Abstract 17825: Heart Rate Fragmentation Analysis May Suggest Non-Autonomic Markers of Sudden Cardiac Death Risk in Adults With Williams-Beuren Syndrome

Abstract

Background: Williams-Beuren syndrome (WBS) is a rare genetic disorder caused by a chromosomal microdeletion (7q11.23). It confers increased arrhythmia and sudden cardiac death (SCD) risk. Mechanisms underlying this risk remain obscure. We recently found HRV abnormalities in individuals with WBS that are known to correlate with sudden death risk in diabetes and following MI and stroke. Heart rate fragmentation (HRF) correlated with adverse CV events in some studies where HRV failed to identify high-risk subjects. Some argue that HRF quantifies non-autonomic CV modulators. We, therefore, sought to further explore non-autonomic modulators of cardiovascular disease by performing HRF analysis in a cohort of adults with WBS. Hypothesis: We hypothesize that those with WBS may exhibit increased sudden death risk from mechanisms not detected by conventional HRV measures. Aims: We aim to 1) Identify biomarkers that are predictive of SCD risk in WBS, and 2) Determine if HRF quantifies non-autonomic CV modulators. Methods: We performed HRF analyses on 24hr ECGs in subjects with WBS (n=18) and age- and sex-matched controls (n=18) enrolled in a prospective NIH study. HRF analyses include the percentage of inflection points (PIP), percentages of hard (PIP H ) and soft (PIP S ) inflection points, and the distribution of “words”, where W 0 ,W 1 ,W 2 , W 3 represent sequences of 4 beats with 0, 1, 2, or 3 inflection points. Inflection points were defined as a change in NN by more than 1/s, where ‘s’ is the sampling frequency. Mann-Whitney tests were used to compare HRF in subjects vs. controls. Spearman’s correlation was used to compare HRF to traditional HRV. Results: HRF markers (PIP, PIP S , and W 3 ) were significantly elevated in WBS subjects (P<0.003)(Fig 1A-C). PIP S and W 3 were negatively correlated with parasympathetic markers HF power and SD1 among WBS subjects (Fig 1D). Conclusion: HRF may quantify some non-autonomic modulators of sudden death risk in those with WBS.