Cardiomyopathy

Question 1

What is the prevalence of long QT syndrome in the general population?

Answer 1

1 in 2500

Question 2

What gene causes Long QT type 1? What is the mechanism?

Answer 2

KCNQ1

Loss of function

Question 3

What gene causes Long QT type 2? What is the mechanism?

Answer 3

KCNH2

Loss of function

Question 4

What gene causes Long QT type 3? What is the mechanism?

Answer 4

SCN5A

Gain of function

Question 5

What gene causes Long QT type 5 and 6? What is the mechanism?

Answer 5

KNCE1 and KNCE2
Loss of function

Question 6

What gene causes Long QT type 8 (Timothy syndrome)? What is the mechanism?

Answer 6

CACNA1C

Gain of function

Question 7

What genes cause Brugada syndrome and what is the mechanism?

Answer 7

SCN5A (LoF)

KCND3 (GoF)

Question 8

What triggers lethal and non-lethal cardiac events in LQT1?

Answer 8

Exercise (75%)

Question 9

What triggers lethal and non-lethal cardiac events in LQT2?

Answer 9

Sleep, rest without arousal (63%)

Emotion (37%)

Question 10

What triggers lethal and non-lethal cardiac events in LQT3?

Answer 10

Sleep, rest without arousal (80%)

Emotion (15%)

Question 11

Which gender has a higher lethal and non-lethal cardiac events in LQT starting in the mid-30s?

Answer 11

Females

Question 12

Which beta blocker is not effective at treating LQTS?

Answer 12

Metoprolol

Question 13

What is the Incidence of sudden death (per year) in Genotype-positive / Phenotype-positive individuals?

Answer 13

15%

Question 14

What is the Incidence of sudden death (per year) in Genotype-negative / Phenotype-positive individuals?

Answer 14

0.4%

Question 15

What is the Incidence of sudden death (per year) in Genotype-positive / Phenotype-negative individuals?

Answer 15

4%

Question 16

What should you avoid if you have LQTS?

Answer 16

Medications known to prolong QT interval
Rapid electrolyte shifts (fever, illness, dehydration, extreme sports)

Question 17

What is Hypertrophic Cardiomyopathy?

Answer 17

A disease in which the heart muscle becomes thickened (hypertrophied).

The thickened heart muscle can make it harder for the heart to pump blood.

Question 18

What syndromic genetic disorders have Hypertrophic Cardiomyopathy?

Answer 18

• Infiltrative conditions
  -Glycogen storage diseases, Pompe’s disease, Danon disease, Fabry disease
  -Amyloidosis, sarcoidosis, etc.
• Other systemic genetic conditions
  -Noonan syndrome, Costello syndrome, etc.

Question 19

What are the two most common genes associated with Hypertrophic Cardiomyopathy?

Answer 19

MYH7 and MYPBC3

Question 20

What are the phenotypic differences between MYH7 and MYPBC3 and TNNT2 mutations in HCM?

Answer 20

• MYH7 tends to present at a young age with severe disease
• MYPBC3 tends to present at an older age; if presenting at a young age often has very severe disease
• TNNT2 has very little hypertrophy but greater cellular disarray and higher incidence of sudden death.

Question 21

What are the treatments in Hypertrophic Cardiomyopathy?

Answer 21

Goal is to decrease amount of obstruction
* Hydration status
* Beta blockers, Calcium channel blockers

Activity restrictions
* Shared decision model

Surgery

Heart transplant

Defibrillator for primary prevention in high-risk individuals

Question 22

What are some high risk signs in an adult with Hypertrophic Cardiomyopathy?

Answer 22

• Family history of early sudden death
• Syncope
• Systolic dysfunction (EF <50%)
• Documented ventricular tachycardia
• Septal diameter of 30mm or greater

Question 23

What is caused by gain of function mutations in RYR2?

Answer 23

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Question 24

What is caused by loss of function mutations in CASQ2?

Answer 24

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Question 25

What can lead to an event in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?

Answer 25

Exercise, emotion, high stress situations

Question 26

What is the treatment for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?

Answer 26

Beta-blockers Sodium-channel blockers Left sympathetic denervation ICD (Early aggressive management warranted)

Question 27

What is Arrhythmogenic Right Ventricular Cardiomyopathy?

Answer 27

* Fibrofatty replacement of myocardium * More commonly effects the Right Ventricle * Mean age of onset early 30’s * Presents earlier in athletes * “An over-use injury of the heart” * Palpitations or syncope is the most common presenting symptom * May present as sudden death

Question 28

What is the treatment in Arrhythmogenic Right Ventricular Cardiomyopathy?

Answer 28

* Treatment first focused on addressing arrhythmias and avoiding sudden death -Anti-arrhythmic medications -Implantable-cardioverter defibrillator * Must avoid strenuous exercise or competitive athletics

Question 29

What are the two most common genes associated with Arrhythmogenic Right Ventricular Cardiomyopathy?

Answer 29

PKP2 and DSP

Question 30

What are the screening recommendation for Arrhythmogenic Right Ventricular Cardiomyopathy?

Answer 30

* Genotype-positive family members -Should avoid strenuous exercise -Should be screened for disease every 12-18 months (age 10-50) * Gene-negative probands / genetic testing not performed -Counseled on symptoms -Should be screened for disease every 3-5 years (minimum) after age 10

Question 31

What is Brugada syndrome?

Answer 31

A rare but serious condition that affects the way electrical signals pass through the heart. It can cause the heart to beat dangerously fast.