Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.

Fetal Cardiac Function in Maternal Diabetes: A Conventional and Speckle-Tracking Echocardiographic Study.

BACKGROUND: Intrauterine exposure to a diabetic environment is associated with adverse fetal myocardial remodeling. The aim of this study was to assess the biventricular systolic and diastolic function of fetuses exposed to maternal diabetes (MD) compared with control subjects, using a comprehensive cardiac functional assessment and exploring the role of speckle-tracking to assess myocardial deformation. The authors hypothesized that fetuses exposed to MD present signs of biventricular dysfunction, which can be detected by deformation analysis. METHODS: A cross-sectional study was conducted in 129 fetuses with structurally normal hearts, including 76 fetuses of mothers with diabetes and 53 of mothers without diabetes. Maternal baseline characteristics, standard fetoplacental Doppler indices, and conventional echocardiographic and myocardial deformation parameters were prospectively collected at 30 to 33 weeks of gestation. RESULTS: Fetuses of mothers with diabetes had a significantly thicker interventricular septum compared with control subjects (median, 4.25 mm [interquartile range (IQR), 3.87-4.50 mm] vs 3.67 mm [IQR, 3.40-3.93 mm), P < .001), but no effect modification was demonstrated on myocardial deformation analysis. No significant differences were found in conventional systolic and diastolic functional parameters for the left ventricle and right ventricle, except for lower left ventricular cardiac output in the MD group (median, 320 mL/min [IQR, 269-377 mL/min] vs 365 mL/min [IQR, 311-422 mL/min], P < .05]. Deformation analysis demonstrated a significantly lower early diastolic strain rate (SRe) and late diastolic strain rate (SRa) for both ventricles in the MD group (left ventricle: SRe 1.85 ± 0.72 vs 2.26 ± 0.68 sec-1, SRa 1.50 ± 0.52 vs 1.78 ± 0.57 sec-1; right ventricle: SRe 1.57 ± 0.73 vs 1.97 ± 0.73 sec-1, SRa 2 ± 0.77 vs 1.68 ± 0.79 sec-1; P < .05), suggesting biventricular diastolic impairment. Additionally, the right ventricle presented a lower global longitudinal strain in the study group (-13.67 ± 4.18% vs -15.52 ± 3.86%, P < .05). Multivariate analysis revealed that maternal age is an independent predictor of left and right ventricular global longitudinal strain (P < .05), with a significant effect only in MD after group stratification. CONCLUSIONS: Fetuses of mothers with diabetes present signs of biventricular diastolic dysfunction and right ventricular systolic dysfunction by deformation analysis in the third trimester of pregnancy. They may represent a special indication group for functional cardiac assessment, independently of septal hypertrophy. Two-dimensional speckle-tracking could offer an additional benefit over conventional echocardiography to detect subclinical unfavorable changes in myocardial function in this population.

[Psychosocial adjustment, psychiatric morbidity and quality of life in adolescents and young adults with congenital heart disease]. / Ajustamento psicossocial, morbilidade psiquiátrica e qualidade de vida em adolescentes e jovens adultos com cardiopatias congénitas.

OBJECTIVES: We aimed to study the psychosocial adjustment (PSA), psychiatric morbidity and quality of life of adolescents and young adults with congenital heart disease (CHD) to determine which demographic and clinical variables negatively affect adjustment and which increase resilience. METHODS: The study included 74 patients with CHD, 41 male and 33 female, aged between 12 and 26 years (mean 18.76±3.86). Demographic information and a complete clinical history were obtained. The participants were interviewed regarding social support, family environment, self-image and physical limitations. A standardized psychiatric interview was conducted, and self-report questionnaires were administered for assessment of PSA (Youth Self Report and Adult Self Report) and quality of life (World Health Organization Quality of Life - Short Version). A caregiver completed an observational version of the PSA questionnaire (Child Behavior Checklist or Adult Behavior Checklist). RESULTS: Female participants showed more feelings of anxiety and depression (U=952.500; p=0.003), thought problems (U=929.500; p=0.005) and aggressive behavior (U=999.000; p=0.000). They also showed a higher rate of psychopathology. Patients with complex forms of CHD reported more thought problems (U=442.000; p=0.027) and internalization (U=429.000; p=0.021). Compared to the Portuguese population as a whole, participants showed better quality of life in the domains of social relationships (t=2.333; p=0.022) and environment (t=3.754; p=0.000). Patients who had undergone surgery had worse quality of life in physical terms (t=-1.989; p=0.050), social relationships (t=-2.012; p=0.048) and general quality of life (U=563.000; p=0.037), compared to those who were not operated. Better social support was associated with better quality of life in physical terms (t=3.287; p=0.002) and social relationships (t=3.669; p=0.000). Better school performance was also associated with better overall quality of life (U=457.000; p=0.046), less withdrawn behavior (U=812.500; p=0.031), fewer feelings of anxiety and depression (U=854.000; p=0.009), fewer attention problems (U=903.500; p=0.001), and lower scores for internalization (U=817.000; p=0.029) and externalization (U=803.500; p=0.042). Physical limitations had a detrimental effect on quality of life (U=947.500; p=0.001). DISCUSSION: Female participants were more prone to worse psychological adjustment and to psychopathology. Patients with complex forms of CHD showed worse PSA, as they need regular care, which restricts social contact with peers and family and integration in school and leisure activities. Patients who had undergone surgery showed worse quality of life as they often have long hospital stays, during which social activities are restricted, making it more difficult for them to develop a good social support network. They require close medical care, and the restrictions on their activities may be life-limiting. Their sense of survival may also be threatened. CONCLUSIONS: Patients with CHD appear to be more prone to psychopathology and female patients are more likely to show worse PSA. Social support was shown to play a crucial role in buffering stress and promoting patients' adjustment.

Quality of life experienced by adolescents and young adults with congenital heart disease.

This study aimed to assess the quality of life (QOL) experienced by adolescents and young adults with congenital heart disease (CHD) and to determine which factors negatively affect adjustment and which factors increase resilience. The participants in the study were 74 patients with CHD (41 males and 33 females) ranging in age from 12 to 26 years (mean age, 18.76 ± 3.86 years). Demographic information and a complete clinical history were obtained. The participants were interviewed regarding topics such as social support, family educational style, self-image, and physical limitations. They responded to questions in a standardized psychiatric interview (SADS-L) and completed a self-report questionnaire (WHOQOL-BREF) for assessment of QOL. Compared with the Portuguese population as a whole, the study patients had better QOL, especially with regard to the environmental dimension (t = 3.754; P = 0.000) and social relationships (t = 2.333; P = 0.022). Patients who had undergone surgery experienced poorer QOL in the physical dimension (t = -1.989; P = 0.050), in social relationships (t = -2.012; P = 0.048) and overall (Mann-Whitney U = 563.000; P = 0.037). Social support played a positive role in the QOL of the patients, both in the physical dimension (t = 3.287; P = 0.002) and in social relationships (t = 3.669; P = 0.000). A higher school achievement also was associated with higher levels of QOL overall (Mann-Whitney U = 457.000; P = 0.046) as well as in the physical (t = 2.045; P = 0.045) and environmental (t = 2.413; P = 0.018) dimensions. Physical limitations had a detrimental impact on general QOL (Mann-Whitney U = 947.500; P = 0.001) and on the physical (t = -2.910; p = 0.005) and psychological (t = -2,046; P = 0.044) dimensions. Patients with CHD tended to perceive QOL as better when their social networks were supportive.

Correlation between plasma levels of apelin and myocardial hypertrophy in rats and humans: possible target for treatment?

OBJECTIVE: To investigate the effects of left ventricular (LV) pressure overload and diabetes on the apelinergic system. RESEARCH DESIGN/METHODS: Pressure overload was established in rats by supra-renal aortic-banding. Six weeks later, diabetes was induced by streptozotocin (65 mg/kg, intraperitoneal), resulting in four groups: sham, banded (BA), diabetic (DM) and diabetic-banded (DM-BA). Twelve weeks later, LV function and structure were evaluated by echocardiography and biopsies and plasma samples collected. Furthermore, plasma samples and LV-endomyocardial biopsies were procured from aortic stenosis and mitral stenosis patients during surgery to evaluate myocardial expression of apelin and APJ-receptor and plasma levels of apelin. RESULTS: Direct correlations between apelin plasma levels and LV-mass index and between apelin and APJ myocardial expression were observed both in humans and rats. Expression of apelin and APJ was not significantly altered by pressure-overload in humans, being downregulated by pressure overload and even more by diabetes in rats. Finally, an inverse correlation between apelin rat plasma levels and its myocardial expression was observed. CONCLUSIONS: While apelin/APJ myocardial expression decreases, apelin plasma levels increase in LV hypertrophy. Considering apelin's positive inotropic and vasodilator properties, this elevation in apelin plasma levels may represent a compensatory mechanism to maintain inotropism and cardiac output during pressure-overload or diabetic cardiomyopathy.

Perinatal profile of ventricular overload markers in congenital diaphragmatic hernia.

BACKGROUND: In congenital diaphragmatic hernia (CDH), pulmonary hypertension increases right ventricle (RV) afterload, which could impair heart function and contribute to poor outcome for most affected infants. Nevertheless, the real significance of vascular pulmonary alterations in perinatal hemodynamics is largely unknown. It is defined that ventricular pressure overload induces increased myocardium gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin (ET)-1 systems. Our aim was to evaluate perinatal myocardium expression of these genes associated with ventricular pressure overload in a nitrofen-induced CDH rat model. METHODS: In the nitrofen-induced CDH rat model, fetuses from dated pregnant Sprague-Dawley rats at 15.5, 17.5, 19.5 and 21.5 days postcoitum as well as newborn pups were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from the RV and left ventricle (LV) were processed for quantification of messenger RNA (mRNA) of BNP, angiotensinogen, and ET-1. RESULTS: The perinatal expression of BNP, angiotensinogen, and ET-1 mRNA in the RV and LV of the control group revealed daily changes. During gestation, the expression of BNP and angiotensinogen mRNA underwent significant oscillation compared with control in both nitrofen-exposed fetuses, although we cannot identify significant differences between the nitrofen and CDH groups. After birth, we found a significant increasing expression of all studied genes only in the RV of CDH pups. CONCLUSIONS: Perinatal myocardial quantification of BNP, angiotensinogen, and ET-1 mRNA levels suggests that both nitrofen-exposed and control pups revealed prenatal variations of expression of the studied genes. Moreover, CDH is associated with significant molecular alterations only in the RV after birth.

Myocardium expression of connexin 43, SERCA2a, and myosin heavy chain isoforms are preserved in nitrofen-induced congenital diaphragmatic hernia rat model.

BACKGROUND: Previous morphological studies had produced controversial results with regard to heart development in congenital diaphragmatic hernia (CDH), whereas a few publications investigated cardiac function and myocardial maturation. Myocardium maturation is associated with age-dependent increasing of gene expression of gap junction protein connexin 43 (Cx43), adenosine triphosphatase of the sarcoplasmic reticulum (SERCA2a), as well as switching of myosin heavy chains (MHCs) from beta to alpha isoforms. Our aim was to evaluate myocardium maturity in nitrofen-induced CDH rat model. METHODS: Fetuses from dated pregnant Sprague-Dawley rats were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from left ventricle free wall were processed to (i) quantification of messenger RNA (mRNA) of Cx43, SERCA2a, alpha and beta MHC isoforms, as well as beta-actin (housekeeping gene); and (ii) separation of MHC isoforms (alpha and beta isoforms) by sodium dodecyl sulfate polyacrylamide gel electrophoresis silver stained. RESULTS: We demonstrated that there is no difference in myocardial gene expression of Cx43 (control, 1.0 +/- 0.1; nitrofen, 1.1 +/- 0.2; CDH, 1.3 +/- 0.2) and SERCA2a (control, 1.0 +/- 0.1; nitrofen, 0.9 +/- 0.1; CDH, 1.0 +/- 0.2). Myocardial gene expressions of alpha and beta mRNA of MHC isoforms were slightly decreased both in nitrofen and CDH fetuses when compared with control fetuses, but evaluation of the alpha-to-beta ratios of MHC isoforms at protein level revealed no significant differences between CDH and control (control, 16.9 +/- 2.5; CDH, 17.0 +/- 2.0). CONCLUSIONS: Myocardial quantification of Cx43 and SERCA2a mRNA, as well as the expression pattern of MHC isoforms at protein levels, was similar in all studied groups. We predict, therefore, that acute heart failure commonly observed in CDH infants might be attributed predominantly to cardiac overload secondary to severe pulmonary hypertension rather than to myocardial immaturity.

Patients with aortic coarctation operated during the first year of life, different surgical techniques and prognostic factors--21 years of experience.

UNLABELLED: The authors reviewed the clinical files of all patients with coarctation of the aorta (CoAo) operated during the first year of life, in a tertiary center, in order to assess the outcome of different surgical techniques and prognostic factors. MATERIAL AND METHODS: The study included all patients operated from 1 June 1980 to 1 June 2001. They were divided into three groups according to diagnosis: Group I--isolated CoAo (with or without persistent ductus arteriosus (PDA), group II--CoAo plus ventricular septal defect (VSD), and group III--CoAo associated with complex heart defects. The surgical techniques were divided into four groups: Group A--resection of the CoAo with end-to-end anastomosis, group B--Waldhausen technique (subclavian flap), group C--enlargement of the aorta with a patch, and group D--Waldhausen technique plus resection of the CoAo with end-to-end anastomosis. Several parameters were analyzed: sex, age at surgery, other surgical procedures during surgery, reoperation, mortality and outcome (good result, recoarctation). RESULTS: 156 patients were operated during the study period (84.5% of them since 1989). 61.5% were male. Surgery was performed between 3 and 336 days of life. 60.9% patients were included in group I, 32.7% in group II and 6.4% in group III. 25.0% of the patients had group A surgery, 60.2% group B surgery, 7.0% group C surgery and 7.7% group D surgery. The PDA was sectioned in 48.0% of the patients. It was necessary to perform banding of the pulmonary artery, during the first surgery, in 19.9% of cases. 18.6% needed a second operation to close the VSD and for debanding or repair of associated defects. Total mortality was 19.2%. Mortality rate per groups was: Group I--15.8%, group II--21.5%, group III--30.0%, group A--18.0%, group B--19.1%, group C--27.2% and group D--16.7%. In 7.6% of the patients recoarctation was found during follow-up. 40% of the patients are doing well with no medication and minor or no residual defects. 29.4% were lost to follow-up. CONCLUSIONS: Total mortality has decreased over the years with the highest mortality found in Group C and Group III. The best results were achieved in patients with isolated CoAo. Long-term results were generally good with few recoarctations and a good quality of life.

Perinatal arrhythmias -- diagnosis and treatment.

We did a retrospective analysis of the clinical files of 26 neonates with arrhythmia born during the period between January 1994 and February 1999. Fourteen (53.8%) of the neonates were male and 16 (61.5%) had prenatal diagnosis. Four (15.3%) had associated congenital heart disease. Twenty-one (80.7%) had abnormal rhythm and five (19.2%) had cardiac conduction disorder. Digoxin was the therapy of first choice to restore normal rhythm, used in 66.6% of the patients, followed by adenosine (16.6%) and electrical cardioversion (16.6%). An epicardial pacemaker was used in two of the three neonates with complete atrioventricular (AV) block. One neonate died due to cerebral hemorrhage. All the neonates were discharged in a clinically stable condition and 16 (88.8%) of them were medicated with digoxin. In a follow-up period that varied from 0 to 71 months (mean of 30.8 months), two patients had an episode of supraventricular tachycardia (SVT) after treatment withdrawal. Perinatal arrhythmias, although uncommon, can be life-threatening, and hence we consider our experience with these situations worth presenting.