"In-patient echocardiography utilization post repair of congenital heart disease. Analysis of data from the Pediatric Health Information System from 2010 to 2019".

BACKGROUND: Echocardiography is a key diagnostic tool for medical decision-making following congenital heart surgery. Overall utilisation of echocardiography for specific congenital heart lesions following cardiac surgery has not previously been reported. This study aims to assess echocardiogram utilisation following the surgical repair of CHD to describe the variation in use across centres and provide clinical benchmarks. METHODS: All patients < 18 years of age undergoing surgical repair of CHD were identified from the Pediatric Health Information System from 2010 to 2019. Surgeries were grouped based on their Risk Adjustment for Congenital Heart Surgery-1 scores. Detailed billing data were used to assess the frequency/cost of post-operative echocardiograms, phase of hospital care, and hospital length of stay. RESULTS: In total, 37,238 surgical encounters were identified for inclusion across 48 centres. Higher Risk Adjustment for Congenital Heart Surgery scores were associated with an increased median number of post-operative echocardiograms (2 versus 4 in Risk Adjustment for Congenital Heart Surgery score 1 versus 6, p < 0.001), and longer median post-operative length of stay (3 days versus 31 days in Risk Adjustment for Congenital Heart Surgery score 1 versus 6, p < 0.001). After accounting for surgical complexity, there was significant variability in echocardiogram utilisation across centres (median daily echocardiogram utilisation range 0.2/day-0.6/day, p < 0.001). There is no difference in the proportion of patients with high surgical complexity (Risk Adjustment for Congenital Heart Surgery ≥ 4) between centres with high versus low echocardiogram utilisation (p = 0.44). CONCLUSIONS: Increasing surgical complexity is associated with longer post-operative length of stay and increased utilisation of echocardiography. There is wide variability in echocardiography resource utilisation across centres, even when accounting for surgical complexity.

Association of cardiovascular magnetic resonance diastolic indices with arrhythmia in repaired Tetralogy of Fallot.

BACKGROUND: Patients with repaired Tetralogy of Fallot (rTOF) experience a high burden of long-term morbidity, particularly arrhythmias. Cardiovascular magnetic resonance (CMR) is routinely used to assess ventricular characteristics but the relationship between CMR diastolic function and arrhythmia has not been evaluated. We hypothesized in rTOF, left ventricular (LV) diastolic dysfunction on CMR would correlate with arrhythmias and mortality. METHODS: Adolescents and adults with rTOF who underwent CMR were compared to healthy controls (n = 58). Standard ventricular parameters were assessed and manual planimetry was performed to generate filling curves and indices of diastolic function. Chart review was performed to collect outcomes. Univariate and multivariable logistic regression was performed to identify outcome associations. RESULTS: One-hundred sixty-seven subjects with rTOF (mean age 32 years) and 58 healthy control subjects underwent CMR. Patients with rTOF had decreased LV volumes and increased right ventricular (RV) volumes, lower RV ejection fraction (RVEF), lower peak ejection rate (PER), peak filling rate (PFR) and PFR indexed to end-diastolic volume (PFR/EDV) compared to healthy controls. Eighty-three subjects with rTOF had arrhythmia (63 atrial, 47 ventricular) and 11 died. Left atrial (LA) volumes, time to peak filling rate (tPFR), and PFR/EDV were associated with arrhythmia on univariate analysis. PER/EDV was associated with ventricular (Odds ratio, OR 0.43 [0.24-0.80], p = 0.007) and total arrhythmia (OR 0.56 [0.37-0.92], p = 0.021) burden. A multivariable predictive model including diastolic covariates showed improved prediction for arrhythmia compared to clinical and conventional CMR measures (area under curve (AUC) 0.749 v. 0.685 for overall arrhythmia). PFR/EDV was decreased and tPFR was increased in rTOF subjects with mortality as compared to those without mortality. CONCLUSIONS: Subjects with rTOF have abnormal LV diastolic function compared to healthy controls. Indices of LV diastolic function were associated with arrhythmia and mortality. CMR diastolic indices may be helpful in risk stratification for arrhythmia.

Machine Learning to Predict Interstage Mortality Following Single Ventricle Palliation: A NPC-QIC Database Analysis.

There is high risk of mortality between stage I and stage II palliation of single ventricle heart disease. This study aimed to leverage advanced machine learning algorithms to optimize risk-prediction models and identify features most predictive of interstage mortality. This study utilized retrospective data from the National Pediatric Cardiology Quality Improvement Collaborative and included all patients who underwent stage I palliation and survived to hospital discharge (2008-2019). Multiple machine learning models were evaluated, including logistic regression, random forest, gradient boosting trees, extreme gradient boost trees, and light gradient boosting machines. A total of 3267 patients were included with 208 (6.4%) interstage deaths. Machine learning models were trained on 180 clinical features. Digoxin use at discharge was the most influential factor resulting in a lower risk of interstage mortality (p < 0.0001). Stage I surgery with Blalock-Taussig-Thomas shunt portended higher risk than Sano conduit (7.8% vs 4.4%, p = 0.0002). Non-modifiable risk factors identified with increased risk of interstage mortality included female sex, lower gestational age, and lower birth weight. Post-operative risk factors included the requirement of unplanned catheterization and more severe atrioventricular valve insufficiency at discharge. Light gradient boosting machines demonstrated the best performance with an area under the receiver operative characteristic curve of 0.642. Advanced machine learning algorithms highlight a number of modifiable and non-modifiable risk factors for interstage mortality following stage I palliation. However, model performance remains modest, suggesting the presence of unmeasured confounders that contribute to interstage risk.

mRNA Coronavirus Disease 2019 Vaccine-Associated Myopericarditis in Adolescents: A Survey Study.

In this survey study of institutions across the US, marked variability in evaluation, treatment, and follow-up of adolescents 12 through 18 years of age with mRNA coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis was noted. Only one adolescent with life-threatening complications was reported, with no deaths at any of the participating institutions.

Comparison of Strain-Encoding and Feature-Tracking Derived Myocardial Deformation Assessment of Left Ventricular Function in a Pediatric and Adult Congenital Heart Disease Cohort.

BACKGROUND: Cardiac magnetic resonance (CMR) strain can be assessed with feature-tracking (FT), which utilizes a post-processing algorithm to quantify myocardial deformation on routine cine images, and strain-encoding magnetic resonance imaging (SENC), which uses parallel magnetization tags combined with out-of-plane phase-encoding gradients to quantify deformation. Assessing agreement is critical to determine whether results can be translated between methods. We compared SENC to FT in the assessment of left ventricle (LV) global longitudinal strain (GLS) and global circumferential strain (GCS) in a cohort of pediatric and adult congenital heart disease (ACHD) patients. METHODS: Pediatric subjects and ACHD patients underwent CMR on 1.5 T Siemens scanners, including balanced steady-state-free precession (bSSFP) cine imaging and SENC acquisitions in apical two and four chamber, left ventricular outflow tract, and short axis views. bSSFP cine imaging FT analysis was completed with Medis QStrain. Myocardial Solutions MyoStrain was used to analyze SENC. Correlation was assessed by Spearman's rank correlation coefficient. Agreement between techniques was assessed with concordance correlation coefficient (CCC) and Bland-Altman. RESULTS: The cohort included 134 patients, 75 with congenital heart disease (56%). The median age was 16.3 years (IQR 13.7, 19.5). Median LV ejection fraction was 57% (IQR 54.4, 61.6). SENC and FT were in poor agreement for GLS (Spearman's ρ = 0.58, p < 0.001; CCC 0.24) and GCS (Spearman's ρ = 0.29, p < 0.001; CCC 0.03). CONCLUSION: There was poor agreement between SENC and FT derived GLS and GCS in a cohort of pediatric and ACHD patients, suggesting that SENC and FT cannot be used interchangeably.

Novel Cardiac Imaging Risk Score for Mortality Prediction in Duchenne Muscular Dystrophy.

Cardiovascular disease is the leading cause of death in patients with Duchenne Muscular Dystrophy (DMD), but there is significant cardiomyopathy phenotypic variability. Some patients demonstrate rapidly progressive disease and die at a young age while others survive into the fourth decade. Criteria to identify DMD subjects at greatest risk for early mortality could allow for increased monitoring and more intensive therapy. A risk score was created describing the onset and progression of left ventricular dysfunction and late gadolinium enhancement in subjects with DMD. DMD subjects prospectively enrolled in ongoing observational studies (which included cardiac magnetic resonance [CMR]) were used to validate the risk score. A total of 69 subjects had calculable scores. During the study period, 12 (17%) died from complications of DMD. The median risk score was 3 (IQR [2,5]; range [0,9]). The overall risk score applied at the most recent imaging age was associated with mortality at a median age of 17 years (IQR [16,20]) (HR 2.028, p < 0.001). There were no deaths in subjects with a score of less than two. Scores were stable over time. An imaging-based risk score allows risk stratification of subjects with DMD. This can be quickly calculated during a clinic visit to identify subjects at greatest risk of early death.

Non-contrast cardiovascular magnetic resonance detection of myocardial fibrosis in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) leads to progressive cardiomyopathy. Detection of myocardial fibrosis with late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) is critical for clinical management. Due to concerns of brain deposition of gadolinium, non-contrast methods for detecting and monitoring myocardial fibrosis would be beneficial. OBJECTIVES: We hypothesized that native T1 mapping and/or circumferential (εcc) and longitudinal (εls) strain can detect myocardial fibrosis. METHODS: 156 CMRs with gadolinium were performed in 66 DMD boys and included: (1) left ventricular ejection fraction (LVEF), (2) LGE, (3) native T1 mapping and myocardial tagging (εcc-tag measured using harmonic phase analysis). LGE was graded as: (1) presence/absence by segment, slice, and globally; (2) global severity from 0 (no LGE) to 4 (severe); (3) percent LGE using full width half maximum (FWHM). εls and εcc measured using feature tracking. Regression models to predict LGE included native T1 and either εcc-tag or εls and εcc measured at each segment, slice, and globally. RESULTS: Mean age and LVEF at first CMR were 14 years and 54%, respectively. Global εls and εcc strongly predicted presence or absence of LGE (OR 2.6 [1.1, 6.0], p = 0.029, and OR 2.3 [1.0, 5.1], p = 0.049, respectively) while global native T1 did not. Global εcc, εls, and native T1 predicted global severity score (OR 2.6 [1.4, 4.8], p = 0.002, OR 2.6 [1.4, 6.0], p = 0.002, and OR 1.8 [1.1, 3.1], p = 0.025, respectively). εls correlated with change in LGE by severity score (n = 33, 3.8 [1.0, 14.2], p = 0.048) and εcc-tag correlated with change in percent LGE by FWHM (n = 34, OR 0.2 [0.1, 0.9], p = 0.01). CONCLUSIONS: Pre-contrast sequences predict presence and severity of LGE, with εls and εcc being more predictive in most models, but there was not an observable advantage over using LVEF as a predictor. Change in LGE was predicted by εls (global severity score) and εcc-tag (FWHM). While statistically significant, our results suggest these sequences are currently not a replacement for LGE and may only have utility in a very limited subset of DMD patients.

Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass.

OBJECTIVES: Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. DESIGN: Single-center prospective observational cohort pilot study. SETTING: Pediatric cardiac ICU at a tertiary children's hospital. PATIENTS: Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008). CONCLUSIONS: Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.

Smartphone interfaced handheld echocardiography for focused assessment of ventricular function and structure in children: A pilot study.

INTRODUCTION: Miniaturized echocardiographic machines improve availability and portability and can be particularly useful for underserved and resource-limited settings. The goal of this study was to compare left ventricular fractional shortening (FS) and left ventricular ejection fraction (LVEF) obtained by a newer handheld echo (HHE) machine to standard transthoracic echocardiogram (TTE) in children. METHODS: Pediatric outpatients (Birth-18 years) undergoing TTE were prospectively enrolled. HHE protocol included 2D and M-mode images from the parasternal long, short, and apical-4 chamber views. HHE and TTE measurements were reviewed for agreement. Kappa statistic was used to analyze qualitative indices while FS and LVEF were analyzed with Lin's concordance correlation coefficient (CCC) and Bland-Altman limits of agreement (loa). RESULTS: Sixty children were enrolled; 55 were included in the quantitative analysis. Mean age was 7.5 ± 5.5 years; 67% males; median HHE image acquisition duration was 2.3(1-5) minutes. Fractional shortening and EF by HHE showed good agreement with TTE [CCC = 0.82, 95%CI (0.73,0.90), mean bias -3.18%, loa (-7.00,6.44%) vs CCC = 0.81 (0.72,0.90), mean bias -0.87%, loa (-6.94,5.17%], respectively. In children ≤5 years, HHE FS (n = 20) and EF (n = 21) agreed with TTE measurement [0.59 (0.31, 0.88), mean bias 0.30%, loa (-8.5, 9.1%); 0.79 (0.63, 0.96), mean bias 0.10%, loa (-5.99, 6.14)]. Kappa values for RV size, function, and LV function were 1.00 (P < .05); 0.75 for LV size (P < .05) and 0.66 for pericardial effusion (P < .05). CONCLUSION: Handheld echo demonstrates good correlation with standard TTE for focused assessment of ventricular chamber sizes and function in children.

Impact of Clinician Engagement on Implementation of the Pediatric Echocardiography Appropriate Use Criteria.

We sought to determine whether awareness of the pediatric appropriate use criteria (AUC) affected transthoracic echocardiogram (TTE) ordering by cardiologists; evaluate for differences in classification of an encounter's AUC clinical scenario by investigator chart review compared with clinicians at the time of the encounter; and assess TTE yield by appropriateness rating. AUC clinical scenario(s) were assigned to patients without prior TTE by investigator chart review of visits in 2014 (n = 209) and 2016 (n = 199), and by clinician classification in 2016 (n = 671). Investigators documented TTE utilization and findings. Between 2014 and 2016, TTE utilization decreased from 54 to 33% (p < 0.001) of "rarely appropriate" (R) encounters, resulting in a decrease in overall TTE utilization from 73 to 55% of encounters (p < 0.001). There was only moderate agreement of AUC appropriateness by investigator chart review and clinician classification (κ = 0.533, p < 0.001). Abnormal TTE findings were detected in 18.7% of R encounters, with 21 of 24 abnormalities in infants younger than 4 months presenting with murmur. A decrease in TTE utilization for R encounters may represent a change in practice from increased awareness of the AUC. AUC scenario classification by clinicians at the time of the encounter could be superior to chart review. TTE abnormalities may be missed in infants younger than 4 months of age when evaluated for murmurs with the AUC.

Sedated Echocardiograms Better Characterize Branch Pulmonary Arteries Following Bidirectional Glenn Palliation with Minimal Risk of Adverse Events.

Patients post-bidirectional Glenn (BDG) operation are at risk of left and right pulmonary artery (LPA and RPA) hypoplasia. Transthoracic echocardiograms (TTE) in active children can miss essential elements of anatomy. Procedural sedation improves image quality but increases risk of adverse events. We hypothesized that echocardiograms performed with sedation in patients post-BDG would improve visualization of branch pulmonary arteries with minimal adverse events. Patients post-BDG between 2007-2016 were identified. Exclusion criteria were > 12 months of age, absence of complete TTE before discharge, death before discharge, conversion to shunt physiology, and prolonged post-operative course > 7 weeks. Of 254 post-BDG patients, 153 met inclusion/exclusion criteria. TTE reports were reviewed for visualization of LPA/RPA and hypoplasia of LPA/RPA. Blinded assessment of image quality was performed (scale of 1[poor] to 5[excellent]). Pertinent clinical data were recorded. Pearson's chi-squared and Wilcoxon Rank Sum tests used for statistical analysis. The median age at surgery and hospital stay were 4.8 months and 10 days. Twenty-three patients underwent sedated TTE (15%). Sedated TTE significantly improved visualization of the RPA (100% vs 82%, p = 0.029) and LPA, though this did not reach statistical significance (100% vs 91%, p = 0.129). Sedated TTEs has significantly better image quality (median of 4 vs 3, p < 0.001). There were no serious adverse events due to sedation. Sedated TTE early post-BDG is safe, improves visualization of the RPA and LPA, and improves overall image quality. Routine sedated TTE in these patients should be considered. Implications for long-term outcome need to be further analyzed.

HUMAN PILOT STUDY OF BARE-METAL STENT: INC-01.

BACKGROUND: The cost of performing a percutaneous coronary intervention is considerably high for the patient as well as for health systems, which have promoted the development of local technology to help meet the need for these devices. METHODS: The INC-01 bare-metal stent was developed at the National Institute of Cardiology in Mexico City and was first implanted on porcine models with technical success in 100% of the evaluated parameters. PRESENTATION OF CASES: We present the first three cases of patients with ischemic heart disease, to whom the INC-01 bare-metal stent was implanted. Intracoronary ultrasonography was performed post-stent implantation, showing all the characteristics of implant success during evaluation and clinical follow-up. CONCLUSIONS: Angiography and intracoronary ultrasound were carried out demonstrating that the INC-01 bare-metal stent has physical, biological, and histological characteristics similar to those found in commercial metallic stents.

Design, manufacture and initial tests of a drug-eluting coronary stent.

INTRODUCTION: A drug-eluting coronary stent is being developed at the National Institute of Cardiology of Mexico for the treatment of ischemic heart disease. OBJECTIVE: To establish the best animal model for the tests, to show the advances in the drug-eluting stent prototype, to assess two drugs' antiproliferative activity and histological results. METHOD: Smooth muscle cell culture tests were performed in order to assess sirolimus and paclitaxel antiproliferative properties. The drugs were encapsulated inside the polymeric matrix of the stents. Rabbits and pigs were used as animal models. RESULTS: Sirolimus and paclitaxel showed an inhibitory effect, which was higher for the latter. Infrared spectroscopy and light and optical microscopy showed that the drug/polymer layer properly adhered to the stent. At a four-week follow-up, both animal models showed satisfactory clinical evolution and adequate histological response, although the porcine model was shown to be more suitable for future protocols. CONCLUSIONS: Preliminary tests of the drug-eluting stent provided bases for the development of a study protocol with an adequate number of pigs and with clinical angiographic and histopathological three-month follow-up.

INTRODUCCIÓN: En el Instituto Nacional de Cardiología de México se desarrolla una endoprótesis (stent) coronaria liberadora de fármacos para el tratamiento de la cardiopatía isquémica. OBJETIVO: Establecer el mejor modelo animal para las pruebas, mostrar los avances en el prototipo del stent liberador de fármacos, evaluar la actividad antiproliferativa de dos fármacos y los resultados histológicos. MÉTODO: Se realizaron cultivos de células de músculo liso para evaluar las propiedades antiproliferativas de sirolimus y paclitaxel. Los fármacos fueron encapsulados en el interior de la matriz polimérica de los stents. Se emplearon conejos y cerdos como modelos animales. RESULTADOS: Sirolimus y paclitaxel mostraron efecto inhibitorio, mayor en el segundo. La espectroscopia infrarroja y la microscopia óptica y electrónica mostraron que la capa del polímero con el fármaco se adhería adecuadamente al stent. A las cuatro semanas de seguimiento, ambos modelos animales mostraron evolución clínica satisfactoria y adecuada respuesta histológica, si bien el modelo porcino resultó más conveniente para protocolos futuros. CONCLUSIONES: Las pruebas preliminares del stent liberador de fármaco brindó bases para desarrollar el protocolo con un número adecuado en cerdos y con seguimiento clínico angiográfico e histopatológico a tres meses.

The Role of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Duchenne Muscular Dystrophy Cardiomyopathy.

BACKGROUND: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy. METHODS AND RESULTS: Prospectively enrolled DMD subjects (n = 42) underwent cardiac magnetic resonance imaging for function and late gadolinium enhancement (LGE), including LGE severity from 0 (no LGE) to 4 (severe). Serum from DMD and healthy male control subjects (n = 15) analyzed for MMPs 1, 2, 3, 7, 9, and 10 and TIMPs 1-4. MMP1, MMP7, and MMP10 were higher in DMD than in control (respectively, median 5080 pg/mL vs 2120 pg/mL [P = .007], 2170 pg/mL vs 1420 pg/mL [P < .001], and 216 pg/mL vs 140pg/mL [P = .040]); TIMP4 was lower in DMD (124 pg/mL vs 263 pg/mL; P = .046). Within DMD, MMP7 correlated inversely with left ventricular ejection fraction (r = -0.40; P = .012) and directly with strain (r = 0.54; P = .001) and LGE severity (r = 0.47; P = .003). MMP7 was higher in DMD patients with LGE compared with those without LGE and control subjects (P < .001). CONCLUSIONS: Multiple MMPs are elevated in DMD compared with control subjects. MMP7 is related to DMD cardiac dysfunction and myocardial fibrosis, possibly through remodeling of the extracellular matrix.

Tissue characterisation and myocardial mechanics using cardiac MRI in children with hypertrophic cardiomyopathy.

INTRODUCTION: Distinguishing between hypertrophic cardiomyopathy and other causes ofleft ventricular hypertrophy can be difficult in children. We hypothesised that cardiac MRI T1 mapping could improve diagnosis of paediatric hypertrophic cardiomyopathy and that measures of myocardial function would correlate with T1 times and extracellular volume fraction. METHODS: Thirty patients with hypertrophic cardiomyopathy completed MRI with tissue tagging, T1-mapping, and late gadolinium enhancement. Left ventricular circumferential strain was calculated from tagged images. T1, partition coefficient, and synthetic extracellular volume were measured at base, mid, apex, and thickest area of myocardial hypertrophy. MRI measures compared to cohort of 19 healthy children and young adults. Mann-Whitney U, Spearman's rho, and multivariable logistic regression were used for statistical analysis. RESULTS: Hypertrophic cardiomyopathy patients had increased left ventricular ejection fraction and indexed mass. Hypertrophic cardiomyopathy patients had decreased global strain and increased native T1 (-14.3% interquartile range [-16.0, -12.1] versus -17.3% [-19.0, -15.7], p < 0.001 and 1015 ms [991, 1026] versus 990 ms [972, 1001], p = 0.019). Partition coefficient and synthetic extracellular volume were not increased in hypertrophic cardiomyopathy. Global native T1 correlated inversely with ejection fraction (ρ = -0.63, p = 0.002) and directly with global strain (ρ = 0.51, p = 0.019). A logistic regression model using ejection fraction and native T1 distinguished between hypertrophic cardiomyopathy and control with an area under the receiver operating characteristic curve of 0.91. CONCLUSION: In this cohort of paediatric hypertrophic cardiomyopathy, strain was decreased and native T1 was increased compared with controls. Native T1 correlated with both ejection fraction and strain, and a model using native T1 and ejection fraction differentiated patients with and without hypertrophic cardiomyopathy.

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 (ε cc) 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 ε cc. Extremes of body weight may result in inappropriate timing of PVR. Extremes of weight lead to abnormalities in global LV ε cc. Although clinical implications of abnormal ε cc are unclear, these patients may be at higher risk for early ventricular dysfunction.

Synthetic hematocrit derived from the longitudinal relaxation of blood can lead to clinically significant errors in measurement of extracellular volume fraction in pediatric and young adult patients.

BACKGROUND: Extracellular volume fraction (ECV) is altered in pathological cardiac remodeling and predicts death and arrhythmia. ECV can be quantified using cardiovascular magnetic resonance (CMR) T1 mapping but calculation requires a measured hematocrit (Hct). The longitudinal relaxation of blood has been used in adults to generate a synthetic Hct (estimate of true Hct) but has not been validated in pediatric populations. METHODS: One hundred fourteen children and young adults underwent a total of 163 CMRs with T1 mapping. The majority of subjects had a measured Hct the same day (N = 146). Native and post-contrast T1 were determined in blood pool, septum, and free wall of mid-LV, avoiding areas of late gadolinium enhancement. Synthetic Hct and ECV were calculated and intraclass correlation coefficient (ICC) and linear regression were used to compare measured and synthetic values. RESULTS: The mean age was 16.4 ± 6.4 years and mean left ventricular ejection fraction was 59% ± 9%. The mean measured Hct was 41.8 ± 3.0% compared to the mean synthetic Hct of 43.2% ± 2.9% (p < 0.001, ICC 0.46 [0.27, 0.52]) with the previously published model and 41.8% ± 1.4% (p < 0.001, ICC 0.28 [0.13, 0. 42]) with the locally-derived model. Mean measured mid-free wall ECV was 30.5% ± 4.8% and mean synthetic mid-free wall ECV of local model was 29.7% ± 4.6% (p < 0.001, ICC 0.93 [0.91, 0.95]). Correlations were not affected by heart rate and did not significantly differ in subpopulation analysis. While the ICC was strong, differences between measured and synthetic ECV ranged from -8.4% to 4.3% in the septum and -12.6% to 15.8% in the free wall. Using our laboratory's normal cut-off of 28.5%, 59 patients (37%) were miscategorized (53 false negatives, 6 false positives) with published model ECV. The local model had 37 miscategorizations (20 false negatives, 17 false positives), significantly fewer but still a substantial number (23%). CONCLUSIONS: Our data suggest that use of synthetic Hct for the calculation of ECV results in miscategorization of individual patients. This difference may be less significant once synthetic ECV is calculated and averaged over a large research cohort, making it potentially useful as a research tool. However, we recommend formal measurement of Hct in children and young adults for clinical CMRs.

Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE). METHODS: Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test. RESULTS: The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs. 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs. 988 ms, p = 0.002, and 1038 ms vs. 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs. 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs. 0.24, p < 0.001) and negative LGE (0.29 vs. 0.24, p = 0.001). CONCLUSIONS: DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials.

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.

Evaluation of post-contrast myocardial t1 in duchenne muscular dystrophy using cardiac magnetic resonance imaging.

The objective of the study was to perform a retrospective pilot study to evaluate the potential of myocardial T1 in assessment of Duchenne muscular dystrophy (DMD) cardiomyopathy. Early identification of DMD cardiac disease, particularly myocardial fibrosis, would allow earlier therapy, potentially improving outcomes. Shortened myocardial T1 measured by cardiac MRI (CMR) is a measure of cardiac fibrosis that may be detected before late gadolinium enhancement (LGE). We hypothesized that the post-contrast T1 obtained from the Look-Locker sequences (T1LL), an easily obtainable surrogate of myocardial T1, would be abnormally shortened in DMD compared with controls. T1LL measurement was performed on 21 DMD subjects and 11 controls; to account for individual variations in gadolinium distribution, myocardial T1LL was divided by blood pool T1LL, deriving T1LL ratios. DMD subjects had shorter mean T1LL ratio than controls (1.42 vs 1.72, p < 0.001). Subset analyses in DMD subjects with normal LVEF and without LGE also demonstrated significantly shorter T1LL ratio (-0.28, p < 0.001 and -0.25, p = 0.028). Post-contrast T1LL ratio is abnormally shortened in DMD compared with controls, even in DMD patients with otherwise normal CMRs. The application of more aggressive therapy for those with shorter T1LL may favorably alter morbidity and improve mortality associated with DMD cardiomyopathy. These data suggest that further prospective evaluation of myocardial T1 will be of benefit to patients with DMD.