Impact of age and sex on left ventricular function determined by coronary computed tomographic angiography

__Background__ Left ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking __Methods and results __ 1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenterregistry (54.5% males, mean age 53.1 + 12.4 years, range: 18 – 92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD (.50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6 + 7.7% vs. 64.6 + 8.1%, P, 0.001). This gender-difference in overall LVEF was caused by a significantly higher LVEF in women ≥70 years when compared with men ≥70 years (69.95 + 8.89% vs. 65.50 + 9.42%, P ¼ 0.004). Accordingly, a significant increase in LVEF was observed with age (P ¼ 0.005 for males and P, 0.001 for females), which was more pronounced in females (5.21%) than in males (2.6%). LV end-diastolic volume decreased in females from 122.48+27.87 (,40 years) to 95.56+23.17 (.70 years; P, 0.001) and in males from 155.22+35.07 (,40 years) to 130.26+27.18 (.70 years; P, 0.001). __Conclusion__ Our findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for

Outcome of Patients With Severe Aortic Stenosis and Normal Coronary Arteries Undergoing Transcatheter Aortic Valve Implantation

Coronary artery disease and severe aortic stenosis (AS) often coexist. This study sought to investigate the impact of normal coronary arteries as negative risk marker in patients undergoing transcatheter aortic valve implantation (TAVI). Consecutive patients with severe AS undergoing TAVI were dichotomized according to the presence or absence of normal coronary arteries, defined as absence of coronary lesions with diameter stenosis ≥30% in vessels ≥1.5 mm in diameter on coronary angiogram in patients without prior coronary revascularization. The primary end point was 1-year mortality. Out of 987 patients with severe AS undergoing TAVI, 258 (26%) patients had normal coronary arteries. These patients were younger, more likely women, and had lower EuroSCORE II and STS risk scores. Although mortality at 30 days was similar in the normal coronary artery and the coronary atherosclerosis groups (3.1% vs 5.6%, p = 0.11), it was lower in those with normal coronary arteries at 1 year (8.9% vs 17%, p = 0.003). In multivariable analysis, the presence of normal coronary arteries on coronary angiogram independently predicted 1-year mortality (adjusted HR 0.57, 95% CI 0.37 to 0.90, p = 0.02). In conclusion, this study defined normal coronary arteries as negative risk marker in patients with severe AS undergoing TAVI

Higher 1-year mortality on rest days in patients with acute coronary syndromes and decompensated heart failure-A SPUM-ACS sub-study.

Acute coronary syndromes (ACS) occurring on rest days have been associated with higher mortality, but the current literature remains inconsistent in this regard. This study included ACS patients presenting with acute decompensated heart failure (ADHF) investigating the relationship between time of coronary catheterization and outcomes. Analyses were performed from the prospective, multicentric Special Program University Medicine Acute Coronary Syndromes and Inflammation (SPUM-ACS) Cohort. Patients were divided into two groups according to time of coronary catheterization on either workdays (Monday, 00:00 to Friday, 23:59) or rest days (Saturday, 00:00 to Sunday, 23:59 and public holidays). ADHF was defined by Killip Class III or IV upon presentation. Patients were followed over 1 year. Out of 4787 ACS patients enrolled in the SPUM-ACS Cohort, 207 (4.3%) presented with ADHF. 52 (25.1%) and 155 (74.9%) patients underwent coronary angiography on rest days or workdays, respectively. Baseline characteristics were similar among these groups. ACS patients with ADHF showed increased 1-year mortality on rest days (34.6% vs. 17.4%, p-value = 0.009). After correction for baseline characteristics, including the GRACE 2.0 Score, rest day presentation remained a significant predictor for 1-year mortality (adjusted hazard ratio = 2.42 [95% confidence interval: 1.14-5.17], p-value = 0.022). One-year all-cause mortality was high in ACS patients with ADHF and doubled for patients admitted on rest days. The present data support the association of a rest day effect and long-term patient survival and indicate a need for further investigations

Residual inflammatory risk at 12 months after acute coronary syndromes is frequent and associated with combined adverse events.

Residual inflammatory risk (RIR) after acute coronary syndromes (ACS) may identify patients likely to benefit from anti-inflammatory therapies. Patients from the Special Program University Medicine ACS cohort were divided into four groups according to level of hsCRP at baseline and after 12 months: persistently high RIR, increased RIR (first low, then high hsCRP), attenuated RIR (first high, then low hsCRP), or persistently low RIR. High RIR was defined as hsCRP ≥ 2 mg/L. An independently adjudicated incident of combined adverse events was defined as the composite of myocardial infarction, clinically indicated coronary revascularization or cerebrovascular events. Among 1209 patients with available hsCRP, clinical and demographic data, 295 (24.4%) patients had persistently high RIR (delta hsCRP median (IQR): 2.3 (-9.9; 0.3) (mg/L) and 72 (5.96%) patients had increased RIR (delta hsCRP median (IQR): +2.45 (1.2; 8.35) (mg/L). A total of 390 (32.26%) patients had attenuated RIR (delta hsCRP median (IQR): 3.55 (-10; -2) (mg/L) and 452 (37.38%) patients had persistently low RIR (delta hsCRP median (IQR): 0.2 (-0.6; 0.1) (mg/L). Of 90 combined adverse events, 31 (10.5%) occurred in the persistently high (multivariable adjusted OR: 1.71, (95% CI 1.08-2.7), p = 0.022) compared with the three other groups combined (increased RIR: 3 (4.2%), attenuated RIR 30 (7.7%), persistently low RIR 26 (5.8%). Persistently elevated hsCRP after ACS is found in a quarter of patients with the highest risk of combined adverse events. This underlines the need to perform anti-inflammatory intervention trials in RIR patients

Predictive value of the age, creatinine, and ejection fraction (ACEF) score in patients with acute coronary syndromes.

This study sought to investigate the predictive value of the age, creatinine, and ejection fraction (ACEF) score in patients with acute coronary syndromes (ACS). The ACEF score (age/left ventricular ejection fraction +1 [if creatinine > 176 μmol/L]) has been established in patients evaluated for coronary artery bypass surgery. Data on its predictive value in all-comer ACS patients undergoing percutaneous coronary intervention are scarce. A total of 1901 patients prospectively enrolled in the Swiss ACS Cohort were included in the analysis. Optimal ACEF score cut-off values were calculated by decision tree analysis, and patients divided into low-risk (≤1.45), intermediate-risk (>1.45 and ≤2.0), and high-risk groups (>2.0). The primary endpoint was all-cause mortality. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, non-fatal myocardial infarction, clinically indicated repeat coronary revascularization, definite stent thrombosis, and transient ischemic attack/stroke. One-year rates of all-cause death increased across ACEF score groups (1.6% versus 5.6% versus 23.0%, p < 0.001). In multivariate analysis, the ACEF score was related with an increased risk of all-cause mortality (adjusted HR 3.53, 95% CI 2.90-4.31, p < 0.001), MACCE (adjusted HR 2.23, 95% CI 1.88-2.65, p < 0.001), and transient ischemic attack/stroke (adjusted HR 2.58, 95% CI 1.71-3.89, p < 0.001) at 1 year. Rates of Thrombolysis in Myocardial Infarction (TIMI) major and Global use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding paralleled the increased ischemic risk across the groups (p < 0.001). The ACEF score is a simple and useful risk stratification tool in patients with ACS referred for coronary revascularization

Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction.

MicroRNAs (miRNA) are important non-coding modulators controlling patterns of gene expression. However, profiling and validation of circulating miRNA levels related to adverse cardiovascular outcome has not been performed in patients with an acute coronary syndrome (ACS). In a multicentre, prospective ACS cohort, 1002 out of 2168 patients presented with ST-segment elevation myocardial infarction (STEMI). Sixty-three STEMI patients experienced an adjudicated major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year of follow-up. From a miRNA profiling in a matched derivation case-control cohort, 14 miRNAs were selected for validation. Comparing 63 cases vs. 126 controls, 3 miRNAs were significantly differentially abundant. In patients with MACE, miR-26b-5p levels (P = 0.038) were decreased, whereas miR-320a (P = 0.047) and miR-660-5p (P = 0.01) levels were increased. MiR-26b-5p has been suggested to prevent adverse cardiomyocyte hypertrophy, whereas miR-320a promotes cardiomyocyte death and apoptosis, and miR-660-5p has been related to active platelet production. This suggests that miR-26b-5p, miR-320a, and miR-660-5p may reflect alterations of different pathophysiological pathways involved in clinical outcome after ACS. Consistently, these three miRNAs reliably discriminated cases from controls [area under the receiver-operating characteristic curve (AUC) in age- and sex-adjusted Cox regression for miR-26b-5p = 0.707, miR-660-5p = 0.683, and miR-320a =0.672]. Combination of the three miRNAs further increased AUC to 0.718. Importantly, addition of the three miRNAs to both, the Global Registry of Acute Coronary Events (GRACE) score and a clinical model increased AUC from 0.679 to 0.720 and 0.722 to 0.732, respectively, with a net reclassification improvement of 0.20 in both cases. This is the first study performing profiling and validation of miRNAs that are associated with adverse cardiovascular outcome in patients with STEMI. MiR-26b-5p, miR-320a, and miR-660-5p discriminated for MACE and increased risk prediction when added to the GRACE score and a clinical model. These findings suggest that the release of specific miRNAs into circulation may reflect the activation of molecular pathways that impact on clinical outcome after STEMI

Safety profile of prasugrel and clopidogrel in patients with acute coronary syndromes in Switzerland.

OBJECTIVE: To assess safety up to 1 year of follow-up associated with prasugrel and clopidogrel use in a prospective cohort of patients with acute coronary syndromes (ACS). METHODS: Between 2009 and 2012, 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort, among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines. Patients with ST-elevation myocardial infarction (STEMI) preferentially received prasugrel, while those with non-STEMI, a history of stroke or transient ischaemic attack, age ≥75 years, or weight <60 kg received clopidogrel or reduced dose of prasugrel to comply with the prasugrel label. RESULTS: After adjustment using propensity scores, the primary end point of clinically relevant bleeding events (defined as the composite of Bleeding Academic Research Consortium, BARC, type 3, 4 or 5 bleeding) at 1 year, occurred at a similar rate in both patient groups (prasugrel/clopidogrel: 3.8%/5.5%). Stratified analyses in subgroups including patients with STEMI yielded a similar safety profile. After adjusting for baseline variables, no relevant differences in major adverse cardiovascular and cerebrovascular events were observed at 1 year (prasugrel/clopidogrel: cardiac death 2.6%/4.2%, myocardial infarction 2.7%/3.8%, revascularisation 5.9%/6.7%, stroke 1.0%/1.6%). Of note, this study was not designed to compare efficacy between prasugrel and clopidogrel. CONCLUSIONS: In this large prospective ACS cohort, patients treated with prasugrel according to current guidelines (ie, in patients without cerebrovascular disease, old age or underweight) had a similar safety profile compared with patients treated with clopidogrel. CLINICAL TRIAL REGISTRATION NUMBER: SPUM-ACS: NCT01000701; COMFORTABLE AMI: NCT00962416