Electromechanical activation and recovery wave imaging for pediatric mitral valve disease characterization

Mitral valve (MV) disease, particularly MV prolapse (MVP) and mitral regurgitation (MR), affects 2 to 5% of the population and poses a substantial arrhythmogenic risk, with 43% of MVP patients developing arrhythmias. Although less common in children, the absence of comorbidities can uniquely isolate early electromechanical alterations that may elucidate mechanisms later contributing to arrhythmic risk and devastating effects such as sudden cardiac death. Conventional echocardiography lacks sensitivity for MV electromechanics, motivating advanced approaches. We introduce Electromechanical Wave Imaging (EWI), a high-frame-rate echocardiography modality, to map MV-complex activation and diastolic recovery in N = 21 MVP, MR, and control pediatric subjects (13.10 ± 4.51 y old, 43% male). A preclinical canine study (n = 3) established EWI’s ability to observe temporally coupled electromechanical wave propagation across the atrioventricular junction through the closed MV-following atrial and preceding ventricular activation (73.0 ms, 60 BPM). MVP patients exhibited significantly delayed left ventricular (LV) activation (76.04 ± 12.51 ms vs. 47.64 ± 2.57 ms in controls, P = 0.0013), primarily in papillary muscles. Both MVP and MR-only subjects exhibited prolonged LV recovery, with MR-only patients showing significantly longer recovery intervals (MR-only: 277.0 ± 27.61 ms, Control: 248.7 ± 10.43 ms, MVP vs. Control: MR-only vs. Control: P = 0.0395). In two arrhythmogenic MVP cases, EWI localized arrhythmic exit sites adjacent to LV papillary muscles, coinciding with regional delayed sinus activation, aligning with invasive electrophysiology. This study demonstrates that atrioventricular valve function dictates cardiac electromechanical function and establishes full-cycle EWI as a transformative tool for diagnosing MV disease electromechanical effects, assessing arrhythmic risk, guiding interventions, and advancing noninvasive cardiac imaging.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-08-17
DOI
https://doi.org/10.1073/pnas.2503559123
Primary Topic
Cardiac Valve Diseases and Treatments
Type
article
Field-Weighted Citation Impact
0.00

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article

Electromechanical activation and recovery wave imaging for pediatric mitral valve disease characterization

Elisa E. Konofagou, Jad El Harake, Youssef Elnabawi, Melina Tourni et al.
Proceedings of the National Academy of Sciences
Cardiac Valve Diseases and Treatments
article

Electromechanical activation and recovery wave imaging for pediatric mitral valve disease characterization

Elisa E. Konofagou, Jad El Harake, Youssef Elnabawi, Melina Tourni, Çağla Özsoy, Seungyeon Julia Han, Alexandra Channing, Leonardo Liberman, Mary Kucinski, Christina Proestaki, Aikaterini Afentouli, Yaffa Wolicki, Johanna B. Tonko, Rachel Weber, Hannah Schleifer, Rosalia Minyety
article en

Abstract

Mitral valve (MV) disease, particularly MV prolapse (MVP) and mitral regurgitation (MR), affects 2 to 5% of the population and poses a substantial arrhythmogenic risk, with 43% of MVP patients developing arrhythmias. Although less common in children, the absence of comorbidities can uniquely isolate early electromechanical alterations that may elucidate mechanisms later contributing to arrhythmic risk and devastating effects such as sudden cardiac death. Conventional echocardiography lacks sensitivity for MV electromechanics, motivating advanced approaches. We introduce Electromechanical Wave Imaging (EWI), a high-frame-rate echocardiography modality, to map MV-complex activation and diastolic recovery in N = 21 MVP, MR, and control pediatric subjects (13.10 ± 4.51 y old, 43% male). A preclinical canine study (n = 3) established EWI’s ability to observe temporally coupled electromechanical wave propagation across the atrioventricular junction through the closed MV-following atrial and preceding ventricular activation (73.0 ms, 60 BPM). MVP patients exhibited significantly delayed left ventricular (LV) activation (76.04 ± 12.51 ms vs. 47.64 ± 2.57 ms in controls, P = 0.0013), primarily in papillary muscles. Both MVP and MR-only subjects exhibited prolonged LV recovery, with MR-only patients showing significantly longer recovery intervals (MR-only: 277.0 ± 27.61 ms, Control: 248.7 ± 10.43 ms, MVP vs. Control: MR-only vs. Control: P = 0.0395). In two arrhythmogenic MVP cases, EWI localized arrhythmic exit sites adjacent to LV papillary muscles, coinciding with regional delayed sinus activation, aligning with invasive electrophysiology. This study demonstrates that atrioventricular valve function dictates cardiac electromechanical function and establishes full-cycle EWI as a transformative tool for diagnosing MV disease electromechanical effects, assessing arrhythmic risk, guiding interventions, and advancing noninvasive cardiac imaging.

Proceedings of the National Academy of SciencesVol. 123(34)
Columbia University Irving Medical Center (US), Neurological Surgery (US), University College London (GB), Columbia University (US)
Alexander S. Onassis Public Benefit Foundation, National Heart, Lung, and Blood Institute
Good health and well-being
Openalex Percentile: Top 10%
Cardiac Valve Diseases and Treatments
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