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Left Ventricular Hypertrophy Revisited

2017; Lippincott Williams & Wilkins; Volume: 136; Issue: 25 Linguagem: Inglês

10.1161/circulationaha.117.029895

1524-4539

Thomas A. Treibel, Rebecca Kozor, Katia Menacho, Silvia Castelletti, Heerajnarain Bulluck, Stefania Rosmini, Sabrina Nordin, Viviana Maestrini, Marianna Fontana, James Moon,

Cardiovascular Effects of Exercise

HomeCirculationVol. 136, No. 25Left Ventricular Hypertrophy Revisited Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLeft Ventricular Hypertrophy RevisitedCell and Matrix Expansion Have Disease-Specific Relationships Thomas A. Treibel, PhD, Rebecca Kozor, PhD, Katia Menacho, MD, Silvia Castelletti, MD, Heerajnarain Bulluck, PhD, Stefania Rosmini, MD, Sabrina Nordin, MD, Viviana Maestrini, MD, Marianna Fontana, PhD and James C. Moon, MD Thomas A. TreibelThomas A. Treibel Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) Institute for Cardiovascular Sciences, University College London, UK (T.A.T., H.B., S.R., S.N., M.F., J.C.M.) , Rebecca KozorRebecca Kozor Sydney Medical School, University of Sydney, Australia (R.K.). , Katia MenachoKatia Menacho Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) , Silvia CastellettiSilvia Castelletti Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) , Heerajnarain BulluckHeerajnarain Bulluck Institute for Cardiovascular Sciences, University College London, UK (T.A.T., H.B., S.R., S.N., M.F., J.C.M.) , Stefania RosminiStefania Rosmini Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) Institute for Cardiovascular Sciences, University College London, UK (T.A.T., H.B., S.R., S.N., M.F., J.C.M.) , Sabrina NordinSabrina Nordin Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) Institute for Cardiovascular Sciences, University College London, UK (T.A.T., H.B., S.R., S.N., M.F., J.C.M.) , Viviana MaestriniViviana Maestrini Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) , Marianna FontanaMarianna Fontana Institute for Cardiovascular Sciences, University College London, UK (T.A.T., H.B., S.R., S.N., M.F., J.C.M.) and James C. MoonJames C. Moon Barts Heart Centre, St Bartholomew's Hospital, London, UK (T.A.T., K.M., S.C., S.R., S.N., V.M., J.C.M.) Institute for Cardiovascular Sciences, University College London, UK (T.A.T., H.B., S.R., S.N., M.F., J.C.M.) Originally published19 Dec 2017https://doi.org/10.1161/CIRCULATIONAHA.117.029895Circulation. 2017;136:2519–2521Left ventricular hypertrophy (LVH), a common pathway in health and disease, occurs because of cellular hypertrophy and expansion of extracellular matrix. Myocardial biopsy can identify extracellular matrix expansion (fibrosis, amyloid) from cellular hypertrophy and disarray and infiltration (iron, amyloid, inflammatory cells), but its invasive nature restricts its use to specific cases. Histology recognizes these cellular (cell death/hypertrophy) and extracellular matrix (fibrosis/infiltration) processes, but conventional cardiac imaging combines them into 1 compartment: the left ventricular mass (LVM).Cardiovascular magnetic resonance (CMR) using T1 mapping can split LVM into cellular and matrix components by measuring the extracellular volume fraction (ECV). The cell volume is LVM/1.05×[1–ECV], and the matrix volume is LVM/1.05×ECV, 1.05 being the specific gravity of the myocardium. We used this approach to explore the biology of LVH.The study was approved by the ethical committee of the UK National Research Ethics Service (07/H0715/101) and conformed to the principles of the Helsinki Declaration. All subjects gave written consent to participate; 190 subjects underwent CMR, including healthy volunteers (HV; n=30, male 44%, 41±11 years of age, no cardiovascular history, and normal ECG and CMR), and 160 subjects with LVH, defined as increased indexed LVM: athletes (AT; n=50, male 80%, 42±14 years of age, >10 endurance events in lifetime), severe aortic stenosis awaiting valve replacement (AS; n=30, male 66%, 74±6 years of age, aortic valve area indexed 0.4±0.1 cm2), Fabry disease (FD; n=20, male 75%, 51±9 years of age, gene-positive), hypertrophic cardiomyopathy (HCM; n=30, male 57%, 50±16 years of age, asymmetrical LVH excluding apical HCM), and cardiac amyloidosis (CA; n=30, all transthyretin amyloid, male 90%, 76±7 years of age). CMR was at 1.5 Tesla with T1 mapping using the Shortened MOdified Look-Locker Inversion recovery method1 before and after a 0.1 mmol/kg bolus of gadoterate meglumine (gadolinium-DOTA, marketed as Dotarem, Guerbet S.A.). Cardiac chamber volumes, LVM, and T1 maps were quantified using CVI42 (Circle Cardiovascular Imaging Inc.) with manual contouring.2 Patients with infarct-pattern late gadolinium enhancement were not included. ECV was derived from pre- and postcontrast short axis T1 maps and blood hematocrit. Matrix and cell volumes were calculated as described above.LVM progressively increased from health (HV) and physiological hypertrophy (AT, AS) to pathological hypertrophy (HV<AT<AS<HCM<FD<CA, P<0.001). ECV was highest in cardiac amyloid (ECVCA=60.6±7.8%) and lowest in young athletes (ECVAT=26.2±2.7%), with increasing ECV from healthy volunteers (ECVHV=28.0±2.9%) to LVH pathologies (ECVAS=28.5±2.6%, ECVHCM=33.1±5.2%, and ECVFD=29.8±4.0%). Matrix volume, generally around a quarter of the myocardial volume, progressively increased from health to disease (HV<AT<AS<HCM<FD<CA, P<0.001) (Figure 1B). Cell volume also progressively increased, with the exception of CA, which, despite having the highest LVM, had a lower cell volume than all cohorts apart from HV (HV<CA<AT<AS<HCM<FD, P<0.001) (Figure 1B). For each etiology apart from CA, cell and matrix volumes correlated strongly (R2=0.6–0.8, all P<0.01; Figure 1B) but with slightly different regression slopes. Cell hypertrophy predominated in AT (slope 2.5. In CA, LVM was predominantly driven by extracellular matrix expansion (slope <1). The regression slope for AT was significantly different than pathological hypertrophy (P=0.01), and CA was significantly different than all other groups (P<0.0001) using ANCOVA.Download figureDownload PowerPointFigure. Extracellular volume fraction imaging by cardiovascular magnetic resonance dichotomizes the myocardium into cell and matrix components.A, Cell and matrix volumes increase proportionally in health and disease, but the ratio of proportional increase differs depending on the etiology of the left ventricular hypertrophy. B, With increasing hypertrophy, both matrix and cell volume increase, apart from cardiac amyloidosis, which is dominated by matrix expansion. ns indicates not significant.We conclude that, for most causes of LVH, on average there is a proportional increase in cellular and matrix components with 2 exceptions: physiological cell hypertrophy in AT (mainly cellular) and amyloidosis (almost exclusively matrix). Thus, ECV-derived volumes provide pathophysiological insights beyond quantifying the degree of hypertrophy. These results are, however, for the average of disease categories. Further intradisease work, and particularly longitudinal follow-up work, is needed.By multiplying by LVM/1.05 (specific gravity for myocardial tissue is assumed as for normal tissue), we move ECV on from a percentage to a volume—providing whole heart quantification, unlike histology. However, it does not distinguish the cause of the matrix increase (fibrosis, amyloid, edema) or the cell type that is expanded, although this is assumed to be myocytes. Similarly, the qualitative nature of the fibrosis, its maturity, its tensile properties, and its collagen subtypes are not assessed. Capillary density and vasodilatation will also have a minor influence. In the future, the measurement of additional parameters will be needed to capture more facets of myocardial biology. Finally, although this CMR approach appears relatively new, we acknowledge the pioneering of Franz Schwarz and colleagues3 who, in 1978, used invasive biopsy to divide LVH into cellular and fibrotic components in aortic stenosis.Thomas A. Treibel, PhD*Rebecca Kozor, PhD*Katia Menacho, MDSilvia Castelletti, MDHeerajnarain Bulluck, PhDStefania Rosmini, MDSabrina Nordin, MDViviana Maestrini, MDMarianna Fontana, PhDJames C. Moon, MDSources of FundingDrs Treibel and Fontana were supported by doctoral research fellowships from the National Institute of Health Research (DRF-2013-06-102) and the British Heart Foundation (FS/12/56/29723), respectively. Dr Moon is directly and indirectly supported by the University College London Hospitals' National Institute of Health Research Biomedical Research Center and Biomedical Research Unit at Barts Hospital. Dr Kozor was sponsored by Heart Research Australia.DisclosuresNone.Footnotes*Drs Treibel and Kozor contributed equally.Circulation is available at http://circ.ahajournals.org.Correspondence to: James C. Moon, MD, Barts Heart Centre, St Bartholomew's Hospital, 2nd Fl, King George V Block, London EC1A 7BE, United Kingdom. E-mail [email protected]References1. Piechnik SK, Ferreira VM, Dall'Armellina E, Cochlin LE, Greiser A, Neubauer S, Robson MD. Shortened modified look-locker inversion recovery (ShMOLLI) for clinical myocardial T1-mapping at 1.5 and 3 T within a 9 heartbeat breathhold.J Cardiovasc Magn Reson. 2010; 12:69. doi: 10.1186/1532-429X-12-69.CrossrefMedlineGoogle Scholar2. Maceira AM, Prasad SK, Khan M, Pennell DJ. Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance.J Cardiovasc Magn Reson. 2006; 8:417–426.CrossrefMedlineGoogle Scholar3. Schwarz F, Flameng W, Schaper J, Langebartels F, Sesto M, Hehrlein F, Schlepper M. Myocardial structure and function in patients with aortic valve disease and their relation to postoperative results.Am J Cardiol. 1978; 41:661–669.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Merlo M, Gagno G, Baritussio A, Bauce B, Biagini E, Canepa M, Cipriani A, Castelletti S, Dellegrottaglie S, Guaricci A, Imazio M, Limongelli G, Musumeci M, Parisi V, Pica S, Pontone G, Todiere G, Torlasco C, Basso C, Sinagra G, Filardi P, Indolfi C, Autore C and Barison A (2022) Clinical application of CMR in cardiomyopathies: evolving concepts and techniques, Heart Failure Reviews, 10.1007/s10741-022-10235-9 Chowdhary A, Thirunavukarasu S, Jex N, Coles L, Bowers C, Sengupta A, Swoboda P, Witte K, Cubbon R, Xue H, Kellman P, Greenwood J, Plein S and Levelt E (2022) Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes, Obesity, 10.1002/oby.23413, 30:5, (1079-1090), Online publication date: 1-May-2022. 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Androulakis E, Mouselimis D, Tsarouchas A, Antonopoulos A, Bakogiannis C, Papagkikas P and Vlachopoulos C (2021) The Role of Cardiovascular Magnetic Resonance Imaging in the Assessment of Myocardial Fibrosis in Young and Veteran Athletes: Insights From a Meta-Analysis, Frontiers in Cardiovascular Medicine, 10.3389/fcvm.2021.784474, 8 Thirunavukarasu S, Jex N, Chowdhary A, Hassan I, Straw S, Craven T, Gorecka M, Broadbent D, Swoboda P, Witte K, Cubbon R, Xue H, Kellman P, Greenwood J, Plein S and Levelt E (2021) Empagliflozin Treatment Is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes, Diabetes, 10.2337/db21-0270, 70:12, (2810-2822), Online publication date: 1-Dec-2021. van der Velde N, Janus C, Bowen D, Hassing H, Kardys I, van Leeuwen F, So-Osman C, Nout R, Manintveld O and Hirsch A (2021) Detection of Subclinical Cardiovascular Disease by Cardiovascular Magnetic Resonance in Lymphoma Survivors, JACC: CardioOncology, 10.1016/j.jaccao.2021.09.015, 3:5, (695-706), Online publication date: 1-Dec-2021. 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FILOMENA D, BIRTOLO L, PENZA M, GUALDI G, DI GIACINTO B and MAESTRINI V The role of cardiovascular magnetic resonance in the screening before the return-to-play of elite athletes after COVID-19: utility o futility?, The Journal of Sports Medicine and Physical Fitness, 10.23736/S0022-4707.21.12764-1, 61:8 Kawada Y, Kitada S, Hachiya K, Kato M, Nakasuka K, Kikuchi S, Seo Y and Ohte N (2021) Left Ventricular Hypertrophic Change Indicating Poor Prognosis in Patients With Normal-Flow, Low-Gradient Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction, Circulation Reports, 10.1253/circrep.CR-21-0011, 3:6, (345-353), Online publication date: 10-Jun-2021. Xu Y, Li W, Wan K, Liang Y, Jiang X, Wang J, Mui D, Li Y, Tang S, Guo J, Guo X, Liu X, Sun J, Zhang Q, Han Y and Chen Y (2020) Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy, Circulation: Heart Failure, 14:1, Online publication date: 1-Jan-2021. 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Maestrini V, Torlasco C, Hughes R and Moon J (2020) Cardiovascular Magnetic Resonance and Sport Cardiology: a Growing Role in Clinical Dilemmas, Journal of Cardiovascular Translational Research, 10.1007/s12265-020-10022-7, 13:3, (296-305), Online publication date: 1-Jun-2020. Dennis M, Ugander M, Kozor R and Puranik R (2020) Cardiovascular Magnetic Resonance Imaging of Inherited Heart Conditions, Heart, Lung and Circulation, 10.1016/j.hlc.2019.12.008, 29:4, (584-593), Online publication date: 1-Apr-2020. Kolentinis M, Maestrini V, Vidalakis E, Cimino S and Arcari L (2020) CMR in Hypertrophic Cardiac Conditions—an Update, Current Cardiovascular Imaging Reports, 10.1007/s12410-020-9533-1, 13:4, Online publication date: 1-Apr-2020. Swoboda P, Garg P, Levelt E, Broadbent D, Zolfaghari-Nia A, Foley A, Fent G, Chew P, Brown L, Saunderson C, Dall'Armellina E, Greenwood J and Plein S (2019) Regression of Left Ventricular Mass in Athletes Undergoing Complete Detraining Is Mediated by Decrease in Intracellular but Not Extracellular Compartments, Circulation: Cardiovascular Imaging, 12:9, Online publication date: 1-Sep-2019. Treibel T, Badiani S, Lloyd G and Moon J (2019) Multimodality Imaging Markers of Adverse Myocardial Remodeling in Aortic Stenosis, JACC: Cardiovascular Imaging, 10.1016/j.jcmg.2019.02.034, 12:8, (1532-1548), Online publication date: 1-Aug-2019. Maksuti E, Westerhof B, Ugander M, Donker D, Carlsson M and Broomé M (2019) Cardiac remodeling in aortic and mitral valve disease: a simulation study with clinical validation, Journal of Applied Physiology, 10.1152/japplphysiol.00791.2018, 126:5, (1377-1389), Online publication date: 1-May-2019. Cuspidi C, Facchetti R, Bombelli M, Tadic M, Sala C, Grassi G and Mancia G (2019) High Normal Blood Pressure and Left Ventricular Hypertrophy Echocardiographic Findings From the PAMELA Population, Hypertension, 73:3, (612-619), Online publication date: 1-Mar-2019. De Innocentiis C, Ricci F, Khanji M, Aung N, Tana C, Verrengia E, Petersen S and Gallina S (2018) Athlete's Heart: Diagnostic Challenges and Future Perspectives, Sports Medicine, 10.1007/s40279-018-0985-2, 48:11, (2463-2477), Online publication date: 1-Nov-2018. González A, Ravassa S, López B, Moreno M, Beaumont J, San José G, Querejeta R, Bayés-Genís A and Díez J (2018) Myocardial Remodeling in Hypertension, Hypertension, 72:3, (549-558), Online publication date: 1-Sep-2018.Kozor R, Moon J and Treibel T (2018) Response by Kozor et al to Letter Regarding Article, "Left Ventricular Hypertrophy Revisited: Cell and Matrix Expansion Have Disease-Specific Relationships", Circulation, 137:24, (2672-2673), Online publication date: 12-Jun-2018.Madias J (2018) Letter by Madias Regarding Article, "Left Ventricular Hypertrophy Revisited: Cell and Matrix Expansion Have Disease-Specific Relationships", Circulation, 137:24, (2670-2671), Online publication date: 12-Jun-2018.Treibel T, Scully P and Moon J (2018) Myocardial Hypertrophy, Matrix Expansion, and Focal Scar, Circulation: Cardiovascular Imaging, 11:6, Online publication date: 1-Jun-2018. Lopez B, Gonzalez A, Díez J, Moon J and Treibel T (2018) Reply, Journal of the American College of Cardiology, 10.1016/j.jacc.2018.04.034, 71:25, (2984-2985), Online publication date: 1-Jun-2018. December 19, 2017Vol 136, Issue 25 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.117.029895PMID: 29255128 Originally publishedDecember 19, 2017 KeywordsT1 mappingextracellular volume fractionleft ventricular hypertrophyPDF download Advertisement SubjectsHypertrophyMagnetic Resonance Imaging (MRI)Remodeling