A novel TGFßR2 splice variant in patient with aortic aneurysm and family history for aortic dissection: a case report.

We report the clinical presentation and genetic screening of a 31-year-old man with dilatation of the aortic root and ascending aorta and a positive family history for aortic dissection and sudden death. A novel heterozygous variant in a splice acceptor site (c.1600-1G>T) of TGFßR2 gene was identified by using a targeted multi-gene panel analysis. Bioinformatics tools predicted that the c.1600-1G>T variant is pathogenic by altering acceptor splice site at - 1 position affecting pre-mRNA splicing. These data confirm that the diverging splicing in the TGF-ß pathway genes may be an important process in aneurismal disease and emphasize the utility of genetic sequencing in the identification of high-risk patients for a more patient's management able to improve outcomes and minimize costs for the care of patients with heritable thoracic aortic aneurysm and dissection.

Impact of 4D-Flow CMR Parameters on Functional Evaluation of Fontan Circulation.

We sought to evaluate the potential clinical role of 4D-flow cardiac magnetic resonance (CMR)-derived energetics and flow parameters in a cohort of patients' post-Fontan palliation. In patients with Fontan circulation who underwent 4D-Flow CMR, streamlines distribution was evaluated, as well a 4D-flow CMR-derived energetics parameters as kinetic energy (KE) and energy loss (EL) normalized by volume. EL/KE index as a marker of flow efficiency was also calculated. Cardiopulmonary exercise test (CPET) was also performed in a subgroup of patients. The population study included 55 patients (mean age 22 ± 11 years). The analysis of the streamlines revealed a preferential distribution of the right superior vena cava flow for the right pulmonary artery (62.5 ± 35.4%) and a mild preferential flow for the left pulmonary artery (52.3 ± 40.6%) of the inferior vena cave-pulmonary arteries (IVC-PA) conduit. Patients with heart failure (HF) presented lower IVC/PA-conduit flow (0.75 ± 0.5 vs 1.3 ± 0.5 l/min/m2, p = 0.004) and a higher mean flow-jet angle of the IVC-PA conduit (39.2 ± 22.8 vs 15.2 ± 8.9, p < 0.001) than the remaining patients. EL/KE index correlates inversely with VO2/kg/min: R: - 0.45, p = 0.01 peak, minute ventilation (VE) R: - 0.466, p < 0.01, maximal voluntary ventilation: R:0.44, p = 0.001 and positively with the physiological dead space to the tidal volume ratio (VD/VT) peak: R: 0.58, p < 0.01. From our data, lower blood flow in IVC/PA conduit and eccentric flow was associated with HF whereas higher EL/KE index was associated with reduced functional capacity and impaired lung function. Larger studies are needed to confirm our results and to further improve the prognostic role of the 4D-Flow CMR in this challenging population.

Psychological Impact of a Prenatal Diagnosis of Congenital Heart Disease on Parents: Is It Time for Tailored Psychological Support?

The prenatal diagnosis of congenital heart disease (CHD) represents, for both parents, a particularly stressful and traumatic life event from a psychological point of view. The present review sought to summarize the findings of the most relevant literature on the psychological impact of prenatal diagnosis of CHD on parents, describing the most common mechanisms employed in order to face this unexpected finding. We also highlight the importance of counseling and the current gaps in the effects of psychological support on this population.

Overcoming Underpowering in the Outcome Analysis of Repaired-Tetralogy of Fallot: A Multicenter Database from the CMR/CT Working Group of the Italian Pediatric Cardiology Society (SICPed).

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population.

SCMR expert consensus statement for cardiovascular magnetic resonance of acquired and non-structural pediatric heart disease.

Cardiovascular magnetic resonance (CMR) is widely used for diagnostic imaging in the pediatric population. In addition to structural congenital heart disease (CHD), for which published guidelines are available, CMR is also performed for non-structural pediatric heart disease, for which guidelines are not available. This article provides guidelines for the performance and reporting of CMR in the pediatric population for non-structural ("non-congenital") heart disease, including cardiomyopathies, myocarditis, Kawasaki disease and systemic vasculitides, cardiac tumors, pericardial disease, pulmonary hypertension, heart transplant, and aortopathies. Given important differences in disease pathophysiology and clinical manifestations as well as unique technical challenges related to body size, heart rate, and sedation needs, these guidelines focus on optimization of the CMR examination in infants and children compared to adults. Disease states are discussed, including the goals of CMR examination, disease-specific protocols, and limitations and pitfalls, as well as newer techniques that remain under development.

Prognostic factors in hypertrophic cardiomyopathy in children: An MRI based study.

BACKGROUND: Clinical and prognostic role of cardiac magnetic resonance (CMR) in adult population with hypertrophic cardiomyopathy (HCM) have been largely assessed. We sought to investigate the role of CMR for predicting cardiovascular events in children with HCM. METHODS: CMR was performed in 116 patients with HCM (37 sarcomeric mutations, 31 other mutations, mean age 10.4 ± 4.3 yrs). CMR protocol included cine imaging for evaluation of morphology and function and late gadolinium enhancement (LGE). Hard cardiac events (sustained VT, resuscitated cardiac arrest, sudden cardiac death, end-stage heart failure, heart transplant and appropriate ICD intervention) were recorded through a median follow-up of 4 (1-7) years. RESULTS: During follow-up 21 heart cardiac events occurred. At maximal-rank statistic the optimal cut-point for LGE extent for predicting events was ≥2%. Syncope, non-sustained ventricular tachycardia (NSVT) and LGE extent ≥2% were independent predictors of events. At Harrel's C statistic combination of LGE extent ≥2% and syncope was the strongest model for predicting events. HR of patients with LGE extent ≥2% and no history of syncope was 3.6 (1.1-12.2) that increased to 37.6 (5.4-161) in those with LGE extent ≥2% and syncope. The median time dependent AUC of LGE extent (0.88, 95% CI 0.86-0.89) was significantly higher than that of syncope (0.63, 95% CI 0.61-0.66, p < 0.0001) and NSVT (0.52, 95% CI 0.50-0.53, p < 0.0001). CONCLUSIONS: In children with HCM, LGE and syncope were independent predictors of hard cardiac events at follow-up.

Recommendations for cardiovascular magnetic resonance and computed tomography in congenital heart disease: a consensus paper from the CMR/CCT working group of the Italian Society of Pediatric Cardiology (SICP) and the Italian College of Cardiac Radiology endorsed by the Italian Society of Medical and Interventional Radiology (SIRM) Part I.

Cardiovascular magnetic resonance (CMR) and computed tomography (CCT) are advanced imaging modalities that recently revolutionized the conventional diagnostic approach to congenital heart diseases (CHD), supporting echocardiography and often replacing cardiac catheterization. Nevertheless, correct execution and interpretation require in-depth knowledge of all technical and clinical aspects of CHD, a careful assessment of risks and benefits before each exam, proper imaging protocols to maximize diagnostic information, minimizing harm. This position paper, written by experts from the Working Group of the Italian Society of Pediatric Cardiology and from the Italian College of Cardiac Radiology of the Italian Society of Medical and Interventional Radiology, is intended as a practical guide for applying CCT and CMR in children and adults with CHD, wishing to support Radiologists, Pediatricians, Cardiologists and Cardiac Surgeons in the multimodality diagnostic approach to these patients. The first part provides a review of the most relevant literature in the field, describes each modality's advantage and drawback, making considerations on the main applications, image quality, and safety issues. The second part focuses on clinical indications and appropriateness criteria for CMR and CCT, considering the level of CHD complexity, the clinical and logistic setting and the operator expertise.

Accuracy of Cardiac Magnetic Resonance Imaging in Diagnosing Pediatric Cardiac Masses: A Multicenter Study.

BACKGROUND: After diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric cardiac magnetic resonance (CMR)-based diagnostic criteria. OBJECTIVES: The goals of this study were to: 1) evaluate the CMR characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information. METHODS: CMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis. RESULTS: Of 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis. CONCLUSIONS: CMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.

Role of cardiac MRI in the prediction of pre-Fontan end-diastolic ventricular pressure.

BACKGROUND: Growing evidence has emphasised the importance of ventricular performance in functionally single-ventricle patients, particularly concerning diastolic function. Cardiac MRI has been proposed as non-invasive alternative to pre-Fontan cardiac catheterisation in selected patients. AIM OF THE STUDY: To identify clinical and cardiac magnetic resonance predictors of high pre-Fontan end-diastolic ventricular pressure. METHOD: In a retrospective single-centre study, 38 patients with functionally univentricular heart candidate for Fontan intervention, who underwent pre-Fontan cardiac catheterisation, beside a comprehensive cardiac MRI, echocardiographic, and clinical assessment were included. Medical and surgical history, cardiac magnetic resonance, cardiac catheterisation, echocardiographic, and clinical data were recorded. We investigated the association between non-invasive parameters and cardiac catheterisation pre-Fontan risk factors, in particular with end-diastolic ventricular pressure. Moreover, the impact of conventional invasive pre-Fontan risk factor on post-operative outcome as also assessed. RESULTS: Post-operative complications were associated with higher end-diastolic ventricular pressure and Mayo Clinic indexes (p < 0.01 and p = 0.05, respectively). At receiver operating characteristic curve analysis end-diastolic ventricular pressure ≥ 10.5 mmHg predicted post-operative complications with a sensitivity of 75% and specificity of 88% (AUC: 0.795, 95% CI 0.576;1.000, p < 0.05). At multivariate analysis, both systemic right ventricle (OR: 23.312, 95% CI: 2.704-200.979, p < 0.01) and superior caval vein indexed flow (OR: 0.996, 95% CI: 0.993-0.999, p < 0.05) influenced end-diastolic ventricular pressure ≥ 10.5 mmHg. CONCLUSIONS: A reduced superior caval vein flow, evaluated at cardiac magnetic resonance, is associated with higher end-diastolic ventricular pressure a predictor of early adverse outcome in post-Fontan patients.

A New Web Score to Predict Health Status in Paediatric Patients with Chronic Diseases: Design and Development of the PENSAMI Study.

Paediatric chronic diseases (CD) are characterised by their ongoing duration and the fact that they are often managed throughout the lifespan, with the need to adjust lifestyle and expectations with the limitations coming from the CD. The aim of the PENSAMI study is to not only cure the disease, but to also care for the person from a clinical and psychosocial perspective. Data will be collected from 150 paediatric patients affected by heart disease, diabetes, and asthma admitted during in-hospital stay or outpatient visits, and from 200 healthy control subjects. The protocol will consist of two phases. The first one will aim at elaborating the predictive model by detecting (clinical, anthropometric at birth, environmental, lifestyle, social context, emotional state, and mental abilities) in order to develop a model predictive of the events considered: (1) re-hospitalisation; (2) severity and progression of the disease; (3) adherence to therapy; (4) HRQoL; (5) obesity and metabolic syndrome; (6) illness-stress related; (7) school drop-out; (8) school performance. The second one will address validating the previous predictive model. This model will aim to: (1) understand, prevent, and halt the progression of childhood CD; (2) develop new and improved diagnostic tools; (3) pave the way for innovative treatments and additional therapies to traditional clinical practice; and (4) create truly personalised therapeutic and preventive strategies in various sectors, such as cardiology, diabetes, and respiratory diseases.

The impact of native Fallot anatomy on future therapeutic requirements and outcomes at follow-up.

BACKGROUND: In patients with repaired Fallot, subsequent surgical or interventional procedures and adverse cardiac events are frequent. We aimed to evaluate the impact of a simple pre-operative anatomic classification based on the size of the pulmonary valve (PV) annulus and branches on future therapeutic requirements and outcomes. METHOD: This is a single-center retrospective analysis of patients operated for Fallot before the age of 2 years, from January 1990. Pre-operative anatomy, surgical and interventional procedures and adverse events were extrapolated from clinical records. RESULTS: Among the 312 patients, a description of the PV and pulmonary arteries (PAs) native anatomy was known in 239 patients (male:147, 61.5%), which were divided in the following 3 groups: group 1 (65 patients) with normal size of both PV and PAs; group 2 (108 patients) with PV hypoplasia but normal size PAs; group 3 (66 patients) with concomitant hypoplasia of the PV and PAs. During the 12.7 years (IQR 6.7-17) follow-up time, 23% of patients required at least one surgical or interventional procedure. At Kaplan-Meier analysis, there was a significant difference in requirement of future surgical or interventional procedures among the 3 groups (p < 0,001). At multivariate Cox regression analysis, hypoplasia of PV and PAs was an independent predictor of subsequent procedures (HR:3.1,CI:1.06-9.1, p = 0.03). CONCLUSION: Native anatomy in Tetralogy of Fallot patients affects surgical strategy and follow-up. It would be therefore advisable to tailor patient's counseling and follow-up according to native anatomy, rather than following a standardized protocol.

Pitfalls in surgical repair of Fallot's tetralogy: The "ventricular subaortic pouch".

Fallot-type ventricular septal defect (VSD) is characterized by anterior malalignment of the outlet septum with variable degree of aortic dextroposition. Correct identification of the borders of the defect is crucial to achieve an optimal surgical repair. We describe a particular postsurgical lesion, identified by cardiac magnetic resonance and cardiac computed tomography, which results from an improper surgical closure technique of anterior malaligned VSD. Based on its anatomical features we defined this entity "subaortic pouch." A comprehensive description of this defect is here provided along with an in-depth analysis of the proper operative technique for Fallot-type VSD repair.

Trans-catheter closure of a rare cause of pre-tricuspid left-to-right shunt: A "double" levoatriocardinal vein without left heart obstructive lesions.

The levoatriocardinal vein is a rare vascular anomalous connection between the left atrium and the superior vena cava (or left innominate vein). This defect is usually associated with left heart obstructive lesions, while it is rarely found in an isolated form. In the former case, the anomalous connection causes a pre-tricuspid left-to-right shunt with right-heart volume overload. We describe the first case of "double" homolateral levoatriocardinal vein in a child with signs and symptoms of right-heart failure and pulmonary blood-flow overload. A trans-catheter closure of both vascular connections was performed with two Amplatzer Vascular Plug type II (Abbott, Plymouth, MN, USA). The percutaneous approach proved to be safe and effective, with early improvement in the signs and symptoms of heart failure. .

Biventricular Reference Values by Body Surface Area, Age, and Gender in a Large Cohort of Well-Treated Thalassemia Major Patients Without Heart Damage Using a Multiparametric CMR Approach.

BACKGROUND: Cardiac MRI plays a critical role in the management of thalassemic patients. No accurate biventricular reference values are available. PURPOSE: To establish the ranges for normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) and LV mass normalized to body surface area (BSA), age, and gender in a large cohort of well-treated beta-thalassemia major (ß-TM) patients without heart damage using a multiparametric MRI. STUDY TYPE: Retrospective/cohort study. POPULATION: In all, 251 ß-TM patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2 * ≥20 msec, and 246 healthy subjects. FIELD STRENGTH/SEQUENCE: 1.5T/cine steady-state free precession (SSFP), gradient-echo T2 *, late gadolinium enhancement (LGE) images. ASSESSMENT: Biventricular end-diastolic volume, end-systolic volume, stroke volume, and LV mass were normalized to BSA (EDVI, ESVI, SVI). STATISTICAL TESTS: Comparisons between the two groups was performed with two-samples t-test or Wilcoxon's signed rank test. For more than two groups, one-way analysis of variance (ANOVA) or a Kruskal-Wallis test were applied. RESULTS: Compared to controls, males with ß-TM showed significantlt higher LVEDVI in all the age groups, while for the other volumes the difference was significant only within one or more age groups. In females the volumes were comparable between ß-TM patients and healthy subjects in all the age groups. In the male ß-TM population we found a significant effect of age on LVEDVI (P = 0.017), LVESVI (P = 0.001), RVESVI (P = 0.029), and RVEF (P = 0.031), while for females none of the biventricular parameters were significantly different among the age groups (LVEDVI: P = 0.614; LVESVI: P = 0.449; LVSVI: P = 0.186; LV mass index: P = 0.071; LVEF: P = 0.059; RVEDVI: P = 0.374; RVESVI: P = 0.180; RVSVI: P = 0.206; RVEF: P = 0.057). In ß-TM patients all biventricular volume indexes as well as the LV mass index were significantly larger in males than in females (P < 0.0001 in all cases). The LV and the RV EF were comparable between the sexes (P = 0.568 and P = 0.268, respectively). DATA CONCLUSION: Appropriate "normal" reference ranges normalized to BSA, sex, and age are recommended to avoid misdiagnosis of cardiomyopathy in ß-TM patients. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Evolution of acute myocarditis in a pediatric population: An MRI based study.

BACKGROUND: Cardiac Magnetic Resonance (CMR) data regarding myocarditis presentation and disease course is still lacking in pediatric patients. We evaluate baseline CMR and evolution of functional and tissue abnormalities in children with acute myocarditis. METHODS: CMR was performed in 125 patients with clinical diagnosis of acute myocarditis. Clinical follow-up was performed for a median of 498 (214-923) days. RESULTS: LVEF was depressed (<55%) in 56 cases (45%) upon baseline CMR. LGE was found in 93 patients (77%) of cases. LGE was exclusively subepicardial in 29 patients (23%), while other LGE patterns (midwall/mixed) were present in 64 (51%). CMR was repeated in 92 (74%) patients. 67% presented recover of function at a median of 170 (70-746) days after onset of symptoms. Midwall/mixed LGE pattern had a statistically significant correlation with absent recover of function (OR 0.20 p 0.036). Thirteen patients (16%) had recovery from LV dysfunction but with persistence of LGE. Sub-epicardial pattern of LGE (OR 3.33, 95% CI 1.08-10.2, p = 0.036) and the presence of fever at admission (OR 4.67, 95% CI 1.16-18.7, p = 0.03) were associated with a significantly higher likelihood of complete normalization while midwall/mixed LGE pattern was associated with non-recovery. CONCLUSIONS: In pediatric myocarditis, midwall/mixed LGE pattern is associated with absent recover of function. Patients with recover of function may still have persistence of LGE, while a complete recovery from functional and tissue abnormalities is found only in a third of patients. Midwall/mixed pattern of LGE at first MRI was associated to worse outcome.

The different surgical impact of the superior cavoatrial incision in children and adults.

INTRODUCTION: The single- and double-patch repairs are undoubtedly the most commonly used techniques for the surgical management of partial anomalous pulmonary venous connection associated with sinus venosus atrial septal defect. The aim of this study was to retrospectively compare early and long-term surgical outcomes in paediatric and adult patients, focusing in particular on the occurrence of ectopic atrial rhythm. MATERIAL AND METHODS: Seventy patients (male: 38, 54.2%) underwent surgical repair for partial anomalous pulmonary venous connection with sinus venosus atrial septal defect. Forty-nine patients (70%) underwent surgical repair in paediatric age (<16 years old), while 21 of (30%) patients were operated in adulthood. Thirty patients (42.8%) underwent single-patch repair and 39 patients (55.7%) underwent double-patch repair. In only one patient, the Warden procedure was performed (1.4%). Median follow-up time was 52 months (IQ 15.1-113). RESULTS: The type of surgical technique didn't affect the incidence of ectopic atrial rhythm (26.6% in single-patch group and 25.6% in double-patch groups, p = 0.9). At long-term follow-up, ectopic atrial rhythm, as an expression of sinoatrial node disturbance, was however significantly more frequent in the paediatric population (28.8% paediatric group and 4.7% adult group, p = 0.02). CONCLUSIONS: The higher incidence of ectopic atrial rhythm in children is probably related to the closer position of the sinus node to the superior cavoatrial incision, which makes irreversible iatrogenic traumatism more likely to occur. Surgical techniques that avoid any manipulation on the superior cavoatrial junction should, therefore, be preferred for children undergoing partial anomalous pulmonary venous connection repair.