10.5061/DRYAD.CJSXKSN4K
Radbill, Andrew
0000-0003-2360-3552
Vanderbilt University Medical Center
Lei, Lucy
University of Calgary
Paranjape, Sachin
Vanderbilt University Medical Center
Abraham, Robert
Vanderbilt University Medical Center
Chew, Derek
University of Calgary
Raj, Satish
University of Calgary
Knollmann, Bjorn
Vanderbilt University Medical Center
Repolarization and contractility in hypertrophic cardiomyopathy patients
Dryad
dataset
2020
FOS: Medical and health sciences
Vanderbilt Clinical and Translational Science Award grant from the
National Center for Advancing Translational Sciences/National Institutes
of Health *
UL1 TR000445
2021-04-27T00:00:00Z
2021-04-27T00:00:00Z
en
https://doi.org/10.1371/journal.pone.0246768
55927 bytes
3
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
Aims: Arrhythmia mechanisms in hypertrophic cardiomyopathy remain
uncertain. Preclinical models suggest hypertrophic cardiomyopathy-linked
mutations perturb sarcomere length-dependent activation, alter cardiac
repolarization in rate-dependent fashion and potentiate triggered
electrical activity. This study was designed to assess rate-dependence of
clinical surrogates of contractility and repolarization in humans with
hypertrophic cardiomyopathy. Methods: All participants had a cardiac
implantable device capable of atrial pacing. Cases had clinical diagnosis
of hypertrophic cardiomyopathy, controls were age-matched. Continuous
electrocardiogram and blood pressure were recorded during and immediately
after 30 second pacing trains delivered at increasing rates. Results: Nine
hypertrophic cardiomyopathy patients and 10 controls were enrolled (47%
female, median 55 years), with similar baseline QRS duration, QT interval
and blood pressure. Median septal thickness in hypertrophic cardiomyopathy
patients was 18mm; 33% of hypertrophic cardiomyopathy patients had peak
sub-aortic velocity >50mmHg. Ventricular ectopy occurred during or
immediately after pacing trains in 4/9 hypertrophic cardiomyopathy
patients and 0/10 controls (P=0.03). At faster drive trains, hypertrophic
cardiomyopathy patients showed a non-significant trend towards a shallower
QT-RR slope than controls. After normalization to the preceding pacing
train QT interval, the normalized QT interval of the first post-pause
recovery beat after pacing trains was similar between cohorts. No
statistically significant differences were seen in surrogate measures for
cardiac contractility. Conclusion: Rapid pacing trains triggered
ventricular ectopy in hypertrophic cardiomyopathy patients, but not
controls. This finding aligns with pre-clinical descriptions of excessive
cardiomyocyte calcium loading during rapid pacing, increased post-pause
sarcoplasmic reticulum calcium release, and subsequent calcium-triggered
activity. Normal contractility at all diastolic intervals argues against
clinical significance of altered length-dependent myofilament activation.