David A. Parra

Evaluation of Echocardiographic Measures of Left Ventricular Function in Patients with Duchenne Muscular Dystrophy: Assessment of Reproducibility and Comparison to Cardiac Magnetic Resonance Imaging

BACKGROUND Patients with Duchenne muscular dystrophy (DMD) require frequent imaging to assess left ventricular (LV) function. Poor imaging windows can limit the diagnostic utility of echocardiography. Cardiac magnetic resonance imaging (CMR) is the gold standard for the assessment of LV function but has not been universally adopted in patients with DMD. The study objectives were (1) to evaluate the reproducibility of echocardiographic measures of LV function, (2) to evaluate which echocardiographic methods correlate best with CMR LV ejection fraction (LVEF), and (3) to evaluate whether CMR provides additional value compared with echocardiography. METHODS Twenty-eight participants with DMD prospectively underwent echocardiography and CMR. Two blinded readers measured fractional shortening from M-mode and two-dimensional images and LVEF using four-chamber, biplane Simpson, 5/6 area-length, and three-dimensional methods. Speckle-tracking echocardiography was used to analyze circumferential strain. Readers subjectively rated function and segmental wall motion. Agreement was assessed using intraclass correlation coefficients, Bland-Altman plots, Spearman correlation, and weighted κ. RESULTS Two-dimensional fractional shortening and 5/6 area-length LVEF had the best combination of reproducibility and correlation with CMR LVEF, though both misclassified approximately 20% as either normal or abnormal function. Other measures of LV function were less reproducible, with worse correlations with CMR LVEF. Thirty-seven percent of segments not visible on echocardiography were believed to have wall motion abnormalities by CMR. CONCLUSIONS Two-dimensional fractional shortening and 5/6 area-length LVEF represent the most accurate and reproducible echocardiographic measures of LV function in patients with DMD. CMR should be considered when neither of these techniques is measurable or when it is necessary to detect more subtle cardiovascular changes.

Left Ventricular Cardiac Fibroma in a Child Presenting with Ventricular Tachycardia

Cardiac tumors in children are rare. Although most are histologically benign, they can be associated with life-threatening arrhythmias and sudden death. We report a 7-year-old boy, with a first episode of symptomatic tachycardia, who was found to have a left ventricular (LV) fibroma. He had a normal echocardiogram prior to an electrophysiology study, which revealed a sustained monomorphic ventricular tachycardia and a radio-opacity near the LV apex. These findings prompted a cardiac MRI, which demonstrated a discrete mass on his LV apex and free wall. Our case emphasizes that structural heart disease should be aggressively pursued in children presenting with ventricular tachycardia.

Evaluation of tricuspid annular plane systolic excursion measured with cardiac MRI in children with tetralogy of Fallot

BACKGROUND Aneurysmal dilation of the right ventricular outflow tract complicates assessment of right ventricular function in patients with repaired tetralogy of Fallot. Tricuspid annular plane systolic excursion is commonly used to estimate ejection fraction. We hypothesised that tricuspid annular plane systolic excursion measured by cardiac MRI approximates global and segmental right ventricular function, specifically right ventricular sinus ejection fraction, in children with repaired tetralogy of Fallot. METHODS Tricuspid annular plane systolic excursion was measured retrospectively on cardiac MRIs in 54 patients with repaired tetralogy of Fallot. Values were compared with right ventricular global, sinus, and infundibular ejection fractions. Tricuspid annular plane systolic excursion was indexed to body surface area, converted into a fractional value, and converted into published paediatric Z-scores. RESULTS Tricuspid annular plane systolic excursion measurements had good agreement between observers. Right ventricular ejection fraction did not correlate with the absolute or indexed tricuspid annular plane systolic excursion and correlated weakly with fractional tricuspid annular plane systolic excursion (r=0.41 and p=0.002). Segmental right ventricular function did not appreciably improve correlation with any of the tricuspid annular plane systolic excursion measures. Paediatric Z-scores were unable to differentiate patients with normal and abnormal right ventricular function. CONCLUSIONS Tricuspid annular plane systolic excursion measured by cardiac MRI correlates poorly with global and segmental right ventricular ejection fraction in children with repaired tetralogy of Fallot. Tricuspid annular plane systolic excursion is an unreliable approximation of right ventricular function in this patient population.

Myocardial T1 and T2 Mapping in Duchenne muscular dystrophy: characterization of late gadolinium Eenhancement

Background In the current era, cardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Pathological studies demonstrate myocardial fibrosis that begins in the subepicardium of the left ventricular free wall. Late gadolinium enhancement (LGE) images demonstrate a similar pattern of extracellular matrix (ECM) expansion. However, based on a baseline pro-inflammatory state and reports of possible myocarditis in DMD subjects, it is unclear whether this LGE represents edema or fibrosis. Our objective was to use extracellular volume (ECV) and T2 mapping to better characterize LGE in boys with DMD.

Left ventricular function by echocardiography correlates poorly with cardiac MRI measures in Duchenne muscular dystrophy

Background Duchenne muscular dystrophy (DMD) causes skeletal muscle weakness and cardiomyopathy (CM). Current recommendations are for annual left ventricular (LV) function assessment after age 10 years. Although echocardiographic image quality in DMD patients can be affected by scoliosis and adipose tissue, recent reviews recommend echocardiography as the standard imaging modality. We hypothesized that objective and subjective LV functional assessment by echocardiography in DMD is suboptimal compared to cardiac MRI (CMR).

Effect of Weight Extremes on Ventricular Volumes and Myocardial Strain in Repaired Tetralogy of Fallot as Measured by CMR

Pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF-TAP) is often based on cardiac MRI (CMR) right ventricular (RV) volumes indexed to body surface area (BSA). Weight extremes result in increased patient morbidity and affect indexed measurements. We hypothesized that patients with rTOF-TAP at extremes of weight have (1) over- or underestimated indexed volumes and (2) altered parameters of cardiac function. CMRs in patients with rTOF-TAP were retrospectively reviewed; analysis included right and left ventricular (LV) volumes and ejection fractions (EF) and peak global LV circumferential strain (εcc) from myocardial tagged images. Indexed volumes were recalculated using ideal BSA. Weight categories were assigned: underweight, appropriate weight, overweight, and obese. Linear regression models with weight category, spline of age, and gender were created to assess the association of weight and parameters of volume and function. When RV volumes were corrected for ideal BSA, 11 (31%) additional overweight and obese patients met published criteria for PVR and 3 (38%) underweight patients no longer met criteria. Obese and overweight patients had larger absolute LV and RV diastolic volumes, but no difference in volumes indexed to ideal BSA. Modeling demonstrated no difference in LVEF or RVEF by weight categories but significant differences in global LV εcc. Extremes of body weight may result in inappropriate timing of PVR. Extremes of weight lead to abnormalities in global LV εcc. Although clinical implications of abnormal εcc are unclear, these patients may be at higher risk for early ventricular dysfunction.

Bidirectional Inferior Cavopulmonary Anastomosis: Pre-Fontan Interim Palliation

We report a novel method of constructing an extracardiac bidirectional inferior cavopulmonary anastomosis. Our patient was a 4-month-old girl with complex single-ventricle anatomy and a small-caliber superior vena cava. A direct anastomosis from the inferior vena cava to the main pulmonary artery was constructed by using all autologous tissue. The resulting pathway remained patent and exhibited growth with age. Furthermore, a pulmonary arteriovenous malformation did not develop. This case demonstrates how a bidirectional inferior cavopulmonary anastomosis is feasible in the human and can provide similar hemodynamic results as the bidirectional superior cavopulmonary anastomosis.

Relation of increased BMI to left atrial volume in repaired tetralogy of Fallot patients

Background Contemporary care of repaired tetralogy of Fallot (rTOF) patients is directed toward detection and avoidance of long-term morbidity and mortality, of which arrhythmias play an important role. Increased arrhythmia risk in the rTOF population has been associated with ventricular dysfunction and chamber dilation. In adults without congenital heart disease, obesity has been related to left atrium (LA) dilation and further associated to arrhythmias. The effect of obesity on LA size, and in turn on arrhythmia, in rTOF patients has not been studied. If related, obesity would represent a modifiable risk factor in this population. We hypothesized that LA dilation is associated with obesity in rTOF patients.

Obesity leads to underestimation of ventricular volumes and abnormal myocardial strain in repaired Tetralogy of Fallot as measured by cardiac MRI

Background Obesity is an increasing epidemic that has not spared children and adults with congenital heart disease. Patients with repaired tetralogy of Fallot with trans-annular patch (rTOF-TAP) have significant pulmonary insufficiency and right ventricular (RV) enlargement. Recommendations for pulmonary valve replacement (PVR) include body surface area (BSA)-indexed RV end diastolic volume (RVEDVi) >150 ml/m2 or indexed RV end systolic volume (RVESVi) >80 ml/m2, estimated by cardiac MRI (CMR). We hypothesized that: 1) overweight and obese patients with rTOF-TAP have underestimated indexed ventricular volumes when compared to volumes indexed to ideal BSA and 2) these patients have altered parameters of cardiac function compared to weight appropriate patients.

T1 mapping is abnormal before decline in EF in patients with Becker and Duchenne muscular dystrophy

Background Patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy (CM) at an earlier age compared to Becker muscular dystrophy (BMD), but the age of onset within each diagnosis is variable. A method to predict CM onset associated with dystrophinopathy could alter therapeutic approaches and improve outcomes. Shortened post-contrast T1 relaxation times are an early marker of myocardial fibrosis and are abnormal in patients with DMD as described in our previous work. To our knowledge, T1 mapping has not been evaluated in BMD patients. We hypothesized that patients with BMD would also have abnormal T1 times and that these abnormalities would precede LV dysfunction. Methods Twenty-six CMR scans from these 2 dystrophinopathy populations (N=5 BMD and N=21 DMD) were compared with 10 CMR scans from control patients without cardiovascular disease. T1 maps were created from the Look-Locker sequence, obtained 10 minutes after gadolinium injection, using MRMap. Using MatLab, T1 times were obtained for every voxel in 6 standard myocardial segments in the short axis at the level of the papillary muscles. Mean T1 times were compared between BMD, DMD and controls using a Kruskal Wallis test. A subset of patients with normal LVEF and dystrophinopathy (BMD or DMD) was compared to controls using a Mann-Whitney U test. Results The mean age of patients was 25.4 ± 8.1 years in the BMD group, 15.7 ± 4.3 years in the DMD group, and 16.9 ± 1.3 years in controls. One patient with BMD and 13 patients with DMD had LVEF < 55%. Two patients from both BMD and DMD had LV dilatation. BMD and DMD patients had significantly shorter mean postcontrast T1 compared with controls (BMD: 355 ms, 95% CI (314, 395), DMD:357 ms, 95% CI (323, 390), control: 420 ms, 95% CI (389, 451), p=0.035) (Figure 1). The subset of BMD and DMD patients and normal LVEF also had a significant decrease in post-contrast T1 when compared to controls (-52.4 ms, 95% CI (-7.2, -97.5), p=0.018) (Figure 2). Conclusions Myocardial post-contrast T1 relaxation times in BMD and DMD are significantly shorter than in controls. They remain significantly decreased in the subset of patients with normal LVEF, suggesting that CMR may have prognostic utility in detecting subclinical myocardial damage associated with loss of dystrophin prior to a decline in LVEF. Further longitudinal study is necessary to evaluate whether T1 times can predict future onset of CM in BMD and DMD. Funding none.