PMID- 31199839 OWN - NLM STAT- MEDLINE DCOM- 20200206 LR - 20200309 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 6 DP - 2019 TI - Defining genotype-phenotype relationships in patients with hypertrophic cardiomyopathy using cardiovascular magnetic resonance imaging. PG - e0217612 LID - 10.1371/journal.pone.0217612 [doi] LID - e0217612 AB - PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. FAU - Miller, Robert J H AU - Miller RJH AUID- ORCID: 0000-0003-4676-2433 AD - Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Heidary, Shahriar AU - Heidary S AD - Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Pavlovic, Aleksandra AU - Pavlovic A AD - Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Schlachter, Audrey AU - Schlachter A AD - Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Dash, Rajesh AU - Dash R AD - Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Fleischmann, Dominik AU - Fleischmann D AD - Department of Radiology, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Ashley, Euan A AU - Ashley EA AD - Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. AD - Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Wheeler, Matthew T AU - Wheeler MT AD - Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. AD - Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. FAU - Yang, Phillip C AU - Yang PC AD - Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190614 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Carrier Proteins) RN - 0 (Contrast Media) RN - 0 (myosin-binding protein C) RN - EC 3.6.4.1 (Myosin Heavy Chains) RN - K2I13DR72L (Gadolinium DTPA) SB - IM MH - Cardiomyopathy, Hypertrophic/diagnosis/*genetics/*pathology MH - Carrier Proteins/genetics MH - Contrast Media/administration & dosage MH - Female MH - Gadolinium DTPA/administration & dosage MH - Genetic Association Studies/methods MH - Genetic Testing/methods MH - Genotype MH - Humans MH - Magnetic Resonance Imaging/methods MH - Male MH - Middle Aged MH - Mutation/genetics MH - Myocardium/pathology MH - Myosin Heavy Chains/genetics MH - Phenotype MH - Retrospective Studies MH - Ventricular Function, Left/genetics/physiology PMC - PMC6568393 COIS- The authors have read the journal's policy and the authors of this manuscript have the following competing interests: RJHM is supported by the Arthur J E Child fellowship grant. GE Healthcare provides equipment research support to PCY, SH. AP was supported by the Breetwor Foundation. AS was supported by a research grant to EAA from MyoKardia. EAA is a consultant and receives researching funding with Myokardia. MTW has ownership interest and is a stockholder in Personalis and has ownership interest, research funding and consulting with MyoKardia. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2019/06/15 06:00 MHDA- 2020/02/07 06:00 PMCR- 2019/06/14 CRDT- 2019/06/15 06:00 PHST- 2019/03/04 00:00 [received] PHST- 2019/05/16 00:00 [accepted] PHST- 2019/06/15 06:00 [entrez] PHST- 2019/06/15 06:00 [pubmed] PHST- 2020/02/07 06:00 [medline] PHST- 2019/06/14 00:00 [pmc-release] AID - PONE-D-19-06302 [pii] AID - 10.1371/journal.pone.0217612 [doi] PST - epublish SO - PLoS One. 2019 Jun 14;14(6):e0217612. doi: 10.1371/journal.pone.0217612. eCollection 2019.