Jason J. Han

Tissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Function

OBJECTIVES Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage. METHODS Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents. RESULTS Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control. CONCLUSIONS We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.

In Vivo Anastomosis and Perfusion of a Three-Dimensionally-Printed Construct Containing Microchannel Networks.

The field of tissue engineering has advanced the development of increasingly biocompatible materials to mimic the extracellular matrix of vascularized tissue. However, a majority of studies instead rely on a multiday inosculation between engineered vessels and host vasculature rather than the direct connection of engineered microvascular networks with host vasculature. We have previously demonstrated that the rapid casting of three-dimensionally-printed (3D) sacrificial carbohydrate glass is an expeditious and a reliable method of creating scaffolds with 3D microvessel networks. Here, we describe a new surgical technique to directly connect host femoral arteries to patterned microvessel networks. Vessel networks were connected in vivo in a rat femoral artery graft model. We utilized laser Doppler imaging to monitor hind limb ischemia for several hours after implantation and thus measured the vascular patency of implants that were anastomosed to the femoral artery. This study may provide a method to overcome the challenge of rapid oxygen and nutrient delivery to engineered vascularized tissues implanted in vivo.

Applying lessons from social psychology to transform the culture of error disclosure

The ability to carry out prompt and effective error disclosure has been described in the literature as an essential skill among physicians that can lead to improved patient satisfaction, staff well‐being and hospital outcomes. However, few studies have addressed the social psychology principles that may influence physician behaviour.

HeartMate II left ventricular assist device geometry on chest radiograph does not correlate with risk of pump thrombosis

Pump thrombosis (PT) is a common and potentially life-threatening complication among HeartMate II (HMII; Thoratec, Pleasanton, CA) patients. There have been efforts to correlate HMII geometry with higher risk of PT. The aim of this study was to test the validity of using HMII inflow cannula angle (ICA) and pump pocket depth (PPD) to predict PT. We performed a retrospective analysis of patients implanted with HMII left ventricular assist devices (LVADs) from January 2011 to March 2014 at our institution. Three blinded reviewers measured ICA and PPD from chest x-rays at postimplantation and most recent follow-up time points. The diagnosis of PT was visually confirmed upon device explantation by benchtop evaluation. HeartMate II was implanted in 90 patients. Sixteen (20%) patients experienced PT. There was no statistical difference between PT and non-PT patients in their initial ICAs (56.0° ± 10.1 vs. 54.6° ± 10.8, p = 0.63) and PPD (86.7 ± 24.9 mm vs. 81.1 ± 32.2 mm, p = 0.46). Prediction of PT using ICA and PPD by receiving operating characteristic was negative (area under curve (AUC) = 0.54 and 0.55, respectively). Changes in HMII geometry were measured over 112.5 (interquartile range = 34.3–337.3) days. A decrease in PPD was observed (p = 0.0001). Initial ICA was a significant predictor of future angle change and suggested a convergence toward the mean (55.4°) (analysis of variance p = 0.002). Pump thrombosis recurred in four (25%) patients. Postoperative ICA and PPD do not appear to predict PT in HMII patients in our experience. HeartMate II geometry changes over time secondary to remodeling with a decrease in PPD and a convergence toward the median in ICAs. Further investigation into the role of geometric ventricular assist device conformation postimplant may be warranted.

See one–practice–do one–practice–teach one–practice: The importance of practicing outside of the operating room in surgical training

From the Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa. Disclosures: Authors have nothing to disclose with regard to commercial support. Received for publication May 23, 2018; revisions received July 18, 2018; accepted for publication July 28, 2018; available ahead of print Oct 25, 2018. Address for reprints: Jason J. Han, MD, Division of Cardiovascular Surgery, Hospital of the University of Pennsylvania, 3400 Spruce St, 6 Silverstein Pavilion, Philadelphia, PA (E-mail: Jason.Han@uphs.upenn.edu). J Thorac Cardiovasc Surg 2019;157:671-7 0022-5223/

Higher Body Mass Index Increases Risk of HeartMate II Pump Thrombosis But Does Not Adversely Affect Long-Term Survival

36.00 Copyright 2018 by The American Association for Thoracic Surgery https://doi.org/10.1016/j.jtcvs.2018.07.108 Jason J. Han, MD, and William L. Patrick, MD

The Perfect ECMO Candidate

BACKGROUND Obesity has been correlated with various adverse events in patients who receive left ventricular assist devices (LVAD). In this study, we sought to further characterize the role of obesity in this patient population.Methods and Results:We performed a retrospective analysis of 164 patients implanted with a HeartMate II from August 2008 to December 2014. Patients were categorized into 2 BMI groups based on WHO guidelines: BMI 18.5-30 kg/m2(n=99) and BMI >30 kg/m2(n=65). Patient demographics, adverse outcome and long-term survival were compared between the 2 groups. For any outcome associated with BMI groups, we performed a Cox regression to identify confounding comorbidities. Preoperative demographics and comorbidities were similar. Patients with BMI >30 were younger (P=0.01) and had a higher incidence of type 2 diabetes (P=0.01). While rate of pump thrombosis was higher among patients with BMI >30 (P=0.02), overall survival at 2 years did not differ. The most common cause of death was hemorrhagic stroke in the obese group. On multivariable cox regression analysis, BMI was an independent risk factor of pump thrombosis. CONCLUSIONS Higher BMI does not reduce survival after VAD implantation but it does appear to increase the risk of pump thrombosis. Further studies to characterize the role of BMI in survival and thrombosis rates are warranted.

Opioid Epidemic and Heart Transplantation: A Trainee’s View

One quiet Saturday morning, as I sat down in front of the computer and began to review my patient charts, an uncomfortably familiar alarm sounded overhead:“Attention please. Cardiothoracic surgery STAT to the medical intensive care unit.” This announcement is used at my hospital, invariably

The Heart Team: A Powerful Paradigm for the Future Training of Cardiovascular Surgeons

The first heart procurement that I observed was from the body of a motor vehicle accident victim in South Carolina. Her face and body were draped by the time our team arrived. I was a second-year medical student, too young to comprehend the bewilderingly complex art and ethics of organ

Is there a difference in bleeding after left ventricular assist device implant: centrifugal versus axial?

An important milestone in the field of cardiovascular medicine was neither a new medication nor an operative technique. Rather, it was the embrace of a mindset, which recognized that complex cardiovascular diseases can be better managed using a multidisciplinary approach than by the solitary efforts