In recent years, there has been an increased appreciation of the need for risk stratification of patients with acute submassive PE who are hemodynamically stable but with evidence of RV dysfunction.6 In these patients, RV dysfunction is defined as the presence of at least one of the following: RV dilatation (apical 4-chamber RV diameter/left ventricular [LV] diameter more than 0.9 on echocardiography or chest CT, or RV systolic dysfunction on echocardiography); elevation of BNP more than 90 pg/mL or N-terminal pro-BNP more than 500 pg/mL; or electrocardiographic changes including new complete or incomplete right bundle branch block, anteroseptal ST-segment elevation or depression, or anteroseptal T-wave inversion. Myocardial necrosis is defined as either elevation of troponin I (> 0.4 ng/mL) or troponin T (> 0.1 ng/mL).4,5 Several studies have shown a 2- to 2.5-fold increased risk of mortality in patients with normal BP and RV dysfunction compared with those without RV dysfunction.4,5
Imaging of the RV with echocardiography detects the changes occurring in the morphology and function of the RV as a result of acute pressure overload in PE.6 Echocardiography also allows for estimation of pulmonary artery pressure. Echocardiographic findings in patients with acute PE include RV hypokinesis and dilatation, interventricular septal flattening and paradoxical motion toward the left ventricle, tricuspid regurgitation, pulmonary hypertension, and loss of inspiratory collapse of the inferior vena cava.1 Several studies including registries have demonstrated an association between echocardiographic parameters of RV dysfunction and a poor in-hospital outcome.6,7,8 Nevertheless, the prognostic value of echocardiography in hemodynamically stable patients appears moderate at best, primarily due to the poor standardization of echocardiographic criteria.7,8 In a prospective randomized trial, Konstantinides et al reported that normotensive patients with submassive PE defined by echocardiography appeared to have a low early mortality risk, regardless of whether they received thrombolysis plus heparin or heparin alone.9
Four-chamber views of the heart on multidetector-row chest CT may, besides visualizing the thrombi in the pulmonary vasculature, also detect RV enlargement and (indirectly) dysfunction.7 In an international prospective cohort study, Becattini et al confirmed the prognostic value of an enlarged right ventricle on CT in patients with acute PE.10 However, RV dilatation on CT has been shown to have resulted in only a small ability to classify risk in these patients.11
Elevated levels of cardiac biomarkers (troponins I or T and BNP), in combination with the presence of RV dilatation or hypokinesis on echocardiography significantly helps with risk stratification for acute PE.12,13,14,15,16 Elevated troponins are often found in hemodynamically stable patients with echocardiographic signs of RV overload suggesting myocardial injury.2 Pruszczyk and colleagues found that an elevated troponin T level more than 0.01 ng/mL was the only parameter to predict adverse events in normotensive patients with acute PE.13 In a multicenter, multinational study, the high-sensitivity troponin was examined in 526 normotensive patients with PE and demonstrated a high negative predictive value (98%).14 Similarly, a meta-analysis of 1132 patients showed that 51% of patients with an acute PE had elevated BNP or NT-pro-BNP and were associated with increased early death and complications during hospitalization.15 However, the positive predictive value of BNP or NT-pro-BNP for higher risk has been rather low.
Heart-type fatty acid-binding protein and growth differentiation factor-15 are 2 promising new cardiac biomarkers that have been shown to provide relevant prognostic information in patients with non-high-risk PE.6 Both of these biomarkers increase sharply after pressure overload or myocardial ischemia and are undergoing further study.
The most extensively validated clinical score for risk stratification of patients presenting with PE is the Pulmonary Embolism Severity Score (PESI).17,18 The PESI allows the clinician to rule out an adverse outcome by having a high negative predictive value at the lowest level of PESI classes. The score is however complex to calculate. A more practical approach is the use of the simplified PESI (sPESI) score with 6 parameters: age more than 80 years, history of cancer, history of either heart failure or chronic lung disease, systolic BP less than 100 mm Hg, heart rate more than 110 beats/min, and an arterial oxyhemoglobin saturation less than 90%.19