Long QT syndrome: importance of reassessing arrhythmic risk after treatment initiation

Abstract

Background and aims: Risk scores are proposed for genetic arrhythmias. Having proposed in 2010 one such score (M-FACT) for the long QT syndrome (LQTS), this study aims to test whether adherence to its suggestions would be appropriate.

Methods: LQT1/2/3 and genotype-negative patients without aborted cardiac arrest (ACA) before diagnosis or cardiac events (CEs) below age 1 were included in the study, focusing on an M-FACT score ≥2 (intermediate/high risk), either at presentation (static) or during follow-up (dynamic), previously associated with 40% risk of implantable cardioverter defibrillator (ICD) shocks within 4 years.

Results: Overall, 946 patients (26 ± 19 years at diagnosis, 51% female) were included. Beta-blocker (βB) therapy in 94% of them reduced the rate of those with a QTc ≥500 ms from 18% to 12% (P < .001). During 7 ± 6 years of follow-up, none died; 4% had CEs, including 0.4% with ACA. A static M-FACT ≥2 was present in 110 patients, of whom 106 received βBs. In 49/106 patients with persistent dynamic M-FACT ≥2, further therapeutic optimization (left cardiac sympathetic denervation in 55%, mexiletine in 31%, and ICD at 27%) resulted in just 7 (14%) patients with CEs (no ACA), with no CEs in the remaining 57. Additionally, 32 patients developed a dynamic M-FACT ≥2 but, after therapeutic optimization, only 3 (9%) had CEs. According to an M-FACT score ≥2, a total of 142 patients should have received an ICD, but only 22/142 (15%) were implanted, with shocks reported in 3.

Conclusions: Beta-blockers often shorten QTc, thus changing risk scores and ICD indications for primary prevention. Yearly risk reassessment with therapy optimization leads to fewer ICD implants (3%) without increasing life-threatening events.

Keywords: Channelopathies; Long QT syndrome; Risk scores; Sudden cardiac death; Ventricular arrhythmias.

Structured Graphical Abstract

Genotype, QTc, and history of arrhythmic events at diagnosis are reported for the whole study population. Kaplan–Meier curves of major cardiac event-free survival during follow-up (FU) are depicted by the static M-FACT score. In the central, upper panel, there is a schematic representation of the evolution over the time of an M-FACT score ≥2, from a static presentation at diagnosis through a dynamic change during FU on beta-blockers (βBs), along with therapy intensification, which leads to a lower number of patients with an intermediate/high level of risk. In the central, lower panel, the impact of βBs on QTc according to the baseline value is shown. On the right, top, the frequency of βB use and of all incremental therapeutic measures implemented during FU is shown; on the right, bottom, the percentage of implantable cardioverter defibrillators actually implanted in the long QT syndrome cohort is plotted against the one expected according to a static M-FACT score ≥2. LCSD, left cardiac sympathetic denervation.

Figure 1

Impact of beta-blocker therapy on QTc according to baseline QTc. The effect of beta-blockers on QTc was assessed, for greater comparability, in all patients with a 12-lead electrocardiogram available before and within 18 months of beta-blocker initiation

Figure 2

Evolution of the 106 patients with long QT syndrome on beta-blockers with a static M-FACT ≥2 at presentation during a mean follow-up of 9 ± 8 years. Post-diagnosis cardiac events on beta-blockers conferring the score one more point, additional therapeutic interventions, and cardiac events occurring despite therapy optimization are shown for patients maintaining or increasing the static score up to a dynamic M-FACT ≥2 (upper half) and for those lowering the score <2 (lower half). Changes in QTc on beta-blockers (<500/550> ms) and in patient age (<20> years) also contributed to any further shift of dynamic M-FACT

Figure 3

Evolution of the 32 patients with long QT syndrome who developed a dynamic M-FACT ≥2 during follow-up. Their static M-FACT <2 is shown on the left, along with cardiac events on beta-blockers conferring the score one more point, additional therapeutic interventions, and cardiac events occurring despite therapy optimization. Changes in QTc on beta-blockers (<500/550> ms) and in patient age (<20> years) also contributed to any further shift of dynamic M-FACT