Rheumatic Heart Disease Screening by Echocardiography
2009; Lippincott Williams & Wilkins; Volume: 120; Issue: 8 Linguagem: Inglês
10.1161/circulationaha.109.849190
ISSN1524-4539
AutoresÉloi Marijon, David S. Celermajer, Muriel Tafflet, Saïd El-Haou, Dinesh Jani, Beatriz Ferreira, Ana Olga Mocumbi, Christophe Paquet, Daniel Sidi, Xavier Jouven,
Tópico(s)Antimicrobial Resistance in Staphylococcus
ResumoHomeCirculationVol. 120, No. 8Rheumatic Heart Disease Screening by Echocardiography Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBRheumatic Heart Disease Screening by EchocardiographyThe Inadequacy of World Health Organization Criteria for Optimizing the Diagnosis of Subclinical Disease Eloi Marijon, MD, David S. Celermajer, PhD, FRACP, Muriel Tafflet, PhD, Saïd El-Haou, PhD, Dinesh N. Jani, MD, Beatriz Ferreira, MD, PhD, Ana-Olga Mocumbi, MD, PhD, Christophe Paquet, MD, MPH, Daniel Sidi, MD, PhD and Xavier Jouven, MD, PhD Eloi MarijonEloi Marijon From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , David S. CelermajerDavid S. Celermajer From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Muriel TaffletMuriel Tafflet From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Saïd El-HaouSaïd El-Haou From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Dinesh N. JaniDinesh N. Jani From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Beatriz FerreiraBeatriz Ferreira From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Ana-Olga MocumbiAna-Olga Mocumbi From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Christophe PaquetChristophe Paquet From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). , Daniel SidiDaniel Sidi From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). and Xavier JouvenXavier Jouven From Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., X.J.); Paris Cardiovascular Research Center, INSERM 970, Université Paris Descartes, AP-HP, Hôpital Européen Georges Pompidou, Paris, France (E.M., M.T., X.J.); Department of Medicine, Sydney University, Sydney, Australia (D.S.C.); INSERM UMRS-956, Université Pierre et Marie Curie, Paris, France (S.E.H.); Instituto do Coração, Maputo, Mozambique (D.N.J., B.F., A.O.M., D.S.); Institut de Veille Sanitaire, Saint Maurice, France (C.P.); and Université Paris Descartes, AP-HP, Hôpital Necker-Enfants Malades, Paris, France (D.S.). Originally published10 Aug 2009https://doi.org/10.1161/CIRCULATIONAHA.109.849190Circulation. 2009;120:663–668Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: August 10, 2009: Previous Version 1 AbstractBackground— 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 1 cm in length, seen in at least 2 planes, a mosaic color jet with a peak velocity >2.5 m/s, persisting throughout systole or diastole.9 On the other hand, the second criteria (combined criteria) consider subclinical RHD as the presence of at least 2 morphological rheumatic valvular features associated with any Doppler-detected valvular regurgitation (diagnosed when color Doppler flow mapping demonstrated reversed flow away from the valve when the valve was closed), seen in at least 2 planes. Morphological criteria were based on the study of (1) leaflet morphology (typical marked thickening of the margins); (2) leaflet mobility (abnormal motion due to the posterior leaflet tip restriction); and (3) subvalvular apparatus morphology (prominent thickening, most often just below the valve, and shortening of chordal structures). Only the aortic and mitral valves were considered in this setting because mild pulmonary or tricuspid regurgitation is frequent and seldom rheumatic in origin. In addition, no valve stenosis was found in this group of relatively young children. Table 1. Criteria Used to Define Subclinical RHD Using EchocardiographyWHO criteria Doppler criteria A regurgitant jet >1 cm in length A regurgitant jet in at least 2 planes A mosaic colour jet with a peak velocity >2.5 m/s The jet persists throughout systole or diastole No morphological criteriaCombined criteria Doppler criteria Any degree of valvular regurgitation seen in at least 2 planes Associated with at least 2 morphological signs Leaflet restriction Subvalvular thickening Valvular thickeningStatistical AnalysesAll patients' characteristics were described as mean±SD or proportions, as appropriate. RHD prevalences with exact 95% confidence intervals (CIs) were computed for the whole sample. The McNemar test for paired data was used for comparison of prevalence rates between the 2 criteria. Regarding the degree of consistency of echocardiographic interpretation of rheumatic valve changes between the 3 echocardiographic experts, we used the pairwise κ coefficient to determine the interobserver variability as well as percentage of concordant cases. Prevalence rates of RHD (according to combined and WHO criteria) between categories of age and between sexes were compared with the use of exact χ2 test. Odds ratios with exact CIs for positive diagnosis were calculated. A 2-sided P value <0.05 was considered statistically significant. All data were analyzed in Paris Cardiovascular Research Center, INSERM 970, Paris, France, with the use of Statistical Analysis System software (version 9.1). This report was prepared in compliance with the STROBE checklist.13 The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.ResultsAmong the 2370 randomly selected children, 200 were not included in the study because no written parental or guardian consent was obtained (8.5%). The study population thus comprised 2170 children, aged 6 to 17 years (mean age, 10.6 [2.5] years; 47.5% male). The majority of children in each class were examined at the first screening visit at school (94.3%); the remaining 5.7% required a mean of 3.2 follow-up visits to allow screening of the entire prespecified group.Clinical evidence of RHD confirmed by echocardiography was found in 5 children, a prevalence of 2.3 per 1000 (95% CI, 0.7 to 5.4). Of these, 2 had clinical and biological Jones criteria for acute rheumatic fever; anti-inflammatory and antibiotic treatment was initiated in each case.In regard to the subclinical evidence of RHD, the results of the systematic echocardiographic screening according to WHO or combined criteria are reported in Figure 1 and Table 2. Among the 208 children (9.6%) with echocardiographic features of at least minimal valve regurgitation, on-site examination identified 18 and 124 children suspected to have RHD according to WHO and combined criteria, respectively (P<0.0001, exact McNemar test). All of the suspected cases were reviewed with the use of the nonportable ultrasound system. After review by the 3 experts, 17 of the 18 were confirmed to have definite RHD according to WHO criteria (94%) (echocardiographic features shown in Figure 2), whereas 66 of the 124 cases were considered to have definite RHD by the use of combined criteria (53%) (echocardiographic features shown in Figure 3). The definite echocardiographic RHD prevalences were thus 7.8 per 1000 (95% CI, 4.6 to 12.5) and 30.4 per 1000 (95% CI, 23.6 to 38.5) for WHO and combined criteria, respectively (P<0.0001, exact McNemar test) (Figure 4). Positive predictive values were calculated at 66 of 124 (53%) and 17 of 18 (94%) for combined and WHO criteria, respectively. On the other hand, and assuming that the use of portable echocardiography in this setting allowed the detection of all RHD cases in the field, maximum sensitivity was calculated at 17 of 68 (25%) and 66 of 68 (97%) for WHO and combined criteria, respectively. Of the 17 children with a definitive diagnosis of RHD by WHO criteria, all were found to have exclusively mitral valve disease. Of the 66 children identified by the combined criteria, 63 (95.5%) had mitral valve disease only, 2 had both aortic and mitral valve disease, and 1 had only aortic valve disease. No cases of mitral or aortic stenosis were seen. None of the children studied had evidence of severe mitral regurgitation with annular dilatation. We found no cases of mitral diastolic flow acceleration in association with limitation of leaflet mobility. Download figureDownload PowerPointFigure 1. Results of systematic echocardiographic screening performed at school (with the use of a portable ultrasound system) and confirmed at hospital in cases of suspected RHD valve lesions (with the use of a nonportable ultrasound system).Table 2. Baseline Characteristics and Prevalence Rates of Echocardiographic Screening for WHO and Combined Criteria for RHDWHO Criteria (n=17)Combined Criteria (n=66)*Number of cases was estimated by applying the observed prevalence in our sample (n=2170) to the whole population of children aged 6 to 17 y in Maputo (n=1 140 000).Baseline characteristics Age, mean (SD), y11.4 (2.0)11.0 (2.5) Males, n (%)9 (52.9)23 (34.8) History of acute rheumatic fever, n (%)2 (11.8)4 (6.1)Prevalence of RHD, per 1000 (exact 95% CI) Prevalence by sex Girls7.0 (3.0–13.8)37.8 (27.5–50.5) Boys8.7 (4.0–16.5)22.3 (14.2–33.3) Prevalence by age tertiles 6-9 y2.7 (0.3–9.7)25.7 (15.5–39.9) 10-11 y8.8 (3.2–19.1)25.0 (14.6–39.7) 12-17 y12.0 (5.5–22.7)40.0 (27.1–56.6)Estimated cases in Maputo City,* n (95% CI)8 892 (5244–14 250)34 656 (26 904–43 890)Download figureDownload PowerPointFigure 2. Significant regurgitation with the use of WHO criteria for subclinical RHD (left parasternal long-axis view).Download figureDownload PowerPointFigure 3. Echocardiographic findings of subclinical RHD with the use of combined criteria (left parasternal long-axis view). A shows evidence of morphological features for RHD—valvular thickening predominantly at the tip of both leaflets and subvalvular apparatus thickening—with minimal mitral regurgitation visible as a blue jet (B).Download figureDownload PowerPointFigure 4. Prevalences of physiological valve regurgitation and RHD according to combined, WHO, and clinical criteria. The I bars indicate the superior limit of 95% CIs.The interobserver variability for diagnosing a subclinical RHD valve abnormality showed excellent agreement for both WHO criteria (noncalculable κ value; mean concordant pairs, 96.3%) and combined criteria (κ value of 0.92 [95% CI, 0.85 to 0.99]; 0.92 [95% CI, 0.85 to 0.99]; and 0.90 [95% CI, 0.83 to 0.98], respectively, for the 3 pairs of independent reviewers; mean concordant pairs, 95.7%). In regard to WHO criteria, of the 18 suspected RHD cases diagnosed at school, 17 were concordantly considered RHD, and 1 presented a discordant diagnosis for RHD. In regard to combined criteria, among the 124 suspected RHD cases diagnosed at school, 66 were concordantly considered RHD, 50 were concordantly considered non-RHD, and 8 showed discordant interpretation from the 3 reviewers.The majority of children with WHO criteria for RHD also had combined criteria for RHD (88%). However, of these 17 children with definite lesions according to WHO criteria, 2 children showed isolated mitral regurgitation without any morphological signs to suggest a rheumatic origin (Table 3). Table 3. Number of Detected Cases According to WHO and Combined CriteriaCombined +Combined −WHO +15217WHO −51210221536621042170The echocardiographic prevalence of RHD rose with increasing age, peaking at 12.0 per 1000 (95% CI, 5.5 to 22.7) for WHO criteria (P=NS) and at 40.0 per 1000 (95% CI, 27.1 to 56.6) in those aged 12 to 17 years for combined criteria (P=NS). Although the prevalence of echocardiographic RHD showed no female predominance regarding children according to WHO criteria (odds ratio, 0.80; 95% CI, 0.27 to 2.35; P=0.8, exact χ2 test), RHD prevalence was significantly higher in girls than in boys (odds ratio, 1.72; 95% CI, 1.00 to 3.01; P=0.04, exact χ2 test) according to combined criteria.DiscussionRecent work has strongly supported the use of portable echocardiography for screening for subclinical RHD in developing nations. Optimizing case detection in this way maximizes the chances of appropriate prevention of advanced RHD. Our results demonstrate, however, that the currently recommended WHO criteria for preclinical RHD may risk missing up to three quarters of cases of subclinically affected and thus potentially treatable children with early RHD, possibly tens of thousands of children worldwide. In adding the diagnostic criterion of morphological valve changes, otherwise well defined in more advanced rheumatic valve lesions, we have detected many children with subclinical RHD but without significant valve regurgitation who would not be eligible for secondary RHD prophylaxis under current international guidelines.Mitral valve prolapse and degenerative valve disease are the most common causes of important left heart valve regurgitation in adults in developed countries. By contrast, mitral and aortic regurgitation are more likely due to RHD in endemic areas. Repetitive attacks of rheumatic fever may lead to valve inflammation, with leaflet and subleaflet thickening.14 Because these changes precede leaflet retraction and regurgitation in rheumatic disease and given that there are almost no other causes of valve thickening in childhood, the identification of morphological valve changes in addition to the detection of regurgitation represents a logical means of enhancing case detection. By contrast, the situation is less clear for the diagnosis of acute rheumatic carditis with valve involvement by ultrasound because of the frequent absence of significant morphological changes and also a lower specificity.15,16 We note, however, that the 2007 Australian guidelines now consider subclinical valve regurgitation a major criterion for acute rheumatic fever with carditis in high-risk children (those living in communities with high rates of acute rheumatic fever).17In many populations, acute rheumatic fever and RHD are more common in females than males. Whether this trend is a result of innate susceptibility or increased exposure to group A streptococcus because of greater involvement of women in child rearing is unclear.1 However, there is now evidence of genetic susceptibility for RHD, including several alleles for major histocompatibility complex class II and tumor necrosis factor.2 Although we found the expected increase of RHD in females using combined criteria, we observed no female predominance using WHO criteria. Moreover, although the majority of children of the present study identified as having significant regurgitation (WHO criteria) also showed morphological changes (combined criteria), 2 boys demonstrated WHO criteria but had no morphological changes suggestive of RHD.We have found that the morphological changes that we regarded as diagnostic of subclinical RHD could be detected with similar certainty compared with the traditional WHO criteria, as assessed by concordance between experienced observers for ultrasound-based diagnosis. In regard to feasibility in the field, the WHO criteria may be easier to use at school with a portable ultrasound system, as attested by the high positive predictive value. However, this set of criteria suffers from a substantially lower sensitivity; thus, the combined criteria are better suited for screening for subclinical RHD. The fact that some children are "overdetected" on-site does not necessarily represent a limitation but emphasizes the importance of eventually confirming suggestive findings with more sophisticated ultrasound equipment. More recent portable ultrasound systems with higher resolution might, in the future, be able to provide more accurate on-site detection rates. In this context of screening, sen
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