Four-dimensional Flow MRI: Principles and Cardiovascular Applications.

In-plane phase-contrast (PC) imaging is now a routine component of MRI of regional blood flow in the heart and great vessels. In-plane PC MRI provides a volumetric, isotropic, time-resolved cine sequence that enables three-directional velocity encoding, a technique known as four-dimensional (4D) flow MRI. Recent advances in 4D flow MRI have shortened imaging times, while progress in big-data processing has improved dataset pre- and postprocessing, thereby increasing the feasibility of 4D flow MRI in clinical practice. Important technical issues include selection of the optimal velocity-encoding sensitivity before acquisition and preprocessing of the raw data for phase-offset corrections. Four-dimensional flow MRI provides unprecedented capabilities for comprehensive analysis of complex blood flow patterns using new visualization tools such as streamlines and velocity vectors. Retrospective multiplanar navigation enables flexible retrospective flow quantification through any plane across the volume with good accuracy. Current flow parameters include forward flow, reverse flow, regurgitation fraction, and peak velocity. Four-dimensional flow MRI also supplies advanced flow parameters of use for research, such as wall shear stress. The vigorous burgeoning of new applications indicates that 4D flow MRI is becoming an important imaging modality for cardiovascular disorders. This article reviews the main technical issues of 4D flow MRI and the different parameters provided by it and describes the main applications in cardiovascular diseases, including congenital heart disease, cardiac valvular disease, aortic disease, and pulmonary hypertension. Online supplemental material is available for this article. ©RSNA, 2019 See discussion on this article by Ordovas .

Tropical Endomyocardial Fibrosis: Natural History, Challenges, and Perspectives.

Tropical endomyocardial fibrosis (EMF) is a neglected disease of poverty that afflicts rural populations in tropical low-income countries, with some certain high-prevalence areas. Tropical EMF is characterized by the deposition of fibrous tissue in the endomyocardium, leading to restrictive physiology. Since the first descriptions in Uganda in 1948, high-frequency areas for EMF have included Africa, Asia, and South America. Although there is no clear consensus on a unified hypothesis, it seems likely that dietary, environmental, and infectious factors may combine in a susceptible individual to give rise to an inflammatory process leading to endomyocardial damage and scar formation. The natural history of EMF includes an active phase with recurrent flare-ups of inflammation evolving to a chronic phase leading to restrictive heart failure. In the chronic phase, biventricular involvement is the most common presentation, followed by isolated right-sided heart disease. Marked ascites out of proportion to peripheral edema usually develops as a typical feature of EMF. EMF carries a very poor prognosis. In addition to medical management of heart failure, early open heart surgery (endocardectomy and valve repair/replacement) appears to improve outcomes to some extent; however, surgery is technically challenging and not available in most endemic areas. Increased awareness among health workers and policy makers is the need of the hour for the unhindered development of efficient preventive and therapeutic strategies.

Differential impact of age and cytomegalovirus infection on the γδ T cell compartment.

γδ T cells represent a subset of unconventional T lymphocytes that are known for their reactivity against different pathogens and considered as intermediate mediators between adaptive and innate immunity. We provide in this paper further insights underlying the changes that affect the γδ T cell compartment with advanced age in humans. We show that both aging and CMV infection impact independently on the γδ T cell compartment. Most γδ T cells are significantly affected by age and present a decreased frequency in the elderly. The decline of the γδ T cell pool appears to be independent from the activity of the thymus, arguing in favor of an extrathymic site of γδ T cell production in humans. Of note, CMV infection, which is directly associated with the activation of the pool of Vδ2(-) γδ T cells, promotes nonetheless the inflation of this compartment throughout life. CMV seropositivity accentuates further the accumulation of highly differentiated lymphocytes in Vδ2(-) γδ T cell subsets with time, in contrast to Vδ2(+) γδ T cells, which maintain a less differentiated phenotype. This is similar to the effect of CMV on αß T cells and suggests that γδ T cells may vary in differentiation phenotype according to distinct stimuli or pathogens.

Lymphopenia-driven homeostatic regulation of naive T cells in elderly and thymectomized young adults.

Reduced thymopoiesis and continuous mobilization of naive T cells into the effector-memory pool can lead to severe alterations of the naive T cell compartment. However, maintenance of the naive T cell population is essential to mount effective immune responses. Evidence of homeostatic regulation of naive T cells is currently debated in animal models. In humans, the situation remains unresolved, in particular with advanced age. In this study, we analyzed the CD4(+) and CD8(+) naive T cell compartments from elderly, young adults thymectomized during early childhood, and HIV-1-infected patients, which are characterized by T lymphocytopenia. We show a direct association between increased turnover and decreased frequency of naive T cells. Moreover, the IL-7-induced pathway was fully functional in naive T cells from elderly and young adults thymectomized during early childhood, who are characterized by elevated IL-7 plasma levels. Our findings support the establishment of homeostatic regulation of naive T cell proliferation in humans. This regulation is particularly active in lymphopenic hosts, such as elderly and thymectomized patients.

Acquired coronary disease in children: the role of multimodality imaging.

Coronary sequelae of Kawasaki disease, post-surgical coronary lesions and cardiac allograft vasculopathy are the main causes of acquired coronary pathology in childhood. Surveillance and timely recognition of coronary problems in children who are at risk of ischemic events are imperative and noninvasive imaging is increasingly utilized for these purposes. Herein, we summarize the causes of acquired coronary disease in children and discuss the role of various imaging techniques that are available to establish the diagnosis and guide management.

Nephrotic syndrome in Kawasaki disease: a report of three cases.

BACKGROUND: Renal manifestations are rare in Kawasaki disease (KD). Acute renal failure with tubular necrosis, tubulointerstitial nephritis and renovascular hypertension have been reported in KD, but only one case of a patient with KD associated with nephrotic syndrome (NS) has been reported to date, with the patient improving on steroid therapy but dying from coronary aneurysm. METHODS: We report the cases of three children, aged 4, 4.5 and 8 years, respectively, who presented with typical KD symptoms (high fever, diffuse maculopapular rash, conjunctivitis, peripheral oedema, cervical adenopathies and high C reactive protein levels) and developed NS. RESULTS: Patient 1 had a haemodynamic shock due to cardiac dysfunction and transient renal failure. Ten days later, he developed a NS which spontaneously disappeared 1 week later. Patient 2 had a NS on admission with normal plasma creatinine and no haematuria. Proteinuria disappeared within 10 days. Patient 3 developed NS 5 days after onset with a moderate increase in plasma creatinine. Proteinuria disappeared within 2 weeks. All three patients were treated with intravenous immunoglobulins, antibiotic therapy and aspirin, but none of them received steroid therapy. To date, all three patients have maintained long-term remission. CONCLUSIONS: In conclusion, proteinuria with NS may develop during the acute phase of KD with persistent remission occurring without steroid therapy.

[Rheumatic heart disease: future prospects]. / Rhumatisme articulaire aigu - Perspectives.

Acute rheumatic fever develops after an inadequate immune response to throat streptococcal infection that induces the production of antibodies reacting against cardiac endothelial cells. Valve damage may lead to irreversible cardiac valve sequela (rheumatic heart disease) with further evolution towards severe valve dysfunction and heart failure. The disease has been almost eradicated in Western countries with the development of living conditions and prevention policies, including primary prevention (treatment of sore throats) and secondary prevention (long term administration of antibiotics). However, rheumatic heart disease remains a major health problem in developing countries. Recently, echocardiography identified children with mild features of the disease, thereby allowing early treatment.

Exome sequencing identifies MRPL3 mutation in mitochondrial cardiomyopathy.

By combining exome sequencing in conjunction with genetic mapping, we have identified the first mutation in large mitochondrial ribosomal protein MRPL3 in a family of four sibs with hypertrophic cardiomyopathy, psychomotor retardation, and multiple respiratory chain deficiency. Affected sibs were compound heterozygotes for a missense MRPL3 mutation (P317R) and a large-scale deletion, inherited from the mother and the father, respectively. These mutations were shown to alter ribosome assembly and cause a mitochondrial translation deficiency in cultured skin fibroblasts resulting in an abnormal assembly of several complexes of the respiratory chain. This observation gives support to the view that exome sequencing combined with genetic mapping is a powerful approach for the identification of new genes of mitochondrial disorders.

A population study of endomyocardial fibrosis in a rural area of Mozambique.

BACKGROUND: Endomyocardial fibrosis is the most common restrictive cardiomyopathy worldwide. It has no specific treatment and carries a poor prognosis, since most patients present with advanced heart failure. On the basis of clinical series, regional variations in distribution have been reported within several countries in Africa, Asia, and South America, but large-scale data are lacking on the epidemiologic features and early stages of the disease. METHODS: We used transthoracic echocardiography to determine the prevalence of endomyocardial fibrosis in a rural area of Mozambique. We screened a random sample of 1063 subjects of all age groups selected by clustering. Major and minor diagnostic criteria were defined, and a severity score was developed and applied. Cases were classified according to the distribution and severity of the lesions in the heart. RESULTS: The estimated overall prevalence of endomyocardial fibrosis was 19.8%, or 211 of 1063 subjects (95% confidence interval [CI], 17.4 to 22.2). The prevalence was highest among persons 10 to 19 years of age (28.1%, or 73 of 260 subjects [95% CI, 22.6 to 33.6]) and was higher among male than among female subjects (23.0% vs. 17.5%, P=0.03). The most common form was biventricular endomyocardial fibrosis (a prevalence of 55.5%, or 117 of 211 subjects [95% CI, 48.8 to 62.2]), followed by right-sided endomyocardial fibrosis (a prevalence of 28.0%, or 59 of 211 subjects [95% CI, 21.9 to 34.1]). Most affected subjects had mild-to-moderate structural and functional echocardiographic abnormalities. Only 48 persons with endomyocardial fibrosis (22.7%) were symptomatic. The frequency of familial occurrence was high. CONCLUSIONS: Endomyocardial fibrosis is common in a rural area of Mozambique. By using echocardiography, we were able to detect early, asymptomatic stages of the disease. These findings may aid in the study of the pathogenesis of the disease and in the development of new management strategies.

[Preventing complications of cardiac malformations in poor countries]. / Les cardiopathies congénitales dans les pays pauvres et la prévention de leurs complications.

Natural selection and therapeutic efficiency limit the type of cardiac malformations that/can be treated in poor countries. Most of the patients studied here are those with left-to-right shunts (arterial, atrial and, especially, ventricular), right-to-left shunts associated with a ventricular septal defect (tetralogy of Fallot) or an atrial septal defect (trilogy of Fallot), and stenosis of the pulmonary or aortic valves. Early diagnosis is crucial, but this will require a new health policy involving specially trained nurses or technicians equipped with cheap portable echo-Doppler machines to examine babies' hearts. We then analyze the follow-up and medical treatment of these common cardiac disorders and the need for "national" centers for open- and closed-heart surgery and catheterization. We feel we have achieved our training goal when a center is able to close a VSD in a 6-month-old baby with a low rate of morbidity and mortality.

[Pediatric heart surgery in developing countries. Twenty years experience of La Chaine de L'espoir (Chain of Hope)]. / La chirurgie cardiaque pédiatrique dans les pays en voie de développement. Vingt ans d'expérience de la chaîne de l'Espoir.

Because of their high incidence, cardiac disorders in children are now a public health issue. These children require multidisciplinary management, but surgery is sometimes unavoidable. The two most frequent types of cardiac disorder in children are congenital defects and rheumatic valve disease. La Chaine de l'Espoir (Chain of Hope) is present in more than 30 countries in Africa, Asia and the Middle East. Due to the socio-economic context and lack of technical resources, pediatric heart surgery has several particular characteristics in developing countries. Infants rarely undergo cardiac surgery, given the complexity of their management and particularly the need for intensive care. Another specificity is the need to limit treatment to reparatory or conservative methods. Surgery is rarely attempted in terminally ill patients. Costs must be kept to a minimum, and this is why we have optedfor local manufacture of mitral rings, led by Daniel Roux. After 20 years of practice we have found that regional hospitals are the smallest structures that can offer acceptable results in terms of patient care and professional training

Rheumatic heart disease screening by echocardiography: the inadequacy of World Health Organization criteria for optimizing the diagnosis of subclinical disease.

BACKGROUND: Early case detection is vital in rheumatic heart disease (RHD) in children to minimize the risk of advanced valvular heart disease by preventive measures. The currently utilized World Health Organization (WHO) criteria for echocardiographic diagnosis of subclinical RHD emphasize the presence of pathological valve regurgitation but do not include valves with morphological features of RHD without pathological regurgitation. We hypothesized that adding morphological features to diagnostic criteria might have significant consequences in terms of case detection rates. METHODS AND RESULTS: We screened 2170 randomly selected school children aged 6 to 17 years in Maputo, Mozambique, clinically and by a portable ultrasound system. Two different echocardiographic sets of criteria for RHD were assessed: "WHO" (exclusively Doppler-based) and "combined" (Doppler and morphology-based) criteria. Independent investigators reviewed all suspected RHD cases using a higher-resolution, nonportable ultrasound system. On-site echocardiography identified 18 and 124 children with suspected RHD according to WHO and combined criteria, respectively. After consensus review, 17 were finally considered to have definite RHD according to WHO criteria, and 66 had definite RHD according to combined criteria, giving prevalence rates of 7.8 (95% confidence interval, 4.6 to 12.5) and 30.4 (95% confidence interval, 23.6 to 38.5) per 1000 children, respectively (P<0.0001, exact McNemar test). CONCLUSIONS: Important consideration should be given to echocardiographic criteria for detecting subclinical RHD because the number of cases detected may differ importantly according to the diagnostic criteria utilized. Currently recommended WHO criteria risk missing up to three quarters of cases of subclinically affected and therefore potentially treatable children with RHD.

Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders.

BACKGROUND: TGFBR2 mutations were recognized recently among patients with a Marfan-like phenotype. The associated clinical and prognostic spectra remain unclear. METHODS AND RESULTS: Clinical features and outcomes of 71 patients with a TGFBR2 mutation (TGFBR2 group) were compared with 50 age- and sex-matched unaffected family members (control subjects) and 243 patients harboring FBN1 mutations (FBN1 group). Aortic dilatation was present in a similar proportion of patients in both the TGFBR2 and FBN1 groups (78% versus 79%, respectively) but was highly variable. The incidence and average age for thoracic aortic surgery (31% versus 27% and 35+/-16 versus 39+/-13 years, respectively) and aortic dissection (14% versus 10% and 38+/-12 versus 39+/-9 years) were also similar in the 2 groups. Mitral valve involvement (myxomatous, prolapse, mitral regurgitation) was less frequent in the TGFBR2 than in the FBN1 group (all P<0.05). Aortic dilatation, dissection, or sudden death was the index event leading to genetic diagnosis in 65% of families with TGFBR2 mutations, versus 32% with FBN1 mutations (P=0.002). The rate of death was greater in TGFBR2 families before diagnosis but similar once the disease had been recognized. Most pregnancies were uneventful (without death or aortic dissection) in both TGFBR2 and FBN1 families (38 of 39 versus 213 of 217; P=1). Seven patients (10%) with a TGFBR2 mutation fulfilled international criteria for Marfan syndrome, 3 of whom presented with features specific for Loeys-Dietz syndrome. CONCLUSIONS: Clinical outcomes appear similar between treated patients with TGFBR2 mutations and individuals with FBN1 mutations. Prognosis depends on clinical disease expression and treatment rather than simply the presence of a TGFBR2 gene mutation.

Prevalence of rheumatic heart disease detected by echocardiographic screening.

BACKGROUND: Epidemiologic studies of the prevalence of rheumatic heart disease have used clinical screening with echocardiographic confirmation of suspected cases. We hypothesized that echocardiographic screening of all surveyed children would show a significantly higher prevalence of rheumatic heart disease. METHODS: Randomly selected schoolchildren from 6 through 17 years of age in Cambodia and Mozambique were screened for rheumatic heart disease according to standard clinical and echocardiographic criteria. RESULTS: Clinical examination detected rheumatic heart disease that was confirmed by echocardiography in 8 of 3677 children in Cambodia and 5 of 2170 children in Mozambique; the corresponding prevalence rates and 95% confidence intervals (CIs) were 2.2 cases per 1000 (95% CI, 0.7 to 3.7) for Cambodia and 2.3 cases per 1000 (95% CI, 0.3 to 4.3) for Mozambique. In contrast, echocardiographic screening detected 79 cases of rheumatic heart disease in Cambodia and 66 cases in Mozambique, corresponding to prevalence rates of 21.5 cases per 1000 (95% CI, 16.8 to 26.2) and 30.4 cases per 1000 (95% CI, 23.2 to 37.6), respectively. The mitral valve was involved in the great majority of cases (87.3% in Cambodia and 98.4% in Mozambique). CONCLUSIONS: Systematic screening with echocardiography, as compared with clinical screening, reveals a much higher prevalence of rheumatic heart disease (approximately 10 times as great). Since rheumatic heart disease frequently has devastating clinical consequences and secondary prevention may be effective after accurate identification of early cases, these results have important public health implications.

Postnatal growth retardation, facial dysmorphism, spondylocarpal synostosis, cardiac defect, and inner ear malformation (cardiospondylocarpofacial syndrome?)--a distinct syndrome?

We report on two unrelated cases born to nonconsanguineous parents with a similar clinical presentation: hypotonia since the neonatal period, severe failure to thrive, postnatal growth retardation, facial dysmorphism, congenital cardiac defects (septal defect and non progressive multiple valve dysplasia), shortened extremities, carpal/tarsal and extensive vertebral synostosis, delayed carpal bone age, deafness, and inner ear malformations. Presently, both patients present with normal psychomotor development. Additional abnormal findings include extra oral frenulum, nasal speech, and vesico-ureteral reflux. Molecular analysis in one patient excluded the Noggin gene and Filamin B (FLNB) was excluded in the other patient. Although some features are similar to spondylocarpotarsal synostosis syndrome, the exclusion of FLNB and this constellation of findings suggest a new entity, closely similar to an autosomal dominant condition reported by Forney et al. 1966 in a unique family. Identification of similarly affected patients should aid in the further elucidation of this syndrome.

Post-operative cardiac lesions after cardiac surgery in childhood.

A new population of patients in cardiology has been growing steadily so that the number of grown-ups with congenital heart disease (GUCH) is almost equal to those under paediatric care. The dramatic improvement in survival should lead to a larger number of GUCH patients than children with CHD in the new millennium. Although echocardiography remains the imaging modality of choice, cross-sectional imaging techniques have a decision-aiding function for the postoperative evaluation of surgical reconstructions as well as in the preparation of complex interventional procedures. Cardiovascular CT and MRI are often complementary in providing comprehensive complex anatomical evaluation, haemodynamic assessment of residual postoperative lesions and complications of surgery. A thorough understanding of postsurgical corrections is a prerequisite for choosing the optimal imaging techniques and achieving an accurate evaluation.

Dosing of clopidogrel for platelet inhibition in infants and young children: primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial.

BACKGROUND: Infants and young children with certain types of heart disease are at increased risk for thromboses. Clopidogrel 75 mg/d is used in adults to prevent thrombotic events. The dose to achieve similar platelet inhibition in children is unknown. The objectives of the present study were (1) to determine the dose of clopidogrel needed in infants and young children to achieve a mean 30% to 50% inhibition of 5-micromol/L ADP-induced platelet aggregation (ie, inhibition similar to that observed with 75 mg in adults) and (2) to assess the safety and tolerability of clopidogrel in infants and young children. METHODS AND RESULTS: We performed a prospective, multicenter, randomized, placebo-controlled trial evaluating the pharmacodynamics of clopidogrel in children (0 to 24 months) with a cardiac condition at risk for arterial thrombosis. Patients were randomized to clopidogrel versus placebo in a 3:1 ratio in 4 sequential groups (0.01, 0.10, 0.20, and 0.15 mg/kg) for > or = 7 and < or = 28 days. Platelet aggregation was assessed at baseline and steady state by light-transmission aggregometry. Of 116 patients enrolled, 92 (50% neonates, 50% infants/toddlers) were randomized, and 73 completed the study. A total of 79% of the randomized and treated patients were taking aspirin. Compared with placebo, clopidogrel 0.20 mg x kg(-1) x d(-1) resulted in a mean 49.3% (95% confidence interval 25.7% to 72.8%) inhibition of the maximum extent of platelet aggregation and a mean 43.9% (95% confidence interval 18.6% to 69.2%) inhibition of the rate of platelet aggregation. There was marked interpatient variability in the degree of platelet aggregation inhibition within each treatment-dose group and age group. No serious bleeding events occurred. CONCLUSIONS: Clopidogrel 0.20 mg x kg(-1) x d(-1) in children 0 to 24 months of age achieves a platelet inhibition level similar to that in adults taking 75 mg/d. Clopidogrel is well tolerated in infants and young children at this dose.

Effects of cardiac resynchronization therapy on echocardiographic indices, functional capacity, and clinical outcomes of patients with a systemic right ventricle.

AIMS: Surgically (SC) or congenitally corrected (CC) transposition of the great arteries (TGA), associated with a systemic right ventricle (RV), is often complicated by heart failure. This retrospective study assessed the functional and mechanical effects of cardiac resynchronization therapy (CRT) in patients presenting with TGA. METHODS AND RESULTS: Seven patients with SC (n = 5) or CC (n = 2) TGA (mean age 24.6 +/- 12 years), a failing systemic RV, and intraventricular dyssynchrony, underwent implantation of a CRT-P. Permanent pacemakers were previously implanted in five patients. The leads were implanted by a combined transvenous and epicardial approach in the five patients with SC TGA. Echocardiography, including tissue Doppler imaging and cardiopulmonary exercise testing were performed before and during CRT. Since, in all patients, ventricular dyssynchrony was due to delayed septal wall contraction, the interventricular septum and RV free wall were stimulated synchronously, with a view to resynchronize a maximum amount of myocardium. After 19.4 +/- 8.1 months of CRT, mean QRS duration decreased from 160 +/- 31 to 120 +/- 28 ms (P = 0.03), intraventricular delay from 104 +/- 27 to 14 +/- 15 ms (P = 0.01), New York Heart Association functional class from 3.0 to 1.57 (P = 0.01), and peak oxygen consumption increased from 13.8 +/- 2.5 to 22.8 +/- 6.7 mL/kg/min (P = 0.03). One patient died suddenly at 23 months of follow-up. CONCLUSIONS: CRT was technically feasible and associated with improvements in cardiac mechanical function and clinical status in patients with TGA, failing systemic RV, and intraventricular dyssynchrony.

Increased central aortic stiffness and left ventricular mass in normotensive young subjects after successful coarctation repair.

BACKGROUND: Hypertension occurs in 20% to 40% of survivors of anatomically successful repair of aortic coarctation (CoA). The aim of the present study was to examine the role of central aortic function in this setting. METHODS: Forty normotensive asymptomatic subjects with successful CoA repair (age 12 +/- 8 years) and 20 age- and sex-matched control subjects underwent detailed magnetic resonance imaging investigation of the thoracic aorta and left ventricle. Aortic distensibility, compliance, and stiffness beta index were calculated in the central (precoarctation) and descending (postcoarctation) aorta. Aortic pulse wave velocity was measured and left ventricular mass was calculated. RESULTS: Compared to control subjects, CoA subjects had markedly decreased central aortic distensibility (2.8 +/- 0.7 vs 4.2 +/- 0.5 mm Hg(-1) x 10(-3), P < .001) and compliance (1.7 +/- 0.3 vs 2.5 +/- 0.6 mm2 mm Hg(-1), P < .001) and increased stiffness beta index (5.2 +/- 1 vs 2.5 +/- 0.6, P < .001). Pulse wave velocity was also significantly increased in the CoA subjects (4.7 +/- 1.3 vs 3.3 +/- 0.6 m/sec, P < .001). Left ventricular mass index was higher in the CoA subjects (84 +/-11 vs 73 +/-10 g/m2, P = .01) and correlated significantly with aortic stiffness beta index (r2 = 0.8, P < .0001). By contrast, descending aortic characteristics were similar in the CoA and control subjects. CONCLUSION: Central aortic stiffness is markedly increased and associated with increased left ventricular mass in normotensive young subjects after successful early repair of CoA.

Late reoperations after neonatal arterial switch operation for transposition of the great arteries.

The arterial switch operation has become the treatment of choice for neonates with transposition of the great arteries. Currently, the early mortality rate is low as well as the need for early reoperation because of surgical failures; in our experience with 803 neonates, these risks were 3.8% and 1.5%, respectively. The late outcome in terms of survival and functional status is excellent. However, surgical repair is far from anatomical and potential late defects were identified as soon as this procedure was introduced: obstruction of the neo-pulmonary outflow tract, development of obstructions of the reimplanted coronary arteries, dysfunction of the neo-aortic valve, and progressive left ventricular dysfunction. Actually, late reoperations are required in 5-10% of patients (4.5% in our experience with a mean follow-up of 5.8 years). The more frequent indications for reoperation are coronary lesions and right ventricular outflow tract obstructions. Coronary obstructions are, in most cases, detected in patients without any clinical or echocardiographic evidence of myocardial ischaemia. Coronary lesions are progressive and repeated coronary evaluation at regular intervals is necessary. Reoperation is indicated when myocardial ischaemia, at rest or under stress, is demonstrated at myocardial imaging. Satisfactory results can be achieved by surgical coronary patch angioplasty; in selected cases, mammary bypass may be necessary. Right ventricular outflow tract obstruction is related either to inadequate growth of the pulmonary anastomotic site, or to inadequate growth of the whole new right ventricular outflow tract in patients with associated aortic arch obstruction. Reoperation is indicated when significant obstruction (gradient >50 mmHg) is detected at routine echo-Doppler evaluation. Although neo-aortic root dilation and minimal aortic valve insufficiency are common, reoperation for severe neo-aortic valve dysfunction is, to date, very rarely necessary. Whether this will remain the case in the decades to come requires further evaluation. Left ventricular function is maintained in the vast majority of patients. Reoperation may be indicated in some patients for other reasons: mitral valve malformation, tracheo-bronchial compression or pulmonary hypertension.