Longitudinal changes in cardiac function in Duchenne muscular dystrophy population as measured by magnetic resonance imaging

Abstract

Background The lack of dystrophin in cardiomyocytes in Duchenne muscular dystrophy (DMD) is associated with progressive decline in cardiac function eventually leading to death by 20–40 years of age. The aim of this prospective study was to determine rate of progressive decline in left ventricular (LV) function in Duchenne muscular dystrophy (DMD) over 5 years. Methods Short axis cine and grid tagged images of the LV were acquired in individuals with DMD (n = 59; age = 5.3–18.0 years) yearly, and healthy controls at baseline (n = 16, age = 6.0–18.3 years) on a 3 T MRI scanner. Grid-tagged images were analyzed for composite circumferential strain (ℇcc%) and ℇcc% in six mid LV segments. Cine images were analyzed for left ventricular ejection fraction (LVEF), LV mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), LV atrioventricular plane displacement (LVAPD), and circumferential uniformity ratio estimate (CURE). LVM, EDV, and ESV were normalized to body surface area for a normalized index of LVM (LVMI), EDV (EDVI) and ESV (ESVI). Results At baseline, LV ℇcc% was significantly worse in DMD compared to controls and five of the six mid LV segments demonstrated abnormal strain in DMD. Longitudinal measurements revealed that ℇcc% consistently declined in individuals with DMD with the inferior segments being more affected. LVEF progressively declined between 3 to 5 years post baseline visit. In a multivariate analysis, the use of cardioprotective drugs trended towards positively impacting cardiac measures while loss of ambulation and baseline age were associated with negative impact. Eight out of 17 cardiac parameters reached a minimal clinically important difference with a threshold of 1/3 standard deviation. Conclusion The study shows a worsening of circumferential strain in dystrophic myocardium. The findings emphasize the significance of early and longitudinal assessment of cardiac function in DMD and identify early biomarkers of cardiac dysfunction to help design clinical trials to mitigate cardiac pathology. This study provides valuable non-invasive and non-contrast based natural history data of cardiac changes which can be used to design clinical trials or interpret the results of current trials aimed at mitigating the effects of decreased cardiac function in DMD.

Prognostic Utility of Cardiovascular Magnetic Resonance–Based Phenotyping in Patients With Muscular Dystrophy

“… 17 , 23 , 24 Several studies have examined the role of myocardial strain in patients with MD. 25 , 26 , 27 , 28 , 29 Of particular relevance, a recent study also applied a 3D strain analysis technique to study conventional, geometry‐dependent measures in 111 patients with a broad range of neuromuscular diseases inclusive of, but not limited, to MD. 29 Similar to our study, they observed both 3D‐GCS and 3D‐GRS are associated with the presence of replacement fibrosis.…”

“… 22 Recognizing LVEF is a well‐established prognostic marker in patients with MD, our study provided objective evidence that myocardial strain delivers incremental prognostic value to LVEF in this vulnerable patient population. 27 , 28 Although speckle‐tracking echocardiography can be used for strain‐based evaluations, its performance can be hindered because of limited acoustic windows as a result of scoliosis, obesity, and lung disease, 9 , 30 which are highly prevalent in patients with MD. 5 CMR imaging is the preferred method for myocardial strain analysis as a high‐resolution, accurate, and reproducible alternative to echocardiography, 11 , 31 , 32 which supports the impact of CMR imaging as part of routine clinical care in patients with MD.…”

Mitochondria in Duchenne Muscular Dystrophy-induced Cardiomyopathy: A Prospective Therapeutic Target to Improve Treatment Response

“…CMR strain correlates more closely with CMR LVEF compared to TTE strain (Buddhe et al, 2016). A sensitive marker used to identify cardiac pathology is peak circumferential strain (εcc) at the mid-ventricular level, which can also assess effects of therapeutic interventions on cardiac function and measure the degree of cardiac pathology (Hor et Batra et al, 2022). This measure was able to detect cardiac pathology as early as 5 years of age and the findings of this study revealed the heterogeneity in cardiac progression in patients with DMD (Batra et al, 2022).…”

Cardiovascular Measures of All-Cause Mortality in Duchenne Muscular Dystrophy

“…The LVEF decline is similar to that of prior single and multicenter studies, suggesting that the cohort is generalizable. [16][17][18] Most trials will be 1 or 2 years in duration and a comprehensive understanding of the change in biomarkers over time is necessary to adequately power a trial. Therefore, our data focuses on 1-and 2-year progression in DMD.…”