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.

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.

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.

[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.

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.

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.

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.

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.

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.

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.

Intramural coronary arteries and outcome of neonatal arterial switch operation.

OBJECTIVE: To evaluate the impact of coronary patterns with intramural arteries on the outcome of arterial switch operation (ASO) in neonates with transposition of the great arteries (TGA). METHODS: Between 1987 and 2008, 919 neonates underwent ASO for TGA. Forty-six (5.0%) had intramural coronary arteries. Intramural course involved the left main coronary artery in 28 of the 46 cases (61%), the left anterior descending artery in 12 patients (26%), the right coronary artery in three and both right and left coronary arteries in three cases. Various techniques were used to manage the coronary arteries: ASO without coronary relocation in one, ASO with coronary transfer as a single coronary button in nine and ASO with coronary transfer as two separate buttons in 36 patients (additional pericardial patches were implanted to orientate the coronary button in nine cases or enlarge the coronary ostium in three cases). The intramural course was unroofed in most cases (after 1995). RESULTS: There were 13 deaths (28%): two intra-operative, nine before discharge from the hospital and two after discharge; during the same period, overall mortality in the 873 neonates with other coronary patterns was 3.9%. Actuarial survival at 10 years was 71 + or - 7%. Most deaths (11/13, i.e., 85%) were related to coronary complications. No time-trend effect was noted regarding mortality. Non-fatal coronary lesions were detected in eight patients (three with clinical evidence of myocardial infarction and five without). Five patients underwent re-operation for coronary revascularisation. Actuarial freedom from coronary events at 10 years was 46 + or - 10%. After a mean follow-up of 8.3 + or - 4.8 years, left ventricular function was normal in 97% of the survivors; minor ischaemic sequelae were present in two patients. CONCLUSIONS: Coronary patterns with intramural arteries remain associated with high coronary mortality and morbidity following neonatal ASO, even in the current era. The association of slit-like deformation of the ostium, stenosis of the intramural course and abnormal angle of take-off might explain the difficulty in coronary transfer. The technique of coronary transfer should be individually adapted to each anatomical situation. The place of patch ostioplasty of the intramural artery remains to be determined.

Transcatheter valve insertion in a model of enlarged right ventricular outflow tracts.

OBJECTIVE: Transcatheter pulmonary valve insertion has recently emerged as an alternative to surgery. To extend its indications to patients with a large right ventricular outflow tract, we previously developed an intravascular device that reduces the diameter of the main pulmonary artery, allowing the insertion of available valved stents. Here we report its use in a model of animals with an enlarged right ventricular outflow tract and pulmonary valve incompetence. METHODS AND RESULTS: The study comprised 33 sheep that first underwent surgical enlargement of the main pulmonary artery. We then intended to implant a filler percutaneously, followed later by the insertion of a valve. Three animals died during the intermediate stage. The remainder were humanely killed either immediately (group 1, n = 6) or after a mean follow-up of 1 (group 2, n = 12) or 2 months (group 3, n = 12). Animals from groups 2 and 3 were equally divided into 2 subgroups according to the difference between diameters of the device inserted and the main pulmonary artery (A < 5 mm, B > or = 5 mm). Fillers were all inserted successfully (n = 30), although one embolized after its insertion (group 3A). A valved stent was implanted in all animals, but in 1 case a balloon ruptured during inflation of the stent leading to incomplete expansion and the death of the animal. Six animals, 5 of which were from group A, had pulmonary regurgitation after valve insertion. CONCLUSION: Pulmonary valve insertion is possible through a transcatheter technique using a pulmonary artery filler. Oversizing the device reduces the risk of embolization and paraprosthetic leak.

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.

Evidence of premature immune aging in patients thymectomized during early childhood.

While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.

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.