Arrhythmogenic inherited conditions

Question 1

What are channelopathies?

Answer 1

Abnormal cardiac cellular electrophysiology which mainly effects the repolarisation phase.

Question 2

If you have a channelopathy, if there a problem with the structure and function of the heart?

Answer 2

No its all normal but you have an abnormal ECG and a propensity to develop both atrial and ventricular arrhythymias

Question 3

Who do channelopathies effect?

Answer 3

Young people. If you get a young person with AF think channelapathy

Question 4

What does a surface ECG show?

Answer 4

The summation of all the ion currents across the cell membrane

Question 5

What causes channelopathies?

Answer 5

Genetically inherited. Many genes and many different mutations but they lead to one phenotype

Question 6

What is congenital long QT syndrome?

Answer 6

Where the QT segment >440milliseconds in men and >450 in women

Question 7

What causes congenital long QT syndrome?

Answer 7

Mutation in many genes. Most common is the potassium voltage gated channel member 1 (KVLQT1). There are 13 subtypes.

Question 8

What are the hallmark arrhythmias of congenital long QT syndrome?

Answer 8

Polymorphic VT and Torsades de Pointes.
Triggered by adrenergic stimulation.

Other associated arrhythmias are AF and heart block

Question 9

How does congenital long QT syndrome present in children?

Answer 9

Syncope or sudden cardiac death

Question 10

What is Romano Ward syndrome?

Answer 10

Isolated long QT syndrome. Autosomal dominant

Question 11

What is Timothy syndrome/Anderson-Tawil syndrome?

Answer 11

Long QT syndrome with extracardiac features. Autosomal dominant

Question 12

What is Jervell syndrome/Lange-Nielson syndrome?

Answer 12

Long QT syndrome associated with deafness. Autosoma recessive

Question 13

What are the mechanisms of long QT syndrome?

Answer 13

Less repolarising current prolongs the action potential (decreased K+ currents)
More depolarising current prolongs the action potential (increased Na+ current)

Question 14

What is the molecular basis for long QT syndrome?

Nature loads the gun but the environment pulls the trigger.

Answer 14

Gene mutations => faulty ion channel
Reduced or dysfunctional diastolic current that prolongs repolarisation.
QT interval extended which predisposes to polymorphic VT
An environmental trigger causes polymorphic VT => syncope/SCD

Question 15

What is a class 1 diagnosis of congenital long QT syndrome?

Answer 15

QT >480ms in repeated 12 lead ECGs
or LQT risk score >3
or LQT syndrome mutation found irrespective of the QT duration

Question 16

What is a class 2 diagnosis of congenital long QT syndrome?

Answer 16

QT >460ms with unexplained syncope in the absence of secondary causes of QT prolongation

Question 17

What is the management of long QT syndrome?

Answer 17

Aviod QT prolonging drugs (www.crediblemed.org)
Correction of electrolyte abnormalities (high K+ diet, especially during diarrhoea, nausea and vomiting episodes)
Avoidance of swimming- strenuous swimming, breath holding and sudden loud noises

Question 18

What causes Brugada syndrome?

Answer 18

Many genes. Most common is Na+ voltage gated channel in the type Valpha subunit.
Autosomal dominant

Question 19

Brugada syndrome is autosomal recessive. T or F?

Answer 19

False. Its autosomal dominant

Question 20

What are the common arrythmias associated with Brugada syndrome?

Answer 20

AF, ST elevation (abnormal doming) and RBBB is V1-V3

Risk of polymorphic VT or VF

Question 21

What are the triggers for VF in Brugada syndrome?

Answer 21

Rest/sleep
Fever
Excessive alcohol/large meals
(More common in patients with previous MI or syncope)

Question 22

Does the genotype and family history of Brugada syndrome influence prognosis?

Answer 22

No

Question 23

How is Brugada syndrome managed?

Answer 23

1) Aviod drugs which may induce ST elevation (www.brugadadrugs.org) Antiarrythmic drugs, psychotrophics (antidepressants) Analgesics and anathetics
2) Aviod excessive alcohol/large meals
3) Prompt treatment of fever with antipyrexials
4) ICD implantation is recommended if patient have a cardiac arrest or documented spontaneous sustained VT and considered in ECG changes with syncope

Question 24

What causes cardiomyopathies?

Answer 24

Many genes and many mutations but only one phenotype.

Question 25

What is hypertrophic cardiomyopathy?

Answer 25

Very large muscular left ventricle. Blood supply insufficient to supply to cardiac muscle => Ischemia (arrhythmias) and infarction

Question 26

What causes hypertrophic cardiomyopathy?

Answer 26

Common gene mutations include beta myosin heavy chain or myosin binding protein C. 60% of mutations are is sarcomeric genes

Question 27

What are the ECG changes suggesting hypertrophic cardiomyopathy?

Answer 27

T inversions and repolarisation abnormalities | Large QRS complex suggestive of hypertrophy

Question 28

What is the clinical presentation of hypertrophic cardiomyopathy?

Answer 28

``` Sudden cardiac death Heart failure Angina AF Assymptomatic Use a risk score to predict SCD and whether to use and ICD ```

Question 29

What is dilated cardiomyopathy?

Answer 29

A condition in which the heart's ability to pump blood is decreased because the heart's main pumping chamber, the left ventricle, is enlarged and weakened. In some cases, it prevents the heart from relaxing and filling with blood as it should.

Question 30

In which populations is the incidence of dilated cardiomyopathy highest?

Answer 30

Males more than females and a lower incidence in childhood

Question 31

Where are gene mutations found in dilated cardiomyopathy?

Answer 31

Sarcomere desmosomal genes (lamin A/C gene) - only in 20% of cases

Question 32

What is a poor prognostic marker in dilated cardiomyopathy?

Answer 32

LV ejection fraction <35%

Question 33

Mutations in the lamin A/C gene in dilated cardiomyopathy are associated with wich arrythmias?

Answer 33

First degree heart block, Supra ventricular tachycardias and increased risk of SCD. Some people have neuromuscular symptoms

Question 34

What is the management for dilated cardiomyopathy with a known genetic mutation?

Answer 34

Internal cardiac defib

Question 35

What is arrhythmogenic right ventricular cardiomyopathy?

Answer 35

Fibro fatty replacement of the cardiomyocytes in the right ventricle. Left ventricle is involved in >50% of cases

Question 36

What causes arrhythmogenic right ventricular cardiomyopathy?

Answer 36

Autosomal dominant mutations of genes for desmosomal proteins. Autosomal recessive mutations in non desmosomal genes.

Question 37

What increases the risk of sudden cardiac death in arrhythmogenic right ventricular cardiomyopathy?

Answer 37

``` Family history of premature SCD Increasing severity of LV and RV dysfunction Frequent, non sustain VT Older age Male gender Long QRS complex ```

Question 38

How is Arrhythmogenic right ventricular cardiomyopathy managed?

Answer 38

Aviod competitive sports Beta blockers of amiodarone ICD in patients with previous arrest Catherter alblation of foci

Question 39

Subcutaineous ICDs look bette, have less risk and the patient has more movement flexibility but they cannot be used to treat some conditions. What are these?

Answer 39

Brady cardia support, cardiac resynchronisation or anti tachycardia pacing

Question 40

Generally how are inherited cardiac conditions managed?

Answer 40

Diagnosis: Clinical and genetic testing. (family members are also at risk Risk management: Pharmacolocial interventions- beta blockers. Non pharmacological interventions- ICD. Lifestyle- aviod high dynamic, high static sport. Cascade screening for families MDT APPROACH

Question 41

Why is population testing not carried out for inherited cardiac conditions?

Answer 41

Increased false positive and anxieties. | Testing professional sports people is done in some countries

Question 42

What are the big impacts on young people with inherited cardiac conditions?

Answer 42

Psycho-social impact Affects school, sports, pregnancy, employment and life insurance ICD therapy for life