Adult Complexities of the Channelopathies
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1 Adult Complexities of the Channelopathies Andrew Krahn MD FHRS Sauder Family and Heart and Stroke Foundation Chair in Cardiology Paul Brunes Chair in Heart Rhythm Disorders University of British Columbia Vancouver Canada
2 Conflict of Interest Consulting: Medtronic Research: Boston Scientific, Medtronic People of BC: Clinical Income Organizations: Canadian Cardiovascular Society, Heart Rhythm Society, Hearts in Rhythm Organization Families of Sudden Death Victims: Paul Brunes Chair in Heart Rhythm Disorders I am an open access person for slides, e mail akrahn@mail.ubc.ca (I will repeat that at the end)
3 The Bottom Line What are we talking about? Long QT Brugada CPVT Some uncommon odds and ends, IVF, Short QT, early repolarization
4 The Bottom Line Doesn't have to be complicated: 1. You have a symptom, a family member or test that makes someone think you might have one of these conditions 2. You go for heart tests, if they are suspicious, you have a genetic test, and you get a diagnosis 3. You get lifestyle advice, maybe a beta blocker, maybe an ICD 4. And its all good If we are lucky, this happens half the time
5 Lets look at an example - Annie 24 year old female, mother died of breast cancer 2 years ago Cousin in Halifax recently fainted and was diagnosed with Long QT Dad urges his daughter to get tested, she finds us online and requests a referral She is well, working after graduating from University Normal QT Borderline QT
6 Lets look at an example 24 year old female, mother died of breast cancer 2 years ago Cousin in Halifax recently fainted and was diagnosed with Long QT Dad urges his daughter to get tested, she finds us online and requests a referral She is well, working after graduating from University Normal QT Borderline QT
7 Next Steps (when it works out) 1. Comes to our clinic with her Dad and has a treadmill test 2. Meets the team and has a family tree compiled 3. Exercise test shows borderline QT that becomes abnormal 4. Told that she is likely to have Long QT, and that she would benefit from genetic testing 5. Given the SADS Long QT booklet, a list of medications to avoid 6. Consent for genetic testing and the national Long QT registry 7. Leaves a spit or blood sample 8. Takes the genetic counsellor s card and contacts her with questions 9. Genetic results from Dr. Gardiner s patient is used to test our patient that confirms Long QT, goes on a beta blocker
8 A Little More Complicated SAME LONG QT MUTATION 21 yo male worrisome fainting 23 yo brother asymptomatic
9 potassium QT Gene Our QT Channels translator Potassium Channel outside inside assembler potassium Heart Cell
10 Crude Schematic mutant GG translator allele 2 strands: normal + = AA translator allele + = Assembly into tetramers Lots of mutant subunits poor channel function longer QT
11 Crude Schematic mutant AA translator allele + = 2 strands: normal GG translator allele + = Assembly into tetramers Lots of normal subunits better channel function shorter QT
12 potassium Bad QT Channels Potassium Channel outside inside assembler potassium Heart Cell
13 potassium Better QT Channels Potassium Channel outside inside assembler potassium Heart Cell
14 And our usual confusing story 27 year old street person Collapses on the street and brought in, has a cardiac arrest in the emergency room, nothing recorded Lives in a shelter, no family contact, using marijuana, previous cocaine use, EKG shows long QT EKG gets better, gets an ICD, sent home Back in hospital with shocks from his ICD, drug overdose Care team calls the genetic team because the QT is long Has genetic testing which does not show anything Put on beta blockers, tells us to our face he won t take them Does he have Long QT?
15 Other Kinds of Complicated 18 year old athlete faints during basketball practice Tests show lots of skipped beats called PVCs Diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC) Family check shows Mom has Brugada!!! Genetic testing is negative This is called Overlap Syndrome
16 Sources of Complicated All of our tests are imperfect Lots of overlap between normal and abnormal Genetic testing is more capable but MUCH more complicated It can be hard to get a whole family picture These conditions are different between family members, and vary from day to day in the same person The number of parts in play is likely 100s to 1000s!
17 Approach to Long QT Symptoms +/- Ventricular Arrhythmia and Suspected LQTS Asymptomatic QT Prolongation on ECG Suspected LQTS Family Member of LQTS Proband Inherited HR Clinic with ECG* QT Treadmill Test Strong Suspicion LQTS Genetic Testing Beta Blocker Possible LQTS Discretionary Genetic Testing +/- Epinephrine Infusion* Unlikely LQTS Repeat Treadmill on Beta Blocker Review Genetic Test Epinephrine + Genetic Testing Beta Blocker Epinephrine +/- Discretionary Genetic Testing and Beta Blocker and Clinic Follow-up Epinephrine - Inherited HR Clinic with Treadmill 1 year Proband + Genetic Testing Inherited HR Clinic or Call Back to Discuss Results No Proband + Family Screening Letter Inherited HR Clinic with Treadmill Every 2 years Discharge from Clinic
18 Urgent in Patient or Clinic Consider ICD symptoms Brugada ECG* * ECG Guide Type 1 Type 2 or 3 Type 1 Procainamide Infusion High Leads and SAECG Inherited Arrhythmia Clinic Type 2 Type 2 or 3 Type 1 Type 3 Syncope, positive family history, fractionation, early repolarization on ECG Follow-up q 2 years yes Reassurance, Permission to Contact Risk Discussion Drug Avoidance Treat Fever Family Screening ± Genetic Testing ± EP Study * ECG should include high lead placement, and baseline signal averaged ECG Discretionary EP testing, generally discouraged CCS Guidelines recommend genetic testing when there is a positive family history or phenotypically affected first degree relative no
19 Comments and Conclusions We all need to be open minded and humble So much to learn Philosophy: More and better information begets better decisions We are a lot further ahead than years ago with systems that are helpful 90% of the time Half the time its clean cut Teams think and work together to help understand the complicated ones Communication, research, exchange I am an open access person for slides, e mail akrahn@mail.ubc.ca
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