Cardiology - Non-QT Channelopathies Flashcards
(37 cards)
Brugada: Who is it more common in?
Male > Female
Asian
Peak prevalence of sudden cardiac death in 4th decade (ie: 30’s)
What mutation is most commonly seen in Brugada?
10-30% have a LOSS-of-function mutation in SCN5A gene encoding voltage gated Na channel
with AUTOSOMAL DOMINANT inheritance
What other genes (other than the most common type) are seen in Brugada?
Alpha-1 and Beta-2 subunits of L-type Calcium Channel
(= CACNA1C and CACNB2)
GPD1-L
SCN1B
When do Brugada patients most commonly present?
After syncope or cardiac arrest
When do arrythmias commonly occur in Brugada?
Typically in the nighttime with nocturnal nightmares and thrashing
What can unmask a Brugada on an ECG?
- Febrile
- Hyper or Hypo kalaemia
- HypERcalcaemia
- Alcohol or cocaine
The unmasking challenge with Flecainide
What arrythmias is Brugada associated with?
AF
Polymorphic VT
ECG features of Brugada?
- Broad P with some PQ prolongation
- Convex/coved ST segment elevation >2mm in one or more of V1-V3
- TWI in V1-V3
- J point elevation
+/- partial RBBB
Which antiarrythmic do we use to ‘unmask’ Brugada?
Flecainide
Management of Brugada?
ICD if syncope or ventricular arrythmias
Quinidine if recurrent syncope or ICD shocks
Prognosis of Brugada?
8% have VF or sudden death within 2 years
Mean age of death 41 years old
What inheritance and genes are involved in Catecholaminergic Polymorphic VT (CPVT)
Autosomal DOMINANT (prevalence 1 in 10,000)
RYR2 (ryanodine receptor) in myocardium sarcoplasmic reticulum
Calsequestin-2 is calcium binding protein in sarcoplasmic reticulum
Catecholaminergic Polymorphic VT (CPVT) has what clinical features
- Sudden cardiac death
- Family history
- Symptoms begin <20 years old
- Provokable arrythmias on EXERCISE or when given ADRENALINE
(–>polymorphic VT or alternating QRS)
In catecholaminergic polymorphic VT (CPVT) what provokes arrythmias and what types of arrythmias?
Provoked by: Exercise & adrenaline
Polymorphic VT
Alternating QRS
Management of catecholaminergic polymorphic VT (CPVT)?
- Flecainide or verapamil
- Betablocker plus ICD
- Abstain from exercise
- Sympathectomy (ESPECIALLY if ICD insertion results in MORE VT)
What channelopathy must you think of if a patient is from Italian or Greece (especially VENETO region of Italy)?
Arrythmogenic Right Ventricular Cardiomyopathy / Dysplasia (ARVC/D)
How common is Arrythmogenic Right Ventricular Cardiomyopathy / Dysplasia (ARVC/D)
1 in 1000-2000
What is the inheritance of Arrythmogenic Right Ventricular Cardiomyopathy / Dysplasia (ARVC/D)
Autosomal DOMINANT with variable penetrance (50%)
What is Naxos Disease?
A variant of Arrythmogenic Right Ventricular Cardiomyopathy / Dysplasia (ARVC/D)
- Autosomal RECESSIVE mutation on Ch17q21 with 100% penetrance
- Associated with:
- –ARVC/D
- –Wooly hair
- –Palmoplantar keratosis
The disease characterised by ARVC/D, wooly hair and palmoplantar keratosis is what? And what gene?
Naxos disease
Autosomal RECESSIVE
Ch17q21
What pathophysiology features are seen in Arrythmogenic Right Ventricular Cardiomyopathy / Dysplasia (ARVC/D)
Right ventricle myocardium gets replaced by fatty and fibrofatty tissue
Due to mutations in DESMOSOMAL proteins at CELL-TO-CELL JUNCTIONS
What genes are associated with ARVC/D
JUP: Plakoglobin DSP: Desmoplakin PKP2: Plakophilin-2 (EARLIER ONSET) DSG2: Desmoglein-2 DSC2: Desmocollin-2 TMEM43
Which ARVC/D associated gene is also associated with an earlier onset?
PKP2: plakophilin-2
How does Arrythmogenic Right Ventricular Cardiomyopathy / Dysplasia (ARVC/D) present clinically?
Presents in 2nd-5th decades
Usually Asymptomatic
But present with palpitations / syncope / sudden cardiac death / heart failure
