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The prestigious Brian Maurer Young Investigator Award, presented at the recent Irish Cardiac Society Annual Scientific Meeting and AGM in Galway, was won by Dr Alan Hanley — who recently received his certificate of satisfactory completion of specialist training — for his presentation titled ‘The Role of ZFHX3 in Atrial Fibrillation (AF).
Dr Hanley and colleagues sought to identify the role of ZFHX3 in the pathophysiology of AF and hypothesised that cardiac-restricted knock-down of this gene in a mammalian model organism would perturb normal cardiac development and function, and illuminate the role of ZFHX3 in AF.
Knock-down was confirmed by organ specific genotyping, said Dr Hanley, and among the study mice, increased inducibility of atrial arrhythmias was observed at in vivo electrophysiology testing when the mice were three months old.
Cardiac structure and function was normal in the knock-down mice at three months, the researchers observed, and premature mortality was noted. MRI revealed severe cardiomyopathy prior to death, with impaired left ventricular function and atrial enlargement. The histology of the affected hearts revealed severely dilated and fibrosed atria containing a large mass consistent with thrombus, the team reported.
Immunofluorescence of mouse hearts from early embryonic to adult stages confirmed cardiac expression of ZFHX3, with a marked atrial predominance, Dr Hanley told the conference.
In his conclusion, Dr Hanley explained: “We have uncovered a role for ZFHX3 in the left-right patterning of cardiac atria. Disruption of this developmental process predisposes to atrial cardiomyopathy, affects atrial electrophysiology properties, and may lead to AF.”