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Background: Only limited data exist describing the histologic and noncardiomyocyte function of human myocardium in end-stage heart failure (HF)., Objectives: The authors sought to determine changes in noncardiomyocyte cellular activity in patients with end-stage HF after left ventricular assist device (LVAD)-induced remodeling to identify mechanisms impeding recovery., Methods: Myocardium was obtained from subjects undergoing LVAD placement and/or heart transplantation. Detailed histological analyses were performed, and, when feasible, mononuclear cells were isolated from fresh, dissociated myocardium for quantitative reverse transcription polymerase chain reaction studies. Echocardiographic and catheterization data were obtained during routine care., Results: Sixty-six subjects were enrolled; 54 underwent 8.0 ± 1.2 months of LVAD unloading. Despite effective hemodynamic unloading and remodeling, there were no differences after LVAD use in capillary density (0.78 ± 0.1% vs. 0.9 ± 0.1% capillary area; n = 42 and 28, respectively; p = 0.40), cardiac fibrosis (25.7 ± 2.4% vs. 27.9 ± 2.4% fibrosis area; n = 44 and 31, respectively; p = 0.50), or macrophage density (80.7 ± 10.4 macrophages/mm 2 vs. 108.6 ± 15 macrophages/mm 2 ; n = 33 and 28, respectively; p = 0.1). Despite no change in fibrosis or myofibroblast density (p = 0.40), there was a 16.7-fold decrease (p < 0.01) in fibroblast-specific collagen expression. Furthermore, there was a shift away from pro-fibrotic/alternative pro-fibrotic macrophage signaling after LVAD use., Conclusions: Despite robust cardiac unloading, capillary density and fibrosis are unchanged compared with loaded hearts. Fibroblast-specific collagen expression was decreased and might be due to decreased stretch and/or altered macrophage polarization. Dysfunctional myocardium may persist, in part, from ongoing inflammation and poor extracellular matrix remodeling. Understanding these changes could lead to improved therapies for HF., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Treatment of end-stage heart failure includes cardiac transplantation or ventricular assist device (VAD) therapy. Although increasingly prevalent, current VAD therapy has inherent complications, including thrombosis. Studies have demonstrated that VAD implantation alters intracardiac blood flow, creating areas of stagnation that predispose to thrombus formation. Two potential surgical configurations exist for VAD implantation: through the apical or diaphragmatic surfaces of the heart. We hypothesized that diaphragmatic implantation causes more stagnation than apical implantation. We also hypothesized that intermittent aortic valve (AV) opening reduces stagnation of blood inside the left ventricle (LV) when compared with a closed AV. To test these hypotheses, a human LV geometry was recreated in silico and a VAD inflow cannula was virtually implanted in each configuration. A computational indicator-dilution study was conducted where "virtually dyed blood" was washed out of the LV by injecting blood with no dye. Simulations demonstrated a substantial reduction in stagnation with intermittent AV opening. In addition, virtual dye was cleared slightly faster in the apical configuration. Simulations from our study demonstrate the clinical importance of VAD management to allow intermittent opening of the AV to prevent subvalvular stagnation, and also suggests that apical configuration might be more hemodynamically favorable.

The current study evaluates quantitatively the impact that intermittent aortic valve (AV) opening has on the thrombogenicity in the aortic arch region for patients under left ventricular assist device (LVAD) therapy. The influence of flow through the AV, opening once every five cardiac cycles, on the flow patterns in the ascending aortic is measured in a patient-derived computed tomography image-based model, after LVAD implantation. The mechanical environment of flowing platelets is investigated, by statistical treatment of outliers in Lagrangian particle tracking, and thrombogenesis metrics (platelet residence times and activation state characterized by shear stress accumulation) are compared for the cases of closed AV versus intermittent AV opening. All hemodynamics metrics are improved by AV opening, even at a reduced frequency and flow rate. Residence times of platelets or microthrombi are reduced significantly by transvalvular flow, as are the shear stress history experienced and the shear stress magnitude and gradients on the aortic root endothelium. The findings of this device-neutral study support the multiple advantages of management that enables AV opening, providing a rationale for establishing this as a standard in long-term treatment and care for advanced heart failure patients.

Background: Allocation of donor hearts in the United States is accomplished by an algorithm based on status, time waited, and geographic boundaries. Although not designed to always transplant the highest acuity candidates, the ability of current United Network for Organ Sharing policies to prioritize highest acuity candidates is unknown., Methods: We analyzed 32,866 adult match runs generated from 2007 to 2014. Each candidate's sequence number within a match run was compared with the candidate's risk of mortality using Kendall's tau-b-a measure of rank correlation. Two primary methods of evaluating risk of mortality were used: status designation-based risk (i.e., status 1A risk > status 1B > status 2) and status justification-based risk (e.g., status 1A justified by presence of a complication)., Results: Median sequence number for transplanted candidates was 3 (interquartile range [IQR]: 1, 9). Median correlation among match runs for status-based risk was 0.57 (IQR: 0.47, 0.66) and for justification-based risk was 0.51 (IQR: 0.39, 0.60). Sensitivity to status 2 candidates was evident when status 2 candidates were removed from the sample (status-based tau-b = 0.31, justification-based tau-b = 0.1) and with restriction of the data set to only the first 20 candidates (status-based tau-b = 0.35, justification-based tau-b = 0.15)., Conclusions: There is only mild correlation between status and priority under the current allocation algorithm and poor concordance when more detailed risks are considered. The geographic allocation rule is responsible for most of the measured discordance., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

We report on the fully percutaneous insertion and removal of the Impella 5.0 microaxial flow device via the axillary artery in a patient with cardiogenic shock and peripheral artery disease. Due to inadequate iliofemoral vasculature and desire for mobility, the axillary artery was felt to be the most appropriate access approach for temporary mechanical circulatory support. The procedure was well tolerated and the patient was supported for 17 days, at which time the device was safely removed in a fully percutaneous manner at the time of permanent left ventricular assist device placement. Percutaneous transaxillary placement of the Impella 5.0 device is a feasible support option in cardiogenic shock in patients with hostile iliofemoral disease.

Background: Heart transplant volumes are not matching growing demand, and donor heart use may be decreasing., Objectives: This study sought to investigate the benefit of heart transplantation compared with waiting while accounting for the estimated risk of a given donor-recipient match., Methods: This study identified 28,548 heart transplant candidates in the Organ Procurement and Transplant Network between July 2006 and December 2015. Donor-recipient match quality was estimated from the donor risk index. A time-dependent covariate Cox model was used to determine the effect of donor-recipient match quality on the likelihood of a composite outcome while waiting for a transplant or after transplantation. The composite outcome was death or delisting as too ill., Results: Donor and recipient risk estimates were inversely related to the candidate urgency. Net benefit from heart transplantation was evident across all estimates of donor-recipient status 1A and 1B candidates: status 1A (lowest-risk quartile hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.31 to 0.43; highest-risk quartile HR: 0.52; 95% CI: 0.44 to 0.61) and status 1B candidates (lowest-risk quartile HR: 0.41; 95% CI: 0.36 to 0.47; highest-risk quartile HR: 0.66; 95% CI: 0.58 to 0.74). Status 2 candidates showed a benefit from heart transplantation; however, survival benefit was delayed. For the highest-risk donor-recipient matches, a net benefit of transplantation occurred immediately for status 1A candidates, after 12 months for status 1B candidates, and after 3 years for status 2 candidates., Conclusions: This study demonstrated a survival benefit of heart transplantation across all ranges of estimated donor-recipient match risk for status 1A and status 1B candidates. Donor heart acceptance should be the favored strategy for these candidates. The benefit of transplantation for status 2 candidates was less apparent and dependent on estimated donor-recipient match risk, suggesting that a measure of donor-recipient match quality may be useful when considering the immediate benefit of heart transplantation for status 2 candidates in stable condition., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Methanol as a green and renewable resource can be used to generate hydrogen by reforming, i.e., its catalytic oxidation with water. In combination with a fuel cell this hydrogen can be converted into electrical energy, a favorable concept, in particular for mobile applications. Its realization requires the development of novel types of structured catalysts, applicable in small scale reactor designs. Here, three different types of such catalysts were investigated for the steam reforming of methanol (SRM). Oxides such as TiO 2 and CeO 2 and mixtures thereof (Ce 1 Ti 2 O x ) were deposited inside a bulk nanoporous gold (npAu) material using wet chemical impregnation procedures. Transmission electron and scanning electron microscopy reveal oxide nanoparticles (1-2 nm in size) abundantly covering the strongly curved surface of the nanoporous gold host (ligaments and pores on the order of 40 nm in size). These catalysts were investigated in a laboratory scaled flow reactor. First conversion of methanol was detected at 200 °C. The measured turn over frequency at 300 °C of the CeO x /npAu catalyst was 0.06 s -1 . Parallel investigation by in situ infrared spectroscopy (DRIFTS) reveals that the activation of water and the formation of OH ads are the key to the activity/selectivity of the catalysts. While all catalysts generate sufficient OH ads to prevent complete dehydrogenation of methanol to CO, only the most active catalysts (e.g., CeO x /npAu) show direct reaction with formic acid and its decomposition to CO 2 and H 2 . The combination of flow reactor studies and in operando DRIFTS, thus, opens the door to further development of this type of catalyst.

The duration of support in patients with HeartMate II implantation as a bridge to transplant or as destination therapy is rising. As clinical experience continues to grow, physiologic changes contributing to pump malfunction are becoming apparent. Once malfunction is noted with increased power spikes, rises in lactate dehydrogenase and low-flow alarms, thrombosis of the pump is at risk. We describe outflow graft compression and offer an expeditious and definitive management strategy. Our novel management stenting strategy for outflow graft compression will continue to evolve as experience is gained., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This study quantifies thrombogenic potential (TP) of a wide range of left ventricular assist device (LVAD) outflow graft anastomosis angles through state-of-the-art techniques: 3D imaged-based patient-specific models created via virtual surgery and unsteady computational fluid dynamics with Lagrangian particle tracking. This study aims at clarifying the influence of a single parameter (outflow graft angle) on the thrombogenesis associated with flow patterns in the aortic root after LVAD implantation. This is an important and poorly-understood aspect of LVAD therapy, because several studies have shown strong inter and intrapatient thrombogenic variability and current LVAD implantation strategies do not incorporate outflow graft angle optimization. Accurate platelet-level investigation, enabled by statistical treatment of outliers in Lagrangian particle tracking, demonstrates a strong influence of outflow graft anastomoses angle on thrombogenicity (platelet residence times and activation state characterized by shear stress accumulation) with significantly reduced TP for acutely-angled anastomosed outflow grafts. The methodology presented in this study provides a device-neutral platform for conducting comprehensive thrombogenicity evaluation of LVAD surgical configurations, empowering optimal patient-focused surgical strategies for long-term treatment and care for advanced heart failure patients.

Background: Heart transplant remains the definitive therapy for advanced heart failure patients but is limited by organ availability. We identified a large number of donor hearts from our organ procurement organization (OPO) being exported to other regions., Methods: We engaged a multidisciplinary team including transplant surgeons, cardiologists, and our OPO colleagues to identify opportunities to improve our center-specific organ utilization rate. We performed a retrospective analysis of donor offers before and after institution of a novel review process., Results: Each donor offer made to our program was reviewed on a monthly basis from July 2013 to June 2014 and compared with the previous year. This review process resulted in a transplant utilization rate of 28% for period 1 versus 49% for period 2 (P = .007). Limiting the analysis to offers from our local OPO changed our utilization rate from 46% to 75% (P = .02). Transplant volume increased from 22 to 35 between the 2 study periods. Thirty-day and 1-year mortality were unchanged over the 2 periods. A total of 58 hearts were refused by our center and transplanted at other centers. During period 1, the 30-day and 1-year survival rates for recipients of those organs were 98% and 90%, respectively, comparable with our historical survival data., Conclusions: The simple process of systematically reviewing donor turndown events as a group tended to reduce variability, increase confidence in expanded criteria for donors, and resulted in improved donor organ utilization and transplant volumes., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: This study investigates the relationship of periportal fibrosis on postoperative outcomes after ventricular assist device (VAD) implantation., Methods: Between July 2005 and August 2014, a total of 233 patients were implanted with continuous flow VADs. Liver biopsy was performed on 16 patients with concern for liver disease. Survival was evaluated using the Kaplan-Meier method. The effect of fibrosis on length of stay (LOS) in the intensive care unit was modeled using Poisson regression. Adjustments were made for age, profile from the Interagency Registry for Mechanically Assisted Circulatory Support, biopsy, and model for end-stage liver disease score., Results: Fourteen of the 16 patients who underwent biopsy had periportal fibrosis without cirrhosis. One-year survival for the groups with and without biopsy-proven fibrosis was 93% ± 7% and 86% ± 2% (P = .97), respectively. The intensive care unit LOS was not different for those with (median, 7 days; interquartile range: 3-14 days) versus without fibrosis (median, 6 days; interquartile range 4-10 days; P = .65). Fibrosis (P = .42), age (0.95), model for end-stage liver disease excluding internal normalized ratio-XI score (P = .64), performance of a biopsy (P = .28), and Interagency Registry for Mechanically Assisted Circulatory Support class (P = .70) were not associated with intensive care unit LOS. Risk was increased of gastrointestinal bleeding (14% vs 4%; P = .026) in the first year among patients with fibrosis., Conclusions: The presence of periportal fibrosis did not affect survival or outcomes in patients undergoing VAD implantation. These findings suggest that carefully selected patients with advanced heart failure and hepatic fibrosis without cirrhosis may achieve acceptable outcomes with VAD implantation., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Measurement of lattice strain is important to characterize semiconductor nanostructures. As strain has large influence on the electronic band structure, methods for the measurement of strain with high precision, accuracy and spatial resolution in a large field of view are mandatory. In this paper we present a theoretical study of precision and accuracy of measurement of strain by convergent nano-beam electron diffraction. It is found that the accuracy of the evaluation suffers from halos in the diffraction pattern caused by a variation of strain within the area covered by the focussed electron beam. This effect, which is expected to be strong at sharp interfaces between materials with different lattice plane distances, will be discussed for convergent-beam electron diffraction patterns using a conventional probe and for patterns formed by a precessing electron beam. Furthermore, we discuss approaches to optimize the accuracy of strain measured at interfaces. The study is based on the evaluation of diffraction patterns simulated for different realistic structures that have been investigated experimentally in former publications. These simulations account for thermal diffuse scattering using the frozen-lattice approach and the modulation-transfer function of the image-recording system. The influence of Poisson noise is also investigated., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Introduction: Mechanical circulatory support for heart failure, including the Total Artificial Heart (TAH, Syncardia, Tucson, AZ, USA) has increased in recent years. This report describes bleeding complications associated with the device., Methods: A single institution prospectively maintained quality improvement database was reviewed encompassing the first year of clinical experience with the TAH. Patients who underwent TAH implantation were identified, and a review of complications and outcomes was undertaken., Results: Ten patients underwent TAH implant. Four patients experienced delayed postoperative bleeding. In three patients the manifestation of bleeding was tamponade and evidenced by TAH decreased cardiac output. In two patients, at postoperative days 31 and 137, there was a partial disruption of the aortic anastomosis along the outer curvature with pseudoaneurysm formation. Both were repaired by primary suture closure, without use of cardiopulmonary bypass. There was no mortality attributable to bleeding., Conclusions: TAH patients are at risk for delayed postoperative bleeding, often manifest as an acute decrease in cardiac output. Due to pulsatility and high dP/dT, bleeding from the aortic anastomosis should be considered in the differential of a patient with low flow and/or tamponade., (© 2015 Wiley Periodicals, Inc.)

Advanced heart failure (AHF) describes the subset of heart failure patients refractory to conventional medical therapy. For some AHF patients, the use of mechanical circulatory support (MCS) provides an intermediary "bridge" step for transplant-eligible patients or an alternative therapy for transplant-ineligible patients. Over the past 20 years, clinical observations have revealed that approximately 1% of patients with MCS undergo significant reverse remodeling to the point where the device can be explanted. Unfortunately, it is unclear why some patients experience durable, sustained myocardial remission, while others redevelop heart failure (i.e. which hearts "hold" and which hearts "fold"). In this review, we outline unmet clinical needs related to treating patients with MCS, provide an overview of protein dynamics in the reverse-remodeling process, and propose specific areas where we expect MS and proteomic analyses will have significant impact on our understanding of disease progression, molecular mechanisms of recovery, and provide new markers with prognostic value that can positively impact patient care. Complimentary perspectives are provided with the goal of making this important topic accessible and relevant to both a clinical and basic science audience, as the intersection of these disciplines is required to advance the field., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

It is now recognized that a majority of single ventricle patients, those with functionally univentricular hearts, who have survived palliative cavopulmonary connection will experience circulatory failure and end-organ dysfunction due to intrinsic inadequacies of a circulation supported by a single ventricle. Thus, there are an increasing number of patients with functional single ventricles presenting with failing circulations that may benefit from mechanical circulatory support (MCS). The paucity of experience with MCS in this population, even at high volume cardiac centers, contributes to limited available data to guide MCS device selection and management. Thus, a registry of MCS in this population would be beneficial to the field. A conference was convened in January 2012 of pediatric and adult cardiologists, pediatric cardiac intensivists, congenital heart surgeons, and adult cardiothoracic surgeons to discuss the current state of MCS, ventricular assist device, and total artificial heart therapy for patients who have undergone cavopulmonary connection, either superior cavopulmonary connection or total cavopulmonary connection. Specifically, individual experience and challenges with VAD therapy in this population was reviewed and creation of a multiinstitutional registry of MCS/ventricular assist device in this population was proposed. This document reflects the consensus from the meeting and provides a descriptive overview of the registry referred to as Mechanical Support as Failure Intervention in Patients with Cavopulmonary Shunts., (© 2013 Wiley Periodicals, Inc.)

Until recently anomalous coronary artery anatomy was only identified either by coronary angiography, at autopsy, or during cardiac surgery. With recent developments in the area of cardiac imaging, ECG-gated cardiac computed tomography (CT) has emerged as a minimally invasive modality to delineate both coronary anatomy and pathology. We present a case of an anomalous right coronary artery origin from the ascending aorta detected by ECG-gated cardiac CT in a 47 year-old male who presented to the emergency department complaining of acute chest pain after intense exercise. Given its relatively non invasive nature, ECG-gated cardiac CT may assist in the diagnosis and management of patients with atypical chest pain in which more invasive diagnostic examinations (i.e. coronary angiography) are not warranted.

Background: Preoperative evaluation of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) has included esophagogastroduodenoscopy (EGD) with little data to substantiate its use., Methods: A retrospective analysis was conducted of patients from Feb 04 to Mar 05 who underwent preoperative EGD and subsequently LRYGBP., Results: 169 patients underwent EGD prior to surgery. Their mean age was 41.1 years (range 14-66), mean BMI 49.7 (range 35-78), and 82% were females. There were no complications from EGD. Significant findings in patients at EGD included gastric ulceration in 3 (2%), duodenal ulcer in 1 (0.7%), Barrett's esophagus in 2 (1.3%), and a GI stromal tumor (GIST) in 1 (0.7%). EGD revealed hiatal hernias in 56 (35.2%), esophagitis in 28 (17%), Schatzki's ring in 5 (3%), gastritis in 43 (27%), gastric polyps in 8 (5%), and duodenitis in 9 (6%). 53 patients (33.3%) had a negative EGD. Ulcer and severe gastritis, esophagitis, and duodenitis diagnosed preoperatively were treated medically before surgery. 9 hiatal hernias were repaired intraoperatively. The patient with the GIST underwent laparoscopic near-total gastrectomy and gastric bypass, while 1 patient with an antral polyp underwent laparoscopic partial gastrectomy in addition to the LRYGBP., Conclusion: EGD is essential for diagnosis of GI diseases including tumors, ulcers, and hiatal hernias that alter the medical and surgical management of patients undergoing gastric bypass.

Of all common malignancies, pancreatic cancer has the lowest survival rate. According to estimates by the American Cancer Society, in 2004, 31,860 Americans were diagnosed, and 31,270 died from this near universally lethal disease. Unfortunately, only a small minority of patients are diagnosed when the extent of disease is still localized and thus potentially curable. These dismal survival results could be improved by developing successful screening and prevention strategies. Routine screening is not currently suggested for pancreatic cancer; however, there may be a benefit in a select group of patients identified to be at high risk for developing this disease. It is recommended that surveillance be performed on these high-risk individuals in a research setting to allow for the development of a successful detection strategy.

There are circumstances that make abdominal wall closure unsafe and technically impossible after laparotomy for trauma. In these difficult cases, prosthetic materials may be necessary to temporarily close the abdominal wall. To determine the optimal prosthetic in these instances, a retrospective chart review was conducted in our urban Level I trauma center. Twenty-five patients received 31 abdominal wall prostheses over a 4-year period. There were 7, 8, and 10 patients with 7 Marlex, 9 Dexon, and 15 Goretex prostheses, respectively. Each patient had only one type of prosthesis placed. The average age was 30.7 +/- 12.0 years, injury severity score was 20.3 +/- 7.4, and abdominal trauma index was 35.9 +/- 18.0; there was no significant difference in these values between groups. Eight patients died soon after the prosthesis was placed (average, 12.9 days) secondary to ongoing shock or multiple organ failure. Three of the seven surviving Goretex patients (43%) were intentionally left with small hernias. Three of the six Dexon patients (50%) were left with hernias; one of these eviscerated on day 150 and subsequently died, and the others have disabling gigantic hernias. Three of the four Marlex patients (75%) developed fistulae as a result of erosion into the small bowel or colon. One Marlex patient suffered with a chronically draining abdominal wound for 398 days prior to definitive closure. Goretex appears to be the best prosthetic for temporary abdominal wall closure because it causes less inflammatory reaction because of its smooth surface. It is therefore easier to retrieve at the time of definitive closure and carries less risk of fistula formation than other prostheses. Our Dexon patients suffered with gigantic hernias and one died because of complications of evisceration. We have abandoned the use of Marlex in abdominal wall closure because of the high incidence of fistula formation. We advocate the use of Goretex in temporary abdominal wall closure in this challenging group of patients.

The synthesis and X-ray diffraction analysis of two dipeptide taste ligands have been carried out as part of our study of the molecular basis of taste. The compounds L-aspartyl-D-alpha-methylphenylalanine methyl ester [L-Asp-D-(alpha Me)Phe-OMe] and L-aspartyl-D-alanyl-2,2,5, 5-tetramethylcyclopentanyl ester [L-Asp-D-Ala-OTMCP] elicit bitter and sweet taste, respectively. The C-terminal residues of the two analogues adopt distinctly different conformations in the solid state. The aspartyl moiety assumes the same conformation found in other dipeptide taste ligands with the side-chain carboxylate and the amino groups forming a zwitterionic ring with a conformation defined by psi, chi 1 = 157.7 degrees, -61.5 degrees for L-Asp-D-Ala-OTMCP and 151.0 degrees, -68.8 degrees for L-Asp-D-(alpha Me)Phe-OMe. In the second residue, a left-handed helical conformation is observed for the (alpha Me)Phe residue of L-Asp-D-(alpha Me)Phe-OMe with phi 2 = 49.0 degrees and psi 2 = 47.9 degrees, while the Ala residue of L-Asp-D-Ala-OTMCP adopts a semi-extended conformation characterized by dihedral angles phi 2 = 62.8 degrees and psi 2 = -139.9 degrees. The solid-state structure of the bitter L-Asp-D-(alpha Me)Phe-OMe is extended: while the crystal structure of the sweet L-Asp-D-OTMCP roughly adopts the typical L-shaped structure shown by other sweeteners. The data of L-Asp-D-(alpha Me)Phe-OMe are compared with those of its diastereoisomer L-Asp-L-(alpha Me)Phe-OMe. Conformational analysis of the two taste ligands in solution by NMR and computer simulations agrees well with our model for sweet and bitter tastes.