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.

Comparison of the analytical performance of the PATHFAST high sensitivity cardiac troponin I using fresh whole blood vs. fresh plasma samples.

OBJECTIVES: The PATHFAST hs-cTnI (high-sensitivity cardiac troponin) assay is the first point-of-care assay with a high-sensitivity designation that received FDA approval for diagnosis of myocardial infarction (MI). Testing from whole blood does not need centrifugation and therefore is faster and more convenient in the emergency room instead of plasma. However, there is sparse evidence whether point-of-care testing of Tn from whole blood is as reliable as from plasma samples. METHODS: We investigated the agreement between plasma and whole blood hs-cTnI by using the PATHFAST hs-cTnI assay. Hs-cTnT measured on Cobas 602 in the central laboratory and compared to a final diagnosis of NSTEMI using serial hs-cTnT served as reference. We assessed biases, limits of agreement (±1.96 SD) and coefficients of correlation, and tested the discriminatory ability of the baseline sample of plasma and whole blood hs-cTnI and plasma hs-cTnT to discriminate non-ST-segment elevation myocardial infarction (NSTEMI). RESULTS: A total of 224 paired fresh samples were collected simultaneously from 191 patients presenting with suspected acute coronary syndrome. There was an excellent correlation between plasma and whole blood hs-cTnI (r=0.99), and a very good inter-rater agreement (k=0.93) between elevated and normal plasma and whole blood results. Precision evaluation according to CLSI ep 15 revealed comparable coefficients of variation (CV) in whole blood and plasma. The discriminatory ability of baseline hs-cTnT, plasma and whole blood hs-cTnI was excellent (AUC 0.967, AUC 0.954 and AUC 0.953) without significant difference. CONCLUSIONS: Whole blood can be used interchangeably with plasma for more convenient and less time and labor-consuming testing of hs-cTnI on the PATHFAST instrument.

Design, Rationale and Initial Findings From HERA-FIB on 10 222 Patients With Atrial Fibrillation Presenting to an Emergency Department Over An 11-Year Period.

BACKGROUND: For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA-FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real-world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. METHODS AND RESULTS: HERA-FIB is a retrospective, observational, single-center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all-cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials. CONCLUSIONS: HERA-FIB is one of the largest real-world single-center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non-vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification in patients with suspected acute coronary syndrome.

BACKGROUND: The clinical chemistry score (CCS) comprising high-sensitivity cardiac troponins (hs-cTn), glucose and estimated glomerular filtration rate has been previously validated with superior accuracy for detection and risk stratification of acute myocardial infarction (AMI) compared to hs-cTn alone. METHODS: The CCS was compared to other biomarker-based algorithms for rapid rule-out and prognostication of AMI including the hs-cTnT limit-of-blank (LOB, <3 ng/L) or limit-of-detection (LOD, <5 ng/L) and a dual marker strategy (DMS) (copeptin <10 pmol/L and hs-cTnT ≤14 ng/L) in 1506 emergency department (ED) patients with symptoms suggestive of acute coronary syndrome. Negative predictive values (NPV) and sensitivities for AMI rule-out, and 12-month combined endpoint rates encompassing mortality, myocardial re-infarction, as well as stroke were assessed. RESULTS: NPVs of 100% (95% CI: 98.3-100%) were observed for CCS = 0, hs-cTnT LoB and hs-cTnT LoD with rule-out efficacies of 11.1%, 7.6% and 18.3% as well as specificities of 13.0% (95% CI: 9.9-16.6%), 8.8% (95% CI: 7.3-10.5%) and 21.4% (95% CI: 19.2-23.8%), respectively. A CCS ≤ 1 achieved a rule-out in 32.2% of all patients with a NPV of 99.6% (95% CI: 98.4-99.9%) and specificity of 37.4% (95% CI: 34.2-40.5%) compared to a rule-out efficacy of 51.2%, NPV of 99.0 (95% CI: 98.0-99.5) and specificity of 59.7% (95% CI: 57.0-62.4%) for the DMS. Rates of the combined end-point of death/AMI within 30 days ranged between 0.0% and 0.7% for all fast-rule-out protocols. CONCLUSIONS: The CCS ensures reliable AMI rule-out with low short and long-term outcome rates for a specific ED patient subset. However, compared to a single or dual biomarker strategy, the CCS displays reduced efficacy and specificity, limiting its clinical utility.

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

AIMS: Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. METHODS: Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1 h and after 6-12 months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1 h algorithm and assessed biological variation at 6-12 months using two established methods: reference change value (RCV) and minimal important difference (MID). RESULTS: Median baseline hs-cTnT concentrations were 34.4 ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6 months (IQR: 6-7). Median concentration change was 1.9 ng/L (IQR: 0.7-3.2) and 0.8 ng/L (IQR: 0-7.0) at 60 min and 6-9 months, respectively. Applying the criteria of the ESC 0/1 h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT ≥ 52 ng/L. Biological variabilities at 6-12 months per MID and RCV were 1.2 ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. CONCLUSIONS: The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12 months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Real-World Evidence on Disparities on the Initiation of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome.

Background Management of patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) is based on 2020 European Society of Cardiology guidelines, which recommend the preferential use of prasugrel over ticagrelor. Because the selection of the respective P2Y12 inhibitor has to consider label restrictions, we sought to evaluate the proportion of patients qualifying for either ticagrelor or prasugrel and reasons for noneligibility in an unselected cohort of patients with acute coronary syndrome. Methods and Results In this retrospective observational study, patients with ST-segment-elevation myocardial infarction (STEMI) or NSTE-ACS presenting consecutively during a 24-month period were enrolled. The eligibility of patients for a dual antiplatelet therapy option was assessed retrospectively. A total of 1502 patients had confirmed acute coronary syndrome (287 STEMI and 1215 NSTE-ACS). Eligibility for ticagrelor and full-dose prasugrel differed significantly for STEMI and NSTE-ACS (93% versus 51%, P<0.0001 versus 80% versus 31%, P<0.0001). Eligibility remained significantly lower (STEMI 78% versus NSTE-ACS 52%) if low-dose prasugrel was considered. Patients eligible for full-dose prasugrel had lower ischemic risk per GRACE (Global Registry of Acute Coronary Events) score (109 points [90-129 points] versus 121 points [98-146 points], P<0.0001) and lower bleeding risk (14 points [13-15 points] versus 20 points [12-29 points], P<0.0001) per PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy) score. Conclusions In real life, eligibility for prasugrel in patients requiring dual antiplatelet therapy is considerably lower than for ticagrelor, even in a cohort with high rates of coronary angiography and percutaneous coronary interventions. The recommended use of prasugrel over ticagrelor in current acute coronary syndrome guidelines contrasts with our observations of a substantial disparity on the eligibility. This important aspect has not received appropriate attention yet. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05774431.

Low-Level Elevations of Procalcitonin Are Associated with Increased Mortality in Acute Heart Failure Patients, Independent of Concomitant Infection.

We aimed to evaluate the prognostic value of procalcitonin (PCT) in acute heart failure (AHF) patients, especially in those without underlying infection. We enrolled patients presenting with acute dyspnea to the emergency department (ED) of Heidelberg University Hospital and studied the prognostic role of PCT on all-cause death. Of 312 patients, AHF was diagnosed in 139 patients. Of these, 125 patients had AHF without signs of infection, and 14 had AHF complicated by respiratory or other infection. The optimal prognostic PCT cutoff value for mortality prediction was calculated by a receiver operating characteristics curve. In patients with AHF, the prognostic PCT cutoff value was 0.08 ng/mL. The Kaplan-Meier survival analysis showed that AHF patients with PCT values > 0.08 ng/mL had a higher all-cause mortality at 120 days than those with PCT values ≤ 0.08 ng/mL (log-rank p = 0.0123). Similar results could be obtained after subdivision into AHF patients with and without signs of overt infection. In both cases, mortality was higher in patients with PCT levels above the prognostic PCT cutoff than in those with values ranging below this threshold. Moreover, we show that the prognostic PCT cutoff values for mortality prediction ranged below the established PCT cutoff for the guidance of antibiotic therapy. In conclusion, the data of our study revealed that low-level elevations of PCT were associated with an increased mortality in patients with AHF, irrespective of concomitant respiratory or other infection. PCT should thus be further used as a marker in the risk stratification of AHF.