Myocardial fibrosis assessed by magnetic resonance imaging in asymptomatic heterozygous familial hypercholesterolemia: the cholcoeur study
Antonio Gallo,
Philippe Giral,
David Rosenbaum,
Alessandro Mattina,
Ali Kilinc,
Alain Giron,
Khaoula Bouazizi,
Moussa Gueda Moussa,
Joe-Elie Salem,
Alain Carrié,
Valérie Carreau,
Sophie Béliard,
Randa Bittar,
Philippe Cluzel,
Eric Bruckert,
Alban Redheuil,
Nadjia Kachenoura
Affiliations
Antonio Gallo
Cardiovascular Prevention Unit, Department of Endocrinology, Metabolism and cardiovascular prevention–University Hospital Pitié-Salpêtrière – Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière – Sorbonne University; Sorbonne University, Biomedical Imaging Laboratory, CNRS, INSERM, Paris, France; Sorbonne University, INSERM, Institute of Cardio-metabolism and Nutrition (ICAN), Imaging Core Lab, Hôpital de la Pitié-Salpêtrière, Paris, France; Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose, Réunion Océan Indien (DéTROI), Saint-Denis de La Réunion, France; Corresponding author: Antonio Gallo, MD PhD, Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose, Réunion Océan Indien (DéTROI), Laboratoire CYROI, 2 Rue Maxime Rivière, 97490 Saint-Denis de La Réunion, France
Philippe Giral
Cardiovascular Prevention Unit, Department of Endocrinology, Metabolism and cardiovascular prevention–University Hospital Pitié-Salpêtrière – Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière – Sorbonne University
David Rosenbaum
Cardiovascular Prevention Unit, Department of Endocrinology, Metabolism and cardiovascular prevention–University Hospital Pitié-Salpêtrière – Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière – Sorbonne University
Alessandro Mattina
Cardiovascular Prevention Unit, Department of Endocrinology, Metabolism and cardiovascular prevention–University Hospital Pitié-Salpêtrière – Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière – Sorbonne University; Diabetes and Islet Transplantation Unit, Department of Diagnostic and Therapeutic Services, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), University of Pittsburgh Medical Center - Italy, Palermo, Italy
Ali Kilinc
Sorbonne University, INSERM, Institute of Cardio-metabolism and Nutrition (ICAN), Imaging Core Lab, Hôpital de la Pitié-Salpêtrière, Paris, France
Alain Giron
Sorbonne University, Biomedical Imaging Laboratory, CNRS, INSERM, Paris, France
Khaoula Bouazizi
Sorbonne University, INSERM, Institute of Cardio-metabolism and Nutrition (ICAN), Imaging Core Lab, Hôpital de la Pitié-Salpêtrière, Paris, France
Moussa Gueda Moussa
Sorbonne University, Biomedical Imaging Laboratory, CNRS, INSERM, Paris, France
Joe-Elie Salem
AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology and CIC-1901, F-75013 Paris, France; INSERM, CIC-1901 and UMR 1166, F-75013 Paris, France, Sorbonne Universités
Alain Carrié
Sorbonne University, Inserm, UMR_S1166, APHP, Department of Biochemistry, Obesity and Dyslipidemia Genetics Unit, Hôpital de la Pitié, Paris, France
Valérie Carreau
Cardiovascular Prevention Unit, Department of Endocrinology, Metabolism and cardiovascular prevention–University Hospital Pitié-Salpêtrière – Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière – Sorbonne University
Sophie Béliard
Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France; Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France
Randa Bittar
Sorbonne University, Inserm, UMR_S1166, Department of Metabolic Biochemistry, Assistance Publique, Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Paris, France
Philippe Cluzel
Cardiovascular and Thoracic Imaging Unit, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne University, INSERM, Paris, France
Eric Bruckert
Cardiovascular Prevention Unit, Department of Endocrinology, Metabolism and cardiovascular prevention–University Hospital Pitié-Salpêtrière – Assistance Publique/Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière – Sorbonne University; Sorbonne University, INSERM, Institute of Cardio-metabolism and Nutrition (ICAN), Imaging Core Lab, Hôpital de la Pitié-Salpêtrière, Paris, France
Alban Redheuil
Sorbonne University, Biomedical Imaging Laboratory, CNRS, INSERM, Paris, France; Sorbonne University, INSERM, Institute of Cardio-metabolism and Nutrition (ICAN), Imaging Core Lab, Hôpital de la Pitié-Salpêtrière, Paris, France; Cardiovascular and Thoracic Imaging Unit, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne University, INSERM, Paris, France
Nadjia Kachenoura
Sorbonne University, Biomedical Imaging Laboratory, CNRS, INSERM, Paris, France; Sorbonne University, INSERM, Institute of Cardio-metabolism and Nutrition (ICAN), Imaging Core Lab, Hôpital de la Pitié-Salpêtrière, Paris, France
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.
