Thirty years of heart transplantation at the University Medical Centre Utrecht.

PURPOSE: To analyse patient demographics, indications, survival and donor characteristics for heart transplantation (HTx) during the past 30 years at the University Medical Centre Utrecht (UMCU). METHODS: Data have been prospectively collected for all patients who underwent HTx at the UMCU from 1985 until 2015. Patients who were included underwent orthotopic HTx at an age >14 years. RESULTS: In total, 489 hearts have been transplanted since 1985; 120 patients (25%) had left ventricular assist device (LVAD) implantation prior to HTx. A shift from ischaemic heart disease to dilated cardiomyopathy has been seen as the leading indication for HTx since the year 2000. Median age at HTx was 49 years (range 16-68). Median waiting time and donor age have also increased from 40 to 513 days and from 27 to 44 years respectively (range 11-65). Donor cause of death is now primarily stroke, in contrast to head and brain injury in earlier years. Estimated median survival is 15.4 years (95% confidence interval 14.2-16.6) There is better survival throughout these years. CONCLUSION: Over the past 30 years, patient and donor demographics and underlying diseases have shifted substantially. Furthermore, the increase in waiting time due to lack of available donor hearts has led to a rise in the use of LVADs as bridge to transplant. Importantly, an improvement in survival rates is found over time which could be explained by better immunosuppressive therapy and improvements in follow-up care

Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts

BACKGROUND: Animal studies have shown that the Ca(2+)-activated Cl(-) current (I(Cl(Ca))) and the Na(+)/Ca(2+) exchange current (I(Na/Ca)) contribute to the transient inward current (I(ti)). I(ti) is responsible for the proarrhythmic delayed afterdepolarizations (DADs). We investigated the ionic mechanism of I(ti) and DADs in human cardiac cells. METHODS AND RESULTS: Human ventricular cells were enzymatically isolated from explanted hearts of patients with end-stage heart failure and studied with patch-clamp methodology. I(ti)s were elicited in the presence of 1 micromol/L norepinephrine by trains of repetitive depolarizations from -80 to +50 mV. DADs were induced in the presence of 1 micromol/L norepinephrine at a stimulus frequency of 1 Hz. I(ti) currents were inwardly directed over the voltage range between -110 and + 50 mV. Neither the Cl(-) channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor changes in [Cl(-)](i) affected I(ti) or DAD amplitude. This excludes an important role for I(Cl(Ca)). Blockade of Na(+)/Ca(2+) exchange by substitution of all extracellular Na(+) by Li(+), conversely, completely inhibited I(ti). In rabbit, I(Cl(Ca)) density in ventricular cells isolated from control hearts did not differ significantly from that in ventricular cells isolated from failing hearts. CONCLUSIONS: In contrast to many animal species, I(ti) and DADs in human ventricular cells from failing hearts consist only of I(Na/Ca). In rabbits, heart failure per se does not alter I(Cl(Ca)) density, suggesting that I(Cl(Ca)) may also be absent during DADs in nonfailing human ventricular cell

Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts

The aim of the study was to assess the occurrence of triggered activity and automaticity in ventricular trabeculae from failing human hearts and normal and failing rabbit hearts during exposure to a normal and altered extracellular environment. Ventricular trabeculae were harvested from failing human hearts (from patients undergoing cardiac transplantation) and from normal and failing rabbit hearts (combined volume and pressure overload). Trabeculae were superfused with normal Tyrode solution followed by a modified Tyrode solution, which mimicked the extracellular milieu in patients with severe heart failure. Modified Tyrode solution contained low potassium (3.0 mM), low magnesium (0.4 mM), and noradrenaline (1 microM). During superfusion with normal Tyrode solution, early afterdepolarisations, delayed afterdepolarisations, and automaticity were not observed in trabeculae from failing hearts. In the modified Tyrode solution, early afterdepolarisations could be induced in 26% of control rabbit and 30% of failing rabbit trabeculae, but never in human trabeculae. During superfusion with the modified solution delayed afterdepolarisations or triggered activity could be induced in 50% of the human failing trabeculae, in 43% of the failing rabbit trabeculae, and in 9% of the normal rabbit trabeculae (p or = 350 ms, but not at shorter cycle lengths. Delayed afterdepolarisations and automaticity, but not early afterdepolarisations, occur more frequently in myocardium from failing hearts, but only during superfusion with a modified Tyrode solution. This emphasises that the extracellular environment is important with respect to arrhythmogenesis in heart failure, apart from the fixed cellular defect due to heart failure per se. Prolongation of the action potential in failing hearts does not occur at physiological and higher heart rates and therefore cannot be regarded as a protective factor in the prevention of reentrant arrhythmias. The rate of triggered and automatic rhythms was slow. Therefore these mechanisms cannot be responsible for clinical ventricular tachycardias or fibrillation, but may serve as triggers for reentrant arrhythmia

Heart transplantation in the Netherlands: quo vadis?

Heart transplantation is limited by the lack of donor organs. Twenty years after the start of the Dutch transplant programmes in Rotterdam and Utrecht the situation has even worsened, despite efforts to increase the donor pool. The Dutch situation seems to be worse than in other surrounding countries, and several factors that may influence donor organ availability and organ utilisation are discussed. The indications and contraindications for heart transplantation are presented, which are rather restrictive in order to select optimal recipients for the scarce donor hearts. Detailed data on donor hearts, rejected for transplantation, are shown to give some insight into the difficult process of dealing with marginal donor organs. It is concluded that with the current low numbers of acceptable quality donor hearts, there is no lack of capacity in the two transplanting centres nor is the waiting list limiting the number of transplants. The influence of our current legal system on organ donation, which requires (prior) permission from donor and relatives, is probably limited. The most important determinants of donor organ availability are: 1. The potential donor pool, consisting of brain dead victims of (traffic) accidents and CVAs and 2. Lack of consent to a request for donation. The potential donor pool is remarkably small in the Netherlands, due to relatively low numbers of (traffic) accidents, with an almost equal number of CVA-related brain dead patients compared with neighbouring countries. Lack of consent can only be pushed back by improved public awareness of the importance of donation and improved skills of professionals in asking permission in case there is no previous consent