Plasma PCSK9 levels and sepsis severity: an early assessment in the emergency department.

The aim of the study is to evaluate the prognostic value of early PCSK9 levels in non-intubated septic patients admitted to the emergency department. This report utilized a portion of the data collected in a prospective study, with the aim of identifying reliable biomarkers for an early sepsis diagnosis. In the period November 2011-December 2016, we enrolled 268 patients, admitted to our High-Dependency Unit from the emergency department with a diagnosis of sepsis. Study-related blood samplings were performed at ED-HDU admission (T0), after 6 h (T6) and 24 h (T24). The primary endpoint was in-hospital mortality rate. PCSK9 circulating levels were higher than the normal value (≤ 313 ng/mL): at T0 661 ± 405 ng/mL, at T6 687 ± 417 ng/mL, at T24 718 ± 430 ng/mL. We divided the study population based on T0 quartiles distribution (≤ 370, 370-600, 600-900 and > 900 ng/ml). At T0, patients with normal PCSK9 showed the highest mortality compared to those in higher quartiles (T0: 39%, 20%, 23% and 18%, p = 0.036). By T6, the mortality curve tended to become U-shaped, with the lowest mortality among patients in the intermediate subgroups and an adverse prognosis in the presence of normal or very high levels of PCSK9 (35%, 26%, 18% and 23%, p = 0.235). A Kaplan-Meier analysis showed an increased mortality in patients with T0 and T6 PCSK9 ≤ 313 ng/ml (T0: 55 vs. 80%, p = 0.001; T6: 62 vs. 78%, p = 0.034). In subgroups with increasing levels of PCSK9, we found the best prognosis in the intermediate subgroups and an increased mortality among patients with normal and high values.

Epidemiology of right ventricular systolic dysfunction in patients with sepsis and septic shock in the emergency department.

We evaluated whether in sepsis, right ventricular (RV) systolic dysfunction (RVSD) predicts short-term all-cause mortality, independently to left ventricular (LV) global longitudinal peak systolic strain (GLS). This is a prospective observational study. We enrolled 252 septic patients (40% with shock) between October 2012 and July 2018 among those admitted to High-Dependency Unit. By echocardiography within 24 h from the admission (T1), RVSD was defined as Tricuspid Annular Plane Systolic Excursion (TAPSE) < 16 mm, while left ventricular systolic dysfunction (LVSD) was defined by bi-dimensional speckle-tracking-based global longitudinal peak systolic strain (GLS) > -14%. We assessed all-cause mortality at day-7 and at day-28 from admission. Mortality rate was 14% by day-7 and 26% by day-28 follow-up. RVSD was found in 85 patients (34%), was isolated in 29% (25/85) and coexisted with LVSD in 71% (60/85) patients. LVSD was present in 63% of patients (159/252), and was isolated in 99 patients. Day-7 mortality rate was twofold higher in the presence of RVSD (20% vs 11%), without reaching the statistical significance (p = 0.097). By day-28, mortality rate was as high as 44% with and 23% without RVSD (p = 0.001). In a Cox survival analysis, RVSD predicted higher mortality rate by day-28 follow-up (RR 2.43, 95% CI 1.47-4.00, p = 0.001), independent to shock and in addition to LVSD. In sepsis, RVSD predicted all-cause mortality by day-28 follow-up, independent to LVSD.

Prognostic value of serial lactate levels in septic patients with and without shock.

To analyze the prognostic value of lactate levels for day-7 and in-hospital mortality, in septic patients with and without shock. In the period November 2011-December 2016, we enrolled 268 patients, admitted to our High-Dependency Unit with a diagnosis of sepsis. Lactate dosage was performed at ED-HDU admission (T0), after 2 h (T2), 6 h (T6) and 24 h (T24); lactate clearance was calculated at T2 and T6 [T2: ((LAC T0-LAC T2/LAC T0)*100)]; T6: [(LAC T0-LAC T6/LAC T0)*100]. The end-points were day-7 and in-hospital mortality. At every evaluation, the lactate level was higher in patients with shock than in those without (T0 3.8 ± 3.8 vs 2.4 ± 2.1; T6 2.9 ± 3.2 vs 1.6 ± 1.1; T24 3.0 ± 4.4 vs 1.4 ± 0.9 meq/L, all p < 0.001). Among patients with shock, an analysis for repeated measures confirmed a more marked lactate level reduction in survivors compared with non-survivors, both by day-7 and in-hospital mortality (p = 0.057 and p = 0.006). A Kaplan-MeIer analysis confirmed a significantly better day-7 survival in patients with T6 (with shock 86% vs 70%; without shock 93% vs 82, all p < 0.05) and T24 (with shock 86% vs 70%; without shock 93% vs 82, all p < 0.05) lactate ≤ 2 meq/L, compared with patients with higher levels. A T6 lactate clearance > 10% was more frequent among in-hospital survivors in the whole study population (57% vs 39%) and in patients with shock (74% vs 46%, all p < 0.05). Higher lactate levels and decreased clearance were associated with an increased short-term and intermediate-term mortality regardless of the presence of shock.

Does an imaging stress-test adds information to prognostic scores in patients with chest pain in the emergency department?

We evaluated the ability of a stress-test (Str-T) to improve the risk stratification based on prognostic scores in patients presenting to the ED with chest pain. Between 2008, June and 2013, December, 1082 patients with chest pain were evaluated with an imaging Str-T. With a retrospective analysis, patients were stratified according to: (1) Florence Prediction Rule as low (0-1, LR-FPR), intermediate (2-4, IR-FPR), high risk (5-6, HR-FPR), respectively, 26, 50 and 24% of patients; (2) HEART score as LR-HEART, (0-3) and HR-HEART (≥4), respectively, 36 and 64%; (3) likelihood of CAD according to NICE guidelines, 10-29% LR-NICE, 30-60% IR-NICE and > 60% HR-NICE, respectively, 12, 18 and 70%. Scores' diagnostic performance was calculated with Str-T as reference. One-month follow-up by a phone call was performed, to investigate the occurrence of new cardiovascular events. In LR and HR patients, FPR and NICE score showed sensitivity 66 vs 93%, specificity 59 vs 19% (both p < 0.001), Positive Predictive Value (PPV) 36 vs 31%, Negative Predictive Value (NPV) 83 vs 87%. Among LR-HEART patients, Str-T was positive for inducible ischemia in 53 (14%) patients and 12 (4%) of them underwent a percutaneous coronary revascularization. The Str-T was negative for inducible ischemia in 760 (70%) patients, positive in 272 (25%), inconclusive in 50 (5%); among patients in the LR and IR subgroups, incidence of CAD (1.3 and 1.6%) and the cumulative incidence of significant events at 1-month follow-up (both 1%) was very low Str-T improved prognostic scores' diagnostic performance in LR- and HR-subgroups.

Prognostic value of sepsis-induced coagulation abnormalities: an early assessment in the emergency department.

To evaluate if the assessment of coagulation abnormalities at ED admission could improve prognostic assessment of septic patients. This report utilizes a portion of the data collected in a prospective study, with the aim to identify reliable biomarkers for an early sepsis diagnosis. In the period November 2011-December 2016, we enrolled 268 patients, admitted to our High-Dependency Unit with a diagnosis severe sepsis/septic shock. Study-related blood samplings were performed at ED-HDU admission (T0), after 6 h (T6) and 24 h (T24): D-dimer, thrombin-antithrombin complex (TAT) and prothrombin fragment F1 + 2 levels were analyzed. The primary end-points were day-7 and in-hospital mortality. Day-7 mortality rate was 16%. D-dimer (T0: 4661 ± 4562 µg/ml vs 3190 ± 7188 µg/ml; T6: 4498 ± 4931 µg/ml vs 2822 ± 5623 µg/ml; T24 2905 ± 2823 µg/ml vs 2465 ± 4988 µg/ml, all p < 0.05) and TAT levels (T0 29 ± 45 vs 22 ± 83; T6 21 ± 22 vs 15 ± 35; T24 16 ± 19 vs 13 ± 30, all p < 0.05) were higher among non-survivors compared to survivors. We defined an abnormal coagulation activation (COAG+) as D-dimer > 500 µg/ml and TAT > 8 ng/ml (for both, twice the upper normal value). Compared to COAG-, COAG+ patients showed higher lactate levels at the earliest evaluations (T0: 3.3 ± 2.7 vs 2.5 ± 2.3, p = 0.041; T6: 2.8 ± 3.4 vs 1.8 ± 1.6, p = 0.015); SOFA score was higher after 24 h (T24: 6.7 ± 3.1 vs 5.4 ± 2.9, p = 0.008). At T0, COAG+ patients showed a higher day-7 mortality rate (HR 2.64; 95% CI 1.14-6.11, p = 0.023), after adjustment for SOFA score and lactate level. Presence of abnormal coagulation at ED admission shows an independent association with an increased short-term mortality rate.

SOFA score in septic patients: incremental prognostic value over age, comorbidities, and parameters of sepsis severity.

Several widely used scoring systems for septic patients have been validated in an ICU setting, and may not be appropriate for other settings like Emergency Departments (ED) or High-Dependency Units (HDU), where a relevant number of these patients are managed. The purpose of this study is to find reliable tools for prognostic assessment of septic patients managed in an ED-HDU. In 742 patients diagnosed with sepsis/severe sepsis/septic shock, not-intubated, admitted in ED between June 2008 and April 2016, SOFA, qSOFA, PIRO, MEWS, Charlson Comorbidity Index, MEDS, and APACHE II were calculated at ED admission (T0); SOFA and MEWS were also calculated after 24 h of ED-High-Dependency Unit stay (T1). Discrimination and incremental prognostic value of SOFA score over demographic data and parameters of sepsis severity were tested. Primary outcome is 28-day mortality. Twenty-eight day mortality rate is 31%. The different scores show a modest-to-moderate discrimination (T0 SOFA 0.695; T1 SOFA 0.741; qSOFA 0.625; T0 MEWS 0.662; T1 MEWS 0.729; PIRO: 0.646; APACHE II 0.756; Charlson Comorbidity Index 0.596; MEDS 0.674, all p < 0.001). At a multivariate stepwise Cox analysis, including age, Charlson Comorbidity Index, MEWS, and lactates, SOFA shows an incremental prognostic ability both at T0 (RR 1.165, IC 95% 1.009-1.224, p < 0.0001) and T1 (RR 1.168, IC 95% 1.104-1.234, p < 0.0001). SOFA score shows a moderate prognostic stratification ability, and demonstrates an incremental prognostic value over the previous medical conditions and clinical parameters in septic patients.

SOFA score and left ventricular systolic function as predictors of short-term outcome in patients with sepsis.

In a group of septic patients, we assess the short-term prognostic value of LV systolic performance, evaluated through conventional left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS). One hundred forty-seven patients with sepsis were recruited; LVEF by planimetry and peak GLS by 2D speckle tracking could be assessed within 24 h. The study population was stratified according to SOFA tertiles assessed at the time of the echocardiogram (G1: SOFA score <5; G2: SOFA score 5-7; G3: SOFA score >7). Day-7 follow-up data were used as reference. Patients in G2 and G3 show a significant hemodynamic derangement, paralleling the more pronounced organ damage by definition; nevertheless, LVEF and GLS are comparable among the three groups (both p > 0.1). All-cause mortality at day-7 follow-up is slightly lower in G1 (9%) versus G2 and G3 (14 and 26%, respectively, p = NS). Analyses through ROC curves focusing on day-7 mortality show that the SOFA score fairly correlates with events (AUC 0.635, p = 0.037), while low LVEF (AUC 0.35, p = 0.022) and less negative GLS (AUC 0.73, p = 0.001) do so. In multivariate analyses, mortality by day-7 follow-up is more likely per higher GLS (i.e., indicative of worst systolic dysfunction, HR 1.22/%, p = 0.005) and per increasing SOFA score (HR 1.22/unit, p = 0.010), whereas LVEF, adjusted for age and SOFA score, does not enter the prognostic model. In the very short term in patients with severe sepsis, LV systolic function assessment by means of GLS predicts the short-term prognosis, independent of SOFA.

High-frequency QRS analysis compared to conventional ST-segment analysis in patients with chest pain and normal ECG referred for exercise tolerance test.

BACKGROUND: The novel analysis of high-frequency QRS components (HFQRS-analysis) has been proposed in patients with chest pain (CP) and normal electrocardiography (ECG) referred for exercise tolerance test (ex-ECG). The aim of the study was to compare the diagnostic value of ex-ECG with ex-HFQRS-analysis. METHODS: Patients with CP and normal ECG, troponin, and echocardiography were considered. All patients underwent ex-ECG for conventional ST-segment-analysis and ex-HFQRS-analysis. A decrease ≥ 50% of the HFQRS signal intensity recorded in at least 2 contiguous leads was considered an index of ischemia, as ST-segment depression ≥ 2 mm or ≥ 1 mm and CP on ex-ECG. Exclusion criteria were: QRS duration ≥ 120 ms and inability to exercise. End-point: The composite of coronary stenosis ≥ 70% or acute coronary syndrome, revascularization, cardiovascular death at 3-month follow-up. RESULTS: Three-hundred thirty-seven patients were enrolled (age 60 ± 15 years). The percent-age of age-adjusted maximal predicted heart rate was 89 ± 10 beat per minute and the maximal systolic blood pressure was 169 ± 23 mm Hg. Nineteen patients achieved the end-point. In multivariate analysis, both ex-ECG and ex-HFQRS were predictors of the end-point. The ex-HFQRS-analysis showed higher sensitivity (63% vs. 26%; p < 0.05), lower specificity (68% vs. 95%; p < 0.001), and comparable negative predictive value (97% vs. 96%; p = 0.502) when compared to ex-ECG-analysis. Receiver operator characteristics analysis showed the incremental diagnostic value of HFQRS (area: 0.655, 95% CI 0.60-0.71) over conventional ex-ECG (0.608, CI 0.55-0.66) and CP score (0.530, CI 0.48-0.59), however without statistical significance in pairwise comparison by C-statistic. CONCLUSIONS: In patients with CP submitted to ex-ECG, the novel ex-HFQRS-analysis shows a valuable incremental diagnostic value over ST-segment-analysis.

Hypertension and atrial fibrillation: prognostic aspects of troponin elevations in clinical practice.

BACKGROUND: Hypertension and atrial fibrillation (AFib) frequently coexist in clinical practice. However, it is unclear whether this association per se or in combination with coronary artery disease (CAD) is a predictor of adverse outcomes. AIM: The aim of this study is to recognize and treat CAD in patients with hypertension and AFib. METHODS: Patients with long-standing hypertension and recent-onset AFib (lasting ≤48 hours) were enrolled and managed with standard care regardless of the presence of troponin elevations (e-TnI) (group 1, n=636, 2010-2011 years) or managed with tailored-care including echocardiography and stress testing when presenting with e-TnI (group 2, n=663, 2012-2013 years). ENDPOINT: The composite of ischemic vascular events including stroke, acute coronary syndrome, revascularization, and death at the 6-month follow-up. RESULTS: Out of 1299 patients enrolled, those with e-TnI (56 and 57 in groups 2 and 1, respectively, P=0.768) were more likely to admit in group 2 vs. group 1 (21 vs. 32, respectively, P=0.060), and less likely to undergo stress testing in group 2 vs. group 1 (15 vs. 1, respectively, P<0.001). Twenty-one patients in group 2 were admitted with positive stress testing (n=9) or high e-TnI (n=12; 1.04±1.98 ng/mL); conversely 35 were discharged with negative stress testing (n=6) or very-low e-TnI (n=29; 0.27±0.22 ng/mL). Finally, 7 patients vs. 1, in groups 2 and 1, respectively, underwent revascularization (P=0.032), and 3 vs. 12 reached the endpoint (P=0.024). On multivariate analysis, e-TnI, known CAD and age were predictors of the endpoint. CONCLUSIONS: In patients with hypertension, AFib, and e-TnI, tailored-care inclusive of echocardiography and stress testing succeeded in recognizing and treating CAD avoiding adverse events without increase in admissions.

Long-term prognostic value of stress echocardiography in patients presenting to the ED with spontaneous chest pain.

PURPOSE: The aims of this study were to evaluate the long-term prognostic value of stress echocardiography (SE) in patients evaluated in emergency department (ED) and to determine SE parameters that best predicted outcome. METHODS: Between June 2008 and July 2012, 626 patients with an episode of spontaneous chest pain underwent SE (exercise stress echocardiography or dobutamine stress echocardiography [DSE]). Between December 2012 and January 2013, all patients were contacted to verify the occurrence of cardiac events. Patients were divided in 3 subgroups according to peak stress Wall Motion Score Index (pWMSI): normal peak wall motion (pWMSI, 1; group A1), mild to moderate peak asynergy (pWMSI, 1.1-1.7; group A2), and severe peak asynergy (pWMSI, >1.7; group A3). RESULTS: Stress echocardiography showed inducible ischemia in 159 patients (25%); it was negative in 425 (68%) and inconclusive in 42 (7%). Patients with cardiac events more frequently showed inducible ischemia (50% vs 26%; P = .015) compared with patients with good prognosis; a normal SE (14% vs 61%) was significantly less common. At a multivariate regression analysis, an increased pWMSI (relative risk: 9.816, 95% confidence interval: 3.665-26.290; P < .0001) was independently associated with a bad outcome. Cumulative event-free survival was significantly worse with an increasing degree of peak wall motion asynergy (99% in group A1; 96%, group A2; and 88% in group A3; P = .011 between A1 and A2 groups, P = .012 between A2 and A3 groups, and P < .0001 between A1 and A3 groups). CONCLUSIONS: Stress echocardiography showed an optimal prognostic value among ED patients evaluated for chest pain. The presence of an extensive asynergic area at peak stress was associated with an adverse prognosis.