Induced pluripotent stem cell (iPSC)-derived cardiovascular progenitor cells represent a suitable autologous cell source for myocardial regeneration as they have the capability to form myocardial cells and to contribute to revascularization. As a first proof of concept we evaluated the potential of a murine iPSC-derived cardiovascular progenitor population, which expresses the surface marker foetal liver kinase-1 (Flk-1), to restore myocardial tissue and improve cardiac function after acute myocardial infarction (MI) in mice. iPSC-derived Flk-1^pos vs. Flk-1^neg cells were selected by fluorescence activated cell sorting (FACS) and injected into the ischaemic myocardium of left anterior descending coronary artery (LAD)-ligated mice. Addressing safety aspects we used an octamer binding factor 4 (Oct4)-enhanced green fluorescent protein (eGFP) expressing iPSC clone from the transgenic Oct4-eGFP reporter mouse strain OG2 to enable FACS-based depletion of undifferentiated cells prior to transplantation. Infarcted animals were treated with placebo (phosphate-buffered saline, n = 13), Flk-1^neg cells (n = 14), or Flk-1^pos cells (n = 11; 5 × 10⁵ cells each). Heart function was evaluated by magnetic resonance imaging and conductance catheter analysis 2 weeks postoperatively. Cardiovascular in vitro and in vivo differentiations were investigated by immunofluorescence staining. Treatment with Flk-1^pos and Flk-1^neg cells resulted in a favourable myocardial remodelling and improved left ventricular function. Engraftment and functional benefits were superior after transplantation of Flk-1^pos compared with Flk-1^neg cells. Furthermore, Flk-1^pos grafts contained considerably more vascular structures in relation to Flk-1^neg grafts. iPSC-derived Flk-1^pos progenitor cells differentiate into cardiovascular lineages in vitro and in vivo and improve cardiac function after acute MI. This proof of concept study paves the way for an autologous iPSC-based therapy of MI.

Nowadays, the worldwide number of left ventricular assist devices (LVADs) being implanted per year is higher than the number of cardiac transplantations. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the pumps, providing increased device durability and a prolonged survival of the patients. The miniaturization process enabled minimally-invasive implantation methods, which are associated with generally benefitting the overall outcome of patients. Therefore, these new implantation strategies are considered the novel state of the art in LVAD surgery. In this paper we provide a comprehensive review on the existing literature on minimally-invasive techniques with an emphasis on the different implantation approaches and their individual surgical challenges.

Induced pluripotent stem cells (iPSC) can be differentiated into cardiomyocytes and represent a possible autologous cell source for myocardial repair. We analyzed the engraftment and functional effects of murine iPSC-derived cardiomyocytes (iPSC-CMs) in a murine model of myocardial infarction. To maximize cardiomyocyte yield and purity a genetic purification protocol was applied. Murine iPSCs were genetically modified to express a Zeocin^™ resistance gene under control of the cardiac-specific α-myosin heavy chain (α-MHC, MYH6) promoter. Thus, CM selection was performed during in vitro differentiation. iPSC-CM aggregates (“cardiac bodies”, CBs) were transplanted on day 14 after LAD ligation into the hearts of previously LAD-ligated mice (800 CBs/animal; 2-3x10⁶ CMs). Animals were treated with placebo (PBS, n = 14) or iPSC-CMs (n = 35). Myocardial remodeling and function were evaluated by magnetic resonance imaging (MRI), conductance catheter (CC) analysis and histological morphometry. In vitro and in vivo differentiation was investigated. Follow up was 28 days (including histological assessment and functional analysis). iPSC-CM purity was >99%. Transplanted iPSC-CMs formed mature grafts within the myocardium, expressed cardiac markers and exhibited sarcomeric structures. Intramyocardial transplantation of iPSC-CMs significantly improved myocardial remodeling and left ventricular function 28 days after LAD-ligation. We conclude that iPSCs can effectively be differentiated into cardiomyocytes and genetically enriched to high purity. iPSC derived cardiomyocytes engraft within the myocardium of LAD-ligated mice and contribute to improve left ventricular function.

OBJECTIVES: Left ventricular assist device (LVAD) exchange is becoming a standard surgical procedure. The exchange procedure is an opportunity to upgrade patients to a new generation pump that offers advanced reduction of adverse events or longer battery hours. METHODS: We performed an analysis of 6 consecutive patients who underwent LVAD exchange to HeartMate 3 either from a HeartWare or HeartMate (HM) II device. Minimally invasive operations were performed through a lateral thoracotomy. Follow-up time was 6 months after LVAD exchange. RESULTS: We present 4 patients with the HM II and 2 patients with the HeartWare ventricular assist device (HVAD) who underwent LVAD exchange to HM III. The average age was 57.5 years. At the time of the LVAD exchange, all patients were classified as Interagency Registry for Mechanically Assisted Circulatory Support level 3. In 5 cases, LVAD infection led to LVAD exchange (83%, 5/6). The remaining patient underwent LVAD exchange due to pump thrombosis (16%, 1/6). The 6-month survival rate after LVAD exchange was 100% (6/6). None of the patients was postoperatively supported by extracorporeal membrane oxygenation. No patient experienced postoperative relevant bleeding. One patient suffered minor cerebral bleeding (16.6%, 1/6). At the 6-month follow-up examination, 1 patient reported a single syncope and several low-flow alarms (1/6). The remaining 5 patients showed no adverse events or technical malfunctions of the VAD (5/6). CONCLUSIONS: LVAD exchanges from HM II as well from HVAD to HM 3 are proven to be technically feasible. Due to the advantages and technical improvements of the new-generation pumps, this procedure is an excellent opportunity to give patients access to a superior generation of assist device.