Background: Familial ST-depression Syndrome (Fam-STD) is a recently identified inherited cardiac disease characterized by a distinct electrocardiographic phenotype and occurrence of arrhythmias and heart failure.
Objective: We aimed to investigate the electrocardiographic prevalence of the Fam-STD and its association with cardiac events in a large, nationwide cohort.
Methods: We used a Danish nationwide ECG database containing 11,952,430 ECGs, from 2,485,987 unique individuals. We excluded ECGs from children <15 years and ECGs with likely secondary causes of ST-segment deviations. The Fam-STD phenotype prevalence was assessed according to the original (Fam-STD-2018) and revised (Fam-STD-2022 probands/relatives) proposed diagnostic criteria. Through linkage with national registries, we evaluated the risk of a composite cardiac endpoint (new-onset atrial fibrillation, ventricular arrhythmias, heart failure, cardiac device implantation) and all-cause mortality using cox proportional hazard models.
Results: A total of 6,352,104 ECGs (1,890,184 individuals; 55% females; 3.4 ECGs per individual) remained after application of the exclusion criteria. We found 56 (3/100,000) individuals fulfilling Fam-STD-2018, 173 (9/100,000) fulfilling Fam-STD-2022-probands, and 4,975 (263/100,000) fulfilling Fam-STD-2022-relatives criteria. During a mean follow-up of 2.4±3.4 years we observed increased risks of the composite cardiac endpoint (hazard ratio (HR) 4.4[CI:1.2-15.9], 3.6[CI:2-6.5], 2.21[CI:2-2.5]) and all-cause mortality (HR 6.2[CI:3.6-10.6], 3.1[CI:1.7-1.9], 1.8[CI:1.7-1.9]), for Fam-STD-2018, Fam-STD-2022-probands and Fam-STD-2022-relatives, respectively, compared to matched controls without ST-deviation.
Conclusion: The Fam-STD ECG proband phenotype is rare and has a prevalence in Denmark of 3-9/100,000, fairly similar to estimates of other inherited arrhythmia syndromes. The increased risk of cardiac events and mortality highlights the importance of early identification to allow preventive interventions.
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