Professor Brigitte Stiller

Professor, Medical Director

Department of Congenital Heart Defects and Pediatric Cardiology
University Heart Center Freiburg – Bad Krozingen
Mathildenstr. 1
79106 Freiburg


Mechanical circulatory support (MCS) remains a last resort that is not initiated until all the conservative treatment options to save a patient’s life have failed. With the rapid and recent progress in MCS technology and management strategies we were able to improve the extended survival and the quality of life of patients suffering advanced heart failure. MCS includes two different kinds of devices for different indication and patient age. First, extracorporeal circulatory life support (ECLS) and extracorporeal membrane oxygenation (ECMO) are playing a growing and important role in our temporary bridging concepts, providing life-saving support for critically ill children.

The Deltastream® DP3 (Xenios, Medos, Germany) is an easy-to-handle miniaturized pump with only 16 ml priming volume which has proven to be very effective in both lung replacement (ECMO mode) and pulmonary and circulatory replacement (ECLS mode). We were the first to treat children with this device, and we subsequently conducted and published a retrospective mutlicenter study, which enabled us to identify risk factors such as bleeding and thrombosis and to modify therapy recommendations appropriately (Fleck et al., 2013; Stiller et al., 2017).

Further research applications for the development of ECLS treatment into a pulsatile mode to improve end organ perfusion in childhood are in progress (ethical approval obtained).

Second, at the same time, the demand for ventricular assist devices (VAD) for long-term support rose due to the scarcity of donor organs for transplantation. The only long-term support system approved for infants and small children with terminal heart failure is the paracorporeal pneumatically driven pulsatile BerlinHeart EXCOR device (Berlin, Germany), which was developed in the 1990s. Over the last 30 years, we have been involved in the further development of this device both in Berlin and in Freiburg (see Publications).

Our data for health related quality of life and for bleeding problems due to AvWF have part of the improvement for these terminally ill children. AvWS is characterized by the loss of high molecular-weight multimers of von Willebrand factor (vWF), which was be shear stress-induced, ultimately impairing vWF’s function. We found that AvWS is characterized by significant variation in the severity of bleeding propensity among pediatric patients during MCS. With detailed clinical and biochemical phenotyping work on the risk-stratification of patients during MCS workup.

Selected recent publications


In the case of terminal heart failure in children, heart transplantation (HTx) is the only long-term therapeutic option that offers a chance of survival. The Department of Pediatric Cardiology and Congenital Heart Defects in Freiburg is one of the three largest pediatric heart transplant centers in Germany, performing 5-10 new pediatric heart transplants per year.

In this area, we have several ongoing projects:

Personalised diagnostics with MRI and liquid biopsy in the first year after pediatric HTx

Team:  Daniela Kocher, Nadja Kocher, Thilo Fleck, Rouven Kubicki, Brigitte Stiller

Funding:  €150,000 from the charity  “Fördergemeinschaft Deutsche Kinderherzen e.V.

In the first post-transplant year, it was recommended that patients have more than 10 routine myocardial biopsies. This standard recommendation has not changed worldwide over the last 25 years. In Freiburg, we are researching a number of innovative techniques (including newly developed MRI algorithms, tissue Doppler, echocardiography and immunological laboratory diagnostics) that would allow invasive biopsies to be avoided by offering non-invasive alternatives for diagnosing transplant rejection like the use of plasma donor-derived, cell-free DNA to monitor acute rejection. In Freiburg we have a cohort of around 50 children under 18, as well as 12 adults with congenital heart defects, all of whom have received heart transplants in Freiburg.

QoL and exercise capacity long term after HTx

Team: Thilo Fleck, Pablov Niradschka

(More information coming soon!)

Ex-vivo allograft perfusion for complex pediatric heart transplant recipients

Team: Thilo Fleck and Pediatric cardiology, together with Prof. Friedhelm Beyersdorf‘s surgical team.

In children suffering from complex congenital heart defects, HTx is limited not only by the shortage of donor organs but also by the technical complexity of the cardiac transplantation itself in this anatomically heterogeneous cohort of patients. Several previous operations and sternotomies cause distinct adhesions and scar tissue. Patients with multiple aorto- pulmonary collaterals together with platelet dysfunction in chronic cyanosis and anticoagulation carry the risk of excessive bleeding while the situs is being prepared for allograft implantation. All these factors together add time-consuming surgical preparation to the procedure. Furthermore, implanting the heart together with reconstructing biventricular circulation is likely to result in prolonged ischemic time, which has been associated with a higher incidence of primary graft failure.

Reducing cold ischemic time could result in less myocardial damage and better short-term outcomes. Ex- vivo perfusion with the Organ Care System (OCS; Transmedics, Andover, MA, USA) keeps the beating donor heart in a physiological state, supplied with warm, oxygenated, nutrient- enriched donor blood, which enables longer “out of body time” while minimizing the detrimental effects of cold ischemic storage. Furthermore, it may provide a precious time buffer for the transplant team to carry out their complex surgical preparations for a good surgical outcome. We have published the world wide first serial clinical experience with the ex- vivo perfusion of donor hearts for pediatric recipients undergoing complex concomitant surgical procedures (Fleck et al 2021).


DFG funding: STI 631/1-1 2012-17

AOBJ: 592986