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Cardiovascular magnetic resonance (CMR) imaging is recommended in patients with congenital heart disease (CHD) in clinical practice guidelines as the imaging standard for a large variety of diseases. As CMR is evolving, novel techniques are becoming available. Some of them are already used clinically, whereas others still need further evaluation. In this statement the authors give an overview of relevant new CMR techniques for the assessment of CHD. Studies with reference values for these new techniques are listed in the supplement.
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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.
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Cardiopatias Congênitas , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Humanos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Criança , Big Data , Imageamento por Ressonância Magnética , Projetos de Pesquisa , Fatores Etários , Adolescente , Pré-EscolarRESUMO
Recent years have witnessed exponential growth in cardiac imaging technologies, allowing better visualization of complex cardiac anatomy and improved assessment of physiology. These advances have become increasingly important as more complex surgical and catheter-based procedures are evolving to address the needs of a growing congenital heart disease population. This state-of-the-art review presents advances in echocardiography, cardiac magnetic resonance, cardiac computed tomography, invasive angiography, 3-dimensional modeling, and digital twin technology. The paper also highlights the integration of artificial intelligence with imaging technology. While some techniques are in their infancy and need further refinement, others have found their way into clinical workflow at well-resourced centers. Studies to evaluate the clinical value and cost-effectiveness of these techniques are needed. For techniques that enhance the value of care for congenital heart disease patients, resources will need to be allocated for education and training to promote widespread implementation.
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Inteligência Artificial , Cardiopatias Congênitas , Humanos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Ecocardiografia , Técnicas de Imagem Cardíaca/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Diastolic dysfunction affects clinical outcomes in patients with a functionally single ventricle (FSV). The objective of this work is to study the association of ventricular mechanics and interventricular dependence on diastolic parameters and early post-Fontan outcomes. Sixty-one patients with FSV underwent echocardiography, cardiac catheterization, and magnetic resonance imaging on the same day before or after the Fontan procedure. Echocardiographic diastolic parameters, ventricular mass, and incoordinate wall motion, defined by the number of dyskinetic segments or by the lateral wall delay, were determined and studied for relationships with invasively measured hemodynamics and early postoperative Fontan course. In subjects with a sizable secondary ventricle, incoordinate motion was additionally analyzed at the left- and right-sided ventricular free walls. Resting ventricular end-diastolic pressure (VEDP) was ≤10 mmHg in most subjects. Individual echocardiographic parameters of the diastolic flow and tissue velocities did not correlate with VEDP, other hemodynamics, or post-Fontan clinical course. Incoordinate wall motion in the dominant and in the sizeable secondary ventricle, defined by the lateral wall delay or by the number of dyskinetic segments, was the only echo parameter that correlated, albeit weakly, with VEDP (r = 0.247, P = 0.040), oxygen saturation (r = -0.417, P = 0.001), pulmonary vascular resistance and flow (Qp) (r = -0.303, P = 0.011), Fontan fenestration flow (r = 0.512, P = 0.009), and duration of endotracheal intubation (r = 0.292, P = 0.022). When the nondominant (secondary) ventricle was accounted for in the analysis of incoordinate wall motion, these associations strengthened. The degree of incoordinate ventricular wall motion in diastole was associated with VEDP and postoperative Fontan course in FSV. Analysis of incoordinate wall motion of the dominant and sizeable secondary ventricle may be warranted and should be included in the assessment of the FSV after the Fontan procedure.NEW & NOTEWORTHY Diastolic dysfunction affects outcomes in patients with functionally single ventricles (FSVs) but is difficult to assess. We found that incoordinate wall motion was the only echo parameter that correlated with FSV end-diastolic pressure, oxygen saturation, pulmonary vascular resistance and flow, and duration of endotracheal intubation. Analysis of incoordinate wall motion in the nondominant (secondary) ventricle strengthened these associations. Analyzing incoordinate wall motion should be included in the assessment of the FSV after the Fontan procedure.
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Cardiopatias Congênitas , Humanos , Diástole , Pressão Ventricular , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração , Ecocardiografia/métodosRESUMO
Progress in the field of congenital heart surgery over the last century can only be described as revolutionary. Recent improvements in patient outcomes have been achieved through refinements in perioperative care. In the current and future eras, the preservation and restoration of myocardial health, beginning with the monitoring of tissue remodeling, will be central to improving cardiac outcomes. Visualization and quantification of fibrotic myocardial remodeling is one of the greatest assets that cardiac MRI brings to the field of cardiology, and its clinical use within the field of congenital heart disease (CHD) has been an area of particular interest in the last few decades. This review summarizes the physical underpinnings of myocardial tissue characterization in CHD, with an emphasis on T1 parametric mapping and late gadolinium enhancement. It describes methods and suggestions for obtaining images, extracting quantitative and qualitative data, and interpreting the results for children and adults with CHD. The tissue characterization observed in different lesions is used to examine the causes and pathomechanisms of fibrotic remodeling in this population. Similarly, the clinical consequences of elevated imaging biomarkers of fibrosis on patient health and outcomes are explored. Keywords: Pediatrics, MR Imaging, Cardiac, Heart, Congenital, Tissue Characterization, Congenital Heart Disease, Cardiac MRI, Parametric Mapping, Fibrosis, Late Gadolinium Enhancement © RSNA, 2023.
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BACKGROUND: Neonatal Marfan syndrome is a rare disease with mortality in the first year of life reported as high as 95% predominantly due to progressive heart failure from valvar regurgitation and cardiomyopathy. Multisystem involvement and uncertain prognosis have historically precluded transplant candidacy, and current management options are of limited success. CASE REPORT: We present a baby girl with a postnatal diagnosis of neonatal Marfan syndrome who at 1 year of age underwent mitral valve and tricuspid valve repair with postoperative profound left ventricular and moderate right ventricular dysfunction necessitating biventricular assist device (BiVAD) support and subsequent heart transplant. A number of noncardiac issues persisted in our patient; however, she enjoyed a good quality of life for the initial 3 years posttransplant. Unfortunately, she subsequently developed rapidly progressive coronary allograft vasculopathy (CAV) with progressive deterioration in function and cardiac arrest. CONCLUSION: To our best knowledge, this is only the second case of neonatal Marfan syndrome to undergo heart transplant reported in the literature and the first with BiVAD support as a bridge to candidacy. This is also the first case of neonatal Marfan syndrome associated with intragenic duplication. This case though demonstrating that earlier listing, ventricular assist device (VAD) support and even primary transplant as treatment in neonatal Marfan syndrome should all be considered viable options but also portends a cautionary tale given the spectrum of comorbidities in this rare and severe disorder.
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Cardiomiopatias , Transplante de Coração , Síndrome de Marfan , Lactente , Recém-Nascido , Feminino , Humanos , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Qualidade de Vida , Cardiomiopatias/complicações , Valva TricúspideRESUMO
OBJECTIVES: Cardiac involvement in neonatal lupus erythematosis (NLE) can present as myocarditis/endocardial fibroelastosis (EFE). It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) is useful in identifying subclinical myocardial inflammation in infants exposed prenatally to anti-Ro antibodies. This study reports hs-cTnT levels in infants exposed to anti-Ro antibodies with/without cardiac NLE and reports cardiac MRI (CMR) findings in a subset of these children. METHODS: The study included 45 consecutive infants exposed prenatally to anti-Ro antibodies with (n = 7) or without (n = 38) cardiac NLE, who were seen at the SickKids NLE Clinic between 2012 and 2014. Hs-cTnT levels were measured at least once, and those infants with values of ≥30 ng/l were offered the opportunity to undergo CMR. Descriptive statistics were performed. RESULTS: Of 38 infants without cardiac NLE, 25 had a hs-cTnT level of ≥30 ng/l (including 1 of >113 ng/l); of these, 8 underwent CMR (all without myocarditis/EFE). All 7 infants with cardiac NLE had at least one hs-cTnT level of ≥30 ng/l, but only 2/7 had a level of >113 ng/l; 4/7 infants with cardiac NLE had CMR (all without myocarditis/EFE); 6/7 infants with cardiac NLE had their steroid treatment adjusted based on the trend in their hs-cTnT levels. CONCLUSION: Only 3/45 anti-Ro antibodies-exposed infants had hs-cTnT values outside the reference range reported in healthy infants. None of 12 infants who had CMR had subclinical myocarditis/EFE. Routine measurement of hs-cTnT in every anti-Ro antibody-exposed infant is not indicated. Further studies are needed to define the role of hs-cTnT as a biomarker for cardiac NLE.
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Miocardite , Troponina T , Recém-Nascido , Criança , Humanos , Lactente , Coração , BiomarcadoresRESUMO
Genome-wide association studies in patients revealed HSD17B13 as a potential new target for the treatment of nonalcoholic steatohepatitis (NASH) and other liver diseases. However, the physiological function and the disease-relevant substrate of HSD17B13 remain unknown. In addition, no suitable chemical probe for HSD17B13 has been published yet. Herein, we report the identification of the novel potent and selective HSD17B13 inhibitor BI-3231. Through high-throughput screening (HTS), using estradiol as substrate, compound 1 was identified and selected for subsequent optimization resulting in compound 45 (BI-3231). In addition to the characterization of compound 45 for its functional, physicochemical, and drug metabolism and pharmacokinetic (DMPK) properties, NAD+ dependency was investigated. To support Open Science, the chemical HSD17B13 probe BI-3231 will be available to the scientific community for free via the opnMe platform, and thus can help to elucidate the pharmacology of HSD17B13.
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Estudo de Associação Genômica Ampla , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ensaios de Triagem em Larga EscalaRESUMO
COVID vaccine-associated myocarditis was first identified in March 2021. There have been numerous case reports that detail the clinical course of paediatric patients older than age 12 with COVID vaccine-associated myocarditis. There are still very few reports of children between the ages of 5 and 11 with COVID vaccine-associated myocarditis. We present an 8 year- old with COVID vaccine-associated myocarditis after his second vaccination against SARS-CoV-2.
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Vacinas contra COVID-19 , COVID-19 , Miocardite , Vacinas , Criança , Pré-Escolar , Humanos , Vacinas contra COVID-19/efeitos adversos , Miocardite/induzido quimicamente , Miocardite/diagnóstico , SARS-CoV-2RESUMO
Right ventricular (RV) pressure loading leads to RV and left ventricular (LV) dysfunction through RV hypertrophy, dilatation and fibrosis. Relief of RV pressure load improves RV function. However, the impact and mechanisms on biventricular reverse-remodelling and function are only partially characterized. We evaluated the impact of RV pressure overload relief on biventricular remodelling and function in a rabbit model of reversible pulmonary artery banding (PAB). Rabbits were randomized to three groups: (1) Sham-operated controls (n = 7); (2) PAB (NDef, n = 7); (3) PAB followed by band deflation (Def, n = 5). Sham and NDef animals were sacrificed at 6 weeks after PAB surgery. Def animals underwent PAB deflation at 6 weeks and sacrifice at 9 weeks. Biventricular geometry, function, haemodynamics, hypertrophy and fibrosis were compared between groups using echocardiography, magnetic resonance imaging, high-fidelity pressure-tipped catheters and histology. RV pressure loading caused RV dilatation, systolic dysfunction, myocyte hypertrophy and LV compression which improved after PAB deflation. RV end-diastolic pressure (RVEDP) decreased after PAB deflation, although remaining elevated vs. Sham. LV end-diastolic pressure (LVEDP) was unchanged following PAB deflation. RV and LV collagen volumes in the NDef and Def group were increased vs. Sham, whereas RV and LV collagen volumes were similar between NDef and Def groups. RV myocyte hypertrophy (r = 0.75, P < 0.001) but not collagen volume was related to RVEDP. LV myocyte hypertrophy (r = 0.58, P = 0.016) and collagen volume (r = 0.56, P = 0.031) correlated with LVEDP. In conclusion, relief of RV pressure overload improves RV and LV geometry, hypertrophy and function independent of fibrosis. The long-term implications of persistent fibrosis and increased biventricular filling pressures, even after pressure load relief, need further study. KEY POINTS: Right ventricular (RV) pressure loading in a pulmonary artery banding rabbit model is associated with RV dilatation, left ventricular (LV) compression; biventricular myocyte hypertrophy, fibrosis and dysfunction. The mechanisms and impact of RV pressure load relief on biventricular remodelling and function has not been extensively studied. Relief of RV pressure overload improves biventricular geometry in conjunction with improved RV myocyte hypertrophy and function independent of reduced fibrosis. These findings raise questions as to the importance of fibrosis as a therapeutic target.
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Disfunção Ventricular Esquerda , Disfunção Ventricular Direita , Animais , Modelos Animais de Doenças , Fibrose , Ventrículos do Coração , Hipertrofia , Artéria Pulmonar , Coelhos , Disfunção Ventricular Esquerda/complicações , Função Ventricular Direita , Pressão VentricularRESUMO
Most cardiac imaging conferences have adopted social media as a means of disseminating conference highlights to a global audience well beyond the confines of the conference location. A deliberate and thoughtful social media campaign has the potential to increase the reach of the conference and allow for augmented engagement. The coronavirus disease 2019 (COVID-19) pandemic triggered a radical transformation in not just the delivery of healthcare but also the dissemination of science within the medical community. In the past, in-person medical conferences were an integral annual tradition for most medical professionals to stay up to date with the latest in the field. Social distancing requirements of the COVID-19 pandemic resulted in either cancelling medical conferences or shifting to a virtual format. Following suit, for the first time in its history, the 2021 Society for Cardiovascular Magnetic Resonance (SCMR) annual meeting was an all-virtual event. This called for a modified social media strategy which aimed to re-create the sociability of an in-person conference whilst also promoting global dissemination of the science being presented. This paper describes the employment of social media as well as the evolution through the SCMR scientific sessions for 2020 and 2021 that serves as a model for future cardiovascular conferences.
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COVID-19 , Mídias Sociais , Humanos , Espectroscopia de Ressonância Magnética , Pandemias , Valor Preditivo dos Testes , SARS-CoV-2RESUMO
BACKGROUND: Right ventricular fibrotic remodeling has been identified pre- and postoperatively in patients with tetralogy of Fallot (ToF) and linked to adverse outcomes. Polymorphisms of hypoxia inducible factor-1-alpha (HIF1A) have been associated with the fibrotic burden by cardiac magnetic resonance (CMR) late gadolinium enhancement imaging. Their association with diffuse fibrotic myocardial remodeling is unknown. We sought to determine whether polymorphisms in HIF1A are related to CMR markers of diffuse myocardial fibrosis. METHODS: Patients with repaired ToF who had undergone CMR with T1 mapping as well as whole genome sequencing were included. Myocardial native T1 was quantified using a modified Look-Locker inversion recovery sequence and measured in the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Patients who had at least one functioning allele of HIF1A were compared to those who did not using the Mann Whitney U test for continuous variables and chi-square or the Fischer test for discrete variables. RESULTS: 46 patients had both CMR and whole genome sequencing. Only one HIF1A variant was identified in the cohort and present in 13 patients. There were no significant differences in demographics, surgical variables, right or left ventricular volumes or function between patients with and without the variant. Despite a trend towards a lower age at the time of CMR (11.3 vs 13.7 years; p = 0.07), patients with HIF1A variants had higher native T1 values (1094 vs. 1050; p = 0.027) in the right ventricular outflow tract myocardium, reflecting increased diffuse interstitial ventricular fibrosis in them. CONCLUSION: Hypoxia-inducible factor is associated with imaging markers of increased diffuse right ventricular fibrosis late after repair of tetralogy of Fallot.
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Subunidade alfa do Fator 1 Induzível por Hipóxia , Tetralogia de Fallot , Meios de Contraste , Fibrose , Gadolínio , Variação Genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imageamento por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/genética , Tetralogia de Fallot/cirurgia , Função Ventricular DireitaRESUMO
BACKGROUND: The extent and significance in of cardiac remodeling in Fontan patients are unclear and were the subject of this study. METHODS: This retrospective cohort study compared cardiovascular magnetic resonance (CMR) imaging markers of cardiac function, myocardial fibrosis, and hemodynamics in young Fontan patients to controls. RESULTS: Fifty-five Fontan patients and 44 healthy controls were included (median age 14 years (range 7-17 years) vs 13 years (range 4-14 years), p = 0.057). Fontan patients had a higher indexed end-diastolic ventricular volume (EDVI 129 ml/m2 vs 93 ml/m2, p < 0.001), and lower ejection fraction (EF 45% vs 58%, p < 0.001), circumferential (CS - 23.5% vs - 30.8%, p < 0.001), radial (6.4% vs 8.2%, p < 0.001), and longitudinal strain (- 13.3% vs - 24.8%, p < 0.001). Compared to healthy controls, Fontan patients had higher extracellular volume fraction (ECV) (26.3% vs 20.6%, p < 0.001) and native T1 (1041 ms vs 986 ms, p < 0.001). Patients with a dominant right ventricle demonstrated larger ventricles (EDVI 146 ml/m2 vs 120 ml/m2, p = 0.03), lower EF (41% vs 47%, p = 0.008), worse CS (- 20.1% vs - 25.6%, p = 0.003), and a trend towards higher ECV (28.3% versus 24.1%, p = 0.09). Worse EF and CS correlated with longer cumulative bypass (R = - 0.36, p = 0.003 and R = 0.46, p < 0.001), cross-clamp (R = - 0.41, p = 0.001 and R = 0.40, p = 0.003) and circulatory arrest times (R = - 0.42, p < 0.001 and R = 0.27, p = 0.03). T1 correlated with aortopulmonary collateral (APC) flow (R = 0.36, p = 0.009) which, in the linear regression model, was independent of ventricular morphology (p = 0.9) and EDVI (p = 0.2). The composite outcome (cardiac readmission, cardiac reintervention, Fontan failure or any clinically significant arrhythmia) was associated with increased native T1 (1063 ms vs 1026 ms, p = 0.029) and EDVI (146 ml/m2 vs 118 ml/m2, p = 0.013), as well as decreased EF (42% vs 46%, p = 0.045) and worse CS (- 22% vs - 25%, p = 0.029). APC flow (HR 5.5 CI 1.9-16.2, p = 0.002) was independently associated with the composite outcome, independent of ventricular morphology (HR 0.71 CI 0.30-1.69 p = 0.44) and T1 (HR1.006 CI 1.0-1.13, p = 0.07). CONCLUSIONS: Pediatric Fontan patients have ventricular dysfunction, altered myocardial mechanics and increased fibrotic remodeling. Cumulative exposure to cardiopulmonary bypass and increased aortopulmonary collateral flow are associated with myocardial dysfunction and fibrosis. Cardiac dysfunction, fibrosis, and collateral flow are associated with adverse outcomes.
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Ventrículos do Coração , Imagem Cinética por Ressonância Magnética , Adolescente , Criança , Fibrose , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/cirurgia , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Função Ventricular EsquerdaRESUMO
PIP4K2A is an insufficiently studied type II lipid kinase that catalyzes the conversion of phosphatidylinositol-5-phosphate (PI5P) into phosphatidylinositol 4,5-bisphosphate (PI4,5P2). The involvement of PIP4K2A/B in cancer has been suggested, particularly in the context of p53 mutant/null tumors. PIP4K2A/B depletion has been shown to induce tumor growth inhibition, possibly due to hyperactivation of AKT and reactive oxygen species-mediated apoptosis. Herein, we report the identification of the novel potent and highly selective inhibitors BAY-091 and BAY-297 of the kinase PIP4K2A by high-throughput screening and subsequent structure-based optimization. Cellular target engagement of BAY-091 and BAY-297 was demonstrated using cellular thermal shift assay technology. However, inhibition of PIP4K2A with BAY-091 or BAY-297 did not translate into the hypothesized mode of action and antiproliferative activity in p53-deficient tumor cells. Therefore, BAY-091 and BAY-297 serve as valuable chemical probes to study PIP4K2A signaling and its involvement in pathophysiological conditions such as cancer.