Non-invasive electromechanical assessment during atrial fibrillation identifies underlying atrial myopathy alterations with early prognostic value

Daniel Enríquez-Vázquez, Jorge G. Quintanilla, Alba García-Escolano, Marinela Couselo-Seijas, Ana Simón-Chica, Peter Lee, José Manuel Alfonso-Almazán, Patricia Mahía, Andrés Redondo-Rodríguez, Javier Modrego, Adriana Ortega-Hernández, Pedro Marcos-Alberca, Ricardo Magni, Enrique Calvo, Rubén Gómez-Gordo, Ping Yan, Giulio Rosa, José Bustamante-Madrión, Carlos Nicolás Pérez-García, F. Javier Martín-Sánchez, David Calvo, Jesús M. Hera, María Jesús García-Torrent, Álvaro García-Osuna, Jordi Ordonez-Llanos, Jesús Vázquez, Julián Pérez-Villacastín, Nicasio Pérez-Castellano, Leslie M. Loew, Javier Sánchez-González, Dulcenombre Gómez-Garre and David Filgueiras-Rama ()
Additional contact information
Daniel Enríquez-Vázquez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Jorge G. Quintanilla: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Alba García-Escolano: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Marinela Couselo-Seijas: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Ana Simón-Chica: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Peter Lee: Essel Research and Development Inc.
José Manuel Alfonso-Almazán: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Patricia Mahía: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)
Andrés Redondo-Rodríguez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Javier Modrego: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Adriana Ortega-Hernández: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)
Pedro Marcos-Alberca: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)
Ricardo Magni: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Enrique Calvo: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Rubén Gómez-Gordo: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)
Ping Yan: University of Connecticut School of Medicine
Giulio Rosa: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
José Bustamante-Madrión: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)
Carlos Nicolás Pérez-García: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
F. Javier Martín-Sánchez: Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)
David Calvo: Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias
Jesús M. Hera: Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias
María Jesús García-Torrent: Universidad Complutense de Madrid
Álvaro García-Osuna: Hospital de la Santa Creu i Sant Pau
Jordi Ordonez-Llanos: Hospital de la Santa Creu i Sant Pau
Jesús Vázquez: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Julián Pérez-Villacastín: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Nicasio Pérez-Castellano: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Leslie M. Loew: University of Connecticut School of Medicine
Javier Sánchez-González: Philips Healthcare Iberia
Dulcenombre Gómez-Garre: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
David Filgueiras-Rama: Centro Nacional de Investigaciones Cardiovasculares (CNIC)

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. This study reports mechanistic insights into the electromechanical remodeling process associated with AF progression and further demonstrates its prognostic value in the clinic. In pigs, sequential electromechanical assessment during AF progression shows a progressive decrease in mechanical activity and early dissociation from its electrical counterpart. Atrial tissue samples from animals with AF reveal an abnormal increase in cardiomyocytes death and alterations in calcium handling proteins. High-throughput quantitative proteomics and immunoblotting analyses at different stages of AF progression identify downregulation of contractile proteins and progressive increase in atrial fibrosis. Moreover, advanced optical mapping techniques, applied to whole heart preparations during AF, demonstrate that AF-related remodeling decreases the frequency threshold for dissociation between transmembrane voltage signals and intracellular calcium transients compared to healthy controls. Single cell simulations of human atrial cardiomyocytes also confirm the experimental results. In patients, non-invasive assessment of the atrial electromechanical relationship further demonstrate that atrial electromechanical dissociation is an early prognostic indicator for acute and long-term rhythm control.

Date: 2023
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DOI: 10.1038/s41467-023-40196-y

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