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Background Patients with coronary heart disease (CHD) with and without diabetes mellitus have an increased risk of recurrent events requiring multifactorial secondary prevention of cardiovascular risk factors. We compared prevalences of cardiovascular risk factors and its determinants including lifestyle, pharmacotherapy and diabetes mellitus among patients with chronic CHD examined within the fourth and fifth EUROASPIRE surveys (EA-IV, 2012–13; and EA-V, 2016–17) in Germany. Methods The EA initiative iteratively conducts European-wide multicenter surveys investigating the quality of secondary prevention in chronic CHD patients aged 18 to 79 years. The data collection in Germany was performed during a comprehensive baseline visit at study centers in Würzburg (EA-IV, EA-V), Halle (EA-V), and Tübingen (EA-V). Results 384 EA-V participants (median age 69.0 years, 81.3% male) and 536 EA-IV participants (median age 68.7 years, 82.3% male) were examined. Comparing EA-IV and EA-V, no relevant differences in risk factor prevalence and lifestyle changes were observed with the exception of lower LDL cholesterol levels in EA-V. Prevalence of unrecognized diabetes was significantly lower in EA-V as compared to EA-IV (11.8% vs. 19.6%) while the proportion of prediabetes was similarly high in the remaining population (62.1% vs. 61.0%). Conclusion Between 2012 and 2017, a modest decrease in LDL cholesterol levels was observed, while no differences in blood pressure control and body weight were apparent in chronic CHD patients in Germany. Although the prevalence of unrecognized diabetes decreased in the later study period, the proportion of normoglycemic patients was low. As pharmacotherapy appeared fairly well implemented, stronger efforts towards lifestyle interventions, mental health programs and cardiac rehabilitation might help to improve risk factor profiles in chronic CHD patients.

BackgroundDue to their prevalence worldwide, the β-lactamases CTX-M and plasmid-mediated CMY-2 are important antimicrobial resistance enzymes in a clinical setting. While culture- and PCR-based detection methods exist for these targets, they are time consuming and require specialist equipment and trained personnel to carry out.MethodsIn this study, three rapid diagnostic single-plex and a prototype triplex assay were developed, using recombinase polymerase amplification with lateral flow detection (RPA-LF), and tested for their sensitivity and specificity using two isolate DNA panels (n = 90 and n = 120 isolates). In addition, the RPA-LF assays were also tested with a small number of faecal extract samples (n = 18).ResultsThe RPA-LF assays were able to detect blaCXT-M-group-1, blaCTX-M-group-9 and blaCMY-2-type variants with high sensitivity (82.1%–100%) and specificity (100%) within a short turnaround time (15–20 min for amplification and detection).ConclusionsRPA-LF assays developed in this study have the potential to be used at or close to the point of care, as well as in low-resource settings, producing rapid results to support healthcare professionals in their treatment decisions.

Background The association of clinically meaningful changes in the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-os) with prognosis in patients with heart failure (HF) is well established. However, most studies have considered several weeks as time intervals for the serial assessments of the KCCQ-os. Therefore, we sought to investigate the changes of the KCCQ-os and their prognostic relevance between discharge and several months. Methods We assessed serial KCCQ data from the Extended Interdisciplinary Network Heart Failure (E-INH) study: between 2004 and 2007, 1022 hospitalized HF patients with a left ventricular ejection fraction (LVEF) Results Of 1022 participants, 604 patients (59%) provided complete serial KCCQ data sets at baseline and after 6, 12, and 18 months: mean (SD) age 65.6 (12.2) years, 24% women, median (quartiles) KCCQ-os at baseline 59.2 (43.2; 77.1). 345 (57%) patients died, median follow-up time 8.9 years (4.1; 10.0). There were significant median changes of KCCQ-os from baseline over time: 6-month 9.9 (−0.8; 26.8), 12-month 12.5 (−1.5; 29.4), and 18-month 13.4 (−1.1; 33.7), respectively (all p Conclusion Amongst patients with HF surviving at least 18 months after being hospitalized for decompensated HF, a change in KCCQ-os identified patients at increased risk in the years to come. This association was apparent regardless of the time point of score collection. Since Patient-Reported Outcomes as the KCCQ may be easily collected via phone or a medical application, our findings not only confirm the prognostic utility of serial health status assessments but also might be useful to triage the frequency of clinical follow-ups. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF

Introduction In heart failure (HF), chronotropic incompetence is a major factor limiting cardiac output and exercise capacity. In patients carrying cardiac implantable electronic devices (CIED), accelerometer-based rate adaption (R-mode) counterbalances chronotropic incompetence during physical activity but fails to modulate heart rate under circumstances of high metabolic demand. Purpose We hypothesized that an activated R-mode, a surrogate of chronotropic incompetence, indicates worse prognosis during and after episodes of acutely decompensated HF (AHF). Methods We analysed 632 patients enrolled between 01/2014 and 02/2018 in an ongoing registry that phenotypes and follows patients admitted for AHF. We compared CIED carriers with activated R-mode (CIED-R; n=37, 16% women) with CIED carriers not in R-mode (CIED-0; n=64, 23% women) and patients without CIEDs (no-CIED; n=511, 43% women). Information on survival status was collected up to 12 months after discharge from index hospitalisation (IH). Uni- and multivariable Cox proportional hazard regression was used to identify predictors of 12-month mortality risk. Results Mean age of the study sample was 74 (11) years, 39% were women, median LVEF on admission was 51 (quartiles 32, 59) % and de novo HF was detected in 20% of all patients. Median length of IH was 10 (7, 14) days. In-hospital mortality was similar across groups, but 12-month mortality risk was affected by chronotropic incompetence as indicated by R-mode activation: age- and sex-associated hazard ratio (HR) for CIED-R was 2.61 (95% CI 1.59–4.29, p Conclusion In AHF, R-mode stimulation was associated with an increased 12-month mortality risk, independent of LVEF, type of CIED, burden of comorbidities and type of presentation. Further, increased resting heart rate at discharge predicted 12-month mortality risk only in patients without an activated R-mode. Our findings suggest that chronotropic incompetence per se worsens outcome in AHF and may not be adequately treated through accelerometer-based R-mode stimulation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Comprehensive Heart Failure Centre (CHFC) Würzburg is funded by the Federal Ministry of Education and Research, Integrated Research and Treatment Centre “Prevention of Heart Failure and its Complications”.

Background Mid-regional proadrenomedullin (MR-proADM) is a blood biomarker indicating critical illness. Its short-term prognostic relevance has been investigated in several conditions including heart failure (HF). Yet, the long-term prognostic utility is unknown. Methods We conducted a post-hoc analysis of the Extended Interdisciplinary Network for Heart Failure (E-INH) study, which investigated the long-term effects of a HF nurse-led remote patient care program (HeartNetCare-HFTM [HNC]). Patients from nine regional centers in Germany hospitalized with HF and a left ventricular ejection fraction (LVEF) Results From 919 out of the 1022 recruited patients (90%), baseline levels of MR-proADM were available: median MR-proADM 0.89 (quartiles 0.63, 1.28) nmol/l; mean age 68±12 years; 28% women; 45% in class III or IV of the New York Heart Association (NYHA) classification. Median LVEF was 31 (25, 37) %. Median levels of NT-proBNP, high sensitive C-reactive protein (hsCRP), tumor necrosis factor (TNF)-a, and interleukin-6 (IL-6) were 3045 (1087, 7759) pg/ml, 9.2 (3.3, 25.2) mg/l, 13.4 (10.4, 17.5) pg/ml, and 4.9 (2.0, 11.4) pg/ml, respectively. Higher levels of MR-proADM at baseline were associated with age, female sex, NYHA class, NT-proBNP, hsCRP, IL-6, and TNF-α, while there was an inverse association with LVEF. In the course of 10 years of follow-up, 691 (68%) patients died. Unadjusted MR-proADM strongly predicted all-cause death when used as a continuous variable (HR 1.31 per nmol/l, 95% CI 1.26–1.37; p Conclusion MR-proADM appears to be a strong and independent predictor for long-term all-cause mortality risk in HF with reduced ejection fraction (HFrEF). Therefore, assessing MR-proADM may contribute to better categorization of risk and tailored care. Its clinical utility needs to be investigated in future studies. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): BMBF

Background: Patients with established coronary artery disease or peripheral artery disease often have diabetes mellitus. These patients are at high risk of future vascular events. Methods: In a prespecified analysis of the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies), we compared the effects of rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) versus placebo plus aspirin in patients with diabetes mellitus versus without diabetes mellitus in preventing major vascular events. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included all-cause mortality and all major vascular events (cardiovascular death, myocardial infarction, stroke, or major adverse limb events, including amputation). The primary safety end point was a modification of the International Society on Thrombosis and Haemostasis criteria for major bleeding. Results: There were 10 341 patients with diabetes mellitus and 17 054 without diabetes mellitus in the overall trial. A consistent and similar relative risk reduction was seen for benefit of rivaroxaban plus aspirin (n=9152) versus placebo plus aspirin (n=9126) in patients both with (n=6922) and without (n=11 356) diabetes mellitus for the primary efficacy end point (hazard ratio, 0.74, P =0.002; and hazard ratio, 0.77, P =0.005, respectively, P interaction =0.77) and all-cause mortality (hazard ratio, 0.81, P =0.05; and hazard ratio, 0.84, P =0.09, respectively; P interaction =0.82). However, although the absolute risk reductions appeared numerically larger in patients with versus without diabetes mellitus, both subgroups derived similar benefit (2.3% versus 1.4% for the primary efficacy end point at 3 years, Gail-Simon qualitative P interaction P interaction =0.02; 2.7% versus 1.7% for major vascular events, P interaction P interaction =0.001). Conclusions: In stable atherosclerosis, the combination of aspirin plus rivaroxaban 2.5 mg twice daily provided a similar relative degree of benefit on coronary, cerebrovascular, and peripheral end points in patients with and without diabetes mellitus. Given their higher baseline risk, the absolute benefits appeared larger in those with diabetes mellitus, including a 3-fold greater reduction in all-cause mortality. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01776424.

Der vollstandige Ausfall der Informationstechnologie (IT) an einem Krankenhaus ist ein elementares Schadensereignis mit einer schweren Storung der Funktionalitat. Unmittelbare Konsequenz ist ein rasch progredienter Verlust an Behandlungskapazitat. Oberstes Ziel in einer solchen Lage ist es, dass kein Patient durch den IT-Ausfall vital gefahrdet wird und/oder bleibenden Schaden erleidet. Eine Moglichkeit, den unkontrollierten Verlust an Behandlungskapazitat zu kanalisieren, um das oben genannte Schutzziel zu erreichen, ist die sofortige Herstellung einer analog organisierten medizinischen Basisversorgung. Ein solcher Ubergang aus einem auf Hochtouren laufenden Regelbetrieb in einen reduzierten Notfallbetrieb findet in Krankenhausern taglich statt (Nachtdienst, Wochenende, Feiertag) und spiegelt die kontrollierte Reduktion der Behandlungskapazitat wider. Dieser Vorgang und das damit verbundene Prozedere sind allseits bekannt, durch Dienstplane sind die Funktionen im Voraus klar definiert, und das Zusammenspiel der Kliniken im Dienstbetrieb ist detailliert geregelt. Zur Realisierung dieser Strategie werden analoge Werkzeuge benotigt. Diese mussen allesamt zuvor mit den Kliniken und Abteilungen konzipiert, festgelegt, geubt und evaluiert werden. Letztendlich mussen alle isolierten IT-Ausfall-Konzepte zu einem kompatiblen und v. a. funktionierenden Gesamtgefuge zusammengefuhrt werden. Diese Struktur ist solange aufrechtzuerhalten, bis eine in Teilen oder komplett funktionierende IT wieder zur Verfugung steht.

About 20% of the German population have a migration background which might influence prevalence of preventable cardiovascular risk factors (CVRF).We report data of the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of inhabitants of the City of Würzburg, Germany, aged 30 to 79 years. Individuals without migration background were defined as follows: German as native language, no other native language, and/or born in Germany. All other participants were defined as individuals with migration background.Of 2473 subjects (51% female, mean age 54 ± 12 years), 291 (12%) reported a migration background: n = 107 (37%) from a country within the EU, n = 117 (40%) from Russia, and n = 67 (23%) from other countries. Prevalence of hypertension, atherosclerotic disease, and diabetes mellitus was similar in individuals with and without migration background. By contrast, prevalence of obesity and metabolic syndrome was significantly higher in individuals with migration background, with the least favourable profile apparent in individuals from Russia (individuals without vs. with migration background: obesity 19 vs. 24%, p 0.05; odds ratio: EU: 1.6, Russia: 2.2*, other countries: 0.6; metabolic syndrome 18 vs. 21%, p 0.05; odds ratio: EU: 1.2, Russia: 1.7*, other countries: 1.5; *p 0.05).Individuals with migration background in Germany might exhibit a higher CVRF burden due to a higher prevalence of obesity and metabolic syndrome. Strategies for primary prevention of heart failure may benefit from deliberately considering the migration background.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The AHF Register is supported by an unrestricted grant of Behringer Ingelheim, and grants of the German Ministry of Research and Education within the Comprehensive Heart Failure Center, Würzburg (BMBF 01E01004 and 01E01504) onbehalf AHF Registry Background & Aim Myocardial Work (MyW) analysis quantifies myocardial performance using non-invasively derived pressure-strain loops. It is considered less load-dependent than left ventricular ejection fraction (LVEF) and longitudinal strain, since it integrates blood pressure into the assessment. We assessed associations between MyW indices, natriuretic peptide (NT-proBNP), and conventional markers of systolic and diastolic cardiac function mirroring the hemodynamic changes occurring during hospitalization, in patients hospitalized for acute heart failure (AHF). Methods Consecutive patients (≥18 years) hospitalized for AHF with serial high-quality pairs of echocardiograms (i.e., early after hospitalization and prior to discharge) were eligible. Exclusion criteria were high output AHF, cardiogenic shock, and being listed for high urgency transplantation. The following MyW measures [definition in brackets] were analyzed from the stored recordings: Global constructive work (GCW) [sum of positive work performed during systolic shortening plus negative work during lengthening in isovolumetric relaxation (IVR)], global wasted work (GWW) [sum of negative work performed during systolic lengthening plus work performed during shortening in IVR], global work efficiency (GWE) [constructive work/(constructive work + wasted work)]; global work index (GWI) [total work performed from mitral valve closure to mitral valve opening]. Associations were determined using scatter plots and Pearson Product-Moment correlation coefficients. Results N = 126 patients (73 ± 12 years, 37% female) were eligible. GWI and GCW proved significantly correlated with surrogates measured both on admission and at discharge, NT-proBNP, LVEF, and e’ (Table). By contrast, GWW did not correlate with any of these variables. GWE was also correlated with NT-proBNP (and e’ at discharge), but at both time points respective correlations were more pronounced. Conclusion In patients hospitalized for AHF, GWI, GCW and GWE were associated with conventional parameters of myocardial stress and LV dysfunction. In contrast, GWW was unrelated with any of these established markers. Future studies in larger cohorts and with longer-term follow-up need to clarify to what extent might GWW carry complementary clinical and prognostic significance. Abstract Figure.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): unrestricted grant from Boehringer Ingelheim Background & Aims Since 2016, heart failure (HF) is classified using left ventricular ejection fraction (LVEF) thresholds of 40% and 50%. However, HF phenotypes may develop across the entire LVEF spectrum depending on individual patient characteristics including the risk and comorbidity profile. Using latent class analysis, we explored the sex-specific distribution of in-hospital LVEF in patients hospitalized for acute heart failure (AHF) at a tertiary care center in Germany. Methods Consecutive patients (≥18 years) hospitalized for AHF were recruited and phenotyped prospectively on a 7/24 basis. Exclusion criteria were high output heart failure, cardiogenic shock, and being listed for high urgency cardiac transplantation. LVEF was determined by transthoracic echocardiography using Simpson´s biplane or monoplane method. First, we estimated the distribution of LVEF in both sexes using histogram and kernel density estimation methods (bandwidth was selected by biased cross-validation). Then, Gaussian Mixture Models were fitted with increasing number of components. To identify the optimal number of subgroups we calculated the Bayesian Information Criterion (BIC). The minimum of the BIC criterion suggests the optimal number of subgroups for the final model. This analysis was performed on subsets including only male and only female patients. Results Out of 629 patients (39.8% female) admitted with AHF between 09/2014 and 12/2017, 93% patients received in-hospital echocardiography, and in 79.2% LVEF could be quantitatively assessed. The BIC suggested two subgroups each for male (Fig. A) and female patients (Fig. B). In the male two-subgroup model, mean ± SD LVEF values were 30 ± 9% and 59 ± 8%, thus covering 48% and 52% of the men, respectively (Fig. C). In the female two-subgroup model, respective LVEF values were 36 ± 13% and 65 ± 8%, thus covering 47% and 53% of patients (Fig. D). The "male" model suggested 45% as cut-point, whilst the "female" model suggested 51% as cut-point differentiating between lower and higher LVEF. Conclusions Using non-parametric and parametric statistical approaches, specific subgroups of patients hospitalized with AHF were identified among male and female patients hospitalized for AHF, which each time comprised subgroups with impaired vs. more preserved LVEF. Future analyses in larger AHF cohorts as well as in populations with chronic stable HF are warranted which take also into consideration sex differences in HF aetiology. Figure A) Minimum number of components (BIC) in men. B) Minimum BIC in women. C) LVEF distribution in men (2 components). D) LVEF distribution in women (2 components). The orange line indicates the respective cut-points between low and high LVEF. Abstract Figure.

Background Secondary mitral regurgitation (SMR) is common in aging population and related with poor outcome. Impact of right ventricular (RV) dysfunction with or without left ventricular (LV) dysfunction in this population remains unclear. The purpose of this study was to investigate the prevalence of isolated RV dysfunction and biventricular dysfunction, and to determine their prognostic implication in moderate to severe SMR without surgical/interventional treatment. Methods A total of 1090 consecutive moderate to severe SMR patients without surgical/interventional treatment hospitalized in our hospital center between 2009 and 2018 (aged 75±12 years, 60.4% male) were included. Transthoracic echocardiography was performed at baseline to define the cardiac morphology, function and severity of MR. Clinical and echocardiographic characteristics were analyzed. All patients completed at least 1-year clinical follow-up by reviewing the medical records or telephone interview. The primary endpoint was defined as all-cause death. Results A total of 521 patients (47.8%) reached the primary endpoint during the follow-up period [median 23 (8–40) months]. Mean left ventricular ejection fraction (LVEF) was 44.6±16.2%, and percent of patients with LVEF 40mmHg). Patients were divided into 4 subgroups: 1) preserved biventricular function: n=136 (12.5%); 2) isolated LV dysfunction: n=97 (8.9%); 3) isolated RV dysfunction: n=308 (28.3%); 4) biventricular dysfunction: n=549 (50.4%). The mortality in above group was 27.2%, 36.1%, 50.0%*† and 53.7%*†, respectively (*P Multivariable survival analysis showed that isolated LV dysfunction (adjusted HR 1.78, P=0.016), isolated RV dysfunction (HR 1.59, P=0.013), or biventricular dysfunction (HR=2.14, P Conclusions Right ventricular dysfunction is associated with significantly higher mortality in patients with secondary mitral regurgitation without surgical/interventional treatment as compared to patients with preserved biventricular function and isolated LV dysfunction. Future studies are warranted to observe if operative strategy could significantly improve the outcome in SMR patients complicating with right ventricular dysfunction. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Federal Ministry of Education and Research

Background Speckle tracking derived global longitudinal strain (GLS) could provide incremental prognostic information over left ventricular ejection fraction (LVEF) in the general population and a variety of cardiovascular diseases. Mitral annular systolic excursion (MAPSE) is a classical echocardiographic index with prognostic implication in patients with various cardiovascular diseases. Present study aimed to test the hypothesis that reduced GLS is superior to MAPSE on predicting all-cause mortality in non-ischemic heart failure patients with reduced ejection fraction. Methods A total of 952 patients with non-ischemic heart failure and reduced LVEF, who referred to our department between 2009 and 2017, were included in this study (mean age: 66±15 years, 68.8% male). All patients underwent a routine transthoracic echocardiography examination at baseline visit. Standard echocardiographic measurements were conducted according to recent guidelines. GLS was derived from the segmental averaging (18-segment) of the three apical views. M-mode MAPSE of septal and lateral walls were obtained from standard apical 4-chamber view. All patients completed at least one-year clinical follow-up by telephone interview or clinical visit. The primary endpoint was defined as all-cause mortality or heart transplantation (HTx). Results Over a median follow-up period of 27 (14–40) months, 259 (27.2%) patients died and 9 (0.9%) underwent HTx. MAPSE_septal was significantly lower in non-survivors than in survivors (6 (5–8) vs. 7 (5–8) mm, P=0.009), while LVEF (36% vs. 36%, P=0.927) and GLS (−9.6% vs. −9.8%, P=0.473) were similar between non-survivors and survivors. All-cause mortality was significant higher in patients with MAPSE_septal Multivariable Cox regression analysis showed that reduced MAPSE_septal ( Subgroup analysis showed that mild DD (n=269), reduced MAPSE_septal were significantly associated with increased all-cause mortality (adjusted HR=3.734, 95% CI=1.850–7.536, P Conclusions Septal MAPSE, but not LVEF or GLS, serves as an independent determinant of all-cause mortality in non-ischemic heart failure patients with reduced LVEF and mild diastolic dysfunction. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Federal Ministry of Education and Research

Background Previous studies have demonstrated that left ventricular ejection fraction (LVEF) is not associated with overall survival in patients with chronic heart failure (CHF). This study aimed to examine if improved EF is associated with better survival in these patients. Methods Study subjects were selected from the database in the REDEAL trial, which included all patients with CHF and a LVEF of Results At baseline, there were 522 patients with BL_EF >35% (aged 68±12 years, male 74.5%, median EF 44%) and 381 patients with BL_EF ≤35% (aged 65±13 years, male 74.5%, median EF 29%). Survival was similar between groups (76.6% vs. 73.8%, P=0.322). Over a median echocardiography follow-up of 17 months, FUP_ EF increased by 1.3% (−4.0–8.0%) in the subgroup of BL-EF>35% and increased by 11.0% (2.0–20.0%) in the subgroup of BL_EF≤35%. Survival analysis showed that absolute change in EF was significantly associated with survival in the subgroup of BL_EF≤35% but not in the subgroup of BL_EF>35%. Therefore, further analysis was conducted among patients in the subgroup of BL_EF≤35%. In this subset of BL_EF≤35%, improved EF was defined as a FUP_EF of >40%. 171 (44.9%) patients presented with improved EF, EF remained unchanged or reduced in the rest 210 patients (55.1%, FUP_EF≤40%). Patients with improved EF was associated with better survival over a median clinical follow-up of 19 (11–32) months (80.7% vs. 68.1%, P=0.001). Multivariable Cox regression analysis showed that improved EF remained an independent determinant of overall survival after adjusted for potential clinical covariates including age, sex, diabetes, hyperuricemia, renal dysfunction, coronary artery bypass grafting, sleep-disordered breathing, and prior ICD or CRT_D implantation (HR 0.59, 95% CI 0.38–0.91, P=0.018). In this subgroup of BL_EF≤35%, age and sex-independent determinants of improved EF included without prior myocardial infarction (OR 0.40, 95% CI 0.24–0.67, P Conclusions Longitudinal improvement in LVEF is significantly associated with survival benefit in the subgroup of baseline EF≤35% but not in the subgroup of baseline EF>35%. In the subgroup of baseline EF≤35%, improved LVEF remains an independent determinant of survival benefit Determinants of improved LVEF in HF patients with baseline EF≤35% include without myocardial infarction, without ICD implantation, and smaller LV chamber at baseline. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by the German Federal Ministry of Education and Research

Background Mitral annular plane systolic excursion (MAPSE) derived from M-mode echocardiography is a classical risk factor of clinical outcome in heart failure patients. Two-dimensional-echocardiography (2DE) derived global longitudinal strain (GLS) is also related to outcome in patients with heart failure. This study aimed to compare the prognostic performance between GLS and MAPSE in ischemic heart failure patients with reduced ejection fraction. We sought to test the hypothesis that GLS might be superior to MAPSE as a risk stratification marker in these patients. Methods In total, 1277 ischemic heart failure patients with reduced left ventricular ejection fraction (LVEF Results At baseline visit, mean age was 70±11 years and 79.6% were men. NYHA class III-IV were identified in 33.5% of patients. Coronary artery disease was confirmed by coronary angiography. 63.0% patients had a history of myocardial infarction, 32.1% underwent PCI, and 16.8% underwent coronary artery bypass grafting. Over a median follow-up period of 26 (14–39) months, 369 (28.9%) patients died and 5 (0.4%) underwent HTx. Median LVEF was 39% (32–45%), and there were 48.0% patients with LVEF between 40–49%, 32.3% patients with LVEF between 30–49% and 19.7% patients with LVEF Clinical covariates significantly associated with all-cause mortality in this cohort included age (HR=1.048), NYHA class III-IV (HR=1.800), AF (HR=1.567), diabetes (HR=1.262), dyslipidemia (HR=0.657), hyperuricemia (HR=1.861), peripheral vascular disease (HR 1.858), chronic respiratory diseases (HR=1.680), and renal dysfunction (HR=2.705). Multivariable Cox regression analysis showed that reduced MAPSE_Avg ( Conclusions Both 2DE-guided GLS and MAPSE could provide additional prognostic information in ischemic heart failure patients with reduced LVEF. Prognostic performance of GLS, MAPSE, and LVEF is similar in ischemic heart failure patients with reduced LVEF. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The German Federal Ministry of Education and Research

The complete blackout of information technology (IT) in a hospital represents a major incident with acute loss of functionality. The immediate consequence is a rapidly progressive loss of treatment capacity. The major priority for the acute management of such an event is to keep patients safe and prevent life-threatening situations. A possibility to channel the uncontrolled loss of treatment capacity in order to achieve the aforementioned protective target is the immediate organization of an analog system for baseline emergency medical care. The switch over from a fully operational routinely functioning system to a reduced emergency state occurs daily in hospitals (night shift, weekends, public holidays) and reflects the controlled reduction of the treatment capacity. This process and the procedures associated with it are universally known, the functions are clearly defined and planned in advance by duty rotas and the interplay of clinics in the organizational schedule is regulated in detail. In order to accomplish this strategy analog instruments are necessary. These must all be conceived, established, practiced and evaluated in advance with the clinics and departments. Ultimately, all isolated IT blackout concepts must be amalgamated into a compatible and functioning total framework. This structure must be maintained for as long as a partially or totally functioning IT has been reinstated.

Additional file 2. EuroAspire IV Germany I Follow-up interview I Questionnaire.

Additional file 1: Supplemental Table 1. Current smokers at index event* (n = 124) stratified by their participation at telephone-based follow-up interview. Supplemental Table 2. Clinical data of current smokers at index event* (n = 104) stratified by their smoking status reported 3.5 years later. Supplemental Table 3. Factors associated with smoking cessation (block-wise multivariable logistic regression).

Background Concomitant aortic stenosis (AS) and functional mitral regurgitation (FMR) are common in patients with left ventricular dysfunction. We evaluated the impact of significant valve diseases on outcome of patients with reduced left ventricular ejection fraction (HFrEF, LVEF Methods A total of 1264 consecutive HFrEF patients referred to our department between 2009 and 2017 were screened. Transthoracic echocardiography was performed at baseline visit in all patients. Patients with primary MR or received mitral valve operation before or after baseline visit (n = 64) as well as patients underwent aortic valve replacement (AVR) before baseline visit (n = 66) were excluded. Finally, 1134 HFrEF patients were included for final analysis, and all completed a median clinical follow-up of 26 (12-40) months by medical record review or telephone interview. The primary endpoint was all-cause mortality or heart transplantation (HTx). Results Moderate or severe FMR or AS was detected in 902 (79.5%) and in 119 (10.5%) patients by echocardiography, respectively. Of patients with significant AS, 47 patients underwent AVR shortly after baseline visit. In total, 353 (31.2%, including HTx n = 11) HFrEF patients died or underwent HTx during follow-up. Age, body mass index, diabetes, atrial fibrillation, coronary artery disease, chronic respiratory diseases, and renal dysfunction (all P Multivariable Cox regression analysis showed significant FMR remained as an independent determinant of all-cause mortality/HTx in patients with HFrEF after adjusted for above mentioned confounders (HR 1.39, 95% CI 1.02-1.90, P = 0.035). Patients with significant AS without AVR faced increased risk of all-cause mortality/HTx as compared to patients without significant AS (HR 2.34, P In the subgroup of HFrEF patients with significant FMR, significant AS without AVR was independently associated with increased all-cause mortality/HTx as compared to patients without significant AS (HR 2.30, P Conclusion Moderate to severe FMR and/or AS is incrementally related to higher all-cause mortality/HTx in HFrEF patients. AVR could significantly improve the survival of HFrEF patients with concomitant significant AS and FMR.

OnBehalf AHF Registry Background & Aim A novel echocardiographic method to non-invasively determine left ventricular (LV) myocardial work (MyW) based on speckle-tracking derived longitudinal strain and blood pressure has recently been validated against invasive reference measurements. MyW is considered less load-dependent than LV ejection fraction (EF) and LV longitudinal strain. We investigated MyW indices in patients with reduced ejection fraction (LVEF Methods The AHF registry is a monocentric prospective follow-up study that comprehensively phenotypes consecutive patients hospitalized for AHF. Echocardiography was performed on the day of admission. MyW assessment was performed off-line using EchoPAC (GE, version 202). Here we present MyW indices and performed two-sided t-tests to analyze differences in numerical baseline covariates. Results We analyzed the echocardiograms of 94 AHF patients (72 ± 10 years; 36% female). 46 patients (49%) had an LVEF Conclusions This analysis in patients with AHF exhibited marked differences in MyW indices according to subgroups with HFrEF and HFpEF, thus adding information to the classical measures of LV function. Future research has to determine whether constructive and/or wasted MyW are valuable diagnostic or therapeutic targets in patients with AHF. Abstract P803 Figure.

Funding Acknowledgements German Research Foundation (BMBF 01EO1004 and 01EO1504) OnBehalf Acute Heart Failure Registry Background & Aim A new, less load-dependent echocardiographic tool to determine left ventricular (LV) myocardial work (MyW) based on longitudinal strain and blood pressure has recently been introduced and validated against invasive measurements. We investigated the impact of change in N-terminal pro-B-natriuretic peptide (NT-proBNP; i.e. surrogate of recompensation) during the hospital phase on changes in MyW (global work efficiency [GWE]; global constructive work [GCW]; and global wasted work [GWW]), in patients admitted for acutely decompensated heart failure (AHF). Methods The AHF registry is a monocentric prospective follow-up study that comprehensively phenotypes consecutive patients hospitalized for AHF. Echocardiography was performed and NT-proBNP measured on the day of admission and within 72 hours prior to discharge. MyW assessment was performed off-line using EchoPAC (GE, version 202). In order to quantify changes in MyW and NT-proBNP, we used the respective discharge-to-admission ratio (DAR). Local polynomial regression was applied to model these associations in patients with LV ejection fraction (LVEF) Results We analyzed 111 patients: mean age 73 ± 11 yrs; 32% female; 46 patients (41.4%) with LVEF Conclusions Our preliminary analysis indicates that a decrease in NT-proBNP may be associated with an improvement in GCW and GWE in patients with reduced LVEF, while these parameters were non-responsive in the other patient group. Although these results require confirmation in a larger cohort, they encourage further research in to MyW as a less load-dependent measure of LV function, shedding new light on echocardiographically manifest alterations of myocardial texture and the timing of healing processes after an acute cardiac event. Figure Discharge-to-admission ratio (DAR) of A) global work efficiency (GWE, >1= improvement), B) global constructive work (GCW, >1= improvement), and C) global wasted work (GWW, Abstract 411 Figure

Funding Acknowledgements German Research Foundation (BMBF 01EO1004 and 01EO1504) OnBehalf AHF Background & Aims Heart failure (HF) is classified according to left ventricular (LV) ejection fraction (EF) into heart failure with reduced (HFrEF) and heart failure with preserved EF (HFpEF). In 2016, a third subgroup, heart failure with mid-range EF (HFmrEF), has been introduced by the ESC. We aimed to identify the number of naturally occurring heart failure subgroups according to LVEF using latent class analysis. Methods The AHF registry is a monocentric prospective follow-up study that comprehensively phenotypes consecutive patients hospitalized for acute heart failure (AHF). Echocardiography was performed within 72 hours prior to discharge. We first estimated the distribution of LVEF using histogram and kernel density estimation methods (bandwidth was selected by biased cross-validation). We then fitted Gaussian Mixture Models with increasing number of components to the data. To select the optimal number of components we calculated the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC). The minimum of each criterion suggests the optimal number of components for the final model. The BIC requires more data to select more components than the AIC and hence is more conservative. Finally, for each criterion the optimal model was determined. Results Out of 629 patients, 585 (93%) patients received echocardiography and in 498 (79.2%) the LVEF could be calculated using Simpson´s biplane or monoplane method. The BIC suggested two (panel B), the AIC three components (panel A). In the two-component model, mean ± SD LVEF values were 60.2 ± 8.7% and 30.8 ± 9.6%, thus covering 56% and 44% of patients, respectively (panel D). In the three-component model, respective LVEF values were 64.9 ± 6.2%, 50.2 ± 6.9%, and 28.4 ± 8.1%, thus covering 35%, 27%, and 38% of patients (panel C). Conclusions Our analysis suggests that LVEF in patients with AHF is not a continuum, but clusters in two or three subgroups. In line with the HFrEF and HFpEF classification, the more conservative model suggested two subgroups of LVEF. The less restrictive model allowed for a third subgroup, compatible with HFmrEF. Future analyses will better characterize the identified subgroups. Abstract P1432 Figure

Background The impact of right ventricular (RV) dysfunction on outcome of heart failure patients with mid-range left ventricular ejection fraction (HFmrEF, 40-49%) is not well characterized yet. In this study, we observed the association between echocardiography defined RV dysfunction with outcomes and if the outcome was jointly affected by co-existed chronic respiratory diseases (CRD: asthma, chronic obstructive pulmonary disease, occupational lung diseases, sleep apnea syndrome) in HFmrEF patients Methods 1090 HFmrEF patients referred to our department between 2009 and 2017 were included in this study. Baseline demographic and clinical data were obtained by reviewing the medical records. All patients subsequently completed a median clinical follow-up of 26 (15-38) months. The primary endpoint was all-cause mortality or heart transplantation (HTx). Right heart morphology and function were assessed with the use of multiple echocardiographic parameters, including right atrial area (RAA), RV mid diameter (RVD), tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP). Results Mean age was 69 ± 13 years and 73.4% were male. The proportion of NYHA functional class III or IV was 24.8%. CRD was identified in 209 (19.2%) patients. 280 patients (25.7%, without CRD: 204, with CRD: 76) died and 2 patients (without CRD) underwent HTx. All-cause mortality/HTx was significantly higher in HFmrEF patients with CRD than without CRD (36.4% vs. 23.4%, P Besides CRD, Cox regression analysis showed that age, body mass index, and cardiac risk factors and comorbidities including diabetes, atrial fibrillation, dyslipidemia, coronary artery disease, kidney dysfunction (eGFR Patients without CRDs were further grouped into those with normal (sPAP ≤ 40mmHg and TAPSE≥14mm, n = 513); mild to moderate (sPAP > 40mmHg or TAPSE 40mmHg and TAPSE Conclusions Increased sPAP and reduced TAPSE are independent determinants of all-cause mortality in HFmrEF patients without CRD, and sPAP is an independent determinant of all-cause mortality in HFmrEF patients with CRD. Moreover, HFmrEF patients with severe RV dysfunction face a 2-fold increased all-cause mortality, as compared to patients with normal RV function and no CRD.

Die Deutsche Gesellschaft fur Kardiologie (DGK) und die Deutsche Gesellschaft fur Thorax‑, Herz- und Gefaschirurgie (DGTHG) haben 2016 die gemeinsame Empfehlung ausgesprochen, Netzwerke einzurichten und zu zertifizieren, in denen uberregionale Zentren mit Schwerpunktkliniken und niedergelassenen Kardiologen kooperieren, um die Versorgung von Patienten mit Herzinsuffizienz sektoren- und klinikubergreifend zu verbessern. Bisher haben sich uberwiegend uberregionale Herzinsuffizienzzentren zertifizieren lassen, aber das Interesse niedergelassener Kardiologen und regionaler Schwerpunktkliniken wachst, und eine flachendeckende Etablierung von Herzinsuffizienznetzwerken ruckt in den Bereich des Moglichen. In diesem Ubersichtsartikel werden die Hintergrunde, die Gegenwart und die Zukunft der Netzwerke dargestellt und Losungsansatze zum besseren Networking diskutiert.

Im Jahr 2017 wurde die Nationale VersorgungsLeitlinie (NVL) „Chronische Herzinsuffizienz“ veroffentlicht. Ihre Empfehlungen weichen teilweise von den „2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure“ (ESC-Leitlinie) der European Society of Cardiology ab. Bei welchen Themen und warum unterscheiden sich Empfehlungen der NVL von denen der ESC-Leitlinie? Die ESC-Leitlinie diente als eine der Grundlagen fur die Empfehlungen der NVL zu medikamentoser und invasiver Therapie der chronischen Herzinsuffizienz. Zusatzlich wurden 14 systematische Recherchen durchgefuhrt. Ein multidisziplinares Gremium aus Vertretern von 17 Fachgesellschaften und Organisationen bewertete die Evidenz und konsentierte in einem formalen Verfahren die Empfehlungen. Abweichungen ergaben sich, wenn die Leitliniengruppe die zugrunde liegende Evidenz von der ESC-Leitlinie abweichend bewertete, wenn eigene Recherchen zusatzliche Evidenz erbrachten und/oder wenn Aspekte adressiert werden sollten, die in den Empfehlungen der ESC-Leitlinie nicht vorkommen. Dies betraf u. a. die Empfehlungen zum Medikament Sacubitril/Valsartan, zur kardialen Resynchronisationstherapie (CRT) bei Patienten mit Arrhythmien und zum Einsatz implantierbarer Kardioverter/Defibrillatoren (ICD) zur Primarprophylaxe des plotzlichen Herztods. Die Abweichungen betrafen beispielsweise den Empfehlungsgrad, die Indikation fur bestimmte Patientensubgruppen oder Hinweise zu Sicherheits- und Versorgungsaspekten. Im Vergleich zur ESC-Leitlinie bewertete die NVL einige Therapieverfahren zuruckhaltender. Fur den Anwender ergibt sich daraus die Notwendigkeit, anhand der begrundenden Texte zu entscheiden, an welcher der Leitlinien er sich orientiert.

Die Herzinsuffizienz ist eine fuhrende Todesursache und haufigster Anlass fur Hospitalisierungen in Deutschland, obwohl die therapeutischen Moglichkeiten v. a. bei reduzierter Pumpfunktion in den letzten Jahren erheblich zugenommen haben. Meist wird, bevor sich eine Herzinsuffizienz auch klinisch manifestiert, eine Phase des kardialen Remodellings durchlaufen. Remodelling wurde ursprunglich morphologisch und mechanisch definiert, vollzieht sich allerdings auch auf zellularer und molekularer Ebene. So sind Heilungsvorgange nach einem akuten Myokardinfarkt gepragt von Inflammation, zellularer Migration und Narbenbildung. Das kardiale Remodelling wird zudem von systemischen Anpassungsvorgangen begleitet. Ein primares Ziel der Therapie sollte daher sein, das Remodelling zu verhindern. Wichtig sind hierfur die moglichst schnelle Diagnostik und Therapieeinleitung. Fruhzeitige Reperfusionstherapie limitiert die Infarktgrose und tragt dazu bei, die linksventrikulare Pumpfunktion zu erhalten. Als medikamentose Standardtherapie sind nach Myokardinfarkt Angiotensinkonversionshemmer, Angiotensin-1-Rezeptor-Blocker und Betablocker etabliert. Auch Mineralokortikoidrezeptorantagonisten zeigen gunstige Wirkungen. Spezifische Medikamente, die darauf abzielen, schon in die Heilung des Infarkts einzugreifen, sind in Entwicklung.

Background and Purpose-Tricuspid valve (TV) apparatus parameters can vary significantly with demographic and anthropometric factors and could be useful for clinical decision making. Our aim was to (1) establish the reference values for TV apparatus parameters using transthoracic three-dimensional (3D) echocardiography; (2) investigate the influence of age, sex, and body size on TV anatomy. Methods-A total of 180 healthy subjects referred in 2015 to our institution for a screening transthoracic echocardiography were enrolled (mean age 49.7+17.4 years, range 20 to 80 years: 30 subjects per age decade were included in the study, 15 for each gender). A real-time zoom 3D image of the TV and full volume 3D data set were collected from an apical window including TV using Philips iE33 and GE Vivid E9 Ultrasound Machines. After acquisition, the 3D data sets were analysed using 3D Qlab and EchoPAC PC softwares. The volumetric data set was analysed with multiplanar reformatting function to obtain three simultaneous orthogonal 2D slices (sagittal, coronal and axial planes). The following TV parameters were obtained and measured: 1. the 3D diastolic annular diameters (Major and Minor diameters); 2. the 3D diastolic annular area (TDAA); 3. the Tricuspid annular fractional area changes (TAFAC). Results are presented as mean ± SD. Differences between and among groups were tested for significance using the independent samples t-test and ANOVA test for continuous variables. Univariate Pearson correlation was used to assess the relation between these parameters and age, and body size. A p 0.05) and normalized MDD (18.1±2.4 vs 18.4±2.3 mm/m2, p>0.05) did not differ significantly between males and females. TTDAA and TAFAC in overall population were 76.7±17.3 mm2 and 29.6±8.6%. TDAA was significantly different between males and females (82.5±18.3 vs 69.7±13.0 mm2, respectively; p 0.05). After normalization for BSA, TDAA in overall population was 43.3±9.0 mm2/m2. Also normalized TDAA was significantly different between males and females (44.4±9.4 vs 42.0±8.4 mm2/m2, p < 0.05). mDD, MDD, TDAA and TAFAC showed no correlation with age (r = 0.16, p 0.04; r = 0.028, p 0.7; r = 0.17, p 0.27; r = 0.16, p 0.16; respectively). Conclusion- This study can provide normal reference values for TV anatomic parameters that may be useful in the clinical practice, considering the effects of age, sex, and body size.

Asymptomatic patients may exhibit symptoms during objective exercise testing, but whether symptoms are due to the obstructively of the valve (typified by the mean gradient) or underlying ventricular function remains unknown. While the mean gradient is an easy parameter to measure no consensus about the measurement of contractile reserve exists. Longitudinal abnormalities may occur in the presence of a normal ejection fraction and the augmentation of these parameters is poorly described. To obtain an objective regarding patients exercise ability is best determined using cardiopulmonary exercise testing. We therefore examined echocardiographic predictors of exercise ability during cardiopulmonary exercise testing.24 asymptomatic patients with moderate to severe or severe aortic stenosis and preserved ejection fraction underwent stress echocardiography with simultaneous cardiopulmonary exercise testing. The primary assessment of exercise ability was the VO2peak and OUES. Echocardiography was measured at rest and during maximal exercise (defined as RER > 1)OUES and VO2peak showed a poor relationship with conventional parameters of severity including peak and mean gradients, AVA and dimensionless index, resting systolic function (by EF and TDI). During exercise systolic augmentation had a good relationship with exercise ability but the exercise mean gradient and exercise LVEF did not.Longitudinal systolic function and particularly systolic augmentation is the strongest predictor of exercise ability when compared to conventional measures of severity.VO2peakOUESS' exerciseRho=0.69 (p=0.001)R= 0.71 (p=0.001)S' restRho=0.52 (p=0.01)R= 0.44 (p=ns)Rest AV max VRho= 0.09 (p=ns)R= -0.08 (p=ns)Rest AV mean PGRho= 0.34 (p=ns)R=-0.10 (p=ns)Exercise AV max VRho=0.43 (p=0.05)R=0.23 (p=ns)Exercise AVmean PGRho= 0.51 (p=0.001)R=0.26 (p=ns)Rest AVARho=0.40 (p=ns)Rho=0.46 (p=0.04)Dimensionless indexRho=0.15 (p=ns)R=0.13 (p=ns)LVEF restRho=-0.18 (p=ns)R=-0.32 (p=ns)LVEF exerciseRho=0.18 (p=ns)R=0.17 (p=ns)S' - systolic velocity; V - velocity; AV - aortic valve; AVA- aortic valve area; LVEF - left ventricular ejection fraction.

Background Depression is frequent in heart failure (HF) and associated with adverse clinical outcomes. The randomized MOOD-HF trial showed that in depressed patients with systolic heart failure (HF) the selective serotonin reuptake inhibitor escitalopram (E) improved neither survival nor depression compared to placebo (P). The hypothalamic-pituitary-adrenocortical axis is known to be altered in depression or HF. This MOOD-HF substudy aimed to clarify whether circadian salivary cortisol levels (SCL) were predictive of adverse events in depressed MOOD-HF participants and whether outcomes differed according to treatment with E. Methods MOOD-HF participants (all suffering from symptomatic systolic HF with left ventricular ejection fraction (LVEF) Results In the total study cohort (146 patients on E, 147 on P) median morning SCL at BL was 0.210 μg/dL (IQR 0.141–0.338 μg/dL) and median evening (pm) SCL 0.067 μg/dL (0.036–0.128 μg/dL, p During 12 months follow-up the composite endpoint (all-cause death or rehospitalization) occurred least in E-treated patients with low pm-SCL and most often in E-treated patients with high pm-SCL (HR 2.02, 95% CI 1.12–3.65, p=0.010); patients on P had comparable event rates irrespective of BL pm-SCL (Figure A). Thus, numerically patients on E with low BL pm-SCL had lower event rates compared with corresponding P-treated patients (HR 0.76 (0.41–1.40, p=0.796)), while patients with high BL pm-SCL had higher event rates (HR 1.29 (0.74–2.24, p=0.799)) than corresponding P-treated patients. Patients with circadian SCL changes above the median receiving P experienced the composite primary endpoint least, while both subgroups with circadian SCL changes below the median and also patients with circadian SCL changes above the median on E had higher event rates (HR 0.66 (0.45–0.97, p=0.039), Figure B). Conclusion In depressed patients with systolic HF high pm-SCL are associated with more severe disease (depression and cardiac dysfunction). Extending primary MOOD-HF results indicating unfavourable outcomes related to E, the current findings suggest a SCL x treatment interaction with higher event rates in (sicker) patients with high pm-SCL and lower event rates in (less sick) patients with low pm-SCL when treated with the antidepressant. Low circadian changes of SCL were always associated with higher event rates. Acknowledgement/Funding BMBF (Grant 01 KG0702) and Lundbeck A/S Denmark

Heart failure (HF) is the leading cause of mortality and morbidity in Western countries. In the past two decades, evidence for the clinical relevance of GPCR-autoimmunity in human HF has substantially increased. Stimulating autoantibodies targeting the second extracellular loop (ECII) of the cardiac beta1-adrenoceptor (beta1-aabs) have been claimed to be involved in the pathogenesis of HF and to increase the risk of cardiovascular death by three-fold. Still, the events triggering the formation of beta1-aabs and their impact on HF-progression are unknown. Methods In total 13 University Hospitals (12 German, 1 Serbian) prospectively recruited 226 patients (pts.) with a first acute myocardial infarction (FAMI), and 140 pts with acute (biopsy- or cMRI-proven) myocarditis (AMitis) into the Etiology, Titer-Course and effect on Survival of cardiac autoantibodies-study (ETiCS-study). This study aimed to investigate whether the presentation of cardiac membrane antigens (e.g., the beta1-adrenoceptor) following cardiac necrosis/inflammation triggers the formation of beta1-aabs. At baseline (BL) and three follow-ups (Fup1–3), blood was sampled to analyze the time-course of beta1-aabs. Beta1-aab titers were measured by FACS using Dyna-beads® M-270-Epoxy coated with increasing amounts of beta1-ECII-peptides (2.5–100 μg/ml), checked versus scrambled peptides (a mixture of same amino-acids). After reacting, the samples were measured by FACScan flow-cytometry; obtained data were analyzed with FlowJo (Treestar). When half-maximal binding was calculable the serum was classified beta1-aab-positive. Results From n=366 pts (226 FAMI/140 AMitis) recruited into the ETiCS-study 45 pts had to be excluded because of unperformed cMRI's; 46 pts stopped the study before Fup-1 (month 3). Only 180/226 FAMI- and 98/140 AMitis-pts had complete Fup1–3 (after 3, 6, and 12 months with clinical assessment, echocardiograms, and cMRI's at BL and Fup-3). In all valid ETiCS-pts (197 FAMI-/123 AMitis-pts) the titer-course of beta1-aabs was compared with the development of echo-LVEF. Relevant (high-affinity) beta1-aab-titers were detected in ∼31% (37/123) of the AMitis-pts compared to only ∼21% (42/197) of the FAMI-pts. In aab-positive AMitis-pts echo-LVEF did not recover and was always significantly inferior to aab-negative AMitis-pts (BL: 38 vs. 49% LVEF; Fup-3: 49 vs. 64% LVEF) whereas such a difference was not noted in FAMI-pts. In addition, aab-positive AMitis-pts had higher NT pro-BNP-, renin-, and aldosterone-levels than aab-negative AMitis-pts. Conclusion The first evaluation of the completed ETiCS-study clearly suggests that acute microbial-induced rather than post-infarction myocardial inflammation triggers the formation of clinically relevant beta1-aabs. AAb-positive AMitis-patients might profit from early intensification of standard HF-therapy (including early beta-blockade) and/or novel antibody-directed experimental therapies which are currently developed. Acknowledgement/Funding BMBF Grant FKZ 01ES0816

Background Right ventricular (RV) dysfunction is common in heart failure patients. In the present study, we determined the impact of echocardiography defined RV dysfunction on outcomes in heart failure patients with reduced ejection fraction ( Methods A total of 1264 HFrEF patients (Mean age: 68±13 years; male: 76.3%) referred to our department between 2009 and 2017 were included. Baseline demographic and clinical data were obtained by reviewing the medical records. All patients subsequently completed a median clinical follow-up of 26 (12–40) months by medical record review or telephone interview. The primary endpoint was all-cause mortality or heart transplantation (HTx). Right heart morphology and function were assessed by multiple echocardiographic parameters, including right atrial area (RAA), RV mid diameter (RVD), tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP). Results The proportion of NYHA functional class III-IV was 42.2%. Mean LVEF was 29.4±7.0%. CRDs was identified in 276 (21.8%) patients, 399 (30.5%, without CRDs n=290, with CRDs n=109) patients died (n=386) or underwent HTx (n=13). All-cause mortality/HTx was significantly higher in HFrEF patients with CRDs than without CRDs (39.5% vs. 29.4%, P=0.001). Cox regression analysis showed that age, BMI, and other cardiac risk factors and comorbidities including diabetes, atrial fibrillation, coronary artery disease, kidney dysfunction, and anemia were associated with all-cause mortality/HTx (all P With the cut-off values (sPAP>40mmHg, TAPSE25cm2, and RVD>36mm) derived from the 3rd quartiles, patients without CRDs were further grouped as normal RV function (all 4 parameters normal, n=427); mild to moderate RV dysfunction (1 or 2 parameters abnormal, n=467) and severe RV dysfunction (≥3 parameters abnormal, n=94). Risk of all-cause mortality/HTx was significantly higher in HFrEF patients with severe (51.1%) and mild to moderate RV dysfunction (34.7%) as compared to patients with normal RV function (18.7%, severe vs. normal: HR 1.616, 95% CI 1.232–2.119, P=0.001; mild to moderate vs. normal HR: 2.657, 95% CI 1.845–3.824, P Conclusions RV dysfunction is significantly associated with increased all-cause mortality in HFrEF patients without CRDs. Increased sPAP, RAA, RVD and decreased TAPSE are independent determinants of worse outcomes in HFrEF patients without CRDs, but not in HFrEF patients with CRDs.

Background The impact of right ventricular (RV) dysfunction on outcome of heart failure patients with mid-range left ventricular ejection fraction (HFmrEF, 40–49%) is not well characterized yet. In this study, we observed the association between echocardiography defined RV dysfunction with outcomes and if the outcome was jointly affected by co-existed chronic respiratory diseases (CRD: asthma, chronic obstructive pulmonary disease, occupational lung diseases, sleep apnea syndrome) in HFmrEF patients Methods 1090 HFmrEF patients referred to our department between 2009 and 2017 were included in this study. Baseline demographic and clinical data were obtained by reviewing the medical records. All patients subsequently completed a median clinical follow-up of 26 (15–38) months. The primary endpoint was all-cause mortality or heart transplantation (HTx). Right heart morphology and function were assessed with the use of multiple echocardiographic parameters, including right atrial area (RAA), RV mid diameter (RVD), tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (sPAP). Results Mean age was 69±13 years and 73.4% were male. The proportion of NYHA functional class III or IV was 24.8%. CRD was identified in 209 (19.2%) patients. 280 patients (25.7%, without CRD: 204, with CRD: 76) died and 2 patients (without CRD) underwent HTx. All-cause mortality/HTx was significantly higher in HFmrEF patients with CRD than without CRD (36.4% vs. 23.4%, P Besides CRD, Cox regression analysis showed that age, body mass index, and cardiac risk factors and comorbidities including diabetes, atrial fibrillation, dyslipidemia, coronary artery disease, kidney dysfunction (eGFR Patients without CRDs were further grouped into those with normal (sPAP≤40mmHg and TAPSE≥14mm, n=513); mild to moderate (sPAP>40mmHg or TAPSE40mmHg and TAPSE Conclusions Increased sPAP and reduced TAPSE are independent determinants of all-cause mortality in HFmrEF patients without CRD, and sPAP is an independent determinant of all-cause mortality in HFmrEF patients with CRD. Moreover, HFmrEF patients with severe RV dysfunction face a 2-fold increased all-cause mortality, as compared to patients with normal RV function and no CRD.

Background Extensive studies have demonstrated prognostic impact of echocardiographic defined diastolic dysfunction (DD) in patients with preserved as well as reduced left ventricular ejection fraction (LVEF). Nevertheless, it remains controversial whether evaluation of DD could provide additional prognostic information in heart failure (HF) patients with impaired systolic function. The purpose of present study, therefore, is to investigate the prognostic impact of echocardiography-defined DD on survival in HF patients hospitalized in our centre from 2009 to 2017 with mid-range LVEF (HFmrEF, LVEF 41–49%) and reduced LVEF (HFrEF, LVEF Methods A total of 2018 patients with echocardiography-evidenced LVEF Results The mean age was 69±13 years in the HFmrEF group and 68±13 years in the HFrEF group. All-cause mortality/HTx rate was significantly higher in the HFrEF (all-cause death n=318 and HTx n=11, 30.9%) group than in patients with HFmrEF (all-cause death n=235 and HTx n=2, 24.9%, P=0.003). All-cause mortality/HTx rate increased in proportion to DD severity in HFmrEF patients: 17.1% (54/315) in the mild DD group, 25.4% (115/452) in the moderate DD group, and 37.0% (68/184) in the severe DD group (P14 (HR 1.41, 95% CI 1.06–1.89, P=0.020) and peak tricuspid regurgitation velocity (TRVmax) >2.8m/s (HR 1.75, 95% CI 1.33–2.29, P14 (HR 1.48, 95% CI 1.08–2.04, P=0.015) remained as an independent determinant of all-cause mortality/HTx in patients with HFrEF after adjustment for clinical and other echocardiographic confounders. Besides DD-related parameters, after adjustment with age and sex, lower tricuspid and mitral annular plane systolic excursions (TAPSE and MAPSE) were also closely related to higher mortality/HTx rate in both HFmrEF and HFrEF patients. Figure 1. Kaplan-Meier curves Conclusion Our results indicate that all-cause mortality/HTx rate increases in proportion to DD severity in both HFmrEF and HFrEF patients.

Background Anaemia (A) and renal impairment (RI) are frequent comorbidities in heart failure (HF) and known to impact adversely on outcome. Purpose In this post-hoc analysis, we allocated HF patients from 4 studies of the Competence Network Heart Failure at baseline to subgroups according to American Heart Association/ American College of Cardiology (AHA/ACC) HF criteria and compared prevalence rates of A and RI at each HF stage and the individual and cumulative long-term impact of these comorbidities on all-cause mortality (ACM) over a 5-year follow-up (FUP) period. Methods To study A and RI prevalence, we performed a cross-sectional analysis in 3344 patients (40.6% female, 65.6±11.2 years, 7.8, 32.3, 38.5, and 21.4% in stages A, B, C1 and C2/D, respectively). FUP data were available for 2496 patients (37.4% female, 66.0±11.3 years, 8.1, 35.3, 32.9, and 23.7% in stages A, B, C1 and C2/D, respectively). A was defined as haemoglobin Results Overall prevalence of A in the stages A, B, C1, and C2/D was 3.1, 7.6, 16.5, and 29.8% (p Conclusions Our results demonstrate a high prevalence in particular of RI even in asymptomatic HF stages and significant individual and cumulative long-term adverse effects of A and RI across the entire HF continuum. This includes also the clinically asymptomatic HF stages. Both prevalence and the individual and cumulative negative prognostic impact increase with increasing HF severity calling for careful consideration and management of these comorbidities in the frame of holistic HF care.

WOS: 000468732700018, PubMed ID: 31054483, Background and aims: One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Methods: Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. Results: At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. Conclusions: The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient., ESC - EORP; AmgenAmgen; Eli LillyEli Lilly; PfizerPfizer; SanofiSanofi-Aventis; Ferrer; Novo NordiskNovo Nordisk, The EUROASPIRE V survey was carried out under the auspices of the ESC - EORP. Since the start of EORP, the following companies have supported the programme: Amgen, Eli Lilly, Pfizer, Sanofi, Ferrer and Novo Nordisk. The sponsors of the EUROASPIRE surveys had no role in the design, data collection, data analysis, data interpretation, decision to publish, or writing the manuscript.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously detected in the water column, associated with particulate matter or in the tissue of marine organisms such as molluscs. PAH exposure and their resultant bioaccumulation in molluscs can cause a range of serious physiological effects in the affected animals. To examine the molecular response of these xenobiotics in bivalves, Sydney rock oysters (Saccostrea glomerata) were exposed to pyrene and fluoranthene for seven days. Chemical analysis of the soft-tissue of PAH stressed S. glomerata confirmed that pyrene and fluoranthene could be bioaccumulated by these oysters. RNA-Seq analysis of PAH-exposed S. glomerata showed a total of 765 transcripts differentially expressed between control and PAH-stressed oysters. Closer examination of the transcripts revealed a range genes encoding enzymes involved in PAH detoxification (e.g. cytochrome P450), innate immune responses (e.g. pathogen recognition, phagocytosis) and protein synthesis. Overall, pyrene and fluoranthene exposure appears to have resulted in a suppression of pathogen recognition and some protein synthesis processes, whereas transcripts of genes encoding proteins involved in clearance of cell debris and some transcripts of genes involved in PAH detoxification were induced in response to the stressors. Pyrene and fluoranthene exposure thus invoked a complex molecular response in S. glomerata, with results suggesting that oysters focus on removing the stressors from their system and dealing with the downstream effects of PAH exposure, potentially at the exclusion of other, less immediate concerns (e.g. protection from infection).

Herzinsuffizienz (HI) geht mit hoher Mortalitat und haufigen Hospitalisierungen einher; Pravalenz und Krankheitskosten steigen kontinuierlich. Zur Optimierung der Versorgung bei HI mussen strukturierte sektorenubergreifende Kooperationen etabliert und die Behandlungsqualitat und -kontinuitat sichergestellt werden. Kooperationspartner sind Hausarzte, kardiologische Praxen, Abteilungen regionaler Krankenhauser und uberregionale Zentren mit umfassendem, auch kardiochirurgischem Behandlungsspektrum. Die Deutsche Gesellschaft fur Kardiologie – Herz- und Kreislaufforschung (DGK) und die Deutsche Gesellschaft fur Thorax-, Herz- und Gefaschirurgie (DGTHG) empfehlen die Einrichtung von Herzinsuffizienz-Netzwerken (HF-NETs), die modular auf den verschiedenen Versorgungsebenen in Herzinsuffizienz-Einheiten („Heart Failure Units“, HFUs) organisiert sind und damit uberprufbare Qualitatsmerkmale fur die sektorenubergreifende Versorgung von HI-Patienten aufweisen. Das dazu vorgelegte Positionspapier wurde von der Kommission fur Klinische Kardiologie mit Vertretern von DGK, DGTHG, sowie des Bundes Niedergelassener Kardiologen (BNK) und der Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte (ALKK) erarbeitet. Es formuliert die Voraussetzungen, die von den modularen HFUs im HF-NET fur eine Zertifizierung erfullt sein sollen.

Die Herzinsuffizienz ist durch eine hohe Hospitalisations- und Mortalitatsrate belastet. Hochspezialisierte Herzinsuffizienzeinheiten (HFU) zielen darauf ab, das Uberleben bei akuter Dekompensation zu sichern und die Krankenhausmortalitat zu senken. Bei einer Minderheit der Patienten werden weiterfuhrende chirurgische Therapiemasnahmen wie die Herztransplantation oder mechanische Unterstutzungssysteme notwendig. Der uberwiegende Anteil leidet chronisch an der Herzinsuffizienz und ist in den ersten Wochen nach Entlassung vital gefahrdet. Daher benotigt die HFU zusatzlich zur Akutversorgung ein strukturiertes poststationares Versorgungsprogramm inklusive eines standardisierten Entlassmanagements, das die kurz- und mittelfristige Betreuung dieser Patienten im ambulanten Sektor regelt und die Versorgungsqualitat verbessert. Ein Positionspapier, das gegenwartig von der Arbeitsgemeinschaft HFU der Deutschen Gesellschaft fur Kardiologie sowie der Deutschen Gesellschaft fur Thorax-, Herz- und Gefaschirurgie ausgearbeitet wird, beschreibt, wie durch Qualitatsstandards und Grundung von regionalen Herzinsuffizienz-Netzwerken (HF-NETs) die Versorgungsebenen untereinander starker vernetzt und die Versorgungssituation der Patienten mit Herzinsuffizienz verbessert werden konnen.