The AAMS open-label clinical study demonstrated the safety and feasibility of epicardial transplantation of autologous right atrial appendage micrografts (AAMs) during coronary artery bypass grafting (CABG) surgery. The study also provided the first indications of therapeutic efficacy of the AAMs, as delivered within an extracellular matrix patch, to reduce ischemic scar and increase viable ventricular wall thickness. To further evaluate the initial beneficial effects observed in the AAMS study, we designed the randomized, double-blinded, and placebo-controlled AAMS2 trial. Focusing on patients with ischemic heart disease (IHD) and myocardial scar, the AAMS2 trial aims to generate state-of-the-art structural and functional imaging data of the myocardium treated with an AAMs-patch during CABG. The AAMS2 trial recruits IHD patients who are set to undergo non-urgent CABG and present with an ischemic myocardial scar in preoperative cardiac magnetic resonance imaging (CMRI) with late gadolinium enhancement. Patients are randomized (1:1) to receive a collagen-based matrix patch (Hemopatch®), with or without AAMs, epicardially onto the scar border. The primary endpoint, assessed by CMRI preoperatively and at 6 months post-operative follow-up, focuses on the left ventricle scar mass. The secondary endpoints center on the change in scar mass by the AAMs-patch site and evaluation of therapy safety and feasibility as well as its effects on myocardial structure and function by echocardiography. Change in blood N-terminal-pro-BNP levels in the timeframe is the co-primary endpoint. Data from the AAMS2 trial provides the first randomized, blinded, and placebo-controlled evaluation of efficacy on epicardial AAMs transplantation for ischemic myocardial scar. This data will pave the road towards rational design of larger AAMs therapeutic efficacy-addressing trial(s). ClinicalTrials.gov, NCT05632432, registered 30 November 2022, https://clinicaltrials.gov/study/NCT05632432.

BACKGROUNDAfter cardiac surgery, complete heparin reversal with protamine is essential. Accordingly, there is a need for an accurate and precise point-of-care device to detect possible residual heparin after protamine administration.OBJECTIVESTo compare two different activated clotting time (ACT) tests and thromboelastometry in detecting postprotamine heparin activity after cardiac surgery.DESIGNA single-centre prospective, observational study.SETTINGUniversity Hospital from September 2021 to February 2023.PARTICIPANTSFifty-five adult, elective cardiac surgical patients.INTERVENTIONSThe ACT-LR and ACT+ tests of Hemochron Signature Elite device, and the coagulation time (CT) ratio from INTEM and HEPTEM tests of ROTEM Sigma device, were analysed after protamine administration and compared to baseline values.MAIN OUTCOME MEASURESBased on postprotamine antifactor Xa (anti-fXa) activity, the patients were divided into heparin (anti-fXa >= 0.2 IU ml-1) and no heparin (anti-fXa <= 0.1 IU ml-1) groups.RESULTSThere was a mean bias of 44 [95% confidence interval (CI) 40 to 47] celite seconds between ACT-LR and ACT+ measurements. The absolute changes in ACT-LR, ACT+ and INTEM:HEPTEM CT ratio were variable and did not differ between the groups. The mean +/- SD percentage changes between postprotamine and baseline ACT-LR and ACT+ values were 5.9 +/- 17.5 and 5.9 +/- 16.9% in the no residual heparin group, compared to 1.4 +/- 8.4 and 9.9 +/- 12.5% in the residual heparin group. Receiver operator characteristic curves for postprotamine INTEM:HEPTEM CT ratio and for percentage changes in ACT-LR and ACT+ to detect an anti-fXa at least 0.2 IU ml-1 had areas under the curve of 0.496 (95% CI, 0.329 to 0.663), 0.425 (95% CI, 0.260 to 0.591) and 0.583 (95% CI, 0.417 to 0.749), respectively.CONCLUSIONBoth the ACT-LR and ACT+ tests of Hemochron Signature Elite device and the INTEM:HEPTEM CT ratio of ROTEM Sigma device have poor ability to detect residual heparin shortly after protamine administration.

BackgroundInfective endocarditis (IE) is an increasingly more common disease with poor prognosis. Recently, a few single-center studies about IE patient characteristics and surgical outcomes have been published from the capital area in Southern Finland. Our aim was to provide the first descriptive analysis of surgically treated IE patients in the northernmost university hospital in Finland.MethodsAll IE patients who had their first operation due to IE between 1998 and 2018 were retrospectively collected from the hospital discharge register, and their electronic patient records were analyzed. Follow-up for survival lasted to the end of 2021. The primary endpoint in survival analyses was all-cause mortality.ResultsA total of 128 novel IE cases were operated between 1998-2018. Twenty (15.6%) of the patients had a history of intravenous drug use. The median (1st-3rd quartile) follow-up after surgery was 76 (26-139) months. A total of 49 (45.5%) of the nonusers and 11 (55.0%) of the drug users died during the follow-up period. The 90-day mortality was significantly higher among nonusers compared with patients using intravenous drugs (18.5% vs. 0.0%, p = 0.036). Staphylococcus aureus was the most common underlying pathogen (42% of all cases) and posed nearly a 2-fold risk for overall mortality even after adjusting for confounding: hazard ratio: 1.781 (95% confidence interval: 1.054-3.008, p = 0.031).ConclusionsIE is a rare disease with poor outcomes. S. aureus is the most common underlying pathogen and a major risk factor for mortality in patients not using intravenous drugs.

OBJECTIVES:Our aim was to assess the association between mixed venous oxygen saturation (SvO2) and cardiac index (CI) among cardiac surgical patients during the initial 4 hours in the intensive care unit (ICU). DESIGN:A single-center retrospective observational study. SETTING:A tertiary-level university hospital. PARTICIPANTS:Adult cardiac surgical patients (N = 4,958) operated on during 2007 to 2020. INTERVENTIONS:Pulmonary artery catheter (PAC) measurements of SvO2 and CI were taken at ICU admission and 4 hours later. Linear regression was used to analyze the association between these variables. MEASUREMENTS AND MAIN RESULTS:Paired CI and SvO2 values were available from 4,958 patients. The median (interquartile range) SvO2 was 68% (63-72%) at ICU admission and 66% (61-71%) 4 hours later. CI was 2.34 L/min/m2 (2.03-2.79) at ICU admission and 2.48 L/min/m2 (2.15-2.86) 4 hours later. In the entire cohort, a 10% change of SvO2 coincided with a CI change of 0.36 L/min/m2 (95% confidence interval 0.34-0.38) at ICU admission and a change of 0.33 L/min/m2 (0.31-0.36) at 4 hours. In patients with SvO2 less than 60%, the association between CI and SvO2 weakened further. CONCLUSIONS:Factors affecting oxygen consumption and demand weaken the association between SvO2 and CI values in the early ICU recovery phase after cardiac surgery. Therefore, SvO2 and CI values should not be relied upon in clinical decision-making as reliable predictors of one another.

OBJECTIVES The aim of the study was to determine if unresponsive mixed venous oxygen saturation (SvO2) values during early postoperative hours are associated with postoperative organ dysfunction. DESIGN A single-center retrospective observational study. SETTING A university hospital. PARTICIPANTS A total of 6,282 adult patients requiring cardiac surgery who underwent surgery in a University Hospital from 2007 to 2020. INTERVENTIONS A pulmonary artery catheter was used to gather SvO2 samples after surgery at admission to the intensive care unit (ICU) and 4 hours later. For the analysis, patients were divided into 4 groups according to their SvO2 values. The rate of organ dysfunctions categorized according to the SOFA score was then studied among these subgroups. MEASUREMENTS AND MAIN RESULTS The crude mortality rate for the cohort at 1 year was 4.3%. Multiple organ dysfunction syndrome (MODS) was present in 33.0% of patients in the early postoperative phase. During the 4-hour initial treatment period, 43% of the 931 patients with low SvO2 on admission responded to goal-directed therapy to increase SvO2 >60%; whereas, in 57% of the 931 patients, the low SvO2 was sustained. According to the adjusted logistic regression analyses, the odds ratio for MODS (4.23 [95% CI 3.41-5.25]), renal- replacement therapy (4.97 [95% CI 3.28-7.52]), time on a ventilator (2.34 [95% CI 2.17-2.52]), and vasoactive-inotropic score >30 (3.62 [95% CI 2.96-4.43]) were the highest in the group with sustained low SvO2. CONCLUSIONS Patients with SvO2 <60% at ICU admission and 4 hours later had the greatest risk of postoperative MODS. Responsiveness to a goal-directed therapy protocol targeting maintaining or increasing SvO2 ≥60% at and after ICU admission may be beneficial.

Background Calcific aortic valve disease (CAVD) is an atheroinflammatory process; finally it leads to progressive calcification of the valve. There is no effective pharmacological treatment for CAVD and many of the underlying molecular mechanisms remain unknown. We conducted a proteomic study to reveal novel factors associated with CAVD. Methods We compared aortic valves from patients undergoing valvular replacement surgery due to non-calcified aortic insufficiency (control group, n = 5) to a stenotic group ( n = 7) using two-dimensional difference gel electrophoresis (2D-DIGE). Protein spots were identified with mass spectrometry. Western blot and immunohistochemistry were used to validate the results in a separate patient cohort and Ingenuity Pathway Analysis (IPA) was exploited to predict the regulatory network of CAVD. Results We detected an upregulation of complement 9 (C9), serum amyloid P-component (APCS) and transgelin as well as downregulation of heat shock protein (HSP90), protein disulfide isomerase A3 (PDIA3), annexin A2 (ANXA2) and galectin-1 in patients with aortic valve stenosis. The decreased protein expression of HSP90 was confirmed with Western blot. Conclusions We describe here a novel data set of proteomic changes associated with CAVD, including downregulation of the pro-inflammatory cytosolic protein, HSP90.

Background and aim of the study: Calcific aortic valve disease (CAVD) is a progressive disease starting from mild valvular sclerosis and progressing to severe aortic stenosis (AS) with calcified valves. The origin of the calcification is proposed to be mesenchymal cells which have differentiated towards an osteoblastic phenotype. Podoplanin is a glycoprotein expressed in the endothelium of lymphatic vessels and in osteoblasts and osteocytes, mesenchymal cells, as well as in many carcinomas and aortic atherosclerotic lesions. In CAVD, its expression has been evaluated only as a marker of the lymphatic vasculature. Materials and methods: We determined podoplanin expression in human aortic valves in four patient groups: control (C, n=7), aortic regurgitation (AR, n=8), aortic regurgitation and fibrosis (AR + f, n=15) and AS (n=49) by immunohistochemistry and quantitative real-time PCR (RT-PCR). Results: Immunohistochemically, podoplanin expression was significantly increased in AR + f and AS groups when compared with the control and AR groups and the level of expression positively correlated with the extent of calcification and vascularity. Podoplanin mRNA levels were 1.7-fold higher in the AS group as compared with the control group (P=.05). Podoplanin-positivity was present not only in lymphatic vessel endothelium but also in osteoblasts, osteocytes, chondrocytes, macrophages and extracellular matrix. The majority of the podoplanin-positivity was in spindle cells with a myofibroblastic phenotype, often associated with calcifications. Tricuspid valves had more calcification-associated podoplanin than bi/unicuspid valves (median 1.52 vs 1.16, P<.001). Conclusions: CAVD is characterized by an increased expression of podoplanin; this is associated with the differentiation of valvular interstitial cells into calcium-producing, myofibroblast-like cells. In addition, tricuspid valves express relatively more podoplanin than bi/unicuspid valves. (C) 2018 Elsevier Inc. All rights reserved.

Calcific aortic valve disease (CAVD) is a progressive pathological condition with no effective pharmacological therapy. To identify novel molecular pathways as potential targets for pharmacotherapy, we studied microRNA (miRNA) profiles of heavily stenotic aortic valves (AS). One of the most upregulated miRNAs in AS valves compared to control valves was miR-125b (1.4-fold; P < 0.05). To identify CAVD-related changes in gene expression, DNA microarray analysis was performed, including an intermediate fibro(sclero)tic stage of the disease. This revealed changes especially in genes related to inflammation and immune response, including chemokine (C-C motif) ligand 3 (CCL3) and 4 (CCL4). CCL3 mRNA level was increased 3.9-fold (P < 0.05) when AS valves were compared to control valves, and a 2.5-fold increase (P < 0.05) in CCL4 gene expression was observed when fibro(sclero) tic valves were compared to control valves. Both CCL3 and CCL4 localized to macrophages by immunofluorescence. To identify chemokine-miRNA target pairs, data from miRNA target prediction databases were combined with valvular miRNA and mRNA expression profiles. MiR-125b was computationally predicted to target CCL4, as confirmed experimentally in cultured human THP-1 macrophages. Collectively, miR-125b and CCL4 appear to be involved in the progression of CAVD and may off er novel therapeutic and diagnostic strategies related to this disease.

BACKGROUND AND AIM OF THE STUDY:Calcified aortic valve disease (CAVD) is an actively regulated disease that shares pathophysiological hallmarks with atherosclerosis. One of these common features is extracellular matrix (ECM) remodeling, which consists of a dynamic degradation and deposition of the ECM composition. Granzymes (Grs) are ECM- degrading and pro-apoptotic proteases that have been detected in atherosclerotic lesions, but their role in CAVD remains unknown.METHODS:The expression of granzymes and perforin was characterized in heavily stenotic valves (n = 20) and control valves (n = 6) using quantitative RT-PCR and immunohistochemistry.RESULTS:Quantitative RT-PCR revealed that levels of granzymes A, B, H, K and M mRNA were 4.9-fold (p < 0.001), 7.1-fold (p < 0.001), 4.6-fold (p < 0.001), 4.7-fold (p < 0.001) and 2.8-fold (p = 0.069) higher, respectively, in stenotic aortic valves than in control valves. Perforin mRNA levels were 3.6-fold (p < 0.001) higher in stenotic valves than in control valves. Granzyme A immunohistochemical positivity was observed in mast cells and lymphocytes, granzyme H in mast cells but not in lymphocytes, and granzyme K in lymphocytes but not in mast cells. A statistical analysis was also performed to investigate the effect of statin treatment on granzyme expression, but no differences were found when compared to non-statin-treated patients.CONCLUSIONS:The data acquired showed that CAVD is characterized by an increased expression of granzymes A, B, H, K, and perforin.

ObjectiveAscending aortic aneurysms result from a degenerative process in the aortic wall, characterized by the loss of smooth muscle cells and elastic fibers. We hypothesized that there would be changes in plasma protein and aortic tissue messenger RNA levels of osteopontin, matrix metalloproteinase type 2, matrix metalloproteinase type 9, and tissue inhibitor of matrix metalloproteinases type 1 in ascending aortic aneurysm samples.MethodsPlasma, aortic tissue, and aortic mRNA samples were collected from patients with an ascending aortic aneurysm or an abdominal aortic aneurysm and from control individuals. Plasma protein levels of osteopontin, matrix metalloproteinase (MMP) types 2 and 9, and tissue inhibitor of matrix metalloproteinases type 1 were determined by quantitative sandwich enzyme-linked immunosorbent assay. Aortic mRNA levels of these same proteins were analyzed with the quantitative real-time polymerase chain reaction (RT-PCR) method and protein levels from the aortic tissues were assayed by immunostaining. Quantitative RT-PCR results were estimated by the normalized expression method (ΔΔCt).ResultsPlasma protein levels were significantly elevated for osteopontin, MMP-2, and MMP-9 in the samples of ascending and abdominal aortic aneurysm group compared with controls. Plasma protein levels of MMP-9 were higher in the nonoperated compared with the operated ascending aortic aneurysm group. Aortic osteopontin, MMP-2, and MMP-9 mRNA levels were increased for ascending aortic aneurysm samples.ConclusionsThis study reveals an important role of osteopontin, MMP-2 and MMP-9 in the development of ascending and abdominal aortic aneurysm.

Background: Calcific Aortic Valve Stenosis (CAVS) is a major valvular disease that leads to myocardial hypertrophy and heart failure. It shares many hallmarks with atherosclerosis, however, many of the specific mechanisms remain to be discovered. We used a DNA-microarray to study the transcriptomic changes in human aortic valve tissue during different stages of stenosis. Methods and Results: RNA was extracted from severely stenotic aortic valves of patients undergoing valve replacement surgery (n=5) and non-sclerotic control valves from patients with aortic insufficiency (n=5). A GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix) was used to study the transcriptomic changes. Among the most upregulated genes were pro-apoptotic Granzymes, which are an integral part of the T-cell-mediated cytotoxic reaction. They have also been shown to be able to degrade the extracellular matrix (ECM). These findings were validated in a larger sample population (n=26) using qRT-PCR. Indeed, significantly increased expression of Granzymes A, B, H, K and M as well as granzyme co-effector Perforin 1 (PRF1) was detected in stenotic valves compared to normal valves. The most significant increase was seen in Granzyme B mRNA levels (7.1-fold; P<0.001) and the gene expression of PRF1 was also markedly upregulated (3.6-fold; P<0.001). Furthermore, the localization of granzymes within the valves and the effect of statin medication on their expression were studied. Conclusions: To our knowledge, this is the first time that the upregulation of the Granzyme system has been studied in human aortic valves. Its involvement indicates an active T-cell-mediated cytotoxic response as well as active degradation of the ECM. This opens up novel possibilities for the treatment and diagnosis of CAVS.

Background and aim of the study: Aortic valve stenosis (AS) is an actively regulated pathobiological process which has an inflammation origin, and manifests as an accumulation of lipids and, ultimately, calcification of the aortic valve tissue. Increased plasma levels of the proinflammatory factor endothelin-1 (ET-1) have been reported in AS. Moreover, increased tissue levels of ET-1 and its ETA receptor, which mediates the fibrotic and proliferative effects of ET-1, have been reported in stenotic aortic valves. The study aim was to determine whether endothelin receptor antagonism has an effect on the supposed receptor-mediated uptake of ET-1 to aortic valves when ET-1 may be involved in the pathogenesis of AS.Methods: By using valve tissue explants in culture, it was determined whether the ETA-ETB receptor antagonist tezosentan was capable of reducing the uptake of I-125-labeled ET-1 to human aortic valves. Aortic valves were obtained from 16 patients (11 males, five females; mean age 71 +/- 11.2 years) and from two donors without AS (as controls) at the time of aortic valve or aortic root surgery. Valve tissue samples were cultured in ET-1 (10 nmol/1), in the presence or absence of tezosentan (10 nmol/1).Results: ET-1 uptake was found to be pronounced in the calcified areas of the valve, and tezosentan markedly reduced the receptor-mediated uptake of I-125-labeled ET-1. The inhibitory effect was most evident in the well-calcified part of the valve. The gene expression levels of the ET receptors ETA and ETB were unaltered in human aortic valves during a four-day exposure to the antagonist.Conclusion: The ability of the ETA-ETB receptor antagonist tezosentan to inhibit ET-1 uptake in valve tissue suggests that continuous ET antagonist therapy might serve as new strategy to slow down the pathophysiological processes of AS.

Ascending aortic aneurysm is a connective tissue disorder. Even though multiple novel gene mutations have been identified, risk profiling and diagnosis before rupture still represent a challenge. There are studies demonstrating shorter telomere lengths in the blood leukocytes of abdominal aortic aneurysm patients. The aim of this study was to measure whether relative telomere lengths are changed in the blood leukocytes of ascending aortic aneurysm patients. We also studied the expression of telomerase in aortic tissue samples of ascending aortic aneurysms. Relative lengths of leukocyte telomeres were determined from blood samples of patients with ascending aortic aneurysms and compared with healthy controls. Telomerase expression, both at the level of mRNA and protein, was quantified from the aortic tissue samples. Mean relative telomere length was significantly longer in ascending aortic aneurysm blood samples compared with controls (T/S ratio 0.87 vs. 0.61, p<0.001). Expressions of telomerase mRNA and protein were elevated in the aortic aneurysm samples (p<0.05 and p<0.01). Our study reveals a significant difference in the mean length of blood leukocyte telomeres in ascending aortic aneurysm and controls. Furthermore, expression of telomerase, the main compensating factor for telomere loss, is elevated at both the mRNA and protein level in the samples of aneurysmal aorta. Further studies will be needed to confirm if this change in telomere length can serve as a tool for assessing the risk of ascending aortic aneurysm.

BACKGROUND:Active involvement of extracellular matrix (ECM) and its composition regulating factors may have a central role in the pathogenesis of calcific aortic valve disease (CAVD). Thrombospondins (TSPs) are highly conserved matricellular proteins regulating inflammation, angiogenesis and ECM remodeling. These processes are strongly associated with progression of aortic valve stenosis (AS). However, the expression of TSPs in CAVD is not known.METHODS:We characterized the expression of TSPs 1-4 in human aortic valves by real-time quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. Control valves (n=8), thickened and stiffened fibro(sclero)tic valves (n=8), and calcified AS valves (n=24) were compared. Furthermore, potential factors regulating TSP-2 expression was studied by western blotting and gel mobility shift assay in another set of control (n=10) and AS (n=20) valves.RESULTS:TSP-2 mRNA levels were increased 4.9-fold (P=0.037) and 4.8-fold (P=0.001) in fibro(sclero)tic and stenotic valves, respectively, whereas the expression of other TSPs did not change significantly. All TSPs 1-4 were detected from aortic valves by immunohistochemistry. Positive TSP-2 immunostaining was seen in the valvular myofibroblasts and patchily in endothelial cells. Semiquantitative analysis of TSP-2 staining indicated increased immunoreactivity for TSP-2 in neo vessels of fibro(sclero)tic and calcified aortic valves. Finally, when compared to controls, AS was associated with significant down regulation of Akt-pathway and diminished binding activity of nuclear factor-κB (NF-κB).CONCLUSIONS:We report for the first time that TSPs 1-4 are expressed in human aortic valves. CAVD is characterized by myofibroblastic proliferation and neovascularization associated upregulation of TSP-2 expression, as well as inactivation of Akt and NF-κB.

AIMS:Aortic valve calcification is an actively regulated process with endothelial dysfunction displaying hallmarks of atherosclerosis. C-type natriuretic peptide (CNP) system has been reported to have a role in the pathogenesis of vascular atherosclerosis and to be distinctly downregulated in aortic valve stenosis (AS). Here we studied gene expressions of CNP and is target receptor natriuretic peptide receptor type B (NPR-B) in human aortic valves. Furthermore, we compared gene expression of CNP system in patients with HMG-coenzyme-A reductase (statin) treatment to non-statin-treated patients in AS group.METHODS AND RESULTS:With the study population of 108 patients, we characterized expression of CNP and NPR-B in human aortic valves and compared normal control valves (n = 12) with valves obtained from patients with aortic regurgitation (AR, n = 16), AR with fibrosis (AR+fibr., n = 19) and AS (n = 61). By reverse transcription-polymerase chain reaction (RT-PCR), CNP mRNA levels were 89% lower (p = 0.022) in stenotic valves, when compared to AR group. Moreover, the mRNA levels of NPR-B, the target receptor of CNP, were 62% lower (p < 0.001) in stenotic valves when compared to control group and 54% lower (p = 0.002) in stenotic valves, when compared to AR group. There was no statistical significant difference in CNP and NPR-B levels in AS group when the statin-treated patients were compared to untreated patients.CONCLUSIONS:These results show for the first time that the gene expression of anti-atherogenic CNP system did not differ between statin-treated and non-statin-treated patients in AS. The research data supports the results of clinical trials with the same drug class.

Background: There is increasing evidence that renin-angiotensin system (RAS) may play a major role in the actively regulated fibrocalcific process in aortic valve stenosis (AS), but the gene expression or function of (pro) renin receptor ((P)RR), prorenin and renin or angiotensin converting enzyme 2(ACE2)/angiotensin-(1-7)/Mas receptor axis in calcific aortic valve disease is not known.Methods and results: We characterized expression of (P) RR, ACE2 and Mas receptor as well as renin, prorenin and angiotensin II type 2 (AT(2)) receptors in human aortic valves, and compared normal control valves (n = 11) with valves obtained from patients with aortic regurgitation (AR, n = 14), AR with fibrosis (n = 20) and AS (n = 61). By immunohistochemistry (P) RR positive staining was seen in the valvular endothelial cells of control and in the neovessels of stenotic valves. By RT-PCR, renin mRNA levels were 72% (P = 0.001) and prorenin mRNA levels 64% lower (P = 0.002) in stenotic aortic valves compared to control valves. ACE2, Mas receptor and AT(2)-receptor mRNA levels were 69% (P < 0.001), 58% (P = 0.008) and 75% (P = 0.001) lower, respectively, in stenotic valves. ACE2 positive staining, existing to lesser extent in stenotic aortic valves, was localized mainly to stromal area in spongiosa layer in control valves.Conclusions: (P)RR, prorenin and renin are expressed in human aortic valves. We also report for the first time expression of ACE2/angiotensin-(1-7)/-Mas receptor axis in human aortic valve cusps. The downregulation of ACE2/angiotensin-(1-7)/-Mas receptor axis as well as AT(2)-receptors may promote fibrosis, proliferation and inflammation in patients with AS. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

During the last few years, progress has been made in the diagnostics and treatment of valvular heart disease. Valvuloplasties have become more common in cases of valve leakage, whereby complications associated with artificial valves and anticoagulant therapy can be avoided. New less invasive catheter valve techniques seem to be as good as conventional ones. In the treatment of aortic valve stenosis, artificial valve replacement via catheter has become almost routine for patients having an excessive risk in open heart surgery.