Comparison of echocardiographic measurements to invasive measurements of diastolic function in infants with single ventricle physiology: a report from the Pediatric Heart Network Infant Single Ventricle Trial.

BACKGROUND: While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis. METHODS: Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman's test. RESULTS: Median age at echocardiogram was 4.6 (range 2.5-7.4) months. Median ventricular end-diastolic pressure was 7 (range 3-19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range -35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = -0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure. CONCLUSION: In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.

Changes in Ventricular Geometry Predict Severity of Right Ventricular Hypertension.

Changes in ventricular geometry are often seen in patients with right ventricular hypertension secondary to pulmonary hypertension (PH). Progressive systolic bowing of the inter-ventricular septum occurs with increasing right ventricular pressure (RVp) and can be quantified with the left ventricular end-systolic eccentricity index (LVEI). Only limited data exist in children to evaluate the relationship between the LVEI and invasive RVp. We sought to assess the correlation between the LVEI and an invasively measured peak systolic RVp to aortic pressure (pAo) ratio. Medical records of patients undergoing echocardiography within 30 days of right and left heart catheterization for evaluation of PH between February 2009 and March 2014 were retrospectively reviewed. Forty-six studies in 29 subjects (median age 3.8 years, 46 % female), with a median time from echocardiogram to catheterization of -1.0 days, were included for analysis. The mean LVEI was 1.6 ± 0.5, and mean RVp/pAo ratio was 0.68 ± 0.26. There was a significant positive correlation (r = 0.76, p < 0.001) between LVEI and RVp/pAo ratio. ROC analysis demonstrated an area under the curve = 0.91 for prediction of RVp/pAo >0.50 by the LVEI. An LVEI >1.48 had a sensitivity of 76 % and specificity of 100 % in predicting RVp/pAo >0.50, while an LVEI >1.24 had a sensitivity of 88 % and specificity of 83 %. Echocardiographically derived LVEI is strongly correlated with invasively determined RVp/pAo ratio. In combination with other noninvasive measures of RVp, LVEI may help minimize the need for invasive patient evaluation.

Myocardial Fibrosis and Left Ventricular Dysfunction in Duchenne Muscular Dystrophy Carriers Using Cardiac Magnetic Resonance Imaging.

The goal of our study was to characterize the degree of myocardial fibrosis and left ventricular dysfunction in our cohort of Duchenne muscular dystrophy (DMD) carriers using cardiac magnetic resonance imaging (CMR). Seventy percent of males with DMD have mothers who are carriers of the Xp21 mutation. Carrier phenotypic characteristics range from asymptomatic to left ventricular (LV) dysfunction and cardiomyopathy. The true prevalence of cardiac involvement in DMD carriers is unknown. We performed a retrospective observational study. All female DMD carriers who underwent clinical CMR studies at Cincinnati Children's Hospital Medical Center from December 6, 2006, to August 28, 2013, were evaluated. Patients underwent standard CMR assessment with LV function assessment and late gadolinium enhancement (LGE). In addition, offline feature tracking strain analysis was performed on the basal, mid, and apical short axis. Twenty-two patients were studied, of which 20 underwent adequate testing for myocardial LGE. Four of 22 patients (18 %) were found to have LV dysfunction (ejection fraction <55 %). Seven of 20 DMD carriers (35 %) were found to have LGE. The patients with evidence of LGE had an overall trend to lower absolute deformation parameters; however, this did not meet statistical significance when correcting for multiple comparisons. Our study demonstrates a high rate of LGE as well as LV dysfunction in DMD carriers. Cardiovascular and musculoskeletal symptoms were not statistically different between those with and without cardiac involvement. This study demonstrates the importance of surveillance CMR evaluation of DMD carriers.

Myocardial fibrosis burden predicts left ventricular ejection fraction and is associated with age and steroid treatment duration in duchenne muscular dystrophy.

BACKGROUND: Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, cardiac dysfunction in Duchenne muscular dystrophy patients may be influenced by myocardial fibrosis and steroid therapy. We examined the longitudinal relationship of myocardial fibrosis and ventricular dysfunction using cardiac magnetic resonance in a large Duchenne muscular dystrophy cohort. METHODS AND RESULTS: We reviewed 465 serial cardiac magnetic resonance studies (98 Duchenne muscular dystrophy patients with ≥4 cardiac magnetic resonance studies) for left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. LVEF was modeled by examining LGE status, myocardial fibrosis burden (as assessed by the number of LGE-positive left ventricular segments), patient age, and steroid treatment duration. An age-only model demonstrated that LVEF declined 0.58 ± 0.10% per year. In patients with both LGE-negative and LGE-positive studies (n=51), LVEF did not decline significantly over time if LGE was absent but declined 2.2 ± 0.31% per year when LGE was present. Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE-positive left ventricular segments; multivariate modeling showed that LVEF declined by 0.93 ± 0.09% for each LGE-positive left ventricular segment, whereas age and steroid treatment duration were not significant. The number of LGE-positive left ventricular segments increased with age, and longer steroid treatment duration was associated with lower age-related increases. CONCLUSION: Progressive myocardial fibrosis, as detected by LGE, was strongly correlated with the LVEF decline in Duchenne muscular dystrophy patients. Longer steroid treatment duration was associated with a lower age-related increase in myocardial fibrosis burden.

Abnormal circumferential strain measured by echocardiography is present in patients with Shwachman-Diamond syndrome despite normal shortening fraction.

BACKGROUND: Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and exocrine pancreatic dysfunction. Heart failure has been described in patients with SDS. Circumferential strain (ε(cc)) is a measure of cardiac performance that may identify dysfunction when standard measures are normal. PROCEDURES: Patients with SDS were identified and the echocardiographic database queried. Cardiac anatomy and function were recorded, and ε(cc) was measured retrospectively. RESULTS: From 1995-2013, 27 patients with biallelic SBDS mutations confirming the diagnosis of SDS were identified at our institution: 14 had at least one echocardiogram available; 10 underwent HSCT, with echocardiograms available in nine. Ejection fraction (EF) was normal in all 14 patients evaluated; however, ε(cc) was decreased in 4/12 studies prior to HSCT. In two patients, ε(cc) was abnormal both before and after HSCT, in one, ε(cc) changed from normal to abnormal after HSCT, and in one, ε(cc) was normal after HSCT despite being abnormal prior. Echocardiogram reports were also available for six patients in the North American SDS registry, all with normal EF. CONCLUSIONS: While EF was normal in all patients with SDS, ε(cc) was abnormal in 33% prior to HSCT and 33% of those who had undergone HSCT. This suggests that SDS is associated with systolic dysfunction. Further studies are needed to define the incidence of dysfunction in this group and the progression to heart failure.

Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophies using cardiac magnetic resonance imaging.

Duchenne and Becker muscular dystrophies are caused by mutations in dystrophin. Cardiac manifestations vary broadly, making prognosis difficult. Current dystrophin genotype-cardiac phenotype correlations are limited. For skeletal muscle, the reading-frame rule suggests in-frame mutations tend to yield milder phenotypes. We performed dystrophin genotype-cardiac phenotype correlations using a protein-effect model and cardiac magnetic resonance imaging. A translational model was applied to patient-specific deletion, indel, and nonsense mutations to predict exons and protein domains present within truncated dystrophin protein. Patients were dichotomized into predicted present and predicted absent groups for exons and protein domains of interest. Development of myocardial fibrosis (represented by late gadolinium enhancement [LGE]) and depressed left ventricular ejection fraction (LVEF) were compared. Patients (n = 274) with predicted present cysteine-rich domain (CRD), C-terminal domain (CTD), and both the N-terminal actin-binding and cysteine-rich domains (ABD1 + CRD) had a decreased risk of LGE and trended toward greater freedom from LGE. Patients with predicted present CTD (exactly the same as those with in-frame mutations) and ABD1 + CRD trended toward decreased risk of and greater freedom from depressed LVEF. In conclusion, genotypes previously implicated in altering the dystrophinopathic cardiac phenotype were not significantly related to LGE and depressed LVEF. Patients with predicted present CRD, CTD/in-frame mutations, and ABD1 + CRD trended toward milder cardiac phenotypes, suggesting that the reading-frame rule may be applicable to the cardiac phenotype. Genotype-phenotype correlations may help predict the cardiac phenotype for dystrophinopathic patients and guide future therapies.

A Rare Case of Pulmonary Artery Sling and Complete Atrioventricular Canal Defect in an Infant With Trisomy 21.

Pulmonary artery sling is a very rare congenital vascular anomaly. Patients usually present in infancy with symptoms of airway compression. Patients with trisomy 21 often have upper airway obstruction, most commonly related to pharyngeal causes or subglottic stenosis. Although the incidence of congenital heart defects in patients with trisomy 21 is very high, a review of the literature showed only one previously reported case of pulmonary artery sling in an infant with trisomy 21. We report a case of pulmonary artery sling and complete atrioventricular canal defect in a one-month-old female with trisomy 21. Echocardiography is an important diagnostic method for pulmonary artery sling, but this anomaly may be easily overlooked in the presence of more commonly anticipated defects in this population.

Relationship of MR elastography determined liver stiffness with cardiac function after Fontan palliation.

PURPOSE: To use MR elastography to assess liver stiffness in patients with congenital heart disease palliated with the Fontan procedure and correlate findings with cardiac index and other functional parameters obtained during cardiac MRI. MATERIALS AND METHODS: We performed a retrospective study of 14 patients (15 examinations) with Fontan circulation who underwent both cardiac MRI and liver MR elastography (MRE) on the same day. Liver stiffness was determined by calculating the mean liver stiffness from four slice locations. The cardiac index and other flow measurements were calculated from phase contrast MR imaging. RESULTS: The MRE was abnormal on all examinations with a median liver stiffness of 4.0 kPa (range, 3.4-6.2 kPa; normal adult liver stiffness is < 2.51 kPa). The cardiac index decreased as the duration of Fontan circulation (Fontan duration) increased (P = 0.005). We found a statistically significant inverse correlation between liver stiffness and cardiac index (P = 0.02), as well as the ejection fraction (P = 0.002). Patients with long Fontan durations (≥ 20 years) had greater liver stiffness compared with those having a shorter duration (P = 0.02). CONCLUSION: MRE shows promise as a monitoring tool in the Fontan population, demonstrating an elevated liver stiffness in all patients, which inversely correlated with the MR determined cardiac index.

Magnetic resonance elastography of the liver in patients status-post fontan procedure: feasibility and preliminary results.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of performing magnetic resonance elastography (MRE) as a screening tool for elevated liver stiffness in patients' status-post Fontan procedure. BACKGROUND: With greater numbers of Fontan patients surviving far into adulthood, a factor increasingly affecting long-term prognosis is the presence of hepatic congestion and fibrosis. If detected early, steps can be taken to potentially slow or halt the progression of fibrosis. MRE is a relatively new, noninvasive imaging technique, which can quantitatively measure liver stiffness and provide an estimate of the extent of fibrosis. METHODS: A retrospective study was conducted using MRE to evaluate liver stiffness in patients with a history of Fontan procedure. An MRE was performed in the same session as a clinical cardiac MRI. The liver was interrogated at four slice locations, and a mean liver stiffness value was calculated for each patient using postprocessing software. The medical records were reviewed for demographic and clinical characteristics. RESULTS: During the time frame of this investigation, 17 MRE exams were performed on 16 patients. All patients had elevated liver stiffness values as defined by MRE standards. The median of the individual mean liver stiffness values was 5.1 kPa (range: 3.4-8.2 kPa). This range of liver stiffness elevation would suggest the presence of mild to severe fibrosis in a patient with standard cardiovascular anatomy. We found a significant trend toward higher liver stiffness values with greater duration of Fontan circulation (rs = 0.55, P = .02). CONCLUSION: Our preliminary findings suggest that MRE is a feasible method for evaluating the liver in Fontan patients who are undergoing surveillance cardiac MRI. Further investigation with histologic correlation is needed to determine the contributions of hepatic congestion and fibrosis to the liver stiffness in this population.