Cardiac conditions that cause sudden death Flashcards
What is sudden cardiac death?
An event that is non-traumatic, non-violent, unexpected and resulting from sudden cardiac arrest within 6 hours of previously witnessed normal health
What are the 2 types of arrythmogenic inherited cardiac conditions?
Channelopathies and cardiomyopathies
Name some inherited channelopathies
Congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome
Name some inherited cardiomyopathies
Hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC)
In channelopathies what is the arrythmogenesis related to?
Ion current imbalance and development of early and late depolarisations
In cardiomyopathies what is the arrhythmogenesis related to?
Scar/electrical barrier formation and subsequent re-entry
What is an afterdepolarisation?
After depolarisations are abnormal depolarisations of cardiac myocytes that interrupt phsae 2,3 or 4 of the cardiac AP in the cardiac conduction system of the heart. After depolarisations can lead to triggered activity seen as sustained cardiac arrythmia
When do early after depolarisations occur?
During phase 2 or 3
What causes early after depolarisations (EADs)?
An increase in the frequency of abortive action potentials before normal repolarisation is completed. Phase 2 may be interrupted due to augmented opening of calcium channels, while phase 3 interruptions are due to the opening of calcium channels
What can occur as a result of EADs?
Torsades de Pointes
What can potentiate and EAD?
Hypokalaemia and drugs that prolong the QT interval, including class Ia and III anti-arrhythmic agents
When do delayed after depolarisations (DADs) occur?
During phase 4, after repolarisation is completed but before another action potential would normally occur via normal conduction systems of the heart
What causes DADs?
Elevated cytosolic calcium concentrations, classically seen with digoxin toxicity
What is the classical feature associated with DADs?
Bidirectional ventricular tachycardia (also seen in CPVT)
How do DADs occur?
The overload of the sarcoplasmic reticulum may cause spontaneous Ca release after repolarisation, causing released Ca to exit the cell through the 3Na/Ca exchanger which results in a net depolarizing current
What mode of inheritance are most cardiac conditions inherited by?
Autosomal dominant inheritance
What occurs as a result of congenital LQTS?
Polymorphic VT (Torsades de Pointes) triggered by adrenergic stimulation
What is the risk of sudden cardiac death in congenital long QT syndrome?
In untreated LQTS risk = 0.33-0.9% and this risk increases with increasing QT duration. Risk also depends on gender (pre-adolescent males and adult females), age, prior syncope and response to beta-blockers
What is the mode of inheritance for congenital LQTS?
Mainly autosomal dominant - isolated LQT = Romano-Ward syndrome. Autosomal recessive is associated with deafness and is called Jervell and Lange-Nielsen syndrome
How many subtypes of congenital LQTS are there?
13 subtypes i.e. 13 genes
What are the diagnostic criteria for LQTS?
Class I = QT interval >/=480ms in repeated 12-lead ECGs or LQTS risk score >3 or the presence of a confirmed pathogenic LQTS mutation irrespective of the QT duration Class IIa - QT interval >/=460ms in repeated 12-lead ECGs in patients with an unexplained syncopal episode in the absence of secondary causes for QT prolongation
What lifestyle changes are recommended in all patients with LQTS?
Avoidance of QT prolonging drugs, correction of electrolyte abnormalities that may occur during diarrhoea, vomiting or metabolic conditions, avoidance of genotype-specific triggers for arrhythmias e.g. strenuous swimming in LQTS1 and loud noises in LQTS2
What causes short QT syndrome?
A mutation in the cardiac K channels
How may short QT syndrome present?
May present in children, may be associated with AF, QT interval <300ms at heart rate of <80bpm
What is the general prognosis for short QT syndrome?
VERY malignant so bad prognosis
What drugs can be used to treat short QT syndrome?
Anti-arrhythmic drugs - quinidine, flecainide
What are the typical ECG findings for Brugada syndrome?
ECG findings may be intermittent, change over time. Can usually see ST elevation and RBBB in V1-3. Diagnostic ECG changes may only be seen with provocative testing with flecainide or ajmaline (drugs that block the cardiac Na channel)
How is Brugada syndrome inherited?
Autosomal dominant, 8x more common in males, 12 associated genes (SCN5A and CACN1Ac)
Ventricular fibrillation can occur in Brugada syndrome, name some of the triggers for this
Rest/sleep, fever, excessive alcohol, large meals
What lifestyle changes are recommended in all patients with Brugada syndrome?
Avoidance of drugs that may induce ST elevation in right precordial leads, avoidance of excessive alcohol intake and large meals and prompt treatment of any fever with antipyretic drugs
When is ICD recommended for patients with Brugada syndrome?
Those who are survivors of an aborted cardiac arrest and/or have documented spontaneous sustained VT. ICD implantation should be considered in patients with a spontaneous diagnostic type I ECG pattern and history of syncope
What drugs should be avoided in Brugada syndrome?
Anti-arrhythmic drugs, psychotropics, analgesics and anaesthetics
What is catecholaminergic polymorphic ventricular tachycardia (CPVT)?
Adrenergic induced bidirectional and polymorphic VT, SVTs, triggered by emotional stress and/or physical activty
What would appear on ECG and ECHO in CPVT?
Normal findings
How is CPVT inherited?
Autsomal dominant - ryanodine receptor mutation Autosomal recessive - cardiac calsequestrin gene
What lifestyle changes are recommended in all patients with CPVT?
Avoidance of competitive sports, strenuous exercise and stressful environments
What treatment is available for patients with CPVT?
Beta-blockers are recommended for all patients, ICD implantation with or without flecainide is recommended in patients who experience cardiac arrest, recurrent syncope or polymorphic/bidirectional VT despite optimal therapy
What features would be seen on an ECG in Wolff-Parkinson-White syndrome?
Short PR interval and delta waves
What is the most common arrhythmia associated with WPWS?
Atrioventricular re-entrant tachycardia
What is the cause of WPWS?
Ventricular pre-excitation
What causes hypertrophic cardiomyopathy?
Mutation in sarcomeric genes in 60% of cases, 5-10% due to MYBPC3 gene mutation
What is the associated mortality with HOCM?
1% cardiovascular mortality/year in unselected patients
What is recommended in HOCM patients to prevent sudden cardiac death?
Avoidance of competitive sports, ICD implantation in patients who have survived cardiac arrest due to VT or VF or who have spontaneous sustained VT causing syncope or haemodynamic compromise and have a life expectancy of >1 year
Describe the prevalence of dilated cardiomyopathy
1 in 2500, low in childhood, males > females
What causes dilated cardiomyopathy?
Sarcomere and desmosomal genes, laminA/C and desmin if there is conduction disease, dystrophin if X-linked. Mutations are found in 20% of cases
What causes arrhythmogenic right ventricular cardiomyopathy (ARVC)?
Fibro-fatty replacement of cardiomyocytes. Autosomal dominant mutations in the genes for desmosomal proteins; autosomal recessive mutations in non-desmosomal genes
How many patients get LV involvement with ARVC?
>50% of cases get left ventricular involvement
What are the risk factors associated with sudden cardiac death in ARVC?
Family history of premature SCD, severity of RV and LV function, frequent non-sustained VT, QRS prolongation on EG, VT induction on electrophysiology study (EPS), male gender and age at presentation
What are the recommended treatments for ARVC?
Avoidance of competitive sports, beta-blockers to the maximum tolerated dose, ICD implantation in patients with a history of aborted SCD and haemodynamically poorly tolerated VT, amiodarone in patients with frequent PVC or NSVT who have contraindications to beta-blockers. If unresponsive to this, catheter ablation should be considered
What is the only known treatment for ventricular fibrillation?
Defibrillation
What does defibrillation do?
Delivers high amounts of energy to cause all cardiac myocytes to fully depolarise. This resets all cardiac myocytes to enable normal electrical activation to recommence. Defibrillation is most successful the quicker it is delivered
Name some complications associated with transvenous leads (ICD)
Endocarditis, perforation, haemothorax, pneuomthorax, thromboembolic events, lead fractures, vascular complications, lead extraction complications, lead dislodgement
When would a subcutaneous ICD (S-ICD) be considered over a transvenous ICD?
In patients with an indication for an ICD when pacing therapy for bradycardia support, cardiac resynchronisation or anti-tachycardia pacing is not needed. It is also useful when venous access is difficult, after the removal of a transvenous ICD for infections or in young patients with a long-term need for ICD therapy
