Background. Heart transplantation (HTx) is, at present, the most effective therapy for end-stage heart failure patients; however, the number of patients on the waiting list is rising globally, further increasing the gap between demand and supply of donors for HTx. First studies using the Organ Care System (OCS) for normothermic machine perfusion show promising results yet are limited in sample size. This article presents a meta-analysis of heart donation either after brain death (OCS-DBD) or circulatory death (OCS-DCD) on using OCS versus static cold storage used for HTx. Methods. A systematic literature search was performed for articles discussing the use of normothermic ex situ heart perfusion in adult patients. Thirty-day survival outcomes were pooled, and odds ratios were calculated using random-effects models. Long-term survival was visualized with Kaplan-Meier curves, hazard ratios were calculated and pooled using fixed-effects models, and secondary outcomes were analyzed. Results. A total of 12 studies were included, with 741 patients undergoing HTx, of which 260 with the OCS (173 DBD and 87 DCD). No differences were found between the 3 groups for early and late survival outcomes or for secondary outcomes. Conclusions. OCS outcomes, for both DBD and DCD hearts, appeared similar as for static cold storage. Therefore, OCS is a safe and effective technique to enlarge the cardiac donor pool in both DBD and DCD, with additional benefits for long-distance transport and surgically complex procedures.

Living myocardial slices (LMS) are ultrathin (150–400 µm) sections of intact myocardium that can be used as a comprehensive model for cardiac arrhythmia research. The recent introduction of biomimetic electromechanical cultivation chambers enables long-term cultivation and easy control of living myocardial slices culture conditions. The aim of this review is to present the potential of this biomimetic interface using living myocardial slices in electrophysiological studies outlining advantages, disadvantages and future perspectives of the model. Furthermore, different electrophysiological techniques and their application on living myocardial slices will be discussed. The developments of living myocardial slices in electrophysiology research will hopefully lead to future breakthroughs in the understanding of cardiac arrhythmia mechanisms and the development of novel therapeutic options.

Living myocardial slices (LMS) are beating sections of intact human myocardium that maintain 3D microarchitecture and multicellularity, thereby overcoming most limitations of conventional myocardial cell cultures. We introduce a novel method to produce LMS from human atria and apply pacing modalities to bridge the gap between in-vitro and in-vivo atrial arrhythmia studies. Human atrial biopsies from 14 patients undergoing cardiac surgery were dissected to tissue blocks of ~ 1 cm2 and cut to 300 µm thin LMS with a precision-cutting vibratome. LMS were placed in a biomimetic culture chamber, filled with standard cell culture medium, under diastolic preload (1 mN) and continuous electrical stimulation (1000 ms cycle length (CL)), resulting in 60 beating LMS. Atrial LMS refractory period was determined at 192 ± 26 ms. Fixed rate pacing with a CL of 333 ms was applied as atrial tachyarrhythmia (AT) model. This novel state-of-the-art platform for AT research can be used to investigate arrhythmia mechanisms and test novel therapies.

Purpose Multiple randomized controlled trials have presented SGLT2 inhibitors (SGLT2i) as novel pharmacological therapy for patients with heart failure, resulting in reductions in hospitalization for heart failure and mortality. Given the absence of SGLT2 receptors in the heart, mechanisms of direct cardioprotective effects of SGLT2i are complex and remain to be investigated. In this study, we evaluated the direct biomechanical effects of SGLT2i empagliflozin on isolated myocardium from end-stage heart failure patients. Methods Ventricular tissue biopsies obtained from 7 patients undergoing heart transplantation or ventricular assist device implantation surgery were cut into 27 living myocardial slices (LMS) and mounted in custom-made cultivation chambers with mechanical preload and electrical stimulation, resulting in cardiac contractions. These 300 µm thick LMS were subjected to 10 µM empagliflozin and with continuous recording of biomechanical parameters. Results Empagliflozin did not affect the maximum contraction force of the slices, however, increased total contraction duration by 13% (p = 0.002) which was determined by prolonged time to peak and time to relaxation (p = 0.009 and p = 0.003, respectively). Conclusion The addition of empagliflozin to LMS from end-stage heart failure patients cultured in a biomimetic system improves contraction and relaxation kinetics by increasing total contraction duration without diminishing maximum force production. Therefore, we present convincing evidence that SGLT2i can directly act on the myocardium in absence of systemic influences from other organ systems.

Living myocardial slices (LMS) are beating sections of intact human myocardium that maintain 3D microarchitecture and multicellularity, thereby overcoming most limitations of conventional myocardial cell cultures. We introduce a novel method to produce LMS from human atria and apply pacing modalities to bridge the gap between in-vitro and in-vivo atrial arrhythmia studies. Human atrial biopsies from 15 patients undergoing cardiac surgery were dissected to tissue blocks of ~ 1 cm2 and cut to 300 µm thin LMS with a precision-cutting vibratome. LMS were placed in a biomimetic cultivation chamber, filled with standard cell culture medium, under diastolic preload (1 mN) and continuous electrical stimulation (1000 ms cycle length (CL)), resulting in 68 beating LMS. Atrial LMS refractory period was determined at 192 ± 26 ms. Fixed rate pacing with a CL of 333 ms was applied as atrial tachyarrhythmia (AT) model. This novel state-of-the-art platform for AT research can be used to investigate arrhythmia mechanisms and test novel therapies.