Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study

EBioMedicine. 2021 Dec;74:103735. doi: 10.1016/j.ebiom.2021.103735. Epub 2021 Dec 2.


Background: Familial Hypercholesterolemia (FH) is an underdiagnosed condition with an increased cardiovascular risk. It is unknown whether lipid accumulation plays a role in structural myocardial changes. Cardiovascular Magnetic Resonance (CMR) is the reference technique for the morpho-functional evaluation of heart chambers through cine sequences and for myocardial tissue characterization through late gadolinium enhancement (LGE) and T1 mapping images. We aimed to assess the prevalence of myocardial fibrosis in FH patients.

Methods: Seventy-two asymptomatic subjects with genetically confirmed FH (mean age 49·24, range 40 to 60 years) were prospectively recruited along with 31 controls without dyslipidaemia matched for age, sex, BMI, and other cardiovascular risk factors. All underwent CMR including cine, LGE, pre- and post-contrast T1 mapping. Extracellular volume (ECV) and enhancement rate of the myocardium (ERM = difference between pre- and post-contrast myocardial T1, normalized by pre-contrast myocardial T1) were calculated.

Findings: Five FH patients and none of the controls had intramyocardial LGE (p= 0·188). While no changes in Native T1 and ECV were found, post-contrast T1 was significantly lower (430·6 ± 55ms vs. 476·1 ± 43ms, p<0·001) and ERM was higher (57·44± 5·99 % vs 53·04±4·88, p=0·005) in HeFH patients compared to controls. Moreover, low post-contrast T1 was independently associated with the presence of xanthoma (HR 5·221 [1·04-26·28], p= 0·045). A composite score combining the presence of LGE, high native T1 and high ERM (defined as ≥ mean ± 1·5 SD) was found in 20·8% of the HeFH patients vs. 0% in controls (p<0·000, after adjustment for main confounders).

Interpretation: CMR revealed early changes in myocardial tissue characteristics in HeFH patients, that should foster further work to better understand and prevent the underlying pathophysiological processes.

Keywords: Familial hypercholesterolemia; cardiac magnetic resonance; cardiovascular imaging; cardiovascular risk; genetic dyslipidaemia; primary prevention.