Dayana Flores

Prohormones in the Early Diagnosis of Cardiac Syncope

Background The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional–pro‐A‐type natriuretic peptide (MRproANP), C‐terminal proendothelin 1, copeptin, and midregional‐proadrenomedullin. Methods and Results We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1‐year follow‐up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C‐terminal proendothelin 1, copeptin, and midregional‐proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes (P<0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76–0.84), 0.69 (95% CI, 0.64–0.74), 0.58 (95% CI, 0.52–0.63), and 0.68 (95% CI, 0.63–0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82–0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87–0.93), which was significantly higher than for the ED probability alone (P=0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of <77 pmol/L and an ED probability of <20% had a sensitivity and a negative predictive value of 99%. Conclusions The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352.

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Background: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. Methods: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. Results: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0–99.9%]; product: NPV 99.4% [95% CI, 98.8–99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2–100%]; NPV validation cohort 99.5% [95% CI, 98.9–99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6–78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7–87.6%]). Conclusions: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. Clinical Trial Registration: URL (APACE): https://www.clinicaltrial.gov. Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au. Unique identifier: ACTRN12611001069943.

Risk stratification in acute heart failure: Risk stratification in acute heart failure

We would like to congratulate Demissei et al. on their important work.1 However, may we ask that they provide some additional data in order to better put their findings into clinical perspective? First, the clinical prediction model used seems incomplete. Clinical experience as well as data from previous studies suggest that the following four routinely available variables substantially impact post-discharge events and should therefore be included in the model: blood pressure at discharge; worsening renal function during hospitalization; frailty; and the total dose of i.v. diuretics administered during the hospital stay. Second, surprisingly, the paper by Demissei et al.1 makes no reference to the two most extensively studied biomarkers in patients with acute heart failure: high-sensitivity cardiac troponin T and NT-proBNP. It is possible that these would outperform all biomarkers reported.2–5 Were the authors also able to measure these? Third, we ask that the authors please report findings in the overall cohort, including patients hospitalized for more than 17 days, who were excluded from the current analysis.

How accurate is clinical assessment of neck veins in the estimation of central venous pressure in acute heart failure? Insights from a prospective study: How accurate is clinical assessment of neck veins in the estimation of central venous pressure in acute heart failure? Insights from a prospective stu

Medical history and physical examination are the primary diagnostic tools when assessing emergency department (ED) patients with suspected acute heart failure (AHF). Among physical signs, positive hepato-jugular reflux (HJR) and jugular vein distention (JVD) are considered to indicate elevated central venous pressure (CVP). Both are major Framingham heart failure criteria and evaluated with priority in dyspnoeic patients presenting to the ED. Unfortunately and in contrast to common perception, the accuracy of clinical neck vein assessment in estimating CVP in AHF patients presenting to the ED is largely unknown. This is a dilemma as treatment decisions are commonly based on estimating CVP from assessing neck veins in AHF. The recent development and validation of a non-invasive forearm vein compression ultrasound technique to reliably measure CVP1,2 allowed us to address this gap in knowledge and to evaluate the diagnostic accuracy of clinical neck vein examination for the detection of elevated CVP in AHF patients at ED presentation. This sub-study of the Basics in Acute Shortness of Breath Evaluation Study ( ClinicalTrials .gov identifier: NCT01831115) prospectively enrolled adult AHF patients at the time of ED presentation. Only patients with a final adjudicated diagnosis of AHF were included in this analysis. The study was approved by the local ethics committee, and patients gave written informed consent. At the time of presentation a physical examination was performed and documented by the treating ED physician using the standardized case report form used universally at the University Hospital Basel. Findings of the examination of the jugular veins were categorized as: normal (HJR–/JVD–), distended Figure 1 Box plots displaying central venous pressure (CVP) levels according to clinical neck vein examination. Comparison between groups by Jonckheere–Terpstra test. HJR+, patients with distended neck veins after provocation with maintained abdominal pressure; JVD+, patients with distended neck veins without provocation; JVD–/HJR–, patients with normal neck veins. HJR, hepato-jugular reflux; JVD, jugular vein distention.

Circadian, weekly, seasonal, and temperature-dependent patterns of syncope aetiology in patients at increased risk of cardiac syncope

AIMS It is unknown whether cardiac syncope, and possibly also other syncope aetiologies exhibit circadian, weekly, seasonal, and temperature-dependent patterns. METHODS AND RESULTS We prospectively recorded the exact time, date, and outside temperature of syncope of patients >40 years old presenting with syncope to the emergency department in a diagnostic multicentre study. Two independent cardiologists/emergency physicians adjudicated the final diagnosis based on all information becoming available during clinical work-up including 1-year follow-up. Among 1230 patients, the adjudicated aetiology was cardiac in 14.6%, reflex in 39.2%, orthostatic in 25.7%, other non-cardiac in 9.7%, and unknown in 10.8% of patients. All syncope aetiologies occurred much more frequently during the day when compared with the night (P < 0.01). While reflex and orthostatic syncope showed a broad peak of prevalence with 80.9% of these events occurring between 4 am and 4 pm, cardiac syncope showed a narrow peak of prevalence with 70.1% of all events occurring between 8 am and 2 pm. A weekly pattern was present for most syncope aetiologies, with events occurring mainly from Monday to Friday (P < 0.01). Reflex syncope displayed a seasonal rhythm and was more common in winter (P < 0.01), while cardiac syncope stayed constant over the year. Syncope occurred most often when the outside temperature was coldest. Overall the patterns observed for cardiac syncope were similar to the patterns observed for its differential diagnosis. CONCLUSION Syncope aetiologies in patients >40 years old display circadian, weekly, seasonal, and temperature-dependent patterns. Unfortunately, these patterns do not allow to reliably differentiate cardiac syncope from other aetiologies.

Effect of Acute Coronary Syndrome Probability on Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin

BACKGROUND There is concern that high-sensitivity cardiac troponin (hs-cTn) may have low diagnostic accuracy in patients with low acute coronary syndrome (ACS) probability. METHODS We prospectively stratified patients presenting with acute chest discomfort to the emergency department (ED) into 3 groups according to their probability for ACS as assessed by the treating ED physician using a visual analog scale: ≤10%, 11% to 79%, and ≥80%, reviewing all information available at 90 min. hs-cTnT and hs-cTnI concentrations were determined in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis. RESULTS Among 3828 patients eligible for analysis, 1189 patients had low (≤10%) probability for ACS. The incidence of non-ST-segment elevation myocardial infarction (NSTEMI) increased from 1.3% to 12.2% and 54.8% in patients with low, intermediate, and high ACS probability, respectively. The positive predictive value of hs-cTnT and hs-cTnI was low in patients with low ACS probability and increased with the incidence of NSTEMI, whereas the diagnostic accuracy of hs-cTnT and hs-cTnI for NSTEMI as quantified by the area under the curve (AUC) was very high and comparable among all 3 strata, e.g., AUC hs-cTnI, 0.96 (95% CI, 0.94-0.97); 0.87 (95% CI, 0.85-0.89); and 0.89 (95% CI, 0.87-0.92), respectively. Findings were validated using bootstrap analysis as an alternative methodology to define ACS probability. Similarly, higher hs-cTnT/I concentrations independently predicted all-cause mortality within 2 years (e.g., hs-cTnT hazard ratio, 1.39; 95% CI, 1.27-1.52), irrespective of ACS probability. CONCLUSIONS Diagnostic and prognostic accuracy and utility of hs-cTnT and hs-cTnI remain high in patients with acute chest discomfort and low ACS probability.ClinicalTrials.gov Identifier: NCT00470587.