What if my panel is negative? How do I manage my patient? · 2016-10-25 · Robert Campbell, MD...

What if my panel is negative? How do I manage my patient?

Robert Campbell, MD September 30, 2016

Children’s Healthcare of Atlanta | Sibley Heart Center Cardiology

NO DISCLOSURES


Negative LQTS gene panel report


Are you surprised?

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj4v9P1pc7OAhUCLSYKHfr2AMoQjRwIBw&url=https://www.pinterest.com/pin/229965124699425758/&bvm=bv.129759880,d.eWE&psig=AFQjCNFprkgIxZPM5q5ptyzonsFuSV9JXQ&ust=1471724144734055

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiEqpnQpc7OAhXF0iYKHewBAb8QjRwIBw&url=https://www.reddit.com/r/aww/comments/4luoa1/our_puppy_hides_from_us_when_he_breaks_a_rule/&bvm=bv.129759880,d.eWE&psig=AFQjCNHLAbRnv_bFrTLl8LGoxc4JcnDQmQ&ust=1471724026043692


Now what?

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiZvcuNyt_OAhUCRCYKHSo8CH8QjRwIBw&url=http://www.iconsdb.com/blue-icons/backspace-icon.html&bvm=bv.131286987,d.eWE&psig=AFQjCNFjyC1g58wBRprj3BJuAaotJSwIbg&ust=1472317976923968





What was your initial level of clinical suspicion?


Clinical Scenario A: Syncope

• 14 year old female • Negative family history • Vasovagal warning signs • Normal ECG

http://www.term.org/wp-content/uploads/2012/02/Fainting.png


Schwartz criteria 2012

Clinical Scenario B: Syncope 14 year old female

http://www.term.org/wp-content/uploads/2012/02/Fainting.png


Clinical Scenario B

QTc = 690ms

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiu6catg87OAhUKKCYKHaQTAswQjRwIBw&url=http://www.nhs.uk/conditions/long-qt-syndrome/Pages/Introduction.aspx&bvm=bv.129759880,d.eWE&psig=AFQjCNFRNWfEVI_jYEvzseam4PQsZoUprw&ust=1471714878564825

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjMsdjKg87OAhUE3SYKHbcqB2gQjRwIBw&url=http://eden-pa.blogspot.com/2012/11/ekg-fun.html&bvm=bv.129759880,d.eWE&psig=AFQjCNGTcs95Rx5GcCcSfkXVO0jdjpSyag&ust=1471714935841708

True Positive False Positive

True Negative False Negative LQTS

gen

otyp

e

Positive

Negative

Patient Truth Positive Negative

A B


What is your LQTS genotype hit rate? GeneDx data: LQTS is 75-80% and has been the same since beginning too, with minimal increase in detection because the main gene players have always been on the panel…


Now What …..??


1. Genetic Counselors

• Obtain multigenerational family pedigree • Explain the role of genetic testing • Obtain sample • EXPLAIN THE RESULTS


• Re-review family history and patient history • Reanalyze all ECGs • Personally review

exercise testing results, epi challenge

Overestimation of QTc Diagnosing LQTS based on “borderline QTc” Confusion with vasovagal syncope

2. “Revisit Clinical Diagnosis”

(Circulation 2007;115;2613-2620)

Diagnostic Miscues in Congenital Long-QT Syndrome


15y QTc 508 Syncope,chest pain Palpitations Prev nl card. Eval KCNQ1

16

36 y SCA 6 days post partum

~40y SCA Cocaine

SCA driving 53y ?valve abnl

21y SCA at rest

ICD

?

5 5

No screen

ICD KCNQ1 +

KCNQ1+

KCNQ1+

17y ICD KCNQ1 + @11y

?

? ?

died in old age, hx of syncope

d.5y SCA

Vfib SCA

?

?

ICD

3. Have you constructed a complete and correct multigenerational family pedigree? Have you tested the right family member?


4. Do you have cascade testing on first degree relatives?

17

14y

MVA ‘fell asleep At the wheel’

45y 44y

16y

Sudden Cardiac Arrest CPVT RYR2 positive

55y

80y

d. 15y d. 55y

MVA Playing outside

d. 32y d. 22y

MVA MVA

RYR2 neg.


5. Gene testing

• Era of the genotype • Research versus clinical • Panel density


6. Consider Comprehensive Arrhythmia Panel? CPVT vs LQTS

http://i0.wp.com/lifeinthefastlane.com/wp-content/uploads/2011/04/ECG-1-BVT1.jpg


7. Next level genetic testing


8. Center of Excellence 2nd Opinion

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwj4-c28t-nOAhVK5iYKHSbcAcwQjRwIBw&url=http://yfashlanso.blogspot.com/2016/04/the-value-system-and-raising-children.html&bvm=bv.131286987,d.eWE&psig=AFQjCNF8REYxLEV4z-lRIgmrp3G_nHQ5Vg&ust=1472656580289930

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjG0dvat-nOAhVFySYKHWioDtAQjRwIBw&url=http://allegianceadvisory.com/news-resources/&bvm=bv.131286987,d.eWE&psig=AFQjCNFB7X8S-VceTEKRtmA6ZJMHP8tbTg&ust=1472656634001488

http://www.i4process.com/iprocess4/wp-content/uploads/2015/04/Screen-Shot-2015-04-20-at-5.17.47-PM.png


9. SADS Scientific Advisory Board review

http://www.sads.org/


Ultimately …. In the absence of a positive genotype …

Confirm a correct clinical diagnosis


Ultimately …..

When uncertain regarding diagnosis will you:

Underdiagnose? • Under-test • Under-treat • Under-restrict • Under-worry • ? Under-protect from SCA

Overdiagnose? • Over-test • Over-treat • Over-restrict • Over-worry • Better protected from SCA


Summary

• Negative genotype does not exclude disease • Negative genotype may confuse/confound diagnosis,

so …. take a deep breath and reconsider all clinical clues

• Consider second opinions, COE • Ultimate goal is correct diagnosis management • Consider repeating genotype in the future

What if my panel is negative? How do I manage my patient? · 2016-10-25 · Robert Campbell, MD...

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