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

被引:5
|
作者
Enriquez-Vazquez, Daniel [1 ,2 ,3 ]
Quintanilla, Jorge G. [1 ,3 ,4 ]
Garcia-Escolano, Alba [1 ,5 ]
Couselo-Seijas, Marinela [1 ]
Simon-Chica, Ana [1 ]
Lee, Peter [6 ]
Alfonso-Almazan, Jose Manuel [1 ]
Mahia, Patricia [4 ]
Redondo-Rodriguez, Andres [1 ]
Modrego, Javier [1 ,3 ,7 ]
Ortega-Hernandez, Adriana [7 ]
Marcos-Alberca, Pedro [4 ]
Magni, Ricardo [1 ]
Calvo, Enrique [1 ,3 ]
Gomez-Gordo, Ruben [7 ]
Yan, Ping [8 ]
La Rosa, Giulio [1 ]
Bustamante-Madrion, Jose [9 ]
Perez-Garcia, Carlos Nicolas [1 ,4 ]
Martin-Sanchez, F. Javier [9 ]
Calvo, David [10 ]
de la Hera, Jesus M. [10 ]
Garcia-Torrent, Maria Jesus [11 ]
Garcia-Osuna, Alvaro [12 ,13 ]
Ordonez-Llanos, Jordi [12 ,14 ,15 ]
Vazquez, Jesus [1 ,3 ]
Perez-Villacastin, Julian [3 ,4 ,16 ]
Perez-Castellano, Nicasio [3 ,4 ,16 ]
Loew, Leslie M. [8 ]
Sanchez-Gonzalez, Javier [17 ]
Gomez-Garre, Dulcenombre [3 ,7 ]
Filgueiras-Rama, David [1 ,3 ,4 ]
机构
[1] Ctr Nacl Invest Cardiovasc CNIC, Novel Arrhythmogen Mech Program, Madrid, Spain
[2] Complexo Hosp Univ A Coruna, Inst Invest Biomed Coruna INIB, Serv Cardiol, La Coruna, Spain
[3] Ctr Invest Biomed Red Enfermedades Cardiovasc CIBE, Madrid, Spain
[4] Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Cardiovasc Inst, Madrid, Spain
[5] Univ Politecn Madrid, ETSI Telecomunicac, Madrid, Spain
[6] Essel Res & Dev Inc, Toronto, ON, Canada
[7] Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Lab Microbiota & Biol Vasc, Madrid, Spain
[8] Univ Connecticut, Sch Med, Richard D Berlin Ctr Cell Anal & Modeling, Farmington, CT USA
[9] Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Emergency Dept, Madrid, Spain
[10] Hosp Univ Cent Asturias, Inst Invest Sanitaria Principado Asturias, Oviedo, Spain
[11] Univ Complutense Madrid, Dept Med, Madrid, Spain
[12] Hosp Santa Creu & Sant Pau, Dept Clin Biochem, Barcelona, Spain
[13] Hosp Santa Creu & Sant Pau, Inst Recerca, Inst Invest Biomed, IIB Sant Pau, Barcelona, Spain
[14] Univ Autonoma Barcelona, Barcelona, Spain
[15] Fdn Clin Biochem & Mol Pathol, Madrid, Spain
[16] Fdn Interhosp Invest Cardiovasc FIC, Madrid, Spain
[17] Philips Healthcare Iberia, Madrid, Spain
关键词
ELECTRICAL CARDIOVERSION; PROGRESSION; SOCIETY; EVENTS; ADULTS; HEART;
D O I
10.1038/s41467-023-40196-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. Here, the authors use non-invasive atrial electromechanical assessment during AF to identify early remodeling changes associated with underlying myopathy, which in the clinic decrease the probability of acute and mid-term successful rhythm control. 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.
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页数:17
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