Dataset Information

Electrocardiogram Abnormalities Suggest Aberrant Cardiac Conduction in Huntington's Disease.

ABSTRACT:

Background

There is increasing evidence that the effects of Huntington's disease (HD) extend beyond the central nervous system. In particular, significant cardiac dysfunction has been described in transgenic mouse models and suggested in symptomatic patients, in whom cardiac involvement could provide an independent risk for sudden cardiac death.

Methods

Standard 12-lead electrocardiograms (ECGs) obtained at screening from 590 early symptomatic (Stage 1 and 2) HD patients participating in a multi-site Phase III study were analyzed.

Results

Evaluating only those ECGs in individuals not on medications or with potentially contributing medical conditions, the prevalence of bradycardia was 28.3% (marked in 5.8%), prolonged QRS 4.9%, intraventricular conduction delay 3.4%, right bundle branch block 1.3%, and QTc prolongation 3.7%.

Conclusion

Significant cardiac abnormalities, characterized primarily by conduction abnormalities, were found in a larger than expected number of patients. Abnormal intraventricular conduction may lead to increased risk for arrhythmia and may be compounded by prescription of QT-prolonging medications.

SUBMITTER: Stephen CD

PROVIDER: S-EPMC6174483 | biostudies-literature | 2018 May-Jun

REPOSITORIES: biostudies-literature

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Publications

Electrocardiogram Abnormalities Suggest Aberrant Cardiac Conduction in Huntington's Disease.

Stephen Christopher D CD Hung Judy J Schifitto Giovanni G Hersch Steven M SM Rosas H Diana HD

Movement disorders clinical practice 20180411 3

<h4>Background</h4>There is increasing evidence that the effects of Huntington's disease (HD) extend beyond the central nervous system. In particular, significant cardiac dysfunction has been described in transgenic mouse models and suggested in symptomatic patients, in whom cardiac involvement could provide an independent risk for sudden cardiac death.<h4>Methods</h4>Standard 12-lead electrocardiograms (ECGs) obtained at screening from 590 early symptomatic (Stage 1 and 2) HD patients participa ...[more]

PMID: 30363459

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Project description:BackgroundGenetic contributors to cardiac arrhythmias are often found in cardiovascular conduction pathways and ion channel proteins. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disease of massive heterotopic ossification caused by a highly recurrent R206H mutation in ACVR1/ALK2. This mutation causes abnormal activation of the bone morphogenetic protein (BMP) pathway in response to Activin A. Prior studies suggested increased risks of cardiopulmonary complications in FOP. We examined participants in a Natural History Study (NHS) of FOP (ClinicalTrials.gov #NCT02322255) to better understand their cardiovascular status.MethodsThe NHS is an ongoing 3 year international multi-center longitudinal study of 114 patients (ages 4-56 years) with genetically confirmed ACVR1/ALK2R206H FOP. Patients were clinically assessed at baseline and 12 months. Electrocardiograms (ECGs) were reviewed in a central ECG laboratory. Conduction abnormalities were compared against clinical data collected in the NHS, and echocardiograms collected from NHS and non-NHS patients.ResultsConduction abnormalities were present in 45.3% of baseline ECGs, with the majority of abnormalities classified as nonspecific intraventricular conduction delay (37.7%). More specifically, 22.2% of patients > 18 years old had conduction abnormalities, which was significantly higher than a prior published study of a healthy population (5.9%; n = 3978) (p < 0.00001). Patients with FOP < 18 years old also had a high prevalence of conduction abnormalities (62.3%). The 12-month follow up data was similar to baseline results. Conduction abnormalities did not correlate with chest wall deformities, scoliosis, pulmonary function test results, or increased Cumulative Analog Joint Involvement Scale scores. Echocardiograms from 22 patients with FOP revealed 8 with structural cardiac abnormalities, only 1 of which correlated with a conduction abnormality.ConclusionsWe found that patients with FOP may have subclinical conduction abnormalities manifesting on ECG, independent of heterotopic ossification. Although clinically significant heart disease is not typically associated with FOP, and the clinical implications for cardiovascular risk remain unclear, knowledge about ECG and echocardiogram changes is important for clinical care and research trials in patients with FOP. Further studies on how ACVR1/ALK2R206H affects cardiac health will help elucidate the underlying mechanism.

Project description:ObjectivesTo investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging.Experimental designFrom the TRACK-HD study, premanifest gene carriers (preHD), early manifest HD and controls were scanned at baseline and 2-year follow-up. Stratification of the preHD group into a far (preHD-A) and near (preHD-B) to predicted disease onset was performed. Age-corrected histograms of whole-brain white matter (WM), gray matter (GM) and striatal diffusion measures were computed and normalised by the number of voxels in each subject's data set.Principle observationsHigher cross-sectional mean, axial and radial diffusivities were found in both WM (P ? 0.001) and GM (P ? 0.001) of the manifest HD compared to the preHD and control groups. In preHD, only WM axial diffusivity (AD) was higher than in controls (P ? 0.01). This finding remained valid only in preHD-B (P ? 0.001). AD was also higher in the striatum of preHD-B compared to controls and preHD-A (P ? 0.01). Fractional anisotropy (FA) lacked sensitivity in differentiating between the groups. Histogram peak heights were generally lower in manifest HD compared to the preHD and control groups. No longitudinal differences were found in the degree of diffusivity change between the groups in the two year follow-up. There was a significant relationship between diffusivity and neurocognitive measures.ConclusionsAlterations in cross-sectional diffusion profiles between manifest HD subjects and controls were evident, both in whole-brain and striatum. In the preHD stage, only AD alterations were found, a finding suggesting that this metric is a sensitive marker for early change in HD prior to disease manifestation. The individual diffusivities were superior to FA in revealing pathologic microstructural brain alterations. Diffusion measures were well related to clinical functioning and disease stage.

Dataset Information

Electrocardiogram Abnormalities Suggest Aberrant Cardiac Conduction in Huntington's Disease.

Background

Methods

Results

Conclusion

Publications

Electrocardiogram Abnormalities Suggest Aberrant Cardiac Conduction in Huntington's Disease.

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