Optimizing resource allocation: Cost-effectiveness of specified D-dimer cut-offs in cancer patients with suspected venous thromboembolism.

An accurate diagnosis of venous thromboembolism (VTE) is crucial, given the potential for high mortality in undetected cases. Strategic D-dimer testing may aid in identifying low-risk patients, preventing overdiagnosis and reducing imaging costs. We conducted a retrospective, comparative analysis to assess the potential cost savings that could be achieved by adopting different approaches to determine the most effective D-dimer cut-off value in cancer patients with suspected VTE, compared to the commonly used rule-out cut-off level of 0.5 mg/L. The study included 526 patients (median age 65, IQR 55-75) with a confirmed cancer diagnosis who underwent D-dimer testing. Among these patients, the VTE prevalence was 29% (n = 152). Each diagnostic strategy's sensitivity, specificity, negative likelihood ratio (NLR), as well as positive likelihood ratio (PLR), and the proportion of patients exhibiting a negative D-dimer test result, were calculated. The diagnostic strategy that demonstrated the best balance between specificity, sensitivity, NLR, and PLR, utilized an inverse age-specific cut-off level for D-dimer [0.5 + (66-age) × 0.01 mg/L]. This method yielded a PLR of 2.9 at a very low NLR for the exclusion of VTE. We observed a significant cost reduction of 4.6% and 1.0% for PE and DVT, respectively. The utilization of an age-adjusted cut-off [patient's age × 0.01 mg/L] resulted in the highest cost savings, reaching 8.1% for PE and 3.4% for DVT. Using specified D-dimer cut-offs in the diagnosis of VTE could improve economics, considering the limited occurrence of confirmed cases among patients with suspected VTE.

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.

Extended dual antiplatelet therapy with ticagrelor 60 mg in patients with prior myocardial infarction: The design of ALETHEIA, a multi-country observational study.

INTRODUCTION: Clinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high-risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited. METHODS: ALETHEIA is an observational, multi-country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post-MI patients who initiate ticagrelor 60 mg in routine clinical practice (NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post-MI. Assuming an a priori threshold of 5000 person-years on-treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta-analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included. DISCUSSION: An increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high-risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision-making and treatment optimization.

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.

Analysis of Symptoms of COVID-19 Positive Patients and Potential Effects on Initial Assessment.

BACKGROUND: SARS-CoV-2 is a highly contagious virus, significantly impacting Germany among other countries since its emergence. Because of heterogeneous symptoms and a subset of patients even being asymptomatic at presentation, fast identification of infected patients remains challenging. OBJECTIVE: The goal of this study is the evaluation of different patient groups with a focus on symptoms and pre-existing illness at admission, as this is important for initial assessment and adequate emergency care. METHODS: COVID-19 positive patients at the University Hospital Heidelberg were retrospectively analyzed for disease history and symptoms at the initial presentation as well as mortality. The authors obtained institutional review board (IRB) approval by the Ethics Committee (Medical Faculty of Heidelberg University) prior to commencing the study. RESULTS: Dyspnea was more common in patients admitted to intermediate care/intensive care units (48 vs 13%, P<0.001) and showed a significantly higher percentage in the deceased (91 vs 48%, P=0.004). The symptoms of all presenting patients were highly variable, and many manifestations commonly associated with COVID-19 like cough, fever, and sore throat were only detected in a subset of patients, 60%, 43%, and 33%, respectively. CONCLUSION: Dyspnea was present significantly more often in patients dying of COVID-19 compared to all patients admitted to the IMC/ICU, necessitating adequate observation and monitoring. In all presenting patients, initial symptoms showed large variation; therefore, COVID should be considered as a main differential diagnosis at every patient presentation, and patients with high pre-test probability should, if possible, be isolated until testing results are known.

Capacity changes in German certified chest pain units during COVID-19 outbreak response.

BACKGROUND: We sought to determine structure and changes in organisation and bed capacities of certified German chest pain units (CPU) in response to the emergency plan set-up as a response to the SARS-CoV-2 pandemic. METHODS AND RESULTS: The study was conducted in the form of a standardised telephone interview survey in certified German CPUs. Analyses comprised the overall setting of the CPU, bed capacities, possibilities for ventilation, possible changes in organisation and resources, chest pain patient admittance, overall availability of CPUs and bail-out strategies. The response rate was 91%. Nationwide, CPU bed capacities decreased by 3% in the early phase of COVID-19 pandemic response, exhibiting differences within and between the federal states. Pre-pandemic and pandemic bed capacities stayed below 1 CPU bed per 50,000 inhabitants. 97% of CPUs were affected by internal reorganisation pandemic plans at variable extent. While we observed a decrease of CPU beds within an emergency room (ER) set-up and on intermediate care units (ICU), beds in units being separated from ER and ICU were even increased in numbers. CONCLUSIONS: Certified German CPUs are able to maintain adequate coverage for chest pain patients in COVID-19 pandemic despite structural changes. However, at this time, it appears important to add operating procedures during pandemic outbreaks to the certification criteria of forthcoming guidelines either at the individual CPU level or more centrally steered by the German Cardiac Society or the European Society of Cardiology.

The Asia-Pacific Society of Cardiology (APSC) Expert Committee Consensus Recommendations for Assessment of Suspected Acute Coronary Syndrome Using High-Sensitivity Cardiac Troponin T in the Emergency Department.

The Asia-Pacific Society of Cardiology (APSC) high-sensitivity troponin T (hs-TnT) consensus recommendations and rapid algorithm were developed to provide guidance for healthcare professionals in the Asia-Pacific region on assessing patients with suspected acute coronary syndrome (ACS) using a hs-TnT assay. Experts from Asia-Pacific convened in 2 meetings to develop evidence-based consensus recommendations and an algorithm for appropriate use of the hs-TnT assay. The Expert Committee defined a cardiac troponin assay as a high-sensitivity assay if the total imprecision is ≤10% at the 99th percentile of the upper reference limit and measurable concentrations below the 99th percentile are attainable with an assay at a concentration value above the assay's limit of detection for at least 50% of healthy individuals. Recommendations for single-measurement rule-out/rule-in cutoff values, as well as for serial measurements, were also developed. The Expert Committee also adopted similar hs-TnT cutoff values for men and women, recommended serial hs-TnT measurements for special populations, and provided guidance on the use of point-of-care troponin T devices in individuals suspected of ACS. These recommendations should be used in conjunction with all available clinical evidence when making the diagnosis of ACS.

Cost analysis of early discharge using combined copeptin/cardiac troponin testing versus serial cardiac troponin testing in patients with suspected acute coronary syndrome.

BACKGROUND: Symptoms indicating acute coronary syndrome are commonly seen in emergency rooms, but only 10% of patients are actually diagnosed with acute myocardial infarction (AMI). The Guidelines for the diagnosis of patients with suspected AMI include either multiple testing of cardiac troponin (cTN) or a single combined test of cTN and copeptin, which facilitates earlier diagnosis or exclusion of AMI. The aim of the present analysis was to investigate the impact of combined copeptin/cTN testing on health care resource consumption and related costs both during and after initial hospital treatment. METHODS AND RESULTS: The analysis was based on the BIC-8 trial and financial data of participating study sites. A cost analysis was carried out primarily from the hospital perspective and secondarily from the perspective of German statutory health insurers. The underlying assumptions of the investigation were tested for robustness in additional sensitivity analyses. In total, the data of 713 patients (n = 359 combined copeptin/cTN testing, n = 354 serial cTN testing) were evaluated. From a hospital perspective, the combined copeptin/cTN testing showed a reduced number of medical procedures and a lower frequency of inpatient admissions. The average staff time was significantly reduced by a mean of 49 minutes (95% confidence interval (CI) 46 to 53) per patient, accompanied by a significant mean reduction of 131 minutes (95%CI 104 to 158) in the time patients stayed in the emergency room. The initial hospital treatment was less cost-intensive. Over the entire study period, no significant cost differences were observed between the groups for health insurance. CONCLUSION: The combined copeptin/cTN testing has the potential to save costs and staff time in acute care and for the entire hospital stay. The primary explanations for these findings are early identification and ruling out patients without AMI along with the associated reduced need for acute medical treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT01498731.

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.

Correction: Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department.

[This corrects the article DOI: 10.1371/journal.pone.0187662.].

Economic evaluation of the one-hour rule-out and rule-in algorithm for acute myocardial infarction using the high-sensitivity cardiac troponin T assay in the emergency department.

BACKGROUND: The 1-hour (h) algorithm triages patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED) towards "rule-out," "rule-in," or "observation," depending on baseline and 1-h levels of high-sensitivity cardiac troponin (hs-cTn). The economic consequences of applying the accelerated 1-h algorithm are unknown. METHODS AND FINDINGS: We performed a post-hoc economic analysis in a large, diagnostic, multicenter study of hs-cTnT using central adjudication of the final diagnosis by two independent cardiologists. Length of stay (LoS), resource utilization (RU), and predicted diagnostic accuracy of the 1-h algorithm compared to standard of care (SoC) in the ED were estimated. The ED LoS, RU, and accuracy of the 1-h algorithm was compared to that achieved by the SoC at ED discharge. Expert opinion was sought to characterize clinical implementation of the 1-h algorithm, which required blood draws at ED presentation and 1h, after which "rule-in" patients were transferred for coronary angiography, "rule-out" patients underwent outpatient stress testing, and "observation" patients received SoC. Unit costs were for the United Kingdom, Switzerland, and Germany. The sensitivity and specificity for the 1-h algorithm were 87% and 96%, respectively, compared to 69% and 98% for SoC. The mean ED LoS for the 1-h algorithm was 4.3h-it was 6.5h for SoC, which is a reduction of 33%. The 1-h algorithm was associated with reductions in RU, driven largely by the shorter LoS in the ED for patients with a diagnosis other than AMI. The estimated total costs per patient were £2,480 for the 1-h algorithm compared to £4,561 for SoC, a reduction of up to 46%. CONCLUSIONS: The analysis shows that the use of 1-h algorithm is associated with reduction in overall AMI diagnostic costs, provided it is carefully implemented in clinical practice. These results need to be prospectively validated in the future.

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.

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 myocardial deformation with cardiac magnetic resonance strain imaging improves risk stratification in patients with dilated cardiomyopathy.

AIMS: To investigate the prognostic impact of left-ventricular (LV) cardiac magnetic resonance (CMR) deformation imaging in patients with non-ischaemic dilated cardiomyopathy (DCM) compared with late-gadolinium enhancement (LGE) quantification and LV ejection fraction (EF). METHODS AND RESULTS: A total of 210 subjects with DCM were examined prospectively with standard CMR including measurement of LGE for quantification of myocardial fibrosis and feature tracking strain imaging for assessment of LV deformation. The predefined primary endpoint, a combination of cardiac death, heart transplantation, and aborted sudden cardiac death, occurred in 26 subjects during the median follow-up period of 5.3 years. LV radial, circumferential, and longitudinal strains were significantly associated with outcome. Using separate multivariate analysis models, global longitudinal strain (average of peak negative strain values) and mean longitudinal strain (negative peak of the mean curve of all segments) were independent prognostic parameters surpassing the value of global and mean LV radial and circumferential strain, as well as NT-proBNP, EF, and LGE mass. A global longitudinal strain greater than -12.5% predicted outcome even in patients with EF < 35% (P < 0.01) and in those with presence of LGE (P < 0.001). Mean longitudinal strain was further investigated using a clinical model with predefined cut-offs (EF < 35%, presence of LGE, NYHA class, mean longitudinal strain greater than -10%). Mean longitudinal strain exhibited an independent prognostic value surpassing that provided by NYHA, EF, and LGE (HR = 5.4, P < 0.01). CONCLUSION: LV longitudinal strain assessed with CMR is an independent predictor of survival in DCM and offers incremental information for risk stratification beyond clinical parameters, biomarker, and standard CMR.

Improvement of risk assessment in systemic light-chain amyloidosis using human placental growth factor.

BACKGROUND: Vascular amyloid deposition is common in light-chain amyloidosis resulting in endothelial dysfunction. Human placental growth factor (PlGF), a member of the vascular endothelial growth factor family was found to be altered in diverse pathological conditions, e.g. endothelial dysfunction. This study evaluated the clinical role of PlGF in light-chain amyloidosis. METHODS: PlGF (cobas-PlGF, Roche Diagnostics, Mannheim, Germany) was analyzed in 125 consecutive patients with AL and correlated with diverse clinical parameters including mortality. RESULTS: Kidney (n = 76) and heart (n = 57) were predominantly affected by amyloid deposition. Median PlGF was 26.3 (21.1-42.1) ng/L, NT-proBNP 3649 (1124-8581) pg/mL, and hs-TnT 42 (21-107) ng/L. PlGF increased with number of organs involved and with deterioration of renal function. A significant correlation of PlGF with hs-TnT (ρ = 0.306; p = 0.0007) and NT-proBNP (ρ = 0.315; p = 0.0006) was observed, but no correlation was observed with clinical, echocardiography, and electrocardiography parameters of cardiac involvement. In this cohort 1-year all-cause mortality was 19.2 %. The best cutoff discriminating survivors and non-survivors was 28.44 ng/L (sensitivity 66.7 %; specificity 78.1 %). A three-step risk model including hs-TnT and NT-proBNP revealed a better discrimination if patients at intermediary risk were additionally stratified by PlGF. Net reclassification index was 37.2 % (p = 0.002). Multivariate analysis revealed PlGF, difference of involved and uninvolved light chain, number of organs involved and risk class according to troponin T and NT-proBNP as independent predictors of mortality. CONCLUSION: Plasma PlGF values in AL are invariably associated with the number of involved organs, but not with clinical, echocardiography, and electrocardiography parameters of cardiac involvement. PlGF provide useful information for risk stratification of patients at intermediary risk according to hs-TnT and NT-proBNP.

Dobutamine stress cardiac magnetic resonance versus echocardiography for the assessment of outcome in patients with suspected or known coronary artery disease. Are the two imaging modalities comparable?

PURPOSE: To compare the value of Dobutamine stress echocardiography (DSE) with that provided by Dobutamine Cardiac Magnetic Resonance (DCMR) for the non-invasive risk stratification of patients with suspected or known coronary artery disease (CAD). METHODS: Patients with suspected or known CAD underwent either DSE or DCMR using the same standardized protocol. Patient matching was then performed retrospectively for age, gender and risk factors. Outcome data including cardiac death and non-fatal myocardial infarction (defined as hard cardiac events) and 'late' revascularization performed >90days after the diagnostic procedures were collected during at least 6months. RESULTS: Follow-up data were available in 1852 patients who completed either DSE (n=884) or DCMR (n=884) during a mean follow-up duration of 4.1±2.4 and 3.9±1.9years, respectively (p=NS). Matched patients exhibited an overall high risk profile (69±9years; 69% male, 70% history of CAD and 26% diabetes mellitus in both groups). Using multivariable analysis, both modalities successfully identified patients with inducible ischemia at higher risk for subsequent hard cardiac events, surpassing the value of conventional risk factors like age, male gender and diabetes (HR=9.2; 95%CI=5.6-14.9 for DCMR versus 2.5; 95%CI=1.7-3.7 for DSE). By testing for interaction the predictive capacity of DCMR was higher than that provided by DSE (p=0.02). Patients with negative DCMR exhibited lower event rates compared to those with negative DSE (annual hard cardiac event rate of 0.8% versus 3.2%, p=0.002). CONCLUSIONS: DSE & DCMR aid the risk stratification of CAD patients. However, inducible WMA during DCMR are associated with a higher risk for subsequent cardiac events. Patients with negative DCMR on the other hand, exhibited a lower event rate compared to those with negative DSE.

Cost-effectiveness of ticagrelor versus clopidogrel for the prevention of atherothrombotic events in adult patients with acute coronary syndrome in Germany.

The aim of this health economic analysis was to compare the cost-effectiveness of ticagrelor versus clopidogrel within the German health care system. A two-part decision model was adapted to compare treatment with ticagrelor or clopidogrel in a low-dose acetylsalicylic acid (ASA) cohort (≤150 mg) for all ACS patients and subtypes NSTEMI/IA and STEMI. A decision-tree approach was chosen for the first year after initial hospitalization based on trial observations from a subgroup of the PLATO study. Subsequent years were estimated by a Markov model. Following a macro-costing approach, costs were based on official tariffs and published literature. Extensive sensitivity analyses were performed to test the robustness of the model. One-year treatment with ticagrelor is associated with an estimated 0.1796 life-years gained (LYG) and gained 0.1570 quality-adjusted life-years (QALY), respectively, over the lifetime horizon. Overall average cost with ticagrelor is estimated to be EUR 11,815 vs. EUR 11,387 with generic clopidogrel over a lifetime horizon. The incremental cost-effectiveness ratio (ICER) was EUR 2,385 per LYG (EUR 2,728 per QALY). Comparing ticagrelor with Plavix(®) or the lowest priced generic clopidogrel, ICER ranges from dominant to EUR 3,118 per LYG (EUR 3,567 per QALY). These findings are robust under various additional sensitivity analyses. Hence, 12 months of ACS treatment using ticagrelor/ASA instead of clopidogrel/ASA may offer a cost-effective therapeutic option, even when the generic price for clopidogrel is employed.

N-terminal pro brain natriuretic peptide in the management of patients in the medical emergency department (PROMPT): correlation with disease severity, utilization of hospital resources, and prognosis in a large, prospective, randomized multicentre trial.

AIMS: N-terminal pro brain natriuretic peptide (NT-proBNP) is a potent marker of heart failure and other cardiac diseases. The value of NT-proBNP testing in the medical emergency department (ED) was assessed in patients >65 years old. METHODS AND RESULTS: This large, prospective, randomized, controlled, multicentre trial was conducted in six medical EDs. Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients. Median NT-proBNP was 582 pg/mL. A total of 16% of patients presented with NT-proBNP <150 pg/mL (low), 55% with NT-proBNP between 150 and 1800 pg/mL (intermediate), and 29% with NT-proBNP >1800 pg/mL (high). NT-proBNP was positively correlated with hospital admission [ odds ratio (OR) for high vs. low 2.9, P < 0.0001], length of stay (8.5 days vs. 3.5 days for high vs. low, P < 0.01), in-hospital death (3.9% vs. 0% for high vs. low, P < 0.01), 6 months re-hospitalization (OR for high vs. low 5.1, P < 0.0001), and 6 months death or re-hospitalization (OR for high vs. low 5.7, P < 0.0001). Knowledge of NT-proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit (IMC/ICU) admission, length of stay, re-hospitalization and death, or re-hospitalization in the total cohort. However, patients with high open NT-proBNP (>1800 pg/mL) were more likely to be admitted to the hospital (P < 0.05) and IMC/ICU (P < 0.05), whereas patients with low open NT-proBNP (<150 pg/mL) were less likely to be admitted (P < 0.05) compared with patients with blinded NT-proBNP. CONCLUSION: Although NT-proBNP does not affect overall hospitalization, it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital resources and prognosis.

Early assessment of infarct size and prediction of functional recovery by quantitative myocardial blush grade in patients with acute coronary syndromes treated according to current guidelines.

PURPOSE: To determine whether quantification of myocardial blush grade (MBG) during cardiac catheterization can aid the determination of follow-up left ventricular (LV)-function in patients with ST-elevation and non-ST-elevation myocardial infarction (STEMI and NSTEMI). METHODS: We prospectively examined patients with first STEMI (n = 46) and NSTEMI (n = 49). ECG-gated angiographic series were used to quantify MBG by analyzing the time course of contrast agent intensity rise. Hereby, the parameter G(max)/T(max) was calculated, derived from the plateau of grey-level intensity (G(max)), divided by the time-to-peak intensity (T(max)). Cardiac magnetic resonance imaging (CMR) deemed as the standard reference for the estimation of infarct size, transmurality and of the LV-function at 6 months of follow-up. RESULTS: Cut-off values of G(max)/T(max)=5.7/sec and 3.8/sec, respectively, yielded similar accuracy as infarct transmurality for the prediction of follow-up ejection fraction >55% (AUC = 0.86 for STEMI and AUC = 0.90 for NSTEMI, by G(max)/T(max) and AUC = 0.85 for STEMI and AUC = 0.89 for NSTEMI, by infarct transmurality, respectively, P = NS). Both clearly surpassed the predictive value of visual MBG (AUC = 0.69 for STEMI and AUC = 0.68 for NSTEMI, P < 0.05). CONCLUSION: G(max)/T(max) is an easy to acquire but highly valuable surrogate parameter for infarct size, which yields equally high accuracy with infarct transmurality and favorably compares with visually assessed blush grades for the prediction of follow-up LV-function in patients with acute ischemic syndromes.

Prognostic value of high-dose dobutamine stress magnetic resonance imaging in 1,493 consecutive patients: assessment of myocardial wall motion and perfusion.

OBJECTIVES: This study sought to determine the prognostic value of wall motion and perfusion assessment during high-dose dobutamine stress (DS) cardiac magnetic resonance imaging (MRI) in a large patient cohort. BACKGROUND: DS-MRI offers the possibility to integrate myocardial perfusion and wall motion analysis in a single examination for the detection of coronary artery disease (CAD). METHODS: A total of 1,493 consecutive patients with suspected or known CAD underwent DS-MRI, using a standard protocol in a 1.5-T magnetic resonance scanner. Wall motion and perfusion were assessed at baseline and during stress, and outcome data including cardiac death, nonfatal myocardial infarction ("hard events"), and "late" revascularization performed >90 days after the MR scans were collected during a 2 ± 1 year follow-up period. RESULTS: Fifty-three hard events, including 14 cardiac deaths and 39 nonfatal infarctions, occurred during the follow-up period, whereas 85 patients underwent "late" revascularization. Using multivariable regression analysis, an abnormal result for wall motion or perfusion during stress yielded the strongest independent prognostic value for both hard events and late revascularization, clearly surpassing that of clinical and baseline magnetic resonance parameters (for wall motion: adjusted hazard ratio [HR] of 5.9 [95% confidence interval (CI): 2.5 to 13.6] for hard events and of 3.1 [95% CI: 1.7 to 5.6] for late revascularization, and for perfusion: adjusted HR of 5.4 [95% CI: 2.3 to 12.9] for hard events and of 6.2 [95% CI: 3.3 to 11.3] for late revascularization, p < 0.001 for all). CONCLUSIONS: DS-MRI can accurately identify patients who are at increased risk for cardiac death and myocardial infarction, separating them from those with normal findings, who have very low risk for future cardiac events. (Prognostic Value of High Dose Dobutamine Stress Magnetic Resonance Imaging; NCT00837005).