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June 3, 2019CirculationOpen Access

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies

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Key result

A new risk prediction model for life-threatening ventricular tachyarrhythmias in laminopathies yielded a validation C-index of 0.800 (95% CI 0.642-0.959) and net reclassified 28.8% of patients.

Why the study?

Accurate estimation of the risk of life-threatening ventricular tachyarrhythmia in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation.

Does a new risk prediction model improve the prediction of life-threatening ventricular tachyarrhythmias and selection for ICD implantation in adult patients with LMNA mutations compared to current guidelines?

Population

839 adult patients with LMNA mutations

Comparison

Risk prediction score vs current clinical practice guidelines

Design

Derivation and external validation cohort study

Follow-up

Median 3.6 years (derivation) and 5.1 years (validation)

Authors

KWKarim WahbiRYRabah Ben YaouEGEstelle Gandjbakhch

Discussion

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Overview

Supports refined ICD selection in LMNA carriers via validated 7% threshold; extends guidelines but needs prospective confirmation.

Key Points

  • To develop and externally validate a new clinical risk prediction model for life-threatening ventricular tachyarrhythmias in patients with LMNA mutations to guide implantable cardioverter-defibrillator therapy.
  • Derived a Fine-Gray competing risk regression model in 444 adult LMNA mutation carriers (mean age 40.6 years) from a French nationwide registry.
  • Externally validated the prognostic model in 145 patients (mean age 38.2 years) across five international tertiary cardiomyopathy centers (NCT03058185).
  • Evaluated life-threatening ventricular tachyarrhythmia outcomes (sudden cardiac death or hemodynamically unstable/ICD-treated arrhythmias) over median follow-ups of 3.6 and 5.1 years.
  • Life-threatening ventricular tachyarrhythmias occurred in 86 of 444 patients (19.3%) in the derivation sample and 34 of 145 patients (23.4%) in the external validation sample.
  • The prediction model—incorporating male sex, nonmissense mutation, atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction—yielded a C-index of 0.776 (95% CI, 0.711–0.842) in derivation and 0.800 (95% CI, 0.642–0.959) in validation.
  • A 5-year estimated risk threshold of ≥7% predicted 96.2% of life-threatening events and achieved a 28.8% net reclassification improvement compared to existing clinical guidelines.

Study Design

Type

Cohort (n=839)

Multicenter

Yes

Structured PICO

Does a new risk prediction model improve the prediction of life-threatening ventricular tachyarrhythmias and selection for ICD implantation in adult patients with LMNA mutations compared to current guidelines?

P
Population
839 adult patients with LMNA mutations followed for a median of 3.6 to 5.1 years to develop and validate a risk prediction model for life-threatening ventricular tachyarrhythmias.
E
Exposure
A new risk prediction model for life-threatening ventricular tachyarrhythmias (LTVTA) using predictors: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction
C
Comparator
Current clinical practice guidelines-based approach
O
Outcome
Life-threatening ventricular tachyarrhythmia (LTVTA), defined as sudden cardiac death or implantable cardioverter defibrillator-treated or hemodynamically unstable VTAcomposite

Main Result

Effect estimate: C-index 0.800 (95% CI 0.642-0.959)

A novel risk prediction model for life-threatening ventricular tachyarrhythmias in patients with LMNA mutations significantly improves risk stratification and reclassifies nearly 30% of patients compared to current guidelines.

Cite This Study

Wahbi et al. (2019) conducted a cohort in Laminopathies (LMNA mutations) (n=839). Risk prediction model for life-threatening ventricular tachyarrhythmias vs. Current clinical practice guidelines was evaluated on Life-threatening ventricular tachyarrhythmia (sudden cardiac death or ICD-treated/hemodynamically unstable VTA) (C-index 0.800, 95% CI 0.642-0.959). A new risk prediction model for life-threatening ventricular tachyarrhythmias in laminopathies yielded a validation C-index of 0.800 (95% CI 0.642-0.959) and net reclassified 28.8% of patients.

synapsesocial.com/papers/6a919efbe2101d5a4a867fbahttps://doi.org/10.1161/circulationaha.118.039410
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