Geoffrey A. Rose

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.

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.

Interobserver and Intraobserver Agreement on Qualitative Assessments of Right Ventricular Dysfunction With Echocardiography in Patients With Pulmonary Embolism

To evaluate observer agreement using qualitative goal‐directed echocardiographic criteria for right ventricular (RV) dysfunction prognostication in submassive pulmonary embolism (PE).