Cláudia Moura

Isolated non-compaction of the myocardium diagnosed in the fetus: two sporadic and two familial cases

Isolated non-compaction of the ventricular myocardium is characterized by numerous and prominent trabeculations and deep intertrabecular recesses. This rare disease is due to an arrest of myocardial morphogenesis. Most cases, when seen in children, are associated with obstructive malformations. Isolated non-compaction is even rarer in childhood, and affects predominantly the myocardium of the left ventricle. Morbidity and mortality resulting from cardiovascular complications is high. In most cases, transplantation is the final option. To our knowledge, this rare cardiac malformation has yet to be diagnosed in the fetus. We report here two sporadic cases, one male and one female, and 2 familial cases, both male, which were diagnosed prenatally and followed by fetal echocardiography. Our study indicates that isolated non-compaction is a primary disorder of early fetal development. Our cross-sectional echocardiographic examinations revealed a fetal cardiomyopathy, with prominent and numerous trabeculations and deep intertrabecular recesses of the myocardium at the apex of the ventricles. In contrast with postnatal experience, we found isolated non-compaction mostly in the right ventricle. Systolic dysfunction was found in all cases. The diagnosis was confirmed by histology in 3 fetuses dying with cardiac failure, and by postnatal cross-sectional echocardiography in the fetus who survived. Two male fetuses belonged to a family in which 3 individuals were subsequently found to be affected. We discuss the issues of prenatal diagnosis, natural history, and myocardial histology.

A cohort study on psychosocial adjustment and psychopathology in adolescents and young adults with congenital heart disease

Objectives Our purpose was to study psychosocial adjustment and psychiatric morbidity of adolescents and young adults with congenital heart disease (CHD). Design All assessment measures were obtained on a single occasion. Clinical data was obtained through the patients clinical records. Setting A teaching and tertiary care facility in Porto, Portugal. Participants We evaluated 110 CHD patients (62 male) aged from 12 to 26 years (mean=18.00±3.617), 58 cyanotic. All assessment measures were obtained on a single occasion in a tertiary hospital. Demographic information and clinical history were collected. Primary and secondary outcome measures Questionnaires regarded topics such as social support, family educational style, self-image and physical limitations, a standardised psychiatric interview Schedule for Affective Disorders and Schizophrenia—Lifetime version (SADS-L), and a self-report questionnaire on psychosocial adjustment, youth self-report or adult self-report. One of the relatives completed an observational version of the same questionnaire (child behaviour checklist (CBCL) or ABCL (adult behaviour checklist)). Results We found a 21.8% lifetime prevalence of psychopathology, 31.3%, in females, 14.5% in males, showing a somewhat increased proneness in CHD patients. Females also showed worse psychosocial adjustment, with more somatic complaints (u=260 000; p=0.011), anxiety/depression (u=984 000; p=0.002), aggressive behaviour (u=920 500; p=0.001), attention problems (u=1123 500; p=0.027), thought problems (u=1069 500; p=0.010), internalisation (u=869 000; p=0.0) and externalisation (u=1163 000; p=0.05). Patients with severe CHD (u=939 000; p=0.03) and surgical repair (u=719 000; p=0.037) showed worse psychosocial adjustment. Those with poor social support showed more withdrawal (u=557 500; p=0.0) and social problems (u=748 500; p=0.023), and patients with unsatisfactory school performance revealed more anxiety/depression (u=916 000; p=0.02) and attention problems (u=861 500; p=0.007). Conclusions CHD males with good social support and good academic performance have a better psychosocial adjustment.

Quality of life of patients with congenital heart diseases

OBJECTIVES To assess the perception of the quality of life of adolescents and young adults with congenital heart disease and to examine the variables that have a negative impact on it and that add a resilience effect. METHODS A total of 22 male and 18 female patients, aged 12-26 years, of whom 27 were admitted to surgery and 13 were not, participated in this study. All patients had complete medical records and were interviewed once; demographic and clinical data were collected, and patients filled a questionnaire on quality of life, the WHOQOL-BREF, and underwent an interview on social support, educational style, self-image, functional limitations, and emotional adjustment. RESULTS/CONCLUSIONS Our patients showed a better perception of quality of life than did the general population, on the basis of psychological, social relationship and environment scales. Older patients hold a better perception of quality of life on the psychological scale. Cyanosis did not show any significant impact over perception of quality of life decay; however, the number of surgical procedures and the persistence of moderate-to-severe residual injuries had considerable detrimental effect. Social support had an impact on increasing resilience, promoting adjustment to illness. Several factors may play a role in adjustment to congenital heart disease, either improving the perception of quality of life or worsening it. We may conclude that some buffer variables on congenital heart disease may play roles in increasing the perception of quality of life of patients during their lifetime, social support probably explaining why the perception of quality of life is better than in the normal population. The number of surgeries and the moderate-to-severe residual injuries, however, reverted that effect.

Echocardiographic evaluation including tissue Doppler imaging in New Zealand white rabbits sedated with ketamine and midazolam.

Limited data are available on the use of more recent echocardiographic parameters in the rabbit. Echocardiographic examination, including conventional echocardiography and tissue Doppler imaging (TDI), was performed on 26 male New Zealand white rabbits under ketamine-midazolam sedation. Particular emphasis was placed on the more recent systolic and diastolic parameters, such as myocardial performance index (Tei index) and mitral annular motion (from septal and lateral sides of the left ventricle) obtained using pulsed TDI. Parameters that assessed systolic and diastolic function (fractional shortening, Tei index, and maximal mitral E- and A-wave velocities) were comparable to those reported in the literature for rabbits in the awake state. The less cardiodepressive anaesthetic protocol could offer a good alternative in performing echocardiographic evaluation whenever such caution is necessary. TDI is feasible in healthy rabbits and potentially suitable for the investigation of left ventricle systolic and diastolic function.

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 apelins 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.

Synergistic impact of endurance training and intermittent hypobaric hypoxia on cardiac function and mitochondrial energetic and signaling

BACKGROUND Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are cardioprotective strategies against stress-stimuli. Mitochondrial modulation appears to be an important step of the process. This study aimed to analyze whether a combination of these approaches provides additive or synergistic effects improving heart-mitochondrial and cardiac-function. METHODS Two-sets of rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5 weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5h/day/5 weeks) and hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In vitro cardiac mitochondrial oxygen consumption and transmembrane potential were evaluated. OXPHOS subunits and ANT protein content were semi-quantified by Western blotting. HIF-1α, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB expressions were measured by qRT-PCR and cardiac function was characterized by echocardiography and hemodynamic parameters. RESULTS Respiratory control ratio (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation-induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial complex-I and -II subunits; however HE completely reverted the decreased content in complex-II subunits. ANT increased in HE. HE presented normalized ventricular-arterial coupling (Ea) and BNP myocardial levels and significantly improved myocardial performance as evaluated by increased cardiac output and normalization of the Tei index vs. HS CONCLUSION Data demonstrates that IHH and ET confer cardiac mitochondria with a more resistant phenotype although without visible addictive effects at least under basal conditions. It is suggested that the combination of both strategies, although not additive, results into improved cardiac function.

Impaired Response to ETB Receptor Stimulation in Heart Failure: Functional Evidence of Endocardial Endothelial Dysfunction?

Inotropic effects of selective ETB receptor stimulation depend on the functional integrity of the endocardial endothelium (EE), which is negative when it is intact and positive when it is damaged. These results have been attributed to the existence of two subtypes of ETB receptors in the heart: (i) ETB1, located on the EE, decreases inotropy; (ii) ETB2, located on myocardial cells, increases inotropy. In the present study we investigated the functional integrity of the EE in a heart failure (HF) model (doxorubicin-induced cardiomyopathy) by evaluating the contractile response to ETB1 receptor stimulation. New Zealand White rabbits were treated with doxorubicin (DOX-HF, 1 mg/kg, iv, twice weekly for 8 weeks) or with saline. Contractile effects of increasing doses of a selective agonist of endothelial ETB receptors, IRL-1620 (10−9 to 10−6 M), were studied in papillary muscles (Krebs-Ringer: 1.8 mM CaCl2, 35°C) from control (n = 10) and DOX-HF rabbits (n = 7). Isotonic and isometric twitches were recorded and analyzed. Reported parameters included active tension (AT) and maximum velocities of tension rise (dT/dtmax) and decline (dT/dtmin). On echocardiography, DOX-HF rabbits had increased left ventricular (LV) end-diastolic and end-systolic diameters and reduced ejection fraction (52% ± 2% vs. 61% ± 1%). Contrary to control papillary muscles, DOX-HF muscles showed a steady decrease in contractility between 1 and 4 Hz. In the control group, IRL-1620 induced dose-dependent negative inotropic and lusitropic effects that decreased at 10−6 M: 26% ± 3%, AT; 17% ± 3%, dT/dtmax; and 16% ± 5%, dT/dtmin. In the DOX-HF group, these effects were significantly reduced. At the same concentration, IRL-1620 decreased AT (8% ± 3%) and dT/dtmax (8% ± 3%), without significantly affecting dT/dtmin. This study showed an impaired response to endothelial ETB receptor stimulation, providing for the first time strong evidence of the occurrence of EE dysfunction in the failing heart and further highlighting the potential use of ETB receptor stimulation as a marker of EE function.

Association of myeloperoxidase levels with cardiometabolic factors and renal function in prepubertal children.

Myeloperoxidase (MPO), an enzyme linking obesity and cardiovascular (CV) risk in adults, has rarely been studied in young children and no studies assessed its association with renal function. We sought to explore a possible association between serum MPO levels, obesity, CV risk factors and renal function in prepubertal children.

Worse cardiac remodeling in response to pressure overload in type 2 diabetes mellitus

BACKGROUND Diabetic cardiomyopathy is characterized by cardiac structural and functional abnormalities. Additionally, chronic pressure overload conditions are highly prevalent amongst diabetic population and this association leads to a more severe myocardial impairment. The differences in myocardial pathophysiology between type 1 and type 2 diabetes mellitus (DM) still remain to be clarified. Thus, we aimed to investigate biventricular structural and functional changes promoted by the two types of DM and the impact of concomitant chronic pressure overload. METHODS Wistar rats were injected with streptozotocin (Type 1 DM, T1DM) or fed with a hypercaloric diet (Type 2 DM, T2DM). Pressure overload was imposed in DM animals by aortic constriction and after 5weeks of DM the cardiac function and structure were evaluated. RESULTS Both types of DM promoted hypertrophy, increased fibrosis and advanced glycation end-products deposition, in the two ventricles. Interestingly, the induced myocardial alterations were distinct. While T1DM stimulated a pronounced hypertrophy and extracellular matrix remodeling, T2DM induced functional impairment. The negative impact of the association of DM with aortic constriction was more pronounced in T2DM, promoting impaired function and increased stiffness, particularly in the right ventricle. CONCLUSIONS Our study demonstrated that the two types of diabetes induce distinct cardiac alterations per se or when combined with chronic pressure overload. T1DM promoted a more extensive remodeling in cardiac structure while T2DM significantly impaired ventricular function. The impact of pressure overload was more notorious in T2DM as observed by worse myocardial remodeling, suggesting a higher susceptibility to the deleterious effects of chronic pressure overload, namely hypertension, among this diabetic population.

Agreement between echocardiographic techniques in assessment of the left ventricular myocardial performance index in rabbits

OBJECTIVE-To report reference values and examine the agreement in the myocardial performance (Tei) index of the left ventricle (LVTI) as measured by tissue Doppler imaging (TDI), pulsed-wave Doppler imaging (PWD), and M-mode echocardiography in clinically normal rabbits. ANIMALS-26 clinically normal male New Zealand White rabbits. PROCEDURES-Echocardiographic examinations that included TDI, PWD, and M-mode echocardiography were performed. Rabbits were sedated by SC administration of ketamine and midazolam. Intraclass correlation coefficients (ICCs) were used to measure absolute agreement among the 3 echocardiographic techniques. Intraclass correlation coefficients were computed for values a and b and for the equation (a - b)/b used to determine LVTI; value a equals the sum of isovolumic contraction time, ejection time, and isovolumic relaxation time, and value b equals the left ventricular ejection time. Values of ICC > 0.75 indicated good agreement between 2 echocardiographic techniques. RESULTS-For value a, Pearson correlation coefficients between pairs of techniques were all high (r r 0.7). However, only the septal TDI and the lateral wall TDI had good agreement (ICC, 0.86). For value b, correlations were generally low with the exception of the correlation between the septal and the lateral wall TDI. For value b, TDI was the only technique with good agreement (ICC, 0.77). For LVTI, only TDI techniques had a significantly positive correlation. All the other correlations were close to zero with a paradoxic moderate negative correlation between PWD-determined LVTI and lateral wall TDI-determined LVTI. CONCLUSIONS AND CLINICAL RELEVANCE-For LVTI, the absolute agreement was poor between all pairs of techniques.