Modern imaging of acute pulmonary embolism.

The first-choice imaging test for visualization of thromboemboli in the pulmonary vasculature in patients with suspected acute pulmonary embolism (PE) is multidetector computed tomography pulmonary angiography (CTPA) - a readily available and widely used imaging technique. Through technological advancements over the past years, alternative imaging techniques for the diagnosis of PE have become available, whilst others are still under investigation. In particular, the evolution of artificial intelligence (AI) is expected to enable further innovation in diagnostic management of PE. In this narrative review, current CTPA techniques and the emerging technology photon-counting CT (PCCT), as well as other modern imaging techniques of acute PE are discussed, including CTPA with iodine maps based on subtraction or dual-energy acquisition, single-photon emission CT (SPECT), magnetic resonance angiography (MRA), and magnetic resonance direct thrombus imaging (MRDTI). Furthermore, potential applications of AI are discussed.

Impact of pulmonary infarction in pulmonary embolism on presentation and outcomes.

BACKGROUND: Pulmonary infarction (PI) is relatively common in pulmonary embolism (PE). The association between PI and persistent symptoms or adverse events is largely unknown. AIM: To evaluate the predictive value of radiological PI signs at acute PE diagnosis on 3-month outcomes. METHODS: We studied a convenience cohort with computed tomography pulmonary angiography (CTPA)-confirmed PE for whom extensive 3-month follow-up data were available. The CTPAs were re-evaluated for signs of suspected PI. Associations with presenting symptoms, adverse events (recurrent thrombosis, PE-related readmission and mortality) and self-reported persistent symptoms (dyspnea, pain and post-PE functional impairment) at 3-month follow-up were investigated using univariate Cox regression analysis. RESULTS: At re-evaluation of the CTPAs, 57 of 99 patients (58 %) had suspected PI, comprising a median of 1 % (IQR 1-3) of total lung parenchyma. Patients with suspected PI more often presented with hemoptysis (11 % vs. 0 %) and pleural pain (OR 2.7, 95%CI 1.2-6.2), and with more proximal PE on CTPA (OR 1.6, 95%CI 1.1-2.4) than patients without suspected PI. There was no association with adverse events, persistent dyspnea or pain at 3-month follow-up, but signs of PI predicted more functional impairment (OR 3.03, 95%CI 1.01-9.13). Sensitivity analysis with the largest infarctions (upper tertile of infarction volume) yielded similar results. CONCLUSIONS: PE patients radiologically suspected of PI had a different clinical presentation than patients without those signs and reported more functional limitations after 3 months of follow-up, a finding that could guide patient counselling.

Pulmonary infarction in acute pulmonary embolism.

Pulmonary infarction results from occlusion of the distal pulmonary arteries leading to ischemia, hemorrhage and ultimately necrosis of the lung parenchyma. It is most commonly caused by acute pulmonary embolism (PE), with a reported incidence of around 30%. Following an occlusion of the pulmonary artery, the bronchial arteries are recruited as primary source of perfusion of the pulmonary capillaries. The relatively higher blood pressure in the bronchial circulation causes an increase in the capillary blood flow, leading to extravasation of erythrocytes (i.e. alveolar hemorrhage). If this hemorrhage cannot be resorbed, it results in tissue necrosis and infarction. Different definitions of pulmonary infarction are used in literature (clinical, radiological and histological), although the diagnosis is nowadays mostly based on radiological characteristics. Notably, the infarcted area is only replaced by a fibrotic scar over a period of months. Hence and formally, the diagnosis of pulmonary infarction cannot be confirmed upon diagnosis of acute PE. Little is known of the impact and relevance of pulmonary infarction in acute PE, and whether specific management strategies should be applied to prevent and/or treat complications such as pain, pneumonia or post-PE syndrome. In this review we will summarize current knowledge on the pathophysiology, epidemiology, diagnosis and prognosis of pulmonary infarction in the setting of acute PE. We highlight the need for dedicated studies to overcome the current knowledge gaps.

Incidence of thrombotic complications and overall survival in hospitalized patients with COVID-19 in the second and first wave.

INTRODUCTION: In the first wave, thrombotic complications were common in COVID-19 patients. It is unknown whether state-of-the-art treatment has resulted in less thrombotic complications in the second wave. METHODS: We assessed the incidence of thrombotic complications and overall mortality in COVID-19 patients admitted to eight Dutch hospitals between September 1st and November 30th 2020. Follow-up ended at discharge, transfer to another hospital, when they died, or on November 30th 2020, whichever came first. Cumulative incidences were estimated, adjusted for competing risk of death. These were compared to those observed in 579 patients admitted in the first wave, between February 24th and April 26th 2020, by means of Cox regression techniques adjusted for age, sex and weight. RESULTS: In total 947 patients with COVID-19 were included in this analysis, of whom 358 patients were admitted to the ICU; 144 patients died (15%). The adjusted cumulative incidence of all thrombotic complications after 10, 20 and 30 days was 12% (95% confidence interval (CI) 9.8-15%), 16% (13-19%) and 21% (17-25%), respectively. Patient characteristics between the first and second wave were comparable. The adjusted hazard ratio (HR) for overall mortality in the second wave versus the first wave was 0.53 (95%CI 0.41-0.70). The adjusted HR for any thrombotic complication in the second versus the first wave was 0.89 (95%CI 0.65-1.2). CONCLUSIONS: Mortality was reduced by 47% in the second wave, but the thrombotic complication rate remained high, and comparable to the first wave. Careful attention to provision of adequate thromboprophylaxis is invariably warranted.

Clinical and computed tomography characteristics of COVID-19 associated acute pulmonary embolism: A different phenotype of thrombotic disease?

INTRODUCTION: COVID-19 infections are associated with a high prevalence of venous thromboembolism, particularly pulmonary embolism (PE). It is suggested that COVID-19 associated PE represents in situ immunothrombosis rather than venous thromboembolism, although the origin of thrombotic lesions in COVID-19 patients remains largely unknown. METHODS: In this study, we assessed the clinical and computed tomography (CT) characteristics of PE in 23 consecutive patients with COVID-19 pneumonia and compared these to those of 100 consecutive control patients diagnosed with acute PE before the COVID-19 outbreak. Specifically, RV/LV diameter ratio, pulmonary artery trunk diameter and total thrombus load (according to Qanadli score) were measured and compared. RESULTS: We observed that all thrombotic lesions in COVID-19 patients were found to be in lung parenchyma affected by COVID-19. Also, the thrombus load was lower in COVID-19 patients (Qanadli score -8%, 95% confidence interval [95%CI] -16 to -0.36%) as was the prevalence of the most proximal PE in the main/lobar pulmonary artery (17% versus 47%; -30%, 95%CI -44% to -8.2). Moreover, the mean RV/LV ratio (mean difference -0.23, 95%CI -0.39 to -0.07) and the prevalence of RV/LV ratio >1.0 (prevalence difference -23%, 95%CI -41 to -0.86%) were lower in the COVID-19 patients. CONCLUSION: Our findings therefore suggest that the phenotype of COVID-19 associated PE indeed differs from PE in patients without COVID-19, fuelling the discussion on its pathophysiology.

Diagnosing upper extremity deep vein thrombosis with non-contrast-enhanced Magnetic Resonance Direct Thrombus Imaging: A pilot study.

Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins. Contrast venography is invasive and has a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI) and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI) sequences that can visualize a thrombus directly by the visualization of methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim of this pilot study was to test the feasibility of diagnosing UEDVT with these MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who were already diagnosed with UEDVT by ultrasonography or contrast venography. In all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic accuracy and management studies have to be performed before these techniques can be routinely used in clinical practice.

Coronary or thoracic artery calcium score in provoked and unprovoked pulmonary embolism: a case-control study.

UNLABELLED: Essentials Patients with unprovoked pulmonary embolism (PE) are at increased risk of arterial thromboembolism. Coronary and thoracic aorta calcium were evaluated in patients with and without (unprovoked) PE. No association was found between (unprovoked) PE and coronary or aortic calcification. Assessment of both calcium scores on computed tomography pulmonary angiography was highly reproducible. SUMMARY: Objective To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presence and extent of coronary artery calcium (CAC) and thoracic aorta calcium (TAC). Methods CAC and TAC derived from computed tomography pulmonary angiography of 100 patients with PE were compared to that of 100 patients in whom PE was ruled out. Results Intraobserver and interobserver agreements for both TAC and CAC were excellent (intraclass correlation > 0.95 for both). In patients with PE vs. patients without PE, no significant differences were found in the presence of CAC or TAC (CAC 64% vs. 67%, odds ratio [OR] 1.0, 95% confidence interval [CI] 0.67-1.6; TAC 46% vs. 59%, OR 1.2, 95% CI 0.80-2.1). Mean CAC and TAC scores were significantly lower in patients with PE than in patients without PE (CAC 3.4 vs. 4.9, absolute difference 1.5, 95% CI 0.2-2.8; TAC 1.1 vs. 1.8, absolute difference 0.9, 95% CI 0.2-1.2). No significant differences were found in the presence of CAC or TAC or in mean CAC and TAC scores between patients with unprovoked PE vs. patients with provoked PE, or between patients with unprovoked PE vs. no PE. Conclusion No significant differences were found between the extent of CAC and TAC in patients with unprovoked PE compared to those with provoked PE or without PE. The observed difference in the extend of CAC and TAC between patients with and without PE was dependent on prevalent cardiovascular risk factors.

Coupling between MRI-assessed regional aortic pulse wave velocity and diameters in patients with thoracic aortic aneurysm: a feasibility study.

AIMS: Thoracic aortic aneurysm (TAA) is potentially life-threatening and requires close follow-up to prevent aortic dissection. Aortic stiffness and size are considered to be coupled. Regional aortic stiffness in patients with TAA is unknown. We aimed to evaluate coupling between regional pulse wave velocity (PWV), a marker of vascular stiffness, and aortic diameter in TAA patients. METHODS: In 40 TAA patients (59 ± 13 years, 28 male), regional aortic diameters and regional PWV were assessed by 1.5 T MRI. The incidence of increased diameter and PWV were determined for five aortic segments (S1, ascending aorta; S2, aortic arch; S3, thoracic descending aorta; S4, suprarenal and S5, infrarenal abdominal aorta). In addition, coupling between regional PWV testing and aortic dilatation was evaluated and specificity and sensitivity were assessed. RESULTS: Aortic diameter was 44 ± 5 mm for the aortic root and 39 ± 5 mm for the ascending aorta. PWV was increased in 36 (19 %) aortic segments. Aortic diameter was increased in 28 (14 %) segments. Specificity of regional PWV testing for the prediction of increased regional diameter was ≥ 84 % in the descending thoracic to abdominal aorta and ≥ 68 % in the ascending aorta and aortic arch. CONCLUSION: Normal regional PWV is related to absence of increased diameter, with high specificity in the descending thoracic to abdominal aorta and moderate results in the ascending aorta and aortic arch.

Ventricular function and cardiac reserve in contemporary Fontan patients.

BACKGROUND/OBJECTIVE: Total cavopulmonary connection (TCPC) has been the preferred treatment for patients with univentricular hearts. Current TCPC-techniques are the intra-atrial lateral tunnel (ILT) and the extracardiac conduit (ECC). We aimed to determine ventricular function during rest and stress, and to compare results for both techniques and for left (LV) versus right ventricular (RV) dominance. METHODS: 99 patients, aged 12.5 ± 4.0 years underwent echocardiography and magnetic resonance imaging (MRI), and 69 patients underwent stress MRI. RESULTS: Echocardiography showed impaired systolic and diastolic function. MRI parameters were comparable between ILT and ECC at rest. During dobutamine there was a decrease in end-diastolic volume (EDVi) (91 ± 21 vs. 80 ± 20 ml/m(2) p<0.001). Ejection fraction (EF) and cardiac index (CI) during dobutamine were lower for ILT patients (59 ± 11 (ILT) vs. 64 ± 7% (ECC), p=0.027 and 4.2 ± 1.0 (ILT) vs. 4.9 ± 1.0L/min/m(2) (ECC), p=0.006), whereas other parameters were comparable. TEI-index was higher in ILT-patients (0.72 ± 0.27 (ILT) vs. 0.56 ± 0.22 (ECC), p=0.002). Diastolic function was frequently impaired in patients with a dominant RV (67% (RV) vs. 39% (LV), p=0.011). Patients with dominant LV's had smaller end-systolic volume (ESVi) (40 ± 13 (LV) vs. 47 ± 16 (RV) ml/m(2), p=0.030) and higher EF (55 ± 8 (LV) vs. 49 ± 9 ml/m(2) (RV), p=0.001) and contractility (2.3 ± 0.8 (LV) vs. 1.9 ± 0.7 mmHg/ml/m(2) (RV), p=0.050) during rest and higher EF during dobutamine (63 ± 8 (LV) vs. 58 ± 10 ml/m(2) (RV), p=0.043). CONCLUSION: Ventricular function is relatively well preserved in modern-day Fontan patients. With dobutamine stress there is a decrease in EDVi. ECC patients have higher CI and EF during stress. Patients with a dominant RV have lower systolic, including impaired contractility, and diastolic function.

Right ventricular function and thrombus load in patients with pulmonary embolism and diagnostic delay.

INTRODUCTION: It has been reported that the time between symptom onset and objective diagnosis of pulmonary embolism (PE) does not affect patients' prognosis with regard to re-thrombosis and mortality risk. However, this observation is contra-intuitive and poorly understood. We further elaborated on this paradox by evaluating thrombus load and right ventricular function in patients with and without diagnostic delay. MATERIALS AND METHODS: We performed a post hoc analysis of a previously published observational prospective outcome study in 113 consecutive PE patients. Qanadli-score and RV/LV ratio were scored in all patients, as was the duration from symptom onset to clinical presentation and diagnosis. Diagnostic delay was defined as a period of more than 7 days between symptom onset and clinical presentation. Further endpoints were mortality and hospital readmission in a 6-week follow-up period. RESULTS: Twenty patients with and 93 patients without delay were studied, who had comparable baseline characteristics and co-morbidities. In linear analyses, Qanadli-score (R² of 0.021; P = 0.130) and RV/LV ratio (R² < 0.001; P = 0.991) were not associated with diagnostic delay. Likewise, longer delay was not predictive of 6-week mortality (odds ratio, 0.65; 95% CI, 0.08-5.57) or hospital readmission (odds ratio, 0.75; 95% CI, 0.15-3.65). CONCLUSION: In our patient cohort, diagnostic delay was not associated with higher thrombus load or right ventricular dysfunction. This provides a possible explanation for the lack of prognostic relevance of diagnostic delay.

Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function.

BACKGROUND: There has been debate over how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment. OBJECTIVES: To compare the Hestia criteria with the European Society of Cardiology (ESC) criteria for selecting low-risk patients with PE for outpatient treatment. METHODS: From 2008 to 2010, 496 patients with acute, symptomatic PE were screened and 275 treated at home and 221 treated in the hospital according to the Hestia Study protocol. The Hestia criteria were used to select patients for outpatient treatment. Right and left ventricular (RV and LV) diameters were measured on computed tomography images. RV dysfunction was defined as an RV/LV ratio > 1.0. Patients were classified according to the ESC criteria into low, intermediate and high-risk groups, based on blood pressure and RV dysfunction. During 3 months follow-up adverse events were scored. RESULTS: Adverse events occurred in 22 patients (4.5%) treated in the hospital vs. none of the patients treated at home (P < 0.001). Sensitivity and negative predictive value for adverse outcome were 100% for the Hestia criteria and 96% and 99% for the ESC criteria, respectively. Of the patients treated at home according to the Hestia criteria, 35% were normotensive but had RV dysfunction and were classified as intermediate risk according to the ESC criteria. No adverse events happened in these patients treated at home. CONCLUSIONS: Clinical criteria, such as the Hestia criteria, could be helpful in selecting patients, including those with RV dysfunction who have a low risk of adverse clinical outcome and could be candidates for outpatient treatment.

The effect of hypertension on aortic pulse wave velocity in type-1 diabetes mellitus patients: assessment with MRI.

To investigate in type-1 diabetes mellitus (DM1) patients the role of hypertension and of DM1 itself on aortic stiffness by using magnetic resonance imaging (MRI). Consecutive patients from the diabetes and hypertension outpatient clinic and healthy volunteers were included in our study. Subjects were divided into four groups: 32 healthy volunteers (mean age: 54.5 ± 6.8 years), 20 DM1 patients (mean age: 48.3 ± 5.9 years), 31 hypertensive patients (mean age: 59.9 ± 7.2 years) and 28 patients with both DM1 and hypertension (mean age: 50.1 ± 6.2 years). Aortic stiffness was measured by means of pulse wave velocity (PWV) using velocity-encoded MRI. Analysis of variance (ANOVA), uni- and multivariable regression models and the Bonferroni-test for multiple testing, were used for statistical analyses. Mean aortic PWV was 5.7 ± 1.2 m/s in healthy volunteers, 5.9 ± 1.2 m/s in DM1 patients without hypertension, 7.3 ± 1.2 m/s in hypertensive patients and 7.3 ± 1.3 m/s in patients with both DM1 and hypertension. Compared to healthy control subjects, aortic PWV was significantly higher in patients with hypertension (P < 0.001) and in patients with both DM1 and hypertension (P < 0.001), whereas aortic PWV was not increased in patients having DM1 alone. Furthermore, aortic PWV was significantly higher in DM1 patients with hypertension than in patients with DM1 alone (P = 0.002). These findings remained after adjustment for confounding factors. Hypertension has a predominant contributive effect on aortic stiffness in DM1 patients whereas the direct diabetic effect on aortic stiffness is small.

Recovery of right and left ventricular function after acute pulmonary embolism.

AIM: To evaluate recovery of cardiac function after acute pulmonary embolism (PE). MATERIALS AND METHODS: Routine breath-held computed tomography (CT)-pulmonary angiography was performed in patients with suspected PE to confirm or exclude the diagnosis of PE at initial presentation. Electrocardiogram (ECG)-triggered cardiac CT was performed to assess biventricular function. After 6 months, cardiac magnetic resonance imaging (MRI) was performed. In total, 15 consecutive patients with PE and 10 without were studied. A significant change in ventricular volume was defined as a >15% change in end-diastolic or -systolic volumes (EDV, ESV), and significant ventricular function improvement as a >5% increase in ejection fraction (EF) as based on reported cut-off values. RESULTS: Right and left ventricular (RV and LV) EDV and ESV changed non-significantly (<1.3%) in the patients without PE, indicating good comparability of those values measured by CT and MRI. PE patients with baseline normal RV function (RVEF ≥ 47%) revealed a >5% improvement in the RVEF (+5.4 ± 3.1%) due to a decrease in the RVESV. Patients with baseline abnormal RV function showed a >5% improvement in the RVEF (+14 ± 15%) due to decreases in both the RVESV and RVEDV. Furthermore, the LVEDV increased in this latter patient group. CONCLUSIONS: The present study demonstrated an improvement in RV function in the majority of patients with PE, independent of baseline RV function. The degree of RV and LV recovery was dependent on the severity of baseline RV dysfunction.

Aortic stiffness is associated with cardiac function and cerebral small vessel disease in patients with type 1 diabetes mellitus: assessment by magnetic resonance imaging.

OBJECTIVE: To evaluate, with the use of magnetic resonance imaging (MRI), whether aortic pulse wave velocity (PWV) is associated with cardiac left ventricular (LV) function and mass as well as with cerebral small vessel disease in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: We included 86 consecutive type 1 DM patients (49 male, mean age 46.9 +/- 11.7 years) in a prospective, cross-sectional study. Exclusion criteria included aortic/heart disease and general MRI contra-indications. MRI of the aorta, heart and brain was performed for assessment of aortic PWV, as a marker of aortic stiffness, systolic LV function and mass, as well as for the presence of cerebral white matter hyperintensities (WMHs), microbleeds and lacunar infarcts. Multivariate linear or logistic regression was performed to analyse the association between aortic PWV and outcome parameters, with covariates defined as age, gender, mean arterial pressure, heart rate, BMI, smoking, DM duration and hypertension. RESULTS: Mean aortic PWV was 7.1 +/- 2.5 m/s. Aortic PWV was independently associated with LV ejection fraction (ss = -0.406, P = 0.006), LV stroke volume (ss = -0.407, P = 0.001), LV cardiac output (ss = -0.458, P = 0.001), and with cerebral WMHs (P < 0.05). There were no independent associations between aortic stiffness and LV mass, cerebral microbleeds or lacunar infarcts. CONCLUSION: Aortic stiffness is independently associated with systolic LV function and cerebral WMHs in patients with type 1 DM.

Aortic elasticity and size are associated with aortic regurgitation and left ventricular dysfunction in tetralogy of Fallot after pulmonary valve replacement.

BACKGROUND: Aortic wall pathology and concomitant aortic dilatation have been described in tetralogy of Fallot (TOF) patients, which may negatively affect aortic valve and left ventricular systolic function. OBJECTIVE: To assess aortic dimensions, aortic elasticity, aortic valve competence and biventricular function in repaired TOF patients after pulmonary valve replacement (PVR) using magnetic resonance imaging (MRI). METHODS: MRI was performed in 16 patients with TOF after PVR (10 male; mean age 31 years (SD 15)) and 16 age and gender-matched healthy subjects. RESULTS: TOF patients showed aortic root dilatation (mean difference 7.8-8.8 mm, p<0.01 at all four predefined levels) and reduced aortic elasticity (pulse wave velocity in aortic arch 5.5 m/s (1.2) vs 4.6 m/s (0.9), p = 0.04; aortic root distensibility 1.4/10(-3) mm Hg (1.7) vs 5.7/10(-3) mm Hg (3.6), p<0.01). Minor degrees of aortic regurgitation (AR) (AR fraction 6% (8) vs 1% (1), p<0.01) and reduced left ventricular ejection fraction (LVEF) were present (51% (8) vs 58% (6), p = 0.01), whereas right ventricular ejection fraction (RVEF) was within normal limits (47% (8) vs 52% (7), p = 0.06). The degree of AR fraction was associated with dilatation of the aortic root (r = 0.39-0.49, p<0.05) and reduced aortic root distensibility (r = 0.44, p = 0.02), whereas reduced LVEF was correlated with degree of AR and RVEF (r = 0.41, p = 0.02 and r = 0.49, p<0.01, respectively). CONCLUSIONS: Aortic root dilatation and reduced aortic elasticity are frequently present in patients with TOF, in addition to minor degrees of AR and reduced left ventricular systolic function. Aortic wall pathology in repaired TOF patients may therefore represent a separate mechanism leading to left ventricular dysfunction, as part of a multifactorial process of left ventricular dysfunction.

Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis.

INTRODUCTION: Several outcome studies have ruled out acute pulmonary embolism (PE) by normal computed tomography pulmonary angiography (CTPA). We performed a meta-analysis in order to determine the safety of this strategy in a specific group of patients with a strict indication for CTPA, that is, 'likely' or 'high' clinical probability for PE, an elevated D-dimer concentration, or both. METHODS: Studies that ruled out PE by normal CTPA, with or without subsequent normal bilateral compression ultrasonography (CUS), in patients with a strict indication for CTPA, were searched for in Medline, EMBASE, Web of Science and the Cochrane dataset. The primary endpoint was the occurrence of (fatal) venous thromboembolism (VTE) in a 3-month follow-up period. RESULTS: Three studies were identified that excluded PE by CTPA alone (2020 patients), and three studies that performed additional CUS of the legs after normal CTPA (1069 patients). The pooled incidence of VTE at 3 months was 1.2% [95% confidence interval (CI) 0.8-1.8] based on a normal CTPA result as a sole test, and 1.1% (95% CI 0.6-2.0) based on normal CTPA and negative CUS findings, resulting in negative predictive values of 98.8% (95% CI 98.2-99.2) and 98.9% (95% CI 98.0-99.4), respectively. This compares favorably with the VTE failure rate after normal pulmonary angiography (1.7%, 95% CI 1.0-2.7). The risk of fatal PE did not differ between the diagnostic strategies (0.6% vs. 0.5%). CONCLUSION: A normal CTPA result alone can safely exclude PE in all patients in whom CTPA is required to rule out this disease. There is no need for additional ultrasonography to rule out VTE in these patients.