Genetic Conditions Flashcards
LQT Genetic Mutation
LQT1 - KCN Q1, IKs - loss of function in the K channel
LQT2 - KCNH2, IKr
LGT3 - SCN5A, INa
LQT Triggers
LQT 1 - Swimmers, exercise
LQT2 - auditory triggers, post partum
LQT3 - nothing particular
Symptomatic Long QT Syndrome Management
*Avoid medications known to prolong the QT interval and the aggressive treatment of electrolyte imbalances
*Most patients should receive an ICD and beta-blocker therapy if the initial presentation was SCA. Importantly, self-limiting syncope/seizures, even if assessed to be LQTS-triggered (ie, secondary to TdP) are not equivalent to SCA.
Universal beta blocker therapy with preferably nadolol or propranolol as a class I recommendation in symptomatic patients or for QTc > 470 msec or class II recommendation in asymptomatic patients with QTc < 470 msec.
*For all patients with congenital LQTS and a history of syncope or seizures, we recommend treatment with a beta blocker (Grade 1B). We suggest propranolol or nadolol, given their superior efficacy in this patient population (Grade 2C). LQT1 responds the best to beta blockers.
*For patients with recurrent, LQTS-triggered arrhythmic events treatment intensification is pursued with either concomitant drug therapy, left cardiac sympathetic denervation, and/or an ICD
Asymptomatic Long QT Syndrome Management
Our approach to treatment of asymptomatic patients:
- beta blocker (Grade 2C). However, for asymptomatic patients with a QTc <470 milliseconds, beta-blocker therapy may not be required.
*We suggest either a prophylactic left cardiac sympathetic denervation (LCSD; PJS) or a prophylactic ICD (MJA) in an asymptomatic patient with either LQT2 or LQT3 whose resting QTc is >550 milliseconds (Grade 2C).
For postpubertal women with LQT2, either prophylactic LCSD (PJS) or a prophylactic ICD (MJA) at a lower QTc threshold (QTc >500 milliseconds) is reasonable.
Importantly, an ICD is never indicated based solely on a family history of LQTS-associated SCD, as family history is not a personal risk factor for the patient.
LQT Indication for ICD
LQT with recurrent symptoms and/or torsades de pointes despite therapy with beta blockers or other high-risk patients.
Importantly, an ICD is never indicated based solely on a family history of LQTS-associated SCD, as family history is not a personal risk factor for the patient.
Long QT Syndrome Exercise Recommendation
Patients with LQTS can continue to be recreationally active, especially those with LQT2 and LQT3.
-Asymptomatic persons who are genotype positive/phenotype negative (ie, with normal QTc at rest) can reasonably participate in all competitive sports with appropriate safety precautions.
-Symptomatic patients may consider participation in competitive athletics (with the exception of swimming in patients with LQT1 genotype) if they remain asymptomatic after three months of treatment and with appropriate cautionary measures.
Catecholaminergic polymorphic VT Genetic Mutation
Mutation in two genes have been identified in patients with CPVT:
- the cardiac ryanodine receptor gene RYR2 (an autosomal dominant form)
- the calsequestrin 2 gene (autosomal recessive).
Both mutations appear to act by inducing diastolic calcium release from the sarcoplasmic reticulum. The resulting intracellular calcium overload leads to delayed afterdepolarizations and triggered activity, which can induce ventricular tachycardia and fibrillation.
Catecholaminergic polymorphic VT Management
- ICD and beta blockers for most patients (Never ICD by itself)
- Avoidance of competitive sports
- Addition of verapamil or flecainide in patients with ongoing ventricular arrhythmias despite initial therapy.
Propranolol is used for acute suppression of recurrent polymorphic VT. For long-term preventive therapy, nadolol (1 to 2 mg/kg) is preferred
Brugada ECG pattern treatment
For patients with the Brugada ECG pattern who are otherwise asymptomatic and have none of the criteria that would suggest Brugada syndrome (ie, family history of sudden cardiac death or type 1 Brugada ECG pattern), we recommend no treatment (Grade 1B).
Brugada Syndrome Genetic Mutation
Loss of function in Na channel = BrS1 , SCN5A
We suggest genetic testing for all patients with documented Brugada syndrome (“probands”). AD inheritance. If the proband has an identified genetic mutation (ie, genotype positive), we pursue genetic testing in all of the proband’s first degree relatives.
We do not recommend genetic testing for Brugada pattern ECG probands or their first degree relatives.
Brugada Syndrome Management
*For patients who have survived sudden cardiac arrest or those with a history of syncope which is felt to be due to ventricular tachyarrhythmias, we recommend implantation of an ICD rather than antiarrhythmic drug therapy (Grade 1A).
*In patients who refuse ICD implantation or are not considered a candidate for ICD implantation due to reduced life expectancy or significant comorbidities, we suggest initial therapy with either quinidine or amiodarone (Grade 2C).
*In patients with an ICD who have recurrent arrhythmias resulting in ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in the RVOT and right ventricular free wall. (Grade 2C). Therapy with quinidine or amiodarone is also an option.
Arrhythmogenic RV Dysplasia Management
-Patients with ARVC should not participate in competitive or endurance sports.
-Beta blockers are an important component of treatment for all patients with clinical manifestations of ARVC but are not indicated for genotype positive/phenotype negative patients.
-Sustained VAs are common in patients with ARVC, and ICD therapy (both antitachycardia pacing and shocks) is effective for both primary and secondary prevention of SCD.
ARVC Indication for ICD
ARVC with LVEF <=35%, unexplained syncope, inducible VT on EPS
Management and diagnostic strategies for Duchene muscular dystrophy
Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X chromosome that is responsible for the production of dystrophin, a high molecular weight protein that is localized to the sarcolemmal membrane of normal skeletal muscle.
DMD causes a primary cardiomyopathy with extensive fibrosis of the posterobasal left ventricular wall, resulting in the characteristic ECG changes of tall right precordial R waves with an increased R/S ratio and deep Q waves in leads I, aVL, and V5-6 . As the cardiac disease progresses, fibrosis can spread to the lateral free wall of the left ventricle. The extent and severity of fibrosis can be assessed by examining the distribution of late gadolinium enhancement with CMR. Significant mitral regurgitation is often present due to involvement of the posteromedial papillary muscle. Cardiac involvement is also associated with conduction abnormalities, especially intraatrial and interatrial but also involving the AV node, and a variety of arrhythmias, primarily supraventricular
Pacing indication for neuromuscular disease
3 or 2nd degree AVB or HV > 70 ms regardless of symptoms
- Class II A Lamin A/C w/ PR >240 ms and LBBB
- Class II B Myotonic Dystrophy/ Kearns-Sayre w/ PR >240 ms, QRS >120 ms, or fascicular block
