Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients

Morgat, C; Fressart, V; Porretta, AP; Neyroud, N; Messali, A; Temmar, Y; Algalarrondo, V; Surget, E; Bloch, A; Leenhardt, A; Denjoy, I; Extramiana, F

doi:10.1093/europace/euae136

Arrhythmias & electrophysiology

Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients

EuropacePublished 3 Jun 2024Retrospective cohort study

Main finding · Cardiac eventsResultHazard ratio 0.34 CI 0.22–0.54

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Authors' conclusion

Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events than other LQT1 patients.

Study context

Population: LQT1 or Jervell and Lange-Nielsen syndrome (JLNS) patients with class IV/V KCNQ1 variants, September 1993 to January 2023KCNQ1 variant carriers
Participants: 789 participants

Exposure: HTZ-JLNS vs HTZ-Non-JLNS
JLNSn = 30
HTZ-JLNSn = 161
HTZ-Non-JLNSn = 550reference
Outcome: QTc duration and incidence of long QT syndrome-related cardiac events

Methodological detailssingle-centre inherited arrhythmia clinic, literature review for JLNS variants

Single-centre inherited arrhythmia clinic
Literature review for JLNS variants

Main finding

Cardiac events

Hazard ratio

0.34

CI 0.22–0.54

P < 0.01

HTZ-JLNS vs HTZ-Non-JLNS

HR 0.34 (CI 0.22–0.54); P < 0.01

As reported in the abstract

Observational data: associations, not effects.

Further findings

QTc at diagnosis

JLNSmean 551 msSD 54

HTZ-JLNSmean 441 msSD 32

HTZ-Non-JLNSmean 467 msSD 36

Genetic parameters independently associated with cardiac events (multivariate analysis)

Comparison	← Lower risk ←→ Higher risk →	HR (CI)	P value
HaploinsufficiencyMultivariate Cox regression	0.20.5125	0.60 (0.37–0.97)	P = 0.04
C-terminal localizationMultivariate Cox regression	0.20.5125	0.67 (0.46–0.98)	P = 0.04
GroupMultivariate Cox regression	0.20.5125	0.43 (0.27–0.69)	P < 0.01
	0.20.5125Hazard ratio (log scale)

Outcome	HR	P value
Genetic parameters independently associated with cardiac events (multivariate analysis)Pore localization · upper CI limit misprinted in abstract · multivariate Cox regression	1.61	P < 0.01

Original publication

Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients. Europace. Published 3 June 2024. doi:10.1093/europace/euae136

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Summarised from the published abstract; every number is checked against it