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ZusammenfassungDiabetes mellitus (DM) stellt eine wichtige Komorbidität bei Patienten mit Herzinsuffizienz dar, die maßgeblich die Prognose der Patienten determiniert. Von entscheidender Bedeutung zur Verbesserung der Prognose dieser Hochrisiko-Patienten ist daher eine frühzeitige Diagnostik und differenzierte medikamentöse Therapie mit Ausschöpfung aller möglichen Therapieoptionen und Absetzen potenziell schädlicher Substanzen. Das gemeinsame Positionspapier der Deutschen Gesellschaft für Kardiologie (DGK) und der Deutschen Diabetes Gesellschaft (DDG) fasst die vorhandene wissenschaftliche Evidenz zusammen und gibt Empfehlungen, was bei der Diagnose und Therapie der Herzinsuffizienz und des DM zu beachten ist, um die Prognose zu verbessern.

Aims Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment.Methods and results In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected. The association between active MCS use and the primary endpoint of 30-day mortality was assessed in a 1:1 propensity-matched cohort. MCS was used in 386 (43%) patients. Patients treated with MCS presented with more severe CS (37% vs. 23% deteriorating CS, 30% vs. 25% in extremis CS) and had a lower left ventricular ejection fraction at baseline (21% vs. 25%). After matching, 267 patients treated with MCS were compared with 267 patients treated without MCS. In the matched cohort, MCS use was associated with a lower 30-day mortality (hazard ratio 0.76, 95% confidence interval 0.59-0.97). This finding was consistent through all tested subgroups except when CS severity was considered, indicating risk reduction especially in patients with deteriorating CS. However, complications occurred more frequently in patients with MCS; e.g. severe bleeding (16.5% vs. 6.4%) and access-site related ischaemia (6.7% vs. 0%).Conclusion In patients with non-ischaemic CS, MCS use was associated with lower 30-day mortality as compared to medical therapy only, but also with more complications. Randomized trials are needed to validate these findings. [GRAPHICS] Open Access funding enabled and organized by Projekt DEAL. Conflict of interest: B.S. reports speaker fees from Abiomed and AstraZeneca, outside of the submitted work. B.N.B. reports honoraria from Siemens Healthineers, outside of the submitted work. S.B. reports grants and personal fees from Abbott Diagnostics, Bayer, Siemens, Thermo Fisher, grants from Singulex, personal fees from Abbott, AstraZeneca, Amgen, Medtronic, Pfizer, Roche, Siemens Diagnostics, Novartis, outside of the submitted work. D.E. reports speaker fees from Abiomed, Bayer, Daiichi Sankyo, outside of the submitted work. P.H. reports travel compensation from Abiomed, outside of the submitted work. P.K. reports research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK) and German Centre for Cardiovascular Research, from several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies in the past, but not in the last 3 years. He is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783; unrelated to the submitted work). S.K. reports research support from Cytosorbents and Daiichi Sankyo. He also received lecture fees from Astra, Bard, Baxter, Biotest, Cytosorbents, Daiichi Sankyo, Fresenius Medical Care, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips and Zoll. He received consultant fees from Fresenius, Gilead, MSD and Pfizer, outside of the submitted work. P.L. reports speaker fees from AstraZeneca, Bayer, EdwardsLifesciences, Medtronic and Pfizer outside the submitted work. N.M. reports lecture fees Pfizer/Bristol-Myers Squibb and grant research from Getinge Global USA and Italfarmaco, outside of the submitted work. M.O. reports speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer vital, Biotronik, Bristol-Myers Squibb, CytoSorbents, Daiichi Sankyo Deutschland, Edwards Lifesciences Services, Sedana Medical, outside of the submitted work. A.P. reports an unrestricted educational grant from Abbott Vascular, outside of the submitted work. T.R. reports speaker fees from AstraZeneca, Daiichy, Bayer, Novartis, Abiomed outside the submitted work. D.W. reports speaker fees from Abiomed, AstraZeneca, Bayer, Berlin-Chemie, Boehringer Ingelheim, Novartis and Medtronic, outside of the submitted work. All other authors have nothing to disclose.

Jo.B. was supported by the Deutsche Forschungsgemeinschaft (KFO 311).

A patent foramen ovale (PFO) persists in about one-quarter of people and is the source of up to 25% of all ischemic strokes, especially strokes in young adults. PFO can be easily diagnosed by transthoracic contrast and/or transesophageal echocardiography. Interventional closure of the PFO via the femoral vein is a commonly used cardiological procedure since several trials have demonstrated the superiority of PFO closure over standard medical therapy in patients with PFO and who have experienced post ischemic, cardioembolic, or cryptogenic stroke. The current paper and video show the procedure of PFO closure in a step-by-step manner.

Background: Inflammatory rheumatic diseases (IRD) are often associated with the involvement of various organs. However, data regarding organ manifestation and organ spread are rare. To close this knowledge gap, this cross-sectional study was initiated to evaluate the extent of solid organ manifestations in newly diagnosed IRD patients, and to present a structured systematic organ screening algorithm. Materials and Methods: The study included 84 patients (63 women, 21 men) with newly diagnosed IRD. None of the patients received any rheumatic therapy. All patients underwent a standardised organ screening programme encompassing a basic screening (including lungs, heart, kidneys, and gastrointestinal tract) and an additional systematic screening (nose and throat, central and peripheral nervous system) on the basis of clinical, laboratory, and immunological findings. Results: Represented were patients with connective tissue diseases (CTD) (72.6%), small-vessel vasculitis (16.7%), and myositis (10.7%). In total, 39 participants (46.5%) had one or more organ manifestation(s) (one organ, 29.7%; two organs, 10.7%; ≥three organs, 6.0%). The most frequently involved organs were the lungs (34.5%), heart (11.9%), and kidneys (8.3%). Lastly, a diagnostic algorithm for organ manifestation was applied. Conclusion: One-half of the patients presented with a solid organ involvement at initial diagnosis of IRD. Thus, in contrast to what has been described in the literature, organ manifestations were already present in a high proportion of patients at the time of diagnosis of IRD rather than after several years of disease. Therefore, in IRD patients, systematic organ screening is essential for treatment decisions.

Background: Various clinical trials provide evidence about the safety, effectiveness, and therapeutic success of percutaneous left atrial appendage closure (LAAC) using various occlusion devices. These devices are foreign materials implanted into the left atrium and may deteriorate left atrial (LA) function. The aim of this study was to evaluate the change in transesophageal echocardiography (TEE)-derived LA strain after LAAC. Methods and Results: The study included 95 patients (age: 75 ± 6.7 years, 67% male) who underwent percutaneous LAAC. LA strain was evaluated at three different time intervals by TEE (baseline, 45 days, and 180 days after the procedure). All data were analyzed using the software Image-Arena (TomTec®). Seventy patients had atrial fibrillation, whereas 25 were in sinus rhythm at baseline and during follow-up. Analysis was performed for peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) from segments of the lateral wall in mid-esophageal four-chamber view. PACS was obtained in patients with sinus rhythm during examinations. Compared to baseline, PALS increased at 45 days after the procedure (12.4% ± 8.4% at baseline vs. 16.0% ± 10.6% after 45 days, P = 0.001) and remained stable from 45 days to 180 days after procedure (13.8% ± 9.1% after 45 days vs. 17.2% ± 12.6% after 180 days, P = 0.092). Similarly, PACS increased at 45 days after the procedure (5.8% ± 3.9% at baseline vs. 10.6% ± 7.6% after 45 days, P = 0.001) and remained stable from 45 days to 180 days after the procedure (7.6% ± 4.5% after 45 days vs. 7.9% ± 3.1% after 180 days, P = 0.876).Conclusions: Our study demonstrated for the first time the improvement in TEE-derived LA strain following LAAC within 45 days of implantation. The findings suggest improved LA function following LAAC.

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Background Pulmonary vascular and right ventricular myocardial remodelling are unique phenomena in PH progression. Both processes are accompanied by an abundant re-expression of the extra-domain A of fibronectin (ED-A+ Fn) therefore qualifying as promising biomarker or even therapeutic target. Nevertheless, its functional role in PH pathogenesis remains unclear until now. Objective: The purpose of our study was to analyse the development of PH and RHF in a mouse model of monocrotaline (MCT)-induced PH comparing C57BL/6 ED-A+ Fn knockout (KO) and wild-type (WT) mice. Methods PH was induced by subcutaneous injection of a single dose of MCT (60 mg/kg body weight). Subgroups were additionally treated with the dual endothelin receptor antagonist Macitentan (MAC, 15mg/kg body weight per day from day 14 to 28). There were 6 experimental groups: sham-treated control WT mice (WTco, n=4); MCT induced PH WT mice (WTPH, n=6); MCT induced PH WT mice treated with MAC (WTPH_MAC, n=6); sham-treated control KO mice (KOco, n=4); MCT induced PH KO mice (KOPH, n=6); MCT induced PH KO mice treated with MAC (KOPH_MAC, n=6). Between day 26 and 28, transthoracic echocardiography and right heart catheterization were performed. Both, lung and cardiac tissue samples were subjected to histological analyses. Results Right heart catheterization revealed significantly increased RVPsys values in WTPH (87.0±16.4mmHg) compared to WTco (36.1±9.4mmHg; p=0.034) animals, which showed, at least in trend, a diminution in the WTPH_MAC group (67.1±20.9mmHg; p=n.s.). There was a non-significant increase in RVPsys in the KOPH (55.6±14.9mmHg) compared to KOco mice (37.2±5.6mmHg; p=n.s.) without any differences compared to the KOPH_MAC group (60.9±14.0mmHg; p=n.s.). When comparing the WTPH and the KOPH group, RVPsys was significantly lower in the KO animals (p=0.014), while there were no differences between the WTPH_MAC and the KOPH_MAC group (p=n.s.). Echocardiographic evaluation including surrogate parameters of right ventricular (RV) overload and failure were significantly altered in WTPH compared to WTco animals (p Conclusions The findings of the current study underline the hypothesis that ED-A+ Fn is a key player in the pathogenesis of PH and associated RHF. Thus, it might represent a promising therapeutic target, e.g., by the administration of neutralizing antibodies. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Jena

Background Infective endocarditis (IE) requires a high degree of suspicion and advanced level of multidisciplinary management. In 2015, the European guidelines recommended the formation of an endocarditis-team (ET) for optimal treatment of IE. In 2011, we already established an ET within the hospital that was only consulted on demand for certain patients. Since 2015, ET has been increasingly involved in the management of almost all patients with IE. In addition, we established in 2015 a statewide endocarditis- (E) network for the referring hospitals. Purpose We investigated the effect of E-network on reducing referral latency and pre-operative IE-related complications. We also investigated the adherence to the ET management recommendations in our hospital and its impact on post-operative stroke and mortality. Methods We retrospectively analyzed data from patients operated for IE in our center between 01/2007 and 03/2018. We conducted univariate analysis using Chi-square or Fisher's exact test, Multivariate logistic regression models for in-hospital mortality and post-operative stroke, and Kaplan-Meier estimate of 5-years survival. Results Among 630 patients operated for IE in our center, 409 (65%) underwent surgery in the 1st era before 12/2014. S. aureus IE was more frequent in the second era (34% vs 25%, p Conclusion Endocarditis-network led to earlier referral of patients, which resulted in less IE-related complications on admission. Lack of ET management recommendations was an independent predictor for post-operative stroke, in-hospital mortality and was associated with worse 5-years survival. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Aims Reduced muscle endurance (RME) in patients with HFpEF and HFrEF is associated with structural and metabolic changes in skeletal muscle. We investigated the role of kynurenine (Kyn) as a potential marker in detecting RME. Additionally, we described the likely distorted metabolic pathways in serum in patients with RME and both preserved (HFpEF) and reduced (HFrEF) ejection fraction. Methods Fifty-five participants were prospectively recruited (17 HFpEF, 18 HFrEF outpatients and 20 healthy controls, HC). All participants underwent echocardiography, CPET, isokinetic muscle function tests. Quantification of metabolites in serum was performed using liquid chromatography tandem mass spectrometry. Results In a linear regression, Kyn was an independent predictor for RME after adjusting for alanine, glutamate, ornithine, spermine and short-chain-ACs (B: −8.2 per 1μM increase, 95% CI: −13.01, −3.30, p=0.001). Kyn showed 83% sensitivity and 70% specificity (area under the curve 0.83) in detecting RME. Patients with RME and HFpEF showed reduced levels of long-chain-, medium-chain-, medium-/long-chain-ACs ratios and alanine (p Conclusions Kyn shows high potential as biomarker for detecting RME. RME was associated with impaired fatty acid oxidation rates in HFpEF patients and with reduced concentrations of AAs in those with HFrEF. Funding Acknowledgement Type of funding sources: None.

Pulse index continuous cardiac output (PiCCO) is used for hemodynamic assessment. This study describes real world extravascular lung water index (EVLWI) measurements at three time points and relates them to other hemodynamic parameters and mortality in critically ill patients admitted to a medical intensive care unit (ICU). A total of 198 patients admitted to a tertiary medical university hospital between February 2004 and December 2010 were included in this retrospective analysis. Patients were admitted for various diseases such as sepsis (n = 22), myocardial infarction (n = 53), pulmonary embolism (n = 3), cardiopulmonary resuscitation (n = 15), acute heart failure (AHF; n = 21) and pneumonia (n = 25). Patients included in this analysis were severely ill as represented by the high simplified acute physiology score 2 (SAPS2, 42 ± 18) and acute physiology and chronic health evaluation score 2 (APACHE2‚ 22 ± 9). Real-world values at three time points are provided. Intra-ICU mortality rates did not differ between the EVLWI > 7 vs. the ELVWI

Blood cholesterol levels are regulated by competing mechanisms of cholesterol synthesis, absorption and excretion. Plant sterols are natural constituents of plants, are not synthesized in humans, and serve as markers for cholesterol absorption. Ezetimibe lowers the intestinal absorption of cholesterol and plant sterols. We analyzed the associations of differences in cholesterol metabolism, in particular increased cholesterol absorption, and the occurrence of in-stent restenosis (ISR) in patients with stable coronary artery disease.Elective stent implantation of de novo stenosis was conducted in 59 patients (74.6 % males, 67.2 ± 9.6 years). Cholesterol and non-cholesterol sterols were quantified in serum samples by gas chromatography or mass spectrometry. ISR was assessed by optical coherence tomography (OCT) and quantitative angiography (QCA) after six months.Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were positively associated with ISR measured by QCA (%diameter stenosis, late lumen loss) and OCT (proliferation volume, %area stenosis), whereas markers for cholesterol synthesis (e.g. lathosterol-to-cholesterol) were negatively associated with ISR (%area stenosis: r = -0.271, p = 0.043). There was no association between ISR and total cholesterol, LDL, HDL, triglycerides. Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were significantly lower in ezetimibe-treated patients compared to patients on a statin only (1.29 ± 0.69 vs. 2.22 ± 1.23; p = 0.007). Combined lipid-lowering with ezetimibe plus statin reduced ISR compared to statin only (13.7 ± 10.4 vs. 22.5 ± 12.1 %diameter stenosis, p = 0.015).Differences in cholesterol metabolism, more specifically increased cholesterol absorption, are associated with ISR.

Degenerative aortic valve stenosis is an inflammatory process that resembles atherosclerosis. Neutrophils release their DNA upon activation and form neutrophil extracellular traps (NETs), which are present on degenerated aortic valves. NETs correlate with pressure gradients in severe aortic stenosis. Transcatheter aortic valve replacement (TAVR) is an established treatment option for aortic valve stenosis. Bioprosthetic valve deterioration promoted by inflammatory, fibrotic and thrombotic processes limits outcome. Deoxyribonuclease is a natural counter mechanism to degrade DNA in circulation. In the present observational study, we investigated plasma levels of double-stranded DNA, deoxyribonuclease activity and outcome after TAVR. 345 consecutive patients undergoing TAVR and 100 healthy reference controls were studied. Double-stranded DNA was measured by fluorescence assays in plasma obtained at baseline and after TAVR. Deoxyribonuclease activity was measured at baseline using single radial enzyme diffusion assays. Follow-up was performed at 12 months, and mean aortic pressure gradient and survival were evaluated. Receiver operating characteristic, Kaplan-Meier curves and Cox regression models were calculated. Baseline double-stranded DNA in plasma was significantly higher compared to healthy controls, was increased at 3 and 7 days after TAVR, and declined thereafter. Baseline deoxyribonuclease activity was decreased compared to healthy controls. Interestingly, low deoxyribonuclease activity correlated with higher C-reactive protein and higher mean transaortic gradient after 12 months. Finally, deoxyribonuclease activity was a strong independent predictor of outcome 12 months after TAVR. Deoxyribonuclease activity is a potential biomarker for risk stratification after TAVR. Pathomechanisms of bioprosthetic valve deterioration involving extracellular DNA and deoxyribonuclease merit investigation.

Introduction Takotsubo syndrome (TTS) is clinically indistinguishable from an acute coronary syndrome (ACS). In the absence of valid markers for differential diagnosis, coronary angiography has been indispensable. Methods In our study, we evaluated the serum levels of sST-2, GDF-15, suPAR and H-FABP in 92 patients with the suspicion of TTS (51 TTS and 41 ACS patients) and 40 gender matched controls (no coronary artery disease or signs of heart failure) at baseline. Results H-FABP was significantly higher in ACS patients compared to TTS patients. Even in in propensity score matching for left ventricular ejection fraction, sex and cardiovascular risk factors, differences in the plasma levels of H-FABP in the matched cohort of TTS vs ACS remained statistically significant. Whereas, sST-2 was significantly elevated in TTS patients. H-FABP was superior for prediction of an ACS with even higher accuracy than hs troponin in differential diagnosis (AUC 0.797, p ≤ 0.0001); the optimal cut off for discrimination towards a TTS was calculated as 2.93 ng/ml (sensitivity 70.0%, specificity 82.4%, PPV 75.7%, NPV 77.4%). sST-2 seemed most appropriate for identification of a TTS (AUC 0.653, p = 0.012). The optimal cut off for differential diagnosis was 11018.06 pg/ml (sensitivity 82.0%, specificity 51.2%, PPV 69.4%, NPV 71.9 %). Conclusion H-FABP and sST-2 are the most promising markers with better accuracy than preexisting biomarkers in differential diagnosis in our study and therefore, could be crucial for the guidance of treatment in patients with high bleeding risk, advanced renal failure or multimorbidity. Graphical abstract

Introduction A very high morbidity and mortality is associated with cardiogenic shock due to left ventricular failure despite encouraging developments in interventional cardiology. Patients suffering from cardiogenic shock often require temporary mechanical circulatory support to stabilize organ perfusion. In addition, an increasing number of patients with complex multi-vessel diseases cannot undergo surgical myocardial revascularization as recommended by recent guidelines due to their comorbidities. Those patients could benefit from a protected PCI approach using a temporary mechanical assist device. The available LVAD systems have specific advantages and disadvantages. Purpose It was our aim to develop a percutaneous, pulsatile assist device that unloads the left ventricle in a physiologic way. Methods The PERKAT-LV (“PERkutane KATheterpumptechnologie”) device consists of a self-expanding nitinol pump chamber which is covered by foils. Those foils carry multiple outflow valves at the proximal part of the pump chamber. A flexible suction tube with a pigtail-shaped tip and inflow holes are attached to its distal part. The system is designed for 16F percutaneous implantation via the femoral artery. Pulling back the outer sheath unfolds the nitinol chamber in the descending aorta while the flexible suction tube bypasses the aortic arch and ascending aorta with its tip in the left ventricle. In the second implantation step, a standard IABP balloon is placed into the pumping chamber and is connected to an external IABP console. Balloon deflation generates a blood flow from the left ventricle into PERKAT LV. During balloon inflation, blood leaves the system through the outflow foil valves in the descending aorta. Positioning and schematic drawing of PERKAT-LV is demonstrated in Figure 1. Results Preliminary in-vitro studies using a prototype of the PERKAT LV device were performed. It was tested in different afterload settings (0, 40, 80 and 120 mmHg) using a standard 30 ccl IABP balloon and varying inflation/deflations rates (70, 80, 90, 100, 110 and 120/min). We detected flow rates ranging from 2.0 to 3.0 L/min depending on the afterload setting and inflation/deflation rate. Conclusion The novel percutaneously implantable and pulsatile working PERKAT-LV device offers left ventricular unloading and circulatory support of up to 3.0 L/min in a first feasibility study. At the moment, the system is extensively studied under in vitro conditions. First in vivo evaluation will follow in the near future. Based on the current results, we believe that the system is a promising novel approach for percutaneous application of temporary left ventricular mechanical support. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Federal Ministry of Education and Research

Introduction Severe aortic stenosis (AS) caused by degenerative calcification is the most frequent acquired valvular heart disease worldwide and mortality rates are considerably high. Transcatheter Aortic Valve Implantation (TAVI) is a well-established method for valve replacement in high risk patients with AS. However, there is a lack of reliable predictors for patients undergoing TAVI since commonly used scores were developed for surgical populations. Materials and methods 208 patients subjected to TAVI were included in this study. Plasma samples were obtained before TAVI and were evaluated for IGFBP-2 using commercially available ELISA kits. IGFBP-2 levels were analyzed for their ability for risk prediction after TAVI. Results IGFBP-2 levels measured before TAVI correlated significantly with left ventricular ejection fraction, EUROSCORE and other functional and prognostic parameters like the 6-minute walking test. When patients were retrospectively divided in two groups with a cut-off of serum IGFBP-2 levels of 275 ng/ml, IGFBP-2 was a strong predictor for 30-day and one-year mortality (3% vs. 11%, p = 0.05 and 18.2% vs. 46.2%; p Conclusions Our results indicate that IGFBP-2 could serve as new outcome predictor for patients undergoing TAVI procedure. By providing additional information to the commonly used EUROSCORE, IGFPB-2 analysis could further assist Heart Team decision making.

Background and aims There are safety issues regarding plant sterol ester-enriched functional food. Oxidized plant sterols, also called oxyphytosterols, are supposed to contribute to plant sterol atherogenicity. This study aimed to analyze associations of plasma oxyphytosterol levels with cardiovascular events. Methods Plasma cholesterol was measured by gas chromatography-flame ionization detection. Plasma campesterol and sitosterol and their 7-oxygenated metabolites were analyzed by gas chromatography-mass selective detection. Results In 376 patients admitted for elective coronary angiography, who were not on lipid-lowering drugs, 82 cardiovascular events occurred during a follow-up period of 4.2 ± 1.8 years. Patients with cardiovascular events had significantly higher 7α-hydroxycampesterol plasma levels (median, 0.46; [interquartile range (IQR) 0.22–0.81] nmol/L vs. median, 0.25 [IQR, 0.17–0.61] nmol/L; p = 0.003) and 7α-hydroxycampesterol-to-cholesterol ratios (median 0.08 [IQR, 0.04–0.14] nmol/mmol vs. median, 0.05 [IQR 0.03–0.11] nmol/mmol; p = 0.005) than controls without such events. Patients above the median were characterized by higher cumulative event rates in Kaplan-Meier-analysis (Logrank-test p = 0.084 and p = 0.025) for absolute and cholesterol corrected 7α-hydroxycampesterol, respectively. After adjustment for influencing factors and related lipids, the hazard ratios per one standard deviation of the log-transformed variables (HR) were 1.19 [95% confidence interval (CI), 0.95–1.48], p = 0.132 for 7α-hydroxycampesterol and HR, 1.18 [95% CI, 0.94–1.48], p = 0.154 for 7α-hydroxycampesterol-to-cholesterol ratio. None of the other investigated oxyphytosterols showed an association with cardiovascular events. Conclusions In patients not on lipid-lowering drugs, absolute plasma levels of 7α-hydroxycampesterol and their ratios to cholesterol are associated with cardiovascular events. Further research is required to elucidate the role of OPS in cardiovascular diseases.

Even though significant progress has been made over the past 3 decades, heart failure remains one of the leading causes of mortality and morbidity in developed countries and contributes significantly to the economic burden of modern health care systems. Especially in patients with preserved ejection fraction, valid therapeutic options are missing due to a lack of evidence. In face of a very heterogeneous condition with an ongoing debate over aetiology and pathophysiology, clinicians face a challenge in providing optimal care for these patients. Recent data suggest that the optimal treatment of the underlying conditions as well as comorbidities that are associated with heart failure might play an ever increasing role in improving outcomes. This focused review summarizes and reviews current data for the treatment of heart failure with both preserved and reduced ejection fractions based on the latest recommendations covering medical therapy and interventional strategies.

We present the case of a 63-year-old man with a history of non-small cell lung carcinoma (NSCLC) and systemic chemotherapy who suffered from progressive shortness of breath and peripheral edema. Transthoracic echocardiography showed a huge non-homogenous mass nearly completely filling the dilated right ventricle. The border of mass was not differentiable from the right ventricular myocardium. The findings of echocardiographic study were highly suggestive for cardiac metastasis. Computed tomography and positron emission computed tomography confirmed the presumed diagnosis. Lung cancer is one of the most common primary tumors of cardiac metastasis and NSCLC accounts for about 85% of all lung cancers. Lymphatic spread or direct invasion usually involves the pericardium or epicardium. However, metastasis to the myocardium and endocardium is extremely rare. The huge size, location, direct invasion to myocardium and echocardiographic features of this cardiac mass have made it a unique case for presentation. .

Background Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied. Methods We retrospectively analysed serum levels of soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR), heart-type fatty acid-binding protein (H-FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed. Results Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF-15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H-FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in μg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT-proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers. Conclusion Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.

Single-shot devices have been developed to simplify pulmonary vein isolation (PVI). Randomized studies of the second-generation cryoballoon (CB 2nd) demonstrated excellent results. There are limited data comparing results of circular pulmonary vein ablation catheter (PVAC) with conventional RF ablation or CB for PVI. Using a sequential registry cohort and a prospective randomized study, we aimed to compare the acute and long-term results of CB 2nd and PVAC Gold. In the registry, consecutive patients with paroxysmal atrial fibrillation (AF) undergoing their first PVI were included. The preferred method used was PVAC Gold in 2014 and CB 2nd in 2015. Subsequently, a randomized study (PVAC vs. CB 2nd) was performed. Ablation success was measured as freedom of AF or atrial tachycardias (AT) off antiarrhythmic drugs. In the registry cohort, PVAC Gold was used in 60 patients and CB 2nd in 56 patients (age 66 ± 11 years, 52% male, LAD 43 ± 6). In the randomized study, 20 patients were treated with PVAC Gold and 22 with CB 2nd (age 67 ± 9; 43% men, LAD 40 ± 7 mm). During a mean follow up of 13.2 ± 3.6 months, success was 54% in PVAC Gold patients and 81% in CB 2nd cases (p = 0.001). In the randomized study 12 months success was 50% versus 86%, p

Background Due to increased operative mortality in high-risk patients treated for severe tricuspid regurgitation (TR), there is a growing interest in interventional therapy in these patients that are otherwise solely treated with medication. The edge-to edge technique with implantation of one or more MitraClips is an therapeutic interventional option for these patients. So far, data for transcatheter TR treatment are sparse. Purpose The present cohort study investigates safety, feasibility and effectiveness of the edge-to-edge technique treating severe TR after starting a transcatheter TR treatment program at our institution in 2017. Methods A total of 17 high-risk patients (79.18±8.76 years, EUROScore II 9.31±8.23%, table) with symptomatic, severe TR were treated using the MitraClip system from 12/2017 until 12/2018. All patients received pre-interventional clinical, echocardiographic and invasive evaluation and were entered into a database. Safety and feasibility of the procedure, reduction of TR grade and clinical outcomes were collected and analyzed at the day of discharge and at 30-day follow-up. Results MitraClip device was successfully implanted in 16 of 17 patients (94.1%). In one patient grasping of the leaflets was impossible due to bad echo conditions by abdominal air. 76.5% of the patients had severe or massive and 23.5% had a torrential TR (figure). A total of 25 Clips were used (22 in anteroseptal, 3 in posteroseptal commissure). No intraprocedural deaths, emergency surgery or major vascular complications occurred. Postprocedural TR was significantly reduced (TR reduction ≥1 grade) from a mean TR grade of 3.8±0.8 at baseline to 1.74±0.59 postprocedural (p Conclusion Interventional treatment of severe TR in high-risk and mostly inoperable patients using the MitraClip technique is safe and effectivly reduces TR grade leading to clinical improvement. However, further investigations are needed to identify clear parameters highly predictive for a favorable acute and midterm procedural success. Also, more data and clinical trials are needed to determine the long-term course in these patients.

Background and aims Diagnosis of Cardiac Allograft Vasculopathy (CAV) following heart transplantation (HTX) is still challenging but of prognostic relevance. Thus, the identification of biomarkers non-invasively detecting the disease is an hitherto unmet clinical need. Fetal variants of the cell adhesion modulating protein Fibronectin (Fn) could be proven to re-occur in the context of chronic rejection in rat and human cardiac tissue after HTX in spatial association to CAV and fibrosis. This study was aimed to determine serum levels of fetal Fn variants in a heterotopic rat HTX model of chronic rejection. Methods Chronic cardiac allograft rejection was induced by heterotopic rat HTX using inbred male Lewis (LEW) rats as donors and Fisher (F344) rats as recipients (n=24). After microsurgical modifications, the allograft was implanted into the abdomen of the recipient animal. Rats were sacrificed after 70 days. Untreated F344 rats were used as controls (n=6). Cardiac tissue was subjected to histological analysis according to a recently established sum-score system between 0 and 10 (0 = no detectable rejection; 1 to 3 = weak rejection; 4 to 7 = moderate rejection; and 8 to 10 = severe rejection). The score includes all relevant parameters of chronic rejection (CAV, lymphocyte infiltration, cardiomyocyte degeneration, fibrosis). Brain natriuretic peptide (BNP) was determined by a commercially available ELISA. Serum levels of both, ED-A domain containing Fn (ED-A+ Fn) and ED-B domain containing Fn (ED-B+ Fn) were quantified using ELISA protocols established in our group. Results Final experiments were performed on day 70, mortality rate was 0%. Histological analysis revealed a chronic cardiac allograft rejection in all transplanted animals (mean sum-score 6.92±1.94) while controls did not exhibit relevant alterations (mean sum-score 0.1±0.2; p Conclusions Chronic cardiac allograft rejection and, in particular, CAV as major long-term prognosis-limiting factor after HTX are accompanied by both, a re-expression and vessel associated tissue deposition of ED-A+ Fn and also a relevant liberation into blood. These results underline the potential impact of ED-A+ Fn as biomarker or potential therapeutic target patients that underwent HTX.

Background Plant sterols are suspected to exert atherosclerotic propensity. Modern drug-eluting stents are superior to bare metal stents but show a late catch up phenomenon for restenosis. Due to its superb resolution, optical coherence tomography (OCT) has the capability to identify and quantifiy very early patterns of in-stent proliferation. Studies have shown that in-stent neointimal proliferation is linked to late in-stent stenosis. Purpose This study aimed to analyze associations of plasma levels for markers of cholesterol homeostasis such as campesterol and sitosterol (markers for cholesterol absorption) as well as lanosterol (marker for cholesterol synthesis)and and their respective oxides with In-stent restenosis after stent deployment in stable coronary artery disease. Methods Plasma cholesterol was measured by gas chromatography-flame ionization detection. Plasma campesterol, sitosterol and lanosterol and their oxides were analyzed by gas chromatography-mass selective detection. In-stent proliferation (restenosis) was assessed after six months by OCT in 33 patients (21 males). A quantitative OCT algorithm was applied to each stent by steps of one mm and in-stent proliferation volumes and areas were calculated and normalized to stent length and area. In-stent proliferation can be measured by OCT as global volumes and focal areas. Results No clinically significant restenosis or angiographic restenosis of >30% was observed at 6-month f/u. Mean cholesterol level was 166,5±62,8 mg/dl and positively correlated with proliferation volume/cm (r=0.316, p=0.037) and absolute median proliferation area (r=0.322, p=0.029). Absolute median proliferation area and relative median proliferation area correlated positively with markers for cholesterol absorption such as campesterol-to-cholesterol (r=0.277, p=0.07 and 0.315, p=0.037) and sitosterol-to-cholesterol (r=0.237, p=0.092 and 0.322, p=0.034), whereas lanosterol (a marker for cholesterol synthesis) and its ratio to cholesterol correlated negatively with proliferation volumes and areas (p Conclusions In this hypothesis-generating study, in-stent proliferation assessed by OCT at six months follow-up was positively associated with markers for cholesterol absorption and negatively associated with markers for cholesterol synthesis. Larger studies will have to evaluate whether patients with high cholesterol absorption might benefit in particular from combined-lipid-lowering therapy with a statin and a cholesterol absorption Inhibitor.

Background Elimination of a permanent metallic stent from standard PCI techniques is desirable since mid- and longterm adverse reactions are attributed to an intracoronary foreign body. Purpose To investigate two “metal-free” PCI techniques using either drug-coated balloons (DCB) or bioresorbable scaffolds (BRS) in stable coronary artery disease regarding their safety and efficacy (NCT02607241) and clinical course. Methods 59 patients (table 1) were prospectively randomized for elective PCI of de novo stenosis with either BRS implantation (N=28) or with DCB only angioplasty (N=31). The DCB only arm was treated by a previously implemented protocol including sequential balloon predilations and repetitive FFR (fractional flow reserve) measurements. Stenting was deferred if FFR was >0.80 and in the absence of flow-limiting dissections after final DCB dilatation. All BRS were post-dilated using a non-compliant balloon. All BVS were post-dilated (non-compliant balloon). Optical coherence tomography (OCT) was performed during index procedure and at 9-month f/u. Results Both groups were well balanced without significant differences in clinical characteristics (table 1). Procedural success was achieved in 89.3% in the BRS and 77.4% in the DCB group. Parameter of quantitative coronary angiography are shown in the table 2. The predefined primary end point (efficacy) net luminal gain was significantly larger in the DCB group (noninferiority t-Test, margin: 0.2mm, 80% power). Accordingly, the secondary endpoint late lumen loss indicated with −0.20±0.73 vessel enlargement at the stenotic site in the DCB group at 9-month f/u. Target lesion failure during 9-month f/u occurred much more in the BRS group (14.3% (N=4) vs. 3.2% (N=1), p=0.180) but did not reach significance in this small sample size. In detail, there were 2 scaffold thrombosis despite OCT-guided index procedure in the BRS group with subsequent myocardial infarction, and 2 restenosis in the BRS vs. 1 restenosis in the DCB group requiring repeat target lesion revascularization. Due to safety concerns of BRS and the worldwide recall of Absorb BRS the study was prematurely terminated. Conclusion Our data add evidence for FFR-guided “DCB only” PCI as an attractive, safe and feasible alternative by showing a favorable longterm course contrary to the late lumen loss of conventional coronary stents. The Absorb BRS is potentially harmful with a high percentage of target lesion failure including scaffold thrombosis despite OCT-guided implantation and should be avoided.

Background Treatment and time goals for STEMI care are clearly defined in national and international guidelines. However, initiation of therapy relies in accurate diagnosis after first medical contact (FMC). Prehospital logistics with fast transfer to the next available 24/7 PCI-center can be challenging, especially in rural areas and for transfers across state-borders in Germany. Objective To analyze quality of STEMI care in a high volume PCI center serving a city and a large rural area with focus on EMS (emergency medical service) logistics. Two groups of patients admitted by EMS: (1) direct PCI-center admission vs. (2) secondary admission after transfer from a non-PCI hospital were compared. Methods Various administrative, procedural, therapeutic and clinical parameters were registered for each patient including timelines of acute treatment (tables). Inaccurate treatment delays were calculated as cumulative time in any prolongation in timely diagnosis or therapy after FMC. Results From 340 consecutive STEMI patients in or registry, 299 patients were transferred by EMS. Reperfusion therapy with PPCI was significantly delayed and required double of the time in patients secondary transferred from a non-PCI hospital (Contact-to-Balloon: 195.6±134.8 min vs. 99.6±45.3 min, p Conclusion Quality of acute STEMI care is significantly worse in rural areas predominantly due to suboptimal prehospital logistics and poor prehospital emergency care. Our data underline the importance to establish local STEMI networks irrespective of state borders with clearly defined prehospital transfer strategies, continuous medial education of EMS personnel and assessement of local quality of care.

Background Soluble (s) ST-2 has been recently evaluated as a monitoring parameter in heart failure (HF). Besides being a marker for cardiac strain and hemodynamic stress, studies also found an influence of ST2 on the immune system, above all mediated through its Janus-Face ligand IL-33, an alarmin released under stress conditions or by cellular death. In contrast to sST2, the role of IL-33 in HF is yet unknown. Objective In this project, we aimed for an analysis of the ST2/IL33 pathway in patients with heart failure with reduced ejection fraction (HFrEF). Methods In total, 200 patients were included in the study: 59 with ischemic (ICM), 65 with dilated (DCM) cardiomyopathy (mean LVEF 38%), as well as 76 control patients without coronary artery disease or signs of heart failure. Serum samples were analyzed by use of ELISA after informed consent. Results sST2 showed a significant elevation in all HF patients (p Analysis of sST2 in heart failure Conclusions We observed a significant increase and correlation with disease severity of sST2 in chronic HFrEF patients of both ischemic and non-ischemic origin, but contrary to our expectations, no significant changes in serum levels of IL-33. Thus, a mechanism independent of ST2/IL33 axis could be responsible of sST2 secretion in HF. Further studies including acute decompensated patients could provide a better understanding of the IL-33 role in HF.

Background and aims Depression negatively affects symptom tolerance as well as clinical endpoints in cardiovascular diseases. For aortic stenosis (AS) patients undergoing Transcatheter Aortic Valve Implantation (TAVI), a reduction of pre-existing depression and anxiety in short term follow-up could be recently shown by our group. The current study was aimed to evaluate these effects in long-term follow-up and to screen for promising biomarkers, e.g., 5-Hydroxytryptamin (5-HT), Endothelin-1 (ET-1), neutrophil gelatinase associated lipocalin (NGAL) and Tenascin-C (Tn-C) variants. These molecules might reflect a pathophysiological link between reverse cardiac remodelling and mental state. Methods The study included 182 out of 226 patients who underwent TAVI at the University Hospital Jena since August 2016. Besides clinical parameters, the EuroQol questionnaire (EQ-5D), the Visual Analog Scale (VAS), the Clinical Frailty Scale (CFS) and, to specifically detect depression and anxiety, the Hospital Anxiety and Depression Scale (HADS-D) were assessed directly before TAVI, at 6-weeks, 6-month as well as 12- months follow-up. Blood samples were withdrawn before TAVI and during 6-weeks and 6-month follow-up. Results Study patients represented a typical moderate- to high-risk TAVI collective (n=182, mean age 78,1±7.9 years, 46,9% male, mean STS-Score 4.6±2,8). Before TAVI, analysis of HADS revealed ≥8 points, defined as pathologic, for depression and/or anxiety in 71 patients (39%) and for depression only in 46 patients (25.3%). In the depressive subgroup, there was a significant improvement after 6 weeks for depression (p Conclusions Already in short-term follow-up after successful TAVI, a remarkable decrease in depression could be detected using HADS. Especially in the depressive subgroup, the patients showed benefit also with respect to other surrogate parameters of mental health and functional performance. Interestingly, these effects were completely maintained not only in mid-term but also in long-term follow-up. We could show that the improvement of depression after TAVI is reflected by a delayed decrease of C+ Tn-C serum levels. C+ Tn-C can be suggested as promising biomarker possibly linked to reactive depression in somatic diseases.

Introduction: Body temperature (BT) abnormalities are frequently observed in critically ill patients. We aimed to assess admission BT in a heterogeneous critically ill patient population admitted to an intensive care unit (ICU) as a prognostic parameter for intra-ICU and long-term mortality. Methods: A total of 6,514 medical patients (64 ± 15 years) admitted to a German ICU between 2004 and 2009 were included. A follow-up of patients was performed retrospectively. The association of admission BT with both intra-ICU and long-term mortality was investigated by logistic regression. Results: Patients with hypothermia (p < 0.001), and a 4-fold increase for the risk of hypothermia (mortality 24%; OR 4.05, 95% CI 3.38–4.85; p < 0.001) with respect to intra-ICU and long-term mortality. Moreover, hypothermia was even more harmful than hyperthermia, and both were strongly associated with intra-ICU mortality, especially in patients admitted with acute coronary syndrome (hypothermia: hazard ratio 6.12, 95% CI 4.12–9.11; p < 0.001; hyperthermia: OR 2.70, 95% CI 1.52–4.79; p< 0.001). Conclusion: Admission BT is an independent risk predictor for both overall intra-ICU and long-term mortality in critically ill patients admitted to an ICU. Therefore, BT at admission might not only serve as a parameter for individual risk stratification but can also influence individual therapeutic decision-making.