**2. Echocardiographic assessment of right ventricular dysfunction**

Transthoracic echocardiography is a noninvasive tool that can be easily utilized at the bedside, even in hemodynamically compromised patients. It can help diagnose conditions that mimic acute PE but are treated differently, such as acute myocardial infarction, aortic dissection, and pericardial tamponade. Although echocardiography is not recommended for the diagnosis of PE, it can detect or exclude RV dysfunction. Moreover, echocardiography is an important tool for risk stratification in patients with PE because RV dysfunction on an echocardiogram is a powerful and independent predictor of mortality (Ribeiro et al., 1997; Torbicki et al., 2003). Echocardiographic findings suggesting RV dysfunction have been reported to occur in at least 25% of patients with PE (Kreit, 2004). A meta-analysis found that patients with echocardiographic signs of RV dysfunction were at greater than two-fold higher risk of PE-related mortality than patients without signs of RV dysfunction (ten Wolde et al., 2004). Importantly, patients with normal echocardiographic findings had excellent outcomes, with in-hospital PE-related mortality rates <1% in most of the reported series. A recent systemic review (Fremont et al., 2008) identified five studies that evaluated the prognostic role of echocardiography in diagnosing RV dysfunction. The unadjusted relative risk of RV dysfunction for predicting death was 2.5 (95% CI 1.2-5.5).

Echocardiography, however, has limitations, including restricted availability and relatively high cost. Moreover, in some patients, including those with chronic obstructive pulmonary disease or morbid obesity, it is difficult to adequately image the RV free wall with a transthoracic approach. More importantly, the lack of a clear echocardiographic definition of RV dysfunction is problematic (ten Wolde et al., 2004). A meta-analysis of eight studies that compared the impact of RV dysfunction measured by echocardiography and CT found that the presence of echocardiographically determined RV dysfunction in patients with submassive PE was associated with increased short-term mortality (OR 2.36, 95% CI: 1.3-43), but that corresponding pooled negative and positive likelihood ratios independent of death rates were unsatisfactory for clinical usefulness in risk stratification (Coutance et al., 2011). Unfortunately, the echocardiographic criteria of RV dysfunction differ among published studies and have included RV dilatation, hypokinesis, increased RV/LV diameter ratio and increased velocity of the tricuspid regurgitation jet. Thus, since there is no universal echocardiographic definition of RV dysfunction, only a completely normal result should be considered as defining low-risk PE. This is particularly important because, in some of trials, echocardiographic signs of RV pressure overload alone (such as increased tricuspid insufficiency peak gradient and decreased acceleration time of RV ejection) were considered sufficient to classify a patient as having RV dysfunction.

#### **2.1 Echocardiographic findings of right ventricular dysfunction**

RV dysfunction is diagnosed by the presence of RV dilatation, defined as a RV/LV enddiastolic dimension ratio >0.6 on a parasternal long-axis view or >0.9 on a four-chamber view (Fig. 1); as RV systolic free wall hypokinesis (McConnell sign); or as systolic pulmonary arterial hypertension, defined as a tricuspid regurgitant velocity >2.6 m/s (Goldhaber, 2002). Indirect signs of RV pressure overload include a flattened interventricular septum, paradoxical systolic motion of the interventricular septum toward the LV, and a dilated inferior vena cava with reduced respiratory variability (Table 1).

Signs of RV dysfunction have been found in 40-70% of patients with PE, and numerous studies have demonstrated that echocardiography is a useful tool for estimating the prognosis of normotensive patients with acute PE (Goldhaber et al., 1999; Ribeiro et al., 1997; Grifoni et al., 2001). A recent meta-analysis found that echocardiographic evidence of RV dysfunction was associated with a significantly elevated risk of death during the acute phase of PE (OR, 2.5; 95% CI, 1.2-5.5%) (Sanchez et al., 2008). However, since large populations of patients with signs of RV dysfunction have low mortality rates, echocardiographic detection of RV dysfunction alone does not justify more aggressive treatment strategies (Goldhaber et al., 1999; Konstantinides, 2008). More importantly, definitions of RV dysfunction differed greatly among these studies, and patients with chronic obstructive pulmonary disease were not excluded (Jimenez et al., 2007). In addition, it is difficult to differentiate chronic from acute RV overload based on standardized criteria (e.g. RV free wall thickness > 6 mm or tricuspid valve regurgitation jet velocity > 2.6 m/sec).
