Characterization of an Emergent Chicken H3N8 Influenza Virus in Southern China: a Potential Threat to Public Health.

Although influenza A viruses of several subtypes have occasionally infected humans, to date only those of the H1, H2, and H3 subtypes have led to pandemics and become established in humans. The detection of two human infections by avian H3N8 viruses in April and May of 2022 raised pandemic concerns. Recent studies have shown the H3N8 viruses were introduced into humans from poultry, although their genesis, prevalence, and transmissibility in mammals have not been fully elucidated. Findings generated from our systematic influenza surveillance showed that this H3N8 influenza virus was first detected in chickens in July 2021 and then disseminated and became established in chickens over wider regions of China. Phylogenetic analyses revealed that the H3 HA and N8 NA were derived from avian viruses prevalent in domestic ducks in the Guangxi-Guangdong region, while all internal genes were from enzootic poultry H9N2 viruses. The novel H3N8 viruses form independent lineages in the glycoprotein gene trees, but their internal genes are mixed with those of H9N2 viruses, indicating continuous gene exchange among these viruses. Experimental infection of ferrets with three chicken H3N8 viruses showed transmission through direct contact and inefficient transmission by airborne exposure. Examination of contemporary human sera detected only very limited antibody cross-reaction to these viruses. The continuing evolution of these viruses in poultry could pose an ongoing pandemic threat. IMPORTANCE A novel H3N8 virus with demonstrated zoonotic potential has emerged and disseminated in chickens in China. It was generated by reassortment between avian H3 and N8 virus(es) and long-term enzootic H9N2 viruses present in southern China. This H3N8 virus has maintained independent H3 and N8 gene lineages but continues to exchange internal genes with other H9N2 viruses to form novel variants. Our experimental studies showed that these H3N8 viruses were transmissible in ferrets, and serological data suggest that the human population lacks effective immunological protection against it. With its wide geographical distribution and continuing evolution in chickens, other spillovers to humans can be expected and might lead to more efficient transmission in humans.

Systolic and diastolic functional reserve of the subpulmonary and systemic right ventricles as assessed by pharmacologic and exercise stress: A systematic review.

We performed a systematic review of the literature on the assessment of subpulmonary and systemic right ventricular (RV) functional reserve during pharmacological and exercise stress in congenital heart patients and patients with pulmonary arterial hypertension (PAH). Literature search was conducted using PubMed, EMBASE, and MEDLINE from their inception up to August 2020. Of 913 records identified, 56 studies with a total of 1730 patients were included. Of the 56 studies, 23 assessed subpulmonary RV functional reserve in repaired tetralogy of Fallot patients, 19 assessed systemic RV reserve in patients with transposition of the great arteries (TGA) after atrial switch and those with congenitally corrected TGA, and 14 assessed subpulmonary RV research in patients with PAH. Pharmacological and exercise stress was used, respectively, in 22 and 34 studies. The main findings were (1) impairment of RV systolic and diastolic functional reserve, (2) associations between impaired functional reserve and worse baseline functional parameters, and (3) prognostic implications of RV systolic functional reserve on clinical outcomes in patients with volume and/or pressure-loaded subpulmonary and systemic right ventricles. Further studies are required to establish the incremental value of incorporating stress studies of RV systolic and diastolic function in the clinical management algorithm of congenital heart patients and patients with PAH.

Right Ventricular-Pulmonary Arterial Coupling in Repaired Tetralogy of Fallot.

We assessed right ventricular (RV)-pulmonary arterial (PA) coupling in patients with repaired tetralogy of Fallot (TOF). Sixty patients (34 males) aged 18.6 ± 8.3 years at 14.8 ± 7.4 years after repair and 60 controls were studied. Two-dimensional, tissue Doppler and speckle tracking echocardiography and colour flow mapping were performed to assess RV end-systolic (ESA) and -diastolic areas, tricuspid valve Doppler and myocardial velocities, left ventricular (LV) and RV deformation and pulmonary (PR), tricuspid regurgitation (TR), respectively. The ratios of RV area change to ESA and peak tricuspid annular systolic (s) velocity to RV ESA indexed to body surface area reflected RV-PA coupling. Patients had greater RV areas and reduced tricuspid annular and myocardial velocities, LV and RV myocardial mechanics compared to controls (all p < 0.05). Both RV area change/ESA ratio and peak tricuspid annular s velocity/indexed RV ESA ratio were reduced in patients (all p < 0.001). Sixty-one and 100% of patients had, respectively, RV area change/ESA ratio and peak tricuspid annular s velocity/indexed RV ESA ratio < -2SD of controls. Indices of RV-PA coupling correlated positively with tricuspid myocardial velocities, LV and RV deformation and inversely with PR and TR (all p < 0.05). Multivariate analysis showed RV systolic strain rate, PR and TR as independent predictors of both RV-PA coupling indices, whilst age, gender and LV systolic strain were also predictors of peak tricuspid annular s velocity/indexed RV ESA ratio (all p < 0.05). In conclusion, RV-PA coupling is impaired and is associated with RV and LV mechanics and severity of PR and TR in patients with repaired TOF.

Managing uncertainty in decision-making of common congenital cardiac defects.

Decision-making in congenital cardiac care, although sometimes appearing simple, may prove challenging due to lack of data, uncertainty about outcomes, underlying heuristics, and potential biases in how we reach decisions. We report on the decision-making complexities and uncertainty in management of five commonly encountered congenital cardiac problems: indications for and timing of treatment of subaortic stenosis, closure or observation of small ventricular septal defects, management of new-onset aortic regurgitation in ventricular septal defect, management of anomalous aortic origin of a coronary artery in an asymptomatic patient, and indications for operating on a single anomalously draining pulmonary vein. The strategy underpinning each lesion and the indications for and against intervention are outlined. Areas of uncertainty are clearly delineated. Even in the presence of "simple" congenital cardiac lesions, uncertainty exists in decision-making. Awareness and acceptance of uncertainty is first required to facilitate efforts at mitigation. Strategies to circumvent uncertainty in these scenarios include greater availability of evidence-based medicine, larger datasets, standardised clinical assessment and management protocols, and potentially the incorporation of artificial intelligence into the decision-making process.

Automated synthesis of (R)-[18 F]MH.MZ on the iPhase Flexlab reaction platform.

(R)-[18 F]MH.MZ ([18 F]MH.MZ) is a promising positron emission tomography (PET) radiotracer for in vivo study of the 5-HT2A receptor. To facilitate clinical trials, a fully automated radiosynthesis procedure for [18 F]MH.MZ was developed using commercially available materials on the iPhase Flexlab module. The overall synthesis time was 100 min with a radiochemical yield of 7 ± 0.9% (n = 3). The radiochemical purity was greater than 99% for [18 F]MH.MZ with a molar activity of 361 ± 57 GBq/µmol (n = 3). The protocol described herein reliably provides [18 F]MH.MZ that meets all relevant release criteria for a GMP radiopharmaceutical.

Circulating high-sensitivity troponin T and microRNAs as markers of myocardial damage during childhood leukaemia treatment.

BACKGROUND: We investigated whether plasma high-sensitivity cardiac troponin T (hs-cTnT) and circulating heart-associated microRNA (miRs) are increased in children with leukaemias during anthracycline-based chemotherapeutic treatment. METHODS: In vitro human pluripotent stem cell (hPSC)-derived cardiomyocyte model showed that miR-1, miR-133a, miR-208a, miR-208b, and miR-499 are released from cells into culture medium in a time- and dose-dependent manner on doxorubicin exposure. Left ventricular (LV) myocardial deformation and circulating heart-associated miRs and plasma hs-cTnT during and after completion of chemotherapy were determined in 40 children with newly diagnosed acute leukaemia. RESULTS: Significant reduction of LV global longitudinal strain and strain rates were found within 1 week after completion of anthracycline therapy in the induction phase of treatment (all p < 0.05). Hs-cTnT level peaked and miR-1 increased significantly at this time point. Log-transformed hs-cTnT correlated negatively with LV global systolic longitudinal strain (r = -0.38, p < 0.001). Receiver operating characteristic analysis revealed that area under the curve for changes in plasma hs-cTnT from baseline and plasma miR-1 levels in detecting a reduction in ≥20% of global longitudinal strain were respectively 0.62 (95% CI 0.38-0.87) and 0.62 (95% CI 0.40-0.84). CONCLUSION: Plasma hs-cTnT and circulating miR-1 may be useful markers of myocardial damage during chemotherapy in children with leukaemias. IMPACT: Heart-associated miRNAs including miR-1, miR-133a, miR-208a, miR-208b,and miR-499 were increased in the culture medium upon exposure of hPSC-derived cardiomyocytes to doxorubicin. Only miR-1 increased significantly during anthracycline-based therapy in paediatric leukaemic patients. In paediatric leukaemic patients, plasma hs-cTnT and circulating level of miR-1 showed the most significant increase within 1 week after completion of anthracycline therapy in the induction treatment phase. The study provides the first evidence of progressive increase in circulating miR-1 and plasma hs-cTnT levels during the course of anthracycline-based therapy in children with leukaemias, with hs-cTnT level also associated with changes in LV myocardial deformation.

Three Decades of Follow-up After Surgical Closure of Subarterial Ventricular Septal Defect.

We determined the occurrence of aortic regurgitation (AR), AR progression and risk factors in patients followed up for up to three decades after closure of subarterial VSD. We reviewed the outcomes of 86 patients categorized into three groups: group I comprised 37 patients without AR and had VSD closure alone, group II comprised 40 patients with AR and had VSD closure without aortic valvoplasty, and group III comprised 9 patients with AR and required both VSD closure and aortic valvoplasty. Patients were followed up for 18.9 ± 7.3 years (median 19.5 years, range 3.5-36.6). At latest follow up, 54.7% (47/86) of patients had AR. The prevalence of progression of AR from any one grade to the next one higher was 37.2% (32/86). Freedom from AR progression was 75.6%, 52.1%, and 22.2% at 20 years of follow-up for groups I, II and III, respectively (p < 0.05). On the other hand, progression to moderate to severe AR occurred only in 4.7% (4/86). Group I and II patients were free from progression to significant AR, while only 33.3% of group III patients were free from progression on follow-up (p < 0.001). Multivariate Cox regression analysis showed that severity of preoperative AR was the significant risk factor for persistence and progression of postoperative AR after VSD closure. In conclusion, aortic regurgitation is common and may progress even after surgical repair of subarterial VSD. Severity of preoperative AR is the most significant predictor of persistence and progression of AR after surgical closure of subarterial VSD.

Left ventricular stiffness in paediatric patients with end-stage kidney disease.

BACKGROUND: We tested the hypothesis that myocardial stiffness is altered in paediatric patients with end-stage kidney disease (ESKD) and explored its association with clinical parameters of chronic kidney disease (CKD). METHODS: Thirty-five patients with ESKD (16 males) aged 17.5 ± 3 years old, 18/35 of whom were receiving dialysis and 17 post kidney transplant, were studied. Left ventricular (LV) myocardial stiffness was determined by measurement of diastolic wall strain (DWS) and stiffness index (SI), while LV diastolic function was interrogated by pulsed-wave and tissue Doppler echocardiography. RESULTS: Compared with available literature data, both dialysis and transplanted patients had significantly lower DWS and greater SI, reduced transmitral early (E) to late diastolic velocity ratio and septal and lateral mitral annular early (e') diastolic velocities, and greater septal and lateral E/e' ratios (all p < 0.05). Multivariate analysis revealed that z score of diastolic blood pressure (ß = 0.43, p = 0.004) and the duration of renal replacement therapy (ß = 0.55, p < 0.001) were significant determinants of LV SI. Subgroup analysis in post-transplant patients showed z score of diastolic blood pressure (ß = 0.54, p = 0.025) remained as a significant determinant of LV SI. CONCLUSION: Increased LV myocardial stiffness is evident in paediatric dialysis and transplanted patients with ESKD, and is associated with blood pressure and duration of renal replacement therapy.

Frontal QRS-T angle and ventricular mechanics in congenital heart disease.

BACKGROUND: The QRS-T angle has been associated with adverse cardiovascular events and sudden cardiac deaths. We determined frontal QRS-T angle in patients with complete transposition of the great arteries (TGA) after atrial switch operation and repaired tetralogy of Fallot (TOF) and explored its relationships with ventricular mechanics. METHODS: Thirty TGA patients aged 32.3 ± 4.4 years after atrial switch operation and 47 repaired TOF patients aged 28.7 ± 6.0 years were studied. The frontal planar QRS-T angle and QRS duration were measured from 12-lead electrocardiograms. Right (RV) and left ventricular (LV) strain parameters were determined using speckle tracking echocardiography. RESULTS: Compared with TOF patients, TGA patients after atrial switch operation had significantly greater frontal QRS-T angle (136.3° ± 43.5° vs 74.5° ± 59.6°, p < 0.001), greater prevalence of QRS-T angle ≥ 100° (83.3% vs 29.8%, p < 0.001), and showed progressive increase in QRS-T angle over a duration of 3.3 ± 1.0 years (p = 0.035). The QRS-T angle correlated positively with QRS duration in both the TGA (r = 0.61, p < 0.001) and TOF (r = 0.30, p < 0.043) groups. Among TGA patients, QRS-T angle was found to correlate negatively with systemic RV global longitudinal strain (r = - 0.49, p = 0.007), early diastolic strain rate (r = - 0.41, p = 0.026), and fractional area change (r = - 0.38, p = 0.045), but not subpulmonary LV strain indices. By contrast, among repaired TOF patients, there were no significant correlations between QRS-T angle and systemic and subpulmonary ventricular strain indices (all p > 0.05). CONCLUSION: Increased frontal QRS-T angle is prevalent in TGA patients after atrial switch operation and is related to worse systemic RV mechanics.

Left Ventricular Stiffness in Adolescents and Young Adults After Arterial Switch Operation for Complete Transposition of the Great Arteries.

We tested the hypothesis that left ventricular (LV) myocardial stiffness is altered in patients with transposition of great arteries (TGA) after arterial switch operation (ASO) and explored its associations with myocardial calibrated integrated backscatter (cIB) and LV myocardial deformation. Thirty-one patients and twenty-two age-matched controls were studied. LV myocardial stiffness was assessed by diastolic wall strain (DWS) and stiffness indices including (E/e)/LV end-diastolic dimension, (E/LV global longitudinal early diastolic strain rate)/LV end-diastolic volume, and (E/LV global circumferential early diastolic strain rate)/LV end-diastolic volume, where E and e are early diastolic transmitral and mitral annular velocities, respectively. LV myocardial cIB and longitudinal and circumferential myocardial deformation were determined by conventional and speckle tracking echocardiography. Patients had significantly lower DWS, higher stiffness indices, and greater myocardial cIB than controls (all p < 0.05). The LV longitudinal and circumferential systolic strain and systolic and diastolic strain rates were significantly lower in patients than controls (all p < 0.05). Greater average myocardial cIB was associated with lower DWS (r = - 0.44, p = 0.002). Worse DWS and LV stiffness indices were found to correlate with lower mitral annular systolic velocity, mitral annular late diastolic velocity, and LV longitudinal late diastolic strain rate (all p < 0.05). LV longitudinal and circumferential systolic strain and strain rate were also found to correlate with DWS (all p < 0.05). In conclusion, LV myocardial stiffening occurs in adolescents and young adults with TGA after ASO and is associated with impairment of ventricular systolic and diastolic myocardial deformation and myocardial fibrosis.

Tricuspid Regurgitation in Adults after Repair of Right Ventricular Outflow Obstructive Lesions.

We determined the prevalence and factors associated with tricuspid regurgitation (TR) in adults with repair of right ventricular (RV) outflow obstruction. A total of 256 patients (128 males) were studied at 25.7 ± 7.2 years after surgery, of whom 179 had repaired tetralogy of Fallot (TOF), 31 had pulmonary atresia with intact ventricular septum (PAIVS), and 46 had pulmonary stenosis (PS). The mitral and tricuspid annulus diameters, maximum right atrial (RA) area, RV end-systolic and end-diastolic areas, and tricuspid and pulmonary regurgitation were assessed using echocardiography. The prevalence of moderate-to-severe TR was 20.7%. Subgroup analysis revealed that prevalence was greater in patients with repaired TOF (20.7%) and PAIVS (35.5%) than PS patients (10.9%). As a group, severity of TR was found to be correlated with RA area (r = 0.35, p < 0.001), RV end-diastolic (r = 0.28, p < 0.001) and end-systolic (r = 0.22, p = 0.001) areas, and tricuspid valve annulus diameter (r = 0.15, p = 0.022). Moderate-to-severe TR was associated with development of cardiac arrhythmias with an odds ratio of 2.9 (95% CI 1.1 to 8.1, p = 0.031). Multivariate analysis revealed maximum RA area (ß = 0.36, p = 0.016) as an independent determinant of severity of TR. Moderate-to-severe TR occurs in about one-fifth of adults with repaired TOF, PAVIS, and PS and is associated with RA dilation and risk of development of cardiac arrhythmias.

Recent Advances in Single-Particle Electron Microscopic Analysis of Autophagy Degradation Machinery.

Macroautophagy (also known as autophagy) is a major pathway for selective degradation of misfolded/aggregated proteins and damaged organelles and non-selective degradation of cytoplasmic constituents for the generation of power during nutrient deprivation. The multi-step degradation process, from sequestering cytoplasmic cargo into the double-membrane vesicle termed autophagosome to the delivery of the autophagosome to the lysosome or lytic vacuole for breakdown, is mediated by the core autophagy machinery composed of multiple Atg proteins, as well as the divergent sequence family of selective autophagy receptors. Single-particle electron microscopy (EM) is a molecular imaging approach that has become an increasingly important tool in the structural characterization of proteins and macromolecular complexes. This article summarizes the contributions single-particle EM have made in advancing our understanding of the core autophagy machinery and selective autophagy receptors. We also discuss current technical challenges and roadblocks, as well as look into the future of single-particle EM in autophagy research.

Fifty-Five Years Follow-Up of 111 Adult Survivors After Biventricular Repair of PAIVS and PS.

There is paucity of long-term data on adult survivors after biventricular repair of pulmonary atresia with intact ventricular septum (PAIVS) and pulmonary stenosis (PS). This study aimed to determine the cardiac and non-cardiac outcomes of adult survivors after biventricular repair of PAIVS and PS. The cardiac, neurodevelopmental and liver problems of 111 adults, 40 with PAIVS and 71 with PS, were reviewed. The median follow-up duration of our patients was 26.5 years (range 14.8-55 years). The freedom from reintervention at 30 years was 17.4% and 73.3% for PAIVS and PS patients (p < 0.001), respectively. Compared with PS patients, PAIVS patients had significantly greater prevalence of right atrial and right ventricular (RV) dilatation, and moderate to severe tricuspid and pulmonary regurgitation (all p < 0.05), and cardiac arrhythmias (22.5% vs. 8.5%, p = 0.047). The freedom from development of cardiac arrhythmias at 30 years of 68.4% and 91.6%, respectively, in PAIVS and PS patients (p = 0.03). Cox proportional hazards model identified PAIVS as an independent risk factor for reintervention (HR 4.0, 95% CI 2.1-7.6, p < 0.001) and development of arrhythmias (HR 4.1, 95% CI 1.1-14.4, p = 0.03). Neurodevelopmental problems were found in 17.5% of PAIVS patients and 7.0% of PS patients (p = 0.11). Liver problems occurred in 2 (5%) PAIVS patients, both of whom required conversion to 1.5 ventricular repair. In conclusion, long-term problems, including the need for reinterventions, cardiac arrhythmias, RV dilation, pulmonary regurgitation, and neurodevelopmental and liver issues are more prevalent in adult PAIVS than PS survivors.

Left and Right Atrial Function and Remodeling in Beta-Thalassaemia Major.

This study aimed to assess left (LA) and right atrial (RA) function in patients with beta-thalassaemia major. Thirty-eight patients (19 males) aged 34.5 ± 10.7 years and 43 (18 males) controls aged 30.3 ± 12.6 years (p = 0.12) were studied. The maximum RA and LA areas were measured using two-dimensional planimetry, while atrial and ventricular strain and strain rates were quantified using speckle-tracking echocardiography. Compared with controls, patients had significantly reduced LA and RA peak positive strain and total strain, and LA strain rate during ventricular systole and at atrial contraction (all p < 0.05). The LA and RA strain parameters were significantly associated (all p < 0.05). The maximum LA (10.2 ± 1.6 cm2/m2 vs. 8.6 ± 1.3 cm2/m2, p < 0.001) and RA (9.2 ± 1.2 cm2/m2 vs. 7.5 ± 1.3 cm2/m2, p < 0.001) areas were significantly greater in patients than controls. The LV and RV strain and early strain rates were similar between patients and controls (all p > 0.05). Four patients with significant myocardial iron overload had larger LA area (p < 0.001) than those without. Functional and structural remodeling of both the right and left atria occurs in patients with beta-thalassaemia major, even in the absence of ventricular diastolic dysfunction.

Deferiprone inhibits iron overload-induced tissue factor bearing endothelial microparticle generation by inhibition oxidative stress induced mitochondrial injury, and apoptosis.

Iron overload-induced cardiovascular toxicity is one of the most common causes of morbidity and mortality in beta-thalassemia major patients. We have previously shown that iron overload-induced systemic arterial changes characterized by endothelial dysfunction are associated with increased endothelial microparticle (EMP) release. In this study, we further demonstrate how EMP release is associated with iron-induced mitochondrial injury and apoptosis of endothelial cells. Iron increased the production of reactive oxygen species (ROS) and calcium influx into mitochondria [Ca2+]m. Iron also disturbed mitochondrial respiration function and eventually led to loss of mitochondrial membrane potential (ΔΨm). A significant increase in apoptotic cells and EMPs were found under iron treatment. EMPs contained tissue factor (TF), which has potential clinical impact on thromboembolic phenomenon. Then, we investigated the salvaging effect of deferiprone (L1) on endothelial cell damage and EMP release. We found that L1 could inhibit iron-induced ROS generation, and decrease mitochondrial damage with the resultant effect of less endothelial cell apoptosis and EMP release. L1 could protect endothelial cells from iron-induced toxic effects and minimize EMP release, which could be potentially helpful in a subgroup of thalassemia patients who have increased thromboembolic complications.

Childhood Obesity and Physical Activity-Friendly School Environments.

OBJECTIVE: Childhood obesity may be related to school environment, but previous studies often focused on food environment only. This study aimed to examine the relationship between school physical activity environment and childhood obesity. STUDY DESIGN: This is a cross-sectional study with multilevel data collected on school physical activity environment using teacher questionnaires, students' growth, and obesity status from electronic health records, and neighborhood socioeconomic status from census data. RESULTS: This study included 208 280 students (6-18 years of age) from 438 schools (45% of Hong Kong). Prevalence of obesity was 5.0%. After controlling for socioeconomic status and intraschool correlation, robust Poisson regression revealed a reduced obesity risk associated with higher teachers' perceived physical activity benefits (risk ratio 0.96, 95% CI 0.94-0.99, P = .02), physical activity teaching experience (0.93, 0.91-0.96, P < .001), school campus size (0.93, 0.87-0.99, P = .02), physical activity ethos (0.91, 0.88-0.94, P < .001), number of physical activity programs (0.93, 0.90-0.96, P < .001), and physical activity facilities (0.87, 0.84-0.90, P < .001). Students in schools with at least 3 physical activity-friendly environmental factors (11.7%) had a much lower risk of obesity (0.68, 0.62-0.75, P < .001) than those without (23.7%). CONCLUSIONS: A physical activity-friendly school environment is associated with lower risk of obesity. School physical activity environment should be considered in future epidemiologic and intervention studies.

Ventricular mechanics after repair of subarterial and perimembranous VSDs.

BACKGROUND: Emerging data suggest impaired biventricular function in adults late after repair of ventricular septal defect (VSD). We assessed and compared right (RV) and left ventricular (LV) mechanics in adolescents and adults after surgical closure of doubly committed subarterial and perimembranous VSDs. METHODS: A total of 75 subjects were studied: 29 patients after subarterial VSD repair (group I), 17 patients after perimembranous VSD repair (group II) and 29 age-matched controls (group III). RV and LV mechanics were assessed using tissue Doppler and speckle-tracking echocardiography, while RV outflow systolic function was quantified by systolic excursion and fractional shortening (FS). RESULTS: Compared with group III, groups I and II had significantly reduced tricuspid annular systolic and diastolic velocities, isovolumic myocardial acceleration, RV global longitudinal systolic and diastolic deformation parameters and RV outflow systolic excursion (all P < .05). Group I, but not II, had reduced RV outflow FS (P = .008) and the lowest global LV longitudinal systolic strain (P = .008) and systolic strain rate (P = .014). In group I, postoperative aortic regurgitation was associated with lower LV longitudinal systolic strain (P = .009) and early diastolic strain rate (P = .002), while right bundle branch block was associated with lower RV systolic strain rate (P = .048). As a group, RV outflow excursion (P < .001) and FS (P = .001) were correlated with LV global systolic strain. CONCLUSION: Adolescents and adults late after repair of subarterial and perimembranous VSDs show impairment of RV systolic and diastolic myocardial deformation. The RV outflow function and LV systolic deformation appear to be worse after repair of subarterial defects.

Circulating MicroRNA in patients with repaired tetralogy of Fallot.

BACKGROUND: Emerging data suggest that heart-related microRNAs (miRs) may serve as circulating biomarkers of myocardial injury. We aimed to determine the circulating profile of miRs in patients with volume-overloaded right ventricles after repair of tetralogy (TOF). MATERIALS AND METHODS: A total of 104 TOF patients and 70 controls were recruited. The study was conducted in two phases: (1) determination of circulating heart-related miRs described in left heart diseases (miR-1, miR-133a, miR-208a, miR-208b and miR423-5p) by quantitative real-time PCR in 49 patients and 30 controls and followed by validation in an independent cohort of 55 patients and 40 controls; (2) expression profiling of serum samples from eight patients and eight controls, followed by validation. Alteration in circulating miRNA expression was related to cardiac functional indices as assessed by 2D speckle tracking and 3D echocardiography. RESULTS: No significant differences in serum levels of left heart-associated miRNAs were found between patients and controls. Of the candidate 19 miRNAs identified by profiling, upregulation of miR-99b and down-regulation of miR-766 were validated. However, no correlations were found between miRs levels and echo indices. CONCLUSION: In young adults with repaired TOF and volume-overloaded right ventricles, circulating levels of miR-99b and miR-766, but not left heart-associated miRNAs, were significantly altered.