Thomas P Mast1, Arco J Teske1, John Walmsley2, Jeroen F van der Heijden1, René van Es1, Frits W Prinzen3, Tammo Delhaas2, Toon A van Veen4, Peter Loh1, Pieter A Doevendans1, Maarten J Cramer1, Joost Lumens5. 1. Department of Cardiology, University Medical Center, Utrecht, the Netherlands. 2. Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands. 3. Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands. 4. Department of Medical Physiology, University Medical Center Utrecht, Utrecht, the Netherlands. 5. Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands; IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France. Electronic address: joost.lumens@maastrichtuniversity.nl.
Abstract
BACKGROUND: Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. OBJECTIVES: The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. METHODS: ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. RESULTS: Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. CONCLUSIONS: Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.
BACKGROUND: Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. OBJECTIVES: The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. METHODS: ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. RESULTS: Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. CONCLUSIONS: Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.
Authors: Christopher M Andrews; Neil T Srinivasan; Stefania Rosmini; Heerajnarain Bulluck; Michele Orini; Sharon Jenkins; Antonis Pantazis; William J McKenna; James C Moon; Pier D Lambiase; Yoram Rudy Journal: Circ Arrhythm Electrophysiol Date: 2017-07
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Authors: Rob W Roudijk; Laurens P Bosman; Jeroen F van der Heijden; Jacques M T de Bakker; Richard N W Hauer; J Peter van Tintelen; Folkert W Asselbergs; Anneline S J M Te Riele; Peter Loh Journal: J Clin Med Date: 2020-02-17 Impact factor: 4.241
Authors: Karim Taha; Mimount Bourfiss; Anneline S J M Te Riele; Maarten-Jan M Cramer; Jeroen F van der Heijden; Folkert W Asselbergs; Birgitta K Velthuis; Arco J Teske Journal: Eur Heart J Cardiovasc Imaging Date: 2021-07-20 Impact factor: 6.875