STATE OF GENETIC TESTING FOR LONG QT SYNDROME (LQTS) Class I (is recommended) Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing is recommended for any patient in whom a cardiologist has established a strong clinical index of suspicion for LQTS based on examination of the patient's clinical history, family history, and expressed electrocardiographic (resting 12-lead ECGs and/or provocative stress testing with exercise or catecholamine infusion) phenotype. Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing is recommended for any asymptomatic patient with QT prolongation in the absence of other clinical conditions that might prolong the QT interval (such as electrolyte abnormalities, hypertrophy, bundle branch block, etc., i.e., otherwise idiopathic) on serial 12-lead ECGs defined as QTc Ͼ480 ms (prepuberty) or Ͼ500 ms (adults). Mutation-specific genetic testing is recommended for family members and other appropriate relatives subsequently following the identification of the LQTS-causative mutation in an index case. Class IIb (may be considered) Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A) targeted LQTS genetic testing may be considered for any asymptomatic patient with otherwise idiopathic QTc values Ͼ460 ms (prepuberty) or Ͼ480 ms (adults) on serial 12-lead ECGs. STATE OF GENETIC TESTING FOR CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT) Class I (is recommended) Comprehensive or CPVT1 and CVPT2 (RYR2 and CASQ2) targeted CPVT genetic testing is recommended for any patient in whom a cardiologist has established a clinical index of suspicion for CPVT based on examination of the patient's clinical history, family history, and expressed electrocardiographic phenotype during provocative stress testing with cycle, treadmill, or catecholamine infusion. Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the CPVT-causative mutation in an index case. STATE OF GENETIC TESTING FOR BRUGADA SYNDROME (BrS) Class I (is recommended) Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the BrS-causative mutation in an index case. Class IIa (can be useful) Comprehensive or BrS1 (SCN5A) targeted BrS genetic testing can be useful for any patient in whom a cardiologist has established a clinical index of suspicion for BrS based on examination of the patient's clinical history, family history, and expressed electrocardiographic (resting 12-lead ECGs and/or provocative drug challenge testing) phenotype. Class III (is not indicated/recommended) Genetic testing is not indicated in the setting of an isolated type 2 or type 3 Brugada ECG pattern. STATE OF GENETIC TESTING FOR PROGRESSIVE CARDIAC CONDUCTION DISEASE (CCD) Class I (is recommended) Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of the CCD-causative mutation in an index case. Class IIb...

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The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD.

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Ongoing loss of sinus rhythm and late peaks in the risk of atrial flutter and death necessitate continued follow-up.

Our findings support that the amount of maternal antibodies, rather than their presence, is associated with fetal tissue injury. As anti-Ro levels correlate with the risk of cardiac complications, serial echocardiography should be limited to women with high anti-Ro-titres.

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