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January 9, 2019European Journal of Heart FailureOpen Access

External Validation of Risk Factors for Malignant Ventricular Arrhythmias in Lamin A/C Mutation Carriers

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Key result

Clinical risk factors (NSVT, LVEF <45%, male sex, non-missense mutations) predicted malignant ventricular arrhythmias in LMNA mutation carriers (C-index 0.76; 95% CI 0.72-0.80; P<0.001).

Why the study?

The prognostic model underlying international ICD recommendations for LMNA mutation carriers had not been validated in an external cohort or in a population composed solely of relatives.

Population

77 LMNA mutation carriers in an external independent validation cohort

Comparison

Stratification by number of clinical risk factors (0 vs 1 vs ≥ 2 risk factors)

Design

Single-centre observational cohort external validation study

Follow-up

Median 3.4 years

Authors

MTMarine ThuillotCMCarole MaupainEGEstelle Gandjbakhch

Discussion

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Member takes

Overview

Supports current ICD recommendations in LMNA cardiomyopathy; leaves open refined risk models for prospective validation.

Study Design

Type

Cohort (n=77)

Multicenter

No

Structured PICO

P
Population
77 LMNA mutation carriers (median age 43 years, 54% female) followed for a median of 3.4 years to validate risk factors for malignant ventricular arrhythmias.
O
Outcome
Malignant ventricular arrhythmias (MVA), defined as appropriate ICD treatment, cardiopulmonary resuscitation, or sudden cardiac deathcomposite

Main Result

Effect estimate: C-index 0.76 (95% CI 0.72-0.80)

Absolute Event Rate: 75% vs 100%

p-value: p=<0.001

This study successfully externally validates a prognostic model using four risk factors (NSVT, LVEF < 45%, male sex, non-missense mutations) to predict malignant ventricular arrhythmias in LMNA mutation carriers.

Limitations

  • small sample size

Cite This Study

Thuillot et al. (2019) conducted a cohort in LMNA mutation carriers (n=77). Clinical risk factors (NSVT, LVEF < 45%, male sex, non-missense mutations) vs. No risk factors was evaluated on MVA-free survival at 3 years (C-index 0.76, 95% CI 0.72-0.80, p=<0.001). Clinical risk factors (NSVT, LVEF <45%, male sex, non-missense mutations) predicted malignant ventricular arrhythmias in LMNA mutation carriers (C-index 0.76; 95% CI 0.72-0.80; P<0.001).

synapsesocial.com/papers/6a93bc3bf3532cd145ebd0e7https://doi.org/10.1002/ejhf.1384
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies2019 · 278 citations
  2. 2Timing of cardioverter-defibrillator implantation in patients with cardiac laminopathies—External validation of the LMNA-risk ventricular tachyarrhythmia calculator2022 · 26 citations
  3. 3FROM ELECTRICAL DISEASE TO STRUCTURAL CARDIOMYOPATHY: A CHALLENGIES IN RISK STRATIFICATION IN ASYMPTOMATIC LMNA VARIANT CARRIERS2026
  4. 4Missense and Non-Missense Lamin A/C Gene Mutations Are Similarly Associated with Major Arrhythmic Cardiac Events: A 20-Year Single-Centre Experience2024 · 5 citations
  5. 5Lamin Missense Mutations—The Spectrum of Phenotype Variability is Increasing2018 · 8 citations