Jackeline Hernandez-Nino

Prospective Evaluation of Right Ventricular Function and Functional Status 6 Months After Acute Submassive Pulmonary Embolism: Frequency of Persistent or Subsequent Elevation in Estimated Pulmonary Artery Pressure

BACKGROUND No published data have systematically documented pulmonary artery pressure over an intermediate time period after submassive pulmonary embolism (PE). The aim of this work was to document the rate of pulmonary hypertension, as assessed noninvasively by estimated right ventricular systolic pressure (RVSP) of >or= 40 mm Hg 6 months after the diagnosis of submassive PE. METHODS We enrolled 200 normotensive patients with CT angiography-proven PE and a baseline echocardiogram to estimate RVSP. All patients received therapy with unfractionated heparin initially, but 21 patients later received alteplase in response to circulatory shock or respiratory failure. Patients returned at 6 months for repeat RVSP measurement, and assessments of the New York Heart Association (NYHA) score and 6-min walk distance (6MWD). RESULTS Six months after receiving a diagnosis, 162 of 180 survivors (90%) returned for follow-up, including 144 patients who had been treated with heparin (heparin-only group) and 18 patients who had been treated with heparin plus alteplase (heparin-plus-alteplase group). Among the heparin-only patients, the RVSP at diagnosis was >or= 40 mm Hg in 50 of 144 patients (35%; 95% CI, 27% to 43%), compared with 10 of 144 patients at follow-up (7%; 95% CI, 3% to 12%). However, the RVSP at follow-up was higher than the baseline RVSP in 39 of 144 patients (27%; 95% CI, 9% to 35%), and 18 of these 39 patients had a NYHA score of >or= 3 or exercise intolerance (6MWD, < 330 m). Among heparin-plus-alteplase patients, the RVSP was >or= 40 mm Hg in 11 of 18 patients at diagnosis (61%; 95% CI, 36% to 83%), compared with 2 of 18 patients at follow-up (11%; 95% CI, 1% to 35%). The RVSP at follow-up was not higher than at the time of diagnosis in any of the heparin-plus-alteplase patients (95% CI, 0% to 18%). CONCLUSIONS Six months after experiencing submassive PE, a significant proportion of patients had echocardiographic and functional evidence of pulmonary hypertension.

Surrogate markers for adverse outcomes in normotensive patients with pulmonary embolism

Background:Although echocardiography has proven utility in risk stratifying normotensive patients with pulmonary embolism, echocardiography is not always available. Objective:Test if a novel panel consisting of pulse oximetry, 12-lead electrocardiography, and serum troponin T would have prognostic equivalence to echocardiography and to examine the prognostic performance of age, previous cardiopulmonary disease, D-dimer, brain natriuretic peptide, and percentage of pulmonary vascular occlusion on chest computed tomography. Design:Prospective cohort study. Patients and Setting:Normotensive (systolic blood pressure of >100 mm Hg) emergency department and hospital inpatients with diagnosed pulmonary embolism who underwent cardiologist-interpreted echocardiography and other measurements within 15 hrs of anticoagulation. Measurements and Main Results:End points were in-hospital circulatory shock or intubation, or death, recurrent pulmonary embolism, or severe cardiopulmonary disability (defined as echocardiographic evidence of severe right ventricular dysfunction with New York Heart Association class III dyspnea or 6-min walk test of <330 m) at 6-month follow-up. The two-one–sided test tested the hypothesis of equivalence with one-tailed &agr; = 0.05 and &Dgr; = 5%. Of 200 patients enrolled, data were complete for 181 (88%); 51 of 181 patients (28%) had an adverse outcome, including in-hospital complication (n = 18), death (n = 11), recurrent pulmonary embolism (n = 2), or cardiopulmonary disability (n = 20). Right ventricular dysfunction on initial echocardiogram was 61% sensitive (95% confidence interval, 46–74%) and 57% specific (48–66%). The panel was 71% sensitive (56–83%) and 62% specific (53–71%). The two-one–sided procedure demonstrated superiority of the panel to echocardiography for both sensitivity and noninferiority for specificity. No other biomarker demonstrated equivalence, noninferiority, or superiority for sensitivity and specificity. Conclusion:Normotensive patients with pulmonary embolism have a high rate of severe adverse outcomes during 6-month follow-up. A panel of three widely available tests can be used to risk stratify patients with pulmonary embolism when formal echocardiography is not available.

Use of pulse oximetry to predict in-hospital complications in normotensive patients with pulmonary embolism

PURPOSE A simple method is needed to risk stratify normotensive patients with pulmonary embolism. We studied whether bedside clinical data can predict in-hospital complications from pulmonary embolism. METHODS We performed a multicenter derivation phase, followed by validation in a single center. All patients were normotensive; the diagnosis of pulmonary embolism was established by objective imaging. Classification and regression analysis was performed to derive a decision tree from 27 parameters recorded from 207 patients. The validation study was conducted on a separate group of 96 patients to determine the derived criterions diagnostic accuracy for in-hospital complications (cardiogenic shock, respiratory failure, or death). RESULTS Mortality in the derivation phase was 4% (n = 8) at 24 hours and 10% (n = 21) at 30 days. A room-air pulse oximetry reading <95% was the most important predictor of death; mortality was 2% (95% confidence interval [CI]: 0% to 6%) in patients with pulse oximetry >or=95% versus 20% (95% CI: 12% to 29%) with pulse oximetry <95%. In the validation phase, the room-air pulse oximetry was <95% at the time of diagnosis in 9 of 10 patients who developed an in-hospital complication (sensitivity, 90%) and >or=95% in 55 of 86 patients without complications (specificity, 64%). CONCLUSION Mortality from pulmonary embolism in normotensive patients is high. A room-air pulse oximetry reading >or=95% at diagnosis is associated with a significantly lower probability of in-hospital complications from pulmonary embolism.

Comparison of 8 biomarkers for prediction of right ventricular hypokinesis 6 months after submassive pulmonary embolism.

BACKGROUND Elevated blood concentrations of troponin proteins or brain natriuretic peptide (BNP) worsen the prognosis of patients with pulmonary embolism (PE). Novel biomarkers that reflect mechanisms of right ventricle (RV) damage from PE may provide additional prognostic value. We compare the prognostic use of BNP, troponin I, D-dimer, monocyte chemoattractant protein-1, matrix metalloproteinase, myeloperoxidase, C-reactive protein, and caspase 3 as biomarkers of RV damage and adverse outcomes in submassive PE. METHODS This article used a prospective cohort study of normotensive (systolic blood pressure always >100 mm Hg) patients with computed tomographic angiography-diagnosed PE. All patients underwent echocardiography and phlebotomy at diagnosis, and survivors had another echocardiography 6 months later. We tested each biomarker for prognostic significance, requiring a lower limit 95% CI >0.50 for the area under the receiver operating characteristic curve (AUROC) with a reference standard positive of RV hypokinesis on either echocardiogram. Biomarkers with prognostic significance were dichotomized at the concentration that yielded highest likelihood ratio positive and mortality rates compared (Fisher exact test). RESULTS We enrolled 152 patients with complete data. Thirty-seven (24%, 95% CI 18%-32%) had RV hypokinesis. Only BNP and troponin had significant AUROC values as follows: 0.71 (95% CI 0.60-0.81) and 0.71 (95% CI 0.62-0.82), respectively. Overall mortality was 13/153 (8.5%); mortality rate for BNP >100 versus < or =100 pg/mL was 23% versus 3% (P = .003), respectively. Mortality rate for troponin I >0.1 versus < or =0.1 ng/mL was 13% versus 6% (P = .205), respectively. CONCLUSIONS Of 8 mechanistically plausible biomarkers, only BNP and troponin I had significant prognostic use with BNP having an advantage for predicting mortality.

Tenecteplase to treat pulmonary embolism in the emergency department

Tenecteplase, a mutant form of alteplase, possesses pharmacological properties that might favor its use for emergent fibrinolysis of acute pulmonary embolism. Contemporaneous search of the World’s literature reveals 14 humans with acute pulmonary embolism treated with tenecteplase. Here, we summarize those cases and report the presentation features, dosing details and outcomes of eight additional patients with acute pulmonary embolism treated with tenecteplase in an academic emergency department. None of our eight patients had a significant hemorrhagic event after tenecteplase, and the outcomes of all eight appear to be acceptable. Taken together, we submit that the present case report and prior case reports are sufficient to comprise a phase I study of the safety and efficacy of tenecteplase to treat acute pulmonary embolism.

The First-Time Seizure Emergency Department Electroencephalogram Study

Study objective Seizures account for 1.2% of all emergency department (ED) visits, with 24% of those representing first‐time seizures. Our primary goal is to determine whether obtaining an electroencephalogram (EEG) in the ED after a first‐time seizure can identify individuals appropriate for initiation of anticonvulsant therapy on ED discharge. Our secondary goals are to determine the association of historical and clinical seizure features with epileptic EEGs and to determine the interobserver agreement for the EEG interpretation. Methods We conducted a prospective study including patients older than 17 years with either a first‐time seizure or previous seizures without a previous EEG, all of whom were candidates for discharge home from the ED without antiepileptic drug treatment. We based seizure diagnosis on provider impression. We excluded patients with laboratory studies or neuroimaging deemed to be the seizure cause. EEG technicians performed a 30‐minute EEG in the ED, which was immediately remotely interpreted by an epileptologist, who made a recommendation on antiepileptic drug initiation. We categorized EEGs as normal, abnormal but not epileptic, or epileptic. In accordance with duplicate EEG interpretation by a second, blinded epileptologist, we calculated interrater agreement for EEG interpretation and antiepileptic drug initiation. As a secondary analysis, according to questionnaires completed by patients and seizure observers, we explored the association of aura, focal symptoms, provocation, or historical risk factors with epilepsy. Results We enrolled 73 patients, 71 of whom had an EEG performed. All EEGs were performed within 11 hours of seizure, with an average of 3.85 hours. Twenty‐four percent of patients (95% confidence interval 15% to 36%) received a diagnosis of epilepsy, and all began receiving antiepileptic drug therapy from the ED. Our final study sample size afforded only an exploratory analysis about an association between aura, focal onset, provocation, or historical risk factors with an epilepsy diagnosis. Weighted &kgr; agreement for EEG interpretation was 0.69 (95% confidence interval 0.55 to 0.82). Of the 34 patients who followed up with an epileptologist, 9 had received a diagnosis of epilepsy in the ED, and none had antiepileptic drug medication stopped at initial follow‐up. Conclusion ED EEG performance in adults with first‐time seizures results in a substantial yield of an epilepsy diagnosis and immediate initiation of antiepileptic drug treatment. A larger study is required to determine whether historical and clinical seizure features are associated with an ED epilepsy diagnosis.