The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

1 | Pathological classification and etiological prevalence of cervicitis and vulvovaginitis in ewes suffering from infertility problems Pathologische Klassifizierung und ethiologische Prevalenz von Zervizitis und Vulvovaginitis in weiblichen Schafen mit Fertilitätsproblemen SKh Abd Elghaffar1; MKh Abd-Elrahman1; AE Zein2; FA Abu Zakaieb2 1Department of Pathology, Faculty of Veterinary Medicine, Assuit University, Assiut, Egypt; 2Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt The purpose of this study is to investigate reproductive problems which may occur in ewes using pathological and bacteriological examination. One hundred ewes slaughtered in abattoirs at Sohag Governorate, Egypt, were included in this study. Their age ranged from 3 to 6 years. According to the owners complain, these animals suffered from many infertility problems such as repeat breeding and anoestrus. After slaughtering, the genital tracts were examined grossly. Bacteriological swabs were taken from the lumen of the uterus, cervix and vagina for bacteriological examination. Cervical and vaginal tissue samples were taken and processed for histopathology. The cervical lesions were classified into acute catarrhal cervicitis (7 cases), chronic catarrhal cervicitis (4 cases), acute necrotic cervicitis (one case), and acute fibrinonecrotic cervicitis (two cases). Vaginal and vulvar lesions were classified into acute granular vulvovaginitis (8 cases), chronic granular vulvovaginitis (2 cases) and ulcerative vulvovaginitis (2 cases). Staph.aureus was isolated from two cases (3.33%), Staph. aureus with Streptococcus species isolated from one (1.66%) case, Streptococcus species was isolated from three cases (5%), Proteus species was isolated from one case (1.66%), E.-coli associated with Salmonella species were isolated from one case (1.66%). The association between pathological and bacteriological findings was discussed. 2 | Von Willebrand factor influences blood vessel architecture and the expression of Integrin αVβ3 and Ang2 in the porcine uterus Der VonWillebrandFaktor beeinflusst die Architektur der Blutgefäße sowie die Expression von Integrin αVβ3 und Ang2 im porzinen Uterus H Allerkamp1,2; S Lehner2; M von Depka Prondzinski2; M Ekhlasi-Hundrieser2; C Detering2; C Pfarrer1 1Institute of Anatomy, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany; 2Werlhof Institute, Hannover, Germany Aim: Von Willebrand Factor (VWF) was shown to influence angiogenesis mainly via Integrin αVβ3 (ITG) and Angiopoietin (Ang)2 in vitro and in mice. Since women with Von Willebrand Disease (VWD) suffer higher rates of miscarriages, we studied the blood vessel conformation and expression of VWF, ITG and Ang2 by immunohistochemistry (IHC) and qPCR of corresponding genes in uteri in a porcine model. Methods: Uteri were harvested from six sows with a natural mutation of the VWFgene (two heterozygous carriers (HC), two homozygous for VWD, two wildtype (WT)animals). Phenoand genotype were attested by blood VWF level and molecular genetic analysis. IHC and qPCR were conducted using CD31 as housekeeping gene. Results: Blood vessels in the lamina propria of WTsows were smaller than in the VWDanimals, which showed groups of dilated and thinwalled arteries and veins. VWF expression in VWDand HCpigs was reduced by 95% compared to WTpigs, which was reflected by IHC. The mRNA expression of ITGAV and ANG2 was more than doubled in the VWDpigs, while the HCs ranged in between. In IHC stainings, ITG and Ang2 showed varying staining patterns among the genotypes. Conclusions: The altered blood vessels in the WTpigs can be classified as angiodysplastic, implicating an impaired angiogenesis. VWF seems to stabilize ITG at the apical membranes in WTsows. In VWDpigs, a stronger cytoplasmic staining of ITG is presumably caused by increased internalization of the protein. Ang2 staining patterns are probably results of a varied, VWFdependent storage capability. 3 | Ovarian characteristics of the roe deer (Capreolus capreolus) during diapause Eierstockcharaktistika von Rehen (Capreolus capreolus) während der Diapause SM Bernal Ulloa; B Drews; A Rudolf-Vegas; V Van der Weidjen; V Milojevic; SE Ulbrich Animal Physiology Group, Institute of Agricultural Sciences, Department of Environmental Systems Science, ETH Zurich, Zurich, Switzerland Embryonic diapause, a period of developmental dormancy described in more than 130 species, is still not completely understood. In the roe deer, the only known ungulate that exhibits this phenomenon, the rut period occurs from midJuly to early August. Thereafter, implantation takes place not until late December/early January. Little is known from the female gonadal stage during this period. Here, we evaluated the roe deer as a model to study ovarian characteristics during the diapause period. Ovaries from a total of 47 hunted animals between October and January were collected and considered for the analyses. The ovarian surface area (mm2), total follicle number and corpora lutea (CL) diameter were evaluated according to the month of sampling. The estimated surface area of right (r) and left (l) side ovaries did not change during the studied period of diapause (Oct: (r) 60.8 ± 6.6, (l) 77.3 ± 8.2; Nov: (r) 82.8 ± 8.6, (l) 72.4 ± 8.6; Dec:

Anticoagulation management in patients with Left Ventricular Assist devices (LVAD) continues to be a challenge. Patients and their clinicians are faced with the daily challenge of needing adequate anticoagulation versus the bleeding risks that are associated with anticoagulation.Warfarin is the recommended oral anticoagulant for all currently available LVAD devices.Warfarin is known to be a difficult medication to manage due to its narrow therapeutic window, and its many interactions .Dlott et al (2014) describe in Circulation the overall time in therapeutic range for patients on warfarin as 53.7%, Time in therapeutic range has been corelated with stroke, bleeding and mortality rates.The goal of our team was to maximise the time patients with VAD's spent in their therapeutic INR range.

Aspirin is used for platelet inhibition in patients with an LVAD. Aspirin levels can be monitored but this is not common practice. Worldwide Aspirin dosing in LVAD patients variesis depending on the availble strength of Aspirin. To date few studies have looked at platelet function in patients with Ventricular Assist Device's insitu.

Bridging to transplantation with devices has become a routine approach in adult heart transplantation (HTx) and both, ventricular assist devices (VADs) as well as the total artificial heart (TAH) are used in patients. However, standared LVADs as the HVAD are used only in a minority of pediatric patients and only 2% of reported TAH patients were under the age 18. Here, we present a case of a pediatric patient who had multiple LVADs as bridge to HTx and a subsequent TAH as bridge to acute redo-HTx

Purpose: Continuous-flow left ventricular assist devices (cf-LVAD) are the standard of care for patients with advanced heart failure as a bridge to heart transplantation (HTx). However transplanting these patients is challenging and the international registries identify it as a risk factor for increased mortality. Ex vivo normothermic preservation minimizes the cold ischemic time and optimizes logistics and meticulous recipients preparation. We analyze the influence of ex-vivo graft perfusion on the outcome in LVAD patients bridged to HTx.

Continuous-flow left ventricular assist devices (cf-LVAD) have become the standard of care for patients with advanced heart failure as a bridge to heart transplantation (HTx). Transplanting these patients is usually challenging and the international registries continue to identify it as a risk factor for increased mortality. Ex vivo normothermic preservation using the Organ Care System (OCS) minimizes the cold ischemic time and allows for optimization of logistics and meticulous recipients preparation. This study analyses the influence of ex-vivo heart perfusion on the outcome in LVAD patients bridged to HTx. Retrospective study of all cf- LVAD patients bridged to HTx at a single center from July 2007 to September 2014 was performed. Low risk patients with cf-LVAD implanted without previous sternotomy (i.e. CircuLite) were excluded. Outcomes in the patients transplanted with the grafts preserved with OCS (n=15) were compared with cold storage preservation (CS) (n=15) During this period 186 patients were implanted with LVAD and 30 (16 %) were bridged to heart transplantation with a cf-LVAD There was a trend towards increased donor age on the OCS group. (41±11 Vs 34±11 yo; p=0.069) There was no significant difference in recipient age (48 (33; 58) Vs 46 (35; 57) yo; p=0.83), however there was a trend towards higher estimated risk of death at 1y according to IMPACT score in the OCS group (15.3 vs. 11.6% p=0.085). Rest of donor and recipient characteristics was comparable. Relevant outcome data is presented in table 1. Despite the significant increase in out of body time we observed better postoperative results in the ex vivo preservation group. The use of the OCS in cf-VAD patients bridged to transplant is now the standard of care in our clinical practice.

Objective: Ventricular assist devices (VAD) have become standard treatment for patients with advanced heart failure. We present data comparing the results after implantation of the HeartMate II (HM II) vs. the Heartware (HW) at our institution.

PurposeSignificant aortic regurgitation (AR) after continuous-flow left ventricular assist device (CF-LVAD) placement affects device performance and patient outcomes. This study examined the influence of blood-pressure on the post-operative development of AR in patients with CF-LVAD implantation.MethodsAll patients with no or

Continuous-flow left ventricular assist devices (LVAD) have become the standard of care for patients with advanced heart failure as a bridge to heart transplant (HTx). Transplanting these patients is usually challenging and the influence of LVAD bridging on post-transplant outcomes remains controversial. Experienced centers have comparable post-transplant results with the LVAD bridging; however, the international registries continue to identify it as a risk factor for increased mortality after HTx. We evaluate the influence of the Organ Care System (OCS) as a method of graft preservation on the postoperative results and early survival in LVAD patients bridged to HTx. Retrospective study of all LVAD patients bridged to HTx at a single center from 07.2007 to 11.2013. Outcomes in the patients transplanted with the grafts preserved with OCS (n=8) were compared with the ones preserved on ice (n=14)-Standard of care (SOC). During this period 135 patients were implanted with LVAD and 22 (16.3%) were bridged to HTx. There was no significant difference in donor age (OCS Vs SOC 38±12 Vs 33±10 yrs; p=0.28) and recipient age (42±15 Vs 46±13 yrs; p=0.48), in the donor characteristics (gender, cause of death, previous cardiac arrest, diabetes mellitus, inotropic support) or recipient baseline characteristics (gender, type of VAD, time on VAD support, driveline infection, pulmonary vascular resistance and renal function. 30 days survival was 100% vs. 78% (OCS vs. SOC). The OCS reduces the cold ischemic time and insult of prolonged cold storage. It allows for optimization of logistics and extended and meticulous preparation of the VAD and recipient. Despite the significant increase in out of body time we observed less right heart failure, better graft function and the recipients required significantly less blood products. Postoperative results are excellent, and use of the OCS in the transplantation of VAD patients has become the standard of care in our clinical practice.

Objectives: Left ventricular assist devices (LVADs) are increasingly used for treatment of therapy refractory advanced heart failure. However, right ventricular failure (RVF) represents one of the devastating postoperative complications. Furthermore a substantial portion of patients may develop therapy refractory RVF requiring right sided mechanical support after LVAD implantation. The aim of this study was to evaluate predictors of therapy refractory RVF with the need for a right ventricular assist device (RVAD) support.

Rotary LVADs which drain the left ventricle (LV) elicit LV decompression proportional to pump speed. However, the effect of residual LV function on the LVAD are poorly characterised. The aim was to examine the relationship between cardiac cycle and LVAD function by analysis of the acoustic properties of the LVAD.

Objectives: While implantation of left Ventricular Assist Devices (LVADs) has become a routine clinical option for patients in end stage heart failure, many patients experience at least a transient decline in right ventricular (RV) function, commencing the initiation of left ventricular support. Of these, a significant percentage develops refractory full RV failure which is associated with a high mortality. We present our institutional experience in this patient group, based on the results using the CentriMag® (Levitronix) for temporary RV support.

Introduction Right heart failure after left Ventricular Assist Device (LVAD) implantation is a severe complication, in extreme cases necessitating additional mechanical assist. We present our institutional experience with the Levitronix CentriMag used for right ventricular support commencing LVAD implantation with refractory right ventricular failure. Material and Methods Between March 2001 and November 2010 109 patients underwent implantation of long term, total implantable, continuous flow LVADs: 60 HeartMate II, 25 Jarvik 2000 and 24 HeartWare. All patients requiring right ventricular support were included (n=24), for which the Levitronix CentriMag continuous flow, paracorporeal device was used. The analysis included patient demographics as well as overall duration of support and outcome parameters, including survival at 30, 90 days and 1 year. Results 24 pts. underwent implantation, age 37.9±13.7 years, gender: M/F-15/9, underlying disease: dilated cardiomyopathy 22(92%), peripartum cardiomyopathy 1(4%), viral myocarditis 1(4%). Median duration of support: 28 days (5–146). 3(12.5%) pts. underwent heart transplantation (HTx) on RV support, 14(58.5%) underwent RVAD explantation. Of these, 3 underwent successful HTx, 4 recovered LV function and underwent successful LVAD explantation, 3 remain on continuing LVAD support, 4 patients died after RVAD explantation (post explantation day 1, months 3 and 4 and at 2 years), 7(29%) patients died during RV support. Median ITU/hospital stay: 19.5 days (6–145)/78.5 days (10–219). 30-day/90-day/1-year survival: 79%/71%/60%. 15(62.5%) patients were discharged from hospital after treatment. Median survival after procedure: 473.5 days (10–1917). Conclusion Levitronix CentriMag right ventricular support is an excellent option for post LVAD implantation treatment of refractory RV failure. It allows either bridging to transplantation or RV function improvement and provides an acceptable rate of survival.

Purpose: We have previously shown that the acoustic properties of the Thoratec Heartmate II, Hearware HVAD and Jarvik 2000 are primarily determined by rotation speed and impeller symmetry [1]. In this study, we hypothesised that pump thrombus is associated with an aberrant LVAD acoustic signature which normalises following successful thrombolytic therapy. Methods and Materials: We recorded the Heartware HVAD acoustic signature from 6 ambulatory patients at rest (control group) and compared them to daily measurements taken from a patient during a pump thrombus episode: plasma free Hb recording 0.5 g/L; 20% change in pump flows and power levels; macroscopic haemoglobinurea; an atypical pump sound detected with a stethoscope in the mitral position.Treatment consisted of a heparin infusion (APTT 60-80). Acoustic profiles were recorded with patients at rest using a phonocardiogram (sampling frequency 5 kHz) stored without data compression and analysed by fast Fourier transform (FFT) (Spike 2 software, v 4.51, Cambridge Electronic Design, Cambridge, UK). Results: For all control group patients, FFT spectral peaks were present at the impeller rotation frequency and at four times this value reflecting the presence of four flow channels in the impeller [1]. For the patient with a pump thrombus, additional FFT spectral peaks in the range 125-175Hz were noted. Successful resolution of the pump thrombus episode after 4 days was associated with normalisation of the FFT of the acoustic signal. Conclusions: The appearance of atypical FFT spectral peaks during pump thrombus episodes is attributed to unbalanced impeller motion. Acoustic monitoring is a simple non-invasive method which may have clinical utility in the management of implantable rotary LVAD pump thrombus episodes. 1. Bowles CT et al. ISHLT abstract/poster 2009.

We actively promote myocardial recovery in our non-ischemic dilated cardiomyopathy (DCM) patients. The aim of this was study was to assess long term outcome of patients recovered with left ventricular assist device (LVAD) up to 8 years post explantation.