Cardiomyopathy Flashcards
What is the prevalence of long QT syndrome in the general population?
1 in 2500
What gene causes Long QT type 1? What is the mechanism?
KCNQ1
Loss of function
What gene causes Long QT type 2? What is the mechanism?
KCNH2
Loss of function
What gene causes Long QT type 3? What is the mechanism?
SCN5A
Gain of function
What gene causes Long QT type 5 and 6? What is the mechanism?
KNCE1 and KNCE2
Loss of function
What gene causes Long QT type 8 (Timothy syndrome)? What is the mechanism?
CACNA1C
Gain of function
What genes cause Brugada syndrome and what is the mechanism?
SCN5A (LoF)
KCND3 (GoF)
What triggers lethal and non-lethal cardiac events in LQT1?
Exercise (75%)
What triggers lethal and non-lethal cardiac events in LQT2?
Sleep, rest without arousal (63%)
Emotion (37%)
What triggers lethal and non-lethal cardiac events in LQT3?
Sleep, rest without arousal (80%)
Emotion (15%)
Which gender has a higher lethal and non-lethal cardiac events in LQT starting in the mid-30s?
Females
Which beta blocker is not effective at treating LQTS?
Metoprolol
What is the Incidence of sudden death (per year) in Genotype-positive / Phenotype-positive individuals?
15%
What is the Incidence of sudden death (per year) in Genotype-negative / Phenotype-positive individuals?
0.4%
What is the Incidence of sudden death (per year) in Genotype-positive / Phenotype-negative individuals?
4%
What should you avoid if you have LQTS?
Medications known to prolong QT interval
Rapid electrolyte shifts (fever, illness, dehydration, extreme sports)
What is Hypertrophic Cardiomyopathy?
A disease in which the heart muscle becomes thickened (hypertrophied).
The thickened heart muscle can make it harder for the heart to pump blood.
What syndromic genetic disorders have Hypertrophic Cardiomyopathy?
- Infiltrative conditions
-Glycogen storage diseases, Pompe’s disease, Danon disease, Fabry disease
-Amyloidosis, sarcoidosis, etc. - Other systemic genetic conditions
-Noonan syndrome, Costello syndrome, etc.
What are the two most common genes associated with Hypertrophic Cardiomyopathy?
MYH7 and MYPBC3
What are the phenotypic differences between MYH7 and MYPBC3 and TNNT2 mutations in HCM?
- 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.
What are the treatments in Hypertrophic Cardiomyopathy?
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
What are some high risk signs in an adult with Hypertrophic Cardiomyopathy?
- Family history of early sudden death
- Syncope
- Systolic dysfunction (EF <50%)
- Documented ventricular tachycardia
- Septal diameter of 30mm or greater
What is caused by gain of function mutations in RYR2?
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
What is caused by loss of function mutations in CASQ2?
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
What can lead to an event in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?
Exercise, emotion, high stress situations
What is the treatment for Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)?
Beta-blockers
Sodium-channel blockers
Left sympathetic denervation
ICD
(Early aggressive management warranted)
What is Arrhythmogenic Right Ventricular Cardiomyopathy?
- 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
What is the treatment in Arrhythmogenic Right Ventricular Cardiomyopathy?
- Treatment first focused on addressing arrhythmias and avoiding sudden death
-Anti-arrhythmic medications
-Implantable-cardioverter defibrillator - Must avoid strenuous exercise or competitive athletics
What are the two most common genes associated with Arrhythmogenic Right Ventricular Cardiomyopathy?
PKP2 and DSP
What are the screening recommendation for Arrhythmogenic Right Ventricular Cardiomyopathy?
- 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
What is Brugada syndrome?
A rare but serious condition that affects the way electrical signals pass through the heart.
It can cause the heart to beat dangerously fast.
