Objective To characterize the epidemiology of and identify risk factors for neonatal cardiac surgery–associated acute kidney injury (CS-AKI) and determine its impact on clinical outcomes. Study ...design Using secondary analysis of data from an ongoing multiprovincial prospective cohort study, we studied 264 neonates undergoing complex cardiac repair. CS-AKI was defined based on the Acute Kidney Injury Network (AKIN) definition. We used regression modeling and survival analysis (adjusting for covariates) to evaluate associations. Results CS-AKI occurred in 64% of the neonates in our study cohort. Lower age, longer cardiopulmonary bypass time, hypothermic circulatory arrest, type of repair, lower preoperative serum creatinine (SCr) level, lower gestational age, and preoperative ventilation were independent risk factors for developing CS-AKI. Neonates with CS-AKI had longer times to extubation, intensive care discharge, and hospital discharge, after adjusting for covariates. Mortality was significantly increased in neonates with AKIN stage 2 or higher CS-AKI. The neonates with CS-AKI had a lower z -score for height at 2-year follow-up and were seen by more specialists. Conclusion Neonatal CS-AKI is common and independently predicts important clinical outcomes, including mortality. Many risk factors are similar to those in older children, but some are unique to neonates. The observation that lower baseline SCr predicts CS-AKI merits further study. The AKIN definition, based on preoperative SCr value, is a reasonable method for defining CS-AKI in neonates. Many previous studies of CS-AKI have excluded neonates; we suggest that future intervention studies on approaches to reducing CS-AKI incidence and improving outcomes should include neonates.
Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel ...posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid β-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and β-hydroxyacyl-CoA dehydrogenase (β-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid β-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and β-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor-1α, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation.
Sildenafil was recently approved for the treatment of pulmonary arterial hypertension. The beneficial effects of phosphodiesterase type 5 (PDE5) inhibitors in pulmonary arterial hypertension are ...thought to result from relatively selective vasodilatory and antiproliferative effects on the pulmonary vasculature and, on the basis of early data showing lack of significant PDE5 expression in the normal heart, are thought to spare the myocardium.
We studied surgical specimens from 9 patients and show here for the first time that although PDE5 is not expressed in the myocardium of the normal human right ventricle (RV), mRNA and protein are markedly upregulated in hypertrophied RV (RVH) myocardium. PDE5 also is upregulated in rat RVH. PDE5 inhibition (with either MY-5445 or sildenafil) significantly increases contractility, measured in the perfused heart (modified Langendorff preparation) and isolated cardiomyocytes, in RVH but not normal RV. PDE5 inhibition leads to increases in both cGMP and cAMP in RVH but not normal RV. Protein kinase G activity is suppressed in RVH, explaining why the PDE5 inhibitor-induced increase in cGMP does not lead to inhibition of contractility. Rather, it leads to inhibition of the cGMP-sensitive PDE3, explaining the increase in cAMP and contractility. This is further supported by our findings that, in RVH protein kinase A, inhibition completely inhibits PDE5-induced inotropy, whereas protein kinase G inhibition does not.
The ability of PDE5 inhibitors to increase RV inotropy and to decrease RV afterload without significantly affecting systemic hemodynamics makes them ideal for the treatment of diseases affecting the RV, including pulmonary arterial hypertension.
We compared the outcome of patients receiving bovine jugular vein grafts versus cryopreserved homografts for right ventricular outflow tract reconstruction.
Between 2000 and 2012, 379 conduits (244 ...bovine jugular vein grafts, 135 homografts) were implanted in 298 patients (median age 50 months) with a median follow-up of 3.4 years.
Freedom from reoperation at 1, 5, and 7 years was 96.3%, 79.3%, and 64.2% after bovine jugular vein graft and 94.6%, 75.7%, and 68.6% after homograft insertion (p = 0.086). There were 24 cases of endocarditis, 23 associated with bovine jugular vein grafts (9.4%) and 1 associated with a homograft (0.7%; p < 0.001) at median follow-up of 44 months (range, 15 days to 10 years) after conduit implantation. After endocarditis, 15 of 24 conduits were replaced. Three patients had recurrent endocarditis in the revised conduit. Multivariate logistic regression analysis showed age less than 3 years and endocarditis to be significant risk factors associated with conduit replacement. Age more than 3 years and bovine jugular vein grafts were significant risk factors for graft endocarditis. Patients more than 3 years of age at bovine jugular vein graft implantation had significantly lower freedom from reoperation (p = 0.01).
Compared with homograft conduits, the use of bovine jugular vein grafts for right ventricular outflow tract reconstruction was associated with a significantly higher incidence of bacterial endocarditis and conduit deterioration in older children at our institution. That may influence decision making regarding conduit choice for right ventricular outflow tract reconstruction. Patients and practitioners should be aware of the late risks of bacterial endocarditis after bovine jugular vein graft implantation.
Objective Infants and children who undergo cardiopulmonary bypass and cardiac surgery are at risk of postoperative fluid overload. Peritoneal dialysis catheter (PDC) and peritoneal dialysis are ...reported to be effective means of postoperative fluid management. We sought to test the hypothesis that PDC insertion in the operating room at the time of Norwood palliation would decrease the time to achieve a negative fluid balance in a group of neonates with hypoplastic left heart syndrome. Methods A single center randomized controlled trial was performed. We randomized neonates with hypoplastic left heart syndrome to prophylactic PDC, with or without dialysis, or standard care (ie, no PDC). Results Twenty-two neonates were included; 10 were randomized to PDC and 12 were randomized to standard care. The mean time to first postoperative negative fluid balance was 2.70 ± 1.06 days for the prophylactic PDC group and 2.67 ± 0.65 days for the standard care group ( P = .93). There was no difference between the 2 groups in time to lactate ≤ 2 mmol/L, maximum vasoactive-inotrope score on postoperative days 2 to 5, time to sternal closure, time to first extubation, modified clinical outcome score, or hospital length of stay. Twenty-one patients (95%) survived to hospital discharge. Four patients randomized to prophylactic PDC had 1 or more serious adverse events compared with no patients in the standard care group ( P = .03). Conclusions Prophylactic PDC, with or without dialysis, did not decrease the time to achieve a negative fluid balance after the Norwood procedure, did not alter physiological variables postoperatively, and was associated with more severe adverse events.
Transplantation of hearts from ABO-incompatible donors is contraindicated because of the risk of hyperacute rejection mediated by preformed antibodies in the recipient to blood-group antigens of the ...donor. This contraindication may not apply to newborn infants, who do not yet produce antibodies to T-cell-independent antigens, including the major blood-group antigens.
We studied 10 infants 4 hours to 14 months old (median, 2 months) who had congenital heart disease or cardiomyopathy and who received heart transplants from donors of incompatible blood type between 1996 and 2000. Serum isohemagglutinin titers were measured before and after transplantation. Plasma exchange was performed during cardiopulmonary bypass; no other procedures for the removal of antibodies were used. Standard immunosuppressive therapy was given, and rejection was monitored by means of endomyocardial biopsy. The results were compared with those in 10 infants who received heart transplants from ABO-compatible donors.
The overall survival rate among the 10 recipients with ABO-incompatible donors was 80 percent, with 2 early deaths due to causes presumed to be unrelated to ABO incompatibility. The duration of follow-up ranged from 11 months to 4.6 years. Two infants had serum antibodies to antigens of the donor's blood group before transplantation. No hyperacute rejection occurred; mild humoral rejection was noted at autopsy in one of the infants with antibodies. No morbidity attributable to ABO incompatibility has been observed. Despite the eventual development of antibodies to antigens of the donor's blood group in two infants, no damage to the graft has occurred. Because of the use of ABO-incompatible donors, the mortality rate among infants on the waiting list declined from 58 percent to 7 percent.
ABO-incompatible heart transplantation can be performed safely during infancy before the onset of isohemagglutinin production; this technique thus contributes to a marked reduction in mortality among infants on the waiting list.
Background
Tricuspid regurgitation (TR) in hypoplastic left heart syndrome (HLHS) is associated with morbidity and mortality. TR mechanisms and the impact of tricuspid valve repair (TVR) are unclear. ...We examined HLHS TR mechanisms, TVR’s impact on tricuspid valve (TV), and features of poor TVR durability.
Methods
We retrospectively compared 35 HLHS TVR cases and 35 age/stage-matched HLHS controls who do not undergo TVR. Pre-operative 3-dimensional echocardiography (3DE) assessed overall TV morphology (prolapse, normal, tethered), leaflet morphology, vena contracta area, and TR location. Two-dimensional echocardiography measured TV annulus diameter, RV fractional area change (RVFAC), sphericity, and TR grade at three time points (pre-op, early post-op, and latest follow-up).
Results
Pre-op, TVR group, and controls had no difference in age, RV function or shape, or TV dimension. TVR group most commonly had anterior leaflet prolapse followed by septal leaflet prolapse or tethering. TR jet arises centrally (63%) and anterior septally (26%). Posterior annuloplasty (69%), commissuroplasty (37%), and leaflet repair (37%) were surgical techniques commonly performed. At early post-op, TR grade and TV annulus decreased. At latest follow-up, TV annulus remained reduced; however, 50% had significant TR. 25% required TV reoperation. Larger vena contracta at TVR was associated with significant TR.
Conclusion
HLHS patients undergoing TVR had more anterior leaflet prolapse and central TR. While TVR initially reduces annular size and TR grade, 50% redevelop significant TR despite maintained annular reduction. The association of greater TR severity prior to repair with post-op recurrence raises the consideration for earlier repair of TR in HLHS patients.
Objective Comprehensive outcome assessment of children receiving cardiac extracorporeal life support. Methods From 2000 to 2004, 39 consecutive children (aged 1 day to 4.4 years) had cardiac ...extracorporeal life support. Neurodevelopmental follow-up of all survivors was performed more than 6 months after life support (aged 53 ± 12 months). Developmental delay was defined as a score of less than 70 on the Bayley Scales of Infant Development II or Wechsler Preschool and Primary Scale of Intelligence. Predictor variables for mortality (at 2 years' follow-up) and delay were examined by univariate and multivariate analyses. Results Indications for extracorporeal life support were progressive low cardiac output in 14 (36%), failed weaning from cardiopulmonary bypass in 13 (33%), cardiac arrest in 9 (23%), and hypoxia in 3 (8%). Cardiac anatomy was single ventricle in 16 (41%), biventricular in 21 (54%), and myocarditis in 2 (5%). Survival was 18 (46%) at hospital discharge and 16 (41%) at 2 years. In survivors, mental score was 73 ± 16 (normal 100 ± 15), and 8 (50%) had mental delay. Initiating extracorporeal life support during cardiopulmonary resuscitation and duration of this resuscitation were not associated with death or mental delay. On multivariable Cox regression, lactate on admission to the pediatric intensive care unit (hazard rate 1.13; 95% confidence intervals 1.08–1.27) and single ventricle anatomy (hazard rate 3.93; 95% confidence intervals 1.62–9.49) were associated with death at 2 years. Stepwise multiple regression found time for lactate to normalize on extracorporeal life support, highest inotrope score during 120 hours of life support, and chromosomal abnormality explained 76.7% of the variance in mental score. Conclusion Cardiac extracorporeal life support had a 41% 2-year survival. Potentially modifiable variables (time for lactate to normalize and highest inotrope score early during extracorporeal life support) explained 69% of mental score variance.
Abstract Failing single-ventricle patients have now come into focus as the next cohort where improvement in outcomes for mechanical circulatory support can be realized. There is a paucity of ...published patient reports or management protocols in this patient population. Increased interest exists in finding answers of how to bridge these patients to transplant. We review the current literature and describe our approach to the patient with univentricular heart needing mechanical circulatory support.
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