Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Statin loading before coronary artery bypass grafting: a randomized trial.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: Additional statin loading before CABG failed to reduce the rate of MACCE occuring within 30 days of surgery.

Redo heart transplantation in a high-risk patient due to severe aortic regurgitation and accompanying right ventricular failure after LVAD implantation and temporary RVAD support.

BACKGROUND: We report a 62-year-old patient who received redo-orthotopic heart transplantation due to worsening severe aortic regurgitation after 19 months of continuous flow left ventricular assist device  (LVAD) (cf-LVAD) and temporary right ventricular assist device (RVAD) support for 1 month. CASE REPORT: The patient received a heartware LVAD (heartware ventricular assist device) and annuloplasty of the tricuspid valve due to end-stage heart failure (as a consequence of dilated cardiomyopathy) and severe tricuspid regurgitation in addition to right-sided extracorporeal membrane oxygenation (ECMO) implantation. Postoperatively due to the inability to wean the implanted ECMO, a temporary RVAD was implanted after which the patient's condition improved so that it had been explanted later and the patient was discharged after 9 months. In immediate postoperative echo, minimal aortic regurgitation was noted but in the follow-up transthoracic echocardiograms, there was a gradual increase in the severity of aortic regurgitation with worsening both right and left ventricular functions. Transcatheter aortic valve implantation was not an option due to unfavorable anatomical issues. That's why the patient was listed for urgent heart transplantation, performed 19 months after the LVAD implantation. The postoperative course was complicated due to acute renal failure. After recompensation, dialysis, and intensive physiotherapy, the patient could be discharged home after 3 months. CONCLUSION: Severe aortic regurgitation is a recognizable complication after cf-LVAD implantation which in our case was managed successfully with orthotopic heart transplantation in this high-risk patient.

The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection, Regeneration, and Failure.

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.

Effects of Statins After Transcatheter Aortic Valve Implantation in Key Patient Populations.

ABSTRACT: Statin therapy after transcatheter aortic valve replacement (TAVI) is associated with better short-term and long-term outcomes. It is of interest to identify specific patient populations that may profit from statin therapy. In this retrospective, observational analysis of 2862 patients with symptomatic aortic stenosis after successful transfemoral TAVI, survival during a three-year observation period was characterized by Kaplan-Meier analyses according to statin therapy. Hazard ratios and potential interactions for specific subgroups of patients were determined by Cox regression analyses. At hospital discharge 1761 patients were on low-intensity or moderate-intensity statins, 246 patients were on high-intensity statins, and 855 patients did not take statins. Statin therapy adherence during the first 3 months post-TAVI was 91%. Mortality rates were 18.5%, 12.9%, and 6.9% for patients with no statin, low-intensity or moderate-intensity statins, and high-intensity statins (P < 0.001). Any statin therapy proved to be effective in patients in different classes of age, risk, and manifest cardiovascular disease and was independent of background medication. Statins were of particular benefit in high-risk patients with coronary artery disease [hazard ratio (HR) = 0.57], ejection fraction <40% (HR = 0.64), or low-flow low-gradient aortic stenosis (HR = 0.58) and showed additional benefit even in patients taking renin-angiotensin system blockers (HR = 0.74). Statins also reduced mortality in patients with malignant disease (HR = 0.47). Our analysis confirmed the beneficial effect of statins on survival after TAVI and documented this phenomenon in key patient subsets. The protective effect of statins in our study is consistent with the cardioprotective mechanisms but must be explained by other, yet undetermined pleiotropic effects of statins.

Long-term results after mitral valve surgery using minimally invasive versus sternotomy approach: a propensity matched comparison of a large single-center series.

BACKGROUND: Mitral valve (MV) surgery has traditionally been performed by conventional sternotomy (CS), but more recently minimally invasive surgery (MIS) has become another treatment option. The aim of this study is to compare short- and long-term results of MV surgery after CS and MIS. METHODS: This study was a retrospective propensity-matched analysis of MV operations between January 2005 and December 2015. RESULTS: Among 1357 patients, 496 underwent CS and 861 MIS. Matching resulted in 422 patients per group. The procedure time was longer with MIS than CS (192 vs. 185 min; p = 0.002) as was cardiopulmonary bypass time (133 vs. 101 min; p < 0.001) and X-clamp time (80 vs. 71 min; p < 0.001). 'Short-term' successful valve repair was higher with MIS (96.0% vs. 76.0%, p < 0.001). Length of hospital stay was shorter in MIS than CS patients (10 vs. 11 days; p = 0.001). There was no difference in the overall 30-day mortality rate. Cardiovascular death was lower after MIS (1.2%) compared with CS (3.8%; OR 0.30; 95%CI 0.11-0.84). The difference did not remain significant after adjustment for procedural differences (aOR 0.40; 95%CI 0.13-1.25). Pacemaker was required less often after MIS (3.3%) than CS (11.2%; aOR 0.31; 95%CI 0.16-0.61), and acute renal failure was less common (2.1% vs. 11.9%; aOR 0.22; 95%CI 0.10-0.48). There were no significant differences with respect to rates of stroke, myocardial infarction or repeat MV surgery. The 7-year survival rate was significantly better after MIS (88.5%) than CS (74.8%; aHR 0.44, 95%CI 0.31-0.64). CONCLUSION: This study demonstrates that good results for MV surgery can be obtained with MIS, achieving a high MV repair rate, low peri-procedural morbidity and mortality, and improved long-term survival.

Safety and efficacy of transvenous lead extraction in octogenarians using powered extraction sheaths.

BACKGROUND: In the aging population equipped with cardiac implantable electronic devices, an increasing number of octogenarians require lead extractions. This patient population is often considered as a high-risk group for surgical procedures. We, therefore, investigated the safety and efficacy of transvenous lead extraction in octogenarians using powered extraction sheaths. METHODS: Between January 2013 and March 2017, 403 patients underwent lead extraction at two high-volume lead extraction centers. A total of 71 octogenarians were treated with laser lead extraction and were included in this analysis. Primary extraction method was laser lead extraction, with additional use of mechanical rotational sheaths or femoral snares, if necessary. Patient-based and procedural data were collected and analyzed retrospectively. RESULTS: Mean age was 83.5 ± 3.3 years, 64.7% were males. A total of 152 leads were extracted. The mean lead dwell time of treated leads was 10.2 ± 5.2 years. Complete procedural success rate was 92.9%, while clinical success was achieved in 98.6%. Failure of extraction occurred in one patient (1.4%). In six (7.7%) patients, additional mechanical rotational sheaths or femoral snares were used. Overall complication rate was 4.2%, including one (1.4%) major (RA perforation) and two (2.8%) minor complications. No procedure-related mortality was observed in any of the patients. CONCLUSION: Transvenous lead extraction in octogenarians with old leads is safe and effective when performed in experienced centers. Patient's age should therefore not be considered as contraindication for lead extraction using powered extraction sheaths.

Rapid Deployment Aortic Valve Replacement with the Perceval S and Intuity Elite.

BACKGROUND: Rapid deployment aortic valve replacement (RDAVR) has emerged as an alternative to conventional aortic valve replacement. This single-center study retrospectively analyzed clinical outcomes and hemodynamic performance of the Perceval S (LivaNova) and Intuity Elite (Edwards LifeSciences) rapid deployment valves (RDVs) in a propensity score matched patient cohort. METHODS: A total of 372 consecutive patients with symptomatic aortic valve stenosis underwent RDAVR between 2012 and 2018 at our institution. The Intuity Elite (INT group) and Perceval S (PER group) were implanted in 251 and 121 patients, respectively. After 1:1 propensity score matching for relevant preoperative comorbidities, 107 patient pairs were compared with respect to relevant perioperative data including hemodynamic parameter, postoperative pacemaker implantation, and 30-day all-cause mortality. RESULTS: Propensity score matching resulted in balanced characteristics between groups. Cardiopulmonary bypass and aortic cross-clamp time did not differ between groups, but more patients in the INT group received coronary artery bypass grafting compared with the PER group (56 vs. 42%; p = 0.055). Thirty-day mortality (4.7 vs. 2.2%) and need for permanent pacemaker implantation (7 versus 4.4%) were comparable between the INT and PER groups for isolated AVR and also for combined procedures, respectively. Cerebrovascular events showed comparable low rates for both RDVs (INT group [1.9%] vs. PER group [2.8%]). Indexed effective orifice area was higher in the INT group (0.90 vs. 0.82 cm2/m2) and coupled to a lower peak (17 ± 7 vs. 22 ± 8) and mean (10 ± 5 vs. 12 ± 4) pressure gradients compared with the PER group. CONCLUSIONS: Our propensity score analysis in AVR patients showed good hemodynamic characteristics with comparable 30-day mortality rate and complications rates for both investigated RDVs.

Preoperative Statin Therapy for Atrial Fibrillation and Renal Failure after Cardiac Surgery.

BACKGROUND: Performing cardiac surgery in patients with cardiovascular risk factors incorporates a steady risk for the development of postoperative complications. Perioperative statin intake was associated with an improvement of perioperative outcomes in these patients. However, the European Association for Cardio-Thoracic Surgery guidelines regarding the perioperative statin treatment were changed recently due to large studies reporting about relevant adverse effects related to statin therapy. METHODS: All relevant databases were searched including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the metaRegister of Controlled Trials. Various registries were screened (National Research Register, the ClinicalTrials.gov, and gray literature) with search on online conference indices of relevant scientific meetings. No language restrictions were applied. RESULTS: We identified 10 randomized controlled studies summarizing 3,468 participants undergoing various kinds of cardiac surgical procedures. All included studies presented with marked differences regarding study design. Pooled analysis indicated that statin pretreatment was associated with a formally reduced incidence of postoperative atrial fibrillation (AF) (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.39-1.00; p = 0.05) but with an increased incidence of renal failure (OR 1.20, 95% CI 1.01-1.44; p = 0.04) compared with control. Substantial heterogeneity was observed among studies reporting about AF. CONCLUSION: Current but sparse evidence reveals that statin pretreatment is associated with a higher rate of postoperative renal failure compared with control therapy but is ineffective to substantially reduce postoperative AF. Given the relevant heterogeneity among included studies, statin pretreatment cannot be generally recommended.

Myocardial Accumulations of Reg3A, Reg3γ and Oncostatin M Are Associated with the Formation of Granulomata in Patients with Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is a poorly understood disease and is characterized by the focal accumulation of immune cells, thus leading to the formation of granulomata (GL). To identify the developmental principles of fatal GL, fluorescence microscopy and Western blot analysis of CS and control patients is presented here. CS is visualized macroscopically by positron emission tomography (PET)/ computed tomography (CT). A battery of antibodies is used to determine structural, cell cycle and inflammatory markers. GL consist of CD68+, CD163+ and CD206+ macrophages surrounded by T-cells within fibrotic areas. Cell cycle markers such as phospho-histone H3, phospho-Aurora and Ki67 were moderately present; however, the phosphorylated ERM (ezrin, radixin and moesin) and Erk1/2 proteins, strong expression of the myosin motor protein and the macrophage transcription factor PU.1 indicate highly active GL. Mild apoptosis is consistent with PI3 kinase and Akt activation. Massive amounts of the IL-1R antagonist reflect a mild activation of stress and inflammatory pathways in GL. High levels of oncostatin M and the Reg3A and Reg3γ chemokines are in accordance with macrophage accumulation in areas of remodeling cardiomyocytes. We conclude that the formation of GL occurs mainly through chemoattraction and less by proliferation of macrophages. Furthermore, activation of the oncostatin/Reg3 axis might help at first to wall-off substances but might initiate the chronic development of heart failure.

Probability of sinus rhythm conversion and maintenance in cardiac resynchronization therapy patients with atrial fibrillation during 5-year follow-up.

INTRODUCTION: There is a high prevalence of atrial fibrillation (AF) in patients with heart failure presented for cardiac resynchronization therapy (CRT). It remains unclear whether an atrial lead should be implanted in these patients. We, therefore, analyzed outcomes and course of rhythm in AF patients undergoing CRT implantation during long-term follow-up. METHODS AND RESULTS: Between 2004 and 2018, 328 consecutive patients with a history of AF receiving CRT implantation were included in this study. 132 patients had preoperatively paroxysmal AF (px-AF), while 70 and 126 patients had persistent AF (ps-AF) and long-standing persistent AF (lp-AF), respectively. The outcome data were collected in our institutional database and analyzed retrospectively. Two hundred and seventy-seven patients received an atrial lead at the time of implantation, nine during follow-up. No major lead implantation-associated complications were observed. In patients with px-AF, sinus rhythm (SR) was present in 78.8% at admission, 95.5% (p < .001) at discharge, and 85.7% (p = .965) after 5 years. In ps-AF patients SR was present in 28.6%, 91.4% (p < .001) and 69.7% (p < .001), while all lp-AF patients showed AF at admission and had SR rate of 50.8% (p < .001) at discharge and 44.1% after 5 years (p < .001). CONCLUSION: We observed a high rate of conversion and long-term persistence of SR in AF patients undergoing CRT implantation. Due to the low rate of lead implantation-associated complications and the high successful SR conversion rates, we recommend the implantation of an atrial lead in CRT patients with AF.

Major Bleeding after Surgical Revascularization with Dual Antiplatelet Therapy.

OBJECTIVE: Patients with acute coronary syndrome are treated with dual antiplatelet therapy containing acetylsalicylic acid (ASA) and P2Y12 antagonists. In case of urgent coronary artery bypass grafting this might be associated with increasing risks of bleeding complications. METHODS: Data from 1200 consecutive urgent operations between 2010 and 2018 were obtained from our institutional patient database. For this study off-pump surgery was excluded. The primary composite end point major bleeding consisted of at least one end point: transfusion ≥ 5 packed red blood cells within 24 hours, rethoracotomy due to bleeding, chest tube output >2000 mL within 24 hours. Demographic data, peri-, and postoperative variables and outcomes were compared between patients treated with mono antiplatelet therapy, ASA + clopidogrel (ASA-C) +ticagrelor (ASA-T) or +prasugrel (ASA-P) < 72 hours before surgery. Furthermore, we compared patients with dual antiplatelet therapy with ASA monotherapy. RESULTS: From 1,086 patients, 475 (44%) received dual antiplatelet therapy. Three-hundred seventy-two received ASA-C (77.7%), 72 ASA-T (15%), and 31 ASA-P (6.5%). Major bleeding (44 vs. 23%, p < 0.0001) was more frequently in patients receiving dual therapy with higher rates of massive drainage loss within 24 hours (23 vs. 11%, p < 0.0001) of mass transfusion (34 vs. 16%, p < 0.0001) and rethoracotomy (10 vs. 5%, p = 0.002) when compared with ASA. In this analysis, ASA-T and ASA-P were not associated with higher bleeding complications compared with ASA-C. CONCLUSION: Dual antiplatelet therapy is associated with higher rates of major bleeding. Further studies should examine the difference in the prevalence of major bleeding complications in the different dual antiplatelet therapy regimes in patients requiring urgent surgery.

Levosimendan Reduces Mortality and Low Cardiac Output Syndrome in Cardiac Surgery.

BACKGROUND: There has been conflicting evidence concerning the effect of levosimendan on clinical outcomes in patients undergoing cardiac surgery. Therefore, we performed a systematic review and conducted this meta-analysis to provide evidence for/against the administration of levosimendan in cardiac surgery patients. METHODS: We performed a meta-analysis from literature search in PubMed, EMBASE, and Cochrane Library. Only randomized controlled trials comparing the administration of levosimendan in cardiac surgery patients with a control group (other inotrope, standard therapy/placebo, or an intra-aortic balloon pump) were included. In addition, at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome (LCOS), acute kidney injury, renal replacement therapy, atrial fibrillation, prolonged inotropic support, length of intensive care unit, and hospital stay. The pooled treatment effects (odds ratio [OR], 95% confidence intervals [CI]) were assessed using a fixed or random effects model. RESULTS: The literature search retrieved 27 randomized, controlled trials involving a total of 3,198 patients. Levosimendan led to a significant reduction in mortality (OR: 0.67; 95% CI: 0.49-0.91; p = 0.0087). Furthermore, the incidence of LCOS (OR: 0.56, 95% CI: 0.42-0.75; p < 0.0001), acute kidney injury (OR: 0.63; 95% CI: 0.46-0.86; p = 0.0039), and renal replacement therapy (OR: 0.70; 95% CI: 0.50-0.98; p = 0.0332) was significantly decreased in the levosimendan group. CONCLUSION: Our meta-analysis suggests beneficial effects for the prophylactic use of levosimendan in patients with severely impaired left ventricular function undergoing cardiac surgery. The administration of levosimendan was associated with a reduced mortality, less LCOS, and restored adequate organ perfusion reflected in less acute kidney injury.

The MEK/ERK Module Is Reprogrammed in Remodeling Adult Cardiomyocytes.

Fetal and hypertrophic remodeling are hallmarks of cardiac restructuring leading chronically to heart failure. Since the Ras/Raf/MEK/ERK cascade (MAPK) is involved in the development of heart failure, we hypothesized, first, that fetal remodeling is different from hypertrophy and, second, that remodeling of the MAPK occurs. To test our hypothesis, we analyzed models of cultured adult rat cardiomyocytes as well as investigated myocytes in the failing human myocardium by western blot and confocal microscopy. Fetal remodeling was induced through endothelial morphogens and monitored by the reexpression of Acta2, Actn1, and Actb. Serum-induced hypertrophy was determined by increased surface size and protein content of cardiomyocytes. Serum and morphogens caused reprogramming of Ras/Raf/MEK/ERK. In both models H-Ras, N-Ras, Rap2, B- and C-Raf, MEK1/2 as well as ERK1/2 increased while K-Ras was downregulated. Atrophy, MAPK-dependent ischemic resistance, loss of A-Raf, and reexpression of Rap1 and Erk3 highlighted fetal remodeling, while A-Raf accumulation marked hypertrophy. The knock-down of B-Raf by siRNA reduced MAPK activation and fetal reprogramming. In conclusion, we demonstrate that fetal and hypertrophic remodeling are independent processes and involve reprogramming of the MAPK.

Impact of Different Aortic Entry Tear Sites on Early Outcomes and Long-Term Survival in Patients with Stanford A Acute Aortic Dissection.

BACKGROUND: Stanford A acute aortic dissection (AAD) is a life-threatening emergency. The aim of this study was to compare the impact of three different aortic entry tear sites on early outcomes and long-term survival of patients with Stanford A AAD. METHODS: From January 2006 to April 2015, a total of 240 consecutive patients with diagnosed Stanford A AAD underwent emergent, isolated surgical aortic repair in our center. Patients were divided into three groups comprising isolated ascending aorta, proximal aortic arch, and distal aortic arch entry tear site and were followed up for up to 9 years. RESULTS: Thirty-day mortality as well as major cerebrovascular events were significantly different between the three groups (p = 0.007 and p = 0.048, respectively). Overall cumulative short- and long-term survival of all patients revealed significant differences (Log-Rank p = 0.002), whereas survival of all patients free from major cerebrovascular events was similar (Log-Rank p = 0.780). Subgroup analysis of short- and long-term survival of patients showed significant differences in terms of men (Log-Rank p = 0.043), women (Log-Rank p = 0.004), patients over 65 years of age (Log-Rank p = 0.007), and hypertensive patients (Log-Rank p = 0.003). Kaplan-Meier survival estimation plots significantly showed poorest survival for distal aortic arch entry tear site group. CONCLUSION: The location of the primary entry tear in patients with Stanford A AAD significantly influences early outcomes, short- and long-term survival of patients, whereas survival of patients free from major cerebrovascular events showed similar results among the three groups. Distal aortic entry tear site showed poorest outcomes and survival.

Stereological assessment of the blood-air barrier and the surfactant system after mesenchymal stem cell pretreatment in a porcine non-heart-beating donor model for lung transplantation.

More frequent utilization of non-heart-beating donor (NHBD) organs for lung transplantation has the potential to relieve the shortage of donor organs. In particular with respect to uncontrolled NHBD, concerns exist regarding the risk of ischaemia/reperfusion (IR) injury-related graft damage or dysfunction. Due to their immunomodulating and tissue-remodelling properties, bone-marrow-derived mesenchymal stem cells (MSCs) have been suspected of playing a beneficial role regarding short- and long-term survival and function of the allograft. Thus, MSC administration might represent a promising pretreatment strategy for NHBD organs. To study the initial effects of warm ischaemia and MSC application, a large animal lung transplantation model was generated, and the structural organ composition of the transplanted lungs was analysed stereologically with particular respect to the blood-gas barrier and the surfactant system. In this study, porcine lungs (n = 5/group) were analysed. Group 1 was the sham-operated control group. In pigs of groups 2-4, cardiac arrest was induced, followed by a period of 3 h of ventilated ischaemia at room temperature. In groups 3 and 4, 50 × 106 MSCs were administered intravascularly via the pulmonary artery and endobronchially, respectively, during the last 10 min of ischaemia. The left lungs were transplanted, followed by a reperfusion period of 4 h. Then, lungs were perfusion-fixed and processed for light and electron microscopy. Samples were analysed stereologically for IR injury-related structural parameters, including volume densities and absolute volumes of parenchyma components, alveolar septum components, intra-alveolar oedema, and the intracellular and intra-alveolar surfactant pool. Additionally, the volume-weighted mean volume of lamellar bodies (lbs) and their profile size distribution were determined. Three hours of ventilated warm ischaemia was tolerated without eliciting histological or ultrastructural signs of IR injury, as revealed by qualitative and quantitative assessment. However, warm ischaemia influenced the surfactant system. The volume-weighted mean volume of lbs was reduced significantly (P = 0.024) in groups subjected to ischaemia (group medians of groups 2-4: 0.180-0.373 µm³) compared with the sham control group (median 0.814 µm³). This was due to a lower number of large lb profiles (size classes 5-15). In contrast, the intra-alveolar surfactant system was not altered significantly. No significant differences were encountered comparing ischaemia alone (group 2) or ischaemia plus application of MSCs (groups 3 and 4) in this short-term model.

Managing Traps and Pitfalls During Initial Steps of an ECMO Retrieval Program Using a Miniaturized Portable System: What Have We Learned From the First Two Years?

The aim of this study was to provide early and mid-term results of the newly established extracorporeal membrane oxygenation (ECMO) retrieval service in a tertiary cardiothoracic center using the miniaturized portable Cardiohelp System (Maquet, Rastatt, Germany). A particular attention was paid to organizational and logistic specifics as well as challenges and pitfalls associated with initial phase of the program. From January 2015 until January 2017 a heterogenic group of 28 consecutive patients underwent ECMO implantation in distant hospitals for acute cardiac, pulmonary or combined failure as a bridge-to-decision and were subsequently transported to our institution. Each cannulation was performed bedside on intensive care units (ICU) using the Seldinger's technique. Early outcomes and mid-term overall survival with up to two-year follow-up along with the impact of ongoing cardiopulmonary resuscitation (CPR) on outcome were presented. Also, changes in hemodynamics and tissue perfusion factors 24 h after ECMO implantation were evaluated. ECMO implantations were performed in 15 distant departments with the median distance of 23(10;40) (maximum 60) km. A total of 15 patients (54%) were cannulated under CPR with the median duration of 30(20;110) (maximum 180) min. After 24 h of support there were significant improvements in SvO2 (P = 0.021), mean arterial pressure (P = 0.027), FiO2 (P = 0.001), lactate (P = 0.001), and pH (P < 0.001). The mean ECMO support duration was 96 ± 100 (maximum 384) hours, whereas 11 patients (40%) were weaned off support and discharged from hospital. Overall cumulative survival in patients without the need for CPR was 61.5% at one week and 38.5% at 1 month, 6 month, and 1 year, whereas patients requiring CPR survived in 40% at one week, and 33.3% at 1 month, 6 month, and 1 year (Log-Rank (Mantel-Cox) P = 0.374, Breslow (Generalized Wilcoxon) P = 0.162). Our initial experience shows that launching new ECMO retrieval programs in centers with sufficient ICU capacities and local ECMO experience can be feasible and associated with acceptable "real world" results despite the initial learning curve. Rapid logistical organization and team flexibility are the key points to ensure comparable survival of patients requiring prolonged CPR.

In vitro evaluation of flow patterns and turbulent kinetic energy in trans-catheter aortic valve prostheses.

OBJECTIVES: The objective of the current work was to evaluate flow and turbulent kinetic energy in different transcatheter aortic valve implants using highly undersampled time-resolved multi-point 3-directional phase-contrast measurements (4D Flow MRI) in an in vitro setup. MATERIALS AND METHODS: A pulsatile flow setup was used with a compliant tubing mimicking a stiff left ventricular outflow tract and ascending aorta. Five different implants were measured using a highly undersampled multi-point 4D Flow MRI sequence. Velocities and turbulent kinetic energy values were analysed and compared. RESULTS: Strong variations of turbulent kinetic energy distributions between the valves were observed. Maximum turbulent kinetic energy values ranged from 100 to over 500 J/m3 while through-plane velocities were similar between all valves. CONCLUSION: Highly accelerated 4D Flow MRI for the measurement of velocities and turbulent kinetic energy values allowed for the assessment of hemodynamic parameters in five different implant models. The presented setup, measurement protocol and analysis methods provides an efficient approach to compare different valve implants and could aid future novel valve designs.

Buckberg versus Calafiore Cardioplegia in Patients with Acute Coronary Syndromes.

BACKGROUND: Choice of cardioplegic solution plays a pivotal role in special subgroups of patients referred for on-pump cardiac surgery. This retrospective analysis aimed to assess the impact of intermittent warm (Calafiore, Cala) versus intermittent cold blood cardioplegia (Buckberg, Buck) in patients referred to coronary artery bypass graft (CABG) surgery due to acute coronary syndromes (ACS). METHODS: From 2008 to 2015, all consecutive patients undergoing urgent on-pump CABG surgery due to ACS (n = 950) were retrospectively analyzed. Intraoperative cardiac arrest was achieved using Buck (n = 273) or Cala (n = 677). Patients were compared regarding clinical outcomes and perioperative myocardial injury (PMI). Propensity score matching was performed to control for differences in preoperative patient characteristics. RESULTS: Prevalences of left main stenosis >50%, COPD, and advanced New York Heart Association (NYHA) class were higher for intermittent warm blood cardioplegia (IWC)-patients while more Buck-patients had preoperative intra-aortic balloon pump (IABP) and redo procedures. Buck-patients needed more intraoperative defibrillations and showed longer cardiopulmonary bypass (CPB) and aortic clamping times. 30-day all-cause mortality (10.6 versus 9.3%), major adverse cardiac events (MACE) (52.7 versus 48.6%), and PMI (50.5 versus 55.7%; all p > 0.05) rates were comparable for Buck- and Cala-patients. Propensity score matching resulted in equal group sizes (n = 212 each) and balanced distribution of preoperative covariates. Although more Buck-patients still needed inotropic support >24 hours postoperatively (25.7 versus 14.7%; p = 0.005) compared with Cala-group, outcome variables of interest did not differ between treatment groups (30-day mortality: 7.5 versus 9.0%; MACE: 49.5 versus 40.6%; PMI: 48.1 versus 37.3%; all p > 0.05). CONCLUSION: Buckberg and Calafiore cardioplegia offer comparable myocardial protection and similar postoperative results in patients undergoing CABG surgery due to ACS.

Localization of Exogenous Mesenchymal Stem Cells in a Pig Model of Lung Transplantation.

BACKGROUND: Mesenchymal stem cells (MSCs) have a great potential for the treatment of acute lung injury. This study provides a detailed immunohistochemical and stereological analysis of the localization and distribution of exogenous MSC in a pig model of lung transplantation after intravascular or endobronchial application. METHODS: MSC derived from human bone marrow were labeled by DiI and administered intravascularly or endobronchially to the lungs of donor pigs after a period of 3 hours warm and 3 hours cold ischemia. The left lung was transplanted to a recipient pig and reperfused for 4 hours before fixation. The right donor lung was fixed for microscopic analysis directly after the ischemia time. RESULTS: After both administration routes, a similar number of exogenous MSC was found in the lungs. Within each animal, the heterogeneity of MSC distribution was high both with respect to left and right lung as well as to the different lobes of each lung. After endobronchial application, MSC were found in alveolar and bronchial/bronchiolar lumen, whereas after intravascular administration, they were mainly observed in blood vessels. CONCLUSION: Although the administration of exogenous MSC is possible by endobronchial or intravascular application, it yields a heterogeneous distribution in the lungs which may warrant strategies to improve a more homogeneous distribution.