Novel Insight Into the Natural History of Short QT Syndrome

Abstract

ObjectivesThis study intends to gain further insights into the natural history, the yield of familial and genetic screening, and the arrhythmogenic mechanisms in the largest cohort of short QT syndrome (SQTS) patients described so far.BackgroundSQTS is a rare genetic disorder associated with life-threatening arrhythmias, and its natural history is incompletely ascertained.MethodsSeventy-three SQTS patients (84% male; age, 26 ± 15 years; corrected QT interval, 329 ± 22 ms) were studied, and 62 were followed for 60 ± 41 months (median, 56 months).ResultsCardiac arrest (CA) was the most frequent presenting symptom (40% of probands; range, <1 month to 41 years). The rate of CA was 4% in the first year of life and 1.3% per year between 20 and 40 years; the probability of a first occurrence of CA by 40 years of age was 41%. Despite the male predominance, female patients had a risk profile superimposable to that of men (p = 0.49). The yield of genetic screening was low (14%), despite familial disease being present in 44% of kindreds. A history of CA was the only predictor of recurrences at follow-up (p < 0.0000001). Two patterns of onset of ventricular fibrillation were observed and were reproducible in patients with multiple occurrences of CA. Arrhythmias occurred mainly at rest.ConclusionsSQTS is highly lethal; CA is often the first manifestation of the disease with a peak incidence in the first year of life. Survivors of CA have a high CA recurrence rate; therefore, implantation of a defibrillator is strongly recommended in this group of patients.

Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction

“…35 It is noteworthy that although we postulate that the loss-of-function of the cardiac potassium channels could induce transmission distortion and contribute to female predominance in LQTS, a marked male predominance, up to 80%, has been observed among patients with a short QT syndrome. 36,37 This syndrome is caused by gain-of-function variants in the same channels where loss-of-function variants lead to LQTS, but only in a limited number of cases. It is tempting to suggest a possible role for channel dysfunction in this male predominance, but this must be tempered by the fact that most of the genetic background of this syndrome has not been elucidated.…”

2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

“…W skrócie, EPS może odegrać rolę u pacjentów z ARVC [113,114] lub DCM [115], natomiast nie przyczynia się do identyfikacji grupy dużego ryzyka wśród pacjentów z HCM (zalecenie klasy III) [116]. W przypadku kanałopatii EPS nie jest wskazane w LQTS [117], CPVT [14] oraz SQTS [118,119], natomiast jego przydatność w zespole Brugadów pozostaje przedmiotem dyskusji [120].…”

“…Z SQTS powiązano 5 genów (KCNH2, KCNQ1, KCNJ2, CACNA1C i CACNB2b), ale przydatność przesiewowych badań genetycznych pozostaje mała (w sumie ok. 20% przypadków) [119].…”

Mutations in voltage-gated L-type calcium channel: implications in cardiac arrhythmia

“…One proband’s ECG showed that the QTc interval of the patient was shorter than that of healthy controls and characterized with aborted CA, and a novel CACNA1C mutation (p.R1977Q) was first identified in this SQTS patient, but the parents didn’t carry this mutation [115]. However, the roles of p.R1977Q mutation in SQTS are still unknown.…”