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

Abstract

AbstractBackgroundDuchenne 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.MethodsA 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.ResultsMost 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.ConclusionThis 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.AbbreviationscTpnICardiac Troponin IDMDDuchenne Muscular DystrophyECGElectrocardiogramGRMDGolden Retriever Muscular DystrophyHFHigh FrequencyHRHeart RateHRVHeart Rate VariabilityLFLow FrequencyLGELate Gadolinium EnhancementLTVLong-Term VariabilityLVEFLeft Ventricular Ejection FractionNT-proBNPN-Terminal part of the pro-Brain Natriuretic PeptidepNN50percentage of interval differences of successive RR intervals of more than 50 mspNN10 %(meanRR)percentage of interval differences of successive RR intervals of more than 10% of the mean RRQTccorrected QT intervalRMSSDsquare root of the mean squared differences of successive RR intervalsSDNNStandard Deviation of the RR intervalsLVFSLeft Ventricular Fractional ShorteningSTVShort-Term VariabilityVLFVery Low FrequencyPVBPremature Ventricular BeatVTVentricular Tachycardia.