Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices (LVADs) in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery not only of contractile function.We herein review the current knowledge on the effects of volume-unloading the left ventricle via different methods of heterotopic heart transplantation in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under reloaded conditions.While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced remodeling of the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients

Editorial: Research reproducibility and preventing fraud.

SCOPUS: ed.jinfo:eu-repo/semantics/publishe

Clinical Relevance of Troponin T Profile Following Cardiac Surgery

Background: Peak post-operative cardiac troponin T (cTnT) independently predicts mid- and long-term outcome of cardiac surgery patients. A few studies however have reported two peaks of cTnT over the first 48–72 h following myocardial reperfusion. The aim of the current study was to better understand underlying reasons of these different cTnT profiles and their possible relevance in terms of clinical outcome.Methods: All consecutive adult cardiac surgical procedures performed with an extra-corporeal circulation during a >6 years period were retrospectively evaluated. Patients with a myocardial infarction (MI) < 8 days were excluded. cTnT profile of patients with at least one value ≥1 ng/mL value were categorized according to the time occurrence of the peak value. Univariable and multivariable analysis were performed to identify factors influencing early vs. late increase of cTnT values, and to verify the correlation of early vs. late increase with clinical outcome.Results: Data of 5,146 patients were retrieved from our prospectively managed registry. From 953 with at least one cTnT value ≥1 ng/mL, peak occurred ≤ 6 h (n = 22), >6 to ≤ 12 h (n = 366), >12 to ≤ 18 h (n = 176), >18 to ≤ 24 h (171), >24 h (218). Age (OR: 1.023; CI: 1.016–1.030) and isolated CABG (OR: 1.779; CI: 1.114–2.839) were independent predictors of a late increase of cTnT over a limit of 1 ng/ml (p < 0.05), whereas isolated valve procedures (OR: 0.685; CI: 0.471–0.998) and cross-clamp duration (OR: 0.993; CI: 0.990–0.997) independently predicted an early elevation (p < 0.05). Delayed elevation as opposed to early elevation correlated with a higher rate of post-operative complications including MI (19.8 vs. 7.2%), new renal insufficiency (16.3 vs. 6.7%), MACCE (32.0 vs. 15.5%), or death (7.4 vs. 4.4%).Conclusion: Profile of cTnT elevation following cardiac surgery depends on patients' intrinsic factors, type of surgery and duration of cross-clamp time. Delayed increase is of higher clinically relevance than prompt post-operative elevation

Myocardial infarction stabilization by cell-based expression of controlled Vascular Endothelial Growth Factor levels

Vascular Endothelial Growth Factor (VEGF) can induce normal or aberrant angiogenesis depending on the amount secreted in the microenvironment around each cell. Towards a possible clinical translation, we developed a Fluorescence Activated Cell Sorting (FACS)‐based technique to rapidly purify transduced progenitors that homogeneously express a desired specific VEGF level from heterogeneous primary populations. Here, we sought to induce safe and functional angiogenesis in ischaemic myocardium by cell‐based expression of controlled VEGF levels. Human adipose stromal cells (ASC) were transduced with retroviral vectors and FACS purified to generate two populations producing similar total VEGF doses, but with different distributions: one with cells homogeneously producing a specific VEGF level (SPEC), and one with cells heterogeneously producing widespread VEGF levels (ALL), but with an average similar to that of the SPEC population. A total of 70 nude rats underwent myocardial infarction by coronary artery ligation and 2 weeks later VEGF‐expressing or control cells, or saline were injected at the infarction border. Four weeks later, ventricular ejection fraction was significantly worsened with all treatments except for SPEC cells. Further, only SPEC cells significantly increased the density of homogeneously normal and mature microvascular networks. This was accompanied by a positive remodelling effect, with significantly reduced fibrosis in the infarcted area. We conclude that controlled homogeneous VEGF delivery by FACS‐ purified transduced ASC is a promising strategy to achieve safe and functional angiogenesis in myocardial ischaemia

A simple preoperative score including the surgeon's experience to predict the probability of a successful mitral valve repair.

OBJECTIVES According to recent guidelines, mitral valve (MV) repair is preferable to replacement. However, replacement is sometimes inevitable. Aims of the study were to identify variables that predict the risk of an unsuccessful MV repair and to evaluate a score that could help in planning MV surgical procedures. METHODS Clinical data of all consecutive adult mitral valve surgical procedures, performed during a 50-month period, were extracted from our clinical registry, and combined with echocardiographic variables. The variables identified by a univariable analysis, together with factors known from the literature as indicating a possible risk of an unsuccessful MV repair, were compiled in a multivariable logistic regression analysis. The surgeon's experience was also taken into account. RESULTS Of 545 MV procedures, 162 (29.7%) were MV replacements. Seven variables were identified as independent predictors of MV replacement (odd ratio; 95% CI): endocarditis (7.8; 3.7-16.5), absence of annular dilatation (3.6; 2.2-5.9), leaflet calcification (6.1; 3.0-12.7), annular calcification (3.7; 1.9-7.3), mitral stenosis (29.6; 9.3-93.8), mitral sclerosis (3.0; 1.7-5.3), surgeon's limited experience (3.9; 1.4-11.0). The ability of this model to discriminate between repair and replacement was calculated, and an area under the ROC curve of 0.87 was shown. A score was calculated for each patient and distributed into four risk categories: low risk (0-6), moderate risk (7-10), high risk (11-16) and very high risk (>16) of MV replacement with, respectively, 10.2 vs 10.0%, 40.5% vs 38.9%, 66.7 vs 70.4% and 93.2 vs 93.2% observed vs predicted probability of MV replacement. CONCLUSIONS Preoperative assessment of seven variables can accurately predict the risk of an unsuccessful MV repair