Genetic characterization and genotype-phenotype associations in a large cohort of patients with hypertrophic cardiomyopathy – An ancillary study of the Portuguese registry of hypertrophic cardiomyopathy

Luis Rocha Lopes, Dulce Brito, Adriana Belo, Nuno Cardim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: We present an ancillary study of the Portuguese Registry of Hypertrophic Cardiomyopathy (PRo-HCM). This is one of the largest HCM genetic studies based on a registry. Methods and results: Collected genetic variants were re-analysed for pathogenicity. Demographic, clinical, imaging and outcome data were analysed for associations with genotype, focusing on comparisons between patients with (G+) vs without (G−) a pathogenic/likely pathogenic (P/LP) variant in one the 9 main causal sarcomeric genes. From the 1042 patients in the registry, 528 (51%) had genetic testing. 152 (28%) were G+ and 98 pts. (19%) had variants of unknown significance. From the patients with the 9 mentioned genes sequenced (424 pts), 14.6% had P/LP variants in MYBPC3, 8.7% MYH7, 4.5% TNNT2, 1.7% TNNI3. Patients were 51 ± 16 years-old, 59% males. Genotype was associated with the following: birthplace (p = 0.005); age (p < 0.001); family history of HCM (p < 0.0005); hypertension (p < 0.0005); chest pain (p = 0.015); pattern of hypertrophy (p = 0.006); left ventricular hypertrophy on the ECG (p < 0.0005); family history of sudden cardiac death (SCD) (p = 0.002). G+ patients more frequently had more than one risk factor for SCD (p = 0.002) and a higher ESC-SCD risk score (p = 0.003). In survival analysis, G+ was associated with SCD (p = 0.017) and MYH7+ with LV systolic dysfunction (p = 0.038). Conclusion: Half of the registry patients had genetic testing. Sarcomere-positive patients had distinct demographics, ECG, imaging characteristics and family history and are at increased risk of SCD. The presence of a MYH7 mutation was associated with evolution towards LV systolic dysfunction.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalInternational Journal of Cardiology
Volume278
DOIs
Publication statusPublished - Mar 2019

Fingerprint

Hypertrophic Cardiomyopathy
Genetic Association Studies
Registries
Sudden Cardiac Death
Genetic Testing
Electrocardiography
Genotype
Demography
Sarcomeres
Left Ventricular Hypertrophy
Survival Analysis
Chest Pain
Hypertrophy
Genes
Virulence
Hypertension
Mutation

Keywords

  • Genetics
  • Genotype-phenotype
  • Hypertrophic cardiomyopathy
  • LV systolic dysfunction
  • Registry
  • Sudden cardiac death

Cite this

@article{99394e6b33884dcfaf4b6f3827a34d52,
title = "Genetic characterization and genotype-phenotype associations in a large cohort of patients with hypertrophic cardiomyopathy – An ancillary study of the Portuguese registry of hypertrophic cardiomyopathy",
abstract = "Background: We present an ancillary study of the Portuguese Registry of Hypertrophic Cardiomyopathy (PRo-HCM). This is one of the largest HCM genetic studies based on a registry. Methods and results: Collected genetic variants were re-analysed for pathogenicity. Demographic, clinical, imaging and outcome data were analysed for associations with genotype, focusing on comparisons between patients with (G+) vs without (G−) a pathogenic/likely pathogenic (P/LP) variant in one the 9 main causal sarcomeric genes. From the 1042 patients in the registry, 528 (51{\%}) had genetic testing. 152 (28{\%}) were G+ and 98 pts. (19{\%}) had variants of unknown significance. From the patients with the 9 mentioned genes sequenced (424 pts), 14.6{\%} had P/LP variants in MYBPC3, 8.7{\%} MYH7, 4.5{\%} TNNT2, 1.7{\%} TNNI3. Patients were 51 ± 16 years-old, 59{\%} males. Genotype was associated with the following: birthplace (p = 0.005); age (p < 0.001); family history of HCM (p < 0.0005); hypertension (p < 0.0005); chest pain (p = 0.015); pattern of hypertrophy (p = 0.006); left ventricular hypertrophy on the ECG (p < 0.0005); family history of sudden cardiac death (SCD) (p = 0.002). G+ patients more frequently had more than one risk factor for SCD (p = 0.002) and a higher ESC-SCD risk score (p = 0.003). In survival analysis, G+ was associated with SCD (p = 0.017) and MYH7+ with LV systolic dysfunction (p = 0.038). Conclusion: Half of the registry patients had genetic testing. Sarcomere-positive patients had distinct demographics, ECG, imaging characteristics and family history and are at increased risk of SCD. The presence of a MYH7 mutation was associated with evolution towards LV systolic dysfunction.",
keywords = "Genetics, Genotype-phenotype, Hypertrophic cardiomyopathy, LV systolic dysfunction, Registry, Sudden cardiac death",
author = "Lopes, {Luis Rocha} and Dulce Brito and Adriana Belo and Nuno Cardim",
year = "2019",
month = "3",
doi = "10.1016/j.ijcard.2018.12.012",
language = "English",
volume = "278",
pages = "173--179",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier Ireland Ltd.",

}

TY - JOUR

T1 - Genetic characterization and genotype-phenotype associations in a large cohort of patients with hypertrophic cardiomyopathy – An ancillary study of the Portuguese registry of hypertrophic cardiomyopathy

AU - Lopes, Luis Rocha

AU - Brito, Dulce

AU - Belo, Adriana

AU - Cardim, Nuno

PY - 2019/3

Y1 - 2019/3

N2 - Background: We present an ancillary study of the Portuguese Registry of Hypertrophic Cardiomyopathy (PRo-HCM). This is one of the largest HCM genetic studies based on a registry. Methods and results: Collected genetic variants were re-analysed for pathogenicity. Demographic, clinical, imaging and outcome data were analysed for associations with genotype, focusing on comparisons between patients with (G+) vs without (G−) a pathogenic/likely pathogenic (P/LP) variant in one the 9 main causal sarcomeric genes. From the 1042 patients in the registry, 528 (51%) had genetic testing. 152 (28%) were G+ and 98 pts. (19%) had variants of unknown significance. From the patients with the 9 mentioned genes sequenced (424 pts), 14.6% had P/LP variants in MYBPC3, 8.7% MYH7, 4.5% TNNT2, 1.7% TNNI3. Patients were 51 ± 16 years-old, 59% males. Genotype was associated with the following: birthplace (p = 0.005); age (p < 0.001); family history of HCM (p < 0.0005); hypertension (p < 0.0005); chest pain (p = 0.015); pattern of hypertrophy (p = 0.006); left ventricular hypertrophy on the ECG (p < 0.0005); family history of sudden cardiac death (SCD) (p = 0.002). G+ patients more frequently had more than one risk factor for SCD (p = 0.002) and a higher ESC-SCD risk score (p = 0.003). In survival analysis, G+ was associated with SCD (p = 0.017) and MYH7+ with LV systolic dysfunction (p = 0.038). Conclusion: Half of the registry patients had genetic testing. Sarcomere-positive patients had distinct demographics, ECG, imaging characteristics and family history and are at increased risk of SCD. The presence of a MYH7 mutation was associated with evolution towards LV systolic dysfunction.

AB - Background: We present an ancillary study of the Portuguese Registry of Hypertrophic Cardiomyopathy (PRo-HCM). This is one of the largest HCM genetic studies based on a registry. Methods and results: Collected genetic variants were re-analysed for pathogenicity. Demographic, clinical, imaging and outcome data were analysed for associations with genotype, focusing on comparisons between patients with (G+) vs without (G−) a pathogenic/likely pathogenic (P/LP) variant in one the 9 main causal sarcomeric genes. From the 1042 patients in the registry, 528 (51%) had genetic testing. 152 (28%) were G+ and 98 pts. (19%) had variants of unknown significance. From the patients with the 9 mentioned genes sequenced (424 pts), 14.6% had P/LP variants in MYBPC3, 8.7% MYH7, 4.5% TNNT2, 1.7% TNNI3. Patients were 51 ± 16 years-old, 59% males. Genotype was associated with the following: birthplace (p = 0.005); age (p < 0.001); family history of HCM (p < 0.0005); hypertension (p < 0.0005); chest pain (p = 0.015); pattern of hypertrophy (p = 0.006); left ventricular hypertrophy on the ECG (p < 0.0005); family history of sudden cardiac death (SCD) (p = 0.002). G+ patients more frequently had more than one risk factor for SCD (p = 0.002) and a higher ESC-SCD risk score (p = 0.003). In survival analysis, G+ was associated with SCD (p = 0.017) and MYH7+ with LV systolic dysfunction (p = 0.038). Conclusion: Half of the registry patients had genetic testing. Sarcomere-positive patients had distinct demographics, ECG, imaging characteristics and family history and are at increased risk of SCD. The presence of a MYH7 mutation was associated with evolution towards LV systolic dysfunction.

KW - Genetics

KW - Genotype-phenotype

KW - Hypertrophic cardiomyopathy

KW - LV systolic dysfunction

KW - Registry

KW - Sudden cardiac death

UR - http://www.scopus.com/inward/record.url?scp=85058242515&partnerID=8YFLogxK

U2 - 10.1016/j.ijcard.2018.12.012

DO - 10.1016/j.ijcard.2018.12.012

M3 - Article

VL - 278

SP - 173

EP - 179

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -