Farah MCK. Disfunção ventricular no pós-operatório da intervenção cirúrgica para correção dos defeitos congênitos da Tetralogia de Fallot. Estudo de correlação clínica e anatomopatológica [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2008. 136p. O estudo investigou de modo prospectivo o remodelamento ventricular histopatológico em crianças submetidas à correção cirúrgica de Tetralogia de Fallot (TF) com o objetivo de detectar possíveis fatores associados aos indicadores ecocardiográficos de disfunção ventricular sistólica e diastólica no período pós-operatório. Pacientes e métodos: foram incluídos 23 pacientes consecutivos portadores de TF (14 masculinos), com idade entre 12 e 186 meses (média=39,6 meses, mediana = 23 meses). A análise do Doppler Tecidual (índice de aceleração isovolumétrica - AVI, velocidade miocárdica sistólica - S\', velocidade miocárdica diastólica precoce - E\') foi realizada em três momentos: antes da cirurgia, nos primeiros três dias de PO e entre 30 a 90 dias após a cirurgia. Durante a cirurgia, além das bandas musculares infundibulares, foram obtidas biópsias subendocárdicas na via de entrada do VD e do VE. Foram avaliados quanto ao grau de hipertrofia miocárdica, colágeno intersticial (picorsirius) e capilaridade (imunohistoquímica-fator VIII). Níveis séricos de troponina T foram mensurados antes e após a cirurgia. Eletrocardiogramas realizados antes e após a cirurgia, características clínicas e uso prévio de propranolol foram avaliados. Este estudo foi aprovado pela comissão de ética da CPPESQUSP. Resultados: Os cardiomiócitos do VD mostraram acentuada hipertrofia. O colágeno intersticial esteve aumentado em ambos os ventrículos. A área ocupada por capilares não diferiu entre as diversas regiões estudadas. Houve diminuição significativa do AVI do VD no terceiro ecocardiograma (p=0,006) o que se correlacionou de modo negativo e significativo com o diâmetro dos cardiomiócitos da via de entrada do VD (r=-0,59; p=0,006). As velocidades de E\' do VD, diminuíram significativamente nos dois períodos pós-operatórios (p<0,001) e tiveram correlação negativa significativa com a porcentagem de colágeno intersticial (r= -0,525; p=0,004). Os níveis séricos de Troponina T aumentaram significativamente em todos os pacientes no período pós-operatório- 27,7 ±18,6 ng/ml e 15,9+11,3 ng/ml respectivamente no segundo e terceiro PO e se correlacionaram de modo positivo e significativo com o tempo de circulação extra corpórea e com o tempo de anoxia (p=0,019 e 0,018, respectivamente) e maior tempo de uso de droga vasoativa no pós-operatório (r=0,552, p=0,006). A duração do QRS aumentou significativamente no PO. Os pacientes que apresentaram aumento do QRS maior que 40ms, também apresentaram maior porcentagem de colágeno intersticial na via de entrada do VD. Conclusão: o remodelamento miocárdico presente no período pré-operatório, a julgar pela avaliação histopatológica morfométrica da hipertrofia celular e colágeno intersticial, influenciou respectivamente a função sistólica e diastólica do ventrículo direito no período pós-operatório da correção cirurgia da Tetralogia de Fallot. / It was investigate prospectively the histopathological myocardial remodeling in children submitted to surgical repair of Fallot\'s tetralogy, in order to detect possible factors associated to postoperative (PO) echocardiographic findings of systolic or diastolic ventricular dysfunction. Patients and Methods: 23 consecutive Fallot patients (14 males), aged 12 to 186 months (mean=39.6, median=23 months) were enrolled in the study. Tissue Doppler echocardiographic analysis (isovolumic acceleration-IVA, systolic myocardial velocity-S\' and early diastolic myocardial velocity-E\') was performed in three moments for both ventricles: before surgery, within the first three postoperative days and later, between the 30th and 90th PO days. During surgery, besides the anomalous infundibular bands resected, subendocardial biopsy samples from the right ventricular (RV) inflow tract and of the left ventricle (LV), through the ventricular septal defect, were obtained for histopathological morphometric evaluation: degree of cell hypertrophy, interstitial collagen (Sirius-red) and capillarity (immunohistochemistry against Factor-VIII). Troponin-T levels were measured before and after surgery. The electrocardiogram performed before and after surgery, some clinical features and previous use propranolol were considered. This study was approved by the Ethical Committee of our Institution. Results: the right ventricular cardyomyocytes showed a significant hypertrophy. The interstitial collagen was increase in both right and left ventricle. The capillary area fraction did not differ among the biopsy samples analyzed. IVA of the RV decreased significantly at the third echocardiographic evaluation (p=0.006) and correlated negatively with the diameter of the RV cardyomyocytes (r= -0.59; p=0.006). E\' measured at the RV decreased significantly in both PO periods (p<0.001) and showed a significant negative correlation with the percentage of interstitial myocardial collagen (r=-0.525; p=0,044). Troponin-T levels increased postoperatively in all patients (27.7 ±18,6ng/ml and 15.9+11.3ng/ml - second and third PO days) and correlated positively with the cardiopulmonary bypass and cross clamping times (p=0.019 and 0.018 respectively). The QRS interval increased significantly in the PO period. The patients in whom the PO electrocardiogram showed an increase of the QRS greater than 40ms, showed a greater interstitial collagen area fraction in the right ventricle inflow tract. Conclusions: Myocardial remodeling present preoperatively, as judged by the morphometric histopathological evaluation of cell hypertrophy and interstitial collagen, influenced respectively the medium term PO systolic and diastolic right ventricular function of repaired Fallot patients.

Introdução: Previamente, demonstramos que o remodelamento histológico do miocárdio à época da correção da tetralogia de Fallot (TF) influenciou na função do ventrículo direito (VD) no pós-operatório (PO) precoce. O impacto da fibrose miocárdica na função ventricular no PO tardio ainda é desconhecido. O objetivo deste estudo foi avaliar ecocardiograficamente na mesma coorte de pacientes a função do VD no PO tardio, comparando com dados anteriormente obtidos por ecocardiografia convencional e morfometria miocárdica. Métodos: Estudamos 20 pacientes no PO da TF (tempo de seguimento = 96,6 ± 13,3 meses), 15 homens (75%), idade média no PO tardio (PO2) 128,3 ± 25,7 meses. As velocidades miocárdicas do VD diastólica precoce (e´), tardia (a\') e sistólica (S\') foram avaliadas pelo Doppler tecidual no pré-operatório, três dias após a cirurgia, entre 30º-90º dia e no PO2. Parâmetros convencionais, como a excursão sistólica do anel da valva tricúspide (TAPSE), variação fracional da área (FAC), volume do átrio direito indexado, pico da velocidade de enchimento diastólico precoce (E) do fluxo transvalvar tricúspide e da deformação miocárdica global e regional, strain longitudinal sistólico (GLS), strain rate sistólico (GLSRs) e o strain no pico do tempo de relaxamento isovolumétrico (GLSTRIV), foram analisados apenas no PO2. Também, nesta fase, realizamos a análise tridimensional da fração de ejeção, e dos volumes diastólico e sistólico finais do VD. Resultados: A velocidade a\' diminuiu nas avaliações iniciais e persistiu anormal no PO2 (RM ANOVA p < 0,001). Houve correlação negativa significante entre a velocidade e\' no PO2 e a fração de área de fibrose miocárdica (FIBR) (p = 0,02; r = -0,54), e correlação positiva entre FIBR e a relação E/e\' (p= 0,0002; r= 0,787). No PO2, o TAPSE (1,50 ± 0,19cm) foi reduzido e FAC normal (47,51± 7,56%). O valor do GLS global foi 18,48 ± 2,97%, com Z score < -2 em 16 pacientes e diferiu regionalmente no segmento médio do septo (Z score < -2 em 5 pacientes) e no segmento médio da parede lateral (Z score < -2 em 1 paciente). Houve correlação negativa entre FIBR e GLS no segmento médio septal (p = 0,0376; r = -0,493), entretanto sem influência no GLS global. No PO2, a insuficiência pulmonar residual foi moderada ou acentuada em 15 pac (75%), sem diferença quanto à FIBR miocárdica em relação ao grau leve (p = 0,58). Estavam aumentados os volumes indexados: diastólico final médio (89,5 ± 34,3ml/m²; Z score > 2DP em 12 pacientes) e sistólico (40,6 ± 9,1ml/m²; Z score > 2DP em 14 pacientes). A fração de ejeção média foi normal 51,8 ± 6,9% e não houve correlação com a FIBR. Conclusões: A avaliação ecocardiográfica tardia identificou alterações evolutivas e adaptativas das funções sistólica e diastólica do VD, com função sistólica preservada e função diastólica anormal e associada ao grau de FIBR avaliado em amostras operatórias; o estudo da deformação miocárdica revelou alterações globais e regionais, possivelmente relacionadas à arquitetura do miocárdio nessa malformação e às adaptações decorrentes da interposição de retalhos e suturas cirúrgicas; a avaliação pelo modo tridimensional correlacionou-se positivamente com as medidas obtidas no modo bidimensional; a insuficiência pulmonar foi lesão residual altamente prevalente / Introduction: We have previously demonstrated that the myocardial remodeling at the time of corrective surgery in tetralogy of Fallot (TF) patients influenced the right ventricular (RV) function in the early post-operative period (PO). The impact of myocardial fibrosis in late follow up (LFU) has not been investigated so far. Our objective was to analyze in the same cohort of patients in LFU, the RV function, comparing the obtained results with echocardiographic data from the early PO and with myocardial morphometry. Methods: 20 patients in the late FLU of TF correction were studied (time of follow up = 96.6 ± 13.3 months), 15 men (75%), mean age at LFU 128.3 ± 25.7months. The early (e\') and late (a\') diastolic and the systolic (S\') myocardial velocities were evaluated through tissue Doppler in the pre-operative period, three days after surgery, between the 30o-90o days and in LFU. We analyzed conventional echocardiographic parameters like the tricuspid annular plane systolic excursion (TAPSE), the fractional area change (FAC), the indexed right atrial volume, the peak early diastolic filling velocity (E) and of myocardial deformation: global longitudinal strain (GLS), global longitudinal systolic strain rate (GLSRs) and global longitudinal strain at the peak of the isovolumetric relaxation time (GLSTRIV) in the LFU. Also in LFU we analyzed by tridimensional echocardiography the ejection fraction and the final RV diastolic and systolic volumes. Results: The a\' velocity decreased in the initial evaluations and persisted abnormal in LFU (RM ANOVA, p < 0.001). There was a significant and negative correlation between e\' in LFU and the area fraction of myocardial fibrosis (FIBR) (p = 0.02; r = -0.54) and a positive correlation between FIBR and E/e\' ratio (p = 0.0002; r = 0.787). In the LFU TAPSE decreased (1.50 ± 0,19cm) and FAC was normal (47.51 ± 7.56%). The GLS value was 18.48 ± 2.97%, with Z score <- 2 SD in 16 patients, and was significantly different in the mid ventricular septum (Z score <- 2 in 5 patients) and in the mid segment of the lateral wall (Z score < -2 in 1 patient). There was a negative correlation between FIBR and GLS in the mid ventricular segment of the septum (p = 0.0376; r = -0.493), however without influence in GLS. In LFU pulmonary regurgitation was considered moderate or severe in 15 patients (75%), with no difference relative to the group with mild regurgitation regarding FIBR (p = 0.58). The final indexed RV volumes were increased: diastolic (89.5 ± 34.3ml/m2; Z score > 2SD in 12 patients) and systolic (40.6 ± 9.1ml/m2; Z score > 2SD in 14 patients). The mean RV ejection fraction was normal (51.8 ± 6.9%), and did not correlate with FIBR. Conclusions: The LFU echocardiographic evaluation identified evolutive and adaptative alterations in RV function, with preserved systolic and abnormal diastolic function, associated with the degree of FIBR assessed in myocardial samples; the study of myocardial deformation indexes revealed regional and global alterations, possibly related to the abnormal myocardial architecture specific for the cardiac malformation and/or to post-surgical adaptation to patches and sutures; the tridimensional echocardiography data correlated positively with those obtained through bidimensional echo; pulmonary regurgitation was a highly prevalent residual lesion

Farah MCK. Disfunção ventricular no pós-operatório da intervenção cirúrgica para correção dos defeitos congênitos da Tetralogia de Fallot. Estudo de correlação clínica e anatomopatológica [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2008. 136p. O estudo investigou de modo prospectivo o remodelamento ventricular histopatológico em crianças submetidas à correção cirúrgica de Tetralogia de Fallot (TF) com o objetivo de detectar possíveis fatores associados aos indicadores ecocardiográficos de disfunção ventricular sistólica e diastólica no período pós-operatório. Pacientes e métodos: foram incluídos 23 pacientes consecutivos portadores de TF (14 masculinos), com idade entre 12 e 186 meses (média=39,6 meses, mediana = 23 meses). A análise do Doppler Tecidual (índice de aceleração isovolumétrica - AVI, velocidade miocárdica sistólica - S\', velocidade miocárdica diastólica precoce - E\') foi realizada em três momentos: antes da cirurgia, nos primeiros três dias de PO e entre 30 a 90 dias após a cirurgia. Durante a cirurgia, além das bandas musculares infundibulares, foram obtidas biópsias subendocárdicas na via de entrada do VD e do VE. Foram avaliados quanto ao grau de hipertrofia miocárdica, colágeno intersticial (picorsirius) e capilaridade (imunohistoquímica-fator VIII). Níveis séricos de troponina T foram mensurados antes e após a cirurgia. Eletrocardiogramas realizados antes e após a cirurgia, características clínicas e uso prévio de propranolol foram avaliados. Este estudo foi aprovado pela comissão de ética da CPPESQUSP. Resultados: Os cardiomiócitos do VD mostraram acentuada hipertrofia. O colágeno intersticial esteve aumentado em ambos os ventrículos. A área ocupada por capilares não diferiu entre as diversas regiões estudadas. Houve diminuição significativa do AVI do VD no terceiro ecocardiograma (p=0,006) o que se correlacionou de modo negativo e significativo com o diâmetro dos cardiomiócitos da via de entrada do VD (r=-0,59; p=0,006). As velocidades de E\' do VD, diminuíram significativamente nos dois períodos pós-operatórios (p<0,001) e tiveram correlação negativa significativa com a porcentagem de colágeno intersticial (r= -0,525; p=0,004). Os níveis séricos de Troponina T aumentaram significativamente em todos os pacientes no período pós-operatório- 27,7 ±18,6 ng/ml e 15,9+11,3 ng/ml respectivamente no segundo e terceiro PO e se correlacionaram de modo positivo e significativo com o tempo de circulação extra corpórea e com o tempo de anoxia (p=0,019 e 0,018, respectivamente) e maior tempo de uso de droga vasoativa no pós-operatório (r=0,552, p=0,006). A duração do QRS aumentou significativamente no PO. Os pacientes que apresentaram aumento do QRS maior que 40ms, também apresentaram maior porcentagem de colágeno intersticial na via de entrada do VD. Conclusão: o remodelamento miocárdico presente no período pré-operatório, a julgar pela avaliação histopatológica morfométrica da hipertrofia celular e colágeno intersticial, influenciou respectivamente a função sistólica e diastólica do ventrículo direito no período pós-operatório da correção cirurgia da Tetralogia de Fallot. / It was investigate prospectively the histopathological myocardial remodeling in children submitted to surgical repair of Fallot\'s tetralogy, in order to detect possible factors associated to postoperative (PO) echocardiographic findings of systolic or diastolic ventricular dysfunction. Patients and Methods: 23 consecutive Fallot patients (14 males), aged 12 to 186 months (mean=39.6, median=23 months) were enrolled in the study. Tissue Doppler echocardiographic analysis (isovolumic acceleration-IVA, systolic myocardial velocity-S\' and early diastolic myocardial velocity-E\') was performed in three moments for both ventricles: before surgery, within the first three postoperative days and later, between the 30th and 90th PO days. During surgery, besides the anomalous infundibular bands resected, subendocardial biopsy samples from the right ventricular (RV) inflow tract and of the left ventricle (LV), through the ventricular septal defect, were obtained for histopathological morphometric evaluation: degree of cell hypertrophy, interstitial collagen (Sirius-red) and capillarity (immunohistochemistry against Factor-VIII). Troponin-T levels were measured before and after surgery. The electrocardiogram performed before and after surgery, some clinical features and previous use propranolol were considered. This study was approved by the Ethical Committee of our Institution. Results: the right ventricular cardyomyocytes showed a significant hypertrophy. The interstitial collagen was increase in both right and left ventricle. The capillary area fraction did not differ among the biopsy samples analyzed. IVA of the RV decreased significantly at the third echocardiographic evaluation (p=0.006) and correlated negatively with the diameter of the RV cardyomyocytes (r= -0.59; p=0.006). E\' measured at the RV decreased significantly in both PO periods (p<0.001) and showed a significant negative correlation with the percentage of interstitial myocardial collagen (r=-0.525; p=0,044). Troponin-T levels increased postoperatively in all patients (27.7 ±18,6ng/ml and 15.9+11.3ng/ml - second and third PO days) and correlated positively with the cardiopulmonary bypass and cross clamping times (p=0.019 and 0.018 respectively). The QRS interval increased significantly in the PO period. The patients in whom the PO electrocardiogram showed an increase of the QRS greater than 40ms, showed a greater interstitial collagen area fraction in the right ventricle inflow tract. Conclusions: Myocardial remodeling present preoperatively, as judged by the morphometric histopathological evaluation of cell hypertrophy and interstitial collagen, influenced respectively the medium term PO systolic and diastolic right ventricular function of repaired Fallot patients.

Introduction. Computational modelling has been used widely in biological and clinical applications, but relatively less in surgical design and optimization. Magnetic resonance image (MRI)-based right ventricle (RV) models were introduced for patients with repaired Tetralogy of Fallot (rTOF) to assess ventricle cardiac function, and to identify morphological and mechanical parameters which can be used to predict and optimize post-surgery cardiac outcome. Tetralogy of Fallot is a common congenital heart defect which includes a ventricular septal defect and severe right ventricular outflow obstruction, account for the majority of cases with late onset RV failure. The current surgical approach for the patients with repaired ToF including pulmonary valve replacement/insertion (PVR) has yielded mixed results. It is of great interest to identify parameters which may be used to predict surgical cardiac function outcome after PVR. Data, Model, and Methods. Cardiac Magnetic Resonance (CMR) data from 20 healthy volunteers (11 males, mean year : 22.8) and 56 TOF patients (37 males, mean year : 25.3) were provided by Children's Hospital - Boston, Harvard Medical School from our NIH-funded project (R01 HL089269). RV wall thickness (WT), circumferential and longitudinal curvature (C-cur and L-cur), surface area (SA) and surface to volume ratio (SVR) were obtained based on CMR data for morphological analysis. 6 healthy volunteers and 16 TOF patients were chosen to construct 3D computational models for mechanical analysis. The 3D CMR-based RV/LV/Patch combination models included a) isotropic and anisotropic material properties, b) myocardial fiber orientation, c) active contraction with two zero-load geometries, and d) fluid-structure interactions. The models were used to obtain the assessment for RV mechanical conditions, which might be helpful for PVR surgical outcome prediction. All the computational models were built and solved in a commercial finite element software ADINA. Statistical methods including Linear Mixed- effort Method and Logistical regression were used in the morphological and mechanical analysis to find out potential indicators for predicting PVR outcome from the morphological and mechanical parameters. Results. In morphological analysis, statistically significant differences were found in RV SA and SVR between better-outcome patient group (BPG) and worse-outcome patient group (WPG). At begin of ejection, mean RV SA of BPG was 13.6% lower than that from WPG (241.1 cm2 v.s. 279.0 cm2, p =0.0161). Mean RV SVR of BPG was 13.1% lower than that from WPG (1.26 cm2/ml v.s. 1.45 cm2/ml, p =0.0271). Similar results were also found in RV SA and SVR at begin of filling. Furthermore, RV EF change from pre- to post-PVR were found negatively correlated with RV SA and SVR. In mechanical analysis, 22 structure-only models with one zero-load geometry (1G) were constructed to obtain stress/strain distributions. Stress-P1 from BPG was found to be closer to that from HG, compared to Stress- P1 of WPG. At the beginning of ejection, mean Stress-P1 of BPG was only 6.8% higher than that from healthy group (p =0.6889), while average Stress-P1 of WPG was 84.1% higher than that of healthy group (p =0.0418). Similar results were also found at begin of filling. The results suggested that comparing patients' RV stress values with healthy RV stress values may help identify patients with possible better outcome. The models with two zero-load geometries (2G models) and FSI models were also constructed. Their numerical results indicated that 2G models can provide end-ejection and end-filling results which were not available in 1G models, and FSI models can provide flow velocity, pressure and shear stress information which lacked in structure-only models (1G and 2G models). Conclusion. In vivo image-based 3D patient- specific computational models could lead to considerable potential gain not only in surgical design and outcome prediction, but also in understanding the mechanisms of RV failure for patients with repaired TOF.

Background: Children with complex congenital heart disease (CHD) are exposed to cyanosis from birth until their surgical repair and are often not expected to participate in physical activities to the same extent as healthy peers because of a limited maximal exercise capacity (V̇O2max). Despite limitations in V̇O2max, these children may still have the capacity to perform most daily physical activity because it requires only a submaximal effort. The purpose of this research was to examine the relationships between submaximal exercise capacity, daily physical activity and cyanosis exposure, in children with complex CHD. Methods: Children with a single functioning ventricle (Fontan), tetralogy of Fallot or transposition of the great arteries, 10 to 17 years old were deemed eligible. The Bruce treadmill protocol with breath-by-breath analysis of oxygen consumption was used to assess submaximal exercise capacity. Five measures of submaximal exercise capacity were evaluated: energy consumption (V̇O2) at the ventilatory threshold, V̇O2 at a heart rate of 130 beats per minute (bpm), metabolic equivalents (METs) at ventilatory threshold, METs at 130 bpm and heart rate at stage 1 of the Bruce protocol. Moderate-to vigorous physical activity (MVPA) was measured (Actical accelerometer with 15 second epochs) for 7 consecutive days. Exposure to cyanosis was calculated by subtracting the child’s date of birth from the date of surgical repair. Results: Participants were children with a Fontan single ventricle (n=5), tetralogy of Fallot (n=4) or transposition of the great arteries (n=7). Daily physical activity was positively associated with V̇O2 at ventilatory threshold (r = 0.78, n = 16, p = < 0.01) and V̇O2 at a heart rate of 130 bpm (r = 0.61, n = 16, p = 0.01). Children who did more than 60 minutes of physical activity per day (n=4) achieved significantly higher energy expenditure before reaching ventilatory threshold, (95% CI of the difference [8.23, 24.85], t(14) = 4.27, p = < 0.01) and at a heart rate of 130 bpm (95% CI of the difference [1.61, 14.33], t(14) = 2.69, p = 0.02). Lastly, V̇O2 at ventilatory threshold was negatively associated with days spent in cyanosis (r = .55, n = 16, p = 0.03), Conclusion: Higher V̇O2 at ventilatory threshold and V̇O2 at a heart rate of 130 bpm was associated with more daily minutes spent in moderate-to-vigorous physical activity. These results suggest that children who meet the recommended 60 minutes of MVPA would have a higher submaximal exercise capacity (V̇O2 at ventilatory threshold or a heart rate of 130 bpm), than children who did not meet the MVPA guidelines. Lastly, children who were exposed to cyanosis for a longer period of time had a lower submaximal V̇O2 at ventilatory threshold, than children who were exposed to cyanosis for a shorter period of time.

Magnetic resonance imaging nowadays supplies a noninvasive method in clinical applications. For tetralogy of Fallot (TOF) patients, after undergoing clinical operation, their cardiac anatomy still cannot supply sufficient blood flow in the pulmonary arteries with respect to the normal. In this study, we use phase contrast MR imaging to evaluate of regurgitation and turbulence of flow in pulmonary arteries after repair of TOF. We use parameters such as coefficient of variance (CV), regurgitant fraction (RF), and normalized area variation (NAV) to analyze the difference between repaired patients and normal controls. Our result also shows that CV and regurgitant fraction have loose relation. This study may provide more information to help doctors in clinical diagnosis. In the meanwhile, another three parameters were used to evaluate patients and normal persons. We use windkessel volume to see the difference of flow volume between inlet and outlet in the pulmonary arteries. We use pulse wave velocity (PWV) to discuss the propagating velocity of pressure wave on the vascular wall. We use pulmonary vascular resistance (PVR) to analyze the resistance of blood wall. PWV and PVR may lose information by means of insufficient points in a cardiac cycle, but the result may still be a kind of reference.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). The understanding of the genetics and inheritance of TOF is limited. Although about 15% of cases are associated with a 22q11.2 deletion, the majority have no known aetiology. Even in 22q11.2 Deletion Syndrome (22q11DS), factors that increase the likelihood of CHD expression are poorly understood. We aimed to determine the prevalence and phenotypes of CHD in relatives of adults with TOF. We also investigated the prevalence of CHD in relatives without a 22q11.2 deletion of individuals with 22q11DS. Offspring of patients with TOF had the greatest prevalence of CHD. Diverse cardiac phenotypes, including left heart obstructive lesions, were found in families. We also found that unaffected relatives of individuals with 22q11DS had a greater prevalence of complex CHD over population expectations, suggesting that modifier genetic factors may be involved in expression of CHD in 22q11DS.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease (CHD). The understanding of the genetics and inheritance of TOF is limited. Although about 15% of cases are associated with a 22q11.2 deletion, the majority have no known aetiology. Even in 22q11.2 Deletion Syndrome (22q11DS), factors that increase the likelihood of CHD expression are poorly understood. We aimed to determine the prevalence and phenotypes of CHD in relatives of adults with TOF. We also investigated the prevalence of CHD in relatives without a 22q11.2 deletion of individuals with 22q11DS. Offspring of patients with TOF had the greatest prevalence of CHD. Diverse cardiac phenotypes, including left heart obstructive lesions, were found in families. We also found that unaffected relatives of individuals with 22q11DS had a greater prevalence of complex CHD over population expectations, suggesting that modifier genetic factors may be involved in expression of CHD in 22q11DS.

Magnetic Resonance Imaging (MRI) provides noninvasive method in clinical application. For the patients of Tetralogy of Fallot underwent surgical correction,regurgitation and turbulence in blood flow may still present in pulmonary arteries.In this study,Phase Contrast MR Imaging will be used to quantitate,and to observe blood flow in after repair Tetralogy of Fallot (TOF) patients.We use 3 parameters,which are Coefficient of Variance (CV),Regurgitant Fraction (RF) and Net Flow analysis to analyze two situations of blood flow in patients¡¦ left pulmonary artery ¡Bright pulmonary artery and main pulmonary artery.We also compare normal subjects to patients in this experiment. The pulmonary circulation is the action of blood flow from right ventricular to main pulmonary artery then to left pulmonary artery and right pulmonary artery. We use three additional parameters: rPA / lPA flow ratio¡BPeak Velocities and Total Flow to observe the pulmonary blood flow. We use rPA / lPA flow ratio to identify the tendency of blood flow, with Peak Velocities to find out Peak Velocity in normal difference between patient.Meanwhile, the measurement of Total Flow is applied to observe the flow from main pulmonary artery to left and right pulmonary artery. We hope to use these parameters that can help doctors on clinical diagnosis.

Recently magnetic resonance imaging has become more and more popular in clinical applications. In clinical studies, the heart of the TOF patient has some congenital defects. These defects lead to insufficient blood flowing into the pulmonary arteries, rendering the necessary of repair for TOF patients. However, even after repair, the blood in pulmonary arteries still cannot flow in the same way with those of normal people. For this reason, studies on the flow behavior of pulmonary arteries in TOF patients would be valuable in clinical applications. In this study, we focus on the quantitative analysis of in-plane flow in branch pulmonary arteries (left and right pulmonary arteries) after repair of tetralogy of Fallot (TOF) by means of phase-contrast MR imaging. The regurgitation and turbulence were evaluated by coefficient of variance (CV) and regurgitant fraction. Vector map of in-plane flow was also included in order to facilitate the observation of flow patterns. Our result shows a positive correlation of CV and regurgitant fraction in terms of turbulence and regurgitation. Therefore, we conclude that CV and regurgitant fraction as well as vector maps may be helpful to quantitate in-plane flow for after repair of TOF patients, providing a more accurate analysis in clinical diagnosis.