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Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension.
Am J Physiol Heart Circ Physiol. 2020 02 01; 318(2):H401-H412.AJ

Abstract

Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR (n = 64) and healthy controls (n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls (P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit.NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening.

Authors+Show Affiliations

Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Department of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, The Netherlands.Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado. Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Pediatric Heart Lung Center, Department of Pediatrics, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Ludwig-Maxmilian Munich University, Faculty of Medicine, Munich, Germany.Section of Congenital Heart Surgery, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Department of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Department of Pediatric Radiology, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver | Anschutz Medical Campus, Aurora, Colorado.

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31858817

Citation

Frank, Benjamin S., et al. "Novel Measures of Left Ventricular Electromechanical Discoordination Predict Clinical Outcomes in Children With Pulmonary Arterial Hypertension." American Journal of Physiology. Heart and Circulatory Physiology, vol. 318, no. 2, 2020, pp. H401-H412.
Frank BS, Schäfer M, Douwes JM, et al. Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension. Am J Physiol Heart Circ Physiol. 2020;318(2):H401-H412.
Frank, B. S., Schäfer, M., Douwes, J. M., Ivy, D. D., Abman, S. H., Davidson, J. A., Burzlaff, S., Mitchell, M. B., Morgan, G. J., Browne, L. P., Barker, A. J., Truong, U., & von Alvensleben, J. C. (2020). Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension. American Journal of Physiology. Heart and Circulatory Physiology, 318(2), H401-H412. https://doi.org/10.1152/ajpheart.00355.2019
Frank BS, et al. Novel Measures of Left Ventricular Electromechanical Discoordination Predict Clinical Outcomes in Children With Pulmonary Arterial Hypertension. Am J Physiol Heart Circ Physiol. 2020 02 1;318(2):H401-H412. PubMed PMID: 31858817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel measures of left ventricular electromechanical discoordination predict clinical outcomes in children with pulmonary arterial hypertension. AU - Frank,Benjamin S, AU - Schäfer,Michal, AU - Douwes,Johannes M, AU - Ivy,D Dunbar, AU - Abman,Steven H, AU - Davidson,Jesse A, AU - Burzlaff,Sandra, AU - Mitchell,Max B, AU - Morgan,Gareth J, AU - Browne,Lorna P, AU - Barker,Alex J, AU - Truong,Uyen, AU - von Alvensleben,Johannes C, Y1 - 2019/12/20/ PY - 2021/02/01/pmc-release PY - 2019/12/21/pubmed PY - 2020/5/6/medline PY - 2019/12/21/entrez KW - MRI KW - discoordination KW - electromechanics KW - pediatrics KW - pulmonary hypertension SP - H401 EP - H412 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 318 IS - 2 N2 - Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR (n = 64) and healthy controls (n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls (P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit.NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/31858817/Novel_measures_of_left_ventricular_electromechanical_discoordination_predict_clinical_outcomes_in_children_with_pulmonary_arterial_hypertension_ L2 - http://journals.physiology.org/doi/full/10.1152/ajpheart.00355.2019?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -