Anaesthesia for patients with hereditary arrhythmias part I: Brugada syndrome
2018; Elsevier BV; Volume: 18; Issue: 6 Linguagem: Inglês
10.1016/j.bjae.2018.03.004
ISSN2058-5357
AutoresDaniel Levy, Colin Bigham, David R. Tomlinson,
Tópico(s)Ion channel regulation and function
ResumoLearning objectivesBy reading this article, you should be able to:•Describe the epidemiology, genetics, and presentation of Brugada syndrome•Identify patients at greatest risk•Recognise a diagnostic Brugada syndrome ECG•Discuss the approach to investigation when diagnostic uncertainty remains•Explain which drugs should be avoided, the available cardiological therapies and perioperative management of a patient with Brugada syndromeKey points•Brugada syndrome is an abnormality of cardiac ion channels that increases the risk of ventricular fibrillation (VF) and sudden cardiac death.•The classic ECG pattern is cove-type ST-segment elevation and T wave inversion in leads V1 and V2.•It is best to avoid local anaesthetics, propofol infusions, and manoeuvres increasing vagal tone during the perioperative period.•Isoprenaline should be available in case of either non-sustained or sustained VF, and is the antiarrhythmic drug of choice for VF storm.•Postoperative ECG monitoring is required after the administration of some anaesthetic agents known to increase the risk of VF in Brugada syndrome. By reading this article, you should be able to:•Describe the epidemiology, genetics, and presentation of Brugada syndrome•Identify patients at greatest risk•Recognise a diagnostic Brugada syndrome ECG•Discuss the approach to investigation when diagnostic uncertainty remains•Explain which drugs should be avoided, the available cardiological therapies and perioperative management of a patient with Brugada syndrome •Brugada syndrome is an abnormality of cardiac ion channels that increases the risk of ventricular fibrillation (VF) and sudden cardiac death.•The classic ECG pattern is cove-type ST-segment elevation and T wave inversion in leads V1 and V2.•It is best to avoid local anaesthetics, propofol infusions, and manoeuvres increasing vagal tone during the perioperative period.•Isoprenaline should be available in case of either non-sustained or sustained VF, and is the antiarrhythmic drug of choice for VF storm.•Postoperative ECG monitoring is required after the administration of some anaesthetic agents known to increase the risk of VF in Brugada syndrome. The Brugada brothers first described the association of right ventricular conduction delay, right precordial ST-segment elevation along with the predisposition to syncopal episodes and sudden cardiac death (SCD) as a result of ventricular arrhythmias in 1992.1Brugada P. Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death; a distinct clinical and electrocardiographic syndrome. A Multicenter report.J Am Coll Cardiol. 1992; 20: 1391-1396Crossref PubMed Scopus (2730) Google Scholar Since then, Brugada syndrome (BrS) has become increasingly recognised as an important cause of SCD in a structurally normal heart and is thought to be responsible for up to 40% of such cases.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar, 3Smith D. Martz D.G. Brugada syndrome: a review of perioperative management for the anesthesiologist.Int J Clin Anesthesiol. 2014; 2: 1019Google Scholar It can exhibit autosomal dominant inheritance, although 60% of patients with BrS have no affected family member; the likely explanation for this is variable expression and incomplete penetrance.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar Although the genotype is distributed equally between the sexes, the phenotype tends to be exhibited more severely in males, in whom it is eight to 10 times more common.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar, 6Steinfurt J. Biermann J. Bode C. Odening K.E. The diagnosis, risk stratification, and treatment of Brugada syndrome.Dtsch Arztebl Int. 2015; 112: 394-401PubMed Google Scholar Brugada syndrome is typically diagnosed in the fourth decade of life although it has been diagnosed in patients as young as 2 days and as old as 84 yr.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 7Morita H. Zipes D.P. Wu J. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.Heart Rhythm. 2009; 6: S34-S43Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar The true prevalence has been difficult to establish as the diagnostic electrocardiographic pattern may only be present transiently and many patients are asymptomatic. It is thought to range from one to five per 10 000 people in Europe to as high as 20 per 10 000 people in South East Asia.3Smith D. Martz D.G. Brugada syndrome: a review of perioperative management for the anesthesiologist.Int J Clin Anesthesiol. 2014; 2: 1019Google Scholar, 4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar, 8Vohra J. Rajagopalan S. CSANZ Genetics Council Writing GroupUpdate on the diagnosis and management of Brugada syndrome.Heart Lung Circ. 2015; 24: 1141-1148Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar If present, symptoms may include palpitations, chest discomfort, syncope and nocturnal agonal respiration. However, as many patients are asymptomatic, BrS is frequently an incidental diagnosis on ECG, at family screening or after presentation with aborted SCD secondary to polymorphic ventricular tachycardia (resembling a rapid form of torsades de pointes) or ventricular fibrillation.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Monomorphic ventricular tachycardia is rare but is more often seen in infants and children.5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar, 8Vohra J. Rajagopalan S. CSANZ Genetics Council Writing GroupUpdate on the diagnosis and management of Brugada syndrome.Heart Lung Circ. 2015; 24: 1141-1148Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Events typically occur during sleep with increased vagal tone, with fever, or can be precipitated by drugs, alcohol, and electrolyte disorders; these potential triggers can all accentuate the ST elevation noted in a Brugada ECG.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar, 3Smith D. Martz D.G. Brugada syndrome: a review of perioperative management for the anesthesiologist.Int J Clin Anesthesiol. 2014; 2: 1019Google Scholar, 4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar Between 20 and 30% of patients experience supraventricular tachycardias (SVTs) such as atrial flutter, atrioventricular nodal re-entry, and pre-excitation syndromes such as Wolff–Parkinson–White syndrome, although atrial fibrillation is seen most commonly.3Smith D. Martz D.G. Brugada syndrome: a review of perioperative management for the anesthesiologist.Int J Clin Anesthesiol. 2014; 2: 1019Google Scholar, 4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 6Steinfurt J. Biermann J. Bode C. Odening K.E. The diagnosis, risk stratification, and treatment of Brugada syndrome.Dtsch Arztebl Int. 2015; 112: 394-401PubMed Google Scholar Patients with apparent supraventricular involvement have potentially more advanced disease as this correlates with increased ventricular irritability and a higher risk of ventricular tachycardia or fibrillation.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar, 4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar In critical care, the most common presentation will be a patient with aborted SCD. The anaesthetist may encounter it as an incidental finding in a patient on an elective or emergency list, or alternatively as a known comorbidity in a patient booked for an elective procedure. A thorough knowledge of BrS management and drugs to be avoided is vital. Diagnosis is based on fulfilling the type I BrS ECG morphological criteria from the most recent Expert Consensus Recommendations5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar: a cove-shaped (i.e. with T-wave inversion) ST-segment elevation ≥2 mm in at least one right precordial leads (V1 or V2) when placed in a standard or superior position (i.e. up to the second intercostal space), either spontaneously or after the administration of a sodium channel blocking agent (e.g. ajmaline/flecainide). Additional ECG morphologies described are type 2 [saddleback-shaped (i.e. with a positive T-wave) ST-segment ≥1 mm in at least one right precordial lead] and type 3 (saddleback or cove-shaped ST-segment elevation 300 identified mutations to this gene and together they account for up to 30% of cases of BrS.7Morita H. Zipes D.P. Wu J. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.Heart Rhythm. 2009; 6: S34-S43Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar The severity of the ion channel dysfunction caused by the mutation appears to be related to the clinical severity of the condition.12Meregalli P.G. Tan H.L. Probst V. et al.Types of SCN5A mutation determines clinical severity and degree of conduction slowing in loss-of-function sodium channelopathies.Heart Rhythm. 2009; 6: 341-348Abstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar It is beyond the scope of this article to discuss all mutations associated with BrS, some of which are extremely rare. An excellent summary can be found in the paper by Antzelevitch and Patocskai.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar In up to 80% of patients no causative genetic mutation can be found, suggesting either further unidentified mutations or other mechanisms for the phenotype.7Morita H. Zipes D.P. Wu J. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.Heart Rhythm. 2009; 6: S34-S43Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar It is possible for mutations in the same gene to lead to other syndromes, such as long QT syndrome 3.7Morita H. Zipes D.P. Wu J. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.Heart Rhythm. 2009; 6: S34-S43Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar Two principal hypotheses have been advanced as the mechanism for BrS and its arrhythmogenicity and resting ECG characteristics. It is possible that both are correct in different patients (see Fig 1, Fig 2, Fig 3, Fig 4).Fig 2Postajmaline provocation in the same patient, with (A) a type 1 Brugada ECG pattern induced in lead V1 (complexes now have subtle convex/'coved' ST shape) and (B) more accentuated but still not type I ECG change in lead V2 (images courtesy of David Tomlinson).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3High precordial lead placement (note V1 and V2 are placed in the second intercostal space). Alternatively, leads V5 and V6 can be moved to the superior position whilst leads V1 and V2 are maintained in their standard position (fourth intercostal space).View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 4The normal cardiac ventricular cell action potential.View Large Image Figure ViewerDownload Hi-res image Download (PPT) As explained above, the myocardial action potential is not uniform across the heart. There is spread in the notch, dome, and refractory periods from endocardium to epicardium. In the repolarisation theory, dysfunction of the cardiac ion channels results in enhancement of the Phase 1 notch. This can lead to deactivation of ICa-L and so loss of the action potential dome at some epicardial sites (most commonly within the right ventricular outflow tract). These sites lose their refractory period and become vulnerable to re-entrant currents. This is termed Phase 2 re-entry. The currents originate from myocardial sites that have retained their Phase 2 dome (Fig. 5).4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 7Morita H. Zipes D.P. Wu J. Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations.Heart Rhythm. 2009; 6: S34-S43Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar The Phase 2 re-entry generates closely coupled premature beats that can induce VT or VF. The deep Phase 1 notch combined with loss of the Phase 2 dome creates a large transmural voltage gradient. This transmural voltage gradient, which is most pronounced in the RVOT, can explain the characteristic ST-segment elevation seen in the precordial leads on the resting ECG.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar T wave inversion, and so the classic coved appearance, will be present when preserved epicardial Phase 2 domes are longer than that of the adjacent endocardium.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar This hypothesises that there are worse conduction delays as a result of the INa abnormalities (for example). The RVOT depolarises later than the rest of the right ventricle creating a potential difference between them. This will result in the characteristic ECG morphology and preponderance to arrhythmias.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar This theory is supported by evidence that the conduction delay at the RVOT is as a result of loss of the gap junction signalling protein connexin-43 and epicardial and intramyocardial fibrosis replacement, not evident macroscopically or on imaging.14Nademanee K. Raju H. de Noronha S.V. et al.Fibrosis, connexin-43, and conduction abnormalities in the Brugada syndrome.J Am Coll Cardiol. 2015; 66: 1976-1986Crossref PubMed Scopus (245) Google Scholar Targeted patient management will depend on clinical context and risk. Broad clinical categories include: (i) assessment of the need for non-immediate cardiology interventions weighing up lifetime arrhythmia risks and complications of therapy; (ii) perioperative management of patient with likely or confirmed BrS; and (iii) urgent management of an electrical storm. It is generally easy to identify those at highest risk of cardiac arrhythmic events but lower risk groups, who can still present with arrhythmias, are more difficult to stratify and there is no validated algorithm.2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar, 5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar, 6Steinfurt J. Biermann J. Bode C. Odening K.E. The diagnosis, risk stratification, and treatment of Brugada syndrome.Dtsch Arztebl Int. 2015; 112: 394-401PubMed Google Scholar Commonly accepted risk factors are listed in Table 1. A positive family history and the use of electrophysiological studies (EPS) to induce VT/VF for risk stratification remains controversial.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google Scholar The presence of symptoms or previous aborted SCD significantly increases the chances of further arrhythmias. The annual event rate in patients with a spontaneous type 1 pattern who are asymptomatic, experience syncopal episodes and who have had previous aborted SCD is 0.5%, 1.9%, and 7.7%, respectively.15Probst V. Veltmann C. Eckardt L. Meregalli P.G. Gaita F. Long-term prognosis of patients diagnosed with Brugada syndrome.Circulation. 2009; 121: 635-643Crossref Scopus (616) Google Scholar No characteristics have yet been found allowing identification of patients most at risk of arrhythmic storms.16Ohgo T. Okamura H. Noda T. et al.Acute and chronic management in patients with Brugada syndrome associated with electrical storm of ventricular fibrillation.Heart Rhythm. 2007; 4: 695-700Abstract Full Text Full Text PDF PubMed Scopus (157) Google ScholarTable 1Risk factors for arrhythmic events in Brugada syndrome2Sieira J. Dendramis G. Brugada P. Pathogenesis and management of Brugada syndrome.Nat Rev Cardiol. 2016; 13: 744-756Crossref PubMed Scopus (69) Google Scholar, 4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.Europace. 2013; 15: 1389-1406Crossref PubMed Scopus (410) Google ScholarSpontaneous type 1 ECG patternMale sexSyncopal episodesNocturnal agonal respirationPrevious ventricular tachycardia/ventricular fibrillationFragmented QRS complex (i.e. increased number of deflections)Prolonged QRST-wave alternansVentricular refractory period <200 ms (identified at invasive electrophysiology study)Early repolarisation pattern in inferolateral leads Open table in a new tab An exhaustive list of drugs to avoid in BrS can be found at www.Brugadadrugs.org.17Postema P.G. Neville J. de Jong J.S. Romero K. Wilde A.A. Woosley R.L. Safe drug use in long QT syndrome and Brugada syndrome: comparison of website statistics.Europace. 2013; 15: 1042-1049Crossref PubMed Scopus (53) Google Scholar Class 1A and 1C antiarrhythmic drugs, lithium, and tricyclic antidepressants are known to increase the degree of ST elevation in BrS, thereby provoking arrhythmias and should be avoided. Other antiarrhythmics such as amiodarone and verapamil, α adrenergic agonists, β adrenergic blockers, vagotonic agents, selective serotonin reuptake inhibitors, or tetracyclic antidepressants and certain antiepileptics such as carbamazepine, phenytoin, and lamotrigine should preferably be avoided; there is currently no substantial evidence that these drugs can cause malignant arrhythmias, although they will provoke the ECG pattern.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 18Olde Nordkamp L.R. Postema P.G. Reinoud E.K. et al.Implantable cardioverter defibrillator harm in young patients with inherited arrhythmia syndromes: a systematic review and meta-analysis of inappropriate shocks and complications.Heart Rhythm. 2016; 13: 443-454Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar Glucose in combination with insulin should be used with caution because of the risk of hypokalaemia.4Antzelevitch C. Patocskai B. Brugada syndrome: clinical, genetic, molecular, cellular and ionic aspects.Curr Probl Cardiol. 2016; 41: 7-57Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar No large-scale trials have been conducted in this rare condition, so management is based on expert consensus.5Priori S.G. Wilde A.A. Horie M. et al.Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of pa
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