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.

Optimisation of individual cardiovascular risk assessment in a German coronary artery disease cohort using a commercial test for genetic polymorphisms - a pilot study.

BACKGROUND AND AIMS: Assessment of cardiovascular risk using established risk scores such as ESC SCORE2 or PROCAM insufficiently emphasise the role of genetic factors. We hypothesise that commercially available genetic assays may provide additional information on hereditary cardiovascular risk in a timely and cost-efficient manner. METHODS: In a cohort of 51 patients treated for coronary artery disease (CAD) at University Hospital Heidelberg, Germany, a subgroup of patients with "unstable" CAD (i.e. recurrent acute coronary syndrome) was identified and compared to patients with "stable" disease (i.e. chronic coronary syndrome). Gene array analysis using a commercial assay for 15 potentially pathogenic polymorphisms revealed our cohort's genetic risk profile regarding atherosclerotic/thromboembolic events. Improvement of cardiovascular risk assessment based on established risk scores was analysed using net reclassification, logistic regression and receiver operating characteristic (ROC) analysis. RESULTS: Discriminatory capacity of traditional risk scores such as SCORE2 or PROCAM with regard to stable and unstable CAD groups was poor (ROC AUC <0.5). Patients with "unstable" CAD exhibited a significantly increased frequency of pathogenic eNOS 894 T and MTHFR 1298 C polymorphisms compared to "stable" CAD patients, and information on these polymorphisms individually as well as combinations with additional polymorphisms included in the assay such as ACE D/D or PAI-1 5 G variants markedly improved risk prediction compared to SCORE2/PROCAM alone (ROC AUC ≥0.75). CONCLUSION: Commercially available assays for genetic polymorphisms may provide valuable information on individual genetic cardiovascular risk, potentially guiding future primary and/or secondary preventative therapies for coronary artery disease.

A head-to-head comparison of fast-SENC and feature tracking to LV long axis strain for assessment of myocardial deformation in chest pain patients.

BACKGROUND: Myocardial strain imaging has gained importance in cardiac magnetic resonance (CMR) imaging in recent years as an even more sensitive marker of early left ventricular dysfunction than left-ventricular ejection fraction (LVEF). fSENC (fast strain encoded imaging) and FT (feature tracking) both allow for reproducible assessment of myocardial strain. However, left-ventricular long axis strain (LVLAS) might enable an equally sensitive measurement of myocardial deformation as global longitudinal or circumferential strain in a more rapid and simple fashion. METHODS: In this study we compared the diagnostic performance of fSENC, FT and LVLAS for identification of cardiac pathology (ACS, cardiac-non-ACS) in patients presenting with chest pain (initial hscTnT 5-52 ng/l). Patients were prospectively recruited from the chest pain unit in Heidelberg. The CMR scan was performed within 1 h after patient presentation. Analysis of LVLAS was compared to the GLS and GCS as measured by fSENC and FT. RESULTS: In total 40 patients were recruited (ACS n = 6, cardiac-non-ACS n = 6, non-cardiac n = 28). LVLAS was comparable to fSENC for differentiation between healthy myocardium and myocardial dysfunction (GLS-fSENC AUC: 0.882; GCS-fSENC AUC: 0.899; LVLAS AUC: 0.771; GLS-FT AUC: 0.740; GCS-FT: 0.688), while FT-derived strain did not allow for differentiation between ACS and non-cardiac patients. There was significant variability between the three techniques. Intra- and inter-observer variability (OV) was excellent for fSENC and FT, while for LVLAS the agreement was lower and levels of variability higher (intra-OV: Pearson > 0.7, ICC > 0.8; inter-OV: Pearson > 0.65, ICC > 0.8; CoV > 25%). CONCLUSIONS: While reproducibility was excellent for both FT and fSENC, it was only fSENC and the LVLAS which allowed for significant identification of myocardial dysfunction, even before LVEF, and therefore might be used as rapid supporting parameters for assessment of left-ventricular function.

Multi-omics assessment of dilated cardiomyopathy using non-negative matrix factorization.

Dilated cardiomyopathy (DCM), a myocardial disease, is heterogeneous and often results in heart failure and sudden cardiac death. Unavailability of cardiac tissue has hindered the comprehensive exploration of gene regulatory networks and nodal players in DCM. In this study, we carried out integrated analysis of transcriptome and methylome data using non-negative matrix factorization from a cohort of DCM patients to uncover underlying latent factors and covarying features between whole-transcriptome and epigenome omics datasets from tissue biopsies of living patients. DNA methylation data from Infinium HM450 and mRNA Illumina sequencing of n = 33 DCM and n = 24 control probands were filtered, analyzed and used as input for matrix factorization using R NMF package. Mann-Whitney U test showed 4 out of 5 latent factors are significantly different between DCM and control probands (P<0.05). Characterization of top 10% features driving each latent factor showed a significant enrichment of biological processes known to be involved in DCM pathogenesis, including immune response (P = 3.97E-21), nucleic acid binding (P = 1.42E-18), extracellular matrix (P = 9.23E-14) and myofibrillar structure (P = 8.46E-12). Correlation network analysis revealed interaction of important sarcomeric genes like Nebulin, Tropomyosin alpha-3 and ERC-protein 2 with CpG methylation of ATPase Phospholipid Transporting 11A0, Solute Carrier Family 12 Member 7 and Leucine Rich Repeat Containing 14B, all with significant P values associated with correlation coefficients >0.7. Using matrix factorization, multi-omics data derived from human tissue samples can be integrated and novel interactions can be identified. Hypothesis generating nature of such analysis could help to better understand the pathophysiology of complex traits such as DCM.

European Society of Cardiology guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 1-epidemiology, pathophysiology, and diagnosis.

AIMS: Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. METHODS AND RESULTS: A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. CONCLUSION: This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities.

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

BACKGROUND: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes. METHODS: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients. RESULTS: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients. CONCLUSION: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.

A complex intervention to promote prevention of delirium in older adults by targeting caregiver's participation during and after hospital discharge - study protocol of the TRAnsport and DElirium in older people (TRADE) project.

BACKGROUND: Among potentially modifiable risk factors for delirium, transfers between wards, hospitals and other facilities have been mentioned with low evidence. TRADE (TRAnsport and DElirium in older people) was set up to investigate i) the impact of transfer and/or discharge on the onset of delirium in older adults and ii) feasibility and acceptance of a developed complex intervention targeting caregiver's participation during and after hospital discharge or transfer on cognition and the onset of delirium in older adults. METHODS: The study is designed according to the guidelines of the UK Medical Research Council (MRC) for development and evaluation of complex interventions and comprises two steps: development and feasibility/piloting. The development phase includes i) a multicenter observational prospective cohort study to assess delirium incidence and cognitive decline associated with transfer and discharge, ii) a systematic review of the literature, iii) stakeholder focus group interviews and iv) an expert workshop followed by a Delphi survey. Based on this information, a complex intervention to better and systematically involve family caregivers in discharge and transport was developed. The intervention will be tested in a pilot study using a stepped wedge design with a detailed process and health economic evaluation. The study is conducted at four acute care hospitals in southwest Germany. Primary endpoints are the delirium incidence and cognitive function. Secondary endpoints include prevalence of caregiver companionship, functional decline, cost and cost effectiveness, quality of discharge management and quality of admission management in admitting hospitals or nursing homes. Data will be collected prior to discharge as well as after 3, 7 and 90 days. DISCUSSION: TRADE will help to evaluate transfer and discharge as a possible risk factor for delirium. In addition, TRADE evaluates the impact and modifiability of caregiver's participation during patient's transfer or discharge on delirium incidence and cognitive decline providing the foundation for a confirmatory implementation study. TRIAL REGISTRATION: DRKS (Deutsches Register für klinische Studien) DRKS00017828 . Registered on 17th September 2019. Retrospectively registered.

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome.

Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.

Spatial relationship between the pulmonary trunk and the left coronaries: Systematic risk assessment based on automated three-dimensional distance measurements.

BACKGROUND: Catheter ablation of right ventricular outflow tract ventricular arrhythmias from above the pulmonary valve is being increasingly reported. OBJECTIVE: The purpose of this study was to systematically analyze the spatial relationship between the pulmonary trunk and the left coronaries. METHODS: Contrast-enhanced computed tomographic scans from 58 patients were analyzed. After segmentation of the pulmonary trunk and the proximal left coronaries, 3-dimensional geometries were generated. Minimal distance between the pulmonary trunk and the coronaries was automatically determined using a newly developed mathematical algorithm. RESULTS: The minimal distance between the pulmonary trunk and the coronaries was 1.4 ± 0.11 mm. Closest relationship was detected 13.8 ± 0.87 mm above the pulmonary valve annulus. Considering a safety margin of 5 mm to render coronary damage unlikely, 84% of patients were found to be at potential risk within the bottom 10 mm of the left sinus cusp. In contrast, positions within or above the right and anterior cusps were less likely to exhibit a close relationship. We identified the anterior aspect of the left cusp as the most critical region. Positions 10-20 mm above the left cusp were found to be critical in 97% of patients. Clinical parameters such as gender, age, height, weight, and body mass index were not predictive of a close spatial relationship. CONCLUSION: Our data provide evidence for a close spatial relationship between the pulmonary trunk and coronary arteries. These results should be considered when performing catheter ablation from above the pulmonary valve.

Temporary oral anticoagulation after MitraClip - a strategy to lower the incidence of post-procedural stroke?

Background: Incidence of stroke within 30 days after percutaneous mitral valve repair using the MitraClip varies from 0.7% and 2.6% between registries. Standard medical treatment after the MitraClip procedure, in the absence of risk factors requiring antithrombotic therapy such as atrial fibrillation, is dual antiplatelet therapy using aspirin and clopidogrel. ESC/EACTS and ACC/AHA surgical guidelines show a Class IIa indication for temporary antithrombotic therapy after mitral valve repair/bioprosthetic valve replacement within the first three months even in patients with no additional risk factors.Methods: 470 patients were treated with the MitraClip receiving oral anticoagulation (Coumadin: INR 2.0-3.0) instead of dual antiplatelet therapy for at least 30 days after the procedure. The incidence of stroke, as well as major adverse events such as bleeding, were analysed in comparison to large registries and multi-centre studies.Results: Incidence of stroke within 30 days was significantly reduced as compared to comparative cohorts (0.2% vs. Median 1.3% [0.7-2.6%]; p < .05). Cardiovascular risk factors such as age, atrial fibrillation, hypertension, diabetes, STS score and prior stroke did not differ significantly between cohorts (ns). Bleeding complications were not increased due to 30 days oral anticoagulation treatment (4.6% vs. Median 7.4% [3.4-13.6%]; ns).Conclusions: Temporary oral anticoagulation might be a strategy to reduce the incidence of stroke within the first 30 days after the MitraClip procedure. Bleeding events were not significantly altered due to temporary oral anticoagulation.

Strain-encoded magnetic resonance: a method for the assessment of myocardial deformation.

This study aims to assess the usefulness of strain-encoded magnetic resonance (SENC) for the quantification of myocardial deformation ('strain') in healthy volunteers and for the diagnostic workup of patients with different cardiovascular pathologies. SENC was initially described in the year 2001. Since then, the SENC sequence has undergone several technical developments, aiming at the detection of strain during single-heartbeat acquisitions (fast-SENC). Experimental and clinical studies that used SENC and fast-SENC or compared SENC with conventional cine or tagged magnetic resonance in phantoms, animals, healthy volunteers, or patients were systematically searched for in PubMed. Using 'strain-encoded magnetic resonance and SENC' as keywords, three phantom and three animal studies were identified, along with 27 further clinical studies, involving 185 healthy subjects and 904 patients. SENC (i) enabled reproducible assessment of myocardial deformation in vitro, in animals and in healthy volunteers, (ii) showed high reproducibility and substantially lower time spent compared with conventional tagging, (iii) exhibited incremental value to standard cine imaging for the detection of inducible ischaemia and for the risk stratification of patients with ischaemic heart disease, and (iv) enabled the diagnostic classification of patients with transplant vasculopathy, cardiomyopathies, pulmonary hypertension, and diabetic heart disease. SENC has the potential to detect a wide range of myocardial diseases early, accurately, and without the need of contrast agent injection, possibly enabling the initiation of specific cardiac therapies during earlier disease stages. Its one-heartbeat acquisition mode during free breathing results in shorter cardiovascular magnetic resonance protocols, making its implementation in the clinical realm promising.

The Charlson Comorbidity and Barthel Index predict length of hospital stay, mortality, cardiovascular mortality and rehospitalization in unselected older patients admitted to the emergency department.

BACKGROUND AND AIMS: The Charlson Comorbidity Index (CCI) is the most widely used assessment tool to report the presence of comorbid conditions. The Barthel index (BI) is used to measure performance in activities of daily living. We prospectively investigated the performance of CCI or BI to predict length of hospital stay (LOS), mortality, cardiovascular (CV) mortality and rehospitalization in unselected older patients on admission to the emergency department (ED). We also studied the association of CCI or BI with costs. METHODS: We consecutively enrolled 307 non-surgical patients ≥ 68 years presenting to the ED with a wide range of comorbid conditions. Baseline characteristic, clinical presentation, laboratory data, echocardiographic parameters and hospital costs were compared among patients. All patients were followed up for mortality, CV mortality and rehospitalization within the following 12 months. A multivariate analysis was performed. RESULTS: Mortality was increased for patients having a higher CCI or BI with a hazard ratio around 1.17-1.26 or 0.75-0.81 (obtained for different models) for one or ten point increase in CCI or BI, respectively. The prognostic impact of a high CCI or BI on CV mortality and rehospitalization was also significant. In a multiple linear regression using the same independent variables, CCI and BI were identified as a predictor of LOS in days. Multiple linear regression analysis did not confirm an association between CCI and costs, but for BI after adjusting for multiple factors. CONCLUSION: CCI and BI independently predict LOS, mortality, CV mortality, and rehospitalization in unselected older patients admitted to ED.

Multimodality cardiac computed tomography angiography and magnetic resonance with clinical-grade scanners provide robust assessment of cardiac morphology and function in rabbits.

BACKGROUND: Non-invasive computer tomography (CT)- and magnetic resonance (MR)-based cardiac imaging still remains challenging in rodents. To investigate the robustness of non-invasive multimodality cardiac imaging in rabbits using clinical-grade CT and MR scanners. METHODS: A total of 16 rabbits (2.7-4.0 kg) serially underwent cardiac-gated imaging using a clinical-grade 256-row CT and a 1.5 Tesla MR-scanner at baseline and at 4-month follow-up (16±1 weeks). Image analysis included image quality (5-grade scale), left ventricular (LV) volumes, LV stroke volume, LV diameters, LV wall thickness and ejection fraction (LVEF). RESULTS: Cardiac MR (CMR) and CT angiography (CTA) provide images with an overall good image quality (excellent or good quality: CMR 82% vs. CTA 78%, P=0.68). Linear regression analysis demonstrated a good correlation of all diameters (diam.) and volumes (vol.) as assessed by CTA and CMR (diam.: r=0.9, 95% CI: 0.8-0.9; vol.: r=0.8, 95% CI: 0.6-0.9; P<0.0001 for both). CTA-based volumetric analysis revealed slightly higher LVEF values as compared to CMR (CTA: 64%±1%, CMR: 59%±1%, P=0.002). Analysis of inter-/intra-observer agreement demonstrated excellent agreements for diameters (CMR: 98.5%/98.7%; CTA: 98.2%/97.4%) and volumes (CMR: 99.9%/98.8%; CTA 98.7%/98.7%). Finally, serial CMR- and CTA-based assessment of cardiac diameters and volumes delivered excellent intersession agreements of baseline versus follow-up data (diam.: CMR: r=0.89; CTA: r=0.92; vol.: CMR: r=0.87; CTA: r=0.96, P<0.0001 for all). CONCLUSIONS: Multimodality non-invasive assessment of cardiac function and aortic hemodynamics is feasible and robust in rabbits using clinical-grade and MR and CT scanners. These imaging modalities could improve serial cardiac assessment for disease monitoring in preclinical settings.

Unidimensional Longitudinal Strain: A Simple Approach for the Assessment of Longitudinal Myocardial Deformation by Echocardiography.

BACKGROUND: Impaired left ventricular (LV) longitudinal function (LF) is a known predictor of cardiac events in patients with heart failure, but two-dimensional strain imaging, the reference method to measure myocardial deformation, is not always feasible or available. Therefore, reliable and reproducible alternatives are needed. The aim of the present study was to evaluate unidimensional longitudinal strain (ULS) as a simple echocardiographic parameter for the assessment of LV LF. METHODS: Two hundred two patients with dilated cardiomyopathy who had their first presentation in the authors' cardiology department, as well as the same number of age- and gender-matched control subjects, were prospectively included in this study. ULS was compared with global longitudinal strain (GLS), the current gold standard for LV LF assessment by echocardiography. Uni- and multivariate Cox regression analyses were conducted to evaluate the prognostic value of ULS. RESULTS: LV LF was higher in the control group compared with patients: GLS -19.5 ± 1.7% versus -12.6 ± 4.8% and ULS -16.3 ± 1.5% versus -10.2 ± 3.9% (P < .001 for each). Correlation between ULS and GLS was excellent (r = 0.94), while Bland-Altman plots revealed lower values for ULS (bias -2.76%, limits of agreement ±3.31%). During a mean follow-up time of 39 months, the combined end point of cardiovascular death or hospitalization for acute cardiac decompensation was reached by 28 patients (13.9%). GLS (hazard ratio, 1.21; 95% CI, 1.10-1.34; P < .001) and ULS (hazard ratio, 1.24; 95% CI, 1.12-1.39; P < .001) had comparable prognostic impact on patient outcomes. CONCLUSIONS: ULS might be an alternative echocardiographic method for the assessment of LV LF, with similar diagnostic and prognostic value compared with GLS.

Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas.

AIMS: To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque. METHODS AND RESULTS: Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). CONCLUSION: Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.

Medical Classification and Terminology Systems in a Secondary Use Context: Challenges and Perils.

Since the introduction of diagnosis-related groups in the German healthcare system, classifying patient diagnosis and procedures with controlled vocabularies have become mandatory and thus creating a large dataset for secondary use in biomedical research. In this paper we present the analysis of an ICD dataset with regards to potentially reimbursement motivated classification and the effects on precision and recall when considering the change history of ICD codes.

Fast assessment of long axis strain with standard cardiovascular magnetic resonance: a validation study of a novel parameter with reference values.

BACKGROUND: Assessment of longitudinal function with cardiovascular magnetic resonance (CMR) is limited to measurement of systolic excursion of the mitral annulus (MAPSE) or elaborate strain imaging modalities. The aim of this study was to develop a fast assessable parameter for the measurement of long axis strain (LAS) with CMR. METHODS: 40 healthy volunteers and 125 patients with different forms of cardiomyopathy were retrospectively analyzed. Four different approaches for the assessment of LAS with CMR measuring the distance between the LV apex and a line connecting the origins of the mitral valve leaflets in enddiastole and endsystole were evaluated. Values for LAS were calculated according to the strain formula. RESULTS: LAS derived from the distance of the epicardial apical border to the midpoint of the line connecting the mitral valve insertion points (LAS-epi/mid) proved to be the most reliable parameter for the assessment of LAS among the different approaches. LAS-epi/mid displayed the highest sensitivity (81.6 %) and specificity (97.5 %), furthermore showing the best correlation with feature tracking (FTI) derived transmural longitudinal strain (r = 0.85). Moreover, LAS-epi/mid was non-inferior to FTI in discriminating controls from patients (Area under the curve (AUC) = 0.95 vs. 0.94, p = NS). The time required for analysis of LAS-epi/mid was significantly shorter than for FTI (67 ± 8 s vs. 180 ± 14 s, p < 0.0001). Additionally, LAS-epi/mid performed significantly better than MAPSE (Delta AUC = 0.09; p < 0.005) and the ejection fraction (Delta AUC = 0.11; p = 0.0002). Reference values were derived from 234 selected healthy volunteers. Mean value for LAS-epi/mid was -17.1 ± 2.3 %. Mean values for men were significantly lower compared to women (-16.5 ± 2.2 vs. -17.9 ± 2.1 %; p < 0.0001), while LAS decreased with age. CONCLUSIONS: LAS-epi/mid is a novel and fast assessable parameter for the analysis of global longitudinal function with non-inferiority compared to transmural longitudinal strain.

Long-term effect of a low-intensity smoking intervention embedded in an adherence program for patients with hypercholesterolemia: Randomized controlled trial.

OBJECTIVE: We evaluated the long-term effect of a smoking intervention embedded in an adherence program in patients with an increased risk for cardiovascular disease. METHOD: Secondary analysis of a randomized controlled trial: In 2002-2004, 8108 patients with hypercholesterolemia were enrolled from general practices in Germany. Patients received a 12-month adherence program and statin medication (intervention) or statin medication only (control). The program aimed to improve adherence to medication and lifestyle by educational material, mailings, and phone calls. Smoking was self-reported at baseline and every 6months during the 3-year follow-up. RESULTS: In total, 7640 patients were analyzed. At baseline, smoking prevalence was 21.7% in the intervention and 21.5% in the control group. Prevalence decreased in both groups to 16.6% vs. 19.5%, 15.3% vs. 16.8%, and 14.2% vs. 15.6% at the 12-, 24-, and 36-month follow-up. The intervention had a beneficial effect on smoking differing over time (group×time: P=0.005). The effect was largest after 6 and 12months [odds ratios (95% confidence intervals): 0.67 (0.54-0.82) and 0.63 (0.51-0.78)]. The effect decreased until the 18-month follow-up [0.72 (0.58-0.90)] and was not significant after 24months. CONCLUSION: A low-intensity smoking intervention embedded in an adherence program can contribute to smoking cessation although the intervention effect diminished over time. TRIAL REGISTRATION: ClinicalTrials.gov (www.clinicaltrials.gov): NCT00379249.

Combined Assessment of High-Sensitivity Troponin T and Noninvasive Coronary Plaque Composition for the Prediction of Cardiac Outcomes.

PURPOSE: To determine the risk-stratification ability of plaque volume and composition assessment with cardiac computed tomographic (CT) angiography and high-sensitivity troponin T (hsTnT) in patients at intermediate risk for coronary artery disease (CAD). MATERIALS AND METHODS: The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients gave written informed consent. Five hundred twenty-one consecutive patients (mean age ± standard deviation, 62 years ± 10; 256 men and 265 women) were included in this prospective, observational, longitudinal, single-center study. Quantitative cardiac CT angiography analysis was performed in all patients (for 7690 coronary segments), whereas biomarkers (hsTnT and high-sensitivity C-reactive protein) were available in 408 patients (78%). To evaluate the incremental value of cardiac CT angiography and hsTnT for the prediction of cardiovascular events, multivariate Cox regression and integrated discrimination improvement analysis were applied. RESULTS: In 521 patients, 13 hard cardiac events occurred during a mean follow-up period of 2.3 years ± 1.1 (median, 2.4 years; range, 0.5-4.5 years), while 23 patients underwent late coronary revascularization. The Duke clinical score was 51% ± 30, indicating intermediate risk. The presence of no plaques or purely calcified versus noncalcified plaques, plaque volume according to tertiles, and increased hsTnT (≥14 pg/mL) was independently associated with hard cardiac events (hazard ratio [HR] = 26.08, 95% confidence interval [CI]: 2.78, 244.99; HR = 12.14, 95% CI: 1.87, 78.74; and HR = 10.31, 95% CI: 2.72, 39.0, respectively; P < .01 for all). Patients with increased hsTnT and plaque burden (n = 53) showed the highest incidence for hard cardiac events (annual rate, 12.7%), followed by those with either increased hsTnT or plaque burden (n = 145; annual rate = 0.44%, P < .03), while those with lower hsTnT and plaque burden exhibited excellent outcomes and no hard event during the follow-up duration (n = 210; annual rate = 0%, P < .001). CONCLUSION: Use of hsTnT as a marker of myocardial microinjury and cardiac CT angiography as a marker of the total atherosclerotic burden improves the prediction of cardiac outcome in patients with presumably stable CAD and may aid in personalized risk stratification in patients at intermediate risk.

Assessment of global longitudinal strain using standardized myocardial deformation imaging: a modality independent software approach.

BACKGROUND: Myocardial deformation measurement is superior to left ventricular ejection fraction in identifying early changes in myocardial contractility and prediction of cardiovascular outcome. The lack of standardization hinders its clinical implementation. The aim of the study is to investigate a novel standardized deformation imaging approach based on the feature tracking algorithm for the assessment of global longitudinal (GLS) and global circumferential strain (GCS) in echocardiography and cardiac magnetic resonance imaging (CMR). METHODS: 70 subjects undergoing CMR were consecutively investigated with echocardiography within a median time of 30 min. GLS and GCS were analyzed with a post-processing software incorporating the same standardized algorithm for both modalities. Global strain was defined as the relative shortening of the whole endocardial contour length and calculated according to the strain formula. RESULTS: Mean GLS values were -16.2 ± 5.3 and -17.3 ± 5.3 % for echocardiography and CMR, respectively. GLS did not differ significantly between the two imaging modalities, which showed strong correlation (r = 0.86), a small bias (-1.1 %) and narrow 95 % limits of agreement (LOA ± 5.4 %). Mean GCS values were -17.9 ± 6.3 and -24.4 ± 7.8 % for echocardiography and CMR, respectively. GCS was significantly underestimated by echocardiography (p < 0.001). A weaker correlation (r = 0.73), a higher bias (-6.5 %) and wider LOA (± 10.5 %) were observed for GCS. GLS showed a strong correlation (r = 0.92) when image quality was good, while correlation dropped to r = 0.82 with poor acoustic windows in echocardiography. GCS assessment revealed only a strong correlation (r = 0.87) when echocardiographic image quality was good. No significant differences for GLS between two different echocardiographic vendors could be detected. CONCLUSIONS: Quantitative assessment of GLS using a standardized software algorithm allows the direct comparison of values acquired irrespective of the imaging modality. GLS may, therefore, serve as a reliable parameter for the assessment of global left ventricular function in clinical routine besides standard evaluation of the ejection fraction.