Sofia Marinko - Institutionen för kliniska vetenskaper, Lund

Title: Non-invasive prediction of clinical outcome in heart failure patients treated with CRT

Main supervisor: Rasmus Borgquist, MD, PhD

Reviewers: Frieder Braunschweig, MD, PhD and Oscar Braun, MD, PhD

Abstract

Background
Cardiac Resynchronization Therapy (CRT) is a well-established treatment for patients with heart failure and left ventricular dyssynchrony. However, only 60–70% of patients respond well to CRT, meaning up to a third may undergo CRT implantation without benefit. As current guideline parameters for CRT do not accurately predict individual prognosis with CRT, there is a need for improved selection criteria. Using advanced digital electrocardiogram (ECG) and vectorcardiographic variables for predicting CRT outcomes may further enhance patient selection.

Research questions
Are ECG and vectorcardiographic parameters associated with survival, risk of heart failure hospitalization, and risk of malignant 
arrhythmias in patients undergoing CRT?

Results
In paper 1, the association between VCG derived QRS area was explored in relation to long-term risk of heart failure hospitalization or death following CRT. In multivariable analysis, it was shown that a larger pre-CRT QRS area and a larger post-CRT QRS area reduction were associated with a reduced risk of these endpoints.
In paper 2, left ventricular activation time (LVAT) was approximated from the 12-lead ECG and explored in relation to heart failure hospitalization or death, following CRT. A longer pre-implant LVAT was associated with a reduced risk of these endpoints. 
Paper 3 explored the association between VCG derived QRS area and ventricular arrhythmias. Preliminary results show that a small pre-CRT QRS area, by itself or in combination with a small reduction of post-CRT QRS area, was strongly associated with a higher risk of ventricular arrhythmias in CRT-D treated patients. 

Paper 4 explored the association between VCG derived measurements on depolarisation-repolarisation vectors and risk of hospitalization or death following CRT. Results show that larger post-CRT spatial peak and mean QRS-T angles (derived from the 12-lead ECG), along with a smaller post-CRT reduction of the mean angle, was associated with an increased risk of heart failure.

Significance
Parameters that accurately predict CRT outcomes are important for the pre-operative selection of CRT candidates. Integrating advanced electro- and vectorcardiographic variables with existing patient selection criteria has the potential of further guiding clinicians in optimizing therapy, enhancing treatment success, and reducing non-beneficial CRT implantations. 

Published studies
Sofia Marinko, Pyotr G. Platonov, Jonas Carlson, Rasmus Borgquist. Baseline QRS Area and Reduction in QRS Area Are Associated with Lower Mortality and Risk of Heart Failure Hospitalization after Cardiac Resynchronization Therapy. 2022 January: Cardiology. doi: 10.1159/000522151.

Status of the remaining projects
Paper 2: Submitted for publication. Data collection, analysis, and manuscript preparation have been completed. The manuscript is currently being revised based on reviewers’ comments.

Paper 3: Data collection has been completed. Final analysis will be conducted after a database merge, with manuscript preparation planned to take place in 2025.

Paper 4: Data collection has been completed. Final analysis will be conducted after a database merge, with manuscript preparation planned to take place in 2024/2025.