Life Threatening EKG’s In The Office

Joseph A Manfredi, MD, FACC, FHRS GHS Cardiovascular Symposium January 24th, 2015 Disclosures

 Speaker Honorariums: STJM, Boston Scientific  Advisory role: Medtronic  Stock: Boston Scientific Willem Einthoven 1903 Willem Einthoven’s Nobel Prize Lecture December 11, 1925

PERICARDITIS

Wolff-Parkinson-White Syndrome

45 year old woman Presented with No prior cardiac history Recently started on Azithromycin Prior history of a “seizure disorder” LONG QT SYNDROME What is a prolonged QTc ?

>0.44 s M vs. >0.46s F

Symptoms

 Range from SCD to syncope or near syncope  Patients who have suffered a SCA have a ominous prognosis with a 12.9 RR of experiencing another event.

Reference: 1. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. 2000;101:616-623. Beta-blocker Therapy for LQTS

17 Reference: 1. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. 2000;101:616-623. Management  Beta-Blockers (Less helpful in LQT3)  Exercise restriction  Pace or Isoproterenol  Avoid QT prolonging drugs www.qtdrugs.org  /electrolytes  AICD  Cervico-sympathectomy  Beta-Blockers immediate post-partum

Probability of Any Cardiac Event

Sauer, A. J. et al. J Am Coll Cardiol 2007;49:329-337

Copyright ©2007 American College of Foundation. Restrictions may apply. Suggested Risk-Stratification Scheme for ACA or SCD in LQTS Patients

Goldenberg, I. et al. J Am Coll Cardiol 2008;51:2291-2300

Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply. to Avoid

 Cardiac: , , , Dofetilide, and Procainamide  Psychiatric: Haldol, Fluoxetine, Sertraline  Antibiotics: Flouroquinolones, Mycins  Narcotics: Methadone SHORT QT SYNDROME Background

 No evidence on whether specific triggers precipitate events  Mutations in at least 3 genes have been identified……. KCNQ1 (Iks), KCNH2 (Ikr), nd KCNJ2 (Ikl)  These are similar to LQTS but with gain of function as opposed to loss of function  Autosomal Dominant Inheritence  EPS ? (usually shows easily inducible ventricular but it is not known if this is predictive of adverse outcomes)

When to Suspect SQT

 Atrial at a very young age  Family member with short QT  Family member with SCD  EKG with tall/peaked T waves  QT interval of < 350 ms at 60 BPM

15 year old presents to the ER with atypical chest pain Brugada Syndrome Risk Stratification Original Brugada description Circ 1998;97;457-460. 63 patients 30% risk of at 3 years EPS is predictive of high risk 60 –90 % inducible ICD usually advised Brugada Syndrome

ST elevation V1 and V2, RBBB ECG changes are variable and dynamic (can be provoked by sodium channel blocking agents – ajmaline, procainamide) M > F 3rd and 4th decades Worldwide, but common in SE Asia Brugada Syndrome Genetics 30% with mutations in SCN5A Autosomal Dominant Usually a loss of function mutation (this gene is also implicated in LQTS3) At least 28 different mutations identified Clinical Presentation

 Syncope  SCA  Usually in males in the 3rd to 4th decade of life (Reported cases of SCA in Neonates)  Fever is a predisposing factor for SCA  Patients with Syncope and a spontaneous Type I ECG have a 6 fold higher risk of SCA than those without syncope and Type I ECG

BRUGADA EKG ECGs from a 35-year-old male who has been successfully resuscitated

1 5

Wilde, A. A.M. et al. Circulation 2002;106:2514-2519 Brugada Syndrome Risk Stratification  High risk pts: baseline ST elevation and syncope – 44% had cardiac arrest; therefore ICD  Intermediate risk patients: spontaneous ST elevation > 2mm without syncope –14% had cardiac arrest; treatment undefined (? ICD)  Low risk patient: diagnostic ECG only after provocation – 5% had cardiac arrest over 4 decades of follow up – reassurance – no ICD –avoid Na channel blockers and TCA’s  Presymptomatic screening of family members without resting ECG abnormalities is not useful Sudden Cardiac Death

Rapid VF or PMVT frequently occurring at rest or during sleep Holter monitoring does not usually show frequent PVC’s or NSVT

Bidirectional VT Catecholaminergic Polymorphic Ventricular (CPMVT) CPMVT Background

 Is one of the most lethal if not recognized and treated.  Characterized by ventricular arrhythmias induced by emotional stress or exercise (present with syncope during exercise, similar to Long QT but with a normal EKG)  Onset usually in childhood and adolescence  Caused by mutations in the cardiac ryanodine receptor (RyR2) in the Autosomal Dominant form  Resting EKG is usually normal

Challenges in Diagnosing CPMVT

 Exercise stress testing is an important part of a CPVT workup. - However, in as many as 20% of CPVT patients, formal exercise stress testing will not produce ventricular ectopy.  During exercise stress testing, bidirectional VT with a beat-to-beat 180 degree rotation of the QRS complex is often observed.1

References: 1. Mohamed U, Napolitano C, Priori SG. Molecular and electrophysiological bases of catecholaminergic polymorphic . J Cardiovasc Electrophysiol. 2007;18(7):791-797. 2. Kontula K, Laitinen PJ, Lehtonen A, Toivonen L, Viitasalo M, Swan H. Catecholaminergic polymorphic ventricular tachycardia: recent mechanistic insights. Cardiovasc Res. 2005;67:379-387. 16 year old boy Cardiac arrest while playing high school basketball Successfully resuscitated No prior history of cardiac disease Hypertrophic

Sudden Death in Young Athletes

NEJM 2003;349:1064 Hypertrophic Cardiomyopathy Apical Variant Hypertrophic Cardiomyopathy Hypertrophic Cardiomyopathy Risk Stratification  Clinical: syncope, FH of SCD, younger age  Testing: VT-NS, Exercise decrease in BP. LVH (septum > 30 mm), LVOT gradient > 30 mm Hg (NEJM 2003;348:295.)

 3 Risk Factors 6%/yr SCD risk Hypertrophic Cardiomyopathy

NEJM 2003;349:1064 14 year old boy Passed out while swimming competitively Required CPR but no defibrillation No prior history of cardiac disease No family history of SCD ARVD-Epsilon wave

ARVD - MRI ARVD Treatment

Minimal data Ablation – multiple foci and high rate of recurrence Antiarrhythmic drugs - ? Sotalol ICD Avoid competitive athletics

Thank you