Differences in Short QT Syndrome Subtypes: A Systematic Literature Review and Pooled Analysis

Abstract

Background: Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types are sparse. Methods: We conducted a pooled analysis of 110 SQTS patients. Patients have been diagnosed between 2000 and 2017 at our institution (n = 12) and revealed using a literature review (n = 98). 29 studies were identified by analysing systematic data bases (PubMed, Web of Science, Cochrane Libary, Cinahl). Results: 67 patients with genotype positive SQTS origin and 43 patients with genotype negative origin were found. A significant difference is documented between the sex with a higher predominance of male in genotype negative SQTS patients and predominance of females in genotype positive SQTS patients (male 52% versus 84%, female 45% versus 14%; p = 0.0016). No relevant difference of their median age (genotype positive 27 ± 19 versus genotype negative 29 ± 15; p = 0.48) was found. Asymptomatic patients and patients reporting symptoms such as syncope, sudden cardiac death, atrial flutter and ventricular fibrillation documented in both groups were similar except atrial fibrillation (genotype positive 19% versus genotype negative 0%; p = 0.0055). The QTc interval was not significantly different in both groups (genotype positive 315 ± 32 versus genotype negative 320 ± 19; p = 0.30). The treatments (medical treatment and ICD implantation) in both groups were comparable. Electrophysiology studies were not significantly higher documented in patients with genotype positive and negative origin (24% versus 9%; p = 0.075). Events at follow up such as VT, VF, and SCD were not higher presented in patients with genotype positive (13% versus 9%) (p = 0.25). 54% of genotype positive SQTS patients showed SQTS 1 followed by STQS 2 (21%) and SQTS 3 (10%). Conclusions: The long-term risk of a malignant arrhythmic event is not higher in patients with genotype positive. However, patients with genotype positive present themselves more often with AF with a female predominance. Also, other events at follow up such as syncope, atrial flutter and palpitation were not significantly higher (9% versus 0%; p = 0.079).

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases

“…There are some phenotypic differences among different genotypes. The onset of arrhythmias in KCNH2 ‐based patients seems to occur later in life than in other subtypes, 232 while the occurrence of AFib is more frequent in this subtype 233 . However, life‐threatening arrhythmias are equally frequent among different genotypes 232 …”

SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes

“…43 It is an extremely rare disease; in a recent systematic literature review, only 110 cases were described. 44 No specific triggers for LTE, including fever, have been described. Hence, on the basis of current knowledge, patients with SQTS do not seem to be at particular risk when they are affected by COVID-19.…”

Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers

“…Channelopathy symptoms depend specifically on what ICT was altered and how and how much its function was affected. Major ICT-related heart diseases include: Brugada syndrome 22 , long 23 and short 24 QT syndromes, and catecholaminergic polymorphic ventricular tachycardia 25 .…”