Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

Lazar Velicki; Djordje G Jakovljevic; Andrej Preveden; Miodrag Golubovic; Marija Bjelobrk; Aleksandra Ilic; Snezana Stojsic; Fausto Barlocco; Maria Tafelmeier; Nduka Okwose; Milorad Tesic; Paul Brennan; Dejana Popovic; Arsen Ristic; Guy A MacGowan; Nenad Filipovic; Lars S Maier; Iacopo Olivotto

doi:10.1186/s12872-020-01807-4

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

Lazar Velicki, Djordje G Jakovljevic, Andrej Preveden, Miodrag Golubovic, Marija Bjelobrk, Aleksandra Ilic, Snezana Stojsic, Fausto Barlocco, Maria Tafelmeier, Nduka Okwose, Milorad Tesic, Paul Brennan, Dejana Popovic, Arsen Ristic, Guy A MacGowan, Nenad Filipovic, Lars S Maier, Iacopo Olivotto

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Abstract

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.

METHODS: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.

RESULTS: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079).

CONCLUSIONS: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

Original language	English
Article number	516
Number of pages	10
Journal	BMC Cardiovascular Disorders
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12872-020-01807-4
Publication status	Published - 9 Dec 2020

Bibliographical note

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Keywords

Hypertrophic cardiomyopathy
HCM
Hereditary cardiac disease
Left ventricular hypertrophy
MYBPC3
MYH7

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Velicki, L., Jakovljevic, D. G., Preveden, A., Golubovic, M., Bjelobrk, M., Ilic, A., Stojsic, S., Barlocco, F., Tafelmeier, M., Okwose, N., Tesic, M., Brennan, P., Popovic, D., Ristic, A., MacGowan, G. A., Filipovic, N., Maier, L. S., & Olivotto, I. (2020). Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy. BMC Cardiovascular Disorders, 20(1), Article 516. https://doi.org/10.1186/s12872-020-01807-4

Velicki, L, Jakovljevic, DG, Preveden, A, Golubovic, M, Bjelobrk, M, Ilic, A, Stojsic, S, Barlocco, F, Tafelmeier, M, Okwose, N, Tesic, M, Brennan, P, Popovic, D, Ristic, A, MacGowan, GA, Filipovic, N, Maier, LS & Olivotto, I 2020, 'Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy', BMC Cardiovascular Disorders, vol. 20, no. 1, 516. https://doi.org/10.1186/s12872-020-01807-4

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abstract = "BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.METHODS: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.RESULTS: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079).CONCLUSIONS: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.",

keywords = "Hypertrophic cardiomyopathy, HCM, Hereditary cardiac disease, Left ventricular hypertrophy, MYBPC3, MYH7",

author = "Lazar Velicki and Jakovljevic, {Djordje G} and Andrej Preveden and Miodrag Golubovic and Marija Bjelobrk and Aleksandra Ilic and Snezana Stojsic and Fausto Barlocco and Maria Tafelmeier and Nduka Okwose and Milorad Tesic and Paul Brennan and Dejana Popovic and Arsen Ristic and MacGowan, {Guy A} and Nenad Filipovic and Maier, {Lars S} and Iacopo Olivotto",

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TY - JOUR

T1 - Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

AU - Velicki, Lazar

AU - Jakovljevic, Djordje G

AU - Preveden, Andrej

AU - Golubovic, Miodrag

AU - Bjelobrk, Marija

AU - Ilic, Aleksandra

AU - Stojsic, Snezana

AU - Barlocco, Fausto

AU - Tafelmeier, Maria

AU - Okwose, Nduka

AU - Tesic, Milorad

AU - Brennan, Paul

AU - Popovic, Dejana

AU - Ristic, Arsen

AU - MacGowan, Guy A

AU - Filipovic, Nenad

AU - Maier, Lars S

AU - Olivotto, Iacopo

N1 - Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

PY - 2020/12/9

Y1 - 2020/12/9

N2 - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.METHODS: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.RESULTS: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079).CONCLUSIONS: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.METHODS: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.RESULTS: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079).CONCLUSIONS: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

KW - Hypertrophic cardiomyopathy

KW - HCM

KW - Hereditary cardiac disease

KW - Left ventricular hypertrophy

KW - MYBPC3

KW - MYH7

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DO - 10.1186/s12872-020-01807-4

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Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

Abstract

Bibliographical note

Keywords

UN SDGs

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