Enhanced Cardiac S100A1 Expression Improves Recovery from Global Ischemia-Reperfusion Injury.

Gene-targeted therapy with the inotropic Ca2 + -sensor protein S100A1 rescues contractile function in post-ischemic heart failure and is being developed towards clinical trials. Its proven beneficial effect on cardiac metabolism and mitochondrial function suggests a cardioprotective effect of S100A1 in myocardial ischemia-reperfusion injury (IRI). Fivefold cardiomyocyte-specific S100A1 overexpressing, isolated rat hearts perfused in working mode were subjected to 28 min ischemia (37 °C) followed by 60 min reperfusion. S100A1 overexpressing hearts showed superior hemodynamic recover: Left ventricular pressure recovered to 57 ± 7.3% of baseline compared to 51 ± 4.6% in control (p = 0.025), this effect mirrored in LV work and dP/dt(max). Troponin T and lactate dehydrogenase was decreased in the S100A1 group, as well as FoxO pro-apoptotic transcription factor, indicating less tissue necrosis, whereas phosphocreatine content was higher after reperfusion. This is the first report of a cardioprotective effect of S100A1 overexpression in a global IRI model.

Characterization of cytoskeleton features and maturation status of cultured human iPSC-derived cardiomyocytes.

Recent innovations in stem cell technologies and the availability of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have opened new possibilities for studies and drug testing on human cardiomyocytes in vitro. Still, there are concerns about the precise nature of such 'reprogrammed' cells. We have performed an investigation using immunocytochemistry and confocal microscopy on several cellular features using commercially available hiPSC-CMs. For some selected developmentally regulated or cardiac chamber-specific proteins, we have compared the results from hiPSC-derived cardiomyocytes with freshly isolated, ventricular cardiomyocytes from adult rats. The results show that all typical cardiac proteins are expressed in these hiPSC-CMs. Furthermore, intercalated disc-like structures, calcium cycling proteins, and myofibrils are present. However, some of these proteins are only known from early developmental stages of the ventricular myocardium or the diseased adult heart. A heterogeneous expression pattern in the cell population was noted for some muscle proteins, such as for myosin light chains, or incomplete organization in sarcomeres, such as for telethonin. These observations indicate that hiPSC-CMs can be considered genuine human cardiomyocytes of an early developmental state. The here described marker proteins of maturation may become instrumental in future studies attempting the improvement of cardiomyocyte in vitro models.

Impact of new technologies and experience on procedural aspects of surgical aortic valve replacement - a process analysis.

BACKGROUND: Surgical aortic valve replacement (SAVR) is the treatment of choice in severe symptomatic aortic valve disease. New techniques and prostheses have been recently developed to facilitate the procedure and reduce aortic cross-clamp time (AOx). The aim of this study was to analyse the different procedural steps in order to identify the most time-consuming part during aortic clamping time and to compare impact of experience on procedural aspects. METHODS: AOx during SAVR was divided into five consecutive steps. Duration of each step was measured. The first procedural step started with clamping of the aorta and ended with the beginning of the second step starting with the resection of the native aortic valve. The third step started with placement of the first valve anchoring suture, the fourth step started with tying of the first suture and the fifth and final step started after the cut of the last suture and ended with removal of the aortic clamp. Surgeons were divided into two groups based on their experience, which in our analysis was defined as a total SAVR experience of more than 100 procedures. RESULTS: From March 2013 to August 2015 57 nonconsecutive patients (33% female; age, median 71.0 years, interquartile range 65.0-76.0) undergoing isolated SAVR for severe aortic valve stenosis in our institution were included in this process analysis. Two different prostheses were implanted. Forty-eight (84%) patients received a tissue valve (Perimount Magna Ease, Edwards Lifesciences, Irvine, USA) and 9 (16%) patients received a mechanical prosthesis (Medtronic AP 360, St-Paul, MN, USA). The mean estimated risk of mortality was 1.1% (0.7-1.6) according to the logistic EUROScore II. Overall duration of AOx was 50.5 ± 13.8 min, with 32.3% (16.4 ± 5.9 min) accounting for placing the sutures into the native annulus and the prosthetic sewing ring and 18.5% (9.2 ± 3.0min) accounting for tying and cutting the sutures. Surgeons with more experience performed 35 operations (61.4%) and needed an average of 44.1 ± 11.5 min versus 60.6 ± 11.0 min (p <0.001) for less experienced surgeons. Surgeons with more experience needed 14.0 ± 5.0 min for the suturing step and 8.4 ± 2.8 min for tying the sutures compared with 20.2 ± 5.2 min and 10.5 ± 3.0 min, respectively, for the less experienced surgeons with (p <0.001 and p = 0.010). CONCLUSION: Placing and tying sutures in the prostheses accounts for over half (50.8%) of AOx during isolated SAVR. Experienced surgeons have significantly reduced AOx. This shortening is equally distributed between all five procedural steps.

Validation of 3D-reconstructed computed tomography images using OsiriX® software for pre-transcatheter aortic valve implantation aortic annulus sizing.

OBJECTIVES: We report validation of OsiriX® -an image processing freeware-to measure multi-slice computed tomography-derived annulus diameters for preprocedural transcatheter aortic valve implantation planning. METHODS: A total of 137 patients (82 ± 6.5 years, 42.3% male, logistic EuroSCORE 24.1 ± 14.2%) with severe aortic stenosis at high surgical risk underwent transcatheter aortic valve implantation assessment: transoesophageal echocardiography, angiography and multi-slice computed tomography. Retrospectively, 3D multi-slice computed tomography reconstructions were generated using OsiriX and the reliability evaluated regarding inter- and intraobserver variability, intermodality correlation and estimation of the clinical impact on transcatheter aortic valve implantation sizing. RESULTS: Reliability of the novel OsiriX software was high with an interobserver mean difference of 0.6 ± 1.4 mm and intraclass correlation of absolute agreement of 0.84 (95% confidence interval 0.74-0.90). The intermodality accuracy between OsiriX measurements and conventional 2D computed tomography reconstructions, transoesophageal echocardiography and angiography revealed significantly larger sizing with OsiriX, with a mean difference to 2D computed tomography of 0.4 ± 2.2 mm, which would have changed valve sizing in 38% of patients. In 28%, a larger size would have been chosen, and this correlated highly with the occurrence of postoperative severe aortic regurgitation (P < 0.001). CONCLUSIONS: While OsiriX measurements are an accurate and reproducible assessment of the aortic annulus, there are distinct and clinically relevant differences in aortic annulus dimensions between OsiriX measurements and previously standard imaging modalities. Sizing with OsiriX resulted in a larger perimeter compared with conventional 2D imaging. Careful assessment of valve size will take into account multiple imaging modalities.

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 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 (hHTX) 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. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX 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 changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients.

Is surgery in acute aortic dissection type A still contraindicated in the presence of preoperative neurological symptoms?

OBJECTIVES: Severe neurological deficit (ND) due to acute aortic dissection type A (AADA) was considered a contraindication for surgery because of poor prognosis. Recently, more aggressive indication for surgery despite neurological symptoms has shown acceptable postoperative clinical results. The aim of this study was to evaluate early and mid-term outcomes of patients with AADA presenting with acute ND. METHODS: Data from 53 patients with new-onset ND who received surgical repair for AADA between 2005 and 2012 at our institution were retrospectively reviewed. ND was defined as focal motor or sensory deficit, hemiplegia, paraplegia, convulsions or coma. Neurological symptoms were evaluated preoperatively using the Glasgow Coma Scale (GCS) and modified Rankin Scale (mRS), and at discharge as well as 3-6 months postoperatively using the mRS and National Institutes of Health Stroke Scale. Involvement of carotid arteries was assessed in the pre- and postoperative computed tomography. Logistic regression analysis was performed to detect predictive factors for recovery of ND. RESULTS: Of the 53 patients, 29 (54.7%) showed complete recovery from focal ND at follow-up. Neurological symptoms persisted in 24 (45.3%) patients, of which 8 (33%) died without neurological assessment at follow-up. Between the two groups (patients with recovery and those with persisting ND), there was no significant difference regarding the duration of hypothermic circulatory arrest (28 ± 14 vs 36 ± 20 min) or severely reduced consciousness (GCS <8). Multivariate analysis showed significant differences for the preoperative mRS between the two groups (P < 0.007). A high preoperative mRS was associated with persistence of neurological symptoms (P < 0.02). Cardiovascular risk factors, age or involvement of supra-aortic branches were not predictive for persistence of ND. CONCLUSION: More than half of our patients recovered completely from ND due to AADA after surgery. Severity of clinical symptoms had a predictive value. Patients suffering from AADA and presenting with ND before surgery should not be excluded from emergency surgery.

Effects of Thoratec pulsatile ventricular assist device timing on the abdominal aortic wave intensity pattern.

Arterial waves are seen as possible independent mediators of cardiovascular risks, and the wave intensity analysis (WIA) has therefore been proposed as a method for patient selection for ventricular assist device (VAD) implantation. Interpreting measured wave intensity (WI) is challenging, and complexity is increased by the implantation of a VAD. The waves generated by the VAD interact with the waves generated by the native heart, and this interaction varies with changing VAD settings. Eight sheep were implanted with a pulsatile VAD (PVAD) through ventriculoaortic cannulation. The start of PVAD ejection was synchronized to the native R wave and delayed between 0 and 90% of the cardiac cycle in 10% steps or phase shifts (PS). Pressure and velocity signals were registered, with the use of a combined Doppler and pressure wire positioned in the abdominal aorta, and used to calculate the WI. Depending on the PS, different wave interference phenomena occurred. Maximum unloading of the left ventricle (LV) coincided with constructive interference and maximum blood flow pulsatility, and maximum loading of the LV coincided with destructive interference and minimum blood flow pulsatility. We believe that noninvasive WIA could potentially be used clinically to assess the mechanical load of the LV and to monitor the peripheral hemodynamics such as blood flow pulsatility and risk of intestinal bleeding.