Acute Pulmonary Vasodilator Testing and Long-Term Clinical Course in Segmental Pulmonary Vascular Disease.

Results of acute pulmonary vasodilator testing (AVT) and the outcome of medical therapy have not been described in patients with segmental pulmonary vascular disease (SPVD). We sought to compare the pulmonary vasodilatory effects of oxygen, oxygen with nitric oxide, and diltiazem, and to describe the clinical course of patients with SPVD and pulmonary hypertension. A retrospective review of 16 patients with pulmonary hypertension and SPVD involving 2-3 major lung segments who underwent AVT between January 2000 and December 2015 was performed. Baseline hemodynamic measurements were obtained with patients breathing ≤ 30% oxygen. AVT was performed using 100% oxygen, 100% oxygen with 20 ppm nitric oxide, 21-35% oxygen, and 21-35% oxygen with intravenous diltiazem. The events associated with their long-term care were described. Nine of 16 patients were acutely responsive during AVT using the Sitbon criteria. The change in mean pulmonary artery pressure with oxygen or oxygen with nitric oxide (19 ± 12 mmHg) was significantly greater than the change with diltiazem (7 ± 5 mmHg). Pulmonary vasodilator therapy was initiated or escalated after AVT in 12 patients. Five patients subsequently experienced a decrease in mean pulmonary artery pressure or normalization in B-type natriuretic peptide. Three patients experienced adverse events associated with therapy. The actuarial survival was 94% over a period of 1-20 years. This study suggests that AVT can be used to identify patients with SPVD who are reactive to oxygen, oxygen with nitric oxide, and diltiazem. Clinical improvement was temporally associated with pulmonary vasodilator therapy in some patients with few adverse effects.

The impact of ischemic time on early rejection after pediatric heart transplant.

Prolonged graft ischemia may be a risk factor for early rejection post-HTx, but this has not been well studied in children. Furthermore, factors moderating the association between IT and early rejection have not been investigated. From 2004 to 2012, pediatric HTx recipients (n = 2381) were identified from the UNOS database. A ROC curve determined the optimal IT discriminating patients by the presence of early rejection. Separate univariate analyses identified factors associated with: (i) early (prior to hospital discharge) rejection, and (ii) IT. A multivariable logistic regression assessed independent risk factors for early rejection. We included interaction terms to evaluate whether IT's independent risk effect on early rejection is moderated via interaction with associated factors found in univariate analysis. Longer IT was associated with an increased risk of early rejection. In multivariable analysis, IT > 3.1 hours was an independent risk factor for early rejection (AOR 1.44, P = .01). No interaction terms between IT and any associated factors were significant. Longer IT is an independent risk for early rejection in pediatric HTx recipients. Better understanding the association between IT and early rejection may identify interventions to mitigate this risk.

Clinical significance of anti-HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis.

While VAD use in pediatric patients has previously been associated with anti-HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of anti-HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients post-HTx (N=1288) with pre-HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and non-MCS groups after stratification by PRA and age. VAD recipients were more likely to produce anti-HLA antibodies than non-MCS patients (25.5% vs 10.5% had PRA>10%, P<.0001). Sensitized VAD patients (PRA>10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized non-MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15-month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of anti-HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VAD-associated antibodies and early rejection is unclear and warrants further investigation.

Immune Abnormalities in Fontan Protein-Losing Enteropathy: A Case-Control Study.

OBJECTIVE: To comprehensively characterize the immunologic characteristics of patients with protein-losing enteropathy (PLE) post-Fontan and compare them with patients without PLE post-Fontan. STUDY DESIGN: Patients with PLE post-Fontan and age-matched controls post-Fontan were prospectively studied with laboratory markers of immune function. Infectious history was obtained by interview and chart review. The groups' demographics, cardiac history, immune characteristics, and infection history were compared using appropriate 2-group statistics. RESULTS: A total of 16 patients enrolled (8 patients with PLE and 8 controls). All patients with PLE had lymphopenia compared with 25% of controls (P = .01). All patients with PLE had markedly depressed CD4 T cell counts (median 58 cells/µL) compared with controls (median 450 cells/µL, P = .0002); CD4% was also low in the PLE group (12.3%) and normal in control (36.9%, P = .004). Both groups had mildly depressed CD8 T cells and normal to slightly elevated natural killer and B-cell subsets. A majority of patients with PLE (62.5%) had negative titers to measles, mumps, and rubella vaccination, compared with no control Fontan with a negative titer (P = .03). Despite profoundly low CD4 counts, the frequency of infection was not different between groups with no reported opportunistic infections. CONCLUSIONS: Patients with Fontan-associated PLE have extensive quantitative immune abnormalities, particularly CD4 deficiency. These immune abnormalities are similar to those found in non-Fontan patients with PLE caused by intestinal lymphangiectasia.

Grand rounds: nephrotoxicity in a young child exposed to uranium from contaminated well water.

CONTEXT: Private wells that tap groundwater are largely exempt from federal drinking-water regulations, and in most states well water is not subject to much of the mandatory testing required of public water systems. Families that rely on private wells are thus at risk of exposure to a variety of unmeasured contaminants. CASE PRESENTATION: A family of seven--two adults and five children--residing in rural northwestern Connecticut discovered elevated concentrations of uranium in their drinking water, with levels measured at 866 and 1,160 microg/L, values well above the U.S. Environmental Protection Agency maximum contaminant level for uranium in public water supplies of 30 microg/L. The uranium was of natural origin, and the source of exposure was found to be a 500-foot well that tapped groundwater from the Brookfield Gneiss, a geologic formation known to contain uranium. Other nearby wells also had elevated uranium, arsenic, and radon levels, though concentrations varied widely. At least one 24-hr urine uranium level was elevated (> 1 microg/24 hr) in six of seven family members (range, 1.1-2.5 microg/24 hr). To assess possible renal injury, we measured urinary beta-2-microglobulin. Levels were elevated (> 120 microg/L) in five of seven family members, but after correction for creatine excretion, the beta-2-microglobulin excretion rate remained elevated (> 40 microg/mmol creatinine) only in the youngest child, a 3-year-old with a corrected level of 90 microg/mmol creatinine. Three months after cessation of well water consumption, this child's corrected beta-2-microglobulin level had fallen to 52 microg/mmol creatinine. SIGNIFICANCE: This case underscores the hazards of consuming groundwater from private wells. It documents the potential for significant residential exposure to naturally occurring uranium in well water. It highlights the special sensitivity of young children to residential environmental exposures, a reflection of the large amount of time they spend in their homes, the developmental immaturity of their kidneys and other organ systems, and the large volume of water they consume relative to body mass.

Usefulness of Diastolic Strain Measurements in Predicting Elevated Left Ventricular Filling Pressure and Risk of Rejection or Coronary Artery Vasculopathy in Pediatric Heart Transplant Recipients.

In pediatric heart transplant recipients, elevated pulmonary capillary wedge pressure (PCWP) is associated with rejection and coronary artery vasculopathy. This study aimed to evaluate which echocardiographic parameters track changes in PCWP and predict adverse outcomes (rejection or coronary artery vasculopathy). This prospective single-center study enrolled 49 patients (median 11.4 years old, interquartile range 7.4 to 16.5) at time of cardiac catheterization and echocardiography. Median follow-up was 2.4 years (range 1.2 to 3.1 years), with serial testing per clinical protocol. Ratio of early mitral inflow to annular velocity (E/E'), left atrial (LA) distensibility, peak LA systolic strain, E/left ventricular (LV) diastolic strain, and E/LV diastolic strain rate were measured from echocardiograms. Increase in PCWP ≥3 mm Hg was associated with changes in LA distensibility, E/E', and E/LV diastolic strain, with highest area under the receiver operating characteristic curve for E/LV diastolic strain (0.76). In 9 patients who subsequently developed rejection or coronary artery vasculopathy, E/LV diastolic strain rate at baseline differed from patients without events (median 57.0 vs 43.6, p = 0.02). On serial studies, only change in LV ejection fraction differed in patients with events (median -10% vs -1%, p = 0.01); decrease in LV ejection fraction of -19% had a specificity of 100% and sensitivity of 44%. In conclusion, LV diastolic strain and strain rate measurements can track changes in PCWP and identify patients at risk for subsequent rejection or coronary artery vasculopathy. Further studies are necessary to confirm these data in a larger cohort.