Inhibition of phosphodiesterase 5 (PDE5) was hypothesized to slow disease progression in Duchenne muscular dystrophy (DMD). Tadalafil, a once-daily PDE5 inhibitor, did not slow loss of ambulation in a phase 3 placebo-controlled trial. This report details the cardiac findings from this study.

Patients with DMD (N = 331) aged 7 to 14 years on stable glucocorticoids were randomized to tadalafil 0.3 mg/kg/day, 0.6 mg/kg/day, or placebo. Ejection fraction (EF), fractional shortening, and M-mode ventricular dimensions were measured on echocardiograms. 12-lead ECGs were centrally evaluated for heart rate and intervals, and qualitative diagnoses. Vital signs and unsolicited adverse events were collected throughout the study. Cardiac MRI (CMR) was collected in a subset of 27 patients. Z-scores for ventricular dimensions and volumes were calculated based on published age-normative reference values. Treatment differences for change in continuous ECG parameters and vital signs were compared using Wilcoxon rank-sum tests. Echocardiogram and CMR parameters were analyzed with an ANCOVA model.

Tadalafil had no adverse effects on echocardiographic left ventricular (LV) EF or fractional shortening, ECG findings, or vital signs. Mean diastolic LV internal dimension (LVIDd) was increased in the tadalafil 0.6 mg/kg group versus placebo at Week 24 (+ 0.13 cm, p =.019) and Week 48 (+ 0.18 cm, p =.008), with a similar pattern observed for LV systolic dimensions (LVIDs). Mean LV end diastolic volume (EDV) measured by CMR also increased at Week 48 in the tadalafil 0.3 mg/kg (+ 13.0 ml, p =.047 vs. placebo) and 0.6 mg/kg (+ 12.0 ml, p =.08 vs. placebo) groups, with numerically smaller increases in LV EDV and commensurate increases in stroke volume and cardiac output. Z-scores for LVIDd and LV EDV were generally below the normal range at baseline and increased toward or within the normal range in the tadalafil groups but not in the placebo group.

No adverse effects of tadalafil on cardiovascular function were evident based on adverse events, echocardiograms, ECG, or vital sign measurements through 48 weeks in patients with DMD. The small mean increases in LVID and LV volume observed with tadalafil are consistent with PDE5 inhibitor pharmacology, but their clinical relevance in the context of LV tonic contraction in DMD is unknown and deserve further study.

NCT01865084 (first registration date: 24-May-2013).

Background/Objectives: Duchenne Muscular Dystrophy (DMD) is a prevalent fatal genetic disorder, and heart failure is the leading cause of mortality. Peak left ventricular (LV) circumferential strain (Ecc), twist, and circumferential-longitudinal shear angle (θCL) are promising biomarkers for the improved and early diagnosis of incipient heart failure. Our goals were as follows: 1) to characterize a spectrum of functional and rotational LV biomarkers in boys with DMD compared with healthy age-matched controls; and 2) to identify LV biomarkers of early cardiomyopathy in the absence of abnormal LVEF or LGE. Methods: Boys with DMD (N = 43) and age-matched healthy volunteers (N = 16) were prospectively enrolled and underwent a 3T CMR exam after obtaining informed consent. Breath-held MRI tagging was used to estimate left ventricular Ecc at the mid-ventricular level as well as the twist, torsion, and θCL between basal and apical LV short-axis slices. A two-tailed t-test with unequal variance was used to test group-wise differences. Multiple comparisons were performed with Holm-Sidak post hoc correction. Multiple-regression analysis was used to test for correlations among biomarkers. A binomial logistic regression model assessed each biomarker's ability to distinguish the following: (1) healthy volunteers vs. DMD patients, (2) healthy volunteers vs. LGE(-) DMD patients, and (3) LGE(-) DMD patients vs. LGE(+) DMD patients. Results: There was a significant impairment in the peak mid-wall Ecc [-17.0 ± 4.2% vs. -19.5 ± 1.9%, p < 7.8 × 10-3], peak LV twist (10.4 ± 4.3° vs. 15.6 ± 3.1°, p < 8.1 × 10-4), and peak LV torsion (2.03 ± 0.82°/mm vs. 2.8 ± 0.5°/mm, p < 2.6 × 10-3) of LGE(-) DMD patients when compared to healthy volunteers. There was a further significant reduction in the Ecc, twist, torsion, and θCL for LGE(+) DMD patients when compared to LGE(-) DMD patients. In the LGE(+) DMD patients, age significantly correlated with LVEF (r2 = 0.42, p = 9 × 10-3), peak mid-wall Ecc (r2 = 0.27, p = 0.046), peak LV Twist (r2 = 0.24, p = 0.06), peak LV torsion (r2 = 0.28, p = 0.04), and peak LV θCL (r2 = 0.23, p = 0.07). In the LGE(-) DMD patients, only the peak mid-wall Ecc was significantly correlated with age (r2 = 0.25, p = 0.006). The peak LV twist outperformed the peak mid-wall LV Ecc and EF in distinguishing DMD patients from healthy volunteer groups (AUC = 0.88, 0.80, and 0.72), as well as in distinguishing LGE(-) DMD patients from healthy volunteers (AUC = 0.83, 0.74, and 0.62). The peak LV twist and peak mid-wall LV Ecc performed similarly in distinguishing the LGE(-) and LGE(+) DMD cohorts (AUC = 0.74, 0.77, and 0.79). Conclusions: The peak mid-wall LV Ecc, peak LV twist, peak LV torsion, and peak LV θCL were significantly impaired in advance of the decreased LVEF and the development of focal myocardial fibrosis in boys with DMD and therefore were apparent prior to significant irreversible injury.

Cardiac dysfunction is a leading cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). Left atrial (LA) function is a poorly understood concept in this patient population, and research suggests underlying structural changes that could affect atrial function. Cardiac magnetic resonance (CMR) imaging may provide an important non-invasive approach to evaluating LA function. This study was a single center retrospective review of consecutive CMR studies over a 1 year period comparing LA phasic function within a cohort of DMD patients, and to those with structurally and functionally normal hearts. LA strain measurements including global reservoir, conduit, boost-pump strain, and LA volumes were obtained retrospectively. Spearman correlation analyses were performed on atrial strain measurements. 107 DMD and 79 normal CMR studies were included. The DMD cohort had worse systolic function (p < 0.001), smaller indexed max LA and left ventricular (LV) volumes (p < 0.001), and greater LA emptying fraction (p < 0.001). In the DMD cohort, emptying fraction decreased with advanced patient age (p < 0.001) and diminishing systolic function (p < 0.001). DMD patients with moderate or severe LV dysfunction demonstrated lower LA emptying fraction (p = 0.002), more impaired 2-chamber LA reservoir (p = 0.003), and LA pump (p = 0.006) and conduit strain (p = 0.018). DMD patients with preserved function have lower indexed LA volumes with higher LA emptying fractions than controls. Progression of disease and age is associated with decreased LA emptying fraction with early manifestations in reservoir and conduit strain. These findings suggest that strain markers of LA compliance and early left ventricular relaxation are associated with worsening cardiomyopathy in the DMD population.

Background: In boys with Duchenne muscular dystrophy (DMD), cardiomyopathy has become the primary cause of death. Although both positive late gadolinium enhancement (LGE) and reduced left ventricular ejection fraction (LVEF) are late findings in a DMD cohort, LV end-systolic circumferential strain at middle wall (Ecc) serves as a biomarker for detecting early impairment in cardiac function associated with DMD. However, Ecc derived from cine Displacement Encoding with Stimulated Echoes (DENSE) has not been quantified in boys with DMD. We aim to: (1) use cine DENSE to quantify regional Ecc in LGE negative (-) boys with DMD and healthy controls; and (2) compare Ecc with LVEF in terms of differentiating DMD boys with LGE (-) from healthy boys. Methods: 10 LGE (-) boys with DMD and 12 healthy boys were enrolled prospectively in an IRB-approved study for CMR at 3T. Navigator-gated cine DENSE was used to obtain short-axis mid-ventricular data and estimate global and regional Ecc. Group-wise differences were tested via a Wilcoxon rank-sum test. Within-group differences were tested via a Skillings-Mack test followed by pairwise Wilcoxon signed-rank tests. A binomial logistic regression model was adopted to differentiate between DMD boys with LGE (-) and healthy boys. Results: When compared to healthy boys, LGE (-) boys with DMD demonstrated significantly impaired septal Ecc [-0.13 (0.01) vs. -0.16 (0.03), p = 0.019]. In comparison to the Ecc in other segments, both groups of boys exhibited significantly reduced septal Ecc and significantly elevated lateral Ecc. Septal Ecc outperformed LVEF in distinguishing DMD boys with LGE (-) from healthy boys. Conclusions: Reduced septal Ecc may serve as an early indicator of cardiac involvement in LGE (-) DMD boys prior to reduced LVEF and a positive LGE finding.

The aim of this study is to assess the effectiveness of conventional and two additional functional markers derived from standard cardiac magnetic resonance (CMR) images in detecting the occurrence of late gadolinium enhancement (LGE) in patients with secondary cardiac amyloidosis (CA) related to multiple myeloma (MM). This study retrospectively included 32 patients with preserved ejection fraction (EF) who had MM-CA diagnosed consecutively. Conventional left ventricular (LV) function markers and two additional functional markers, namely myocardial contraction fraction (MCF) and LV long-axis strain (LAS), were obtained using commercial cardiac post-processing software. Logistic regression analyses and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive performances. (1) There were no notable distinctions in clinical features between the LGE+ and LGE- groups, with the exception of a reduced systolic blood pressure in the former (105.60 ± 18.85 mmHg vs. 124.50 ± 20.95 mmHg, P = 0.022). (2) Patients with MM-CA presented with intractable heart failure with preserved ejection fraction (HFpEF). The LVEF in the LGE+ group exhibited a greater reduction (54.27%, IQR 51.59-58.39%) in comparison to the LGE- group (P < 0.05). And MM-CA patients with LGE+ had significantly higher LVMI (90.15 ± 23.69 g/m2), lower MCF (47.39%, IQR 34.28-54.90%), and the LV LAS were more severely damaged (- 9.94 ± 3.42%) than patients with LGE- (all P values < 0.05). (3) The study found that MCF exhibited a significant independent association with LGE, as indicated by an odds ratio of 0.89 (P < 0.05). The cut-off value for MCF was determined to be 64.25% with a 95% confidence interval ranging from 0.758 to 0.983. The sensitivity and specificity of this association were calculated to be 95% and 83%, respectively. MCF is a simple reproducible predict marker of LGE in MM-CA patients. It is a potentially CMR-based method that promise to reduce scan times and costs, and boost the accessibility of CMR.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene, resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with the development of cardiomyopathy-the leading cause of death-inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD; treatment is aimed at delaying disease progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to the development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial dysfunction is thought to be a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but the effects of such agents on cardiac function remain unclear. The synergistic integration of small molecule- and gene-target-based drugs with metabolic-, immune-, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.

Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials.

Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (P<0.0001). Rate of increase in indexed left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (P=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups.

Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.

Cine Cardiac Magnetic Resonance (CMR) is the gold standard for cardiac function evaluation, incorporating ejection fraction (EF) and strain as vital indicators of abnormal deformation. Rare pathologies like Duchenne muscular dystrophies (DMD) are monitored with repeated late gadolinium-enhanced (LGE) CMR for identification of myocardial fibrosis. However, it is judicious to reduce repeated gadolinium exposure and rather employ strain analysis from cine CMR. This solution is limited so far since full strain curves are not comparable between individual cardiac cycles and current practice mainly neglects diastolic deformation patterns. Our novel Deep Learning-based approach derives strain values aligned by key frames throughout the cardiac cycle. In a reproducibility scenario (57+82 patients), our results reveal five times more significant differences (22 vs. 4) between patients with scar and without, enhancing scar detection by +30%, improving detection of patients with preserved EF by +61%, with an overall sensitivity/specificity of 82/81%.

Poor acoustic windows make interval assessment of systolic function in patients with (Duchenne Muscular Dystrophy) DMD by echocardiography (echo) difficult. Cardiac magnetic resonance imaging (CMR) can be challenging in DMD patients due to study duration and patient discomfort. We developed an abbreviated CMR (aCMR) protocol and hypothesized that aCMR would compare favorably to echo in image quality and clinical utility without significant differences in exam duration, patient satisfaction, and functional measurements.

DMD patients were recruited prospectively to undergo echo and aCMR. Modalities were compared with a global quality assessment score (GQAS), clinical utility score (CUS), and patient satisfaction score (PSS). Results were compared using Wilcoxon signed-rank tests, Spearman correlations, intraclass correlations, and Bland-Altman analyses.

Nineteen DMD patients were included. PSS scores and exam duration were equivalent between modalities, while CUS and GQAS scores favored aCMR. ACMR scored markedly higher than echo in RV visualization and assessment of atrial size. Older age was negatively correlated with echo GQAS and CUS scores, as well as aCMR PSS scores. Higher BMI was positively correlated with aCMR GQAS scores. Nighttime PPV requirement and non-ambulatory status were correlated with worse echo CUS scores. Poor image quality precluding quantification existed in five (26%) echo and zero (0%) aCMR studies. There was moderate correlation between aCMR and echo for global circumferential strain and left ventricular four chamber global longitudinal strain.

The aCMR protocol resulted in improved clinical relevance and quality scores relative to echo, without significant detriment to patient satisfaction or exam duration.

The diagnosis of Duchenne-linked cardiomyopathy may be challenging. Conventional echocardiographic measurements typically show deterioration beyond the second decade. Global longitudinal strain has been proposed as an earlier marker than left ventricular ejection fraction.

A prospective, observational, cross-sectional, case-control study was carried out. Both Duchenne patients and control subjects underwent transthoracic echocardiogram in order to assess left ventricle function. Bayesian linear regression was the main tool for inference. Age effects were parameterised by means of a spline function because of its simplicity to characterise continuous variables and smooth contributions. The posterior distribution of the marginal age effects was used to assess the earliest age of deterioration of each marker.

Sixteen Duchenne patients and twenty-two healthy male subjects were enrolled. On overage, cardiac function measures were found for ejection fraction and longitudinal strain among different groups. Age effects on global longitudinal strain are more reliably found at ages of 6 and above, while ejection fraction starts to deteriorate at an older age. Progressive left ventricular dysfunction in Duchenne patients is one of the key issues and starts at an early age with subtle symptoms.

This cross-sectional study provides supporting evidence that global longitudinal strain is an earlier marker of disease progression than ejection fraction in Duchenne patients.

Duchenne muscular dystrophy (DMD) and related dystrophinopathies are neuromuscular conditions with great unmet medical needs that require the development of effective medical treatments.

To aid sponsors in clinical development of drugs and therapeutic biological products for treating DMD across the disease spectrum by integrating advancements, patient registries, natural history studies, and more into a comprehensive guidance.

This guidance emerged from collaboration between the FDA, the Duchenne community, and industry stakeholders. It entailed a structured approach, involving multiple committees and boards. From its inception in 2014, the guidance underwent revisions incorporating insights from gene therapy studies, cardiac function research, and innovative clinical trial designs.

The guidance provides a deeper understanding of DMD and its variants, focusing on patient engagement, diagnostic criteria, natural history, biomarkers, and clinical trials. It underscores patient-focused drug development, the significance of dystrophin as a biomarker, and the pivotal role of magnetic resonance imaging in assessing disease progression. Additionally, the guidance addresses cardiomyopathy's prominence in DMD and the burgeoning field of gene therapy.

The updated guidance offers a comprehensive understanding of DMD, emphasizing patient-centric approaches, innovative trial designs, and the importance of biomarkers. The focus on cardiomyopathy and gene therapy signifies the evolving realm of DMD research. It acts as a crucial roadmap for sponsors, potentially leading to improved treatments for DMD.

Dilated cardiomyopathy (DCM) is one of the most common types of non-ischemic cardiomyopathy. DCM is characterized by left ventricle (LV) dilatation and systolic dysfunction without coronary artery disease or abnormal loading conditions. DCM is not a single disease entity and has a complex historical background of revisions and updates to its definition because of its diverse etiology and clinical manifestations. In cases of LV dilatation and dysfunction, conditions with phenotypic overlap should be excluded before establishing a DCM diagnosis. The differential diagnoses of DCM include ischemic cardiomyopathy, valvular heart disease, burned-out hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, and non-compaction. Cardiac magnetic resonance (CMR) imaging is helpful for evaluating DCM because it provides precise measurements of cardiac size, function, mass, and tissue characterization. Comprehensive analyses using various sequences, including cine imaging, late gadolinium enhancement imaging, and T1 and T2 mapping, may help establish differential diagnoses, etiological work-up, disease stratification, prognostic determination, and follow-up procedures in patients with DCM phenotypes. This article aimed to review the utilities and limitations of CMR in the diagnosis and assessment of DCM.

Duchenne muscular dystrophy is a devastating muscle disease characterized by muscle deterioration and cardiomyopathy. The cardiomyopathy is progressive in nature, marked by the accumulation of myocardial scarring and the loss of contractile function. The presence of cardiac disfunction is nearly universal in individuals with Duchenne muscular dystrophy with dysfunction being evident in patients < 10 years of age. In recognition of importance of prophylactic treatment, clinical guidelines recommend beginning treatment of the heart disease in Duchenne muscular dystrophy patients at 10 years of age, even in the absence of cardiac dysfunction. This manuscript evaluates the current practices of treatment of dystrophic cardiomyopathy. We make use of clinical data compiled by the Muscular Dystrophy Association to assess changes in medical management of cardiac disease in Duchenne muscular dystrophy patients in response to changes in guidelines. We find since the issuance of new guidelines Duchenne muscular dystrophy patients receiving cardiac-directed therapy are beginning it at significantly younger ages. However, we show that 64 % of individuals with Duchenne muscular dystrophy are not receiving the recommended cardiac therapies. The underlying causes of this gap in guideline adherence are complex but correcting this deficiency represent a significant opportunity to improve the clinical management of dystrophic cardiomyopathy.

Left ventricular (LV) strain and rotation are emerging functional markers for early detection of LV dysfunction and have been associated with the burden of myocardial fibrosis in several disease states. This study examined the association between LV deformation (i.e., LV strain and rotation) and extent and location of LV myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy (DMD).

34 pediatric patients with DMD underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) to assess LV myocardial fibrosis. Offline CMR feature-tracking analysis was used to assess global and segmental longitudinal and circumferential LV strain, and LV rotation. Patients with fibrosis (n = 18, 52.9%) were older than those without fibrosis (14 ± 3 years (yrs) vs 11 ± 2 yrs., p = 0.01). There was no significant difference in LV ejection fraction (LVEF) between subjects with and without fibrosis (54 ± 6% vs 56 ± 4%, p = 0.18). However, lower endocardial global circumferential strain (GCS), but not LV rotation, was associated with presence of fibrosis (adjusted Odds Ratio 1.25 [95% CI 1.01-1.56], p = 0.04). Both GCS and global longitudinal strain correlated with the extent of fibrosis (r = .52, p = 0.03 and r = .75, p < 0.01, respectively). Importantly, segmental strain did not seem to correspond to location of fibrosis.

A lower global, but not segmental, strain is associated with presence and extent of LV myocardial fibrosis in pediatric DMD patients. Therefore, strain parameters might detect structural myocardial alterations, however currently more research is needed to evaluate its value (e.g., prognostic) in clinical practice.

In Duchenne muscular dystrophy (DMD), the right ventricle (RV) tends to be relatively well preserved, but characterization remains difficult due to its complex architecture. Tissue phase mapping (TPM) is a phase contrast cine MRI technique that allows for multidirectional assessment of myocardial velocities.

To use TPM to elucidate relationships between myocardial structure, function, and clinical variables in DMD.

Retrospective.

A total of 20 patients with muscular dystrophy (median age: 16 years); 18 age-matched normal controls (median age: 15 years).

Three-directional velocity encoded cine gradient echo sequence (TPM) at 1.5 T, balanced steady-state free procession (bSSFP), T1 mapping with extracellular volume (ECV), and late gadolinium enhancement (LGE).

TPM in basal, mid, and apical short-axis planes was performed as part of a standard MRI study with collection of clinical data. Radial, circumferential, and longitudinal velocities (Vr, Vφ, and Vz, respectively) and corresponding time to peak (TTP) velocities were quantified from TPM and used to calculate RV twist as well as intraventricular and interventricular dyssynchrony. The correlations between TPM velocities, myocardial structure/function, and clinical variables were assessed.

Unpaired t-test, Wilcoxon rank-sum test, Bland-Altman analyses were used for comparisons between DMD patients and controls and between DMD subgroups. Pearson's test was used for correlations (r). Significance level: P < 0.05.

Compared to controls, DMD patients had preserved RV ejection fraction (RVEF 53% ± 8%) but significantly increased interventricular dyssynchrony (Vφ: 0.49 ± 0.21 vs. 0.72 ± 0.17). Within the DMD cohort, RV dyssynchrony significantly increased with lower LV ejection fraction (intraventricular Vr and Vz: r = -0.49; interventricular Vz: r = 0.48). In addition, RV intraventricular dyssynchrony significantly increased with older age (Vz: r = 0.67).

RV remodeling in DMD occurs in the context of preserved RVEF. Within DMD, this abnormal RV deformation is associated with older age and decreased LVEF.

4.

Stage 2.

Multicenter studies in pediatric cardiovascular magnetic resonance (CMR) improve statistical power and generalizability. However, a structured process for identifying important research topics has not been developed. We aimed to (1) develop a list of high priority knowledge gaps, and (2) pilot the use of a wiki survey to collect a large group of responses. Knowledge gaps were defined as areas that have been either unexplored or under-explored in the research literature. High priority goals were: (1) feasible and answerable from a multicenter research study, and (2) had potential for high impact on the field of pediatric CMR. Seed ideas were contributed by a working group and imported into a pairwise wiki survey format which allows for new ideas to be uploaded and voted upon ( https://allourideas.org ). Knowledge gaps were classified into 2 categories: 'Clinical CMR Practice' (16 ideas) and 'Disease Specific Research' (22 ideas). Over a 2-month period, 3,658 votes were cast by 96 users, and 2 new ideas were introduced. The 3 highest scoring sub-topics were myocardial disorders (9 ideas), translating new technology & techniques into clinical practice (7 ideas), and normal reference values (5 ideas). The highest priority gaps reflected strengths of CMR (e.g., myocardial tissue characterization; implementation of technologic advances into clinical practice), and deficiencies in pediatrics (e.g., data on normal reference values). The wiki survey format was effective and easy to implement, and could be used for future surveys.

Feature-tracking cardiac magnetic resonance (FT-CMR), with the ability to quantify myocardial deformation, has a unique role in the evaluation of subclinical myocardial abnormalities. This review aimed to evaluate the clinical use of cardiac FT-CMR-based myocardial strain in patients with various systemic diseases with cardiac involvement, such as hypertension, diabetes, cancer-therapy-related toxicities, amyloidosis, systemic scleroderma, myopathies, rheumatoid arthritis, thalassemia major, and coronavirus disease 2019 (COVID-19). We concluded that FT-CMR-derived strain can improve the accuracy of risk stratification and predict cardiac outcomes in patients with systemic diseases prior to symptomatic cardiac dysfunction. Furthermore, FT-CMR is particularly useful for patients with diseases or conditions which are associated with subtle myocardial dysfunction that may not be accurately detected with traditional methods. Compared to patients with cardiovascular diseases, patients with systemic diseases are less likely to undergo regular cardiovascular imaging to detect cardiac defects, whereas cardiac involvement in these patients can lead to major adverse outcomes; hence, the importance of cardiac imaging modalities might be underestimated in this group of patients. In this review, we gathered currently available data on the newly introduced role of FT-CMR in the diagnosis and prognosis of various systemic conditions. Further research is needed to define reference values and establish the role of this sensitive imaging modality, as a robust marker in predicting outcomes across a wide spectrum of patients.

Understanding and effectively treating dystrophin-deficient cardiomyopathy is of high importance for Duchenne muscular dystrophy (DMD) patients due to their prolonged lifespan. We used two-dimensional speckle tracking echocardiography to analyze more deeply the non-uniformity of myocardial strain within the left ventricle during the progression of cardiomyopathy in golden retriever muscular dystrophy (GRMD) dogs.

The circumferential strain (CS) and longitudinal strain (LS) of left ventricular (LV) endocardial, middle and epicardial layers were analyzed from three parasternal short-axis views and three apical views, respectively, in GRMD (n = 22) and healthy control dogs (n = 7) from 2 to 24 months of age.

In GRMD dogs, despite normal global systolic function (normal LV fractional shortening and ejection fraction), a reduction in systolic CS was detected in the three layers of the LV apex but not in the LV middle-chamber and base at 2 months of age. This spatial heterogeneity in CS progressed with age, whereas a decrease in systolic LS could be detected early at 2 months of age in the three layers of the LV wall from three apical views.

Analyzing the evolution of myocardial CS and LS in GRMD dogs reveals spatial and temporal non-uniform alterations of LV myocardial strain, providing new insights into the progression of dystrophin-deficient cardiomyopathy in this relevant model of DMD.

Dilated cardiomyopathy (DCM) is a common cause of non-ischaemic heart failure, conferring high morbidity and mortality, including sudden cardiac death due to systolic dysfunction or arrhythmic sudden death. Within the DCM cohort exists a group of patients with familial disease. In this article we review the pathophysiology and cardiac imaging findings of familial DCM, with specific attention to known disease subtypes. The role of advanced cardiac imaging cardiovascular magnetic resonance is still accumulating, and there remains much to be elucidated. We discuss its potential clinical roles as currently known, with respect to diagnostic utility and risk stratification. Advances in such risk stratification may help target pharmacological and device therapies to those at highest risk.

Cardiomyopathy (CMP) is the most common cause of mortality in Duchenne muscular dystrophy (DMD), though the age of onset and clinical progression vary. We applied a novel 4D (3D + time) strain analysis method using cine cardiovascular magnetic resonance (CMR) imaging data to determine if localized strain metrics derived from 4D image analysis would be sensitive and specific for characterizing DMD CMP.

We analyzed short-axis cine CMR image stacks from 43 DMD patients (median age: 12.23 yrs [10.6-16.5]; [interquartile range]) and 25 male healthy controls (median age: 16.2 yrs [13.3-20.7]). A subset of 25 male DMD patients age-matched to the controls (median age: 15.7 yrs [14.0-17.8]) was used for comparative metrics. CMR images were compiled into 4D sequences for feature-tracking strain analysis using custom-built software. Unpaired t-test and receiver operator characteristic area under the curve (AUC) analysis were used to determine statistical significance. Spearman's rho was used to determine correlation.

DMD patients had a range of CMP severity: 15 (35% of total) had left ventricular ejection fraction (LVEF) > 55% with no findings of myocardial late gadolinium enhancement (LGE), 15 (35%) had findings of LGE with LVEF > 55% and 13 (30%) had LGE with LVEF < 55%. The magnitude of the peak basal circumferential strain, basal radial strain, and basal surface area strain were all significantly decreased in DMD patients relative to healthy controls (p < 0.001) with AUC values of 0.80, 0.89, and 0.84 respectively for peak strain and 0.96, 0.91, and 0.98 respectively for systolic strain rate. Peak basal radial strain, basal radial systolic strain rate, and basal circumferential systolic strain rate magnitude values were also significantly decreased in mild CMP (No LGE, LVEF > 55%) compared to a healthy control group (p < 0.001 for all). Surface area strain significantly correlated with LVEF and extracellular volume (ECV) respectively in the basal (rho = - 0.45, 0.40), mid (rho = - 0.46, 0.46), and apical (rho = - 0.42, 0.47) regions.

Strain analysis of 3D cine CMR images in DMD CMP patients generates localized kinematic parameters that strongly differentiate disease from control and correlate with LVEF and ECV.

Cardiomyopathy (CM) is the leading cause of death for individuals with Duchenne muscular dystrophy (DMD). While DMD CM progresses rapidly and fatally for some in teenage years, others can live relatively symptom-free into their thirties or forties. Because CM progression is variable, there is a critical need for biomarkers to detect early onset and rapid progression. Despite recent advances in imaging and analysis, there are still no reliable methods to detect the onset or progression rate of DMD CM. Cardiac strain imaging is a promising technique that has proven valuable in DMD CM assessment, though much more work has been done in adult CM patients. In this review, we address the role of strain imaging in DMD, the mechanical and functional parameters used for clinical assessment, and discuss the gaps where emerging imaging techniques could help better characterize CM progression in DMD. Prominent among these emerging techniques are strain assessment from 3D imaging and development of deep learning algorithms for automated strain assessment. Improved techniques in tracking the progression of CM may help to bridge a crucial gap in optimizing clinical treatment for this devastating disease and pave the way for future research and innovation through the definition of robust imaging biomarkers and clinical trial endpoints.

We provide succinct, evidence-based and/or consensus-based best practice guidance for the cardiac care of children living with Duchenne muscular dystrophy (DMD) as well as recommendations for screening and management of female carriers of mutations in the DMD-gene.

Initiated by an expert working group of UK-based cardiologists, neuromuscular clinicians and DMD-patient representatives, draft guidelines were created based on published evidence, current practice and expert opinion. After wider consultation with UK-cardiologists, consensus was reached on these best-practice recommendations for cardiac care in DMD.

The resulting recommendations are presented in the form of a succinct care pathway flow chart with brief justification. The guidance signposts evidence on which they are based and acknowledges where there have been differences in opinion. Guidelines for cardiac care of patients with more advanced cardiac dystrophinopathy at any age have also been considered, based on the previous published work of Quinlivan et al and are presented here in a similar format. The recommendations have been endorsed by the British Cardiovascular Society.

These guidelines provide succinct, reasoned recommendations for all those managing paediatric patients with early or advanced stages of cardiomyopathy as well as females with cardiac dystrophinopathy. The hope is that this will result in more uniform delivery of high standards of care for children with cardiac dystrophinopathy, so improving heart health into adulthood through timely earlier interventions across the UK.

Cardiovascular magnetic resonance (CMR) has been utilized in the management and care of pediatric patients for nearly 40 years. It has evolved to become an invaluable tool in the assessment of the littlest of hearts for diagnosis, pre-interventional management and follow-up care. Although mentioned in a number of consensus and guidelines documents, an up-to-date, large, stand-alone guidance work for the use of CMR in pediatric congenital 36 and acquired 35 heart disease endorsed by numerous Societies involved in the care of these children is lacking. This guidelines document outlines the use of CMR in this patient population for a significant number of heart lesions in this age group and although admittedly, is not an exhaustive treatment, it does deal with an expansive list of many common clinical issues encountered in daily practice.

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.

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).

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.

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.

Cardiovascular magnetic resonance has been utilized in the management and care of pediatric patients for nearly 40 years. It has evolved to become an invaluable tool in the assessment of the littlest of hearts for diagnosis, pre-interventional management and follow-up care. Although mentioned in a number of consensus and guidelines documents, an up-to-date, large, stand-alone guidance work for the use of cardiovascular magnetic resonance in pediatric congenital 36 and acquired 35 heart disease endorsed by numerous Societies involved in the care of these children is lacking. This guidelines document outlines the use of cardiovascular magnetic resonance in this patient population for a significant number of heart lesions in this age group and although admittedly, is not an exhaustive treatment, it does deal with an expansive list of many common clinical issues encountered in daily practice.

Hereditary cardiomyopathy comprises a heterogeneous group of diseases of the cardiac muscle that are characterized by the presence of genetic mutations. Cardiac MRI is central to evaluation of patients with cardiomyopathy owing to its ability to allow evaluation of many different tissue properties in a single examination. For example, cine MRI is the standard of care for assessment of myocardial structure and function. It clearly shows regions of asymmetric wall thickening that are typical of hypertrophic cardiomyopathy and allows it to be differentiated from other hereditary disorders such as Fabry disease or transthyretin cardiac amyloidosis that produce concentric hypertrophy. Late gadolinium enhancement provides a different tissue property and allows these latter two causes of concentric hypertrophy to be distinguished on the basis of their enhancement appearances (Fabry disease shows midwall basal inferolateral enhancement, and amyloidosis shows global subendocardial enhancement). Native T1 mapping may similarly allow differentiation between Fabry disease and amyloidosis without the use of contrast material. T2*-weighted MRI is important in the detection and quantification of iron overload cardiomyopathy. Other hereditary entities for which comprehensive MRI has proven essential include Danon disease, familial dilated cardiomyopathy, hereditary muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy, and ventricular noncompaction. As a result of the diagnostic power of cardiac MRI, cardiac MRI examinations are being requested with increasing frequency, not only in academic centers but also in community practices. The genetic background, pathophysiologic characteristics, and clinical presentation of patients with hereditary cardiomyopathy are described; the characteristic cardiac MRI features of hereditary cardiomyopathy are discussed; and the role of MRI in risk stratification, treatment, and prognostication in patients with cardiomyopathy is reviewed. ^©RSNA, 2022 Online supplemental material is available for this article.

Cardiomyopathy is an important cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD). Early diagnosis is a prerequisite for timely institution of cardioprotective therapies.

We compared cardiac MRI (CMRI) with transthoracic echocardiography (TTE) including tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for diagnosis of cardiomyopathy in early ambulatory boys with DMD.

This cross-sectional study was conducted between June 2018 and December 2020. Consecutive boys between 7 and 15 years of age with DMD were enrolled. Percentage ejection fraction (EF), fractional shortening, wall motion abnormalities, early diastolic mitral annulus velocity (Ea), medial mitral annulus ratio (E/Ea), and global strain were measured with STE. CMRI-derived EF, segmental hypokinesia, and late gadolinium enhancement (LGE) were studied and compared.

A total of 38 ambulatory boys with DMD were enrolled. The mean age was 8.8 ± 1.6 years, and none had clinical features suggestive of cardiac dysfunction. In the TTE, EF was ≤55% in 5 (15%), FS was ≤28% in 3 (9%), and one each had left ventricular wall thinning and wall hypokinesia. In TDI, none had diastolic dysfunction, and STE showed reduced global strain of < 18% in 3 (9%) boys. CMRI-derived EF was ≤55% in 20 (53%) boys and CMRI showed the presence of left ventricular wall hypokinesia in 9 (24%) and LGE in 4 (11%) boys.

Cardiomyopathy remains clinically asymptomatic among early ambulatory boys with DMD. A significantly higher percentage of boys revealed early features of DMD-related cardiomyopathy in CMRI in comparison with echocardiography.

Muscular dystrophies are inherited disorders sharing similar clinical features and dystrophic changes on muscle biopsy. Duchenne muscular dystrophy is the most common inherited muscle disease of childhood, and Becker muscular dystrophy is a milder allelic variant with a slightly lower prevalence. Myotonic dystrophy is the most frequent form in adults. Cardiac magnetic resonance is the gold standard technique for the quantification of cardiac chamber volumes and function, and also enables a characterisation of myocardial tissue. Most cardiac magnetic resonance studies in the setting of muscular dystrophy were carried out at single centres, evaluated small numbers of patients and used widely heterogeneous protocols. Even more importantly, those studies analysed more or less extensively the patterns of cardiac involvement, but usually did not try to establish the added value of cardiac magnetic resonance to standard echocardiography, the evolution of cardiac disease over time and the prognostic significance of cardiac magnetic resonance findings. As a result, the large and heterogeneous amount of information on cardiac involvement in muscular dystrophies cannot easily be translated into recommendations on the optimal use of cardiac magnetic resonance. In this review, whose targets are cardiologists and neurologists who manage patients with muscular dystrophy, we try to summarise cardiac magnetic resonance findings in patients with muscular dystrophy, and the results of studies evaluating the role of cardiac magnetic resonance as a tool for diagnosis, risk stratification and follow-up. Finally, we provide some practical recommendations about the need and timing of cardiac magnetic resonance examination for the management of patients with muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a recessive hereditary myopathy due to deficiency of functional dystrophin. Current therapeutic interventions need more investigation to slow down the progression of skeletal and cardiac muscle weakness. In humans, there is a lack of an adapted training program. In animals, the murine Mdx model with a DBA/2J background (D2-mdx) was recently suggested to present pathological features closer to that of humans. In this study, we characterized skeletal and cardiac muscle functions in males and females D2-mdx mice compared to control groups. We also evaluated the impact of high intensity interval training (HIIT) in these muscles in females and males. HIIT was performed 5 times per week during a month on a motorized treadmill. Specific maximal isometric force production and weakness were measured in the tibialis anterior muscle (TA). Sedentary male and female D2-mdx mice produced lower absolute and specific maximal force compared to control mice. Dystrophic mice showed a decline of force generation during repetitive stimulation compared to controls. This reduction was greater for male D2-mdx mice than females. Furthermore, trained D2-mdx males showed an improvement in force generation after the fifth lengthening contraction compared to sedentary D2-mdx males. Moreover, echocardiography measures revealed a decrease in left ventricular end-diastolic volume, left ventricular ejection volume and left ventricular end-diastolic diameter in sedentary male and female D2-mdx mice. Overall, our results showed a serious muscle function alteration in female and male D2-mdx mice compared to controls. HIIT may delay force loss especially in male D2-mdx mice.

Background Phenylketonuria is the most common inborn error of amino acid metabolism, where oxidative stress and collateral metabolic abnormalities are likely to cause cardiac structural and functional modifications. We aim herein to characterize the cardiac phenotype of adult subjects with phenylketonuria using advanced cardiac imaging. Methods and Results Thirty-nine adult patients with phenylketonuria (age, 30.5±8.7 years; 10-year mean phenylalanine concentration, 924±330 µmol/L) and 39 age- and sex-matched healthy controls were investigated. Participants underwent a comprehensive cardiac magnetic resonance and echocardiography examination. Ten-year mean plasma levels of phenylalanine and tyrosine were used to quantify disease activity and adherence to treatment. Patients with phenylketonuria had thinner left ventricular walls (septal end-diastolic thickness, 7.0±17 versus 8.8±1.7 mm [P<0.001]; lateral thickness, 6.1±1.4 versus 6.8±1.2 mm [P=0.004]), more dilated left ventricular cavity (end-diastolic volume, 87±14 versus 80±14 mL/m² [P=0.0178]; end-systolic volume, 36±9 versus 29±8 mL/m² [P<0.001]), lower ejection fraction (59±6% versus 64±6% [P<0.001]), reduced systolic deformation (global circumferential strain, -29.9±4.2 % versus -32.2±5.0 % [P=0.027]), and lower left ventricular mass (38.2±7.9 versus 47.8±11.0 g/m² [P<0.001]). T1 native values were decreased (936±53 versus 996±26 ms [P<0.001]), with particular low values in patients with phenylalanine >1200 µmol/L (909±48 ms). Both mean phenylalanine (P=0.013) and tyrosine (P=0.035) levels were independently correlated with T1; and in a multiple regression model, higher phenylalanine levels and higher left ventricular mass associate with lower T1. Conclusions Cardiac phenotype of adult patients with phenylketonuria reveals some traits of an early-stage cardiomyopathy. Regular cardiology follow-up, tighter therapeutic control, and prophylaxis of cardiovascular risk factors, in particular dyslipidemia, are recommended.

Dystrophin is a large protein serving as local scaffolding repetitively bridging cytoskeleton and the outside of striated muscle cell. As such dystrophin is a critical brick primarily in dystrophin-associated protein complex (DAGC) and in a larger submembranous unit, costamere. Accordingly, the lack of functional dystrophin laying at the root of Duchenne muscular dystrophy (DMD) drives sarcolemma instability. From this point on, the cascade inevitably leading to the death of myocyte begins. In cardiomyocytes, intracellular calcium overload and related mitochondrial-mediated cell death mainly contribute to myocardial dysfunction and dilation while other protein dysregulation and/or mislocalization may affect electrical conduction system and favor arrhythmogenesis. Although clinically DMD manifests as progressive muscle weakness and skeletal muscle symptoms define characteristic of DMD, it is the heart problem the biggest challenge that most often develop in the form of dilated cardiomyopathy (DCM). Current standards of treatment and recent progress in respiratory care, introduced in most settings in the 1990s, have improved quality of life and median life expectancy to 4th decade of patient's age. At the same time, cardiac causes of death related to DMD increases. Despite preventive and palliative cardiac treatments available, the prognoses remain poor. Direct therapeutic targeting of dystrophin deficiency is critical, however, hindered by the large size of the dystrophin cDNA and/or stochastic, often extensive genetic changes in DMD gene. The correlation between cardiac involvement and mutations affecting specific dystrophin isoforms, may provide a mutation-specific cardiac management and novel therapeutic approaches for patients with CM. Nonetheless, the successful cardiac treatment poses a big challenge and may require combined therapy to combat dystrophin deficiency and its after-effects (critical in DMD pathogenesis). This review locates the multifaceted heart problem in the course of DMD, balancing the insights into basic science, translational efforts and clinical manifestation of dystrophic heart disease.

Cardiomyopathy is the leading cause of mortality in boys with Duchenne muscular dystrophy (DMD). Left ventricular (LV) peak mid-wall circumferential strain (E_cc) is a sensitive early biomarker for evaluating both the subtle and variable onset and the progression of cardiomyopathy in pediatric subjects with DMD. Cine Displacement Encoding with Stimulated Echoes (DENSE) has proven sensitive to changes in E_cc, but its reproducibility has not been reported in a pediatric cohort or a DMD cohort. The objective was to quantify the intra-observer repeatability, and intra-exam and inter-observer reproducibility of global and regional E_cc derived from cine DENSE in DMD patients (N = 10) and age-and sex-matched controls (N = 10). Global and regional E_cc measures were considered reproducible in the intra-exam, intra-observer, and inter-observer comparisons. Intra-observer repeatability was highest, followed by intra-exam reproducibility and then inter-observer reproducibility. The smallest detectable change in E_cc was 0.01 for the intra-observer comparison, which is below the previously reported yearly decrease of 0.013 ± 0.015 in E_cc in DMD patients.

We proposed a novel method called HARP-I, which enhances the estimation of motion from tagged Magnetic Resonance Imaging (MRI). The harmonic phase of the images is unwrapped and treated as noisy measurements of reference coordinates on a deformed domain, obtaining motion with high accuracy using Radial Basis Functions interpolations. Results were compared against Shortest Path HARP Refinement (SP-HR) and Sine-wave Modeling (SinMod), two harmonic image-based techniques for motion estimation from tagged images. HARP-I showed a favorable similarity with both methods under noise-free conditions, whereas a more robust performance was found in the presence of noise. Cardiac strain was better estimated using HARP-I at almost any motion level, giving strain maps with less artifacts. Additionally, HARP-I showed better temporal consistency as a new method was developed to fix phase jumps between frames. In conclusion, HARP-I showed to be a robust method for the estimation of motion and strain under ideal and non-ideal conditions.

Duchenne muscular dystrophy is caused by mutations in the DMD gene, resulting in cardiomyopathy in all affected children by 18 years. Although cardiomyopathy is now the leading cause of mortality in these children, there is ongoing debate regarding timely diagnosis, secondary prevention, and treatment of this condition. The purpose of this study was to use exercise cardiac magnetic resonance imaging in asymptomatic young boys with Duchenne muscular dystrophy to describe their heart function and compare this with healthy controls.

We studied 11 boys with Duchenne muscular dystrophy aged 8.6 to 13.9 years and 11 healthy age- and sex-matched controls.

Compared with the controls, boys with Duchenne muscular dystrophy had lower ejection fraction at rest (57% versus 63%; P = 0.004). During submaximal exercise, they reached similar peak tachycardia but increased their heart rate and cardiac output only half as much as controls (P = 0.003 and P = 0.014, respectively). End-systolic volume remained higher in boys with Duchenne muscular dystrophy both at rest and during exercise. When transthoracic echocardiography was compared with cardiac magnetic resonance imaging, 45% of the echocardiograms had suboptimal or poor views in the Duchenne muscular dystrophy group.

Boys with Duchenne muscular dystrophy had abnormalities in left ventricular systolic function that were exaggerated by exercise stress. Exercise cardiac magnetic resonance imaging is feasible in a select population of children with Duchenne muscular dystrophy, and it has the potential to unmask early signs of cardiomyopathy.

There have been significant improvements in the skeletal muscle and respiratory care for patients with Duchenne muscular dystrophy (DMD) over the last two decades. This has resulted in longer expected survival as many patients will live into their 20s and 30s. This timeline has resulted in a greater proportion of patients experiencing heart failure and cardiac-related mortality. Herein, we describe the current indications for medical therapy for patients with DMD.

Duchene muscular dystrophy (DMD) is a rare but devastating disease resulting in progressive loss of ambulation, respiratory failure, DMD-associated cardiomyopathy (DMD-CM), and premature death. The use of corticosteroids and supportive respiratory care has improved outcomes, such that DMD-CM is now the leading cause of death. Historically, most programs have focused on skeletal myopathy with less attention to the cardiac phenotype. This omission is rather astonishing since patients with DMD possess an absolute genetic risk of developing cardiomyopathy. Unfortunately, heart failure signs and symptoms are vague due to skeletal muscle myopathy leading to limited ambulation. Traditional assessment of cardiac symptoms by the New York Heart Association American College of Cardiology/American Heart Association Staging (ACC/AHA) classification is of limited utility, even in advanced stages. Echocardiographic assessment can detect cardiac dysfunction late in the disease course, but this has proven to be a poor surrogate marker of early cardiovascular disease and an inadequate predictor of DMD-CM. Indeed, one explanation for the paucity of cardiac therapeutic trials for DMD-CM has been the lack of a suitable end-point. Improved outcomes require a better proactive treatment strategy; however, the barrier to treatment is the lack of a sensitive and specific tool to assess the efficacy of treatment. The use of cardiac imaging has evolved from echocardiography to cardiac magnetic resonance imaging to assess cardiac performance. The purpose of this article is to review the role of cardiac imaging in characterizing the cardiac natural history of DMD-CM, highlighting the prognostic implications and an outlook on how this field might evolve in the future.