Heart transplantation across preformed donor-specific antibody barriers using a perioperative desensitization protocol.

Heart transplantation across preformed donor-specific HLA-antibody barriers is associated with impaired short- and long-term survival. Therefore, in recipients with preformed anti-HLA antibodies, waiting for crossmatch-negative donors is standard practice. As an alternative strategy, recipients with preformed anti-HLA donor specific antibodies have been managed at our institutions with a perioperative desensitization regimen. A retrospective analysis was performed comparing heart transplant recipients with preformed donor-specific HLA-antibodies to recipients without donor-specific antibodies. Recipients with a positive virtual crossmatch received a perioperative desensitization protocol including tocilizumab intraoperatively, plasma exchange and rituximab followed by a six-month course of IgGAM. Among the 117 heart-transplanted patients, 19 (16%) patients underwent perioperative desensitization, and the remaining 98 (84%) patients did not. Cold ischemic time, posttransplant extracorporeal life support for primary graft dysfunction, and intensive care unit stay time did not differ between groups. At 1-year follow-up, freedom from pulsed steroid therapy for presumed rejection and biopsy-confirmed acute cellular or humoral rejection did not differ between groups. One-year survival amounted to 94.7% in the treated patients and 81.4% in the control group. Therefore, heart transplantation in sensitized recipients undergoing a perioperative desensitization appears safe with comparable postoperative outcomes as patients with a negative crossmatch.

Simultaneous heart-kidney transplantation results in respectable long-term outcome but a high rate of early kidney graft loss in high-risk recipients - a European single center analysis.

BACKGROUND: In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization. METHODS: This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe's largest transplant centers. RESULTS: Median follow-up was 100.33 (0.46-362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%). CONCLUSIONS: Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a "kidney-after-heart" program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.

Five-year outcomes of patients supported with HeartMate 3: a single-centre experience.

OBJECTIVES: The HeartMate 3 left ventricular assist device was first implanted in 2014 and received the Conformité Européenne mark in 2015. Since then, several trials demonstrated its high haemocompatibility associated with good survival and low adverse events rates. Herein, we report our institutional experience with patients supported with HeartMate 3 for 5 years. METHODS: This prospective cohort study included patients receiving a HeartMate 3 implantation in 2014 as part of the HeartMate 3 Conformité Européenne Mark clinical trial. Patients had follow-up visits every 3 months while on left ventricular assist device support, and all patients completed the 5-year follow-up. The primary end point was survival at 5 years. Secondary end points included adverse events, health status and quality of life. RESULTS: Eight patients (men: 75%) aged 59 years (min-max: 52-66 years) were enrolled. At 5 years, survival was 100%. Patients remained on support for a median time of 1825 days (min-max: 101-1825 days); 2 patients successfully received cardiac transplants. No right heart failure, haemolysis, pump thrombosis, pump malfunction or neurological events occurred in any patients. A driveline infection was observed in 6 patients (0.25 events/patient-year). Compared to baseline, a significant improvement in quality of life and in New York Heart Association functional class was noted after the implant and for the whole follow-up time. A slight decline in kidney function and in the 6-min walk test results occurred after 3 years. CONCLUSIONS: This study reports the longest single-centre follow-up of the HeartMate 3, showing excellent haemocompatibility over time with high survival and low complication rates at 5 years.

Should kidney allografts from old donors be allocated only to old recipients?

In several deceased donor kidney allocation systems, organs from elderly donors are allocated primarily to elderly recipients. The Eurotransplant Senior Program (ESP) was implemented in 1999, and since then, especially in Europe, the use of organs from elderly donors has steadily increased. The proportion of ≥60-year-old donors reported to the Collaborative Transplant Study (CTS) by European centers has doubled, from 21% in 2000-2001 to 42% in 2016-2017. Therefore, in the era of organ shortage it is a matter of debate whether kidney organs from elderly donors should only be allocated to elderly recipients or whether <65-year-old recipients can also benefit from these generally as "marginal" categorized organs. To discuss this issue, a European Consensus Meeting was organized by the CTS on April 12, 2018, in Heidelberg, in which 36 experts participated. Based on available evidence, it was unanimously concluded that kidney organs from 65- to 74-year-old donors can also be allocated to 55- to 64-year-old recipients, especially if these organs are from donors with no history of hypertension, no increased creatinine, no cerebrovascular death, and no other reasons for defining a marginal donor, such as diabetes or cancer.

Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from six months after heart transplantation: the randomized MANDELA study.

In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (i) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n=71), or to (ii) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n=74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at radomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 post-transplant post-randomization) with superiority of the CNI-free group versus EVR/redCNI : mean 64.1mL/min/1.73m2 versus 52.9mL/min/1.73m2 ; difference +11.3mL/min/1.73m2 (p<0.001). By month 18, estimated GFR had increased by ≥10mL/min/1.732 in 31.8% and 55.2% of EVR/redCNI and CNI-free patients, respectively, and by ≥25 mL/min/1.73m2 in 4.5% and 20.9%. Rates of biopsy-proven acute rejection (BPAR) were 6.8% and 21.1%; all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI versus the CNI-free regimen (p=0.015); 6/15 episodes in CNI-free patients occurred with EVR concentration <5ng/mL. Rates of adverse events and associated discontinuations were comparable EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One-year renal function can be improved by early conversion to EVR-based CNI-free therapy but requires close EVR monitoring. This article is protected by copyright. All rights reserved.

Novel Cytokine Score and Cardiac Allograft Vasculopathy.

To date, there are no established noninvasive biomarkers available for prediction of cardiac allograft vasculopathy (CAV) after orthotopic heart transplantation (OHT). Inflammatory processes are supposed to play a central role in the pathogenesis of CAV. Recent studies have suggested that immune mediators could serve as biomarkers for cardiovascular diseases. We hypothesized particular cytokines or a combination thereof may serve as noninvasive biomarkers for CAV. Plasma cytokines were screened from 27 patients with CAV and 27 patients without CAV after OHT. The concentrations of interleukins-4, -6, -10, -21, -23, -31, -33, interferon gamma, tumor necrosis factor alpha, and the soluble activation marker CD40 ligand were determined using Luminex-based multiplex analyses. Although concentrations of all cytokines except interferon gamma were on average higher in the CAV group, there were no significant differences between the groups for any 1 cytokine. Using a binary logistic regression model, we were able to develop a probability score for detecting patients at elevated risk for advanced CAV with a sensitivity of 92.31% and a specificity of 60.71% (receiver-operating characteristic area under the curve 0.799 ± 0.06; p<0.0001). In conclusion, analyzing the concentration of specific inflammatory cytokines could be meaningfully included in evaluation of CAV after OHT.

Wearable Cardioverter-Defibrillators following Cardiac Surgery-A Single-Center Experience.

BACKGROUND: A wearable cardioverter-defibrillator (WCD) can terminate ventricular fibrillation and ventricular tachycardias via electrical shock and thus give transient protection from sudden cardiac death. We investigated its role after cardiac surgery. METHODS: We retrospectively analyzed all patients who were discharged with a WCD from cardiac surgery department. The WCD was prescribed for patients with a left ventricular ejection fraction (LVEF) of ≤35% or an explanted implantable cardioverter-defibrillator (ICD). RESULTS: A total of 100 patients were included in this study, the majority (n = 59) had received coronary artery bypass graft surgery. The median wearing time of a WCD patient was 23.5 hours per day. LVEF was 28.9 ± 8% after surgery and improved in the follow-up to 36.7 ± 11% (p < 0.001). Three patients were successfully defibrillated. Ten patients experienced ventricular tachycardias. No inappropriate shocks were given. An ICD was implanted in 25 patients after the WCD wearing period. CONCLUSION: Ventricular arrhythmias occurred in 13% of the investigated patients. LVEF improved significantly after 3 months, and thus a permanent ICD implantation was avoided in several cases. Sternotomy did not impair wearing time of the WCD. A WCD can effectively protect patients against ventricular tachyarrhythmias after cardiac surgery.

One-year outcomes with the HeartMate 3 left ventricular assist device.

BACKGROUND: The HeartMate 3 (HM3; Abbott Laboratories, Lake Forest, Ill) left ventricular assist device (LVAD) received its Conformité Européenne mark for Europe in October 2015 and is currently under investigation of the Food and Drug Administration to gain approval in the United States. Within this study, we present the first real-world experiences, 1-year outcomes, and adverse events of a single-center cohort treated with the HM3. METHODS: We prospectively studied midterm results of 27 consecutive patients receiving the HM3 at a single institution. After HM 3 implantation, survival, causes of death, and complications were recorded for all patients. Follow up was 100% complete. RESULTS: Twenty-seven patients were enrolled into the study. Within 1 year after HM3 implantation, 3 patients underwent heart transplantation and 3 patients died. Thirty-day survival was 88.9%, 6-month 85.2%, and 1-year survival 85.2%. No pump thrombosis and no strokes were observed within the study group. One incident of gastrointestinal bleeding was observed (3.7%). Right heart failure was diagnosed in 1 patient after HM3 implantation (3.7%). No technical complications of the pump were documented. No pump exchanges were necessary. The main complication was LVAD-related infection (22.2%). CONCLUSIONS: The novel LVAD HM3 has already shown excellent Conformité Européenne mark trial results. Within this cohort, 1-year survival after HM3 implantation was 85%. The HM3 showed excellent midterm results with 0% stroke and 0% pump thrombosis rates 1 year after implantation.

Five-year results of patients supported by HeartMate II: outcomes and adverse events.

OBJECTIVES: Improved outcomes over the past decade have increased confidence of physicians and patients in extended duration of left ventricular assist device (LVAD) support. This single-centre cohort study reports 5-year outcomes with the HeartMate II (HMII) LVAD. METHODS: We describe a cohort of 89 patients who received a HMII LVAD between February 2004 and December 2010. The causes of death and adverse events were assessed by examination of medical records. A total of 202.74 patient-years were analysed. RESULTS: After 5 years, of the 89 patients, 15 patients remained on device therapy, 39 patients died, 28 patients underwent heart transplantation and 7 patients underwent explantation of the HMII for recovery. One year after the HMII implantation, there was a survival of 71% in the study cohort. In the following years, the survival rate was 65% in the 2nd year, 63% in the 3rd year, 56% in the 4th year and 54% after 5 years of LVAD support. Ten LVAD exchanges were performed in 8 (11%) patients. Currently (March 2017), 12 patients still remain on their original device. The longest ongoing patient on the HMII has been supported for over 11 years (4097 days). The most common adverse events were bleeding (68%; 1.5837 events per patient-year) and LVAD infection [49%; 1.0666 events per patient-year]. Seven cases of pump thrombosis were described (8%; 0.1131 events per patient-year). CONCLUSIONS: This is the first single-cohort study to describe a 5-year survival of HMII patients on extended duration of support. A 5-year survival of 54% was observed in this single-centre cohort.

Mid-term results of bilateral lung transplant with postoperatively extended intraoperative extracorporeal membrane oxygenation for severe pulmonary hypertension.

OBJECTIVES: In severe pulmonary hypertension, diastolic dysfunction of the left ventricle causes significant morbidity and mortality after lung transplantation, which may be successfully reversed using a protocol based on perioperative veno-arterial extracorporeal membrane oxygenation (ECMO) and early extubation. Here, we present echocardiographic data and mid-term outcomes. METHODS: The records of lung transplanted patients at our institution between May 2010 and January 2016 were retrospectively reviewed. Echocardiography data were collected preoperatively, at discharge, 3 and 12 months after transplantation. RESULTS: During the study period, 717 patients underwent lung transplantation at our institution, 38 (5%) patients being transplanted for severe pulmonary hypertension. All patients underwent bilateral lung transplantation on veno-arterial ECMO cannulated in the groin, through a sternum sparing thoracotomy in 36 (95%) patients. Extubation was performed early, after a median of 2 days, and awake ECMO was extended for at least 5 days after transplantation. The survival at 3 months, 1 year and 5 years was not different in comparison to patients transplanted for other underlying diseases ( P = 0.45). At 1 year, tricuspid valve regurgitation had disappeared in all patients. The median of the left ventricular end-diastolic dimension improved from 40 (32-44) mm preoperatively to 45 (44-47) mm at 12 months after lung transplantation ( P < 0.05). The median of the proximal right ventricular outflow diameter decreased to 25 (23-27) mm after 12 months, compared to 48 (43-51) mm preoperatively ( P < 0.05). CONCLUSIONS: The routine application of a prophylactic postoperative veno-arterial ECMO protocol in patients with severe pulmonary hypertension undergoing lung transplantation decreases postoperative mortality and favours achievement of normal cardiac function after 1 year.

Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II.

AIMS: A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS: Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION: For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.

Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation.

OBJECTIVES: Pulmonary autografts (PAs) represent the substitute of choice for aortic valve (AV) replacement, especially in children and young adults. Similarly, decellularized aortic valve allografts (DAVAs) have shown excellent mid-term function when implanted in the systemic circulation. The aim of this study was to compare the performance of DAVAs with that of pulmonary autografts after a Ross procedure in the growing sheep model. METHODS: AV root replacement was performed in female lambs (25 ± 3.4 kg) using either DAVAs (n = 5) or pulmonary autografts (n = 5) as in the Ross procedure. Sheep undergoing the Ross procedure received a decellularized pulmonary allograft in place of pulmonary valve. Haemodynamics was investigated by echocardiography and magnetic resonance imaging. The roots were explanted at 20 months and examined by histology to determine the degree of repopulation and quality of the extracellular matrix, and by immunohistochemistry to characterize the repopulating cells. RESULTS: The mean valve diameter increased from 16 to 21 and from 16 to 25 mm in DAVAs and PAs, respectively. At explantation, one PA and one DAVA exhibited moderate insufficiency. Significant differences in transvalvular gradient were only found in PAs between implantation and prior to explantation. The cusps of all implants were soft, pliable and showed no major signs of degeneration. In the decellularized allografts, cell repopulation occurred at the wall and cusp level with a well-maintained, three-layered cusp structure. Ventricular cusp surface of decellularized allografts was more strongly repopulated than the arterial surface. Cusps were covered with cells positive for endothelial markers and were also repopulated by interstitial cells. CONCLUSIONS: DAVAs and PAs provide adequate haemodynamics after AV replacement in the growing sheep. While decellularized grafts are repopulated by endothelial and interstitial cells, autografts maintain in general their native cell distribution. Maintenance of valvular competence during enlargement of the valve ring is, in our opinion, representative of the capacity for physiological growth in both graft types.

HeartWare left ventricular assist device for the treatment of advanced heart failure.

The importance of mechanical circulatory support in the therapy of advanced heart failure is steadily growing. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the assist devices, providing increased pump durability and prolonged patient survival. The HeartWare left ventricular assist device system (HeartWare Inc., Framingham, MA, USA) is a mechanical ventricular assist device with over 8000 implantations worldwide. Compared with other available assist devices it is smaller in size and used in a broad range of patients. The possibility of minimally invasive procedures is one of the major benefits of the device - allowing implants and explants, as well as exchanges of the device with reduced surgical impact. We present here a review of the existing literature on the treatment of advanced heart failure using the HeartWare left ventricular assist device system.

Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients.

BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0-40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS: We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS: The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION: In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00761787.

Circulatory support exceeding five years with a continuous-flow left ventricular assist device for advanced heart failure patients.

Continuous-flow left ventricular assist devices (CF-LVAD) are now providing years of safe circulatory support with enhanced quality of life. We present four cases of patients with advanced heart failure who received support for greater than 5-years with the HeartMate II CF-LVAD. One patient continues with support at 7.5 years and has decided to not undergo cardiac transplantation. Another patient has also had LVAD support for 7.7 years, initially with a pulsatile flow LVAD, and then was switched to the HeartMate II, which has continued to support him for the last 6.6 years. Two other patients have undergone heart transplant after support times of 5.46 years and 5.75 years. Few complications occurred and the patients had very active lifestyles during support. Explant analysis revealed very low bearing wear and minimal pannus.

Gastrointestinal Endoscopy Is Safe in Patients Before and After Lung or Heart Transplantation.

BACKGROUND: Gastrointestinal complications are common in patients after lung and heart transplantation. Endoscopy is a standard method for the assessment of gastrointestinal morbidities. The aim of this study was to analyze the number and type of complications during endoscopic procedures in patients before and after lung or heart transplantation. METHODS: A retrospective single centre analysis of endoscopic procedures in patients before and after lung and heart transplantation from May 1999 to September 2012 was performed compared to a control group. RESULTS: Four hundred fifty-nine endoscopic procedures were performed in 175 patients after transplantation (84 lung and 91 heart) and 213 procedures in 160 transplant candidates on the waiting list for lung (n = 126) or heart (n = 34) transplantation. In 26% (n = 56/214) of the endoscopic examinations, an intervention was necessary in the lung transplant group compared to 32% (n = 79/245) in the heart transplant group and 27% (n = 43/160) and 21% (n = 11/53) in the lung and heart transplant candidates, respectively. In the control group, endoscopic interventions were performed in 24% (n = 195/805) of the examinations. Overall, 14 (1%) complications resulted from 1,477 endoscopic examinations. Only four (0.9%) of 459 endoscopic examinations were followed by complications in the transplant recipients, whereas in the control group, 10 complications (1.2%) of 805 endoscopies were documented. No endoscopic complication occurred in the lung and heart transplant candidates. CONCLUSION: Diagnostic and therapeutic endoscopies can be safely performed after lung and heart transplantation and in patients on the waiting list for these organs.

Acquired von Willebrand syndrome in patients with a centrifugal or axial continuous flow left ventricular assist device.

OBJECTIVES: The aim of this study was to determine whether differences in continuous flow left ventricular assist devices (LVADs) may lead to differences in the von Willebrand profile and the occurrence of bleeding and thromboembolic events. BACKGROUND: The HeartMate II (Thoratec Corp., Pleasanton, California) and HeartWare Ventricular Assist Device (HVAD) (HeartWare, Inc., Framingham, Massachusetts) systems are the most frequently implanted LVADs worldwide. In all patients with an axial-flow HeartMate II, acquired von Willebrand syndrome (AvWS) due to the loss of large molecular weight multimers was found. The large molecular weight multimers of the von Willebrand factor (vWF) play a key role in primary hemostasis through interactions with platelets. METHODS: This was a retrospective study of the vWF profile and incidence of bleeding and thromboembolic events in 102 patients receiving the HeartMate II (n = 51) and HVAD (n = 51). Between January 2003 and December 2010, vWF testing was performed in 102 of 175 consecutive patients after LVAD implantation. RESULTS: AvWS was found in all patients, demonstrated by a decrease in the high molecular weight multimers of vWF to 30 ± 14% in HeartMate II patients and 34 ± 13% in patients with an HVAD. Significant predictors of vWF antigen included age (p = 0.011), number of days on the device (p = 0.035), C-reactive protein (p < 0.001), and blood group (p = 0.007). Bleeding and thromboembolic event rates were similar. However, lower fractions of vWF antigen and high molecular weight multimers did not correlate with the rate of bleeding complications or thromboembolic events. CONCLUSIONS: AvWS developed in all patients after centrifugal or axial flow pump implantation. Different patterns of AvWS were seen between the devices as well as individually. However, the complication rates after implantation were similar.

Tracheal cartilage - evaluating the potential of a novel biomaterial for reconstructive cardiovascular procedures.

Modern cardiovascular medicine aims for procedures that preferably involve biological materials and, ideally, living implants. Thereby, the regenerative capacity of the target organ may be preserved or even supported, with a potential implant growth capacity during the following time. In the current study we sought to evaluate the integrative capacity of vital and non-vital tracheal cartilage rings (TCRs) of allogenic or xenogenic origin (allo-/xeno-vTCR; allo-/xeno-nvTCR) as biomaterials under the in vivo functional load of the circulatory system. Ovine and porcine vTCRs and nvTCRs were implanted in the mitral valve (MV) position for 3 and 9 months (n = 3 each), respectively, in lambs. MV function and TCR position were analysed by echocardiography. Tissue morphology (planimetry), vitality (live/dead-assay) and implant endothelialization (scanning electron microscopy) were analysed. No functional impairment or significant MV insufficiency or stenosis was observed in any group. TCR shrinkage was observed in all xeno-TCRs and allo-nvTCRs at 3 months. Only TCRs of allogenic groups at 9 months and allo-vTCRs at 3 months showed a ring area comparable to its size at implantation. Moreover, allogenic vital cartilage showed superior tissue integration, greater endothelialization, less inflammation and calcification. Interestingly, in this group viable cartilage cells were found up to 9 months after implantation. Allogenic viable cartilage may represent a well-suited living material for reconstructive cardiovascular procedures, and further studies are warranted to elucidate the benefits of this novel material, particularly as a structurally supportive component in growing recipients.

Moderate and severe periodontitis are independent risk factors associated with low cardiorespiratory fitness in sedentary non-smoking men aged between 45 and 65 years.

AIM: To investigate the association between periodontal disease severity and cardiorespiratory fitness (CRF) in a cross-sectional study of sedentary men. MATERIALS & METHODS: Seventy-two healthy men (45-65 years) who did not join any sport activity and had a preferentially sitting working position were recruited. Periodontal status was recorded and CRF was measured by peak oxygen uptake (VO2 peak ) during exercise testing on a cycle ergometer. Physical activity was assessed by a validated questionnaire and data were transformed to metabolic equivalent of task scores. Univariate and multivariate regression analyses were performed to investigate associations. RESULTS: Differences between VO2 peak levels in subjects with no or mild, moderate or severe periodontitis were statistically significant (p = 0.026). Individuals with low VO2 peak values showed high BMI scores, high concentrations of high-sensitive C-reactive protein, low levels of high-density lipoprotein-cholesterol, and used more glucocorticoids compared to individuals with high VO2 peak levels. Multivariate regression analysis showed that high age (p = 0.090), high BMI scores (p < 0.001), low levels of physical activity (p = 0.031) and moderate (p = 0.087), respectively, severe periodontitis (p = 0.033) were significantly associated with low VO2 peak levels. CONCLUSIONS: This study demonstrated that moderate and severe periodontitis were independently associated with low levels of CRF in sedentary men aged between 45 and 65 years.

Everolimus in heart transplantation: an update.

The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.