The aim of this study was to validate the clinical performance of the Beckman Access high-sensitivity cardiac troponin I (hs-cTnI) assay.
We enrolled patients presenting to the emergency department ...with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists with all clinical information including cardiac imaging twice: first, using serial hs-cTnT (Elecsys, primary analysis), and second, using hs-cTnI (Architect, secondary analysis) measurements in addition to the clinically used hs-cTn. hs-cTnI Access was measured at presentation and at 1 h. The primary objective was a direct comparison of diagnostic accuracy as quantified by the area under the ROC curve (AUC) of hs-cTnI Access vs the hs-cTnT Elecsys and hs-cTnI Architect assays. Secondary objectives included the derivation and validation of an hs-cTnI Access-specific 0/1-h algorithm.
AMI was the adjudicated final diagnosis in 243 of 1579 (15.4%) patients. The AUC at presentation for hs-cTnI Access was 0.95 (95% CI, 0.94-0.96), higher than hs-cTnI Architect 0.92 (95% CI, 0.91-0.94;
< 0.001) and comparable to hs-cTnT Elecsys 0.94 (95% CI, 0.93-0.95;
= 0.12). Applying the derived hs-cTnI Access 0/1-h algorithm (derivation cohort n = 686) to the validation cohort (n = 680), 60% of patients were ruled out sensitivity, 98.9% (95% CI, 94.3-99.8), and 15% of patients were ruled in specificity, 95.9% (95% CI, 94.0-97.2). Patients ruled out by the 0/1-h algorithm had a survival rate of 100% at 30 days. Findings were confirmed in the secondary analyses by the adjudication including serial measurements of Architect hs-cTnI.
Diagnostic accuracy and clinical utility of the Beckman hs-cTnI Access assay are very high and at least comparable to Roche hs-cTnT and Abbott hs-cTnI assays.
NCT00470587.
Aims
Whereas up to about half of patients with heart failure with reduced ejection fraction (HFrEF) report no or only mild symptoms and are considered as clinically stable, the progressive nature of ...HFrEF, often silent, renders clinical stability a misleading situation, especially if disease progression is unrecognized. We highlight the challenges in the definition of clinical stability and mild symptomatic status in HFrEF, outline clinical characteristics and available diagnostic tools, and discuss evidence and gaps in the current guidelines for the management of these patients.
Methods and Results
This is a state‐of‐the‐art review that focuses on clinical, diagnostic, and therapeutic aspects in mildly symptomatic HFrEF patients; summarizes the challenges; and proposes directions for future research in this group of patients. The New York Heart Association classification has been widely used as a measure of prognosis in HFrEF, but it lacks objectivity and reproducibility in terms of symptoms assessment. The definition of clinical stability as described in current guidelines is vague and may often lead to underdiagnosis of disease progression in patients who appear to be ‘stable' but in fact are at an increased risk of clinical worsening, hospitalization, or death. Although an increasing number of clinical trials proved that the efficacy of HFrEF therapies was unrelated to the symptomatic status of patients and led to their implementation early in the course of the disease, clinical inertia in terms of under‐prescription or underdosing of guideline‐recommended medications in mildly symptomatic HFrEF patients is still a challenging issue to deal with.
Conclusions
Mildly symptomatic status in a patient with HFrEF is very frequent; it should not be ignored and should not be regarded as an index of disease stability. The application of risk scores designed to predict mortality and mode of death should be engaged among mildly symptomatic patients, not only to identify the most suitable HF candidates for cardioverter defibrillator implantation, but also to identify patients who might benefit from early intensification of medical treatment before the implementation of more interventional approaches.
The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments.
The extent ...of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324).
In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF 1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both
< 0.001, respectively. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF 41 (24-71) versus 33 (19-59) ng/L,
< 0.001. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10;
< 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort.
Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.
Aims
Readmission and mortality are the most common and often combined endpoints in acute heart failure (AHF) trials, but an association between these two outcomes is poorly investigated. The aim of ...this study was to determine whether unplanned readmission is associated with a greater subsequent risk of death in patients with acute dyspnoea due to cardiac and non‐cardiac causes.
Methods and results
Derivation cohort (1371 patients from the LEDA study) and validation cohort (1986 patients from the BASEL V study) included acute dyspnoea patients admitted to the emergency department. Cox regression analysis was used to determine the association of 6 month readmission and the risk of 1 year all‐cause mortality in AHF and non‐AHF patients and those readmitted due to cardiovascular and non‐cardiovascular causes. In the derivation cohort, 666 (49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. Six month readmission was associated with an increased 1 year mortality risk in both the derivation cohort adjusted hazard ratio (aHR) 3.0 (95% confidence interval, CI 2.2–4.0), P < 0.001 and the validation cohort (aHR 1.8, 95% CI 1.4–2.2, P < 0.001). The significant association was similarly observed in AHF (aHR 3.2, 95% CI 2.1–4.9, P < 0.001) and other causes of acute dyspnoea (aHR 2.9, 95% CI 1.9–4.5, P < 0.001), and it did not depend on the aetiology aHR 2.2, 95% CI 1.6–3.1 for cardiovascular readmissions; aHR 4.1, 95% CI 2.9–5.7 for non‐cardiovascular readmissions (P < 0.001 for both) or timing of readmission.
Conclusions
Our study demonstrated a long‐lasting detrimental association between readmission and death in AHF and non‐AHF patients with acute dyspnoea. These patients should be considered ‘vulnerable patients’ that require personalized follow‐up for an extended period.
Aims
The aim of this study was to investigate the diagnostic and prognostic utility of the QRS‐T angle, an electrocardiogram (ECG) marker quantifying depolarization–repolarization heterogeneity, in ...patients with suspected acute decompensated heart failure (ADHF).
Methods and results
We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of ADHF. The QRS‐T angle was automatically derived from a standard 12‐lead ECG recorded at presentation. The primary diagnostic endpoint was a final adjudicated diagnosis of ADHF. The primary prognostic endpoint was all‐cause mortality during 2 years of follow‐up. Among the 1915 patients enrolled, those with higher QRS‐T angles were older, were more commonly male, and had a higher rate of co‐morbidities such as arterial hypertension, coronary artery disease, or chronic kidney disease. ADHF was the final adjudicated diagnosis in 1140 (60%) patients. The QRS‐T angle in patients with ADHF was significantly larger than in patients with non‐cardiac causes of dyspnoea {median 110° inter‐quartile range (IQR) 46–156° vs. median 33° IQR 15–57°, P < 0.001}. The diagnostic accuracy of the QRS‐T angle as quantified by the area under the receiver operating characteristic curve (AUC) was 0.75 95% confidence interval (CI) 0.73–0.77, P < 0.001, which was inferior to N‐terminal pro‐B‐type natriuretic peptide (AUC 0.93, 95% CI 0.92–0.94, P < 0.001), but similar to that of high‐sensitivity troponin T (AUC 0.78, 95% CI 0.76–0.80, P = 0.09). The AUC of the QRS‐T angle for discrimination between ADHF and non‐cardiac dyspnoea remained similarly high in subgroups of patients known to be diagnostically challenging, including patients older than 75 years 0.71 (95% CI 0.67–0.74), renal failure 0.79 (95% CI 0.71–0.87), and atrial fibrillation at presentation 0.68 (95% CI 0.60–0.76). Mortality rates according to QRS‐T angle tertiles were 4%, 6%, and 10% after 30 days (P < 0.001) and 24%, 31%, and 43% after 2 years (P < 0.001). After adjustment for clinical, laboratory, and ECG parameters, the QRS‐T angle remained an independent predictor for 2 year mortality with a 4% increase in mortality for every 20° increase in QRS‐T angle (P = 0.02).
Conclusions
The QRS‐T angle is a readily available and inexpensive marker that can assist in the discrimination between ADHF and non‐cardiac causes of acute dyspnoea and may aid in the risk stratification of these patients.
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