Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart DiseaseCLINICAL PERSPECTIVE
Background—Plastic bronchitis is a potentially fatal disorder occurring in children with single-ventricle physiology, and other diseases, as well, such as asthma. In this study, we report findings of abnormal pulmonary lymphatic flow, demonstrated by MRI lymphatic imaging, in patients with plastic bronchitis and percutaneous lymphatic intervention as a treatment for these patients.
Methods and Results—This is a retrospective case series of 18 patients with surgically corrected congenital heart disease and plastic bronchitis who presented for lymphatic imaging and intervention. Lymphatic imaging included heavy T2-weighted MRI and dynamic contrast-enhanced magnetic resonance lymphangiogram. All patients underwent bilateral intranodal lymphangiogram, and most patients underwent percutaneous lymphatic intervention. In 16 of 18 patients, MRI or lymphangiogram or both demonstrated retrograde lymphatic flow from the thoracic duct toward lung parenchyma. Intranodal lymphangiogram and thoracic duct catheterization was successful in all patients. Seventeen of 18 patients underwent either lymphatic embolization procedures or thoracic duct stenting with covered stents to exclude retrograde flow into the lungs. One of the 2 patients who did not have retrograde lymphatic flow did not undergo a lymphatic interventional procedure. A total of 15 of 17(88%) patients who underwent an intervention had significant symptomatic improvement at a median follow-up of 315 days (range, 45–770 days). The most common complication observed was nonspecific transient abdominal pain and transient hypotension.
Conclusions—In this study, we demonstrated abnormal pulmonary lymphatic perfusion in most patients with plastic bronchitis. Interruption of the lymphatic flow resulted in significant improvement of symptoms in these patients and, in some cases, at least temporary resolution of cast formation.
Plastic bronchitis (PB) is a relatively rare but devastating complication in patients after single-ventricle palliation. Noncardiac causes of PB include cystic fibrosis, sickle cell anemia, and asthma, and lymphangiomatosis, as well.1,2 The disease is caused by exudation of proteinaceous material and cells in the airways leading to branching cast formation. Once formed, the casts are either expectorated by coughing or can lead to asphyxiation.
Clinical Perspective on p 1170
The prevalence of PB in patients after total cavopulmonary connection (TCPC) is estimated to be 4%.3,4 The diagnosis is often difficult, and physical examination and radiological findings are nonspecific and may consist of diminished breath sounds and patchy consolidations on chest x-rays. Spontaneous expectoration of the cast is often the first presentation of the disease, and bronchoscopy is performed to confirm the diagnosis by demonstrating casts in the airways. Lymphatic involvement has been considered to be part of the pathological process in PB because of the dilation of the lymphatic vessels found at lung biopsies and the abnormal lung tracer intake shown by lymphoscintigraphy.5–7
Poor understanding of the pathogenesis of the disease has resulted in variability in therapies across centers. Interventions aimed at lowering venous pressure have been reported to reduce cast formation.8 Medical treatment with sildenafil, steroids, and mucolytics have also been reported to improve symptoms.9–11 Finally, heart transplantation can result in long-term resolution of the disease.12 Assuming central lymphatic involvement, thoracic duct (TD) ligation has been performed with reports of symptomatic improvement in some cases.7,13,14 The wide range of therapies reported is a testament to the fact that none are reliably efficacious; and, most importantly, morbidity and mortality for the condition remain high.4
Dynamic contrast-enhanced magnetic resonance lymphangiogram (DCMRL) has recently been described as a method of imaging the central lymphatic system.15,16 Dori et al16,17 have recently reported on the use of this technique and T2-weighted MRI to characterize lymphatic abnormalities in patients with PB.
Percutaneous lymphatic procedures, such as TD embolization, are well-established, less invasive alternatives to surgical interventions in cases of chylous leaks.18 Recently, we described the first reported case of the successful use of a modification of this technique and DCMRL in the successful treatment of a patient with PB.16
In this study, we expand on the previous case report and examine our broader experience and short-term outcome with the percutaneous treatment of PB in patients with congenital heart diseases. Preprocedure imaging using DCMRL and T2 lymphatic mapping provided insight into the etiology and pathogenesis of PB and were used to guide the procedures.
Permission from the Institutional Review Board was obtained before the initiation of this study. This study is a retrospective review of data of 18 patients with PB and congenital heart disease who have undergone lymphatic imaging and interventions at our institution. All procedures were performed under general anesthesia. Flexible bronchoscopy was initially performed to remove residual casts and to facilitate general anesthesia. Extracted casts were sent for pathology examination.
Magnetic Resonance Imaging
MRI was performed in an XMR suite that couples an MR scanner with a catheterization laboratory (Siemens, Erlangen, Germany). With the use of ultrasound guidance, bilateral inguinal lymph nodes were directly accessed with 25-gauge spinal needles attached to a short connector tubing (BD Medical, Franklin Lakes, NJ), similar to the method described by Nadolski et al.19 A small amount of Lipiodol (Guerbet LLC; Bloomington, IN) was injected under fluoroscopic guidance to confirm the correct position of the needles inside the lymph nodes. After stabilizing the needle, the patients were transferred to the MRI suite.
MRI was performed on a 1.5 T Siemens Magnetom Avanto scanner (Siemens, Erlangen, Germany). T2-weighted MRI lymphatic imaging was performed by using a respiratory navigated and cardiac-gated 3-dimensional turbo spin echo sequence with the following parameters: matrix 256×256, field of view 300 to 450, repetition time 2500, time to echo 650, flip angle 140, voxel size 1.2×1.2×1.2 mm, scan time 2 to 5 minutes. For dynamic imaging 2 to 8 mL of undiluted gadopentetate dimeglumine (Magnevist, Bayer Healthcare Pharmaceuticals Inc., Wayne, NJ) was injected by hand into each lymph node at a rate of 0.5 to 1 mL/min. One minute after the injection, scanning was initiated by using the Syngo TWIST sequence. Typical scanning parameters were: matrix 320×240, field of view 300 to 450, repetition time 3, time to echo 1, flip angle 25, slice thickness 1.2, isotropic voxel size 1.2×1.2×1.2, scan time ≈15 minutes. This was followed by additional scans with a high-resolution navigator gated 3-dimensional flash inversion recovery sequence. Typical scanning parameters were as follows: matrix 320×240, field of view 300 to 450, repetition time 300, time to echo 1.5, flip angle 20, slice thickness 1.2, isotropic voxel size 1.2×1.2×1.2. In all patients, the scan area covered the neck, chest, and abdomen as caudally as feasible. Volume rendering and further processing of the 3-dimensional volume, maximum intensity projection, and coronary projection were performed on a Syngo InSpace Dynamic workstation (Siemens, Erlangen, Germany).
All patients in the study underwent cardiac catheterization before lymphatic intervention. Embolization of venovenous collateral vessels near the main lymphovenous junction was performed to reduce the risks of systemic embolization from shunting of the Lipiodol into systemic circulation through the collateral vessels. In patients with a fenestration, temporary balloon occlusion of the fenestration during the lymphatic intervention procedure was performed for the same reason.
Initially, by using the method of Nadolski and Itkin,20 intranodal lymphangiogram was performed to opacify a target central lymphatic vessel. After identification of the target vessel (larger lumbar lymphatics or cisterna chyli), access to this vessel was performed by using the transabdominal approach as previously described.20 In short, the target lymphatic vessel was accessed through an anterior transabdominal approach using a 21- to 22-gauge Chiba needle (Cook Medical Inc, Bloomington, IN). A V18 control guide wire (Boston Scientific, Natick, MA) was then advanced into the TD and manipulated cephalad. Over the wire, a 60-cm 2.3F Rapid Transit microcatheter (Cordis Corp, Warren, NJ) was advanced further into the TD. Imaging of the TD and its branches was then performed. Embolization of the lymphatic ducts were performed using Lipiodol, MReye coils (Cook Medical, Bloomington, IN), and glue (TRUFILL n-BCA Liquid Embolic System, DePuy Synthes, Warsaw, IN). Four embolization techniques were used in this study: (1) embolization of the TD with endovascular coils and glue; (2) selective embolization of the branches of the TD with Lipiodol and glue; (3) embolization of TD with Lipiodol while impeding flow in the TD by external compression of cutaneous lymphatic collaterals and transvenous balloon occlusion of the lymphovenous junction at the subclavian vein (Tyshak II, B. Braun Medical Inc, Bethlehem, PA); and (4) isolation of the branches of the TD by stenting of the TD with covered stent (Viabahn, Gore Medical, Flagstaff, AZ).
In 3 patients, bronchoscopy was performed immediately after catheterization of the TD while injecting Isosulfan Blue (Lymphazurin, Tyco Healthcare Group, Mansfield, MA) to help us identify the pathways of pulmonary lymphatic perfusion in cases where the origin of the pulmonary lymphatic flow was unclear.
In this study, we report on the casting frequency (number of casts per time) as reported by the patients, patients physician, or family. In 2 patients, there was no report of a regular pattern of casting; thus, they were labeled as intermittent.
Demographic and procedural variables were summarized by using standard descriptive statistics and expressed as mean±standard deviation for normally distributed continuous variables, median with range for skewed continuous variables, and count with percentage of total for categorical variables.
Casting Frequency and Number of Medications
Before conducting the prepost test analysis, we converted the descriptive casting frequency to a numeric number (casts per month). For those with irregular casting frequency (intermittent), we counted approximate episodes in a certain time period (casts per year) and converted this number into casts per month. We then created a difference variable by subtracting the precasting frequency from the postcasting frequency and prenumber of medications. For the primary analysis, we used generalized estimating equations within the GENMOD procedure in SAS 9.4 to compare outcomes (casting rate and number of medications) before and after the intervention. A Poisson distribution with a log link function was assumed, while adjusting for clustering of data at the patient level by specifying the exchangeable covariance structure.
After conducting the primary analysis, we executed sensitivity analyses where we considered the negative binomial, normal distribution, and a nonparametric Wilcoxon sign rank test, as well. The statistical significance was set at the 0.05 level.
Patient demographics, diagnosis, and surgical history are shown in Table 1. Fifteen patients had undergone a previous TCPC, 1 had undergone a previous hemifontan, 1 was post–heart transplant, and 1 was post–biventricular repair of pulmonary atresia with intact ventricular septum. A history of prolonged postoperative chylous effusions (>2 weeks) had occurred in 14 of the 15 patients who presented after TCPC.
A detailed summary of the preprocedure PB course is presented in Table 1. Eight patients expectorated bronchial casts daily. Seventeen patients were treated with inhaled tissue plasminogen activator and 16 were treated with sildenafil. Thirteen patients underwent cardiac interventions in an attempt to improve TCPC hemodynamics. These included fenestration creation or enlargement and pulmonary artery or pulmonary vein angioplasty with or without stent placement, and embolization of systemic to pulmonary collaterals. One patient (patient 8) presented with an acute onset of PB immediately after TCPC surgery. In this patient, postsurgical extubation was not possible and TCPC takedown was considered.
All patients in this study underwent bronchoscopy. Bronchoscopy demonstrated bronchial casts in 7 patients. In 5 of these, the constitution of the casts was mucin and fibrin with inflammatory cells. In 1 patient (patient 10), the casts consisted of mixed cells, and 1 patient (patient 18) had mucin and fibrin casts with mixed inflammatory and eosinophil cells.
Cardiac Catheterization Results
Right-sided cardiac catheterization was performed in all patients. Two patients underwent balloon occlusion of the cardiac fenestration and embolization of venovenous collaterals. In 3 patients, only embolization of the venovenous collaterals was performed, and, in 1 patient, only balloon occlusion of the fenestration was performed. Mean central venous pressure (CVP) in the cohort was 12.5 mm Hg with range (1–20). Ten of the fifteen patients (67%) with TCPC had pulmonary arterial pressure of ≤14 mm Hg.
Magnetic Resonance Imaging
MRI was performed in 17 patients. One patient (patient 10) could not undergo MRI because of a pacemaker. In all but 1 patient (patient 1), MRI and lymphatic intervention were done as part of 1 procedure. In 16 of 17 patients, T2 imaging demonstrated dilated peribronchial lymphatic networks. In 15of 17 patients, DCMRL demonstrated retrograde lymphatic flow from the TD toward lung parenchyma or lymphatic perfusion of the mediastinum or both. In 2 of 17 patients, there was no retrograde lymphatic flow. In 10 of 15 patients, the lymphatic networks and retrograde flow were unilateral and predominantly on the right side.
Intranodal lymphangiogram was successful in all 18 patients. Following the intranodal lymphangiogram, catheterization of the TD or its contributories was performed successfully in 17 patients during the same procedure and in 1 patient (patient 14) during a second procedure. Contrast lymphangiography in the TD, through a microcatheter, confirmed retrograde pulmonary lymphatic flow in all 15 patients with the finding of retrograde lymphatic flow on DCMRL (Figure 1). Retrograde lymphatic flow was also demonstrated in the patient in whom DCMRL was not possible because of the presence of the pacemaker. Five of 18 patients had an occluded TD outlet and 3 of 18 patients had a persistent left-sided TD.
Review of the images of contrast injection in the thoracic duct revealed 5 lymphangiography patterns of retrograde lymphatic flow toward lung parenchyma or bronchi (Figure 2):
Type 1. Patent TD with retrograde flow in 1 branch (1/16 patients).
Type 2. Patent TD with retrograde flow in multiple branches (10/16 patients).
Type 3. Double TD with left duct supplying the lungs (2/16 patients).
Type 4. Complete occlusion of the TD outlet with retrograde flow in multiple branches (1/16 patients).
Type 5. Absence of any identifiable anatomic TD and diffuse perfusion of the lungs (2/16 patients).
In 2 patients, methylene blue injection in TD with simultaneous bronchoscopy confirmed the lymphatic perfusion of the bronchi (Figure 3). In 1 patient (patient 18), retrograde pulmonary lymphatic perfusion was not demonstrated on DCRML, conventional lymphangiogram, or injection of Lymphazurin in the TD during bronchoscopy.
The correlation between DCRML and TD lymphangiogram was excellent.
DCRML was much more sensitive in showing the degree of lymphatic perfusion of the lungs and mediastinum. TD lymphangiogram was subjectively able to demonstrate more reliably the patency of the TD and anatomy of the TD and its branches.
Lymphatic embolization was performed in 17 of 18 patients. Patient 18 did not undergo a lymphatic embolization procedure because of the lack of pulmonary lymphatic perfusion. A detailed summary of the specific embolization techniques for each patient is presented in Table 2. In 2 of 17 (12%) patients, exclusion of the retrograde pulmonary flow was performed with a stent graft (Viabahn, Gore Medical; Figure 4). Selective embolization procedures were performed in 12 of 17 (70%) the patients undergoing an embolization procedure. In 4 of 17 (24%) patients, complete embolization of the TD was performed.
There was a statistically significant difference between pre and post results for casting rate assuming a Poisson distribution (P<0.0001). The sensitivity analyses considering other distribution assumptions yielded consistent findings.
Overall, 15 of 17 (88%) patients that had embolization had significant improvement of the symptoms. One patient (patient 11) had no change in expectoration of casts. In this patient, no retrograde pulmonary lymphatic perfusion was demonstrated. Of 16 of 17 patients that had retrograde pulmonary perfusion on DCMRL or lymphangiogram or both, 15 of 16 (94%) had improvement in symptoms after embolization. One patient (patient 8) presented 3 days after TCPC surgery with PB and high ventilator support. The patient had type 5 PB with diffuse perfusion of the lungs on DCMRL (Figure 5). The patient underwent embolization with Lipiodol, and, 4 days after the embolization, the patient was weaned off ventilation and was discharged home. Because of persistent cast formation, the patient underwent an additional embolization 5 months later that resulted in improvement but not complete resolution of the symptoms. This patient subsequently underwent a heart transplant for severe ventricular dysfunction. Ten of the 16 patients (59%) had immediate complete resolution of the symptoms, and 4 of 17 (25%) patients had 1 to 2 casting episodes within several weeks of the procedure.
In 5 of 16 patients, there have been additional subjectively milder late casting episodes, usually in the setting of viral respiratory infection. These casting events were characterized by expectoration of small casts that responded to a short course (5–7 days) of oral steroids. In this group, 1 of 5 patients (patient 13), 3 months after the procedure, had a recurrence of casts after surgery for placement of a valved conduit. Repeat TD embolization procedure was performed at a lower level, which led to resolution of symptoms. Fifteen (15/17) patients that had an intervention were weaned off respiratory medication and other therapies, with the exception of sildenafil. There was a statistically significant difference between pre and post results for the number of medications, assuming a Poisson distribution (P<0.0001). The sensitivity analyses considering other distribution assumptions yielded consistent findings. Patient 18, in whom embolization was not performed because of the absence of evidence of retrograde pulmonary lymphatic perfusion, had resolution of cast formation with a high dose of steroids
One patient in this study (patient 18) did not have retrograde pulmonary flow on DCMRL and lymphangiogram and did not undergo an embolization procedure (Figure 6). This patient had eosinophils in her cast and had resolution of symptoms on steroid therapy.
Median follow-up for this cohort is 315 days (range, 45–770 days). Median time to discharge after the procedure was 7 days (3–45 days).
The most common complications from the procedure were transient abdominal pain in 10 of 18 cases and transient hypotension in 14 of 18 cases. One patient (patient 1) had acute onset of severe chest pain 48 hours after the procedure, which resolved spontaneously. One patient required a bronchoscopy 3 days after the procedure for removal of residual casts in the setting of respiratory distress. One patient (patient 13) had a unique finding on lymphangiography of lymphovenous connections between lymphatic ducts and pulmonary veins. He presented with right-sided neurological deficits 1 day after the second embolization procedure. Nonenhanced computed tomography of the head demonstrated diffuse deposition of the contrast material in brain tissue. There was a complete resolution of his neurological symptoms within a month of the procedure. One patient (patient 3) died 1.5 months after the procedure because of unrelated multiorgan system failure.
PB is a rare complication of single-ventricle palliation. The reported mean mortality in congenital heart disease associated PB is 33% (14%–50%).2 Lymphatic involvement has been shown and is believed to play a role in the disease process, but the pathogenesis of PB associated with it is poorly understood.7,21–23
Treatments of PB in patients post-TCPC have focused primarily on facilitation of cast expectoration (inhaled tissue plasminogen activator, heparin inhalations, dornase, hypertonic saline, and vibration vest), reduction of CVP (fenestration and sildenafil), and steroid anti-inflammatory therapy. It is possible that improvement of CVP is 1 mechanism by which heart transplantation results in cessation or cure of PB. However, other mechanisms such as return of pulsatile flow to the lungs and increased cardiac output could also be important.
In this study, we found abnormal lymphatic pulmonary flow in the majority of patients with PB. Using DCMRL and lymphangiogram, we demonstrated that 16 of 18 patients had flow from the TD toward the peribronchial lymphatic vessels and lung parenchyma. We have termed this phenomenon pulmonary lymphatic perfusion syndrome. We believe that the lymphatic vessels that carry this flow represent a congenital anatomic lymphatic variant. This anatomic variant manifests clinically as PB because of the overloading of the lymphatic system in patients with elevated CVP. Several earlier lymphangiographic studies described the development of chylous effusion caused by lymphatic reflux similar to our observation.24,25 Gray et al26 reported complete occlusion of flow in the TD and retrograde flow of lymph toward lung parenchyma in congenital chylothorax similar to the type 4 pattern. In 5 of 16 patients, the TD was occluded primarily at the distal end. Although this occlusion can be a sequela of previous surgical chest intervention, the cervical location of most of these occlusions, outside the surgical area, argues against this possibility and supports a congenital etiology.
The increase in lymphatic flow overload in patients with right-sided heart failure is attributable to a combination of increase in lymphatic production and increase in impedance to lymphatic drainage.27,28 However, there is a poor correlation between the severity of the cardiac failure and the presence or severity of PB. In fact in our study, 10 of 15 patients had what are conventionally considered acceptable pulmonary arterial pressures of ≤14 mm Hg, but these CVP values are still significantly higher than those seen in normal circulation.
The mechanism of cast formation in PB is probably attributable to abnormal perfusion of the bronchial submucosa with lymph and slow seepage of lymph proteins into the bronchial lumen. We were able to demonstrate this perfusion visually by injection of Lymphazurin during bronchoscopy resulting in formation of a blue cast. Once in the airway the proteins dry and denature, thus causing cast formation. PB is known to be exacerbated during bouts of upper respiratory tract disease, especially with influenza A virus, suggesting that bronchial mucosal inflammation may affect permeability and contribute to cast formation. This may explain the temporary improvement of symptoms with steroid treatment reported in some cases.10 This is also the reason that care must be exercised when using medications such as inhaled tissue plasminogen activator that are known to produce bleeding and inflammation in the airway.
In our study, we observed significant anatomic variations of the central lymphatic system, which include double TD, central and left location of the lower TD, and even absence of the intrathoracic TD. For that reason, we believe that preprocedure and intraprocedure imaging are crucial to achieve a high rate of success of any central lymphatic intervention procedure.
The goal of the lymphatic intervention in this cohort was to eliminate or reduce the flow from the TD toward lung parenchyma, while maintaining the flow of lymph through the TD into the venous system. In the majority of the patients, we managed to maintain this patency by selective embolization of the peribronchial lymphatic ducts assisted by temporary cessation of the flow in the TD. In 2 cases, stenting of the TD was performed to exclude flow into lymphatic vessels originating from the TD that were too small and numerous to catheterize. Embolization of the distal lymphatic networks by Lipiodol or particles injection can potentially improve the outcome of these procedures and reduce the risk of recurrence. In 4 cases, maintenance of the patency of the TD was not possible because of an unfavorable anatomy. Type 2, 4, and 5 patients represent the anatomic variants, which are more difficult to selectively embolize because of the presence of multiple lymphatic collaterals.
In 1 patient (patient 8) severe respiratory deterioration and PB occurred immediately after TCPC surgery. This patient was a candidate for TCPC takedown or heart transplant. However, lymphatic embolization significantly improved respiratory function by selective embolization of the branches of the TD and alleviated the need for TCPC takedown or emergent transplant. We believe that acute lymphatic overflow or failure, as a cause of TCPC failure, should be considered in a patient with persistent effusions and respiratory distress shortly after the TCPC procedure.
Most TCPC patients in this study had persistent chylous pleural effusions, which have been shown to be a major risk factor for the development of PB.4 Two PB patients in this study did not have retrograde lymphatic flow: 1 patient with TCPC and no history of persistent chylous pleural effusions and 1 patient after orthotropic heart transplant. Currently, we do not understand the etiology of PB in these patients. It is possible that these patients belong to a separate group of PB patients who do not have cardiac disease.2 Alternatively, it is possible that the imaging techniques we used are not sensitive enough to detect subtle lymphatic perfusion abnormalities and, as such, were unable to demonstrate the mechanism of the disease in these patients. Further investigations will need to be done to determine the etiology and best treatment strategy for this group of patients.
Lymphatic embolization does not address the elevated CVP in these patients, which leads to significant lymphatic congestion. For that reason, we believe that the optimization of the TCPC pathway and cardiovascular circulation should be considered as an important part of the treatment of PB. Thus, despite weaning off the respiratory treatments such as inhaled tissue plasminogen activator and albuterol in all patients, we have continued treatment with pulmonary vasodilators to encourage pulmonary vasodilation and thereby perhaps reduce the impetus for recurrence of PB. However, this approach is empirical and warrants further investigation.
In our first 18 cases, abdominal pain a day after the procedure and transient hypotension were the most common complications. Transient abdominal pain was presumably a consequence of transabdominal access. The cause of the transient hypotension is unknown. The cause of the transient chest pain in 2 patients is also unknown but could be a reaction to embolization with Lipiodol. The use of an oil-based contrast agent in children with right-to-left shunting poses a risk for systemic embolization, which occurred in 1 case. To mitigate this risk, we performed systemic-to-pulmonary venous collateral embolization and temporary fenestration occlusion in these patients. Sheybani et al29 described cerebral embolization in patients without right-to-left shunt resulting in neurological deficit. The mechanism by which systemic embolization occurred in the 1 patient in this study is not completely understood because the patient already had complete occlusion of the TD and he did not have any known right-to-left shunts. However, numerous lymphovenous connections were seen in this patient between lymphatic collaterals and the pulmonary veins, which is possibly the source of the shunting and the etiology of the stroke. Consequently, minimizing the amount of oily contrast agent used is of utmost importance.
In this study, institutional review board permission was granted for a retrospective review. Before performing the first procedures there was a discussion about the need to apply for a prospective institutional review board permission. The institutional review board concluded that this was not needed because of several factors. First, the techniques we use are not experimental, because they are used extensively to treat patients with chylous leaks such as chylothorax. Second, given that PB is a potentially fatal illness without a known treatment, the benefits of performing the procedures would likely outweigh the risks. Last, these procedures were clinically indicated and not part of a research study. Despite this conclusion, we believe that, when radical new treatments are offered, it is of utmost importance to provide patients with an accurate description of the potential benefits and risks without producing false hope. In addition, we believe that it is important early on to incorporate radical new treatments into formal research protocols.
The major limitation of this study is the short-term follow-up in the majority of the patients.
Longitudinal study is required to further define the long-term effect of this treatment.
In this report, we demonstrate that retrograde pulmonary lymphatic flow from the central lymphatic system was present in the majority of cardiac patients with PB. Embolization or stent graft exclusion of these lymphatic networks proved effective in a large percentage of our patients and appears to be safe. This treatment has the potential to offer long-term improvement of PB for these patients with a major impact on morbidity and mortality and, potentially, alleviation of the need for heart transplant.
- Received September 29, 2015.
- Accepted February 1, 2016.
- © 2016 American Heart Association, Inc.
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Plastic bronchitis is a rare and often devastating complication in patients after single-ventricle palliation but can also occur secondary to noncardiac causes such as cystic fibrosis and sickle cell anemia. The disease is caused by the exudation of proteinaceous material and cells in the airways leading to cast formation. Casts are often spontaneously expectorated or they can lead to asphyxiation. To date, there has been a poor understanding of the etiology of the disease, which has led to limited treatment options, variability in treatments between centers, and poor patient outcomes. In this report, we demonstrate by dynamic contrast magnetic resonance lymphangiography, conventional lymphangiography, and blue dye injection into lymphatic ducts that abnormal pulmonary lymphatic perfusion originating from the central lymphatic system is present in the majority of cardiac patients with plastic bronchitis. We have termed this phenomenon pulmonary lymphatic perfusion syndrome and have identified 5 patterns of this abnormal flow. Diverting the lymphatic fluid away from the lungs by embolization of these abnormal lymphatic ducts or stent graft exclusion of these lymphatic networks resulted in significant improvement and often cessation of casting in these patients without significant complications. We believe that this treatment has the potential to offer long-term improvement of plastic bronchitis for these patients; it could have a major impact on morbidity and mortality and alleviate the need for heart transplant.