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

Abstract

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