Improvement in fetal pulmonary hypertension and maturity after reversal of ductal constriction: prospective cohort study.

OBJECTIVES: To test the hypotheses that estimated mean pulmonary arterial pressure (MPAP) decreases and pulmonary vascular maturation, assessed by the ratio of pulmonary arterial flow acceleration time to ejection time (AT/ET ratio), increases after reversal of fetal ductus arteriosus constriction by reducing maternal intake of the causal agent (prostaglandin inhibitors, such as polyphenol-rich foods or non-steroidal anti-inflammatory drugs), and that these effects are independent of gestational age, which are inferences not yet demonstrated in the clinical setting. METHODS: This was a prospective cohort study comparing Doppler echocardiographic ductal flow dynamics, MPAP and pulmonary arterial flow AT/ET ratio in third-trimester fetuses (≥ 28 weeks' gestation) with ductus arteriosus constriction, at the time of diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors either by suspending the use of pharmacological agents with potential for prostaglandin inhibition or by restricting the consumption of polyphenol-rich foods. MPAP was estimated using the Dabestani equation (MPAP = 90 - (0.62 × AT)), and pulmonary vascular maturity was assessed using the AT/ET ratio, according to reported validation studies. Student's t-test was used for comparison of variables at diagnosis with those after reversal of ductal constriction. Change in MPAP and pulmonary AT/ET ratio between the two assessments was compared with the expected change in the same gestational period in normal fetuses based on reference curves of MPAP and pulmonary AT/ET ratio constructed in normal fetuses from healthy pregnant women at 19-37 weeks' gestation, encompassing the same gestational age range as the study group (28-37 weeks). RESULTS: Seventy pregnancies with fetal ductus arteriosus constriction were included in the study. After 2 weeks of reduced maternal intake of prostaglandin inhibitors, normalization of mean systolic (change from 1.86 ± 0.34 m/s at diagnosis to 1.38 ± 0.41 m/s; P < 0.001) and diastolic (change from 0.41 ± 0.11 m/s to 0.21 ± 0.065 m/s; P < 0.001) ductal velocities and of mean pulsatility index (change from 1.99 ± 0.20 to 2.55 ± 0.42; P < 0.001) was demonstrated. MPAP decreased between the assessments (change from 66.7 ± 6.90 mmHg at diagnosis to 54.5 ± 6.70 mmHg after 2 weeks; P < 0.001) and mean pulmonary AT/ET ratio increased (change from 0.20 ± 0.06 to 0.33 ± 0.07; P < 0.001). Change in MPAP between diagnosis and after 2 weeks of reduced maternal intake of prostaglandin inhibitors was -12.2 ± 0.30 mmHg, which was 5.3-times higher than that in 305 normal fetuses over 2 weeks during the same gestational period (-2.3 ± 0.19 mmHg) (P < 0.001), and change in pulmonary AT/ET ratio between the two assessments was 0.13 ± 0.08, which was 8.7-times higher than that in normal fetuses in the same gestational period (0.015 ± 0.08) (P < 0.001). CONCLUSIONS: Resolution of fetal ductal constriction is followed by a fall in MPAP and by an increase in pulmonary vascular maturity, to a significantly greater degree than is observed in normal fetuses in the same gestational-age period. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Increase of prostaglandin E2 in the reversal of fetal ductal constriction after polyphenol restriction.

OBJECTIVE: Anti-inflammatory substances that inhibit the synthesis of prostaglandins, such as non-steroidal anti-inflammatory drugs (NSAIDs) and polyphenol-rich foods, can cause constriction of the fetal ductus arteriosus. This study aimed to test the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods, in the third trimester of pregnancy, is accompanied by increased plasma levels of prostaglandin E2 (PGE2). METHODS: This was a controlled clinical trial of women with singleton pregnancy ≥ 28 weeks undergoing fetal echocardiography. The intervention group included pregnancies with diagnosis of fetal ductal constriction and not exposed to NSAIDs. The control group consisted of third-trimester normal pregnancies. Both groups answered a food frequency questionnaire to assess the amount of total polyphenols in their diet, underwent Doppler echocardiographic examination and had blood samples collected for analysis of plasma levels of PGE2. Intervention group participants received dietary guidance to restrict the intake of polyphenol-rich foods. The assessments were repeated after 2 weeks in both groups. RESULTS: Forty normal pregnancies were assessed in the control group and 35 with fetal ductal constriction in the intervention group. Mean maternal age (26.6 years) and mean body mass index (30.12 kg/m2 ) were similar between the two groups. Intragroup analysis showed that dietary guidance reduced the median consumption of polyphenols (from 1234.82 to 21.03 mg/day, P < 0.001), increasing significantly the plasma concentration of PGE2 (from 1091.80 to 1136.98 pg/mL, P < 0.05) in the intervention group after 2 weeks. In addition, Doppler echocardiography showed reversal of fetal ductal constriction in the intervention group. No significant changes were observed in the control group. CONCLUSIONS: Dietary intervention for maternal restriction of polyphenol-rich foods in the third trimester of pregnancy is accompanied by increase in plasma levels of PGE2 and reversal of fetal ductal constriction. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

ESR1 polymorphisms and statin therapy: a sex-specific approach.

Lipid-lowering therapy has shown a high degree of variability in clinical response and there is evidence that the variability in drug response between individuals is due to genetic factors. Thirteen single nucleotide polymorphisms (SNPs) within the ESR1 gene were evaluated with basal lipid and lipoprotein levels, as well as response to lipid-lowering therapy, in 495 hypercholesterolemic individuals of European descent receiving simvastatin or atorvastatin. Significant associations were detected between rs4870061 (P=0.040, corrected P-value (PC)=0.440), rs1801132 (P=0.002, PC=0.022) and the SNP rs3020314 (P=0.013, PC=0.143) with triglyceride (TG) baseline levels. The rs4870061 was also associated with high-density lipoprotein cholesterol (HDL-C) baseline levels (P=0.045, PC=0.495). Regarding statin efficacy, rs2234693 C/C was associated with greater HDL-C increase (P=0.037; PC=0.407) and rs3798577 T allele was associated with greater total cholesterol (TC) reduction (P=0.019; PC=0.209) and greater TG reduction (P=0.026; PC=0.286). These associations suggest that ESR1 polymorphisms are in part responsible for the TC, HDL-C and TG variation levels and this effect may be sex-specific.

Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes.

We investigated the effect of single-nucleotide polymorphisms in sterol regulatory element-binding factors-1a and -2 (SREBF-1a and SREBF-2) and SREBF cleavage-activating protein (SCAP) genes on lipid-lowering response to simvastatin. In all, 146 hypercholesterolemic patients of European descent were prospectively treated with simvastatin 20 mg/day for over 6 months. Of these 99 subjects completed the 6-month follow-up. Plasma lipids and lipoproteins were measured before and throughout the study. The mean percentage decrease in plasma total cholesterol (TC) was greater in subject carriers of SCAP 2386G allele compared with those homozygous for 2386A allele (-29.6+/-13.4 vs -22.1+/-13.8%, P=0.007). About 61% of the 2386G carriers were above-average responders for TC levels (DeltaTC -27.8%), whereas only 29% of 2386A homozygous reached this reduction (P=0.009). Our data suggest that the SCAP 2386A>G gene polymorphism was a significant predictor of TC and triglyceride responses to simvastatin treatment.

[Surgical myocardial revascularization in young patients]. / Cirurgia de revascularização miocárdica em pacientes jovens.

PURPOSE: To determine early and late results of surgical myocardial revascularization (SMR) in young patients. METHODS: We studied retrospectively 73 patients aging less than 40 years and submitted to SMR between 1975 and 1989. The method used was patient card review and thelephone contact with the patient or his physician. RESULTS: Follow-up was obtained in all cases in a period of 2 to 185 (59.9 +/- 41.0) months. Of the coronary risk factors smoking was the most frequent. One vessel coronary artery disease was observed in 16 (21.9%) patients, 2 and 3 vessel coronary artery disease in 26 (35.6%) and 32 (43.8%) patients respectively. SMR was considered complete in 68 (93.2%) patients. An associated procedure was performed on 10 cases: Left ventricular aneurysm repair in 9 (12.3%) and mitral valve replacement in one (1.4%). Perioperative myocardial infarction occurred in 7 (9.5%) patients and one of them died (operative mortality: 1.4%). During follow-up, 6 (8.3%) patients died with an actuarial survival rate of 89.1% at 15 years. An event free survival rate of 68.3% was observed at 10 years. From 66 survivors, 53 (80.3%) were asymptomatic at late follow-up and 48 (72.7%) patients returned to work. CONCLUSION: Surgical myocardial revascularization in young patients associated with medical treatment, has good early and late results with a high percentage of patients asymptomatic and reemployed at a late follow-up.

Cirurgia de revascularização miocárdica em pacientes jovens / Surgical myocardial revascularization in young patients

Objetivo - avaliar os resultados imediatos e tardios da cirurgia de revascularizaçäo em pacientes jovens. Métodos - foram estudados retrospectivaemnte 73 pacientes com idades inferiores a 40 anos e submetidos a cirurgia de revascularizaçäo miocárdica no período de 1975 a 1989, utilizando-se a revisäo dos prontuários e o contato telefônico com os pacientes e/ou médicos-assitentes. Resultados - todos os pacientes foram acompanhados por um período de 2 a 185 (média 59, 9 +/- 41,0) meses. Dentre os fates de risco, o tabagismo foi o mais frequente (89,0 por cento). Dezesseis (21,9 por cento) pacientes apresentavam lesäo coronariana uniarterial, 26 (35,6 por cento) tinham doença biarterial e 32 (43,8 por cento) apresentavam doença triarterial. A revascularizaçäo foi considerada completa em 93, 2 por cento dos casos, sendo que 12,3 por cento foram também submetidos à aneurismectomia do ventrículo esquerdo. Desenvolveram infarto agudo do miocárdio perioperatório 7 (9,5 por cento) doentes, tendo ocorrido móbito hospitalar (1,3 por cento). Tardiamente, 6 (8,3 por cento) pacientes faleceram perfazendo probabilidade de sobrevida de 89, 1 por cento em 15 anos e probabilidade de sobrevida livre de eventos de 68,3 por cento em 10 anos. Encontram-se assintomáticos 80,3 dos pacientes, sendo que 72,7 por cento retornaram ao trabalho. Conclusäo a cirurgia de revascularizaçäo miocárdica em pacientes jovens, associada ao tratamento clínico, mostrou bons resultados a curto e longo prazo, com lata percentagem de pacints sobreviventes, assintomáticos e reassumindo suas atividades trabalhísticas.

Purpose - To determine early and late results of surgical myocardial revascularization (SMR) in young patients. Methods - We studied retrospectively 73 patients aging less than 40 years and submitted to SMR between 1975 and 1989. The method used was patient card review and thelephone contact with the patient or his physician. Results - Follow-up was obtained in all cases in a period of 2 to 185 (59.9±41.0) months. Of the coronary risk factors smoking was the most frequent. One vessel coronary artery disease was observed in 16 (21.9%) patients, 2 and 3 vessel coronary artery disease in 26 (35.ó%) and 32 (43.8%) patients respectively. SMR was considered complete in 68(93.2%) patients. An associated procedure was performed on 10 cases: Left ventricular aneurysm repair in 9 (12.3%) and mitral valve replacement in one (1.4%). Perioperative myocardial infarction occured in 7 (9.5%) patients and one of them died (operative mortality: 1.4%). During follow-up, 6 (8.3%) patients died with an actuarial survival rate of 89.1 % at 15years. An eventfree survival rate of 68.3% was observed at 10 years. From 66 survivors,53 (80.3%) were asymptomatic at late follow-up and 48 (72.7%) patients returned to work Conclusion - Surgical myocardial revascularization in young patients associated with medical treatment, has good early and late results with a high percentage of patients asymptomatic and reemployed at a late follow-up