Echocardiography-Guided Genetic Testing in Hypertrophic Cardiomyopathy: Septal Morphological Features Predict the Presence of Myofilament Mutations

Binder, Josepha; Ommen, Steve R.; Gersh, Bernard J.; Van Driest, Sara L.; Tajik, A. Jamil; Nishimura, Rick A.; Ackerman, Michael J.
April 2006
Mayo Clinic Proceedings;Apr2006, Vol. 81 Issue 4, p459
Academic Journal
OBJECTIVE: To examine the relationship among age, septal morphological subtype, and presence of hypertrophic cardiomyopathy (HCM)-associated myofilament mutations. PATIENTS AND METHODS: Comprehensive mutation analysis of the 8 HCM susceptibility genes that encode the myofilaments of the cardiac sarcomere was performed previously in 382 unrelated patients with HCM. Blinded to genotype status, we used echocardiography to characterize the left ventricular morphological features. Multivariate regression was used to assess the relationship among morphological subtypes, clinical data, and genetic variables. RESULTS: The mean ± SD age of the patients was 41.6 ± 19.0 years, with 126 patients 50 years or older at Initial diagnosis. The septal morphological subtype was sigmoid in 181 (47%), reverse in 132 (35%), apical variant in 37 (10%), and neutral in 32 (8%). The HCM-associated myofilament mutations were identified in 143 patients (37%). Multivariate analysis showed that the reverse curvature septal morphological subtype was a strong predictor of genotype-positive status (odds ratio, 21; P < .001). Overall, the yield of HCM genetic testing was 79% in the setting of reverse curvature HCM but only 8% in sigmoid septal HCM. CONCLUSION: in stark contrast to HCM in young patients, elderly patients with HCM display a predominantly sigmoid septal morphological subtype and uncommonly have perturbations of known HCM susceptibility genes, independent of age, septal morphological subtype strongly predicts the presence or absence of HCM-associated myofilament mutations and may enable echocardiography-guided genetic testing for HCM.


Related Articles

  • Identification of Myofilament Mutations: Its Role in the Diagnosis and Management of Hypertrophic Cardiomyopathy. Dandona, Sonny; Roberts, Robert // Mayo Clinic Proceedings;Jun2008, Vol. 83 Issue 6, p626 

    The article presents the authors' perspective on a study concerning the identification of myofilament mutations and its role in the diagnosis and management of hypertrophic cardiomyopathy (HCM), which is published within the issue. They remark that the observation of the study should be...

  • Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing. Sun, Zhongsheng; Xu, Jing; Dong, Ming; Li, Jinxin; Shi, Xingjuan; Zhang, Yu; Xie, Wei; Liu, Xiangdong; Li, Zhongshan; Ren, Xianguo; Dai, Qiming // Scientific Reports;11/20/2015, p16609 

    Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with high heterogeneity. Limited knowledge concerning the genetic background of nearly 40% HCM cases indicates there is a clear need for further investigation to explore the genetic pathogenesis of the disease. In this study, we...

  • Evaluation of Subtle Left Ventricular Systolic Abnormalities in Adult Patients with Hypertrophic Cardiomyopathy. SHETTY, RANJAN; SAMANTH, JYOTHI; NAYAK, KRISHNANAND; SARANG, AROHI; THAKKAR, ASHOK // Journal of Clinical & Diagnostic Research;Dec2014, Vol. 8 Issue 12, p5 

    Background: Hypertrophic cardiomyopathy (HCM), an autosomal dominant disorder due to mutation of genes encoding sarcomeric proteins, leads to left ventricular diastolic dysfunction. Recently, the research in this area suggests that systolic dysfunction exists in the patients with HCM even though...

  • Myofilament Protein Gene Mutation Screening and Outcome of Patients With Hypertrophic Cardiomyopathy. Olivotto, Iacopo; Girolami, Francesca; Ackerman, Michael J.; Nistri, Stefano; Bos, J. Martijn; Zachara, Elisabetta; Ommen, Steve R.; Theis, Jeanne L.; Vaubel, Rachael A.; Re, Federica; Armento, Corinna; Poggesi, Corrado; Torricelli, Francesca; Cecchi, Franco // Mayo Clinic Proceedings;Jun2008, Vol. 83 Issue 6, p630 

    OBJECTIVE: To determine the influence of a positive genetic test for hypertrophic cardiomyopathy (HCM) on clinical outcome. PATIENTS AND METHODS: A cohort of 203 unrelated patients with HCM (mean ± SD age, 50±18 years) was enrolled from January 1, 2002, through December 31, 2003. They were...

  • Clinical and imaging description of the Maron subtypes of hypertrophic cardiomyopathy. Reant, Patricia; Donal, Erwan; Schnell, Frederic; Reynaud, Amelie; Daudin, Magalie; Pillois, Xavier; Dijos, Marina; Landelle, Mathieu; Peyrou, Jerome; Cornolle, Claire; Laurent, François; Montaudon, Michel; Roudaut, Raymond; Lafitte, Stephane // International Journal of Cardiovascular Imaging;Jan2015, Vol. 31 Issue 1, p47 

    Longitudinal strain analysis enables early detection of left ventricular (LV) contraction abnormalities in patients with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) is associated with low values of regional and global longitudinal myocardial deformations. In addition to...

  • Heart failure and cardiomyopathy: Left ventricular twist mechanics in patients with apical hypertrophic cardiomyopathy: assessment with 2D speckle tracking echocardiography. Chang, S.-A.; Kim, H.-K.; Kim, D.-H.; Kim, J.-C.; Kim, Y.-J.; Kim, H.-C.; Sohn, D.-W.; Oh, B.-H.; Park, Y.-B. // Heart;Jan2010, Vol. 96 Issue 1, p49 

    Objective: Left ventricular (LV) apical rotation significantly contributes to LV twist, which has been reported to have a vital role in maintaining LV systolic and diastolic function. Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathological LV hypertrophy at the apex. We...

  • Cardiac vignette: A curious case of left ventricular hypertrophy. Bhat, A.; Gan, G.; Fernandez, F.; Denniss, A. // Heart, Lung & Circulation;2015 Supplement 3, Vol. 24, pS329 

    No abstract available.

  • Evaluation of left ventricular outflow tract gradient during treadmill exercise and in recovery period in orthostatic position, in patients with hypertrophic cardiomyopathy. Miranda, Rita; Cotrim, Carlos; Cardim, Nuno; Almeida, Sofia; Lopes, Luís; Loureiro, Maria José; Simões, Otília; Cordeiro, Pedro; Fazendas, Paula; João, Isabel; Carrageta, Manuel // Cardiovascular Ultrasound;2008, Vol. 6, Special section p1 

    Background-: Left ventricular outflow tract obstruction is an independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). The classical quantification of intraventricular obstruction is performed in resting conditions in supine position, but this assessment does not reflect...

  • A Novel Myosin Essential Light Chain Mutation Causes Hypertrophic Cardiomyopathy with Late Onset and Low Expressivity. Andersen, Paal Skytt; Hedley, Paula Louise; Page, Stephen P.; Syrris, Petros; CatharinaMoolman-Smook, Johanna; JohnMcKenna, William; Elliott, Perry Mark; Christiansen, Michael // Biotechnology Research International;2012, p1 

    Hypertrophic cardiomyopathy (HCM) is caused by mutations in genes encoding sarcomere proteins. Mutations in MYL3, encoding the essential light chain of myosin, are rare and have been associated with sudden death. Both recessive and dominant patterns of inheritance have been suggested. We studied...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics