Paulo Zielinsky

World experience of percutaneous ultrasound-guided balloon valvuloplasty in human fetuses with severe aortic valve obstruction

Prenatal alleviation of severe fetal aortic valve obstructions by percutaneous ultrasound-guided balloon valvuloplasty has been performed to improve the fate of affected fetuses. The purpose of this study was to analyze the current world experience of these procedures in human fetuses. Data from 12 human fetuses were available for analysis. The mean gestational age at intervention was 29.2 weeks (range 27 to 33). The mean time period between initial presentation and intervention was 3.3 weeks (range 3 days to 9 weeks). Technically successful balloon valvuloplasties were achieved in 7 fetuses, none of whom had an atretic valve. Only 1 of these fetuses remains alive today. Of the 5 remaining technical failures, 1 patient with severe aortic stenosis underwent successful postnatal intervention and remains alive. Six patients who survived prenatal intervention died from cardiac dysfunction or at surgery in the first days or weeks after delivery. Four fetuses died early within 24 hours after the procedure, 1 from a bleeding complication, 2 from persistent bradycardias, and 1 at valvotomy after emergency delivery. Thus, the early clinical experience of percutaneous ultrasound-guided fetal balloon valvuloplasty in human fetuses with severe aortic valve obstruction has been poor due to selection of severe cases, technical problems during the procedure, and high postnatal operative mortality in fetuses who survived gestation. Improved patient selection and technical modifications in interventional methods may hold promise to improve outcome in future cases.

Isolated Atrioventricular Block in the Fetus A Retrospective, Multinational, Multicenter Study of 175 Patients

Background— Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome.nnMethods and Results— We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000–2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1–21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age <20 weeks, ventricular rate ≤50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4±2.9 versus 24.9±4.9 weeks; P =0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy.nnConclusions— Risk factors associated with a poor outcome were gestation <20 weeks, ventricular rate ≤50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.nn# Clinical Perspective {#article-title-22}Background— Isolated complete atrioventricular block in the fetus is a rare but potentially lethal condition in which the effect of steroid treatment on outcome is unclear. The objective of this work was to study risk factors associated with death and the influence of steroid treatment on outcome. Methods and Results— We studied 175 fetuses diagnosed with second- or third-degree atrioventricular block (2000–2007) retrospectively in a multinational, multicenter setting. In 80% of 162 pregnancies with documented antibody status, atrioventricular block was associated with maternal anti-Ro/SSA antibodies. Sixty-seven cases (38%) were treated with fluorinated corticosteroids for a median of 10 weeks (1–21 weeks). Ninety-one percent were alive at birth, and survival in the neonatal period was 93%, similar in steroid-treated and untreated fetuses, regardless of degree of block and/or presence of anti-Ro/SSA. Variables associated with death were gestational age <20 weeks, ventricular rate ⩽50 bpm, fetal hydrops, and impaired left ventricular function at diagnosis. The presence of ≥1 of these variables was associated with a 10-fold increase in mortality before birth and a 6-fold increase in the neonatal period independently of treatment. Except for a lower gestational age at diagnosis in treated than untreated (23.4±2.9 versus 24.9±4.9 weeks; P=0.02), risk factors were distributed equally between treatment groups. Two-thirds of survivors had a pacemaker by 1 year of age; 8 children developed cardiomyopathy. Conclusions— Risk factors associated with a poor outcome were gestation <20 weeks, ventricular rate ⩽50 bpm, hydrops, and impaired left ventricular function. No significant effect of treatment with fluorinated corticosteroids was seen.

Subaortic fibrous ridge and ventricular septal defect: role of septal malalignment.

The purpose of this study was to test the hypothesis that the presence of a subaortic ridge associated with a ventricular septal defect (VSD) is related to a malaligned ventricular septum caused by anterior or posterior deviation of the infundibular septum with or without obstructive lesions of the aortic arch. Thirty-two of 295 patients in whom a diagnosis of VSD was made by two-dimensional echocardiography and who were studied from June 1983 to April 1985 presented with a subaortic shelf. Every patient (p less than .00001) had a malalignment type of defect; the defect was produced by anterior deviation of the outlet septum (without compromise of the right ventricular outflow tract) in 28 and by posterior deviation of the infundibular septum in four. The prevalence of a subaortic shelf in the malalignment VSD group was 82% (32/39). Among the 28 patients with a subaortic ridge and anterior deviation of the outlet septum only three had aortic coarctation, but all four patients with subaortic stenosis and posterior infundibular malalignment had obstructive lesions of the aortic arch--coarctation in three and interruption of the aortic arch in one (p less than .001). We conclude that a malalignment type of VSD may be a consistent feature in patients with VSD and associated discrete subaortic stenosis. We also noted a high prevalence of subaortic ridge in the presence of a malalignment VSD and therefore speculate that there may be a common morphogenesis for malalignment VSD, subaortic shelf, and obstructive lesions of the aortic arch.

Assessment of diastolic ventricular function in fetuses of diabetic mothers using tissue Doppler

OBJECTIVEnTo identify the presence of ventricular diastolic dysfunction by tissue Doppler in fetuses of diabetic mothers, with or without septal hypertrophy, in comparison to fetuses of nondiabetic mothers.nnnMETHODSnA contemporary transverse study in fetuses with a gestational age between 25 weeks to term, studying diastolic function by assessment using tissue Doppler and pulsed wave Doppler of the atrioventricular diastolic flow. The mothers of the fetuses all had previous or gestational diabetes, and were referred to the Fetal Cardiology Unit of the Institute of Cardiology in Porto Alegre, Brazil. We analysed variance with the Student-Neumann-Keuls post hoc test. An alfa of 0.05 was considered significant for statistical analysis.nnnRESULTSnThe mean myocardial velocities of the Eand A waves at the mural mitral annulus, in fetuses of diabetic mothers with myocardial hypertrophy, were, respectively, 7.00 plus or minus 1.6 centimetres per second, and 10.24 plus or minus 3.3 centimetres per second. In the fetuses of diabetic mothers group without myocardial hypertrophy, the comparable values were 7.19 plus or minus 2.4 centimetres per second and 10.77 plus or minus 3.77 centimetres per second, respectively. In the control group, they were 4.81 plus or minus 0.85 centimetres per second and 8.01 plus or minus 2.2 centimetres per second. The difference between the velocities in fetuses of diabetic mothers and in fetal normal mothers was statistically significant (p less than 0.05). Statistically significant differences were also observed in E and A diastolic waves at the aortic mitral annulus, as well as for the tricuspid annulus when tissue Doppler assessment was carried out in the same sample. The mean ratio between the E and E of mitral and tricuspid waves in the control fetuses of normal mothers was significantly higher than in fetuses of diabetic mothers.nnnCONCLUSIONnPulsed tissue Doppler, when used in fetuses of diabetic mothers and compared with fetuses of nondiabetic mothers, shows evidence of impaired diastolic function, independently of the presence of myocardial hypertrophy.

Acute and Subchronic Toxicity Evaluation of Poly(ɛ-Caprolactone) Lipid-Core Nanocapsules in Rats

Owing to concerns over the effects of the physicochemical properties of nanoparticles and their interaction with biological systems, further investigation is required. We investigated, for the first time, the toxicity of lipid-core nanocapsules (LNCs) containing a polymeric wall of poly(ε-caprolactone) and a coating of polysorbate 80 used as drug delivery devices (~245nm) in Wistar rats after single- and repeated-dose treatments. The suspensions were prepared by interfacial deposition of the polymer and were physicochemically characterized. Toxicological effects were determined after single doses of 18.03, 36.06, and 72.12 × 10(12) LNC/kg and repeated doses of 6.01, 12.02, and 18.03 × 10(12) LNC/kg for 28 days by ip administration. The results for both the treatments showed no mortality or permanent body weight changes during the experiments. A granulomatous foreign body reaction was observed in the liver and spleen of higher dose groups in acute and subchronic treatments. Most of the hepatotoxicity and nephrotoxicity markers were within the reference values and/or were similar to the control group. However, a slight alteration in the hematologic parameters was observed in both the studies. Thus, to verify a possible methodological influence, we performed an in vitro test to confirm such influence. These findings are in agreement with earlier reports regarding no appreciable toxicity of biodegradable polymeric nanoparticles, indicating that LNC might be a safe candidate for drug delivery system. Furthermore, the results presented in this study are important for health risk assessment and to implement strategies for testing biodegradable polymeric nanoparticles.

Myocardial hypertrophy and dysfunction in maternal diabetes.

Diabetes in pregnancy, both pre-gestational and gestational, is a frequent cause of fetal myocardial hypertrophy, partly due to fetal hyperinsulinism. In fetal life, cardiac function may be impaired, especially during diastole, as a result of decreased left ventricular distensibility and altered left atrial dynamics secondary to myocardial hypertrophy. In neonates, the hypertrophy is a transient disorder, with spontaneous regression of the increased myocardial thickness during the first months of life. Nevertheless, cardiac hypertrophy may be associated with neonatal cardiomegaly and respiratory distress secondary to poor left ventricular compliance. The development of a number of new echocardiographic parameters discussed in this article, and primarily based on the pathophysiological consequences of myocardial hypertrophy, highlight an area of research priority: the assessment of diastolic function in fetuses of diabetic mothers with (and without) myocardial hypertrophy. A score for grading the severity of fetal diastolic dysfunction in these fetuses is proposed.

Alternative parameters for echocardiographic assessment of fetal diastolic function

Alternative methods to assess ventricular diastolic function in the fetus are proposed. Fetal myocardial hypertrophy in maternal diabetes was used as a model of decreased left ventricular compliance (LVC), and fetal respiratory movements as a model of increased LVC. Comparison of three groups of fetuses showed that, in 10 fetuses of diabetic mothers (FDM) with septal hypertrophy (SH), the mean excursion index of the septum primum (EISP) (ratio between the linear excursion of the flap valve and the left atrial diameter) was 0.36 +/- 0.09, in 8 FDM without SH it was 0.51 +/- 0.09 (P=0.001), and in the 8 normal control fetuses (NCF) it was 0.49 +/- 0.12 (P=0.003). In another study, 28 fetuses in apnea had a mean EISP of 0.39 +/- 0.05 which increased to 0.57 +/- 0.07 during respiration (P<0.001). These two studies showed that the mobility of the septum primum was reduced when LVC was decreased and was increased when LVC was enhanced. Mean pulmonary vein pulsatility was higher in 14 FDM (1.83 +/- 1.21) than in 26 NCF (1.02 +/- 0.31; P=0.02). In the same fetuses, mean left atrial shortening was decreased (0.40 +/- 0.11) in relation to NCF (0.51 +/- 0.09; P=0.011). These results suggest that FDM may have a higher preload than normal controls, probably as a result of increased myocardial mass and LV hypertrophy. Prenatal assessment of LV diastolic function by fetal echocardiography should include analysis of septum primum mobility, pulmonary vein pulsatility, and left atrial shortening.

Rastreamento populacional de anormalidades cardíacas fetais por ecocardiografia pré-natal em gestações de baixo risco no município de Porto Alegre

OBJETIVO: Estudar as anormalidades morfo-funcionais do sistema cardiovascular fetal detectaveis por ultra-sonografia. METODOS: Foram submetidos 3.980 fetos de gestantes sem risco obstetrico ou cardiologico, do municipio de Porto Alegre, de julho/1996 a novembro/2000, ao ecocardiograma de rastreamento para malformacoes cardiovasculares atraves dos cortes de quatro câmaras e vias de saida dos ventriculos direito e esquerdo. RESULTADOS: Houve 103 diagnosticos de anormalidades cardiovasculares fetais, correspondendo a 2,5% (103/3.980) da populacao estudada, ou 25,8/1000, sendo que 47 referiam-se a alteracoes morfo-funcionais do coracao fetal, prevalencia global de 11,8/1000 (47/3.980), e 56 exibiam alteracoes na refringencia (golf ball). Tres falso-negativos e nenhum falso-positivo elevaram a prevalencia global para 12.5/1000 (50/3.980), ou 26,6/1000 (106/3.980), quando incluidas tambem as alteracoes de refringencia. CONCLUSAO: A deteccao das malformacoes cardiovasculares ainda no periodo intra-uterino, visando planejamento perinatal e possivel, confirmando a experiencia internacional. E sugerida implantacao do rastreamento de malformacoes cardiovasculares, aninhada em rede de atencao rotineira de ultra-sonografia obstetrica.

New insights on fetal ductal constriction: role of maternal ingestion of polyphenol-rich foods

Fetal ductus arteriosus constriction is a clinical disorder that occurs as a result of inhibition of the prostaglandin synthesis pathway, and has long been associated to maternal intake of nonsteroidal anitiinflammatory drugs in late pregnancy. As a consequence of an increased right ventricular pressure, with tricuspid regurgitation and heart failure, there is a risk for the development of neonatal pulmonary artery hypertension. This artcile reviews the basic knowledge of the mechanisms involved in this important disorder. Clinical and experimental evidence that maternal consumption of polyphenol-rich substances, such as herbal teas, orange and grape juice, chocolate, and others, may interfere with fetal ductus arteriosus dynamics are discussed. Preventive measures to avoid fetal ductal constriction in the third trimester of pregnancy are discussed, including the possible need to change maternal dietary orientation, aiming to limit ingestion of foods with high concentrations of polyphenol-rich substances.

Short- and long- term results of percutaneous balloon valvuloplasty in pulmonary valve stenosis

OBJECTIVEnTo assess the long-term results of percutaneous balloon valvuloplasty at a single institution.nnnMETHODSnThis study comprised 189 patients with pulmonary valve stenosis undergoing percutaneous balloon valvuloplasty from 1984 to 1996, whose mean age was 7.97+/-9.25 years. The procedure was classified as successful when the RV-PA gradient was reduced to levels < 36 mmHg; restenosis was indicated by RV-PA gradients > 36 mmHg after an effective procedure.nnnRESULTSnAfter the procedure, the peak-to-peak transvalvular gradient decreased from 70.12+/-30.06 to 25.11 +/-20.23 mmHg (P<0.001). Immediate success was obtained in 148 (78.72%) patients. A later reduction in the gradient to values < 36 mmHg was obtained in 24 other patients previously categorized as unsuccessful. Therefore, percutaneous balloon valvuloplasty was considered effective in 172 (91.01%) patients. Effectiveness increased to 93.53% (159/170) in the cases of typical morphology. Follow-up ranged from 4.39+/-3 years to 13.01 years. Restenosis was observed in 24 (13.95%) patients. Pulmonary regurgitation was detected in 95.1% of the patients, being more intense than mild in 29.5% of the patients. The probability of maintaining an appropriate result, at any time point, with no restenosis was 92.29% in 2 years, 87.38% in 5 years, 82.46% in 8 years, and 64.48% in 10 years.nnnCONCLUSIONnPercutaneous balloon valvuloplasty was effective and safe for the treatment of pulmonary valve stenosis with excellent short- and long-term results.OBJETIVO: Determinar os resultados em longo prazo da valvoplastia percutânea por balao em uma instituicao isolada. METODOS: Estudados 189 pacientes com estenose valvar pulmonar submetidos a valvoplastia percutânea por balao, entre 1984-1996, com idade media de 7,97±9,25 anos, classificando-se como bem sucedida, a reducao do gradiente VD-AP em niveis 36mmHg apos procedimento eficaz. RESULTADOS: Apos o termino do procedimento, o gradiente pico a pico transvalvar reduziu-se de 70,12±30,06 para 25,11±20,23 mmHg (p<0,001). Obtiveram sucesso imediato 148 (78,72%) pacientes. Houve reducao posterior do gradiente para valores < 36mmHg em outros 24 pacientes categorizados sem sucesso no grupo. Assim a valvoplastia percutânea por balao foi considerada efetiva em 172 (91,01%) pacientes. A efetividade aumentou para 93,53% (159/170) nos casos de morfologia tipica. O tempo de seguimento foi de 4,39±3anos ate o periodo maximo de 13,01 anos. Observou-se reestenose em 24 (13,95%). A presenca de regurgitacao pulmonar foi detectada em 95,1% dos pacientes, sendo que em 29,5% com grau maior do que leve. A probabilidade de se manter um resultado adequado, ate qualquer ponto no tempo, sem a ocorrencia de reestenose, foi de 92,29% em 2 anos, de 87,38 % em 5 anos, de 82,46% em 8 anos e de 64,48% em 10 anos. CONCLUSAO: A valvoplastia percutânea por balao foi efetiva e segura no tratamento da estenose valvar pulmonar com excelentes resultados imediatos e a longo prazo.