[The last 50 years of pediatric cardiology (1971-2021): from Fontan operation to the present time]. / Cinquant'anni di cardiologia pediatrica (1971-2021): dall'intervento di Fontan ai nostri giorni.

Pediatric cardiology has matured profoundly over the last 50 years, paralleled by a similar development in pediatric cardiac surgery and cardiac anesthesia. This field of medicine provides structured and effective care for a very heterogeneous group of diseases including congenital heart disease, cardiomyopathies and heart failure, myocarditis, rheumatic heart disease, inherited and acquired arrhythmias, Kawasaki disease and more recently multisystemic inflammatory syndrome of children related to primary infection by SARS-CoV-2. This review summarizes achievements and results in selected topics of pediatric cardiology and cardiac surgery with focused attention to the diagnosis and management of congenital heart diseases.

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.

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.

[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.

Rasmussen's aneurysm in childhood: a case report.

In medical literature, few cases of Rasmussen's aneurysm have been reported until now, and to the best of our knowledge, there has been no description of a case of Rasmussen's aneurysm in childhood. The child described in the case report had a restrictive cardiomyopathy, complicated by pulmonary hypertension, in association with miliary tuberculosis.

Exercise training improves exercise capacity in adult patients with a systemic right ventricle: a randomized clinical trial.

OBJECTIVE: To assess whether exercise training in adult patients with a systemic right ventricle (RV) improves exercise capacity and quality of life and lowers serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels. DESIGN: Multi-centre parallel randomized controlled trial. PARTICIPANTS: Patients with a systemic RV due to congenitally or surgically corrected transposition of the great arteries. METHODS: Fifty-four adult patients with a systemic RV, were randomized using unmarked opaque envelopes to an intervention group (n = 28) with three training sessions per week for 10 consecutive weeks, and a control group (n = 26). Randomization was stratified by participating centre. At baseline, and follow-up, we determined maximal exercise capacity (V'O(2peak)), serum NT-proBNP levels, and quality of life by means of the SF-36, and the TAAQOL Congenital Heart Disease questionnaires. The final analysis was performed by linear regression, taking into account the stratified randomization. RESULTS: Forty-six patients were analysed (male 50%, age 32 ± 11 years, intervention group n = 24, control group n = 22). Analysis at 10 weeks showed a significant difference in V'O(2peak) (3.4 mL/kg/min, 95% CI: 0.2 to 6.7; P = 0.04) and resting systolic blood pressure (-7.6 mmHg, 95% CI: -14.0 to -1.3; P = 0.03) in favour of the exercise group. No significant changes were found in serum NT-proBNP levels or quality of life in the intervention group or in the control group nor between groups. None of the patients in the intervention group had to discontinue the training programme due to adverse events. CONCLUSION: In adult patients with a systemic RV exercise training improve exercise capacity. We recommend to revise restrictive guidelines, and to encourage patients to become physically active. ( TRIAL REGISTRATION: The study was registered at http://trialregister.nl. Identifier: NTR1909.).

[Results and complications of permanent pacing in pediatric patients with congenital or acquired atrioventricular block]. / Risultati e complicanze dell'impianto di pacemaker definitivo in pazienti pediatrici con blocco atrioventricolare congenito ed acquisito.

BACKGROUND: Currently there is no evidence to prefer an endocardial or epicardial approach for pacing in pediatric patients. This analysis was aimed at defining the complications of pacemaker implantation in a pediatric population with atrioventricular block according to a strategy of choosing an epicardial system for patients <10 kg and an endocardial system for patients >10 kg. METHODS: This is a retrospective study performed on 27 patients, with and without congenital heart disease, implanted with a permanent pacemaker because of idiopathic or acquired atrioventricular block at our Pediatric Cardiology and Cardiac Surgery Unit of S. Orsola-Malpighi Hospital in Bologna (Italy) between 1981 and 2010. Patients were divided into two groups: 70% of the population (group A) was implanted with an epicardial system, 30% (group B) with an endocardial system. RESULTS: After a mean follow-up of 14 years (17 ± 8 years for group A, 7 ± 5 years for group B), the most frequent complications were lead failure (44%) and infection (18%). Both were more common in the epicardial system group: lead failure rate 53% in group A vs 25% in group B (p=0.0001); infection rate 26% in group A vs 0% in group B (p=0.0001); rate of system revision or implantation of a new electrode 42% in group A vs 12% in group B (p=0.0001). CONCLUSIONS: The present study demonstrates a high complication rate in patients undergoing an epicardial pacing system implantation. However, in patients <10 kg the epicardial system allows subclavian venous access protection for endocardial system implantation after somatic growth, avoiding high-risk procedures of system revision or lead extraction and subclavian vein occlusion in the long term.

[The ECG in pediatric patients: what the cardiologist needs to know]. / L'ECG in età pediatrica: cosa deve sapere il cardiologo dell'adulto.

During life ECG is always changing according to postnatal circulation adaptation, position of the heart in the chest, and body mass. Reference values and normal morphologies of P wave, PR interval, QRS complex, ST segment, T wave, and QTc interval are reported. Some clues to detect congenital and acquired heart diseases are also provided. Finally, a brief look at the most common diseases and arrhythmias in the neonatal and pediatric period is reported. When the pediatric ECG is too "young" for a cardiologist? When we need to stop doing the report? ... never! The baby is the father of the adult. The heart is made of signs: we have to decipher them.

Calcified Thrombus in Right Atrium: Rare but Treatable Complication of Long-term Indwelling Central Venous Catheter.

Catheter-related central thrombosis is a rare complication of long-term central line. We describe the case of an asymptomatic boy who was diagnosed a calcified thrombus in right atrium eight years after the removal of a long-term central venous device. Although the most appropriate therapeutic approach for managing floating right heart thrombi remains to be determined, surgical removal is an effective and safe procedure for calcified long-standing thrombus and it is to be preferred in elective conditions especially in young asymptomatic patients without hemodynamic involvement, that are at low risk of surgery-related morbidity and mortality.

An Unusual Case of Sinus of Valsalva Aneurysm in a GUCH Patient: An Unusual Side of the Aorto-Cardiac Fistula.

Sinus of Valsalva aneurysm can be congenital or acquired. The major complication is rupture: this can represent an evolution or an abrupt event. In case of rupture or of large aneurysm, a surgical approach is justified. We report a case of ruptured sinus of Valsalva aneurysm in a seventeen years old girl, who had underwent surgical correction of Fallot tetralogy. As soon as the rupture of sinus of Valsalva aneurysm is suspected, echocardiographic examination is the easiest and most straightforward tool to make a correct diagnosis.

Role of atrial fibrillation after transcatheter closure of patent foramen ovale in patients with or without cryptogenic stroke.

BACKGROUND: Atrial fibrillation (AF) after transcatheter closure of patent foramen ovale (PFO) is not a rare complication. However little is known about the effect of atrial septal device implantation on the occurrence of this arrhythmia. OBJECTIVE: The aim of this study was to evaluate the occurrence of AF in two groups of patients who underwent transcatheter PFO closure: those with a previous cryptogenic stroke and those with other index events respectively. MATERIALS AND METHODS: Patient population included 276 patients with documented PFO who underwent percutaneous closure at our institution. Patients were grouped on the basis of two distinct clinical presentations: a) 246 patients with history of previous cryptogenic cerebrovascular ischemic event (CIE) or b) 30 patients with other different index events. AF after PFO closure was detected by 12-lead electrocardiography or by 24-h-Holter monitoring. RESULTS: During a mean follow-up of 17 months, new-onset AF was documented in 10 patients (4%), all included in the group with a previous cryptogenic CIE, at a mean of 1.6 months post-procedure. Comparing patients with and without AF, age (mean 56 years vs 46 years, p = 0.012) and left atrial size (4.4 cm vs 3.7 cm, p = 0.001) resulted to differ significantly. The type and size of occluder devices do not seem to impact the occurrence of AF after PFO closure. CONCLUSION: In patients presenting with cryptogenic stroke, especially in those with slightly enlarged left atria and age above 50­55 years, detection of a PFO should prompt an extended monitoring for excluding AF.

Predictors of morbidity and mortality in contemporary Fontan patients: results from a multicenter study including cardiopulmonary exercise testing in 321 patients.

AIMS: previous studies have established an association between exercise intolerance and increased morbidity and mortality in congenital heart disease patients. We aimed to clarify if exercise intolerance is associated with poor outcome in Fontan patients and to identify risk factors for mortality, transplantation, and cardiac-related hospitalization. METHODS AND RESULTS: a total of 321 Fontan patients (57% male, mean age 20.9 ± 8.6 years) who underwent cardiopulmonary exercise testing (CPET) at four major European centres between 1997 and 2008 were included. During a median follow-up of 21 months, 22 patients died and 6 patients underwent cardiac transplantation (8.7%), resulting in an estimated 5-year transplant-free survival of 86%. Parameters of CPET were strongly related to increased risk of hospitalization, but-with the exception of heart rate reserve-unrelated to risk of death or transplantation. In contrast, patients with clinically relevant arrhythmia had a 6.0-fold increased risk of death or transplantation (P < 0.001). Furthermore, patients with atriopulmonary/-ventricular Fontan had a 3.7-fold increased risk of death or transplantation compared with total cavopulmonary connection patients (P= 0.009). The combination of clinically relevant arrhythmia, atriopulmonary/-ventricular Fontan, and signs of symptomatic or decompensated heart failure was associated with a particularly poor outcome (3-year mortality 25%). CONCLUSION: on short-term follow-up, most parameters of CPET are associated with increased risk of hospitalization but not death or transplantation in contemporary Fontan patients. Only decreased heart rate reserve and a history of clinically relevant arrhythmia, atriopulmonary/-ventricular Fontan, and/or heart failure requiring diuretic therapy are associated with poor prognosis, potentially identifying patients requiring medical and/or surgical attention.

Dilated cardiomyopathy presenting in childhood: aetiology, diagnostic approach, and clinical course.

OBJECTIVE: To determine the outcome of dilated cardiomyopathy presenting in childhood and the features that might be useful for prognostic stratification. METHODS: Retrospective study of 41 consecutive children affected by dilated cardiomyopathy - aged 0-14 years; median 33.4 plus or minus 49.25 - between 1993 and 2008. We reviewed the medical history to determine age at diagnosis, family history, previous viral illness, aetiology, symptoms and signs at presentation, treatment, and outcome. The diagnosis was made on the basis of cardiomegaly and evidence of poor left ventricular function by echocardiography. We also carried out a metabolic evaluation including blood lactate, pyruvate, carnitine, amino acids, urine organic acids, assessment of respiratory chain enzymes, and analysis of histopathological material. Survival curves were constructed by the Kaplan-Meier method. RESULTS: Follow-up ranged from 10 days to 162 months - median 45.25 plus or minus 41.15 months. Freedom from death or cardiac transplantation was 68.3% at 5 years. The primary end-point of death/cardiac transplantation was associated with the need for intravenous inotropic support. A trend towards a poorer prognosis was found for age at diagnosis of more than 5 years and for a metabolic aetiology of dilated cardiomyopathy. For the children affected by cardiomyopathy as part of a multi-system involvement, mortality was 50%. CONCLUSIONS: In children, dilated cardiomyopathy is a diverse disorder with outcomes that depend on cause, age, and cardiac failure status at presentation. Overt cardiac failure at presentation is a major prognostic factor for death or cardiac transplantation. Older age at presentation and metabolic aetiology may be associated with a poorer prognosis.

Long-term coronary artery outcome after arterial switch operation for transposition of the great arteries.

OBJECTIVE: To analyse the long-term patency of coronary arteries after neonatal arterial switch operation (ASO). METHODS: A retrospective study of the operative reports, follow-up and postoperative catheterisation data of 119 patients, who underwent the great arteries (TGA) repair since 1991, has been carried out. PATIENT POPULATION: Among the 133 survivors of the 137 ASOs performed between 1991 and 2007, 119 patients have been studied by routine control cardiac catheterisation and form the study population. Median time between repair and the coronary angiography was 2.9±1.9 years. A comparison between the eight patients (6.7% out of the entire study population), known to have postoperative coronary obstructions (group I) and the rest of the cohort with angiographic normal coronary vessels (group II) was performed by univariate analysis of variance and logistic regression models. One patient had surgical plasty of the left coronary main stem with subsequent percutaneous angioplasty, three patients had primary coronary stent implantation and four patients had no further intervention at all. In group I, all but one patient denied symptoms of chest pain and echocardiography failed to show any difference between the two groups in terms of left ventricular systolic function (ejection fraction group I 61±2% vs 62±6% of group II, p=1.0). RESULTS: The association of coronary obstruction with complex native coronary anatomy (Yacoub type B to E) was evident at both univariate (62% of group I vs 22% of group II, p=0.04) and logistic regression (p=0.007, odds ratio (OR) 8.1) models. The type of coronary reimplantation (i.e., coronary buttons on punch vs trap-door techniques) was similar between the two groups (punch reimplantation in 25% of patients of group I vs 31% of group II, p=0.1) as was the relative position of the great vessels (aorta anterior in 100% of patients of group I vs 96% of group II; univariate, p=0.1). CONCLUSIONS: The late outcome in terms of survival and functional status after ASO is excellent. Nevertheless, the risk of a clinically silent late coronary artery obstruction of the reimplanted coronary arteries warrants a prolonged follow-up protocol involving invasive angiographic assessment.

[Percutaneous aortic valvuloplasty in congenital aortic valve stenosis performed in patients older than one month: a good alternative to surgery]. / Valvuloplastica percutanea della stenosi aortica congenita oltre il primo mese di vita: una valida alternativa alla chirurgia.

BACKGROUND: Percutaneous aortic valvuloplasty is an effective means of treatment for congenital aortic valve stenosis. The aim of this study was to evaluate the immediate results of valvuloplasty, to analyze the medium to long-term outcome and to assess its efficacy in preventing or postponing a new percutaneous valvuloplasty or aortic valve surgery. METHODS: We retrospectively analyzed the reports of 37 patients aged > 1 month (mean age 6.3 years) who underwent aortic valvuloplasty for severe aortic stenosis. Associated congenital cardiac defects were present in 16% of the patients. The average time of follow-up was 5.07 years. Particular attention was focused on occurrence and progression of aortic regurgitation. RESULTS: Hemodynamic gradient after aortic valvuloplasty decreased from 58.5 to 22.5 mmHg, with an average decrease of 61.5%. On echography, the maximum gradient decreased from 93.0 to 40.5 mmHg, with an average decrease of 56.5%; mean gradient decreased from 52.0 to 20.5 mmHg with an average decrease of 60.6%. At last follow-up the average maximum and mean gradient on echo were 50.0 and 27.0 mmHg. A reintervention was needed in 21.6% of cases: a second valvuloplasty in 8.1% and aortic surgery in 13.5%. The mortality rate was 2.7%. Survival after 14 years was 97.2%; freedom from aortic valve surgery was 85.5%, from a second valvuloplasty was 89.5%, and from any type of procedure was 76.1%. CONCLUSIONS: Percutaneous aortic valvuloplasty is a safe and effective treatment for congenital aortic stenosis in patients aged > 1 month. Aortic regurgitation is the main concern in the follow-up. Nonetheless, 14 years after valvuloplasty, over 75% of patients are free from any type of aortic valve reintervention.

[The "big heart" of carnitine]. / Il "grande cuore" della carnitina.

Fat is the primary energy source for heart muscle. In the heart, carnitine is essential for normal fatty acid beta-oxidation and even partial deficiency could lead to organ dysfunction. Dilated cardiomyopathy is one of the cardinal manifestations of carnitine deficiency in children. We report the case of a female infant referred to our hospital at the age of 15 months with a 2-week history of dyspnea. She presented signs and symptoms of congestive heart failure. Severe cardiomegaly was seen on chest radiographs, while the echocardiogram showed a dilated and hypokinetic left ventricle with depressed systolic function, decreased fractional shortening and ejection fraction, and left atrial enlargement. Laboratory investigations showed carnitine deficiency. She needed intravenous inotropic support in association with conventional heart failure therapy. Treatment with L-carnitine was started as soon as the samples for laboratory testing were taken. Cardiac function clearly and rapidly improved while on treatment.

Incompatibility between intravenous amiodarone and heparin in an infant.

Amiodarone is an effective antiarrhythmic agent and represents the drug of choice in the treatment of severe arrhythmias, especially in the setting of ventricular dysfunction. Amiodarone has the potential for interaction with many cardiac and non-cardiac drugs. Nonetheless few incompatibilities have been reported. We report the incompatibility between amiodarone and heparin administrated in the same vein in a case of a one month old baby with atrial flutter. This topic needs more attention, due to the frequent co-administration of these two drugs in tachyarrhythmias with high thromboembolic risk.

Determinants of exercise capacity after arterial switch operation for transposition of the great arteries.

Patients who undergo the arterial switch operation for transposition of the great arteries (TGA) are at risk of reduced exercise capacity, with most reports focusing on chronotropic incompetence as the cause. Residual right ventricular outflow tract (RVOT) obstruction is relatively common after the arterial switch operation, but its effect on exercise capacity is unknown. We studied 60 patients (44 males, age 13.3 +/- 3.4 years) who had undergone a neonatal arterial switch operation using the cardiopulmonary exercise test and transthoracic echocardiography. The peak exercise oxygen uptake (VO(2)), and heart rate were recorded and are expressed as the percentage of predicted values. The greatest velocity detected by echocardiography across the pulmonary valve, pulmonary trunk, or pulmonary branches was used in the analysis as an index of RVOT obstruction. The peak VO(2)% was 84 +/- 15%, and the peak heart rate percentage was 97 +/- 8%. Of the 60 patients, 29 had an abnormal peak VO(2)% (< or =84%) and 3 (5%) had an abnormal peak heart rate percentage (< or =85%). The maximal RVOT velocity was 2.3 +/- 0.6 m/s, and it correlated with the peak VO(2)% (r = -0.392, p = 0.004). On multivariate analysis, the presence of residual RVOT obstruction (p = 0.0007) was the only variable associated with a reduced peak VO(2)%. Patients with a RVOT maximal velocity > or =2.5 m/s had a lower peak VO(2)% than those with lower velocities (p <0.0001). No relation was found between age at testing and the peak VO(2)%. In conclusion, a reduced exercise capacity is relatively common in children and young adults who have undergone an arterial switch operation, but it does not decrease with age. The presence of residual RVOT obstruction seems to have an effect on exercise capacity.