Faculty Bibliography

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) provides life-saving support in severe coronavirus disease-19 (COVID-19) infections resulting in acute hypoxemic respiratory failure refractory to conventional medication support. We examine the trend of inflammatory markers, including D-dimers, in COVID-19 patients requiring extracorporeal support.
METHOD(S): We retrospectively analyzed 29 patients with COVID-19 infection requiring veno-venous (VV) ECMO. Demographics, pre-ECMO characteristics, complications, and blood product requirements were compared between patients with D-dimer levels < 3,000 versus >3,000 ng/ mL using independent two-sample Student's t-tests for continuous variables and chi-squared test for categorical variables. Inflammatory marker levels for patients before and after circuit exchanges were compared using paired samples t-tests.
RESULT(S): COVID-19 patients with pre-cannulation D-dimer levels >3,000 ng/mL had a significantly shorter time from admission to cannulation (4.78 vs 8.44 days, p=0.049) compared to those with D-dimer < 3,000 ng/mL. Furthermore, patients with D-dimer >3,000 ng/mL had a trend of lower pH (7.24 vs 7.33), higher pCO2 (61.33 vs 50.69), and higher VIS scores (7.23 vs 3.97) at time of cannulation, however these were not statistically significant. This cohort of patients also required longer duration of ECMO support (51.44 vs 31.25 days). 13 patients required at least one ECMO-circuit exchange and 16 patients did not require any exchanges. There was a consistent drop in D-dimer values after every circuit exchange, which was not observed in any of the other examined inflammatory markers including Ferritin, LDH, or CRP.
CONCLUSION(S): Elevated D-dimer levels (>3,000 ng/mL) likely reflect increased disease severity in COVID-19, and predict a longer ECMO course. Once on ECMO, however, the D-Dimer level consistently decreased with circuit exchange and may reflect thrombus within the oxygenator rather than disease severity

INTRODUCTION: An extracorporeal membrane oxygenation (ECMO) circuit exchange is a commonly encountered procedure with potential for significant hemodynamic risks in patients with already compromised physiology. We aim to examine potential predictors and safety of circuit exchanges (CE) in COVID-19 patients receiving veno-venous (VV) ECMO support.
METHOD(S): This is a single-center, retrospective study of 29 patients with COVID-19 infection requiring VV ECMO support between March 2020 and April 2020. Pre- ECMO characteristics, complications, and blood product requirements were compared between patients with and without CE using independent two-sample Student's t-tests for continuous variables and chi-squared test for categorical variables.
RESULT(S): Overall survival to discharge was 97% (28/29). 13 patients did not require any CE and 16 patients required a total of 42 CEs. There was no difference in baseline characteristics, pre-ECMO ventilator settings, SOFA, or VIS scores between patients who required a circuit exchange versus those who did not. However, patients who required circuit exchanges had a higher lactate at time of cannulation (1.83 vs 1.32, p=0.011). The CE group had a longer duration of ECMO support (53.31 vs 13.31 days, p=0.004), higher pulmonary complications defined as hemothorax or pneumothorax (8/16 vs 0/13, p=0.003), and higher blood product transfusions including packed red blood cell (5,525 mL vs 1,261 mL, p=0.0001), cryoprecipitate (1,735 mL vs 501 mL, p=0.004), and platelet (486 mL vs 111 mL, p=0.019). In the 42 CEs, no major complications, including hemodynamic instability or cardiac arrest, occurred during the exchange.
CONCLUSION(S): Severity of underlying lung injury, ECMO duration, and pre-cannulation lactate may be markers for potential CE in COVID-19 patients requiring ECMO. They may be associated with higher blood product transfusion requirements and while CEs are procedures performed in hemodynamically tenuous patients, they are able to be performed safely

BACKGROUND:Extracorporeal membrane oxygenation (ECMO) can provide crucial support for single ventricle (SV) patients at various stages of palliation. However, characterization of the utilization and outcomes of ECMO in these unique patients remains incompletely studied. METHODS:We performed a single-center retrospective review of SV patients between 2010 and 2017 who underwent ECMO cannulation with primary end point of survival to discharge and secondary end point of survival to decannulation or orthotopic heart transplantation (OHT). Multivariate analysis was performed for factors predictive of survival to discharge and survival to decannulation. RESULTS:= .011). CONCLUSIONS:Extracorporeal membrane oxygenation can be useful to rescue SV patients with approximately half surviving to discharge, although complications are frequent. Early recognition of the role of heart transplant is imperative. Further study is required to identify areas for improvement in this population.

BACKGROUND:Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used to rescue patients with cardiac arrest refractory to conventional therapy, necessitating evaluation of factors that may affect outcomes. METHODS:A single-center retrospective review of pediatric patients (<21 years old) who underwent ECPR from January 2010 to November 2017. Comparisons between nonsurvivors and survivors, to decannulation and discharge, were made. Factors associated with survival and rate of complications were examined. RESULTS:= .02). There were no differences in bleeding or thrombotic complications or radiographically established neurologic injury. CONCLUSIONS:Although ECPR effectively increases overall survival, a better characterization of long-term outcomes is needed.

OBJECTIVES:Standards for neuromonitoring during extracorporeal membrane oxygenation support do not currently exist, and there is wide variability in practice. We present our institutional experience at an academic children's hospital since establishment of a continuous electroencephalography monitoring protocol for extracorporeal membrane oxygenation patients. DESIGN:Retrospective, single-center study. SETTING:Neonatal ICU and PICU in an urban, quaternary care center. PATIENTS:All neonatal and pediatric patients requiring extracorporeal membrane oxygenation. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:During the study period, 70 patients were cannulated for extracorporeal membrane oxygenation and had continuous electroencephalography monitoring for greater than 24 hours. Electroencephalographic seizures were observed in 16 of 70 patients (23%), including five patients (7%) who were in status epilepticus. Among patients with continuous electroencephalography seizures, nine (56%) had subclinical nonconvulsive status epilepticus and eight (50%) had seizures in the initial 24 hours of extracorporeal membrane oxygenation support. Survival to hospital discharge was significantly greater for extracorporeal membrane oxygenation patients without seizures (74% vs 44%; p = 0.02). CONCLUSIONS:Seizures occur in a significant proportion of pediatric and neonatal extracorporeal membrane oxygenation patients, frequently in the initial 24 hours after extracorporeal membrane oxygenation cannulation. Because seizures are associated with significantly decreased survival, neuromonitoring early in the extracorporeal membrane oxygenation course is important and useful. Further studies are needed to correlate electroencephalography findings with neurologic outcome.

OBJECTIVES:Hemolysis is a known complication of pediatric extracorporeal membrane oxygenation associated with renal failure and mortality. We sought to identify predictors of hemolysis in pediatric extracorporeal membrane oxygenation patients and determine its influence on outcomes. DESIGN:Retrospective, single-center study. SETTING:Urban, quaternary care center pediatric and neonatal ICU. PATIENTS:Ninety-six patients requiring extracorporeal membrane oxygenation. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Daily measurements of plasma-free hemoglobin were obtained while patients were on extracorporeal membrane oxygenation. Patients with a prior extracorporeal membrane oxygenation run, on extracorporeal membrane oxygenation for less than 24 hours, or without complete medical records were excluded from the study. Ninety-six patients met inclusion criteria, of which, 25 patients (26%) had plasma-free hemoglobin greater than 30 mg/dL. Of those patients, 15 of 25(60%) had plasma-free hemoglobin greater than 50 mg/dL, and 21 of 25(84%) occurred during the first 7 days on extracorporeal membrane oxygenation. Compared with patients without hemolysis, those with hemolysis were younger (0.2 mo [0.06-3.2 mo] vs 8.2 mo [0.6-86 mo]; p < 0.001), had a higher pericannulation international normalized ratio (3.9 [3.5-5.5] vs 2.6 [1.8-3.7]; p = 0.003), lower pericannulation platelet count (33 × 10/μL [22-42 × 10/μL] vs 61 × 10/μL [38-86 × 10/μL]; p < 0.001), and had a less negative inlet pressure (-3.5 mm Hg [-14 to 11.5 mm Hg] vs -19 mm Hg [-47 to 0 mm Hg]; p = 0.01). A greater proportion of patients with hemolysis had a heparin assay less than 0.2 mg/dL (50% vs 17%; p = 0.001) and had fluid removal via slow continuous ultrafiltration (32% vs 6%; p < 0.001). Patients with hemolysis had increased risk of in-hospital mortality (odds ratio 10.0; 95% CI 3.4-32; p < 0.001). On multivariable analysis, continuous ultrafiltration (odds ratio, 8.0; 95% CI, 1.9-42; p = 0.007) and pericannulation international normalized ratio greater than 3.5 (odds ratio, 7.2; 95% CI, 2.3-26; p = 0.001) were significantly associated with hemolysis. CONCLUSIONS:Hemolysis is a common complication of pediatric extracorporeal membrane oxygenation. We found that patients with hemolysis (plasma-free hemoglobin > 30 mg/dL) had a 10-fold increase in in-hospital mortality. In our study cohort, hemolysis was associated with continuous ultrafiltration use, but not continuous renal replacement therapy. Additionally, our results suggest that the degree of coagulopathy (international normalized ratio > 3.5) at the time of cannulation influences hemolysis. Additional prospective studies are necessary to define further strategies to prevent hemolysis and improve outcomes in pediatric extracorporeal membrane oxygenation patients.

Over the past several years, endoscopic ablation and resection have become a new standard of care in the management of Barrett esophagus (BE) with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC). Risk factors for failure of endoscopic therapy and the need for subsequent esophagectomy have not been well elucidated. The aims of this study were to determine the efficacy of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) in the management of BE with HGD or IMC, to discern factors predictive of endoscopic treatment failure, and to assess the effect of endoscopic therapies on esophagectomy volume at our institution. Data were obtained retrospectively for all patients who underwent endoscopic therapies or esophagectomy for a diagnosis of BE with HGD or IMC in our department between January 1, 2004, and December 31, 2012. Complete remission (CR) of BE or HGD or IMC was defined as 2 consecutive biopsy sessions without BE or HGD or IMC and no subsequent recurrence. Recurrence was defined by the return of BE or HGD or IMC after initial remission. Progression was defined as worsening of HGD to IMC or worsening of IMC to submucosal neoplasia or beyond. Overall, 57 patients underwent RFA with or without EMR for BE with HGD (n = 45) or IMC (n = 12) between 2007 and 2012, with a median follow-up duration of 35.4 months (range: 18.5-52.0 months). The 57 patients underwent 181 ablation sessions and more than half (61%) of patients underwent EMR as a component of treatment. There were no major procedural complications or deaths, with only 2 minor complications including 1 symptomatic stricture requiring dilation. Multifocal HGD or IMC was present in 43% (25/57) of patients. CR of IMC was achieved in 100% (12/12) at a median of 6.1 months, CR of dysplasia was achieved in 79% (45/57) at a median of 11.5 months, and CR of BE was achieved in 49% (28/57) at a median of 18.4 months. Following initial remission, 28% of patients (16/57) had recurrence of dysplasia (n = 12) or BE (n = 4). Progression to IMC occurred in 7% (4/57). All patients without CR continue endoscopic treatment. No patient required esophagectomy or developed metastatic disease. Overall, 6 patients died during the follow-up interval, none from esophageal cancer. Factors associated with failure to achieve CR of BE included increasing length of BE (6.0 ± 0.6 vs 4.0 ± 0.6cm, P = 0.03) and shorter duration of follow-up (28.5 ± 3.8 months vs 49.0 ± 5.8 months, P = 0.004). Shorter surveillance duration (17.8 ± 7.6 months vs 63.9 ± 14.4 months, P = 0.009) and shorter follow-up (21.1 ± 6.1 months vs 43.2 ± 4.1 months) were the only significant factors associated with failure to eradicate dysplasia. Our use of esophagectomy as primary therapy for BE with HGD or IMC has diminished since we began using endoscopic therapies in 2007. From a maximum of 16 esophagectomies per year for early Barrett neoplasia in 2006, we performed only 3 esophageal resections for such early disease in 2012, all for IMC, and we have not performed an esophagectomy for HGD since 2008. Although recurrence of BE or dysplasia/IMC was not uncommon, RFA with or without EMR ultimately resulted in CR of IMC in all patients, CR of HGD in the majority (79%), and CR of BE in nearly half (49%). No patient treated endoscopically for HGD or IMC subsequently required esophagectomy. In patients with BE with HGD or IMC, RFA and EMR are safe and highly effective. The use of endoscopic therapies appears justified as the new standard of care in most cases of BE with early esophageal neoplasia.

BACKGROUND:Cardiac magnetic resonance (CMR) is established for assessment of left ventricular (LV) systolic function but has not been widely used to assess diastolic function. This study tested performance of a novel CMR segmentation algorithm (LV-METRIC) for automated assessment of diastolic function. METHODS AND RESULTS/RESULTS:A total of 101 patients with normal LV systolic function underwent CMR and echocardiography (echo) within 7 days. LV-METRIC generated LV filling profiles via automated segmentation of contiguous short-axis images (204+/-39 images, 2:04+/-0:53 minutes). Diastolic function by CMR was assessed via early:atrial filling ratios, peak diastolic filling rate, time to peak filling rate, and a novel index-diastolic volume recovery (DVR), calculated as percent diastole required for recovery of 80% stroke volume. Using an echo standard, patients with versus without diastolic dysfunction had lower early:atrial filling ratios, longer time to peak filling rate, lower stroke volume-adjusted peak diastolic filling rate, and greater DVR (all P<0.05). Prevalence of abnormal CMR filling indices increased in relation to clinical symptoms classified by New York Heart Association functional class (P=0.04) or dyspnea (P=0.006). Among all parameters tested, DVR yielded optimal performance versus echo (area under the curve: 0.87+/-0.04, P<0.001). Using a 90% specificity cutoff, DVR yielded 74% sensitivity for diastolic dysfunction. In multivariate analysis, DVR (odds ratio, 1.82; 95% CI, 1.13 to 2.57; P=0.02) was independently associated with echo-evidenced diastolic dysfunction after controlling for age, hypertension, and LV mass (chi(2)=73.4, P<0.001). CONCLUSIONS:Automated CMR segmentation can provide LV filling profiles that may offer insight into diastolic dysfunction. Patients with diastolic dysfunction have prolonged diastolic filling intervals, which are associated with echo-evidenced diastolic dysfunction independent of clinical and imaging variables.

OBJECTIVE: To assess the utility of stress electrocardiography (ECG) for identifying the presence and severity of obstructive coronary artery disease (CAD) defined by coronary computed tomographic angiography (CCTA) among patients with normal nuclear myocardial perfusion imaging (MPI). METHODS: The study population comprised 119 consecutive patients with normal MPI who also underwent CCTA (interval 3.5+/-3.8 months). Stress ECG was performed at the time of MPI. CCTA and MPI were interpreted using established scoring systems, and CCTA was used to define the presence and extent of CAD, which was quantified by a coronary artery jeopardy score. RESULTS: Within this population, 28 patients (24%) had obstructive CAD identified by CCTA. The most common CAD pattern was single-vessel CAD (61%), although proximal vessel involvement was present in 46% of patients. Patients with CAD were nearly three times more likely to have positive standard test responses (1 mm ST-segment deviation) than patients with patent coronary arteries (36 vs. 13%, P=0.007). In multivariate analysis, a positive ST-segment test response was an independent marker for CAD (odds ratio: 2.02, confidence interval: 1.09-3.78, P=0.03) even after adjustment for a composite of clinical cardiac risk factors (odds ratio: 1.85, confidence interval: 1.05-3.23, P=0.03). Despite uniformly normal MPI, mean coronary jeopardy score was three-fold higher among patients with positive compared to those with negative ST-segment response to exercise or dobutamine stress (1.9+/-2.7 vs. 0.5+/-1.4, P=0.03). CONCLUSION: Stress-induced ST-segment deviation is an independent marker for obstructive CAD among patients with normal MPI. A positive stress ECG identifies patients with a greater anatomic extent of CAD as quantified by coronary jeopardy score.