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Background Concerns regarding long-term durability of surgical repair for functional mitral regurgitation are based on short-term data, with few comparisons of ischemic (IMR) versus non-ischemic (NIFMR) etiology. Methods 788 consecutive patients receiving mitral repair for functional mitral regurgitation were evaluated from a prospectively maintained database. Patients with other surgical procedures were included. Propensity score matching was used to compare outcomes in IMR versus NIFMR. Results Unmatched IMR patients tended to be older men with greater comorbidities. 198 matched pairs of IMR versus NIFMR patients had similar demographics with relatively preserved ejection fraction 40±13% and end-systolic diameter 4.3±1.1cm. Concomitant coronary revascularization occurred in 70% of matched IMR patients. All patients received an annuloplasty ring, usually 24-26 mm. Heart failure class improved from 2.8 preop to 1.5 at 5 years (P =2+) mitral regurgitation (27±4% v 26±4%, P=0.4), severe regurgitation (10±3% v 8±2%, P=0.5), and mitral reoperation (3±1% v 3±1%, P=0.4) were not different between IMR v NIFMR. Recurrent moderate regurgitation was associated with heart failure readmission but not with mortality. Conclusions In propensity-matched patients, IMR versus NIFMR had worse survival but similar repair durability, with moderate regurgitation in 27% at 10 years and rare severe regurgitation or mitral reoperation. In selected patients with relatively preserved function, mitral repair for IMR or NIFMR can improve symptoms with durable mild regurgitation in most patients out to 10 years.

Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

The durability of surgical repair for degenerative versus ischemic mitral regurgitation (MR) is thought to be markedly different. We, therefore, examined late outcomes and durability for mitral repair in a large cohort of patients receiving a single annuloplasty device.A total of 749 consecutive patients receiving mitral repair for degenerative mitral regurgitation (DMR) or ischemic mitral regurgitation (IMR) were evaluated from a prospective database. Patients with tricuspid or maze surgery were included. Papillary muscle rupture and mixed valve etiologies were excluded. Outcomes were compared for IMR versus DMR.Patients with DMR were younger and less urgent. Patients with IMR had mean end-systolic diameter 4.5 ± 1.1 cm. All patients received the same complete semirigid annuloplasty device with median ring size 32 mm for DMR and 24 mm for IMR. New York Heart Association failure class improved from 2.8 to 1.5 (p .001). Patients with DMR had lower operative mortality (1/384 [0.3%] vs. 26/365 [7%], p .0001) and shorter length of stay. A 15-year survival was better with DMR (63% ± 3% vs. 13% ± 2%, p .001). At 10 years, the incidence of recurrent ≥2+ MR (10% ± 2% vs. 16% ± 2%, p = .16) was not significantly different. Predictors of recurrent ≥2+ MR were female gender (odds ratio [OR]: 3.0 (1.9-4.8, p .0001), and prior operation (OR: 2.4 [1.3-4.5], p = .02) but not IMR (OR: 1.4 [0.9-2.3], p = .15).In this series, where patients with IMR had relatively preserved ventricular dimensions, the primary determinants of late recurrent MR were female gender and prior operation but not IMR versus DMR. Selected patients with IMR can obtain relatively durable mitral repair despite higher operative risk and lower survival compared to DMR.

Background: Poor preoperative health-related quality of life (HRQoL) has been associated with reduced short-term survival after coronary artery bypass graft surgery (CABG); however, it’s impact on long-term mortality is unknown. This study’s objective was to determine if baseline HRQoL status predicts five-year post-CABG mortality. Methods: This pre-specified, Randomized On/Off Bypass Follow-up Study (ROOBY-FS) sub-analysis compared baseline patient characteristics and HRQoL scores, obtained from the Seattle Angina Questionnaire (SAQ) and Veterans Rand Short Form 36 (VR-36), between five-year post-CABG survivors and non-survivors. Standardized sub-scores were calculated for each questionnaire. Multivariable logistic regression assessed whether HRQoL survey sub-components independently predicted five-year mortality (p < 0.05). Results: Of the 2,203 ROOBY-FS enrollees, 2,104 (95.5%) completed baseline surveys. Significant differences between five-years post-CABG deaths (n = 286) and survivors (n = 1818) included age, history of chronic obstructive pulmonary disease, stroke, peripheral vascular disease, renal dysfunction, diabetes, lower left ventricular ejection fraction, atrial fibrillation, depression, non-white race/ethnicity, lower education status, and off-pump CABG. Adjusting for these factors, baseline VR-36 Physical Component Summary score (PCS) [p = 0.01], VR-36 Mental Component Summary score (MCS) (p < 0.001) and SAQ Physical Limitation score (SAQ-PL) (p = 0.003) were all associated with five-year all-cause mortality. Conclusions: Pre-CABG HRQoL scores may provide clinically relevant prognostic information beyond traditional risk models and prove useful for patient-provider shared decision making and enhancing pre-CABG informed consent.

Poor preoperative health-related quality of life (HRQoL) has been associated with reduced short-term survival after coronary artery bypass graft (CABG) surgery; however, its impact on long-term mortality is unknown. This study's objective was to determine if baseline HRQoL status predicts 5-year post-CABG mortality.This prespecified, randomized on/off bypass follow-up study (ROOBY-FS) subanalysis compared baseline patient characteristics and HRQoL scores, obtained from the Seattle Angina Questionnaire (SAQ) and Veterans RAND Short Form-36 (VR-36), between 5-year post-CABG survivors and nonsurvivors. Standardized subscores were calculated for each questionnaire. Multivariable logistic regression assessed whether HRQoL survey subcomponents independently predicted 5-year mortality (p ≤ .05).Of the 2203 ROOBY-FS enrollees, 2104 (95.5%) completed baseline surveys. Significant differences between 5-year post-CABG deaths (n = 286) and survivors (n = 1818) included age, history of chronic obstructive pulmonary disease, stroke, peripheral vascular disease, renal dysfunction, diabetes, lower left ventricular ejection fraction, atrial fibrillation, depression, non-White race/ethnicity, lower education status, and off-pump CABG. Adjusting for these factors, baseline VR-36 physical component summary score (p = .01), VR-36 mental component summary score (p .001), and SAQ physical limitation score (p = .003) were all associated with 5-year all-cause mortality.Pre-CABG HRQoL scores may provide clinically relevant prognostic information beyond traditional risk models and prove useful for patient-provider shared decision-making and enhancing pre-CABG informed consent.

There is currently no consensus regarding the optimal type of peritoneal dialysis catheter (PDC). We compared the outcomes of PDCs according to the number of cuffs, intercuff and intraperitoneal segment shape, and presence of a weighted tip. A systematic review of the literature was performed using the MEDLINE and Cochrane Library databases (end-of-search date: October 16th, 2019). We included studies comparing double-cuff vs. single-cuff, swan-neck vs. straight-neck, coiled-tip vs. straight-tip, and weighted vs. non-weighted PDCs for the outcomes of interest. We performed meta-analyses using the random-effects model. We assessed the risk of bias using the Newcastle–Ottawa scale and the Cochrane Collaboration’s Tool. In total, 38 studies were identified, of which 20 were randomized controlled trials (RCTs) and 18 were observational studies. No statistically significant differences were detected between double-cuff vs. single-cuff, swan-neck vs. straight-neck, and coiled-tip vs. straight tip PDCs in any of the outcomes of interest. Weighted catheters were associated with significantly lower rates of tunnel infection (relative risk [RR] 0.52, 95% confidence interval [CI] 0.31–0.95, p = 0.03), migration (RR 0.07, 95% CI 0.03–0.16, p

No consensus currently exists regarding the optimal approach for peritoneal dialysis catheter placement. We aimed to compare the outcomes of percutaneous and surgical peritoneal dialysis catheter placement. A systematic review of the literature was performed using the MEDLINE, Cochrane Library, and Scopus databases (end-of-search date: August 29th, 2020). We included studies comparing percutaneous (blind, under fluoroscopic/ultrasound guidance, and “half-perc”) and surgical peritoneal dialysis catheter placement (open and laparoscopic) in terms of their infectious complications (peritonitis, tunnel/exit-site infections), mechanical complications (leakage, inflow/outflow obstruction, migration, hemorrhage, hernia, bowel perforation) and long-term outcomes (malfunction, removal, replacement, surgery required, and mortality). Thirty-four studies were identified, including thirty-two observational studies (twenty-six retrospective and six prospective) and two randomized controlled trials. Percutaneous placement was associated with significantly lower rates of tunnel/exit-site infection [relative risk (RR) 0.72, 95% confidence interval (CI) 0.56–0.91], catheter migration (RR 0.68, 95% CI 0.49, 0.95), and catheter removal (RR 0.73, 95% CI 0.60–0.88). The 2-week and 4-week rates of early tunnel/exit-site infection were also lower in the percutaneous group (RR 0.45, 95% CI 0.22–0.93 and RR 0.41, 95% CI 0.27–0.63, respectively). No statistically significant difference was observed regarding other outcomes, including catheter survival and mechanical complications. Overall, the quality of published literature on the field of peritoneal dialysis catheter placement is poor, with a small percentage of studies being randomized clinical trials. Percutaneous peritoneal dialysis catheter placement is a safe procedure and may result in fewer complications, such as tunnel/exit-site infections, and catheter migration, compared to surgical placement. PROSPERO CRD42020154951.

A patient-specific airflow simulation was developed to help address the pressing need for an expansion of the ventilator capacity in response to the COVID-19 pandemic. The computational model provides guidance regarding how to split a ventilator between two or more patients with differing respiratory physiologies. To address the need for fast deployment and identification of optimal patient-specific tuning, there was a need to simulate hundreds of millions of different clinically relevant parameter combinations in a short time. This task, driven by the dire circumstances, presented unique computational and research challenges. We present here the guiding principles and lessons learned as to how a large-scale and robust cloud instance was designed and deployed within 24 hours and 800 000 compute hours were utilized in a 72-hour period. We discuss the design choices to enable a quick turnaround of the model, execute the simulation, and create an intuitive and interactive interface.

Complete revascularization (CR) at the time of coronary artery bypass graft (CABG) surgery improves long-term cardiac outcomes. No studies have previously reported angiographically confirmed CR rates post-CABG. This study's aim was to assess the impact upon long-term outcomes of CR versus incomplete revascularization (IR), confirmed by coronary angiography 1 year after CABG. Randomized On/Off Bypass Study patients who returned for protocol-specified 1-year post-CABG coronary angiograms were included. Patients with a widely patent graft supplying the major diseased artery within each diseased coronary territory were considered to have CR. Outcomes were all-cause mortality and major adverse cardiovascular events (MACE; all-cause mortality, nonfatal myocardial infarction, repeat revascularization) over the 4 years after angiography. Of the 1,276 patients, 756 (59%) had CR and 520 (41%) had IR. MACE was 13% CR versus 26% IR, p0.001. This difference was driven by fewer repeat revascularizations (5% CR vs 18% IR; p0.001). There were no differences in mortality (7.1% CR vs 8.1% IR, p = 0.13) or myocardial infarction (4% in both). Adjusted multivariable models confirmed CR was associated with reduced MACE (odds ratio 0.44, 95% confidence interval 0.33 to 0.58, p0.01), but had no impact on mortality. In conclusion, CR confirmed by post-CABG angiography was associated with improved MACE but not mortality. Repeat revascularization of patients with IR, driven by knowledge of the research angiography results, may have ameliorated potential mortality differences.

Background Failure to Rescue (FTR) is a valuable surgical quality improvement metric. The aim of this study is to assess the relationship between center volume and FTR following lung transplantation. Methods Using the database of the United Network for Organ Sharing (UNOS) all adult, primary, isolated lung recipients in the United States between May 2005 and March 2016 were identified. FTR was defined as operative mortality after any of five specific complications. FTR was compared across terciles of transplantation centers stratified based on operative volume. Results 17,185 lung recipients met study criteria. The composite FTR rate (Death following at least one complication) was 20.7%. Following stratification by volume, FTR rates increased from high to middle tercile centers (19.3% vs. 23.0%). Multivariate logistic regression models suggested an independent relationship between higher center volume and lower FTR rates (p Conclusion Higher volume lung transplantation centers have lower rates of failure to rescue.

This study sought to determine the indications, characteristics, and outcomes of cardiovascular implantable electronic device (CIED) surgery in patients with LVAD.Many patients with a left ventricular assist device (LVAD) will require implantable cardioverter-defibrillator generator change or device revision or are candidates for de novo implantable cardioverter-defibrillator implantation following LVAD implantation.We performed an observational retrospective study of all LVAD recipients who subsequently underwent CIED surgery at Duke University Hospital from 2009 to 2019.A total of 159 patients underwent CIED surgery following LVAD implantation, including generator change (n = 93), device revision (n = 38), and de novo implant (n = 28). The median (interquartile range) time from LVAD implantation to CIED surgery was 18.1 months (5.5 to 35.1 months). Pre-operative risk for infection was elevated in the overall cohort with a median (interquartile range) Prevention of Arrhythmia Device Infection Trial (PADIT) score of 7.0 (5.0 to 9.0). Pocket hematoma occurred in 21 patients (13.2%) following CIED surgery. Antimicrobial envelops were used in 43 patients (27%). Device infection due to CIED surgery occurred in 5 (3.1%) patients and occurred only in patients who developed post-operative pocket hematoma (p 0.001). Mortality at 1 year following CIED surgery was 20% (n = 32).CIED surgery following LVAD implantation is associated with an increased risk for pocket hematoma and CIED infection. Further studies are needed to determine the risk-benefit ratio of CIED surgery in patients with LVADs.

Background Short duration, antimicrobial prophylaxis that includes antistaphylococcal activity is recommended at the time of left ventricular assist device (LVAD) implantation to reduce infection-related complications. There continues to be wide variability in surgical infection prophylaxis (SIP) regimens among implantation centers. The aim of this study is to characterize current SIP regimens at different LVAD centers. Methods A survey study was conducted from 26 September 2017 to 25 October 2017. Surveys were distributed electronically to LVAD coordinators and infectious diseases specialists at 75 US medical centers identified as having an LVAD program. Data collection included information about antimicrobial selection, duration, Staphylococcus aureus screening, and decolonization procedures. Results We received 29 survey responses. The majority of surveys were completed by infectious diseases physicians (72.4% [21 out of 29]). Most responding centers reported LVAD programs established for greater than 10 years (20 out of 29 [69%]). Cardiac transplantation was performed in 28 out of 29 (96%) centers. Of centers reporting a defined SIP regimen for non-penicillin allergic patients (96% [28 out of 29]), 17.9% (5 out of 28) reported a four-drug regimen, 35.7% (10 out of 28) reported a three-drug regimen, and 46.4% (13 out of 28) reported a two-drug regimen, while no centers reported a single-drug regimen. Empiric fluconazole was common (50% [14 out of 28]) and 96.4% (27 out of 28) of regimens included vancomycin. Duration of antimicrobial prophylaxis (24 hours to 5 days), S. aureus screening, decolonization procedures, and alterations due to drug allergies varied across participating centers. Conclusions Our survey results indicate wide variation in SIP regimens among participating LVAD centers. These results highlight the need for studies evaluating the implications of SIP regimens, and whether clinical factors that prolong antimicrobial duration impact postoperative infection rates.

The generation of an experimental animal model often requires considerable investment of both time and money. Typically, investigators are interested in specific organs and when experimental animals are euthanized, tissues that are not the focus of the research project are discarded. However, the remaining tissues from these animals could provide valuable scientific information if efficient, error-proof and economical approaches to collect and biobank them were available. We have developed a device that, when incorporated into our tissue processing workflow, allows for high-throughput collection and processing of multiple rodent organ systems. This device, the mouse Processing Aid Device, or mouse PAD, helps to standardize organ collection and increase its efficiency.

Objectives The goal of this study was to assess the utility of transvenous lead extraction for cardiovascular implantable electronic device (CIED) infection in patients with a left ventricular assist device (LVAD). Background The utility of transvenous lead extraction for the management CIED infection in patients with a durable LVAD has not been well described. Methods Clinical and outcomes data were collected retrospectively among patients who underwent lead extraction for CIED infection after LVAD implantation at Duke University Hospital. Results Overall, 27 patients (n = 6 HVAD; n = 15 HeartMate II; n = 6 Heartmate III) underwent lead extraction for infection. Median (interquartile range) time from LVAD implantation to infection was 6.1 (2.5, 14.9) months. Indications included endocarditis (n = 16), bacteremia (n = 9), and pocket infection (n = 2). Common pathogens were Staphylococcus aureus (n = 10), coagulase-negative staphylococci (n = 7), and Enterococcus faecalis (n = 3). Sixty-eight leads were removed, with a median lead implant time of 5.7 (3.6, 9.2) years. Laser sheaths were used in all procedures, with a median laser time of 35.0 (17.5, 85.5) s. Mechanical cutting tools were required in 11 (40.7%) and femoral snaring in 4 (14.8%). Complete procedural success was achieved in 25 (93.6%) patients and clinical success in 27 (100%). No procedural failures or major adverse events occurred. Twenty-one patients (77.8%) were alive without persistent endovascular infection 1 year after lead extraction. Most were treated with oral suppressive antibiotics after extraction (n = 23 [82.5%]). Persistent infection after extraction occurred in 4 patients and was associated with 50% 1-year mortality. Conclusions Transvenous lead extraction for LVAD-associated CIED infection can be performed safely with low rates of persistent infection and 1-year mortality.

Objective Efficient flow of fluids through drainage/infusion catheters is affected by surrounding tissue, organ compression, and scar tissue development, limiting or completely obstructing flow through drainage holes. In this work, we introduce a novel three-dimensional (3D) drainage catheter with protected side holes to reduce flow blockages. We then compare its drainage performance to standard straight and pigtail catheters using computer-generated catheter designs and flow analysis software. Methods Drainage performance was computed as flow rate through the catheter for a given pressure differential. Each catheter contained drainage holes on the distal (insertion) end and a single outlet (hub) hole open to atmosphere. Computational fluid dynamics using ANSYS AIM 18.2 was used to simulate flow through the catheter and examine drainage performance based on variations to the following parameters: (1) side hole shape, (2) cross-sectional area of the catheters, (3) number of side holes, and (4) cross-sectional area of the side holes. Results Drainage through the newly introduced catheter in all simulations was nearly identical to standard pigtail and straight catheters. While working to optimize the 3D catheter design, we found that the changes in side hole shape and side hole cross-sectional area had little effect on the total flow rate through the catheters but had a large impact on flow rate through the side hole nearest to the hub (proximal hole). Additionally, the majority of flow in all catheters occurred at the most proximal 1 to 3 side holes closest to hub, with relatively little flow occurring at side holes more distally located (closest to insertion end). The 3D catheter demonstrated no changes in flow characteristics when the coiled segment was occluded, giving it an advantage over other catheter types when the catheter is compressed by surrounding tissue or other external obstruction. Conclusions The majority of fluid flow in catheters with a diameter of 4.67 mm (14 Fr) or smaller occurred at the most proximal 1 to 3 side holes. A novel 3D coiled catheter design can protect these proximal holes from external blockage while maintaining drainage performance compared with standard straight and pigtail catheters.

Background There is no standard of care with respect to the use of neoadjuvant chemotherapy (NAC) in resectable malignant pleural mesothelioma (MPM). We performed an intention-to-treat analysis with data from a single institution and the National Cancer Database (NCDB) to identify whether the use of NAC impacts survival in resectable MPM. Methods Patients with MPM who had surgery with curative intent at Duke University from 1995 to 2017 were selected, and the 2004–2015 NCDB was used to identify MPM patients with clinical stage I–IIIB who underwent definitive surgery. For both cohorts, patients were stratified by receipt of NAC. Primary outcomes were overall survival and postresection survival (RS), which were estimated using Kaplan-Meier and multivariable Cox proportional hazards models. Results A total of 257 patients met inclusion criteria in the Duke cohort. Compared with immediate resection (IR), NAC was associated with similar overall survival but an increased risk for postresection mortality in both unmatched (adjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.21 to 2.83) and propensity-matched (HR = 1.62, 95% CI = 1.03 to 2.55) cohorts. A total of 1949 NCDB patients were included: 1597 (81.9%) IR and 352 (18.1%) NAC. RS was worse for patients undergoing NAC in both unmatched (HR = 1.85, 95% CI = 1.21 to 2.83) and propensity-matched (HR = 1.29, 95% CI = 1.06 to 1.57) analyses compared with patients receiving IR. Conclusions In this intention-to-treat study, NAC was associated with worse RS compared with IR in patients with MPM. The risks and benefits of induction therapy should be weighed before offering it to patients with resectable MPM.

The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) isolated from zebrafish can direct targeted, injury-associated gene expression from viral DNA vectors delivered systemically in small and large adult mammalian species. When employed in combination with CRISPR-based epigenome editing tools in mice, zebrafish TREEs stimulated or repressed the expression of endogenous genes after ischemic myocardial infarction. Intravenously delivered recombinant AAV vectors designed with a TREE to direct a constitutively active YAP factor boosted indicators of cardiac regeneration in mice and improved the function of the injured heart. Our findings establish the application of contextual enhancer elements as a potential therapeutic platform for spatiotemporally controlled tissue regeneration in mammals.

Cardiac transplantation remains the gold standard therapy for end stage heart failure. However, it remains limited by the number of available donor hearts and by complications such as primary graft dysfunction and graft rejection. The recent clinical use of an ex vivo perfusion device in cardiac transplantation introduces a unique opportunity for treating cardiac allografts with therapeutic interventions to improve function and avoid deleterious recipient responses. Establishing a translational, large-animal model for therapeutic delivery to the entire allograft is essential for testing novel therapeutic approaches in cardiac transplantation. The porcine, heterotopic heart transplantation model in the intra-abdominal position serves as an excellent model for assessing the effects of novel interventions as well as the immunopathology of graft rejection. This model additionally offers long-term survival for the pig given that the graft is not required to maintain the recipient’s circulation. The aim of this protocol is to provide a reproducible and robust approach for achieving ex vivo delivery of a therapeutic to the entire cardiac allograft prior to transplantation and provide technical details to perform a survival heterotopic transplant of the ex vivo perfused heart.

Introduction: The optimal cardiac delivery route for stem cell and gene therapeutics is poorly understood. Direct intramyocardial (IM) injection has been proposed as the gold standard, however, it is invasive and not studied in detail against targeted intra-coronary (IC) delivery techniques. We sought to compare effectiveness of IM and targeted IC methods using cardiac magnetic resonance imaging (CMR) of nanoparticles in a porcine model. Hypothesis: IM provides the highest retention of delivered therapeutic, while targeted IC delivery yields high-volume retention in the perfused coronary territory. Methods: In Yorkshire swine (n=10), 5ml of ferumoxytol iron oxide (IO) nanoparticles, similar in size to therapeutic viral vectors, were injected: 1) IM via thoracotomy (n=3), 2) catheter based IC balloon-occlusion (BO) with distal infusion of the LAD (n=4), 3) IC with perforated balloon side wall (SW) infusion in the LAD (n=2), or 4) IC non-selective left main (LM) (n=1). Hearts were harvested and imaged with CMR using T1 and 3D inversion-recovery sequences. Retention of nanoparticles was quantified by percent of myocardium occupied. Results: IM delivery yielded the highest retention (16.3±5.5% of myocardial volume, p=0.04). Of the IC approaches, BO had the highest retention (8.7±2.2%, p=0.13 vs IM) compared to SW (5.5±4.9%) and LM (0%). On 3D CMR, BO yielded consistent uptake in the distal LAD territory, including the anterior wall and septum. IM delivery was limited to the anterior wall with no nanoparticles in the septum. Troponin increased 15,600±4,910 with IM vs.184±262 with IC (p=0.14). Conclusions: Direct IM injection offers the highest retention of delivered therapeutics to the heart. IC balloon occlusion-distal infusion has highest retention among IC techniques and provides an effective approach to direct therapeutics to the vascular bed most impacted by an infarct.

The complex and inaccessible space radiation environment poses an unresolved risk to astronaut cardiovascular health during long-term space exploration missions. To model this risk, healthy male c57BL/6 mice aged six months (corresponding to an astronaut of 34 years) were exposed to simplified galactic cosmic ray (GCR

Stanford Type B aortic dissection (TBAD) is a deadly cardiovascular disease with mortality rates as high as 50% in complicated cases. Patients with TBAD are often medically managed, but in ~20--40% of cases, patients experience aneurysmal degeneration in the dissected aorta, and surgical intervention is required. In this work, we simulated blood flow using computational fluid dynamics (CFD) to determine relationships between hemodynamics and aneurysmal degeneration, providing an important step towards predicting the need for intervention prior to significant aneurysm occurrence. Currently, surgeons intervene in TBAD cases based on the aneurysms growth rate and overall size, as well as a variety of other factors such as malperfusion, thrombosis, and pain, but predicting future risk of aneurysmal degeneration would allow earlier intervention leading to improved patient outcomes. Here, we hypothesized that hemodynamic metrics play an important role in the formation of aneurysms and that these metrics could be used to predict future aneurysmal degeneration in this patient population. Our retrospective dataset consisted of 16 patients with TBAD where eight required intervention due to aneurysmal degeneration and eight were medically managed. The patients with surgical intervention were examined in our study prior to the formation of an aneurysm. For each patient, we segmented and reconstructed the aortic geometry and simulated blood flow using the lattice Boltzmann method. We then compared hemodynamic metrics between to the two groups of patients, including time-averaged wall shear stress, oscillatory shear index, relative residence time, and flow fractions to the true and false lumen. We found significant differences in each metric between the true and false lumen. We also showed that flow fractions to the false lumen was higher in patients with aneurysmal degeneration (p = 0.02). These results are an important step towards developing more precise methods to predict future aneurysmal degeneration and the need for intervention in TBAD patients.

Stroke remains a significant complication of left ventricular assist device (LVAD) therapy. We performed a single-center retrospective study evaluating patients undergoing first-time HeartWare HVAD (Medtronic Inc) or HeartMate 3 (Abbott Inc) implantation from September 2009-February 2018.Exclusion criteria were age18 and preoperative ECMO. The primary endpoint was stroke-free survival. Stroke was defined as new neurological deficits persisting24 hours with corresponding radiographic evidence. Risk factors evaluated included demographics, medical comorbidities, heart failure etiology, LVAD indication, INTERMACS profile, and device type. Univariate predictors (P .15) and variables clinically suspected to raise stroke risk were entered in a multivariate hazard regression model, specified using backward selection of covariates and accounting for competing risks of transplant/LVAD exchange.A total of 163 HVAD and 84 HM3 patients were analyzed. Median follow up (until death, censoring for transplant/LVAD removal, or end of follow up) was 1.2 years in HVAD patients and 1.4 years in HM3 patients. Stroke occurred in 24 HVAD patients (15 ischemic, 9 hemorrhagic) and 6 HM3 patients (4 ischemic, 2 hemorrhagic). One-year stroke-free survival was 76.8% for HVAD and 84.3% for HM3. Thirty-day mortality following stroke was 41.7% for HVAD and 66.7% for HM3; 54.2% of HVAD strokes were disabling compared to 83.3% of HM3 strokes. Age, LVAD indication, and device type were associated (P .15) with stroke on univariate analysis. On multivariate analysis, the HVAD was associated with significantly higher stroke risk (hazard ratio, 2.57; 95% confidence interval, 1.02-6.44; P = .045).Different LVAD models appear to be associated with significantly different stroke risks.

Clinically, both percutaneous and surgical approaches to deliver viral vectors to the heart either have resulted in therapeutically inadequate levels of transgene expression or have raised safety concerns associated with extra-cardiac delivery. Recent developments in the field of normothermic ex vivo cardiac perfusion storage have now created opportunities to overcome these limitations and safety concerns of cardiac gene therapy. This study examined the feasibility of ex vivo perfusion as an approach to deliver a viral vector to a donor heart during storage and the resulting bio distribution and expression levels of the transgene in the recipient post-transplant. The influence of components (proprietary solution, donor blood, and ex vivo circuitry tubing and oxygenators) of the Organ Care System (OC) (TransMedics, Inc., Andover MA) on viral vector transduction was examined using a cell-based luciferase assay. Our ex vivo perfusion strategy, optimized for efficient Adenoviral vector transduction, was utilized to deliver 5 × 1013 total viral particles of an Adenoviral firefly luciferase vector with a cytomegalovirus (CMV) promotor to porcine donor hearts prior to heterotopic implantation. We have evaluated the overall levels of expression, protein activity, as well as the bio distribution of the firefly luciferase protein in a series of three heart transplants at a five-day post-transplant endpoint. The perfusion solution and the ex vivo circuitry did not influence viral vector transduction, but the serum or plasma fractions of the donor blood significantly inhibited viral vector transduction. Thus, subsequent gene delivery experiments to the explanted porcine heart utilized an autologous blood recovery approach to remove undesired plasma or serum components of the donor blood prior to its placement into the circuit. Enzymatic assessment of luciferase activity in tissues (native heart, allograft, liver etc.) obtained post-transplant day five revealed wide-spread and robust luciferase activity in all regions of the allograft (right and left atria, right and left ventricles, coronary arteries) compared to the native recipient heart. Importantly, luciferase activity in recipient heart, liver, lung, spleen, or psoas muscle was within background levels. Similar to luciferase activity, the luciferase protein expression in the allograft appeared uniform and robust across all areas of the myocardium as well as in the coronary arteries. Importantly, despite high copy number of vector genomic DNA in transplanted heart tissue, there was no evidence of vector DNA in either the recipient’s native heart or liver. Overall we demonstrate a simple protocol to achieve substantial, global gene delivery and expression isolated to the cardiac allograft. This introduces a novel method of viral vector delivery that opens the opportunity for biological modification of the allograft prior to implantation that may improve post-transplant outcomes.

Background Subclavian artery revascularization is frequently performed in the setting of thoracic endovascular aortic repair (TEVAR). However, there is little information on the short- and long-term outcomes of patients undergoing carotid to subclavian artery bypass in this clinical setting. As such, this study sought to define the early and late outcomes associated with this procedure. Methods Patients undergoing carotid-subclavian bypass in conjunction with TEVAR between June 2005 and September 2016 were retrospectively identified from a prospectively maintained, single-center aortic surgery database. The 30-day outcomes specific to the carotid-subclavian bypass procedure were analyzed, including cervical plexus nerve injury, bleeding complications, and local vascular complications. All preoperative and postoperative chest radiographs were carefully analyzed to assess for hemidiaphragm elevation indicative of phrenic nerve palsy. Long-term outcomes included primary graft patency and anastomotic complications. Results Of 579 consecutive patients undergoing TEVAR during this time interval, 112 patients (19%) underwent concomitant carotid-subclavian bypass. The cohort was 38% female (n = 43), with a mean age of 65 ± 14 years. The majority of conduits were 8-mm polytetrafluoroethylene grafts (n = 107 [95.5%]), with a minority being reversed saphenous vein (n = 4 [3.6%]) or Dacron (n = 1 [0.9%]) grafts. The bypass procedure was done concurrently at the time of TEVAR in 91% (n = 102) of cases. The short-term complication rate attributed specifically to the carotid-subclavian bypass was 29% (n = 33). These complications included phrenic nerve palsy in 25% (n = 27), recurrent laryngeal nerve palsy in 5% (n = 6), axillary nerve palsy in 2% (n = 2), and neck hematoma requiring re-exploration in 1% (n = 1) of patients. The 30-day in-hospital all-cause mortality rate was 5% (n = 6), and the rate of permanent paraparesis or paraplegia was 0.9% (n = 1). Of the operative survivors (n = 106), follow-up imaging of the bypass graft was available in 87% (n = 92) of patients. Actuarial primary graft patency was 97% at 5 years. There were three patients (3%) with bypass graft occlusions, two of which were clinically silent and detected on follow-up imaging. The third was detected because of symptoms of subclavian steal and required repeated revascularization. Two patients (2%) developed a late anastomotic pseudoaneurysm requiring either endovascular (n = 1) or surgical (n = 1) intervention. Conclusions Carotid-subclavian bypass for revascularization of the subclavian artery performed in the setting of TEVAR is durable, although the true complication rate is likely higher than is generally reported in the literature because of a not insignificant rate of phrenic nerve palsy. These data should serve well as “gold standard” comparison data for emerging branch graft devices.

BACKGROUND: Donors with characteristics that may increase the likelihood of disease transmission with transplantation are noted as increased risk via Public Health Service criteria. This study aimed to establish the implications of declining an increased-risk donor (IRD) organ offer in lung transplantation. METHODS: Adult candidates waitlisted for isolated lung transplantation in the United States using the Organ Procurement and Transplantation Network/United Network of Organ Sharing registry from 2007 to 2017 were identified. Individual match run files identified candidate recipients who matched to an IRD offer. Competing-risks analysis ascertained the likelihood of survival to transplantation. A stratified Cox model and restricted mean survival times estimated the survival benefit associated with the acceptance of an IRD organ. RESULTS: A total of 6,963 candidates met inclusion criteria, and 1,473 (21.2%) accepted an IRD offer. Candidates who accepted an IRD offer were older, more likely to be male, and had a higher lung allocation score at the time of listing (all p < 0.05). At 1 year after an IRD offer decline, 70.5% of candidates underwent a lung transplant, 13.8% died or decompensated, and 14.9% were still awaiting transplant. Compared with those who declined, candidates who accepted the IRD offer had significantly improved cumulative mortality at 1 year (14.1% vs 23.9%, p < 0.001) and 5 years (48.4% vs 53.8%, p < 0.001). CONCLUSIONS: IRD organ declination is associated with a decreased rate of lung transplantation and worse survival. Overall post-transplant survival rates for those who survive to transplantation are equivalent.

Intra-aortic balloon pump (IABP) is often used to support patients in decompensated heart failure. Placement of the IABP via the axillary artery facilitates long-term support with the device and may allow for the conversion of an acute heart failure (HF) patient into a chronic HF patient using a modified weaning protocol; allowing for medical symptom management and removal of mechanical support. We will discuss strategies for supporting these complicated patients.

Stroke is a devastating complication of left ventricular assist device (LVAD) therapy. Understanding the characteristics, risk factors and outcomes of strokes associated with the centrifugal flow LVADs is important to devise better strategies for management and prevention. This is a retrospective cohort study at a single US academic medical center. The cohort includes patients who received a first time Heartmate 3 (HM3) or Heartware (HVAD) LVAD between September 2009 through February 2018 and had a stroke while the LVAD was in place. Descriptive statistics were used when appropriate. A logistic regression analysis was used to determine predictors of poor outcome. Out of a total of 247 patients, 12.1% (N = 30, 24 HVAD and 6 HM3) had a stroke (63% ischemic) and 3 of these patients had pump thrombosis. Events per patient year (EPPY) were similar for HVAD and HM3 patients (0.3 ± 0.1). INR was subtherapeutic in 47.4% of ischemic stroke patients and supratherapeutic in 18.2% of hemorrhagic stroke patients. Concurrent infections were more common in the setting of hemorrhagic stroke than ischemic stroke (45.4% vs 5.3%, p = 0.008). Strokes were severe in most cases, with initial NIH stroke scale (NIHSS) higher in HM3 patients compared to HVAD patients (mean 24.6 vs 16) and associated with high in-patient mortality (21.1% of ischemic stroke vs. 88.8% of hemorrhagic stroke). Predictors of death within 30 days and disability at 90 days included creatinine at stroke onset, concurrent infection, hemorrhaghic stroke, and initial stroke severity (NIHSS). A score derived from these variables predicted with 100% certainty mortality at 30 days and mRS ≥ 4 at 90 days. For patients with centrifugal flow LVADs, ischemic strokes were more common but hemorrhagic strokes were associated with higher in-patient mortality and more frequently seen in the setting of concurrent infections. Infections, sub or supratherapeutic INR range, and comorbid cardiovascular risk factors may all be contributing to the stroke burden. These findings may inform future strategies for stroke prevention in this population.

There is currently no consensus regarding the optimal type of peritoneal dialysis catheter (PDC). We compared the outcomes of PDCs according to the number of cuffs, intercuff and intraperitoneal segment shape, and presence of a weighted tip.A systematic review of the literature was performed using the MEDLINE and Cochrane Library databases (end-of-search date: October 16th, 2019). We included studies comparing double-cuff vs. single-cuff, swan-neck vs. straight-neck, coiled-tip vs. straight-tip, and weighted vs. non-weighted PDCs for the outcomes of interest. We performed meta-analyses using the random-effects model. We assessed the risk of bias using the Newcastle-Ottawa scale and the Cochrane Collaboration's Tool.In total, 38 studies were identified, of which 20 were randomized controlled trials (RCTs) and 18 were observational studies. No statistically significant differences were detected between double-cuff vs. single-cuff, swan-neck vs. straight-neck, and coiled-tip vs. straight tip PDCs in any of the outcomes of interest. Weighted catheters were associated with significantly lower rates of tunnel infection (relative risk [RR] 0.52, 95% confidence interval [CI] 0.31-0.95, p = 0.03), migration (RR 0.07, 95% CI 0.03-0.16, p 0.001), drainage failure (RR 0.62, 95% CI 0.39-0.96, p = 0.03), cuff extrusion (RR 0.40, 95% CI 0.21-0.74, p 0.001), and complication-related removal (RR 0.53, 95% CI 0.44-0.64, p 0.001).Among the different types of PDCs, weighted catheters result in lower complication rates and superior long-term outcomes compared to non-weighted catheters. Other aspects of the catheter design do not significantly affect PDC outcomes.PROSPERO 2020 CRD42020158177.

Novel atherosclerosis models are needed to guide clinical therapy. Here, we report an in vitro model of early atherosclerosis by fabricating and perfusing multi-layer arteriole-scale human tissue-engineered blood vessels (TEBVs) by plastic compression. TEBVs maintain mechanical strength, vasoactivity, and nitric oxide (NO) production for at least 4 weeks. Perfusion of TEBVs at a physiological shear stress with enzyme-modified low-density-lipoprotein (eLDL) with or without TNFα promotes monocyte accumulation, reduces vasoactivity, alters NO production, which leads to endothelial cell activation, monocyte accumulation, foam cell formation and expression of pro-inflammatory cytokines. Removing eLDL leads to recovery of vasoactivity, but not loss of foam cells or recovery of permeability, while pretreatment with lovastatin or the P2Y11 inhibitor NF157 reduces monocyte accumulation and blocks foam cell formation. Perfusion with blood leads to increased monocyte adhesion. This atherosclerosis model can identify the role of drugs on specific vascular functions that cannot be assessed in vivo., Human microphysiological systems (MPS) have some advantages over animal models to study the mechanisms of disease. Here the authors use a tissue-engineered blood vessel MPS to create a model of early stage atherosclerosis and assess the effect of several drugs.