Current Management of Acute Pulmonary Embolism

Purpose: Acute pulmonary embolism (PE) remains a significant cause of morbidity and requires prompt diagnosis and management. While non-surgical approaches have supplanted surgery as primary treatment, surgical pulmonary embolectomy (SPE) remains a vital option for select patients. We review the current management of acute PE, with a focus on surgical therapy. Methods: A PubMed search was performed to identify literature regarding PE and treatment. Results were filtered to include the most comprehensive publications over the past decade. Results: PE is stratified based on presenting hemodynamic status or degree of mechanical pulmonary arterial occlusion. Although systemic or catheter-guided fibrinolysis is the preferred first-line treatment for the majority of cases, patients who are not candidates should be considered for SPE. Studies demonstrate no mortality benefit of thrombolysis over surgery. Systemic anticoagulation is a mainstay of treatment regardless of intervention approach. Following surgical embolectomy, direct oral anticoagulants (DOACs) have been shown to reduce recurrence of thromboembolism. Conclusions: Acute PE presents with varying degrees of clinical stability. Patients should be evaluated in the context of various available treatment options including medical, catheter-based, and surgical interventions. SPE is a safe and appropriate treatment option for appropriate patients

Inhibition of the HEG1-KRIT1 interaction increases KLF4 and KLF2 expression in endothelial cells

The Kruppel-like Factors 2 and 4 (KLF2/4) are transcription factors and master regulators of endothelial cells (ECs) phenotype and homeostasis. KLF2/4 are important blood-flow-responsive genes within ECs that differentially regulate the expression of factors that confer anti-inflammatory, antithrombotic, and antiproliferative effects in ECs. We found that genetic inactivation of endothelial Krit1 (Krev interaction trapped protein 1) or Heg1 (Heart of glass) led to upregulation of KLF2/4 expression levels. We also observed that vasoprotective proteins, endothelial nitric oxide synthase (eNOS) and thrombomodulin (TM), are upregulated by the increase of KLF2/4 as a result of loss of endothelial KRIT1. Here, we developed a high-throughput screening assay to identify inhibitors of the HEG1-KRIT1 interaction and identified sirtinol (HKi001) as a promising hit inhibitor. The crystal structure of sirtinol bound to the KRIT1 FERM domain confirmed the primary screening results and ultimately led to the identification of a fragment-like inhibitor (HKi002), which occupies the HEG1 pocket producing comparable activity. These findings suggest that these inhibitors block the interaction by competing with the HEG1 for binding to KRIT1 FERM domain. Moreover, our results demonstrate that HKi002 upregulates KLF2/4 gene expression in two types of human ECs. These results reveal an unexpected role of inhibiting the HEG1-KRIT1 interaction and provide a proof-of-concept that pharmacological manipulation of this complex may offer new opportunities to induce expression of KLF2/4 as vasoprotective factors

Two Decades Using Stentless Porcine Aortic Root in Right Ventricular Outflow Tract Reconstruction

Background The stentless porcine aortic root prosthesis (SPAR) has been described as a suitable valve for right ventricular outflow tract reconstruction (RVOTR). Indiana University Methodist Hospital in Indianapolis, Indiana began using this valve for RVOTR in 1998. This study reports medium-term to late- term outcomes of the valve in the pulmonary position. Methods A retrospective chart review was conducted of patients older than 18 years of age who underwent RVOTR with a SPAR between April 2000 and October 2019. Primary outcomes included survival and freedom from any valvular reintervention. Secondary outcomes included endocarditis and conduit dysfunction detected by routine echocardiography or cardiac magnetic resonance imaging. Results A total of 135 patients underwent RVOTR with a SPAR at a median age of 32.4 years (range, 18 to 71 years). Of these patients, 129 had previous surgery. Indications included pulmonary insufficiency (90.4%), stenosis (34.8%), endocarditis (7.4%), and carcinoid (4.4%). Median follow-up was 2.97 years (interquartile range, 0.6 to 8.0 years). Overall survival was 93.3%, with 3 perioperative death and 6 late deaths. Endocarditis developed in 4 patients (2.9%), 2 of whom required reoperation. Progressive conduit degradation was evident at 10 years, with 22.2% and 7.7% having moderate stenosis and insufficiency, respectively. Eight (5.9%) reinterventions included 2 surgical replacements, 3 percutaneous replacements, and 3 balloon valvuloplasties at means of 8.5, 7.4, and 2.2 years, respectively. Overall freedom from reintervention at 1, 5, and 10 years was 99.1%, 94.7% and 90.7%, respectively. Conclusions In this large, single-institution experience with a long follow-up period, use of the SPAR demonstrated excellent midterm to long-term durability, low rates of endocarditis, and high freedom from reintervention

Eleven-Year Experience Treating Blunt Thoracic Aortic Injury at a Tertiary Referral Center

Background Blunt thoracic aortic injury treatment has evolved over the past decade particularly with respect to endovascular intervention options. We investigated the trends in blunt thoracic aortic injury management and outcomes over an 11-year span at the sole tertiary referral center in our state. Methods We retrospectively reviewed all patients who presented to our institution with blunt traumatic aortic injury between 2007 and 2017. Baseline demographics including aortic injury grade, injury severity score, and abbreviated injury scale were collected. Outcomes were compared by type and timing of treatment, which included either nonoperative management, endovascular repair, or open surgical repair. Bivariate and multivariable analyses were performed to examine treatment group differences and factors associated with 30-day mortality. Results In total, 229 patients were reviewed. The distribution of injury severity was grade 1 (30%), grade 2 (8%), grade 3 (30%), and grade 4 (31%). Overall, 27% of patients underwent endovascular repair, 29% open surgery, and 44% definitive nonoperative management. Over the study period, there was a dramatic decline in open surgery and a corresponding rise in endovascular treatment. Thirty-day mortality for the entire cohort was 22%. Mortality by treatment subgroup was 30% for nonoperative management, 8.2% for endovascular treatment, and 21% for open surgery. Delaying endovascular or open surgical treatment by at least 24 hours after admission was associated with significantly improved 30-day survival. Conclusions Procedural intervention, whether endovascular or surgical, is associated with improved mortality compared with nonoperative treatment. Delayed intervention, particularly in the case of high-grade injuries, may allow for initial patient stabilization and improved outcomes