Reference ranges for cardiac structure and function using cardiovascular magnetic resonance (CMR) in Caucasians from the UK Biobank population cohort

Steffen E Petersen, Nay Aung, Mihir M Sanghvi, Filip Zemrak, Kenneth Fung, Jose Miguel Paiva, Jane M Francis, Mohammed Y Khanji, Elena Lukaschuk, Aaron M Lee, Valentina Carapella, Young Jin Kim, Paul Leeson, Stefan K Piechnik, Stefan Neubauer, Steffen E Petersen, Nay Aung, Mihir M Sanghvi, Filip Zemrak, Kenneth Fung, Jose Miguel Paiva, Jane M Francis, Mohammed Y Khanji, Elena Lukaschuk, Aaron M Lee, Valentina Carapella, Young Jin Kim, Paul Leeson, Stefan K Piechnik, Stefan Neubauer

Abstract

Background: Cardiovascular magnetic resonance (CMR) is the gold standard method for the assessment of cardiac structure and function. Reference ranges permit differentiation between normal and pathological states. To date, this study is the largest to provide CMR specific reference ranges for left ventricular, right ventricular, left atrial and right atrial structure and function derived from truly healthy Caucasian adults aged 45-74.

Methods: Five thousand sixty-five UK Biobank participants underwent CMR using steady-state free precession imaging at 1.5 Tesla. Manual analysis was performed for all four cardiac chambers. Participants with non-Caucasian ethnicity, known cardiovascular disease and other conditions known to affect cardiac chamber size and function were excluded. Remaining participants formed the healthy reference cohort; reference ranges were calculated and were stratified by gender and age (45-54, 55-64, 65-74).

Results: After applying exclusion criteria, 804 (16.2%) participants were available for analysis. Left ventricular (LV) volumes were larger in males compared to females for absolute and indexed values. With advancing age, LV volumes were mostly smaller in both sexes. LV ejection fraction was significantly greater in females compared to males (mean ± standard deviation [SD] of 61 ± 5% vs 58 ± 5%) and remained static with age for both genders. In older age groups, LV mass was lower in men, but remained virtually unchanged in women. LV mass was significantly higher in males compared to females (mean ± SD of 53 ± 9 g/m2 vs 42 ± 7 g/m2). Right ventricular (RV) volumes were significantly larger in males compared to females for absolute and indexed values and were smaller with advancing age. RV ejection fraction was higher with increasing age in females only. Left atrial (LA) maximal volume and stroke volume were significantly larger in males compared to females for absolute values but not for indexed values. LA ejection fraction was similar for both sexes. Right atrial (RA) maximal volume was significantly larger in males for both absolute and indexed values, while RA ejection fraction was significantly higher in females.

Conclusions: We describe age- and sex-specific reference ranges for the left ventricle, right ventricle and atria in the largest validated normal Caucasian population.

Keywords: Atrial function; Cardiovascular magnetic resonance; Reference values; Ventricular function.

Figures

Fig. 1
Fig. 1
Examples of ventricular and atrial contours. The above panels are representative of analysis undertaken on each CMR examination. a and b demonstrate contouring of the left and right ventricle from base to apex at end-diastole and end-systole, respectively. d and e demonstrate contouring of the left and right atrium in the four-chamber view. f and g demonstrate contouring of the left atrium in the two-chamber view
Fig. 2
Fig. 2
Case selection flowchart
Fig. 3
Fig. 3
Exemplar Bland-Altman plots for inter- and intra-observer variability of left ventricular parameters
Fig. 4
Fig. 4
Exemplar Bland-Altman plots for inter- and intra-observer variability of right ventricular parameters
Fig. 5
Fig. 5
Exemplar Bland-Altman plots for inter- and intra-observer variability of atrial parameters

References

    1. 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;8:417–26. doi: 10.1080/10976640600572889.
    1. Hudsmith L, Petersen S, Francis J, Robson M, Neubauer S. Normal human left and right ventricular and left atrial dimensions using steady state free precession magnetic resonance imaging. J Cardiovasc Magn Reson. 2005;7:775–82. doi: 10.1080/10976640500295516.
    1. Alfakih K, Plein S, Thiele H, Jones T, Ridgway JP, Sivananthan MU. Normal human left and right ventricular dimensions for MRI as assessed by turbo gradient echo and steady-state free precession imaging sequences. J Magn Reson Imaging. 2003;17:323–9.
    1. Kawel-Boehm N, Maceira A, Valsangiacomo-Buechel ER, Vogel-Claussen J, Turkbey EB, Williams R, et al. Normal values for cardiovascular magnetic resonance in adults and children. J Cardiovasc Magn Reson BioMed Central. 2015;17:29. doi: 10.1186/s12968-015-0111-7.
    1. Yeon SB, Salton CJ, Gona P, Chuang ML, Blease SJ, Han Y, et al. Impact of age, sex, and indexation method on MR left ventricular reference values in the Framingham Heart Study offspring cohort. J Magn Reson Imaging NIH Public Access. 2015;41:1038–45. doi: 10.1002/jmri.24649.
    1. Foppa M, Arora G, Gona P, Ashrafi A, Salton CJ, Yeon SB, et al. Right ventricular volumes and systolic function by cardiac magnetic resonance and the impact of sex, age, and obesity in a longitudinally followed cohort free of pulmonary and cardiovascular disease. Circ Cardiovasc Imaging Lippincott Williams & Wilkins. 2016;9:e003810. doi: 10.1161/CIRCIMAGING.115.003810.
    1. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med Public Library of Science. 2015;12:e1001779.
    1. Petersen SE, Matthews PM, Bamberg F, Bluemke DA, Francis JM, Friedrich MG, et al. Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches. J Cardiovasc Magn Reson. 2013;15:46. doi: 10.1186/1532-429X-15-46.
    1. Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, et al. UK Biobank’s cardiovascular magnetic resonance protocol. J Cardiovasc Magn Reson BioMed Central Ltd. 2016;18:8. doi: 10.1186/s12968-016-0227-4.
    1. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1–39.e14. doi: 10.1016/j.echo.2014.10.003.
    1. Carapella V, Jimenez-Ruiz E, Lukaschuk E, Aung N, Fung K, Paiva J, et al. Towards the semantic enrichment of free-text annotation of image quality assessment for UK Biobank cardiac Cine MRI scans. Lect Notes Comput Sci. 2016;238–48. 1.
    1. Solberg HE. The theory of reference values Part 5. Statistical treatment of collected reference values. Determination of reference limits. J. Clin. Chem. Clin. Biochem. Zeitschrift für Klin. Chemie und Klin. Biochem. 1983;21:749–60.
    1. Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med. 1916;17:863–71. doi: 10.1001/archinte.1916.00080130010002.
    1. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet (London, England) 1986;1:307–10. doi: 10.1016/S0140-6736(86)90837-8.
    1. Hallgren KA. Computing inter-rater reliability for observational data: an overview and tutorial. Tutor Quant Methods Psychol NIH Public Access. 2012;8:23–34. doi: 10.20982/tqmp.08.1.p023.
    1. R Core Team. R: A Language and Environment for Statistical Computing. Vienna; 2016.
    1. Dweck MR, Joshi S, Murigu T, Gulati A, Alpendurada F, Jabbour A, et al. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:50. doi: 10.1186/1532-429X-14-50.
    1. Sievers B, Kirchberg S, Franken U, Bakan A, Addo M, John-Puthenveettil B, et al. Determination of normal gender-specific left atrial dimensions by cardiovascular magnetic resonance imaging. J Cardiovasc Magn Reson. 2005;7:677–83. doi: 10.1081/JCMR-200065621.
    1. Maceira AM, Cosín-Sales J, Roughton M, Prasad SK, Pennell DJ. Reference left atrial dimensions and volumes by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2010;12:65. doi: 10.1186/1532-429X-12-65.
    1. Maceira AM, Cosín-Sales J, Roughton M, Prasad SK, Pennell DJ, Sanfilippo A, et al. Reference right atrial dimensions and volume estimation by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson BioMed Central. 2013;15:29. doi: 10.1186/1532-429X-15-29.
    1. Gandy SJ, Lambert M, Belch J, Cavin I, Crowe E, Littleford R, et al. 3T MRI investigation of cardiac left ventricular structure and function in a UK population: The tayside screening for the prevention of cardiac events (TASCFORCE) study. J Magn Reson Imaging. 2016;44:1186–96.
    1. Le Ven F, Bibeau K, De Larochellière É, Tizón-Marcos H, Deneault-Bissonnette S, Pibarot P, et al. Cardiac morphology and function reference values derived froma large subset of healthy young Caucasian adults by magnetic resonance imaging. Eur Heart J Cardiovasc Imaging. 2016;17:981–90.
    1. Helge Erik Solberg DS. IFCC recommendation: the theory of reference values. Part 4. Control ofanalytical variation in the production, transfer and application of reference values. J Automat Chem Hindawi Publishing Corporation. 1991;13:231. doi: 10.1155/S146392469100038X.
    1. Lieb W, Xanthakis V, Sullivan LM, Aragam J, Pencina MJ, Larson MG, et al. Longitudinal tracking of left ventricular mass over the adult life course: clinical correlates of short- and long-term change in the framingham offspring study. Circulation American Heart Association Journals. 2009;119:3085–92.
    1. Fuchs A, Mejdahl MR, Kühl JT, Stisen ZR, Nilsson EJP, Køber LV, et al. Normal values of left ventricular mass and cardiac chamber volumes assessed by 320-detector computed tomography angiography in the Copenhagen General Population Study. Eur Hear. J Cardiovasc Imaging. Oxford University Press. 2016;322:1561–6.
    1. Chung AK, Das SR, Leonard D, Peshock RM, Kazi F, Abdullah SM, et al. Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume: the Dallas Heart Study. Circulation American Heart Association Journals. 2006;113:1597–604.
    1. Natori S, Lai S, Finn JP, Gomes AS, Hundley WG, Jerosch-Herold M, et al. Cardiovascular Function in Multi-Ethnic Study of Atherosclerosis: Normal Values by Age, Sex, and Ethnicity. Am J Roentgenol. American Roentgen Ray Society; 2012.
    1. Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin NIH Public Access. 2012;8:143–64. doi: 10.1016/j.hfc.2011.08.011.
    1. Schulman SP, Lakatta EG, Fleg JL, Lakatta L, Becker LC, Gerstenblith G. Age-related decline in left ventricular filling at rest and exercise. Am J Physiol. 1992;263:H1932–8.
    1. Kitzman DW, Scholz DG, Hagen PT, Ilstrup DM, Edwards WD. Age-related changes in normal human hearts during the first 10 decades of life. Part II (maturity): a quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc. 1988;63:137–46. doi: 10.1016/S0025-6196(12)64946-5.
    1. Margossian R, Schwartz ML, Prakash A, Wruck L, Hurwitz LM, Marcus E, et al. Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (From the Pediatric Heart Network Multicenter Fontan Cross-Sectional Study) Am J Cardiol. 2010;104:419–28. doi: 10.1016/j.amjcard.2009.03.058.
    1. Teo KSL, Carbone A, Piantadosi C, Chew DP, Hammett CJK, Brown MA, et al. Cardiac MRI assessment of left and right ventricular parameters in healthy Australian normal volunteers. Hear Lung Circ. 2008;17:313–7. doi: 10.1016/j.hlc.2007.11.136.
    1. Rider OJ, Francis JM, Ali MK, Byrne J, Clarke K, Neubauer S, et al. Determinants of left ventricular mass in obesity; a cardiovascular magnetic resonance study. J Cardiovasc Magn Reson BioMed Central. 2009;11:9. doi: 10.1186/1532-429X-11-9.
    1. Rider OJ, Petersen SE, Francis JM, Ali MK, Hudsmith LE, Robinson MR, et al. Ventricular hypertrophy and cavity dilatation in relation to body mass index in women with uncomplicated obesity. Heart. BMJ Publishing Group Ltd and British Cardiovascular Society. 2011;97:203–8.
    1. Health and Social Care Information Centre. Statistics on Obesity, Physical Activity and Diet. 2016.

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