TY - JOUR
T1 - Cardiovascular Measures of All-Cause Mortality in Duchenne Muscular Dystrophy
AU - Soslow, Jonathan H.
AU - Xu, Meng
AU - Slaughter, James C.
AU - Crum, Kimberly
AU - Kaslow, Jacob A.
AU - George-Durrett, Kristen
AU - Raucci, Frank J.
AU - Wilkinson, James D.
AU - Cripe, Linda H.
AU - Hor, Kan N.
AU - Spurney, Christopher F.
AU - Markham, Larry W.
N1 - Funding Information:
Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under awards K23HL123938 and R56HL141248 (Bethesda, MD; Dr Soslow) and K08HL155852 (Dr Raucci). The project was supported by the National Center for Research Resources, grant UL1 RR024975-01, and is now at the National Center for Advancing Translational Sciences, grant 2 UL1 TR000445-06 (Bethesda, MD). This project was supported by Food and Drug Administration Orphan Products grant R01FD006649 (Dr Soslow). This project was supported by the Fighting Duchenne Foundation and the Fight Duchenne Muscular Dystrophy/Jonah & Emory Discovery Grant (Nashville, TN; Dr Soslow). The sponsors and funders had no role in the design and conduct of the study or in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Background: Cardiopulmonary failure is the leading cause of death in Duchenne muscular dystrophy (DMD). Research into DMD-specific cardiovascular therapies is ongoing, but there are no Food and Drug Administration-approved cardiac end points. To adequately power a therapeutic trial, appropriate end points must be chosen and the rate of change for these end points reported. The objective of this study was to evaluate rate of change for cardiac magnetic resonance and blood biomarkers and to determine which measures associate with all-cause mortality in DMD. Methods: Seventy-eight DMD subjects underwent 211 cardiac magnetic resonance studies analyzed for left ventricular (LV) ejection fraction, indexed LV end diastolic and systolic volumes, circumferential strain, late gadolinium enhancement presence and severity (global severity score, and full width half maximum), native T1 mapping, T2 mapping, and extracellular volume. Blood samples were analyzed for BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), and troponin I. Cox proportional hazard regression modeling was performed with all-cause mortality as the outcome. Results: Fifteen subjects (19%) died. LV ejection fraction, indexed end systolic volumes, global severity score, and full width half maximum worsened at 1 and 2 years while circumferential strain and indexed LV end diastolic volumes worsened at 2 years. LV ejection fraction, indexed LV end diastolic and systolic volumes, late gadolinium enhancement full width half maximum, and circumferential strain associated with all-cause mortality (P<0.05). NT-proBNP was the only blood biomarker that associated with all-cause mortality (P<0.05). Conclusions: LV ejection fraction, indexed LV volumes, circumferential strain, late gadolinium enhancement full width half maximum, and NT-proBNP are associated with all-cause mortality in DMD and may be the best end points for use in cardiovascular therapeutic trials. We also report change over time of cardiac magnetic resonance and blood biomarkers.
AB - Background: Cardiopulmonary failure is the leading cause of death in Duchenne muscular dystrophy (DMD). Research into DMD-specific cardiovascular therapies is ongoing, but there are no Food and Drug Administration-approved cardiac end points. To adequately power a therapeutic trial, appropriate end points must be chosen and the rate of change for these end points reported. The objective of this study was to evaluate rate of change for cardiac magnetic resonance and blood biomarkers and to determine which measures associate with all-cause mortality in DMD. Methods: Seventy-eight DMD subjects underwent 211 cardiac magnetic resonance studies analyzed for left ventricular (LV) ejection fraction, indexed LV end diastolic and systolic volumes, circumferential strain, late gadolinium enhancement presence and severity (global severity score, and full width half maximum), native T1 mapping, T2 mapping, and extracellular volume. Blood samples were analyzed for BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), and troponin I. Cox proportional hazard regression modeling was performed with all-cause mortality as the outcome. Results: Fifteen subjects (19%) died. LV ejection fraction, indexed end systolic volumes, global severity score, and full width half maximum worsened at 1 and 2 years while circumferential strain and indexed LV end diastolic volumes worsened at 2 years. LV ejection fraction, indexed LV end diastolic and systolic volumes, late gadolinium enhancement full width half maximum, and circumferential strain associated with all-cause mortality (P<0.05). NT-proBNP was the only blood biomarker that associated with all-cause mortality (P<0.05). Conclusions: LV ejection fraction, indexed LV volumes, circumferential strain, late gadolinium enhancement full width half maximum, and NT-proBNP are associated with all-cause mortality in DMD and may be the best end points for use in cardiovascular therapeutic trials. We also report change over time of cardiac magnetic resonance and blood biomarkers.
KW - biomarkers
KW - brain natriuretic peptide
KW - gadolinium
KW - human
KW - magnetic resonance imaging
KW - troponin I
UR - http://www.scopus.com/inward/record.url?scp=85165098608&partnerID=8YFLogxK
U2 - 10.1161/CIRCHEARTFAILURE.122.010040
DO - 10.1161/CIRCHEARTFAILURE.122.010040
M3 - Article
C2 - 37288563
AN - SCOPUS:85165098608
SN - 1941-3289
VL - 16
SP - E010040
JO - Circulation: Heart Failure
JF - Circulation: Heart Failure
IS - 8
ER -