Purpose
To assess the feasibility of direct intra-lymphatic administration of diluted ferumoxytol as a T1-positive contrast agent for dynamic contrast-enhanced MR lymphangiography (DCMRL) imaging of ...the central lymphatics in children with renal disease.
Methods
In vitro scan of dilute ferumoxytol was initially performed using time-resolved and high-resolution 3D gradient echo (GRE) sequences with short TE values (1 to 1.5 ms). A ferumoxytol concentration of 0.25 to 0.40 mg/mL was found to retain high signal in the T1-weighted sequences. DCMRL was then performed in 4 children with renal disease with the same 3D GRE sequences administrating diluted ferumoxytol via intra-mesenteric (IM), intra-hepatic (IH), and intra-nodal (IN) routes (6 to 9 mL to each site; average total dose of 0.75 mg/kg) by slow hand injection (0.5 to 1.0 mL/min). The signal-to-noise ratio (SNR) of the lymphatics was measured for quantitative evaluation.
Results
Ferumoxytol-enhanced DCMRL was technically successful in all patients. Contrast conspicuity within the lymphatics was sufficient without subtraction. The mean SNR was significantly higher than the muscle (50.1 ± 12.2 vs 13.2 ± 2.8;
t
= 15.9;
p
< .001). There were no short-term complications attributed to the administration of ferumoxytol in any of the four patients.
Conclusion
Magnetic resonance lymphangiography using ferumoxytol via IN, IH, and IM access is a new method to directly visualize the central lymphatic system and can be applied safely in patients with renal failure based on our preliminary report of four cases. Ferumoxytol-enhanced DCMRL shows diagnostic image quality by using 3D GRE sequences with short TE values and appropriate dilution of ferumoxytol.
Key Points
•
MR lymphangiography using ferumoxytol
via
intra-nodal, intra-hepatic, and intra-mesenteric access is a new method to directly visualize the central lymphatic system from the groin to the venous angle.
•
FDCMRL can be applied safely in patients with renal failure based on our preliminary report of four cases.
•
FDCMRL shows diagnostic image quality by using 3D GRE sequences with short TE values and appropriate dilution of the ferumoxytol.
Operative correction of tetralogy of Fallot frequently results in pulmonary insufficiency and chronic volume overload, which have been linked to increased risk for adverse outcomes. No consensus ...recommendations for the timing of pulmonary valve replacement (PVR) exist. The aim of this study was to examine the pattern of PVR in the United States from 2004 to 2012. The Pediatric Health Information Systems database was used to perform an observational study of children and adults ≥10 years of age with diagnoses of tetralogy of Fallot who underwent PVR at 35 centers in the United States from 2004 and 2012, to assess the rate of PVR and the age at which is performed. Mixed-effects multivariate regression was used to account for patient-level covariates and center-level covariance. Additional analyses assessed for trends in cost, hospital length of stay (LOS), intensive care unit LOS, and in-hospital mortality over the study period. In total, 799 subjects at 35 centers underwent PVR over the study period. The number of PVRs performed per year increased significantly over the study period. There was significant between-center heterogeneity in age at PVR (p <0.001). Age at PVR, intensive care unit LOS, hospital LOS, and cost did not change over the study period. In conclusion, PVR in patients with tetralogy of Fallot is being performed more frequently, without an accompanying change in the age at PVR or other measurable outcomes. There is significant variability in the age at which PVR is performed among centers across the United States. This highlights the need for additional research guiding the optimal timing of PVR.
Plastic bronchitis is a rare, potentially life-threatening complication after Fontan operation. Hemodynamic alterations (elevated central venous pressure and low cardiac output) likely contribute to ...the formation of tracheobronchial casts composed of inflammatory debris, mucin, and fibrin. Pathologic studies of cast composition support medical treatment with fibrinolytics such as inhaled tissue plasminogen activator (t-PA).
This was a retrospective case series of medical, surgical, and catheter-based treatment of patients with plastic bronchitis after cavopulmonary palliation.
Included were 14 patients (86% male, 93% white). Median age at Fontan operation was 2.7 years (range, 1.2 to 4.1 years), with median interval to plastic bronchitis presentation of 1.5 years (range, 9 days to 15.4 years). Cast composition was available for 11 patients (79%) and included fibrin deposits in 7. All patients were treated with pulmonary vasodilators, and 13 (93%) were treated with inhaled t-PA. Hemodynamically significant lesions in the Fontan pathway were addressed by catheter-based (n=9) and surgical (n=3) interventions. Three patients (21%) underwent heart transplantation. Median follow-up was 2.7 years (range, 0.6 to 8.7 years). Symptoms improved, such that 6 of 13 patients (46%) were weaned off t-PA. Rare or episodic casts are successfully managed with outpatient t-PA in most of the other patients. Of the 3 patients who underwent heart transplant, 2 are asymptomatic and 1 has recurrent casts in the setting of elevated filling pressures and rejection.
A systematic step-wise algorithm that includes optimization of hemodynamics, aggressive pulmonary vasodilation, and inhaled t-PA is an effective treatment strategy for patients with plastic bronchitis after cavopulmonary connection.
A need exists to develop alternative approaches to VT ablation that provide an improved delineation of the arrhythmogenic substrate.
The aim of this study was to evaluate the hypotheses that: (1) the ...heterogeneous zone (HZ, a mixture of normal-appearing tissue and scar) in magnetic resonance imaging (MRI) contains the critical isthmus(es) for ventricular tachycardia (VT), (2) successful ablation of VT would include ablation in the HZ, and (3) inadequate ablation of HZ allows for VT recurrence.
MRI and an electrophysiology study (EP) were performed in a model of chronic myocardial infarction in 17 pigs. In animals that were inducible for VT, ablations were done guided by standard EP criteria and blinded to the MRI. After ablation, electroanatomic mapping results were co-registered with MRI.
In 8 animals, 22 sustained monomorphic VTs were generated. The HZ was substantially larger in inducible (n = 8) compared with noninducible animals (n = 9) 25% ± 10% vs 13% ± 5% of total scar, respectively, P = .007. Acutely, all targeted VTs were successfully ablated, and postprocedure analysis showed that at least 1 ablation was in the HZ in each animal. In 5 animals, a second EP and MRI were performed 1 week after ablation. Three animals had inducible VTs, and MRI showed that the HZ had not been completely ablated. In contrast, the 2 animals without inducible VT revealed no remaining HZ.
These findings show that MRI can define an HZ and determine the location of ablated lesions. The HZ may be a promising ablation target to cure ischemic VTs. Remnants of HZ after ablation may be the substrate for clinical relapses.
Objectives
To characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after lymphatic ...intervention.
Methods
In this retrospective study, patients with intra-hepatic lymphangiography from May 2014 – April 2019 at our institution were included. Imaging review was performed and hepatic lymphatic connections and flow patterns were characterized. Clinical data were reviewed and comparisons between patients undergoing lymphatic intervention with or without abnormal hepatic lymphatics were performed.
Results
During the study period, 105 patients underwent intra-hepatic lymphangiography. Primary clinical presentation included ascites (19/105), chylothorax (27/105), plastic bronchitis (PB) (17/105), and protein losing enteropathy (PLE) (42/105). Five categories of hepatic lymphatic connections and flow patterns were identified (%): normal (25%, 26/105), hepatoperitoneal (12%, 13/105), hepatopulmonary (10.5%, 11/105), hepatomesenteric (7.5%, 8/105), and hepatoduodenal (41%, 43/105) with four patients having more than one abnormal pattern. A comparison between clinical presentation and imaging category revealed an increased likelihood of having ascites with hepatoperitoneal (
p
< .0001), chylothorax/PB with hepatopulmonary (
p
= .01), and PLE with hepatoduodenal (
p
< .001) connections. Seventy-six patients had a lymphatic intervention, 24% with normal, and 76% with abnormal liver lymphatics. There was no difference in length of hospital stay or mortality between the two groups, but there was a prolonged time to symptom resolution (
p
= .006) and persistent symptoms after 6 months (5% vs 44%,
p
= .002) in the group with abnormal liver lymphatics.
Conclusion
We identified five liver lymphatic imaging categories with a substantial correlation to presenting lymphatic disease. Abnormal imaging patterns correlated with increased morbidity. Evaluation of liver lymphatics should be considered in patients with a systemic lymphatic disease if central lymphatic imaging is normal.
Key Points
•
We identified five liver lymphatic imaging patterns: normal, hepatoperitoneal, hepatomesenteric, hepatopulmonary, and hepatoduodenal.
•
Imaging patterns were correlated with disease presentation (normal – chylothorax/PB, hepatoperitoneal – ascites/chylothorax, hepatopulmonary – chylothorax/PB, hepatoduodenal – PLE).
•
Abnormal imaging patterns correlated with increased morbidity.
Children with hypoplastic left heart syndrome share unique hemodynamic features that alter lymphatic integrity at all stages of palliation. Lymphatic congestion is almost universal in this patient ...group to some extent. It may lead to reversal of lymphatic flow, the development of abnormal lymphatic channels and ultimately decompression and loss of protein rich lymphatic fluid into extra lymphatic compartments in prone individuals. Some of the most devastating complications that are associated with single ventricle physiology, notably plastic bronchitis and protein losing enteropathy, have now been proven to be lymphatic in origin. Based on the new pathophysiologic concept new diagnostic and therapeutic strategies have recently been developed. Dynamic contrast magnetic resonance lymphangiography is now mainstay in diagnosis of lymphatic insufficiency and allows a thorough assessment of anatomy and function of the main lymphatic compartments through intranodal, intrahepatic and intramesenteric lymphatic imaging. Contrast enhanced ultrasound can evaluate thoracic duct patency and conventional fluoroscopic lymphangiography has been refined for evaluation of patients where magnetic resonance imaging cannot be performed. Novel lymphatic interventional techniques, such as thoracic duct embolization, selective lymphatic duct embolization and liver lymphatic embolization allow to seal abnormal lymphatic networks minimally invasive and have shown to resolve symptoms. Innominate vein turn-down procedures, whether surgical or interventional, have been designed to reduce lymphatic afterload and increase systemic preload effectively in the failing Fontan circulation. Outflow obstruction can now be managed with new microsurgical techniques that create lympho-venous anastomosis. Short term results for all of these new approaches are overall promising but evidence is sparse and long-term outcome still has to be defined. This review article aims to summarize current concepts of lymphatic flow disorders in single ventricle patients, discuss new emerging diagnostic and therapeutic strategies and point out lacks in evidence and needs for further research on this rapidly growing topic.
Background Recent studies suggest that lymphatic congestion plays a role in development of late Fontan complications, such as protein-losing enteropathy. However, the role of the lymphatic ...circulation in early post-Fontan outcomes is not well defined. Methods and Results This was a retrospective, single-center study of patients undergoing first-time Fontan completion from 2012 to 2017. The primary outcome was
≤6 months after surgery, a composite of death, Fontan takedown, extracorporeal membrane oxygenation, chest tube drainage >14 days, cardiac catheterization, readmission, or transplant. Complication causes were assigned to 1 of 4 groups: (1) Fontan circuit obstruction, (2) ventricular dysfunction or atrioventricular valve regurgitation, (3) persistent pleural effusions
Fontan obstruction or ventricular dysfunction, and (4) chylothorax or plastic bronchitis. T2-weighted magnetic resonance imaging sequences were used to assess for lymphatic perfusion abnormality. The cohort consisted of 238 patients. Fifty-eight (24%) developed early complications: 20 of 58 (34.5%) in group 1, 8 of 58 (14%) in group 2, 18 of 58 (31%) in group 3, and 12 of 58 (20%) in group 4. Preoperative T2 imaging was available for 126 (53%) patients. Patients with high-grade lymphatic abnormalities had 6 times greater odds of developing early complications (
=0.001). Conclusions There is substantial morbidity in the early post-Fontan period. Half of those who developed early complications had lymphatic failure or persistent effusions unrelated to structural or functional abnormalities. Preoperative T2 imaging demonstrated that patients with higher-grade lymphatic perfusion abnormalities were significantly more likely to develop early complications. This has implications for risk stratification and optimization of patients before Fontan palliation.
Outcomes for transcatheter pulmonary valve replacement (TC-PVR) and operative pulmonary valve replacement (S-PVR) are excellent. Thus, their respective cost is a relevant clinical outcome. We ...performed a retrospective cohort study of children and adults who underwent PVR at age ≥8 years from January 1, 2011, to December 31, 2013, at 35 centers contributing data to the Pediatric Health Information Systems database to address this question. A propensity score–adjusted multivariable analysis was performed to adjust for known confounders. Secondary analyses of department-level charges, risk of re-admission, and associated costs were performed. A total of 2,108 PVR procedures were performed in 2,096 subjects (14% transcatheter and 86% operative). The observed cost of S-PVR and TC-PVR was not significantly different (2013US $50,030 vs 2013US $51,297; p = 0.85). In multivariate analysis, total costs of S-PVR and TC-PVR were not significantly different (p = 0.52). Length of stay was shorter after TC-PVR (p <0.0001). Clinical and supply charges were greater for TC-PVR (p <0.0001), whereas laboratory, pharmacy, and other charges (all p <0.0001) were greater for S-PVR. Risks of both 7- and 30-day readmission were not significantly different. In conclusion, short-term costs of TC-PVR and S-PVR are not significantly different after adjustment.
Background Protein-losing enteropathy (PLE) is a significant cause of morbidity and mortality in congenital heart disease patients with single ventricle physiology. Intrahepatic dynamic ...contrast-enhanced magnetic resonance lymphangiography (IH-DCMRL) is a novel diagnostic technique that may be useful in characterizing pathologic abdominal lymphatic flow in the congenital heart disease population and in diagnosing PLE. The objective of this study was to characterize differences in IH-DCMRL findings in patients with single ventricle congenital heart disease with and without PLE. Methods and Results This was a single-center retrospective study of IH-DCMRL findings and clinical data in 41 consecutive patients, 20 with PLE and 21 without PLE, with single ventricle physiology referred for lymphatic evaluation. There were 3 distinct duodenal imaging patterns by IH-DCMRL: (1) enhancement of the duodenal wall with leakage into the lumen, (2) enhancement of the duodenal wall without leakage into the lumen, and (3) no duodenal involvement. Patients with PLE were more likely to have duodenal involvement on IH-DCMRL than patients without PLE (
<0.001). Conclusions IH-DCMRL findings of lymphatic enhancement of the duodenal wall and leakage of lymph into the duodenal lumen are associated with PLE. IH-DCMRL is a useful new modality for characterizing pathologic abdominal lymphatic flow in PLE and might be useful as a risk-assessment tool for PLE in at-risk patients.
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