Echocardiographic screening

The median duration of echocardiographic examination by hand-held machine was six minutes (4–8). The overall prevalence of individuals with CHD detected by Vscan was 172 (11.368 per 1,000 persons; 95% CI, 9.740 to 13.188). After re-examination in hospital echocardiography clinic, the true prevalence of CHD was found to be 152 (10.046 per 1,000 persons; 95% CI, 8.519 - 11.766). Of the 152 individuals, 113 (7.468 per 1,000 persons; 95% CI: 6.2 to 9) students had not been diagnosed. All CHDs are summarized in Table 2. Ten (0.660 per 1,000 persons; 95% CI, 0.317 to 1.215) students had a combination of CHDs (Appendix Table 3).

Table 2

The frequency of CHDs and cardiomyopathies among students.

NUMBERS DETECTED BY VSCAN (%) NUMBERS DETECTED BY STE, % (95% CONFIDENCE INTERVAL) CRUDE RATE, PER 1000 PERSONS (95% CONFIDENCE INTERVAL) Total CHD* 172 (1.137%) 152, 1.005% (0.852 - 1.180) 10.046 (8.519 – 11.766)     Atrial septal defect 54 (0.357%) 50, 0.330% (0.245 – 0.435) 3.305 (2.454 – 4.355)     Patent foramen ovale 37 (0.245%) 33, 0.220% (0.150 – 0.306) 2.181 (1.502 – 3.062)     Bicuspid aortic valve 24 (0.159%) 20, 0.132% (0.080 – 0.204) 1.322 (0.808 – 2.041)     Patent ductus arteriosus 18 (0.119%) 16, 0.106% (0.060 – 0.172) 1.058 (0.605 – 1.717)     Ventricular septal defect 17 (0.112%) 16, 0.106% (0.060 – 0.172) 1.058 (0.605 – 1.717)     Coarctation of aorta 6 (0.040%) 6, 0.040% (0.015 – 0.090) 0.397 (0.145 – 0.863)     Isolated PA dilatation 5 (0.033%) 2, 0.013% (0.001 – 0.048) 0.132 (0.016 – 0.478)     Sub-aortic web 4 (0.026%) 4, 0.026% (0.007 – 0.068) 0.264 (0.072 – 0.677)     Isolated sinus valsalva dilatation 4 (0.026%) 2, 0.013% (0.001 – 0.048) 0.132 (0.016 – 0.478)     Persistent LSVC 3 (0.019%) 3, 0.020% (0.004 – 0.058) 0.198 (0.040 – 0.580)     Pulmonary valve stenosis 2 (0.013%) 2, 0.013% (0.001 – 0.048) 0.132 (0.016 – 0.478)     Isolated right aortic arch 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Supravalvular mitral mass 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Quadricuspid aortic valve 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Aortic valve stenosis 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Isolated aorta dilatation 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Situs inversus 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Tetralogy of Fallot 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)     Transposition of great arteries 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370) Other abnormalities*     Redundant interatrial septum 862 (5.700%) NA NA     Aneurysmal interatrial septum 47 (0.310%) NA NA     Cardiomyopathies 32 (0.212%)† 9, 0.065% (0.023 – 0.113) 0.595 (0.272 – 1.129)     Idiopathic PAH‡ 1 (0.007%) 1, 0.007% (0.001 – 0.037) 0.070 (0.001 – 0.370)

CHD denotes congenital heart disease, LSVC left superior vena cava, NA not applicable, PA pulmonary artery, PAH pulmonary arterial hypertension, and STE standard transthoracic echocardiography.

* All pathologies included those of known/repaired cases and newly diagnosed cases.

† These cases identified by Vscan included isolated reduced left ventricular ejection fraction (ie, less than 55% by the eyeball assessment), isolated ventricular hypertrophy and/or isolated cardiac chamber dilatation with or without reduced ventricular function suggestive for cardiomyopathies, myocarditis, or other organ damages requiring further evaluations.

‡ Patient had finger clubbing and decreased levels of arterial oxygen saturation.

When examined by Vscan, 32 (2.115 per 1,000 persons; CI, 1.447 to 2.985) students were identified to have isolated reduced left ventricular ejection fractions, isolated ventricular hypertrophy, and/or isolated cardiac chamber dilatation with or without reduced ventricular systolic function, suggestive of cardiomyopathies, myocarditis, or other organ damage requiring further evaluations. Re-evaluations in hospital clinics confirmed nine cases of cardiomyopathy (0.595 per 1,000 persons; 95% CI, 0.272 to 1.129): five cases of hypertrophic cardiomyopathy (0.330, per 1,000 persons; 95% CI, 0.107 to 0.771), three cases of dilated cardiomyopathy (0.198 per 1,000 persons; 95% CI, 0.040 – 0.580), and one case of arrhythmogenic right ventricular cardiomyopathy (0.070 per 1,000 persons; 95% CI, 0.001 to 0.370; Table 2).

Based on the screening protocol for the Vscan, 518 students had mitral and/or aortic valve regurgitation (due to bi-valvular involvements in some cases, the numbers of individuals are less than the number of pathologies in Table 3). After re-evaluations for identifying RHD based on the world heart federation (WHF) criteria, 143 (9.451 per 1,000 persons; 95% CI, 7.971 to 11.124) individuals were diagnosed with RHD. The rates of definite and borderline RHD based on the WHF criteria detected by standard echocardiography were 30 (1.982 per 1,000 persons; 95% CI, 1.338 to 2.829) and 113 (7.468 per 1,000 persons; 95% CI, 6.159 to 8.972), respectively. There was only one known case of definite RHD in a 16-year-old boy on a penicillin regimen.

Table 3

The frequency of valvular involvements among students.

NUMBERS DETECTED BY VSCAN (%) NUMBERS DETECTED BY STE, % (95% CONFIDENCE INTERVAL) CRUDE RATE, PER 1000 PERSONS (95% CONFIDENCE INTERVAL) AV pathologies     AV regurgitation ≤mild severity 164 (1.084%) 25, 0.165% (0.107 – 0.243) 1.652 (1.070 – 2.438)     AV regurgitation >mild severity 14 (0.092%) 14, 0.092% (0.050 – 0.155) 0.925 (0.506 – 1.552)     AV billowing 10 (0.06%) NC …     AV prolapse of any grade 2 (0.013%) 2, 0.013% (0.001 – 0.047) 0.132 (0.016 – 0.477) MV pathologies     MV regurgitation ≤mild severity 863 (5.703%) NC …     MV regurgitation >mild severity 384 (2.538%) 90, 0.595% (0.478 – 0.730) 5.950 (4.786 – 7.307)     MV billowing 530 (3.502%) NC …     MV prolapse ≥mild severity 302 (1.996%) NC … TV pathologies     TV regurgitation ≤mild severity 1624 (10.733%) NC …     TV regurgitation ≥moderate severity 55 (0.363%) 55, 0.363% (0.274 – 0.473) 3.635 (2.740 – 4.730)     TV prolapse any grade 2 (0.013%) 2, 0.013% (0.001 – 0.047) 0.132 (0.016 – 0.477) PV pathologies     PV regurgitation ≤mild severity 1014 (6.701%) NC …     PV regurgitation ≥moderate severity 44 (0.290%) 44, 0.290% (0.211- 0.390) 2.908 (2.114 – 3.902)

AV denotes aortic valve, MV mitral valve, NC not checked, PV pulmonary valve, STE standard transthoracic echocardiography, TV tricuspid valve.

* Other valvular pathologies are categorized as congenital heart disease in prior table.

Non-rheumatic VHD was calculated after excluding individuals with a diagnosis of definite RHD and those with physiologic changes (ie, valvular regurgitation ≤mild severity). Non-rheumatic VHD confirmed in hospital echocardiography clinic comprised tricuspid valve regurgitation with a minimum of moderate severity (3.635 per 1,000 persons, 95% CI, 2.740 to 4.730), any grades of tricuspid valve prolapse (0.132 per 1,000 persons; 95% CI, 0.016 to 0.477), pulmonary valve regurgitation with a minimum of moderate severity (2.908 per 1,000 persons; 95% CI, 2.114 to 3.902), mitral valve regurgitation with greater than mild severity (5.950 per 1,000 persons; 95% CI CI, 4.786 to 7.307), any grades of mitral valve prolapse (19.960 per 1,000 persons; 95% CI, 17.791 to 22.316), any grades of aortic valve regurgitation (2.578 per 1,000 persons; 95% CI, 1.834 to 3.522), and any grades of aortic valve prolapse (0.132 per 1,000 persons; 95% CI, 0.016 to 0.477). Therefore, the prevalence of individuals with non-rheumatic VHD was found to be 30.733 per 1,000 persons (95% CI, 28.041 to 33.608; Table 3).

Given the results of handheld and standard echocardiographic evaluations, the positive predictive values (PPV) for CHDs, cardiomyopathies, and >mild severity of VHDs were 88.4%, 28%, and 41%, respectively. The number of false positive findings for moderate mitral valve regurgitation was extensively higher than other heart valves. There were no false positive findings for aortic, tricuspid, and pulmonary heart valves (PPV 100% for >mild severity of aortic, tricuspid, and pulmonary heart valves). When we considered only severe mitral valve regurgitation, the PPV was found to be 100% for mitral valve too.

Predictors of echocardiographic findings

The prevalence of SHD, CHD, and RHD were comparable between the age distributions from 6 to 18 years old, while non-rheumatic VHD was significantly increased by advancing age (Appendix Figure). After the categorization of the patients based on age [13], the frequency of CHD was significantly higher in the age group of 6 to 11 years than in the age group of 12 to 18 years (1.3% [95% CI, 1 to 1.6] vs 0.8% [95% CI, 0.6 to 1]; P = 0.004). All the study participants with or without CHD were compared regarding their baseline characteristics (Table 4). Those with CHD were younger (P = 0.026), were lighter (P = 0.049), and had a higher rate of parental consanguinity (P < 0.001) compared with their counterparts without it. Additionally, the baseline characteristics were compared across groups by the presence of SHD (Appendix Table 7), non-rheumatic VHD (Appendix Table 8), and RHD (Appendix Tables 9 and 10) with those who had normal echocardiographic screening findings.

Table 4

The comparison of individuals with or without CHD.

WITH CHD N = 152 WITHOUT CHD N = 14978 P VALUE Age, years 11.7 ± 2.9 12.2 ± 3.1 0.026 Gender 0.353     Boys 85 (55.9%) 7809 (52.1%)     Girls 67 (44.1%) 7169 (47.9%) School type 0.367     Public 136 (89.5%) 13031 (87%)     Private 16 (10.5%) 1947 (13%) Parental consanguinity 63 (41.4%) 3887 (26%) <0.001 Father literacy* 0.061     High school diploma or less 122 (80.3%) 10240 (73.5%)     University degrees 30 (19.7%) 3689 (26.5%) Mother literacy* 0.514     High school diploma or less 120 (78.9%) 10747 (76.7%)     University degrees 32 (21.1%) 3265 (23.3%) Number of children in family 0.718     1 child 31 (20.4%) 3366 (22.5%)     2 children 75 (49.3%) 7554 (50.4%)     3 children 31 (20.4%) 2910 (19.4%)     ≥4 children 15 (9.9%) 1148 (7.7%) Height, cm 149.5 ± 16.2 151.3 ± 17.2 0.200 Weight, kg 45.3 ± 16.6 48.4 ± 18.8 0.049 Waist circumference, cm 68.8 ± 10.5 70.2 ± 11.4 0.130 Systolic blood pressure, mm Hg 113 ± 12.1 113.9 ± 12.2 0.351 Diastolic blood pressure, mm Hg 71.8 ± 7.8 72.3 ± 7.6 0.468 Arterial oxygen saturation, % 97 ± 2.6 97.2 ± 1.6 0.089

CHD denotes congenital heart disease.

* These data were not available in 6–7% of individuals.

Data are presented as number (%) or mean ± SD.

After the variables were entered into multivariable models, parental consanguinity was the strongest predictor of CHD and SHD (odds ratio [OR], 1.907, 95% CI, 1.358 to 2.680; P < 0.001 and OR, 1.855, 95% CI, 1.334 to 2.579; P < 0.001, respectively). Apropos the predictors of valvular pathologies, the strongest predictors of non-rheumatic VHD and RHD were the female sex (OR, 1.262, 95% CI, 1.013 to 1.573; P = 0.038) and a lower level of fathers’ literacy (OR, 1.872, 95% CI, 1.068 to 3.281; P = 0.029), respectively. The findings of the multivariable analyses are summarized in Figure 2.

Figure 2 

Multivariable analyses showing predictors of echocardiographic findings among individuals with (A) SHD, (B) CHD, (C) non-rheumatic VHD, and (D) RHD. The horizontal lines indicate the 95% confidence intervals (CIs) for the odds ratios (ORs), and the diamonds in the middle of the horizontal lines indicate the OR of the predictor entered in the multivariable model.