Histologic characterization of hypertrophic cardiomyopathy with and without myofilament mutations

Christopher J. McLeod, J. Martijn Bos, Jeanne L. Theis, William D. Edwards, Bernard J. Gersh, Steve R. Ommen, Michael John Ackerman

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Between 30% and 60% of clinical cases of hypertrophic cardiomyopathy (HC) can be attributed to mutations in the genes encoding cardiac myofilament proteins. Interestingly, it appears that the likelihood of an underlying myofilament mutation can be predicted by echocardiographic assessment of left ventricular morphology. However, it is not known whether genotypically characterized HC exists as a separate entity with discrete phenotypic morphology and histology or to what extent recognized polymorphisms of the renin-angiotensin-aldosterone system (RAAS) influence this relationship. The presence of cardiac myofilament and mutations and RAAS polymorphisms will have a strong association with the severity of histologic features of HC and characteristic septal shape. Methods: We conducted a retrospective review of histology specimens, obtained at septal myectomy among 181 patients with medically refractory symptomatic HC. All patients underwent comprehensive genetic analysis for mutations in 8 myofilament-encoding genes; a subset was genotyped for 6 known RAAS-polymorphisms. Patients underwent comprehensive echocardiography by an expert blinded to genotype and microscopic status. Results: Microscopically, severity of myocyte hypertrophy appears to be associated with the presence of recognized HC cardiac myofilament mutations (P = .03). Other histologic features characteristic of HC were not consistently associated with myofilament mutation status. A higher burden of pro-LVH RAAS polymorphisms also appeared to predict only myocyte hypertrophy (P = .01). The presence of RAAS polymorphisms was not associated with the development of a specific septal morphology (P = .6). Conclusion: Myofilament-positive HC does not appear to represent a distinct clinical phenotypic entity as evidenced by specific histologic characteristics and septal shape.

Original languageEnglish (US)
Pages (from-to)799-805
Number of pages7
JournalAmerican Heart Journal
Volume158
Issue number5
DOIs
StatePublished - Nov 2009

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Myofibrils
Hypertrophic Cardiomyopathy
Renin-Angiotensin System
Mutation
Muscle Cells
Hypertrophy
Histology
Genes
Echocardiography
Genotype
Proteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Histologic characterization of hypertrophic cardiomyopathy with and without myofilament mutations. / McLeod, Christopher J.; Bos, J. Martijn; Theis, Jeanne L.; Edwards, William D.; Gersh, Bernard J.; Ommen, Steve R.; Ackerman, Michael John.

In: American Heart Journal, Vol. 158, No. 5, 11.2009, p. 799-805.

Research output: Contribution to journalArticle

McLeod, Christopher J. ; Bos, J. Martijn ; Theis, Jeanne L. ; Edwards, William D. ; Gersh, Bernard J. ; Ommen, Steve R. ; Ackerman, Michael John. / Histologic characterization of hypertrophic cardiomyopathy with and without myofilament mutations. In: American Heart Journal. 2009 ; Vol. 158, No. 5. pp. 799-805.
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N2 - Background: Between 30% and 60% of clinical cases of hypertrophic cardiomyopathy (HC) can be attributed to mutations in the genes encoding cardiac myofilament proteins. Interestingly, it appears that the likelihood of an underlying myofilament mutation can be predicted by echocardiographic assessment of left ventricular morphology. However, it is not known whether genotypically characterized HC exists as a separate entity with discrete phenotypic morphology and histology or to what extent recognized polymorphisms of the renin-angiotensin-aldosterone system (RAAS) influence this relationship. The presence of cardiac myofilament and mutations and RAAS polymorphisms will have a strong association with the severity of histologic features of HC and characteristic septal shape. Methods: We conducted a retrospective review of histology specimens, obtained at septal myectomy among 181 patients with medically refractory symptomatic HC. All patients underwent comprehensive genetic analysis for mutations in 8 myofilament-encoding genes; a subset was genotyped for 6 known RAAS-polymorphisms. Patients underwent comprehensive echocardiography by an expert blinded to genotype and microscopic status. Results: Microscopically, severity of myocyte hypertrophy appears to be associated with the presence of recognized HC cardiac myofilament mutations (P = .03). Other histologic features characteristic of HC were not consistently associated with myofilament mutation status. A higher burden of pro-LVH RAAS polymorphisms also appeared to predict only myocyte hypertrophy (P = .01). The presence of RAAS polymorphisms was not associated with the development of a specific septal morphology (P = .6). Conclusion: Myofilament-positive HC does not appear to represent a distinct clinical phenotypic entity as evidenced by specific histologic characteristics and septal shape.

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