Donor heart selection and outcomes: An analysis of over 2,000 cases.

BACKGROUND: Decision-making when offered a donor heart for transplantation is complex, and supportive data describing outcomes according to acceptance or non-acceptance choices are sparse. Our aim was to analyze donor heart acceptance decisions and associated outcomes at a single center, and after subsequent acceptance elsewhere. METHODS: This investigation was a retrospective analysis of data obtained from the University of Vienna Medical Center and Eurotransplant centers for the period 2001 to 2015. RESULTS: Our center accepted 31.8% (699 of 2,199) of donor hearts offered. Unlike other centers, the acceptance rate, with or without transplantation, did not increase over time. Of the donor hearts rejected by our center, 38.1% (572 of 1,500) were later accepted elsewhere. Acceptance rates were twice as high for donor hearts initially rejected for non-quality reasons (339 of 601, 56.4%) compared with initial rejection for quality reasons (233 of 899, 25.9%). Three-year patient survival rate was 79% at Vienna; for donor hearts initially rejected by Vienna for non-quality reasons or quality reasons, it was 73% and 63%, respectively (p < 0.001). Outcomes at other centers after transplantation of grafts rejected by Vienna varied according to the reason for rejection, with good 3-year survival rates for rejection due to positive virology (77%), high catecholamines (68%), long ischemic time (71%), or low ejection fraction (68%), but poor survival was observed for hearts rejected for hypernatremia (46%), cardiac arrest (21%), or valve pathology (50%). CONCLUSIONS: A less restrictive policy for accepting donor hearts at our center, particularly regarding rejection for non-quality reasons or for positive virology, high catecholamine levels, longer ischemic time, or low ejection fraction, could expand our donor pool while maintaining good outcomes.

[Use of ECMO in adult patients with cardiogenic shock: a position paper of the Austrian Society of Cardiology]. / Positionspapier der Österreichischen Kardiologischen Gesellschaft zum Einsatz der extrakorporalen Membranoxygenation (ECMO) bei Erwachsenen kardiologischen Patienten.

The use of ECMO to stabilize critically ill patients with severely depressed cardiac function and hemodynamics increased in the last years due to broader availability, better performance and easier implantation of the devices. The present guidelines of the Austrian Society of Cardiology focus on the use of ECMO in adult non-operated patients with cardiac diseases. Not only indications and contraindications are highlighted, but also the equally important issues of monitoring, complication management, measures during implantation and operation, and weaning of the devices are treated in detail. Thereby the present guidelines aim to optimize the use of ECMO in the individual centers, and aim to help current non-ECMO centers in developing a local ECMO-program or to contact ECMO-centers for discussion of individual patients.

[Use of ECMO in adult patients with cardiogenic shock: a position paper of the Austrian Society of Cardiology]. / Positionspapier der Österreichischen Kardiologischen Gesellschaft zum Einsatz der extrakorporalen Membranoxygenation (ECMO) bei Erwachsenen kardiologischen Patienten.

The use of ECMO to stabilize critically ill patients with severely depressed cardiac function and hemodynamics increased in the last years due to broader availability, better performance and easier implantation of the devices. The present guidelines of the Austrian Society of Cardiology focus on the use of ECMO in adult non-operated patients with cardiac diseases. Not only indications and contraindications are highlighted, but also the equally important issues of monitoring, complication management, measures during implantation and operation, and weaning of the devices are treated in detail. Thereby the present guidelines aim to optimize the use of ECMO in the individual centers, and aim to help current non-ECMO centers in developing a local ECMO-program or to contact ECMO-centers for discussion of individual patients.

The role of serum albumin in the prediction of malnutrition in patients at least five yr after heart transplantation.

OBJECTIVES: Malnutrition after heart transplantation (HTX) is related to graft sclerosis. The risk for malnutrition is often underestimated by conventional measurements. We aimed to compare these with objective assessors for malnutrition. METHODS: Recipients at least five yr after HTX were included. Body mass index (BMI), bioimpedance analysis (BIA), serum albumin (SA) and subjective global assessment (SGA) malnutrition, and concomitant diseases were assessed. The BIA was used as gold standard, and a phase difference (PD) <4 was defined as cutoff. RESULTS: Sixty recipients (47 male, 13 female) were analyzed. The prevalence of malnutrition was according to SGA 6.6% (4/60), BMI 8.3% (5/60), SA 31.6% (19/60), and BIA 48.3% (19/60). PD values did not correlate with BMI (r = 0.118; p = 0.079) or SGA (r = 0.289; p = 0.65), but with SA (r = 0.458; p = 0.001). Multivariate analysis yield SA and sCr as independent predictors for an existing malnutrition. ROC analysis showed an area under the receiver operating characteristic curve of 0.606 for SA as compared to 0.515 for the BMI and 0.698 for sCr in the prediction of existing malnutrition as defined by the PD. CONCLUSION: The BMI or the SGA did not show as much power in predicting an existing alimentary deficiency for heart recipients as did SA.

The role of CYP2C8 genotypes in dose requirement and levels of everolimus after heart transplantation.

Everolimus is an immunosuppressive drug metabolized by enzymes of the CYP family. A common variant of the CYP2C8 gene, CYP2C8*3, results in strongly decreased CYP2C8 activity, but its role for the pharmacogenetics of everolimus remains unclear. Aim of the present study was to examine the role of CYP2C8 variants in everolimus dose and drug levels after heart transplantation. The present study comprised 30 patients with everolimus based maintenance therapy after heart transplantation. CYP2C8 genotypes were determined and correlated with clinical data. In all, 21 subjects carried the CYP2C8 *1/*1 genotype and 9 subjects carried the CYP2C8 *1/*3 genotype. Neither everolimus dose nor everolimus levels were associated with CYP2C8 genotype at any point of time (p < 0.05). During follow-up, graft rejection reactions were observed in two patients and infections were observed in seven patients. In one patient, type 2 diabetes was diagnosed during follow-up. None of these adverse events were significantly associated with CYP2C8 genotypes. We conclude that in adult patients after heart transplantation, CYP2C8 genotypes are not associated with dose requirements or levels of everolimus.

The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus after heart transplantation.

BACKGROUND: tacrolimus and everolimus are immunosuppressive drugs metabolized by enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A5*3, results in strongly decreased CYP3A5 activity and has been shown to influence Tacrolimus blood concentrations, but its role for the pharmacogenetics of Everolimus remains unclear. Aim of the study was to examine the role of CYP3A5*3 variant in tacrolimus and everolimus dose and drug levels after heart transplantation. METHODS: The present study comprised 15 patients with Tacrolimus and 30 patients with Everolimus-based maintenance therapy after heart transplantation. CYP3A5 genotypes were determined and correlated with clinical data. RESULTS: In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared to non-expressors. Tacrolimus levels were not significantly different at any point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither Everolimus dose nor levels were significantly different between CYP3A5 expressors and non-expressors at any point of time. DISCUSSION: We conclude that in adult patients after heart transplantation, CYP3A5 genotypes have a strong influence on Tacrolimus, but not Everolimus dose requirement.

[Evaluation of the potential organ donor with special regards to heart donation]. / Der potentielle Organspender - Evaluierung unter besonderer Berücksichtigung der Herzentnahme.

Regarding limited availability of organ donors for heart transplantation, it is necessary to discuss optimal donor evaluation and donor management. In this manuscript general donor-related parameters as well as heart-specific parameters are discussed regarding international literature. In addition, "marginal" donors and in contrast "optimal" donors are defined. Donor management including optimal hemodynamic management and additional specific intensive care aspects are presented. Exact donor evaluation allows for matching the organ to the most suitable recipient and is therefore especially in the context of marginal donors a crucial step within transplantation process.

Serum cystatin C is an easy to obtain biomarker for the onset of renal impairment in heart transplant recipients.

OBJECTIVE: With the increasing longevity of heart transplant recipients, the long-term effects of cyclosporine on renal function have become more evident. Highly sensitive, early, and effective monitoring of posttransplant renal function is still being researched. This study aimed to evaluate the prognostic value of cystatin C for patients after heart transplantation. METHODS: Seventy-three long-term recipients of a heart transplant more than 5 years before the study start were included in the analysis with a follow-up of 4 years. Serum creatinine, renal glomerular filtration rate calculated by the Modification of Diet in Renal Disease formula, and serum cystatin C levels were collected, and risk factors for renal dysfunction were assessed. Statistical analysis was performed for all patients. RESULTS: Univariate analysis showed a prognostic impact of antihypertensive medication and onset of diabetes (P < .001) on renal failure after transplantation. Multivariate analysis yielded cystatin C measured at the study start as a superior prognostic parameter for all time points (area under the receiver operating characteristic 12 months: 0.963; 24 months: 0.910; 48 months: 0.949) compared with the conventionally used creatinine levels. CONCLUSIONS: Our results showed an enormous potential of serum cystatin C as an early prognostic and easy to obtain biomarker for renal dysfunction after heart transplantation.

Establishing extracorporeal membrane oxygenation in a university clinic: case series.

OBJECTIVES: Although extracorporeal membrane oxygenation (ECMO) is well established for respiratory failure in neonates, application in adults is still considered controversial. The survival of patients with acute respiratory distress syndrome and ECMO therapy is 50% to 70%. DESIGN: A retrospective analysis of 10 patients, who were placed on ECMO from September 2004 to December 2005, was performed. SETTING: University clinic. INTERVENTIONS: Venoarterial ECMO was established in 7 patients, venovenous ECMO in 2 patients, and combined venoarterial and venovenous ECMO in 1 patient. MEASUREMENTS AND MAIN RESULTS: Indications were pneumonia, acute respiratory distress syndrome, near drowning, pericardial tamponade with shock lung, right-heart failure after heart transplantation, shock lung after cardiopulmonary resuscitation, and right-heart failure in chronic thromboembolic pulmonary hypertension. Median maintenance of ECMO therapy was 56.5 hours (range, 36-240). The median Murray score was 3.3 for survivors and 4 for nonsurvivors. Overall mortality was 30%; 70% were weaned from ECMO and survived until discharge. Median pre-ECMO risk for fatal outcome according to Hemmila was 0.43 for survivors and 0.92 for nonsurvivors (p < 0.02). In 2 cases, surgical reintervention was necessary because of bleeding in one, and a side switch of the cannulae had to be performed because of femoral venous thrombosis in the other. CONCLUSIONS: ECMO has been shown to be a successful therapy for acute respiratory distress syndrome when conventional strategies have failed. Pre-ECMO risk assessment may be useful in the evaluation of patients.