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 .

Cardiac surgery in low-income settings: 10 years of experience from two countries.

BACKGROUND: Access to cardiac surgery is limited in low-income settings, and data on patient outcomes are scarce. AIMS: To assess characteristics, surgical procedures and outcomes in patients undergoing open-heart surgery in low-income settings. METHODS: This was a cohort study (2001-2011) in two low-income countries, Cambodia and Mozambique, where cardiac surgery had been promoted by visiting non-governmental organizations. RESULTS: In Cambodia and Mozambique, respectively, 1332 and 767 consecutive patients were included; 547 (41.16%) and 385 (50.20%) were men; median age at first surgery was 11 years (interquartile range [IQR] 4-14) and 11 years (IQR 3-18); rheumatic heart disease affected 490 (36.79%) and 268 (34.94%) patients; congenital heart disease (CHD) affected 834 (62.61%) and 390 (50.85%) patients, with increasingly more CHD patients over time (P<0.001); and the number of patients lost to follow-up reached 741 (55.63%) and 112 (14.6%) at 30 days. A total of 249 (32.46%) patients were lost to follow-up in Mozambique, remoteness being the only influencing factor (P<0.001). Among patients with known vital status, the early (<30 days) postoperative mortality rate was 6.10% (n=40) in Mozambique and 3.05% (n=18) in Cambodia. Overall, 109 (8.18%) patients in Cambodia and 94 (12.26%) patients in Mozambique underwent re-do surgery. In Mozambique, a further 50/518 (9.65%) patients died at a median of 23months (IQR 7-43); in Cambodia, a further 34/591 (5.75%) patients died at a median of 11.5months (IQR 6-54.5). CONCLUSIONS: Cardiac surgery is feasible in low-income countries with acceptable in-hospital mortality and proof of capacity building. Patient outcomes after cardiac surgery in low-income countries remain unknown, given the strikingly high numbers of lost to follow-up.

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.

High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.

Acyl-CoA dehydrogenase family, member 9 (ACAD9) mutation is a frequent, usually fatal cause of early-onset cardiac hypertrophy and mitochondrial respiratory chain complex I deficiency in early childhood. We retrospectively studied a series of 20 unrelated children with cardiac hypertrophy and isolated complex I deficiency and identified compound heterozygosity for missense, splice site or frame shift ACAD9 variants in 8/20 patients (40%). Age at onset ranged from neonatal period to 9 years and 5/8 died in infancy. Heart transplantation was possible in 3/8. Two of them survived and one additional patient improved spontaneously. Importantly, the surviving patients later developed delayed-onset neurologic or muscular symptoms, namely cognitive impairment, seizures, muscle weakness and exercise intolerance. Other organ involvement included proximal tubulopathy, renal failure, secondary ovarian failure and optic atrophy. We conclude that ACAD9 mutation is the most frequent cause of cardiac hypertrophy and isolated complex I deficiency. Heart transplantation in children surviving neonatal period should be considered with caution, as delayed-onset muscle and brain involvement of various severity may occur, even if absent prior to transplantation.

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.

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.

Mechanisms of coronary complications after the arterial switch for transposition of the great arteries.

BACKGROUND: The arterial switch operation (ASO) for transposition of the great arteries requires transfer of the coronary arteries from the aorta to the proximal pulmonary artery (neoaorta). This is complicated by variable coronary anatomy before transfer. In 8% to 10% of cases, there is evidence of late coronary stenosis and/or occlusion, often with catastrophic clinical consequences. The mechanism of such complications has not been well studied. METHODS AND RESULTS: We analyzed 190 consecutive high-resolution computed tomographic scans from the ASO procedure (patients aged 5-16 years) and found 17 patients with significant (>30% up to occlusion) coronary lesions (8.9%); all were later confirmed by conventional angiography. The left main coronary artery was abnormal in 9 patients (ostium in all), the left anterior descending artery in 3, the circumflex in 2, and the right coronary artery in 3 patients. Using multiplanar and 3-dimensional reconstructions of the coronary arteries, aorta, and pulmonary artery, we identified the commonest mechanisms of coronary abnormalities. For the left main and left anterior descending artery, anterior positioning of the transferred left coronary artery (between 12 and 1 o'clock on the neoaorta) appeared to predispose to a tangential course of the proximal left coronary artery promoting stenosis. All circumflex lesions occurred in Yacoub type D coronaries where a long initially retroaortic artery was stretched by its new positioning behind an enlarged neoaorta. Right coronary artery lesions occurred only in cases in which the reimplantation site was very high above the right coronary sinus with potential compression from the main pulmonary artery bifurcation immediately above. CONCLUSIONS: Thus detailed multiplanar computed tomographic scanning can elucidate the mechanisms of late coronary complications after the ASO. Understanding these aspects could help to improve surgical technique to minimize the risk of late coronary obstructions.

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.

[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.

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.

Screening for rheumatic heart disease: evaluation of a simplified echocardiography-based approach.

AIMS: Portable echocardiography has emerged as a potential tool to detect rheumatic heart disease (RHD) early. Complex echocardiographic criteria used in recent epidemiological studies may be difficult to translate into daily practice in areas where the burden of RHD is greatest and skilled practitioners are lacking. The aim of this study was to evaluate a simplified echo approach for RHD screening among children in low-income countries. METHODS AND RESULTS: Retrospective analysis of data from a cross-sectional echocardiography-based study carried out in 2005 through the examination of 2170 school children in Maputo, Mozambique. We aimed to evaluate the value of a reference set of criteria (defined as a combination of Doppler and morphological rheumatic features of the aortic and/or mitral valves) compared with an easy-to-use single mitral regurgitation jet-length criterion (simplified set of criteria). All suspected lesions (according to reference or simplified criteria) detected in the field by a portable echo machine were reassessed by non-portable echocardiography and then read by three independent experts. Definite RHD cases in both groups were finally ascertained according to the reference criteria. Portable echocardiography detected valve regurgitation in 208 children. According to the reference criteria, 18 children were detected with suspected RHD on site. Of these, 15 children (83%) were considered to have definite RHD, giving a prevalence of 6.9 per 1000 (95% CI: 3.9-11.4). The simplified mitral regurgitation jet-length criteria detected 12 children at school, 11 of whom were subsequently confirmed to have definite RHD, giving an estimated prevalence of 5.1 per 1000 (95% CI: 2.5-9.1) (P = 0.12, exact McNemar test). When compared with the reference criteria, the simplified approach yields a maximum sensitivity of 73% for case detection, with a positive predictive value of 92%. CONCLUSION: Simplified echocardiography-based screening for RHD appears feasible, allowing rapid and appropriate detection of a significant number of RHD cases on site.

Bidirectional cavopulmonary shunt with additional pulmonary blood flow: a failed or successful strategy?

OBJECTIVES: In patients with single ventricle physiology, Fontan circulation is considered as the optimal surgical approach, although it entails a growing incidence of late complications. It has been speculated that the association of bidirectional cavopulmonary shunt (BCPS) and additional pulmonary blood flow (APBF) might provide long-lasting palliation. The present study was undertaken to assess the long-term outcome of this strategy. METHODS: A group of 70 patients with single ventricle physiology, who underwent BCPS with APBF between 1990 and 2000, were reviewed retrospectively. Median age at operation was 2 years (range: 0.1-27 years). Unilateral BCPS was performed in 60 patients (86%), bilateral BCPS in 9 and the Kawashima procedure in 1. APBF was provided through antegrade pulmonary outflow tract in 43 patients (61%) and by aortopulmonary shunt in 27 (39%). Two patients died early and three were lost to follow-up. Mean follow-up of the 65 remaining patients was 13.5 ± 4 years. End-points were death, need for heart transplantation (HTx) or Fontan completion and functional outcome. RESULTS: Five patients died (two after HTx, three from ventricular failure); overall actuarial survival was 89 ± 4% at 15 years. Six patients underwent HTx (one after Fontan completion) with two early deaths and no late mortality. Fifty-one patients underwent Fontan completion (11 with additional palliative procedures before completion); there was no early or late mortality following Fontan completion; one patient underwent HTx. Among the remaining six patients with BCPS and APBF, two were not suitable for Fontan completion and four remained suitable. Overall, clinical failure (mortality, HTx, unsuitability for Fontan completion) occurred in 13 patients (19%). Risk factors for clinical failure were older age at BCPS (P = 0.01) and postoperative complications after BCPS (P = 0.001). Considering late mortality, HTx and Fontan completion as strategic failures, the actuarial freedom from these events was 20 ± 5% at 10 years. CONCLUSIONS: BCPS with APBF approach: (i) fails as a strategy for definitive palliation, (ii) provides a high survival rate, (iii) does not preclude a successful Fontan completion and (iv) may delay the long-term deleterious consequences of Fontan circulation. Palliation by BCPS with APBF should be achieved early in life.

[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

[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.

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.

Loan applications in adult patients with congenital heart disease: a French study.

BACKGROUND: Improvements in the treatment of children with congenital heart disease have led to most of these patients reaching adulthood. Despite the increase in lifespan, very little is known about their quality of life - in particular, their ability to obtain a mortgage or consumer loan. AIM: To investigate the outcome of mortgage and loan applications made by adults with differential severities of congenital heart disease. METHODS: Four hundred and seventy-six patients were invited to participate in a questionnaire-based interview by phone. Of these patients, one hundred and forty-two responded. Respondents were classified into three categories ('significant', 'complex' and 'mild') based on congenital heart disease severity according to the Bethesda conference. RESULTS: Ninety patients (64%) had applied for loans; 17 (16.5%) did not report their heart disease to the insurance company, 13 were refused insurance and 39 were asked to pay surplus fees. The imposed fees concerned patients classified in the 'significant' and 'complex' groups (P<0.0001 and P<0.003, respectively, compared with those classified in the 'mild' group). Age, sex, other diseases, cardiovascular risk factors and duration of the loan had no influence on loan application outcomes. CONCLUSION: Adults with congenital heart disease are considerably more likely to have difficulty obtaining a mortgage or loan, independent of their congenital heart disease severity. Moreover, despite an increased obtainment of a loan in patients classified as 'mild', the refusal rates were identical for patients classified as having 'significant' or 'complex' congenital heart disease, although their prognosis is different.

Challenges on the management of congenital heart disease in developing countries.

INTRODUCTION: While in developed countries prenatal diagnosis is currently used to detect Congenital Heart Disease before (CHD) before birth, in developing countries only a minority of children with CHD is detected and few benefit from surgical treatment. Having created a referral unit for diagnosis and treatment of cardiovascular diseases in a resource-deprived country we designed a study aiming at describing the spectrum and characteristics of CHD and discuss the challenges of its management. POPULATION AND METHODS: We studied retrospectively all patients assisted at a referral unit between 2001 and 2007, collecting epidemiological, clinical, echocardiographic and surgical data from hospital files. RESULTS: We studied 534 patients with median age at diagnosis of 4 years (range 0-79); 296 were females (55.4%). Only 282 (52.8%) patients were diagnosed under the age of two years, and complications were present in 155 (29.0%) at time of diagnosis. We operated 196 patients with mean age of 8±10 years. Only 29 of the 111 complex defects were considered for surgery. The 30-days post-operative mortality was 8/196 (4.0%). The most important post-surgical complications were post pericardectomy syndrome (22). DISCUSSION: A pattern of late presentation accompanied by high rate of complications was found. In resource-deprived settings the approach to the management of CHD emphasizes the treatment of "curable" malformations. Surgery for CHD in these settings must be linked to early detection and a referral system in which general practitioners, pediatricians, obstetricians and cardiologists interact in the design and implementation protocols for diagnosis, management and follow-up of patients.

Early prophylactic pulmonary artery banding in isolated congenitally corrected transposition of the great arteries.

OBJECTIVE: Mid-term evaluation of an aggressive surgical management of isolated congenitally corrected transposition of the great arteries (ccTGA) by pulmonary artery (PA) banding in early infancy. METHODS: Between 2001 and 2009, 11 asymptomatic patients (seven neonates and four infants) underwent a dilatable, partially adjustable, homemade PA banding for ccTGA with intact ventricular septum. PA band circumference was correlated to body weight (22 mm+1 mm kg(-1)) and ideally adjusted to obtain flat septal geometry. Mean age at operation was 1.5±1.4 months. RESULTS: There was no hospital mortality. Mean ventilation time and intensive care unit (ICU) stay were 20±9 h and 2.6±1.5 days, respectively. Five patients required postoperative inotropic support. One late death occurred suddenly at 4 months; normal biventricular function and no tricuspid regurgitation were noted at last follow-up, 1 week before death. Mean follow-up was 21.5±26 months. Mean band velocity increased over time from 2.65±0.7 m s(-1) postoperatively to 3.7±0.3 at 6 months and 4.5±0.4 m s(-1) at 2 years. Tricuspid regurgitation remained stable in seven patients, decreased in three and worsened in one. Flat septal geometry was obtained in all patients after the third postoperative month. One patient underwent a double-switch procedure at 7 years due to suprasystemic morphologically left ventricular pressure. The postoperative course was uneventful. CONCLUSIONS: In neonates with isolated ccTGA, prophylactic PA banding is safe and carries a low morbidity. At mid-term evaluation, tricuspid valve function is stabilised or improved and systemic competence of the left ventricle is maintained, thus allowing double switch if indicated.