Clinical Features, Long-Term Prognosis, and Clinical Management of Genotype-Negative Long QT Syndrome Patients.

BACKGROUND

Approximately 15% to 20% of patients clinically diagnosed with long QT syndrome (LQTS) are genotype-negative (GEN-). Whether they have a different arrhythmic risk or should be managed differently remains unclear, often leading to incomplete treatment.

OBJECTIVES

The purpose of this study was to compare clinical aspects of GEN- and genotype-positive (GEN+) LQTS patients.

METHODS

We retrospectively evaluated 832 LQTS patients genetically screened in Japan (n = 347) and Italy (n = 485), including 698 with a disease-causing variant in the KCNQ1, KCNH2, and SCN5A genes (GEN+), and 134 without variants in these LQTS-related genes (GEN-).

RESULTS

At diagnosis, the Japanese patients were more often probands (86% vs 60%), symptomatic (39% vs 18%), and of younger age than the Italian patients; conversely, they used less β-blockers (65% vs 95%), more rarely had a family history (FH) of LQTS (42% vs 73%), and had more cardiac events during follow-up (13% vs 4%) (P < 0.001 for all comparisons). Within the Japanese cohort, the GEN- had more cardiac arrests, used less β-blockers, and had much less FH for LQTS compared their GEN+ counterpart. The Italian cohort was more homogeneous, with just more LQTS FH among the GEN+. QTc shortening (close to 30 ms in all groups) during follow-up was similar between Japanese and Italian patients, irrespective of their being GEN+ or GEN-. In both cohorts, during an average follow-up of 6 and 7 years, respectively, GEN+ and GEN- patients showed a comparable clinical outcome.

CONCLUSIONS

Arrhythmic risk is similar between GEN+ and GEN- LQTS patients; they should be managed and treated in the same way.

Informations de copyright

Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Funding Support and Author Disclosures This work has been partially supported by a grant from Health Science Research Grant from the Ministry of Health, Labor and Welfare of Japan (21FC1004, 23FC1003 to Dr Aiba), a Japanese Circulation Society research grant for genome analysis project in cardiovascular diseases (to Drs Horie and Aiba), the Italian Ministry of Health Ricerca Corrente grant ‘Registry of Cardiac Channelopathies’, the EJP RD Joint Transnational Call for Proposals 2019–Project LQTS-NEXT–EJPRD19-187, and the Fondation Leducq grant 18CVD05 “Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies” (to Drs Crotti and Schwartz). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.