Sensitized heart transplant candidates are evaluated for donor-specific anti-HLA IgG antibody (DSA) by Luminex single-antigen bead (SAB) testing (SAB-IgG) to determine donor suitability and help ...predict a positive complement-dependent cytotoxicity crossmatch (CDC-XM) by virtual crossmatching (VXM). However, SAB testing used for VXM does not correlate perfectly with CDC-XM results and individual transplant programs have center-specific permissible thresholds to predict crossmatch positivity. A novel Luminex SAB-based assay detecting C1q-binding HLA antibodies (SAB-C1q) contributes functional information to SAB testing, but the relationship between SAB strength and complement-binding ability is unclear.
In this retrospective study, we identified 15 pediatric and adult heart allograft candidates with calculated panel-reactive antibody (cPRA) >50% by SAB-IgG and compared conventional SAB-IgG results with SAB-C1q testing.
Pre- and post-transplant DSA by SAB-C1q correlated with DSA by SAB-IgG and also with CDC-XM results and early post-transplant endomyocardial biopsy findings. Individual HLA antibodies by SAB-IgG in undiluted sera correlated poorly with SAB-C1q; however, when sera were diluted 1:16, SAB-IgG results were well correlated with SAB-C1q. In some sera, HLA antibodies with low mean fluorescent intensity (MFI) by SAB-IgG exhibited high SAB-C1q MFIs for the same HLA antigens. Diluting or heat-treating these sera increased SAB-IgG MFI, consistent with SAB-C1q results. In 13 recipients, SAB-C1q-positive DSA was associated with positive CDC-XM and with early clinical post-transplant antibody-mediated rejection (cAMR).
Risk assessment for positive CDC-XM and early cAMR in sensitized heart allograft recipients are correlated with SAB-C1q reactivity.
Carnitine palmitoyl transferase II (CPT II) catalyzes the release of activated long-chain fatty acids from acylcarnitines into mitochondria for subsequent fatty acid oxidation. Depending on residual ...enzyme activity, deficiency of this enzyme leads to a spectrum of symptoms from early onset hypoglycemia, hyperammonemia, cardiomyopathy and death to onset of recurrent rhabdomyolysis in adolescents and young adults. We present a case of successful orthotopic heart transplantation in a patient with severe infantile onset cardiomyopathy due to CPT II deficiency identified through newborn screening. Excellent cardiac function is preserved 12 years post-transplantation; however, the patient has developed intermittent episodes of hyperammonemia and rhabdomyolysis later in childhood and early adolescence readily resolved with intravenous glucose. Successful heart transplant in this patient demonstrates the feasibility of this management option in patients with even severe forms of long chain fatty acid oxidation disorders.
•Excelent cardiac function can be maintained for at least a decade post-transplantation.•Cardiac transplantation may not prevent later onset rhabdomyolysis.
Cardiomyopathy is the most common presenting feature of Barth syndrome, often presenting in infancy with severe heart failure and cardiac dysfunction. Historically, affected infants commonly died ...early after presentation, sometimes before a diagnosis of Barth syndrome was made. With increases in awareness of Barth syndrome and in the care of infants with severe heart failure, survival of children with Barth syndrome and severe heart failure has improved. We describe our experience caring for five unrelated boys with Barth syndrome who presented with severe cardiomyopathy and heart failure prior to age 2 who have had marked improvement with long‐term response to medical heart failure therapy.
We have developed a new clinical research approach for the quantification of cellular proliferation in human infants to address unanswered questions about tissue renewal and regeneration. The ...approach consists of oral 15N-thymidine administration to label cells in S-phase, followed by Multi-isotope Imaging Mass Spectrometry for detection of the incorporated label in cell nuclei. To establish the approach, we performed an observational study to examine uptake and elimination of 15N-thymidine. We compared at-home label administration with in-hospital administration in infants with tetralogy of Fallot, a form of congenital heart disease, and infants with heart failure.
We examined urine samples from 18 infants who received 15N-thymidine (50 mg/kg body weight) by mouth for five consecutive days. We used Isotope Ratio Mass Spectrometry to determine enrichment of 15N relative to 14N (%) in urine.
15N-thymidine dose administration produced periodic rises of 15N enrichment in urine. Infants with tetralogy of Fallot had a 3.2-fold increase and infants with heart failure had a 4.3-fold increase in mean peak 15N enrichment over baseline. The mean 15N enrichment was not statistically different between the two patient populations (p = 0.103). The time to peak 15N enrichment in tetralogy of Fallot infants was 6.3 ± 1 hr and in infants with heart failure 7.5 ± 2 hr (mean ± SEM). The duration of significant 15N enrichment after a dose was 18.5 ± 1.7 hr in tetralogy of Fallot and in heart failure 18.2 ± 1.8 hr (mean ± SEM). The time to peak enrichment and duration of enrichment were also not statistically different (p = 0.617 and p = 0.887).
The presented results support two conclusions of significance for future applications: (1) Demonstration that 15N-thymidine label administration at home is equivalent to in-hospital administration. (2) Two different types of heart disease show no differences in 15N-thymidine absorption and elimination. This enables the comparative analysis of cellular proliferation between different types of heart disease.
Pericardial Decompression Syndrome Das, Nikkan; Feingold, Brian
The New England journal of medicine,
2023-Dec-21, Letnik:
389, Številka:
25
Journal Article
Identify pediatric heart transplant (HT) recipients with heterotaxy and other complex arrangements of cardiac situs (heterotaxy/situs anomaly) and compare mortality, morbidities, length of stay ...(LOS), and costs to recipients with congenital heart disease without heterotaxy/situs anomaly.
Using linked registry data (2001-2016), we identified 186 HT recipients with heterotaxy/situs anomaly and 1254 with congenital heart disease without heterotaxy/situs anomaly. We compared post-HT outcomes in univariable and multivariable time-to-event analyses. LOS and cost from HT to discharge were compared using Wilcoxon rank-sum tests. Sensitivity analyses were performed using stricter heterotaxy/situs anomaly group inclusion criteria and through propensity matching.
HT recipients with heterotaxy/situs anomaly were older (median age, 5.1 vs 1.6 years; P < .001) and more often black, Asian, Hispanic, or “other” nonwhite (54% vs 32%; P < .001). Heterotaxy/situs anomaly was independently associated with increased mortality (hazard ratio, 1.58; 95% confidence interval, 1.19-2.09; P = .002), even among 6-month survivors (hazard ratio, 1.86; 95% confidence interval, 1.09-3.16; P = .021). Heterotaxy/situs anomaly recipients more commonly required dialysis (odds ratio, 2.58; 95% confidence interval, 1.51-4.42; P = .001) and cardiac reoperation (odds ratio, 1.91; 95% confidence interval, 1.17-3.11; P = .010) before discharge. They had longer ischemic times (19.2 additional minutes range, 10.9-27.5 minutes; P < .001), post-HT intensive care unit LOS (16 vs 13 days; P = .012), and hospital LOS (26 vs 23 days; P = .005). Post-HT hospitalization costs were also greater ($447,604 vs $379,357; P = .001).
Heterotaxy and other complex arrangements of cardiac situs are associated with increased mortality, postoperative complications, LOS, and costs after HT. Although increased surgical complexity can account for many of these differences, inferior late survival is not well explained and deserves further study.
A male infant presented with neutropenia, growth delay, and death of a maternal uncle at age 2 years. Despite extensive evaluation over 10 years, Barth syndrome was not diagnosed until he presented ...in acute heart failure. Although late-onset cardiomyopathy is rare, persistence of common Barth features should have enabled earlier diagnosis
Sarcopenia is an increasingly recognized marker of frailty in cardiac patients. Patients with a history of congenital heart disease and Fontan procedure have a higher risk of developing progressive ...muscle wasting. Our objective was to determine if we could use routine cardiac MRI (CMR) for the surveillance of muscle wasting.
A retrospective study of all Fontan patients (n = 75) was conducted at our institution, with CMR performed from 2010 to 2022 and exercise stress testing performed within 12 months (4.3 ± 4.2 months). The skeletal muscle area (SMA) for the posterior paraspinal and anterior thoracic muscles were traced and indexed for body surface area (BSA). Patients were stratified by percentile into the upper and lower quartiles, and the two groups were compared. Multivariable regression was performed to control for sex and age.
There was a significant positive association of both anterior (r = 0.34,
= 0.039) and paraspinal (r = 0.43,
= 0.007) SMA to peak VO
. Similarly, paraspinal but not anterior SMA was negatively associated with the V
/V
(r = -0.45,
= 0.006). The upper quartile group had significantly more males (18/19 vs. 8/20;
= 0.0003) and demonstrated a significantly higher peak VO
(32.2 ± 8.5 vs. 23.8 ± 4.7,
= 0.009), a higher peak RER (1.2 ± 0.1 vs. 1.1 ± 0.04,
= 0.007), and a significantly lower V
/V
(32.9 ± 3.6 vs. 40.2 ± 6.2,
= 0.006) compared to the lowest quartile. The association of SMA to VO
peak and V
/V
was redemonstrated after controlling for sex and age.
Thoracic skeletal muscle area may be an effective surrogate of muscle mass and is correlated to several measures of cardiorespiratory fitness post-Fontan. CMR would be an effective tool for the surveillance of sarcopenia in post-Fontan patients given its accessibility and routine use in these patients.
Protein losing enteropathy after the Fontan operation Alsaied, Tarek; Lubert, Adam M.; Goldberg, David J. ...
International journal of cardiology congenital heart disease,
March 2022, 2022-03-00, 2022-03-01, Letnik:
7
Journal Article
Recenzirano
Odprti dostop
The Fontan or Fontan Kreutzer procedure is the culmination of staged, surgical palliation of functional single ventricle congenital heart disease, offering the potential for survival and good quality ...of life well into adulthood. As more patients with Fontan circulation age, a variety of complications involving almost every organ system may occur. Protein-losing enteropathy is a major cause of morbidity and mortality after the Fontan operation, occurring more often in patients with adverse hemodynamics and presenting weeks to years after Fontan surgery. The causes are not well understood, but likely include a combination of lymphatic insufficiency, high central venous pressure, loss of heparan sulfate from intestinal epithelial cells, abnormal mesenteric circulation, and intestinal inflammation. A comprehensive evaluation including multimodality imaging and cardiac catheterization is necessary to diagnose and treat any reversible causes. In advanced cases, early referral for heart transplantation evaluation or lymphatic decompression procedures (if the single ventricle function remains adequate) is indicated. Despite the improvement in detection and management options, the mortality remains high. Standardization of protein-losing enteropathy definition and management strategies will help facilitate interpretation of research and clinical experience, potentially fostering the identification of new therapies. Based on the published data, this review suggests a standardized approach to diagnosis and treatment.
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