PO-01-126 SEXUAL DIMORPHISM AND CARDIAC ARRHYTHMIAS IN A MOUSE MODEL OF FRIEDREICH'S ATAXIA: WHAT DO WE KNOW?

Friedreich ataxia (FA) is a monogenic recessive disorder caused by the reduction of mitochondrial protein, frataxin (FXN). Despite neurological deficits place patients with FA in wheelchairs, most die from lethal cardiomyopathy their 40s. develop progressive cardiac disease characteristics similar to primary hypertrophic but more fibrosis, both diastolic and systolic dysfunction, arrhythmias. However, mechanisms leading arrhythmias are poorly understood. To characterize electrical signal propagation function mouse model which imitates late-stage patients. Cardiac-specific McK-Cre FXN knockout (FXN cKO) mice were used as severe characteristic for FA. Due premature death, animals either sex at 8-weeks age assess in-vivo echocardiography surface electrocardiogram (ECG). We found that cKO developed idiosyncratic varying time durations beat-to-beat (RR) intervals heart rate variability (HRV) parameters such root mean squared successive differences (RMSSD, p<0.0358), revealing increased vagal activity. Mice presented extended P-wave (p<0.0113) QTc (>150 ms, p<0.0015), suggesting impaired atrial left-ventricular function, resembling human HRV frequency showed low-frequency (0.023), high-frequency (p<0.264) total (p<0.0326) power. Non-linear short-term variation (SD1, p<0.019), long-term (SD2, p<0.0017) ellipse area values (S, p<0.0074). Poincare plots males included multiple clustering RR RR+1 identities while females generally sustained single clustered (area, p<0.028). Similarly, mostly males. Contractile dysfunction was also evident left ventricular fractional shortening, ejection fraction, stroke volume output. Our study revealed sexual dimorphism significant impairment contractile compared females. A detailed characterization signals hearts will build platform drug testing treat