Discussion

School surveys are the most common method of assessing the prevalence of rheumatic heart disease at the community level. ^{Reference Sika-Paotuni, Beaton, Raghu, Steer, Carapetis, Ferretti, Stevens and Fischetti13–Reference Zühlke and Mayosi15} This is the first and largest echocardiographic screening study for subclinical rheumatic heart disease in Turkish schoolchildren. There is a limited number of studies displaying the prevalence of rheumatic heart disease in Turkey, and the diagnosis of rheumatic heart disease was previously confirmed by only auscultation. As obtained by Imamoğlu et al, the prevalence of rheumatic heart disease was found to be 9.4/1000 among 3039 schoolchildren in 1976; however, Imamoğlu et al specified that the prevalence of such disease was decreased to 5.6/1000 after 10 years. ^{Reference Imamoğlu and Ozen11} In another study conducted by Olguntürk et al the prevalence was found to be 3.7/1000 in schoolchildren in 1999. ^{Reference Olguntürk, Aydın, Tunaoğlu and Akalın12}

This study demonstrated a high prevalence of subclinical rheumatic heart disease in Ankara. Evidence of definite subclinical rheumatic heart disease was found in 39 students (15.0 per 1000 children), while 20 students were diagnosed with borderline rheumatic heart disease (8.0 per 1000 children). The prevalence rates of rheumatic heart disease diagnosed with echocardiography give estimates which are much higher than previously reported data based on only auscultation in Ankara. Similar studies also noted that echocardiographic screening reveals approximately 10 times higher prevalence of rheumatic heart disease, as compared to clinical evaluation. ^{Reference Carapetis, Hardy and Fakakovikaetau5,Reference Marijon, Tafflet and Jouven6,Reference Bahaya, Panwar, Beniwal and Panvar16} Rothenbühler et al reported that the prevalence of rheumatic heart disease was 2.9 per 1000 people by auscultation as compared to 12.9 per 1000 by echocardiography. ^{Reference Rothenbühler, O’Sullivan and Stortecky17}

The first study to use Doppler echocardiography was conducted in rural schools of Kenya in 1996.^{Reference Anabwani and Bonhoeffer18} The highest prevalence rates have been documented in Southeast Asia, Africa, Australia, India, Fiji, and New Zealand.^{Reference Reményi, Wilson and Steer10} Since different criteria were used to define echocardiographic rheumatic heart disease, differences were seen regarding rheumatic heart disease prevalence.^{Reference Carapetis, Hardy and Fakakovikaetau5,Reference Zühlke and Mayosi15,Reference Saxena, Zühlke and Wilson19–22} Earlier studies used the World Health Organization definition of pathologic mitral regurgitation (jet length ≥ 1 cm compared with ≥2 cm in the World Heart Federation criteria) as a marker for rheumatic heart disease.²² Most of the echocardiographic screening studies used either World Health Organization or modified World Health Organization criteria to diagnose rheumatic heart disease.^{Reference Bahaya, Panwar, Beniwal and Panvar16,Reference Saxena, Zühlke and Wilson19,22–Reference Marijon, Celermajer and Tafflet26}

Previous studies based on World Health Organization, World Health Organization/National Institute Health 2005, or modified World Health Organization criteria showed high rates (ranging from 14.8 per 1000 to 56.5 per 1000) of subclinical rheumatic heart disease in endemic areas.^{Reference Carapetis, Hardy and Fakakovikaetau5,Reference Paar, Berrios and Rose7,Reference Bahaya, Panwar, Beniwal and Panvar16,Reference Anabwani and Bonhoeffer18,Reference Beaton, Okello, Lwabi, Mondo, McCarter and Sable27,Reference Webb, Wilson, Lennon, Wilson and Nicholson28} The World Health Organization criteria were exclusively Doppler based and inadequate to diagnose subclinical cases, thus prompting the development of new morphology-based modified criteria.^{Reference Marijon, Celermajer and Tafflet26} The modified World Health Organization criteria also may overestimate the prevalence of rheumatic heart disease in some cases by classifying physiological mitral regurgitation as pathological.^{Reference Saxena, Zühlke and Wilson19}

Recently, World Heart Federation proposed new echocardiography criteria to diagnose subclinical rheumatic heart disease.^{Reference Reményi, Wilson and Steer10} The 2012 World Heart Federation criteria are currently considered gold standard as they involve both morphologic and Doppler features and are more specific in differentiating pathologic lesions from physiologic.^{Reference Reményi, Wilson and Steer10} Very few studies have been reported using these criteria.^{Reference Saxena, Desai and Narvencar29,Reference Huang, Favazza and Legg20,Reference Nascimento, Sable and Nunes30,Reference Davis, Remenyi and Draper31} The largest population study (16,294 schoolchildren) in India documented that the prevalence of definite rheumatic heart disease was 7.7/1000, and borderline rheumatic heart disease was 5.7/1000 using World Heart Federation criteria.^{Reference Saxena, Desai and Narvencar29} Another study documented that the prevalence of definite rheumatic heart disease was 0.5 per 1000 and borderline rheumatic heart disease was 4.0 per 1000 in 12,048 schoolchildren in Brazil.^{Reference Nascimento, Sable and Nunes30} The prevalence of definite or borderline rheumatic heart disease in 1058 schoolchildren was found to be 12.9 per 1000 in American Samoa.^{Reference Huang, Favazza and Legg20} Similar to our findings, Davis et al had found that the prevalence of definite rheumatic heart disease was 18.3 per 1000 in Timor-Leste.^{Reference Davis, Remenyi and Draper31} The prevalence of rheumatic heart disease was higher than we expected to be seen in Ankara. This study was performed by paediatric cardiologists with experience in the diagnosis of rheumatic heart disease. We do not think over-diagnosis is responsible for this high prevalence because the diagnosis of rheumatic heart disease in all cases was reached by the consensus of at least two experienced paediatric cardiologists.

Among demographic and socio-economic factors, age and sex seem to be independently associated with the prevalence of rheumatic heart disease. In the present study, subclinical rheumatic heart disease was associated with advancing age and female sex, as in other studies.^{Reference Saxena, Zühlke and Wilson19,Reference Saxena, Desai and Narvencar29,Reference Nascimento, Sable and Nunes30,Reference Davis, Remenyi and Draper31} We found that the prevalence of definite rheumatic heart disease increased with age: 23 per 1000 in 14–18-year-old children (odds ratio 3.263) (95% confidence intervals 1.247–8.543, p = 0.016) with a prevalence of 17 per 1000 children aged 10–13 years and 7 per 1000 children aged 5–9 years. The risk of rheumatic heart disease was found to be increased 7.7-fold in girls and children aged between 14 and 18 years. There were no significant differences in the proportion of age groups or gender among patients with definite and borderline rheumatic heart disease. Nascimento et al had found that the prevalence of rheumatic heart disease was higher among girls who were older than 12 years old.^{Reference Nascimento, Sable and Nunes30} Roberts et al also reported the prevalence of both definite and borderline rheumatic heart disease increased with age.^{Reference Roberts, Cannon and Atkinson32} However, they did not observe significant differences in the proportion of girls among cases of definite or borderline rheumatic heart disease.

In the present study the number of definite cases is almost two times more than that of borderline cases. Although most of reported studies show borderline cases to be more frequent than definite ones, some studies found definite rheumatic heart disease dominance, as in the case of the present study.^{Reference Beaton, Okello, Lwabi, Mondo, McCarter and Sable27,Reference Webb, Wilson, Lennon, Wilson and Nicholson28,Reference Nascimento, Sable and Nunes30,Reference Roberts, Maguire and Brown33–Reference Ali, Domi and Abbo35}

Rheumatic heart disease has been consistently associated with poor socio-economic conditions, lower income, and rural areas.^{Reference Huang, Favazza and Legg20,Reference Reeves, Kado and Brook21,Reference Ali, Domi and Abbo35,Reference Periwal, Gupta, Panwar, Khatri, Raja and Gupta36} In the present study, the prevalence of definite rheumatic heart disease in children in private schools situated in high-income areas of Ankara is higher than expected. These findings contrast with the findings of previously published studies. ^{Reference Sika-Paotuni, Beaton, Raghu, Steer, Carapetis, Ferretti, Stevens and Fischetti13,Reference Roberts, Maguire and Brown33} As it is known, group A beta-hemolytic streptococci infection is more common among people living in crowded areas.^{Reference Sika-Paotuni, Beaton, Raghu, Steer, Carapetis, Ferretti, Stevens and Fischetti13,Reference Reeves, Kado and Brook21} In Turkey, private schools provide full-time education and public-schools provide part-time education. We suggest that children in private schools are together for a longer period of time, unlike public schools. Besides, they often go to school by school bus instead of walking, as in the case of public schoolchildren. Furthermore, children tend to be in more crowded areas, such as sports halls, pools, and dining halls, in private schools, and this may also be a factor increasing the spread of group A beta-hemolytic streptococci infection. Also, the parents whose children are in private schools have more concerns about using antibiotics, and we suggest that this may be another factor for the higher prevalence of rheumatic heart disease in private schools. Nascimento et al found that the prevalence rates of rheumatic heart disease were also more than expected in private schools located in high-income areas in Brazil. ^{Reference Nascimento, Sable and Nunes30}

The involvement of valve disease is detailed in Table 4. In the present study, the mitral valve was the most commonly involved in children with both definite rheumatic heart disease and borderline rheumatic heart disease, as in other similar studies.^{Reference Beaton, Lu and Aliku9,Reference Huang, Favazza and Legg20,Reference Periwal, Gupta, Panwar, Khatri, Raja and Gupta36,Reference Ayabakan, Ozkutlu and Kılıc37} Aortic valve and mitral valve morphologic changes should be evaluated carefully by echocardiography. Minor congenital mitral valve anomalies and mitral valve prolapse should be differentiated from rheumatic mitral morphologic changes.^{Reference Webb, Gentles, Stirling, Lee, O’Donnell and Wilson8} Aortic regurgitation may be associated with a bicuspid aortic valve or a dilated abnormal aortic root or sinus.^{Reference Webb, Gentles, Stirling, Lee, O’Donnell and Wilson8,Reference Saxena, Zühlke and Wilson19} These anomalies are easily excluded by detailed echocardiography. In the present study, physiologic mitral regurgitation was differentiated from borderline rheumatic heart disease according to the 2012 World Heart Federation criteria and was found to be present in 155 children (6%).^{Reference Reményi, Wilson and Steer10} Previous reports found that the rates of physiologic mitral regurgitation in normal children to be between 2.5 and 45%. ^{Reference Webb, Gentles, Stirling, Lee, O’Donnell and Wilson8,Reference Ayabakan, Ozkutlu and Kılıc37,Reference Thomson, Allen and Gibbs38}

The clinical significance of borderline rheumatic heart disease and the need for secondary prophylaxis remains unknown.^{Reference Sika-Paotuni, Beaton, Raghu, Steer, Carapetis, Ferretti, Stevens and Fischetti13} Some studies reported that with borderline rheumatic heart disease a benign prognosis was expected.^{Reference Paar, Berrios and Rose7,Reference Beaton, Okello and Aliku14} Nevertheless, recent studies have found that the valvular lesions of children with borderline rheumatic heart disease may progress and definite rheumatic heart disease may develop.^{Reference Kotit, Said, ElFaramawy, Mahmoud, Phillips and Yacoub34,Reference Ali, Domi and Abbo35,Reference Bhaya, Beniwal, Panwar and Panwar39} Remond et al. reported that among 55 Aborigines with borderline disease, 13 of them (23%) progressed to definite rheumatic heart disease after an interval of 2.5–5 years.^{Reference Rémond, Atkinson and White40} Kotit et al evaluated the way subclinical findings detected by echocardiography progressed during the subsequent 4–5 years.^{Reference Kotit, Said, ElFaramawy, Mahmoud, Phillips and Yacoub34} Follow-up progression was documented in 14 of 72 children (19.4%) and regression in 30 children (41.7%). Ten of the borderline cases had regressed, 10 remained unchanged, and 6 had developed definite rheumatic heart disease. They also emphasised that functional defects of the valve tended to have higher rates of regression than structural changes of the valve.^{Reference Kotit, Said, ElFaramawy, Mahmoud, Phillips and Yacoub34} It has also been reported by Bahaya et al that if the mitral regurgitation coexists with valve deformities, mitral valve disease is more likely to persist.^{Reference Bahaya, Panwar, Beniwal and Panvar16} According to the findings of Kotit, children with borderline rheumatic heart disease should be frequently evaluated by echocardiography.^{Reference Kotit, Said, ElFaramawy, Mahmoud, Phillips and Yacoub34} Moreover, we previously reported the progression of valvular regurgitation in 6 children (30%) among 20 children who were diagnosed with subclinical rheumatic heart disease, after a follow-up of 43.4 ± 25 months.^{Reference Pekpak, Atalay, Karadeniz, Demir, Tutar and Uçar41} Therefore, we suggest long-term penicillin prophylaxis in children with subclinical rheumatic heart disease. It is known that secondary prophylaxis improves the prognosis of this disease and prevents recurrence.^{Reference Sika-Paotuni, Beaton, Raghu, Steer, Carapetis, Ferretti, Stevens and Fischetti13,Reference Ayabakan, Ozkutlu and Kılıc37,42,Reference Engelman, Mataika and Kado43}