PO-04-159 PREVALENCE AND CHARACTERISTICS OF PATIENTS WITH LONG QT SYNDROME (LQTS) WHO APPEAR NON-RESPONSIVE TO CONVENTIONAL LQTS THERAPIES

Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy with 1% to 5% annual risk of LQTS-triggered syncope/seizures or sudden arrest/death (SCA/SCD). Despite maximal LQTS-directed therapies, subset patients experience breakthrough events (BCEs). To describe the phenotype “non-responders” defined as LQTS recurrent BCEs despite therapy. Among 1731 evaluated and treated at Mayo Clinic, retrospective analysis was performed identify those who experienced ≥1 BCE while on maximum treatment (combination ≥2 device/denervation and/or pharmacologic therapies maximally tolerated doses). Basic demographics, clinical characteristics, frequency/type syncope/seizures, appropriate ICD shocks, SCA, SCD were extracted from electronic medical record. Overall, 32/1731 (2%) 13 (41%) occurring in setting medication nonadherence. Of remaining 19 (1% all patients; 37% female, mean age last event 11±8 years QTc 537±92ms), 7 (37%) had compound heterozygous (n=6) homozygous (n=1) disease involving either KCNQ1 KCNH2, including one Jervell Lange-Nielsen patient, 2 (11%) high-risk minor genotypes (CALM2-mediated CACNA1C-mediated Timothy syndrome). Notably, 5 (26%) complex sodium predominant features LQT3 multifocal ectopic Purkinje-related premature contractions. The treatment-refractory LQT2 (n=3; 16%) (n=2; 11%). At follow-up, died 4 underwent transplant. For patients, escalated after their BCE. Twelve (92%) received an atrial pacing (AP) + beta-blocker (BB) mexiletine (MEX) [n=1, 8%], AP left sympathetic denervation (LCSD) antiarrhythmic drugs (AADs) [n=4, 31%], bilateral BB [n=2, 15%], LCSD AAD [n=5, 38%]. One patient (8%) MEX. safe effective options, Adherence outlined program needs be reinforced. In addition, heterozygous/homozygous KCNQ1-mediated SCN5A-mediated channelopathies represent subsets need alternative management strategies.