Background
There is no comprehensive analysis of transthoracic echocardiographic findings of pulmonary embolism (PE). The aim of this study was to assess the frequency of right ventricular (RV) dysfunction (RVD), typical echocardiographic signs of acute PE (TES), and incidental abnormalities.
Methods
A single-center, retrospective analysis was conducted of 511 consecutive patients (281 women; mean age, 64.0 ± 18.6 years) with PE confirmed by contrast-enhanced multidetector computed tomography who underwent transthoracic echocardiography for the assessment of left ventricular and RV alterations. The McConnell sign, the “60/60” sign, and right heart thrombus were regarded as TES. RVD included RV free wall hypokinesis and RV to LV end-diastolic ratio > 0.9. Incidental echocardiographic alterations were also reported.
Results
RV enlargement, RV free wall hypokinesis, and interventricular septal flattening were found in 27.4%, 26.6%, and 18.4% of patients, respectively. Tricuspid regurgitation peak systolic gradient > 30 mmHg and pulmonary ejection acceleration time < 80 msec were measured in 46.6% and 37.2% of patients, respectively. RVD was found in 20.0% of patients, while normal RV function was present in 33.4% of patients. The McConnell sign, 60/60 sign, and right heart thrombus were found in 19.8%, 12.9%, 1.8% of subjects, respectively. All 16 hemodynamically unstable patients with PE presented enlarged hypokinetic right ventricle and at least one TES. However, in three of them, RV to LV end-diastolic ratio was <0.9. Incidental abnormalities were found in 9.6% of 364 stable patients with PE without RVD and TES.
Conclusions
Transthoracic echocardiography showed no significant abnormalities suggestive of PE in 71% of patients with PE, while in approximately 10%, transthoracic echocardiography revealed incidental findings. The coexistence of an enlarged hypokinetic right ventricle with the McConnell sign together with the 60/60 sign seems to be the most useful echocardiographic criterion for RVD.
Suspected high-risk acute pulmonary embolism (PE) presenting with shock or hypotension is a life-threatening situation, and according to international guidelines it requires urgent diagnostic workup and therapy. When immediate computed tomographic angiography is not feasible, transthoracic echocardiography (TTE) can provide evidence of right ventricular (RV) dysfunction (RVD) justifying lifesaving primary thrombolysis. In normotensive patients, TTE is not recommended as a diagnostic tool, but it can be performed for risk stratification in this group. RVD, when detected, indicates a worse prognosis. Moreover, because TTE is one of the most available noninvasive imaging methods, it is also frequently included in the diagnosis of acute dyspnea, chest pain, and hemodynamic decompensation. In patients with PE, TTE can show not only RVD but also in some cases more typical echocardiographic signs of acute PE (TES). The McConnell sign, defined as hypokinesis of the RV free wall with normal contraction of the apical segment ( Figure 1 , Video 1 ; available at www.onlinejase.com ) ; the “60/60” sign, the coexistence of shortened pulmonary ejection acceleration time (AcT) (<60 msec) with midsystolic velocity deceleration (“notch”) measured in the RV outflow tract and tricuspid regurgitation peak systolic gradient (TRPG) < 60 mmHg ( Figure 2 ) ; and right heart thrombus ( Figure 3 , Video 2 ; available at www.onlinejase.com ) strongly suggest PE, even if not suspected. Moreover, echocardiography can also reveal alternative causes of the observed clinical picture, such as cardiac tamponade, left ventricular (LV) systolic dysfunction, and unexpected significant valvular lesions. The clinical manifestation of PE is often nonspecific, sometimes even suggestive of other cardiopulmonary pathologies. Therefore, because echocardiography can reveal other coexisting heart abnormalities that can potentially explain acute signs and symptoms of PE, the detection of such abnormalities may postpone diagnostic PE workup or even lead to PE’s being overlooked, especially when the clinical probability of this disease is rated as low. According to our knowledge, no comprehensive analysis has been published in which the investigators described echocardiographic findings that are typical of PE in a large group of patients with documented PE. In addition, it is important to note that in some cases, incidental echocardiographic findings can suggest alternative reasons for a patient’s signs and symptoms, even though the patient has also experienced acute PE. Therefore, we aimed to assess the frequency of RVD, TES, and potentially incidental echocardiographic abnormalities in unselected consecutive patients with proven symptomatic acute PE.
Methods
This was a retrospective analysis of 511 consecutive patients with confirmed symptomatic acute PE managed in our department between 2007 and 2015. The diagnosis of PE was confirmed when thromboemboli were visualized in an at least segmental pulmonary artery on contrast-enhanced multidetector computed tomography. Acute PE was diagnosed when symptoms suggestive of PE had been present for no longer than 14 days before the diagnosis. Patients with established chronic thromboembolic hypertension were excluded from this study.
Hemodynamic instability was defined according the European Society of Cardiology as systemic systolic blood pressure <90 mm Hg or a need for vasopressors without other coexisting causes such as hypovolemia or sepsis. Patients with systemic systolic blood pressure of ≥90 mmHg who showed no signs of peripheral hypoperfusion were regarded as hemodynamically stable. An analysis of the prognostic value of echocardiographic parameters in a subgroup of this population has been published previously.
Echocardiography
Standardized TTE focused on the assessment of the right ventricle and left heart valve function was performed and interpreted according to a previously described protocol by an experienced physician using a Philips iE33 or Philips HD11XE system (Philips Medical Systems, Andover, MA), as soon as possible after admission, preferably within the first 24 hours. The examinations were digitally recorded. LV and RV diameters were measured in the apical four-chamber view at the level of the mitral and tricuspid valve tips at end-diastole (defined by the electrocardiographic R wave). RV enlargement was diagnosed when RV four-chamber basal diameter was >42 mm. We assessed the presence of the McConnell sign or RV free wall hypokinesis. Tricuspid annular plane systolic excursion was measured in the M-mode presentation. Tricuspid valve regurgitation was assessed qualitatively (color Doppler), and TRPG was calculated by applying a simplified Bernoulli formula, using tricuspid regurgitant systolic flow peak velocity (continuous-wave Doppler). In the parasternal short-axis view, flattening of the interventricular septum was assessed qualitatively, and AcT was measured in the RV outflow tract, proximal to the pulmonary valve (pulsed-wave Doppler). Presence of the 60/60 sign with a midsystolic notch in the pulmonary outflow Doppler profile was determined.
LV ejection fraction was measured using the modified biplane Simpson method. Aortic and mitral valve morphology and function were evaluated.
Hemodynamically significant valvular disease was assessed and diagnosed according to the recommendations of the European Association of Cardiovascular Imaging, guidelines of the European Society of Cardiology, and the European Association for Cardio-Thoracic Surgery. In patients with normal cardiac output, severe aortic stenosis (AS) was diagnosed when aortic valve area (AVA) was <1 cm 2 , indexed AVA was <0.6 cm 2 /m 2 body surface area, maximal jet velocity was >4.0 m/sec, mean gradient was >40 mmHg, and velocity ratio was <0.25. Severe low-flow, low-gradient AS was defined when a significant leaflet calcification with severely reduced leaflet motion was found with AVA < 1 cm 2 and resting aortic maximal jet velocity < 4.0 m/sec or mean gradient < 40 mm Hg in patients with reduced LV ejection fraction (<50%). We diagnosed moderate AS when AVA was 1.0 to 1.5 cm 2 , indexed AVA was 0.6 to 0.9 cm 2 /m 2 body surface area, and mean systolic gradient was 25 to 40 mmHg in the presence of normal flow conditions. Severe aortic regurgitation (AR) was recognized according to the following criteria: significant coaptation defect and large color flow regurgitant jet with dense Doppler signal, vena contracta (VC) width ≥ 6 mm, pressure half-time < 200 msec, holodiastolic flow reversal in the descending aorta with end-diastolic velocity > 0.2 m/sec, effective regurgitant orifice area (EROA) ≥ 30 mm 2 , AR volume ≥ 60 ml, and LV enlargement, whereas VC width 3 to 5 mm, pressure half-time 200 to 500 msec, EROA 10 to 29 mm 2 , and AR volume 30 to 59 ml characterized moderate AR.
The criteria for severe mitral regurgitation (MR) were defined as follows: large leaflet coaptation defect with wide central or eccentric jet with dense continuous-wave signal, large flow convergence zone, VC width ≥ 7 mm, systolic pulmonary vein flow reversal, EROA ≥ 40 mm 2 , MR volume ≥ 60 ml, and left atrial and LV enlargement. We recognized moderate MR when an intermediate color flow jet, an intermediate flow convergence zone, VC width 3 to 6 mm, EROA 20 to 39 mm 2 , and MR volume 30 to 59 ml were observed.
The examination was completed by the measurement of the inferior vena cava (IVC) at late expiration in the subcostal view. A distended IVC was defined as an IVC diameter > 2.1 cm with decreased inspiratory collapsibility (<50%).
RVD was diagnosed according to American Heart Association and European Society of Cardiology guidelines, when echocardiography showed RV free wall hypokinesis, and the RV to LV end-diastolic ratio was >0.9 in the four-chamber apical view.
RV overload that did not meet the above criteria included the presence of at least one of the following findings: RV enlargement in the four-chamber view, at least moderate RV free wall hypokinesis, interventricular septal flattening, TRPG > 30 mm Hg, AcT < 80 msec and distended IVC with diminished respiratory collapsibility.
TES included the McConnell sign, the 60/60 sign, and right heart thrombus. Incidental echocardiographic findings were defined as systolic heart failure with LV ejection fraction ≤ 35%, at least moderate AS or AR, and at least moderate MR.
Intraclass correlation coefficients for echocardiographic parameters were calculated to assess inter- and intraobserver variation by three echocardiographers in a sample of 40 randomly selected patients from the studied group. The intraclass correlation coefficients were calculated on mean values, with a value of 1 representing a perfect correlation. The inter- and intraobserver agreement for echocardiographic parameters was 94.2% (95% CI, 88.8–97.0) and 98.0% (95% CI, 96.4–99.1), respectively. The agreement analysis showed high interclass correlation for Doppler parameters (interobserver agreement = 97.3% [95% CI, 94.8%–98.6%], intraobserver agreement = 99.1% [95% CI, 97.7%–99.7%]), while intraclass correlation coefficients were only slightly lower for two-dimensional or M-mode data (interobserver agreement = 91.1% [95% CI, 82.8%–95.4%], intraobserver agreement = 96.9% [95% CI, 95.0%–98.4%]).
Statistical Analysis
Data characterized by a normal distribution are expressed as mean ± SD, while parameters without such a distribution are expressed as medians with ranges. Qualitative data were compared using χ 2 tests. The Mann-Whitney U test was used to analyze data without normal distributions, whereas normally distributed data were analyzed using Student’s t test. Analyses were performed using STATISTICA version 10 (StatSoft, Tulsa, OK). P values < .05 were considered to indicate statistical significance.
The protocol of this observational study was approved by the local ethics committee (No. KB/272/2012).
Results
Patients Characteristics
The study included 511 consecutive patients with confirmed PE (281 women and 230 men; mean age, 64.0 ± 18.6 years). There were 16 cases (3.1%) of high-risk PE, while the remaining 495 patients (96.9%) were hemodynamically stable on admission (non-high-risk PE). The clinical characteristics of the whole study group are presented in Table 1 .
| Parameter | All PE ( n = 511) | High-risk PE ( n = 16) | P | Non-high-risk PE ( n = 495) |
|---|---|---|---|---|
| Women | 281 (55.0) | 8 (50.0) | NS | 273 (55.2) |
| Age (yrs) | 64.0 ± 18.6 | 70.2 ± 21.2 | .25 | 63.8 ± 18.5 |
| Heart rate (beats/min) | 89.3 ± 20.5 | 102.0 ± 22.8 | .04 | 88.8 ± 20.3 |
| SBP (mm Hg) | 128.0 ± 21.4 | 81.7 ± 11.1 | <.0001 | 129 ± 20.4 |
| Comorbidities ∗ | 164 (32.1) | 5 (31.2) | .31 | 159 (32.1) |
∗ Comorbidities were defined as the presence of chronic obstructive pulmonary disease, chronic heart failure, or history of cancer.
RV Overload
RV enlargement in the four-chamber apical view, which is a frequent echocardiographic sign of RV pressure overload, was found in 140 patients (27.4%). At least moderate RV free wall hypokinesis was present in 136 patients (26.6%), interventricular septal flattening in 94 patients (18.4%), TRPG > 30 mmHg in 238 subjects (46.6%), AcT < 80 msec in 190 patients (37.2%), and distended IVC with diminished respiratory collapsibility in 66 patients (12.9%). The predefined RVD (RV free wall hypokinesis with RV to LV end-diastolic ratio > 0.9 measured in the four-chamber apical view) was found in 102 patients (20.0%). Completely normal RV morphology with preserved function was found in 171 patients (33.4% of the whole study group). However, signs of RV pressure overload of a lesser degree, not meeting prespecified RVD criteria, were observed in the remaining 238 subjects (46.6%).
Among 495 hemodynamically stable patients, only 89 (18.0%) had prespecified RVD on TTE. As mentioned earlier, normal RV morphology and function were found in 171 patients (34.5%), and all were hemodynamically stable. In the remaining 235 cases (47.5%) of this group, echocardiographic abnormalities did not meet RVD criteria. All hemodynamically unstable patients with PE presented echocardiographic signs of RV overload. However, the predefined RVD was not present in three of these patients (18.8%). Importantly, in all three high-risk patients, TTE also showed RV dilatation with significant hypokinesis of the free wall, but the prespecified RVD criterion of RV to LV end-diastolic ratio > 0.9 was not met, because of the presence of an enlarged left ventricle. Significant bilateral central pulmonary thromboembolism was detected on multislice computed tomography in all of them. Echocardiographic parameters of 511 patients with confirmed PE according to the severity of PE are presented in Table 2 .
| Parameter | All PE ( n = 511) | High-risk PE ( n = 16) | P | Non-high-risk PE ( n = 495) |
|---|---|---|---|---|
| LV dimension (mm) | 41.5 ± 6.8 | 38.1 ± 11.0 | .19 | 41.6 ± 6.5 |
| RV dimension (mm) | 38.3 ± 8.1 | 45.0 ± 8.3 | .004 | 38.0 ± 8.0 |
| RV/LV | 0.94 ± 0.3 | 1.3 ± 0.4 | .003 | 0.92 ± 0.3 |
| TRPG (mmHg) | 34.4 ± 16.4 | 49.2 ± 22.3 | .02 | 33.9 ± 16.0 |
| AcT (msec) | 87.4 ± 28.8 | 60.6 ± 12.6 | <.0001 | 88.3 ± 28.8 |
| TAPSE (mm) | 21.2 ± 5.8 | 16.5 ± 4.9 | .40 | 21.3 ± 5.8 |
| Flattened IVS | 94 (18.4) | 11 (68.8) | <.0001 | 83 (16.8) |
| RVD ∗ | 102 (20.0) | 13 (81.2) | <.0001 | 89 (18.0) |
| McConnell sign | 101 (19.8) | 12 (75.0) | .0003 | 89 (18.0) |
| RiHT | 9 (1.8) | 3 (18.8) | <.0001 | 6 (1.2) |
| 60/60 sign | 66 (12.9) | 5 (31.2) | .14 | 61 (12.3) |
| Distended IVC | 66 (12.9) | 3 (18.7) | .80 | 63 (12.7) |
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