Background Mortality for infants undergoing complex cardiac surgery is >10% with a 30% to 40% risk of complications. Early identification and treatment of high‐risk infants remains challenging. Metabolites are small molecules that determine the minute‐to‐minute cellular phenotype, making them ideal biomarkers for postsurgical monitoring and potential targets for intervention. Methods and Results We measured 165 serum metabolites by tandem mass spectroscopy in infants ≤120 days old undergoing cardiopulmonary bypass. Samples were collected prebypass, during rewarming, and 24 hours after surgery. Partial least squares–discriminant analysis, pathway analysis, and receiver operator characteristic curve analysis were used to evaluate changes in the metabolome, assess altered metabolic pathways, and discriminate between survivors/nonsurvivors as well as upper/lower 50% intensive care unit length of stay. Eighty‐two infants had preoperative samples for analysis; 57 also had rewarming and 24‐hour samples. Preoperation, the metabolic fingerprint of neonates differed from older infants ( R 2 =0.89, Q 2 =0.77; P <0.001). Cardiopulmonary bypass resulted in progressive, age‐independent metabolic disturbance ( R 2 =0.92, Q 2 =0.83; P <0.001). Multiple pathways demonstrated changes, with arginine/proline ( P =1.2×10 −35 ), glutathione ( P =3.3×10 −39 ), and alanine/aspartate/glutamate ( P =1.4×10 −26 ) metabolism most affected. Six subjects died. Nonsurvivors demonstrated altered aspartate ( P =0.007) and nicotinate/nicotinamide metabolism ( P =0.005). The combination of 24‐hour aspartate and methylnicotinamide identified nonsurvivors versus survivors (area under the curve, 0.86; P <0.01), as well as upper/lower 50% intensive care unit length of stay (area under the curve, 0.89; P <0.01). Conclusions The preoperative metabolic fingerprint of neonates differed from older infants. Large metabolic shifts occurred after cardiopulmonary bypass, independent of age. Nonsurvivors and subjects requiring longer intensive care unit length of stay showed distinct changes in metabolism. Specific metabolites, including aspartate and methylnicotinamide, may differentiate sicker patients from those experiencing a more benign course.

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Pulmonary Hypertension (PH), the syndrome of elevated pressure in the pulmonary arteries, is associated with significant morbidity and mortality for affected children. PH is associated with a wide variety of potential underlying causes, including cardiac, pulmonary, hematologic and rheumatologic abnormalities. Regardless of the cause, for many patients the natural history of PH involves progressive elevation in pulmonary arterial resistance and pressure, right ventricular dysfunction, and eventually heart failure. In recent years, a number of pulmonary arterial hypertension (PAH)-targeted therapies have become available to reduce pulmonary artery pressure and improve outcome. A growing body of evidence in both the adult and pediatric literature demonstrates enhanced quality of life, functional status, and survival among treated patients. This review provides a description of select etiologies of PH seen in pediatrics and an update on the most recent data pertaining to evaluation and management of children with PH/PAH. The available evidence for specific classes of PAH-targeted therapies in pediatrics is additionally discussed.

1 -4 can be differentiated in patients with complete subclavian steal 5 -10 resulting from occlusion of the proximal subclavian or innominate artery (permanently reversed blood flow in the vertebral artery throughout the whole cardiac cycle). In the most common form of a vertebro-vertebral collateral circulation, the obstruction is bypassed by retrograde blood flow from the ipsilateral vertebral into the subclavian artery distal to the occlusion, and the reversed flow is fed by the contralateral vertebral artery. If the capacity of the contralateral vertebral artery is additionally reduced by stenosis or if this artery is occluded, a carotid-basilar collateral circulation with reversed basilar artery blood flow can develop. Furthermore, collateral circulation can arise from external carotid branches (occipital artery) that anastomose with muscular branches of the vertebral artery and with the thyrocervical and costocervical trunks. Only in innominate artery occlusion is there the possibility of a carotid-subclavian collateral circulation with reversed carotid and vertebral artery blood flow.The majority of these collateral pathways can be detected by directional continuous-wave (CW) Doppler ultrasonography. With vertebro-vertebral collateral circulation, the Doppler pulse curve of the

Background Kawasaki Disease (KD), a systemic vasculitis of medium sized vessels, is the most common cause of acquired heart disease among children in the developed world. Some KD patients demonstrate echocardiographic evidence of depressed myocardial mechanics. However, the incidence, etiology, and reversibility of abnormal mechanics in KD patients remain undefined. Methods and results We retrospectively studied 41 KD patients and measured myocardial strain and strain rate by velocity vector imaging from pre-treatment and convalescent echocardiograms. Pre-treatment procalcitonin, C-reactive protein (CRP), and coronary artery z-scores were obtained in all patients and compared between the groups with preserved versus depressed acute phase mechanics. The change in mechanics between the acute and convalescent phases was also assessed. Patients with initially low longitudinal strain improved by the convalescent period (mean difference - 4.0%; p<0.005) with the greatest improvement occurring in patients with the lowest initial strain (−7.3%; p<0.05). Patients with higher initial strain did not change significantly by the convalescent period. Patients with lower longitudinal and circumferential strain demonstrated higher median procalcitonin levels (1.2 vs. 0.3 ng/mL; p<0.05 and 1.8 vs. 0.4 ng/mL; p<0.05 respectively) and a trend towards higher CRP, but no difference in coronary artery z-scores. Strain rate was not associated with inflammatory markers or coronary artery z-scores. Conclusions The range of strain found in our cohort was large. Improvement in mean strain was driven primarily by patients with lower initial strain. Lower strain was associated with increased markers of systemic inflammation, but not proximal coronary artery changes.

One-stage surgery is a possible approach to highly symptomatic patients with severe multivascular disease and has acceptable early morbidity and mortality. Patients with severely impaired left ventricular function and unstable CAD carry a high risk of left heart failure and/or myocardial infarction during abdominal aortic surgery. Extracorporeal circulation protects the heart from the hemodynamic changes after aortic clamping or declamping during abdominal aortic surgery. The present study demonstrates that one-stage procedure is a reasonable option for this patient subgroup.

Adverse ventricle-ventricle interaction and resultant left ventricular (LV) dysfunction are a recognized pathophysiological component of disease progression in pulmonary arterial hypertension (PAH) and can be associated with electrical and mechanical dyssynchrony. The purpose of this study was to investigate the clinical and mechanistic implications of LV electromechanical dyssynchrony in children with PAH by using novel systolic stretch and diastolic relaxation discoordination indexes derived noninvasively from cardiac MRI (CMR). In children with PAH referred for CMR ( n = 64) and healthy controls ( n = 20), we calculated two novel markers of ventricular discoordination, systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF and DRF were evaluated with respect to 1) electrical dyssynchrony, 2) functional status, and 3) composite clinical outcomes. SSF was increased in patients with PAH compared with controls ( P = 0.004). There was no difference in DRF between PAH and control groups. There were no differences between groups in standard mechanical dyssynchrony and LV global circumferential strain. Increased SSF was associated with greater electrical dyssynchrony (QRS duration) as well as worse WHO functional class. SSF, DRF, mechanical dyssynchrony, and right ventricular (RV) volumes were prognostic for worse clinical outcomes. LV dyssynchrony indexes are altered in pediatric patients with PAH compared with controls in proportion with greater degrees of RV dilation. Patients with PAH with greater dyssynchrony have worse clinical outcomes. RV-induced increased LV electromechanical dyssynchrony therefore may be an important link in the causal pathway from PAH to clinically significant LV dysfunction. Since dyssynchrony could precede overt LV dysfunction, addition of ventricular synchrony analysis to CMR postprocessing protocols may be of clinical benefit. NEW & NOTEWORTHY We demonstrate that left ventricular discoordination indexes are altered in pediatric patients with pulmonary arterial hypertension compared with controls and pediatric patients with pulmonary arterial hypertension with greater dyssynchrony have worse clinical outcomes. Furthermore, there is evidence for the mechanism of right ventricular-induced left ventricular discoordination to include a combination of delayed early systolic electromechanical activation, late-systolic septal shift, and prolonged, postsystolic septal thickening.

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