title: Novel insight into the natural history of short QT syndrome.
abstract: OBJECTIVE
  This 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.
  
  
  BACKGROUND
  SQTS is a rare genetic disorder associated with life-threatening arrhythmias, and its natural history is incompletely ascertained.
  
  
  METHODS
  Seventy-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).
  
  
  RESULTS
  Cardiac 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.
  
  
  CONCLUSIONS
  SQTS 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.
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mazzanti
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Ajita
authors.initials: A
authors.lastname: Kanthan
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Monteforte
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Memmi
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Novelli
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Miceli
authors.affiliation: Cardiovascular Genetics Program, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Rourke
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Borio
authors.affiliation: Department of Cardiology and Electrotherapy, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zienciuk-Krajka
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Curcio
authors.affiliation: Smartech, Milan, Italy.
authors.forename: Andreea Elena
authors.initials: AE
authors.lastname: Surducan
authors.affiliation: Smartech, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy; Cardiovascular Genetics Program, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York.
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.affiliation: Molecular Cardiology, IRCCS Salvatore Maugeri Foundation, Pavia, Italy; Cardiovascular Genetics Program, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York; Department of Molecular Medicine, University of Pavia, Pavia, Italy. Electronic address: silvia.priori@fsm.it.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Priori
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D055815:Young Adult
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D004247:DNA
keywords: genetics; short QT syndrome; sudden cardiac death; ventricular arrhythmias