Timing of cardioverter-defibrillator implantation in patients with cardiac laminopathies — External validation of the LMNA-risk ventricular tachyarrhythmia calculator
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Background: LMNA genotype-positive patients have high risk of experiencing life-threatening ventricular tachyarrhythmias (VTAs). The LMNA-risk VTA calculator published in 2019 has not been externally validated. Objective: The purpose of this study was to validate the LMNA-risk VTA calculator. Methods: We included LMNA genotype-positive patients without previous VTAs from 2 large Scandinavian centers. Patients underwent electrocardiography, 24-hour Holter monitoring, and echocardiographic examinations at baseline and repeatedly during follow-up. Validation of the LMNA-risk VTA calculator was performed using Harrell's C-statistic derived from multivariable Cox regression analysis. Results: We included 118 patients (age 37 years [IQR 27–49 years]; 39 [33%] probands; 65 [55%] women; 100 [85%] with non-missense LMNA variants). Twenty-three patients (19%) experienced VTA during 6.1 years (interquartile range 3.0–9.1 years) follow-up, resulting in 3.0% (95% confidence interval 2.0%–4.5%) yearly incidence rate. Atrioventricular block and reduced left ventricular ejection fraction were independent predictors of VTAs, while nonsustained ventricular tachycardia, male sex, and non-missense LMNA variants were not. The LMNA-risk VTA calculator showed 83% sensitivity and 26% specificity for identifying patients with VTAs during the coming 5 years, and a Harrell's C-statistic of 0.85, when applying ≥7% predicted 5-year VTA risk as threshold. The sensitivity increased to 100% when reevaluating risk at the time of last consultation before VTA. The calculator overestimated arrhythmic risk in patients with mild and moderate phenotype, particularly in men. Conclusion: Validation of the LMNA-risk VTA calculator showed high sensitivity for subsequent VTAs, but overestimated arrhythmic risk when using ≥7% predicted 5-year risk as threshold. Frequent reevaluation of risk was necessary to maintain the sensitivity of the model.
Originalsprog | Engelsk |
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Tidsskrift | Heart Rhythm |
Vol/bind | 20 |
Udgave nummer | 3 |
Sider (fra-til) | 423-429 |
ISSN | 1547-5271 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
Funding Sources: This work was supported by Precision Health Care Center for optimized cardiac care (ProCardio) supported by the Norwegian Research Council (grant number #309762), European Research Area Network on Cardiovascular Diseases (EMPATHY project, NFR grant number #298736), the Innovation Fund Denmark (PM Heart), NordForsk, the Independent Research Fund Denmark (grant 0134-00363B, to Dr Christensen), and the Novo Nordisk Foundation , Denmark (NNF20OC0065799, to Dr Christensen).
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© 2022 Heart Rhythm Society
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