Ultrasonic Assessment of Myocardial Microstructure in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers With and Without Left Ventricular Hypertrophy.
The noninvasive assessment of altered myocardium in patients with genetic mutations that are associated with hypertrophic cardiomyopathy (HCM) remains challenging. In this pilot study, we evaluated whether a novel echocardiography-based assessment of myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations in HCM sarcomere mutation carriers with and without left ventricular hypertrophy.



We studied 3 groups of genotyped individuals: sarcomere mutation carriers with left ventricular hypertrophy (clinical HCM; n=36), mutation carriers with normal left ventricular wall thickness (subclinical HCM; n=28), and healthy controls (n=10). We compared measurements of echocardiographic SIC with validated assessments of cardiac microstructural alteration, including cardiac magnetic resonance measures of interstitial fibrosis (extracellular volume fraction), as well as serum biomarkers (NTproBNP, hs-cTnI, and PICP). In age-, sex-, and familial relation-adjusted analyses, the SIC was quantitatively different across subjects with overt HCM, subclinical HCM, and healthy controls (P<0.001). Compared with controls, the SIC was 61% higher in overt HCM and 47% higher in subclinical HCM (P<0.001 for both). The SIC was significantly correlated with extracellular volume (r=0.72; P<0.01), with left ventricular mass and E' velocity (r=0.45, -0.60, respectively; P<0.01 for both), and with serum NTproBNP levels (r=0.36; P<0.001).



Our findings suggest that the SIC could serve as a noninvasive quantitative tool for assessing altered myocardial tissue characteristics in patients with genetic mutations associated with HCM. Further studies are needed to determine whether the SIC could be used to identify subclinical changes in patients at risk for HCM and to evaluate the effects of interventions.
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Pranoti
P
Hiremath
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Patrick R
PR
Lawler
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Jennifer E
JE
Ho
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Andrew W
AW
Correia
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Siddique A
SA
Abbasi
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Raymond Y
RY
Kwong
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.).
Michael
M
Jerosch-Herold
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.). cho@partners.org scheng@rics.bwh.harvard.edu.
Carolyn Y
CY
Ho
From the Cardiovascular Division, Department of Medicine (P.H., P.R.L., R.Y.K., C.Y.H., S.C.) and Department of Radiology (M.J.-H.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); SessionM, Boston, MA (A.W.C.); and Division of Cardiology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI (S.A.A.). cho@partners.org scheng@rics.bwh.harvard.edu.
Susan
S
Cheng
D000328:Adult; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D015150:Echocardiography, Doppler / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009154:Mutation; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D055815:Young Adult
D015415:Biomarkers
echocardiography; hypertrophic cardiomyopathy; left ventricular hypertrophy; myocardium; sacromeres