Introduction: Females can be more arrhythmogenic than males, and this sex difference can persist with development of chronic heart failure (CHF). The aim of this study was to investigate sex differences in the arrhythmogenic substrate in control dogs and in a new arrhythmogenic canine model of CHF.
Methods: CHF was induced in 30 dogs by aortic insufficiency and aortic constriction. Holter monitoring assessed VT and PVCs from 30 dogs, as well as traditional HRV measures and nonlinear dynamics (including correlation dimension (CD), detrended fluctuations analysis α1 (DFAα1), and Shannon entropy (SE)) at baseline, 240 days (240d) and 720 days (720d) after CHF induction.
Results: At baseline, females had lower LF/HF (0.27±0.03 vs 0.33±0.02, p=0.04), CD (1.60±0.17 vs 2.21±0.15, p=0.01), DFAα1 (0.62±0.03 vs 0.72±0.03, p=0.03), and SE (2.99±0.02 vs 3.10±0.03, p=0.03 vs males). Females lacked circadian variation in LF/HF, DFAα1, and SE while males had circadian variation in all of these. Of 11 dogs with frequent runs of VT and PVCs, 95% and 91% of total VT runs and total PVCs, respectively, were in females. With CHF, all these linear and nonlinear parameters progressively declined in males and females. CHF females had less decline in LF/HF than males so that by 720 days there was no more sex difference (0.24±0.06, 0.17±0.03 in females vs 0.22±0.05, 0.18±0.01 in males at 240d, 720d). However, for nonlinear parameters of CD, DFAα1, and SE, CHF females had lower values than males (CD: 1.56±0.21, 0.99±0.32 vs 1.87±0.24, 1.50±0.34; DFAα1: 0.51±0.05, 0.43±0.04 vs 0.54±0.07, 0.48±0.04; and SE 2.93±0.08, 2.76±0.08 vs 3.01±0.11, 2.91±0.04 in females vs males at 240d, 720d). With CHF, circadian variation in CD, DFAα1, and SE were lost in both males and females.
Conclusions: There are sex differences in the arrhythmogenic substrate in control dogs and in this new arrhythmogenic canine model of moderate CHF. At baseline, females have lower sympathetic stimulation, reduced cardiac chaos, and loss of circadian variation in nonlinear dynamics. With CHF, sex differences in nonlinear dynamics persist; this reflects a loss of complexity and fractal properties that could contribute to increased arrhythmias in female CHF dogs.