Background: The systemic inflammatory response to coronary artery bypass grafting (CABG) is highly variable and a key driver of complications. We hypothesised that a pre-existing pro-inflammatory immune state, characterised by a skewed monocyte profile, ‘primes’ patients for an exaggerated response. This pilot prospective study aimed to test this hypothesis and to evaluate the Neutrophil-to-Albumin Ratio (NAR) as an integrated biomarker of this response, comparing it against the established Neutrophil-to-Lymphocyte Ratio (NLR). Methods: In this pilot prospective, single-centre pilot study, we enrolled 34 patients with multivessel coronary artery disease (CAD) scheduled for off-pump CABG and 20 control subjects. Preoperatively, peripheral blood monocyte subsets were quantified by flow cytometry. Neutrophil, lymphocyte, and albumin levels were measured before and after surgery to calculate NAR and NLR. Multivariable linear regression was used to test for independent predictors of the inflammatory response. Results: Preoperatively, CAD patients exhibited a reduced percentage of the classical monocyte subpopulation (p < 0.001), with a skew toward intermediate and non-classical subpopulations. Postoperatively, both NAR and NLR increased significantly (p < 0.001) and performed comparably in discriminating the postoperative state (AUC: 0.89 vs. 0.86, p > 0.05). Critically, in multivariable linear regression analysis, the preoperative percentage of classical monocytes remained a significant and independent predictor of the magnitude of the postoperative NAR surge (β = −0.028, p = 0.007), after adjusting for clinical confounders including atherosclerotic burden. Conclusion: A patient’s preoperative immune profile, specifically the degree of monocyte skew, is an independent predictor of the acute inflammatory response to CABG. This finding supports a ‘priming’ mechanism in high-risk patients. While NAR and NLR perform similarly as monitoring tools, the independent link between the underlying immunology and the postoperative outcome suggests that combining preoperative immunophenotyping with simple biomarker monitoring could offer a powerful new strategy for personalised risk stratification in cardiac surgery.

Background/Objectives: Patient-derived mesenchymal stem cells (MSCs) represent a promising avenue for myocardial regeneration, yet therapeutic application remains limited by inconsistent differentiation capacity and the absence of standardized cardiogenic induction protocols. This study demonstrates a proof-of-concept for guiding patient-specific bone marrow MSCs toward a functional cardiomyocyte phenotype using paracrine signals from differentiating iPSC-derived cardiomyocytes (iPSC-CMs). Materials and Methods: MSCs were maintained in conditioned medium from a concurrent, validated iPSC-CM differentiation protocol, with evaluation via immunocytochemistry, optical mapping, and whole-cell patch-clamp recordings. Results: Differentiated MSCs acquired organized sarcomeric architecture with cross-striations and displayed spontaneous calcium oscillations with decay kinetics matching source iPSC-CMs (CaT50 ≈ 283 ms vs. 301 ms). In co-culture, MSC-derived cells exhibited synchronized calcium dynamics with iPSC-CMs, confirming functional coupling, while patch-clamp detected hallmark cardiac ion currents (INa, ICa,L, and IKv). Morphologically, MSC-CMs displayed more mature, elongated rod-like shapes. Conclusions: Although current densities indicate partial immaturity, their reproducible detection validates successful cardiomyogenic commitment. This “parallel differentiation” platform eliminates donor-specific protocol tuning, providing a streamlined, paracrine-mediated approach to generate autologous cardiomyocyte-like cells for disease modeling, pharmacological testing, and future regenerative applications.

Background: Matrix metalloproteinase 9 (MMP9) has recently emerged as a risk predictor in patients with cardiovascular diseases (CVD). However, little is known regarding the significance of elevated plasma MMP9 levels in patients during the long-term period following myocardial revascularisation. We aimed to investigate the role of MMP9 in relation to myocardial status before and after myocardial revascularisation and to assess its long-term prognostic value. Methods: This prospective observational study included 200 male patients with ischaemic heart disease. All patients underwent direct myocardial revascularisation on a beating heart (off-pump surgery). Plasma MMP9 levels were analysed preoperatively, at 48 h postoperatively, and during the long-term follow-up period (one year postoperatively). Key echocardiographic parameters, specifically left ventricular ejection fraction (LVEF) and Left Ventricular End-Diastolic Volume (LVEDV), were also assessed. Results: MMP9 levels decreased significantly at 48 h postoperatively (p < 0.0001). During the long-term postoperative period, a clear relationship was demonstrated: higher 1-year MMP9 levels were associated with lower 1-year LVEF, whilst lower 1-year MMP9 levels were associated with higher 1-year LVEF. No significant correlation was observed between preoperative MMP9 levels and age or most other baseline laboratory parameters. Conclusions: Our study established an association between 1-year postoperative MMP9 levels and key parameters of left ventricular function during the long-term follow-up period. This suggests that MMP9 may serve as a novel biomarker for predicting outcomes following myocardial revascularisation.