Pulmonary hypertension in infants with bronchopulmonary dysplasia: risk factors, mortality and duration of hospitalisation.

OBJECTIVES: Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD) and associated with increased mortality and morbidity. Our aim was to identify, in infants with BPD, the effect of PH on health-care utilisation and health related cost of care. METHODS: An electronic data recording system was used to identify infants ≤32 weeks of gestation who developed BPD. PH was classified as early (≤28 days after birth) or late (>28 days after birth). RESULTS: In the study period, 182 infants developed BPD; 22 (12.1%) developed late PH. Development of late PH was associated with a lower gestational age [24.6 (23.9-26.9) weeks, p=0.001] and a greater need for positive pressure ventilation on day 28 after birth (100%) compared to infants without late PH (51.9%) (odds ratio (OR) 19.5, 95% CI: 2.6-148), p<0.001. Late PH was associated with increased mortality (36.4%) compared those who did not develop late PH (1.9%) after adjusting for gestational age and ventilation duration (OR: 26.9, 95% CI: 3.8-189.4), p<0.001. In infants who survived to discharge, late PH development was associated with a prolonged duration of stay [147 (118-189) days] compared to the infants that did not develop late PH [109 (85-149) days] (p=0.03 after adjusting for gestational age). Infants who had late PH had a higher cost of stay compared to infants with BPD who did not develop late PH (median £113,494 vs. £78,677, p=0.016 after adjusting for gestational age). CONCLUSIONS: Development of late PH was associated with increased mortality, a prolonged duration of stay and higher healthcare cost.

Dual ß-Catenin and γ-Catenin Loss in Hepatocytes Impacts Their Polarity through Altered Transforming Growth Factor-ß and Hepatocyte Nuclear Factor 4α Signaling.

Hepatocytes are highly polarized epithelia. Loss of hepatocyte polarity is associated with various liver diseases, including cholestasis. However, the molecular underpinnings of hepatocyte polarization remain poorly understood. Loss of ß-catenin at adherens junctions is compensated by γ-catenin and dual loss of both catenins in double knockouts (DKOs) in mice liver leads to progressive intrahepatic cholestasis. However, the clinical relevance of this observation, and further phenotypic characterization of the phenotype, is important. Herein, simultaneous loss of ß-catenin and γ-catenin was identified in a subset of liver samples from patients of progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. Hepatocytes in DKO mice exhibited defects in apical-basolateral localization of polarity proteins, impaired bile canaliculi formation, and loss of microvilli. Loss of polarity in DKO livers manifested as epithelial-mesenchymal transition, increased hepatocyte proliferation, and suppression of hepatocyte differentiation, which was associated with up-regulation of transforming growth factor-ß signaling and repression of hepatocyte nuclear factor 4α expression and activity. In conclusion, concomitant loss of the two catenins in the liver may play a pathogenic role in subsets of cholangiopathies. The findings also support a previously unknown role of ß-catenin and γ-catenin in the maintenance of hepatocyte polarity. Improved understanding of the regulation of hepatocyte polarization processes by ß-catenin and γ-catenin may potentially benefit development of new therapies for cholestasis.

3D printed models in patients with coronary artery fistulae: anatomical assessment and interventional planning.

AIMS: Coronary artery fistulae represent one of the most challenging anatomical defects to define accurately. We aimed to investigate the additional benefit conferred by volume rendering of tomographic images and 3D printing for diagnosis and interventional planning. METHODS AND RESULTS: Four cases of coronary fistulae were considered for transcatheter closure. Multidetector computed tomography (three cases) or cardiac magnetic resonance (one case) images were acquired and segmented using Mimics software. Each case was reviewed after incremental consideration of diagnostic resources: two cardiologists reported source and volume-rendered images; device closure was discussed by the interventional cardiology team. All diagnoses and planned management were reviewed after inspection of a 3D model. Using source images alone, both cardiologists correctly described the course and drainage in two out of four cases. Aided by volume rendering, this improved to three out of four cases. Inspection of the 3D printed model prompted the planned interventional approach and device sizing to be altered in two out of four cases. In one out of four cases, the intervention was abandoned after inspection of the 3D printed model. CONCLUSIONS: Diagnosis and management of patients with coronary artery fistulae rely on detailed image analyses. 3D models add value when determining the feasibility of, and the approach to intervention in these cases.

Assessment of right ventricular volumes in hypoplastic left heart syndrome by real-time three-dimensional echocardiography: comparison with cardiac magnetic resonance imaging.

BACKGROUND: Accurate assessment of right ventricular (RV) volumes and function is important in patients with hypoplastic left heart syndrome (HLHS). We prospectively sought to determine the reproducibility of three-dimensional (3D) echocardiography and its agreement with cardiac magnetic resonance imaging (CMR) in HLHS. METHODS AND RESULTS: Twenty-eight patients underwent CMR followed immediately by transthoracic 3D echocardiography under general anaesthesia. Semi-automated border detection software was used to determine echocardiographic RV volumes. Inter- and intra-observer variability, correlation and levels of agreement between techniques were determined. The median age was 0.37 years (0.18-9.28 years) and weight 6.24 kg (3.42-32.50 kg). Intra- and inter-observer variability was excellent for both techniques. Median (range) measurements for 3D echocardiography and CMR were; end-diastolic volume (EDV) 23.6 mL (6.5-63.2) and 30.6 mL (11.8-87.9), end-systolic volume (ESV) 12.6 mL (3.7-37.0) and 14.9 mL (5.8-33.9), stroke volume (SV) 11.2 mL (2.8-33.0) and 17.1 mL (6.0-54.1), ejection fraction (EF) 48.2% (31.2-64.9), and 56.5% (42.7-72.2). Correlation coefficients were r = 0.85, 0.84, 0.83, and 0.74, respectively (P < 0.01 for all). Volumetric data were expressed as a percentage of the echocardiographic volume to CMR volume. When compared with CMR, 3D echocardiography underestimated EDV, ESV and SV by 26.7% (SD ± 20.2), 10.6% (±28.1), and 37.5% (±20.1), respectively. The difference in volume appeared largest at low ventricular volumes. EF was 8.3% (±7.3) lower by 3D echocardiography compared with CMR. CONCLUSION: Both 3D echocardiography and CMR volumes appear highly reproducible. Measurements obtained by 3D echocardiography are significantly lower than those obtained by CMR, with wide limits of agreement such that these two methods cannot be used interchangeably.

Single breath-hold assessment of cardiac function using an accelerated 3D single breath-hold acquisition technique--comparison of an intravascular and extravascular contrast agent.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the current gold standard for the assessment of left ventricular (LV) function. Repeated breath-holds are needed for standard multi-slice 2D cine steady-state free precession sequences (M2D-SSFP). Accelerated single breath-hold techniques suffer from low contrast between blood pool and myocardium. In this study an intravascular contrast agent was prospectively compared to an extravascular contrast agent for the assessment of LV function using a single-breath-hold 3D-whole-heart cine SSFP sequence (3D-SSFP). METHODS: LV function was assessed in fourteen patients on a 1.5 T MR-scanner (Philips Healthcare) using 32-channel coil technology. Patients were investigated twice using a 3D-SSFP sequence (acquisition time 18-25 s) after Gadopentetate dimeglumine (GdD, day 1) and Gadofosveset trisodium (GdT, day 2) administration. Image acquisition was accelerated using sensitivity encoding in both phase encoding directions (4xSENSE). CNR and BMC were both measured between blood and myocardium. The CNR incorporated noise measurements, while the BMC represented the coeffiancy between the signal from blood and myocardium [1]. Contrast to noise ratio (CNR), blood to myocardium contrast (BMC), image quality, LV functional parameters and intra-/interobserver variability were compared. A M2D-SSFP sequence was used as a reference standard on both days. RESULTS: All 3D-SSFP sequences were successfully acquired within one breath-hold after GdD and GdT administration. CNR and BMC were significantly (p < 0.05) higher using GdT compared to GdD, resulting in an improved endocardial definition. Using 3D-SSFP with GdT, Bland-Altman plots showed a smaller bias (95% confidence interval LVEF: 9.0 vs. 23.7) and regression analysis showed a stronger correlation to the reference standard (R2 = 0.92 vs. R2 = 0.71), compared to 3D-SSFP with GdD. CONCLUSIONS: A single-breath-hold 3D-whole-heart cine SSFP sequence in combination with 32-channel technology and an intravascular contrast agent allows for the accurate and fast assessment of LV function.

Noninvasive assessment of pulmonary artery flow and resistance by cardiac magnetic resonance in congenital heart diseases with unrestricted left-to-right shunt.

OBJECTIVES: To determine whether noninvasive assessment of pulmonary artery flow (Qp) by cardiac magnetic resonance (CMR) would predict pulmonary vascular resistance (PVR) in patients with congenital heart disease characterized by an unrestricted left-to-right shunt. BACKGROUND: Patients with an unrestricted left-to-right shunt who are at risk of obstructive pulmonary vascular disease require PVR evaluation preoperatively. CMR cardiac catheter (XMR) combines noninvasive measurement of Qp by phase contrast imaging with invasive pressure measurement to accurately determine the PVR. METHODS: Patients referred for clinical assessment of the PVR were included. The XMR was used to determine the PVR. The noninvasive parameters, Qp and left-to-right shunt (Qp/Qs), were compared with the PVR using univariate regression models. RESULTS: The XMR was undertaken in 26 patients (median age 0.87 years)-ventricular septal defect 46.2%, atrioventricular septal defect 42.3%. Mean aortic flow was 2.24 +/- 0.59 l/min/m(2), and mean Qp was 6.25 +/- 2.78 l/min/m(2). Mean Qp/Qs was 2.77 +/- 1.02. Mean pulmonary artery pressure was 34.8 +/- 10.9 mm Hg. Mean/median PVR was 5.5/3.0 Woods Units (WU)/m(2) (range 1.7 to 31.4 WU/m(2)). The PVR was related to both Qp and Qp/Qs in an inverse exponential fashion by the univariate regression equations PVR = exp(2.53 - 0.20[Qp]) and PVR = exp(2.75 - 0.52[Qp/Qs]). Receiver-operator characteristic (ROC) analysis was used to determine cutoff values for Qp and Qp/Qs above which the PVR could be regarded as clinically acceptable. A Qp of > or =6.05 l/min/m(2) predicted a PVR of < or =3.5 WU/m(2) with sensitivity 72%, specificity 100%, and area under the ROC curve 0.90 (p = 0.002). A Qp/Qs of > or =2.5/1 predicted a PVR of < or =3.5 WU/m(2) with sensitivity 83%, specificity 100%, and area under the curve ROC 0.94 (p < 0.001). CONCLUSIONS: Measurement of Qp or left-to-right shunt noninvasively by CMR has potential to predict the PVR in patients with an unrestricted left-to-right shunt and could potentially determine operability without having to undertake invasive testing.