Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.

Background: Coronary artery bypass grafting has remained an important treatment option for acute coronary syndromes, particularly in patients (1) with ongoing ischemia and large areas of jeopardized myocardium, if percutaneous coronary intervention (PCI) cannot be performed; (2) following successful PCI of the culprit lesion with further indication for coronary artery bypass grafting; and (3) where PCI is incomplete, not sufficient, or failed. Methods and Results: We aimed to analyze coronary artery bypass grafting outcome following prior PCI in acute coronary syndromes from the North‐Rhine‐Westphalia surgical myocardial infarction registry comprising 2616 patients. Primary end points were in‐hospital all‐cause mortality and major adverse cardio‐cerebral event. Patients were 68±11 years of age, had 3‐vessel and left main‐stem disease in 80.4% and 45.3%, presenting a logistic EuroSCORE of 15.1% in unstable angina, 20.3% in non–ST‐segment–elevation myocardial infarction, and 23.5% in ST‐segment–elevation myocardial infarction. A history of PCI was present in 36.2% and PCI was performed within 24 hours before surgery in 5.2% in unstable angina, 5.9% in non–ST‐segment–elevation myocardial infarction, and 16.1% in ST‐segment–elevation myocardial infarction. PCI failed in 5.3% in unstable angina, 6.8% in non–ST‐segment–elevation myocardial infarction and 17.2% in ST‐segment–elevation myocardial infarction, and 28.8% of patients presented with cardiogenic shock. In‐hospital mortality without PCI was 7.4%, but increased to 8.7% with prior PCI >24 hours, 14.5% with prior PCI <24 hours, and 14.1% with failed PCI ( P 24 hours, 25.6% with prior PCI <24 hours, and 41.3% with failed PCI ( P =0.014). Multivariable logistic regression analysis showed prior PCI ( P =0.039), as well as failed PCI ( P =0.001) to be predictors for in‐hospital all‐cause mortality and major adverse cardio‐cerebral event. Conclusions: In the current PCI era, immediately prior or failed PCI before coronary artery bypass grafting in acute coronary syndromes is associated with high perioperative risk, cardiogenic shock, and increased morbidity and mortality.

Following cardiac surgery, postoperative cognitive decline (POCD) is a common complication that can impair the quality of life and increase mortality. The aim of this study was to investigate whether early postoperative cognitive training can decrease POCD after cardiac surgery. The study was a multi-centred, two-arm, randomized (1:1 ratio), controlled trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation. Recruitment took place at the Department of Cardiac Surgery of the Kerckhoff-Clinic in Bad Nauheim (Germany) and the University-Hospital in Giessen (Germany). The patients were randomized to either a paper-and-pencil-based cognitive training group or a standard rehabilitation care control group. The cognitive training started 1 week after surgery and lasted about 3 weeks until discharge from rehabilitation. To detect POCD, neuropsychological functions were assessed prior to surgery, upon discharge from rehabilitation (primary outcome), and 3 months after discharge (secondary outcome). Data were primarily analysed in a per-protocol fashion. The frequency of POCD at discharge from rehabilitation (training group, n = 37; control group, n = 44) was 50% in the control group and 19% in the training group (χ²[1] = 8.45, P = 0.004; odds ratio = 4.29, 95% confidence interval [1.56–11.80]). Three months after the cognitive training (training group, n = 33; control group, n = 34), POCD frequency was 29% in the control group and 6% in the training group (χ²[1] = 6.21, P = 0.013; odds ratio = 6.46, 95% confidence interval [1.29–32.28]). Since our cognitive training showed beneficial effects, it could be a promising method to prevent POCD.

OBJECTIVES: Transvenous lead extraction using mechanical rotational- or laser sheaths is an established procedure. Lead dwell time has been recognized as a risk factor for extraction failure and procedure-related complications. We therefore investigated the safety and efficacy of transvenous extraction of leads with an implant duration of more than 10 years. METHODS: Between January 2013 and March 2017, a total of 403 patients underwent lead extraction in 2 high-volume lead extraction centres. One hundred and fifty-four patients with extraction of at least 1 lead aged over 10 years were included in this analysis. Laser lead extraction was the primary extraction method, with additional use of mechanical rotational sheaths or femoral snares, if necessary. All procedural- and patient-based data were collected into a database and retrospectively analysed. RESULTS: Mean patient’s age was 65.8 ± 15.8 years, 68.2% were male. Three hundred and sixty-two leads had to be extracted. The mean lead dwell time of treated leads was 14.0 ± 6.1 years. Complete procedural success was achieved in 91.6% of cases, while clinical success was achieved in 96.8%. Failure of extraction occurred in 3.2%. Leads that could not be completely removed had a significantly longer lead dwell time (18.2 vs 13.2 years; P = 0.016). Additional mechanical rotational sheaths or femoral snares were used in 26 (16.9%) patients. Overall complication rate was 4.6%, including 5 (3.3%) major and 2 (1.3%) minor complications. There was no procedure-related mortality. CONCLUSIONS: Transvenous lead extraction in leads aged over 10 years is safe and effective when performed in specialized centres and with use of multiple tools and techniques. Leads that could not be completely extracted had a statistically significant longer lead dwell time.

Evidence suggests that a high-dose statin loading before a percutaneous coronary revascularization improves outcomes in patients receiving long-term statins. This study aimed to analyse the effects of such an additional statin therapy before surgical revascularization. This investigator-initiated, randomized, double-blind, and placebo-controlled trial was conducted from November 2012 to April 2019 at 14 centres in Germany. Adult patients (n = 2635) with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting (CABG) were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery using a web-based system. The primary outcome of major adverse cardiac and cerebrovascular events (MACCE) was a composite consisting of all-cause mortality, myocardial infarction (MI), and a cerebrovascular event occuring within 30 days after surgery. Key secondary endpoints included a composite of cardiac death and MI, myocardial injury, and death within 12 months. Non-statistically relevant differences were found in the modified intention-to-treat analysis (2406 patients; 1203 per group) between the statin (13.9%) and placebo groups (14.9%) for the primary outcome [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.74–1.18; P = 0.562] or any of its individual components. Secondary endpoints including cardiac death and MI (12.1% vs. 13.5%; OR 0.88, 95% CI 0.69–1.12; P = 0.300), the area under the troponin T-release curve (median 0.398 vs. 0.394 ng/ml, P = 0.333), and death at 12 months (3.1% vs. 2.9%; P = 0.825) were comparable between treatment arms. Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery. This randomized clinical trial enrolled 2635 adult patients with a long-term statin treatment (≥30 days) who were scheduled for isolated coronary artery bypass grafting at 14 centres in Germany. Patients were randomly assigned to receive a statin-loading therapy or placebo at 12 and 2 h prior to surgery. The primary outcome of major adverse cardiocerebral events was a composite consisting of all-cause mortality, myocardial infarction, and a cerebrovascular event occuring within 30 days after surgery. CABG, coronary artery bypass grafting; CI, confidence interval.

Cell loss after transplantation is a major limitation for cell replacement approaches in regenerative medicine. To assess the survival kinetics of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CM) we generated transgenic murine iPSC lines which, in addition to CM-specific expression of puromycin N-acetyl-transferase and enhanced green fluorescent protein (EGFP), also constitutively express firefly luciferase (FLuc) for bioluminescence (BL) in vivo imaging. While undifferentiated iPSC lines generated by random integration of the transgene into the genome retained stable FLuc activity over many passages, the BL signal intensity was strongly decreased in purified iPS-CM compared to undifferentiated iPSC. Targeted integration of FLuc-expression cassette into the ROSA26 genomic locus using zinc finger nuclease (ZFN) technology strongly reduced transgene silencing in iPS-CM, leading to a several-fold higher BL compared to iPS-CM expressing FLuc from random genomic loci. To investigate the survival kinetics of iPS-CM in vivo, purified CM obtained from iPSC lines expressing FLuc from a random or the ROSA26 locus were transplanted into cryoinfarcted hearts of syngeneic mice. Engraftment of viable cells was monitored by BL imaging over 4 weeks. Transplanted iPS-CM were poorly retained in the myocardium independently of the cell line used. However, up to 8% of cells survived for 28 days at the site of injection, which was confirmed by immunohistological detection of EGFP-positive iPS-CM in the host tissue. Transplantation of iPS-CM did not affect the scar formation or capillary density in the periinfarct region of host myocardium. This report is the first to determine the survival kinetics of drug-selected iPS-CM in the infarcted heart using BL imaging and demonstrates that transgene silencing in the course of iPSC differentiation can be greatly reduced by employing genome editing technology. FLuc-expressing iPS-CM generated in this study will enable further studies to reduce their loss, increase long-term survival and functional integration upon transplantation.