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Background: Currently, the primary graft dysfunction (PGD) score is used to measure allograft function in the early post-lung transplant period. Although PGD grades at later time points (T48 hours and T72 hours) are useful to predict mid- and long-term outcomes, their predictive value is less relevant within the first 24 hours after transplantation. This study aimed to evaluate the capability of PGD grades to predict prolonged mechanical ventilation (MV) and compare it with a model derived from ventilation parameters measured on arrival at the intensive care unit (ICU)., Methods: A retrospective single-center analysis of 422 double lung transplantations (LTxs) was performed. PGD was assessed 2 hours after arrival at ICU, and grades were associated with length of MV (LMV). In addition, peak inspiratory pressure (P IP ), ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (P/F ratio), and dynamic compliance (cDyn) were collected, and a logistic regression model was created. The predictive capability for prolonged MV was calculated for both (the PGD score and the model). In a second step, the created model was externally validated using a prospective, international multicenter cohort including 102 patients from the lung transplant centers of Vienna, Toronto, and Budapest., Results: In the retrospective cohort, a high percentage of extubated patients was reported at 24 hours (35.1%), 48 hours (68.0%), and 72 hours (80.3%) after transplantation. At T0 (time point defined as 2 hours after arrival at the ICU), patients with PGD grade 0 had a shorter LMV with a median of 26 hours (interquartile range [IQR]: 16-47 hours) than those with PGD grade 1 (median: 42 hours, IQR: 27-50 hours), PGD grade 2 (median: 37.5 hours, IQR: 15.5-78.5 hours), and PGD grade 3 (median: 46 hours, IQR: 27-86 hours). However, IQRs largely overlapped for all grades, and the value of PGD to predict prolonged MV was poor. A total of 3 ventilation parameters (P IP , cDyn, and P/F ratio), determined at T0, were chosen on the basis of clinical reasoning. A logistic regression model including these parameters predicted prolonged MV (>72 hours) with an optimism-corrected area under the curve (AUC) of 0.727. In the prospective validation cohort, the model proved to be stable and achieved an AUC of 0.679., Conclusions: The prediction model reported in this study combines 3 easily obtainable variables. It can be employed immediately after LTx to quantify the risk of prolonged MV, an important early outcome parameter., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: R-Spondins (RSPOs) and leucine-rich repeat-containing G-protein coupled receptors (LGRs) play a critical role in embryonic and cancer development through potentiation of WNT/ß-catenin signaling, but their prognostic significance in head and neck squamous cell carcinoma (HNSCC) is still unclear. HNSCC is a group of neoplasms that include, amongst others, oropharyngeal squamous cell carcinoma (OPSCC), some of which are induced by human papillomavirus (HPV). We aimed to investigate the potential prognostic value of RSPO2 and LGR4/5/6 on overall survival (OS) and disease-free survival (DFS) in HNSCC patients., Methods: We examined RSPO and LGR expression by means of immunohistochemistry in 126 HNSCC patients. Furthermore, in order to validate our findings externally, we examined RSPO2 and LGR6 mRNA expression levels using independent secondary datasets., Results: The five-year OS of our cohort was 59.6%. RSPO2 and LGR4/5/6 expression were not associated with OS or DFS in multivariable analyses. Within the HPV+ cases (n = 26, 33%), however, we observed a difference in OS by RSPO2 expression (5-year OS: RSPO+ 45.4% vs. RSPO2- 84.6%) and LGR6 expression (5-year OS: LGR6+ 52.9% vs. LGR6-100%). Evidence for an interaction of HPV status with RSPO2 and LGR6 was found for OS. Relative to HPV+/LGR6- patients, HPV+/LGR6+ patients were 12 times more likely to die. These results were replicated in the second dataset., Conclusion: Our results indicated that the expression status of LGR6 had an influence on the aggressiveness of HPV+ OPSCC, potentially making this receptor a useful marker for identifying patients with a high risk of death., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cardiovascular prevention guidelines advocate the use of statistical risk equations to predict individual cardiovascular risk. However, predictive accuracy and clinical value of existing equations may differ in populations other than the one used for their development. Using baseline and follow-up data of the Austrian health-screening program, we assessed discrimination, calibration, and clinical utility of three widely recommended equations-the Framingham 1991 and 2008 general cardiovascular disease (CVD) equations, and the Pooled Cohort equations predicting atherosclerotic CVD., Methods: The validation cohort comprised 1.7 M individuals aged 30-79, without documented CVD history who participated in the program from 2009 to 2014. CVD events were defined by a cardiovascular cause of hospitalization or death., Results: The observed five-year general CVD risk was 4.66%. Discrimination c-indices (0.72-0.78) were slightly lower than those reported for the development cohorts. C-indices for women were always higher than for men. CVD risk was overestimated by the Framingham 2008 equation, but underestimated by the Pooled Cohort equations. The Framingham 1991 equation was well-calibrated, especially for individuals up to 64 years. If applied to recommend health interventions at a predicted five-year risk between 5 and 10%, the equations were clinically useful with their net benefits, weighting true positives against false positives, ranging from 0.13 to 3.43%., Conclusion: The equations can discriminate high-risk from low-risk individuals, but predictive accuracy (especially for high-risk individuals) might be improved by recalibration. The Framingham 1991 equation yielded the most accurate predictions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes.

Background: Patients with cancer are at an increased risk for venous thromboembolism (VTE). The risk varies markedly in different patient populations. Factor V (FV) Leiden is the most common genetic risk factor for VTE, and the impact of FV Leiden on cancer-associated thrombosis is not yet fully elucidated., Objective: To study the impact of FV Leiden on the risk of thrombosis in cancer patients., Methods: In the prospective observational Vienna Cancer And Thrombosis Study (CATS), 982 patients were included and were followed until occurrence of VTE or death, for a maximum period of 2 years. FV Leiden was determined by genotyping at inclusion. Main outcome measures were symptomatic or lethal objectively confirmed VTE., Results: Of the 982 patients, FV Leiden was diagnosed in 72 (7.3%, 70 were heterozygous and 2 were homozygous). Ten of 72 (13.9%) patients with FV Leiden developed VTE, whereas this was the case in 69 of 910 (7.6%) patients without FV Leiden. In multivariate analysis that included age, sex, different tumor types, tumor stage, newly diagnosed vs. recurrence of disease, and the treatment modalities, the hazard ratio was 2.0 (95% confidence interval 1.0-4.0). In Kaplan-Meier analysis, the probability for development of VTE was 13% in those with and 5.7% in those without FV Leiden after 6 months; after 1 year, the corresponding risks were 15% and 7.3%., Conclusions: FV Leiden is a genetically determined and thus disease-independent parameter, which is associated with VTE in cancer patients and could therefore be used for individual risk assignment., (© 2014 International Society on Thrombosis and Haemostasis.)

Patients are often advised to reduce sodium and potassium intake, but supporting evidence is limited. To help provide such evidence we estimated 24 h urinary sodium and potassium excretion in 28,879 participants at high cardiovascular risk who were followed for a mean of 4.5 years in the ONTARGET and TRANSCEND trials. The primary outcome was eGFR decline of 30% or more or chronic dialysis. Secondary outcomes were eGFR decline of 40% or more or chronic dialysis, doubling of serum creatinine or chronic dialysis, an over 5%/year loss of eGFR, progression of albuminuria, and hyperkalemia. Multinomial logit regression with multivariable fractional polynomials, adjusted for confounders, determined the association between urinary sodium and potassium excretion and renal outcomes, with death as a competing risk. The primary outcome occurred in 2,052 (7.6%) patients. There was no significant association between sodium and any renal outcome (primary outcome odds ratio 0.99; 95% CI 0.89-1.09 for highest [median 6.2 g/day] vs. lowest third [median 3.3 g/day]). Higher potassium was associated with lower odds of all renal outcomes (primary outcome odds ratio 0.74; 95% CI 0.67-0.82 for highest [median 2.7 g/day] vs. lowest third [median 1.7 g/day], except hyperkalemia nonsignificant. Thus, urinary potassium, but not sodium, excretion predicted clinically important renal outcomes. Our findings do not support routine low sodium and potassium diets for prevention of renal outcomes in people with vascular disease with or without chronic kidney disease.

Background: The proportion of older donors and recipients is constantly rising in heart transplantation (HTX). The impact of age on different outcomes after HTX has been studied; however, effects of interaction between donor and recipient age remain elusive., Methods: This retrospective cohort study comprised 1,190 patients who underwent HTX between 1984 and 2011 at the Medical University Vienna. Multivariable models consisted of a basic set that included donor age, recipient age, and transplant eras and were adjusted for 2 sets of 6 possible confounders and 3 mediator variables. Cox models were used to estimate the risk of death. To search for age-related effects on the development of cardiac allograft vasculopathy (CAV), we applied cause-specific Cox models and proportional sub-distribution hazard models for competing risk data., Results: Survival was 80%, 77%, 69%, and 56% after 1, 2, 5, and 10 years, respectively. Donor age (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.0-1.2), recipient age (HR, 1.1; 95% CI, 1.0-1.2), admission from intensive care unit to HTX (HR, 1.5; 95% CI, 1.2-1.9), and diabetes (HR, 1.4; 95% CI, 1.1-1.7) were identified as significant independent risk factors for death. Significant risk factors for CAV were donor age (HR, 1.4; 95% CI, 1.3-1.5) and male recipient sex (HR, 1.5; 95% CI, 1.0-2.2). Recipient age was inversely associated with initiation of CAV (HR, 0.8; 95% CI, 0.8-1.0). Analysis of the interaction between donor and recipient age was not significant for death (p = 0.8) or CAV (p = 0.6)., Conclusions: We found no interaction between donor and recipient age negatively affecting mortality and CAV. The identified independent risk factors may have implications for allocation strategies in elderly recipients., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Arterial catheterization is painful and is associated with patient stress and anxiety. Analgesia is usually provided by subcutaneous injection of local anaesthetic. An alternative is topical anaesthesia, such as Rapydan which is a novel topical anaesthetic patch containing 70 mg each of lidocaine and tetracaine. We therefore tested the hypothesis that Rapydan patch analgesia is non-inferior to subcutaneous local anaesthetic., Methods: Ninety patients undergoing elective major cardiac surgery were included in this prospective, double-blind clinical trial. Patients were randomly assigned to receive either a lidocaine/tetracaine patch, followed by subcutaneous injection 0.5 ml of normal saline solution, or placebo patch with subsequent subcutaneous injection of 0.5 ml of lidocaine 1%. Pain during arterial catheterization using 100-mm-long visual analogue scale (VAS) was the primary outcome. Other outcomes were pain during anaesthetic/saline injection and plasma tetracaine concentrations., Results: VAS pain scores during arterial puncture were comparable in both groups and Rapydan was non-inferior to subcutaneous lidocaine. Pain scores at the time of subcutaneous injection were significantly lower (better) in patients assigned to the lidocaine/tetracaine patch than to lidocaine (P=0.001). Plasma tetracaine concentrations never exceeded the detection limit of 25 ng ml(-1) at any time in any patient., Conclusions: Both the lidocaine/tetracaine patch and subcutaneous injection of lidocaine provided comparable pain control during arterial catheter insertion. Subcutaneous lidocaine caused discomfort during injection, whereas the lidocaine/tetracaine patch required placement 20 min before the procedure. Given adequate time, the patch provided better overall analgesia by obviating the need for subcutaneous infiltration.

Background: The incidence of venous thromboembolism (VTE) is increased among cancer patients., Objective: We assessed serum levels of C-reactive protein (CRP) in order to study their prognostic significance for VTE and survival in the prospective observational Cancer and Thrombosis Study (CATS)., Patients and Methods: This study includes patients with recently diagnosed cancer or progression of disease after remission. Occurrence of VTE and information on the patients' anti-cancer-treatment are recorded. Observation ends with occurrence of objectively confirmed VTE, death or after 2 years. CRP levels were determined by an immunonephelometric method., Results: We included 705 consecutive patients with solid tumors. During the observation period, VTE occurred in 43 (6.1%) patients and 413 (58.6%) died. The cumulative probability of VTE was 6.6% after 1 year. In univariate analysis, CRP (as metric variable, per double increase) was associated with VTE [hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.1-1.3 P = 0.048]. However, in multivariable analysis including chemotherapy, surgery and radiotherapy, metastasis, cancer-site and sP-selectin the association with VTE (HR 1.0, 95% CI 0.9-1.2 P = 0.932) was no longer observed. CRP was clearly associated with worse survival probability with a HR of 1.3 (95% CI 1.2-1.3, P < 0.0001) in multivariable analysis. The cumulative survival after 12 months was 43% in patients with CRP above the 75th percentile (1.8 mg dL(-1) ) and 82% in those below the 75th percentile., Conclusions: In cancer patients elevated CRP was not independently associated with VTE. CRP was significantly associated with worse survival., (© 2010 International Society on Thrombosis and Haemostasis.)

The risk of venous thromboembolism (VTE) is increased in cancer patients. To improve prediction of VTE in cancer patients, we performed a prospective and observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. A previously developed risk scoring model for prediction of VTE that included clinical (tumor entity and body mass index) and laboratory (hemoglobin level and thrombocyte and leukocyte count) parameters was expanded by incorporating 2 biomarkers, soluble P-selectin, and D-Dimer. Of 819 patients 61 (7.4%) experienced VTE during a median follow-up of 656 days. The cumulative VTE probability in the original risk model after 6 months was 17.7% in patients with the highest risk score (≥ 3, n = 93), 9.6% in those with score 2 (n = 221), 3.8% in those with score 1 (n = 229), and 1.5% in those with score 0 (n = 276). In the expanded risk model, the cumulative VTE probability after 6 months in patients with the highest score (≥ 5, n = 30) was 35.0% and 10.3% in those with an intermediate score (score 3, n = 130) as opposed to only 1.0% in patients with score 0 (n = 200); the hazard ratio of patients with the highest compared with those with the lowest score was 25.9 (8.0-84.6). Clinical and standard laboratory parameters with addition of biomarkers enable prediction of VTE and allow identification of cancer patients at high or low risk of VTE.

Background: In cancer patients, laboratory parameters that predict venous thromboembolism (VTE) are scarce. Increased platelet count has been found to be a risk factor for VTE in cancer patients receiving chemotherapy (CHT). We have assessed high platelet count as a risk predictor for VTE in patients with cancer undergoing discriminative anti-cancer treatments and investigated whether platelet count correlates with thrombopoietin (TPO) levels., Design and Methods: The Cancer and Thrombosis Study (CATS) is an ongoing prospective observational study of patients with newly diagnosed cancer or progression of disease, which started in October 2003. Occurrence of VTE and information on the patients' anti-cancer treatment during follow-up were recorded., Results: Between October 2003 and February 2008, 665 patients with solid tumors were included (314 female/351 male, mean age 62 years). VTE occurred in 44 patients (18 female/26 male, mean age 62 years). The cumulative probability of VTE after 1 year was 34.3% in patients with a platelet count (PC) above the 95th percentile representing 443 x 10(9)/L compared with 5.9% in those below 443 x 10(9)/L. High platelet count [hazard ratio (HR): 3.50, 95% confidence interval (CI): 1.52-8.06, P = 0.0032], soluble P-selectin [HR: 2.66, 95% CI: 1.42-4.96, P = 0.0021] and surgery [HR: 4.05, 95% CI: 1.74-9.46, P = 0.0012] were statistically significant risk factors for VTE in multivariable analysis along with leucocyte count, age, gender, radio- and CHT. We found no correlation between platelet count and TPO levels., Conclusions: High PC is a clinically important, independent risk predictor for VTE in cancer patients. PC was not found to be associated with TPO levels.

Background: Renal dysfunction as a risk factor with the use of left ventricular assist devices (LVAD) is controversial. We determined the effect of renal function on outcomes after continuous flow LVAD implantation., Methods: Eighty-six patients with advanced heart failure undergoing continuous flow LVAD implantation as bridge to transplantation from November 1998 to July 2007 were retrospectively analyzed. Renal function was assessed using the Modification of Diet in Renal Disease study-derived glomerular filtration rates (GFR [mL x min(-1) x 1.73 m(-2)]). Patients were categorized into two groups based on pre-LVAD GFR: those with normal renal function (GFR > 60, n = 46), and those with renal dysfunction (GFR < 60, n = 40)., Results: Post-LVAD survival at 1, 3, and 6 months for GFR greater than 60 was 91.3%, 79.9%, 72.6%, respectively, and for GFR less than 60, it was 92.5%, 66.5%, 47.9%, respectively (p = 0.038). Bridge-to-transplant rate was lower for GFR less than 60 than for GFR greater than 60 (40.0% versus 63.0%, p = 0.033). For GFR less than 60, GFR improved on LVAD support: implant to month 6, 41.7 +/- 11.5 to 62.7 +/- 25.0 (p = 0.021). Post-LVAD survival was improved in GFR less than 60 patients who after LVAD implantation recovered renal function to GFR greater than 60 (p < 0.001). Patients with post-LVAD renal failure had significantly lower post-LVAD survival regardless of pre-LVAD renal function (p < 0.001)., Conclusions: Patients with renal dysfunction have poorer outcomes after continuous flow LVAD implantation. However, renal function improves after LVAD implantation and is associated with improved survival. Our data underscore the importance of end-organ function in patient selection for LVAD therapy.

Objective: The effect of age on outcomes after continuous-flow left ventricular assist device (LVAD) implantation as a bridge to transplantation (BTT) was determined., Methods: From November 1998 to July 2007, 86 patients with advanced heart failure underwent continuous-flow LVAD implantation as BTT and were retrospectively analyzed. Patients were categorized into 2 groups by age at LVAD implantation: 56 patients (65.1%) younger than 60, Group 1; and 30 (34.9%) aged 60 years or older, Group 2., Results: Group 2 patients had a higher incidence of heart failure caused by ischemic heart disease (63.3% vs 32.1%, p = 0.005) and more severely impaired renal function by Modification of Diet in Renal Disease-derived glomerular filtration rates (51.9 +/- 15.9 vs. 68.0 +/- 20.5 ml/min/1.73 m(2), p < 0.001) than Group 1. Age was the only independent predictor of post-LVAD death (hazard ratio, 1.4 p = 0.003). The BTT rate was lower (33.3% vs 62.5%, p = 0.010), and incidence of post-LVAD renal failure was higher (53.3% vs 30.4%, p = 0.037) in Group 2 vs Group 1. Post-LVAD survival at 1, 3, and 6 months was 92.9%, 79.9%, and 74.0% for Group 1 and 90.0%, 62.0%, and 37.0% for Group 2 (p = 0.007). Post-transplant survival at 1, 3, and 5 years was 87.8%, 82.3%, and 76.0% for Group 1 and 90.0%, 67.5%, 67.5% for Group 2 (p = 0.517)., Conclusions: Patients aged 60 years and older have inferior post-LVAD survival; however, post-transplant survival is excellent. We advocate LVAD placement as bridge-to-transplant therapy only in carefully selected older patients most well suited for transplantation.

Cancer patients are at high risk for venous thromboembolism (VTE). Laboratory parameters with a predictive value for VTE could help stratify patients into high- or low-risk groups. The cell adhesion molecule P-selectin was recently identified as risk factor for VTE. To investigate soluble P-selectin (sP-selectin) in cancer patients as risk predictor for VTE, we performed a prospective cohort study of 687 cancer patients and followed them for a median (IQR) of 415 (221-722) days. Main tumor entities were malignancies of the breast (n = 125), lung (n = 86), gastrointestinal tract (n = 130), pancreas (n = 42), kidney (n = 19), prostate (n = 72), and brain (n = 80); 91 had hematologic malignancies; 42 had other tumors. VTE occurred in 44 (6.4%) patients. In multivariable analysis, elevated sP-selectin (cutoff level, 53.1 ng/mL, 75th percentile of study population) was a statistically significant risk factor for VTE after adjustment for age, sex, surgery, chemotherapy, and radiotherapy (hazard ratio = 2.6, 95% confidence interval, 1.4-4.9, P = .003). The cumulative probability of VTE after 6 months was 11.9% in patients with sP-selectin above and 3.7% in those below the 75th percentile (P = .002). High sP-selectin plasma levels independently predict VTE in cancer patients. Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE.

Background: In an attempt to monitor the pharmacodynamics of mycophenolate mofetil (MMF) we investigated the association of inosine monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells with the expression of lymphocyte activation markers in stable cardiac transplant recipients treated with MMF., Methods: Twenty-four study patients were switched from azathioprine to MMF 7.2+/-4.1 years after heart transplantation., Results: While the MPA trough level remained unchanged, the mean activity of IMPDH declined from 890 to 462 pmol/10(6)PBMC/h three months after onset of MMF therapy, was almost completely inhibited at six months and partially restored to 160 pmol/10(6)PBMC/h 12 months after switch to MMF (p< .0001). We detected also significant changes in a number of activated lymphocyte subsets: CD4+/25+, CD8+/38+, CD19+/69+, CD3+/16+/56+, natural killer (NK) cells, and monocytes. Moreover, the IMPDH activity profile correlated positively with the number of CD8+/38+ T cells (correlation coefficient (CC) +0.53), and inversely with NK cells (CC -0.52) and CD19+/69+ cells (CC -0.61)., Conclusions: We revealed a close association of IMPDH baseline activity in mononuclear cells with the expression of lymphocyte activation markers in stable heart transplant patients after introduction of MMF therapy. This supports the assumption of a rather immunomodulatory than immunosuppressive effect of MMF.

Background: The purpose of this study was to evaluate outcome in patients with a small aortic root receiving either a standard CarboMedics mechanical aortic valve or a Top Hat CarboMedics valve (CarboMedics, Austin, TX), specifically designed for the small aortic root., Methods: Between 1986 and 2006, 316 consecutive patients underwent 19- or 21-mm mechanical aortic valve replacement, receiving either a CarboMedics Top Hat bileaflet valve (n = 56; mean age, 66 +/- 14 years) or a standard CarboMedics aortic valve replacement (n = 260; mean age, 60 +/- 13 years) at our institution based on institutional indications for the choice of type of valve prostheses. Median follow-up time was 83.5 months. We studied survival, valve-related and non-valve-related events, and hemodynamic performance by serial echocardiographic follow-up studies., Results: In-hospital mortality was 8.9% in the Top Hat group and 10.0% in the standard group (p = 0.354). Five- and ten-year survival in patients in the Top Hat group was 83% and 67%, respectively. Five- and ten-year survival in the standard group was 73% and 59%, respectively (log-rank = 0.331). There were no differences in regard to valve-related and non-valve-related events. Cox regression analysis revealed age (hazard ratio, 1.045; 95% confidence interval, 1.026 to 1.066), previous cardiac surgery (hazard ratio, 1.812; 95% confidence interval, 1.101 to 2.982), additional procedures at the time of valve replacement (hazard ratio, 2.604; 95% confidence interval, 1.651 to 4.108), New York Heart Association class IV (hazard ratio, 3.645; 95% confidence interval, 1.214 to 10.945), and severely impaired left ventricular ejection fraction (hazard ratio, 2.253; 95% confidence interval, 1.289 to 3.941) to be independent predictors of survival., Conclusions: Mechanical aortic valve replacement in the small aortic root is associated with substantial perioperative mortality, in particular in the subset of patients requiring additional cardiac surgical procedures. Nevertheless, long-term outcome is satisfying. Because the type of prosthesis does not predict outcome in the multivariate Cox model, we conclude that use of the smaller Top Hat prosthesis can be recommended for the challenging cohort of patients with a small aortic root.

Background: This study was designed to determine the effect of continuous vs pulsatile flow devices on renal function after left ventricular assist device (LVAD) implantation., Methods: Ninety-two patients undergoing LVAD implantation as bridge-to-transplant therapy were retrospectively analyzed. Patients receiving continuous flow devices (n = 63, 68.5%) were compared with patients receiving pulsatile flow devices (n = 29, 31.5%). Renal function was assessed by 2 calculated glomerular filtration rates (GFR) using the Modification of Diet in Renal Disease (MDRD)-derived GFR (ml/min/1.73 m(2)) and the Cockcroft-Gault-derived creatinine clearance (CrCl, ml/min)., Results: Mean GFR/CrCl was comparable between the groups at LVAD implantation, in the post-implantation period, and at transplantation. Both groups had a significant increase in mean GFR at Week 1 post-implantation (continuous, 59.4 +/- 22.8 to 76.4 +/- 38.6, p = 0.001; pulsatile, 52.5 +/- 21.1 to 69.2 +/- 34.7; p = 0.007), Week 4 (continuous, 59.9 +/- 23.0 to 84.3 +/- 32.9; p < 0.001; pulsatile, 50.3 +/- 21.1 to 79.9 +/- 38.7, p = 0.007), and Week 12 (continuous, 60.3 +/- 23.1 to 75.3 +/- 30.2, p = 0.004; pulsatile, 55.5 +/- 23.1 to 74.2 +/- 27.2, p = 0.037) that was also seen with the Cockcroft-Gault-calculated CrCl. No significant increase occurred in mean GFR/CrCl to transplantation. Incidence of post-implantation renal failure was comparable between the groups (continuous, 38.1%; pulsatile, 31.0%; p = 0.512)., Conclusions: After LVAD implantation, patients with continuous flow devices and patients with pulsatile flow devices have comparable renal function.

Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.

Background: Alloantigen-activated T cells express high-affinity interleukin-2 receptor (IL-2R). Specific blockade of this receptor has been associated with lower rejection episodes in clinical transplantation when compared with placebo. The first short-term results of the newer IL-2R antagonists are becoming available but little is known about the long-term effects of these drugs. The aim of the study was to compare the clinical efficacy of the IL-2R antagonist BT563 with polyclonal rabbit anti-thymocyte globulin (ATG) in heart transplant recipients., Methods: Forty patients undergoing cardiac transplantation were randomly assigned to receive either BT563 or rabbit ATG as induction therapy, combined with triple immunosuppression thereafter. Ten-year surveillance for rejection, infection, allograft vasculopathy and tumorgenicity was performed. Allograft rejection and vasculopathy were assessed by endomyocardial biopsy and coronary angiography, respectively. Screening for infection included blood, urine or tracheobronchial cultures and serology., Results: No difference was detected in terms of 10-year survival between the two groups (50% for the IL-2R group and 70% for the ATG group, p = 0.16). Actuarial incidence of severe rejection was significantly higher in the IL-2R group (55% vs 10% at 10 years post-operatively, p = 0.028; 55% vs 5% during the first month post-operatively, p = 0.0005). Patients receiving ATG had a higher incidence of viral infection. Freedom from allograft vasculopathy was significantly higher in the ATG group (80% vs 60%, p = 0.031)., Conclusions: BT563/BB10 is less effective than ATG for prevention of both acute allograft rejection and allograft vasculopathy after cardiac transplantation. Clinically relevant infections or tumorgenicity were not increased with the use of ATG.

Background: Our aim was to study the process of microcirculatory reconstitution in the bronchial stump after pneumonectomy., Methods: Eighteen juvenile pigs (median weight 40.6 kg) were randomly assigned to three groups. In all animals left pneumonectomy was performed and the stapled bronchial stump (median length 3.8 cm) carefully denuded. Group I animals received coverage of the stump by intercostal flap. In group II, the stump was covered with TachoComb, an impermeable hemostatic fleece; and group III served as a control without any coverage of the stump. Animals were sacrificed at day 14 after surgery. Vascular density was evaluated in serial histologic sections at multiple levels stained with CD-31 antibody. One-way analysis of variance and the Wilcoxon test were used for data analysis., Results: At autopsy, stumps of group III animals were totally covered by adjacent mediastinal structures. In group I, intercostal flaps were viable and completely healed to the bronchial stumps. There were no signs of infection or stump insufficiency in these groups. In all group II animals, empyema developed, and stumps were found necrotic at macroscopic and histologic evaluation. Statistical analysis revealed significantly lower vascular density of mature vessels in the area of the bronchial stump in group II compared with both other groups., Conclusions: Reconstitution of microcirculation of the denuded bronchial stump after pneumonectomy takes place in a centripetal way from adjacent viable tissue. Hence, the purpose of covering the bronchial stump is the improvement of blood supply rather than mechanical reinforcement.

Background: The heme oxygenase-1 (HO-1) isoenzyme has recently been suggested to protect transplants from ischemia-reperfusion and immunologic injury. Inducibility of this enzyme is modulated by a (GT)n dinucleotide length polymorphism in the HO-1 gene promoter. Short (class S) repeats are associated with greater up-regulation of HO-1 than are long repeats. In the present study, we investigated the impact of the promoter polymorphism on the development of cardiac allograft vasculopathy (CAV) in human heart transplants., Methods: We enrolled 152 recipients of a heart allograft with at least 1 year survival post-transplantation in this retrospective study. The HO-1 genotype was assessed using genomic DNA isolated from paraffin-embedded allograft biopsy specimens. Patients were followed angiographically for CAV. Angiographic vessel-wall abnormalities were defined as CAV, and a stenosis of more than 50% in at least 1 vessel area was defined as severe CAV., Results: Eighty-seven patients (57%) had received a heart from a donor with at least 1 class S allele. Within the mean follow-up period of 9 years, 95 patients (63%) showed signs of CAV, among which 60 patients (40%) developed severe CAV. The frequency of CAV and severe CAV was not significantly different between class S allele recipients and non-recipients (CAV, 57/87 vs 38/65, p = 0.12; severe CAV, 35/87 vs 25/65, p = 0.30)., Conclusion: In contrast to recent findings in renal allografts and vascular injury, the HO-1 gene promoter polymorphism does not show an association with the development of CAV in heart transplants.

Background: We compared our experience of minimal tissue dissection and target vessel revascularization without cardiopulmonary bypass (CPB) with the standard procedure of total dissection of the heart and complete revascularization with CPB in patients who had elective reoperative coronary artery bypass grafting (redo-CABG)., Methods: We analyzed recurrence of angina and clinical outcome in 118 patients who had elective redo-CABG between January 1995 and April 2002. Seventy-four patients had redo-CABG with CPB, and 44 patients had redo-CABG without CPB., Results: Perioperative outcome was comparable with regard to morbidity and mortality rates. At follow-up, the mean Canadian Cardiovascular Society score was 1.3 +/- 0.6 in patients who had redo-CABG with CPB and 1.7 +/- 0.8 in patients who had redo-CABG without CPB (p = 0.02). At follow-up, patients who had redo-CABG without CPB had a higher rate of recurrence of angina (log rank = 0.001) and higher use of nitrates (p = 0.015). Target vessel revascularization was an independent predictor of recurrence of angina in younger patients (< 75 years; p = 0.012) but not in the elderly (> or = 75 years; p = 0.142)., Conclusions: In elective redo-CABG patients, minimal tissue dissection and target vessel revascularization without cardiopulmonary bypass did not add significant benefit with regard to perioperative morbidity and mortality. The unsatisfactory relief of symptoms does not seem to justify target vessel revascularization by a less invasive approach. Therefore, this technique should be offered exclusively to patients at high risk with complete revascularization using CPB, such as the elderly.

Background: Cytomegalovirus (CMV) has emerged as the most important pathogen to affect the post-operative course after heart transplantation. We performed a retrospective analysis to evaluate the efficiency of CMV hyperimmune globulin (CMVIG) prophylaxis in preventing CMV disease in aggressively immunosuppressed patients after heart transplantation., Methods: We studied 377 heart transplant recipients who received quadruple-immunosuppressive therapy and CMVIG as sole CMV prophylaxis. The study population was categorized into 4 groups according to donor and recipient CMV serology at the time of transplantation (D+/R+, D+/R-, D-/R+, D-/R-) and was monitored for CMV immediate early antigen in peripheral blood cells, in urine sediments, and in throat washings; for the presence of serum CMV immunoglobulin M and CMV immunoglobulin G; and for clinical evidence of CMV-related symptoms. In addition, we compared the incidence of cardiac allograft vasculopathy and infection among the groups., Results: During the first 5 years after transplantation, CMV disease developed in 79 patients (20.96%). Comparison among the groups showed significantly increased risk for CMV disease in allograft recipients of organs from seropositive donors (D+, 27.31%; D-, 11.33%; p = 0.0003). We observed 6 CMV-associated deaths, all in CMV-antibody-negative recipients. Additionally CMV-positive recipients had a greater incidence of cardiac allograft vasculopathy (p = 0.048), and a greater overall infection rate (p = 0.0034)., Conclusions: Cytomegalovirus hyperimmune globulin administration prevents CMV disease and infection in aggressively immunosuppressed heart transplant recipients. Because fatal CMV disease in CMV-negative recipients of organs from seropositive donors could not be prevented with CMVIG alone, we recommend the additional use of prophylactic ganciclovir in this CMV-mismatched population.