KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation.
BACKGROUND
A 53-year-old female presented with a 10-year history of paroxysmal atrial fibrillation (AF), precipitated by activity and refractory to medical therapy. In the absence of traditional risk factors for disease, a genetic defect in electrical homeostasis underlying stress-induced AF was explored.


METHODS
Echocardiography, cardiac perfusion stress imaging, invasive electrophysiology with isoproterenol provocation, genomic DNA sequencing of K(ATP) channel genes, exclusion of mutation in 2,000 individuals free of AF, reconstitution of channel defect with molecular phenotyping, and verification of pathogenic link in targeted knockout.


METHODS
K(ATP) channelopathy caused by missense mutation (Thr1547Ile) of the ABCC9 gene conferring predisposition to adrenergic AF originating from the vein of Marshall.


RESULTS
Disruption of arrhythmogenic gene-environment substrate at the vein of Marshall by radiofrequency ablation.
Olson
Timothy M
TM
Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. olson.timothy@mayo.edu
Alekseev
Alexey E
AE
Moreau
Christophe
C
Liu
Xiaoke K
XK
Zingman
Leonid V
LV
Miki
Takashi
T
Seino
Susumu
S
Asirvatham
Samuel J
SJ
Jahangir
Arshad
A
Terzic
Andre
A
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000235:genetics* / Q000601:surgery*; D017115:Catheter Ablation / Q000379:methods*; D053447:Channelopathies / Q000235:genetics* / Q000628:therapy; D002908:Chronic Disease; D003331:Coronary Vessels / Q000503:physiopathology; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D018570:Risk Assessment; D013614:Tachycardia, Paroxysmal / Q000000981:diagnostic imaging / Q000235:genetics / Q000601:surgery; D016896:Treatment Outcome
D018528:ATP-Binding Cassette Transporters; D051666:Kv1.5 Potassium Channel