Related Experiment Video

Updated: Sep 6, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

11.1K

Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC

Alexandros Protonotarios1,2, Riccardo Bariani3, Chiara Cappelletto4,5

  • 1Institute of Cardiovascular Science, University College London, London, UK.

European Heart Journal
|June 29, 2022
PubMed

Insights

The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model performs well for gene-positive patients, especially those with PKP2 mutations. However, its accuracy is limited in gene-elusive ARVC cases, suggesting genotype inclusion in future models.

Area of Science:

  • Cardiology
  • Genetics
  • Medical Diagnostics

Background:

  • Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disease.
  • Accurate risk stratification is crucial for managing ARVC patients and preventing sudden cardiac death.
  • Current risk models may not fully account for genetic heterogeneity in ARVC.

Purpose of the Study:

  • To evaluate the performance of the 2019 ARVC risk model across different genetic subtypes of the disease.
  • To determine if patient genotype influences the model's accuracy in predicting ventricular arrhythmia (VA).

Main Methods:

  • A cohort of 554 ARVC patients without prior sustained ventricular arrhythmia (VA) was analyzed.
  • The 2019 ARVC risk model's discriminative and calibration abilities were assessed.
  • Performance was compared across four genotype groups: PKP2, desmoplakin (DSP), other desmosomal genes, and gene-elusive patients.

Main Results:

  • The 2019 ARVC risk model demonstrated reasonable discriminative ability but tended to overestimate risk.
  • Model performance varied significantly by genotype, with highest discrimination in the PKP2 group and lowest in the gene-elusive group.
  • Clinical risk markers like ventricular dimensions and function showed genotype-dependent significance.

Conclusions:

  • The 2019 ARVC risk model is reasonably effective for gene-positive ARVC, particularly PKP2-related cases.
  • The model's utility is limited in gene-elusive ARVC patients.
  • Incorporating genetic information into future ARVC risk models is recommended for improved accuracy.
Abstract

Keywords:
Arrhythmogenic right ventricular cardiomyopathyGenotypeRisk stratificationSudden cardiac deathVentricular arrhythmia

More Related Videos

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia09:36

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia

Published on: December 22, 2023

1.3K
Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography07:11

Morphological and Functional Assessment of the Right Ventricle Using 3D Echocardiography

Published on: October 28, 2020

3.0K

Related Concept Videos

Cardiomyopathy I: Introduction and Classification01:25

Cardiomyopathy I: Introduction and Classification

Cardiomyopathy, or CMP, is a group of diseases affecting the myocardial structure, impairing its ability to pump blood effectively. This condition can lead to arrhythmias, heart failure, or sudden cardiac death.Cardiomyopathies are classified into primary and secondary categories:Primary Cardiomyopathy refers to conditions involving only the heart muscle that are often idiopathic (of unknown cause) or genetic. They primarily affect the myocardium without the involvement of other systemic...
49
Cardiomyopathy IV: Restrictive Cardiomyopathy01:29

Cardiomyopathy IV: Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare heart muscle disease characterized by impaired ventricular filling due to stiffened ventricular walls, leading to significant diastolic dysfunction.EtiologyRestrictive cardiomyopathy can arise from both inherited and acquired diseases, many of which are systemic. It is categorized into four main types: infiltrative, storage, non-infiltrative, and endomyocardial diseases.Infiltrative diseases, such as amyloidosis, lead to RCM by depositing amyloid...
23
Relative Risk01:12

Relative Risk

Relative risk (RR) is a statistical measure commonly used in epidemiology to compare the likelihood of a particular event occurring between two groups. This metric is important for evaluating the relationship between exposure to a specific risk factor and the probability of a particular outcome. It plays a crucial role in medical research, public health studies, and risk assessment. Relative risk quantifies how much more (or less) likely an event is to occur in an exposed group compared to an...
330
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...
45
Cardiomyopathy II: Dilated Cardiomyopathy01:30

Cardiomyopathy II: Dilated Cardiomyopathy

Dilated cardiomyopathy, or DCM, is a progressive myocardial disorder characterized by ventricular chamber dilation and contractile dysfunction.EtiologyVarious factors can cause DCM, including hypertension and heavy alcohol intake, which contribute to the weakening and enlargement of the heart muscle. Viral infections, such as Coxsackievirus B, adenoviruses, and influenza, can lead to DCM by causing inflammation and damage to heart tissue. Certain chemotherapeutic agents, including daunorubicin,...
21
Heart Failure IV: Classification and Diagnostic Evaluation01:30

Heart Failure IV: Classification and Diagnostic Evaluation

Heart failure can be classified in various ways, with the most common classifications based on physical activity limitations, disease progression, severity, and treatment strategies.The Functional Classification of Heart Failure divides patients into four categories based on physical activity limitation due to symptom burden.Class I: Patients in this class have cardiac disease but no physical activity limitations. Ordinary activities like walking, climbing stairs, or routine tasks do not cause...
28