CineECG analysis provides new insights into Familial ST-segment Depression Syndrome

• Published in: Europace (London, England) Vol. 25; no. 5
• Main Authors: Frosted, Rasmus, Paludan-Müller, Christian, Vad, Oliver Bundgaard, Olesen, Morten Salling, Bundgaard, Henning, van Dam, Peter, Christensen, Alex Hørby
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 19-05-2023
• Subjects: Arrhythmias, Cardiac - diagnosis; Arrhythmias, Cardiac - genetics; Electrocardiography - methods; Female; Humans; Male; Middle Aged; Syndrome; Translational Research; Familial ST-segment Depression Syndrome; Arrhythmia; Electrocardiogram; Electrical activation pathway; ECGsim; CineECG
• ISSN: 1099-5129; 1532-2092
• DOI: 10.1093/europace/euad116

Abstract
Aims
Familial ST-segment Depression Syndrome (Fam-STD) is a novel inherited cardiac disease associated with arrhythmias and sudden cardiac death. This study aimed at investigating the cardiac activation pathway in patients with Fam-STD, modelling the electrocardiogram (ECG) phenotype, and performing in-depth ST-segment analyses.
Methods and results
CineECG analysis of patients with Fam-STD and age- and sex-matched controls. The groups were compared using the CineECG software which included the trans-cardiac ratio and the electrical activation pathway. We simulated the Fam-STD ECG phenotype by adjusting action potential duration (APD) and action potential amplitude (APA) in specific cardiac regions. High-resolution ST-segment analyses were performed per lead by dividing the ST-segment into nine 10 ms subintervals. Twenty-seven Fam-STD patients (74% females, mean age 51.6 ± 6.2 years) and 83 matched controls were included. Among Fam-STD patients, electrical activation pathway analysis in the anterior-basal orientation showed significantly abnormal direction toward the basal areas of the heart starting from QRS 60–89 ms until Tpeak-Tend (all P < 0.001). Simulations with shortened APD and reduced APA in the left ventricle basal regions recapitulated the Fam-STD ECG phenotype. Detailed ST-segment analyses showed significant differences in all nine 10 ms subintervals (all P < 0.01), with the most prominent findings during the 70–79/80–89 ms intervals.
Conclusion
CineECG analyses indicated abnormal repolarization with basal directions, and the Fam-STD ECG phenotype was simulated by reducing APD and APA in the left ventricle basal regions. Detailed ST-analysis showed amplitudes consistent with the proposed diagnostic criteria for Fam-STD patients. Our findings provide new insight into the electrophysiological abnormalities of Fam-STD.
Graphical Abstract
Graphical Abstract