Stefano Grifoni

Short-Term Clinical Outcome of Patients With Acute Pulmonary Embolism, Normal Blood Pressure, and Echocardiographic Right Ventricular Dysfunction

BACKGROUND The role of echocardiographic right ventricular (RV) dysfunction in predicting clinical outcome in clinically stable patients with pulmonary embolism (PE) is undefined. In this study, we assessed the prevalence and clinical outcome of normotensive patients with RV dysfunction among a broad spectrum of PE patients. METHODS AND RESULTS This prospective clinical outcome study included cohort of 209 consecutive patients (age, 65+/-15 years) with documented PE. Acute RV dysfunction was diagnosed in the presence of >/=1 of the following: RV dilatation (without hypertrophy), paradox septal systolic motion, and Doppler evidence of pulmonary hypertension. Four groups were identified: 28 patients presenting with shock or cardiac arrest (13%), 19 hypotensive patients without shock (9%), 65 normotensive patients with echocardiographic RV dysfunction (31%), and 97 normotensive patients without RV dysfunction (47%). Among normotensive patients with RV dysfunction, 6 (10%) developed PE-related shock after admission: 3 of these patients died, and 3 were successfully treated with thrombolytic agents. In comparison, none of the 97 normotensive patients without RV dysfunction developed shock or died as a result of PE. CONCLUSIONS A significant proportion (31%) of normotensive patients with acute PE presents with RV dysfunction; these patients with latent hemodynamic impairment have a 10% rate of PE-related shock and 5% in-hospital mortality and may require aggressive therapeutic strategies. Conversely, normotensive patients without echocardiographic RV dysfunction have a benign short-term prognosis. Thus, early detection of echocardiographic RV dysfunction is of major importance in the risk stratification of normotensive patients with acute PE.

Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test

AIMS In patients with acute pulmonary embolism (PE), right ventricular dysfunction at echocardiography is associated with increased in-hospital mortality. The aims of this study in patients with acute PE were to identify a sensitive and simple criterion for right ventricular dysfunction at multidetector computed tomography (MDCT) using echocardiography as the reference standard and to evaluate the predictive value of the identified MDCT criterion for in-hospital death or clinical deterioration. METHODS AND RESULTS Right ventricular dysfunction at MDCT was defined as the right-to-left ventricular dimensional ratio and was centrally assessed by a panel unaware of clinical and echocardiographic data. A right-to-left ventricular dimensional ratio ≥0.9 at MDCT had a 92% sensitivity for right ventricular dysfunction [95% confidence interval (CI) 88-96]. Overall, 457 patients were included in the outcome study: 303 had right ventricular dysfunction at MDCT. In-hospital death or clinical deterioration occurred in 44 patients with and in 8 patients without right ventricular dysfunction at MDCT (14.5 vs. 5.2%; P< 0.004). The negative predictive value of right ventricular dysfunction for death due to PE was 100% (95% CI 98-100). Right ventricular dysfunction at MDCT was an independent predictor for in-hospital death or clinical deterioration in the overall population [hazard ratio (HR) 3.5, 95% CI 1.6-7.7; P= 0.002] and in haemodynamically stable patients (HR 3.8, 95% CI 1.3-10.9; P= 0.007). CONCLUSION In patients with acute PE, MDCT might be used as a single procedure for diagnosis and risk stratification. Patients without right ventricular dysfunction at MDCT have a low risk of in-hospital adverse outcome.

Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism

INTRODUCTION The clinical benefit of thrombolytic treatment over heparin in patients with pulmonary embolism without hemodynamic compromise remains controversial. In these patients bolus tenecteplase has the potential to provide an effective and safe thrombolysis. METHODS We evaluated the effect of tenecteplase on right ventricle dysfunction (RVD) assessed by echocardiography in hemodynamically stable patients with PE in a multicenter, randomized, double-blind, placebo-controlled study. RVD was defined as right/left ventricle end-diastolic dimension ratio >1 in the apical 4-chamber view. Patients were randomized to receive weight-adjusted single-bolus tenecteplase or placebo. All patients received unfractionated heparin. Reduction of RVD at 24 hours was the primary efficacy end-point and was evaluated by an independent committee unaware of treatment allocation. RESULTS Overall, 58 patients were randomized. Echocardiograms were adequate for efficacy analysis in 51 patients, 23 randomized to tenecteplase and 28 to placebo. The reduction of right to left ventricle end-diastolic dimension ratio at 24 hours was 0.31+/-0.08 in patients randomized to tenecteplase as compared to 0.10+/-0.07 in patients randomized to placebo (p=0.04). One patient randomized to tenecteplase suffered a clinical event (recurrent pulmonary embolism) in comparison to three patients randomized to placebo (1 recurrent pulmonary embolism; 1 clinical deterioration and 1 non pulmonary embolism-related death). Two non fatal major bleedings occurred with tenecteplase (1 intracranial) and one with placebo. CONCLUSION In hemodynamically stable patients with PE, treatment with single bolus tenecteplase is feasible at the same dosages used for acute myocardial infarction and is associated with reduction of RVD at 24 hours. Whether this benefit is associated with an improved clinical outcome without excessive bleeding is currently explored in a large clinical trial.

Utility of an integrated clinical, echocardiographic, and venous ultrasonographic approach for triage of patients with suspected pulmonary embolism

The potential role of ultrasound techniques in diagnosing acute pulmonary embolism (PE) has been investigated in severe cases with hemodynamic compromise, but is still unclear for the whole clinical spectrum of patients with suspected PE. The aim of this study was to assess the utility of an integrated bedside evaluation for PE based on the combination of a clinical score, 2-dimensional echocardiography, and color venous duplex scanning. A group of 117 consecutive patients with suspected PE was assessed using a clinical likelihood score, echocardiography, and venous duplex scanning in order to obtain a preliminary diagnosis of PE, which was subsequently compared with the final diagnosis obtained by lung perfusion scintigraphy and angiography. A preliminary diagnosis of PE was made in 70 patients; a final diagnosis of PE was made in 63 patients, of which 56 had and 7 did not have a preliminary diagnosis of PE. The preliminary diagnosis therefore showed 89% sensitivity and 74% specificity, with a total accuracy of 82%. In patients with massive PE, sensitivity and negative predictive values of the preliminary diagnosis were 97% and 98%, respectively. Echocardiography was poorly sensitive (51%) but highly specific (87%) for PE. Thus, the integration of clinical likelihood, echocardiography, and venous duplex scanning provides a practical approach to patients with suspected PE, allows the rapid implementation of appropriate management strategies, and may reduce or postpone the need for further instrumental evaluation of more limited access.

Accuracy of Point-of-Care Multiorgan Ultrasonography for the Diagnosis of Pulmonary Embolism

BACKGROUND Presenting signs and symptoms of pulmonary embolism (PE) are nonspecific, favoring a large use of second-line diagnostic tests such as multidetector CT pulmonary angiography (MCTPA), thus exposing patients to high-dose radiation and to potential serious complications. We investigated the diagnostic performance of multiorgan ultrasonography (lung, heart, and leg vein ultrasonography) and whether multiorgan ultrasonography combined to Wells score and D-dimer could safely reduce MCTPA tests. METHODS Consecutive adult patients suspected of PE and with a Wells score > 4 or a positive D-dimer result were prospectively enrolled in three EDs. Final diagnosis was obtained with MCTPA. Multiorgan ultrasonography was performed before MCTPA and considered diagnostic for PE if one or more subpleural infarcts, right ventricular dilatation, or DVT was detected. If multiorgan ultrasonography was negative for PE, an alternative ultrasonography diagnosis was sought. Accuracies of each single-organ and multiorgan ultrasonography were calculated. RESULTS PE was diagnosed in 110 of 357 enrolled patients (30.8%). Multiorgan ultrasonography yielded a sensitivity of 90% and a specificity of 86.2%, lung ultrasonography 60.9% and 95.9%, heart ultrasonography 32.7% and 90.9%, and vein ultrasonography 52.7% and 97.6%, respectively. Among the 132 patients (37%) with multiorgan ultrasonography negative for PE plus an alternative ultrasonographic diagnosis or plus a negative D-dimer result, no patients received PE as a final diagnosis. CONCLUSIONS Multiorgan ultrasonography is more sensitive than single-organ ultrasonography, increases the accuracy of clinical pretest probability estimation in patients with suspected PE, and may safely reduce the MCTPA burden. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01635257; URL: www.clinicaltrials.gov.

Prognostic Value of ECG Among Patients with Acute Pulmonary Embolism and Normal Blood Pressure

OBJECTIVE To investigate the prognostic value of electrocardiography (ECG) alone or in combination with echocardiography in patients with acute pulmonary embolism and normal blood pressure. METHODS Consecutive adult patients presenting to the emergency department at Azienda Ospedaliero-Universitaria Careggi with the first episode of pulmonary embolism were included. Patients with systolic blood pressure less than 100 mm Hg were excluded. ECG and echocardiography were performed within 1 hour from diagnosis and evaluated in a blinded fashion. Right ventricular strain was diagnosed in the presence of one or more of the following ECG findings: complete or incomplete right ventricular branch block, S1Q3T3, and negative T wave in V1-V4. The main outcome measurement was clinical deterioration or death during in-hospital stay. The association of variables with the main outcome was evaluated by multivariate Cox survival analysis. RESULTS A total of 386 patients with proved pulmonary embolism were included in the study; 201 patients (52%) had right ventricular dysfunction according to echocardiography, and 130 patients (34%) showed right ventricular strain. Twenty-three patients (6%) had clinical deterioration or died. At multivariate survival analysis, right ventricular strain was associated with adverse outcome (hazard ratio 2.58; 95% confidence interval, 1.05-6.36) independently of echocardiographic findings. Patients with both right ventricular strain and right ventricular dysfunction (26%) showed an 8-fold elevated risk of adverse outcome (hazard ratio 8.47; 95% confidence interval, 2.43-29.47). CONCLUSION Right ventricular strain pattern on ECG is associated with adverse short-term outcome and adds incremental prognostic value to echocardiographic evidence of right ventricular dysfunction in patients with acute pulmonary embolism and normal blood pressure.

Accuracy of lung ultrasound for the diagnosis of consolidations when compared to chest computed tomography

OBJECTIVES Despite emerging evidences on the clinical usefulness of lung ultrasound (LUS), international guidelines still do not recommend the use of sonography for the diagnosis of pneumonia. Our study assesses the accuracy of LUS for the diagnosis of lung consolidations when compared to chest computed tomography (CT). METHODS This was a prospective study on an emergency department population complaining of respiratory symptoms of unexplained origin. All patients who had a chest CT scan performed for clinical reasons were consecutively recruited. LUS was targeted to evaluate lung consolidations with the morphologic characteristics of pneumonia, and then compared to CT. RESULTS We analyzed 285 patients. CT was positive for at least one consolidation in 87 patients. LUS was feasible in all patients and in 81 showed at least one consolidation, with a good inter-observer agreement (k = 0.83), sensitivity 82.8% (95% CI 73.2%-90%) and specificity 95.5% (95% CI 91.5%-97.9%). Sensitivity raised to 91.7% (95% CI 61.5%-98.6%) and specificity to 97.4% (95% CI 86.5%-99.6%) in patients complaining of pleuritic chest pain. In a subgroup of 190 patients who underwent also chest radiography (CXR), the sensitivity of LUS (81.4%, 95% CI 70.7%-89.7%) was significantly superior to CXR (64.3%, 95% CI 51.9%-75.4%) (P<.05), whereas specificity remained similar (94.2%, 95% CI 88.4%-97.6% vs. 90%, 95% CI 83.2%-94.7%). CONCLUSIONS LUS represents a reliable diagnostic tool, alternative to CXR, for the bedside diagnosis of lung consolidations in patients with respiratory complains.

Multidetector CT scan for acute pulmonary embolism: Embolic burden and clinical outcome

BACKGROUND In patients with acute pulmonary embolism (PE), the correlation between the embolic burden assessed by multidetector CT (MDCT) scan and clinical outcomes remains unclear. Patients with symptomatic acute PE diagnosed based on MDCT angiography were included in a multicenter study aimed at assessing the prognostic role of the embolic burden evaluated with MDCT scan. METHODS Embolic burden was assessed as (1) localization of the emboli as central (saddle or at least one main pulmonary artery), lobar, or distal (segmental or subsegmental arteries) and (2) the obstruction index by the scoring system of Qanadli. The primary outcome was 30-day all-cause death or clinical deterioration. Predictors of all-cause death or clinical deterioration were identified by Cox regression statistics. RESULTS Overall, 579 patients were included in the study; 60 (10.4%) died or had clinical deterioration at 30 days. Central localization of emboli was not associated with all-cause death or clinical deterioration (hazard ratio [HR], 2.42; 95% CI, 0.77-7.59; P 5 .13). However, in 516 hemodynamically stable patients, central localization of emboli (HR, 8.3; 95% CI, 1.0-67; P 5 .047) was an independent predictor of all-cause death or clinical deterioration, whereas distal emboli were inversely associated with these outcome events (HR, 0.12; 95% CI, 0.015-0.97; P 5 .047). No correlation was found between obstruction index (evaluated in 448 patients) and all-cause death or clinical deterioration in the overall study population and in the hemodynamically stable patients. CONCLUSIONS In hemodynamically stable patients with acute PE, central emboli are associated with an increased risk for all-cause death or clinical deterioration. This risk is low in patients with segmental or subsegmental PE.

Comparison of two prognostic models for acute pulmonary embolism: clinical vs. right ventricular dysfunction‐guided approach

Summary.  Background: Recently, some prognostic models for acute pulmonary embolism (PE) have been proposed. We investigated whether the Pulmonary Embolism Severity Index (PESI) and the European Society of Cardiology (ESC) prognostic approaches result in different prognoses. Methods: Consecutive adult patients with acute PE were included. According to the ESC guidelines, high‐risk patients were identified by the presence of shock/hypotension, intermediate‐risk patients by elevated troponin I or right ventricular dysfunction as assessed by echocardiography, and low‐risk patients by the absence of any of the above. In the PESI model, 11 clinical variables, easily accessible at the bedside, were used to generate three risk classes. The main outcomes were all‐cause and PE‐related in‐hospital mortality. Results: Forty‐one patients (8%, 95% confidence interval [CI] 5.8–10.8) of 510 died. According to the ESC model, 40% were at low risk of short‐term mortality, 54% at intermediate risk, and 6% at high risk. The distribution according to the PESI model was 31% (P < 0.05 vs. ESC), 49% and 20% (P < 0.05 vs. ESC), respectively. Mortality increased through the risk classes (P < 0.01), without significant differences between the models. The ESC model identified with higher accuracy than the PESI model both high‐risk and low‐risk patients (P < 0.05 for both). When patients with shock/hypotension were excluded, the PESI model stratified patients into classes with increasing PE‐related mortality (0.7%, 4.3%, and 11.6%, P < 0.05). Troponin I and right ventricular dysfunction added incremental prognostic value to the PESI model, particularly in normotensive patients at intermediate risk. Conclusions: The ESC model showed higher accuracy than the PESI model in identifying high‐risk and low‐risk patients. In normotensive patients, the PESI model could guide clinical management as well as troponin I and echocardiography testing.

Delayed neuropsychological sequelae after carbon monoxide poisoning: predictive risk factors in the Emergency Department. A retrospective study

BackgroundDelayed neuropsychological sequelae (DNS) commonly occur after recovery from acute carbon monoxide (CO) poisoning. The preventive role and the indications for hyperbaric oxygen therapy in the acute setting are still controversial. Early identification of patients at risk in the Emergency Department might permit an improvement in quality of care. We conducted a retrospective study to identify predictive risk factors for DNS development in the Emergency Department.MethodsWe retrospectively considered all CO-poisoned patients admitted to the Emergency Department of Careggi University General Hospital (Florence, Italy) from 1992 to 2007. Patients were invited to participate in three follow-up visits at one, six and twelve months from hospital discharge. Clinical and biohumoral data were collected; univariate and multivariate analysis were performed to identify predictive risk factors for DNS.ResultsThree hundred forty seven patients were admitted to the Emergency Department for acute CO poisoning from 1992 to 2007; 141/347 patients participated in the follow-up visit at one month from hospital discharge. Thirty four/141 patients were diagnosed with DNS (24.1%). Five/34 patients previously diagnosed as having DNS presented to the follow-up visit at six months, reporting a complete recovery. The following variables (collected before or upon Emergency Department admission) were associated to DNS development at one month from hospital discharge in the univariate analysis: CO exposure duration >6 hours, a Glasgow Coma Scale (GCS) score <9, seizures, systolic blood pressure <90 mmHg, elevated creatine phosphokinase concentration and leukocytosis. There was no significant correlation with age, sex, voluntary exposure, headache, transient loss of consciousness, GCS between 14 and 9, arterial lactate and carboxyhemoglobin concentration. The multivariate analysis confirmed as independent prognostic factors GCS <9 (OR 7.15; CI 95%: 1.04-48.8) and leukocytosis (OR 3.31; CI 95%: 1.02-10.71).ConclusionsOur study identified several potential predictive risk factors for DNS. Treatment algorithms based on an appropriate risk-stratification of patients in the Emergency Department might reduce DNS incidence; however, more studies are needed. Adequate follow-up after hospital discharge, aimed at correct recognition of DNS, is also important.