Arrhythmia/channelopathies

Question 1

What are the three most common exacerbators of AF?

Answer 1

Obesity
OSA (but less convincing evidence that managing OSA helps AF)
Alcohol

Question 2

What is the commonest non-ischemic cause of SCD in young?

Answer 2

Hypertrophic cardiomyopathy

90% of SCD are due to ischemic heart disease

Question 3

What is the most common rhythm in SCD?

Answer 3

Ventricular fibrillation

Anti-arrhythmic drugs are not beneficial in preventing SCD

Question 4

What are the indications for ICD?

Answer 4

1. Resuscitated VT/VF cardiac arrest (not due to reversible cause)
2. VT sustained or symptomatic, not ablatable and failed anti-arrhythmic or LVEF <40%
3. Hereditary cardiac conditions (primary and secondary prevention)
   - Hypertrophic cardiomyopathy
   - Long QT syndrome
   - Arrhythmogenic right ventricular dysplasia (ARVD)
   - Brugada syndrome
4. Others - at least 1 month post-MI and LVEF <30%, CHF with LVEF <35%

NOT RECOMMENDED in non-ischemic cardiomyopathy with LVEF <35% (except young people)

Question 5

What are the predictors of sudden cardiac death in hypertrophic cardiomyopathy?

Answer 5

Resuscitated cardiac arrest (12%)
Early symptom onset (6%)
Family hx of SCD (esp >1) (6%)
VT on Holter (6%)
Syncope 
Septal hypertrophy >30mm
Exertional hypotension/ischemia
Specific mutations - Myosin R403Q, troponin T

Question 6

What is the normal QTc interval?

Answer 6

Men - up to 430ms

Women - up to 450ms

Question 7

What is the channelopathy associated with congenital LQTS?

Answer 7

LQT1 (commonest) - affect K channel (underactive), triggered by exercise (68%) and emotional stress (14%). Associated with Jervell-Lange-Nielsen syndrome with bilateral sensorineural hearing loss
LQT2 - affect K channel (underactive), triggered by emotional stress (49%) and exercise (29%)
LQT3 - affect Na channel (overactive), triggered by sleep/bradycardia

LQT3 event rate is lowest but more malignant

Question 8

What are the risk factors for syncope/SCD in LQTS?

Answer 8

QTc >500 (esp >600)
Prior syncope or resuscitated cardiac arrest
Family history of SCD
LQT3 in males 
LQT2 in females 
Deafness 
T wave alternans 
Infant<1yo/neonates

Question 9

What are the QT prolonging drugs?

Answer 9

Anti-arrhythmics - Class 1 (Procainamide, Flecainide, Lidocaine) and Class 3 (Amiodarone, Sotalol)
Anti-depressant - TCA, SSRI, MAO inhibitor
Antibiotics - Erythromycin, Cotrimoxazole
Antifungal -conazoles
Anti-pychotics - Haloperidol, Lithium, Phenothiazine
Terfenadine, Astemizole, Diphenhydramine
Catecholamines
Diuretic (K wasting)
Methadone

Question 10

Anti-arrhythmic drug classes

Answer 10

Class 1 - block Na channel (Procainamide, Lidocaine, Flecainide)
Class 2 - beta blocker (block adrenergic receptor)
Class 3 - block K channel (Amiodarone, Sotalol)
Class 4 - calcium channel blocker (Verapamil, Diltiazem)
Class 5 - other or unknown mechanism

Question 11

Strong risk factors for stroke in the context of AF

Answer 11

Age - scores 2 points
Previous stroke/TIA/thromboembolism - scores 2 points

But if you have valvular heart disease e.g. mitral stenosis - risk of stroke is 20x higher compared to non-valvular 4x

Question 12

CHA2DS2VASc

Answer 12

CHF
HTN
Age ≥75 - 2 points 
Diabetes
Stroke/TIA/thromboembolism - 2 points 
Vascular disease 
Age 65-74 - 1 point 
Sex (female) 

Maximum score you can get is 9
If ≥2 anticoagulation indicated
If score 1 anticoagulation still probably superior to Aspirin (but except when 1 point only due to female sex without other risk factor)

Question 13

When do you use NOAC vs Warfarin?

Answer 13

NOAC is superior to Warfarin in non-valvular AF (bleeding risk was similar, less fatal/intracranial bleeding, lower mortality)

Question 14

When should you use rhythm control for AF?

Answer 14

In young pt usually fit and well and AF onset <48hrs
Flecainide - use if no underlying structural heart disease/CAD, effective in short duration <24hr AF
Amiodarone - can be used in presence of structural heart disease

Cardioversion (DCCV) indicated in haemodynamic instability - severe acute HF, hypotension

Symptomatic persistent AF can be cardioverted but need anticoagulation prior (should be therapeutically anticoagulated for at least 4 weeks

NOTE: AFFIRM study comparing rhythm vs rate control showed no reduction in mortality, higher hospitalisation, no reduction in stroke with rhythm control approach

Question 15

What is the commonest Long QT syndrome?

Answer 15

LQT1 type is commonest - mutation in K channel KVLQT1/KCNQ1 (underactive)
Triggered by exercise (64%) and emotional stress (14%)
Associated with Jervell-Lange-Nielsen syndrome - bilateral sensorineural hearing loss

Amount of repolarising current reduced leading to increased action potential duration. Myocyte refractory phase lengthened.

Question 16

What are the features of LQT3?

Answer 16

Mutation in Na channel (SCN5A) - becomes overactive
Slow inactivation of sodium channel results in prolonged Na influx during depolarisation

Can be triggered by bradycardia/sleep - don’t use B-blocker in LQT3

Question 17

What are the HIGH risk factors for SCD in LQTS?

Answer 17

QTc >500 (especially >600)

LQT1, LQT2, male sex LQT3

Question 18

What is the treatment for LQTS?

Answer 18

Beta blockers first line in LQT1 and LQT2 types (NOT in LQT3) - Propranolol or Nadolol preferred (they reduce syncope and SCD)

Avoid QT prolonging meds, correct electrolyte imbalance

ICD for primary vs secondary prevention
Family history alone is not an indication of ICD. Not everyone with congenital LQTS have ICD

Question 19

What is Andersen Tawil Syndrome?

Answer 19

It is LQT7 affecting K channel (KCNJ2 mutation) - autosomal dominant
QT can be prolonged or normal
Can get ventricular arrhythmia - rarely fatal
Periodic paralysis - potassium responsive
Dysmorphic features - hyperteleorism, short stature, micrognathia, broad forehead, scoliosis

Question 20

What are the features of Brugada syndrome?

Answer 20

Na channel mutation - same as LQT3 but here Na channel is underactive
Autosomal dominant inheritance, common in young south east asian males

Right precordial (pseudo RBBB) ST elevation on ECG - typically V1, V2
Sudden death, VF - especially during sleep
Increased risk of atrial arrhythmia mainly AF
Exacerbating factors are fever, class 1 anti-arrhythmic drugs e.g. Flecainide
Treatment with ICD

All 1st degree relatives should be tested with ECG
Type 1 pattern - coved type ST, T wave negative
Type 2 pattern - saddle back ST, T wave positive or biphasic

Question 21

What are the features of arrhythmogenic right ventricular dysplasia?

Answer 21

Inherited myocardial disease associated with paroxysmal ventricular arrhythmia and SCD (2nd most common cause of SCD after HCM in young)

ECG - Epilson wave (small positive deflection at the end of QRS complex, this is most specific finding), T wave inversion in V1-V3, localised QRS widening V1-V3

Question 22

What is catecholamine induced polymorphic VT?

Answer 22

Exercise or emotion induced ventricular arrhythmia - symptoms generally develop <20yo, high mortality 30-50%
Normal QT interval
Most common mutation is Ryanodine receptor mutation (found in myocardial sarcoplasmic reticulum) - autosomal dominant
Rare mutation is Calsequestrin CASQ2 - autosomal recessive
Both mutations act by inducing diastolic calcium release from the sarcoplasmic reticulum —> resulting in intracellular calcium overload —> delayed afterdepolarisation and triggered activity

Treatment with ICD, beta blockers
Genetic testing for any patient suspected of having CPVT and all relatives where a pathological mutation identified

Question 23

What are the non-selective beta blockers (both B1 and B2)?

Answer 23

Propranolol
Carvedilol - also alpha blocking
Labetalol - also alpha blocking
Nadolol

Question 24

What are the selective beta blockers (cardioselective, B1)?

Answer 24

Atenolol
Bisoprolol
Metoprolol
Celiprolol
Esmolol
Nebivolol