Quantitative echocardiographic criteria for severe MR in primary and secondary disease of the mitral valve [16].
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
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Milk processing allows the preservation of milk for days, weeks, or months and helps to reduce food-borne illness.",isbn:"978-1-78985-730-6",printIsbn:"978-1-78985-729-0",pdfIsbn:"978-1-78985-919-5",doi:"10.5772/intechopen.73442",price:119,priceEur:129,priceUsd:155,slug:"milk-production-processing-and-marketing",numberOfPages:202,isOpenForSubmission:!1,hash:"d0b383fbc5e2a2fcc9da5bd58766529d",bookSignature:"Khalid Javed",publishedDate:"July 17th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6911.jpg",keywords:null,numberOfDownloads:6071,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfDimensionsCitations:3,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 12th 2018",dateEndSecondStepPublish:"August 2nd 2018",dateEndThirdStepPublish:"October 1st 2018",dateEndFourthStepPublish:"December 20th 2018",dateEndFifthStepPublish:"February 18th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:"Edited by",kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"136829",title:"Dr.",name:"Khalid",middleName:null,surname:"Javed",slug:"khalid-javed",fullName:"Khalid Javed",profilePictureURL:"https://mts.intechopen.com/storage/users/136829/images/system/136829.jpeg",biography:"Dr. Khalid Javed is a Professor of Animal Breeding and Genetics in the Department of Livestock Production at the University of Veterinary and Animal Sciences, Lahore. He graduated in Animal Husbandry from University of Agriculture, Faisalabad in 1982. He earned his Master’s and Doctorate degrees in Animal Breeding and Genetics from University of Agriculture, Faisalabad. He joined Government of Punjab, Livestock and Dairy Development as Veterinary Officer in 1983 and remained engaged in research in different capacities. Dr. Khalid conducted research, trainings and teaching in the fields of Animal Breeding, Population/Quantitative Genetics, and Statistical Genetics. He analyzed the production data of various livestock species (e.g., cattle, buffalo, sheep, goats, chicken) to characterize the phenotypic and genetic structure related to different traits of economic importance and subsequent selection. Moreover, he has been engaged in inter-disciplinary collaborative research with colleagues from various academic and research institutes to study the genetic, breeding, management and environmental factors affecting productivity of livestock species. He joined University of Veterinary and Animal Sciences during 2003 as Assistant Professor where he was later selected and appointed as Associate Professor and Professor, in 2006 and 2011 respectively. His research focus is on selection and breeding of large and small ruminants. He also supervises and evaluates postgraduate research to ensure successful and timely completion of the projects focusing on genetic improvement, enhancing breeding efficiency and production enhancement of farm animals. In addition, he participates and conducts trainings, workshops, conferences and seminars, and writes scientific publications to disseminate knowledge and techniques to the researchers and livestock producers about various areas of animal husbandry for improving behaviour, health, growth, fertility and production of livestock. He has more than 200 publications/research articles published and is working as Senior Editor of an internationally recognized Journal of Animal and Plant Sciences-JAPS.",institutionString:"University of Veterinary and Animal Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Veterinary and Animal Sciences",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"326",title:"Food Industry",slug:"food-industry"}],chapters:[{id:"65652",title:"Current Standing and Future Challenges of Dairying in Pakistan: A Status Update",slug:"current-standing-and-future-challenges-of-dairying-in-pakistan-a-status-update",totalDownloads:1359,totalCrossrefCites:0,authors:[{id:"270832",title:"Dr.",name:"Muhammad Naeem",surname:"Tahir",slug:"muhammad-naeem-tahir",fullName:"Muhammad Naeem 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This functional disorder of the mitral valve is more common and far more complex than organic MR. In secondary MR, mitral valve is structurally normal (or almost normal) but its geometry and function are disrupted due to an imbalance between closing and tethering forces secondary to alterations in the geometry and function of the left ventricle. Functional MR can promote progressive LV remodeling. This results in a vicious circle, with both LV dilatation and functional MR acting as self-perpetuating processes. While prognosis is affected only in severe organic MR, even a mild functional MR may significantly worsen the outcome. However, it is unclear whether the unfavorable impact of functional MR on prognosis is independent of underlying LV dysfunction. We still do not know if mitral valve surgery, effective in the treatment of organic diseases of the mitral valve, can be equally beneficial in functional MR, since the surgical correction of valve dysfunction does not reverse the underlying LV pathology. Thus, indications for mitral valve surgery in heart failure (HF) patients with functional MR are not well defined in any currently available guidelines. Also the role of other treatment modalities, such as medical and interventional therapies, still raises controversies because of their limited effectiveness in functional MR management. This is related to both the underlying heart disease and the complexity of functional MR phenomenon. Also, adequate assessment of functional MR mechanisms and severity by means of imaging studies prior to making any therapeutic decisions constitute a challenge for clinicians. Cardiac dyssynchrony is a mechanism that provides a pathophysiologic basis for potential improvement of functional MR after the use of cardiac resynchronization therapy (CRT).
\nThis part of the book presents the pathomechanism of functional MR with particular emphasis on the influence of cardiac dyssynchrony on mitral valve function, as well as the mechanisms of MR improvement after implantation of a CRT device, and prognostic value of both functional MR and its regression in response to CRT in patients with chronic heart failure.
\nFunctional MR is a common, but often ‘silent,’ finding in heart failure patients [1–6]. Reported prevalence of functional MR varies depending on a diagnostic method (angiography, color Doppler echocardiography) and heart failure etiology (ischemic, non-ischemic) [1–5]. The incidence of functional MR after myocardial infarction varies from 20 to 50% but exceeds 50% in patients with non-ischemic dilated cardiomyopathy [4–6]. According to general estimates, nearly a half of heart failure patients may have a functional MR of some degree, and approximately one-third of them may suffer from moderate or severe functional MR [1, 3, 7].
\nFunctional MR is an independent predictor of worse prognosis in patients with either ischemic or non-ischemic etiology of heart failure [3]. In patients with non-ischemic LV dysfunction, functional MR is associated with a two- to three-fold increased risk of heart failure episodes and cardiac mortality [4]. After myocardial infarction the presence of at least moderate functional MR is associated with a 3-fold increased risk of heart failure and a 1.6-fold increased risk of death at the 5-year follow-up [2]. Assessment of mitral valve function is included in routine risk stratification after myocardial infarction.
\nFunctional MR is present in a large proportion of patients eligible for cardiac resynchronization therapy, with the incidence varying slightly from population to population and depending on the evaluation method. Significant—that is, at least moderate—functional MR is present in about 40% of patients qualified to CRT [8–10]. Nowadays, functional MR no longer disqualifies patients from resynchronization therapy if such treatment is indicated. Furthermore, a decrease in functional MR severity is a determinant of response to CRT [10–12].
\nAdequate evaluation of functional MR requires detailed clinical information (including functional NYHA class), physical examination, electrocardiography, and imaging studies. Echocardiography is essential for the evaluation of mitral valve anatomy and quantification of MR severity [13]. Transthoracic and transesophageal echocardiography may provide complementary clinically useful information, especially in the context of surgical or transcatheter repair feasibility. Usually, transesophageal echocardiography is more suitable for the evaluation of underlying anatomical conditions and identification of functional MR mechanism. However, due to changes in LV loading conditions during transesophageal evaluation (vasodilatory effect of sedation, hypovolemia, or anesthesia), the severity of functional MR may be underestimated; this favors transthoracic echocardiography as a method to quantify mitral regurgitation. Moreover, transthoracic examination is more suitable for the evaluation of other important parameters, such as LV volume, function and sphericity, left atrial size, pulmonary artery pressure, and function of the right ventricle and tricuspid valve. Three-dimensional (3D) echocardiography (either transesophageal or transthoracic) may provide additional information about MR severity, especially with regard to noncircular orifice geometry in functional MR [14]. 3D echocardiography overcomes some limitations of two-dimensional (2D) imaging; for example, it can be used for direct planimetric measurement of vena contracta area, a parameter which corresponds directly to the effective regurgitant orifice area (EROA) irrespective of the orifice shape or number of jets. However, both 3D and 2D color Doppler flows tend to overestimate the jet area (volume) due to their known bias in correct assessment of a turbulent stream. Considering all the difficulties previously mentioned, it needs to be stressed that no single parameter (also “quantitative”) is sufficient to adequately assess the severity of functional MR and thus, this condition should be evaluated with multiple methods [14].
\nIn practical terms, echocardiographic severity of MR can be graded as mild, moderate or severe. Since available evidence suggests that functional MR of lesser severity may have similar or greater impact on mortality than primary MR [2], distinguishing between moderate and severe MR becomes of vital importance [15]. While severe primary MR is defined as EROA ≥ 40 mm2 and regurgitant volume ≥ 60 mL, in line with current guidelines, severe secondary MR should be diagnosed whenever EROA ≥ 20 mm2 and regurgitant volume ≥ 30 mL [13, 15] (Table 1) [16]. However, adequate evaluation of functional MR severity in a clinical setting is far more challenging. In functional MR, both regurgitant orifice and jet area depend strongly on the mechanism of mitral regurgitation. Functional MR severity may be overestimated if determined based on the jet size on color Doppler imaging, or underestimated if assessed using other traditional measures of mitral regurgitation such as proximal isovelocity surface area (PISA) and vena contracta width [14]. Also the limitations of the volumetric method in the assessment of regurgitant volume and fraction are well-known issues [14]. Furthermore, low inter- and intra-observer agreement between cardiologists reviewing the same dataset was documented [17]. It is now known that due to the limitations inherent to each available method, no single parameter is accurate enough to quantify the degree of MR. Therefore, current guidelines recommend an integrative approach including multiple qualitative and quantitative parameters, along with certain signs and measures of MR severity, such as left ventricular size and function, left atrial size, mitral valve leaflet morphology and motion, mitral filling pattern, pulmonary venous flow pattern and others [13, 16]. If during the first attempt MR is not unequivocally defined as mild or severe, the integrative approach should be used to exclude the severe character of mitral regurgitation.
\n\n | Primary (organic) MR | \nSecondary (functional) MR | \n
---|---|---|
EROA | \n≥0.4 cm2 | \n≥0.2 cm2 | \n
Regurgitant volume | \n≥60 mL | \n≥30 mL | \n
Regurgitant fraction | \n≥50% | \n≥50% | \n
Vena contracta | \n≥0.7 cm | \n— | \n
Jet area | \nCentral jet >40% LA or holosystolic eccentric jet | \n— | \n
Quantitative echocardiographic criteria for severe MR in primary and secondary disease of the mitral valve [16].
Functional MR is an evidently dynamic phenomenon. A typical phasic variation in regurgitant volume and orifice, with the maximum values observed in early and late systole and minimum ones in mid-systole (at peak transmitral pressure gradient generated by LV), is documented [18]. This intra-beat variability (referred to as the “loitering pattern”) hinders functional MR assessment, which is traditionally carried out in mid-systole. The severity of functional MR may also show a beat-to-beat variability depending on changes in loading conditions and hemodynamic parameters (e.g., during arrhythmia). The dynamic nature of functional MR has particular practical meanings in two situations: during physical exertion and intraoperative assessment. Induction of anesthesia and inotropic agents may significantly reduce MR and thus, may directly affect intraoperative decisions regarding its repair. Owing the dynamic nature of functional MR, in patients whose symptoms at rest are inadequate to assess the severity of mitral regurgitation, more accurate information may be obtained during exercise echocardiography. Exercises contribute to a greater cardiac load and thus, may also trigger dynamic geometric changes in the LV and mitral valve apparatus (even despite the lack of provoked ischemia), which may eventually result in acute “flash pulmonary edema” [19]. This may be a reason behind worse prognosis associated with even a mild functional MR. An exercise-induced increase in EROA by at least 13 mm2 was shown to correlate with higher morbidity and mortality [20]. Exercise echocardiography may also unmask increasing pulmonary artery pressure and the lack of LV contractile reserve, both being important predictors of the outcome [19, 20]. Finally, exercises may reveal or trigger greater LV dyssynchrony with increased functional MR [21]. Despite some caveats of this approach, current guidelines recommend echocardiographic quantification of secondary MR during exercises, as this may provide prognostically important information about dynamic characteristics of this condition [13]. Owing to documented limitations of echocardiography in this setting, newer imaging techniques, such as cardiac magnetic resonance and multidetector-row computed tomography, play an increasing role in the evaluation of patients with heart failure and functional MR. Both these techniques provide complementary data, such as true volumetric measures of cardiac chamber size and function, and can be used to assess myocardial viability and scars.
\nThe term “functional mitral regurgitation” refers to a dysfunction of the valve without its primary organic damage. Optimal function of the mitral valve provides nonrestrictive blood flow during diastole and leak tightness during systole. This diastolic and systolic competence is possible due to a synchronous coordination of all components of the mitral valve apparatus, acting under a balanced influence of closing and opening forces. Mitral valve apparatus is an integrated unit consisting of mitral valve itself (formed by two leaflets and mitral annulus) and subvalvular components (chordae tendineae, two papillary muscles, left ventricle and posterior left atrial wall). An effective function of the mitral valve is determined not only by the compatible cooperation between its components but also by their appropriate structural and spatial relations.
\nAll changes in LV function and geometry affect functioning of mitral valve through opposing strength vectors: the tethering force (created by displacement of papillary muscles) and the LV-generated leaflet closing force (created by effective contraction causing transmitral pressure gradient) (Figure 1) [22]. Global LV dilation results in incomplete mitral leaflet closure and mitral regurgitation, which correlates with LV dysfunction. Local or global dilation of the LV is a prerequisite for incomplete mitral leaflet closure [22]. However, functional MR does not result from LV dilatation per se but from an increase in LV sphericity and resultant posterolateral displacement of the papillary muscles [23, 24]. If functional MR has an ischemic etiology, it does not necessarily need to be preceded by global systolic dysfunction [25]. Regional abnormalities in cardiac wall motion after inferior myocardial infarction may contribute to mitral valve tethering (with systolic tenting of the leaflets), which is strong enough to cause severe mitral regurgitation despite preserved LV ejection fraction (LVEF) [25].
\nMechanism of functional mitral regurgitation. (A) Balance of closing and tethering forces acting on mitral leaflets during systole. (B) Disrupted balance of closing and tethering forces due to local LV remodeling (dark shading). LA: left atrium; LV: left ventricle; PM: papillary muscle; Ao: aorta; ME: mitral regurgitation.
Two main patterns of leaflet tethering can be distinguished in functional mitral regurgitation (Figure 2) [26, 27]. The symmetric pattern is characterized by global LV dilation with increased sphericity and predominant apical displacement of both leaflets with central regurgitant jet direction. Also the mitral valve annulus dilates symmetrically, primarily in the septal-lateral direction [26, 27]. This configuration is typical for non-ischemic functional MR (Carpentier type III B symmetric) [27, 28]. The asymmetric pattern is typically resulted from local remodeling of the posterior papillary muscle-bearing wall segment, with posterior tenting of both leaflets and a posteriorly directed asymmetric regurgitant jet (Carpentier type III B asymmetric) [25–28]. While the displacement of posterior papillary muscle is similar regardless of the leaflet tethering pattern, symmetric tethering is characterized by greater posterior and lateral displacement of anterior papillary muscle and longer inter-papillary distance [27]. Both patterns of leaflet tethering can be observed in ischemic MR [25–27]. The occurrence of the symmetric pattern in ischemic MR is associated with more advanced systolic dysfunction, global remodeling and increased LV sphericity [23, 24, 27]. This pattern is typical for non-ischemic dilated cardiomyopathy [26].
\nPatterns of leaflet tenting in functional mitral regurgitation. (A) Normal coaptation of mitral leaflets. (B) Asymmetric pattern—predominant posterior displacement of both leaflets with prevent restriction of posterior leaflet and large eccentric regurgitant jet. (C) Symmetric pattern—predominant apical displacement of both leaflets with central regurgitant jet.
While geometric changes of LV are an essential component of functional MR pathomechanism, it is the tethering distance between the tip of posterior papillary muscle and the anterior pole of mitral annulus (“posterior papillary-fibrosa distance”), which constitutes the final common pathway determining the plane of leaflet coaptation [22, 29]. Mitral annular dilation typically occurs at late stage of ischemic MR [30, 31]. Isolated dilation and flattening of mitral valve annulus are occasionally the cause of severe mitral regurgitation, representing type I in Carpentier’s classification [28, 30, 31]. Although atrial fibrillation constitutes a quite frequent cause of functional MR, it rarely results in severe valve dysfunction. Isolated enlargement of the left atrium, with concomitant atrial fibrillation or without, leads to dilatation of mitral annulus and reduced leaflet coaptation [32]. Diastolic MR results from a reversal of atrioventricular pressure gradient during diastole. This form of MR occurs in patients with atrioventricular block, cardiomyopathy and aortic regurgitation, as well as in individuals with long filling periods in atrial tachyarrhythmia [31].
\nDyssynchrony, defined as an uncoordinated regional myocardial contraction [33, 34], may manifest as (1) “primary electrical dyssynchrony” (i.e., electrical conduction delay which causes non-uniform timing of myocyte depolarization), (2) abnormalities in excitation-contraction coupling (a surrogate for regional electromechanical coupling is the interval between the onset of QRS complex in ECG and the onset of systolic velocity in spectral pulsed-wave tissue Doppler imaging), or (3) “primary mechanical dyssynchrony” (i.e., a regional delay in onset shortening and in time to peak shortening of LV segments) [34]. Primary electrical dyssynchrony is typical for left bundle branch block (LBBB) and primary mechanical dyssynchrony—for regional ischemia or fibrosis [33, 34]. Currently, QRS duration remains the only clinically significant surrogate for the timing of myocardial contraction and the only criterion amenable for CRT [35, 36]. Clinical significance of “clear” primary mechanical dyssynchrony remains ambiguous [37, 38]. CRT does not provide any benefit (and may be even harmful) in heart failure patients with mechanical dyssynchrony without QRS widening (<130 ms) [38]. Various echocardiographic measures of dyssynchrony turned out not to be a superior selection criterion for CRT [39, 40]. Moreover, unacceptable variability, poor reproducibility and limited practical predictive value of the most echocardiographic parameters of dyssynchrony are documented [41]. Thus, although the predictive value of prolonged QRS also varies from study to study [42, 43], qualification to CRT is still based primarily on this parameter [35, 36].
\nFunctional MR correlates strongly with QRS duration. Left bundle branch block and right ventricular pacing (which produce a conduction abnormality similar to LBBB), but not right bundle branch block or left anterior hemi-block, are strongly associated with functional MR [44]. The relationship between right ventricular pacing and mitral regurgitation indicates that the key determinant of functional MR is a conduction abnormality, rather than the underlying disease causing LBBB [44]. Those findings have important implications for biventricular pacing as a treatment option in heart failure patients with functional MR.
\nLV dyssynchrony is a less important determinant of functional MR than systolic valvular tenting, which is the strongest predictor of EROA [45]. However, the impact of systolic valvular tenting on functional MR in different subsets of patients with LV dysfunction varies. Mitral valve tenting and local LV remodeling (in the papillary muscle-bearing wall segments), but not regional dyssynchrony, are independent predictors of functional MR degree in ischemic LV dysfunction; these local changes result directly from ischemic lesions. In non-ischemic LV dysfunction, regional dyssynchrony exacerbates functional MR independently of LV geometry but as a factor of lesser importance [45].
\nCardiac resynchronization therapy is an established treatment option for patients with advanced chronic heart failure and prolonged QRS duration [35, 36]. The benefits of CRT are attributed mainly to increased efficiency of LV filling and ejection, resulting from the improvement in atrioventricular coupling, intra- and interventricular synchronization [46–48]. CRT can attenuate heart failure symptoms and improve exercise capacity and survival in patients with heart failure and prolonged QRS duration [49–51]. In line with current ESC guidelines, cardiac resynchronization therapy is recommended (class I recommendation) in symptomatic (despite optimal medical therapy) patients with heart failure in sinus rhythm, with LBBB and QRS duration of at least 130 ms, with LVEF ≤ 35%, and in individuals with LV dysfunction (regardless of the NYHA class) who have an indication for ventricular pacing and high degree atrioventricular block [36]. The outcome of cardiac resynchronization therapy is determined by a number of clinical factors, and improvement of functional mitral regurgitation is currently considered as one of the mechanisms underlying the beneficial effect of the treatment.
\nEchocardiographic studies demonstrate that cardiac resynchronization therapy may correct the pathophysiologic determinants of functional MR. The following mechanisms are considered to mediate the clinical efficacy of CRT.
Restoration of the LV and papillary muscle synchronous contraction improves spatial relations and function of the subvalvular apparatus and the mitral valve itself (a decrease in mitral valve tethering force); the effect is specific for this therapeutic method [52, 53].
Improved coordination of LV wall contraction and resultant improvement of LV ejection function contribute to an increase in transmitral pressure gradient (greater mitral valve closing force); the effect is specific for this therapeutic method [54, 55].
Remote reverse remodeling of the LV with the reduction of LV volume and sphericity induce favorable changes in the geometry of mitral valve apparatus (a decrease in tethering force) and contribute to further improvement in LV systolic function (an increase in mitral valve closing force); the effect is not specific for this therapeutic method and particularly pronounced at the later phase of CRT [53, 55–57].
The effect of cardiac resynchronization therapy on mitral valve annular size and function (through the recoordination of contraction in LV basal segments and then through reverse remodeling of the LV) is uncertain [52, 53].
Optimization of atrioventricular delay with the restoration of proper timing for atrioventricular synchrony/atrioventricular relaxation contributes to generation of an adequate transmitral pressure gradient during the cardiac cycle and eliminates diastolic MR (if present); this effect is only partially specific for this therapeutic method [58].
The improvement of functional MR after the use of cardiac resynchronization therapy has two phases:
Immediate, short-term functional MR reduction occurring directly after the implantation of a CRT device. The effect manifests as better-coordinated contraction of the papillary muscle-bearing segment (diminished tethering force) and improvement of LV ejection function (an increase in transmitral pressure gradient—LV dP/dt, which represents the mitral valve closing force) [52–54]. CRT contributes primarily to a decrease in early-systolic MR [59, 60].
Late, long-term functional MR reduction occurring weeks to months after the implantation of a CRT device. This phase manifests primarily as reverse remodeling of the LV. A decrease in LV volume and sphericity induces favorable geometric changes in mitral valve apparatus, with the reduction of tethering force. The improvement of LV systolic function is reflected by an increase in closing force [53, 55, 57]. Attenuation of both resting and exercise-induced functional MR usually can be observed in this phase, along with the improvement of cardiopulmonary performance [61].
In fact, the two phases of functional MR improvement may be less distinct. LV reverse remodeling can occur relatively early [10]. Subacute improvement in systolic shape of the LV (lesser sphericity) and subvalvular traction after CRT implementation are also probably related to an increase in LV longitudinal function [56].
\nEffective CRT reduces the transmitral regurgitant volume in about 40% of patients immediately and in the next 20% of them at a later stage [53]. The sequence of functional MR improvement may depend on a pattern of baseline dyssynchrony. Early and late responders may show a similar extent of LV dyssynchrony; however, the site of latest activation in early responders is mostly inferior or posterior (adjacent to the posterior papillary muscle), whereas in late responders, the latest activation occurs primarily in the lateral wall [53]. Late responders may also show acute improvement in LV end-systolic volume, presumably as an effect of recoordinated and, hence, more effective LV contraction. Acting through the mechanisms described above, CRT can attenuate moderate-to-severe functional mitral regurgitation to a clinically non-significant MR in about one-third of heart failure patients. Published data about the association between baseline functional MR and response to CRT are ambiguous [8, 62–64]. The post-CRT improvement of functional MR may be relatively more frequent in patients with greater severity of mitral regurgitation at the baseline. Moreover, an acute or subacute attenuation of functional MR is a predictor of further improvement [8]. Lack of improvement in functional MR in response to CRT is associated with worse prognosis (unfavorable profile of clinical evolution, higher incidence of arrhythmic events and lesser occurrence of LV reverse remodeling [62, 65]). This raises a question about the predictors of functional MR response to CRT.
\nDespite appropriate selection of candidates for CRT, not all of them respond to the treatment. The mechanisms responsible for post-CRT improvement in functional MR are complex. Although QRS duration is the main determinant of primary electrical dyssynchrony and a primary criterion considered during selection of patients for CRT, it is not a good predictor of response to the treatment [42, 43]. Aside from dyssynchrony, the post-CRT improvement in functional MR may also depend on other factors, such as myocardial viability, presence of scar/fibrosis and the extent of LV remodeling at the baseline [10, 66, 67].
\nMany echocardiographic measures of dyssynchrony do not confirm their value as the predictors of CRT outcomes [39–41]. Inter-ventricular mechanical delay (IVMD, the time difference between right ventricular and left ventricular ejection, determined as the time elapsed since the onset of the QRS to the onset of left ventricular vs. right ventricular ejection, usually measured using pulsed Doppler flow) seems to be a simple and reproducible parameter of dyssynchrony, correlating well with the response to CRT, either LV reverse remodeling or functional MR improvement [10, 41, 68, 69]. Also, speckle-tracking radial strain imaging (time difference in peak septal to posterior wall strain) appears as a relatively simple measure of dyssynchrony, having established a predictive value with regard to CRT outcome [67]. There is no unambiguous evidence regarding the site of the latest activation as an independent predictor of the improvement in functional MR [10, 53]. Myocardial viability (in heart failure with ischemic etiology) and contractile reserve (in non-ischemic cardiomyopathy) are important determinants of CRT effectiveness in terms of functional MR improvement [10, 70–73]. The outcome of CRT may be also associated with the location of contractile reserve (particularly in relation to the papillary muscle-bearing segments and to the paced LV region), as well as with the size of the contractile reserve area [10, 66, 72, 73]. The importance of discordant LV lead position and myocardial scar, especially extensive scar burden, as the predictors of CRT outcomes, is documented [74, 75]. The potential role of myocardial fibrosis stimulates research on biochemical predictors of CRT responses (among them on galactin-3, a protein involved in fibrogenesis) [76].
\nThe change in LV end-diastolic volume after the use of cardiac resynchronization therapy proved to be the most powerful independent predictor of death [77]. CRT effectively reversed LV remodeling, both in patients with moderate-to-severe heart failure (NYHA III/IV class) and in individuals with mild heart failure (NYHA I/II class) [49, 50]. The response to CRT may be influenced by the presence of functional mitral regurgitation prior to the implantation of a CRT device and by its persistence despite the treatment. Patients, who do not respond to CRT, present with a significant functional MR more often than the responders [78]. On the other hand, an improvement in pre-existing functional MR contributes to LV reverse remodeling during follow-up after the implantation of a CRT device [60]. The incidence of reverse remodeling, defined as an improvement in LVEF and forward stroke volume, is the highest in patients who show a reduction of total functional MR, intermediate in individuals with mild functional MR or lack thereof at the baseline and the lowest in persons who do not show an improvement in total functional MR after 3 months of post-CRT follow-up [60]. Correlation between clinical and echocardiographic indices of post-CTR improvement is rather weak [10, 77]. However, the direction and magnitude of LV reverse remodeling correlate with survival, and a 1-year mortality after CRT implementation is predicted by echocardiographic parameters, rather than by clinical indices [77].
\nFinally, volumetric limitation for functional MR improvement in response to cardiac resynchronization therapy needs to be emphasized. Not only irreversibly damaged ischemic myocytes respond less to CRT, the post-CRT improvement in functional MR is also less likely in patients who present with greater degree of LV dilatation at the baseline. Lesser baseline LV diameters (end-diastolic and end-systolic) and volumes are the independent predictors of functional MR improvement in response to CRT [10, 67, 79–81]. The cut-off value for LV end-diastolic dimension is close to 75 mm [10, 82] and for LV end-systolic dimension index 29 mm/m2 [67]. Non-responders present a significantly higher baseline LV dilatation. CRT may be insufficient to overcome poor natural history of systolic heart failure but may slow down its progression. The effectiveness of all currently available therapeutic options is limited, and critical enlargement of the left ventricle may trigger the previously mentioned vicious circle of self-perpetuating LV dilatation and functional mitral regurgitation [10, 83, 84].
\nTherapeutic targets in patients with functional MR include attenuation of symptoms, lesser number of heart failure hospitalizations, better quality of life and, potentially, survival. At present, the most effective therapies of functional MR are aimed at the underlying LV dysfunction. Therefore, as the first step, optimal medical therapy according to the guidelines for the management of heart failure should be used [36]. As the second step, whenever appropriate, CRT should be implemented in line with the respective guidelines [35, 36]. In patients who remain symptomatic despite optimal medical therapy and CRT (if indicated), mitral valve intervention (surgical or transcatheter repair) should be considered; however, there is no evidence that a reduction of functional MR improves survival [13]. Moreover, the surgery has never clearly been demonstrated to alter the natural history of the primary disease (dilated cardiomyopathy) [85]. Limited empirical data contribute to a lower level of evidence for management recommendations, highlighting the importance of decisions made by the Heart Team. The multidisciplinary Heart Team consisting of imaging experts, heart failure and electrophysiology specialists, interventional cardiologists, and cardiac surgeons should try to reach a consensus on appropriate care. Not only the feasibility of the procedure but also comorbidities, the level of surgical risk, and surgeon experience should be considered [13]. In patients undergoing revascularization, the evaluation and decision to treat (or not to treat) ischemic MR should be made prior to surgery. There is an overall agreement that severe functional MR should be addressed at the time of coronary artery bypass grafting (CABG). The management of moderate functional MR in patients undergoing CABG still raises controversies [86]. The thresholds of functional MR severity are also a matter of debate (as stated earlier). Surgical options in patients with functional MR include mitral valve repair and replacement. Mechanical LV-assisted devices and heart transplantation should be considered in the most advanced stage of heart failure.
\nThe controversies regarding an optimal surgical approach should be emphasized [87]. After surgical annuloplasty (undersized complete ring to restore leaflet coaptation), residual or recurrent functional MR is frequently observed (in approximately one-third of the cases) [88]. Valve-sparing mitral valve replacement techniques (leaving the leaflet and subvalvular apparatus intact to preserve the LV function) should be considered in patients with echocardiographic predictors of repair failure (Table 2) [88]. The surgery should also be considered in heart failure patients with severe functional MR and LVEF <30% but with an option for CABG and the evidence of myocardial viability. Qualification for surgical treatment of functional MR should be restrained if concomitant revascularization is not indicated [89].
\nMitral valve deformation | \nCoaptation distance ≥1 cm Tenting area > 2.5–3 cm2 Complex jets originating centrally and posteromedially Posterolateral angle >45° (high posterior leaflet tethering) | \n
Local LV remodeling | \nInterpapillary muscle distance >20 mm Posterior papillary-fibrosa distance >40 mm Lateral wall motion abnormality | \n
Global LV remodeling | \nEDD >65 mm, ESD >51 mm (ESV >140 mL) (low likelihood of reverse LV remodeling after repair and poor long-term outcome) Systolic sphericity index >0.7 | \n
Unfavorable TTE characteristics for mitral valve repair in secondary MR [88].
EDD, end-diastolic diameter; ESD, end-systolic diameter; ESV, end-systolic volume; LV, left ventricle.
Percutaneous edge-to-edge repair (MitraClip device) for FMR is a low-risk procedure and may be considered in patients during high surgical risk, whenever feasible [90]. The treatment may attenuate symptoms, improve quality of life and promote LV reverse remodeling but is inferior to surgical methods in terms of functional MR reduction. Valve intervention is generally contraindicated in patients with LVEF < 15% [13]. Two investigational extracardiac devices, CorCap (Acorn Cardiovascular) [91] and Coapsys (Myocor, Inc., Maple Grove, Minnesota) [92], which have been used to reshape the LV and thus to reduce the degree of functional MR, remained an interesting experiment. In cases of more advanced LV dysfunction (LVEF ≤ 30%) with no option for CABG, the Heart Team should choose between a palliative treatment of functional MR (surgical or transcatheter procedures, ventricular assist devices, heart transplantation) and a conservative therapy, after careful individual appraisal of the patient [13].
\nIrrespective of heart failure etiology, functional mitral regurgitation has a significant unfavorable impact on prognosis. The benefits of surgical treatment in functional mitral regurgitation are unclear and thus, resynchronization therapy remains a valuable option in eligible patients. Indications for such treatment should be considered as early as possible, before the development of a severe left ventricular dilatation, a predictor of failure in resynchronization therapy.
\nCABG | coronary artery bypass grafting |
CRT | cardiac resynchronization therapy |
EROA | effective regurgitant orifice area |
HF | heart failure |
LBBB | left bundle branch block |
LV | left ventricle |
LVEF | left ventricular ejection fraction |
MR | mitral regurgitation |
NYHA | New York Heart Association |
PISA | proximal isovelocity surface area |
Retail stores manage millions of items on a day to day basis to deliver to their customers. Point of Sales (POS) systems with barcodes were among the first technologies used to track products across the supply chain and in stores. Barcodes, as an identification technology, are not utilized at item-level but usually represent a group of products. Retailers need to scan products at pallet level at the point of receiving shipments, in inventories entrance and exit places, and at the POS to keep track of what is coming into and leaving stores [1]. With barcode systems, inventory inaccuracy is created because stores barcode scanning are not always performed at the right time and the right location. This inventory inaccuracy leads to a significant loss at retailers. Retailers needed to explore new ways of tracking their items to lower the inventory inaccuracy and prevent consequent losses. Radio Frequency Identification (RFID) technology appears to be the new technology solution that could improve the inventory record accuracy of stores for various items.
\nRFID technology applications have been recognized in many areas such as healthcare, finance, manufacturing, and retail. The share of the RFID market in retail is projected to be the largest of all sectors with about 34% by 2026, followed by transportation sector (25%), financial and security services (22%), and other industries such as healthcare and manufacturing at smaller portions [2]. RFID tags can store more information about each item at real time and can have individualized identification for items versus barcodes with a small data storage capacity that can only identify a group of items. RFID readers do not need to be on the line of sight to read RFID tags information which means items can be scanned more frequently and faster at any movement. These capabilities allow little mistakes in tracking records and largely eliminates inventory inaccuracy.
\nRFID technology’s benefits to retailers were identified early at the beginning of the 21st century. However, RFID’s applications in retail stores on a large scale took a while to be implemented. This paper reviews utilizing RFID, as an ideal solution to retail operations, since earlier this century and will cover a twenty-year horizon (2001–2020) divided into three equally long periods of 2001–2007, 2008–2014, and 2015–2020.
\nIn studies done earlier in this century, RFID was recognized as the next major identification technology to replace barcode systems in the retail industry [3, 4, 5, 6, 7]. Barcode systems have been used to track customer purchases, to manage inventory records, and to offer promotion and advertising in retail since 1970 [8]. Barcode tags, however, need to be on the line of readers to be read, a requirement that makes physical inventory counting a labor-intensive task and prevents stores from updating their inventory records frequently and on time. Therefore, with barcode systems, inventory inaccuracy is significant [9]. Inventory inaccuracy refers to the difference between inventory on record and the actual number of items on hand in stores. Inventory inaccuracy is caused by many factors such as transaction errors in the POS system, or shrinkage caused by possible employee/customer theft. Inventory inaccuracy means that stores may not be able to place inventory orders on time, resulting in out-of- stock conditions and consequently losing sales and hurting customer shopping experience. RFID technology, on the other hand, enhances product visibility in store operations and across the supply chain through the ease of reading RFID tag information and updating inventory records on a real-time basis.
\nStudies have investigated RFID benefits in different areas of retail operations, such as supply chain management, and show how inventory inaccuracy and consequently out-of-stock conditions are improved with the implementation of RFID across the supply chain [10, 11, 12]. Enhanced information visibility, provided by RFID in the supply chain, decreases uncertainties and lowers high inventory costs associated with the uncertainties [13, 14].
\nMany pilot studies during this period investigated and explored the applications of this technology at the pallet level, case level, and item levels in stores [1, 6, 12, 15, 16]. [1] conducted a case study in 2005 to analyze pallet and case-level implementation of RFID and enhanced visibility generated at the receiving gates and entrance doors from backstore to sales floors. They demonstrated that safety stock and inventory holdings can be significantly reduced and RFID benefits are broad, ranging from labor efficiencies to inventory management improvements. Cost–benefit analyses in this period showed that pallet-level implementations of RFID were more cost effective than case-level implementations.
\nMetro Group in Germany conducted some case studies in their stores to show item-level RFID applications can improve customers’ shopping experiences as well. They introduced some tools provided by RFID technology such as automatic checkout, smart carts that help customers navigate stores and find their items easier and faster, and smart dressing rooms that help customers find their desired apparel items more conveniently [6, 16]. They demonstrated that utilizing these tools significantly enhances customers’ shopping experience.
\nWalmart retail stores in the US were the first retailers that decided to mandate the implementation of RFID at pallet and case level across some of their supply chain in 2005. Walmart also did a pilot study with 24 stores over a period of around 6 months to measure how RFID can improve inventory management. They demonstrated out-of-stock conditions were significantly reduced with the implementation of RFID technology [12].
\nIn Asia, two Singaporean fashion retailers piloted item-level RFID on their apparel stores and reported significant reduction in stocking time from hours to minutes that consequently increased the frequency of counting items with handheld readers and improved inventory accuracy [17].
\nFinancial crises and the great recession that started in 2008 did not work to the advantage of retailers that were planning to implement RFID applications in their stores. During financial crises, businesses tend to adopt strategies that could help them sustain and survive by spending low and investing less. RFID technology implementation plans were mostly postponed or slowed down during the financial crises. However, this period was the best time to develop some foundations with respect to policies, regulations, and standardization of the technology.
\nPrivacy issues raised by consumer protection agencies and standardization issues across different platforms put forward by case studies and pilot projects led to the development of some regulations and privacy policies by governments, institutions, and businesses. European Commission (EC) took an active role by funding many initiatives across Europe [18]. Initiatives such as Coordinating European efforts for promoting the European RFID value chain (CE RFID) [19] and Building Radio frequency Identification solutions for the Global Environment (BRIDGE) [20], conducted from 2006 to 2009, highlighted that wide implementation of RFID technology needs some regulations, standardizations, and privacy policies in place. For example, the BRIDGE project, coordinated by GS1, helped the industry to develop standardizations such as establishing a common format for the data stored on RFID tags, or the availability of possible frequency bands.
\nRFID tags can store identifiable consumers’ private data, which need to be protected. Therefore, EU members signed an agreement on the Privacy Impact Assessment framework in order to protect consumer privacy [21, 22, 23]. This agreement established some rules to be followed in the design of smart chips such as RFID tags to protect the privacy of consumers’ data. Consumers should be informed if RFID tags are utilized in stores. In addition, tags must be deactivated at the point of sales at no cost [24]. This framework was later expanded to cover some rules for smart meters as well. In the United States, lawsuits against RFID application patents as well as privacy issues in 2011–2013 were setbacks for large-scale implementations of the technology. The National Institute of Standards and Technology (NIST) in the US has helped to establish some guidelines to help retailers; however, most of the development of policies and standardizations have been initiated by corporations in the US.
\nIn addition to developing policies and standardizations, businesses had more chances to identify and learn broader applications of RFID technology in retail. The focus of most of earlier pilot studies was how this new tracking technology helps manage inventories better in order to avoid out-of-stock conditions. However, the applications of the technology go beyond only inventory management and tracking items throughout the supply chain. As shown in the balanced scorecard developed in [25], RFID benefits extend to marketing and merchandising operations in retail as well (Figure 1).
\nBalanced scorecard for RFID applications in retail.
In marketing, stores can monitor the behavior of consumers better when customers use tools such as smart carts or smart dressing rooms provided by RFID. Retailers can learn about consumers’ preferences and reflect that in the promotion and advertising offered to customers in real time while they shop. The available tools such as smart dressing rooms and smart carts also enhance customer shopping experience. Use of these tools enables customers to find their desired items more conveniently and faster, which eventually leads to higher customer satisfaction and increase in sales.
\nIn merchandising, enhanced visibility on consumer behavior in stores provided by RFID can help retailers identify better assortments of products. In addition, an enhanced visibility means better shelf-replenishment; that is stores can reduce the shelf space since enhanced visibility on shelves allows retailers to replenish them as soon as they become emptied. Less shelf space leads to holding less number of items on shelves at any given time and consequently less inventory and capital held in stores, which allows retailers to invest in carrying more variety for products in stores.
\nThere were also more studies during this period conducting cost–benefit analysis of the implementation of the technology. The fixed cost of implementation includes middleware, fixed antennas, sensors, and readers and the variable cost includes the cost of tags per item. The cost of tags can be added to the cost of each product but then the big question is who has to pay for that cost. Should the cost be transferred to consumers or should that be shared between retailers and manufacturers? The tag cost as the variable cost of utilizing the technology is huge and cost–benefit analysis studies have shown it to be a major barrier to the implementation of the technology during this period. [26] showed that the cost of tags in item-level implementation of RFID, as the variable cost, is cumbersome. Moreover, the cost can exceed the benefits in some cases depending on the extent to which stores implement RFID applications. The cost barrier was expected to weigh less as the cost of tags became lower over time.
\nSurveys of businesses show the implementation of RFID has picked up in this period. A survey of 60 retail executives throughout the United States and Europe showed about 73% of retailers had plans to implement RFID in 2016 [27]. Another survey in 2018 [28], however, showed that 92% of retailers in North America plan on implementing RFID, which is about a 20% increase from the 2016 results.
\nThe cost of implementation has been decreasing over time, as expected, and at the same time retailers have learned how to partially implement the technology. Retailers realized that they do not need to fully implement the technology. In some cases, only tags and hand-held readers are used to add visibility of items in stores without many of the infrastructures such as antennas. Cloud services, on the other hand, have allowed retailers to eliminate some of the middleware cost as well. The leading European fashion stores C & A is one of many retailers that explored lower cost implementations with partial utilization of the technology [29].
\nRFID platforms can generate big data that are the records of tracking items throughout the supply chain and stores in real time. Businesses need big data and business analytics capabilities to fully utilize technologies [30]. The results of the analysis of such data can help retailers improve their processes such as shelf-replenishment process as well as variety and assortment planning that have been used in the same format for many years. A new timely replenishment process can result in better management of physical space, layouts, and lowering holding costs in stores. Furthermore, a better variety and assortment planning means fulfilling customers’ expectations and eliminating unpopular items that releases some capital and allow investment opportunities in other areas in retail.
\nCompeting technologies to RFID have been developed and utilized over time as well. For example, Quick Response (QR) codes give retailers better ability to manage items compared to barcodes, Near-Field Communication (NFC) technology has some capabilities compared to UHF RFID, and most recently Amazon’s cameras increase product visibilities in stores for fast checkouts. In addition, retailers have different priorities in investing in new technologies and there is competition for dollars invested in various technologies by retailers. For instance, a retail chain can focus on improving inventory operations, but another retailer may be focused on improving marketing operations and customer shopping experience in stores by developing new apps that can assist customers make decisions during their shopping time in stores. In a different example, Gucci as an Italian luxury brand name does not suffer from inventory inaccuracy issues but their priority is customer shopping experience and they have utilized RFID tags to protect customers against counterfeiting across the supply chain until products reach their customers [31].
\nOmnichannel retail has been widely available during this period of time. Retailers’ customers can shop at any time, in any place, and via any shopping channel. Omnichannel retailing needs accurate inventories and enhanced product visibility more than any other time. Item-level RFID can, therefore, accommodate the needs of omnichannel retail more than other technologies available [32]. In addition, blockchain as the latest technology in retail can provide automatic exchange of product data carried by RFID tags between different partners across the supply chain. The blockchain in retail solutions are currently being studied in a consortium of large retailers such as Nike, Macy’s, and Dillard’s in an RFID lab at Auburn University [33].
\nThe 3-S model (substitution, scale, and structure) introduced in [34] discussed and projected different phases of the adoption of RFID earlier when this technology was introduced. Later the 3-S model was adapted by [35] to describe the current stage of retailers’ implementation of RFID applications in retail (Figure 2). The substitution and scale stages are covering mostly what has been achieved during the three periods discussed in this paper. In the substitution phase, the RFID technology was utilized to replace the applications of barcode systems in tracking products. In the scale phase, the RFID applications are enabling retailers to manage their operations with more accuracy, efficiencies, and at a higher speed and scale. The structure phase, that is re-engineering processes and completely overhauling retail operations, is still underway. The RFID technology will enable retailers to accomplish things they could not imagine before and allows retailers to tap into completely new domains and applications.
\n3-S model for RFID retail adoption.
Retailers have different needs based on the way they operate in stores. Some retailers must manage large inventories in stores. An enhanced visibility on their products help them improve inventory accuracies and avoid out-of-stock and increase their efficiencies. On the other hand, some retailers have small backstore inventories and every item they receive is put directly on their shelves and available to their customers. Inventory management is not their priority, but they need to focus more on customer shopping experience. Therefore, the enhanced visibility of items in stores is expected to promote retailers’ marketing operations. Depending on the way retailers operate and what their priorities are, retailers have to plan on implementing appropriate applications of RFID technology.
\nAs discussed in this paper, RFID has been utilized broadly with various applications. As a revolutionary technology, RFID’s implementation can go beyond improving the current processes in retail operations. The current processes can innovatively change to debut completely new applications that are only possible with the enhanced visibility of items in real time. The ensuing big data that is derived from the visibility provided by RFID tags can be analyzed, leading to innovations in retail operations.
\nImplementing item-level RFID needs to be part of omnichannel strategy in the retail sector. With the wide-spread usage of online retail services such as Amazon, the competition in retail is tougher than ever before. In omnichannel services, retailers need to grant their customers easy access via different channels and make their products available in a variety of delivery services. The accessibility and fast delivery will not be possible with the level of visibility provided by barcode systems. Utilization of technology in retail is evolving quickly and RFID technology is the one that can definitely help retailers win in this overhaul.
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