Faculty Bibliography

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

Objective: Abdominal aortic aneurysm (AAA) is a fatal vascular disease on rupture with still limited mechanistic knowledge of the pathophysiologic process. We sought to determine the heterogeneous cell subtypes and to characterize the spectrum of transcriptome signatures in each cell population within the aneurysmal wall by unbiased single-cell RNA sequencing (scRNA-seq) of human AAA tissue.
Method(s): Aortic specimens were collected from AAA and control healthy organ donor. Samples were processed by enzymatic digestion and mechanical disruption to generate single-cell suspension. Single-cell RNA libraries were prepared after generation of single-cell beads in emulsion. Sequencing was performed on a NovaSeq 6000 platform (Illumina, San Diego, Calif). After alignment, barcode assignment, and sample de-multiplexing, data analysis was performed on t-distributed stochastic neighbor embedding charts of cell transcriptome. Cell clusters were identified by unsupervised proximity based on Euclidian distance and supervised identification of biologic markers within clusters. Pathway analysis algorithms were used to outline biologically relevant networks.
Result(s): Unbiased analysis of scRNA-seq data sets showed 19 different cell clusters with unique transcriptomic signatures in AAA. A total of 8826 significant differentially expressed genes were identified in AAA vs control. Notably, gene transcription-associated extracellular matrix remodeling (COL1A1, COL3A1, COL1A2, LUM), Wnt signaling modulation (SFRP2), and synthetic cellular phenotypes (RPS29, RPS27, RPL13A, RPL28) were among the top increased profiles in AAA tissue. Pathway enrichment analysis of AAA vs control libraries revealed significant modulation of cell proliferation, cell-extracellular matrix interaction, neoangiogenesis, and inflammation. Five novel cell clusters with distinct immune synthetic phenotypes were predominantly abundant in AAA wall compared with the healthy aorta. A robust enrichment in immune cell entities was identified in AAA but not in control tissues, including expansion of CD19⁺ B lymphocytes and a subset of CD3E⁺ T lymphocytes significantly expressing IL32 and CCL5. In contrast, smooth muscle cell (ACTA2⁺MYH11⁺) number declined in AAA but revealed increased transcription of the protease ADAMTS4 and inflammatory signals (CCL19, CCL21, IL6, CCL2). Intercluster pathway analysis revealed enrichment of eukaryotic initiation factor 2 and mechanistic target of rapamycin signaling in the AAA macrophage population along with an increased number of inflammatory and T-cell activation cascades.
Conclusion(s): To the best of our knowledge, this is the first report of scRNA-seq analysis on human AAA. This cutting-edge technique uncovered novel cell clusters and provided a comprehensive understanding of cellular spatiotemporal changes within the AAA wall. Here we provide novel interconnected mechanistic insights into this complex disease to enrich our understanding of AAA development.
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INTRODUCTION/BACKGROUND:Horseshoe kidney is a congenital abnormality, with an incidence of 0.25% of the total population. Only 0.12% of patients who undergo an abdominal aortic aneurysm repair might also have a coexisting horseshoe kidney. We present a series of ten cases auspiciously treated with an endovascular approach along with their respective patient evolutions. A review of the literature is also presented. MATERIALS AND METHODS/METHODS:A retrospective review of the medical records (January 2004- December 2013) of 10 patients with abdominal aortic aneurysms and horseshoe kidney treated with endovascular repair, with information from six different centers at three different countries. Demographics, clinical status, medical history, anatomical morphology of the aneurysms and kidneys, as well as surgical outcomes were all analyzed. RESULTS:The median age was 67.5 years (range 47-81), and the median aortic aneurysmal diameter was 57 mm (49-81mm). A total of 35 arteries provided renal perfusion. There were 13 right renal arteries and 13 left renal arteries, all successfully preserved, with 9 isthmus arteries covered. Median hospital stay consisted of 3.5 days (1-14 days). All aortic aneurysms were successfully excluded with no endoleaks, hematomas, wound infections, or renal failure. During a median follow up of seven years, three patients died of myocardial infarction seven years after EVAR, and the other seven patients are doing well, with a median aneurysm reduction size sac of 16.5 mm. CONCLUSIONS:Endovascular repair is a safe and efficient endovascular option for the treatment of patients presenting concomitant aortic aneurysm and horseshoe kidney, with excellent short and medium-term outcomes. To our knowledge, our study represents the largest series of cases with horseshoe kidney successfully treated via endovascular aortic repair without significant complications.

Objective: Pulmonary embolism response teams (PERTs)have become increasingly popular at institutions around the country, although only anecdotal evidence is available to support their efficacy. PERTs are mechanisms for rapid involvement of a multidisciplinary team in the management of a time-sensitive condition with many treatment options spanning multiple specialties. We aimed to evaluate time to management of pulmonary embolisms and outcomes since 2016 under our institution's PERT. Method(s): We retrospectively reviewed 151 patients with PERT activations since inception, collecting data on demographics, time to treatment, treatment modality, and in-hospital outcomes. Result(s): The average age was 62.4 years (range, 30-95 years), and 54% of patients were male; 39.4% of patients had normal echocardiographic recordings, with 27% showing right ventricular (RV)hypokinesis, 9.1% showing elevated pulmonary artery pressures, and 6.1% showing RV enlargement. Anticoagulation alone was received by 91.4% of patients; 4.5% had catheter-directed therapy (CDL), and 3.0% had systemic administration of tissue plasminogen activator (tPA). The average time to invasive intervention was 665 minutes (95% confidence interval [CI], 249-1080 minutes)for CDL and 22 minutes (95% CI, 0-456 minutes)for systemic tPA. Average time to anticoagulation was 3 minutes (95% CI, 154-160 minutes). For patients with echocardiographic findings suggestive of RV strain, 21.4% (95% CI, 0.04-0.51)had tPA or an invasive intervention. Of patients with echocardiographic findings consistent with RV strain who underwent conservative management, 80% were discharged home after an average length of stay of 6.0 days (95% CI, 4.5-7.5). Twenty (14.1%; 95% CI, 5.5-22.5)patients receiving anticoagulation alone had bleeding events, whereas none of the patients undergoing CDL or tPA had bleeding. Sixteen (11.2%; 95% CI, 5.7-16.3)patients who had anticoagulation died in the hospital or were discharged to hospice, and none of the patients receiving CDL or tPA died or were discharged to hospice. The odds of in-hospital death were lower for patients receiving anticoagulation than for those without (odds ratio, 0.29), suggesting appropriate identification of high-risk patients. Average hospital stay was 6.5 days (95% CI, 4.9-8.5)for patients who received anticoagulation, 5.3 days for CDL (95% CI, 0-11.2), and 8 days for tPA (95% CI, 2.6-13.4). Conclusion(s): We found that a dedicated PERT team leads to efficient delivery of care and excellent outcomes. The majority of pulmonary embolisms can be managed with anticoagulation alone. CDT and systemic tPA are safe adjunctive treatments for select patients.

BACKGROUND:Inferior vena cava thrombosis (IVCT), although rare, has a potential for significant morbidity and mortality. IVCT is often a result of IVC filter thrombosis, but it can also occur de novo. Although anticoagulation remains the standard of care, endovascular techniques to restore IVC patency have become key adjunctive therapies in recent years. This study examines a single-center experience with diagnosis and management of IVCT. METHODS:A retrospective Institutional Review Board-approved review of a single-center institutional database was screened to identify IVCT thrombosis using International Classification of Diseases code 453.2 over a 3-year period. Etiology of IVCT was separated into 2 groups: those with IVC thrombosis in the setting of prior IVC filter place and those in whom IVCT occurred de novo. Patient demographics, presenting characteristics, and management of IVCT were examined. Treatment options included expectant management with anticoagulation versus catheter-directed thrombolysis (CDT), mechanical thrombectomy, stenting, or a combination. For those who underwent intervention, technical success, defined as restoration of IVC patency, was assessed. RESULTS:Forty-one unique patients were identified with radiographically confirmed diagnosis of ICVT (mean age 61, range 25-91; 21 female, 51.2%). Eighteen (43.9%) patients presented with thrombosed IVC filter. Risk factors for venous thromboembolism included tobacco usage, current or prior smoking (n = 17, 41.5%), history of prior deep vein thrombosis (n = 25, 61.0%), malignancy (n = 17, 41.5%), use of hormonal supplements (n = 3, 7.3%), known thrombophilia (n = 4, 9.8%), and obesity (body mass index: mean 29, range 18.8-58.53). Eleven patients (26.8%) presented with pulmonary embolism (PE), and of those 63.6% had IVC filter thrombosis (n = 7). Risk of PE was not significantly different between those patients presenting with a thrombosed IVC filter compared to those with de novo IVCT (38.9% vs. 17.4%, P = 0.12) Management of IVCT included anticoagulation alone (n = 27, 65.9%), CDT (n = 5, 12.2%), mechanical thrombolysis (n = 10, 24.4%), and adjunctive IVC stent (n = 3, 7.3%). Among the 14 (34.1%) patients who had intervention for IVCT, patency was restored in 12 patients (85.7%). CONCLUSIONS:IVCT is a rare event and is associated with known risk factors for venous thromboembolism. PE can occur in roughly 25% of patients presenting with IVCT. Presence of a filter does not appear to confer an advantage in preventing PE when IVCT occurs. Although majority of IVCT is managed with anticoagulation alone, endovascular interventions, including lysis and stenting, can safely restore patency in most properly selected patients.