The clinical use of the MOGE(S) classification in the differential diagnosis between idiopathic hypertrophic cardiomyopathy and its phenocopies

Aim. To determine  the relation between  idiopathic hypertrophic  cardiomyopathy (HCM) and HCM phenocopies, as well as to study the etiological pattern  of HCM phenocopies in patients  of the  North-Western  region  of Russia  in different age groups.

Material  and  methods. The  study  included  321  patients  with left  ventricular hypertrophy ≥15 mm according  to an echocardiography. All the necessary clinical, laboratory and instrumental  diagnostic  methods  for verification of HCM and HCM phenocopies was carried out. In the diagnosis, the MOGE(S) classification was used.

Results.  At  a  young  age,   idiopathic  HCM accounts  for  92%  (n=62),  HCM phenocopies — 8% (Danon disease (n=1 (2%)), isolated cardiac  sarcoidosis (n=1 (2%)) and systemic AL amyloidosis (n=3(4%)). Idiopathic HCM is also found in the vast majority of middle-aged patients — in 85% of cases (n=86). HCM phenocopies (15%) were in isolated  cardiac  sarcoidosis (n=3 (3%)), systemic amyloidosis variants (n=12 (12%)) — AL amyloidosis with predominant cardiac injury (n=11,11%), hereditary transthyretin amyloidosis (n=1,1%). Of the 153 examined  patients  with HCM aged  ≥60 years  old, 85% (n=131) were diagnosed with idiopathic HCM. HCM phenocopies were detected in 15% of cases (n=22). In the etiological pattern  of HCM phenocopies, transthyretin  amyloidosis was  10%:  non-hereditary   transthyretin  amyloidosis  — 6%  (n  =  9),  hereditary transthyretin  amyloidosis — 4% (n=6); AL amyloidosis — 4% (n=6). In 1 patient, acromegalic  cardiomyopathy (1%) was verified. In this article, we present 3 clinical cases that demonstrate the difficulty of differential diagnosis  between  idiopathic HCM and various HCM phenocopies.

Conclusion. In all age groups,  idiopathic HCM predominates. Lysosomal storage diseases classify as  rare  diseases. Isolated  cardiac  injury with amyloidosis  and sarcoidosis is widely met but less often diagnosed. We determined a high frequency of isolated cardiac injury with amyloidosis under the age of 45 years. The etiological pattern  of HCM phenocopies in the elderly is represented mainly by transthyretin cardiomyopathic  amyloidosis of hereditary and non-hereditary  variants.

1. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. European heart journal. 2014;35:2733-79. doi:10.1093/eurheartj/ehu284.

2. Linhart A, Cecchi F. Common presentation of rare diseases: Left ventricular hypertrophy and diastolic dysfunction. Int J Cardiol. 2018;15(257):344-50. doi:10.1016/j.ijcard.2018.01.006.

3. Arbustini E, Narula N, Dec GW, et al. The MOGE(S) classification for a phenotype-genotype nomenclature of cardiomyopathy: endorsed by the World Heart Federation. J. Am. Coll. Cardiol. 2013;62(22):2046-72. doi:10.1016/j.jacc.2013.08.1644.

4. Shlyakhto ЕV, Polyakova АА, Semernin ЕN, et al. Acromegalic cardiomyopathy with dynamic obstruction of the left ventricle outflow tract. Russ J Cardiol. 2018;2(154):115-20. (In Russ.) doi:10.15829/1560-4071-2018-2-115-120.

5. Maron BJ, Roberts WC, Arad M, et al. Clinical outcome and phenotypic expression in LAMP2 cardiomyopathy. Jama. 2009;301(12):1253-9. doi:10.1001/jama.2009.371.

6. Kostareva AA, Pervunina TM, Moiseeva OM, et al. Genetic variants of cardiomyopathies with the neuromuscular phenotype. Russian Heart Failure Journal. 2016;4(97):278-86. (In Russ.) doi:10.18087/rhfi.2016.4.2241.

7. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015;17:405-24. doi:10.1038/gim.2015.30.

8. Roslan A, Kamsani SH, Nay TW, et al. Echocardiographic and electrocardiographic presentations of patients with endomyocardial biopsy-proven cardiac amyloidosis. Med J Malaysia. 2018;73(6):388-92.

9. Semernin EN, Polyakova AA, Krutikov AA, et al. Systemic forms of amyloidosis in a cohort of patients with refractory chronic heart failure in St. Petersburg. In: Rare orphan diseases and congenital malformations. Modern possibilities of diagnosis, prevention, treatment and rehabilitation. St. Petersburg: Feniks. 2014:204-18. (In Russ.)

10. Gudkova AYa, Amelin AV, Krutikov AN, et al. Val30Met-transchyrethin amyloid polyneuropathy and cardiomyopathy (review of literature and clinical observation). Consilium Medicum. 2017;19(12):109-16. (In Russ.) doi:10.26442/2075-1753_19.12.109-116

11. Solovyov KV, Grudinina NA, Morozova IV, et al. Transthyretin gene V30M, H90N, and (del9) mutations in cardiomyopathy patients from St. Petersburg. Russian Gournal of Genetics. 2011;47(4):543-9. (In Russ.) doi:10.1134/s1022795411020165.

12. Gudkova АYa, Polyakova АА, Amelin АV, et al. Non-Val30Met-transthyretin amyloid cardiomyopathy. Literature review and clinical case. Russ J Cardiol. 2018;23(2):121-8. (In Russ.) doi:10.15829/1560-4071-2018-2-121-128.

13. Okada DR, Bravo PE, Vita T, et al. Isolated cardiac sarcoidosis: a focused review of an underrecognized entity. J Nucl Cardiol. 2018;25(4):1136-46. doi:10.1007/s12350-016-0658-1.

14. Tezuka D, Terashima M, Kato Y, et al. Clinical characteristics of definite or suspected isolated cardiac sarcoidosis: application of cardiac magnetic resonance imaging and 18f-fluoro-2-deoxyglucose positron-emission tomography/computerized tomography. J Card Fail. 2015;21:313-22. doi:10.1016/j.cardfail.2014.12.004.

15. Sperry BW, Oldan J, Hachamovitch R, et al. Insights into biopsy-proven cardiac sarcoidosis in patients with heart failure. J Heart Lung Transpl. 2016;35:392-3. doi:10.1016/j.healun.2015.12.005.