Recognition of specific electrocardiographic (ECG) patterns remains a cornerstone in the diagnosis of inherited arrhythmia syndromes. We recently described a novel inherited arrhythmia disease (1), familial ST-segment depression syndrome, characterized by pronounced ECG changes including persistent, nonischemic ST-segment depressions and risk of atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. We proposed diagnostic criteria (1).

We have now identified 7 additional, apparently unrelated, Danish families fulfilling diagnostic criteria resulting in a total of 10 families; all probands were inhabitants of Eastern Denmark. The study was approved by Danish Data Protection Agency and Patient Safety Authority and Ethics Committee for the Capital Region Copenhagen (H-17034423).

All families had ≥2 members with unexplained, persistent ST-segment depressions with a characteristic concave appearance (Figure 1A); ECG changes were not explained by structural or coronary artery disease. From the 10 Danish families, we evaluated 32 individuals (47% men) with the ST-segment depression phenotype. Mean age at diagnosis was 47 years (range 10 to 79 years). Pedigree analyses were consistent with autosomal dominant inheritance and the penetrance appeared high, as approximately 50% of first-degree family members displayed the ECG phenotype. The ST-segment depressions were most pronounced in leads V4, V5, and II and persisted over time, that is, without episodes of normalization. The mean PR-, QRS-, and QTc (Bazett)-intervals were 166 ± 24 ms, 91 ± 12 ms, and 396 ± 27 ms, respectively. Echocardiography showed a mean left ventricular ejection fraction (LVEF) of 55 ± 11% (range 20% to 60%), left ventricular end-diastolic diameter of 52 ± 6 mm (range 44 to 72 mm), and interventricular septal thickness of 9 ± 2 mm (range 6 to 12 mm).