Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging.
<h4>Purpose</h4>HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with conf...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0217612 |
| _version_ | 1819029176849530880 |
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| author | Robert J H Miller Shahriar Heidary Aleksandra Pavlovic Audrey Schlachter Rajesh Dash Dominik Fleischmann Euan A Ashley Matthew T Wheeler Phillip C Yang |
| author_facet | Robert J H Miller Shahriar Heidary Aleksandra Pavlovic Audrey Schlachter Rajesh Dash Dominik Fleischmann Euan A Ashley Matthew T Wheeler Phillip C Yang |
| author_sort | Robert J H Miller |
| collection | DOAJ |
| description | <h4>Purpose</h4>HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with confirmed HCM and high prevalence of genetic testing.<h4>Methods</h4>Patients with a diagnosis of HCM, who had undergone contrast-enhanced CMR were identified. Left ventricular mass index (LVMI) and volumes were measured from steady-state free precession sequences. Late gadolinium enhancement (LGE) was quantified using the full width, half maximum method. All patients were prospectively followed for the development of septal reduction therapy, arrhythmia or death.<h4>Results</h4>We included 273 patients, mean age 51.2 ± 15.5, 62.9% male. Of those patients 202 (74.0%) underwent genetic testing with 90 pathogenic, likely pathogenic, or rare variants and 13 variants of uncertain significance identified. Median follow-up was 1138 days. Mean LVMI was 82.7 ± 30.6 and 145 patients had late gadolinium enhancement (LGE). Patients with beta-myosin heavy chain (MYH7) mutations had higher LV ejection fraction (68.8 vs 59.1, p<0.001) than those with cardiac myosin binding protein C (MYBPC3) mutations. Patients with MYBPC3 mutations were more likely to have LVEF < 55% (29.7% vs 4.9%, p = 0.005) or receive a defibrillator than those with MYH7 mutations (54.1% vs 26.8%, p = 0.020).<h4>Conclusions</h4>We found that patients with MYBPC3 mutations were more likely to have impaired ventricular function and may be more prone to arrhythmic events. Larger studies using CMR phenotyping may be capable of identifying additional characteristics associated with less frequent genetic causes of HCM. |
| first_indexed | 2024-12-21T06:10:06Z |
| format | Article |
| id | doaj.art-24842e109bf643f6982bec2e2cebcf52 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T06:10:06Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-24842e109bf643f6982bec2e2cebcf522022-12-21T19:13:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01146e021761210.1371/journal.pone.0217612Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging.Robert J H MillerShahriar HeidaryAleksandra PavlovicAudrey SchlachterRajesh DashDominik FleischmannEuan A AshleyMatthew T WheelerPhillip C Yang<h4>Purpose</h4>HCM is the most common inherited cardiomyopathy. Historically, there has been poor correlation between genotype and phenotype. However, CMR has the potential to more accurately assess disease phenotype. We characterized phenotype with CMR in a cohort of patients with confirmed HCM and high prevalence of genetic testing.<h4>Methods</h4>Patients with a diagnosis of HCM, who had undergone contrast-enhanced CMR were identified. Left ventricular mass index (LVMI) and volumes were measured from steady-state free precession sequences. Late gadolinium enhancement (LGE) was quantified using the full width, half maximum method. All patients were prospectively followed for the development of septal reduction therapy, arrhythmia or death.<h4>Results</h4>We included 273 patients, mean age 51.2 ± 15.5, 62.9% male. Of those patients 202 (74.0%) underwent genetic testing with 90 pathogenic, likely pathogenic, or rare variants and 13 variants of uncertain significance identified. Median follow-up was 1138 days. Mean LVMI was 82.7 ± 30.6 and 145 patients had late gadolinium enhancement (LGE). Patients with beta-myosin heavy chain (MYH7) mutations had higher LV ejection fraction (68.8 vs 59.1, p<0.001) than those with cardiac myosin binding protein C (MYBPC3) mutations. Patients with MYBPC3 mutations were more likely to have LVEF < 55% (29.7% vs 4.9%, p = 0.005) or receive a defibrillator than those with MYH7 mutations (54.1% vs 26.8%, p = 0.020).<h4>Conclusions</h4>We found that patients with MYBPC3 mutations were more likely to have impaired ventricular function and may be more prone to arrhythmic events. Larger studies using CMR phenotyping may be capable of identifying additional characteristics associated with less frequent genetic causes of HCM.https://doi.org/10.1371/journal.pone.0217612 |
| spellingShingle | Robert J H Miller Shahriar Heidary Aleksandra Pavlovic Audrey Schlachter Rajesh Dash Dominik Fleischmann Euan A Ashley Matthew T Wheeler Phillip C Yang Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. PLoS ONE |
| title | Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. |
| title_full | Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. |
| title_fullStr | Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. |
| title_full_unstemmed | Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. |
| title_short | Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. |
| title_sort | defining genotype phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging |
| url | https://doi.org/10.1371/journal.pone.0217612 |
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