging modalities [1]. The anatomy of the aortic root includes the annulus, sinuses of Valsalva, sinotubular junction and ascending aorta [1], with the size being a function of a patient’s biologic variables such as height, age, BSA, and gender [1, 2]. However, while natural variations in the size of the aortic root are well known, the identification of progression from normal to pathologic AoD is a key clinical diagnosis that carries significant cardiovascular risk including aortic dissection, rupture, valvular regurgitation and cardiac tamponade [1, 3, 4, 5]. The etiology of pathological AoD is varied, ranging from congenital, infectious, autoimmune, and idiopathic conditions; and influences the medical and surgical management [1, 5]. Due to the variety of clinical conditions that can result in AoD, and the risks associated with worsening AoD, a thorough understanding of the pathophysiology of AoD, noninvasive imaging modalities and pharmacologic therapies is critical. The aim of this chapter is to review the most common conditions associated with AoD, appropriate imaging modalities, and treatment strategies to manage AoD.
\n
\n
\n
2. Etiologies of aortic root dilation
\n
Multiple etiologies of AoD exist such as Marfan syndrome, bicuspid aortic valve, Loeys-Dietz and Ehler-Danlos syndromes, idiopathic conditions, hypertension, infections, and inflammatory disorders. In this chapter, we will discuss the various etiologies categorized into two standardized groups—genetically-mediated and nongenetically mediated AoD.
\n
\n
2.1 Genetically-mediated aortic root dilation
\n
Genetically-mediated aortic root dilation or enlargement is the leading cause of thoracic aortic aneurysms. Marfan syndrome (MFS), the prototype condition for AoD, and bicuspid aortic valve has led to a greater understanding of AoD pathophysiology, pharmacologic treatment, timing of surgical intervention and optimal surveillance strategies with noninvasive imaging [6].
\n
\n
2.1.1 Marfan syndrome
\n
MFS is one of the most common hereditary disorders of connective tissues and is characterized by manifestations in cardiovascular, skeletal, and ocular systems [7]. MFS is the most common genetic cause of thoracic aortic aneurysms (TAAs). Its inheritance is almost exclusively autosomal dominant and mostly involves a mutation of the fibrillin-1 (FBN1) gene encoding the connective tissue structural protein fibrillin-1 [8]. The widely accepted incidence of Marfan syndrome is ~1 in 5000 individuals [9].
\n
Although the inheritance pattern is predominantly autosomal dominant, rare cases of autosomal recessive FBN1 gene mutations has been described [10]. While patients with Marfan phenotypes usually have an affected family member, 25% of the cases are sporadic due to de novo mutations [9]. In addition, in <10% of Marfan cases, no mutation of FBN1 was determined [11]. Since it was first identified as the main cause of Marfan syndrome, FBN1 mutations, depending on how it is mutated, were linked to a variety of syndromes and phenotypes [12]. Animal studies investigating the pathophysiology of the disease demonstrated over-expression of TGF-β in the mitral valve preceding prolapse, the aorta associated with dilatation, skeletal muscle associated with myopathy, and the dura leading to ectasia [12]. Later, mutations in TGF-beta receptor 2 (TGFBR2) and TGFBR1 genes were identified in some patients with Marfan phenotypes and subsequently implicated in the disease process in FBN1 mutation negative individuals [13, 14, 15]. These genes were also linked to another condition later, namely Loeys-Dietz syndrome (LDS) [14].
\n
The diagnosis of Marfan syndrome is established by using a combination of clinical manifestations, family history, and the presence of FBN1 mutation. In order to facilitate accurate recognition of the syndrome and improve patient management and counseling, a set of defined clinical criteria, called the Ghent nosology was developed [16] and later revised [17] (Table 1). Apart from the genetic testing for FBN1 mutation, Ghent nosology uses a systemic score calculation using clinical manifestations of Marfan and an aortic root dilatation Z-score (see noninvasive imaging below).
\n
\n
\n\n
\n
Patients with family history of Marfan disease
\n
\n
\n
\n
Ectopia lentis
\n
\n
\n
\n
\n
Systemic score ≥ 7
\n
\n
\n
\n
\n
Aortic root dilatation Z-score
≥2 in patients above 20 years old
≥2 in patients below 20 years old
\n
\n
\n
\n
Patients without family history of Marfan disease
\n
\n
\n
\n
Aortic root dilatation Z-score ≥ 2 and Ectopia lentis
\n
\n
\n
\n
\n
Aortic root dilatation Z-score ≥ 2 and FBN1 mutation
Ectopia lentis and FBN1 mutation associated with aortic root dilatation
\n
\n
\n\n
Table 1.
Revised Ghent nosology.
\n
One of the major causes of mortality and clinical hallmark of Marfan syndrome is aortic root dilation and related complications such as dissection, rupture and/or aortic valvular regurgitation. Aortic root dilation is typically first identified on echocardiography in 60–80% of Marfan patients [18]. Therefore, surveillance echocardiography has been routinely used to serially monitor aortic dimensions. If the aortic root diameter is above 4.5 cm in adults, aortic dilation rates are above 0.5 cm/year, and/or significant aortic insufficiency is already present, more frequent monitoring is recommended [6] (see Diagnosis and Surveillance of Aortic Root Dilation below for more detailed guidelines).
\n
\n
\n
2.1.2 Bicuspid aortic valve
\n
Bicuspid aortic valve is one of the most frequent congenital heart anomalies in adults, affecting 0.9–2% of the population [19]. Most cases of bicuspid aortic valve are familial and studies show that heritability of the disease is ~90% making it an autosomal dominant pattern with incomplete penetrance [20]. Bicuspid aortic valve can occur alone or with other congenital cardiovascular disorders such as coarctation of the aorta, supravalvular or subvalvular aortic stenosis, and ventricular septal defect [21].
\n
The diagnosis is often established by transthoracic echocardiogram (TTE), which has high sensitivity (~92%) and specificity (~96%) [22]. TTE is also useful for surveillance of potential complications of bicuspid aorta such as aortic stenosis, aortic dilation, aortic regurgitation, and infective endocarditis [23]. Given the risk of inheritance, first degree relatives are also recommended to be screened with TTE [21].
\n
Prevalence of aortic dilation in patients with bicuspid aortic valve disease ranges from 20 to 84% depending on the criteria used in different studies [24]. The risk of aortic dilation increases with age and the risk of dissection increases as the aortic diameter increases [25, 26]. When the aortic root diameter is above 4.5 cm, there is a family history of aortic dissection, or aortic diameter change is rapid it is recommended to perform echocardiogram annually [21]. More frequent surveillance is recommended for patients with aortic root diameters approaching surgical thresholds (see Surgical Interventions section below).
\n
\n
\n
2.1.3 Loeys-Dietz syndrome
\n
Loeys-Dietz syndrome (LDS) is a rare congenital syndrome characterized by hypertelorism (widely spaced eyes), a split uvula or cleft palate, tortuous arteries and aortic aneurysms. LDS shares many features with Marfan syndrome [14]. Most of the LDS cases are sporadic or show an autosomal dominant pattern of inheritance [14].
\n
The incidence and prevalence of the disease is still not well established.
\n
Loeys-Dietz syndrome was initially classified into two subtypes based on the severity of the cutaneous and craniofacial features but later was divided into six subtypes stratified by genotypes [27]. These subtypes are labeled 1–6 and associated with mutations in TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, SMAD2, respectively [27]. Type 1 and type 2 are the most commonly seen subtypes with frequencies of 20 and 55% among all subtypes, respectively [28].
\n
Aortic root dilation is a hallmark feature of this disease entity and is frequently seen in patients (~80%) [29]. Another vascular manifestation is aneurysms throughout the arterial tree. This is a concerning clinical manifestations of the disease and can cause aggressive arteriopathy; therefore, early operative intervention at ascending aortic diameters of ≥42 mm is recommended [30].
\n
\n
\n
2.1.4 Ehler-Danlos syndrome
\n
Ehlers-Danlos syndromes (EDS) are a heterogeneous and relatively rare group of connective tissue disorders characterized by skin hyperextensibility, joint hypermobility, and tissue fragility [31]. Ehler-Danlos syndrome can present with a variety of clinical manifestations and can be caused by different kinds of genetic mutations. Overall prevalence of EDS is ~1 in 5000 and EDS hypermobile (hEDS) is the most common type [31].
\n
Vascular complications can be seen with different types of EDS; however, it is most commonly seen in type IV (vascular or arterial ecchymotic type; vESD), characterized by an autosomal dominant mutation in COL3A1 (collagen, type III, α-1 gene) encoding type III procollagen [32]. Up to 80% with vESD patients suffer from vascular complications by the age 40 years [32]. Therefore EDS patients, especially vEDS, patients should be routinely evaluated for aortic root disease. These patients are recommended to undergo elective operation at smaller diameters (4.0–5.0 cm) to avoid acute dissection or rupture. Patients with a growth rate of more than 0.5 cm/year in an aorta that is <5.5 cm in diameter are recommended to be considered for operation [33].
\n
\n
\n
\n
2.2 Nongenetic
\n
\n
2.2.1 Idiopathic
\n
Aortic root dilation is an established phenomenon that has shown strong correlations to key pathobiological factors such as age, body surface area (BSA), height and gender. The correlation of aortic root size with age and BSA were initially described in the development of screening nomograms using M-mode echocardiograms [34]. Follow up studies with 2D echocardiography further validated these correlations, allowing for the development of nomograms for normal patient populations or adjusted for patients with underlying congenital disorders (i.e., Marfan syndrome) [2, 35]. These studies evaluating AoD by echocardiograms are further supported by reviews of autopsy data that show clear correlations to key pathobiological factors such as increased age and height with AoD [36].
\n
Despite the validation of age as being correlated strongly with AoD, the mechanism of age on the development of AoD still remains an area of active research. One of the predominant hypotheses is based on the idea of cyclic stress, and how the aorta degrades through gradual mechanical decline of elastin proteins [37]. Elastic arteries, namely the aorta, are estimated to dilate by 10% with each beat [38]. It is hypothesized that the shear stress over a normal lifetime results in the degradation of elastic lamella, resulting in arterial dilation and stiffening [38]. This is corroborated by histologic data demonstrating damage to medial elastin of the proximal aorta [38]. Furthermore, there is evidence to suggest that in the absence of risk factors such as hypertension or atherosclerosis, the aortic wall undergoes age-associated reprograming that is proinflammatory promotes progression of arterial disease [39]. Wang et al. demonstrated in pathologic samples of aortas that age correlated with increased smooth muscle cell invasion, and increased production of downstream angiotensin II mediators [39].
\n
In addition to age and BSA, gender is another key factor which can increase the risk and progression of AoD [40]. In the Framingham study of 1849 men and 2152 women, not currently diagnosed with cardiac disease or having a cardiac history, aortic root was 2.4 mm smaller in women than men with m-mode echocardiography [40]. A systematic review in 2014 of 10,741 patients with hypertension revealed men had a significantly higher incidence of AoD relative to women [41].
\n
In conclusion, a series of biological variables are correlated with AoD, and it is important to take these into account as they are potential confounders or contributors in the evaluation of patients with pathologic AoD. Even exercise capacity has been correlated with AoD, with a recent meta-analysis showing that athletes defined by participation in National Collegiate Athletic Association (NCAA) or international equivalent had an aortic root diameter that was larger than nonathletic controls [42], and a statistically significant increase by measurement of sinuses of Valsalva and aortic root annulus [42]. It is important to understand the significance of biological variables such as age, height, BSA, or gender to fully evaluate pathologic AoD without the influence of known confounders.
\n
\n
\n
2.2.2 HTN
\n
Hypertension is a well-known risk factor for aortic dissection, and in some studies, it is estimated to factor into roughly half of the overall risk for aortic dissection [43]. A recent prospective cohort study of 30,447 patients, 86% of patients who developed aortic dissection had hypertension [4]. However the relationship between hypertension and AoD is not as clearly established. In a Framingham study of 3195 patients, there was no relationship between the development of AoD with hypertension [44]. A subsequent follow up study of Framingham participants evaluating aortic root diameter was positively correlated with mean arterial pressure, but negatively associated with pulse pressure, indicating that the mechanism behind AoD is more complicated [45]. Moreover, investigations have shown that in patients with other comorbidities for AoD, such as, Turner syndrome, hypertension is significantly associated with increased prevalence of AoD [45]. This has led to interesting insights into the cyclic stress hypothesis of the development of AoD [43]. If AoD develops due to chronic shear stress, then it would be expected that AoD is correlated with higher pulse pressure (PP), which would presumably lead to greater stress and aortic dilation [43]. However, studies have reported an inverse relationship between AoD and PP [43]. Additionally a systematic review in 2014 showed that in a population of 10,791 hypertensive patients, 9.1% had AoD with a significant gender skew toward men [41]. However there was no significant correlation of mean arterial pressure or pulse pressure values and AoD [41]. While hypertensive patients have a higher incidence of AoD, the mechanism remains to be further investigated. Moreover, these unclear correlations between MAP, PP, and AoD suggest that the aorta is not static, but a dynamic structure whose response to stress, such as hypertension, is still being elucidated [43].
\n
\n
\n
2.2.3 Infections
\n
Since the first mass production of penicillin in 1945, the modern era of antibiotics has resulted in a decrease in the prevalence of mycotic aneurysms due to bacterial infections in developed countries [46, 47]. However they can still be found in developing countries, and are rare but well described causes of mycotic aneurysms [46]. Most common pathogens include Salmonella, Staphylococcus and Streptococcus pneumonia, and while rare have been in the pathogenesis of mycotic aneurysms of the aortic root [46, 48, 49]. Other common bacteria include Mycobacterium tuberculosis and Treponema pallidum, which will be discussed below, and more rare causes include Listeria, Bacteroides, Clostridium septicum, and Campylobacter jejuni [46]. With the majority of bacterial aortitis, aneurysm development is generally saccular, and Salmonella has been reported in case studies to predominantly affect the abdominal aorta than the thoracic [46, 48]. Infections with Staphylococcal species generally are related to underlying aortic valve infections, but have been reported to progress into aneurysms of the aortic root [46, 49].
\n
\n
2.2.3.1 Treponema pallidum\n
\n
\nTreponema pallidum, a sexually transmitted spirochete which is the causative organism of syphilis, is a well characterized cause of aortitis [46, 50, 51]. Cardiovascular involvement is limited to late stage, or tertiary syphilis, and generally occurs 5 to upwards of 40 years after primary infection [50, 51]. Aortitis, and aneurysm development is due to invasion of the vasa vasorum, resulting in obliterative endarteritis that leads to degradation of the aortic media [50, 51]. The chronic inflammation results in fibrosis of the intima, a phenomenon known as “tree-barking” that ultimately progresses to aneurysm development. In an autopsy study in 1960 of 51 aortic aneurysms secondary to syphilitic aortitis, 7.8% were found at the sinuses of Valsalva and 29.4% involved the ascending aorta, representing a majority of the sample [52]. This predominance to the ascending thoracic aorta have been further corroborated in later studies, however the detailed echocardiographic analysis of syphilitic aortitis, specifically in relation to AoD is limited due to the rarity of the disease presentation [46, 50].
\n
\n
\n
2.2.3.2 Tuberculosis
\n
Tuberculosis is a relatively common infection especially in developing countries [53]. Mycobacterium tuberculosis, the causative pathogen, is a known cause of mycotic aortic aneurysms [46, 50]. Pathogenesis of tuberculous mycotic aneurysm is believed to be due to lymphatic spread or hematogenous seeding, and mortality rates are reported as high as 60% in patients who develop this complication [50]. While more commonly affecting the distal aortic arch and descending aorta, there are case reports detailing aortic root aneurysms due to tuberculosis [50, 54].
\n
\n
\n
2.2.3.3 HIV
\n
There have been case reports proposing an association between aortic aneurysms and HIV [50]. In a variety of these cases the causes are generally multifactorial, as the majority of cases have reported coinfections (Q fever and leishmaniasis) or comorbid autoimmune conditions (giant cell arteritis) [55, 56]. It is still an area of investigation as to whether there is a true association, and there is sparse data showing a relationship with AoD.
\n
\n
\n
\n
2.2.4 Inflammatory disorders
\n
\n
2.2.4.1 Ankylosing spondylitis
\n
Ankylosing spondylitis, a seronegative spondyloarthropathy, is a chronic, progressive rheumatologic disorder, and was one of the first found to be associated with aortitis [50, 57]. The proposed mechanism of AoD in ankylosing spondylitis is fibrous growth development along the intima, which leads to subsequent weakening [57]. Prior TEE studies further evaluated the prevalence of AoD in ankylosing spondylitis, and 82% of patients with ankylosing spondylitis had aortic root abnormalities [58]. Specifically, 61% of patients had aortic root thickening and 25% of patients had AoD [58]. AoD in these populations is a relatively common phenomenon and is associated with significant cardiac morbidity [45, 57].
\n
\n
\n
2.2.4.2 Relapsing polychondritis
\n
Relapsing polychondritis is another autoimmune disorder, which is a multisystem inflammatory disorder that primarily affects the cartilaginous structures of the body [59]. Cardiovascular involvement is common, estimated to be the second most frequent cause of death and can result in aneurysm development in 5% of cases of both thoracic and abdominal aorta [50, 59]. AoD has been known to occur, albeit rare, with cases of requiring surgical revision after the development of aortic regurgitation [60, 61].
\n
\n
\n
2.2.4.3 Takayasu arteritis
\n
Takayasu arteritis is a chronic granulomatous large vessel vasculitis, predominantly found in pediatric populations [50, 62]. A rare disorder, the pathogenesis is characterized by granulomatous panarteritis that can affect the entirety of the aorta and major branches, however predominantly affects the common carotid and subclavian artery [62]. While rare, there are reports of AoD from Takayasu arteritis resulting in aortic regurgitation [63, 64].
\n
\n
\n
2.2.4.4 Giant cell arteritis
\n
Giant cell arteritis is a large vessel vasculitis that is characterized by chronic granulomatous inflammation [50]. While commonly affecting carotid, temporal and vertebral arteries, it has been known to affect the ascending aorta, at times resulting in dissection or aortic valve insufficiency [50]. The development of AoD from GCA may be influenced by other comorbid conditions such as HIV; however, this association is currently only supported with case reports [55].
\n
\n
\n
\n
2.2.5 Other
\n
\n
2.2.5.1 Left ventricular hypertrophy
\n
Additionally left ventricular hypertrophy is reported to be positively correlated with AoD. Early retrospective reviews of echocardiographic studies have shown a positive relationship between LVH and AoD, and this has been further supported in subsequent systematic reviews [41, 65]. Patients with AoD with concomitant left ventricular hypertrophy are shown to have an increased risk of adjusted cardiovascular events [66]. However as with previous studies, the exact mechanism between LVH and AoD is still being determined.
\n
\n
\n
\n
\n
\n
3. Diagnosis and surveillance of aortic dilation
\n
\n
3.1 Clinical manifestations
\n
Aortic root dilation is typically a silent disease, with most cases being diagnosed incidentally on imaging. AoD can become symptomatic as the aneurysm enlarges. Aortic root aneurysms grow at an average of 1–4 mm/year [5], with a faster rate of growth noted in patients with bicuspid aortic valves, Marfan syndrome, ESRD, male gender, and smokers [5, 67]. When the aneurysm enlarges to the point of compressing surrounding structures the patient may begin to observe symptoms—the most common of which is chest pain, seen in up to 75% of patients [5, 68]. Other nonspecific symptoms can include back pain, abdominal pain and fatigue (though only present in 5% of patients).
\n
Additionally, patients may present with symptoms secondary to complications of a dilated aortic root such as aortic insufficiency and congestive heart failure. Thus, patients can develop dyspnea as the presenting symptom of aortic root dilation up to 40% of the time [68]. Other presenting symptoms may be related to the complications noted in Table 2 [69, 70, 71, 72, 73, 74].
Complications and presenting symptoms of aortic root dilation.
\n
\n
3.1.1 Complications of aortic root dilation
\n
Acute aortic emergencies that occur secondary to aortic root dilation include dissection, rupture, and aortic insufficiency. As the aortic root diameter increases, the risk for aortic dissection and rupture rises [75]. Aortic dissections are the most common acute aortic emergencies [76], and can be classified depending on the segment of the aorta affected: type A dissections involve the ascending aorta (seen in aortic root dilation), while type B dissections are those that occur distal to the left subclavian artery.
\n
Aortic dissection most commonly presents with acute onset chest pain that may radiate to the back. The character of the pain has traditionally been described as ripping or tearing in nature, however over half of patients may instead complain of sharp pain [77]. In addition, geriatric populations are less likely to have an acute onset of pain [78]. Physical exam findings that may be present include unequal blood pressures in the upper extremities, a new diastolic murmur indicative of acute aortic regurgitation, or muffled heart sounds secondary to tamponade (with proximal extension of the dissection). Imaging may be notable for widening of the mediastinum on CXR [77]. In order to aid in the diagnosis of a dissection, an aortic dissection detection risk score (ADD-RS) has been developed. The score is comprised of three categories: the presence of high risk conditions such as Marfan syndrome, the presence of typical symptoms (such as abrupt onset chest pain), and the presence of physical exam findings such as unequal blood pressure readings in the upper extremities. Each group is given a score of 1 if a feature is present, and the total score helps pave the next steps of workup—a score of 0 can be followed by diagnostic workup of other pathologies, while scores of 2–3 should be followed by expedited workup and immediate surgical consultation for possible aortic dissection [79].
\n
Aortic rupture is also an acute and life-threatening complication of aortic root dilation. It can present similarly to aortic dissection with regards to chest pain, however rupture can lead to severe and abrupt hypotension. Moreover, contingent with the site of rupture the patient may have symptoms such as hemoptysis [80] (if there is rupture into the lung), hematemesis [81] (if there is rupture into the esophagus), or cardiogenic shock [82] (if there is rupture into the pericardial cavity with resultant tamponade physiology).
\n
Aortic root dilation may also lead to aortic insufficiency. Roughly 30% of aortic insufficiency is now recognized as being caused by aortic root dilation, surpassing the incidence of any valvular cause [83]. The pathophysiology is related to stretching of the aortic valve annulus secondary to aortic root dilation, which results in incomplete closure of the aortic leaflets during diastole. Unfortunately, at the onset of aortic regurgitation, patients may be asymptomatic; therefore, congestive heart failure can develop when the regurgitant valve goes unnoticed.
\n
\n
\n
3.1.2 Impact/burden on public health
\n
While aortic root aneurysms are known to grow at an average of 1–4 mm/year [5], it is difficult to ascertain how fast an individual’s aortic root aneurysm will grow, therefore necessitating surveillance imaging. The frequency of surveillance imaging recommended is dependent on the etiology of the aortic root dilatation as well as its size, with genetically mediated aortic disease having a lower threshold for more frequent (biannual) imaging [84]. At the very least however patients are recommended to have annual imaging for aortic root dilation to closely monitor the aortic diameter. The impact that frequent imaging (CT, MR angiography or echocardiography) has on public health is likely significant, with cumulative costs. In addition, any patient with a bicuspid aortic valve should be screened for a thoracic aortic aneurysm, as well as screening all first-degree family members of a patient with genetic conditions such as Marfan syndrome [85].
\n
\n
\n
\n
3.2 Noninvasive imaging
\n
The aortic root is the most proximal segment of the aorta. It extends from the annulus of the aortic valve to the sinotubular junction (STJ). It is composed of the left, right, and non coronary sinuses of Valsalva. The diameter of the aorta decreases as it moves distally. The aortic root is assessed using multimodality imaging techniques. These include transthoracic echocardiogram (TTE), cardiac magnetic resonance imaging (cMRI), and cardiac computed tomography angiography (cCTA).
\n
\n
3.2.1 Transthoracic echocardiogram
\n
TTE is widely used for the detection and monitoring of aortic root pathology. Early studies established age- and sex-specific nomograms for aortic root measurements [86]. These studies used the motion mode (M-mode) of TTE, in which the amplitude of the ultrasound pulses amplitudes is converted to corresponding level on gray-scale imaging [86]. Using the M-mode, the American Society of Echocardiography (ASE) has recommended using the leading-edge to leading-edge approach for measuring the aortic root [87]. Later studies used 2D TTE and obtained reference measurements of the aortic root. This is now preferred over M-mode images, which may be off-axis and are subject to aortic motion that may produce erroneous measurements.
\n
On echocardiogram, the aortic root diameter is typically measured in the parasternal long-axis view from the right coronary sinus to the opposite sinus of Valsalva. When unable to obtain the long axis view, the parasternal short axis view may provide more accurate measurements. However, universal landmarks to measure the root in this view have not been established. Some suggest measuring the diameter from the right coronary sinus to the opposite commissure. These measurements are typically performed at end diastole, as this represents the resting aortic diameter [88]. In adults, these measurements correlate with age and body size. In addition, the aorta is about 2 mm larger in men compared to women due to differences in body size [89]. Normal values stratified by body surface area and age have been published by the ASE [87].
\n
Importantly, TTE is limited by its two-dimensional images and thus does not give a complete depiction of the aortic root. It is also limited by patient factors that limit the visualization windows and thus aortic root measurement. Since the aorta is not a straight tube, it can be imaged obliquely leading to over-estimation of its true diameter. Newer modalities, such cMRI and cCTA, can provide three-dimensional images.
\n
\n
\n
3.2.2 Cardiac magnetic resonance imaging
\n
Despite ECG-gated CT being the most accurate modality for evaluating the thoracic aorta, it is limited by the radiation and contrast exposure. This is particularly important in younger patients with connective tissue disorders that require serial follow up imaging. Cardiac MRI provides an alternative approach for imaging the thoracic aorta including the aortic root and is considered the preferred modality in select groups. It can be performed with ECG gating to provide motion-free evaluation of the aorta. In addition, young patients, in whom this is more commonly used, can hold their breath for longer periods, allowing acquisition of images with high spatial resolution.
\n
Cardiac MRI evaluation of the aorta does not require contrast use. MRI sequences used include balanced steady-state free precession (SSFP) sequences, fast imaging employing steady-state acquisition (FIESTA), true fast imaging with steady-state precession (FISP), and balanced fast-field echo (FFE) sequences. These sequences provide a high signal-to-noise ratio and adequate contrast between vessel wall and blood pool [90]. When used with ECG gating and contrast enhanced MRA, images tend to have less artifact, higher resolution, and overall short imaging time. Another approach is to use ECG gating 2D balanced SSFP sequence that is oriented perpendicular to the aortic root in two planes to assess the aortic valve and root throughout the cardiac cycle. In addition, prospective ECG gating and respiratory navigation with three-dimensional balanced SSFP sequences can provide 3D aortic imaging without contrast administration [91, 92].
\n
It is important to note that different methods of aortic measurement have been described and guidelines are less well defined. Aortic root measurements can be challenging given different approaches. Burman et al. found in the Framingham Heart Study that cusp-commissure dimensions better corresponded with reference echocardiographic aortic root measurements [89, 93]. This best correlated with study measurements after averaging the three end-diastolic cusp-commissure measurements [93]. In addition, there is a lack of consensus with regard to measurements used (inner lumen only versus lumen and wall) and whether measurements should be adjusted to body surface area, sex, and age.
\n
\n
\n
3.2.3 Cardiac computed tomography
\n
Although TTE is widely used for the imaging and surveillance of aortic root, cardiac computed tomography angiography (cCTA) is currently the most commonly used technique for the study of the thoracic aorta. Main advantages of cCTA are fast scanning times, low artifact sensibility, and wide availability including emergency rooms operating 24 h [94].
\n
The new generation CT scanners acquire high-resolution 3D datasets of the thoracic aorta, showing sensitivities up to 100% and specificities of 98–99% [95]. ECG synchronization is vital for detailed assessment of the aortic root anatomy since it allows suppression of pulsation artifacts [96]. ECG gating also allows viewing images in a particular phase of the cardiac cycle. Unfortunately, the ECG-gated technique can increase the acquisition time and required breath-hold time. In order to minimize the increased acquisition times, employment of a 64 or wider ECG-gated row detector system is suggested [95, 97].
\n
Modern CT scanners can be used to employ several different cardiac synchronization methods such as prospective ECG triggering where images are only acquired during a specified portion of the cardiac cycle, starting at a predetermined delay from the R wave; retrospective ECG gating where the desired cardiac phase is selected retrospectively from the raw data [95, 97]. The details of each technique will not be discussed in this chapter; however, it is important to determine the advantages and disadvantages of different techniques. The main limitations of CT are related to the radiation exposure and the use of iodinated contrast media and different techniques come at a higher cost of each limitation.
\n
For the surveillance of aortic root, any technique can be used and be useful; therefore, the technique with the least amount of radiation exposure should be selected such as prospective sequential triggering without padding, retrospective gating with tube-current modulation optimized for diastolic-phase datasets only, or a prospectively triggered high-pitch helical acquisition [95, 97]. Retrospective ECG gating acquires redundant helical CT data which allows the reconstruction of images at different cardiac phases and providing detailed images which can be useful in complicated cases and pre-/post-operative imaging since pseudoaneurysm or small leaks which are some of the most common complications of aortic root surgery can only be detected during a specific phase of the cardiac cycle. Iodinated contrast-media is another risk related to CT imaging given the risk of contrast induced nephropathy and allergic reactions of various severity. Surveillance CT data for the dimensions of aortic root can be acquired without contrast injection; however, a complete endoluminal evaluation can only be achieved by the injection of contrast-medium [97].
\n
It is standard of care to monitor the size of aortic aneurysms that are below surgical threshold, <5.5 cm for nongenetic aneurysms and <5.0 cm for genetically-mediated aneurysms [98]. In general, physicians should be conscientious about patient cumulative radiation exposure as there is evidence that it can increase cancer incidence and cancer mortality [99]. One study estimated that ionizing radiation exposure results in 0.7% of total expected baseline cancer incidence and 1% of total cancer mortality. These rates increase with greater cumulative exposure [99]. Therefore, physicians should opt to perform serial CT imaging with longer intervals in the most appropriate patients. A study investigating patients with moderate-risk thoracic aortic aneurysms (defined as size <5.0 cm) showed that patients with aneurysms below 4.3 cm had overall lower risk of significant aneurysm growth or size reaching surgical threshold. Thus, the authors suggested that these subset of patients undergo surveillance CT scans less frequently.
\n
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\n
\n
4. Management and prevention of aortic root dilation
\n
Management focuses on slowing the rate of growth and the complications of aortic root dilation. The line of management that is chosen for a patient depends on symptoms and size of the aneurysm. For patients who are asymptomatic and have root dilation <55 mm, medical management is advised. In patients with Marfan syndrome or a bicuspid aortic valve, the cut off of ≤50 mm is used for medical management [1, 100].
\n
\n
4.1 Medical management
\n
\n
4.1.1 Beta blockers
\n
The use of beta blockers has shown a survival benefit in patients with aortic root dilation secondary to Marfan syndrome [101]. While data on survival benefits for patients with bicuspid aortic valves is sparse, the common practice is to also prescribe beta blockers given that both conditions share a similar pathology and therefore both are likely to benefit from beta blockade. The mechanism by which beta blockers slow the progression of aortic root dilation is through their negative inotropic and chronotropic effects, reducing the peak left ventricular ejection rate and therefore decreasing shear stress and the rate of aortic dilation [102].
\n
\n
\n
4.1.2 Other agents for blood pressure control
\n
The goal blood pressure for patients with thoracic aortic aneurysms is <130/80 mmHg. In patients who cannot tolerate beta blockers, calcium channel blockers (CCB) are an alternative group of medications available. While less studied as compared to beta blockers, CCB have also been found to reduce the rate of aortic root dilation [103]. Other agents that can be used for additional blood pressure control include ACE-inhibitors and ARBs.
\n
\n
\n
4.1.3 Management of other cardiovascular risk factors
\n
In order to reduce the risk for complications such as aortic dissection, patients should be counseled on smoking cessation, and cessation of drugs that increase aortic wall stress such as cocaine or other stimulants. In addition patients should have dyslipidemia well controlled, which can be achieved through the use of atorvastatin 40–80 mg daily in individuals with aortic root aneurysms [104, 105].
\n
\n
\n
4.1.4 Lifestyle modifications and pregnancy
\n
Patients should be counseled on avoiding high intensity and collision sports, such as boxing and cycling. Instead patients should take part in low dynamic sports, such as, golf [5, 106]. Pregnancy should be avoided in patients with Marfan syndrome with an aortic diameter >40 mm, if a patient does chose to become pregnant however there must be close follow up with surveillance imaging of the aortic diameter [5, 101].
\n
\n
\n
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4.2 Surgical management
\n
\n
4.2.1 Indications for surgery
\n
Emergent surgical interventions are indicated for management of an aortic dissection or rupture, or a symptomatic aneurysm. In addition, surgical repair can be performed electively in high risk patients to prevent propagation of an aneurysm (Table 3). Indications for elective surgical intervention include the absolute size of the aneurysm—if the diameter is over 55 mm, or over 50 mm in patients with Marfan syndrome or bicuspid valves. Other indications for elective surgery include if the rate of growth of an aneurysm surpasses 10 mm/year, and if there is concurrent aortic insufficiency [1, 100]. In addition, patients who undergo aortic insufficiency repair who have concurrent aortic root dilation should be considered for aortic replacement at the time of their surgery—that is since 25% of patients with aortic root diameters >40 mm will eventually also require intervention for their aortic aneurysm [107].
\n
\n
\n
\n\n
\n
Emergent surgical repair
\n
Elective surgical repair
\n
\n\n\n
\n
\n
Aortic rupture
Aortic dissection
Symptomatic aortic root dilation (may represent an impeding rupture)
\n
\n
\n
Aortic dilation >55 mm
Aortic dilation >50 mm in individuals with Marfan syndrome or bicuspid valves
Rate of growth >10 mm/year
Aortic insufficiency (decision largely based on diameter of aortic dilation)
\n
\n
\n\n
Table 3.
Indications for emergent and elective surgical repair of aortic root dilation.
\n
\n
\n
4.2.2 Surgical interventions
\n
As opposed to supravalvular aortic aneurysms, aortic root aneurysms involve the coronary ostia as well as the aortic valve, which have implications on the type of surgical procedure available for patients. There are two approaches for a surgical intervention: radical and conservative. In a radial surgical intervention the patient’s aortic valve and root are replaced (commonly referred to as the Bentall procedure), whereas in conservative interventions only the aortic root is replaced [108].
\n
The Bentall procedure involves replacing the aortic valve with a prosthetic valve, and thus has the caveat of requiring indefinite anticoagulation [5]. If patients have a high bleeding risk it may therefore be worthwhile investigating replacement of the aortic root while preserving the valve. In addition, it is important to note that a large number of patients with aortic root dilation are young (secondary to its association with Marfan syndrome), and therefore lifelong anticoagulation in cases such as these confers a cumulative bleeding risk. Preserving the aortic valve while surgically treating the aortic root dilatation is made possible by the development of two surgical procedures: the first is removing the aortic root while keeping the valve intact. The second method is through re-implantation of the aortic valve [5]. Both the Bentall procedure as well as aortic valve-preserving procedures have been shown to have comparable short and long-term outcomes with regards to the risk of death and valve associated complications. The main difference however is that patients undergoing valve sparing operations were significantly more likely to develop moderate to severe aortic regurgitation later [108].
\n
In patients with both severe aortic stenosis and ascending aortic aneurysm, undergoing surgical aortic valve replacement (sAVR) and concomitant surgical intervention for aortic aneurysms above 4.5 cm is recommended by the American College of Cardiology (ACC) foundation guidelines [84]. However, in high-risk surgical patients, undergoing a transcatheter aortic valve replacement (TAVR) has become an alternative approach that obviates the need for parallel surgical aortic aneurysm intervention. This raises the concern for the safety of TAVR catheter-based delivery system in patients with aortic aneurysms since intraoperative rupture or dissection risk potentially increases. However, a clinical study showed that TAVR does not increase intraoperative aortic dissection/rupture risk or mortality with a median follow-up of 14 months [109]. Therefore, there are no recommendations against performing TAVR in patients with ascending aortic aneurysms.
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Conflict of interest
None.
\n',keywords:"aortic root, enlargement, dilation, aneurysm, noninvasive imaging",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/67492.pdf",chapterXML:"https://mts.intechopen.com/source/xml/67492.xml",downloadPdfUrl:"/chapter/pdf-download/67492",previewPdfUrl:"/chapter/pdf-preview/67492",totalDownloads:1504,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:1,impactScore:0,impactScorePercentile:35,impactScoreQuartile:2,hasAltmetrics:1,dateSubmitted:"September 20th 2018",dateReviewed:"April 12th 2019",datePrePublished:"July 26th 2019",datePublished:"September 9th 2020",dateFinished:"June 4th 2019",readingETA:"0",abstract:"Aortic root dilation (AoD) imparts increased risk of aortic complications such as dissection, rupture, and valvular regurgitation. Multiple etiologies of AoD exist, such as Marfan syndrome, bicuspid aortic valve, Ehler-Danlos syndrome, infections, and idiopathic conditions. Due to the variety of clinical conditions that can result in AoD, and the risks associated with worsening AoD, a thorough understanding of the pathophysiology of AoD, noninvasive imaging modalities, and pharmacologic therapies is critical. This chapter will review the various etiologies of AoD, pathophysiological basis of each disease entity, overview of the diagnosis of AoD, noninvasive imaging modalities employed for detection and surveillance, pharmacological therapies used in the prevention and management, and the factors that guide intervention such as surgical repair.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/67492",risUrl:"/chapter/ris/67492",book:{id:"8217",slug:"aortic-aneurysm-and-aortic-dissection"},signatures:"Ozan Unlu, Zaid I. Almarzooq, Diala Steitieh, Matthew Brandorff and Parmanand Singh",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Etiologies of aortic root dilation",level:"1"},{id:"sec_2_2",title:"2.1 Genetically-mediated aortic root dilation",level:"2"},{id:"sec_2_3",title:"Table 1.",level:"3"},{id:"sec_3_3",title:"2.1.2 Bicuspid aortic valve",level:"3"},{id:"sec_4_3",title:"2.1.3 Loeys-Dietz syndrome",level:"3"},{id:"sec_5_3",title:"2.1.4 Ehler-Danlos syndrome",level:"3"},{id:"sec_7_2",title:"2.2 Nongenetic",level:"2"},{id:"sec_7_3",title:"2.2.1 Idiopathic",level:"3"},{id:"sec_8_3",title:"2.2.2 HTN",level:"3"},{id:"sec_9_3",title:"2.2.3 Infections",level:"3"},{id:"sec_9_4",title:"2.2.3.1 Treponema pallidum\n",level:"4"},{id:"sec_10_4",title:"2.2.3.2 Tuberculosis",level:"4"},{id:"sec_11_4",title:"2.2.3.3 HIV",level:"4"},{id:"sec_13_3",title:"2.2.4 Inflammatory disorders",level:"3"},{id:"sec_13_4",title:"2.2.4.1 Ankylosing spondylitis",level:"4"},{id:"sec_14_4",title:"2.2.4.2 Relapsing polychondritis",level:"4"},{id:"sec_15_4",title:"2.2.4.3 Takayasu arteritis",level:"4"},{id:"sec_16_4",title:"2.2.4.4 Giant cell arteritis",level:"4"},{id:"sec_18_3",title:"2.2.5 Other",level:"3"},{id:"sec_18_4",title:"2.2.5.1 Left ventricular hypertrophy",level:"4"},{id:"sec_22",title:"3. Diagnosis and surveillance of aortic dilation",level:"1"},{id:"sec_22_2",title:"3.1 Clinical manifestations",level:"2"},{id:"sec_22_3",title:"3.1.1 Complications of aortic root dilation",level:"3"},{id:"sec_23_3",title:"3.1.2 Impact/burden on public health",level:"3"},{id:"sec_25_2",title:"3.2 Noninvasive imaging",level:"2"},{id:"sec_25_3",title:"3.2.1 Transthoracic echocardiogram",level:"3"},{id:"sec_26_3",title:"3.2.2 Cardiac magnetic resonance imaging",level:"3"},{id:"sec_27_3",title:"3.2.3 Cardiac computed tomography",level:"3"},{id:"sec_30",title:"4. Management and prevention of aortic root dilation",level:"1"},{id:"sec_30_2",title:"4.1 Medical management",level:"2"},{id:"sec_30_3",title:"4.1.1 Beta blockers",level:"3"},{id:"sec_31_3",title:"4.1.2 Other agents for blood pressure control",level:"3"},{id:"sec_32_3",title:"4.1.3 Management of other cardiovascular risk factors",level:"3"},{id:"sec_33_3",title:"4.1.4 Lifestyle modifications and pregnancy",level:"3"},{id:"sec_35_2",title:"4.2 Surgical management",level:"2"},{id:"sec_35_3",title:"Table 3.",level:"3"},{id:"sec_36_3",title:"4.2.2 Surgical interventions",level:"3"},{id:"sec_42",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nBoyer JK, Gutierrez F, Braverman AC. Approach to the dilated aortic root. Current Opinion in Cardiology. 2004;19(6):563-569\n'},{id:"B2",body:'\nRoman MJ et al. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. The American Journal of Cardiology. 1989;64(8):507-512\n'},{id:"B3",body:'\nKim JB et al. Risk of aortic dissection in the moderately dilated ascending aorta. Journal of the American College of Cardiology. 2016;68(11):1209-1219\n'},{id:"B4",body:'\nLandenhed M et al. Risk profiles for aortic dissection and ruptured or surgically treated aneurysms: A prospective cohort study. Journal of the American Heart Association. 2015;4(1):e001513\n'},{id:"B5",body:'\nNataf P, Lansac E. Dilation of the thoracic aorta: Medical and surgical management. Heart. 2006;92(9):1345-1352\n'},{id:"B6",body:'\nDouglas PS et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use Criteria for Echocardiography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance American College of Chest Physicians. Journal of the American Society of Echocardiography. 2011;24(3):229-267\n'},{id:"B7",body:'\nSingh MN, Lacro RV. Recent clinical drug trials evidence in Marfan syndrome and clinical implications. The Canadian Journal of Cardiology. 2016;32(1):66-77\n'},{id:"B8",body:'\nSakai LY et al. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. The Journal of Biological Chemistry. 1991;266(22):14763-14770\n'},{id:"B9",body:'\nJudge DP, Dietz HC. Marfan’s syndrome. Lancet. 2005;366(9501):1965-1976\n'},{id:"B10",body:'\nHilhorst-Hofstee Y et al. The clinical spectrum of missense mutations of the first aspartic acid of cbEGF-like domains in fibrillin-1 including a recessive family. Human Mutation. 2010;31(12):E1915-E1927\n'},{id:"B11",body:'\nDietz H. Marfan syndrome. 2001. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1335/\n\n'},{id:"B12",body:'\nPyeritz RE. Recent progress in understanding the natural and clinical histories of the Marfan syndrome. Trends in Cardiovascular Medicine. 2016;26(5):423-428\n'},{id:"B13",body:'\nAkhurst RJ. TGF beta signaling in health and disease. Nature Genetics. 2004;36(8):790-792\n'},{id:"B14",body:'\nLoeys BL et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nature Genetics. 2005;37(3):275-281\n'},{id:"B15",body:'\nMizuguchi T et al. Heterozygous TGFBR2 mutations in Marfan syndrome. Nature Genetics. 2004;36(8):855-860\n'},{id:"B16",body:'\nDe Paepe A et al. Revised diagnostic criteria for the Marfan syndrome. American Journal of Medical Genetics. 1996;62(4):417-426\n'},{id:"B17",body:'\nLoeys BL et al. The revised Ghent nosology for the Marfan syndrome. Journal of Medical Genetics. 2010;47(7):476-485\n'},{id:"B18",body:'\nRoman MJ et al. Prognostic significance of the pattern of aortic root dilation in the Marfan syndrome. Journal of the American College of Cardiology. 1993;22(5):1470-1476\n'},{id:"B19",body:'\nRoberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. The American Journal of Cardiology. 1970;26(1):72-83\n'},{id:"B20",body:'\nCripe L et al. Bicuspid aortic valve is heritable. Journal of the American College of Cardiology. 2004;44(1):138-143\n'},{id:"B21",body:'\nWarnes CA et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults with Congenital Heart Disease). Developed in collaboration with the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Journal of the American College of Cardiology. 2008;52(23):e143-e263\n'},{id:"B22",body:'\nAyad RF et al. Accuracy of two-dimensional echocardiography in determining aortic valve structure in patients >50 years of age having aortic valve replacement for aortic stenosis. The American Journal of Cardiology. 2011;108(11):1589-1599\n'},{id:"B23",body:'\nNishimura RA et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-2492\n'},{id:"B24",body:'\nVerma S, Siu SC. Aortic dilatation in patients with bicuspid aortic valve. The New England Journal of Medicine. 2014;370(20):1920-1929\n'},{id:"B25",body:'\nBonderman D et al. Mechanisms underlying aortic dilatation in congenital aortic valve malformation. Circulation. 1999;99(16):2138-2143\n'},{id:"B26",body:'\nWard C. Clinical significance of the bicuspid aortic valve. Heart. 2000;83(1):81-85\n'},{id:"B27",body:'\nMacCarrick G et al. Loeys-Dietz syndrome: A primer for diagnosis and management. Genetics in Medicine. 2014;16(8):576-587\n'},{id:"B28",body:'\nMeester JAN et al. Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome. Annals of cardiothoracic surgery. 2017;6(6):582-594\n'},{id:"B29",body:'\nAttias D et al. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders. Circulation. 2009;120(25):2541-2549\n'},{id:"B30",body:'\nErbel R et al. 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). European Heart Journal. 2014;35(41):2873-2926\n'},{id:"B31",body:'\nBeighton P et al. Ehlers-Danlos syndromes: Revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). American Journal of Medical Genetics. 1998;77(1):31-37\n'},{id:"B32",body:'\nFreeman LA et al. CT and MRI assessment of the aortic root and ascending aorta. AJR. American Journal of Roentgenology. 2013;200(6):W581-W592\n'},{id:"B33",body:'\nHiratzka LF et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Journal of the American College of Cardiology. 2010;55(14):e27-e129\n'},{id:"B34",body:'\nHenry WL, Gardin JM, Ware JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation. 1980;62(5):1054-1061\n'},{id:"B35",body:'\nRozendaal L et al. Marfan syndrome in children and adolescents: An adjusted nomogram for screening aortic root dilatation. Heart. 1998;79(1):69-72\n'},{id:"B36",body:'\nSawabe M et al. Age is a major pathobiological determinant of aortic dilatation: A large autopsy study of community deaths. Journal of Atherosclerosis and Thrombosis. 2011;18(2):157-165\n'},{id:"B37",body:'\nOkamoto RJ et al. The influence of mechanical properties on wall stress and distensibility of the dilated ascending aorta. The Journal of Thoracic and Cardiovascular Surgery. 2003;126(3):842-850\n'},{id:"B38",body:'\nO\'Rourke MF, Hashimoto J. Mechanical factors in arterial aging: A clinical perspective. Journal of the American College of Cardiology. 2007;50(1):1-13\n'},{id:"B39",body:'\nWang M et al. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension. 2007;50(1):219-227\n'},{id:"B40",body:'\nVasan RS, Larson MG, Levy D. Determinants of echocardiographic aortic root size. The Framingham Heart Study. Circulation. 1995;91(3):734-740\n'},{id:"B41",body:'\nCovella M et al. Echocardiographic aortic root dilatation in hypertensive patients: A systematic review and meta-analysis. Journal of Hypertension. 2014;32(10):1928-1935; discussion 1935\n'},{id:"B42",body:'\nIskandar A, Thompson PD. A meta-analysis of aortic root size in elite athletes. Circulation. 2013;127(7):791-798\n'},{id:"B43",body:'\nMitchell GF et al. Aortic diameter, wall stiffness, and wave reflection in systolic hypertension. Hypertension. 2008;51(1):105-111\n'},{id:"B44",body:'\nIngelsson E et al. Aortic root diameter and longitudinal blood pressure tracking. Hypertension. 2008;52(3):473-477\n'},{id:"B45",body:'\nLam CS et al. Aortic root remodeling over the adult life course: Longitudinal data from the Framingham Heart Study. Circulation. 2010;122(9):884-890\n'},{id:"B46",body:'\nGornik HL, Creager MA. Aortitis. Circulation. 2008;117(23):3039-3051\n'},{id:"B47",body:'\nAminov RI. A brief history of the antibiotic era: Lessons learned and challenges for the future. Frontiers in Microbiology. 2010;1:134\n'},{id:"B48",body:'\nSoravia-Dunand VA, Loo VG, Salit IE. Aortitis due to Salmonella: Report of 10 cases and comprehensive review of the literature. Clinical Infectious Diseases. 1999;29(4):862-868\n'},{id:"B49",body:'\nFeigl D, Feigl A, Edwards JE. Mycotic aneurysms of the aortic root. A pathologic study of 20 cases. Chest. 1986;90(4):553-557\n'},{id:"B50",body:'\nRestrepo CS et al. Aortitis: Imaging spectrum of the infectious and inflammatory conditions of the aorta. Radiographics. 2011;31(2):435-451\n'},{id:"B51",body:'\nPaulo N, Cascarejo J, Vouga L. Syphilitic aneurysm of the ascending aorta. Interactive Cardiovascular and Thoracic Surgery. 2012;14(2):223-225\n'},{id:"B52",body:'\nHeggtveit HA. Syphilitic aortitis. A clinicopathologic autopsy study of 100 cases, 1950 to 1960. Circulation. 1964;29:346-355\n'},{id:"B53",body:'\nGlaziou P et al. Global epidemiology of tuberculosis. Seminars in Respiratory and Critical Care Medicine. 2013;34(1):3-16\n'},{id:"B54",body:'\nSharma D et al. Dissecting aortic root aneurysm and severe aortic regurgitation following pulmonary tuberculosis. Egyptian Journal of Chest Diseases and Tuberculosis. 2014;63(2):523-527\n'},{id:"B55",body:'\nJaved MA, Sheppard MN, Pepper J. Aortic root dilation secondary to giant cell aortitis in a human immunodeficiency virus-positive patient. European Journal of Cardio-Thoracic Surgery. 2006;30(2):400-401\n'},{id:"B56",body:'\nHaenen F, Laga S, Rodrigus I. Q fever infection: Inflammatory aortic root aneurysm in an HIV positive patient. Acta Cardiologica. 2012;67(2):261-264\n'},{id:"B57",body:'\nOzkan Y. Cardiac involvement in ankylosing spondylitis. Journal of Clinical Medical Research. 2016;8(6):427-430\n'},{id:"B58",body:'\nRoldan CA et al. Aortic root disease and valve disease associated with ankylosing spondylitis. Journal of the American College of Cardiology. 1998;32(5):1397-1404\n'},{id:"B59",body:'\nSharma A et al. Relapsing polychondritis: A review. Clinical Rheumatology. 2013;32(11):1575-1583\n'},{id:"B60",body:'\nSelim AG et al. Active aortitis in relapsing polychondritis. Journal of Clinical Pathology. 2001;54(11):890-892\n'},{id:"B61",body:'\nSharma A et al. Successful treatment of aortic root dilatation in a patient with relapsing polychondritis. Clinical Rheumatology. 2013;32(Suppl 1):S59-S61\n'},{id:"B62",body:'\nMason JC. Takayasu arteritis—Advances in diagnosis and management. Nature Reviews Rheumatology. 2010;6(7):406-415\n'},{id:"B63",body:'\nMurayama M et al. A case of severe aortic regurgitation caused by Takayasu’s arteritis showing end-diastolic opening of aortic valve. CASE. 2018;2(6):248-253\n'},{id:"B64",body:'\nKaku Y et al. Surgery for aortic regurgitation and aortic root dilatation in Takayasu arteritis. Asian Cardiovascular & Thoracic Annals. 2015;23(8):901-906\n'},{id:"B65",body:'\nIarussi D et al. Association of left ventricular hypertrophy and aortic dilation in patients with acute thoracic aortic dissection. Angiology. 2001;52(7):447-455\n'},{id:"B66",body:'\nCuspidi C et al. Clinical and prognostic value of hypertensive cardiac damage in the PAMELA study. Hypertension Research. 2017;40(4):329-335\n'},{id:"B67",body:'\nDavies RR et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: Simple prediction based on size. The Annals of Thoracic Surgery. 2002;73(1):17-27; discussion 27-28\n'},{id:"B68",body:'\nLiddicoat JE et al. Ascending aortic aneurysms. Review of 100 consecutive cases. Circulation. 1975;52(2 Suppl):I202-I209\n'},{id:"B69",body:'\nErbel R, Eggebrecht H. Aortic dimensions and the risk of dissection. Heart. 2006;92(1):137-142\n'},{id:"B70",body:'\nNajafi H et al. Aortic insufficiency secondary to aortic root aneurysm or dissection. Archives of Surgery. 1975;110(11):1401-1407\n'},{id:"B71",body:'\nPabisiak K et al. Ascending aorta aneurysm as a cause of superior vena cava syndrome. Polski Merkuriusz Lekarski. 2014;37(218):104-107\n'},{id:"B72",body:'\nEccles SR, Banks J, Kumar P. Ascending aortic aneurysm causing hoarse voice: A variant of Ortner’s syndrome. BML Case Reports. 2012;2012:bcr2012007111\n'},{id:"B73",body:'\nKim JH et al. A patient with dysphagia due to an aortic aneurysm. Korean Circulation Journal. 2009;39(6):258-260\n'},{id:"B74",body:'\nKumar A et al. Vascular airway compression management in a case of aortic arch and descending thoracic aortic aneurysm. Annals of Cardiac Anaesthesia. 2016;19(3):568-571\n'},{id:"B75",body:'\nHahn RT et al. Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves. Journal of the American College of Cardiology. 1992;19(2):283-288\n'},{id:"B76",body:'\nPretre R, Von Segesser LK. Aortic dissection. Lancet. 1997;349(9063):1461-1464\n'},{id:"B77",body:'\nHagan PG et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA. 2000;283(7):897-903\n'},{id:"B78",body:'\nMehta RH et al. Acute type A aortic dissection in the elderly: Clinical characteristics, management, and outcomes in the current era. Journal of the American College of Cardiology. 2002;40(4):685-692\n'},{id:"B79",body:'\nRogers AM et al. Sensitivity of the aortic dissection detection risk score, a novel guideline-based tool for identification of acute aortic dissection at initial presentation: Results from the international registry of acute aortic dissection. Circulation. 2011;123(20):2213-2218\n'},{id:"B80",body:'\nSun D, Mehta S. Hemoptysis caused by erosion of thoracic aortic aneurysm. CMAJ. 2010;182(4):E186\n'},{id:"B81",body:'\nGerrard AD, Batool S, Isaacs P. Ruptured thoracic aneurysm causing hematemesis. ACG Case Reports Journal. 2016;3(4):e182\n'},{id:"B82",body:'\nFukui T et al. Cardiac tamponade secondary to rupture of a distal aortic arch aneurysm. The Japanese Journal of Thoracic and Cardiovascular Surgery. 2002;50(5):227-230\n'},{id:"B83",body:'\nRoman MJ et al. Aortic root dilatation as a cause of isolated, severe aortic regurgitation. Prevalence, clinical and echocardiographic patterns, and relation to left ventricular hypertrophy and function. Annals of Internal Medicine. 1987;106(6):800-807\n'},{id:"B84",body:'\nHiratzka LF et al. ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010, 2010;121(13):e266-e369\n'},{id:"B85",body:'\nSaliba E, Sia Y. The ascending aortic aneurysm: When to intervene? International Journal of Cardiology. Heart & Vasculature. 2015;6:91-100. DOI: 10.1016/j.ijcha.2015.01.009. eCollection 2015 Mar 1\n'},{id:"B86",body:'\nVasan RS et al. Echocardiographic reference values for aortic root size: The Framingham Heart Study. Journal of the American Society of Echocardiography. 1995;8(6):793-800\n'},{id:"B87",body:'\nGoldstein SA et al. Multimodality imaging of diseases of the thoracic aorta in adults: From the American Society of Echocardiography and the European Association of Cardiovascular Imaging: Endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance. Journal of the American Society of Echocardiography. 2015;28(2):119-182\n'},{id:"B88",body:'\nSolomon SD, Wu J, Gillam LD. Essential Echocardiography: A Companion to Braunwald’s Heart Disease. Philadelphia, PA: Elsevier Health Sciences; 2017\n'},{id:"B89",body:'\nSteinberg CR, Archer M, Steinberg I. Measurement of the abdominal aorta after intravenous aortography in health and arteriosclerotic peripheral vascular disease. The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine. 1965;95(3):703-708\n'},{id:"B90",body:'\nNayak KS et al. Spiral balanced steady-state free precession cardiac imaging. Magnetic Resonance in Medicine. 2005;53(6):1468-1473\n'},{id:"B91",body:'\nCarr JC et al. Cine MR angiography of the heart with segmented true fast imaging with steady-state precession. Radiology. 2001;219(3):828-834\n'},{id:"B92",body:'\nGebker R et al. Comparison of different MRI techniques for the assessment of thoracic aortic pathology: 3D contrast enhanced MR angiography, turbo spin echo and balanced steady state free precession. The International Journal of Cardiovascular Imaging. 2007;23(6):747-756\n'},{id:"B93",body:'\nBurman ED, Keegan J, Kilner PJ. Aortic root measurement by cardiovascular magnetic resonance: Specification of planes and lines of measurement and corresponding normal values. Circulation. Cardiovascular Imaging. 2008;1(2):104-113\n'},{id:"B94",body:'\nBrenner DJ, Hall EJ. Computed tomography—An increasing source of radiation exposure. The New England Journal of Medicine. 2007;357(22):2277-2284\n'},{id:"B95",body:'\nDi Cesare E et al. CT and MR imaging of the thoracic aorta. Open medicine (Warsaw, Poland). 2016;11(1):143-151\n'},{id:"B96",body:'\nLitmanovich D et al. CT and MRI in diseases of the aorta. AJR - American Journal of Roentgenology. 2009;193(4):928-940\n'},{id:"B97",body:'\nHanneman K et al. Pre- and post-operative imaging of the aortic root. Radiographics. 2016;36(1):19-37\n'},{id:"B98",body:'\nMcLarty AJ, Bishawi M, Yelika SB, Shroyer AL, Romeiser J. Surveillance of moderate-size aneurysms of the thoracic aorta. Journal of Cardiothoracic Surgery. 2015;10:17\n'},{id:"B99",body:'\nSodickson A. Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology. 2009;251(1):175-184\n'},{id:"B100",body:'\nElefteriades JA. Natural history of thoracic aortic aneurysms: Indications for surgery, and surgical versus nonsurgical risks. The Annals of Thoracic Surgery. 2002;74(5):S1877-S1880; discussion S1892-S1898\n'},{id:"B101",body:'\nJondeau G et al. Marfan syndrome. Archives des Maladies du Coeur et des Vaisseaux. 2003;96(11):1081-1088\n'},{id:"B102",body:'\nDanyi P, Elefteriades JA, Jovin IS. Medical therapy of thoracic aortic aneurysms: Are we there yet? Circulation. 2011;124(13):1469-1476\n'},{id:"B103",body:'\nRossi-Foulkes R et al. Phenotypic features and impact of beta blocker or calcium antagonist therapy on aortic lumen size in the Marfan syndrome. The American Journal of Cardiology. 1999;83(9):1364-1368\n'},{id:"B104",body:'\nAronow WS. Treatment of thoracic aortic aneurysm. Annals of Translational Medicine. 2018;6(3):66\n'},{id:"B105",body:'\nStone NJ et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2014;63(25 Pt B):2889-2934\n'},{id:"B106",body:'\nMitchell JH et al. Task force 8: Classification of sports. Journal of the American College of Cardiology. 2005;45(8):1364-1367\n'},{id:"B107",body:'\nIsselbacher EM. Thoracic and abdominal aortic aneurysms. Circulation. 2005;111(6):816-828\n'},{id:"B108",body:'\nLim JY et al. Surgical management of aortic root dilatation with advanced aortic regurgitation: Bentall operation versus valve-sparing procedure. The Korean Journal of Thoracic and Cardiovascular Surgery. 2012;45(3):141-147\n'},{id:"B109",body:'\nRylski B et al. Transcatheter aortic valve implantation in patients with ascending aortic dilatation: Safety of the procedure and mid-term follow-up. European Journal of Cardio-Thoracic Surgery. 2014;46(2):228-233\n'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Ozan Unlu",address:null,affiliation:'
Department of Medicine, Weill Cornell Medicine, USA
'},{corresp:null,contributorFullName:"Zaid I. Almarzooq",address:null,affiliation:'
Department of Cardiology, Brigham and Women’s Hospital, USA
Department of Cardiology, Weill Cornell Medicine, USA
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1. Introduction
Since the concept of high-entropy alloys (HEAs) was first proposed by Yeh and Cantor in 2004 [1, 2, 3], this type of new metallic material has drawn increasingly more attention due to their unique characteristics (e.g. high configuration entropy, sluggish atomic diffusion, and large lattice distortion) and resultant extraordinary properties (e.g. high strength, high low-temperature fracture toughness, good corrosion resistance and high-temperature properties) [4, 5, 6]. Yeh and co-workers firstly defined HEAs as alloys composed of five or more principal elements in equiatomic ratios [1], with single-phase solid-solution (SS) microstructure in either face-centered cubic (FCC) or body-centered cubic (BCC) or hexagonal close-packed (HCP) lattice [4, 5, 6, 7, 8, 9], due to the “high-entropy effect” [10, 11]. At the early stage of research on HEAs, the majority of the works focused on the exploration of single-phase HEAs and their corresponding microstructure and mechanical properties. In recent years, the coverage of HEAs has been extended to include the multiple phase structure with less than five non-equiatomic principal elements [5, 11]. As a result, numerous non-equiatomic alloys were designed and studied based on the equiatomic single-phase HEA system in pursuit of superior mechanical properties [12, 13]. Different terms have been used for these non-equiatomic variants, including multicomponent alloys, multi-principal element alloys and composition complex alloys (CCAs).
It is noteworthy that the current composition design strategy for HEAs usually results in alloys with a high content of expensive metals (e.g. Co, Ta, Hf, V, Nb, W, and Mo). For instance, the above-mentioned HEAs usually contain a Co element, which is common in most of the HEAs [5]. Obviously, using expensive elements increases the overall cost of HEAs. On the other hand, high-entropy alloys usually exhibit comprehensive properties due to their combined effects of multi-principal elements, which makes them suitable for applications in extreme environments. However, majority of the current researches focuses on the mechanical properties only while other properties are ignored. Thus, the development of cost-effective HEAs with comprehensive properties is critical to promote industrial applications of HEAs.
In the past decade, some cost-effective Fe-rich HEAs have been designed and developed, such as the FeNiCrMo alloy that has comprehensive properties [14] and the metastable FeMnCoCr that exhibits superior mechanical properties [12]. Fe-rich HEAs are also named as Fe-rich CCAs [15], Fe-rich medium-entropy alloy (MEA) [16], high-entropy steel [17] and compositionally complex steels [18]. As the entropy value of this type of alloys is not at the high-entropy level, they are generally classified as medium-entropy alloys according to the classification proposed by Yeh [7]. Nevertheless, the entropy of the Fe-rich alloys is indeed higher than traditional steels due to their multicomponent characteristic. To avoid the ambiguity, Fe-rich HEAs are used in this review.
Several reviews on HEAs [4, 5, 6, 19, 20] focused on the microstructure and mechanical properties of different types of HEAs, but there is a lack of reviews with a focus on cost-effective HEAs, particularly on Fe-rich HEAs, that is badly needed to guide industrial applications. The present work would fill the gap through overviewing the composition design, manufacturing, processing, microstructure, and properties of the cost-effective Fe-rich HEAs. Based on the review, key challenges for promoting the industry applications of the cost-effective HEAs are proposed.
2. Alloy design strategy
In the past decades, various methods have been developed for composition design of traditional alloys, including physical model methods, computational methods and machine learning methods [21, 22]. These design strategies have also been proved effective to assist the development of HEAs, which has been reviewed several times. More details can be found in Refs. [14, 22, 23]. Using these design strategies, many cost-effective HEAs have been developed. For instance, the Co-free HEAs with relatively lower cost include the equiatomic FeMnCrNi, AlCrFeNi [24], FeCrNiMnCu [25], NiMnFeCu [26], AlFeMnSi [27] and FeCrNiTiAl [28] alloys. But these alloy systems are equiatomic or near-equiatomic, there is less potency for further exploitation of the new alloys with better performance. In recent years, several non-equiatomic HEAs with one enriched element have been developed, which includes the Fe-rich HEAs [14], Ni-rich HEAs [29, 30], Cr-rich HEAs [31, 32], Co-rich HEAs [33, 34, 35], Ti-rich HEAs [36] and Al-rich HEAs [37, 38]. Among these non-equiatomic HEAs, Fe-rich HEAs show high potential for industrial applications due to their superior properties and relatively low cost. To the best of the authors’ knowledge, there is no definition for Fe-rich HEAs. Generally, Fe content of these Fe-rich HEAs is in the range of 35–50%, while the content of expensive elements (e.g. Co, Mo, V) is less than 10 at.%. As aforementioned, Fe-rich HEAs are also named Fe-rich CCAs [15], Fe-rich medium-entropy alloy (MEA) [16], high-entropy steel [17] and compositionally complex steels [18]. Up to now, a few Fe-rich HEAs have been developed based on the equiatomic 3d transition metal HEAs, including the FeNiCrMo, FeMnCoCr, FeMnNiCr, FeCoNiCr, FeNiMnAlCr, FeMnNiAlCr and FeMnCrSiNi, through increasing the Fe content in the equiatomic HEAs system. The compositions of these Fe-rich HEAs are listed in Table 1.
Previous research work has confirmed that the increasing Fe content may result in different effects on the microstructure and properties in different HEA systems. For instance, Yu and co-workers proposed a new strategy to develop Fe-rich HEAs with eutectic structures [47]. Based on the current pseudo-binary design strategy of eutectic HEAs, the eutectic composition can be experimentally identified by adjusting the atomic content ratio of the intermetallic forming elements to the face-centered cubic (FCC) forming elements in an equiatomic HEA system [47]. As shown in Figure 1, a series of cost-effective Fe-rich HEAs with various compositions (Fe50−xNi25Cr25Mox) and corresponding structures (i.e. the hyper-eutectic, eutectic, hypo-eutectic and near single FCC structure) were produced through decreasing the ratio of the intermetallic forming elements (Mo) to the FCC forming elements (Fe) from 1 to 3/7 [47].
Figure 1.
(a–d) Microstructure of as-cast Fe50−xNi25Cr25Mox alloys: (a) x = 20, hyper-eutectic; (b) x = 15, fully-eutectic; (c) x = 10, hypo-eutectic; (d) x = 5, divorced-eutectic; (e) XRD analyses of Fe50−xNi25Cr25Mox HEAs [47].
The strategies proposed by Yu and co-workers [47] is suitable for HEAs with intermetallic-dominated phase. For HEAs with a single solid solution phase, the increase in the ratio of Fe to other elements may not result in the formation of a eutectic structure. Instead, it may change the phase constituents of the solid solution phase matrix. For instance, by increasing the Fe content in the Fe80−xMnxCo10Cr10 [12] and Fe40−xMn20Co20Cr20Nix [13] HEAs, the structure of the alloys shifted from single FCC phase to dual-phase (FCC and HCP). By increasing the content of Fe or decreasing the content of other elements in an equiatomic HEA, the thermal stability and mechanical stability can be decreased due to the reduced “high-entropy effect”, which may result in precipitation during heat treatment [48] or TRIP effect during deformation [13], which will be further discussed in Sections 3 and 4.
3. Microstructure
3.1 Microstructure of the as-cast and homogenization treated alloys
The currently reported Fe-rich HEAs can be classified into different groups in terms of their phase constituent, namely single or near single FCC phase alloys, FCC/HCP dual-phase alloys and BCC/B2 dual-phase alloys. The FCC single phase and FCC/HCP dual-phase Fe-rich HEAs have been comprehensively studied while very few researches focus on the BCC/B2 dual-phase Fe-rich HEAs.
As shown in Table 1, the Fe-rich HEAs with single FCC phase include the Fe50Mn27Ni10Cr13, Fe40Mn27Ni26Co5Cr2 and Fe40.4Mn34.8Ni11.3Al7.5Cr6. The Fe50−xNi25Cr25Mox HEAs have a near single FCC structure matrix with an intermetallic phase. Yao and co-workers developed a non-equiatomic Fe40Mn27Ni26Co5Cr2 alloy based on the equiatomic FeMnNiCoCr Cantor alloy and their microstructure is shown in Figure 2a-f [42]. The EBSD and EDS results of the recrystallized alloy in Figure 2 reveals that the non-equiatomic variant of Cantor alloy has a homogenized solid solution matrix despite its comparably low configurational entropy [42], indicating that equimolarity may not be a compulsory requirement to achieve single-phase solid solution in multicomponent systems [42]. A similar conclusion can be drawn from Yu and co-workers’ work. As shown in Figure 1, with the increasing of the ratio of Fe to Mo in the FeNiCrMo HEA, the equiatomic FeNiCrMo was transformed into a non-equiatomic alloy, resulting in a lower configuration entropy value of the alloy system. However, the equiatomic FeNiCrMo is composed of an intermetallic phase while the non-equiatomic Fe45Ni25Cr25Mo5 alloy with the lowest entropy value shows the near FCC phase with low fraction of intermetallic (Figure 2g-i). Obviously, this cannot be explained using the “high-entropy effect” proposed by Yeh and co-workers. This can be related to the decreased atom size difference due to the increasing of Fe content, which is usually ignored by the current “high-entropy effect”. As a consequence, much more compositions of non-equiatomic HEAs can be designed to gain single solid solution phase by decreasing the atom size difference even the maximum entropy value may not be achieved.
Figure 2.
(a–f) Microstructure of the recrystallized Fe40Mn27Ni26Co5Cr2: a. OM image, b. SE image, c and d. EBSD phase maps and e and f. EDS maps [42]; (g–i) Microstructure of the as-cast Fe45Ni25Cr25Mo5: g. SEM image, h. EDS mapping and i. XRD spectrum [15]; (j–m) Microstructure of the homogenized and water-quenched Co20Cr20Fe34Mn20Ni6 HEA: j. EBSD phase map; k and l. ECCI image; m. EDS maps [13]; (n and o) Microstructure of the Fe36Mn21Cr18Ni15Al10 alloy in the as-cast condition: a. BSE image, c. bright-field TEM image [45].
The current dual-phase Fe-rich HEAs were developed based on the equiatomic FeMnCoCr and FeMnCoCrNi. Increasing the ratio of Fe to Mn in the FeMnCoCr HEA and the ratio of Fe to Ni in the FeMnCoCrNi HEA decreased the phase stability of single solid solution phase. Hence, both the non-equiatomic Fe80−xMnxCo10Cr10 (x < 30 at.%) and Fe40−xMn20Co20Cr20Nix (x < 6 at.%) systems involved partial martensitic transformation from FCC to the HCP phase during quenching (Figures 2j–m and 3). As shown in Figure 2j–m, the homogenized Co20Cr20Fe34Mn20Ni6 alloy after water quenching shows an FCC and HCP dual-phase structure with homogeneous composition. The SEM-BSE image reveals a high density of stacking faults in the FCC phase, indicating a very low stacking fault energy of the new alloy. The effect of the metastable phase on the mechanical properties will be further discussed in Section 4.1.
Figure 3.
XRD patterns and EBSD phase maps of Fe80−xMnxCo10Cr10 (x = 45 at.%, 40 at.%, 35 at.% and 30 at.%) HEAs [12]; XRD patterns of homogenized Co20Cr20Fe40−xMn20Nix (x = 20 at.%, 6 at.% and 0) HEAs reveal the variations of phase configurations with changing the x value [13].
In addition, in contrast to the FeMnCrNiAl variant (Fe40.4Mn34.8Ni11.3Al7.5Cr6) with a single FCC phase, a Fe-rich HEA (Fe36Mn21Cr18Ni15Al10) with BCC/B2 dual-phase structure has been developed. As shown in Figure 2n–o, the as-cast alloy has a dual-phase structure consisting of a BCC matrix and homogeneously distributed cuboidal B2 ordered particles. The BCC/B2 dual-phase structure has been widely reported in the refractory HEAs [49, 50], which usually exhibit superior high-temperature properties. However, nearly all the current refractory HEAs (e.g. MoNbTaW, MoNbTaVW and HfNbTaTiZr) contain expensive elements, such as the Ta, Hf, V, Nb, Mo, W. In contrast, the newly developed BCC/B2 dual-phase HEA (Fe36Mn21Cr18Ni15Al10) is Fe-enriched and only contains inexpensive elements, which sheds light on the development of cost-effective refractory HEAs.
3.2 Microstructure after annealing
Although HEAs with single-phase were initially considered more stable due to the high-entropy effect, such as the CoCrFeMnNi HEA, they are recognized as a supersaturated solid solution at intermediate temperature in recent years because precipitation of the second phase or decomposition in the single solid solution phase occurs in the alloys. Decomposition was observed in both the FCC and BCC HEAs, such as the CoCrFeMnNi [51] with FCC structure and HfNbTaTiZr HEA [52, 53] with BCC structure, after long-period annealing at intermediate temperatures. It is believed that the annealing at intermediate temperatures for a long-time results in a weakened “high-entropy effect” due to the temperature-dependent contribution of mixing entropy to total Gibbs free energy and thus decreases the phase stability of the solid solution phase.
For Fe-rich HEAs, the phase stability of their solid solution can be further weakened due to the non-equiatomic and reduced entropy value, including thermal stability and mechanical stability. As aforementioned, the decreased thermal stability of the solid solution phase results in phase transformation during cooling, such as the partial martensitic transformation from FCC to the HCP phase when quenching as shown in Figures 2j and 3. The decreased mechanical stability will introduce phase transformation during deformation. Both the reduced thermal stability and mechanical stability contribute to the improvement of mechanical properties, which will be further discussed in Section 4.1. In addition, the decreased thermal stability may result in the precipitation of the second phase in the metastable solid solution phase, which can be used to manipulate the microstructure and thus their mechanical properties. For instance, Yu and co-workers investigated the precipitation behavior of the cost-effective Fe45Ni25Cr25Mo5 HEA with a face-cantered cubic (FCC) matrix [48]. As shown in Figure 4, with the increasing aging time at 900°C, the volume fraction of needle-shaped precipitates increased significantly in the FCC matrix of Fe45Ni25Cr25Mo5 HEA. This resulted in a high age-hardening effect, which raised the hardness from 192 HV5 to nearly 300 HV5. However, the peak-aged sample exhibited room-temperature brittleness due to the precipitation of a large needle-shaped intermetallic phase. To decrease the brittleness, thermomechanical processing can be applied to decrease the size of precipitates, which will be discussed in Section 3.3.
Figure 4.
(a and b) Novel heterogeneous lamella (HL) structure in the Fe35Ni35C25Mo5 HEA: STEM bright-field image of the thin-foil sample. The yellow arrows indicate the σ precipitates (a) [39]; Schematic illustration of the HL microstructure with nanoprecipitates and twins (b). (c) Schematic plot of producing hierarchical grain structure in the Fe49.5Mn30Co10Cr10C0.5 alloy [41].
Precipitation or phase decomposition is also reported in the dual-phase Fe-rich HEAs, for instance, the Fe36Mn21Cr18Ni15Al10 HEA with BBC and B2 phases. Interestingly, annealing at a high temperature of 1200°C for 24 h barely changed the structure (Figures 2n–o and 5h), but annealing at a relatively lower temperature of 1000°C resulted in precipitation of the FCC phase along the grain boundaries and within the matrix (Figure 5i-j). Due to the presence of the soft and ductile FCC phase at temperatures lower than 1000°C, the alloy is softened and thus may not be suitable for applications under 1000°C. However, the nanometer scaled cuboid B2 phase remains unchanged at 1200°C for 24 h, which is abnormal. Generally, high-temperature treatment will result in the coarsening of the second phase. This suggests a high stability of the nanometer scaled dual-phase structure, and therefore maintaining superior mechanical properties at temperatures close to 1200°C. Future work is needed to verify the high stability and evaluate the high-temperature (>1000°C) properties.
Figure 5.
(a–f) SEM images of the Fe45Ni25Cr25Mo5 samples aged at 900°C for different hours; (g) EDS map of the peaked aged Fe45Ni25Cr25Mo5 HEA [48]; (h–j) Microstructure of the Fe36Mn21Cr18Ni15Al10 alloy after annealing at 1200 (h) and 1000°C (i, j) for 24 h: h and i. BSE images, j. EBSD phase map (FCC phase in red and BCC/B2 phase in green) [45].
3.3 Microstructure after the thermomechanical process
In contrast to the simplicity of microstructure in the as-cast and as-aged Fe-rich HEAs, microstructure after thermomechanical processing can be more diverse, which provides much more opportunities for microstructure and mechanical properties manipulation. Similar to traditional alloys or equiatomic HEAs, thermomechanical processing is performed to control the grain size, phase constituents or phase fraction in Fe-rich HEAs (Fe80-xMnxCo10Cr10 and Fe49.5Mn30Co10Cr10C0.5) [12, 13, 40, 54], which corresponds to the grain-refinement strengthening, TWIP or TRIP effect. Except for the above traditional microstructure control methods, heterogeneous or hierarchical microstructure design (e.g. heterogeneous lamella structures, gradient structures, laminate structures, and harmonic structures) [19, 55, 56] has been proved effective in the property improvement of HEAs. This has been an active research topic.
Unique heterogeneous lamella (HL) structure was introduced in a cost-effective FCC HEA (Fe35Ni35Cr25Mo5) through a single-step heat treatment (800°C for 1 h) after cold rolling. As shown in Figure 4a and b, the HL structure consists of alternative layers of coarse-grained FCC matrix, and ultra-fine grains or subgrains layer with nanoprecipitates and annealing twins (ATs). According to Yu and co-workers, the preferential precipitation of σ phase at the shear bands with a high density of lattice defects (e.g. high-density dislocation walls and nano deformation twins) restrict the growth of recrystallized grains, resulting in the partial recrystallization and thus the formation of HL structure [39]. In addition, Su and co-workers [41] demonstrated a hierarchical microstructure design strategy to improve the mechanical properties of an Fe-rich HEA (Fe49.5Mn30Co10Cr10C0.5) by a thermomechanical processing. As shown in Figure 4c, three distinguished regions with different levels of dislocation density formed in the as-homogenized FCC matrix after cold rolling, including the deformation-induced HCP phase with the lowest dislocation density, residual FCC region with medium dislocation density, and severe shear bands region with the highest dislocation density. After annealing at a temperature above 400°C, the HCP phase is reversed to FCC phase while twins which co-existed with martensite lamellae got thickened in the parent grains. Due to the different dislocation densities and thus different recrystallization kinetics, trimodal grain structures were finally produced and characterized by small recrystallized grains associated with shear bands, medium-sized grains recrystallized from parent grains and unrecrystallized large grains. Such a grain size hierarchy promotes the variation in phase stability and results in a joint activation of transformation-induced plasticity (TRIP) and twinning-induced plasticity (TWIP) effects upon loading and thus a good strength-ductility synergy [41].
The above findings indicate that the non-equiatomic alloys (e.g. Fe-rich HEAs) not only enable more alloys with different compositions to be designed, but also broaden the window for microstructure and properties tuning due to the reduced thermal and mechanical stability of the solid solution phase.
3.4 Microstructure during deformation
As aforementioned, the decreased thermal stability and mechanical stability of Fe-rich HEAs can be applied to manipulate the microstructure via different deformation mechanisms (e.g. dislocation slip, twinning and the formation of stacking faults) and strengthening effects (e.g. TRIP effect, precipitation strengthening or integrated strengthening effect), and thus to achieve better mechanical properties. For instance, Zhiming and co-workers [12] reported that the improvement in the mechanical property of the metastable DP HEA (Fe50Mn30Co10Cr10) is related to the thermally induced DP structure and mechanically induced HCP phase [12]. As shown in Figure 6a and b, a large number of stacking faults is observed in the metastable FCC phase in the Fe50Mn30Co10Cr10 HEA, which acted as phase-formation nuclei (FCC → HCP) during deformation. When strain is lower than 30%, the stress-induced transformation from the FCC to HCP phase is the dominant deformation mechanism. With increasing strain to over 30%, the density of stacking faults and nano-twins increased in both the initial and mechanically induced HCP phase, which contributes significantly to strain hardening. Further increase of the strain to over 45% resulted in the formation of a high density of dislocations. Therefore, the thermally and mechanically induced HCP phase plays an important role in plastic accommodation and hardening at later stages of deformation via multiple deformation mechanisms, including dislocation slip, twinning, and the formation of stacking faults [12]. In addition, Yu and co-workers [39] introduced a unique heterogeneous lamella (HL) grain structure with a high density of nanoprecipitates, annealing twins and low angle boundaries in the Fe35Ni35Cr25Mo5 HEA (Figure 4a and b), resulting in a superior tensile property, with yield strength over 1.0 GPa and total elongation of ~13%. It is reported that the superior tensile properties were resulted from the hetero-deformation induced (HDI) strengthening, precipitation strengthening and the coexistence of multiple deformation mechanisms [39]. As shown in Figure 6c-f, the as-deformed Fe35Ni35Cr25Mo5 HEA shows a complex hierarchical microstructure including stacking faults (SFs), dislocation, annealing/deformation twins (DTs), low-angle grain boundaries (LAGBs), nanoprecipitates and HL interfaces. During deformation, the hierarchical microstructure (a high density of LAGBs, HL interfaces and precipitates) in the HL Fe35Ni35Cr25Mo5 alloy interact with the subsequently activated dislocations, SFs and DTs and thus significantly promote the strain hardening ability and prevent early necking.
Figure 6.
(a and b) Deformation micro-mechanisms in the TRIP-DP-HEA with increasing tensile deformation at room temperature [12]; (c–f) Microstructural evolution upon tensile deformation in the HL Fe35Ni35Cr25Mo5 HEA [39].
4. Properties
4.1 Mechanical properties
The room-temperature tensile properties (yield strength and fracture strain) of the current cost-effective Fe-rich HEAs/CCAs and a few commercial steels (for comparison purpose) are summarized in Figure 7. Obviously, the tensile properties of the current Fe-rich HEAs significantly vary, depending on their composition and microstructure. The widely reported strength-ductility trade-off can be identified in both the Fe-rich HEAs and commercial steels. Most Fe-rich HEAs or steels with high yield strength correspond to low elongation and vice versa. For instance, the ductile Fe50Mn30Co10Cr10 alloy with high elongation of over 70% has a yield strength of less than 500 MPa [12], while the Fe35Ni35Cr25Mo5 HEAs [39] and Fe49.5Mn30Co10Cr10C0.5 [41] after thermomechanical process exhibit a very high strength over 1 GPa but with ductility around 10%. Some HEAs exhibit balanced strength and ductility, such as the Fe49.5Mn30Co10Cr10C0.5 HEA [41]. After cold rolling and annealing at 650°C for 3 min, a good combination of yield strength (824 MPa), UTS (1.05 GPa) and ductility (33%) are attained due to the hierarchical grain structure (Figure 4c) and the sequential activation of transformation-induced plasticity (TRIP) and twinning-induced plasticity (TWIP) effects during deformation [41]. Some HEAs also exhibit quite low tensile performance, for instance, the BCC/B2 dual-phase Fe36Mn21Cr18Ni15Al10 HEA with severe brittleness, the elongation of which is less than 3%. Furthermore, most FCC Fe-rich HEAs exhibit very low strength (<250 MPa) at as-cast condition, which is close to that of the 316 L stainless steel.
Figure 7.
Tensile properties of most currently reported Fe-rich HEAs [12, 13, 14, 39, 40, 41, 42, 43, 44, 45, 46] compared with different types of steels (Data of steels is from Ref. [57, 58]).
Compared with commercial steels, the mechanical properties of the currently reported Fe-rich HEAs overlap most of the commercial steels, but are still lower than some high strength steels, particularly the maraging steels (number 2 in Figure 6) and D&P steels (number 1 in Figure 6) with ultra-high strength [57, 59, 60]. For instance, the low-cost D&P steel (FeMn9.95C0.44Al1.87V0.67) possesses a superior tensile property, with the yield strength and elongation of nearly 2 GPa and 22.0%, respectively [60]. Thus, it is essential to improve the mechanical properties of Fe-rich HEAs to further enhance their application potential.
4.2 Wear resistance
Except for the tensile or compressive properties, data of other mechanical properties, such as wear resistance, impact toughness, fatigue properties, or creep resistance, of Fe-rich HEAs is very limited. Based on the cost-effective age-hardenable Fe45Ni25Cr25Mo5 HEA, Yu and co-workers developed an intermetallics and carbides reinforced Fe40.5Ni22.5Cr22.5Mo4.5Ti5C5 HEA with superior wear resistance [46]. As shown in Figure 8a-d, the as-cast FeNiCrMoTiC alloy consists of an FCC solid solution matrix with randomly-distributed carbides and FCC/intermetallics eutectic structures. Aging at 800°C for 96 h effectively increases the hardness (Figure 8e) and wear resistance (Figure 8f) of the alloy due to the precipitation strengthening of intermetallics. It is noteworthy that, although the hardness of high-chromium cast iron (HCCI) is much higher than that of the peak-aged FeNiCrMoTiC alloy, the wear resistance of the latter is superior (Figure 8f). This is attributed to their different wear behavior during dry friction (Figure 8g). In contrast to the severe delamination in the HCCI, the peak-aged FeNiCrMoTiC alloy shows moderate abrasive wear and minor delamination under sliding friction due to its combined effect of ductile FCC matrix and fine reinforced particles, including the in-situ formed carbides/eutectic structures and precipitates formed during aging treatment [46]. On one hand, the fine reinforced particles with lower cracking susceptibility effectively strengthen the soft FCC matrix and thus reduce both the material loss by abrasive wear and severe brittle delamination. Moreover, the spalled fine particles (e.g. carbides or intermetallics) were found welded back into the FCC phase during friction and thus further strengthening the matrix and decreasing the abrasive wear. On the other hand, the propagation of micro-cracks from the brittle particles is inhibited by the ductile FCC matrix, which also suppresses the severe brittle delamination [46].
Figure 8.
SEM-BSE images (a–b) and the corresponding EDS map (c) and line-scan results (d) of the as-cast Fe40.5Ni22.5Cr22.5Mo4.5Ti5C5 HEC; (e) Hardness aging curves of the HEC at 800°C for up to 240 h, with inserted BSE images of the as-cast sample and peak-aged (800°C, 96 h) HEC; (f) Wear resistance of the HECs and destabilized HCCI are plotted against their hardness values; (g) Comparison of wear mechanism of the HCCI and as-aged HEC [46].
4.3 Oxidation and corrosion resistance
As shown in Table 1, all the currently reported Fe-rich HEAs contain Cr, most of which is over 10 at.%. Generally, alloys with high content of Cr show high oxidation and corrosion resistance. It is reasonable to assume that most currently reported Fe-rich HEAs possess superior oxidation and corrosion resistance. However, corrosion behavior of Fe-rich HEAs is rarely reported. Yu and co-workers evaluated the high-temperature oxidation resistance of the Fe-rich Fe45Ni25Cr25Mo5 HEA in comparison to two commercial alloys (i.e. 316 L stainless steel and Inconel 625 superalloy) [15]. In contrast to the catastrophic oxidation behavior of 316 L stainless steel and severe oxide spallation on Inconel 625 superalloy, the Fe-rich HEA showed outstanding oxidation resistance at 1200°C, including low oxidation rate and high spallation resistance. As shown in Figure 9a-l, catastrophic oxidation and spallation occurred on the 316 L stainless steel at 1200°C mainly due to the high oxidation rate and the intergranular cracking in the coarse-grained FeO scale. For Inconel 625 superalloy, the high densities of pores, cracks and Nb oxides in the Cr2O3 scale promoted the oxidation process. Meanwhile, the selective formation of Nb2O5 along the Cr2O3 scale/substrate interface resulted in severe oxide spallation and thus reduction of the oxidation resistance [15]. In contrast, an exclusive and compact chromia scale with better mechanical properties (e.g. high hardness and elastic modulus) formed on the Fe-rich HEA, protecting the matrix from further oxidation and high resistance against interface cracking during the oxidation process. As a result, the Fe-rich HEA showed the lowest oxidation rate at 1200°C compared with that of 316 L stainless steel and Inconel superalloy (Figure 9m) [15].
Figure 9.
EBSD analysis of the FeO oxide scale formed on the 316 L SS (a–d), on the Inconel 625 superalloy (e–h) and the Fe45Ni25Cr25Mo5 CCA (i-l) after oxidation at 1200°C in the air for 48 h: (a, e, and i) band contrast map; (b, f, and j) IPF map; (c, g, and k) phase map; (d, h, and l) KAM map; The isothermal oxidation kinetics of the Fe-rich CCA as compared with the 316 L SS and the Inconel 625 alloy at 1200°C in the air for 48 h [15].
Yu and co-workers also qualitatively evaluated the corrosion resistance of the Fe45Ni25Cr25Mo5 and Fe40.5Ni22.5Cr22.5Mo4.5Ti5C5 alloys using the immersion experiment [46, 48], both of which have superior corrosion resistance in an acid environment. As shown in Figure 10a, after immersion in the 5% HCl solution at room temperature for 10 days, obvious surface corrosion occurred on the 316 L stainless steel, but no visible corrosion was found on the Fe45Ni25Cr25Mo5 HEA [48]. Similarly, catastrophic corrosion was identified in the stainless steel while only minor corrosion pits are visible on the Fe40.5Ni22.5Cr22.5Mo4.5Ti5C5 HEA after immersion in 20% HCl solution for 150 days (Figure 10b) [46]. In-depth future work about the corrosion mechanisms of the Fe-rich HEAs is necessary.
Figure 10.
(a) Surface morphologies of the Fe45Ni25Cr25Mo5 HEA and the 316 L SS after immersion in the 5%HCl solution at room temperature for 10 days. (b) Surface morphologies of the aged Fe40.5Ni22.5Cr22.5Mo4.5Ti5C5 HEA and 316 L SS before and after immersion in the 20% HCl solution at room temperature for 150 days [46, 48].
5. Conclusions and outlook
Fe-rich HEAs exhibit a high potential for industrial applications owing to their superior properties and relatively low cost. Upon reviewing the currently reported Fe-rich HEAs the following conclusions are achieved.
The Fe-rich HEAs reported most recently were developed based on the 3d transition-metal HEAs, including single or near single FCC, FCC/HCP dual-phase and BCC/B2 dual-phase alloys. The FCC and FCC/HCP dual-phase Fe-rich HEAs have been widely studied, but few researches focused on the BCC/B2 dual-phase Fe-rich HEAs.
The compositions of various Fe-rich HEAs can be designed by simply increasing the Fe content in the equiatomic HEAs system, which may result in different effects on the microstructure and properties of different HEA systems. By increasing the content of Fe or decreasing the content of other elements in equiatomic HEAs, the thermal stability and mechanical stability are reduced because of lowering the “high-entropy effect”. The decreased thermal stability of the solid solution phase facilitates precipitation during heat treatment or phase transformation (e.g., FCC to HCP transformation) during cooling. The decreased mechanical stability enables stress-induced phase transformation during deformation. Like conventional alloys, these phenomena can be used to tailor the microstructure, introduce different deformation mechanisms (e.g., dislocation slip, twinning and the formation of stacking faults) and strengthening effects (e.g. TRIP effect, precipitation strengthening or integrated strengthening effect), and thus achieve improved mechanical properties.
Like the processing of traditional alloys or equiatomic HEAs, a thermomechanical process can be used to tailor the grain size, phase constituents or fraction of the Fe-rich HEAs (e.g., Fe80-xMnxCo10Cr10 and Fe49.5Mn30Co10Cr10C0.5), in order to improve the mechanical properties of the alloys.
The tensile properties of the currently reported Fe-rich HEAs vary within a wide range, depending on their composition and microstructure. The widely reported strength-ductility trade-off can be identified in both the Fe-rich HEAs and commercial steels. The mechanical properties of the currently reported Fe-rich HEAs are better than most of the commercial steels, but are still lower than some high strength steels, such as the maraging steels and D&P steels with ultra-high strength.
Except for the tensile or compressive properties, data of other mechanical properties of Fe-rich HEAs is limited, such as wear resistance, impact toughness, fatigue properties or creep resistance. In addition, although most Fe-rich HEAs are supposed to possess superior oxidation and corrosion resistance, very few research results are reported.
Some Fe-rich HEAs exhibit superior properties including mechanical properties, and oxidation and corrosion resistance. However, the greatest challenge is how to commercialize such alloys for industrial application. Systematic and comprehensive research is needed, which should focus more on the aspects of composition design, microstructure control, and properties evaluation and improvement. Here, combining the opinions proposed by other experts in the field of HEAs [23, 61] the authors propose a few topics that are of particular significance for the application of Fe-rich HEAs.
Except for the current 3d transition metal Fe-rich HEAs with FCC or FCC/HCP dual-phase structure, the Fe-rich HEAs with BCC structure should also be developed. Such studies are expected to shed some light on the development of low-cost refractory alloys. This can be achieved by introducing refractory elements (i.e., Ti, V, Zr, Nb, Hf, and W) or other elements (e.g., Al, Si) with a low valence electron concentration (VEC) value. Due to the high strength of the BCC phase at elevated temperatures, the cost-effective Fe-rich HEAs with BCC structure can be a new type of promising refractory HEAs. For instance, the Fe-rich HEAs (Fe36Mn21Cr18Ni15Al10) exhibit a very stable fine BCC/B2 DP structure at 1200°C, which can be a cost-effective alloy for high-temperature application [45].
The mechanical properties of the Fe-rich HEAs developed need further improvement. Different strategies should be explored to optimize their composition, microstructure, and process. For instance, other than C, the addition of other interstitial elements e.g., N, B, O, in Fe-rich HEAs may be used for property improvement. In addition, thermomechanical processing can be an effective method for microstructure control and properties manipulation.
The properties of Fe-rich HEAs need to be evaluated comprehensively to explore their potential applications in extreme environments. Except for the most widely reported room-temperature tensile properties, other mechanical properties like low/high-temperature tensile properties, impact toughness, fatigue resistance, creep resistance and wear resistance should be characterized. Further exploration of other properties like oxidation and corrosion resistance should also be conducted.
Acknowledgments
This work was financially supported by the ARC Discovery Project (No. DP200101408).
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"cost-effective, high-entropy alloys, multicomponent alloys, composition complex alloys, alloy design, microstructure, properties, application",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81896.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81896.xml",downloadPdfUrl:"/chapter/pdf-download/81896",previewPdfUrl:"/chapter/pdf-preview/81896",totalDownloads:20,totalViews:0,totalCrossrefCites:0,dateSubmitted:null,dateReviewed:"April 27th 2022",datePrePublished:"June 8th 2022",datePublished:null,dateFinished:"May 21st 2022",readingETA:"0",abstract:"High-entropy alloys (HEAs) have attracted increased attention due to their extraordinary properties. However, the multicomponent characteristic of equiatomic HEAs inevitably leads to high material costs, which thus limits their widespread industrial applications. Although HEAs are claimed to be suitable for applications in extreme environment due to their comprehensive properties, the actual properties of HEAs dramatically vary with compositions and processes. Therefore, the development of cost-effective HEAs with comprehensive properties is indispensable for industrial uses. Till now, although comprehensive review papers on HEAs are available, few works focused on the cost-effectiveness of HEAs, particularly Fe-rich HEAs recently developed. This review thus aims to fill this gap by reviewing the current research progress in Fe-rich HEAs with a focus on the composition design, microstructure, and properties, including mechanical properties, and resistances for oxidation, wear, and corrosion. The challenges for applying cost-effective Fe-rich HEAs into industries are also arising as future research topics.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81896",risUrl:"/chapter/ris/81896",signatures:"Yu Yin, Andrej Atrens, Han Huang and Ming-Xing Zhang",book:{id:"11468",type:"book",title:"High Entropy Alloys - Recent Advances, New Perspectives and Applications",subtitle:null,fullTitle:"High Entropy Alloys - Recent Advances, New Perspectives and Applications",slug:null,publishedDate:null,bookSignature:"Prof. Yong A Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/11468.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80356-111-0",printIsbn:"978-1-80356-110-3",pdfIsbn:"978-1-80356-112-7",isAvailableForWebshopOrdering:!0,editors:[{id:"203937",title:"Prof.",name:"Yong",middleName:"A",surname:"Zhang",slug:"yong-zhang",fullName:"Yong Zhang"}],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. Alloy design strategy",level:"1"},{id:"sec_3",title:"3. Microstructure",level:"1"},{id:"sec_3_2",title:"3.1 Microstructure of the as-cast and homogenization treated alloys",level:"2"},{id:"sec_4_2",title:"3.2 Microstructure after annealing",level:"2"},{id:"sec_5_2",title:"3.3 Microstructure after the thermomechanical process",level:"2"},{id:"sec_6_2",title:"3.4 Microstructure during deformation",level:"2"},{id:"sec_8",title:"4. Properties",level:"1"},{id:"sec_8_2",title:"4.1 Mechanical properties",level:"2"},{id:"sec_9_2",title:"4.2 Wear resistance",level:"2"},{id:"sec_10_2",title:"4.3 Oxidation and corrosion resistance",level:"2"},{id:"sec_12",title:"5. Conclusions and outlook",level:"1"},{id:"sec_13",title:"Acknowledgments",level:"1"},{id:"sec_16",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Yeh JW, Chen SK, Lin SJ, Gan JY, Chin TS, Shun TT, et al. 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Advanced Engineering Materials. 2010;12(1-2):44-49'},{id:"B36",body:'Hori T, Nagase T, Todai M, Matsugaki A, Nakano T. Development of non-equiatomic Ti-Nb-Ta-Zr-Mo high-entropy alloys for metallic biomaterials. Scripta Materialia. 2019;172:83-87'},{id:"B37",body:'Li C, Zhao M, Li JC, Jiang Q. B2 structure of high-entropy alloys with addition of Al. Journal of Applied Physics. 2008;104(11):113504'},{id:"B38",body:'Yang T, Xia S, Liu S, Wang C, Liu S, Zhang Y, et al. Effects of AL addition on microstructure and mechanical properties of AlxCoCrFeNi High-entropy alloy. Materials Science and Engineering: A. 2015;648:15-22'},{id:"B39",body:'Yin Y, Tan Q , Sun Q , Ren W, Zhang J, Liu S, et al. Heterogeneous lamella design to tune the mechanical behaviour of a new cost-effective compositionally complicated alloy. Journal of Materials Science & Technology. 2022;96:113-125'},{id:"B40",body:'Li Z, Tasan CC, Springer H, Gault B, Raabe D. Interstitial atoms enable joint twinning and transformation induced plasticity in strong and ductile high-entropy alloys. Scientific Reports. 2017;7:40704'},{id:"B41",body:'Su J, Raabe D, Li Z. Hierarchical microstructure design to tune the mechanical behavior of an interstitial TRIP-TWIP high-entropy alloy. Acta Materialia. 2019;163:40-54'},{id:"B42",body:'Nutor RK, Azeemullah M, Cao QP, Wang XD, Zhang DX, Jiang JZ. Microstructure and properties of a Co-free Fe50Mn27Ni10Cr13 high entropy alloy. Journal of Alloys and Compounds. 2021;851:156842'},{id:"B43",body:'Yao MJ, Pradeep KG, Tasan CC, Raabe D. A novel, single phase, non-equiatomic FeMnNiCoCr high-entropy alloy with exceptional phase stability and tensile ductility. Scripta Materialia. 2014;72-73:5-8'},{id:"B44",body:'Wang Z, Baker I. Interstitial strengthening of a f.c.c. FeNiMnAlCr high entropy alloy. Materials Letters. 2016;180:153-156'},{id:"B45",body:'Shaysultanov DG, Salishchev GA, Ivanisenko YV, Zherebtsov SV, Tikhonovsky MA, Stepanov ND. Novel Fe36Mn21Cr18Ni15Al10 high entropy alloy with bcc/B2 dual-phase structure. Journal of Alloys and Compounds. 2017;705:756-763'},{id:"B46",body:'Yin Y, Zhao Y, En Koey K, Tan Q , Zhang M-X, Huang H. In-situ synthesized age-hardenable high-entropy composites with superior wear resistance. Composites Part B: Engineering. 2022;235:109795'},{id:"B47",body:'Yin Y, Zhang JQ , Tan QY, Zhuang W, Mo N, Bermingham M, et al. Novel cost-effective Fe-based high entropy alloys with balanced strength and ductility. Materials & Design. 2019;162:24-33'},{id:"B48",body:'Yin Y, Chen Z, Mo N, Kent D, Candella AR, Koey KE, et al. High-temperature age-hardening of a novel cost-effective Fe45Ni25Cr25Mo5 high entropy alloy. Materials Science and Engineering: A. 2020;788:139580'},{id:"B49",body:'Senkov ON, Miracle DB, Chaput KJ, Couzinie J-P. 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A TRIP-assisted dual-phase high-entropy alloy: Grain size and phase fraction effects on deformation behavior. Acta Materialia. 2017;131:323-335'},{id:"B55",body:'Zhu Y, Ameyama K, Anderson PM, Beyerlein IJ, Gao H, Kim HS, et al. Heterostructured materials: Superior properties from hetero-zone interaction. Materials Research Letters. 2021;9(1):1-31'},{id:"B56",body:'Hasan MN, Liu YF, An XH, Gu J, Song M, Cao Y, et al. Simultaneously enhancing strength and ductility of a high-entropy alloy via gradient hierarchical microstructures. International Journal of Plasticity. 2019;123:178-195'},{id:"B57",body:'He BB, Hu B, Yen HW, Cheng GJ, Wang ZK, Luo HW, et al. High dislocation density-induced large ductility in deformed and partitioned steels. Science. 2017;357(6355):1029-1032'},{id:"B58",body:'Huang H, Wu Y, He J, Wang H, Liu X, An K, et al. Phase-transformation ductilization of brittle high-entropy alloys via metastability engineering. Advanced Materials. 2017;29(30):1701678'},{id:"B59",body:'Xu SS, Li JP, Cui Y, Zhang Y, Sun LX, Li J, et al. Mechanical properties and deformation mechanisms of a novel austenite-martensite dual phase steel. International Journal of Plasticity. 2020;128:102677'},{id:"B60",body:'Liu L, Yu Q , Wang Z, Ell J, Huang MX, Ritchie RO. Making ultrastrong steel tough by grain-boundary delamination. Science. 2020;368(6497):1347-1352'},{id:"B61",body:'Li Z, Raabe D. Strong and ductile non-equiatomic high-entropy alloys: Design, processing, microstructure, and mechanical properties. JOM. 2017;69(11):2099-2106'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Yu Yin",address:null,affiliation:'
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It is a leading cause of disability in children. Congenitally infected neonates often appear asymptomatic at birth or have nonspecific symptoms. An early diagnosis and subsequent early antiviral therapy associated to nonpharmacological therapy (e.g., hearing rehabilitation, speech-language therapy, and cochlear implants) can reduce long-term disability. Much research has been done in this field, but further studies are still necessary. Looking back at the most recent papers, we will draw a review on this topic trying to answer to the question: could universal CMV screening be a useful and cost-effective diagnostic tool?",book:{id:"8728",slug:"update-on-critical-issues-on-infant-and-neonatal-care",title:"Update on Critical Issues on Infant and Neonatal Care",fullTitle:"Update on Critical Issues on Infant and Neonatal Care"},signatures:"Sara Lunardi, Francesca Lorenzoni and Paolo Ghirri",authors:null},{id:"44446",doi:"10.5772/54310",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14749,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"38034",doi:"10.5772/34698",title:"Maternal Socio-economic Status and Childhood Birth weight: A Health Survey in Ghana.",slug:"maternal-socio-economic-status-and-childhood-birth-weight-a-health-survey-in-ghana-",totalDownloads:3608,totalCrossrefCites:2,totalDimensionsCites:3,abstract:null,book:{id:"741",slug:"neonatal-care",title:"Neonatal Care",fullTitle:"Neonatal Care"},signatures:"Edward Nketiah-Amponsah, Aaron Abuosi and Eric Arthur",authors:[{id:"101268",title:"Dr.",name:"Edward",middleName:null,surname:"Nketiah-Amponsah",slug:"edward-nketiah-amponsah",fullName:"Edward Nketiah-Amponsah"}]}],mostDownloadedChaptersLast30Days:[{id:"44446",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14749,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"53683",title:"Pre and Postoperative Management of Pediatric Patients with Congenital Heart Diseases",slug:"pre-and-postoperative-management-of-pediatric-patients-with-congenital-heart-diseases",totalDownloads:4889,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Stabilization during preoperative cardiac surgery especially in neonates has an important role to predict outcome for pediatric congenital heart surgery. We tried to elaborate general guidelines on how to diagnose and some anticipations for emergency treatments tailored by the type of congenital heart disease in neonates. Stabilization consists of medical treatment including emergent prostaglandin institution in some types of duct dependent lesion. The role of interventional catheterization such as patent ductus arteriosus (PDA) stent, balloon pulmonary valvotomy, etc. as modalities for stabilization before surgery was also elaborated. Some general and specific guidelines based on the type of surgeries for postoperative management were also discussed.",book:{id:"5473",slug:"pediatric-and-neonatal-surgery",title:"Pediatric and Neonatal Surgery",fullTitle:"Pediatric and Neonatal Surgery"},signatures:"Eva Miranda Marwali, Beatrice Heineking and Nikolaus A. 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It is more common during the neonatal period than at any other age with the estimated incidence of 0.25 per 1000 live births. The absence of specific clinical presentation makes diagnosis of meningitis more difficult in neonates than in older children. Culture of cerebrospinal fluid is the traditional gold standard for diagnosis of bacterial meningitis, so all newborn infants with proven or suspected sepsis should undergo lumbar puncture. However, deciding when to perform lumbar puncture and interpretation of the results are challenging. Although the pathophysiology of neonatal meningitis is complex and not fully understood, researches on diagnostic and prognostic tools are ongoing. Prevention of neonatal sepsis, early recognition of infants at risk, development of novel, rapid diagnostics and adjunctive therapies, and appropriate and aggressive antimicrobial treatment to sterilize cerebrospinal fluid as soon as possible may prevent the lifelong squeal of bacterial meningitis in newborn infants.",book:{id:"7527",slug:"neonatal-medicine",title:"Neonatal Medicine",fullTitle:"Neonatal Medicine"},signatures:"Mehmet Şah İpek",authors:[{id:"267903",title:"Associate Prof.",name:"Mehmet Şah",middleName:null,surname:"İpek",slug:"mehmet-sah-ipek",fullName:"Mehmet Şah İpek"}]},{id:"71427",title:"Factors Influencing Maternal Decision-Making on Infant Feeding Practices",slug:"factors-influencing-maternal-decision-making-on-infant-feeding-practices",totalDownloads:984,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The decision to formula feed or breastfeed a child typically begins with an established prenatal intention. 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\r\n\tSustainable development focuses on linking economic development with environmental protection and social development to ensure future prosperity for people and the planet. To tackle global challenges of development and environment, the United Nations General Assembly in 2015 adopted the 17 Sustainable Development Goals. SDGs emphasize that environmental sustainability should be strongly linked to socio-economic development, which should be decoupled from escalating resource use and environmental degradation for the purpose of reducing environmental stress, enhancing human welfare, and improving regional equity. Moreover, sustainable development seeks a balance between human development and decrease in ecological/environmental marginal benefits. Under the increasing stress of climate change, many environmental problems have emerged causing severe impacts at both global and local scales, driving ecosystem service reduction and biodiversity loss. Humanity’s relationship with resource exploitation and environment protection is a major global concern, as new threats to human and environmental security emerge in the Anthropocene. Currently, the world is facing significant challenges in environmental sustainability to protect global environments and to restore degraded ecosystems, while maintaining human development with regional equality. Thus, environmental sustainability with healthy natural ecosystems is critical to maintaining human prosperity in our warming planet.
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