Skip to main content

Genotype positive hypertrophic cardiomyopathy is associated with myocardial perfusion abnormalities

Background

Hypertrophic cardiomyopathy (HCM) is a highly heterogenous disease both genotypically and phenotypically. Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) for fibrosis detection and adenosine stress perfusion are key techniques for HCM phenotyping. Recent advances in DNA sequencing, in particular high throughput next generation sequencing (NGS), have enabled more extensive genetic analysis of larger cohorts of patients. We sought to assess the link between genotype and the microvascular circulation in a cohort of patients with HCM.

Methods

We recruited 288 patients with HCM according to standard criteria, who were undergoing clinical CMR. All patients had assessment of LV volumes, mass and function and LGE, except 1 for volumes and 2 for LGE. Overall, 214 (74%) also underwent adenosine stress perfusion. Detailed demographic and outcome data were collected over a mean of 3 years follow up. 120 genes with a known or putative role in cardiomyopathy were sequenced in every patient using SureSelect target DNA capture and SOLiD next-generation sequencing, and variants were identified using GATK and LifeScope. Subjects were stratified according to the presence or absence of a likely causative genetic variant in the principal sarcomeric HCM genes.

Results

Clinical data are presented in table 1 and genetic data in table 2. Thirty-five percent of patients carried a likely causative variant (genotype positive). Genotype positive patients were younger at diagnosis (p = 0.005), with a trend to a higher death rate during follow up. Adenosine stress perfusion was more frequently abnormal in genotype positive patients (82% v. 64%, p = 0.015). LV mass index was on average 12% greater in genotype negative patients (p = 0.005). There were no significant differences between groups for LV volumes, maximum wall thickness, or extent of LGE.

Table 1 Genotype Phenotype correlations in HCM [mean (SD) unless stated]
Table 2 Genotype positive by gene

Conclusions

The main finding of this study is that genotype positive patients are more likely to have abnormal myocardial perfusion. It is known that genotype positive HCM patients have a higher rate of sudden cardiac death (and a trend towards death was seen in this study), and this has been postulated to be related to ischemia. Our finding that sarcomeric variants were associated with lower LV mass was unexpected and is worthy of further study given the comparatively large size of this cohort. Previous studies have highlighted the association between maximum LV wall thickness and extent of LGE with the presence of a known HCM mutation, but this finding was not replicated in the present study. More comprehensive genetic analyses enabled by next generation technologies, coupled with cutting-edge phenotypic evaluation, may enable the dissection of genotype-phenotype relationships in HCM.

Funding

This work was supported by the National Institute of Health Research Cardiovascular Biomedical Research Unit at the Royal Brompton Hospital and Imperial College, London.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Niall G Keenan.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Reprints and Permissions

About this article

Cite this article

Keenan, N.G., Varkey, S., Buchan, R.J. et al. Genotype positive hypertrophic cardiomyopathy is associated with myocardial perfusion abnormalities. J Cardiovasc Magn Reson 16, P342 (2014). https://doi.org/10.1186/1532-429X-16-S1-P342

Download citation

Keywords

  • Cardiovascular Magnetic Resonance
  • Late Gadolinium Enhancement
  • Hypertrophic Cardiomyopathy
  • Maximum Wall Thickness
  • Royal Brompton Hospital