Results of the clinical genetic testing pilot study for cardiomyopathies conducted in Dubrava University Hospital

    Authors

    Keywords

    cardiomyopathy, genetic counselling, genetic testing, hereditary

    DOI

    https://doi.org/10.15836/ccar2022.265

    Full Text

    **Background:** Cardiomyopathies represent an important cause of heart failure and genetic testing for cardiomyopathies has become an established care pathway in contemporary cardiology practice (1, 2). **Patients and Methods:** In this pilot study we have conducted genetic testing for cardiomyopathies in selected patients with clear non-ischemic cardiomyopathy phenotypes. Genetic testing was performed in Dubrava University Hospital genetic laboratory using standard next-generation sequencing (NGS) Illumina cardiomyopathy gene panel covering 174 genes most associated with cardiomyopathies, arrhythmias and aortopathies. The results were uploaded and analyzed using Variant Interpreter Illumina, a cloud-based interpretation and reporting platform for genomic data. **Results:** From June 2020 to March 2021 16 patients underwent genetic testing (10 males, 33.6±18.7 years), as a part of a pilot testing. Of these patients, 7 had previously undergone heart transplantation (HTx), while one was on the waiting list for HTx, 7 were in a regular follow up and one analysis was postmortem. Clinically, 12 patients were classified as having dilated cardiomyopathy (DCM), two had hypertrophic cardiomyopathy (HCM) and two arrhythmogenic cardiomyopathy (ACM). Diagnostic yield of the performed genetic testing was relatively high, in only two patients out of 16 we did not identify any mutations **(****Table 1****).** This testing led to the detection of Danon’s disease in one family, and to change of clinical treatment in one patient. The results were discussed with the clinical geneticist; in seven cases the patients were referred to genetic counseling, while further family screening was initiated in five cases. ### TABLE 1: Short summary of the detected variants, classified according to the clinically observed phenotypes. | | Number (males) — Average age — Previous HTx | **DCM** — 12 (8) — 27.8±16.9 — 6 | **HCM** — 2 (1) — 56.5±10.6 — 0 | **ACM** — 2 (1) — 45.5±14.8 — 1 | | --- | --- | --- | --- | --- | | Variant classification | Pathogenic | 5 | 0 | 1 | | Likely pathogenic | 2 | 1 | 0 | | | VUS | 4 | 0 | 1 | | | negative | 1 | 1 | 0 | | [†] HTx = heart transplantation; VUS = variant of unknown significance; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; ACM = arrhythmogenic cardiomyopathy. **Conclusion:** Genetic testing provides insight into diagnosis, treatment, and prognosis of patients with non-ischemic cardiomyopathies, and directs screening which allows the identification of relatives at risk and initiation of appropriate medical and device therapies (1).

    Literature

    1. Yogasundaram H, Alhumaid W, Dzwiniel T, Christian S, Oudit GY. Cardiomyopathies and Genetic Testing in Heart Failure: Role in Defining Phenotype-Targeted Approaches and Management. Can J Cardiol. 2021 April;37(4):547–59. https://doi.org/10.1016/j.cjca.2021.01.016
    2. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 September 21;42(36):3599–726. https://doi.org/10.1093/eurheartj/ehab368
    Cardiologia Croatica
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    Results of the clinical genetic testing pilot study for cardiomyopathies conducted in Dubrava University Hospital

    Extended Abstract
    Issue9-10
    Published
    Pages265
    PDF via DOIhttps://doi.org/10.15836/ccar2022.265
    cardiomyopathy
    genetic counselling
    genetic testing
    hereditary

    Authors

    Mario Udovičić*ORCIDDubrava University Hospital, Zagreb, Croatia
    Ana LivunORCIDDubrava University Hospital, Zagreb, Croatia
    Željko SutlićORCIDDubrava University Hospital, Zagreb, Croatia
    Rajko KušecORCIDDubrava University Hospital, Zagreb, Croatia
    Danijela GrizeljORCIDDubrava University Hospital, Zagreb, Croatia
    Tamara ŽigmanORCIDUniversity Hospital Centre Zagreb, Zagreb, Croatia
    Katica Cvitkušić LukendaORCIDGeneral Hospital Slavonski Brod, Slavonski Brod, Croatia
    Diana RudanORCIDDubrava University Hospital, Zagreb, Croatia
    Šime ManolaORCIDDubrava University Hospital, Zagreb, Croatia

    *Correspondence email: mario.udovicic@gmail.com

    Full Text

    Background: Cardiomyopathies represent an important cause of heart failure and genetic testing for cardiomyopathies has become an established care pathway in contemporary cardiology practice (1, 2).

    Patients and Methods: In this pilot study we have conducted genetic testing for cardiomyopathies in selected patients with clear non-ischemic cardiomyopathy phenotypes. Genetic testing was performed in Dubrava University Hospital genetic laboratory using standard next-generation sequencing (NGS) Illumina cardiomyopathy gene panel covering 174 genes most associated with cardiomyopathies, arrhythmias and aortopathies. The results were uploaded and analyzed using Variant Interpreter Illumina, a cloud-based interpretation and reporting platform for genomic data.

    Results: From June 2020 to March 2021 16 patients underwent genetic testing (10 males, 33.6±18.7 years), as a part of a pilot testing. Of these patients, 7 had previously undergone heart transplantation (HTx), while one was on the waiting list for HTx, 7 were in a regular follow up and one analysis was postmortem. Clinically, 12 patients were classified as having dilated cardiomyopathy (DCM), two had hypertrophic cardiomyopathy (HCM) and two arrhythmogenic cardiomyopathy (ACM). Diagnostic yield of the performed genetic testing was relatively high, in only two patients out of 16 we did not identify any mutations (Table 1). This testing led to the detection of Danon’s disease in one family, and to change of clinical treatment in one patient. The results were discussed with the clinical geneticist; in seven cases the patients were referred to genetic counseling, while further family screening was initiated in five cases.

    TABLE 1: Short summary of the detected variants, classified according to the clinically observed phenotypes.

    Variant classification
    Number (males) — Average age — Previous HTx
    Pathogenic
    DCM — 12 (8) — 27.8±16.9 — 6
    5
    HCM — 2 (1) — 56.5±10.6 — 0
    0
    ACM — 2 (1) — 45.5±14.8 — 1
    1
    Likely pathogenic
    Number (males) — Average age — Previous HTx
    2
    DCM — 12 (8) — 27.8±16.9 — 6
    1
    HCM — 2 (1) — 56.5±10.6 — 0
    0
    VUS
    Number (males) — Average age — Previous HTx
    4
    DCM — 12 (8) — 27.8±16.9 — 6
    0
    HCM — 2 (1) — 56.5±10.6 — 0
    1
    negative
    Number (males) — Average age — Previous HTx
    1
    DCM — 12 (8) — 27.8±16.9 — 6
    1
    HCM — 2 (1) — 56.5±10.6 — 0
    0

    HTx = heart transplantation; VUS = variant of unknown significance; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; ACM = arrhythmogenic cardiomyopathy.

    Conclusion: Genetic testing provides insight into diagnosis, treatment, and prognosis of patients with non-ischemic cardiomyopathies, and directs screening which allows the identification of relatives at risk and initiation of appropriate medical and device therapies (1).

    Literature

    1. 1.
      Yogasundaram H, Alhumaid W, Dzwiniel T, Christian S, Oudit GY. Cardiomyopathies and Genetic Testing in Heart Failure: Role in Defining Phenotype-Targeted Approaches and Management. Can J Cardiol. 2021 April;37(4):547–59.DOI
    2. 2.
      McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 September 21;42(36):3599–726.DOI