Utility of Cardiovascular Magnetic Resonance-Derived Wave Intensity Analysis As a Marker of Ventricular Function in Children with Heart Failure and Normal Ejection Fraction.

OBJECTIVE: This study sought to explore the diagnostic insight of cardiovascular magnetic resonance (CMR)-derived wave intensity analysis to better study systolic dysfunction in young patients with chronic diastolic dysfunction and preserved ejection fraction (EF), comparing it against other echocardiographic and CMR parameters. BACKGROUND: Evaluating systolic and diastolic dysfunctions in children is challenging, and a gold standard method is currently lacking. METHODS: Patients with presumed diastolic dysfunction [n = 18; nine aortic stenosis (AS), five hypertrophic, and four restrictive cardiomyopathies] were compared with age-matched control subjects (n = 18). All patients had no mitral or aortic incompetence, significant AS, or reduced systolic EF. E/A ratio, E/E' ratio, deceleration time, and isovolumetric contraction time were assessed on echocardiography, and indexed left atrial volume (LAVi), acceleration time (AT), ejection time (ET), and wave intensity analyses were calculated from CMR. The latter was performed on CMR phase-contrast flow sequences, defining a ratio of the peaks of the early systolic forward compression wave (FCW) and the end-systolic forward expansion wave (FEW). RESULTS: Significant differences between patients and controls were seen in the E/E' ratio (8.7 ± 4.0 vs. 5.1 ± 1.3, p = 0.001) and FCW/FEW ratio (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10-5 m/s, p < 0.001), as well as-as expected-LAVi (80.7 ± 22.5 vs. 51.0 ± 10.9 mL/m2, p < 0.001). In particular, patients exhibited a lower FCW (2.5 ± 1.6 vs. 7.2 ± 4.2 × 10-5 m/s, p < 0.001) in the face of preserved EF (67 ± 11 vs. 69 ± 5%, p = 0.392), as well as longer isovolumetric contraction time (49 ± 7 vs. 34 ± 7 ms, p < 0.001) and ET/AT (0.35 ± 0.04 vs. 0.27 ± 0.04, p < 0.001). CONCLUSION: This study shows that the wave intensity-derived ratio summarizing systolic and diastolic function could provide insight into ventricular function in children, on top of CMR and echocardiography, and it was here able to identify an element of ventricular dysfunction with preserved EF in a small group of young patients.

Investigating Cardiac Motion Patterns Using Synthetic High-Resolution 3D Cardiovascular Magnetic Resonance Images and Statistical Shape Analysis.

Diagnosis of ventricular dysfunction in congenital heart disease is more and more based on medical imaging, which allows investigation of abnormal cardiac morphology and correlated abnormal function. Although analysis of 2D images represents the clinical standard, novel tools performing automatic processing of 3D images are becoming available, providing more detailed and comprehensive information than simple 2D morphometry. Among these, statistical shape analysis (SSA) allows a consistent and quantitative description of a population of complex shapes, as a way to detect novel biomarkers, ultimately improving diagnosis and pathology understanding. The aim of this study is to describe the implementation of a SSA method for the investigation of 3D left ventricular shape and motion patterns and to test it on a small sample of 4 congenital repaired aortic stenosis patients and 4 age-matched healthy volunteers to demonstrate its potential. The advantage of this method is the capability of analyzing subject-specific motion patterns separately from the individual morphology, visually and quantitatively, as a way to identify functional abnormalities related to both dynamics and shape. Specifically, we combined 3D, high-resolution whole heart data with 2D, temporal information provided by cine cardiovascular magnetic resonance images, and we used an SSA approach to analyze 3D motion per se. Preliminary results of this pilot study showed that using this method, some differences in end-diastolic and end-systolic ventricular shapes could be captured, but it was not possible to clearly separate the two cohorts based on shape information alone. However, further analyses on ventricular motion allowed to qualitatively identify differences between the two populations. Moreover, by describing shape and motion with a small number of principal components, this method offers a fully automated process to obtain visually intuitive and numerical information on cardiac shape and motion, which could be, once validated on a larger sample size, easily integrated into the clinical workflow. To conclude, in this preliminary work, we have implemented state-of-the-art automatic segmentation and SSA methods, and we have shown how they could improve our understanding of ventricular kinetics by visually and potentially quantitatively highlighting aspects that are usually not picked up by traditional approaches.

Detecting Clinically Meaningful Shape Clusters in Medical Image Data: Metrics Analysis for Hierarchical Clustering Applied to Healthy and Pathological Aortic Arches.

OBJECTIVE: Today's growing medical image databases call for novel processing tools to structure the bulk of data and extract clinically relevant information. Unsupervised hierarchical clustering may reveal clusters within anatomical shape data of patient populations as required for modern precision medicine strategies. Few studies have applied hierarchical clustering techniques to three-dimensional patient shape data and results depend heavily on the chosen clustering distance metrics and linkage functions. In this study, we sought to assess clustering classification performance of various distance/linkage combinations and of different types of input data to obtain clinically meaningful shape clusters. METHODS: We present a processing pipeline combining automatic segmentation, statistical shape modeling, and agglomerative hierarchical clustering to automatically subdivide a set of 60 aortic arch anatomical models into healthy controls, two groups affected by congenital heart disease, and their respective subgroups as defined by clinical diagnosis. Results were compared with traditional morphometrics and principal component analysis of shape features. RESULTS: Our pipeline achieved automatic division of input shape data according to primary clinical diagnosis with high F-score (0.902 ± 0.042) and Matthews correlation coefficient (0.851 ± 0.064) using the correlation/weighted distance/linkage combination. Meaningful subgroups within the three patient groups were obtained and benchmark scores for automatic segmentation and classification performance are reported. CONCLUSION: Clustering results vary depending on the distance/linkage combination used to divide the data. Yet, clinically relevant shape clusters and subgroups could be found with high specificity and low misclassification rates. SIGNIFICANCE: Detecting disease-specific clusters within medical image data could improve image-based risk assessment, treatment planning, and medical device development in complex disease.

Utility of adenosine stress perfusion CMR to assess paediatric coronary artery disease.

AIMS: Cardiovascular magnetic resonance (CMR), using adenosine stress perfusion and late-gadolinium enhancement (LGE), is becoming the 'gold standard' non-invasive imaging modality in the assessment of adults with coronary artery disease (CAD). However, despite its proved feasibility in paediatric patients, clinical utility has not been demonstrated. Therefore, this study aims to establish the role of adenosine stress perfusion CMR as a screening test in paediatric patients with acquired or congenital CAD. METHODS AND RESULTS: A total of 58 paediatric patients underwent 61 consecutive clinically indicated coronary artery assessments for diagnostic and clinical decision-making purposes. The diagnosis was based on X-ray or computed tomography coronary angiography for anatomy, adenosine stress CMR imaging for myocardial perfusion and LGE for tissue characterization. Two studies were aborted because of unwanted side effects of adenosine stress, thus 59 studies were completed in 56 patients [median age 14.1 years (interquartile range 10.9-16.2)]. When compared with coronary anatomical imaging, adenosine stress perfusion CMR performed as follows: sensitivity 100% (95% confidence interval, CI: 71.6-100%), specificity 98% (95% CI: 86.7-99.9%), positive predictive value (PPV) 92.9% (95% CI: 64.2-99.6%), and negative predictive value 100% (95% CI: 89.9-100%). CONCLUSION: In paediatric CAD, adenosine stress perfusion CMR imaging is adequate as an initial, non-invasive screening test for the identification of significant coronary artery lesions, with anatomical imaging used to confirm the extent of the culprit lesion.

A statistical shape modelling framework to extract 3D shape biomarkers from medical imaging data: assessing arch morphology of repaired coarctation of the aorta.

BACKGROUND: Medical image analysis in clinical practice is commonly carried out on 2D image data, without fully exploiting the detailed 3D anatomical information that is provided by modern non-invasive medical imaging techniques. In this paper, a statistical shape analysis method is presented, which enables the extraction of 3D anatomical shape features from cardiovascular magnetic resonance (CMR) image data, with no need for manual landmarking. The method was applied to repaired aortic coarctation arches that present complex shapes, with the aim of capturing shape features as biomarkers of potential functional relevance. The method is presented from the user-perspective and is evaluated by comparing results with traditional morphometric measurements. METHODS: Steps required to set up the statistical shape modelling analyses, from pre-processing of the CMR images to parameter setting and strategies to account for size differences and outliers, are described in detail. The anatomical mean shape of 20 aortic arches post-aortic coarctation repair (CoA) was computed based on surface models reconstructed from CMR data. By analysing transformations that deform the mean shape towards each of the individual patient's anatomy, shape patterns related to differences in body surface area (BSA) and ejection fraction (EF) were extracted. The resulting shape vectors, describing shape features in 3D, were compared with traditionally measured 2D and 3D morphometric parameters. RESULTS: The computed 3D mean shape was close to population mean values of geometric shape descriptors and visually integrated characteristic shape features associated with our population of CoA shapes. After removing size effects due to differences in body surface area (BSA) between patients, distinct 3D shape features of the aortic arch correlated significantly with EF (r = 0.521, p = .022) and were well in agreement with trends as shown by traditional shape descriptors. CONCLUSIONS: The suggested method has the potential to discover previously unknown 3D shape biomarkers from medical imaging data. Thus, it could contribute to improving diagnosis and risk stratification in complex cardiac disease.

Performance monitoring of the arterial switch operation: a moving target.

OBJECTIVES: Twenty years ago our institution published an analysis of a cluster of failures associated with the arterial switch operation (ASO). The concept of 'near miss' was explored to detect warning signs of suboptimal performance. The aim of the current study was to review the parameters best suited to monitoring early ASO outcomes in the modern setting and re-examine the concept of near misses as failure equivalents. METHODS: All ASOs performed in our institution between 1983 and 2012 were reviewed. The experience was divided into three eras (1983-92, 1993-2002 and 2003-12). The cumulative sum graphic for sequential monitoring was used for early mortality. The need to re-establish cardiopulmonary bypass (CPB), CPB time >240 min and extracorporeal membrane oxygenation (ECMO) were explored as variables of near misses. RESULTS: The cohort consisted of 606 patients. The 30-day mortality rate was 23% (n = 29) in Era 1, 6% (n = 14) in Era 2 and 1% (n = 3) in Era 3. There were further 4, 8 and 6 deaths between 30 and 90 days in the three eras, respectively. In Era 3, the majority of deaths occurred between 30 and 90 days. In the current era, ECMO and CPB time >240 min as a marker of near miss was associated with an increased risk of death both within 30 days and 90 days after ASO. CONCLUSIONS: The 30-day outcomes of ASO have significantly improved over the last 30 years. As life-saving mechanical support after surgery has been implemented more often, an extended 90-day window of reporting can offer a more realistic outcome indicator of performance.

3D morphometric analysis of the arterial switch operation using in vivo MRI data.

The arterial switch operation (ASO) is widely used nowadays as the surgical strategy of choice to repair transposition of the great arteries (TGA). Residual morphological and geometrical abnormalities of the aorta, pulmonary arteries and coronary arteries, however, have not been fully studied in a three-dimensional (3D) domain. These morphometric complications might have implications on long-term outcomes of ASO patients, hence the need to explore them in detail and study them with reference to healthy controls of comparable age and body surface area. These anatomical characteristics were examined using 3D patient-specific anatomical models reconstructed from cardiovascular magnetic resonance (CMR) images of 20 ASO patients (mean age 14.4 ± 2.4 years, 16 males and 4 females) compared with healthy controls (mean age 15.2 ± 2.0 years, 17 males and 3 females). It was found that the aorta, pulmonary arteries and re-implanted coronary arteries of ASO patients were significantly different morphologically and geometrically to those of healthy controls. In particular, the aortic root was dilated, with abnormal 3D angulation and additional acute angulation of the curvature of the aortic arch in the ASO group compared with controls. This could theoretically impinge on aortic flow profiles and physiological stresses, which can act as a primer for the development of early atherosclerotic disease in the ASO population.

Ventriculoarterial coupling in palliated hypoplastic left heart syndrome: Noninvasive assessment of the effects of surgical arch reconstruction and shunt type.

OBJECTIVE: To assess the coupling efficiency in hypoplastic left heart syndrome, considering the effect of surgical arch reconstruction and the shunt type received during the Norwood procedure. METHODS: Ventriculoarterial coupling was assessed before Fontan completion in 32 patients with hypoplastic left heart syndrome (19 modified Blalock-Taussig and 13 Sano shunts at stage 1). Cardiovascular magnetic resonance data were analyzed, deriving functional parameters and 3-dimensional volumes. Dimensional indexes were computed from 3-dimensional data sets as the area ratio of the isthmus to the descending aorta (Risthmus) and the isthmus to surgically enlarged transverse arch (Rarch). Wave intensity was calculated from cardiac magnetic resonance, using the peaks of the forward compression and expansion waves in early and late systole as surrogate indicators of ventriculoarterial coupling. RESULTS: Aortic distensibility (3.6±2.7×10(-3) 1/mm Hg) was not associated with the time elapsed from stage 1 palliation (P=.94), suggesting an early loss of elasticity that did not progress thereafter. Risthmus was 1.0±0.4, and Rarch was 0.3±0.1, indicating the dilated reconstructed arch was the main anatomic feature. The forward compression wave correlated significantly with Rarch (R2=0.23, P=.006) but not with Risthmus (R2<0.01, P=.63). Patients with a reduced ejection fraction exhibited a larger ventricular mass (R2=0.28, P=.003). The Sano shunt patients had a lower ejection fraction (51%±6% vs 57%±6%, P=.02); however, neither the forward compression nor expansion wave varied significantly between shunt type or the other functional parameters. CONCLUSIONS: Ventriculoarterial coupling in operated hypoplastic left heart syndrome was affected by aortic arch size mismatch but not by the type of shunt placed at the Norwood operation.

Aortic arch shape is not associated with hypertensive response to exercise in patients with repaired congenital heart diseases.

BACKGROUND: Aortic arch geometry is linked to abnormal blood pressure (BP) response to maximum exercise. This study aims to quantitatively assess whether aortic arch geometry plays a role in blood pressure (BP) response to exercise. METHODS: 60 age- and BSA-matched subjects--20 post-aortic coarctation (CoA) repair, 20 transposition of great arteries post arterial switch operation (ASO) and 20 healthy controls--had a three-dimensional (3D), whole heart magnetic resonance angiography (MRA) at 1.5 Tesla, 3D geometric reconstructions created from the MRA. All subjects underwent cardiopulmonary exercise test on the same day as MRA using an ergometer cycle with manual BP measurements. Geometric analysis and their correlation with BP at peak exercise were assessed. RESULTS: Arch curvature was similarly acute in both the post-CoA and ASO cases [0.05 ± 0.01 vs. 0.05 ± 0.01 (1/mm/m²); p = 1.0] and significantly different to that of normal healthy controls [0.05 ± 0.01 vs. 0.03 ± 0.01 (1/mm/m²), p < 0.001]. Indexed transverse arch cross sectional area were significantly abnormal in the post-CoA cases compared to the ASO cases (117.8 ± 47.7 vs. 221.3 ± 44.6; p < 0.001) and controls (117.8 ± 47.7 vs. 157.5 ± 27.2 mm²; p = 0.003). BP response to peak exercise did not correlate with arch curvature (r = 0.203, p = 0.120), but showed inverse correlation with indexed minimum cross sectional area of transverse arch and isthmus (r = -0.364, p = 0.004), and ratios of minimum arch area/ descending diameter (r = -0.491, p < 0.001). CONCLUSION: Transverse arch and isthmus hypoplasia, rather than acute arch angulation plays a role in the pathophysiology of BP response to peak exercise following CoA repair.

Trends in pediatric cardiovascular magnetic resonance imaging.

Cardiac magnetic resonance (CMR) imaging has significantly evolved over the last decade, becoming an integral part of the contemporary assessment of both congenital and acquired pediatric heart disease. Recent trends show that there is a growing interest in clinical applications and research in this field. An attempt to discuss the evolving technologies, techniques, and applications of CMR in pediatrics is not complete without understanding the current strengths of the modality. CMR complements readily available echocardiography, in many cases information from CMR can remove the need for invasive angiographic catheterization, and in other cases can be used to augment cardiac catheterisation.

The role of cardiovascular magnetic resonance in pediatric congenital heart disease.

Cardiovascular magnetic resonance (CMR) has expanded its role in the diagnosis and management of congenital heart disease (CHD) and acquired heart disease in pediatric patients. Ongoing technological advancements in both data acquisition and data presentation have enabled CMR to be integrated into clinical practice with increasing understanding of the advantages and limitations of the technique by pediatric cardiologists and congenital heart surgeons. Importantly, the combination of exquisite 3D anatomy with physiological data enables CMR to provide a unique perspective for the management of many patients with CHD. Imaging small children with CHD is challenging, and in this article we will review the technical adjustments, imaging protocols and application of CMR in the pediatric population.