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Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population.Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx.The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p.0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p.001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p.0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF.Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.

Background Endomyocardial biopsy (EMB) is a well-established procedure for the diagnosis of specific myocardial diseases and represents the gold standard in monitoring allografts after heart transplantation. In our study, we compared 2 different approaches for harvesting EMB in order to optimize patient safety and efficacy of the procedure. Methods As a standard approach for harvesting EMB, a venous introducer sheath was inserted percutaneously via the internal jugular vein using the Seldinger technique. Thereafter, a bioptome was repeatedly introduced throughout this sheath into the right ventricle (RV), each time passing the tricuspid valve (TV). Alternatively, a coronary sinus catheter was inserted via an introducer sheath placed in the subclavian vein and only once was introduced into RV cavity. Hence, just a unique passage of TV was required. Thereafter, a bioptome was introduced via this catheter and precisely guided to the targeted biopsy site. Results A standard approach was used with 34 patients, and a modified technique was used with 37 patients. Patient characteristics were comparable in both cohorts, and analyses of peri-procedural parameters identified only marginal differences between the groups. Interestingly, the number of harvested tissue samples per procedure was higher in the modified approach compared to the standard approach. No complications occurred. Conclusion The modified approach for EMB is a safe procedure. The facilitated bioptome-guidance and enhanced protection of TV may prevent periprocedural complications.

Background The implantation of cardiac implantable electronic devices is a globally established therapy to treat cardiac arrhythmias with low complication rates. Apart from technical problems, however, complications can arise from the implanted material. This can lead to bleeding, infections, or chronic irritation of the generator pocket, resulting in swellings, seromas, perforations, or fistulas. However, the cause of tissue changes is not always clear, and therefore, we would like to report on a rare tissue degeneration diagnosed in a patient. Case summary After a history of ventricular fibrillation, a 46-year-old patient received an implantable cardioverter-defibrillator (ICD) for secondary prevention. Six years later, the generator pocket swelled without evidence of infection. With the suspected diagnosis of a chronically irritated pocket, the device was then surgically relocated. After a 2-year symptom-free period, the patient presented again with a severely swollen but only slightly painful device pocket. Once again, there were no signs of infection, and so the pocket was revised again, assuming a chronic irritant effusion. Intraoperatively, a lipomatous structure (12 × 6 × 3 cm) emerged from the subpectoral ICD pocket. After its complete removal, the histopathological examination revealed a lipoma. A bacterial genesis could be ruled out by microbiological samples, and the wound healed cosmetically well and without further discomfort. Conclusion This case shows that the reason of chronically irritated generator pockets, in addition to the usually known tissue changes, can also be tumours. Therefore, resected tissue should be examined histopathologically and, if indicated, specific therapy initiated.

Various devices are available for endoscopic radial artery harvesting during coronary artery bypass grafting. Thermal spread and graft damage, however, are common concerns. The aim of this study was to compare the MiFusion TLS2 system (Endotrust, Nettetal Germany) with direct heat technique and the LigaSure Maryland system (Medtronic, Dublin, Ireland) using advanced bipolar technique in a prospective randomized study.One hundred consecutive patients undergoing coronary artery bypass grafting with endoscopic radial artery harvesting were prospectively included and randomized 1:1. The proximal (brachial) ends of the grafts were analyzed using fluorescence microscopy with focus on graft integrity. In addition, harvesting time, graft sealing, residual bleeding, and incidence of neurological disorders were compared.Patient age was 67 ± 8 years. Mean harvesting time was 26.5 ± 9 minutes for the TLS2 and 23.2 ± 8 minutes for the LigaSure (P = .049). Overall graft integrity was good in both groups. A significantly better graft integrity was observed in the LigaSure group (scale 0 to 3; 3 = best) with 2.5 ± 0.6 for TLS2 and 2.8 ± 0.4 for LigaSure (P = .031). LigaSure provided significantly better graft sealing (scale 0 to 2; 0 = best) with 0.6 ± 0.7 vs 1.0 ± 0.6 (TLS2) (P = .006) and less residual bleeding (scale 1 to 5; 1 = best) with 1.4 ± 0.6 vs 2.0 ± 0.9 (TLS2) (P.001). Transient sensibility disorders were less frequently observed with LigaSure (2% vs 16%, P = .015).Endoscopic radial artery harvesting can be performed with excellent results and good graft integrity using both devices. Compared with the MiFusion TLS2, the LigaSure device led to faster procedural times and resulted in better graft integrity. Along with providing a better seal, LigaSure was associated with less sensibility disorders.

Background We aimed to find out how the concomitant performance of tricuspid valve repair (TVR) affects outcomes of patients undergoing mitral valve surgery (MVS). Methods Single-centre, retrospective analysis of 1357 patients who underwent MVS between January 2005 and December 2015, including 1165 patients with isolated MVS and 192 patients with MVS plus TVR. We used propensity scores to match patients for baseline characteristics other than valve related parameters and arrived at a matched sample of 182 patients per group. Results The overall procedure duration was longer in the MVS + TVR (224 min) versus the MVS group (176 min; p p p p p = 0.037). There was no difference in death rates within 30 days, stroke, myocardial infarction or repeat MVS. The long-term survival rate was 60.8% in the MVS + TVR vs. 57.5% in the isolated MVS group (HR 1.048; 95%CI 0.737–1.492; p = 0.794). The rate of grade III/IV tricuspid regurgitation (TR) remained low after MVS + TVR during long-term follow-up while the rate of grade ≥ II TR increased slightly in the isolated MVS group. Conclusion The data show that the concomitant performance of TVR in patients undergoing MVS is a safe and effective procedure with good long-term outcomes. Patients can undergo MVS + TVR with confidence as it improves their prognosis up to the level of patients undergoing isolated MVS.

The muscle-specific miR-1 and miR-133a RNAs lock cardiomyocytes in a differentiated state by suppressing OSMR/FGFR signaling.

Description, The muscle-specific miR-1 and miR-133a RNAs lock cardiomyocytes in a differentiated state by suppressing OSMR/FGFR signaling., Dedifferentiation of cardiomyocytes is part of the survival program in the remodeling myocardium and may be essential for enabling cardiomyocyte proliferation. In addition to transcriptional processes, non-coding RNAs play important functions for the control of cell cycle regulation in cardiomyocytes and cardiac regeneration. Here, we demonstrate that suppression of FGFR1 and OSMR by miR-1/133a is instrumental to prevent cardiomyocyte dedifferentiation and cell cycle entry in the adult heart. Concomitant inactivation of both miR-1/133a clusters in adult cardiomyocytes activates expression of cell cycle regulators, induces a switch from fatty acid to glycolytic metabolism, and changes expression of extracellular matrix genes. Inhibition of FGFR and OSMR pathways prevents most effects of miR-1/133a inactivation. Short-term miR-1/133a depletion protects cardiomyocytes against ischemia, while extended loss of miR-1/133a causes heart failure. Our results demonstrate a crucial role of miR-1/133a–mediated suppression of Osmr and Ffgfr1 in maintaining the postmitotic differentiated state of cardiomyocytes.

Background Resection (triangular or quadrangular) is considered the gold standard for the treatment of posterior leaflet prolapse and loop implantation a more recent alternative. We aimed to compare the long-term outcomes of triangular or quadrangular resection vs loop implantation. Methods Single-centre, retrospective analysis of mitral valve (MV) surgeries conducted from January 2005 to December 2015. Propensity score matching was based on seven key baseline variables. Results Data from 721 patients were analyzed; 358 patients received loop implantation and 363 patients underwent resection. Patients had a mean age of 62 years, 33.0% were female and 50.6% had hypertension. Propensity score matching resulted in a matched group of 263 patients who received loop implantation or underwent resection, respectively. Postoperatively, the patients' mitral insufficiency was reduced from grade III/IV to either zero or trace (45.8%) or I (49.8%) and New York Heart Association class reduced from 66.9% in class III/IV preoperatively to 8.3% with no significant differences between groups. Fewer patients receiving loops had procedure-related complications. Fewer patients in the loop implantation group required permanent pacemaker implantation at 30 days (8.4% vs 2.3%; P = .002). The 10-year survival for patients in the resection (88.0%) and loop implantation (89.3%) groups had a hazard ratio of 1.224 (95% confidence interval, 0.633-2.367). Conclusion Our study showed that both loop implantation and resection were associated with comparable long-term survival in patients with posterior leaflet prolapse. Loop implantation is associated with a significantly higher rate of a successful repair, a significantly lower rate of MV replacement after repair failure, fewer procedure-related complications and better 30-day at comparable long-term outcomes.

Clinicians can feel confident about performing mitral repair/replacement in patients who have previously undergone mammoplasty. It may also have applications in performing atrial septal defect closure, Maze procedures for atrial fibrillation, and tricuspid valve surgery in patients with breast implants.

Objectives Ischemia-reperfusion injury is correlated with a substantial inflammatory response. Inflammation triggers the migration of cells through vessel endothelium and leads to serious tissue injury. Our hypothesis was that an early application of mammalian target of rapamycin inhibitors has an impact on human vessels after ischemia-reperfusion injury. Materials and methods After exposure to ischemia for 5 hours, human vessels (veins and arteries) from 20 patients were reperfused for 120 minutes in an in vitro bioreactor with heparinized human blood after oxygenation and warming to 37 °C. The vessels were treated with mammalian target of rapamycin inhibitor everolimus (5 ng/mL, n = 7) or sirolimus (10 ng/mL, n = 6). As a control group, untreated human vessels were reperfused (n = 7). During the reperfusion period, blood samples were collected continuously (after 0, 15, 30, 60, 120 minutes); vessel biopsies were performed at the end. Oxygen consumption was measured during reperfusion to determine vessel viability. Inflammatory markers (interleukin 6, tumor necrosis factor α, vascular endothelial growth factor) were analyzed in blood samples. To quantify vascular inflammation, we investigated the expression of CD11 and CD31. Results Physiological oxygen consumption and pH values verified vessel viability. After reperfusion, interleukin 6 and vascular endothelial growth factor levels were significantly increased in the control group over time, whereas everolimus and sirolimus showed no significant differences. Furthermore, tumor necrosis factor α level increased significantly in the sirolimus group, whereas the everolimus and control groups showed constant values. A significant decrease of expression of CD11b and CD31 in both mammalian target of rapamycin inhibitor cohorts compared with control cohort was investigated. Conclusions Early use of mammalian target of rapamycin inhibitors may limit an inflammatory rise of interleukin 6 and vascular endothelial growth factor after ischemia-reperfusion injury and could be associated with a restriction in vascular cell transmigration.

Minimally invasive cardiac surgery (MICS) via right lateral mini thoracotomy is the gold standard treatment approach for mitral and tricuspid valve disorders. Other selected procedures (e.g. transapical aortic valve implantation, MIDCAB) require a left lateral mini thoracotomy for surgical access. Advantages of MICS over complete sternotomy are well known, but access-related complications post MICS, such as pulmonary herniation, are often underestimated/overlooked. In males, a pulmonary herniation in the proximity of the former thoracotomy is often clinically visible, especially when the intrathoracic pressure rises (e.g. during coughing). In females, clinical symptoms may be hidden by the breast and patients often have unspecific complaints or occasional pain when coughing, making identification of a lung herniation more difficult. Chest computed tomography is the diagnostic tool of choice for pulmonary herniations. Using a series of 20 patients with pulmonary herniation post MICS, we report our findings in diagnosis and treatment of this condition.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, requiring lifelong anticoagulation or interventional, transseptal left atrial appendage (LAA) occluder implantation to minimize stroke risk. Incomplete LAA closure post implantation is a frequent observation. Incomplete LAA occlusion after transseptal occluder implantation necessitates anticoagulation in cases of persistent AF to minimze risk of embolism and/or apoplexy. Patients with contraindications to lifelong anticoagulation therapy are challenging to treat and alternative options are needed. We present a case of a patient with persistent AF who underwent frustraneous LAA occluder implantation. The patient’s anatomy necessitated surgical closure of the LAA, which was accomplished with an LAA clip 4 weeks after implantation. The patient was discharged in excellent clinical status 5 days after the surgery. No further complications were observed within the following year.

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.

Background. Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling—involving the expression of fetal genes—is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Methods. NRC and ARC were stimulated with serum and cardiac morphogens derived from DCM hearts. Protein synthesis (PS) as well as protein accumulation (PA) was measured, and cell survival was determined under ischemic conditions. Fetal markers were investigated by Western blot. Biomarkers of remodeling were analyzed in controls, DCM, and 2- to 6-month-old children with tetralogy of Fallot as well as in neonatal and adult rats by immunofluorescence. Results. In NRC, serum and morphogens strongly stimulated PS and PA and the reestablishment of cell-cell contacts (CCC). In ARC, both stimulants increased PS and CCC, but PA was only elevated after serum stimulation. In contrast to serum, morphogen treatment resulted in the expression of fetal genes in ARC as determined by nonmuscle α-actinin-1 and α-actinin-4 expression (NM-actinins) and was associated with increased survival under ischemia. NM-actinins were present in cardiomyocytes of DCM in a cross-striated pattern reminiscent of sarcomeres as well as in extensions of the area of the intercalated disc (ID). NM-actinins are expressed in NRC and in the developing heart. Radixin staining revealed remodeling of the area of the ID in DCM almost identical to stimulated cultured ARC. Conclusions. Remodeling was similar in ARC and in cardiomyocytes of DCM suggesting evolutionary conserved mechanisms of regeneration. Despite activation of fetal genes, the atrophy of ARC indicates differences in their regenerative capacity from NRC. Cardiac-derived factors induced NM-actinin expression and increased survival of ischemic ARC while circulating molecules were less effective. Identification of these cardiac-derived factors and determination of their individual capacity to heal or damage are of particular importance for a biomarker-guided therapy in adult patients.

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.

Heart transplantation (HTx) represents the “gold standard” in end-stage heart failure therapy. Due to their severe heart failure and for prevention of sudden cardiac death, the majority of patients presenting for HTx will have a history of an implanted cardioverter-defibrillator (ICD). Usually, within the scope of HTx, all cardiac-implanted electronic device components are removed. In rare cases these efforts fail and some material remains. The abandoned lead fragments can cause serious complications. The case presented herein involves a patient with recurrent bacteremia after successful HTx originating from an abandoned and infected lead fragment. In 2016, a 64-year-old man received a donor heart transplant due to end-stage heart failure. Unfortunately, during the procedure, not all components of an ICD implanted in 2007 could be removed. An initially event-free period was followed by recurrent fever attacks and staphylococcal bacteremia was diagnosed. After an extensive search, the source of the bacteremia was identified by positron emission tomography–computed tomography (PET-CT), and percutaneous extraction of the abandoned and infected ICD lead fragment was scheduled. The fragment was extracted using a minimally invasive approach via percutaneous femoral vein access. The patient was discharged 3 days later, with no further complications. This case highlights the need for conscientious and complete removal of foreign material in the HTx setting. Difficult-to-diagnose sources of infection could be reliably identified by PET-CT. When required, extraction of the foreign body should be done using a minimally invasive approach.

Text of a paper presented at the conference "Reformation from the perspective of 500 years. History-Culture-Society" at Siedlce University in November 8, 2017.

Pediatric heart transplantation (pHTx) represents only a small proportion of cardiac transplants. Due to these low numbers, clinical data relating to induction therapy in this special population are far less extensive than for adults. Induction is used more widely in pHTx than in adults, mainly because of early steroid withdrawal or complete steroid avoidance. Antithymocyte globulin (ATG) is the most frequent choice for induction in pHTx, and rabbit antithymocyte globulin (rATG, Thymoglobulin®) (Sanofi Genzyme) is the most widely-used ATG preparation. In the absence of large, prospective, blinded trials, we aimed to review the current literature and databases for evidence regarding the use, complications, and dosages of rATG. Analyses from registry databases suggest that, overall, ATG preparations are associated with improved graft survival compared to interleukin-2 receptor antagonists. Advantages for the use of rATG have been shown in low-risk patients given tacrolimus and mycophenolate mofetil in a steroid-free regimen, in sensitized patients with pre-formed alloantibodies and/or a positive donor-specific crossmatch, and in ABO-incompatible pHTx. Registry and clinical data have indicated no increased risk of infection or post-transplant lymphoproliferative disorder in children given rATG after pHTx. A total rATG dose in the range 3.5-7.5 mg/kg is advisable.

Key Clinical Message In times of donor organ shortage, organs with extended allocation criteria, for example, valve pathologies, have to be taken into consideration for transplantation. The donor pool can be extended to hearts with mitral valve insufficiency. Mitral valve repair can rapidly be performed in the donor heart on the back table with excellent results.

Dilated cardiomyopathy (DCM) is an important cause of heart failure. Single gene mutations in at least 50 genes have been proposed to account for 25–50% of DCM cases and up to 25% of inherited DCM has been attributed to truncating mutations in the sarcomeric structural protein titin (TTNtv). Whilst the primary molecular mechanism of some DCM-associated mutations in the contractile apparatus has been studied in vitro and in transgenic mice, the contractile defect in human heart muscle has not been studied. In this study we isolated cardiac myofibrils from 3 TTNtv mutants, and 3 with contractile protein mutations (TNNI3 K36Q, TNNC1 G159D and MYH7 E1426K) and measured their contractility and passive stiffness in comparison with donor heart muscle as a control. We found that the three contractile protein mutations but not the TTNtv mutations had faster relaxation kinetics. Passive stiffness was reduced about 38% in all the DCM mutant samples. However, there was no change in maximum force or the titin N2BA/N2B isoform ratio and there was no titin haploinsufficiency. The decrease in myofibril passive stiffness was a common feature in all hearts with DCM-associated mutations and may be causative of DCM.

PDGF-AB and FGF-2 (GFs) induce smooth muscle cell (SMC) proliferation which is indispensible for arteriogenesis. While there is common agreement that GFs stimulate SMC proliferation through phosphorylation (P-) of MEK1/2 at Ser218/222, we previously demonstrated that the MEK inhibitors PD98059 and UO126 did not inhibit P-Ser218/222 as originally proposed but caused strong hyperphosphorylation. Here, we demonstrate that GFs increased phosphorylation of MEK1 at Thr292 while UO126 and PD98059 blocked this phosphorylation. This was again surprising since phosphorylation of Thr292 is regarded as a negative feedback loop. Our findings suggest that inhibition of Thr292 phosphorylation in combination with hyperphosphorylation of Ser218/222 serves as an "off" switch of SMC proliferation and potentially of arteriogenesis.

We report on a 61-year-old man with a previously unknown interruption of the inferior vena cava who was scheduled to undergo minimally invasive mitral and tricuspid valve surgery. We aimed to establish a cardiopulmonary bypass using femorofemoral cannulation under transoesophageal echocardiography. In spite of multiple attempts, the positioning of the venous wire in the right atrium was not accomplished. The intervention was subsequently performed by an open sternotomy. Further to the intervention, the patient underwent thoraco-abdominal multislice computed tomography that excluded the presence of an abdominal tumour or vena cava thrombosis but revealed atresia of the inferior vena cava.

Myocarditis is characterized by infiltration and activation of cytokine as well as chemokine receptors frequently producing heart failure. Causes are often infections triggering inflammatory and immune responses but these initial lines of defense might be finally disastrous. To identify mediators we screened various receptors by confocal microscopy and identified cardiac interleukin-7 (IL-7) receptor-α (IL-7Rα) expressing cells in patients with myocarditis. IL-7Rα+ cells were analyzed by markers for leukocytes (CD45), B cells (CD19), T cells (CD3, CD4, CD8) and macrophages (CD68, CD163, CD206). Immune cells were hardly detected in controls. In patients with myocarditis main inflammatory populations consisted of macrophages and T cells. B cells were hardly present. 90% of CD68+ macrophages but less than 20% of CD3+ T cells were IL-7Rα+. This was surprising since T and B lymphocytes are generally regarded as the major IL-7Rα+ cells. Since IL-7 acts as a chemokine, the expression of its receptor might orchestrate cardiac macrophage infiltration. In contrast, consumption of IL-7 by IL-7Rα+ cardiac macrophages might potentially prevent a certain overshooting immune reaction and sepsis by reducing proliferation and survival of lymphocytes. Our data suggest a participation of IL-7Rα+ macrophages in the development of myocarditis and heart failure.

Background Pediatric patients show an impressive capacity of cardiac regeneration. In contrast, severely deteriorated adult hearts do usually not recover. Since cardiac remodeling—involving the expression of fetal genes—is regarded as an adaptation to stress, we compared hearts of adult patients suffering from dilated cardiomyopathy (DCM) with remodeling of cultured neonatal (NRC) as well as adult (ARC) rat cardiomyocytes and the developing postnatal myocardium. Methods NRC and ARC were stimulated with serum and cardiac morphogens derived from DCM hearts. Protein synthesis (PS) as well as protein accumulation (PA) was measured, and cell survival was determined under ischemic conditions. Fetal markers were investigated by Western blot. Biomarkers of remodeling were analyzed in controls, DCM, and 2- to 6-month-old children with tetralogy of Fallot as well as in neonatal and adult rats by immunofluorescence. Results In NRC, serum and morphogens strongly stimulated PS and PA and the reestablishment of cell-cell contacts (CCC). In ARC, both stimulants increased PS and CCC, but PA was only elevated after serum stimulation. In contrast to serum, morphogen treatment resulted in the expression of fetal genes in ARC as determined by nonmuscle α-actinin-1 and α-actinin-4 expression (NM-actinins) and was associated with increased survival under ischemia. NM-actinins were present in cardiomyocytes of DCM in a cross-striated pattern reminiscent of sarcomeres as well as in extensions of the area of the intercalated disc (ID). NM-actinins are expressed in NRC and in the developing heart. Radixin staining revealed remodeling of the area of the ID in DCM almost identical to stimulated cultured ARC. Conclusions Remodeling was similar in ARC and in cardiomyocytes of DCM suggesting evolutionary conserved mechanisms of regeneration. Despite activation of fetal genes, the atrophy of ARC indicates differences in their regenerative capacity from NRC. Cardiac-derived factors induced NM-actinin expression and increased survival of ischemic ARC while circulating molecules were less effective. Identification of these cardiac-derived factors and determination of their individual capacity to heal or damage are of particular importance for a biomarker-guided therapy in adult patients.

Background This study compared long-term outcomes of biological and mechanical mitral valve replacement (MVR) in patients requiring replacement of the mitral valve where repair was not feasible. Methods A single-centre registry of patients receiving MVR between 2005 and 2015 was established. Thirty-day mortality and long-term outcomes were analysed and compared. Results Three hundred twenty four patients underwent MVR (265 biological; 59 mechanical valves). Patients receiving biological valves were older (p

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.