FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2510663617> ?p ?o ?g. }

• W2510663617 endingPage "339" @default.
• W2510663617 startingPage "315" @default.
• W2510663617 abstract "The J-wave syndromes (JWSs), consisting of the Brugada syndrome (BrS) and early repolarization syndrome (ERS), have captured the interest of the cardiology community over the past 2 decades following the identification of BrS as a new clinical entity by Pedro and Josep Brugada in 1992 [1]. The clinical impact of ERS was not fully appreciated until 2008 [2]-[4]. Consensus conferences dedicated to BrS were held in 2000 and 2004 [5], [6], but a consensus conference specifically focused on ERS has not previously been convened other than that dealing with terminology, and guidelines for both syndromes were last considered in 2013 [7]. A great deal of new information has emerged since. The present forum was organized to evaluate new information and highlight emerging concepts with respect to differential diagnosis, prognosis, cellular and ionic mechanisms, and approaches to therapy of the JWSs. Leading experts, including members of the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asian-Pacific Heart Rhythm Society (APHRS), met in Shanghai, China, in April 2015. The Task Force was charged with a review of emerging concepts and assessment of new evidence for or against particular diagnostic procedures and treatments. Every effort was made to avoid any actual, potential, or perceived conflict of interest that might arise as a result of outside relationships or personal interest. This consensus report is intended to assist health care providers in clinical decision-making. The ultimate judgment regarding care of a particular patient, however, must be made by the health care provider based on all of the facts and circumstances presented by the patient. Members of this Task Force were selected to represent professionals involved with the medical care of patients with the JWSs, as well as those involved in research into the mechanisms underlying these syndromes. These selected experts in the field undertook a comprehensive review of the literature. Critical evaluation of methods of diagnosis, risk stratification, approaches to therapy, and mechanistic insights was performed, including assessment of the risk- to-benefit ratio. The level of evidence and the strength of the recommendation of particular management options were weighed and graded. Recommendations with class designations are taken from HRS, EHRA, APHRS, and/or European Society of Cardiology (ESC) consensus statements or guidelines [8], [9]. Recommendations without class designations are derived from unanimous consensus of the authors. The consensus recommendations in this document use the commonly used Class I, IIa, IIb, and III classifications and the corresponding language: “is recommended” for a Class I consensus recommendation; “can be useful” or “is reasonable” for a Class IIa consensus recommendation; “may be considered” for a Class IIb consensus recommendation; and “is not recommended” for a Class III consensus recommendation. The appearance of prominent J waves in the electrocardiogram (ECG) have long been reported in cases of hypothermia [10]-[12] and hypercalcemia [13], [14]. More recently, accentuation of the J wave has been associated with life-threatening ventricular arrhythmias [15]. Under these circumstances, the accentuated J wave typically may be so broad and tall as to appear as an ST-segment elevation, as in cases of BrS. In humans, the normal J wave often appears as a J-point elevation, with part of the J wave buried inside the QRS. An early repolarization pattern (ERP) in the ECG, consisting of a distinct J-wave or J-point elevation, or a notch or slur of the terminal part of the QRS with and without an ST-segment elevation, has traditionally been viewed as benign [16], [17]. The benign nature of an ERP was challenged in 2000 [18] based on experimental data showing that this ECG manifestation predisposes to the development of polymorphic ventricular tachycardia (VT) and ventricular fibrillation (VF) in coronary-perfused wedge preparations [15], [18]-[20]. Validation of this hypothesis was provided 8 years later by Haissaguerre et al. [2], Nam et al. [3] and Rosso et al. [4]. These seminal studies together with numerous additional case-control and population-based studies have provided clinical evidence for an increased risk for development of life-threatening arrhythmic events and sudden cardiac death (SCD) among patients presenting with an ERP, particularly in the inferior and inferolateral leads. The lack of agreement regarding the terminology relative to early repolarization (ER) has led to a great deal of confusion and inconsistency in reporting [21]-[23]. A recent expert consensus report that focused on the terminology of ER recommends that the peak of an end QRS notch and/or the onset of an end QRS slur be designated as Jp and that Jp should exceed 0.1 mV in ≥2 contiguous inferior and/or lateral leads of a standard 12-lead ECG for ER to be present [24]. It was further recommended that the start of the end QRS notch or J wave be designated as Jo and the termination as Jt. ERS and BrS are thought to represent 2 manifestations of the JWSs. Both syndromes are associated with vulnerability to development of polymorphic VT and VF leading to SCD [1]-[3], [15] in young adults with no apparent structural heart disease and occasionally to sudden infant death syndrome [25]-[27]. The region generally most affected in BrS is the anterior right ventricular outflow tract (RVOT); in ERS, it is the inferior region of the left ventricle (LV) [2], [4], [28]-[32]. As a consequence, BrS is characterized by accentuated J waves appearing as a coved-type ST-segment elevation in the right precordial leads V1−V3, whereas ERS is characterized by J waves, Jo elevation, notch or slur of the terminal part of the QRS, and ST segment or Jt elevation in the lateral (type 1), inferolateral (type 2), or inferolateral þ anterior or right ventricular (RV) leads (type III) [15]. An ERP is often encountered in ostensibly healthy individuals, particularly in young males, black individuals, and athletes. ERP is also observed in acquired conditions, including hypothermia and ischemia [15], [33], [34]. When associated with VT/VF in the absence of organic heart disease, ERP is referred to as ERS. The prevalence of BrS with a type 1 ECG in adults is higher in Asian countries, such as Japan (0.15–0.27%) [35], [36] and the Philippines (0.18%) [37], and among Japanese-Americans in North America (0.15%) [38] than in western countries, including Europe (0%–0.017%) [39]-[41] and North America (0.005–0.1%) [42], [43]. In contrast, the prevalence of an ERP in the inferior and/or lateral leads with a J-point elevation ≥0.1 mV ranges between 1% and 24% and for J-point elevation ≥0.2 mV ranges between 0.6% and 6.4% [44]-[46]. No significant regional differences in the prevalence of an ERP have been reported [47]. However, ERP is significantly more common in blacks than in Caucasians. Little in the way of regional differences in the manifestation of ERS has been reported. ERP appears to be more common in Aboriginal Australians than in Caucasian Australians [48]. According to the 2013 consensus statement on inherited cardiac arrhythmias [8] and the 2015 guidelines for the management of patients with ventricular arrhythmias and prevention of SCD [9]: “BrS is diagnosed in patients with ST- segment elevation with type 1 morphology ≥2 mm in ≥1 lead among the right precordial leads V1, V2, positioned in the 2nd, 3rd or 4th intercostal space occurring either spontaneously or after provocative drug test with intravenous administration of Class I antiarrhythmic drugs. BrS is diagnosed in patients with type 2 or type 3 ST-segment elevation in ≥1 lead among the right precordial leads V1, V2 positioned in the 2nd, 3rd or 4th intercostal space when a provocative drug test with intravenous administration of Class I antiarrhythmic drugs induces a type I ECG morphology.” The present Task Force is concerned that this could result in overdiagnosis of BrS, particularly in patients displaying a type 1 ECG only after a drug challenge. Data suggest the latter population is at very low risk and that the presumed false- positive rate of pharmacologic challenge is not trivial [49]. Although a rigorous process was undertaken to establish the preceding guidelines, there remains no gold standard for establishing a diagnosis, particularly in patients with weak evidence of disease. Accordingly, we recommend adoption of the following diagnostic criteria and score system for BrS. Consistent with the recommendation of the 2013 and 2015 guidelines, only a type 1 (“coved-type”) ST-segment elevation is considered diagnostic of BrS (Fig. 1), and BrS is characterized by ST-segment elevation ≥2 mm (0.2 mV) in ≥1 right precordial leads (V1−V3) positioned in the 4th, 3rd, or 2nd intercostal space. However, as a departure from the guidelines, this consensus report recommends that when a type 1 ST-segment elevation is unmasked using a sodium channel blocker (Table 1), diagnosis of BrS should require that the patient also present with 1 of the following: documented VF or polymorphic VT, syncope of probable arrhythmic cause, a family history of SCD at o45 years old with negative autopsy, coved-type ECGs in family members, or nocturnal agonal respiration. Inducibility of VT/VF with 1 or 2 premature beats supports the diagnosis of BrS under these circumstances [50]. Three types of ST-segment elevation associated with Brugada syndrome. Only type 1 is diagnostic of Brugada syndrome. A type 2 (“saddle-back type”) or type 3 ST-segment elevation cannot substitute for a type 1, unless converted to type 1 with fever or sodium drug challenge. A drug challenge–induced type 1 can be used to diagnose BrS only if accompanied by 1 of the criteria specified above. Type 2 is characterized by ST-segment elevation ≥0.5 mm (generally ≥2 mm in V2) in ≥1 right precordial lead (V1−V3), followed by a convex ST. The ST segment is followed by a positive T wave in V2 and variable morphology V1. Type 3 is characterized by either a saddleback or coved appearance with an ST-segment elevation o1 mm. Placement of the right precordial leads in more cranial positions (in the 3rd or 2nd intercostal space) in a 12-lead resting ECG or 12-lead Holter ECG increases the sensitivity of ECG [51]-[53]. It is recommended that ECG recordings be obtained in the standard and superior positions for the V1 and V2 leads. Veltman et al. [54]. showed that RVOT localization using magnetic resonance imaging (MRI) correlates with type 1 ST-segment elevation in BrS and that lead positioning according to RVOT location improves the diagnosis of BrS. Interestingly, in most cases a type I pattern was found in the 3rd intercostal space in the sternal and left parasternal positions [54]. In reviewing ECGs of a large cohort of BrS patients, Richter et al [55]. concluded that lead V3 does not yield diagnostic information in BrS. A proposed diagnostic score system for BrS, referred to as the Proposed Shanghai BrS Score, is presented in Table 2. These recommendations are based on the available literature and the clinical experience of the Task Force members [8], [56]-[60]. Weighting of variables is based on expert opinion informed by cohort studies that typically do not include all variables presented. Thus, rigorous, objectively weighted coefficients were not derived from large-scale risk factor and outcome- informed datasets. Nonetheless, the authors believed that some inferential weighting would be of benefit when applied to patients. As with all such recommendations, they will need to undergo initial and ongoing validation in future studies. When there is clinical suspicion of BrS in the absence of spontaneous type 1 ST-segment elevation, a pharmacologic challenge using a sodium channel blocker is recommended. A list of agents used for this purpose is presented in Table 1 (also see www.brugadadrugs.org). The test is considered positive only if a type 1 ECG pattern is obtained, and it should be discontinued in case of frequent ventricular extrasystoles or other arrhythmias, or widening of the QRS 4130% over the baseline value [6]. As an alternative, the “full stomach test” has been proposed for diagnosing BrS [61]. In this case, ECGs are performed before and after a large meal. The use of “high electrodes” increases the sensitivity for recognizing spontaneous type I ST-segment elevation at night or after heavy meals [62]. A type 1 ST-segment elevation recorded using a Holter is a spontaneous type 1, and it is reasonable to assume that a spontaneous type 1 recorded by Holter at night or after a large meal has more value—both diagnostic and prognostic—than a drug-induced type 1. Drug challenge is not indicated in asymptomatic patients displaying the type 1 ECG under baseline conditions because of the lack of the additional diagnostic value. These provocative drug tests are also not recommended in cases in which fever has been documented to induce a type I ECG, other than for research purposes. Much debate has centered around the definition of a false-positive sodium channel block challenge [63]. The consensus is that a false-positive is difficult to define because of the lack of a gold standard. The development of a type 1 ST-segment elevation in response to sodium block challenge should be considered as probabilistic, rather than binary, in nature. As will be discussed later, a similar approach is recommended in evaluating the ability of genetic variants to promote the BrS phenotype. Asymptomatic patients with a family history of BrS or SCD should be informed of the availability of a sodium channel blocker challenge test to provide a more definitive diagnosis of BrS. However, patients should be advised that no therapy may be recommended regardless of the outcome because the long- term risk of patients with BrS diagnosed by this test is significantly lower than the risk of patients with spontaneous type 1. Patients also should be informed about the risk of the test and about the emotional consequences of having a positive test not followed by definitive therapy. The decision as to whether to undergo the drug challenge ultimately should be left up to the well-informed patient. Performing an ajmaline test in children is problematic for 2 reasons. First, the test is apparently less sensitive in children than in adults. In fact, in 1 study, a repeat ajmaline challenge performed after puberty unmasked BrS in 23% of relatives with a previously negative drug test performed during childhood [64]. Second, the test is associated with greater risk than in adults. In 1 series, 10% of children undergoing the ajmaline test, including 3% of the asymptomatic subgroup, developed sustained VT [64], [65]. Caution also should be exercised when performing a sodium blocker challenge in adults with a known pathogenic sodium channel mutation or in patients with prolonged PR intervals, pointing to a carrier of such a mutation [66]. Other causes of ST-segment elevation should be excluded before establishing the diagnosis of BrS (Table 3). Artifacts secondary to low-pass filtering should be ruled out [67]. Circumstances that produce a type 1 Brugada-like ECG include right bundle branch block (RBBB), pectus excavatum, arrhythmogenic right ventricular cardiomyopathy (ARVC), and occlusion of the left anterior descendent artery or the conus branch of the right coronary artery, which supplies the RVOT (Table 3A). Discrimination between BrS and ARVC is particularly challenging. Although debate continues as to the extent to which structural abnormalities are present in BrS, most investigators consider BrS to be a channelopathy. Concealed structural abnormalities, such as histologic myocardial fibrosis of the RVOT, which may not become evident using conventional imaging techniques, have been proposed to account for or contribute to delayed conduction and ventricular arrhythmias in BrS. MRI and electron beam computed tomographic studies of BrS patients consistently show subtle abnormalities, including wall motion abnormalities and reduced contractile function of the RV and, to a lesser extent, of the LV, and dilation of the RVOT [68]-[71]. In the only study that discriminated between patients with and those without SCN5A mutations, no difference was observed in RVOT dimensions or RV ejection fraction between these patients. Slightly greater depressions of LV dimensions and ejection fraction were observed in patients with SCN5A mutations. Significant differences were observed in RV and LV dimensions and ejection fraction compared to healthy controls [72]. Cardiac dilation and reduced contractility in all of these studies were attributed to structural changes (fibrosis, fatty degeneration). However, as noted by van Hoorn et al. [72] virtually no signs of fibrosis or fatty degeneration could be detected, perhaps because the spatial resolution of the imaging used was too low to detect such subtle changes. Antzelevitch and colleagues have long suggested an alternative explanation [31], [73], [74]. Loss of the action potential (AP), which has been shown in experimental models to create the arrhythmogenic substrate in BrS, leads to contractile changes that could explain the wall motion abnormalities observed. The all-or-none repolarization at the end of phase 1 of the epicardial AP responsible for loss of the dome causes the calcium channel to inactivate very soon after it activates. As a consequence, calcium channel current is dramatically reduced, the cell becomes depleted of calcium, and contractile function ceases in those cells. This is expected to lead to wall motion abnormalities, particularly in the RVOT, dilation of the RVOT region, and reduced ejection fraction observed in patients with BrS. It has also been proposed that the loss of the AP dome, because it creates a hibernation-like state, may, over long periods of time, lead to mild structural changes, including intracellular lipid accumulation, vacuolization, and connexin 43 redistribution. These structural changes may, in turn, contribute to the arrhythmogenic substrate of BrS, although they are very different from those encountered in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) [31], [75]. This hypothesis would predict that some of the changes observed by recent studies may be the result of, rather than the cause of, the BrS phenotype [76]. In a recent study, Nademanee et al. [76]. reported additional evidence pointing to pathologic changes in the RVOT of patients with BrS that have proved undetectable by echocardiography or MRI. In contrast, imaging techniques in ARVC clearly display morphologic and functional changes (e.g., dilation, bulging/ aneurysms, wall motion abnormalities). ARVC is an inherited cardiac disease resulting from genetically defective desmosomal (DS) proteins [77], [78], characterized by fibrofatty myocardial replacement predisposing to scar-related ventricular arrhythmias that may lead to SCD, mostly in young people and athletes [79]. Life-threatening ventricular arrhythmias may occur early, during the “concealed phase” of the disease, before overt structural changes [77], [78], [80]. Recent experimental studies demonstrated that loss of expression of DS proteins may induce electrical ventricular instability by causing sodium channel dysfunction and current reduction as a consequence of the cross-talk between these molecules at the intercalated discs, which predisposes to sodium current-dependent lethal arrhythmias, similar to those leading to SCD in patients with J-wave syndromes [80]-[82]. Further evidence of the overlap between phenotypic manifestation of ARVC and BrS comes from (1) clinicopathologic studies showing that a subset of ARVC patients may share ECG changes and patterns of ventricular arrhythmias with BrS [83]; and (2) genotype–phenotype correlation studies demonstrating that PKP2 mutation may cause a Brugada phenotype in the human heart by reducing sodium current [84]. These findings support the concept that specific DS gene mutations involved in the pathogenesis of ARVC can lead to a decreased depolarization reserve that manifests as J-wave/BrSs. Thus, ARVC and J wave syndromes are not completely different conditions but are the ends of a spectrum of structural myocardial abnormalities and sodium current deficiency that share a common origin as diseases of the connexome [84]. The ECG abnormalities in ARVC are not dynamic and display a constant T-wave inversion, epsilon waves, and, in the progressive stage, reduction of the R amplitude. End-stage ARVC is usually associated with monomorphic VT with left bundle branch morphology and is precipitated by catecholamines [85], whereas BrS is associated with polymorphic VT predominantly during sleep or rest [86]. A positive ajmaline challenge has been reported in 16% of patients with ARVC [87], [88]. Sympathovagal balance, hormones, metabolic factors, and pharmacologic agents are thought to modulate not only ECG morphology but also explain the development of ventricular arrhythmias under certain conditions [89]. Any of these modulating factors, if present, should be promptly corrected (Table 3B). The Brugada ECG is often concealed and can be unmasked with a wide variety of drugs and conditions, including a febrile state, vagotonic agents and maneuvers, α-adrenergic agonists, β-adrenergic blockers, Class IC antiarrhythmic drugs, tricyclic or tetracyclic antidepressants, hyperkalemia, hypokalemia, hypercalcemia, and alcohol and cocaine toxicity [90]-[100]. Preexcitation of RV can unmask the BrS phenotype in cases of RBBB [101]. An up-to-date list of agents known to unmask the Brugada ECG that should be avoided by patients with BrS can be found at www.brugadadrugs.org [89]. Environmental factors leading to the appearance of an ECG similar or identical to a type 1 BrS pattern in the absence of any apparent genetic dysfunction has been suggested to represent a Brugada ECG phenocopy [102]. Features of the Brugada phenocopies include (1) Brugada- like ECG pattern; (2) presence of an identifiable underlying condition; (3) disappearance of the ECG pattern after resolution of the condition; (4) absence of family history of sudden death in relatively young first-degree relatives (≤45 years) or of type 1 BrS pattern; (5) absence of symptoms such as syncope, seizures, or nocturnal agonal respiration; and (6) a negative sodium channel blocker challenge test. Debate continues as to the appropriateness of this terminology given that it is very difficult to rule out a genetic predisposition, which is a prerequisite for designating the ECG manifestation as a phenocopy. Designation of these conditions as acquired forms of Brugada ECG pattern or BrS may be more appropriate and better aligned with the terminology used in the long QT syndrome. ERS is generally diagnosed in patients who display ER in the inferior and/or lateral leads presenting with aborted cardiac arrest, documented VF, or polymorphic VT. Consistent with the recent consensus report on ERP [24], ER is recognized if (1) there is an end QRS notch (J wave) or slur on the downslope of a prominent R wave with and without ST-segment elevation; (2) the peak of the notch or J wave (Jp) ≥0.1 mV in ≥2 contiguous leads of the 12-lead ECG, excluding leads V1−V3; and (3) QRS duration (measured in leads in which a notch or slur is absent) o120 ms. Table 4 lists the exclusion criteria in the differential diagnosis of ERS. A proposed diagnostic score system for ERS, referred to as the Proposed Shanghai ERS Score, is presented in Table 5. The scoring system is based on evidence available in the literature to date. As in BrS, weighting of variables is based on expert opinion informed by cohort studies that do not include all variables presented. Thus, rigorous, objectively weighted coefficients were not derived from large-scale risk factor- and outcome-informed datasets. Nonetheless, the authors believed that some inferential weighting would be of benefit when applied to patients. As with all such recommendations, they will need to undergo initial and ongoing validation in future studies. BrS and ERS display several clinical similarities, suggesting similar pathophysiology (Table 6) [19], [21], [103]-[105]. Males predominate in both syndromes, with BrS presenting in 71–80% among Caucasians and 94–96% among Japanese [106], [107]. In the setting of ERP, VF occurred mainly in males (72%) when studied in an international cohort [2] but in a much higher percentage in a report by Japanese investigators [108]. BrS and ERS patients may be totally asymptomatic until they present with cardiac arrest. In both syndromes, the highest incidence of VF or SCD occurs in the third decade of life, perhaps related to testosterone levels in males [109]. In both syndromes, the appearance of accentuated J waves and ST-segment elevation is generally associated with bradycardia or pauses [110], [111]. This can explain why VF in both syndromes often occurs during sleep or during a low level of physical activities [108], [112]. The QT interval is relatively short in patients with ERS [2], [113], and BrS who carry mutations in calcium channel genes [114]. As will be discussed in more detail later, ERS and BrS also share similarities with respect to the response to pharmacologic therapy. In both, electrical storms and associated J-wave manifestations can be suppressed using β- adrenergic agonists [115]-[118]. Chronic oral pharmacologic therapy using quinidine [119], [120], bepridil [117], denopamine [115], [121], and cilostazol [115], [117], [121]-[125] is reported to suppress the development of VT/VF in both ERS and BrS secondary to inhibition of Ito, augmentation of ICa, or both [3], [122], [126]. Differences between the 2 syndromes include (1) the region of the heart most affected (RVOT vs inferior LV); (2) the presence of (discrete) structural abnormalities in BrS but not in ERS; (3) the incidence of late potentials in signal- averaged ECGs (BrS 60% 4 ERS 7%) [108]; and (4) greater elevation of Jo, Jp, or Jt (ST-segment elevation) in response to sodium channel blockers in BrS vs ERS and higher prevalence of atrial fibrillation in BrS vs ERS [127]. Early studies suggested a different pathophysiologic basis for ERS and BrS based on the observation that sodium channel blockers unmask or accentuate J-wave manifestation in BrS but reduces the amplitude in ERS [108]. However, the recent study by Nakagawa et al. [357]. showed that J waves recorded using unipolar LV epicardial leads introduced into the left lateral coronary vein in ERS patients are indeed augmented, even though J waves recorded in the lateral precordial leads are diminished, due principally to engulfment of the surface J wave by the widened QRS [29], [108]. The case report of Nakagawa et al. has recently been supplemented with additional cases in which this technique was used; 2 of these 3 cases showed pilsicainide-induced accentuation of the J waves in electrograms recorded from the epicardial surface of the LV (H. Morita, unpublished observations). Also in support of the thesis that these ECG patterns and syndromes are closely related are reports of cases in which ERS transitions into ERS plus BrS [105], [128]. The principal difference between BrS and ERS is related to the region of the ventricle most affected. Epicardial mapping studies in BrS patients report accentuated J waves and fragmented and/or late potentials in the epicardial region of the RVOT [129]-[131], whereas in ERS only accentuated J waves, particularly in the inferior wall of LV, are observed [29]. Fractionated electrogram activity and late potentials have been observed in experimental models of ERS [30] but have not yet been reported clinically. Noninvasive mapping electroanatomic studies have reported very steep localized repolarization gradients across the inferior/lateral regions of LV of ERS patients, preceded by normal ventricular activation [132], whereas in BrS both slow discontinuous conduction and steep dispersion of repolarization are present in the RVOT [133]. Another presumed difference is the presence of structural abnormalities in BrS, which have not yet been described in ERS [76]. Although J waves are accentuated or induced by both hypothermia and fever [33], [34], [134]-[139], the development of arrhythmias in ERS is much more sensitive to hypothermia, and arrhythmogenesis in BrS appears to be promoted only by fever [33], [34], [138], [139]. Hypothermia has been reported to increase the risk of VF in ERS [33], [34], [134], [135], [140], and fever is well recognized as a major risk factor in BrS [138], [139]. It is noteworthy that hypothermia can diminish the manifestation of a BrS ECG when already present [141], [142]. An ERP is associated with an increased risk for VF in patients with acute myocardial infarction[143] and hypothermia [33], [144]. A concomitant ERP in the inferolateral leads has also been reported to be associated with an increased risk of arrhythmic events in patients with BrS. Kawata et al. [145]. reported that the prevalence of ER in inferolateral leads was high (63%) in BrS patients with documented VF. BrS has been associated with variants in 18 genes (Table 7). To date, more than 300 BrS-related variants in SCN5A have been described [21], [146]-[148] Fig. 2 shows the overlap syndromes attributable to genetic defects in SCN5A. Loss-of- function mutations in SCN5A contribute to the development of both BrS and ERS, as well as to a variety of conduction diseases, Lenegre disease, and sick sinus syndrome. The available evidence suggests that the presence of a prominent Ito determines whether loss-of-function mutations resulting in a reduction in INa will manifest as BrS/ERS or as conduction disease [59], [149]-[151]. Schematic showing overlap syndromes resulting from genetic defects r" @default.
• W2510663617 created "2016-09-16" @default.
• W2510663617 creator A5002151074 @default.
• W2510663617 creator A5005749391 @default.
• W2510663617 creator A5008259359 @default.
• W2510663617 creator A5023748663 @default.
• W2510663617 creator A5024543642 @default.
• W2510663617 creator A5026028224 @default.
• W2510663617 creator A5031012881 @default.
• W2510663617 creator A5031348911 @default.
• W2510663617 creator A5034392769 @default.
• W2510663617 creator A5035866982 @default.
• W2510663617 creator A5052029560 @default.
• W2510663617 creator A5055125250 @default.
• W2510663617 creator A5061201423 @default.
• W2510663617 creator A5067057991 @default.
• W2510663617 creator A5068607834 @default.
• W2510663617 creator A5073867081 @default.
• W2510663617 creator A5091171967 @default.
• W2510663617 date "2016-08-21" @default.
• W2510663617 modified "2023-10-18" @default.
• W2510663617 title "J‐Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge" @default.
• W2510663617 cites W1022680635 @default.
• W2510663617 cites W138498855 @default.
• W2510663617 cites W140924846 @default.
• W2510663617 cites W1454709072 @default.
• W2510663617 cites W1490466277 @default.
• W2510663617 cites W1513728380 @default.
• W2510663617 cites W1523848836 @default.
• W2510663617 cites W1524320730 @default.
• W2510663617 cites W1529616046 @default.
• W2510663617 cites W1534498799 @default.
• W2510663617 cites W1540071197 @default.
• W2510663617 cites W1547678659 @default.
• W2510663617 cites W1554002772 @default.
• W2510663617 cites W1560833314 @default.
• W2510663617 cites W1579505500 @default.
• W2510663617 cites W1585924413 @default.
• W2510663617 cites W1586581147 @default.
• W2510663617 cites W175934965 @default.
• W2510663617 cites W1762744290 @default.
• W2510663617 cites W1874320426 @default.
• W2510663617 cites W1892542784 @default.
• W2510663617 cites W1897152789 @default.
• W2510663617 cites W1963847400 @default.
• W2510663617 cites W1964246552 @default.
• W2510663617 cites W1964248172 @default.
• W2510663617 cites W1966498420 @default.
• W2510663617 cites W1967011394 @default.
• W2510663617 cites W1967512105 @default.
• W2510663617 cites W1968088618 @default.
• W2510663617 cites W1968876226 @default.
• W2510663617 cites W1969311237 @default.
• W2510663617 cites W1969744712 @default.
• W2510663617 cites W1970314318 @default.
• W2510663617 cites W1970345729 @default.
• W2510663617 cites W1970683067 @default.
• W2510663617 cites W1970838979 @default.
• W2510663617 cites W1970951995 @default.
• W2510663617 cites W1973297720 @default.
• W2510663617 cites W1974227886 @default.
• W2510663617 cites W1974252599 @default.
• W2510663617 cites W1974719485 @default.
• W2510663617 cites W1975780081 @default.
• W2510663617 cites W1976237310 @default.
• W2510663617 cites W1976940560 @default.
• W2510663617 cites W1978167180 @default.
• W2510663617 cites W1978186491 @default.
• W2510663617 cites W1978663892 @default.
• W2510663617 cites W1978710193 @default.
• W2510663617 cites W1979306645 @default.
• W2510663617 cites W1980361970 @default.
• W2510663617 cites W1982031117 @default.
• W2510663617 cites W1983007693 @default.
• W2510663617 cites W1984153793 @default.
• W2510663617 cites W1984307540 @default.
• W2510663617 cites W1984314206 @default.
• W2510663617 cites W1985898469 @default.
• W2510663617 cites W1989115606 @default.
• W2510663617 cites W1990826945 @default.
• W2510663617 cites W1991572483 @default.
• W2510663617 cites W1992747804 @default.
• W2510663617 cites W1993190948 @default.
• W2510663617 cites W1996735711 @default.
• W2510663617 cites W1996829258 @default.
• W2510663617 cites W1997696957 @default.
• W2510663617 cites W1997956247 @default.
• W2510663617 cites W1999175334 @default.
• W2510663617 cites W2000208388 @default.
• W2510663617 cites W2001355461 @default.
• W2510663617 cites W2001847491 @default.
• W2510663617 cites W2001892782 @default.
• W2510663617 cites W2003611049 @default.
• W2510663617 cites W2003646765 @default.
• W2510663617 cites W2003964447 @default.
• W2510663617 cites W2004145576 @default.
• W2510663617 cites W2004190093 @default.
• W2510663617 cites W2005221088 @default.

• next