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Approved research

Genetic substrate of valvular heart disease and its arrhythmic complications

Principal Investigator: Dr Francesca Delling
Approved Research ID: 26751
Approval date: September 25th 2018

Lay summary

We aim at identifying the genetic determinants of valvular heart disease associated with atrial or ventricular arrhythmias. We will focus on left sided valve diseases (aortic regurgitation and stenosis, mitral regurgitation and stenosis) Knowledge of the genetic basis of atrial and ventricular arrhythmias in valvular heart disease will provide insight into the mechanisms of arrhythmias in this population, thus allowing better risk stratification and development of potential medical therapies. The genetic information in participants with valvular disease with arrhythmias will be compared with the genetic information of 1) individuals with arrhythmias without valvular disease and 2) individuals with valvular disease without arrhythmias. Diagnosis of valvular disease will be based on ICD9/ICD10 coding and cardiac MRI when applicable. Diagnosis of cardiac arrhythmia (atrial fibrillation, ventricular tachycardia, ventricular fibrillation, history of sudden cardiac arrest, and cardiac defibrillator implantantion) will be based on ICD9/ICD10 coding. Individuals with a diagnosis of valvular heart disease and/or atrial fibrillation or ventricular tachycardia within the full cohort. Discovery and replication phases will both occur using UK Biobank data.

Scope extension:

We aim at identifying the genetic determinants of valvular heart disease associated with atrial or ventricular arrhythmias. We will focus on left sided valve diseases (aortic regurgitation and stenosis, mitral regurgitation and stenosis)

Knowledge of the genetic basis of atrial and ventricular arrhythmias in valvular heart disease will provide insight into the mechanisms of arrhythmias in this population, thus allowing better risk stratification and development of potential medical therapies. The genetic information in participants with valvular disease with arrhythmias will be compared with the genetic information of 1) individuals with arrhythmias without valvular disease and 2) individuals with valvular disease without arrhythmias. Diagnosis of valvular disease will be based on ICD9/ICD10 coding and cardiac MRI when applicable. Diagnosis of cardiac arrhythmia (atrial fibrillation, ventricular tachycardia, ventricular fibrillation, history of sudden cardiac arrest, and cardiac defibrillator implantation) will be based on ICD9/ICD10 coding. Individuals with a diagnosis of valvular heart disease and/or atrial fibrillation or ventricular tachycardia within the full cohort. Discovery and replication phases will both occur using UK Biobank data.

In addition to continuing all of the plans described above in the old scope, we seek to more fully leverage data that has become available (including whole genome sequencing data) in the interim and extend the duration of our ongoing projects with more contemporary follow-up. We will use ICD9/ICD10 codes to define diagnoses of valvular heart disease (aortic regurgitation and stenosis, mitral valve prolapse, regurgitation and stenosis, tricuspid regurgitation) and comorbid conditions (including atrial fibrillation). We will calculate the incidence of new valvular heart disease diagnoses and run Cox regression models to quantify the association of baseline demographic variables and comorbid conditions with incident valvular heart disease. We will use the same codes, together with procedural OPCS codes defining treatment with valvular interventions, to calculate mortality among these patients. Finally, we will utilize the new genetic sequencing data to enrich our investigations into the underlying inherited propensities that may enrich our understanding of these diseases.