Anti-Thymocyte Globulin as a Therapy for Chronic Lung Allograft Dysfunction: A Single-Center Experience.

INTRODUCTION: Anti-thymocyte globulin (ATG) is a polyclonal antibody formulation which has been used as a second-line therapy for chronic lung allograft dysfunction (CLAD). Limited data exist evaluating its efficacy; however, several single-center retrospective studies have variably demonstrated either improvement or stabilization of spirometry parameters after administration of ATG. ATG has been in use at UT Southwestern for treatment of CLAD since at least 2010; here, we seek to evaluate the effectiveness of this intervention at our center.  METHODS: A retrospective chart review was conducted of a total of 136 patients who underwent lung transplantation at UT Southwestern Medical Center between 2010 and 2022. Of these, 72 patients had received ATG specifically for treatment of CLAD, and the remaining 64 had never received ATG. Two separate analyses were performed: in the first, among those who received ATG for CLAD, spirometry data from the 6 months preceding and following ATG administration were reviewed and rates of change in FEV1 were calculated for each time period. Descriptive statistics were performed to summarize the baseline clinical characteristics and outcomes after ATG, with patients classified as having either a full response (positive rate of change in FEV1) or partial response (>20% attenuation in rate of FEV1 decline) to ATG.  In the second analysis, survival was described among those who received ATG for CLAD and comparison was provided between propensity-score matched cohorts from the ATG and non-ATG groups. RESULTS: Of the 63 patients who received ATG for treatment of CLAD (and had adequate spirometry measurements available to trend FEV1), 49 (77.8%) had at least a partial response to therapy; 8 (12.7%) experienced an overall improvement in FEV1. Response to ATG was found to be associated with a more rapid rate of pre-ATG decline in FEV1; no other baseline parameters were found to be predictive of a response to ATG. Median post-CLAD graft survival was 31.7 months among those who received ATG, and only baseline absolute neutrophil count was found to be associated with worse post-CLAD graft survival among this group. CONCLUSION: Anti-thymocyte globulin therapy, when given for CLAD, was associated with at least a modest attenuation in rate of FEV1 decline in most patients but only rarely preceded an absolute improvement in FEV1. Further study is warranted to better define the role for ATG in treatment of CLAD, a challenging disease state with limited therapeutics available.

Diaphragmatic plication among lung transplant patients: A single-center experience.

BACKGROUND: There is lack of data reporting outcomes among patients needing diaphragmatic plication (DP) during or after lung transplantation (LT). We sought to assess the association of DP with post-transplant spirometry among other outcomes. METHODS: We included all patients who underwent LT between 2012 and 2016 (n = 324, mean age 56.3±13.4 years; M:F 198:126). We compared early and late outcomes based on the need for DP. RESULTS: The frequency of diaphragmatic dysfunction (DD) on pre-transplant fluoroscopy was 52.2%. A total of 38 DP procedures were performed among 37 patients (11.4% of LT patients). DP was done for anatomic (sizing or spacing issues) or functional indications (symptomatic DD). While patients with DP had significantly lower spirometry throughout the 3-year follow-up period, their slope of decline, functional assessments at the first annual visit, the risk of CLAD, and mortality were similar to patients without DP. A sub-group analysis limited to patients with restrictive lung diseases as the transplant indication had similar findings. CONCLUSIONS: Pre-transplant DD is common among LT candidates although it did not predict the need for DP. DP may be performed for functional or anatomic indications especially for addressing the donor-recipient size mismatch. Despite the lack of favorable effect on post-transplant spirometry, patients undergoing DP have acceptable and comparable early and late outcomes.

Cardiac transplantation in adults with congenital heart disease: A single center case series.

BACKGROUND: Adult congenital heart disease (CHD) transplant recipients historically experienced worse survival early after transplantation. We aim to review updated trends in adult CHD transplantation. METHODS: We performed a single center case series of adult cardiac transplants from January 2013 through July 2020. Outcomes of patients with CHD were compared to non-CHD. The primary outcome was overall survival. Secondary outcomes included a variety of post-operative complications. RESULTS: 18/262 (7%) transplants were CHD recipients. CHD patients were younger with median age 41 (32-47) versus 58 (48-65) (P < .001). Fontan circulation for single ventricle physiology was present in 4/18 (22%) of CHD recipients, while 16/18 (89%) had systemic right ventricles. CHD recipients had higher rates of previous cardiovascular operations (94% vs. 51%, P < .001). 9/18 (50%) of CHD patients required reconstructive procedures at the time of transplant. Operative and cardiopulmonary bypass times were longer for the CHD cohort (7.5 h [6.6-8.5] vs. 5.6 h [4.6-7] P < .001) and (197 min [158-240] vs. 130 [105-167] P < .001), respectively. There were no differences in operative complications or survival between CHD and non-CHD recipients. CONCLUSIONS: These data highlight the added technical challenges of performing adult CHD transplants. However, similar outcomes can be achieved as for non-CHD recipients. SUMMARY: Modern advances in palliation of congenital heart defects (CHD) has led to increased survival into adulthood. Many of these patients require heart transplantation as adults. There are limited data on adult CHD transplantation. Historically, these patients have had worse perioperative outcomes with improved long-term survival. We retrospectively analyzed 262 heart transplants at a single center, 18 of which were for adult CHD. Here, we report our series of 18 CHD recipients. We detail the palliative history of all CHD patients and highlight the added technical challenges for each of the 18 patients at transplant. In our analysis, CHD patients had more prior cardiovascular surgeries as well as longer transplant operative and bypass times. Despite this, there were no differences in perioperative and long-term outcomes. We have added patient and institution specific data for transplanting patients with adult CHD. We hope that our experience will add to the growing body of literature on adult CHD transplantation.

Can the Public-Private Business Model Provide a Sustainable Quality Pediatric Cardiac Surgery Program in Low- and Middle-Income Countries?

Over 90% of the world's children with congenital heart disease do not have access to cardiac care. Although many models provide pediatric cardiac surgery in low- and middle-income countries, sustainability poses a barrier. We explore one model providing care for the underserved in Chennai, India, that came into existence through trial and error over 30 years across three phases. Phase 1 was a Tamilnadu state government-sponsored program that soon became unsustainable with unmet demands. Phase 2 utilized a grassroots foundation of a public-private partnership (PPP) with few donors and a hospital with suboptimal infrastructure. Phase 3 is the ongoing fine-tuning of the PPP model, with upgraded infrastructure and a well-trained team. Through indigenization, an average cardiac surgery costs Rupees (Rs.) 1,80,000 ($2400). The government funds Rs. 60,000 to 80,000 ($800-$1066.67), and the rest is funded through the fund pool. The goal is to perform 100 free surgeries annually by maintaining a fund pool of Rs. 50 lakhs ($66,666.67), which supplements government funds. This ensures equitable distribution of funds with no compromise on resources (disposables, single-use cannulas, etc). Our model ensures the dignity of the patient, fair compensation for workers, and is practical, affordable, and easily adaptable. Thus far, this model provided free cardiac surgery for 357 children from Risk Adjusted Congenital Heart Surgery Score of 1 to 4, with an overall mortality of 2.73%. The prerequisites for this model are having a "spark plug," a dedicated surgical team, a partnership with state-of-the-art infrastructure, and a steady flow of funds.

A Randomized, Multicenter, Blinded Pilot Study Assessing the Effects of Gaseous Nitric Oxide in an Ex Vivo System of Human Lungs.

INTRODUCTION: Normothermic ex vivo lung perfusion (EVLP) is used to evaluate and condition donor lungs for transplantation. The objective of this study was to determine whether administration of exogenous nitric oxide during EVLP contributes to improvement of lung health. METHODS: A multicenter, blinded, two-arm, randomized pilot study evaluated the effect of gaseous nitric oxide (gNO) administered during EVLP on donor lungs rejected for transplantation. gNO introduced into the perfusate at 80 parts per million (ppm) was compared with perfusate alone (P). An open-label substudy assessed inhaled nitric oxide gas (iNO) delivered into the lungs at 20 ppm via a ventilator. Primary endpoints were an aggregate score of lung physiology indicators and total duration of stable EVLP time. Secondary endpoints included assessments of lung weight and left atrium partial pressure of oxygen (LAPO2). RESULTS: Twenty bilateral donor lungs (blinded study, n = 16; open-label substudy, n = 4) from three centers were enrolled. Median (min, max) total EVLP times for the gNO, P, and iNO groups were 12.4 (8.6, 12.6), 10.6 (6.0, 12.4), and 12.4 (8.7, 13.0) hours, respectively. In the blinded study, median aggregate scores were higher in the gNO group compared to the P group at most time points, suggesting better lung health with gNO (median score range [min, max], 0-3.5 [0, 7]) vs. P (0-2.0 [0, 5] at end of study). In the substudy, median aggregate scores did not improve for lungs in the iNO group. However, both the gNO and iNO groups showed improvements in lung weight and LAPO2 compared to the P group. CONCLUSIONS: The data suggest that inclusion of gNO during EVLP may potentially prolong duration of organ stability and improve donor lung health, which warrants further investigation.

Advanced imaging and digitization of preserved heart specimens using virtual reality - A primer.

Introduction: Preserved congenital heart specimens are an important component of training professionals working with children and adults with congenital heart disease. They are curated in few institutions worldwide and not freely accessible. This was a proof-of-concept project to explore the use of advanced cardiac imaging modalities (computed tomography [CT] and magnetic resonance imaging [MRI]) and virtual reality (VR) simulation to assess the feasibility and identify the best method of imaging curated cardiac pathology specimens. Methods: Seven specimens in glass jars with formalin, with varied anatomic lesions, from a curated collection were imaged using MRI and high-dose CT to compare the fidelity of models created via each modality. Three-dimensional (3D) models were created and loaded into a VR headset and viewed in virtual space. Two independent physicians performed a "virtual dissection" and scored the resultant models. Results: The highest fidelity and tissue characterization of more delicate structures was achieved with T2 spoiled gradient-echo sequences on MRI (median score of 4 out of 5). CT (median score of 3), while excellent for external anatomy, lost some fidelity with delicate internal anatomy, even at high-radiation doses. No specimens were damaged. Conclusions: We believe that in vitro heart specimens can be easily scanned with high fidelity at a relatively low cost, without causing damage, using high-dose CT and MRI. The ability to "walk through" different chambers of the heart makes the understanding of anatomy easy and intuitive. VR and 3D printing are technologies that could be easily adapted to digitize preserved heart specimens, making it globally accessible for teaching and training purposes.

Lung transplantation: how we do it.

Lung transplantation is considered the gold standard for patients with chronic end-stage pulmonary disease. However, due to the complexity of management and relatively lower median survival as compared to other solid organs, many programs across the world have been slow to adopt the same. In our institution, we started lung transplantation in September 1990. And since then, we performed close to 900 lung transplantations. Here, we describe in detail the operative steps adopted in our institution for a successful lung transplantation. There have been very few variations over the years. We believe that having a standardized technique is one of the important features for success of a lung transplant program.

Ex vivo lung perfusion: how we do it.

Lung transplantation is an established treatment for patients with end-stage lung disease. However, a shortage of donors, low lung utilization among potential donors, and waitlist mortality continue to be challenges. In the last decade, ex vivo lung perfusion (EVLP) has expanded the donor pool by allowing prolonged evaluation of marginal donor lungs and allowing reparative therapies for lungs, which are otherwise considered not transplantable. In this review, we describe in detail our experience with EVLP including our workflow, setup, operative technique, and protocols. Our multidisciplinary EVLP program functions with the collaboration of surgeons, pulmonologists, and EVLP nurses who run the pump. EVLP program has been a valuable addition to our program. Since Food and Drug Administration (FDA) approval in 2019, we experienced incremental increased lung transplant volume of 12% annually.

Novel Suture Technique for Slide Tracheoplasty for the Treatment of Long-Segment Tracheal Stenosis.

Long-segment tracheal stenosis is a rare, life-threatening condition. Slide tracheoplasty is the surgical treatment of choice but is associated with significant morbidity and mortality. We examined our institutional outcomes utilizing a running, everting horizontal mattress suture technique. From August 2012 to January 2019, 7 infants and children underwent slide tracheoplasty with a single surgeon utilizing a running, everting horizontal mattress suture technique. Demographics and patient clinical data were obtained through chart review, and a retrospective analysis was performed. Median age was 7 months (range, 4 days-19 months) and median weight was 5.5 kg (range, 2.8-9.4). All patients underwent slide tracheoplasty using a running, everting horizontal mattress suture technique. One patient died on postoperative day 45 of multisystem organ failure, unrelated to his patent airway. Length of postoperative ventilation in survivors was 7 days (range, 0-20 days). Average follow-up was 3 years. There were no instances of significant postoperative airway stenosis, anastomotic leak, granulation tissue formation, or figure-of eight deformity. A running, everting horizontal mattress suture technique is safe and efficacious for slide tracheoplasty, prevents figure-of-eight deformity, and may decrease the incidence of tracheal stenosis, airway granulation tissue formation, and anastomotic leak.

Pediatric Cardiac Surgery in Low-and Middle-Income Countries: Present Status and Need for a Paradigm Shift.

In low and mid-income countries, there has been a 50% global decrease in the incidence of preventable deaths of children since 1990. However, the mortality from non-communicable diseases (NCD) such as congenital heart disease (CHD) has not changed. Of the estimated 1.3 million children born with CHD annually, over 90% do not have access to cardiac care. With the increasing fertility rates in sub-Saharan Africa, the health burden of CHD will increase as well. Over the last 30 years much has been achieved with short term cardiac medical missions. However, much remains to be done to provide long term solutions needed to achieve the sustainable development goal of reducing deaths of children <5 years of age. This review discusses the present status and the need for a paradigm shift to achieve long term sustainability.

A review of the Nunn modified single patch technique for atrioventricular septal defect repair.

Atrioventricular septal defect (AVSD) is a common congenital cardiac surgical problem. Over the years, younger and smaller infants are having operations for this condition before irreversible cardio pulmonary changes occur. Traditionally a single or two patch techniques have been used to repair this defect. However, in the past two decades an innovative method of modified single patch technique popularized by Dr. Graham Nunn has gained worldwide popularity. This review discusses the origin, surgical principles, technique and outcomes of this method, popularly known as Nunn or Australian technique. Research comparing the modified single patch technique to classic single and double patch techniques has shown good preservation of atrioventricular valve function, no residual ventricular septal defect (VSDs), low incidence of left ventricular outflow obstruction, preserved conduction, easy reproducibility, and improved perioperative and long-term mortality.

Right ventricular outflow tract obstruction: a quest for ideal management.

Management of right ventricular outflow tract obstruction has undergone much change over the last century. Techniques described in the literature include anatomical repairs and the use of various patches, conduits, and innovative grafts. However, many of these approaches require reoperations or catheter-based interventions, leading to increased morbidity, mortality, and cost. The search for the ideal long-lasting conduit continues and there are new techniques on the horizon, using genetic engineering and nanotechnology. This review discusses the evolution of various techniques for repair of right ventricular outflow tract obstruction, past and current conduits, as well as ongoing research.

'Near death' thromboembolic episode following device closure of atrial septal defect.

Life-threatening pulmonary thromboembolism is a rare complication following device closure of an atrial septal defect (ASD). Our case is a 17-year old female who presented with a sudden cardiorespiratory arrest due to pulmonary thromboembolism, 5 months following a device closure of her ASD. She was successfully resuscitated and then underwent removal of the device with the associated clots and patch closure of the ASD. She made an uneventful recovery. We report this case to highlight that life-threatening thromboembolic complications can occur with ASD device closure.

Late endocarditis of Amplatzer atrial septal occluder device in a child.

Bacterial endocarditis following atrial septal defect closure using Amplatzer device in a child is extremely rare. We report a 10-year-old girl who developed late bacterial endocarditis, 6 years after placement of an Amplatzer atrial septal occluder device. Successful explantation of the device and repair of the resultant septal defect was carried out using a homograft patch. The rare occurrence of this entity prompted us to highlight the importance of long-term follow up, review the management and explore preventive strategies for similar patients who have multiple co-morbidities and a cardiac device. A high index of suspicion is warranted particularly in pediatric patients.

Surgery following primary right ventricular outflow tract stenting for Fallot's tetralogy and variants: rehabilitation of small pulmonary arteries.

OBJECTIVES: Primary surgical repair of Tetralogy of Fallot (ToF) in small infants with small pulmonary arteries (PAs) or complex anatomies can be hazardous. We assessed the effect of right ventricular outflow tract (RVOT) stenting on subsequent surgical intervention with attention to growth of the PAs. METHODS: Primary RVOT stenting was performed in 32 symptomatic patients with ToF physiology. Twenty patients had surgical intervention, with 15 undergoing complete repair to date. Median age at stenting was 61 (range 8-406) days, and median weight, 3.9 (range 1.8-12.2) kg. RESULTS: Stenting improved saturations from 72 ± 8 to 92 ± 2% (P < 0.001). Four patients required early surgical palliation for persistent desaturation (within 4 weeks). Twenty patients went on to have surgical intervention at a median time of 220 days after stenting. There was no operative mortality after complete repair. Removing the stent lengthened the procedure time and 86% required transannular patch (TAP; bypass time 109 ± 42 min, cross clamp 68 ± 29 min). Median intensive therapy unit stay was 2 days. There was 1 late death at 3 months due to chronic lung disease. The median left PA Z-score increased from a preinterventional value of -1.27 (-0.19 to -2.87) to a presurgical value of +0.11 (-4.12 to +1.97). The median right PA Z-score increased from -2.02 (-1.77 to -4.68) to -0.65 (-0.29 to -2.04) over the preinterventional and presurgical time intervals. Growth was greatest in the right PA. CONCLUSIONS: Primary RVOT stenting facilitates staged palliation for ToF in small infants and complex anatomies. Improved PA blood flow generated by the stent leads to growth of the branch PAs and may improve the substrate for subsequent surgical repair. Surgery is safe; however, the majority will require a TAP.