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Abstract Aims Acute heart failure (AHF) can result in worsening of heart failure (WHF), cardiogenic shock (CS), or death. Risk factors for these adverse outcomes are not well characterized. This study aimed to identify predictors for WHF or new‐onset CS in patients hospitalized for AHF. Methods and results Prospective cohort study enrolling consecutive patients with AHF admitted to a large tertiary care centre with follow‐up until death or discharge. WHF was defined by the RELAX‐AHF‐2 criteria. CS was defined as SCAI stages B–E. Potential predictors were assessed by fitting logistic regression models adjusted for age and sex. N = 233 patients were enrolled, median age was 78 years, and 80 were women (35.9%). Ischaemic cardiomyopathy was present in 82 patients (40.8%). Overall, 96 (44.2%) developed WHF and 18 (9.7%) CS. In‐hospital death (8/223, 3.6%) was related to both events (WHF: OR 6.64, 95% CI 1.21–36.55, P = 0.03; CS: OR 38.27, 95% CI 6.32–231.81, P

Abstract Background Lipids, including phospholipids and bile acids, exert various signaling effects and are thought to contribute to the development of coronary artery disease (CAD). Here, we aimed to compare lipidomic and bile acid profiles in the blood of patients with and without CAD stratified by sex. Methods From 2015 to 2022, 3,012 patients who underwent coronary angiography were recruited in the INTERCATH cohort. From the overall cohort, subgroups were defined using patient characteristics such as CAD vs. no CAD, 1st vs. 3rd tertile of LDL-c, and female vs. male sex. Hereafter, a matching algorithm based on age, BMI, hypertension status, diabetes mellitus status, smoking status, the Mediterranean diet score, and the intake of statins, triglycerides, HDL-c and hs-CRP in a 1:1 ratio was implemented. Lipidomic analyses of stored blood samples using the Lipidyzer platform (SCIEX) and bile acid analysis using liquid chromatography with tandem mass spectrometry (LC‒MS/MS) were carried out. Results A total of 177 matched individuals were analyzed; the median ages were 73.5 years (25th and 75th percentile: 64.1, 78.2) and 71.9 years (65.7, 77.2) for females and males with CAD, respectively, and 67.6 years (58.3, 75.3) and 69.2 years (59.8, 76.8) for females and males without CAD, respectively. Further baseline characteristics, including cardiovascular risk factors, were balanced between the groups. Women with CAD had decreased levels of phosphatidylcholine and diacylglycerol, while no differences in bile acid profiles were detected in comparison to those of female patients without CAD. In contrast, in male patients with CAD, decreased concentrations of the secondary bile acid species glycolithocholic and lithocholic acid, as well as altered levels of specific lipids, were detected compared to those in males without CAD. Notably, male patients with low LDL-c and CAD had significantly greater concentrations of various phospholipid species, particularly plasmalogens, compared to those in high LDL-c subgroup. Conclusions We present hypothesis-generating data on sex-specific lipidomic patterns and bile acid profiles in CAD patients. The data suggest that altered lipid and bile acid composition might contribute to CAD development and/or progression, helping to understand the different disease trajectories of CAD in women and men. Registration https://clinicaltrials.gov/ct2/show/NCT04936438 , Unique identifier: NCT04936438.

Lipoprotein (a) (Lp(a)) is a risk factor for cardiovascular diseases and mainly regulated by the complex LPA gene. We investigated the types of variation in the LPA gene and their predictive performance on Lp(a) concentration. We determined the Kringle IV-type 2 (KIV-2) copy number (CN) using the DRAGEN LPA Caller (DLC) and a read depth-based CN estimator in 8351 short-read whole genome sequencing samples from the GENESIS-HD study. The pentanucleotide repeat in the promoter region was genotyped with GangSTR and ExpansionHunter. Lp(a) concentration was available in 4861 population-based subjects. Predictive performance on Lp(a) concentration was investigated using random forests. The agreement of the KIV-2 CN between the two specialized callers was high (r = 0.9966; 95% confidence interval [CI] 0.9965–0.9968). Allele-specific KIV-2 CN could be determined in 47.0% of the subjects using the DLC. Lp(a) concentration can be better predicted from allele-specific KIV-2 CN than total KIV-2 CN. Two single nucleotide variants, 4925G>A and rs41272114C>T, further improved prediction. The genetically complex LPA gene can be analyzed with excellent agreement between different callers. The allele-specific KIV-2 CN is more important for predicting Lp(a) concentration than the total KIV-2 CN.

Background Biomarkers simplifying the diagnostic workup by discriminating between non–ST‐segment–elevation myocardial infarction (NSTEMI) and infarct‐like myocarditis are an unmet clinical need. Methods and Results A total of 105 subjects were categorized into groups as follows: ST‐segment−elevation myocardial infarction (n=36), NSTEMI (n=22), infarct‐like myocarditis (n=19), cardiomyopathy‐like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase‐1 (MMP‐1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non‐ST‐segment‐elevation, for example NSTEMI or infarct‐like myocarditis, categorized as the non−ST‐segment−elevation acute coronary syndrome−like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP‐1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non−ST‐segment−elevation acute coronary syndrome−like cohort, MMP‐1 concentrations discriminated infarct‐like myocarditis and NSTEMI with an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI, 0.89−1.00), whereas high‐sensitivity cardiac troponin T performed inferiorly (AUC, 0.74 [95% CI, 0.58−0.90]; P=0.012). Application of an optimal MMP‐1 cutoff had 94.4% sensitivity (95% CI, 72.7%−99.9%) and 90.9% specificity (95% CI, 70.8%−98.9%) for the diagnosis of infarct‐like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68−0.97). As assessed by likelihood ratio tests, incorporating MMP‐1 or PICP with age and C‐reactive protein into composite prediction models enhanced their diagnostic performance. Conclusions MMP‐1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct‐like myocarditis in individuals with non−ST‐segment−elevation acute coronary syndrome‐like presentation, though further research is needed to validate their clinical applicability.

Abstract Aims Cardiomyopathies (CMPs) are a heterogeneous group of diseases that are defined by structural and functional abnormalities of the cardiac muscle. Dilated cardiomyopathy (DCM), the most common CMP, is defined by left ventricular dilation and impaired contractility and represents a common cause of heart failure. Different phenotypes result from various underlying genetic and acquired causes with variable effects on disease development and progression, prognosis, and response to medical treatment. Current treatment algorithms do not consider these different aetiologies, due to lack of insights into treatable drivers of cardiac failure in patients with DCM. Our study aims to precisely phenotype and genotype the various subtypes of DCM and hereby lay the foundation for individualized therapy. Methods and results The Geno‐ And Phenotyping of PrImary Cardiomyopathy (GrAPHIC) is a currently ongoing prospective observational monocentric cohort study that recruits patients with DCM after exclusion of other causes such as coronary artery disease, valvular dysfunction, myocarditis, exposure to toxins, and peripartum CMP. Patients are enrolled at our heart failure outpatient clinic or during hospitalization at the University Hospital Hamburg. Clinical parameters, multimodal imaging and functional assessment, cardiac biopsies, and blood samples are obtained to enable an integrated genomic, functional, and biomarker analysis. Conclusions The GrAPHIC will contribute to a better understanding of the heterogeneous nature of primary CMPs focusing on DCM and provide improved prognostic approaches and more individualized therapies.

Abstract The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization.

ObjectivesPatients with atrial fibrillation (AF) have lower left atrial (LA) strain, which is a predictor for LA function. Here, we evaluated the prognostic value of LA strain to predict the rhythm outcome in patients with persistent AF undergoing LA cryoablation concomitant to minimally invasive mitral valve repair.MethodsBetween 01/2016 and 12/2020, 72 patients with persistent AF underwent LA cryoablation during minimally invasive mitral valve surgery. All patients received a complete LA lesion set and left atrial appendage (LAA) closure with a clip. All patients received preoperative transthoracic echocardiography (TTE) with LA and left ventricular strain measurements. Preoperative LA and LV strain analysis was correlated with postoperative rhythm outcome.ResultsThe mean age of the patients was 66.9 ± 7.2 years, of whom 42 (58%) were male patients. No major ablation-related complications occurred in any of the patients. Successful LAA closure was confirmed by intraoperative echocardiography in all patients. The 1-year survival rate was 97%. Freedom from AF at 12 months was 72% and 68% off antiarrhythmic drugs. Preoperative LA strain values were statistically significantly higher in patients with freedom from AF at 12 months of follow-up (12.7% ± 6.9% vs. 4.9% ± 4.1%, p = 0.006). Preoperative LV strain value was not associated with postoperative rhythm outcome. In multivariate logistic regression analysis, LA strain (p

Abstract Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (β per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p

Sulfonylureas (SUs) are a class of antidiabetic drugs widely used in the management of diabetes mellitus type 2. They promote insulin secretion by inhibiting the ATP-sensitive potassium channel in pancreatic β-cells. Recently, the exchange protein directly activated by cAMP (Epac) was identified as a new class of target proteins of SUs that might contribute to their antidiabetic effect, through the activation of the Ras-like guanosine triphosphatase Rap1, which has been controversially discussed. We used human embryonic kidney (HEK) 293 cells expressing genetic constructs of various Förster resonance energy transfer (FRET)-based biosensors containing different versions of Epac1 and Epac2 isoforms, alone or fused to different phosphodiesterases (PDEs), to monitor SU-induced conformational changes in Epac or direct PDE inhibition in real time. We show that SUs can both induce conformational changes in the Epac2 protein but not in Epac1, and directly inhibit the PDE3 and PDE4 families, thereby increasing cAMP levels in the direct vicinity of these PDEs. Furthermore, we demonstrate that the binding site of SUs in Epac2 is distinct from that of cAMP and is located between the amino acids E443 and E460. Using biochemical assays, we could also show that tolbutamide can inhibit PDE activity through an allosteric mechanism. Therefore, the cAMP-elevating capacity due to allosteric PDE inhibition in addition to direct Epac activation may contribute to the therapeutic effects of SU drugs.

Abstract Background Long-chain acyl-carnitines (ACs) are potential arrhythmogenic metabolites. Their role in atrial fibrillation (AF) remains incompletely understood. Using a systems medicine approach, we assessed the contribution of C18:1AC to AF by analysing its in vitro effects on cardiac electrophysiology and metabolism, and translated our findings into the human setting. Methods and results Human iPSC-derived engineered heart tissue was exposed to C18:1AC. A biphasic effect on contractile force was observed: short exposure enhanced contractile force, but elicited spontaneous contractions and impaired Ca2+ handling. Continuous exposure provoked an impairment of contractile force. In human atrial mitochondria from AF individuals, C18:1AC inhibited respiration. In a population-based cohort as well as a cohort of patients, high C18:1AC serum concentrations were associated with the incidence and prevalence of AF. Conclusion Our data provide evidence for an arrhythmogenic potential of the metabolite C18:1AC. The metabolite interferes with mitochondrial metabolism, thereby contributing to contractile dysfunction and shows predictive potential as novel circulating biomarker for risk of AF.

Abstract Aims Whether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre‐transplant characteristics and outcomes after HTx. Methods and results From 1995 to 2019, 49 200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all‐cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49 200 patients (median age 55 years, interquartile range 46–62; 24.6% women), 49 732 events occurred during a median follow‐up of 8.1 years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11–3.42; P

ABSTRACT: Background: The presence of myocardial scar is associated with poor prognosis in several underlying diseases. Late-gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging reveals clinically silent “unrecognized myocardial scar” (UMS), but the etiology of UMS often remains unclear. This population-based CMR study evaluated prevalence, localization, patterns, and risk factors of UMS. Methods: The study population consisted of 1064 consecutive Hamburg City Health Study participants without a history of coronary heart disease or myocarditis. UMS was assessed by standard-phase-sensitive-inversion-recovery LGE CMR. Results: Median age was 66 [quartiles 59, 71] years and 37% (388/1064) were females. UMS was detected in 244 (23%) participants. Twenty-five participants (10%) had ischemic, and 217 participants (89%) had non-ischemic scar patterns, predominantly involving the basal inferolateral left-ventricular (LV) myocardium (75%). Two participants (1%) had coincident ischemic and non-ischemic scar. The presence of any UMS was independently associated with LV ejection fraction (odds ratios (OR) per standard deviation (SD) 0.77 (confidence interval (CI) 0.65–0.90), p = 0.002) and LV mass (OR per SD 1.54 (CI 1.31–1.82), p

Abstract Aims We aim to develop a pragmatic screening tool for heart failure at the general population level. Methods and results This study was conducted within the Hamburg‐City‐Health‐Study, an ongoing, prospective, observational study enrolling randomly selected inhabitants of the city of Hamburg aged 45–75 years. Heart failure was diagnosed per current guidelines. Using only digital electrocardiograms (ECGs), a convolutional neural network (CNN) was built to discriminate participants with and without heart failure. As comparisons, known risk variables for heart failure were fitted into a logistic regression model and a random forest classifier. Of the 5299 individuals included into this study, 318 individuals (6.0%) had heart failure. Using only the digital ECGs instead of several risk variables as an input, the CNN provided a comparable predictive accuracy for heart failure versus the logistic regression model and the random forest classifier [area under the curve (AUC) of 0.75, a sensitivity of 0.67 and a specificity of 0.69 for the CNN; AUC 0.77, a sensitivity of 0.63 and a specificity of 0.76 for the logistic regression; AUC 0.79, a sensitivity of 0.67 and a specificity of 0.72 for the random forest classifier]. Conclusions Using a CNN build on digital ECGs only and requiring no additional input, we derived a screening tool for heart failure in the general population. This could be perfectly embedded into clinical routine of general practitioners, as it builds on an already established diagnostic tool and does not require additional, time‐consuming input. This could help to alleviate the underdiagnosis of heart failure.

Abstract Coffee, next to water the most widespread beverage, is attributed both harmful and protective characteristics concerning cardiovascular health. This study aimed to evaluate associations of coffee consumption with cardiac biomarkers, echocardiographic, electrocardiographic parameters and major cardiovascular diseases. We performed a cross-sectional analysis of 9009 participants of the population-based Hamburg City Health Study (HCHS), enrolled between 2016 and 2018 median age 63 [IQR: 55; 69] years. Coffee consumption was classified into three groups: 4 cups/day (high). In linear regression analyses adjusted for age, sex, body mass index, diabetes, hypertension, smoking, and additives, high coffee consumption correlated with higher LDL-cholesterol (β = 5.92; 95% CI 2.95, 8.89; p

BackgroundValve-in-valve (ViV) transfemoral transcatheter aortic valve implantation (TAVI) for failing aortic surgical bioprostheses or transcatheter heart valves (THV) has demonstrated a reasonable clinical and hemodynamic efficacy. Traditionally, self-expanding (SE) supra-annular THV are considered to result in superior hemodynamics compared with balloon-expandable intra-annular THV after ViV. However, so far no data are found on latest-generation intra-annular SE THV for aortic ViV procedures which might be superior with regard to coronary access or subsequent valve reintervention.AimWe herein aim to evaluate a latest-generation SE intra-annular THV for aortic ViV procedures.Materials and methodsBetween May 2022 and November 2022, five consecutive patients (4/5 female with mean age of 76.2 years and mean Society of Thoracic Surgeons predicted risk of mortality score of 2.9%) received ViV TAVI using the Navitor system (Abbott, Chicago, IL, USA) for treatment of failing surgical bioprostheses or THV. Data were retrospectively analyzed according to updated Valve Academic Research Consortium 3 (VARC-3) definitions.ResultsAt 30 days, absence of mortality and VARC-3 adjudicated clinical endpoints were documented. Echocardiography at 30 days revealed complete absence of paravalvular leakage and single-digit mean transvalvular gradients (mean of 6.0 mmHg) in all patients.ConclusionThe investigated intra-annular SE THV results in excellent 30-day outcomes for aortic ViV procedures for failing surgical bioprostheses or THV. Despite the intra-annular design, hemodynamic results were excellent, even in small bioprostheses. Ease of use of this valve platform is reflected by only two cycles of resheathing in five ViV procedures with hemodynamic stability during all steps of valve deployment.

Abstract Aims Data on the association between periodontitis and preclinical cardiac alterations remain scarce. The aim of the current study is to determine if periodontitis is associated with morphological and functional cardiac changes measured by transthoracic echocardiography as well as different heart failure (HF) phenotypes. Methods Participants from the population‐based Hamburg City Health Study [ClinicalTrial.gov (NCT03934957)], who underwent transthoracic echocardiography and periodontal screening were included. Periodontitis was classified according to Eke and Page (none/mild, moderate, severe). The 2021 ESC HF guidelines were applied and HF was classified into HF with preserved ejection fraction (HFpEF, ejection fraction ≥50%), HF with mid‐range and reduced ejection fraction [HF(m)rEF, ejection fraction

Abstract Strain is an important imaging parameter to determine myocardial deformation. This study sought to 1) assess changes in left ventricular strain and ejection fraction (LVEF) from acute to chronic ST-elevation myocardial infarction (STEMI) and 2) analyze strain as a predictor of late gadolinium enhancement (LGE). 32 patients with STEMI and 18 controls prospectively underwent cardiac magnetic resonance imaging. Patients were scanned 8 $$\pm$$ ± 5 days and six months after infarction (± 1.4 months). Feature tracking was performed and LVEF was calculated. LGE was determined visually and quantitatively on short-axis images and myocardial segments were grouped according to the LGE pattern (negative, non-transmural and transmural). Global strain was impaired in patients compared to controls, but improved within six months after STEMI (longitudinal strain from −14 ± 4 to −16 ± 4%, p

Abstract Rapid advances in high-throughput DNA sequencing technologies have enabled the conduct of whole genome sequencing (WGS) studies, and several bioinformatics pipelines have become available. The aim of this study was the comparison of 6 WGS data pre-processing pipelines, involving two mapping and alignment approaches (GATK utilizing BWA-MEM2 2.2.1, and DRAGEN 3.8.4) and three variant calling pipelines (GATK 4.2.4.1, DRAGEN 3.8.4 and DeepVariant 1.1.0). We sequenced one genome in a bottle (GIAB) sample 70 times in different runs, and one GIAB trio in triplicate. The truth set of the GIABs was used for comparison, and performance was assessed by computation time, F1 score, precision, and recall. In the mapping and alignment step, the DRAGEN pipeline was faster than the GATK with BWA-MEM2 pipeline. DRAGEN showed systematically higher F1 score, precision, and recall values than GATK for single nucleotide variations (SNVs) and Indels in simple-to-map, complex-to-map, coding and non-coding regions. In the variant calling step, DRAGEN was fastest. In terms of accuracy, DRAGEN and DeepVariant performed similarly and both superior to GATK, with slight advantages for DRAGEN for Indels and for DeepVariant for SNVs. The DRAGEN pipeline showed the lowest Mendelian inheritance error fraction for the GIAB trios. Mapping and alignment played a key role in variant calling of WGS, with the DRAGEN outperforming GATK.

Abstract Aim Aim of this study was to investigate the association between periodontitis and arterial hypertension, both of which show correlations with classical cardiovascular risk factors and inflammatory activity. Materials and methods A cross-sectional analysis of data from a large population-based health survey (the Hamburg City Health Study, HCHS) including 5934 participants with complete periodontal examination and blood pressure data, of whom 5735 had medical records regarding anti-hypertensive medication, was performed. Probing depths, gingival recessions, bleeding on probing (BOP), dental plaque, and decayed-missing-filled teeth (DMFT) indices were recorded as measures of oral health. Clinical attachment loss (CAL) per tooth was calculated and periodontitis was staged into three groups (no/mild, moderate, severe). Arterial hypertension was diagnosed based on the participants’ medication history and systolic and diastolic blood pressure values. Logistic regression models were constructed accounting for a set of potential confounders (age, sex, smoking, body mass index (BMI), diabetes, educational level, alcohol intake) and high sensitivity-C-reactive protein (hsCRP). Results The odds of arterial hypertension increased significantly along with periodontitis severity (OR for severe periodontitis: 2.19; 95% CI 1.85–2.59; p

Abstract Transthoracic echocardiography (TTE) and cine cardiac magnetic resonance imaging (CMR) are established imaging methods of the aortic root. We aimed to evaluate the comparability of measurements in TTE and standard cine CMR sequences of the aortic root. Our study included 741 subjects (mean age 63.5 ± 8 years, 43.7% female) from the Hamburg City Health Study (HCHS). Subjects underwent CMR and TTE. Aortic root measurements were performed at the level of the aortic annulus (AoAn), sinus of Valsalva (SoV), and sinotubular junction (STJ) by standard cine CMR in left ventricular long axis and left ventricular outflow tract view. Measurements were performed applying the leading-edge to leading-edge (LL) convention and inner-edge to inner-edge (II) convention in TTE and the II convention in CMR. Inter correlation coefficients (ICCs) demonstrated high inter- and intraobserver reproducibility for CMR and TTE measurements of SoV and STJ (ICCs 0.9–0.98) and moderate reproducibility for AoAn (ICCs 0.68–0.91). CMR measurements of SoV and STJ showed strong agreement with TTE: while correlations were comparable (r = 0.75–0.85) bias was lower with TTE II (bias − 0.1 to − 0.74) versus TTE LL measurements (mean bias − 1.49 to − 2.58 mm). The agreement for AoAn was fair (r = 0.51–0.57) with variable bias (mean bias 0.39–3.9). Standard cine CMR and TTE derived aortic root measurements are reproducible and comparable with higher agreement for TTE II instead of LL measurements. These results support an interchangeable application of TTE and standard CMR for screening of aortic root diseases thereby possibly reducing redundant multimodality imaging.

Abstract Aim The diagnosis of heart failure (HF) has been refined in several steps in recent years, reflecting evolving diagnostic and therapeutic approaches. The European Society of Cardiology (ESC) recently published a modified definition of HF in the 2021 heart failure (HF) guidelines. The impact of this new diagnostic algorithm on the prevalence of HF is not known. The aim of this study was to describe the contemporary prevalence of HF in a representative, completely phenotyped sample from the general population. Methods and results This analysis was conducted among 7074 participants (aged 45–78 years, 51.5% women) from the population‐based Hamburg City Health Study. Compared with the 2016 version, HF prevalence increased with the 2021 HF guidelines from 4.31% to 4.83% (12% increase). This increase was driven by a higher number of subjects with HF with reduced/mildly‐reduced ejection fraction (0.47% to 0.52%; 1.37% to 2.12%), while the number of subjects with HF with preserved ejection fraction decreased from 2.46% to 2.19%. Importantly, this did not impact the known risk factor profiles of the phenotypes. Although four drugs are recommended for all subjects with HFrEF in the new guidelines, several adjunctive therapies are recommended for dedicated cases/scenarios (e.g.

Abstract Background Endothelin-1 (ET-1) and adrenomedullin (ADM) are commonly known as vasoactive peptides that regulate vascular homeostasis. Less recognised is the fact that both peptides could affect glucose metabolism. Here, we investigated whether ET-1 and ADM, measured as C-terminal-proET-1 (CT-proET-1) and mid-regional-proADM (MR-proADM), respectively, were associated with incident type 2 diabetes. Methods Based on the population-based Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium data, we performed a prospective cohort study to examine associations of CT-proET-1 and MR-proADM with incident type 2 diabetes in 12,006 participants. During a median follow-up time of 13.8 years, 862 participants developed type 2 diabetes. The associations were examined in Cox proportional hazard models. Additionally, we performed two-sample Mendelian randomisation analyses using published data. Results CT-proET-1 and MR-proADM were positively associated with incident type 2 diabetes. The multivariable hazard ratios (HRs) [95% confidence intervals (CI)] were 1.10 [1.03; 1.18], P = 0.008 per 1-SD increase of CT-proET-1 and 1.11 [1.02; 1.21], P = 0.016 per 1-SD increase of log MR-proADM, respectively. We observed a stronger association of MR-proADM with incident type 2 diabetes in obese than in non-obese individuals (P-interaction with BMI

Background High‐sensitivity cardiac troponin (hs‐cTn)‐based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs‐cTnI and hs‐cTnT and applied the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs‐cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1‐hour: FP, 53.3% [95% CI, 45.0–61.4] versus RP, 76.9 [95% CI, 71.6–81.7]; 0/3‐hour: FP, 56.9% [95% CI, 42.2–70.7] versus RP, 78.1% [95% CI, 74.0–81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1‐hour (31.3% versus 55.8%) and 0/3‐hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs‐cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs‐cTnI 2.3 [95% CI, 1.7–3.2]; RP adjusted HR, hs‐cTnI 1.8 [95% CI, 1.4–2.4]). Findings were similar for hs‐cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

Abstract Aims Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. The aim of this study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. We also included an assessment of baseline biomarkers of inflammation, myocardial injury, and left ventricular dysfunction with risk of AF and HF, respectively, to shed light on the potential underlying pathophysiology. Methods and results This study was conducted within the BiomarCaRE project using harmonized data from 12 European population‐based cohorts (n = 48 518 participants). Renal function was assessed by glomerular filtration rate estimated using the combined Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation with standardized serum creatinine (Cr) and non‐standardized serum cystatin C (CysC). Incidence of AF and HF respectively, during a median follow‐up of 8 years was recorded. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and the competing risk of mortality after adjustment for covariates. The mean age at baseline was 51.4 (standard deviation 12.1) years, 49% were men. Overall, 4.3% of subjects had CKD at baseline. The rate for AF was 3.8 per 1000 person‐years during follow‐up. The HR for AF in patients with CKD compared with patients without CKD was 1.28 (95% confidence interval 1.07–1.54) after adjustment for covariates. The rate for incident HF was 4.1 per 1000 person‐years and the HR of CKD for HF was 1.71 (95% confidence interval 1.45–2.01. In subjects with CKD, N‐terminal‐pro‐brain natriuretic peptide (NT‐proBNP) showed an association with AF, whereas NT‐proBNP and C‐reactive protein were associated with HF. Conclusions Chronic kidney disease is an independent risk factor for subsequent AF and is even more closely associated with HF. In these relatively young participants with CKD, NT‐proBNP was strongly associated with subsequent risk of AF. For HF, in addition, elevated levels of hs‐C‐reactive protein at baseline were related to incident events.

Background As only a small proportion of patients with chest pain suffers from myocardial infarction (MI), safe rule-out of MI is of immense importance. Recently an ultrasensitive microphone performing diastolic heart sound analysis (CADScorSystem) for rule-out of coronary artery disease (CAD) has emerged. In this explorational study, we aimed to evaluate the feasibility of the CADScorSystem for diagnosis of MI in the setting of a large emergency department.Methods Patients presenting to the emergency department with suspected MI were included. Acoustic heart sound analysis was performed in all patients and automated CAD-score values were calculated via a device-embedded algorithm, which also requires inclusion of three clinical variables: age, sex and presence of hypertension. Patients additionally received serial high-sensitive troponin T measurement measurements to assess the final diagnosis according to third Universal Definition of Myocardial Infarction applying the European Society of Cardiology 0 hour/3 hours algorithm. Diagnostic parameters for MI, considering different CAD-score cut-offs, were computed.Results Of 167 patients, CAD-scores were available in 61.1%. A total of eight patients were diagnosed with MI. At a cut-off value of

Abstract Aims Although absolute (AID) and functional iron deficiency (FID) are known risk factors for patients with cardiovascular (CV) disease, their relevance for the general population is unknown. The aim was to assess the association between AID/FID with incident CV disease and mortality in the general population. Methods and results In 12 164 individuals from three European population‐based cohorts, AID was defined as ferritin

Abstract Aims Despite signals from clinical trials and mechanistic studies implying different resilience to heart failure (HF) depending on gender, the impact of gender on presentation and outcomes in patients with HF remains unclear. This study assessed the impact of gender on clinical presentation and outcomes in patients with HF referred to a specialised tertiary HF service. Methods and results Consecutive patients with HF referred to a specialised tertiary HF service offering advanced therapy options including left ventricular assist devices (LVAD) and heart transplantation were prospectively enrolled from August 2015 until March 2018. We assessed clinical characteristics at baseline and performed survival analyses and age‐adjusted Cox regression analyses in men vs. women for all‐cause death and a combined disease‐related endpoint comprising death, heart transplantation, and LVAD implantation. Analyses were performed for the overall study population and for patients with HF with reduced ejection fraction (HFrEF). Of 356 patients included, 283 (79.5%) were male. The median age was 58 years (interquartile range 50–67). Two hundred and fifty‐one (74.5%) patients had HFrEF. HF aetiology, ejection fraction, functional status measures, and most of the cardiac and non‐cardiac comorbidities did not differ between men and women. In a median follow‐up of 3.2 years, 50 patients died (45 men, 5 women), 15 patients underwent LVAD implantation, and 8 patients heart transplantation. While all‐cause death was not significantly different between both genders in the overall population [16.9 vs. 6.0%, P = 0.065, hazard ratio (HR) 2.29 (95% confidence interval 0.91–5.78), P = 0.078], in the HFrEF subgroup, a significant difference between men and women was observed [20.7% vs. 3.9%, P = 0.017, HR 3.67 (95% confidence interval 1.13–11.91), P = 0.031]. The combined endpoint was more often reached in men than in women in both the overall population [21.6% vs. 9.0%, P = 0.053, HR 2.51 (1.08–5.82), P = 0.032] and the HFrEF subgroup [27.1% vs. 7.7%, P = 0.015, HR 3.58 (1.29–9.94), P = 0.014]. Conclusions Patients referred to a specialised tertiary HF service showed a similar clinical profile without relevant gender differences. In the mid‐term follow‐up, more male than female patients died or underwent heart transplantation and LVAD implantation. These findings call for independent validation and for further research into gender‐specific drivers of HF progression.

Abstract Background Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A1c (HbA1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA1c with cardiovascular outcomes in the general population. Methods Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N = 32,496) and with diabetes (N = 3684). Results Kaplan–Meier curves showed higher event rates with increasing HbA1c levels (log-rank-test: p

Abstract Echocardiography is the most common routine cardiac imaging method. Nevertheless, only few data about sex-specific reference limits for right atrium (RA) dimensions are available. Transthoracic echocardiographic RA measurements were studied in 9511 participants of the Gutenberg-Health-Study. A reference sample of 1942 cardiovascular healthy subjects without chronic obstructive pulmonary disease was defined. We assessed RA dimensions and sex-specific reference limits were defined using the 95th percentile of the reference sample. Results showed sex-specific differences with larger RA dimensions in men that were attenuated by standardization for body-height. RA-volume was 20.2 ml/m in women (5th–95th: 12.7–30.4 ml/m) and 26.1 ml/m in men (5th–95th: 16.0–40.5 ml/m). Multivariable regressions identified body-mass-index (BMI), coronary artery disease (CAD), chronic heart failure (CHF) and atrial fibrillation (AF) as independent key correlates of RA-volume in both sexes. All-cause mortality after median follow-up-period of 10.7 (9.81/11.6) years was higher in individuals who had RA volume/height outside the 95% reference limit (HR 1.70 [95%CI 1.29–2.23], P = 0.00014)). Based on a large community-based sample, we present sex-specific reference-values for RA dimensions normalized for height. RA-volume varies with BMI, CHF, CAD and AF in both sexes. Individuals with RA-volume outside the reference limit had a 1.7-fold higher mortality than those within reference limits.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is common in patients presenting with dyspnoea. Recently, clinical tools were developed to facilitate the diagnosis of HFpEF. Here, we apply the European Society of Cardiology (ESC) 2016 heart failure guidelines and the H2FPEF and HFA‐PEFF scores to a middle‐aged sample of the general population and compared the different groups with each other. Methods and results This study included the first 10 000 participants of the population‐based Hamburg City Health Study. A total of 5613 subjects, aged 62 ± 8.7 years (51.1% women), qualified for the analysis. Unexplained dyspnoea was present in 407 (7.3%) subjects. In those, the estimated prevalence of HFpEF was 20.4% (ESC 2016), 12.3% (H2FPEF), and 7.6% (HFA‐PEFF). The majority of subjects was classified as HFpEF not excludable according to the HFA‐PEFF (57.7%) and H2FPEF (59.2%) scores. For all algorithms, subjects diagnosed with HFpEF showed elevated age and body mass index as well as a higher prevalence of atrial fibrillation, diabetes, and arterial hypertension compared with those without HFpEF or HFpEF not excludable. The distribution of those co‐morbidities and risk factors varied between the differently diagnosed HFpEF groups with the highest burden in the HFpEF group defined by the H2FPEF score. The overlap of subjects diagnosed with HFpEF according to the different algorithms was very limited. Conclusions Unexplained dyspnoea is common in the middle‐aged general population. The ESC 2016 algorithm and the H2FPEF and HFA‐PEFF scores detect different, discordant subpopulations of probands with breathlessness. Further classification of the HFpEF syndrome is desirable.

Abstract Background The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers. Methods In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure. Results Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49–2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59–2.69]; non-diabetes: HR 1.85 [1.68–2.02]), BMI (diabetes: HR 1.30 [1.18–1.42]; non-diabetes: HR 1.40 [1.35–1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55–2.75]; non-diabetes: HR 2.86 [2.50–3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82–2.80]; non-diabetes: HR 2.97 [2.21–4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19–1.34]; non-diabetes: HR 1.43 [1.39–1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04–1.16]; non-diabetes: HR 1.13 [1.10–1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03–1.24]; non-diabetes: HR 1.29 [1.25–1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9–52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3–16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7–17.4]), and hyperglycemia (glucose, 12.0% [4.2–19.9]). Conclusions The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.

Background and aims: We aimed to determine the association of carotid intima media thickness (CIMT), carotid plaques, and heart function with peak systolic velocity (PSV) of the common (CCA) and internal carotid artery (ICA) in a cross-sectional study. Methods: In the population-based Hamburg-City-Health-Study participants between 45 and 74 years were recruited. Cardio-vascular risk factors were assessed by history, blood samples, and clinical examination. CIMT, plaques, and PSV were determined by carotid ultrasound. Serum N-terminal brain natriuretic peptide (NT-proBNP) was determined as a biomarker for cardiac dysfunction, and left ventricular ejection fraction (LVEF) was quantified by echocardiography. Participants with carotid stenosis were excluded. Data were analyzed by multivariate linear regression. Results: We included 8567 participants, median age was 62 years, 51.8% were women. Median CIMT was 0.75 mm, NT-proBNP 80 pg/ml, LVEF 58.5%, and 30.4% had carotid plaques. For women PSV decreased in decades from 89 to 73 cm/s in CCAs and 78 to 66 cm/s in ICAs, and for men from 91 to 76 cm/s in CCAs and from 70 to 66 cm/s in ICAs. Corrected for age, sex, red blood cell count, and blood pressure, in CCAs lower PSV was associated with carotid plaques (p

Background: While cardiac-specific troponin (cTn) allows for rapid diagnosis of acute type 1 myocardial infarction (T1MI), its performance to differentiate acute myocardial injury (AI) or type 2 myocardial infarction (T2MI) is limited. The objective was to combine biomarkers to improve discrimination of different myocardial infarction (MI) aetiologies. Methods: We determined levels of cardiac troponin T and I (cTnT, cTnI), cardiac myosin-binding protein C (cMyBP-C), NT-proBNP and ten miRNAs, known to be associated with cardiac pathology in a total of n = 495 serial plasma samples at three time points (on admission, after 1 h and 3 h) from 57 NSTEMI (non-ST-elevation myocardial infarction), 18 AI, and 31 STEMI patients, as defined by fourth universal definition of MI (UDMI4) and 59 control individuals. We then applied linear mixed effects model to compare the kinetics of all molecules in these MI sub-types. Results: Established (cTnT, cTnI) and novel (cMyBP-C) cardiac necrosis markers failed in differentiating T1MI vs T2MI at early time points. All cardiac necrosis markers were higher in T1MI than in T2MI at 3 h after admission. Muscle-enriched miRNAs (miR-1 and miR-133a) were correlated with cardiac necrosis protein markers and did not offer better discrimination. Established cardiac strain marker NT-proBNP differentiated AI and T1MI at all time points but failed to discriminate T2MI from T1MI. However, the combination of NT-proBNP and cTnT along with age returned an overall AUC of 0.76 [95 % CI 0.67–0.84] for differentiating T1MI, T2MI and AI. Conclusions: Rather than using single biomarkers of myocardial necrosis, a combination of clinical biomarkers for cardiac necrosis (troponin) and cardiac strain (NT-proBNP) might aid in differentiating T1MI, T2MI and AI.

Background The association between high‐sensitivity troponin T (hsTnT) and high‐sensitivity troponin I (hsTnI) and outcome when adjusted for confounders including the angiographical severity of coronary artery disease (CAD) remains largely unknown. We therefore aimed to explore whether hsTnT and hsTnI blood levels increase with CAD severity and add independent predictive information for future major adverse cardiovascular events and all‐cause mortality in stable patients. Methods and Results Patients from the INTERCATH cohort with available coronary angiography and hsTnT and hsTnI concentrations were included. Troponin concentrations were quantified via hsTnT (Roche Elecsys) and hsTnI (Abbott ARCHITECT STAT). To investigate the association of hsTnT and hsTnI with outcome, a multivariable analysis adjusting for classical cardiovascular risk factors, low‐density lipoprotein cholesterol, estimated glomerular filtration rate, hs‐CRP (high‐sensitivity C‐reactive protein), NT‐proBNP (N‐terminal pro–brain natriuretic peptide), and Gensini score was carried out. Of 1829 patients, 27.9% were women, and the mean age was 68.6±10.9 years. Troponin blood concentrations were higher in patients with diagnosed CAD compared with those without. Using a linear regression model current smoking, arterial hypertension, estimated glomerular filtration rate, hs‐CRP, NT‐proBNP, and CAD severity as graded by the Gensini and SYNTAX scores were associated with high‐sensitivity troponin levels. Patients were followed for 4.4 years (25th and 75th percentiles: 4.3, 4.4). After multivariable adjustment, all‐cause mortality was predicted by hsTnT (hazard ratio [HR], 1.7 [95% CI, 1.5–2.2], P

The standardization of data from medical studies and hospital information systems to a common data model such as the Observational Medical Outcomes Partnership (OMOP) model can help make large datasets available for analysis using artificial intelligence approaches. Commonly, automatic mapping without intervention from domain experts delivers poor results. Further challenges arise from the need for translation of non-English medical data. Here, we report the establishment of a mapping approach which automatically translates German data variable names into English and suggests OMOP concepts. The approach was set up using study data from the Hamburg City Health Study. It was evaluated against the current standard, refined, and tested on a separate dataset. Furthermore, different types of graphical user interfaces for the selection of suggested OMOP concepts were created and assessed. Compared to the current standard our approach performs slightly better. Its main advantage lies in the automatic processing of German phrases into English OMOP concept suggestions, operating without the need for human intervention. Challenges still lie in the adequate translation of nonstandard expressions, as well as in the resolution of abbreviations into long names.

Abstract Aims The increased incidence of heart failure in men suggests that endogenous sex hormones might play a role in the development of heart failure, but epidemiological data remain sparse. Here, we evaluated the predictive value of low testosterone levels on future heart failure in the large population‐based FINRISK97 study. Methods and results Baseline serum testosterone concentrations were measured in 7855 subjects (3865 men and 3990 women) of the FINRISK97 study. During a median follow‐up (FU) of 13.8 years, a total of 564 heart failure events were recorded. The age‐adjusted baseline testosterone levels did not differ significantly between subjects developing incident heart failure during FU and those without incident events during FU (men: 16.6 vs. 17.1 nmol/L, P = 0.75; women: 1.15 vs. 1.17 nmol/L, P = 0.32). Relevant statistically significant correlations of testosterone levels were found with high‐density lipoprotein cholesterol levels (R = 0.22; P

Abstract Aims Differences between female and male patients in clinical presentation, causes and treatment of cardiogenic shock (CS) are poorly understood. We aimed to investigate sex differences in presentation with and treatment of CS. Methods and results We analysed data of 978 patients presenting with CS to a tertiary care hospital between October 2009 and October 2017. Multivariable adjusted logistic/Cox regression models were fitted to investigate the association between sex and clinical presentation, use of treatments and 30 day mortality. Median age was 70 years (interquartile range 58–79 years), and 295 (30.2%) patients were female. After adjustment for multiple relevant confounders, female patients were more likely to be older [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.02–1.42, P = 0.027], but other relevant presentation characteristics did not differ between both sexes. Despite the similar presentation, female patients were less likely to be treated with percutaneous left ventricular assist devices (OR 0.78, 95% CI 0.64–0.94, P = 0.010), but more likely to be treated with catecholamines (OR 1.21, 95% CI 1.02–1.44, P = 0.033) or vasopressors (OR 1.26, 95% CI 1.05–1.50, P = 0.012). A 30 day mortality risk in female patients was as high as in male patients (hazard ratio 1.08, 95% CI 1.00–1.18, P = 0.091). Conclusions In this large, contemporary cohort, clinical presentation was comparable in female and male patients, and both sexes were associated with a comparably high mortality risk. Nevertheless, female patients received different treatment for CS and were most importantly less likely to be treated with percutaneous left ventricular assist devices.

Abstract Transjugular intrahepatic portosystemic shunt (TIPS) reduces portal hypertension in patients with liver cirrhosis. The exact cardiac consequences of subsequent increase of central blood volume are unknown. Cardiovascular magnetic resonance (CMR) imaging is the method of choice for quantifying cardiac volumes and ventricular function. The aim of this study was to investigate effects of TIPS on the heart using CMR, laboratory, and imaging cardiac biomarkers. 34 consecutive patients with liver cirrhosis were evaluated for TIPS. Comprehensive CMR with native T1 mapping, transthoracic echocardiography, and laboratory biomarkers were assessed before and after TIPS insertion. Follow-up (FU) CMR was obtained in 16 patients (47%) 207 (170–245) days after TIPS. From baseline (BL) to FU, a significant increase of all indexed cardiac chamber volumes was observed (all P

BackgroundThe instant, single-sampling rule-out of acute myocardial infarction (AMI) is still an unmet clinical need. We aimed at testing and comparing diagnostic performance and prognostic value of two different single-sampling biomarker strategies for the instant rule-out of AMI.MethodsFrom the Biomarkers in Acute Cardiac Care (BACC) cohort, we recruited consecutive patients with acute chest pain and suspected AMI presenting to the Emergency Department of the University Medical Center Hamburg-Eppendorf, Hamburg, Germany. We compared safety, effectiveness and 12-month incidence of the composite endpoint of all-cause death and myocardial infarction between (i) a single-sampling, dual-marker pathway combining high-sensitivity cardiac troponin I (hs-cTnI) and ultra-sensitive copeptin (us-Cop) at presentation (hs-cTnI ≤ 27 ng/L, us-Cop < 10 pmol/L and low-risk ECG) and (ii) a single-sampling pathway based on one-off hs-cTnI determination at presentation (hs-cTnI < 5 ng/L and low-risk ECG). As a comparator, we used the European Society of Cardiology (ESC) 0/1-h dual-sampling algorithm.ResultsWe enrolled 1,136 patients (male gender 65%) with median age of 64 years (interquartile range, 51–75). Overall, 228 (20%) patients received a final diagnosis of AMI. The two single-sampling instant rule-out pathways yielded similar negative predictive value (NPV): 97.4% (95%CI: 95.4–98.7) and 98.7% (95%CI: 96.9–99.6) for dual-marker and single hs-cTnI algorithms, respectively (P = 0.11). Both strategies were comparably safe as the ESC 0/1-h dual-sampling algorithm and this was consistent across subgroups of early-comers, low-intermediate risk (GRACE-score < 140) and renal dysfunction. Despite a numerically higher rate of false-negative results, the dual-marker strategy ruled-out a slightly but significantly higher percentage of patients compared with single hs-cTnI determination (37.4% versus 32.9%; P < 0.001). There were no significant between-group differences in 12-month composite outcome.ConclusionsInstant rule-out pathways based on one-off determination of hs-cTnI alone or in combination with us-Cop are comparably safe as the ESC 0/1 h algorithm for the instant rule-out of AMI, yielding similar prognostic information. Instant rule-out strategies are safe alternatives to the ESC 0/1 h algorithm and allow the rapid and effective triage of suspected AMI in patients with low-risk ECG. However, adding copeptin to hs-cTn does not improve the safety of instant rule-out compared with the single rule-out hs-cTn at very low cut-off concentrations.

Growth differentiation factor-15 (GDF15) is a stress response cytokine that is elevated in several cardiometabolic diseases and has attracted interest as a potential therapeutic target. To further explore the association of GDF15 with human disease, we conducted a broad study into the phenotypic and genetic correlates of GDF15 concentration in up to 14,099 individuals. Assessment of 772 traits across 6610 participants in FINRISK identified associations of GDF15 concentration with a range of phenotypes including all-cause mortality, cardiometabolic disease, respiratory diseases and psychiatric disorders, as well as inflammatory markers. A meta-analysis of genome-wide association studies (GWAS) of GDF15 concentration across three different assay platforms (n=14,099) confirmed significant heterogeneity due to a common missense variant (rs1058587; p.H202D) in GDF15, potentially due to epitope-binding artefacts. After conditioning on rs1058587, statistical fine mapping identified four independent putative causal signals at the locus. Mendelian randomisation (MR) analysis found evidence of a causal relationship between GDF15 concentration and high-density lipoprotein (HDL) but not body mass index (BMI). Using reverse MR, we identified a potential causal association of BMI on GDF15 (IVW pFDR = 0.0040). Taken together, our data derived from human population cohorts do not support a role for moderately elevated GDF15 concentrations as a causal factor in human cardiometabolic disease but support its role as a biomarker of metabolic stress.

Abstract Aim The management of cardiogenic shock remains a clinical challenge even in well‐developed healthcare systems, best illustrated by its high mortality despite numerous innovative proposals for management. The aim of this study was to describe temporal trends in incidence, causes, use of mechanical circulatory support, and mortality in cardiogenic shock in Germany. Methods and results Data on all cardiogenic shock patients treated in German hospitals between 2005 and 2017 were obtained from the Federal Bureau of Statistics. The data set comprised 441 696 patients with cardiogenic shock, mean age 71 (±13.8) years, 171 383 (39%) female patients. Incidence rates increased from 33.1/100 000 population in 2005 (27 246 cases) to 51.7/100 000 population in 2017 (42 779 cases). Acute myocardial infarction was the most common cause of cardiogenic shock in 2005–07 (43 422 of 82 037 cases, 52.9%), but the proportion of cases caused by it decreased until 2014–17 (73 274 of 165 873 cases, 44.2%). Over time, intra‐aortic balloon pump (2005: 5104; 2017: 973 cases) was used less frequently, whereas use of extracorporeal‐membrane‐oxygenation (2007: 35; 2017: 2414 cases) and percutaneous left ventricular assist devices (2005: 27; 2017: 1323 cases) increased. Mortality remained high at around 60% without relevant temporal trends in patients without acute myocardial infarction and slightly decreased in patients with acute myocardial infarction. Conclusions In this large, nation‐wide study, annual incidence of cardiogenic shock was growing, its causes were changing, and mortality was high despite a shift towards use of novel mechanical circulatory support devices. This highlights the need to address the evidence gap in this field, in particular for cardiogenic shock caused by diseases other than acute myocardial infarction.

Abstract Myocardial rupture after thrombolysis is an often fatal consequence. For patients with myocardial infarction and ischemic stroke within a short timeframe, a catheter‐based therapy to retrieve emboli poses a valid therapeutic option in case of a treatment target in CT‐Angiography.

Background: In light of overlapping symptoms, discrimination between non-ST-elevation (NSTE) acute coronary syndrome (ACS) and acute heart failure (HF) is challenging, particularly in patients with equivocal clinical presentation for suspected ACS. We sought to evaluate the diagnostic and prognostic properties of copeptin in this scenario. Methods: Data from 1088 patients from a single-center observational registry were used to test the ability of serial high sensitivity cardiac troponin T (hs-cTnT)—compared to copeptin, or a combination of copeptin with hs-cTnT—to discriminate acute HF from uncomplicated non-ST-elevation myocardial infarction (NSTEMI) and to evaluate all-cause mortality after 365 days. Patients with STEMI, those with unstable angina and either normal or undetectable hs-cTnT concentrations were excluded. The findings were validated in an independent external NSTE-ACS cohort. Results: A total of 219 patients were included in the analysis. The final diagnosis was acute HF in 56 and NSTE-ACS in 163, with NSTEMI in 78 and unstable angina having stable elevation of hs-cTnT >ULN in 85. The rate of all-cause death at 1 year was 9.6% and occurred significantly more often in acute HF than in NSTE-ACS (15 vs. 6%, p < 0.001). In the test cohort, the area under the receiver operator curve (AUC) for the discrimination of acute HF vs. NSTE-ACS without HF was 0.725 (95% confidence interval [CI] 0.625–0.798) for copeptin and significantly higher than for hs-cTnT at 0 h (AUC = 0.460, 0.370–0.550) or at 3 h (AUC = 0.441, 0.343–0.538). Copeptin and hs-cTnT used either as continuous values or at cutoffs optimized to yield 90% specificity for acute HF were associated with significantly higher age- and sex-adjusted risk for all-cause mortality at 365 days. The findings from the test cohort were consistently replicated in the independent external NSTE-ACS validation cohort. Conclusions: High concentrations of copeptin in patients with suspected NSTE-ACS and equivocal clinical presentation suggest the presence of acute HF compared to uncomplicated NSTE-ACS and are associated with higher rates of all-cause death at 365 days.

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45–74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.