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Background Percutaneous mitral valve repair (PMVR) requires a puncture of the atrial septum, resulting in iatrogenic atrial septal defect (iASD), which usually causes a transient left-to-right shunt. However, the influencing risk factors for iASD persistence and functional consequences are not fully understood. This meta-analysis aimed to summarise available data on the persistence of iASD following PMVR. Methods The authors conducted a literature search in PubMed/MEDLINE and EMBASE databases to identify studies investigating iASD persistence in PMVR patients. Results Six observational studies (n = 361) met inclusion criteria for the final analysis. Prevalence of persistent iASD was documented with 28% after 12 months follow-up. iASD size increased over time with a diameter of 5.3 ± 0.76 mm after one month and 6.5 ± 0.21 mm after 12 months. Possible predictors of iASD persistence after PMVR appeared to be pre-existing AF (RR 1.24; p = .03), residual mitral regurgitation > II° (RR 2.06; p = .03) and prolonged fluoroscopic time (RR 8.27; p = .01). Patients with iASD persistence had a higher risk for development of right heart overload regarding the increased area of the right atrium (MD 5.24; p = .004) and enlarged diameter of the right ventricle (MD 3.33; p Conclusions This meta-analysis proved iASD persistence in 28% of PMVR after 12 months follow-up with a higher risk for right heart volume overload and more frequent rehospitalization compared to patients without iASD persistence. Since percutaneous catheter-based treatments with transseptal approaches are rising, further evidence about the hemodynamic impact of persistent iASD is warranted.

Objectives Optimizing valve implantation depth (ID) plays a crucial role in minimizing conduction disturbances and achieving optimal functional integrity. Until now, the impact of intraprocedural fast (FP) or rapid ventricular pacing (RP) on the implantation depth has not been investigated. Therefore, we aimed to (1) evaluate the impact of different pacing maneuvers on ID, and (2) identify the independent predictors of deep ID. Methods 473 TAVR patients with newer-generation self-expanding devices were retrospectively enrolled and one-to-one propensity-score-matching was performed, resulting in a matching of 189 FP and RP patients in each cohort. The final ID was analyzed, and the underlying functional, anatomical, and procedural conditions were evaluated by univariate and multivariate analysis. Results The highest ID was reached under RP in severe aortic valve calcification and valve size 26 mm. Multivariate analysis identified left ventricular outflow (LVOT) calcification [OR 0.50 (0.31–0.81) p = 0.005*], a “flare” aortic root [OR 0.42 (0.25–0.71), p = 0.001*], and RP (OR 0.49 [0.30–0.79], p = 0.004*) as independent highly preventable predictors of a deep ID. In a model of protective factors, ID was significantly reduced with the number of protective criteria (0–2 criteria: − 5.7 mm ± 2.6 vs. 3–4 criteria − 4.3 mm ± 2.0; p Conclusion Data from this retrospective analysis indicate that RP is an independent predictor to reach a higher implantation depth using self-expanding devices. Randomized studies should prove for validation compared to fast and non-pacing maneuvers during valve delivery and their impact on implantation depth. Trail registration Clinical Trial registration: NCT01805739. Graphic abstract Study design: Evaluation of the impact of different pacing maneuvers (fast ventricular pacing—FP vs. rapid ventricular pacing—RP) on implantation depth (ID). After one-to-one-propensity-score-matching, independent protective and risk factors for a very deep ID beneath 6 mm toward the LVOT (®. AVC aortic valve calcification.

Thromboembolic events (TEs) are a feared complication in patients supported by a continuous-flow left ventricular assist device (LVAD). The aim of the study was to analyze the role of circulating microparticles (MPs) in activating the coagulation system in LVAD patients, which might contribute to the occurrence of TEs. First, we analyzed the effect of LVAD support on endothelial function, on the levels of endothelial MPs (EMPs) and platelet MPs (PMPs), and on the procoagulative activity of circulating MPs (measured as MP-induced thrombin formation) before LVAD implantation, post-implantation, and at a 3 month follow-up (n = 15). Second, these parameters were analyzed in 43 patients with ongoing LVAD support who were followed up for the occurrence of TEs in the following 12 months. In patients undergoing LVAD implantation, the levels of PMPs and MP-induced thrombin formation increased post-LVAD implantation. The flow-mediated vasodilation (FMD) decreased, while the levels of EMPs increased post-LVAD implantation. TEs occurred in eight patients with ongoing LVAD support despite adequate coagulation. The levels of PMPs and MP-induced thrombin formation were higher in LVAD patients with TEs than in LVAD patients without TEs and were independent predictors for the risk of TEs under LVAD support. As conclusion, implantation of LVAD enhanced MP-induced coagulation, which was independently associated with the occurrence of TEs. These parameters may serve in risk stratification for early transplantation and individualized modification of standard LVAD therapy.

The aim of this study was to investigate the procedural and short-term safety and efficacy of a new leaflet-based transcatheter mitral valve repair system.The PASCAL repair system has been recently approved for percutaneous treatment of mitral regurgitation (MR). Novel characteristics are broad paddles positioned around a central spacer and the ability for independent leaflet capture.Procedural and 30-day outcomes were investigated in the first 309 patients with symptomatic MR 3+/4+ treated with the PASCAL repair system at 10 sites. Primary efficacy endpoints were technical success and degree of residual MR at discharge. The primary safety endpoint was the rate of major adverse events (MAE).Among the 309 patients (mean age 77 ± 10 years, 42% women, mean European System for Cardiac Operative Risk Evaluation II score 5.8 ± 4.5%) included in this study, MR etiology was degenerative in 33%, functional in 52%, and mixed in 16%. Eighty-six percent of patients were in New York Heart Association functional class III or IV. The technical success rate was 96%. Of 308 patients discharged alive, MR was ≤2+ in 93.5%. At 30 days, the MAE rate was 4.1%, with an estimated all-cause mortality rate of 2.0%, and 72% of patients were in New York Heart Association functional class ≤II (p 0.001). Rates of device success and CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) trial-defined clinical success were 81.9% and 86.9%, respectively. Single-leaflet device attachment occurred in 7 patients (2.3%).Mitral valve repair with the PASCAL system in the early post-approval phase was effective and safe, with high procedural success rates and low rates of MAE. MR was significantly reduced, accompanied by significant improvement in functional status.

Cardiac mitochondrial alterations are suspected to play a key role in the development of diabetes-related heart failure as reported in some animal and few human studies in type 2 diabetes (1). It is yet unclear whether these alterations are induced by diabetes-related metabolic changes or develop secondary to other factors underlying heart failure including micro- and macrovascular disease. We hypothesized that 1 ) exposure to type 2 diabetes provokes myocardial mitochondrial impairment prior to apparent left ventricular heart failure in humans and 2 ) these mitochondrial alterations are accompanied by increased oxidative stress, edema, and intracellular inflammation. The cohort of this cross-sectional clinical study (study number 5263R; ClinicalTrials.gov NCT03386864) comprised adult heart transplant recipients undergoing routine transcatheter ventricular endomyocardial biopsies (EMB) post-transplantation, who received heart transplants of donors without type 2 diabetes. Thus, time between transplantation and EMB (2.9 ± 2.4 years) corresponded to the exposure of the hearts to type 2 diabetes. The first post-transplantation visit was included; exclusion criteria comprised allograft rejection (>0R according to International Society for Heart and Lung Transplantation criteria) and coronary artery disease (assessed via coronary angiography). Participants underwent oral glucose tolerance tests to assess glucose tolerance and insulin sensitivity (oral glucose insulin sensitivity [OGIS]). Cardiac magnetic resonance imaging was conducted at 1.5T to determine ventricular volumes and function, left ventricular T2 relaxation time, global left ventricular longitudinal strain (GLS), and diastolic strain rate. EMBs were attained for assessment of allograft rejection, mRNA expression of nuclear factor κ-light-chain-enhancer of activated B cells p105 subunit (NF-κB1), Toll-like receptor 9 (TLR9), and mitochondrially encoded cytochrome c oxidase I (CO1) and mitochondrial function using high-resolution respirometry in permeabilized …

ZusammenfassungDie Wahrnehmung der Bedeutung der Funktion des rechten Herzens hat sich in den letzten Jahren in Forschung und Klinik grundlegend geändert. Im klinischen Alltag erlaubt die Echokardiografie eine rasche Beurteilung der RV-Anatomie und -Funktion (RV: rechter Ventrikel). Den Goldstandard der Bildgebung bildet die MRT, die neben einer anatomischen Darstellung des RV und einer exakten Quantifizierung der RV-Funktion auch die Charakterisierung des Myokards ermöglicht. Die Rechtsherzkatheteruntersuchung stellt einen wichtigen Bestandteil in der Diagnostik dar, erlaubt eine exakte Bewertung hämodynamischer Kenngrößen der Rechtsherzinsuffizienz und kann in besonderen klinischen Szenarien um eine Belastungsuntersuchung erweitert werden.

Type 2 diabetes mellitus (T2D) is one of the prominent risk factors for the development and progression of calcific aortic valve disease. Nevertheless, little is known about molecular mechanisms of how T2D affects aortic valve (AV) remodeling. In this study, the influence of hyperinsulinemia and hyperglycemia on degenerative processes in valvular tissue is analyzed in intact AV exposed to an either static or dynamic 3D environment, respectively. The complex native dynamic environment of AV is simulated using a software-governed bioreactor system with controlled pulsatile flow. Dynamic cultivation resulted in significantly stronger fibrosis in AV tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on fibrosis. The expression of key differentiation markers and proteoglycans were altered by diabetic conditions in an environment-dependent manner. Furthermore, hyperinsulinemia and hyperglycemia affect insulin-signaling pathways. Western blot analysis showed increased phosphorylation level of protein kinase B (AKT) after acute insulin stimulation, which was lost in AV under hyperinsulinemia, indicating acquired insulin resistance of the AV tissue in response to elevated insulin levels. These data underline a complex interplay of diabetic conditions on one hand and biomechanical 3D environment on the other hand that possesses an impact on AV tissue remodeling.

Acute kidney injury (AKI) is a common complication post-PCI. Here, in a single-center observational registry, we compared the frequency of AKI in patients at elevated risk for AKI (based on Mehran risk stratification scoring) who underwent VA-ECMO- or Impella-supported high-risk PCI. A total of 28 patients scheduled for elective high-risk PCI with mechanical circulatory support were studied prospectively. All patients were turned down for surgery due to exceedingly high risk. Allocation to VA-ECMO (n=11) or Impella (n=17) was performed according to site-specific restrictions on the daily availability of the VA-ECMO platform as a prospective enrollment and performed prior to initiation of PCI. We analyzed AKI incidence as our primary endpoint, as well as PCI success, duration, and peripheral complications. All patients were successfully revascularized and had MCS weaned at the end of the procedure. Baseline GFR and procedural contrast media were similar. Despite similar risks for AKI as calculated by the Mehran score (35 ± 18.9 vs. 31 ± 16.6 %; p=0.55), patients supported by Impella during PCI demonstrated a reduced incidence of AKI (55 vs. 12 %; p=0.03). MCS-assisted high-risk PCI with VA-ECMO or Impella is feasible. However, Impella is associated with a shorter procedure time and a lower incidence of AKI.

We aimed to identify predictors of mitral regurgitation recurrence (MR) after percutaneous mitral valve repair (PMVR) in patients with functional mitral regurgitation (FMR). Patients with FMR were enrolled who underwent PMVR using the MitraClip® device. Procedural success was defined as reduction of MR of at least one grade to MR grade ≤ 2 + assessed at discharge. Recurrence of MR was defined as MR grade 3 + or worse at one year after initially successful PMVR. A total of 306 patients with FMR underwent PMVR procedure. In 279 out of 306 patients (91.2%), PMVR was successfully performed with MR grade ≤ 2 + at discharge. In 11.4% of these patients, MR recurrence of initial successful PMVR after 1 year was observed. Recurrence of MR was associated with a higher rate of heart failure rehospitalization during the 12 months follow-up (52.0% vs. 30.3%; p = 0.029), and less improvement in New York Heart Association (NYHA) functional class [68% vs. 19% of the patients presenting with NYHA functional class III or IV one year after PMVR when compared to patients without recurrence (p = 0.001)]. Patients with MR recurrence were characterized by a higher left ventricular sphericity index {0.69 [Interquartile range (IQR) 0.64, 0.74] vs. 0.65 (IQR 0.58, 0.70), p = 0.003}, a larger left atrium volume [118 (IQR 96, 143) ml vs. 102 (IQR 84, 123) ml, p = 0.019], a larger tenting height 10 (IQR 9, 13) mm vs. 8 (IQR 7, 11) mm (p = 0.047), and a larger mitral valve annulus [41 (IQR 38, 43) mm vs. 39 (IQR 36, 40) mm, p = 0.015] when compared to patients with durable optimal long-term results. In a multivariate regression model, the left ventricular sphericity index [Odds Ratio (OR) 1.120, 95% Confidence Interval (CI) 1.039–1.413, p = 0.003)], tenting height (OR 1.207, 95% CI 1.031–1.413, p = 0.019), and left atrium enlargement (OR 1.018, 95% CI 1.000–1.038, p = 0.047) were predictors for MR recurrence after 1 year. In patients with FMR, baseline parameters of advanced heart failure such as spherical ventricle, tenting height and a large left atrium might indicate risk of recurrent MR one year after PMVR.

ObjectivesThe aim of this study was to investigate the impact of acute left ventricular unloading by percutaneous left ventricular assist device on pulmonary congestion and pneumonia in patients with cardiogenic shock (CS).MethodsIn this retrospective study, we analysed patients with CS who received the Impella percutaneous left ventricular assist device (n=50) compared with those who received intra-aortic balloon pump (IABP) support (n=50). Pulmonary congestion was longitudinally assessed while on support by calculating characteristic findings on the chest X-ray using the Halperin score. The rate of pneumonia and early mortality were assessed as a secondary endpoint.ResultsThe groups (Impella vs IABP) did not differ in terms of age, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology, Chronic Health Evaluation (APACHE) II score or serum lactate levels. Pulmonary congestion decreased in patient treated with Impella at each time point postimplantation. No change in congestion status was observed in patients supported with IABP. Multivariate analysis indicated Impella support as an independent predictor for pulmonary decongestion (OR 4.06, 95% CI 1.15 to 14.35, p=0.030). The rate of early pneumonia was lower in the Impella group compared with the IABP group (54% vs 74%, p=0.037). Failure of pulmonary decongestion during mechanical circulatory support independently predicted early pneumonia (OR 0.28, 95% CI 0.12 to 0.70, p=0.006).ConclusionPulmonary decongestion may facilitate treatment of pneumonia in patients with CS. Left ventricular unloading by Impella device might support pulmonary decongestion, although a larger prospective trial in this patient population is required.

Background Bleeding and ischemic complications are the main cause of morbidity and mortality in critically ill cardiogenic shock patients, supported by short-term percutaneous mechanical circulatory support (pMCS) devices. Hence, finding the optimal antithrombotic regimen is challenging. Bleeding not only occurs because of heparin and antiplatelet therapy (both required in the prevention of pump and acute stent thrombosis) but also because of device- and disease related coagulopathy. To prevent clotting-related device failure, most centers target full therapeutic heparin anticoagulation levels in left ventricular (LV) Impella™ supported patients in analogy with Veno-Arterial Extracorporeal Membrane Oxygenation. We aimed to investigate the safety (related to bleeding and thrombotic complications) of targeting low-dose versus therapeutic heparin levels in left Impella™-supported cardiogenic shock patients on dual antiplatelet therapy (DAPT). Methods In this hypothesis generating pilot study, we investigated 114 patients supported for at least two days by LV Impella™ mechanical support due to cardiogenic shock at three tertiary ICUs, highly specialized in mechanical support. Low-dose heparin (aPTT 40–60s or anti-Xa 0.2–0.3) was compared to standard of care (aPTT 60–80s or anti-Xa 0.3–0.5). Major adverse cardio- and cerebrovascular events (MACCE; composite of death, myocardial infarction, stroke/transient ischemic attack) and BARC bleeding (bleeding academic research consortium classification) during 30 day follow-up were assessed. Inverse probability of treatment weighting (IPTW) analysis was calculated with age, gender, arterial hypertension, diabetes mellitus, smoking, chronic kidney disease, previous stroke, previous myocardial infarction, previous coronary arterial bypass grafting, hypercholesterolemia and DAPT as matching variables. COX regression analysis was conducted to test for robustness. Results IPTW revealed 52 patients in the low-dose heparin group and 62 patients in the therapeutic group. Mean age of patients after IPTW was 62±16 years in the intermediate and 62±13 years in the therapeutic group (p=0.99). 25% and 42.2% were male (p=0.92). Overall bleeding events and major (BARC3b) bleeding events were higher in the therapeutic heparin group (overall bleeding: Hazard ratio [HR]=2.58, 95% confidence interval [CI] 1.2–5.5; p=0.015; BARC 3b: HR=4.4, 95% CI 1.4–13.6, p=0.009). Minor bleeding (BARC3a) as well as MACCE and its single components (ischemic events) did not differ between both groups. These findings were robust in the COX regression analysis. Conclusion In this pilot analysis, low-dose heparin in 114 LV Impella™ cardiogenic shock patients was associated with less bleeding without increased ischemic events, adjusted for DAPT. Reducing the target heparin levels in critically ill patients supported by LV Impella™ might improve the outcome of this precarious group. These findings need to be validated in randomized clinical trials. Funding Acknowledgement Type of funding source: None

Background Right ventricular (RV) dysfunction is a predictor of poor clinical outcome in patients with heart failure and valvular heart disease. However, in patients undergoing MitraClip implantation, only limited data exist regarding the prognostic role of RV function and dimensions on outcomes. Previous studies suggested that RV dysfunction may be associated with poor clinical outcome following MitraClip, while other studies demonstrated contractionary results. Purpose The purpose of this study was to assess whether cardiac magnetic resonance (CMR) imaging derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair with the MitraClip. Methods Sixty-one patients (mean age 77±9 years; 72% functional MR; logistic EuroScore 24±15) with severe mitral regurgitation (MR) were included and underwent CMR imaging and right heart catheterization prior MitraClip procedure. We divided patients into groups according to the presence of RV systolic dysfunction defined by RV ejection fraction (RVEF) Results Patients with RV systolic dysfunction displayed increased left and right ventricular volumes as well as reduced LVEF (all p Conclusion The assessment of RV volumes and function by CMR imaging yields important prognostic information that enable an estimation of heart failure severity and prognosis. In this regard, not only RV systolic dysfunction, but also RV dilatation was associated with increased 1-year mortality, while patients presenting with both exhibit additive high mortality risk. Therefore, current criteria for patient selection that are mainly based on mitral valve characteristics only, should also consider RV volumes and function as can be accurately assessed by CMR. Funding Acknowledgement Type of funding source: None

Background Reliable risk scores in patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) are lacking. Heart failure is common in these patients, and risk scores derived from heart failure populations might help stratify TMVR patients. Methods Consecutive patients from three Heart Centers undergoing TMVR were enrolled to investigate the association of the “Get with the Guidelines Heart Failure Risk Score” (comprising the variables systolic blood pressure, urea nitrogen, blood sodium, age, heart rate, race, history of COPD) with all-cause mortality. Results Among 815 patients with available data 177 patients died during a mean follow-up time of 419 days. Estimated one-year mortality by quartiles of the score (0–37; 38–42, 43–47 and more than 47 points) was 6%, 10%, 23% and 30%, respectively (p Conclusion The “Get with the Guidelines Heart Failure Risk Score” showed a strong association with mortality in patients undergoing TMVR with additive information beyond traditional risk factors. Given the routinely available variables included in this score, application is easy and broadly possible. Funding Acknowledgement Type of funding source: None

Background Reliable risk scores in patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) are lacking. Heart failure is common in these patients, and risk scores derived from heart failure populations might help stratify TMVR patients. Methods Consecutive patients from three Heart Centers undergoing TMVR were enrolled to investigate the association of the “Get with the Guidelines Heart Failure Risk Score” (comprising the variables systolic blood pressure, urea nitrogen, blood sodium, age, heart rate, race, history of chronic obstructive lung disease) with all-cause mortality. Results Among 815 patients with available data 177 patients died during a median follow-up time of 365 days. Estimated 1-year mortality by quartiles of the score (0–37; 38–42, 43–46 and more than 46 points) was 6%, 10%, 23% and 30%, respectively (p p = 0.46). Every increase of one score point was associated with a 9% increase in the hazard of mortality (95% CI 1.06–1.11%, p Conclusion The “Get with the Guidelines Heart Failure Risk Score” showed a strong association with mortality in patients undergoing TMVR with additive information beyond traditional risk factors. Given the routinely available variables included in this score, application is easy and broadly possible. Graphic abstract

BACKGROUND Although minimally invasive mitral valve surgery (MIMVS) has become the first choice for primary mitral regurgitation (MR) in recent years, clinical evidence in this field is yet limited. The main focus of this study was the analysis of preoperative (Pre), postoperative (Post), and 1-year follow-up (Fu) data in our series of MIMVS to identify factors that have an impact on the left ventricular ejection fraction (LVEF) evolution after MIMVS. METHODS We reviewed the perioperative and 1-year follow-up data from 436 patients with primary MR (338 isolated MIMVS und 98 MIMVS combined with tricuspid valve repair) to analyze patients' baseline characteristics, the change of LV size, the postoperative evolution of LVEF and its factors, and the clinical outcomes. RESULTS The overall mean value of ejection fraction (EF) slightly decreased at 1-year follow-up (mean change of LVEF: -2.63 ± 9.00%). A significant correlation was observed for preoperative EF (PreEF) und EF evolution, the higher PreEF the more pronounced decreased EF evolution (in all 436 patients; r = -.54, p

The lifetime risk of developing heart failure is approximately 20%, and survival rates remain poor. Myocardial mitochondrial function has been suggested to play a pivotal role in heart failure pathophysiology. Human studies on ex vivo mitochondrial function have mostly been limited to atrial tissue obtained during open heart surgery and have provided contradictory results. This study aimed at measuring myocardial mitochondrial function in transcatheter ventricular endomyocardial biopsies and assessing the relationship between oxidative capacity and heart function. We enrolled 40 heart failure patients undergoing ventricular assist device surgery or heart transplantation (34 males, age 57 ± 11 years, body mass index 26.6 ± 4.8 kg/m2) and 29 heart transplant recipients of comparable age and body mass index with normal left ventricular function undergoing surveillance biopsies (23 males, 57 ± 12 years, body mass index 26.2 ± 4.1 kg/m2). High-resolution respirometry was established in the myocardium to measure oxidative capacity ex vivo. The mitochondrial oxidative capacity was 90% higher in ventricular compared to atrial tissues (n = 11, p, Heart failure: Energy metabolism reflects cardiac function The capacity of mitochondria in heart muscle cells to use oxygen to produce energy correlates with cardiac function. Julia Szendroedi at Heinrich-Heine University, Düsseldorf, Germany, and colleagues have established a technique to reliably evaluate mitochondrial energy metabolism in patients with or recovering from heart failure. They showed that the mitochondrial oxidative capacity of cells in the lower heart chambers (ventricles) was significantly higher than in the upper heart chambers (atria). Moreover, they found that mitochondrial oxidative capacity was reduced by 44% in heart muscle biopsies from patients with heart failure compared with biopsies from heart transplant recipients with normal ventricular function. Stimulating the respiration rate of mitochondria in ventricular heart cells could be a promising strategy for improving cardiac function.

The objective of this study was to assess the prognostic value of the Model for End-stage Liver Disease (MELD)-XI score in patients undergoing PMVR with the MitraClip system.MELD-XI score, which was originally developed for prognostic assessment in patients with advanced liver disease, has been reported as a predictor of outcome in heart failure patients.A total of 192 consecutive patients undergoing percutaneous mitral valve repair (PMVR) were included into final analysis. MELD-XI score was calculated on the day of the procedure and patients were categorized into three groups based on MELD-XI score and compared with regards to clinical characteristics and outcomes following PMVR.MELD-XI 12 was associated with male gender, higher logistic EuroSCORE, reduced left ventricular ejection fraction, enlarged right ventricular end-diastolic diameter, degree of mitral regurgitation, increased NT-proBNP serum levels and elevated right atrial pressures. Youden-Index revealed a cutoff of 16 in the MELD-XI score as best predictor of one-year all-cause mortality. Kaplan-Meier analysis and the log-rank test confirmed increased one-year mortality in patients with critically high score above 16 (mortality MELD-XI score 16 vs 16-12 vs12:39% vs 9%. vs 15%; P = 0.005). Compared to patients with lower MELD-XI score, these patients exhibited a more than 3-fold increased one-year mortality after PMVR.Given the high mortality in patients with a MELD-XI score 16, these patients require a high-risk preoperative assessment and should undergo a careful discussion within the heart team for the best treatment option given the considerable one-year mortality following PMVR.

Background and aims Circulating endothelial microparticles (EMPs) are increased in arterial hypertension. The role of physicomechanical factors that may induce EMP release in vivo is still unknown. We studied the relationship of EMPs and physicomechanical factors in stable arterial hypertension and hypertensive emergencies, and investigated the pattern of EMP release after mechanical endothelial injury. Methods In a pilot study, 41 subjects (50% hypertensives) were recruited. EMPs were discriminated by flow-cytometry (CD31+/41-, CD62e+, CD144+). Besides blood pressure measurements, pulse-wave-analysis was performed. Flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), and wall-shear-stress (WSS) were measured ultrasonographically in the brachial artery; microvascular perfusion by laser-Doppler (Clinicaltrials.gov: NCT02795377). We studied patients with hypertensive emergencies before and 4 h after BP lowering by urapidil (n = 12) and studied the release of EMPs due to mechanical endothelial injury after coronary angiography (n = 10). Results Hypertensives exhibited increased EMPs (CD31+/41-, CD144+, CD62e+) as compared to normotensives and EMPs univariately correlated with systolic BP (SBP), augmentation index, and pulse wave velocity and inversely with FMD. CD31+/41--EMPs correlated with diameter and inversely with WSS and NMD. CD62e+ and CD144+-EMPs inversely correlated with microvascular function. During hypertensive emergency, only CD62e+ and CD144+-EMPs were further elevated and FMD was decreased compared to stable hypertensives. Blood pressure lowering decreased CD62e+ and CD144+-EMPs and increased FMD. CD31+/41—EMPs, diameter, and WSS remained unaffected. Similar to hypertensive emergency, catheter-related endothelial injury increased only CD144+ and CD62e+-EMPs. Conclusions EMP release in hypertension is complex and may involve both physicomechanical endothelial injury and activation (CD144+, CD62e+) and decreased wall shear stress (CD31+/41-). Graphical abstract In arterial hypertension, increased systolic blood pressure and decreased wall shear stress (due to greater arterial diameter) are associated with the release of endothelial microparticles (EMPs). We linked this with distinct patterns of mechanical injury, activation, and endothelial dysfunction (CD62e+ and CD144+-EMPs) and decreased endothelial protection (CD31+/41--EMPs), respectively. EMPs may be part of a vicious self-perpetuating cycle involving endothelial dysfunction.

Endothelial microparticles (EMPs) are markers of endothelial injury and activation. The role of EMPs in arterial hypertension is not well understood and EMPs are increased both in arterial hypertension and coronary artery disease (CAD). The data presented here show EMPs as defined by CD31+/41−, CD62e+, and CD144+ surface markers and vascular hemodynamic parameters including office and central blood pressure, heart rate, aortic augmentation index, pulse wave velocity, flow-mediated dilation, nitroglycerin-mediated dilation, brachial artery diameter, hyperemic wall shear stress, and laser Doppler perfusion of the cutaneous microcirculation of normotensives and hypertensives with and without CAD.

Peripartum cardiomyopathy (PPCM) is an idiopathic cardiomyopathy presenting with heart failure due to left ventricular systolic dysfunction towards the end of pregnancy or in the months following delivery, where no other cause of heart failure is found. We report a case of a woman with PPCM who developed a critical cardiogenic shock with repeated cardiopulmonary resuscitation. We show for the first time that mechanical circulatory support combined with high-dose bromocriptine therapy to suppress systemic prolactin levels may serve as an effective therapeutic option in patients with fulminant PPCM and cardiogenic shock. Myocardial cathepsin D was overexpressed in our patient underscoring a potential role of cathepsin D-induced cleavage of prolactin in the pathophysiology of PPCM.

Background In-stent restenosis (ISR) is still a major concern in interventional cardiology. Drug coated balloon (DCB) angioplasty has been shown to be a promising option in treatment of ISR. However heterogeneity of different DCBs in suppression of neointimal growth has been described in a porcine model of coronary ISR. Therefore, in this registry analysis, we compared two frequently used paclitaxel eluting DCBs, the SeQuent Please and the Pantera Lux DCB. Methods 571 patients were treated with DCB angioplasty at the Heinrich-Heine University Dusseldorf between 2009 and 2012. Follow-up was conducted during ambulatory care at our department. Major adverse cardiac events (death, myocardial infarction [MI] and target lesion revascularization) were registered during hospitalization and follow-up. Results Patient characteristics, prior diseases, clinical presentation, ejection fraction, procedural success and lost-for-follow-up did not differ between patients treated with the SeQuent Please and. The Pantera Lux DCB. MACE during hospital course were similar as well (Pantera Lux: 6 patients [1.6%] vs. SeQuent®Please: 3 patients [1.5%], relative risk 1.06, 95% confidence interval 0.3–4.2, P=0.93). Event free survival was significantly longer in patients treated with the Pantera Lux DCB as compared to SeQuent Please DCB (Hazard ratio: 0.65, 95% confidence interval 0.43–0.98; P value of log-rank test: 0.0405). Conclusion MACE free survival was longer in Pantera Lux DCB treated patients as compared to SeQuent Please treated patients. This finding has to be confirmed in future clinical trials.

Background In secondary MR, data on left ventricular (LV) remodeling after MitraClip procedure are rare, even this information may impact patient selection. This study investigated changes in LV structure and function by cardiovascular magnetic resonance (CMR) following MitraClip implantation for secondary mitral regurgitation (MR) in order to assess extent and predictors of LV reverse remodeling (LVRR). Methods and Results Twenty-nine patients underwent CMR imaging prior to and six months after MitraClip procedure. LVRR was defined by a decrease of LV end-diastolic volume index (LVEDVi) > 15% compared to baseline. According to the definition of LVRR, 34% of patients displayed LVRR at follow-up CMR. Baseline LV stroke volume index (LVSVi), LV ejection fraction (LVEF), LV circumferential strain and MR volume at baseline were predictors of LVRR at follow-up. At second CMR, we detected an improvement in hemodynamic status as illustrated by an increase in effective LVSVi (28 ± 8 ml/m2 vs. 33 ± 8 ml/m2; p = 0.053) and cardiac index (2.0 ± 0.5 vs. 2.3 ± 0.5 l/min; p = 0.016), while LVEF and LV strain parameters did not change (p > 0.05). Improvements in effective LVSVi were associated with the decrease of MR volume (r = 0.509; p = 0.018) and MR fraction (r = 0.629; p = 0.002) by MitraClip. Conclusions Together, MitraClip implantation is associated with LVRR in one third of patients. Baseline LV function and magnitude of MR are important predictors of LVRR. Improvement of hemodynamic status may be assessed by effective stroke volume index and correlates with the reduction of MR by MitraClip implantation, rather than an increase in LV contractility.

Objectives To investigate in a series of 232 patients whether the MitraClip® procedure can be performed safely using deep sedation (DS) without general anesthesia (GA). Background Transcatheter mitral valve repair using the MitraClip® system is a safe and effective therapy for severe mitral regurgitation (MR) in patients who are at high operative risk or are unsuitable for surgery. For these patients, avoidance of GA might be beneficial. Methods Between 2011 and 2015, we performed 232 MitraClip® procedures for the treatment of severe MR. Of those, 76 procedures were performed using GA, while the remaining 156 procedures were performed using DS. Results Age, logistic EuroScore, severity of MR, left and right ventricular function, and renal function did not differ between the groups. The primary combined safety endpoint, which was defined as the occurrence of major adverse cardiac and cerebrovascular events, conversion to surgery, major vascular complications or pneumonia, did not differ between MitraClip® procedures performed using GA and MitraClip® procedures performed using DS. Intraprocedural conversion to GA was required in 2% of the patients in the DS group. There were no differences in procedural success or clinical outcome between the groups at the 3-month follow-up. Preparation time in the catheterization laboratory and intensive care unit (ICU) stay were shorter in the DS group compared to the GA group. Conclusion The MitraClip® implantation performed using DS is as safe and effective as MitraClip® implantation performed using GA. © 2017 Wiley Periodicals, Inc.

Nicht-Vitamin-K-antagonistische orale Antikoagulanzien (NOAK) werden in den letzten Jahren vermehrt bei Patienten mit nichtvalvularem Vorhofflimmern, venoser Thrombose und Lungenembolie eingesetzt. Allerdings sind die Erfahrungen mit diesen neuen Substanzen im Rahmen des periinterventionellen, perioperativen und intensivmedizinischen Managements noch sehr eingeschrankt. Aufgrund der fehlenden Evidenz basieren die aktuellen Empfehlungen zum Umgang mit Patienten unter NOAK in diesem Rahmen auf Analysen der Pharmakokinetik in Kombination mit patientenspezifischen Charakteristiken, dem jeweiligen Blutungsrisiko des geplanten Eingriffs und der Dringlichkeit der Prozedur. Dieser Review fasst die Evidenz und Empfehlungen zum optimalen periinterventionellen/perioperativen/intensivmedizinischen antithrombotischen Management bei Patienten unter NOAK-Therapie zusammen.

Aims To evaluate whether CMR-derived RV assessment can facilitate risk stratification among patients undergoing transcatheter mitral valve repair (TMVR). Background In patients undergoing TMVR, only limited data exist regarding the role of RV function. Previous studies assessed the impact of pre-procedural RV dysfunction stating that RV failure may be associated with increased cardiovascular mortality after the procedure. Methods Sixty-one patients underwent CMR, echocardiography and right heart catheterization prior TMVR. All-cause mortality and heart failure hospitalizations were assessed during 2-year follow-up. Results According to RV ejection fraction (RVEF) Conclusion In patients undergoing TMVR, pre-existing RV dysfunction and RV dilatation are associated with reduced survival, in progressive additive fashion. The assessment of RV volumes and function by CMR may aid in risk stratification prior TMVR in these high-risk patients.

Background: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. Methods: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. Results: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P =0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P P =0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. Conclusions: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

This study tested the hypothesis that a reduction of pulmonary congestion achieved by a reduction of mitral regurgitation (MR) severity in heart failure (HF) patients is associated with reduced event lengths of sleep-disordered breathing (SDB). We prospectively enrolled 20 consecutive HF patients who underwent MitraClip implantation. Patients underwent cardiorespiratory polygraphic recording prior to and after percutaneous mitral valve repair (PMVR). Beyond routinely established indicators of apneas and hypopneas per hour (respiratory event index), we manually analyzed apnea event lengths. MitraClip implantation led to marked reduction of MR severity and a reduction in left atrial pressure. These hemodynamic changes were accompanied by changes in SDB: the subtype of SDB switched from CSA to OSA in 4 patients. Likewise, quantitative indicators of SDB were altered in both forms of SDB with a reduction in circulatory delay (CSA 38 ± 14 vs. 33 ± 15 s.; p = 0.002 and OSA 34 ± 9 vs. 28 ± 6 s.; p = 0.02) and a corresponding reduction in ventilation lengths in CSA patients (42 ± 15 vs. 37 ± 13 s.; p = 0.05). A reduction of pulmonary congestion as achieved by a decrease of left atrial pressure through successful MitraClip implantation is associated with a reduction in respiratory event lengths, further pointing towards a relation between SDB and HF.

Both pre-existing atrial fibrillation (AF) and mitral valve pressure gradients (MVPG) created by MitraClip implantation have demonstrated predictive power for unfavorable outcomes. Therefore, we aimed to assess the impact of MVPG following MitraClip on outcomes in patients with and without AF. A total of 200 patients who underwent MitraClip implantation in our institution were enrolled. Echocardiography was obtained before and after the procedure. The primary endpoint of the study was all-cause mortality 1-year after MitraClip implantation. Secondary end points were clinical improvements in NYHA functional class and reduction in MR severity after MitraClip implantation. Two hundred patients (74 ± 10 years, left ventricular ejection fraction 41% ± 14%, logistic EuroSCORE I 21 ± 15) were enrolled into the final analysis. One hundred twelve patients (56%) had pre-existing AF. One-year all-cause mortality was 17% without any differences between patients with or without pre-existing AF. Comparing postprocedural MVPG of surviving and deceased patients, deceased patients with pre-existing AF exhibited significantly elevated postprocedural MVPG compared with surviving patients without AF (4.8 ± 2.1 mm Hg vs 3.6 ± 1.8 mm Hg; p = 0.010). ROC analysis and Kaplan–Meier survival curves identified significantly reduced survival in AF patients with postprocedural MVPG above 4.0 mm Hg (p = 0.011). After MitraClip, a MVPG above 4.0 mm Hg in patients with pre-existing AF was a significant outcome predictor in univariate and multivariate analysis. In conclusion, we identified a high-risk cohort characterized by postprocedural MVPG above 4.0 mm Hg and pre-existing AF predicting poor long-term outcome.

Acute heart failure is still characterized by poor prognosis with high mortality. Diagnosis is based on clinical symptoms and hemodynamic measurements. Early coronary revascularization in cardiogenic shock complicating myocardial infarction improves outcome. The further contemporary therapeutic options in the management of acute heart failure are limited to a merely symptomatic effect with relief of dyspnea, reduction of volume overload and improvement of hemodynamic parameters by vasodilators (in hypertension) or inotropic and vasopressor agents (in hypotension). However, so far no medical therapy has been shown to positively affect clinical outcomes of patients with acute heart failure. Early identification of impending circulatory collapse coupled with rapid implementation of mechanical circulatory support may contribute to mortality reduction as a combined concept of the management of acute heart failure.

Background The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction. Methods Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253 + ), leukocyte (CD45 + ), platelet (CD31 + /CD41 + ), and endothelial cell (CD31 + /CD41 − , CD62e + , CD144 + ) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay. Results FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx. Conclusions Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.

AIMS: Degenerative aortic valve stenosis (AVS) is independently associated with endothelial dysfunction and increased levels of circulating endothelium-derived microparticles (EMPs) as a marker of compromised endothelial integrity. The aim of this study was to investigate whether therapy for severe AVS by transcatheter aortic valve implantation (TAVI) improves endothelial function and decreases EMPs. METHODS AND RESULTS: Fifty-six patients with indication for TAVI due to symptomatic severe AVS were prospectively enrolled. Brachial wall shear stress (WSS), endothelial function and circulating microparticles (MPs) were measured before and three months following TAVI. Endothelial function was assessed as flow-mediated dilation (FMD) using ultrasound. MP subpopulations were discriminated by flow cytometry according to the expression of established surface antigens: CD31+/CD41-, CD144+ and CD62E+ as EMPs and CD41+ as platelet-derived MPs (PMPs). In patients with severe AVS, decreased brachial WSS was an independent predictor of low FMD. At three-month follow-up after TAVI, WSS and FMD increased along with decreased levels of EMPs as compared to pre TAVI. Decrease of CD31+/CD41-, CD144+ and CD62E+ EMP levels correlated with the increase of FMD. CONCLUSIONS: Therapy for AVS by TAVI was associated with improved endothelial function and integrity indicating beneficial effects of TAVI on systemic arterial function.

Limited data exist on the occurrence of acute kidney injury (AKI) associated with percutaneous mitral valve repair (PMVR). The objectives of the present study were (1) to assess the prevalence of AKI after MitraClip (Abbott Vascular, Santa Clara, California) implantation, (2) to analyze the predictive factors of AKI, and (3) to evaluate the prognostic value of AKI after PMVR with a view to optimizing the management of high-risk patients. A total of 206 patients (serum creatinine [SCr] 1.3 ± 0.6 mg/dl, estimated glomerular filtration rate 55 ± 24 ml/min) who underwent PMVR were included. AKI was defined as an increase in SCr by ≥0.3 mg/dl within 48 hours or an increase in SCr by ≥1.5 times baseline. AKI was assessed during the first 5 days after MitraClip implantation. The incidence of AKI after MitraClip was 18% and none of the patients required dialysis. Age, logistic EuroSCORE, baseline renal function, N-terminal pro-B-type natriuretic peptide levels, serum glycated hemoglobin A1c, serum C-reactive protein, diuretic usage, and elevated right atrial pressure were the risk factors of AKI. Incidence of AKI was associated with poor outcome. Short-term mortality was increased (30-day mortality rate AKI vs no AKI: 18% vs 1%; p 0.001). Likewise, Kaplan-Meier analysis and log-rank test confirmed reduced long-term survival of patients with AKI (1-year all-cause mortality of patients with AKI vs patients with no AKI: 34% vs 13 %; p 0.001). In conclusion, every fifth patient experienced AKI after MitraClip implantation, which was associated with increased short-term mortality and a more than threefold increase in the risk of death 1 year after PMVR.

Mechanical ventricular unloading in advanced heart failure (HF) has been shown to induce reverse remodeling in myocardial tissues. Little is known about the impact of ventricular unloading on myocardial energy metabolism. We hypothesized that left ventricular unloading reduces myocardial mitochondrial reactive oxygen species (ROS) production and improves mitochondrial coupling efficiency in patients suffering from advanced HF. Left ventricular tissue specimens were harvested from explanted hearts at the time of transplantation. We compared myocardial metabolism in explanted hearts supported with an unloading ventricular assist device prior to transplantation (LVAD-HTX; n = 9) with tissue specimens of unsupported failing hearts (HTX; n = 6). Myocardial mitochondrial ROS production was decreased by 40% in LVAD-HTX compared to HTX patients (1.5 ± 0.3 vs. 0.9 ± 0.1 pmol/(s/mg); p

Transcatheter mitral valve repair with the MitraClip system (Abbott Vascular GmbH, Santa Clara, California) is an established therapy of severe mitral regurgitation in patients at increased surgical risk. Periprocedural thrombus formation on the MitraClip device is a rare but dreaded complication

Eravacycline is a novel fluorocycline, highly active against Gram-positive and Gram-negative pathogens in vitro , including those with tetracycline and multidrug resistance. This phase 2, randomized, double-blind study was conducted to evaluate the efficacy and safety of two dose regimens of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). Patients with confirmed cIAI requiring surgical or percutaneous intervention and antibacterial therapy were randomized (2:2:1) to receive eravacycline at 1.5 mg/kg of body weight every 24 h (q24h), eravacycline at 1.0 mg/kg every 12 h (q12h), or ertapenem at 1 g (q24h) for a minimum of 4 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 10 to 14 days after the last dose of study drug therapy. Overall, 53 patients received eravacycline at 1.5 mg/kg q24h, 56 received eravacycline at 1.0 mg/kg q12h, and 30 received ertapenem. For the ME population, the clinical success rate at the TOC visit was 92.9% (39/42) in the group receiving eravacycline at 1.5 mg/kg q24h, 100% (41/41) in the group receiving eravacycline at 1.0 mg/kg q12h, and 92.3% (24/26) in the ertapenem group. The incidences of treatment-emergent adverse events were 35.8%, 28.6%, and 26.7%, respectively. Incidence rates of nausea and vomiting were low in both eravacycline groups. Both dose regimens of eravacycline were as efficacious as the comparator, ertapenem, in patients with cIAI and were well tolerated. These results support the continued development of eravacycline for the treatment of serious infections, including those caused by drug-resistant Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01265784.)

The aim of this study was to determine the value of T2 mapping for the non-invasive assessment of myocardial inflammation in different stages of systolic left ventricular dysfunction in dilated cardiomyopathy (DCM) in comparison with endomyocardial biopsy (EMB).A total of 132 subjects were enrolled between 2013 and 2016 (62 controls and 70 patients with DCM). All patients underwent CMR at 1.5 T and received coronary angiogram and EMB. CMR applied standard protocols including T2 mapping with Gradient And SpinEcho sequence (GRASE). Global T2 relaxation time was significantly increased in patients with DCM compared to the healthy controls (T2 time DCM vs. controls: 65.9 ± 6.2 vs. 60.0 ± 4.2 ms; P 0.001). Of note, patients with the presence of inflammatory cells in EMB exhibited further elevation of T2 values (T2 time in patients with the presence of inflammatory cells vs. T2 time in patients without: 68.8 ± 5.8 vs. 64.7 ± 5.9 ms; P = 0.02). Receiver operating characteristic analysis of our data deciphered a global myocardial T2 time65.3 ms as the best cut-off for distinction between the healthy controls and patients with myocardial inflammation [sensitivity 93%, specificity 90%, P 0.01, area under the curve (AUC) 0.95]. In patients with DCM, this threshold identified patients with biopsy-proven inflammation with a sensitivity of 79% and specificity 58% (AUC 0.72).In patients with DCM and presence of inflammatory cells in the myocardium, myocardial T2 relaxation times may help to non-invasively detect myocardial inflammation. Although there is an overlap of T2 values between patients and healthy controls, T2 mapping may facilitate the identification of patients who may benefit from EMB for therapeutic decision-making.

Detection of myocardial inflammation in patients with clinically suspected acute myocarditis (sAMC) is of prognostic importance but remains a challenge in routine clinical practice [(1)][1]. Compared with endomyocardial biopsy (EMB), the diagnostic gold standard, cardiovascular magnetic resonance (

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold, p &lt, 0.05) and myocardial (2.4 fold, 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold, 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold, 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.

Objective Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs. Methods In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41+, endothelium-derived MPs (EMPs) as CD144+, CD62E+ and CD31+/CD41-, leukocyte-derived MPs as CD45+, and erythrocyte-derived MPs as CD235+. Results In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41+: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144+: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E+: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P