Promotion policies of renewable energy in several countries [21].
\r\n\t
\r\n\tRecently in 2019, International Council on Systems Engineering (INCOSE) has released the latest version of the “Guidelines for the Utilization of ISO/IEC/IEEE 15288 in the Context of System of Systems (SoS) Engineering” to industry for review and comments. The document was developed under the Partner Standards Development Organization cooperation agreement between ISO and IEEE, as it was approved by Council Resolution 49/2007. This document provides guidance for the utilization of ISO/IEC/IEEE 15288 in the context of SoS in many domains, including healthcare, transportation, energy, defense, corporations, cities, and governments. This document treats an SoS as a system whose elements are managerially and/or operationally independent systems, and which together usually produce results that cannot be achieved by the individual systems alone. This INCOSE guide book perceives that SoS engineering demands a balance between linear procedural procedures for systematic activity and holistic nonlinear procedures due to additional complexity from SoS perspectives.
\r\n\tThe objective of this book is to provide a comprehensive reference on Systems-of-Systems Engineering, Modeling, Simulation and Analysis (MS&A) for engineers and researchers in both system engineering and advanced mathematical modeling fields.
\r\n\tThe book is organized in two parts, namely Part I and Part II. Part I presents an overview of SOS, SOS Engineering, SOS Enterprise Architecture (SOSEA) and SOS Enterprise (SOSE) Concept of Operations (CONOPS). Part II discusses SOSE MS&A approaches for assessing SOS Enterprise CONOPS (SOSE-CONOPS) and characterizing SOSE performance behavior. Part II focuses on advanced mathematical application concepts to address future complex space SOS challenges that require interdisciplinary research involving game theory, probability and statistics, non-linear programming and mathematical modeling components.
\r\n\tPart I should include topics related to the following areas:
\r\n\t- SOS and SOS Engineering Introduction
\r\n\t- Taxonomy of SOS
\r\n\t- SOS Enterprise (SOSE), SOSE CONOPS, Architecture Frameworks and Decision Support Tools
\r\n\tPart II should address the following research areas:
\r\n\t- SOS Modeling, Simulation & Analysis (SOS M&SA) Methods
\r\n\t- SOS Enterprise Architecture Design Frameworks and Decision Support Tools
\r\n\t- SOS Enterprise CONOPS Assessment Frameworks and Decision Support Tools.
Building energy consumption is generally recognized as one of the main sectors contributing to the whole primary energy consumption and greenhouse gas emissions in the world, which greatly raise public awareness on building energy conservation in recent years. Green building (GB), low-energy building (LEB), and nearly/net-zero energy building (ZEB/nZEB/NZEB) are widely developed for the advantages of low-energy demand in the building, efficient energy system operation, and integration of renewable energy system [1, 2, 3, 4, 5]. In addition, numerous incentive policies, such as investment subsidies, feed-in tariff, net-metering schemes, etc., have been applied to promote the application of renewable energy sources [6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16], thus paving the way for future zero target for buildings.
\nThe concept of ZEB/nZEB is extended from autonomous buildings that are targeted to operate off-grid by installing enough solar PV and/or wind turbine for the generation of all the energy the building required to include grid-connected ZEB that is aimed to balance annual energy exchange with the grid. The off-grid ZEB has also been named “autonomous” or “stand-alone” building as shown in Figure 1, which can be defined as “Zero Stand Alone Buildings are buildings that do not require connection to the grid or only as a backup. Stand-alone buildings can autonomously supply themselves with energy, as they have the capacity to store energy for night-time or wintertime use” [17].
\nBasic elements in the definition of off-grid zero energy building.
The on-grid ZEB is a “grid-connected” or “grid-integrated” net-zero energy building that is connected to one or more energy infrastructure as shown in Figure 2; it can be defined as “Zero Net Energy Buildings are buildings that over a year are neutral, meaning that they deliver as much energy to the supply grids as they use from the grids. Seen in these terms they do not need any fossil fuel for heating, cooling, lighting or other energy uses although they sometimes draw energy from the grid” [17].
\nBasic elements in the definition of on-grid net-zero energy building.
However, no national ZEB codes and international standards have been developed since numerous proposed approaches spotlight different aspects of ZEB. The metric applied for the “zero” balance is a vital issue since it affects how renewable energy system will be selected to achieve this goal. Torcellini et al. [18] introduced four different nZEB definitions, including site nZEB, source nZEB, emissions nZEB, and cost nZEB, as defined below:
Site nZEB: A site nZEB produces at least as much energy as it uses in a year when accounted for at the site.
Source nZEB: A source nZEB produces at least as much energy as it uses in a year when accounted for at the source. Source energy refers to the primary energy used to generate and deliver the energy to the site.
Emission nZEB: A net-zero emission building produces at least as much emission-free renewable energy as it uses from emission-producing energy sources.
Cost nZEB: In a cost nZEB, the amount of money the utility pays the building owner for the energy the building exports to the grid is at least equal to the amount the owner pays the utility for the energy services and energy used over the year.
The concept of balance can be defined in the following mathematical equations, the balance between export and import energies (Eq. (1)) or the balance between load and generation (Eq. (2)) [19]. The balance between load and generation is generally used as a basic requirement during the design phase of ZEB. By contrast, the balance between export and import energies is particularly useful for evaluating its matchability between load and generation and the interaction between building and grid. In the previous study, most studies defined “net” as the building energy consumption and RES generation to be equal:
Substantial policies and regulations have been provided to support the installation of RES power plants and thus simulate the widespread of ZEB applications. Under the support of these policies, an increasing number of ZEB case studies have been conducted, and there are over 360 ZEB projects which had been identified in different countries till 2013, as shown in Figure 3.
\nWorld map of more than 360 internationally known net-zero energy buildings [20].
The continued growth in ZEB projects is mainly driven by the progressive financial incentives on renewable energy promotion, which is summarized for several countries from different parts of the world, as shown in Table 1. The main support policies on RES in different countries are described as follows [6]:
Investment subsidies: Based on a percentage of the renewable energy output or the specific investment upfront cost.
Feed-in tariff: The producer receives total payments per kWh of generated electricity at a fixed price. It is guaranteed by the government.
Net-metering schemes: Net-metering (NM) and self-consumption (SC) schemes. Billing agreement between utilities and their customers to feed electricity the producer does not use back into the grid.
Tradable Green Certificates: Certificates that can be sold in the market, allowing RES generators to obtain revenue, in addition to the earnings from the sale of electricity fed into the grid.
Incentive policies | \nAustralia | \nBelgium | \nChina | \nFrance | \nGermany | \nItaly | \nJapan | \nSpain | \nThe United Kingdom | \nThe United States | \n
---|---|---|---|---|---|---|---|---|---|---|
Renewable energy targets | \nO | \nO | \nR | \nR | \nO | \nO | \nR | \nO | \nO | \nR* | \n
Feed-in tariff/premium payment | \n• | \n\n | R | \nR | \nR | \nR | \nR | \n\n | O | \nR* | \n
Electric utility quota obligation/RPS | \nO | \n• | \nO | \n\n | \n | \n | O | \n\n | O | \nR* | \n
Net metering | \n\n | • | \n\n | \n | \n | O | \nO | \nO | \n\n | R* | \n
Tradable REC | \nO | \nO | \n\n | O | \n\n | O | \nO | \nO | \nO | \n• | \n
Capital subsidy, grant, or rebate | \nO | \n• | \nO | \nO | \nO | \nO | \nO | \nO | \nO | \nO | \n
Reduc-tions in sales, energy, CO2, VAT, or other taxes | \n\n | O | \nO | \nO | \nO | \nO | \n\n | \n | O | \nO | \n
Public invest-ment, loans, or grants | \nO | \n\n | O | \nO | \nO | \nO | \nO | \n\n | O | \nO | \n
Promotion policies of renewable energy in several countries [21].
O, existing national (may also include state/provincial); •, existing subregional (e.g., state/provincial); R, revised (*indicates state/provincial).
Although no exact approach has been developed for the target of zero balance during the design phase of ZEB, there are still some consensus and several common design elements for designing ZEB. A thorough design approach was proposed which involves 12 steps containing four foundational procedures, that is, applied metrics (e.g., primary energy, the cost), passive design (e.g., building envelope, orientation), active design (e.g., HVAC, lighting), and renewable energy system design (e.g., photovoltaic panel, wind turbine) for the design of ZEB [22, 23], as shown in Figure 4. Theoretically, design optimization of ZEB should be conducted considering the three vital design steps, that is, steps 7, 8, and 9, simultaneously to obtain a comprehensive combined design option for ZEB. Therefore, design optimization for ZEB is usually solved by integration of two or more software.
\nThe main steps to designing nZEB.
Passive design is an important procedure to reduce the building energy demand as much as possible. Then, high-efficiency active energy systems such as heating, cooling, and ventilation systems and lighting systems should be applied and improved together with high-performance control strategies; these could further reduce operational energy consumption in the building. Lastly, the feasibility of renewable energy technology should be assessed and selected as an on-site power supply system which works together with the power grid to reach the target of zero energy demand.
\nVarious software tools have been developed to facilitate the selection of passive design, active design, and RES for buildings; several popular software are listed and compared in Tables 2 and 3. In ZEB design, the building energy demand can be firstly evaluated by using building energy simulation software such as EnergyPlus or TRNSYS. The selection of suitable renewable energy system for the building can then be conducted in software such as HOMER and TRNSYS. The design optimization software, HOMER, is developed by the US National Renewable Energy Laboratory (NREL) to assist in design optimization of hybrid energy systems for both grid-connected and autonomous building based on net present cost [24, 25, 26, 27]. However, HOMER can only address a single-objective function for minimizing the net present cost, and it cannot solve multi-objective problems [28].
\n\n | DOE-2 | \neQUEST | \nEnergyPlus | \nESP-r | \nDeST | \nTRNSYS | \n
---|---|---|---|---|---|---|
Room heat balance calculation | \n\n | √ | \n√ | \n√ | \n√ | \n√ | \n
Humidity calculation | \n\n | √ | \n√ | \n√ | \n√ | \n√ | \n
Heat comfort calculation | \n\n | \n | √ | \n√ | \n√ | \n√ | \n
Nature ventilation calculation | \n\n | √ | \n√ | \n√ | \n√ | \n√ | \n
Sunlight analysis | \n√ | \n√ | \n√ | \n√ | \n√ | \n√ | \n
Greenhouse gas | \n√ | \n√ | \n√ | \n√ | \n√ | \n√ | \n
Connection with other software | \n\n | \n | √ | \n√ | \n√ | \n√ | \n
Comparison of building energy consumption software [29].
\n | HOMER | \nHYBRID2 | \niHOGA | \nRETScreen | \n
---|---|---|---|---|
Economical analysis | \n√ | \n√ | \n√ | \n√ | \n
Technical analysis | \n√ | \n√ | \n√ | \n√ | \n
PV system | \n√ | \n√ | \n√ | \n√ | \n
WT system | \n√ | \n√ | \n√ | \n√ | \n
Generator set | \n√ | \n√ | \n√ | \n\n |
Storage device | \n√ | \n√ | \n√ | \n√ | \n
Bioenergy | \n√ | \n\n | \n | \n |
Hydro energy | \n√ | \n\n | √ | \n\n |
Thermal system | \n\n | √ | \n\n | \n |
Advantage | \nUser-friendly, easy to understand, efficient graphical representation of results, hourly data-handling capacity | \nUser-friendly, multiple electrical load options, detailed dispatching option | \nmulti- or mono-objective optimization, sensitivity analysis, low computational time, net balance | \nUser-friendly, strong product database, financial analysis | \n
Comparison of renewable energy simulation software [30].
It is important to determine the evaluation criteria at the design stage. Various criteria have been proposed from a different perspective of users, which can be classified into four aspects covering technical and environmental issues, economic factors, and the interaction between building and grid, as shown in Figure 5.
\nThe main four factors for evaluating ZEB performance.
In terms of technological factors, recent researches have been focused on feasibility and/or reliability study of different technologies (passive design, active design, RES) for ZEB.
Feasibility: Available technologies should be assessed to identify the possibility for the building to achieve zero energy building for a particular region.
Reliability: The criterion estimates the ability of the selected combined technologies for the building to perform its required function for a specified time.
In terms of economic factors, ZEB users are more concerned about the economic value, especially the cost and its payback period of installing on-site RES.
Economic value [life cycle analysis (LCA), net present cost (NPC)]: The proposed renewable energy alternative will be assessed using one of the engineering economic techniques which are net present cost (NPC), life cycle analysis (LCA), benefit/cost analysis, and payback period.
In terms of environmental factors, the reduction of building load will definitely reduce the energy required from the grid and on-site RES size, which can be measured as pollutant emission.
Pollutant emission: The criterion measures the equivalent emission of CO2, air emissions which are the results of applying different technologies in ZEB for a particular period.
In terms of grid interaction factors, the two-way electricity flow between building and grid poses more than technological challenges; those ZEB homeowners may make heavier use of the grid than the conventional building under one-way power flow. Grid interaction index is one of the indicators used to assess the grid stress caused by ZEB.
Grid interaction index (GII): The criterion is defined as the standard deviation of the building-grid interaction over the specified time (e.g., 1 year). It is used to estimate the average stress of building on the grid, and a low standard deviation is preferred [28].
It is reported that there are more than 50% of design optimization problems that are addressed as single-objective optimization problems, and they are usually focused on the most important criteria such as economic cost or environmental issues. For designing ZEB, the optimization may be conducted by focusing on the only one aspect of ZEB performance, e.g., NPC and CO2 emissions. Besides, since multi-objective design optimization problems can also be transformed into single-objective optimization problems by using weighting factor, it is reasonable to convert all of the concerned ZEB performance indices into one combined function, as shown in (Eq. (3)). Where X represents a vector of design variables at the design stage, fave and fi (i = 1, 2…n) are the combined objective and the normalized sub-objectives, respectively; wi is the corresponding weighting factor for each sub-objective:
s.t.
\n
\n
The design and operation of ZEB are actually integrated with building owners, environment, energy source, and smart grid; it is, therefore, a multi-objective design optimization problem with even contradicting objectives. In general, genetic algorithm (GA) is the most popular optimization approach for single-objective and multi-objective optimizations of energy systems in numerous studies [31, 32]. Besides, particle swarm optimization (PSO) is another favored method for optimal design of energy systems in recent papers [33, 34]. A typical optimization process is shown in Figure 6.
\nSingle-/multi-objective design optimization using GA/NSGA-II.
Although the progressive incentive policies have been recognized to widely encourage the installation of renewable energy system for buildings, the financial support scheme is forecasted to be downtrend and RES cost to be high, which are a barrier for promoting future buildings to be zero energy buildings. Therefore, a penalty cost scheme may be a good solution to build up the public’s confidence and encourage them to be actively involved in ZEB application.
\nA comparison of the building cost under different mismatch ratios is shown in Figure 7. It is found that the minimum total cost is supposed to be located in O1 under mismatch ratio less than 0, possibly between −1.0 and 0.0, indicating that the selection of design option under mismatch ratio of 1.0 is not cost-effective. However, the introduction of penalty cost can move the minimum cost from O1 to O2, or the higher mismatch ratio the less cost, depending on the type of penalty cost designed by designers.
\nThe cost of building under different mismatch ratios.
The total cost (TC) of the building basically consists of the initial cost (IC) of RES (e.g., PV, WT) and the operation cost (OC) during the building usage stage due to the electricity consumption from grid and oil consumption (Eq. (4)). The penalty cost can be expressed as a mathematic expression, which is assumed to follow a segmented function, as shown in Eq. (5). It should be noted that the cost results may be greatly different according to the designed penalty cost:
In recent years, wide ranges of researches are available on the topic of RES design/control for an off-grid building or a village in a remote area [25, 26, 27]. However, the question is, are the buildings better to be designed as individual ZEB separately (Figure 8) or a ZEB cluster (Figure 9) when the grid power is available? By considering the dynamic electricity price from the power grid and dynamic financial incentives of sell back price from RES, the investment of RES is supposed to be different, while electricity exchange between the building and the grid is also supposed to be greatly different since the building in ZEB cluster can share on-site generation among these grouped buildings. In the study of Sun et al. [35], performance potentials are investigated by comparing single-building level using non-collaborative controls and building-group level using collaborative controls. However, a systematic and comprehensive comparison of the differences between design/control strategies for individual on-grid ZEB and on-grid ZEB cluster should be further explored and formed for ZEB development.
\nA typical diagram of individual on-grid ZEB.
A typical diagram of on-grid ZEB cluster.
ZEB is generalized as a type of sensitive building since its target is affected not only by the variation of building energy load but also by the fluctuation of local renewable energy resources. In general, a comprehensive sensitivity analysis is required to be conducted by considering both on-site generation and building energy load, as shown in Figure 10.
\nFour aspects in terms of sensitivity analysis for ZEB.
In terms of on-site RES generation, the availability of renewable resources (e.g., solar radiation and/or wind speed) and RES parameters (e.g., PV/WT efficiency and life time) can directly affect on-site energy generation for building electricity supply and thus greatly affect RES selection as well as the corresponding building performance.
\nIn terms of building energy load, building design parameters (e.g., indoor set temperature and humidity, thermal insulation of external walls, window area, etc.), operational parameters (e.g., outdoor temperature and humidity, solar radiation, etc.), and energy system efficiency (e.g., lighting efficiency, HVAC efficiency, etc.) are the main parameters affecting building load.
\nEconomic parameters including the price of RES, feed-in tariff, and electricity price from/to the grid are also key parameters affecting RES selection and ZEB performance. In addition, many researches have found that both the building energy load and the local renewable resources are different even for the same building located in different climate zones, which indicate that different key design parameters may exist for different climate zones and should be further identified.
\nTherefore, there are many uncertain parameters which may cause great performance discrepancy between the design stage and operation stage of ZEB. The impact of uncertain parameters on system selection can be illustrated in Figure 11. In convention building, since it has no constraint on the mismatch between building energy consumption and on-site generation, the optimal design option O is usually selected within all the design options (Area of A), which is located below the net-zero balance line with 100% confidence level. When designing ZEB using deterministic approach, the constraint of annual energy balance is achieved for the design year, and thus the optimal design option O′ is usually selected within a few design options (Area of B), which is located on the net-zero balance line with approximately 50% confidence level. When uncertain parameters are concerned for a robust ZEB design, a narrowed area of C is identified as the selected option is required to satisfy many years of operation. Therefore, the optimal design option O″ is selected on/above the net-zero balance line with 100% confidence level. In the study of Lu [36], the RES size should be selected with a mismatch ratio of about 30% to ensure a probability of 100% of being ZEB in different years.
\nImpact of uncertain parameters on ZEB performance. Note: A, all design options; B, design options for nZEB based on deterministic condition; C, design options for nZEB under uncertainties; O/O′/O″, optimal design option.
As mentioned in Figure 12, various parameters can affect ZEB system selection and performance. Six key parameters are selected here and grouped in pairs according to their specifications, i.e., PV price (ranges between 1200 and 2000 $/kW) and converter price (ranges between 400 and 800 $/kW), electricity price (EP) (ranges between 0.04 and 0.12 $/kWh) and sellback price (SP) (ranges between 0.04 and 0.12 $/kWh), and demand load ratio (ranges between 0.8 and 1.2) and the type of ZEB (ranges between 0.2 and 1.0), respectively. The impact of the group in pairs on NPC and GII is compared based on a hypothetical residential house (an area of 120 m2) that is located in Shanghai, China. Under the selected ranges of parameters, electricity price, sellback price, demand load ratio and the type of ZEB are identified to be more important on NPC than PV and CONV price. It should be noted that the results may be different when applied for different parameter variation ranges.
\nVariations of NPC and GII under the effect of two factors (Note: The point B is the value under basic case.).
This chapter aims to present a comprehensive view of the key issues related to the development of zero energy building including the definition, supporting incentives, evaluation criteria, design methodologies, and uncertainty analysis. Although a wide range of researches can be found to investigate one aspect of the ZEB study, there are still a lot of challenges faced to be solved in the future:
A consensus definition and interpretation of national/regional ZEB should be further declared; then, the design/control strategies with the corresponding performance of ZEB can be investigated and compared under the same standard.
Since a lot of factors/parameters can cause the discrepancies between predicted and realized target and ZEB performance, it should be noted that even the same factors may have a different effect on ZEB design for a specified region considering the applied energy systems and its financial support. So, it is necessary to identify and classify the key factors affecting ZEB performance for different conditions.
The future grid-connected ZEB seems to definitely pose a great challenge for smart grid considering the new complex energy usage as well as on-site RES generation features of ZEB. The stress caused by ZEB on the grid is different from conventional buildings, which should be further identified and taken into consideration on ZEB design.
ZEB is generally catering for an individual building, while the investigation of zero energy building cluster, zero energy community, and zero energy high-rise building is still required and thus forms some standards for the design/control strategies in each type of ZEB application.
The existing financial incentives are mostly proposed to promote the widespread application of RES, while a systematic financial scheme should be developed to further assist and stimulate ZEB development in a standard and rapid way.
Our thanks to the National Natural Science Foundation of China (Project No. 51608001 and Project No. 51478001) for financial support on this research work reported in this chapter. The authors also acknowledge the support from the China Scholarship Council (CSC) and the Anhui University of Technology and research support from the University of Birmingham in the UK.
\nAortic 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.
\nMultiple 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.
\nGenetically-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].
\nMFS 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].
\nAlthough 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].
\nThe 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).
\nPatients with family history of Marfan disease | \n
\n
| \n
\n
| \n
\n
| \n
Patients without family history of Marfan disease | \n
\n
| \n
\n
| \n
\n
| \n
\n
| \n
Revised Ghent nosology.
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).
\nBicuspid 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].
\nThe 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].
\nPrevalence 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).
\nLoeys-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].
\nThe incidence and prevalence of the disease is still not well established.
\nLoeys-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].
\nAortic 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].
\nEhlers-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].
\nVascular 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].
\nAortic 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].
\nDespite 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].
\nIn 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].
\nIn 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.
\nHypertension 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].
\nSince 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\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].
\nTuberculosis 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].
\nThere 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.
\nAnkylosing 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].
\nRelapsing 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].
\nTakayasu 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].
\nGiant 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].
\nAdditionally 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.
\nAortic 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).
\nAdditionally, 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].
\nComplication of aortic root aneurysm | \nPresenting symptom | \n
---|---|
Aortic insufficiency, aortic regurgitation | \nDyspnea, diastolic murmur, congestive heart failure symptoms | \n
Aortic dissection | \nSharp chest pain, may radiate to the back | \n
Thromboembolism | \nSymptoms of stroke | \n
Compression of tracheal or bronchus | \nHemoptysis, cough, recurrent pneumonitis | \n
Compression of left recurrent laryngeal nerve | \nHoarseness | \n
Compression of superior vena cava | \nSigns of superior vena cava syndrome | \n
Compression of esophagus | \nDysphagia | \n
Complications and presenting symptoms of aortic root dilation.
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.
\nAortic 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].
\nAortic 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).
\nAortic 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.
\nWhile 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].
\nThe 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).
\nTTE 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.
\nOn 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].
\nImportantly, 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.
\nDespite 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.
\nCardiac 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].
\nIt 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.
\nAlthough 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].
\nThe 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].
\nModern 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.
\nFor 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].
\nIt 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.
\nManagement 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].
\nThe 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].
\nThe 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.
\nIn 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].
\nPatients 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].
\nEmergent 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].
\nEmergent surgical repair | \nElective surgical repair | \n
---|---|
\n
| \n\n
| \n
Indications for emergent and elective surgical repair of aortic root dilation.
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].
\nThe 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].
\nIn 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.
\nNone.
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\\n\\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\\n\\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\\n\\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\\n\\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\\n\\n5. TERMINATION
\\n\\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\\n\\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\\n\\n6. INTECHOPEN’S DUTIES AND RIGHTS
\\n\\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\\n\\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\\n\\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\\n\\n7. MISCELLANEOUS
\\n\\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\\n\\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\\n\\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\\n\\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\\n\\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\\n\\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\\n\\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\\n\\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\\n\\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\\n\\nLast updated: 2020-11-27
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The Corresponding Author (acting on behalf of all Authors) and INTECHOPEN LIMITED, incorporated and registered in England and Wales with company number 11086078 and a registered office at 5 Princes Gate Court, London, United Kingdom, SW7 2QJ conclude the following Agreement regarding the publication of a Book Chapter:
\n\n1. DEFINITIONS
\n\nCorresponding Author: The Author of the Chapter who serves as a Signatory to this Agreement. The Corresponding Author acts on behalf of any other Co-Author.
\n\nCo-Author: All other Authors of the Chapter besides the Corresponding Author.
\n\nIntechOpen: IntechOpen Ltd., the Publisher of the Book.
\n\nBook: The publication as a collection of chapters compiled by IntechOpen including the Chapter. Chapter: The original literary work created by Corresponding Author and any Co-Author that is the subject of this Agreement.
\n\n2. CORRESPONDING AUTHOR'S GRANT OF RIGHTS
\n\n2.1 Subject to the following Article, the Corresponding Author grants and shall ensure that each Co-Author grants, to IntechOpen, during the full term of copyright and any extensions or renewals of that term the following:
\n\nThe aforementioned licenses shall survive the expiry or termination of this Agreement for any reason.
\n\n2.2 The Corresponding Author (on their own behalf and on behalf of any Co-Author) reserves the following rights to the Chapter but agrees not to exercise them in such a way as to adversely affect IntechOpen's ability to utilize the full benefit of this Publication Agreement: (i) reprographic rights worldwide, other than those which subsist in the typographical arrangement of the Chapter as published by IntechOpen; and (ii) public lending rights arising under the Public Lending Right Act 1979, as amended from time to time, and any similar rights arising in any part of the world.
\n\nThe Corresponding Author confirms that they (and any Co-Author) are and will remain a member of any applicable licensing and collecting society and any successor to that body responsible for administering royalties for the reprographic reproduction of copyright works.
\n\nSubject to the license granted above, copyright in the Chapter and all versions of it created during IntechOpen's editing process (including the published version) is retained by the Corresponding Author and any Co-Author.
\n\nSubject to the license granted above, the Corresponding Author and any Co-Author retains patent, trademark and other intellectual property rights to the Chapter.
\n\n2.3 All rights granted to IntechOpen in this Article are assignable, sublicensable or otherwise transferrable to third parties without the Corresponding Author's or any Co-Author’s specific approval.
\n\n2.4 The Corresponding Author (on their own behalf and on behalf of each Co-Author) will not assert any rights under the Copyright, Designs and Patents Act 1988 to object to derogatory treatment of the Chapter as a consequence of IntechOpen's changes to the Chapter arising from translation of it, corrections and edits for house style, removal of problematic material and other reasonable edits.
\n\n3. CORRESPONDING AUTHOR'S DUTIES
\n\n3.1 When distributing or re-publishing the Chapter, the Corresponding Author agrees to credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen. The Corresponding Author warrants that each Co-Author will also credit the Book in which the Chapter has been published as the source of first publication, as well as IntechOpen, when they are distributing or re-publishing the Chapter.
\n\n3.2 When submitting the Chapter, the Corresponding Author agrees to:
\n\nThe Corresponding Author will be held responsible for the payment of the Open Access Publishing Fees.
\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
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