Novel 4D Strain Associates with Mortality in Duchenne Muscular Dystrophy Cardiomyopathy

Presenting Author(s)

• KG

  Kristen George-Durrett, BSc, RT

  Research MRI Technologist
  Vanderbilt University Medical Center
  Nashville, Tennessee, United States

Primary Author(s)

• JS

  Jonathan H. Soslow, MD

  Assistant Professor, Division of Pediatric Cardiology
  Vanderbilt University Medical Center
  Nashville, Tennessee, United States

Co-Author(s)

• 

  Marco A. Prado, BSc

  PhD Candidatee
  Purdue University
  West Lafayette, Indiana, United States
• CE

  Conner Earl, BSc

  MD/PhD Candidate
  Purdue University, Indiana, United States
• LM

  Larry Markham, MD

  Professor
  Riley Hospital for Children at IU Health, Indiana, United States
• 

  Kan N. Hor, MD

  Director, Advanced Cardiovascular Imaging and Fellowship Program, Associate Division Chief for Research
  Nationwide Children's Hospital and The Ohio State University
  Columbus, OH, USA, Ohio, United States
• MS

  Madison Sullivan, MSc

  Graduate Research Assistant
  Purdue University, United States
• GL

  Guang Lin, PhD

  Professor
  Purdue University, United States
• CG

  Craig Goergen, PhD

  Professor
  Purdue University, Indiana, United States

Background: The most common cause of mortality in Duchenne Muscular Dystrophy (DMD) is Cardiomyopathy. Cardiac MRI (CMR) strain associates with mortality in DMD. However, conventional 2D circumferential strain analysis methods only evaluate strain in 3 slices, disregarding the rest of the heart. We have developed a novel 4D strain analysis package that analyzes all slices then generates average regional strain (base, mid, apex). The objective of this study was to evaluate the association of 4D strain analysis with mortality.

Methods: CMR was performed on DMD patients as part of a prospective observational study. For each patient, standard volumes and function were analyzed using Medis QMass. Gadolinium was administered to evaluate for presence of late gadolinium enhancement (LGE). For 4D strain, we used a custom graphical user interface in MATLAB to compile short-axis CMR image stacks into four-dimensional sequences. Using feature tracking, we generated a deformable 3D mesh throughout the cardiac cycle which allowed us to calculate peak circumferential strain (Ecc) at the base, mid, and apex using multiple slices for each region. Global Ecc was generated by averaging the base, mid, apex Ecc. Systolic strain rate (SR) and early and late diastolic SR were also assessed. Cox proportional hazard regression modeling was performed with all-cause mortality as the outcome.

Results: Sixty-two patients with DMD were included with a median age of 12 y/o, interquartile range (IQR) (10, 17). The median LVEF was 58%, IQR (40.7, 61), with 35% (N=22) having an LVEF < 55% and 70% (N=43) having LGE. Ten patients had a mortality event during the study period. Ecc at the base, mid, and apex associated strongly with all-cause mortality (hazard ratio, HR 1.25 p=0.001, HR 1.17 p=0.001, and HR 1.15 p< 0.001, respectively). Global Ecc associated strongly with all-cause mortality (HR 1.22 p< 0.001). A cutpoint of -16% was chosen based on clinical significance; this cutpoint demonstrated statistically significant survival differences between groups (Figure 1). Systolic SR and early and late diastolic SR also associated with mortality (Table 1)

Conclusion: 4D Ecc strongly associates with all-cause mortality in DMD. Future work will include validation in a larger cohort and analysis of optimal cutpoints.

Cox regression analysis of systolic, early diastolic, and late diastolic strain rate with all-cause mortality as outcome

Measure	Hazard Ratio	p-value
Base systolic circumferential strain rate (SR)	27.3 (3.6, 210)	0.001
Mid systolic circumferential strain rate (SR)	11.3 (2.5, 51)	0.002
Apex systolic circumferential strain rate (SR)	5.0 (1.7, 15)	0.004
Global systolic circumferential strain rate (SR)	21 (4.1, 110)	< 0.001
Base early diastolic circumferential SR	0.05 95% CI (0.004, 0.72)	0.027
Mid early diastolic SR	0.11 (0.02, 0.57)	0.008
Apex early diastolic SR	0.1 (0.03, 0.40)	0.001
Global early diastolic SR	0.05 (0.01, 0.32)	0.001
Base late diastolic SR	0.03 (0.001, 0.64)	0.025
Mid late diastolic SR	0.18 (0.02, 1.6)	0.122
Apex late diastolic SR	0.19 (0.06, 0.60)	0.04
Global late diastolic SR	0.05 (0.005, 0.47)	0.009

Figure 1: All-cause mortality in patients with Duchenne muscular dystrophy stratified by global circumferential strain (Ecc) ≤-16% or >-16%.