NEXT GENERATION SEQUENCING HELPS IN DIFFERENTIAL DIAGNOSIS OF PATHOLOGICAL LEFT VENTRICULAR HYPERTROPHY IN ELITE ATHLETES


Cite item

Full Text

Abstract

To detect the reason of left ventricular hypertrophy (LVH) may be difficult in some cases especially in elite athletes. Object. To evaluate the efficiency of next generation sequencing (NGS) genetic test in differential diagnostics of pathological LVH in elite athletes. Material and methods. Analysis of echocardiographic data from 791 elite athletes revealed 15 individuals with LVH > 12 mm (1,9%). Based on the criteria of abnormality (asymmetric, severe and changes on electrocardiogram) 5 (0,6%) athletes were selected for genetic test. TruSight Cardio panel (“Illumina”) was used to identify variants of 174 genes with known associations to inherited cardiac conditions. Results. In 3 out of 5 athletes the pathogenic variants in MBPC3 and LMNA genes previously associated with HCM and other CMs were found. One athlete with negative genetic test result had severe untreated arterial hypertension as a possible cause for LVH. The second athlete didn’t have LVH in magnetic resonance imaging. Conclusions. In elite athletes, the asymmetric LVH should be considered as pathological finding which requires comprehensive clinical evaluation and NGS genetic test.

Keywords

About the authors

O S Chumakova

ФГБУ ДПО «ЦГМА» УДП РФ; ФГБУ ФНКЦ ФМБА России; ГБУЗ ГКБ №17 ДЗМ

Email: chumakovaolga@bk.ru
к.м.н., доцент кафедры терапии, кардиологии и функциональной диагностики с курсом нефрологии; ведущий научный сотрудник лаборатории генетики; врач-кардиолог

M Yu Isaeva

ФГБУ ФНКЦ ФМБА России

Email: maris_07@mail.ru
к.м.н., врач-кардиолог клинико-диагностического центра

M I Abushenko

ФГБУ ФНКЦ ФМБА России

Email: marina-abushenko@mail.ru
врач-кардиолог клинико-диагностического центра

M V Vorobieva

ФГБУ ФНКЦ ФМБА России

Email: Ilyashenko-mv@mail.ru
врач-кардиолог клинико-диагностического центра

L E Guseinova

ФГБУ ФНКЦ ФМБА России

Email: ms.ruzanka@inbox.ru
врач-кардиолог клинико-диагностического центра

R R Gasanova

ФГБУ ФНКЦ ФМБА России

врач-терапевт клинико-диагностического центра

G I Speshilov

Геномный центр ChromaSpark

Email: g.speshilov@chromaspark.com
руководитель генетической лаборатории

A G Nikitin

ФГБУ ФНКЦ ФМБА России

Email: avialn@gmail.com
к.б.н., заведующий лабораторией генетики; заведующий кафедрой терапии, кардиологии и функциональной диагностики с курсом нефрологии

A V Averyanov

ФГБУ НИИ Пульмонологии ФМБА Росссии

Email: pulmo_fmba@mail.ru
доктор медицинских наук, профессор, директор

D A Zateyshchikov

ГБУЗ ГКБ №51 ДЗМ; ФГБУ ДПО «ЦГМА» УДП РФ; ФГБУ ФНКЦ ФМБА России

Email: dz@bk.ru
д.м.н., профессор, руководитель первичного сосудистого отделения; ведущий научный сотрудник лаборатории генетики

References

  1. Papadakis M., Carre F., Kervio G., Rawlins J. et al. The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin. Eur Heart J 2011;32(18):2304-2313.
  2. Chandra N., Bastiaenen R., Papadakis M., Sharma S. Sudden cardiac death in young athletes: practical challenges and diagnostic dilemmas. J Am Coll Cardiol 2013;61(10):1027-1040.
  3. Berge H.M., Isern C.B., Berge E. Blood pressure and hypertension in athletes: a systematic review. Br J Sports Med 2015;0:1-10.
  4. Lakdawala N.K., Thune J.J., Maron B.J., Chirino A.L. et al. Electrocardiographic Features of Sarcomere Mutations Carriers With versus Without Clinically Overt Hypertrophic Cardiomyopathy. Am J Cardiol 2011; 108(11):1606-1613.
  5. Pelliccia A., Maron B.J., Spataro A., Proschan M.A. et al. The upper limit of physiologic cardiac hypertrophy in highly trained elite athletes. N Engl J Med 1991; 324: 295-301.
  6. Basavarajaiah S., Boraita A., Whyte G., Wilson M. et al. Ethnic differences in left ventricular remodeling in highly-trained athletes relevance to differentiating physiologic left ventricular hypertrophy from hypertrophic cardiomyopathy. J Am Coll Cardiol 2008; 51:2256-2262.
  7. Baxi A.J., Restrepo C.S., Vargas D., Marmol-Velez A. et al. Hypertrophic Cardiomyopathy from A to Z: Genetics, Pathophysiology, Imaging, and Management. RadioGraphics 2016; 36: 335-354.
  8. Elliott P.M., Anastasakis A., Borger M.A., Borggrefe M et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. Eur Heart J. 2014 Oct 14;35(39):2733-79. doi: 10.1093/eurheartj/ ehu284.
  9. Thomas M.J., Battle R.W. Something old, something new. Using family history and genetic testing to diagnose and manage athletes with inherited cardiovascular disease. Clin Sports Med 2015; 34:517-537.
  10. Shimizu M., Sugihara N., Shimizu K., Yoshio H. et al. Asymmetrical septal hypertrophy in patients with hypertension: a type of hypertensive left ventricular hypertrophy or hypertrophic cardiomyopathy combined with hypertension? Clin Cardiol 1993;16(1):41-6.
  11. Kobayashi S., Sakai Y., Taguchi I., Utsunomiya H. et al. Causes of an increased pressure gradient through the left ventricular outflow tract: a West Coast experience. J Echocardiogr 2017 Sep 18. doi: 10.1007/s12574-017-0352-6.
  12. Maron B.J., Udelson J.E., Bonow R.O., Nishimura R.A. at al. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: T ask F orce 3: Hypertrophic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy and Other Cardiomyopathies, and Myocarditis. A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation. 2015 Dec 1;132(22):e273-80. doi: 10.1161/ CIR.0000000000000239
  13. Charron P., Carrier L., Dubourg O., Tesson F. et al. Penetrance of familial hypertrophic cardiomyopathy. Genet Couns 1997; 8(2): 107-14.
  14. Quarta G., Syrris P., Ashworth M., Jenkins S. at al. Mutations in the Lamin A/C gene mimic arrhythmogenic right ventricular cardiomyopathy. EHJ 2012; 33: 1128-36.
  15. Genschel J., Bochow B., Kuepferling S., Ewert R. at al. A R644C mutation within lamin A extends the mutations causing dilated cardiomyopathy. Hum Mutat. 2001 Feb;17(2):154.
  16. Mercuri E., Brown S., Nihoyannopoulos P., Poulton J. et al. Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin a/c gene. Muscle Nerve 2005; 31(5): 602-9.

Copyright (c) 2017 Chumakova O.S., Isaeva M.Y., Abushenko M.I., Vorobieva M.V., Guseinova L.E., Gasanova R.R., Speshilov G.I., Nikitin A.G., Averyanov A.V., Zateyshchikov D.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies