Non-ischemic Primary and Secondary Cardiomyopathy
George Joy, MBBS
Research Fellow
University College London, United Kingdom
George Joy, MBBS
Research Fellow
University College London, United Kingdom
Christopher I. Kelly, PhD
Research Fellow
Leeds Institute of Cardiovascular and Metabolic Medicine, United Kingdom
Matthew Webber, MD, BSc
Clinical Research Fellow
University College London, United Kingdom
Iain Pierce, PhD
Scientist
Barts Heart Centre at St Bartholomew's Hospital, United Kingdom
Irvin Teh, PhD
Senior Research Fellow
Leeds Institute of Cardiovascular and Metabolic Medicine
Leeds, England, United Kingdom
Jurgen E. Schneider, PhD
Professor of Biomedical Imaging
Leeds Institute of Cardiovascular and Metabolic Medicine
Leeds, England, United Kingdom
Christopher Nguyen, PhD, FACC, FSCMR
Director
Cleveland Clinic
Cleveland, Ohio, United States
Peter Kellman, PhD
Senior Scientist
National Institutes of Health, Maryland, United States
Rebecca Hughes, MD
Clinical Research Fellow
University College London and Barts Heart Centre
London, United Kingdom
Louise McGrath, BSc MSc
Senior Radiographer
Royal Brompton Hospital, United Kingdom
Paula Velazquez
Clinical Fellow
Barts Heart Centre at St Bartholomew's Hospital, United Kingdom
Huafrin Kotwal
Genetic Counsellor
Barts Heart Centre at St Bartholomew's Hospital, United Kingdom
Arka Das
Research Fellow
Leeds Institute of Cardiovascular and Metabolic Medicine, United Kingdom
Michele Orini, PhD
Senior Research Fellow
University College London, United Kingdom
Charlotte Manisty
Consultant Cardiologist
University College London and Barts Heart Centre
London, England, United Kingdom
Pier Lambiase, MD, PhD
Professor of Cardiology
University College London, United Kingdom
Maite Tome
Consultant Cardiologist and Honorary Reader
St George's University Hospitals NHS Foundation Trust, United Kingdom
Gabriella Captur, n/a
Consultant Cardiologist, Senior Clinical Lecturer
UCL
London, England, United Kingdom
Erica Dall’Armellina
Associate Professor and Honorary Consultant Cardiologist
University of Leeds, England, United Kingdom
James C. Moon, MD
Clinical Director, Imaging
Barts Heart Centre and UCL
London, England, United Kingdom
Luis R. Lopes, PhD
Associate Professor
University College London and Barts Heart Centre, United Kingdom
Microvascular dysfunction and myocyte disarray associate with adverse events in hypertrophic cardiomyopathy (HCM) and both are now quantifiable by novel CMR. We investigate these in both subclinical HCM (no LVH (G+LVH-) carrying pathogenic/likely pathogenic sarcomere gene variants) and overt HCM (LVH+), and their relationship to electrical changes and genotype (genotype positive (G+LVH+) & genotype negative (G-LVH+).
Methods:
200 subjects were studied: 28 Healthy volunteers (HV), 75 subclinical HCM with no LVH (G+LVH-) and 97 patients with overt HCM (48 G+LVH+, 49 G-LVH+), underwent 12-lead ECG, quantitative stress perfusion CMR (measuring myocardial blood flow (MBF) and visual perfusion defects) and spin-echo cardiac diffusion tensor imaging (cDTI) providing fractional anisotropy (FA), mean diffusivity (MD,units 10-3mm2/s) and second eigenvector angle (E2A°).
Results:
Demographics were: HV (median age 34(32-40) years, 50% female, 0% abnormal ECG), G+LVH- (age 34(24-41), 55% female, 35% abnormal ECG), overt HCM (age 56(47-61), 20% female, 82% abnormal ECG).
Overt disease vs HV (Table): cDTI: Overt HCM patients had DTI parameters suggestive of more disarray (lower FA, higher MD, higher E2A). Perfusion: Overt HCM had lower stress MBF and more perfusion defects (93%). Overt disease (G+ vs G-). Both G+ and G- had DTI parameters suggestive of disarray, although G- had higher E2A (G-LVH+: 61.9±5.8 vs 59.2±6.8 p=0.035). Visual perfusion defects were found in all G+LVH+ (100%) but 17% of G-LVH+ did not have perfusion defects, p=0.003. Subclinical HCM vs HV (Table): cDTI: G+LVH- also had DTI parameters suggestive of more disarray (lower FA, higher MD and higher E2A) but less marked than overt disease. Perfusion: G+LVH- had more perfusion defects (25%(19) vs 0 HV p=0.005). Associations: Overt disease: Perfusion: All three DTI parameters were associated with stress MBF (all p< 0.035) but when accounting for LVH and burden of focal or diffuse fibrosis, only E2A was independently predictive (multivariable analysis β=-0.27,95%CI -0.08,-0.46 p=0.003). ECG: Compared to those with normal ECG, those with abnormal ECG had lower FA, higher MD, higher E2A (all p</span>≤0.001) and lower stress MBF (p< 0.001), regardless of the amount of LVH or burden of focal or diffuse fibrosis (on multivariable analysis: FA: β=-0.27, 95%CI: -0.056,-0.49 p=0.015, MD:β=0.24, 95%CI 0.02,0.49, p=0.036, E2A: β=0.38, 95%CI 0.17,0.60, p=< 0.001). Subclinical HCM: Perfusion: G+LVH- with perfusion defects had lower FA and higher E2A than G+LVH- without perfusion defects (both p< 0.024). ECG: G+LVH- with abnormal ECG had higher MD and higher E2A than those with normal ECG (both p< 0.003). Microvascular dysfunction and DTI changes suggestive of disarray are measurable, correlate and relate to ECG abnormalities in subclinical and overt HCM. Changes occur before LVH and are exacerbated in its presence. G+LVH+ and G-LVH+ have distinct microstructural and microvascular phenotypes.
Conclusion: