T1 Measurements Identify Extracellular Volume Expansion in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy

OBJECTIVES:  Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations appear to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance (CMR) with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV).

METHODS:  Sarcomere mutation carriers with LVH (G+/LVH+, n = 37) and without LVH (G+/LVH-, n = 29); HCM patients without mutations (sarcomere-negative HCM, n = 11); and healthy controls (n = 11) underwent contrast CMR, measuring T1 times pre- and post-gadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset.

RESULTS: Compared to controls, ECV was increased in patients with overt HCM, as well as G+/LVH- mutation carriers (ECV= 0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH-, controls, respectively, P≤0.001 for all comparisons). ECV correlated with NT-proBNP levels (r = 0.58, P<0.001) and global E’ velocity (r = -0.48, P<0.001). Late gadolinium enhancement (LGE) was present in >60% of overt HCM patients but absent from G+/LVH- subjects. Both ECV and LGE were more extensive in sarcomeric HCM than sarcomere-negative HCM.

CONCLUCIONS: Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis. 

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One Comment

  1. A paper validating T1 measurements for extracellular volume was just published on-line:

    Comprehensive Validation of Cardiovascular Magnetic Resonance Techniques for the Assessment of Myocardial Extracellular Volume.
    Christopher A. Miller, Josephine Naish, Paul Bishop, Glyn Coutts, David Clark, Sha Zhao, Simon G. Ray, Nizar Yonan, Simon G. Williams, Andrew S. Flett, James C. Moon, Andreas Greiser, Geoffrey J.M. Parker, and Matthias Schmitt.
    Circ Cardiovasc Imaging. April 3, 2013.
    []

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