Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population
IntroductionIn hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) represents myocardial fibrosis and is associated with sudden cardiac death. However, CMR requires particular expertise and is expensive and time-consuming. Therefore, it is...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.839409/full |
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| author | Bradley S. Lander Yanling Zhao Kohei Hasegawa Mathew S. Maurer Albree Tower-Rader Michael A. Fifer Muredach P. Reilly Muredach P. Reilly Yuichi J. Shimada |
| author_facet | Bradley S. Lander Yanling Zhao Kohei Hasegawa Mathew S. Maurer Albree Tower-Rader Michael A. Fifer Muredach P. Reilly Muredach P. Reilly Yuichi J. Shimada |
| author_sort | Bradley S. Lander |
| collection | DOAJ |
| description | IntroductionIn hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) represents myocardial fibrosis and is associated with sudden cardiac death. However, CMR requires particular expertise and is expensive and time-consuming. Therefore, it is important to specify patients with a high pre-test probability of having LGE as the utility of CMR is higher in such cases. The objective was to determine whether plasma proteomics profiling can distinguish patients with and without LGE on CMR in the HCM population.Materials and MethodsWe performed a multicenter case-control (LGE vs. no LGE) study of 147 patients with HCM. We performed plasma proteomics profiling of 4,979 proteins. Using the 17 most discriminant proteins, we performed logistic regression analysis with elastic net regularization to develop a discrimination model with data from one institution (the training set; n = 111) and tested the discriminative ability in independent samples from the other institution (the test set; n = 36). We calculated the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity.ResultsOverall, 82 of the 147 patients (56%) had LGE on CMR. The AUC of the 17-protein model was 0.83 (95% confidence interval [CI], 0.75–0.90) in the training set and 0.71 in the independent test set for validation (95% CI, 0.54–0.88). The sensitivity of the training model was 0.72 (95% CI, 0.61–0.83) and the specificity was 0.78 (95% CI, 0.66–0.90). The sensitivity was 0.71 (95% CI, 0.49–0.92) and the specificity was 0.74 (95% CI, 0.54–0.93) in the test set. Based on the discrimination model derived from the training set, patients in the test set who had high probability of having LGE had a significantly higher odds of having LGE compared to those who had low probability (odds ratio 29.6; 95% CI, 1.6–948.5; p = 0.03).ConclusionsIn this multi-center case-control study of patients with HCM, comprehensive proteomics profiling of 4,979 proteins demonstrated a high discriminative ability to distinguish patients with and without LGE. By identifying patients with a high pretest probability of having LGE, the present study serves as the first step to establishing a panel of circulating protein biomarkers to better inform clinical decisions regarding CMR utilization. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-12T14:37:49Z |
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| spelling | doaj.art-1d4b77c3a8b64e2fb5174549fc8032752022-12-22T03:29:00ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01910.3389/fcvm.2022.839409839409Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy PopulationBradley S. Lander0Yanling Zhao1Kohei Hasegawa2Mathew S. Maurer3Albree Tower-Rader4Michael A. Fifer5Muredach P. Reilly6Muredach P. Reilly7Yuichi J. Shimada8Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United StatesDepartment of Surgery, Columbia University Irving Medical Center, New York, NY, United StatesDepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United StatesCardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesCardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United StatesIrving Institute for Clinical and Translational Research, Columbia University Irving Medical Center, New York, NY, United StatesDivision of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, United StatesIntroductionIn hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) represents myocardial fibrosis and is associated with sudden cardiac death. However, CMR requires particular expertise and is expensive and time-consuming. Therefore, it is important to specify patients with a high pre-test probability of having LGE as the utility of CMR is higher in such cases. The objective was to determine whether plasma proteomics profiling can distinguish patients with and without LGE on CMR in the HCM population.Materials and MethodsWe performed a multicenter case-control (LGE vs. no LGE) study of 147 patients with HCM. We performed plasma proteomics profiling of 4,979 proteins. Using the 17 most discriminant proteins, we performed logistic regression analysis with elastic net regularization to develop a discrimination model with data from one institution (the training set; n = 111) and tested the discriminative ability in independent samples from the other institution (the test set; n = 36). We calculated the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity.ResultsOverall, 82 of the 147 patients (56%) had LGE on CMR. The AUC of the 17-protein model was 0.83 (95% confidence interval [CI], 0.75–0.90) in the training set and 0.71 in the independent test set for validation (95% CI, 0.54–0.88). The sensitivity of the training model was 0.72 (95% CI, 0.61–0.83) and the specificity was 0.78 (95% CI, 0.66–0.90). The sensitivity was 0.71 (95% CI, 0.49–0.92) and the specificity was 0.74 (95% CI, 0.54–0.93) in the test set. Based on the discrimination model derived from the training set, patients in the test set who had high probability of having LGE had a significantly higher odds of having LGE compared to those who had low probability (odds ratio 29.6; 95% CI, 1.6–948.5; p = 0.03).ConclusionsIn this multi-center case-control study of patients with HCM, comprehensive proteomics profiling of 4,979 proteins demonstrated a high discriminative ability to distinguish patients with and without LGE. By identifying patients with a high pretest probability of having LGE, the present study serves as the first step to establishing a panel of circulating protein biomarkers to better inform clinical decisions regarding CMR utilization.https://www.frontiersin.org/articles/10.3389/fcvm.2022.839409/fullhypertrophic cardiomyopathylate gadolinium enhanced (LGE)myocardial fibrosisproteomicscardiac magnetic resonance (MRI) |
| spellingShingle | Bradley S. Lander Yanling Zhao Kohei Hasegawa Mathew S. Maurer Albree Tower-Rader Michael A. Fifer Muredach P. Reilly Muredach P. Reilly Yuichi J. Shimada Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population Frontiers in Cardiovascular Medicine hypertrophic cardiomyopathy late gadolinium enhanced (LGE) myocardial fibrosis proteomics cardiac magnetic resonance (MRI) |
| title | Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population |
| title_full | Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population |
| title_fullStr | Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population |
| title_full_unstemmed | Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population |
| title_short | Comprehensive Proteomics Profiling Identifies Patients With Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in the Hypertrophic Cardiomyopathy Population |
| title_sort | comprehensive proteomics profiling identifies patients with late gadolinium enhancement on cardiac magnetic resonance imaging in the hypertrophic cardiomyopathy population |
| topic | hypertrophic cardiomyopathy late gadolinium enhanced (LGE) myocardial fibrosis proteomics cardiac magnetic resonance (MRI) |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.839409/full |
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