Echocardiographic Evaluation of Pulmonary Pressures and Right Ventricular Function after Pediatric Cardiac Surgery: A Simple Approach for the Intensivist.

Pulmonary hypertension (PH) is diagnosed using cardiac catheterization and is defined as an elevation of mean pulmonary artery pressure (PAP) greater than 25 mmHg. Although invasive hemodynamics remains the gold standard and is mandatory for disease confirmation, transthoracic echocardiography (TTE) is an extremely useful non-invasive and widely available tool that allows for screening and follow-up, in particular, in the acute setting. TTE may be a valuable alternative, allowing for direct measurement and/or indirect assessment of PAP. Because of the complex geometric shape and pattern of contraction of the right ventricle (RV), as well as the inherent complexity of cardiac repair, no single view or measurement can provide definite information on RV function and PAP and/or pulmonary vascular resistance. In addition, specific training and expertise may be necessary to obtain the views and measurements required. Some simple measurements may be of help when rapid evaluation is mandatory and potentially life saving: the assessment of tricuspid and/or pulmonary valve regurgitant jet and the use of the Bernoulli equation allow for measurement of PAP. Measurements such as the analysis of the pulmonary Doppler wave flow, the septal curvature, or the eccentricity index, assessing ventricular interdependence, are useful for indirect assessment. A four-chamber view of the RV gives information on its size, hypertrophy, function (fractional area change), and tricuspid annular plane systolic excursion as an evaluation of the longitudinal function. Based on these simple measurements, TTE can provide detection of PH, measurement or estimation of PAP, and assessment of cardiac function. TTE is also of importance in follow up of PH as well as providing an assessment of therapeutic strategies in the postoperative setting of cardiac surgery. However, PAP may be misleading as it is dependent on cardiac output and requires accurate measurements. In the presence of residual lesions, analyses of some Doppler measurements may be misleading and not reflect real PAP. Should the TTE evaluation reveal non-conclusive, invasive hemodynamics remains the gold standard

Increase of Fungal Endocarditis in Children

Background:: Infective endocarditis (IE) is a rare and feared infection that mainly occurs in patients with underlying cardiac disease or altered function of the immune system. Recent epidemiological data on both sepsis and nosocomial infections indicate a rise in gram-negative bacterial and fungal infection, particularly in patients requiring critical care support. This study sought to characterize the change in the spectrum of IE encountered in a single pediatric tertiary care center during the last 18 years, to evaluate emergence of fungal IE and to identify contributing factors. Patients and Methods:: Review of all cases of IE diagnosed between January 1986 and August 2003 at a single university children's hospital. Patients were distributed between two equal time periods and compared according to the era of IE diagnosis. Results:: In 43 patients, 44 episodes of IE were identified with most cases occurring in children with congenital or acquired heart disease. The annual number of diagnosed cases fluctuated during the study (mean 2.4 cases/year). Blood or specimen cultures were positive in 34 cases (77%) with gram-positive organisms most frequently observed (n = 20, 44.4%). Fungal IE cases (n = 9, 20%) occurred preferentially during the second period (p < 0.03), and were more common in children with noncardiac diseases (p = 0.023). Factors associated with fungal IE were the use of broad-spectrum antibiotics (p < 0.001) and the presence of an infected central venous catheter (p = 0.01). Overall mortality did not differ between the two eras. Conclusion:: The incidence of fungal IE seems to have significantly increased in more recent years. Use of broadspectrum antibiotics for prolonged time or/and central venous catheters were identified as predisposing factors to fungal infective endocarditi

Pediatric Population Pharmacokinetic Modeling and Exposure-Response Analysis of Ambrisentan in Pulmonary Arterial Hypertension and Comparison With Adult Data.

This study aimed to develop a population pharmacokinetic (PK) model of ambrisentan in pediatric patients (8 to &lt;18 years) with pulmonary arterial hypertension (PAH) and compare pediatric ambrisentan systemic exposure with previously reported adult data. Association of ambrisentan exposure with efficacy (6-minute walking distance) and safety (adverse events) were exploratory analyses. A population PK model was developed using pediatric PK data. Steady-state systemic exposure metrics were estimated for the pediatric population and compared with previously reported data in adult patients with PAH and healthy subjects. No covariates had a significant effect on PK parameters; therefore, the final covariate model was the same as the base model. The pediatric population PK model was a 2-compartment model including the effect of body weight (allometric scaling), first-order absorption and elimination, and absorption lag time. Steady-state ambrisentan exposure was similar between the pediatric and adult population when accounting for body weight differences. Geometric mean area under the concentration-time curve at steady state in pediatric patients receiving ambrisentan low dose was 3% lower than in the adult population (and similar in both populations receiving high dose). Geometric mean maximum plasma concentration at steady state in pediatric patients receiving low and high doses was 11% and 18% higher, respectively, than in the adult population. There was no apparent association in the pediatric or adult population between ambrisentan exposure and change in 6-minute walking distance or incidence of ambrisentan-related adverse events in pediatric patients. The similar ambrisentan exposure and exposure-response profiles observed in pediatric and adult populations with PAH suggests appropriateness of body-weight-based dosing in the pediatric population with PAH

Effects of PDE-5 Inhibition on the Cardiopulmonary System After 2 or 4 Weeks of Chronic Hypoxia.

In pulmonary hypertension (PH), hypoxia represents both an outcome and a cause of exacerbation. We addressed the question whether hypoxia adaptation might affect the mechanisms underlying PH alleviation through phosphodiesterase-5 (PDE5) inhibition. Eight-week-old male Sprague-Dawley rats were divided into two groups depending on treatment (placebo or sildenafil, a drug inhibiting PDE5) and were exposed to hypoxia (10% O &lt;sub&gt;2&lt;/sub&gt; ) for 0 (t0, n = 9/10), 2 (t2, n = 5/5) or 4 (t4, n = 5/5) weeks. The rats were treated (0.3 mL i.p.) with either saline or sildenafil (1.4 mg/Kg per day). Two-week hypoxia changed the body weight (- 31% vs. - 27%, respectively, P = NS), blood hemoglobin (+ 25% vs. + 27%, P = NS) and nitrates+nitrites (+ 175% vs. + 261%, P = 0.007), right ventricle fibrosis (+ 814% vs. + 317%, P &lt; 0.0001), right ventricle hypertrophy (+ 84% vs. + 49%, P = 0.007) and systolic pressure (+ 108% vs. + 41%, P = 0.001), pulmonary vessel density (+ 61% vs. + 46%, P = NS), and the frequency of small (&lt; 50 µm wall thickness) vessels (+ 35% vs. + 13%, P = 0.0001). Most of these changes were maintained for 4-week hypoxia, except blood hemoglobin and right ventricle hypertrophy that continued increasing (+ 52% vs. + 42%, P = NS; and + 104% vs. + 83%, P = 0.04). To further assess these observations, small vessel frequency was found to be linearly related with the right ventricle-developed pressure independent of hypoxia duration. Thus, although hypoxia adaptation is not yet accomplished after 4 weeks, PH alleviation by PDE5 inhibition might nevertheless provide an efficient strategy for the management of this disease

A 0.4 nJ Excitation Energy Bridge-to-Digital Converter for Implantable Pulmonary Artery Pressure Monitoring

This paper presents an energy-efficient, duty-cycled, and spinning excitation bridge-to-digital converter (BDC) suitable for measuring the pulmonary artery pressure of heart failure patients with an implantable system. The duty-cycled bridge uses resistances of 6.2 kΩ and, with a supply of 1.2 V, consumes 0.4 nJ excitation energy. A novel spinning method is applied to the bridge and the capacitive DAC simultaneously in such a way to achieve an offset-independent digital output and to eliminate the need for complex instrumentation amplifiers with offset-reduction techniques or calibration. The SAR ADC fabricated in 0.18-μm CMOS consumes 19 nW at 1.2 V. With a sampling rate of 1 kS/s, the converter achieves the ENOB of 9.2 bits

Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure

Aims To determine whether impaired brachial endothelial (flow-mediated dilation, FMD) and smooth muscle function (nitroglycerin-mediated dilation, NTGMD), and remodelling of the common carotid artery (CCA) develop before puberty in obese children. Methods and results Arterial intima-media thickness (IMT), FMD and NTGMD were measured by high-resolution ultrasound in 48 obese and 23 lean pre-pubertal children (8.8 ± 1.5 years old). We assessed central pulse pressure, incremental elastic modulus (Einc), casual and ambulatory systolic (SBP) and diastolic blood pressure (DBP), and body fatness by DXA. Obese children had significantly lower FMD (4.5 ± 4.0 vs. 8.3 ± 1.7%), NTGMD (19.0 ± 9.0 vs. 25.8 ± 6.1%), and increased Einc (13.9 ± 5.2 vs. 10.4 ± 5.2 mmHg/102), ambulatory SBP (121.3 ± 12.6 vs. 106.6 ± 7.1, mmHg), and DBP (69.1 ± 5.7 vs. 63.7 ± 4.5) than lean subjects, whereas IMT was not augmented. Ambulatory systolic hypertension was present in 47% of obese subjects. FMD, NTGMD, and Einc were correlated with body fatness, body mass index, and blood pressure (BP). Conclusion Impaired endothelial and smooth muscle functions and altered wall material develop before puberty in obese children, however remodelling of the CCA is not yet present. Arterial dysfunction may be considered as the first marker of atherosclerosis and is associated with elevated BP. Ambulatory blood pressure monitoring may be a potential tool to improve risk stratification in obese childre

Adapting the "Chester step test" to predict peak oxygen uptake in children.

Maximal exercise testing may be difficult to perform in clinical practice, especially in obese children who have low cardiorespiratory fitness and exercise tolerance. We aimed to elaborate a model predicting peak oxygen consumption (VO2) in lean and obese children with use of the submaximal Chester step test. We performed a maximal step test, which consisted of 2-minute stages with increasing intensity to exhaustion, in 169 lean and obese children (age range: 7-16 years). VO2 was measured with indirect calorimetry. A statistical Tobit model was used to predict VO2 from age, gender, body mass index (BMI) z-score and intensity levels. Estimated VO2peak was then determined from the heart rate-VO2 linear relationship extrapolated to maximal heart rate (220 minus age, in beats.min-1). VO2 (ml/kg/min) can be predicted using the following equation: VO2 = 22.82 - [0.68*BMI z-score] - [0.46*age (years)] - [0.93*gender (male = 0; female = 1)] + [4.07*intensity level (stage 1, 2, 3 etc.)] - [0.24*BMI z-score *intensity level] - [0.34*gender*intensity level]. VO2 was lower in participants with high BMI z-scores and in female subjects. The Chester step test can assess cardiorespiratory fitness in lean and obese children in clinical settings. Our adapted equation allows the Chester step test to be used to estimate peak aerobic capacity in children

Pulmonary stenosis development and reduction of pulmonary arterial hypertension in atrioventricular septal defect: a case report

A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008

Coarctation of the aorta: pre and postoperative evaluation with MRI and MR angiography; correlation with echocardiography and surgery

Aims: To compare MRI and MRA with Doppler-echocardiography (DE) in native and postoperative aortic coarctation, define the best MR protocol for its evaluation, compare MR with surgical findings in native coarctation. Materials and methods: 136 MR studies were performed in 121 patients divided in two groups: Group I, 55 preoperative; group II, 81 postoperative. In group I, all had DE and surgery was performed in 35 cases. In group II, DE was available for comparison in 71 cases. MR study comprised: spin-echo, cine, velocity-encoded cine (VEC) sequences and 3D contrast-enhanced MRA. Results: In group I, diagnosis of coarctation was made by DE in 33 cases and suspicion of coarctation and/or aortic arch hypoplasia in 18 cases. Aortic arch was not well demonstrated in 3 cases and DE missed one case. There was a close correlation between VEC MRI and Doppler gradient estimates across the coarctation, between MRI aortic arch diameters and surgery but a poor correlation in isthmic measurements. In group II, DE detected a normal isthmic region in 31 out of 35 cases. Postoperative anomalies (recoarctation, aortic arch hypoplasia, kinking, pseudoaneurysm) were not demonstrated with DE in 50% of cases. Conclusions: MRI is superior to DE for pre and post-treatment evaluation of aortic coarctation. An optimal MR protocol is proposed. Internal measurement of the narrowing does not correspond to the external aspect of the surgical narrowin

Echocardiographic Changes and Long-Term Clinical Outcomes in Pediatric Patients With Pulmonary Arterial Hypertension Treated With Bosentan for 72 Weeks:A Post-hoc Analysis From the FUTURE 3 Study

FormUlation of bosenTan in pUlmonary arterial hypeRtEnsion (FUTURE) 3 was a 24-week open-label, prospective, and randomized phase 3 study that assessed the pharmacokinetics of bosentan 2 mg/kg b.i.d. or t.i.d. in children with pulmonary arterial hypertension (PAH). We report findings from a post-hoc analysis that explored the prognostic value of echocardiographic changes during FUTURE 3 in relation to clinical outcomes observed during the 24-week core study and 48-week extension. Patients aged ≥3 months to <12 years (n = 64) received oral doses of bosentan 2 mg/kg b.i.d. or t.i.d. (1:1) for 24 weeks, after which they were eligible to enter the extension with continued bosentan administration. Echocardiographic evaluations were performed at baseline, Week 12, and 24 of the core study via central reading, and analyzed post-hoc for correlation with clinical outcomes (time to PAH worsening, time to death, and vital status). Sixty-four patients were randomized in the core study [median (IQR) age 3.8 (1.7–7.8) years]; and 58 patients (90.6%) entered the 48-week extension. Most of the patients (68.8%) were receiving ≥1 PAH medication at baseline. Echocardiographic changes during the core study were small but with high variability. There were statistically significant associations at Week 24 between worsening of the parameters, systolic left ventricular eccentricity index (LVEIS) and E/A ratio mitral valve flow, and the outcomes of time to death and time to PAH worsening. Additional studies that utilize simple and reproducible echocardiographic assessments are needed to confirm these findings and subsequently identify potential treatment goals in pediatric PAH