Donor-recipient risk assessment tools in heart transplant recipients: the Bad Oeynhausen experience.

AIMS: Some risk assessment tools have been developed to categorize mortality risk in heart transplant recipients, but it is unclear whether these tools can be used interchangeable in different transplant regions. METHODS AND RESULTS: We performed a retrospective single-centre study in 1049 adult German heart transplant recipients under jurisdiction of Eurotransplant. Univariable and multivariable Cox regression analysis was used to generate a risk scoring system. C-statistics were used to compare our score with a US score and a French score regarding their ability to discriminate between 1 year survivors and non-survivors within our study cohort. Of 38 parameters assessed, seven recipient-specific parameters [age, height, dilated cardiomyopathy (DCM), ischaemic cardiomyopathy (ICM), total bilirubin, extracorporeal membrane oxygenation (ECMO), and biventricular assist device/total artificial heart (BVAD/TAH) implant], one donor-specific parameter (cold ischaemic time), and one recipient-independent and donor-independent other parameter (late transplant era) were statistically significant in predicting 1 year mortality. The initial score was generated by using the regression coefficients from the multivariable analysis as follows: 1.70 * ln age - 4.0 * ln height - 0.9 * diagnosis (= 1 if diagnosis = DCM) - 0.67 * diagnosis (= 1 if diagnosis = ICM) + 0.33 * ln total bilirubin + 1.74 * ln cold ischaemic time + 0.98 * mechanical circulatory support (MCS) implant (= 1 if MCS implant = ECMO) + 0.47 * MCS implant (= 1 of MCS implant = BVAD/TAH) - 0.66 * transplant era (= 1 if transplant era = 2017-2018). The initial score was converted into the Bad Oeynhausen (BO) score as a positive integer variable by means of the following formula: BO score = (initial score + 8) * 3. In patients scoring 2 to <7 points (n = 112), 7 to <11 points (n = 580), 11 to <15 points (n = 339), and 15 to 20 points (n = 18), 1 year survival was 93.1%, 84.2%, 66.9%, and 27.8%, respectively. The c-index of our score was 0.73 [95% confidence interval (CI): 0.69-0.77]. Values were in our cohort for the US and French scores 0.66 (95% CI: 0.62-0.70) and 0.63 (95% CI: 0.59-0.67), respectively. CONCLUSIONS: Data indicate that our score, but also risk assessment tools from other transplant regions, may be used as a reliable support for risk-adjusted organ allocation and potentially help to improve outcomes in heart transplantation. Further developments will have to include as yet unaccounted risk factors for even more reliable predictions.

Distinct Myocardial Transcriptomic Profiles of Cardiomyopathies Stratified by the Mutant Genes.

Cardiovascular diseases are the number one cause of morbidity and mortality worldwide, but the underlying molecular mechanisms remain not well understood. Cardiomyopathies are primary diseases of the heart muscle and contribute to high rates of heart failure and sudden cardiac deaths. Here, we distinguished four different genetic cardiomyopathies based on gene expression signatures. In this study, RNA-Sequencing was used to identify gene expression signatures in myocardial tissue of cardiomyopathy patients in comparison to non-failing human hearts. Therefore, expression differences between patients with specific affected genes, namely LMNA (lamin A/C), RBM20 (RNA binding motif protein 20), TTN (titin) and PKP2 (plakophilin 2) were investigated. We identified genotype-specific differences in regulated pathways, Gene Ontology (GO) terms as well as gene groups like secreted or regulatory proteins and potential candidate drug targets revealing specific molecular pathomechanisms for the four subtypes of genetic cardiomyopathies. Some regulated pathways are common between patients with mutations in RBM20 and TTN as the splice factor RBM20 targets amongst other genes TTN, leading to a similar response on pathway level, even though many differentially expressed genes (DEGs) still differ between both sample types. The myocardium of patients with mutations in LMNA is widely associated with upregulated genes/pathways involved in immune response, whereas mutations in PKP2 lead to a downregulation of genes of the extracellular matrix. Our results contribute to further understanding of the underlying molecular pathomechanisms aiming for novel and better treatment of genetic cardiomyopathies.

Renal Function in Patients with or without a Left Ventricular Assist Device Implant During Listing for a Heart Transplant.

BACKGROUND Left ventricular assist device (LVAD) implantation may improve kidney function, but in patients awaiting heart transplantation, the long-term effects of LVAD implantation on renal function and subsequent clinical outcome are unclear. MATERIAL AND METHODS We analyzed data in patients with LVAD implants (n=139) and without LVAD implants (n=1038) who were listed for a heart transplant at our institution between 2000 and 2019. The primary endpoint was an impairment in renal function (decrease of creatinine-based estimated glomerular filtration rate [eGFR] by ≥30%) up to a maximum of 2 years after listing. Secondary endpoints were chronic kidney disease stage 4 or 5, heart transplantation, survival during listing, and 1-year survival after transplantation. RESULTS Values for eGFR increased after LVAD implantation (P=0.001) and were higher at the time of waitlisting in the LVAD group than in the non-LVAD group (P=0.002), but were similar between groups at the end of waitlisting (P=0.75). Two-year freedom from renal impairment was 50.6% and 66.7% in the LVAD and non-LVAD groups, respectively, with a multivariable-adjusted hazard ratio for the LVAD versus the non-LVAD group of 1.78 (95% confidence interval 1.19-2.68; P=0.005). Two-year freedom from chronic kidney disease stages 4-5 was similar between study groups (LVAD group: 83.5%; non-LVAD group: 80.1%; =0.50). The 2-year probability of transplantation was slightly lower in the LVAD group than in the non-LVAD group (50.0% and 55.8%, respectively, P=0.017). However, 2-year survival on the waiting list and 1-year survival after transplantation did not differ significantly between study groups (P-values >0.20). CONCLUSIONS Our data indicate a transient improvement in creatinine-based eGFR values by LVAD implantation without influencing survival.

Long-term experiences on cardiac retransplantation in adults.

BACKGROUND: It remains disputed whether cardiac retransplantation should be performed. This study aimed to evaluate our long-term experiences on cardiac retransplantation in adults. PATIENTS AND METHODS: Between March 1989 and December 2004, 2% (28/1290) of cardiac retransplantations were performed. RESULTS: The reasons for cardiac retransplantation were cardiac allograft vasculopathy (n=13; 47%), primary graft failure (n=11; 39%), and refractory acute rejection (n=4; 14%). The 30-day mortality risk was 29% (acute rejection: 50%; primary graft failure: 36%; cardiac allograft vasculopathy: 15%, p=0.324), compared to 8.5% for primary cardiac transplantation (p<0.001). The causes of early death were acute rejection (n=3; 37%), multiorgan failure (n=3; 37%), primary graft failure (n=1; 13%), and right ventricular failure (n=1; 13%). The late mortality rate was 96/1000 patient-years. The causes of late death were acute rejection (n=4; 50%), cardiac allograft vasculopathy (n=2; 25%), multiorgan failure (n=1; 13%), and infection (n=1; 13%). The 1-, 5-, 10-, and 15-year survival was respectively 78, 68, 54, and 38% (primary cardiac transplantation), and 46, 41, 32, and 32% (cardiac retransplantation) (p=0.003). The short-term survival for cardiac retransplantation due to cardiac allograft vasculopathy was likely better than primary graft failure and refractory acute rejection (p=0.09). CONCLUSION: The overall outcomes of cardiac retransplantation are significantly inferior to primary cardiac transplantation. Cardiac retransplantation should be only performed for selected patients.

[Predictive value of ECG changes for acute cardiac rejections in heart transplant recipients]. / Diagnostische Wertigkeit von EKG-Veränderungen bei akuten kardialen Abstossungsreaktionen nach orthotoper Herztransplantation.

BACKGROUND AND PURPOSE: Currently, endomyocardial biopsy is the most reliable method to detect an acute rejection after heart transplantation. However, as an invasive procedure it is associated with a definite risk for complications. Therefore, it was examined whether changes in QT time and QT dispersion on the surface ECG are able to predict an acute cellular rejection. PATIENTS AND METHODS: During the first 3 months after heart transplantation, QT time, heart rate-corrected QT time (QTc time), QT dispersion, and heart rate-corrected QT dispersion (QTc dispersion) were analyzed in 100 patients with acute cellular rejection grade > or = II according to the International Society for Heart and Lung Transplantation (ZA group), and in 100 patients without or with only mild rejection episodes (< or = grade I; MA group). Results were obtained by determining the difference in the ZA group between the QT interval in the presence of a rejection and the QT interval at other time points, which were then compared with the results of the MA group at matched time points. RESULTS: At the time point of rejection, the ZA group showed a mean prolongation in both QTc time and QTc dispersion of > 40 ms compared with other time points. Such differences were not seen in the MA group (p < 0.001 for comparisons between study groups). If prolongations in QTc time and QTc dispersion of > 25 ms were used as predictors for an acute rejection, sensitivity was 77% and 70%, respectively, and specificity was 96% and 95%, respectively. CONCLUSION: Provided that ECGs are performed regularly, measurements of QTc time and QTc dispersion can reliably be used to detect an acute rejection in the early phase after heart transplantation.

Long-term results of pediatric heart transplantation.

OBJECTIVE: We retrospectively reviewed 104 consecutive patients who underwent orthotopic heart transplantation between November 1989 and February 2004. PATIENTS AND METHODS: From November 1989 to February 2004, the total number of heart transplantations were 1,340 cases at our institute. One hundred four (7.8%) of these 1,340 patients were pediatrics. Average age was 6.2 years, ranging from 4 months to 16 years. The cause of heart disease before transplantation was: idiopathic dilated cardiomyopathy (DCM) in 74 patients (71%), and congenital heart disease (CHD) in 30 (29%). RESULTS: Hospital mortality rate was 14.4% (15 patients). Late complications were rejection in 23 (22.1%), infection in 11 (10.6%), gingival hyperplasia in 28 (26.9%), hypertention in 22 (21.1%), coronary artery disease (CAD) in 12 (12.5%), graft failure in 11(10.5%), and malignancy in 2 (1.9%). Late mortality occurred in 11 (10.6%) patients. Causes of death were sudden death in 2 (1.9%), CAD in 3 (2.8%), graft failure in 1 (1.0%), acute rejection in 4 (4.6%), and infection in 1 (1.0%). Actuarial survival rates in pediatrics at 1, 5, 10 years were 82%, 80%, and 78%, respectively. On the other hand, actuarial survival rates in adults at 1, 5, 10 years were 78%, 75%, 59%, respectively. CONCLUSION: Heart transplantation for pediatrics is an effective therapy with acceptable morbidity and mortality. The long-term survival results in pediatrics are comparable to those of adult heart transplantations. However, the actuarial survival rate in pediatrics after 10 years is significantly better than in adults' cases. Renal function in pediatric heart transplantation recipients treated with cyclosporine remains stable during long-term follow-up.

Creatine kinase and troponin after myocardial preservation using HTK solution (Custoidol) for clinical heart transplantation.

Myocardial preservation by Bretschneider histidine-tryptophan-ketoglutarate (HTK) solution (Custoidol) was studied in transplanted patients. Post-operative creatine kinase (CK), CK-MB and troponin I were higher in patients with an ischemic time of >or=4 hours; however, values were within the acceptable range for clinical heart transplantation.