Diagnosis of acute aortic syndromes with ultrasound and d-dimer: the PROFUNDUS study.

BACKGROUND: In patients complaining common symptoms such as chest/abdominal/back pain or syncope, acute aortic syndromes (AAS) are rare underlying causes. AAS diagnosis requires urgent advanced aortic imaging (AAI), mostly computed tomography angiography. However, patient selection for AAI poses conflicting risks of misdiagnosis and overtesting. OBJECTIVES: We assessed the safety and efficiency of a diagnostic protocol integrating clinical data with point-of-care ultrasound (POCUS) and d-dimer (single/age-adjusted cutoff), to select patients for AAI. METHODS: This prospective study involved 12 Emergency Departments from 5 countries. POCUS findings were integrated with a guideline-compliant clinical score, to define the integrated pre-test probability (iPTP) of AAS. If iPTP was high, urgent AAI was requested. If iPTP was low and d-dimer was negative, AAS was ruled out. Patients were followed for 30 days, to adjudicate outcomes. RESULTS: Within 1979 enrolled patients, 176 (9 %) had an AAS. POCUS led to net reclassification improvement of 20 % (24 %/-4 % for events/non-events, P < 0.001) over clinical score alone. Median time to AAS diagnosis was 60 min if POCUS was positive vs 118 if negative (P = 0.042). Within 941 patients satisfying rule-out criteria, the 30-day incidence of AAS was 0 % (95 % CI, 0-0.41 %); without POCUS, 2 AAS were potentially missed. Protocol rule-out efficiency was 48 % (95 % CI, 46-50 %) and AAI was averted in 41 % of patients. Using age-adjusted d-dimer, rule-out efficiency was 54 % (difference 6 %, 95 % CI, 4-9 %, vs standard cutoff). CONCLUSIONS: The integrated algorithm allowed rapid triage of high-probability patients, while providing safe and efficient rule-out of AAS. Age-adjusted d-dimer maximized efficiency. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04430400.

Pre-Test Probability Assessment and d-Dimer Based Evaluation in Patients with Previous Acute Aortic Syndrome.

Background and Objectives. Acute aortic syndromes (AASs) are emergencies burdened by high morbidity and mortality. Guideline-recommended diagnostic workup is based on pre-test probability assessment (PPA) and d-dimer testing. However, the performance of PPA and d-dimer has never been studied in individuals with previous AAS (pAAS), which represent a challenging population. Materials and Methods. We analyzed a registry of patients with pAAS evaluated in two Emergency Departments (EDs) for suspected novel AAS (nAAS). Enrolment criteria were history of pAAS and the presence of truncal pain, syncope or perfusion deficit. All patients underwent advanced imaging. Clinical data were registered prospectively and PPA was performed by applying the aortic dissection detection (ADD) and an aorta simplified (AORTAs) score. Results. A total of 128 patients were enrolled, including 77 patients with previous Stanford type A aortic dissection and 45 patients with previous Stanford type B aortic dissection. The final diagnosis was nAAS in 40 (31%) patients. Clinical variables associated with nAAS were: aortic valve disease, thoracic aortic aneurysm, severe pain, sudden pain, ripping/tearing pain and hypotension/shock. ADD score ≥ 2 had a sensitivity of 65% and a specificity of 83% for nAAS; AORTAs score ≥ 2 had a sensitivity of 48% and a specificity of 88%. d-dimer (cutoff ≥ 500 ng/mL or age-adjusted cutoff) had a sensitivity of 97% and a specificity of 13%/14.7%, for diagnosis of nAAS. Patients that were candidates for guideline-compliant PPA/d-dimer integrated rule-out were: 5 (4.9%) with ADD ≤ 1/d-dimer and 8 (7.8%) with AORTAs ≤ 1/d-dimer < age-adjusted cutoff. None of them had a nAAS. Conclusions. Patients with pAAS evaluated in the ED for red-flag symptoms showed intermediate-to-high pre-test probability of nAAS. The ADD score had lower sensitivity and specificity than in unselected patients. d-dimer, alone and integrated with PPA, was highly sensitive for nAAS, but very unspecific. PPA/d-dimer integrated strategies are unlikely to significantly reduce the number of patients with pAAS undergoing advanced imaging.

Comparison of Troponin I levels versus myocardial dysfunction on prognosis in sepsis.

In the context of sepsis, we tested the relationship between echocardiographic findings and Troponin, and their impact on prognosis. In this prospective study, we enrolled 325 septic patients (41% with shock), not mechanically ventilated, between October, 2012 and June, 2019 among those admitted to our High-Dependency Unit. By echocardiography within 24 h from the admission, sepsis-induced myocardial dysfunction (SIMD) was defined as left ventricular (LV) systolic dysfunction (speckle-tracking-based global longitudinal peak systolic strain, GLS, > - 14%) and/or right ventricular (RV) systolic dysfunction (Tricuspid Annular Plane Systolic Excursion, TAPSE < 16 mm). Troponin I levels were measured upon admission (T0) and after 24 h (T1); it was considered normal if > 0.1 ng/mL. Mortality was assessed at day-7 and day-28 end-points. One-hundred and forty-two patients had normal Troponin level at T0 and T1 (G1), 69 had abnormal levels at T0 or T1 (G2) and 114 showed abnormal Troponin levels at both T0 and T1 (G3). Compared to G1, patients in G3 had worse LV and RV systolic function (GLS - 11.6 ± 3.4% vs - 14.0 ± 3.5%, p < 0.001; TAPSE 18 ± 0.5 vs 19 ± 0.5 mm, p = 0.047) and greater day-28 (34% vs 20%, p = 0.015) mortality. In a Cox survival analysis including age, Troponin and SOFA score, mortality was predicted by the presence of SIMD (RR 3.24, 95% CI 1.72-6.11, p < 0.001) with no contribution of abnormal Troponin level. While abnormal Troponin levels were associated with SIMD diagnosed by echocardiography, only the presence of SIMD predicted the short- and medium-term mortality rate, without an independent contribution of increased Troponin levels.

Prognostic stratification in septic patients with overt and cryptic shock by speckle tracking echocardiography.

We evaluated the prevalence and prognostic value of left (LV) and right (RV) ventricular systolic dysfunction in the presence of overt and cryptic shock. In this prospective study, between October 2012 and June 2019, we enrolled 354 patients with sepsis, 41% with shock, among those admitted to the Emergency Department High-Dependency Unit. Patients were grouped based on the presence of shock, or by the presence of lactate levels ≥ (LAC +) or < 2 mmol/L (LAC-) evaluated within the first 24 h. By echocardiography performed within 24 h from the admission, LV systolic dysfunction was defined as global longitudinal strain (GLS) > -14%; RV systolic dysfunction as Tricuspid Annular Plane Systolic Excursion (TAPSE) < 16 mm. All-cause mortality was assessed at day-7 and day-28 follow-up. Mean values of LV GLS (-12.3 ± 3.4 vs -12.9 ± 3.8%) and TAPSE (1.8 ± 0.7 vs 1.8 ± 0.5 cm, all p = NS) were similar in patients with and in those without shock. LV GLS was significantly worse in LAC + than LAC- patients (- 11.2 ± 3.1 vs - 12.9 ± 3.7%, p = 0.001). In patients without shock, as well as in those LAC-, LV dysfunction was associated with increased day-28 mortality rate (78% vs 57% in non-survivors and survivors without shock and 74% vs 53% in non-survivors and survivors LAC-, all p < 0.01). LV (RR 2.26, 95% CI 1.37-3.74) and RV systolic dysfunction (RR 1.85, 95% CI 1.22-2.81) were associated with increased 28-day mortality rate in addition and independent to LAC + (RR 1.81, 95% CI 1.15-2.84). In conclusion, LV and RV ventricular dysfunction were independently associated with an increased mortality rate, altogether with the presence of cryptic shock.

Duplex Sonography of Vertebral Arteries for Evaluation of Patients with Acute Vertigo.

We evaluated the role of vertebral artery extracranial color-coded duplex sonography (VAECCS) in predicting vertebrobasilar stroke in consecutive patients presenting to the emergency department with vertigo of suspected ischemic origin. The final diagnosis was established by a panel of experts consisting of an emergency physician, a neurologist, and an otoneurologist. Vertebrobasilar stroke was diagnosed when an acute brain ischemic lesion congruent with symptoms was detected by neuroimaging during the index visit or a stroke was diagnosed within a 3-mo period after emergency department presentation. Among 126 patients, 28 (22%) were diagnosed with vertebrobasilar stroke. Fifteen (75%) of 20 patients with abnormal VAECCS results and 13 (12%) of 106 with normal VAECCS results had a final diagnosis of vertebrobasilar stroke. The sensitivity and specificity of VAECCS were 53.6% and 94.9%, respectively. Detecting an abnormal flow pattern at VAECCS significantly increased the risk of vertebrobasilar stroke (odds ratio = 21.5). The flow patterns most frequently related to vertebrobasilar stroke were absence of flow and high resistance pattern velocity (odds ratio = 9.3 and 22.7, respectively). VAECCS predicts vertebrobasilar stroke and could be a useful bedside screening tool in patients with vertigo.