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1.
Artigo em Inglês | MEDLINE | ID: mdl-33367540

RESUMO

AIMS: This study determined the associations between right atrial (RA) and right ventricular (RV) mechanics and liver stiffness in adults with repaired tetralogy of Fallot (TOF), pulmonary atresia with intact ventricular septum (PAVIS), and pulmonary stenosis (PS). METHODS AND RESULTS: Ninety subjects including 26 repaired TOF, 24 PAIVS, and 20 PS patients and 20 controls were studied. Hepatic shear wave velocity and tissue elasticity (E), measures of liver stiffness, were assessed by two-dimensional shear wave elastography, while RA and RV mechanics were assessed by speckle tracking echocardiography. Deformation analyses revealed worse RV systolic strain and strain rate, and RA peak positive and total strain, and strain rates at ventricular systole and at early diastole in all of the patient groups compared with controls (all P < 0.05). Compared with controls, all of the patient groups had significantly greater shear wave velocity and hepatic E-value (all P < 0.05). Shear wave velocity and hepatic E-value correlated negatively with RV systolic strain rate, and RA positive strain, total strain, and strain rate at ventricular systole and at early diastole (all P < 0.05). Multivariate analyses revealed RA strain rate at early diastole (P = 0.015, P < 0.001), maximum RA size (P < 0.001, P < 0.001), and severity of pulmonary regurgitation (P = 0.05, Pp = 0.014) as significant correlates of shear wave velocity and hepatic E-value. CONCLUSION: In adults with repaired TOF, PAIVS, and PS, RA dysfunction and pulmonary regurgitation are associated with liver stiffness.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33196317

RESUMO

Background - Human heterotaxy is a group of congenital disorders characterized by misplacement of one or more organs according to the left-right axis. The genetic causes of human heterotaxy are highly heterogeneous. Methods - We performed exome sequencing in a cohort of 26 probands with heterotaxy followed by gene burden analysis for the enrichment of novel rare damaging mutations. Transcription activator-like effector nuclease (TALEN) was used to generate somatic loss-of-function mutants in a zebrafish model. Ciliary defects were examined by whole-mount immunostaining of acetylated α-tubulin. Results - We identified a significant enrichment of novel rare damaging mutations in the CC2D1A gene. Seven occurrences of CC2D1A mutations were found to affect four highly conserved amino acid residues of the protein. Functional analyses in the TALEN-mediated zebrafish knock-out models and identified heterotaxy phenotypes of the cardiovascular and gastrointestinal systems in both somatic and germline mutants. Defective cilia were identified by whole-mount immunostaining of acetylated α-tubulin. These abnormalities were rescued by wild-type cc2d1a mRNA, but not cc2d1a mutant mRNA, strongly suggesting a loss-of-function mechanism. On the other hand, over-expression of cc2d1a orthologous mutations cc2d1a P559L and cc2d1a G808V (orthologous to human CC2D1A P532L and CC2D1A G781V) did not affect embryonic development. Conclusions - Using a zebrafish model, we were able to establish a novel association of CC2D1A with heterotaxy and ciliary dysfunction in the F2 generation via a loss-of-function mechanism. Future mechanistic studies are needed for a better understanding of the role of CC2D1A in left-right patterning and ciliary dysfunction.

3.
J Am Heart Assoc ; 9(20): e016528, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33059525

RESUMO

Background To understand the intrinsic cardiac developmental and functional abnormalities in pulmonary atresia with intact ventricular septum (PAIVS) free from effects secondary to anatomic defects, we performed and compared single-cell transcriptomic and phenotypic analyses of patient- and healthy subject-derived human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and engineered tissue models. Methods and Results We derived hiPSC lines from 3 patients with PAIVS and 3 healthy subjects and differentiated them into hiPSC-CMs, which were then bioengineered into the human cardiac anisotropic sheet and human cardiac tissue strip custom-designed for electrophysiological and contractile assessments, respectively. Single-cell RNA sequencing (scRNA-seq) of hiPSC-CMs, human cardiac anisotropic sheet, and human cardiac tissue strip was performed to examine the transcriptomic basis for any phenotypic abnormalities using pseudotime and differential expression analyses. Through pseudotime analysis, we demonstrated that bioengineered tissue constructs provide pro-maturational cues to hiPSC-CMs, although the maturation and development were attenuated in PAIVS hiPSC-CMs. Furthermore, reduced contractility and prolonged contractile kinetics were observed with PAIVS human cardiac tissue strips. Consistently, single-cell RNA sequencing of PAIVS human cardiac tissue strips and hiPSC-CMs exhibited diminished expression of cardiac contractile apparatus genes. By contrast, electrophysiological aberrancies were absent in PAIVS human cardiac anisotropic sheets. Conclusions Our findings were the first to reveal intrinsic abnormalities of cardiomyocyte development and function in PAIVS free from secondary effects. We conclude that hiPSC-derived engineered tissues offer a unique method for studying primary cardiac abnormalities and uncovering pathogenic mechanisms that underlie sporadic congenital heart diseases.

4.
Int J Cardiol Heart Vasc ; 30: 100612, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32817881

RESUMO

Background: This study aimed to assess diffuse myocardial fibrosis of the systemic right ventricle and subpulmonary left ventricle in patients after Senning or Mustard operation for complete transposition of the great artery (TGA) using cardiac magnetic resonance (CMR) T1 mapping. Methods: Thirty-one adult TGA patients after Senning (n = 24) or Mustard (n = 7) operation were studied at the age of 33.3 ± 4.0 years. Systemic right ventricular (RV) and subpulmonary left ventricular (LV) volumes, ejection fraction, and myocardial T1 values and extracellular volume fraction (ECV) were determined using CMR. Results: The RV and LV ejection fractions were 47.0 ± 10.9% and 61.3 ± 7.4%, respectively. Compared to published normative values, patients had significantly greater RV and LV native T1 and ECV values (all p < 0.001). For each of the basal, mid, and apical segments, the LV native T1 and ECV values were significantly greater in the left than the right ventricle (all p < 0.05). There is a significant trend on progressive increase in ECV value from the basal towards the apical segments in both the right (p = 0.002) and the left (p < 0.001) ventricle. Modestly strong correlations were found between RV and LV native T1 (r = 0.60, p < 0.001) and ECV (r = 0.49, p = 0.005) values but not with ejection fractions of the respective ventricles. Conclusions: Differential myocardial fibrosis, with greater involvement of the subpulmonary left ventricle than the systemic right ventricle, is present in patients with TGA after atrial switch operation. Associations between the magnitude of RV and LV fibrosis suggests adverse ventricular-ventricular interaction at the cardiac extracellular matrix level.

5.
Pediatr Res ; 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32634817

RESUMO

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.

6.
J Am Soc Echocardiogr ; 33(7): 788-801, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32624088

RESUMO

In patients with repaired tetralogy of Fallot (TOF), dysfunction of the right and left ventricles remains an important issue. Adverse right ventricular (RV) remodeling has been related to RV dilation secondary to pulmonary regurgitation, electromechanical dyssynchrony, and myocardial fibrosis. Left ventricular (LV) dysfunction is attributed among other factors to altered ventricular-ventricular interaction. Advancements in echocardiography and cardiac magnetic resonance imaging have enabled direct interrogation of myocardial deformation of both ventricles in terms of myocardial strain and strain rate. Emerging evidence suggests that myocardial deformation imaging may provide incremental information for clinical use. In children and adults with repaired TOF, there is a growing body of literature on the use of myocardial deformation imaging in the assessment of ventricular mechanics and its clinical and prognostic values. The present review aims to provide an overview of impairment in RV and LV mechanics, associations between RV and LV deformation, changes in ventricular deformation after pulmonary valve replacement, and associations between measures of RV and LV deformation and outcomes and to highlight the clinical translational potential of myocardial deformation imaging in patients with repaired TOF.

7.
Pediatr Cardiol ; 41(6): 1153-1159, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32394061

RESUMO

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.


Assuntos
Insuficiência da Valva Tricúspide/etiologia , Obstrução do Fluxo Ventricular Externo/cirurgia , Adolescente , Adulto , Arritmias Cardíacas/etiologia , Estudos Transversais , Ecocardiografia , Feminino , Átrios do Coração/patologia , Humanos , Masculino , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/complicações , Adulto Jovem
8.
Heart Vessels ; 35(9): 1299-1306, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32246195

RESUMO

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.

9.
Front Physiol ; 11: 165, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226389

RESUMO

Although biomimetic stimuli, such as microgroove-induced alignment (µ), triiodothyronine (T3) induction, and electrical conditioning (EC), have been reported to promote maturation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), a systematic examination of their combinatorial effects on engineered cardiac tissue constructs and the underlying molecular pathways has not been reported. Herein, human embryonic stem cell-derived ventricular cardiomyocytes (hESC-VCMs) were used to generate a micro-patterned human ventricular cardiac anisotropic sheets (hvCAS) for studying the physiological effects of combinatorial treatments by a range of functional, calcium (Ca2+)-handling, and molecular analyses. High-resolution optical mapping showed that combined µ-T3-EC treatment of hvCAS increased the conduction velocity, anisotropic ratio, and proportion of mature quiescent-yet-excitable preparations by 2. 3-, 1. 8-, and 5-fold (>70%), respectively. Such electrophysiological changes could be attributed to an increase in inward sodium current density and a decrease in funny current densities, which is consistent with the observed up- and downregulated SCN1B and HCN2/4 transcripts, respectively. Furthermore, Ca2+-handling transcripts encoding for phospholamban (PLN) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were upregulated, and this led to faster upstroke and decay kinetics of Ca2+-transients. RNA-sequencing and pathway mapping of T3-EC-treated hvCAS revealed that the TGF-ß signaling was downregulated; the TGF-ß receptor agonist and antagonist TGF-ß1 and SB431542 partially reversed T3-EC induced quiescence and reduced spontaneous contractions, respectively. Taken together, we concluded that topographical cues alone primed cardiac tissue constructs for augmented electrophysiological and calcium handling by T3-EC. Not only do these studies improve our understanding of hPSC-CM biology, but the orchestration of these pro-maturational factors also improves the use of engineered cardiac tissues for in vitro drug screening and disease modeling.

10.
Pediatr Cardiol ; 41(4): 747-754, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32006085

RESUMO

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.


Assuntos
Transposição das Grandes Artérias/efeitos adversos , Ventrículos do Coração/fisiopatologia , Transposição dos Grandes Vasos/cirurgia , Disfunção Ventricular Esquerda/etiologia , Adolescente , Criança , Ecocardiografia/métodos , Feminino , Fibrose , Humanos , Masculino , Miocárdio/patologia , Estudos Retrospectivos , Disfunção Ventricular Esquerda/patologia , Adulto Jovem
11.
Pediatr Nephrol ; 35(6): 1051-1060, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32016625

RESUMO

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.

12.
Ultrasound Med Biol ; 45(8): 1896-1908, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31153717

RESUMO

We performed a systematic review of the literature on assessment of right atrial (RA) and left atrial (LA) deformation by myocardial strain imaging in patients with repaired tetralogy of Fallot. Ten studies with a total of 536 adolescent and adult patients were included, of which 5 evaluated RA deformation, 2 studied LA deformation and 3 assessed deformation of both atria. Seven studies used speckle tracking echocardiography, 2 employed tissue Doppler imaging and 1 applied cardiac magnetic resonance feature tracking. Main findings were (i) reduced regional and/or global RA and LA strain and strain rate consistent with reduced conduit, reservoir and contractile function of the two atria in patients; (ii) associations between RA and LA deformation indices suggestive of atrial-atrial interaction; and (iii) relationships between RA deformation and indices of right ventricular systolic and diastolic function. The lack of data on prognostic value of atrial strain is an important knowledge gap.


Assuntos
Ecocardiografia/métodos , Imagem por Ressonância Magnética/métodos , Tetralogia de Fallot/cirurgia , Adolescente , Adulto , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Humanos
13.
Pediatr Cardiol ; 40(5): 1001-1008, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30972436

RESUMO

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.


Assuntos
Função do Átrio Esquerdo/fisiologia , Função do Átrio Direito/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Talassemia beta/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Ecocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem , Adulto Jovem
15.
Int J Cardiovasc Imaging ; 35(6): 999-1007, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30848401

RESUMO

We aimed to interrogate sex differences in cardiac mechanics using two-(2D) and three-(3D) dimensional speckle tracking echocardiography (STE) in survivors of childhood cancers. 83 survivors (43 males) aged 25.6 ± 6.1 years at 16.0 ± 6.1 years after anthracycline therapy and 42 healthy controls (21 males) were studied. 2D STE was performed to assess LV linear deformation in three principal directions, while 3D STE was performed to assess LV ejection fraction, global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS). Receiver operating characteristic (ROC) curves were generated to to determine the usefulness of 2D and 3D echocardiographic indices to discriminate between survivors and controls. Survivors of both sex had significantly lower 2D and 3D strain indices compared with sex-specific controls (all p < 0.05). Among survivors, 2D GLS and GRS and all of the 3D indices were similar between males and females (all p > 0.05). Among cancer survivors, multivariate analysis revealed age at study (ß = - 0.26, p = 0.022) as a significant determinant of 3D GLS. The area under the ROC curve for 3D GLS was the largest at 0.89 amongst all 3D and 2D strain parameters, while that of 2D GLS was 0.83. For 3D GLS, a cut-off of 16.4% had a sensitivity of 85.7% and a specificity of 80.7% of differentiating survivors from controls. Notwithstanding the finding of impaired LV myocardial mechanics, the present study did not reveal evidence of sexual dimorphism in cardiac mechanics in long term survivors of childhood cancers.


Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Ecocardiografia Tridimensional , Contração Miocárdica , Neoplasias/tratamento farmacológico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Adolescente , Adulto , Idade de Início , Fenômenos Biomecânicos , Cardiotoxicidade , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Hong Kong , Humanos , Masculino , Contração Miocárdica/efeitos dos fármacos , Neoplasias/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
16.
J Am Soc Echocardiogr ; 32(2): 277-285, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30598366

RESUMO

BACKGROUND: The aim of this study was to test the hypothesis that left ventricular (LV) and right ventricular (RV) functional reserves are altered in anthracycline-treated long-term survivors of childhood cancers. METHODS: One hundred three survivors (55% men) aged 25.0 ± 5.8 years at 15.2 ± 5.8 years after chemotherapy and 61 healthy control subjects (52% men) were studied. Tissue Doppler-derived mitral and tricuspid systolic (s) and early diastolic (e) velocities and LV myocardial acceleration during isovolumic contraction (IVA) were determined at rest and during bicycle exercise. The slope of the LV force-frequency relationship was derived from changes in IVA with heart rate during exercise (ΔIVA/Δ[heart rate]). LV and RV functional reserves were further assessed by the systolic functional reserve index (Δs × [1 - 1/s at baseline]) and diastolic functional reserve index (Δe × [1 - 1/e at baseline]). RESULTS: At baseline, mitral annular tissue Doppler indices were similar between survivors and control subjects (P > .05 for all), while tricuspid s and e velocities were significantly lower in survivors (P < .05 for both). The force-frequency relationship slope (P < .001), LV systolic functional reserve index (P < .001), and RV systolic functional reserve index (P = .001) were significantly lower in survivors than control subjects. For diastolic functional reserve, LV but not RV diastolic functional reserve index was significantly lower in survivors (P < .001). Multivariate analysis revealed survivor status (ß = -0.39, P < .001) and baseline LV IVA (ß = 0.15, P < .044) as significant determinants of the LV force-frequency relationship. CONCLUSIONS: LV and RV functional reserves during exercise are impaired in anthracycline-treated long-term survivors of childhood cancer.


Assuntos
Antraciclinas/uso terapêutico , Ecocardiografia/métodos , Previsões , Ventrículos do Coração/fisiopatologia , Neoplasias/tratamento farmacológico , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Adolescente , Adulto , Sobreviventes de Câncer , Criança , Diástole , Teste de Esforço , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Masculino , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Adulto Jovem
17.
Sci Rep ; 9(1): 162, 2019 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-30655554

RESUMO

This study determined the circulating levels of TGF-ß1 and its association with aortic dilation and elastic properties in congenital heart patients. Forty-six patients after tetralogy of Fallot (TOF) repair, 21 patients post arterial switch and 15 patients post atrial switch for transposition of the great arteries (TGA), 27 patients post Fontan procedure, and 36 controls were studied. Aortic dimensions and elastic properties and ventricular function were assessed by echocardiography. Serum TGF-ß1, metalloproteinase (MMP)-2 and MMP-9 levels were quantified. Compared with controls, all groups of patients had significantly larger ascending aortic dimensions and worse elastic properties (all p < 0.05). Aortic stiffness correlated positively with sinus dimension (r = 0.48, p < 0.001) and negatively with indices of ventricular deformation (all p < 0.001). Patients with repaired TOF had significantly higher levels of TGF-ß1 (p = 0.005), MMP-2 (p = 0.001) and MMP-9 (p < 0.001) than controls, while patients after atrial switch operation (p = 0.034) and Fontan procedures (p < 0.001) had higher MMP-2 levels. In patients as a group, circulating TGF-ß1 levels correlated with MMP-9 (r = 0.44, p < 0.001) and aortic sinus dimension (r = 0.22, p = 0.035). In conclusion, increased circulating TGF-ß1, MMP-2, and MMP-9 levels were found in patients with repaired TOF, and increased circulating MMP-2 levels were also evident in patients after atrial switch operation and Fontan procedure.


Assuntos
Aorta/fisiopatologia , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/fisiopatologia , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Fator de Crescimento Transformador beta1/sangue , Adulto , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Masculino , Adulto Jovem
19.
Pediatr Cardiol ; 40(2): 374-383, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30539241

RESUMO

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.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Atresia Pulmonar/cirurgia , Estenose da Valva Pulmonar/cirurgia , Adulto , Arritmias Cardíacas/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia/métodos , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Ventrículos do Coração/cirurgia , Humanos , Masculino , Atresia Pulmonar/complicações , Estenose da Valva Pulmonar/complicações , Reoperação/estatística & dados numéricos , Fatores de Risco , Sobreviventes , Resultado do Tratamento
20.
J Cardiol Cases ; 18(2): 65-69, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30279913

RESUMO

This case report presents a 16-month-old boy with isolated mild cyanosis diagnosed to have complex pulmonary arteriovenous malformations. Three-dimensional computed tomography with volume rendering has provided the diagnosis, enabled detailed imaging, and facilitated transcatheter device occlusion of the complex arteriovenous malformations by vascular plugs and coils. Magnetic resonance of the brain revealed associated dural arteriovenous malformation. Genetic testing showed a missense disease-causing variant in the ENG gene that encodes endoglin, and the diagnosis of hereditary hemorrhagic telangiectasia was made. .

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