The Development of the Catecholaminergic Nervous System in ...
Catecholaminergic Polymorphic Ventricular...
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Catecholaminergic Polymorphic Ventricular Tachycardia Jessica J. Wall, MD, MPH* and Ramesh V. Iyer, MD† Abstract: Catecholaminergic polymorphic ventricular tachycardia is a rare cause of exercise-induced arrhythmia and sudden cardiac death in the pediatric patient. This arrhythmia is difficult to diagnose in the emer- gency department, given the range of presentations; thus, a familiarity with and high index of suspicion for this pathology are crucial. Furthermore, recognition of the characteristic electrocardiogram findings and knowledge of the management of the symptomatic patient are necessary, given the risk of arrhythmia recurrence and cardiac arrest. In this review, we discuss the presentation, differential diagnosis, and management of catecholaminergic polymorphic ventricular tachycardia for the emergency care provider. Key Words: catecholaminergic polymorphic ventricular tachycardia, sudden cardiac arrest (Pediatr Emer Care 2017;33: 427–433) TARGET AUDIENCE This CME activity is intended for pediatric emergency medi- cine physicians, emergency medicine physicians, and pediatricians. LEARNING OBJECTIVES After completion of this article, the reader should be able to: 1. Define catecholaminergic polymorphic ventricular tachycardia 2. Review pathophysiology of catecholaminergic polymorphic ventricular tachycardia; 3. Review presentation and diagnosis of catecholaminergic poly- morphic ventricular tachycardia; 4. Review electrocardiogram findings indicative of catecholamin- ergic polymorphic ventricular tachycardia; and 5. Discuss current consensus guidelines for the acute and chronic management strategies catecholaminergic polymorphic ventricular tachycardia. A 13-year old child presents to the emergency department after collapsing while running in a soccer game. He required car- diopulmonary resuscitation and 1 defibrillation by an automated external defibrillator prior to emergency medical services arrival. His parents report that he has collapsed previously, but he always recovered within a few minutes. The paramedics show you the electrocardiogram (ECG) (Fig. 1) obtained en route to the emergency department. What is the likely diagnosis, and what is your manage- ment in the emergency department? DEFINITION AND EPIDEMIOLOGY Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac arrhythmia characterized by an emotion- or exercise- induced polymorphic ventricular tachycardia. 1 Although previ- ously described in case reports in 1975, 2 CPVT was defined by Leenhardt et al 1 in 1995 as an etiology of polymorphic ventricular tachycardia with exercise in patients with an otherwise normal resting ECG and structurally normal heart. The characteristic ECG finding when symptomatic is bidirectional ventricular tachycar- dia, as seen in Figure 2. While the exact incidence of CPVT is un- known, it is estimated to be 1 in 10,000. 3,4 When left untreated, symptomatic CPVT has a mortality of 30% by the age of 40 years. 5,6 Typical age at presentation ranges from early child- hood to early adulthood, with an average between 11 and 21 years; however, incident symptomatic cases have been reported in adults up to 40 years old. 1,5,7 Furthermore, CPVT is often misdiagnosed initially as vasovagal syncope, seizure disorder, and other arrhyth- mic conditions such as long QT syndrome (LQTS), resulting in an average delay to diagnosis of up to 2 years. 7 PATHOPHYSIOLOGY AND GENETICS While the overarching mechanism of CPVT is related to an increase in the release of calcium (Ca 2+ ) from the junctional sarco- plasmic reticulum (SR) into the cytoplasm of the cardiac myocyte, there are multiple mechanisms and concomitant gene mutations associated with this pathology. 6 Understanding the regulation of Ca 2+ release in a myocyte is crucial to understanding this patho- physiology (Fig. 3). In response to the action potential propagat- ing throughout the myocardium, calcium enters the cell through the voltage-gated Ca 2+ channel (L-type channels). Once in the cell, the elevated Ca 2+ level induces the ryanodine (RyR2) channel lo- cated in the junctional SR to release calcium from the SR into the cytoplasm of the cell, so-called “Ca 2+ -induced Ca 2+ release. ” The resultant elevation in intracellular Ca 2+ induces contraction of the sarcomere by binding to troponin in the myofilaments. The RyR2 channel is additionally activated by stimulation from β-adrenergic receptors via a cAMP mechanism, increasing Ca 2+ in the SR. The Ca 2+ is then removed from the cytoplasm by Ca 2+ ATPase and sodium-dependent mechanisms transporting it back into the SR and the extracellular space. 8–10 There are 4 genes that have been directly linked to CPVT, all of which affect Ca 2+ release in the cardiac myocyte. Currently, only 60% of cases of CPVT are found to have a genetic mutation, and additional genes are currently under investigation. 11 The first identified genetic mutation was described in the cardiac ryanodine receptor (RYR2 or CPVT1) gene, which accounts for 50% to 55% of CPVT cases. 1,3,12 This mutation is autosomal dominant and re- sults in diastolic “leak” of Ca 2+ into the SR leading to elevated Ca 2+ levels in the cytoplasm. This effect is noted to be more pro- nounced in high β-adrenergic states and hence the association of arrhythmias with exercise. 2,12,13 The second genetic mutation identified in CPVT patients is the CASQ2 (CPVT2) gene, which encodes cardiac calsequestrin, a Ca 2+ -buffering protein in the SR *Fellow (Wall), Division of Emergency Medicine and †Associate Clinical Professor (Iyer), Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA. The authors, faculty, and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interest in, any commercial organizations pertaining to this educational activity. Reprints: Jessica J. Wall, MD, MPH, Division of Emergency Medicine, Children’s Hospital of Philadelphia, 3501 Civic Center Blvd, 9th Floor/ CTRB 9013 B, Philadelphia, PA 19104 (e‐mail: [email protected]). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0749-5161 CME REVIEW ARTICLE Pediatric Emergency Care • Volume 33, Number 6, June 2017 www.pec-online.com 427
Transcript of Catecholaminergic Polymorphic Ventricular...
CME REVIEWARTICLE
Catecholaminergic Polymorphic Ventricular Tachycardia
Jessica J. Wall, MD, MPH* and Ramesh V. Iyer, MD†Abstract: Catecholaminergic polymorphic ventricular tachycardia is arare cause of exercise-induced arrhythmia and sudden cardiac death inthe pediatric patient. This arrhythmia is difficult to diagnose in the emer-gency department, given the range of presentations; thus, a familiarity withand high index of suspicion for this pathology are crucial. Furthermore,recognition of the characteristic electrocardiogram findings and knowledgeof the management of the symptomatic patient are necessary, given the riskof arrhythmia recurrence and cardiac arrest. In this review, we discuss thepresentation, differential diagnosis, and management of catecholaminergicpolymorphic ventricular tachycardia for the emergency care provider.
Key Words: catecholaminergic polymorphic ventricular tachycardia,sudden cardiac arrest
(Pediatr Emer Care 2017;33: 427–433)
TARGET AUDIENCEThis CME activity is intended for pediatric emergency medi-
cine physicians, emergency medicine physicians, and pediatricians.
LEARNING OBJECTIVESAfter completion of this article, the reader should be able to:
1. Define catecholaminergic polymorphic ventricular tachycardia2. Review pathophysiology of catecholaminergic polymorphic
ventricular tachycardia;3. Review presentation and diagnosis of catecholaminergic poly-
morphic ventricular tachycardia;4. Review electrocardiogram findings indicative of catecholamin-
ergic polymorphic ventricular tachycardia; and5. Discuss current consensus guidelines for the acute and
chronic management strategies catecholaminergic polymorphicventricular tachycardia.
A 13-year old child presents to the emergency department aftercollapsing while running in a soccer game. He required car-
diopulmonary resuscitation and 1 defibrillation by an automatedexternal defibrillator prior to emergency medical services arrival.His parents report that he has collapsed previously, but he alwaysrecovered within a few minutes. The paramedics show you theelectrocardiogram (ECG) (Fig. 1) obtained en route to the emergency
*Fellow (Wall), Division of Emergency Medicine and †Associate ClinicalProfessor (Iyer), Division of Cardiology, Children’s Hospital of Philadelphia,Philadelphia, PA.The authors, faculty, and staff in a position to control the content of this CME
activity and their spouses/life partners (if any) have disclosed that they haveno financial relationships with, or financial interest in, any commercialorganizations pertaining to this educational activity.
Reprints: Jessica J. Wall, MD, MPH, Division of Emergency Medicine,Children’s Hospital of Philadelphia, 3501 Civic Center Blvd, 9th Floor/CTRB 9013 B, Philadelphia, PA 19104(e‐mail: [email protected]).
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.ISSN: 0749-5161
Pediatric Emergency Care • Volume 33, Number 6, June 2017
department. What is the likely diagnosis, and what is your manage-ment in the emergency department?
DEFINITION AND EPIDEMIOLOGYCatecholaminergic polymorphic ventricular tachycardia (CPVT)
is a cardiac arrhythmia characterized by an emotion- or exercise-induced polymorphic ventricular tachycardia.1 Although previ-ously described in case reports in 1975,2 CPVTwas defined byLeenhardt et al1 in 1995 as an etiology of polymorphic ventriculartachycardia with exercise in patients with an otherwise normalresting ECG and structurally normal heart. The characteristic ECGfinding when symptomatic is bidirectional ventricular tachycar-dia, as seen in Figure 2. While the exact incidence of CPVT is un-known, it is estimated to be 1 in 10,000.3,4 When left untreated,symptomatic CPVT has a mortality of 30% by the age of40 years.5,6 Typical age at presentation ranges from early child-hood to early adulthood, with an average between 11 and 21 years;however, incident symptomatic cases have been reported in adultsup to 40 years old.1,5,7 Furthermore, CPVT is often misdiagnosedinitially as vasovagal syncope, seizure disorder, and other arrhyth-mic conditions such as longQT syndrome (LQTS), resulting in anaverage delay to diagnosis of up to 2 years.7
PATHOPHYSIOLOGY AND GENETICSWhile the overarching mechanism of CPVT is related to an
increase in the release of calcium (Ca2+) from the junctional sarco-plasmic reticulum (SR) into the cytoplasm of the cardiac myocyte,there are multiple mechanisms and concomitant gene mutationsassociated with this pathology.6 Understanding the regulation ofCa2+ release in a myocyte is crucial to understanding this patho-physiology (Fig. 3). In response to the action potential propagat-ing throughout the myocardium, calcium enters the cell throughthe voltage-gated Ca2+ channel (L-type channels). Once in the cell,the elevated Ca2+ level induces the ryanodine (RyR2) channel lo-cated in the junctional SR to release calcium from the SR into thecytoplasm of the cell, so-called “Ca2+-induced Ca2+ release.” Theresultant elevation in intracellular Ca2+ induces contraction of thesarcomere by binding to troponin in the myofilaments. The RyR2channel is additionally activated by stimulation from β-adrenergicreceptors via a cAMPmechanism, increasing Ca2+ in the SR. TheCa2+ is then removed from the cytoplasm by Ca2+ ATPase andsodium-dependent mechanisms transporting it back into the SRand the extracellular space.8–10
There are 4 genes that have been directly linked to CPVT, allof which affect Ca2+ release in the cardiac myocyte. Currently,only 60% of cases of CPVTare found to have a genetic mutation,and additional genes are currently under investigation.11 The firstidentified genetic mutation was described in the cardiac ryanodinereceptor (RYR2 or CPVT1) gene, which accounts for 50% to 55%of CPVT cases.1,3,12 This mutation is autosomal dominant and re-sults in diastolic “leak” of Ca2+ into the SR leading to elevatedCa2+ levels in the cytoplasm. This effect is noted to be more pro-nounced in high β-adrenergic states and hence the association ofarrhythmias with exercise.2,12,13 The second genetic mutationidentified in CPVT patients is the CASQ2 (CPVT2) gene, whichencodes cardiac calsequestrin, a Ca2+-buffering protein in the SR
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FIGURE 1. Electrocardiogram of a 13-year-old boy with CPVT.
Wall and Iyer Pediatric Emergency Care • Volume 33, Number 6, June 2017
that inhibits the RYR2 protein.1,14 This mutation is autosomal re-cessive and accounts for only 2% to 5% of CPVT patients.3,4 Thethird gene identified in association with CPVT is CALM1, whichis autosomal dominant and encodes calmodulin, a protein that bindscalcium and stabilizes the RyR2 channel and accounts for lessthan 1% of cases.3,5,6,15 Finally, in 2012, the gene TRDN wasidentified in 2 families with CPVT.1,5,7,16 TRDN encodes triadin,a protein that links RyR2 and celsequestrin in the SR.
PRESENTATION AND DIAGNOSISThe most common clinical presentation of CPVT is syncope,
followed by cardiac arrest as in our case presentation. However, itshould be noted that given the ability to test for genetic mutationsassociated with this pathology, asymptomatic patients (especiallyrelatives of affected patients) are now being identified in up to19% of cases.1,5,7,17 In the largest cohort study to date, 64% of pa-tients presented with syncope, 33% with cardiac arrest, 7% withpalpitations, and 4% with chest pain.7–10 The average age at pre-sentation is approximately 11 years old.7,11
Clinical diagnosis is based on the documentation of a poly-morphic ventricular tachycardia that is induced by adrenergicstimuli (emotion or exercise) without any additional structural orelectrical cardiac abnormality.4 Catecholaminergic polymorphic
FIGURE 2. Example of bidirectional ventricular tachycardia in apatient with CPVT.
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ventricular tachycardia can be diagnosed further via genetic test-ing in the absence of symptoms at the time of presentation.4,18
A family history of sudden unexpected death in a relative youngerthan 40 years, an ECG showing exercise-induced ventricular ectopy,or a seizure during exercise (commonmisdiagnosis in CPVT) shouldalso raise suspicion of CPVT.
While genetic testing has become a standard in diagnosis forCPVT, Holter monitoring, exercise stress testing (EST), and iso-proterenol or epinephrine challenge may be useful in making thediagnosis and differentiating from LQTS. The baseline ECG ina CPVT patient typically is normal, occasionally marked by mildbradycardia.19 Progressive ventricular ectopy during EST may bea hallmark for diagnosing these patients. Appearance of prematureventricular beats (PVCs), bigeminy or trigeminy, polymorphicPVCs, and finally nonsustained to sustained bidirectional ventric-ular tachycardia have been described in CPVT.1,3,20 The character-istic bidirectional ventricular tachycardia is rarely found on ECG;more common are polymorphic PVCs; thus, careful attention tothe ECG and telemetry is necessary for clinical diagnosis.
Current guidelines recommend genetic testing for CPVTgenes in patients who exhibit symptoms or if there is a suspiciousfamily history. In addition, once a pathogenic mutation is identi-fied, given the high risk to family members, complete cardiacevaluation and testing including mutation-specific genetic testingare recommended in relatives of the index case.11
For the emergency provider, the basis for diagnosis of CPVTis heightened clinical awareness of the pathology and attention tothe history of presentation. In general, patients who present atyounger than 18 years with exertional syncope have a likelihoodof a cardiac etiology of approximately 50%.21 Table 1 summarizesfindings concerning for cardiac etiology and CPVT of patientspresenting to the emergency department.7
ACUTE MANAGEMENT STRATEGIESAt the outset, it is important to distinguish benign syncope
(such as vasovagal syncope) from the arrhythmogenic syncope in-duced by exercise in conditions such as CPVT and LQTS. Thiscan be done by taking a detailed history of the event with particularinquiry of prodromal symptoms (such as dizziness, lightheadedness,or visual or auditory stimuli) that may suggest a more benign eti-ology. Emergencymanagement of symptomatic CPVTwith ongo-ing arrhythmia is guided by the presentation and stability of thepatient. Polymorphic ventricular tachycardia of any etiology shouldbe differentiated into pulseless patients and patients with a pulse,which can further be subdivided into stable and unstable based onsigns of hemodynamic compromise.
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FIGURE 3. Components of calcium release unit (CRU) and mitochondria involved in excitation-contraction coupling. Interface betweenT-tubule and SR with RyR2 receptors (RyR2s) is circled in red. RyR2 indicates ryanodine receptor; Trdn, triadin; Calm1, calmodulin; Casq2,calsequestrin; SR, junctional SR; L-type Ca2+ channel, voltage-gated calcium channel; NCX, sodium-calcium exchanger. Calcium is releasedfrom the SR via RyR2 interaction with the myofilaments to cause muscle contraction (red arrows). During muscle relaxation, calciumreuptake into the SR and mitochondria occurs (green arrows). Reprinted (with modification) by permission from Macmillan Publishers Ltd(Bers DM. Cardiac excitation-contraction coupling. Nature 2002;415:198–205; copyright 2016).
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PulselessPulseless patients, as in our introductory case, should be treated
following Pediatric Advanced Life Support and Advanced CardiacLife Support guidelines.22–25 Specific therapies for polymorphicventricular tachycardia include defibrillation (2–4 up to 10 J/kg),25 magnesium administration (20–50 mg/kg),25 intravenousβ-blocker therapy (esmolol 500 μg/kg bolus followed by a dripof 50–300 μg/kg per minute),23 and amiodarone (5 mg/kg, maybe repeated twice up to 15 mg/kg, maximum dose 300 mg).23,25
With a PulsePolymorphic ventricular tachycardia likely associated with
CPVTwith a pulse should be managed with removal of catechol-amine stimulus (such as pain or anxiety), β-blocker therapy, andsedation to decrease catecholamine release when stable.26 The ba-sis of this management strategy is to neutralize the adrenergicstimulation from the RyR2 channel resulting in the abnormalCa2+ release. Thus, it is imperative to reduce pain, treat anxiety/agitation, and provide sedation for painful procedures to reducethe adrenergic surge that will potentiate the arrhythmia.
In patients who are unstable and nearing pulseless arrest,management is targeted at immediate cessation of the rhythm,
TABLE 1. Presenting Symptoms of CPVT
Syncope associated with emotional stress or physical exerciseSeizuresPalpitationsChest pain with exerciseCardiac arrestFamily history of sudden unexplained deathECG with ventricular ectopy
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including synchronized cardioversion/defibrillation (polymorphicventricular tachycardia may not permit identification of the QRSfor cardioversion; thus, defibrillation may be necessary),23,25 mag-nesium administration (20–50 mg/kg),25 intravenous β-blockertherapy (propranolol 0.1 mg/kg up to 3 mg over 10 minutes oresmolol 500-μg/kg bolus followed by a drip of 50–300 μg/kgper minute),23 and amiodarone (5 mg/kg over 20–60 minutes).25
Exercise-Related SyncopeApproximately half of pediatric patients who present with
exercise-related syncope are found to have a cardiac etiology.21 Thedifferential diagnoses for syncope with exertion include LQTS,Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy,pulmonary hypertension, Brugada, intermittent heart block,arrhythmogenic right ventricular dysplasia, CPVT, and rarelyneurocardiogenic syncope when all other etiologies have beenruled out.27,28 Tretter and Kavey29 proposed screening for exercise-related syncope with family history of cardiac events or suddenunexplained death, abnormal physical examination, and abnormalECG. If 1 or more of these parameters is positive in a child withsyncope, screening for underlying cardiac disease should be un-dertaken. The etiology of exertional syncope may not be elucidatedin the emergency department, given limited testing; however, thesepatients should be further investigated with an exercise stress test,echocardiography, and cardiology referral.
CHRONIC MANAGEMENT STRATEGIESLong-term management of CPVT is targeted at reduction in
adrenergic stimulation to the RyR2 channel with β-blockers andlifestyle modifications. In patients who continue to be at risk ofventricular arrhythmia, an implantable defibrillator can be placedto prevent sudden cardiac arrest.
Lifestyle modification is the first tenant of management inCPVT patients with the modification or cessation of exercise.7,18,30
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Wall and Iyer Pediatric Emergency Care • Volume 33, Number 6, June 2017
Initial pharmacologic intervention includes β-blocker therapywith propranolol or nadolol; however, there is a 25% treatmentfailure with this intervention.4,7,18 In the setting of incompletecontrol of the ventricular arrhythmia or intolerance of β-blockertherapy, flecainide, which is a direct RyR2-channel blocker, maybe added. In the past, the calcium-channel blocker verapamil wasincluded in the pharmacologic management of CPVT, but effec-tiveness is controversial.4,18
Implantable cardiac defibrillator (ICD) placement is a class Irecommendation for CPVT patients with a history of cardiac ar-rest, recurrent syncope, or polymorphic ventricular tachycardia de-spite pharmacologic therapy.18,31 Even after placement of an ICD,pharmacologic management needs to be optimized to reduce thenumber of shocks a patient experiences. The last line of therapy forCVPT is left cardiac sympathetic denervation, which has been shownto be effective in patients who continue to experience syncope,polymorphic ventricular tachycardia, and/or several appropriateshocks from an ICD despite maximal pharmacologic therapy.18,32
Current research involving gene therapy in a mouse CASQ2CPVT model has shown promise putting a new treatment on thehorizon with implications such as not only CPVT but also heartfailure–associated arrhythmias.33,34
CONCLUSIONSFor our introductory case, he converted to a normal sinus
rhythm with intravenous β-blockade and anxiolysis. He wasstarted on chronic β-blocker therapy with lifestyle modificationsto limit intense physical activity, but was able to return to recrea-tional sports with an automated external defibrillator available atall times. Genetic testing was done for prognostication and toaid in the screening of his immediate family members.
Catecholaminergic polymorphic ventricular tachycardia is arare but life-threatening genetic condition characterized by ven-tricular arrhythmia that can progress to polymorphic ventriculartachycardia in high adrenergic states. The emergency providershould have a high index of suspicion for this pathology in pa-tients presenting with exercise-induced syncope or seizure-likeactivity in the presence of a normal examination, echocardiogram,and baseline ECG.
REFERENCES1. Leenhardt A, Lucet V, Denjoy I, et al. Catecholaminergic polymorphic
ventricular tachycardia in children: a 7-year follow-up of 21 patients.Circulation. 1995;91:1512–1519.
2. Reid DS, TynanM, Braidwood L, et al. Bidirectional tachycardia in a child.A study using His bundle electrography. Br Heart J. 1975;37:339–344.
3. Napolitano C, Priori SG, Bloise R. Catecholaminergic PolymorphicVentricular Tachycardia. In: Pagon RA, AdamMP, Ardinger HH, et al, eds.GeneReviews® [Internet]. Seattle, WA: University of Washington,Seattle; 1993–2017.
4. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expertconsensus statement on the diagnosis and management of patients withinherited primary arrhythmia syndromes: document endorsed by HRS,EHRA, and APHRS inMay 2013 and by ACCF, AHA, PACES, and AEPCin June 2013. Heart Rhythm. 2013;10:1932–1963.
5. Hayashi M, Denjoy I, Extramiana F, et al. Incidence and risk factors ofarrhythmic events in catecholaminergic polymorphic ventriculartachycardia. Circulation. 2009;119:2426–2434.
6. Priori SG. Clinical and molecular characterization of patients withcatecholaminergic polymorphic ventricular tachycardia. Circulation.2002;106:69–74.
7. Roston TM, Vinocur JM, Maginot KR, et al. Catecholaminergicpolymorphic ventricular tachycardia in children: analysis of therapeutic
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strategies and outcomes from an international multicenter registry. CircArrhythm Electrophysiol. 2015;8:633–642.
8. Watanabe H, Knollmann BC. Mechanism underlying catecholaminergicpolymorphic ventricular tachycardia and approaches to therapy.J Electrocardiol. 2011;44:1–6.
9. Fabiato A. Calcium-induced release of calcium from the cardiacsarcoplasmic reticulum. Am J Physiol. 1983;245:C1–C14.
10. Wehrens XH, Lehnart SE, Marks AR. Intracellular calcium release andcardiac disease. Annu Rev Physiol. 2005;67:69–98.
11. Ackerman MJ, Priori SG, Willems S, et al. HRS/EHRA expert consensusstatement on the state of genetic testing for the channelopathies andcardiomyopathies this document was developed as a partnership betweenthe Heart Rhythm Society (HRS) and the European Heart RhythmAssociation (EHRA). Heart Rhythm. 2011;8:1308–1339.
12. Priori SG, Napolitano C, Tiso N, et al. Mutations in the cardiac ryanodinereceptor gene (hRyR2) underlie catecholaminergic polymorphic ventriculartachycardia. Circulation. 2001;103:196–200.
13. Lehnart SE. Sudden death in familial polymorphic ventricular tachycardiaassociated with calcium release channel (ryanodine receptor) leak.Circulation. 2004;109:3208–3214.
14. Lahat H, Pras E, Olender T, et al. A missense mutation in a highlyconserved region of CASQ2 is associated with autosomal recessivecatecholamine-induced polymorphic ventricular tachycardia in Bedouinfamilies from Israel. Am J Hum Genet. 2001;69:1378–1384.
15. Nyegaard M, Overgaard MT, Søndergaard MT, et al. Mutations incalmodulin cause ventricular tachycardia and sudden cardiac death.Am J Hum Genet. 2012;91:703–712.
16. Roux-Buisson N, CacheuxM, Fourest-Lieuvin A, et al. Absence of triadin,a protein of the calcium release complex, is responsible for cardiacarrhythmia with sudden death in human. Hum Mol Genet. 2012;21:2759–2767.
17. Sy RW, Gollob MH, Klein GJ, et al. Arrhythmia characterization andlong-term outcomes in catecholaminergic polymorphic ventriculartachycardia. Heart Rhythm. 2011;8:864–871.
18. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. 2015 ESCGuidelines for the management of patientswith ventricular arrhythmias andthe prevention of sudden cardiac death: the Task Force for the Managementof Patients with Ventricular Arrhythmias and the Prevention of SuddenCardiac Death of the European Society of Cardiology (ESC). Endorsed by:Association for European Paediatric and Congenital Cardiology (AEPC).Eur Heart J. 2015;36:2793–2867.
19. Postma AV. Catecholaminergic polymorphic ventricular tachycardia:RYR2 mutations, bradycardia, and follow up of the patients. J Med Genet.2005;42:863–870.
20. Imberti JF, Underwood K, Mazzanti A, et al. Clinical challenges incatecholaminergic polymorphic ventricular tachycardia. Heart Lung Circ.2016;25:1–7.
21. Miyake CY, Motonaga KS, Fischer-Colbrie ME, et al. Risk of cardiacdisease and observations on lack of potential predictors by clinical historyamong children presenting for cardiac evaluation of mid-exertionalsyncope. Cardiol Young. 2016;26:894–900.
22. Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult AdvancedCardiovascular Life Support: 2015 American Heart Association guidelinesupdate for cardiopulmonary resuscitation and emergency cardiovascularcare. Circulation. 2015;132:S444–S464.
23. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult AdvancedCardiovascular Life Support: 2010 American Heart Association guidelinesfor cardiopulmonary resuscitation and emergency cardiovascular care.Circulation. 2010;122(18 suppl 3):S729–S767.
24. de Caen AR, Berg MD, Chameides L, et al. Part 12: Pediatric AdvancedLife Support: 2015 American Heart Association guidelines update forcardiopulmonary resuscitation and emergency cardiovascular care.Circulation. 2015;132:S526–S542.
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25. Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: PediatricAdvanced Life Support: 2010 American Heart Association guidelines forcardiopulmonary resuscitation and emergency cardiovascular care.Circulation. 2010;122(18 suppl 3):S876–S908.
26. Kenyon CA, Flick R, Moir CR, et al. Anesthesia for videoscopic leftcardiac sympathetic denervation in children with congenital long QTsyndrome and catecholaminergic polymorphic ventriculartachycardia—a case series. Paediatr Anaesth. 2010;20:465–470.
27. Friedman KG, Alexander ME. Chest pain and syncope in children:a practical approach to the diagnosis of cardiac disease. J Pediatr. 2013;163:896–901. e1–e3.
28. Driscoll DJ, Jacobsen SJ, Porter C-BJ, et al. Syncope in children andadolescents. J Am Coll Cardiol. 1997;29:1039–1045.
29. Tretter JT, Kavey RE. Distinguishing cardiac syncope fromvasovagal syncope in a referral population. J Pediatr. 2013;163:1618.e1–1623.e1.
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30. Hammond-Haley M, Patel RS, Providência R, et al. Exercise restrictionsfor patients with inherited cardiac conditions: current guidelines,challenges and limitations. Int J Cardiol. 2016;209:234–241.
31. McNamara DA, Goldberger JJ, Berendsen MA, et al. ImplantableDefibrillators Versus Medical Therapy for Cardiac Channelopathies.McNamara DA, ed. Chichester, UK: John Wiley & Sons, Ltd; 1996.
32. De Ferrari GM, Dusi V, Spazzolini C, et al. Clinical managementof catecholaminergic polymorphic ventricular tachycardia: the roleof left cardiac sympathetic denervation.Circulation. 2015;131:2185–2193.
33. Denegri M, Bongianino R, Lodola F, et al. Single delivery of anadeno-associated viral construct to transfer the CASQ2 gene to knock-inmice affected by catecholaminergic polymorphic ventricular tachycardia isable to cure the disease from birth to advanced age. Circulation. 2014;129:2673–2681.
34. Hajjar RJ, Lyon AR. Gene therapy for the treatment of catecholaminergicpolymorphic ventricular tachycardia. Circulation. 2014;129:2633–2635.
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Wall and Iyer Pediatric Emergency Care • Volume 33, Number 6, June 2017
CME EXAMINATION
JUNE 2017Please mark your answers on the ANSWER SHEET.
Catecholaminergic Polymorphic Ventricular Tachycardia, Wall and Iyer.
1. What is the initial therapy for symptomatic catecholaminergicpolymorphic ventricular tachycardia (CPVT) with a pulse inthe emergency department?a. treatment of pain and/or anxietyb. synchronized cardioversionc. intravenous amiodaroned. external pacing
2. Which enzyme is not associatedwith pathway leading to CPVT?a. triadinb. calmodulinc. troponind. calsequestrin
3. When asymptomatic, what electrocardiogram (ECG) finding ismost characteristic of CPVT?a. ST elevation in the precordial leadsb. prolongation of the QT segment
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c. normal sinus rhythmd. first-degree atrioventricular block
4. What presentation is concerning for CPVT?a. first-time seizure with minimal tonic-clonic activityb. syncopec. palpitations with exercised. family history of CPVTe. all of the above
5. What is the key to diagnosis of CPVT?a. high index of suspicion and thorough historyb. abnormal ECGc. echocardiogramd. cardiac magnetic resonance imaging
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Pediatric Emergency Care • Volume 33, Number 6, June 2017 Polymorphic Ventricular Tachycardia
ANSWER SHEET FOR THE PEDIATRIC EMERGENCY CARECME PROGRAM EXAM
June 2017Please answer the questions on page 432 by filling in the appropriate circles on the answer sheet below. Please mark the one best
answer and fill in the circle until the letter is no longer visible. To process your exam, you must also provide the following information:Name (please print): ___________________________________________________________________________________________Street Address _______________________________________________________________________________________________City/State/Zip _______________________________________________________________________________________________Daytime Phone ______________________________________________________________________________________________Specialty ___________________________________________________________________________________________________
Your completion of this activity includes evaluating them. Please respond to the following questions below.Please rate this activity (1 – minimally, 5 – completely) 1 2 3 4 5Was effective in meeting the educational objectives � � � � �Was appropriately evidence-based � � � � �Was relevant to my practice � � � � �Please rate your ability to achieve the following objectives, both before this activity and after it:1 (minimally) to 5 (completely)
1. Define catecholaminergic polymorphic ventricular tachycardia. � � � � � � � � � �2. Review pathophysiology of catecholaminergic polymorphic ventricular tachycardia. � � � � � � � � � �3. Review presentation and diagnosis of catecholaminergic polymorphic ventricular tachycardia. � � � � � � � � � �4. Reviewelectrocardiogram findings indicative of catecholaminergic polymorphic ventricular tachycardia.� � � � � � � � � �5. Discuss current consensus guidelines for the acute and chronic management strategies
catecholaminergic polymorphic ventricular tachycardia.� � � � � � � � � �
How many of your patients are likely to be impacted by what you learned from these activities?
○ <20% ○ 20%–40% ○ 40%–60% ○ 60%–80% ○ >80%Do you expect that these activities will help you improve your skill or judgmentwithin the next 6 months? (1 - definitely will not change, 5 - definitely will change)
1 2 3 4 5� � � � �
How will you apply what you learned from these activities (mark all that apply):In diagnosing patients ○In monitoring patients ○In educating students and colleagues ○As part of a quality or peformance improvement project ○For maintenance of board certification ○To consider enrolling patients in clinical trials ○
In making treatment decisions ○As a foundation to learn more ○In educating patients and their caregivers ○To confirm current practice ○For maintenance of licensure ○
Other ______________________________________________________________________________________________________Please list at least one strategy you learned from this activity that you will apply in practice:Please list at least one (1) change you will make to your practice as a result of this activity:Did you perceive any bias for or against any commercial products or devices? Yes No
� �If yes, please explain:How long did it take you to complete these activities? _______ hours _______ minutesWhat are your biggest clinical challenges related to pediatric emergency care?[ ] Yes! I am interested in receiving future CME programs from Lippincott CME Institute! (Please place a check mark in the box )
1. �A�B�C�D�E2. �A�B�C�D�E3. �A�B�C�D�E4. �A�B�C�D�E5. �A�B�C�D�E
Mail by May 31, 2018 toLippincott CME Institute, Inc.
Wolters Kluwer HealthTwo Commerce Square
2001 Market Street, 3rd FloorPhiladelphia, PA 19103
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