Identifying high-risk Fontan phenotypes using K-means clustering of cardiac magnetic resonance-based dyssynchrony metrics.

BACKGROUND: Individuals with a Fontan circulation encompass a heterogeneous group with adverse outcomes linked to ventricular dilation, dysfunction, and dyssynchrony. The purpose of this study was to assess if unsupervised machine learning cluster analysis of cardiovascular magnetic resonance (CMR)-derived dyssynchrony metrics can separate ventricles in the Fontan circulation from normal control left ventricles and identify prognostically distinct subgroups within the Fontan cohort. METHODS: This single-center, retrospective study used 503 CMR studies from Fontan patients (median age 15 y) and 42 from age-matched controls from January 2005 to May 2011. Feature tracking on short-axis cine stacks assessed radial and circumferential strain, strain rate, and displacement. Unsupervised K-means clustering was applied to 24 mechanical dyssynchrony metrics derived from these deformation measurements. Clusters were compared for demographic, anatomical, and composite outcomes of death, or heart transplantation. RESULTS: Four distinct phenotypic clusters were identified. Over a median follow-up of 4.2 y (interquartile ranges 1.7-8.8 y), 58 (11.5%) patients met the composite outcome. The highest-risk cluster (largely comprised of right or mixed ventricular morphology and dilated, dyssynchronous ventricles) exhibited a higher hazard for the composite outcome compared to the lowest-risk cluster while controlling for ventricular morphology (hazard ratio [HR] 6.4; 95% confidence interval [CI] 2.1-19.3; P value 0.001) and higher indexed end-diastolic volume (HR 3.2; 95% CI 1.04-10.0; P value 0.043) per 10 mL/m2. CONCLUSION: Unsupervised machine learning using CMR-derived dyssynchrony metrics identified four distinct clusters of patients with Fontan circulation and healthy controls with varying clinical characteristics and risk profiles. This technique can be used to guide future studies and identify more homogeneous subsets of patients from an overall heterogeneous population.

Rare cardiac inflammatory pseudotumor in a toddler: Complementary roles of cardiac magnetic resonance and positron emission tomography.

We present a rare pediatric case of cardiac inflammatory pseudotumor (IPT) with a unique presentation of fever of unknown origin with markedly elevated inflammatory markers. A right atrial mass was discovered incidentally by echocardiography. The cardiac magnetic resonance (CMR) signal characteristics and mass location were not consistent with any of the common benign cardiac tumors of childhood. The presence of high signal intensity on T2 imaging and late gadolinium enhancement, in conjunction with intense metabolic activity at the mass site on positron emission tomography (PET), raised the possibility of an inflammatory or malignant mass. The diagnosis of IPT was confirmed by biopsy. Our case highlights the utility of PET imaging to confirm the inflammatory nature and extent of an IPT.

Morphology, Clinical Associations, and Pathologic Follow-up of Quadricuspid Aortic Valves in Children.

While quadricuspid morphology is commonly observed in truncal valves, quadricuspid aortic valves (QAV) are rare and their natural history is not well described. This retrospective study of 37 patients describes the diagnostic associations and morphologic variability of QAVs in children (median age at diagnosis 4.3 y IQR 0-12 y). Associated congenital heart diseases were present in 54% (most commonly tetralogy of Fallot (TOF) and valvar pulmonary stenosis). Among patients with isolated QAV, 11 had genetic syndrome and 5 had skeletal anomalies. Valve morphology was most commonly type B (41%) and A (35%; Hurvitz and Roberts). Dilated aortic root (Z ≥ 2) was present in 5 and dilated ascending aorta in 9 patients at diagnosis. All patients with type C (n = 3) and G (n = 1) had aortic dilation. At diagnosis, >mild AR was rare (n = 1), mild regurgitation was common (n = 12, 32%), >mild AS was rare (n = 2), and mild AS was uncommon (n = 4). Over a median follow-up of 3.3y (IQR 0.9-11y), progression of AR was seen in 2 patients and progression of aortic root or ascending aorta dilation (increase in Z score by ≥ 2) was seen in 5 patients. In conclusion, QAV is a rare congenital anomaly and about half of the cases are found in hearts that are otherwise structurally normal. A relatively high prevalence is seen in patients with TOF, pulmonary stenosis, skeletal deformities, and genetic syndromes. Meticulous evaluation of aortic valve morphology should be conducted on echocardiograms performed for these indications.

Design and implementation of multicenter pediatric and congenital studies with cardiovascular magnetic resonance: Big data in smaller bodies.

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.

Mitral valve orifice area predicts outcome after biventricular repair in patients with hypoplastic left ventricles.

BACKGROUND: Identification of risk factors for biventricular (BiV) repair in children with hypoplastic left ventricles (HLV) has been challenging. We sought to identify preoperative cardiovascular magnetic resonance (CMR) predictors of outcome in patients with HLVs who underwent BiV repair, with a focus on the mitral valve (MV). METHODS: Single-center retrospective analysis of preoperative CMRs on patients with HLV (≤50 mL/m2) and no endocardial fibroelastosis who underwent BiV repair from 2005-2022. CMR measurements included MV orifice area in diastole. The primary composite outcome included time to death, transplant, BiV takedown, heart failure admission, left atrial decompression, or unexpected reoperation; and the secondary outcome included more than or equal to moderate mitral stenosis and/or regurgitation. RESULTS: Median follow-up was 0.7 (interquartile range 0.1, 2.2) years. Of 122 patients [59 atrioventricular canal (AVC) and 63 non-AVC] age 3 ± 2.8 years at the time of BiV repair, freedom from the primary outcome at 2 years was 53% for AVC and 69% for non-AVC (log rank p = 0.12), and freedom from the secondary outcome at 2 years was 49% for AVC and 79% for non-AVC (log rank p < 0.01). Independent predictors of primary outcome for AVC patients included MV orifice area z-score <-2 and transitional AVC; for non-AVC patients, predictors included MV orifice area z-score <-2, abnormal MV anatomy, and conal-septal ventricular septal defect. Independent predictors of secondary outcome for AVC patients included older age at surgery, transitional AVC, and transposition of the great arteries. CONCLUSION: In children with HLV, low MV orifice area and pre-existing MV pathology are risk factors for adverse outcome after BiV repair.

Effect of In utero Non-steroidal anti-inflammatory drug therapy for severe ebstein anomaly or tricuspid valve dysplasia (NSAID therapy for fetal ebstein anomaly)

Abstract: Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) are rare congenital malformations associated with nearly 50% mortality when diagnosed in utero. The diseases often produce severe tricuspid regurgitation (TR) in the fetus and in some cases, pulmonary regurgitation (PR) and circular shunting ensue. Since the ductus arteriosus (DA) plays a critical role in the circular shunt and may be constricted by transplacental non-steroidal anti-inflammatory drugs (NSAIDs), we sought to assess the effect of NSAIDs on fetuses with EA/TVD. We reviewed mothers of singleton fetuses with EA/TVD and PR, indicative of circular shunting, who were offered NSAIDs at multiple centers from 2010-2018. Initial dosing consisted of indomethacin, followed by ibuprofen in most cases. Twenty-one patients at 10 centers were offered therapy 4 at a median gestational age (GA) of 30.0 weeks (range: 20.9-34.9). Most (15/21=71%) mothers received NSAIDs, and 12/15 (80%) achieved DA constriction after a median of 2.0 days (1.0-6.0). All fetuses with DA constriction had improved PR; 92% had improved Doppler patterns. Median GA at pregnancy outcome was 36.1 weeks (30.7-39.0) in fetuses with DA constriction vs. 33 weeks (23.3-37.3) in fetuses who did not receive NSAIDs or achieve DA constriction (p=0.040). Eleven of 12 patients (92%) with DA constriction survived to live-birth, whereas 4/9 patients (44%) who did not receive NSAIDs or achieve DA constriction survived (p=0.046). In conclusion, our findings demonstrate the proof of concept that NSAIDs mitigate circular shunt physiology by DA constriction and improve PR among fetuses with severe EA/TVD. Although the early results are encouraging, further investigation is necessary to determine safety and efficacy.