Search

OBJECTIVES: Late hypertension after coarctation repair is associated with high mortality, but its risk factors remain unclear. This study aims to determine early and late postoperative risk factors for late hypertension after coarctation repair. METHODS: A cross-sectional study including transthoracic echocardiogram and 24-h blood pressure (BP) monitoring was performed in 144 patients aged ≥10 years with previous coarctation repair. Median age at repair was 39 days (interquartile range 0-3 years). Early postoperative hypertension was evaluated by calculating the mean of BP measurements taken on the same day before hospital discharge or the need for antihypertensives prior to discharge. Multivariable analyses were performed to adjust for gender, surgical age, and followup age. RESULTS: After a mean follow-up period of 22 ± 7 years, 59% (84/142) of patients were hypertensive: 58% (82/142) on 24-h BP monitoring and 1% (2/142) on antihypertensives. Early postoperative hypertension was present in 58% (73/126): 39% (49/126) on BP measurements and 19% (24/126) on antihypertensives. Early and late arch reobstruction (transthoracic echocardiogram peak gradient ≥25 mmHg) was present in 37% (23/62) and 23% (33/144), respectively. On multivariable logistic analysis, early postoperative hypertension and maximum descending arch velocity on echocardiography were associated with late hypertension on 24-h BP monitoring (odds ratio 2.21, 95% confidence interval 1.05-4.66, P = 0.04; and odds ratio 2.28, 95% confidence interval 1.08-4.81, P = 0.03; respectively). CONCLUSIONS: There is a high prevalence of late hypertension after coarctation repair. Arch reobstruction may be a major determinant of late hypertension. Early postoperative hypertension may identify very early in life those at risk of developing late hypertension. [ABSTRACT FROM AUTHOR]

Background Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality. Methods Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability. Results Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intraclass correlation (ICC) (n = 20) was 0.90 (95%CI 0.76, 0.96), mean difference 1.5 μm (95%LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95%CI 0.82, 0.97) mean difference 2 μm (95%LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95%CI 0.80, 0.87) mean difference 5 μm (95%LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95%LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality. Conclusion In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. [ABSTRACT FROM AUTHOR]

Mitochondrial complex I (CI) deficiency is the most common mitochondrial enzyme defect in humans. Treatment of mitochondrial disorders is currently inadequate, emphasizing the need for experimental models. In humans, mutations in the NDUFS6 gene, encoding a CI subunit, cause severe CI deficiency and neonatal death. In this study, we generated a CI-deficient mouse model by knockdown of the Ndufs6 gene using a gene-trap embryonic stem cell line. Ndufs6gt/gt mice have essentially complete knockout of the Ndufs6 subunit in heart, resulting in marked CI deficiency. Small amounts of wild-type Ndufs6 mRNA are present in other tissues, apparently due to tissue-specific mRNA splicing, resulting in milder CI defects. Ndufs6gt/gt mice are born healthy, attain normal weight and maturity, and are fertile. However, after 4 mo in males and 8 mo in females, Ndufs6gt/gt mice are at increased risk of cardiac failure and death. Before overt heart failure, Ndufs6gt/gt hearts show decreased ATP synthesis, accumulation of hydroxyacylcarnitine, but not reactive oxygen species (ROS). Ndufs6gt/gt mice develop biventricular enlargement by 1 mo, most pronounced in males, with scattered fibrosis and abnormal mitochondrial but normal myofibrillar ultrastructure. Ndufs6gt/gt isolated working heart preparations show markedly reduced left ventricular systolic function, cardiac output, and functional work capacity. This reduced energetic and functional capacity is consistent with a known susceptibility of individuals with mitochondrial cardiomyopathy to metabolic crises precipitated by stresses. This model of CI deficiency will facilitate studies of pathogenesis, modifier genes, and testing of therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Aortic intima-media thickness measured by transabdominal ultrasound (aIMT) is an intermediate phenotype of cardiovascular risk. We aimed to (1) investigate the reproducibility of aIMT in a population-derived cohort of infants; (2) establish the distribution of aIMT in early infancy; (3) compare measurement by edge-detection software to that by manual sonographic calipers; and (4) assess the effect of individual and environmental variables on image quality.Methods: Participants were term infants recruited to a population-derived birth cohort study. Transabdominal ultrasound was performed at six weeks of age by one of two trained operators. Thirty participants had ultrasounds performed by both operators on the same day. Data were collected on environmental (infant sleeping, presence of a sibling, use of sucrose, timing during study visit) and individual (post-conception age, weight, gender) variables. Two readers assessed image quality and measured aIMT by edge-detection software and a subset by manual sonographic calipers. Measurements were repeated by the same reader and between readers to obtain intra-observer and inter-observer reliability.Results: Aortic IMT was measured successfully using edge-detection in 814 infants, and 290 of these infants also had aIMT measured using manual sonographic calipers. The intra-reader intra-class correlation (ICC) (n = 20) was 0.90 (95% CI 0.76, 0.96), mean difference 1.5 μm (95% LOA -39, 59). The between reader ICC using edge-detection (n = 20) was 0.92 (95% CI 0.82, 0.97) mean difference 2 μm (95% LOA -45.0, 49.0) and with manual caliper measurement (n = 290) the ICC was 0.84 (95% CI 0.80, 0.87) mean difference 5 μm (95% LOA -51.8, 61.8). Edge-detection measurements were greater than those from manual sonographic calipers (mean aIMT 618 μm (50) versus mean aIMT 563 μm (49) respectively; p < 0.001, mean difference 44 μm, 95% LOA -54, 142). With the exception of infant crying (p = 0.001), no associations were observed between individual and environmental variables and image quality.Conclusion: In a population-derived cohort of term infants, aIMT measurement has a high level of intra and inter-reader reproducibility. Measurement of aIMT using edge-detection software gives higher inter-reader ICC than manual sonographic calipers. Image quality is not substantially affected by individual and environmental factors. [ABSTRACT FROM AUTHOR]