Myocardial fibrosis in repaired tetralogy of Fallot; Predicting ventricular arrhythmia and sudden cardiac death
File(s)
Author(s)
Ghonim, Sarah
Type
Thesis
Abstract
We are faced with new challenges in the growing population of adult survivors with repaired tetralogy of Fallot (rTOF). The risk of premature death persists and drives eager pursuit for the accurate identification of patients at high-risk of malignant ventricular tachycardia (VT) and sudden cardiac death (SCD).
It is previously known that inducible VT predicts mortality in rTOF patients. We show that the burden of right ventricular (RV) late gadolinium enhancement (LGE) defined fibrosis > 25cm3 quantified by high-sensitivity 3D LGE can predict inducible VT as a proxy endpoint for mortality. Patients with minimal RV LGE < 10cm3 were extremely unlikely to have inducible VT suggesting those with minimal RVLGE avoid an invasive study.
In a prospective study of 550 rTOF patients, a high-risk subgroup of patients with a 4.4% annualised risk of death and 3.7% annualised risk of life-threatening VT/SCD were identified. RVLGE was a strong predictor of outcome. We demonstrated how RVLGE can be integrated with other independent predictors into weighted risk scores ready for clinical use.
Diffuse fibrosis defined by RV T1 shows promise as a subtle biomarker of adverse remodelling. An imbalance in the expression of fibrosis biomarkers suggests that a state of high-collagen turnover exists and correlates with adverse remodelling.
In conclusion, myocardial fibrosis plays a central role in predicting death and malignant VT in rTOF. This work identifies biomarkers to help risk stratify and enable more personalised and targeted care in the life-long follow up of adult rTOF patients.
It is previously known that inducible VT predicts mortality in rTOF patients. We show that the burden of right ventricular (RV) late gadolinium enhancement (LGE) defined fibrosis > 25cm3 quantified by high-sensitivity 3D LGE can predict inducible VT as a proxy endpoint for mortality. Patients with minimal RV LGE < 10cm3 were extremely unlikely to have inducible VT suggesting those with minimal RVLGE avoid an invasive study.
In a prospective study of 550 rTOF patients, a high-risk subgroup of patients with a 4.4% annualised risk of death and 3.7% annualised risk of life-threatening VT/SCD were identified. RVLGE was a strong predictor of outcome. We demonstrated how RVLGE can be integrated with other independent predictors into weighted risk scores ready for clinical use.
Diffuse fibrosis defined by RV T1 shows promise as a subtle biomarker of adverse remodelling. An imbalance in the expression of fibrosis biomarkers suggests that a state of high-collagen turnover exists and correlates with adverse remodelling.
In conclusion, myocardial fibrosis plays a central role in predicting death and malignant VT in rTOF. This work identifies biomarkers to help risk stratify and enable more personalised and targeted care in the life-long follow up of adult rTOF patients.
Version
Open Access
Date Issued
2021-05
Date Awarded
2021-12
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Babu-Narayan, Sonya
Gatzoulis, Michael
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)