Ambulatory electrocardiographic longitudinal monitoring in dystrophin-deficient dogs identifies decreased Very Low Frequency power as a hallmark of impaired Heart Rate Variability in Duchenne Muscular Dystrophy

Background Duchenne muscular dystrophy (DMD) patients exhibit a late left ventricular systolic dysfunction preceded by an occult phase, during which myocardial fibrosis progresses and some early functional impairments can be detected. These latter include electrocardiographic (ECG) and heart rate variability (HRV) abnormalities. Methods A longitudinal study aiming at describing the sequence of ECG and HRV abnormalities, relative to cardiac function degradation, using Holter ECG, was performed in the GRMD (Golden retriever muscular dystrophy) dog model, known to develop a DMD-like disease, including cardiomyopathy. Results Most of the known ECG and HRV abnormalities described in DMD patients were also found in GRMD dogs, and several of them could be detected months before the decrease of fractional shortening. One of the earliest evidenced abnormalities was a decrease in the very low frequency (VLF) component of the power spectrum, and this decrease was correlated with the further reduction of fractional shortening. Such decreased VLF probably reflects impaired autonomic function and abnormal vasomotor tone. Conclusion This study provides new insights into the knowledge of the GRMD dog model and DMD cardiomyopathy and emphasizes the interest to monitor the VLF power in DMD patients, still unexplored in this disease, whilst it is highly predictive of deleterious clinical events in many other pathological conditions. Abbreviations cTpnI Cardiac Troponin I DMD Duchenne Muscular Dystrophy ECG Electrocardiogram GRMD Golden Retriever Muscular Dystrophy HF High Frequency HR Heart Rate HRV Heart Rate Variability LF Low Frequency LGE Late Gadolinium Enhancement LTV Long-Term Variability LVEF Left Ventricular Ejection Fraction NT-proBNP N-Terminal part of the pro-Brain Natriuretic Peptide pNN50 percentage of interval differences of successive RR intervals of more than 50 ms pNN10 %(meanRR) percentage of interval differences of successive RR intervals of more than 10% of the mean RR QTc corrected QT interval RMSSD square root of the mean squared differences of successive RR intervals SDNN Standard Deviation of the RR intervals LVFS Left Ventricular Fractional Shortening STV Short-Term Variability VLF Very Low Frequency PVB Premature Ventricular Beat VT Ventricular Tachycardia.