Author + information
- Received April 19, 2016
- Revision received July 8, 2016
- Accepted August 9, 2016
- Published online November 15, 2016.
- Thomas P. Mast, MDa,
- Arco J. Teske, MD, PhDa,
- John Walmsley, PhDb,
- Jeroen F. van der Heijden, MD, PhDa,
- René van Es, PhDa,
- Frits W. Prinzen, PhDc,
- Tammo Delhaas, MD, PhDb,
- Toon A. van Veen, PhDd,
- Peter Loh, MD, PhDa,
- Pieter A. Doevendans, MD, PhDa,
- Maarten J. Cramer, MD, PhDa and
- Joost Lumens, PhDb,e,∗ ()
- aDepartment of Cardiology, University Medical Center, Utrecht, the Netherlands
- bDepartment of Biomedical Engineering, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
- cDepartment of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
- dDepartment of Medical Physiology, University Medical Center Utrecht, Utrecht, the Netherlands
- eIHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France
- ↵∗Reprint requests and correspondence:
Dr. Joost Lumens, Department of Biomedical Engineering (UNS50, room H3.362), CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, PO Box 616, 6200 MD Maastricht, the Netherlands.
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.
This work was partially funded through a personal grant within the Dr. E. Dekker framework of the Dutch Heart Foundation to Dr. Lumens (grant 2015T082). Dr. Prinzen has received research grants from Medtronic, EBR Systems, Merck Sharp & Dohme Corp, St. Jude Medical, Biological Delivery Systems, Biotronik, and Sorin. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Cramer and Lumens contributed equally to this work.
- Received April 19, 2016.
- Revision received July 8, 2016.
- Accepted August 9, 2016.
- American College of Cardiology Foundation