Gabriella Captur1, Luis R Lopes1, Vimal Patel1, Chunming Li1, Paul Bassett1, Petros Syrris1, Daniel M Sado1, Viviana Maestrini1, Timothy J Mohun1, William J McKenna1, Vivek Muthurangu1, Perry M Elliott1, James C Moon2. 1. From Division of Cardiovascular Imaging and Inherited Cardiovascular Disease Unit, The Heart Hospital, part of University College London NHS Foundation Trust, London, United Kingdom (G.C., L.L., V.P., P.S., D.M.S., V. Maestrini, W.J.M., P.M.E., J.C.M.); UCL Institute of Cardiovascular Science (G.C., L.L., V.P., P.B., P.S., D.M.S., V. Maestrini, W.J.M., V. Muthurangu, P.M.E., J.C.M.) and Biostatistics Joint Research Office (P.B.), University College London, London, United Kingdom; Department of Radiology, University of Pennsylvania, Philadelphia (C.L.); Developmental Biology Division, MRC National Institute for Medical Research, London, United Kingdom (T.J.M.); and UCL Centre for Cardiovascular Imaging and Great Ormond Street Hospital for Children (GOSH), London, United Kingdom (V. Muthurangu). 2. From Division of Cardiovascular Imaging and Inherited Cardiovascular Disease Unit, The Heart Hospital, part of University College London NHS Foundation Trust, London, United Kingdom (G.C., L.L., V.P., P.S., D.M.S., V. Maestrini, W.J.M., P.M.E., J.C.M.); UCL Institute of Cardiovascular Science (G.C., L.L., V.P., P.B., P.S., D.M.S., V. Maestrini, W.J.M., V. Muthurangu, P.M.E., J.C.M.) and Biostatistics Joint Research Office (P.B.), University College London, London, United Kingdom; Department of Radiology, University of Pennsylvania, Philadelphia (C.L.); Developmental Biology Division, MRC National Institute for Medical Research, London, United Kingdom (T.J.M.); and UCL Centre for Cardiovascular Imaging and Great Ormond Street Hospital for Children (GOSH), London, United Kingdom (V. Muthurangu). james.moon@uclh.nhs.uk.
Abstract
BACKGROUND: Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy. Subtle abnormalities of the myocardium may be present in mutation carriers without left ventricular hypertrophy (G+LVH-) but are difficult to quantify. Fractal analysis has been used to define trabeculae in left ventricular noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance images are abnormal in G+LVH- patients, providing a preclinical marker of disease in hypertrophic cardiomyopathy. METHODS AND RESULTS: Cardiovascular magnetic resonance was performed on 40 G+LVH- patients (33±15 years, 38% men), 67 patients with a clinical diagnosis of hypertrophic cardiomyopathy (53±15 years, 76% men; 31 with a pathogenic mutation [G+LVH+]), and 69 matched healthy volunteers (44±15 years, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension, a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH- patients, apical left ventricular trabeculation was increased compared with controls (maximal apical fractal dimension, 1.249±0.07 versus 1.199±0.05; P=0.001). In G+LVH+ and G-LVH+ cohorts, maximal apical fractal dimension was greater than in controls (P<0.0001) irrespective of gene status (G+LVH+: 1.370±0.08; G-LVH+: 1.380±0.09). Compared with controls, G+LVH- patients also had a higher frequency of clefts (28% versus 8%; P=0.02), longer anterior mitral valve leaflets (23.5±3.0 versus 19.7±3.1 mm; P<0.0001), greater septal systolic wall thickness (12.6±3.2 versus 11.2±2.1 mm; P=0.03), higher ejection fraction (71±4% versus 69±4%; P=0.03), and smaller end-systolic volumes (38±9 versus 43±12 mL; P=0.03). CONCLUSIONS: Increased myocardial trabecular complexity is one of several preclinical abnormalities in hypertrophic cardiomyopathy sarcomere gene mutation carriers without LVH.
BACKGROUND: Mutations in genes coding for sarcomeric proteins cause hypertrophic cardiomyopathy. Subtle abnormalities of the myocardium may be present in mutation carriers without left ventricular hypertrophy (G+LVH-) but are difficult to quantify. Fractal analysis has been used to define trabeculae in left ventricular noncompaction and to identify normal racial variations. We hypothesized that trabeculae measured by fractal analysis of cardiovascular magnetic resonance images are abnormal in G+LVH- patients, providing a preclinical marker of disease in hypertrophic cardiomyopathy. METHODS AND RESULTS: Cardiovascular magnetic resonance was performed on 40 G+LVH- patients (33±15 years, 38% men), 67 patients with a clinical diagnosis of hypertrophic cardiomyopathy (53±15 years, 76% men; 31 with a pathogenic mutation [G+LVH+]), and 69 matched healthy volunteers (44±15 years, 57% men). Trabeculae were quantified by fractal analysis of cine slices to calculate the fractal dimension, a unitless index of endocardial complexity calculated from endocardial contours after segmentation. In G+LVH- patients, apical left ventricular trabeculation was increased compared with controls (maximal apical fractal dimension, 1.249±0.07 versus 1.199±0.05; P=0.001). In G+LVH+ and G-LVH+ cohorts, maximal apical fractal dimension was greater than in controls (P<0.0001) irrespective of gene status (G+LVH+: 1.370±0.08; G-LVH+: 1.380±0.09). Compared with controls, G+LVH- patients also had a higher frequency of clefts (28% versus 8%; P=0.02), longer anterior mitral valve leaflets (23.5±3.0 versus 19.7±3.1 mm; P<0.0001), greater septal systolic wall thickness (12.6±3.2 versus 11.2±2.1 mm; P=0.03), higher ejection fraction (71±4% versus 69±4%; P=0.03), and smaller end-systolic volumes (38±9 versus 43±12 mL; P=0.03). CONCLUSIONS: Increased myocardial trabecular complexity is one of several preclinical abnormalities in hypertrophic cardiomyopathy sarcomere gene mutation carriers without LVH.
Authors: Nadine Kawel-Boehm; Scott J Hetzel; Bharath Ambale-Venkatesh; Gabriella Captur; Christopher J Francois; Michael Jerosch-Herold; Michael Salerno; Shawn D Teague; Emanuela Valsangiacomo-Buechel; Rob J van der Geest; David A Bluemke Journal: J Cardiovasc Magn Reson Date: 2020-12-14 Impact factor: 5.364
Authors: Gabriella Captur; Wendy E Heywood; Caroline Coats; Stefania Rosmini; Vimal Patel; Luis R Lopes; Richard Collis; Nina Patel; Petros Syrris; Paul Bassett; Ben O'Brien; James C Moon; Perry M Elliott; Kevin Mills Journal: Mol Cell Proteomics Date: 2019-06-26 Impact factor: 5.911
Authors: Mashael Alfarih; João B Augusto; Kristopher D Knott; Nasri Fatih; M Praveen Kumar; Redha Boubertakh; Alun D Hughes; James C Moon; Sebastian Weingärtner; Gabriella Captur Journal: BMC Med Imaging Date: 2022-07-07 Impact factor: 2.795
Authors: Gaetano D'Amato; Guillermo Luxán; Gonzalo del Monte-Nieto; Beatriz Martínez-Poveda; Carlos Torroja; Wencke Walter; Matthew S Bochter; Rui Benedito; Susan Cole; Fernando Martinez; Anna-Katerina Hadjantonakis; Akiyoshi Uemura; Luis J Jiménez-Borreguero; José Luis de la Pompa Journal: Nat Cell Biol Date: 2015-12-07 Impact factor: 28.824
Authors: Gabriella Captur; Filip Zemrak; Vivek Muthurangu; Steffen E Petersen; Chunming Li; Paul Bassett; Nadine Kawel-Boehm; William J McKenna; Perry M Elliott; João A C Lima; David A Bluemke; James C Moon Journal: Radiology Date: 2015-06-10 Impact factor: 11.105
Authors: Gabriella Captur; Audrey L Karperien; Alun D Hughes; Darrel P Francis; James C Moon Journal: Nat Rev Cardiol Date: 2016-10-06 Impact factor: 32.419
Authors: Gabriella Captur; Luis R Lopes; Timothy J Mohun; Vimal Patel; Chunming Li; Paul Bassett; Gherardo Finocchiaro; Vanessa M Ferreira; Maite Tome Esteban; Vivek Muthurangu; Mark V Sherrid; Sharlene M Day; Charles E Canter; William J McKenna; Christine E Seidman; David A Bluemke; Perry M Elliott; Carolyn Y Ho; James C Moon Journal: Circ Cardiovasc Imaging Date: 2014-09-16 Impact factor: 7.792
Authors: Sylvia Krupickova; Suzan Hatipoglu; Giovanni DiSalvo; Inga Voges; Daniel Redfearn; Sandrine Foldvari; Christian Eichhorn; Sian Chivers; Filippo Puricelli; Grazia Delle-Donne; Courtney Barth; Dudley J Pennell; Sanjay K Prasad; Piers E F Daubeney Journal: J Cardiovasc Magn Reson Date: 2021-07-08 Impact factor: 5.364