Dilated cardiomyopathy in a pediatric population: etiology and outcome predictors - a single-center experience.

AIM: The aim of the study was to assess predictors of outcome in patients hospitalized for dilated cardiomyopathy (DCM) and severe left ventricular dysfunction. Patients & methods: 83 pediatric patients hospitalized for heart failure due to DCM with coexistent left ventricular dysfunction were enrolled. RESULTS: Overall, 5-year survival free from heart transplantation was 69.8%. Normalization of left ventricular function was achieved in 39.8% of patients during follow-up: younger age, less necessity of inotropic support and other than idiopathic DCM predicted left ventricular function, while familial history for cardiac disease or sudden death and inotropic support during hospitalization were associated with poorer outcome. CONCLUSION: Almost 40% of patients with DCM experienced a complete normalization of cardiac function. Outcome was extremely variable according to the type of DCM.

Multimodality imaging, single center, cross-sectional study in adolescents or young adults with repaired tetralogy of Fallout.

BACKGROUND: Proper integration of multiple imaging modalities in the routine follow-up of patients with repaired tetralogy of Fallout (TOF) is poorly supported by data. We report our single center comparative study between cardiac magnetic resonance (CMR) and echocardiography to assess equipoise in the clinical utility of these two imaging methods in an unselected consecutive cohort of TOF patients referred to our outpatient clinic. MATERIAL AND METHODS: In this cross-sectional study, repaired TOF patients who underwent CMR and echocardiography within a 4-week period between 2010 and 2011 at our Center were included. Linear regression was used to analyze degree of inter modality correlation. A prediction model tested the association between functional data/probrain natriuretic peptide (Pro-BNP) with CMR. RESULTS: Fifty patients were included in the study (mean age 31 ±â€Š18 years). The best predictors of right ventricle (RV) ejection fraction at CMR were tricuspid anular plane systolic excursion (tricuspid valve anular plane systolic excursion, R 0.37, P < 0.0001) and RV peak S-wave velocity (R 0.40, P < 0.001). Pro-BNP levels did present weak correlation with New York Heart Association functional class (R 0.31, P < 0.002) and QRS duration (R 0.32, P < 0.002) and a moderate correlation with right atrium area at CMR (R 0.46, P < 0.0001). CONCLUSION: We found limited correlation between the two imaging modalities in the evaluation of RV after intracardiac repair of TOF. Pro-BNP level presents moderate correlation with right atrium area measured with echocardiography. Serial CMR evaluations are needed in this patient population, but they may be interchanged by routine echocardiography in particular in patients with normal or stable echocardiographic parameters.

Tissue Doppler Imaging for anthracycline cardiotoxicity monitoring in pediatric patients with cancer.

BACKGROUND: Cardiotoxic effects of anthracycline therapy are a major cause of morbidity for childhood cancer survivors. The aim of this retrospective evaluation is to assess the efficacy of Tissue Doppler Imaging in the early detection of myocardial alterations in these patients. METHODS: A population of 50 childhood cancer survivors (32 males and 18 females) who have been treated with anthracyclines was evaluated by standard and TDI echocardiographic examination of the basal and median region of the interventricular septum (IVSb, IVSm), of the left ventricular posterior wall (LVPWb, LVPWm), and of the mitral annulus; the results were compared with those obtained from a population of 50 healthy age-matched and sex-matched controls by using the Student test. The clinical and echocardiographic data of the two groups were compared also with the independent samples t-test. All data were expressed as mean ± standard deviation. A two-tailed P-value < 0.05 was considered statistically significant. Statistical analysis was performed using STATA 7.0. RESULTS: The case-control analysis showed statistically significant differences (p < 0,05) between the patients and the controls values. The systolic performance of the patients was normal (LVEF (p = 0,0029) and LVFS (p = 0,0002)). Statistically significant differences between patients and controls were found for diastolic function measurements obtained with PW Doppler such as IVRT (p = 0,0000), DT (p = 0,0041), E (p = 0,0000), A (p = 0,0458), even if E/A ratio was not altered. TDI analysis also show significant differences between patients and controls in both LVPW and IVS (basal and middle segments); E/E' ratio and E'/A' ratio did not vary significantly. Linear Regression and multivariate analysis showed that Hematopoietic Stem Cell Transplantation had the highest impact on our measurements. CONCLUSIONS: The results showed a myocardial diastolic impairment with preserved ejection fraction. Since the median follow-up time of our cohort was 2 years, further evaluation is needed to better define the diastolic alterations. TDI analysis showed high sensitivity for the detection of mild myocardial dysfunction; the implementation of this novel method as standard practice in the follow-up of selected childhood cancer survivors might help to achieve a better management of long-term complications of cardiotoxic chemotherapy.

Upside-down position for the out of hospital management of children with supraventricular tachycardia.

BACKGROUND: The upside-down position is a little known modified Valsalva manoeuvre (VM). The aim of this study was to investigate the safety and the efficacy of the upside-down position for the treatment of paroxysmal SVT in children. METHODS: Twenty-four paediatric patients followed for SVT were enrolled. The patients were assigned (1:1) to a standard VM or to an upside-down position at the first episode of SVT at home. If no cardioversion occurred, a second attempt was undertaken with the other VM. At the patient's first relapse, the intervention protocol was applied in the opposite order at home. RESULTS: The upside-down position compared to standard VM reached 67% vs 33% rate of cardioversion at a first attempt, followed by 50% vs 0% rate of cardioversion in patients who had failed the first attempt. After having reversed the order of intervention in case of SVT recurrence, we recorded 67% vs 25% and 71% vs 42% success rates in favour of the upside-down position. There were no adverse events. CONCLUSION: The upside-down position was safe and tended to be more effective than standard VM for out of hospital SVT treatment. Doctors and parents should be more aware of this effective but overlooked manoeuvre.

Consensus Document of the Italian Association of Hospital Cardiologists (ANMCO), Italian Society of Pediatric Cardiology (SICP), and Italian Society of Gynaecologists and Obstetrics (SIGO): pregnancy and congenital heart diseases.

The success of cardiac surgery over the past 50 years has increased numbers and median age of survivors with congenital heart disease (CHD). Adults now represent two-thirds of patients with CHD; in the USA alone the number is estimated to exceed 1 million. In this population, many affected women reach reproductive age and wish to have children. While in many CHD patients pregnancy can be accomplished successfully, some special situations with complex anatomy, iatrogenic or residual pathology are associated with an increased risk of severe maternal and fetal complications. Pre-conception counselling allows women to come to truly informed choices. Risk stratification tools can also help high-risk women to eventually renounce to pregnancy and to adopt safe contraception options. Once pregnant, women identified as intermediate or high risk should receive multidisciplinary care involving a cardiologist, an obstetrician and an anesthesiologist with specific expertise in managing this peculiar medical challenge. This document is intended to provide cardiologists working in hospitals where an Obstetrics and Gynecology Department is available with a streamlined and practical tool, useful for them to select the best management strategies to deal with a woman affected by CHD who desires to plan pregnancy or is already pregnant.

Acquired intracranial arterial aneurysm and stroke after vessel dissection in a child with coarctation of the aorta.

Vascular events in patients with coarctation of the aorta have been extensively reported and account for the majority of morbidity and mortality in untreated patients. The exact mechanism for this association is not completely understood and may include acquired anomalies or congenital abnormalities of intracranial vessel. Here we report a case of intracranial internal carotid artery dissection with subsequent formation of acquired large carotid aneurysm in a child with severe systemic hypertension and coarctation of the aorta. Endovascular aneurysm exclusion was pursued and it was able to control this potentially lethal complication. This case supports the notion of acquired nature of intracranial vessel abnormalities and underscores the clinical role of interventional neuroradiology in a subset of patients with congenital heart disease.

Recurrent Stroke after Transcatheter PFO Closure in Cryptogenic Stroke or Tia: Long-Term Follow-Up.

BACKGROUND: There are few data on the mechanism of recurrent neurological events after transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA. METHODS: We retrospectively reviewed PFO closure procedures for the secondary prevention of cryptogenic stroke/TIA performed between 1999 and 2014 in Bologna, Italy. RESULTS: Written questionnaires were completed by 402 patients. Mean follow-up was 7 ± 3 years. Stroke recurred in 3.2% (0.5/100 patients-year) and TIA in 2.7% (0.4/100 patients-year). Ninety-two percent of recurrent strokes were not cryptogenic. Recurrent stroke was noncardioembolic in 69% of patients, AF related in 15% of patients, device related in 1 patient, and cryptogenic in 1 patient. AF was diagnosed after the procedure in 21 patients (5.2%). Multivariate Cox's proportion hazard model identified age ≥ 55 years at the time of closure (OR 3.16, p=0.007) and RoPE score < 7 (OR 3.21, p=0.03) as predictors of recurrent neurological events. CONCLUSION: Recurrent neurological events after PFO closure are rare, usually noncryptogenic and associated with conventional vascular risk factors or AF related. Patients older than 55 years of age and those with a RoPE score < 7 are likely to get less benefit from PFO closure. After transcatheter PFO closure, lifelong strict vascular risk factor control is warranted.

[ANMCO/SICP/SIGO Consensus document: Pregnancy and congenital heart disease]. / Documento di consenso ANMCO/SICP/SIGO: Gravidanza e cardiopatie congenite.

The success of cardiac surgery over the past 50 years has increased numbers and median age of survivors with congenital heart disease (CHD). Adults now represent two-thirds of patients with CHD; in the United States alone the number is estimated to exceed 1 million.In this population many affected women reach reproductive age and wish to have children. While in many CHD patients pregnancy can be accomplished successfully, some special situations with complex anatomy, iatrogenic or residual pathology are associated with an increased risk of severe maternal and fetal complications. Pre-conception counseling allows women to come to truly informed choices. Risk stratification tools can also help high-risk women to eventually renounce to pregnancy and to adopt safe contraception options. Once pregnant, women identified as intermediate or high-risk should receive multidisciplinary care involving a cardiologist, an obstetrician and an anesthesiologist with specific expertise in managing this peculiar medical challenge.This document is intended to provide cardiologists working in hospitals where an Obstetrics and Gynecology Department is available with a streamlined and practical tool, useful for them to select the best management strategies to deal with a woman affected by CHD who desires to plan pregnancy or is already pregnant.

Incidence of Respiratory Disease During the First Two Years of Life in Children with Hemodynamically Significant Congenital Heart Disease in Italy: A Retrospective Study.

Children affected by hemodynamically significant congenital heart disease (HSCHD) experience severe respiratory complications that can increase the frequency of hospitalizations. The aim of the SINERGY study was to describe the incidence of respiratory diseases and to collect information on active and passive immunoprophylaxis in the first 2 years of life. In this retrospective, multicenter, and epidemiologic study, children with HSCHD were enrolled across 11 Italian sites. Children born between December 31, 2007, and December 31, 2012, were observed during their first 2 years of life. Data were collected through hospital database searches and parent interviews. Four hundred twenty children were enrolled: 51.7 % were female, 79.5 % were born full-term (≥37 weeks), and 77.6 % weighed >2500 g at birth. The most frequent heart defects were ventricular septal defect (23.1 %) and coarctation of the aorta (14.3 %). The incidence of respiratory diseases was 63.1 %. Frequent respiratory diseases not requiring hospitalization were upper respiratory tract infections (76.4 %), acute bronchitis (43.3 %), and influenza (22.1 %), while those requiring hospitalization were bronchitis and bronchiolitis (8.3 % each one). While active immunoprophylaxis was applied with wide compliance (diphtheria/pertussis/tetanus, 99.5 %; Haemophilus influenzae type b, 72.5 %; pneumococcus, 79.9 %; meningococcus, 77.4 %), only 54 % of children received respiratory syncytial virus (RSV) passive prophylaxis (palivizumab). Of the 35 hospitalizations due to bronchiolitis, 27 (77.1 %) did not receive prophylaxis against RSV, compared with 8 (22.9 %) who received prophylaxis (P < 0.0001). Children with HSCHD are at major risk of respiratory diseases. Passive immunoprophylaxis can help to prevent hospitalizations for bronchiolitis.

[Pulmonary embolism in complex corrected congenital heart disease]. / La tromboembolia polmonare nelle cardiopatie congenite complesse operate.

Pulmonary embolism is an uncommon but potentially fatal disease in children, especially with congenital heart disease where pulmonary perfusion depends on caval flow. Anticoagulation is the mainstay of therapy for children with pulmonary embolism. However, thrombolytic therapy can also be considered. The outcome of pediatric pulmonary embolism is uncertain and needs further investigation. We suggest increased awareness and a high index of suspicion in the presence of suggestive clinical signs in high-risk patients in order to initiate prompt diagnostic imaging and treatment.

Diagnostic Accuracy of Aortic Root Cross-sectional Area/Height Ratio in Children and Young Adults with Marfan and Loeys-Dietz Syndrome.

BACKGROUND: Accurate quantification of aortic dilatation is critical in children with syndromes associated with thoracic aortic aneurysm, yet classification of normality is difficult. Current methods of normalization use body surface area to account for growth, despite a nonlinear relationship of body surface area to aortic root dimensions. In contrast, height has a linear relationship with aortic root dimensions in normal children, is simple to measure and requires no secondary calculation. We evaluated the diagnostic accuracy of an height-based aortic root-indexing method, aortic root cross-sectional area/height ratio (AHr), in children with Marfan and Loeys-Dietz syndromes. METHODS: A cohort of 54 children with Marfan or Loeys-Dietz syndromes, aged 3 months to 17 years, were evaluated with a transthoracic echocardiogram. AHr was measured in diastole at sinuses of Valsalva (SoV) and proximal ascending aorta (pAA) in a group of normal subjects matched for age and body surface area and normal values were provided. AHr values were recorded for patients and compared with z-scores results obtained with Gautier's and Campens's nomograms. RESULTS: AHr values in the group of normal subjects were 2.6 ± 0.6 at SoV and 2 ± 0.5 at pAA. Categorization of z-scores and AHr showed good correspondence between AHr and Gautier's method (P = .341 at SoV and .185 at pAA) and AHr and Campens method (P =.465 at SoV and 0.110 at pAA). CONCLUSIONS: There was a good correspondence of AHr results with two different z-scores. AHr is a simple to use and valid option to quantify aortic root dilatation in pediatric patients.

Endomyocardial biopsy safety and clinical yield in pediatric myocarditis: An Italian perspective.

OBJECTIVES: The objective of this investigation is to evaluate the safety, the impact of endomyocardial biopsy (EMB) results in myocarditis management and the incidence of different etiologies of myocarditis in a pediatric population. BACKGROUND: Although EMB is an established diagnostic tool to evaluate suspected myocarditis, there is lack of clear diagnostic and management guidelines for myocarditis in pediatric patients, particularly in infants. METHODS: We performed a retrospective database review and subsequent outcomes analysis from five Italian pediatric cardiology centers to identify patients aged 0-18 years who underwent EMB for suspected myocarditis or inflammatory cardiomyopathy (ICMP) between 2009 and 2011. RESULTS: EMB was performed in 41 children, of which 16 were male. The population ranged between 16 days of age to 17 years (mean age at EMB = 5.2 ± 4.9 years). The overall incidence of EMB-related complications was 15.5% (31.2% in infants, and 6.8% in children > 1 year of age; P = 0.079) while the incidence of EMB-driven treatment changes was 29.2%. Histological examination together with PCR on heart biopsy specimens allowed an etiological diagnosis in 26/41 patients (63%). Among the 15 patients (36.5%) with diagnosis of dilated cardiomyopathy (DCM) 11 had idiopathic DCM. Finally, we found an overall incidence of death/cardiac transplantation of 24%. CONCLUSIONS: In a pediatric population with suspected myocarditis/ICMP, EMB was useful in confirming the diagnosis only in 41% of cases but showed an overall diagnostic power of 63%. As complications of EBM are not negligible, particularly in infants, the risk/benefit ratio should be taken into account in each patient.

A 74-year-old unoperated univentricular heart: the oldest reported survival.

Univentricular heart is a rare congenital heart malformation. Nowadays prognosis is considered to be strictly linked to surgical intervention, and survival into late adulthood is unusual. In some patients native haemodynamic circulation balances pulmonary and systemic blood flow, allowing long-term survival without the need for surgery. We report the case of a 74-year-old man with a univentricular heart in natural history, and we discuss the factors that might contribute to his extraordinary long-term survival.

[Aortic root dilatation rate in pediatric patients with Marfan syndrome treated with losartan]. / Progressione della dilatazione aortica nel paziente pediatrico con sindrome di Marfan in terapia medica con losartan.

BACKGROUND: Medical therapy with angiotensin II receptor blockers/angiotensin-converting enzyme inhibitors and/or beta-blockers was reported to reduce aortic root dilatation rates in pediatric patients with Marfan syndrome. No data are available in the literature on losartan effects after 3 years of therapy. The aim of our study was to establish whether losartan reduces aortic root dilatation rates in pediatric patients with Marfan syndrome in the mid and long term. METHODS: This is a retrospective analysis of 38 pediatric patients with Marfan syndrome followed at the Marfan Clinic of S. Orsola-Malpighi Hospital of the University of Bologna (Italy). Aortic diameters were measured at sinuses of Valsalva and proximal ascending aorta with transthoracic echocardiography. RESULTS: After a mean follow-up of 4.5 ± 2.5 years (range 2-9 years), aortic root z score at sinuses of Valsalva and proximal ascending aorta remained stable. The average annual rate of change in aortic root z score was -0.1 ± 0.4 and 0 ± 0.3 at sinuses of Valsalva and proximal ascending aorta, respectively. The mean dose of losartan was 0.7 ± 0.3 mg/kg/day. Three patients were non-responders, probably because of late beginning or low dose of therapy. Eight patients underwent cardiac surgery (aortic root surgery in 5 and mitral valve repair in 3), all of them started losartan later in life. CONCLUSIONS: Despite the retrospective design of the study and the small sample size, a beneficial effect of losartan therapy was observed in pediatric patients with Marfan syndrome in the mid and long term. Late beginning or low doses of losartan can turn off the effects of therapy.

Frequency of Intracranial Aneurysms Determined by Magnetic Resonance Angiography in Children (Mean Age 16) Having Operative or Endovascular Treatment of Coarctation of the Aorta (Mean Age 3).

Coarctation of the aorta (CofA) has been associated with an increased risk of intracranial aneurysm (IA). This magnetic resonance angiography (MRA) study investigates the prevalence of IAs in 80 children treated in early life for CofA. MRA was performed at mean age of 15.7 ± 7.1 years, and surgical or endovascular treatment for CofA occurred at a mean age of 2.6 ± 4.4 years. No IA was found. In contrast with earlier findings in adult patients with late treatment for CofA, this first systematic study of very early treated patients for CofA failed to confirm the association between CofA and IAs. Our results call the abnormal developmental relation between CofA and IAs into question and suggest that modifiable risk factors like hypertension may be responsible for IA development in patients with CofA with adult diagnosis and treatment. In conclusion, our data suggest that early treatment of CofA can reduce the formation of IAs in children so as to make MRA screening less valuable in this young population.

Quadricuspid aortic valve and anomalous origin of the left circumflex coronary artery in a young man with Down syndrome.

The Authors present the case of an asymptomatic 36-year-old man, affected by Down syndrome, with an unexpected quadricuspid aortic valve coupled with the anomalous origin of the left circumflex coronary artery from the proximal right coronary artery. This is the first report of the concomitant presence of these three conditions.

Long-term benefits of exercise training in patients with a systemic right ventricle.

OBJECTIVES: The aim of the present study is to determine the long-term effects of a ten-week exercise training program in adult patients with a systemic right ventricle. METHODS: All patients who participated in a 2009 randomized controlled trial were approached. At approximately three years of follow-up from initial baseline, patients underwent cardiopulmonary exercise testing, filled out two quality of life questionnaires, and NT proBNP levels were measured. All examinations were performed according to the protocols of the 2009 trial. In addition, patients were asked about their current sports habits. RESULTS: Of the 54 patients who were randomized in the 2009-trial 40 participated in the current re-evaluation (male 50%, ccTGA 35%, age 36 ± 10 years, intervention group n=22, control group n=18). After three years, no persistent effect of exercise training on V'O2peak training remained (-2% of predicted, 95% CI -3% to 5%; p=.56). However, patients who already participated in regular sports or exercise at baseline (n=23/40 (58%)) showed higher V'O2peak of 13% of predicted (95% CI 4% to 23%; p>.01) and a decrease of 62% in plasma NT-proBNP (95% CI -115% to -10%; p>.03) during follow-up, when compared to patients who did not. Moreover, sports were associated with a lower incidence of clinical events (p=.032). CONCLUSION: Short-term beneficial effects of exercise training did not persist over a three-year follow-up period. However, sports participation at baseline was associated with better exercise capacity, lower neurohormone levels, and increased event-free survival.

Congenitally corrected transposition of the great arteries in an 83-year-old asymptomatic patient: description and literature review.

We describe the case of an 83-year-old asymptomatic man followed in our centre. Transoesophageal echocardiography disclosed congenitally corrected transposition of great arteries (CCTGA) with no associated anomalies and only mild aortic regurgitation. Cardiac MR confirmed the diagnosis and revealed preserved systemic ventricle systolic function with a normal perfusional pathway. This report is a demonstration that CCTGA without associated anomalies can reach older life in an asymptomatic condition. This is the oldest asymptomatic living patient with CCTGA ever described.

Sex differences in congenital heart defects and genetically induced arrhythmias.

Sex medicine can be applied to define the effect of male or female sex-associated differences on the prevalence of congenital heart defects (CHDs), on clinical manifestation of the latter, on means of dealing with the defects and facing consequent surgical treatment, as well as on the success of surgery. The widespread use of modern databases has undoubtedly enhanced the possibility of these observations compared to the past, when findings were limited to case series from single cardiology or paediatric heart surgery units. The aim of the present review is to assess all publications present in the literature on sex differences and CHD, placing particular emphasis on both contradictory aspects and less acknowledged issues. Furthermore, a section of the review is devoted to the effect of sex differences on cardiac arrhythmias, particularly the largely genetically predetermined electrophysiological differences observed between men and women.