Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • In a recent study Nademanee

    2019-04-15

    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 Anti-infection Compound Library 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].
    Modulating factors 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).
    Acquired Brugada pattern and phenocopies 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.