Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.

BACKGROUND: Infants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes. METHODS: Prospective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls. We targeted pre- and post-op absolute serum quantification of 9 key members of the arginine metabolism pathway by tandem mass spectrometry. Primary outcomes were length of stay (LOS) and post-Stage 2 hypoxemia. RESULTS: Pre-op cases showed alteration in 6 metabolites including decreased arginine and increased asymmetric dimethyl arginine (ADMA) levels compared to controls. Post-op cases demonstrated decreased arginine and citrulline levels persisting through 48 h. Adjusting for clinical variables, lower pre-op and 2 h post-op concentrations of multiple metabolites, including arginine and citrulline, were associated with longer post-op LOS (p < 0.01). Increased ADMA at 24 h was associated with greater post-op hypoxemia burden (p < 0.05). CONCLUSION: Arginine metabolism is impaired in interstage SVHD infants and is further deranged following Stage 2 palliation. Patients with greater metabolite alterations experience greater post-op morbidity. Decreased arginine metabolism may be an important driver of pathology in SVHD. IMPACT: Interstage infants with SVHD have significantly altered arginine-nitric oxide metabolism compared to healthy children with deficiency of multiple pathway intermediates persisting through 48 h post-Stage 2 palliation. After controlling for clinical covariates and classic catheterization-derived predictors of Stage 2 readiness, both lower pre-operation and lower post-operation circulating metabolite levels were associated with longer post-Stage 2 LOS while increased post-Stage 2 ADMA concentration was associated with greater post-op hypoxemia. Arginine metabolism mapping offers potential for development using personalized medicine strategies as a biomarker of Stage 2 readiness and therapeutic target to improve pulmonary vascular health in infants with SVHD.

Mitral Valve Replacement in Infants and Children: Five-Year Outcomes of the HALO Clinical Trial.

BACKGROUND: Repair is preferable for children with mitral valve disease, but mitral valve replacement (MVR) is occasionally necessary. This report presents the results of a multiinstitutional Investigational Device Exemption trial of the 15-mm St Jude (SJM) mechanical mitral valve (Abbott Structural Heart). METHODS: From May 2015 to March 2017, 23 children aged 0.4 to 27.4 months (mean, 7.8 months; 85% <1 year) weighing 2.9 to 10.9 kg (mean, 5.5 kg) at 15 centers underwent MVR with a 15-mm SJM mechanical mitral valve (intraannular, 45%; supraannular, 55%). A total of 21 (91%) of the children had undergone previous cardiac operations. Follow-up until death, valve explantation, or 5 years postoperatively was 100% complete. RESULTS: There were 6 deaths, all in the first 12 months; no death was valve related. Four patients required a pacemaker (2 supraannular, 2 intraannular). Three patients had thrombosis requiring valve explantation at 13, 21, and 35 days postoperatively. Two of these 3 patients were receiving low-molecular-weight heparin for anticoagulation, and the third had factor V Leiden deficiency. There were 5 nonfatal bleeding complications within 4 months of MVR (1-year freedom from bleeding, 71.0%). The 1- and 5-year freedom from death or valve explantation was 71.0%. CONCLUSIONS: In small children with severe mitral valve disease requiring MVR, the 15-mm SJM mechanical mitral valve provides satisfactory hemodynamics. Mortality and complications in these patients are not trivial. Low-molecular-weight heparin likely should be avoided as primary anticoagulation. Eventual valve replacement is inevitable.

Non-invasive myocardial tissue deformation and discoordination indices predict cardiac allograft vasculopathy in pediatric heart transplantation patients.

There is an urgent need for non-invasive imaging-based biomarkers suitable for diagnostic surveillance of cardiac allograft vasculopathy (CAV) in pediatric heart transplant (PHT) patients. The purpose of this study was to comprehensively investigate left ventricular (LV) myocardial deformation in conjunction with electromechanical discoordination in PHT. PHT patients with and without CAV were evaluated for echocardiography derived global longitudinal strain (GLS) and electromechanical discoordination indices including systolic stretch fraction (SSF) and diastolic relaxation fraction (DRF). SSF was increased in CAV(+) patients at the time of CAV diagnosis (median CAV(+) 5.0 vs. median CAV(-) 0.0, P = 0.008) and in the echocardiogram preceding the CAV diagnosis (median CAV(+) 29.0 vs. median CAV(-) 0.0, P < 0.001). DRF was also increased in the echocardiogram that preceded CAV diagnosis in CAV(+) patients (0.31 ± 0.08 vs. 0.25 ± 0.05, P = 0.008). The final model using indices 6-12 months prior to CAV diagnosis included GLS, SSF, and DRF providing AUC of 0.94 with sensitivity 98.5%, specificity 80.0%, positive predictive value 85.0%, and negative predictive value 94.1%. Systolic and diastolic electro-mechanical discoordination indices are significantly worse in PHT patients experiencing CAV. Non-invasive imaging guided surveillance using echocardiographic myocardial deformation indices can be improved by adding SSF and DRF to standard GLS measurements.

Hemi-Fontan and bidirectional Glenn operations result in flow-mediated viscous energy loss at the time of stage II palliation.

Background: Superior cavopulmonary connection (SCPC) for stage II palliation of hypoplastic left heart syndrome (HLHS) is achieved most frequently by either a bidirectional Glenn (BDG) or hemi-Fontan (HF) operation. The comparison of flow hemodynamic efficiency at the region of surgical reconstruction and in proximal pulmonary arteries has been evaluated primarily using computational modeling techniques with conflicting reports. The purpose of this descriptive study was to compare flow hemodynamics following stage II (BDG vs HF) using 4-dimensional flow magnetic resonance imaging (4D-Flow MRI) with particular focus on flow-mediated viscous energy loss (EL') under matched hemodynamic conditions. Methods: Patients with hypoplastic left heart syndrome (HLHS) who underwent either HF or BDG as part of stage II palliation underwent pre-Fontan 4D-Flow MRI. Patients were matched by the pulmonary vascular resistance index, net superior vena cava (SVC) flow, right pulmonary artery (RPA) and left pulmonary artery (LPA) size, and age. Maximum EL' throughout the cardiac cycle was calculated along the SVC-RPA and SVC-LPA tracts. Results: Eight patients who underwent HF as part of their stage II single ventricle palliation were matched with 8 patients who underwent BDG. There were no differences between the 2 groups in median volumetric indices, including end-diastolic volume (P = .278) and end-systolic volume (P = .213). Moreover, no differences were observed in ejection fraction (P = .091) and cardiac index (P = .324). There also were no differences in peak EL' measured along the SVC-RPA tract (median, 0.05 mW for HF vs 0.04 mW for BDG; P = .365) or along the SVC-LPA tract (median, 0.05 mW vs 0.04 mW; P = .741). Conclusions: The second stage of surgical palliation of HLHS using either HF or BDG results in similar flow-mediated viscous energy loss throughout the SCPC junction. 4D-Flow MRI and computational methods should be applied together to investigate flow hemodynamic patterns throughout the Fontan palliation and overall efficiency of the Fontan circuit.