Misha Bhat- Institutionen för kliniska vetenskaper, Lund

Title: Non-invasive predictors of outcomes in tetralogy of Fallot

Main supervisor: Petru Liuba

Reviewers: Håkan Wåhlander/ barnkardiolog, Göteborg and Joanna Hlebowicz/ universitetslektor, GUCH, Lund

Abstract

Background

Tetralogy of Fallot (TOF) is a common complex congenital heart defect. Long-term survival is excellent but there are frequent residual lesions, including pulmonary regurgitation. Patients may develop ventricular dysfunction, arrhythmias, and sudden cardiac death. Many need reoperations including pulmonary valve replacement (PVR). Current modalities are insufficient in identifying those at risk for complications and optimal timing for re-intervention in the individual patient. In identifying patients needing neonatal surgery is challenging. 

AIMS

1. Identifying fetal CMR-based biomarkers that predict high-risk variants of TOF.
2. Describing the frequency of electrocardiogram-based biomarkers in repaired tetralogy of Fallot (rTOF) and correlation with dysfunction, maturity, and type of repair. 
3. Identifying circulating biomarkers of adaptation and maladaptation in rTOF.
4. Identifying circulating biomarkers predicting recovery after PVR.

Preliminary results

Study I – (Ongoing) – Prospective study using fetal MRI and echo-based parameters. Outcomes: need for neonatal intervention or presence of MAPCAs. 

Study II - (1 Published + 1 preparing for submission) – Retrospective review of 219 patients and 882 ECGs. There is a high burden of high-risk ECG abnormalities. PQ interval may be an emerging marker of right ventricular volume load. 

Premature patients have shorter PQ times even in longer follow-ups compared to those born at term. 

Study III – (Ongoing) - Prospective study looking at circulating biomarkers in relation to echo and MRI biomarkers around the time of primary repair and in one year follow-up. 27 patients have been recruited, 10 have undergone 1-year follow-up. Outcomes include function and complications. 

Study IV – (Ongoing) -  Prospective study looking at circulating biomarkers in rTOF patients undergoing MRI due to right ventricular dysfunction. Patients undergoing PVR undergo follow-up MRI and biomarkers. 24 clinical MRI + 8 PVR patients have been recruited. Outcomes: heart function including recovery, length of stay, and complications. 

Significance

By better identifying high-risk patients during fetal life we can optimize counselling, care, and delivery at tertiary care centers. 

ECG-based biomarkers can help us select patients needing complex work-up for surgery and who are at increased risk for complications. 

Identifying circulating biomarkers associated with maladaptive remodelling in rTOF will allow us to find which patients need repeat surgery. 

Published studies

Bhat M, Malm T, Sjöberg G, Nordenstam F, Hanséus K, Rosenkvist CJ, Liuba P. Longitudinal ECG changes in tetralogy of Fallot and association with surgical repair. Front Cardiovasc Med. 2024 Mar 28;11:1349166. doi: 10.3389/fcvm.2024.1349166. PMID: 38606378; PMCID: PMC11007042.

References