Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism

Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism Omid Kiamanesh, Graeme Prosperi-Porta, Lea Harper, Kevin Solverson, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1598950/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose During acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE. Methods We assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and right ventricular fractional area change (FAC)/PASP as well as stroke volume index (SVI)/PASP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis. Results In 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1mm/mmHg decrease in TAPSE/PASP the odds of an adverse event increased by 2.5-fold (adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46–4.24, p = 0.001), for every 0.1%/mmHg decrease in FAC/PASP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09–1.86, p = 0.010), and for every 0.1mL/mmHg•m 2 decrease in SVI/PASP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72–4.50, p < 0.001). In multivariate analysis, TAPSE/PASP and SVI/PASP were independent of other risk stratification methods including computed tomography-derived RVD, the Bova score, and subjective assessment of TTE-derived RVD. Conclusion In patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are strongly associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD. Pulmonary embolism transthoracic echocardiography right ventricular dysfunction right ventricle-pulmonary artery coupling Figures Figure 1 Introduction Acute pulmonary embolism (PE) is a common cardiopulmonary disorder with a high morbidity and mortality [ 1 ]. While the presence of right ventricular dysfunction (RVD) is associated with poor outcomes in normotensive patients [ 2 , 3 ], upfront thrombolytic therapy in the PEITHO trial demonstrated an unfavourable risk-benefit profile whereby it improves hemodynamic outcomes at the expense of major intracranial bleeding [ 4 ]. In PE, the primary physiologic abnormality is an acute increase in pulmonary arterial pressure and right ventricular (RV) afterload, hypoxic vasoconstriction, and neurohormonal activation [ 1 ]. A compensatory increase in RV contractility is required to match increased RV afterload and maintain right ventricular-pulmonary arterial (RV-PA) coupling. If the RV is unable to match the increased afterload, RV-PA decoupling occurs with resultant reduction of cardiac output and RV failure [ 5 ]. Current international guidelines on the diagnosis and management of PE recommend consideration of transthoracic echocardiography (TTE) for risk stratification although there are no standardized echocardiographic measures to define the presence or absence of RVD [ 6 ]. The prognostic importance of TTE-derived RV-PA coupling indices such as tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and stroke volume/PASP have been recently reported [ 7 – 10 ]. However, questions regarding the role of RV-PA coupling in PE still exist. First, multiple TTE markers of RV-PA coupling exist which have not been directly compared to determine which is most accurate or reliable. Second, for clinical use, RV-PA coupling indices should have incremental value over other common and proven methods of risk stratification such as cardiac biomarkers [ 11 ], RVD determined by computed tomography pulmonary angiography (CTPA) [ 12 ], the conventional definition of RVD used in the PEITHO trial [ 4 ], the Bova score [ 13 ], and an echocardiographer’s subjective evaluation of RVD on TTE. Therefore, we aimed to evaluate the association between several candidate markers of RV-PA coupling assessed by TTE and adverse outcomes in a large cohort of normotensive patients with PE. We hypothesized that TTE markers of RV-PA decoupling would be associated with PE-related outcomes and would have incremental value when added to conventional tools used in guideline-based risk stratification. Methods Study population This retrospective multi-site cohort study was performed at 4 academic hospitals in Calgary, Alberta, Canada. The methods of the study are previously reported [ 14 , 15 ]. Briefly, we included all normotensive patients age ≥ 18 years admitted to hospital with PE between January 1, 2012 - March 31, 2017 who underwent TTE within 48 hours of admission. We excluded patients who had: (1) hemodynamic instability on presentation, (2) diagnosis of PE > 24 hours after admission, (3) no imaging confirmation of PE, (4) recurrent PE within 6 months, (5) incidental or asymptomatic PE, (6) reperfusion therapy at presentation, or (7) a palliative approach to care. The research study was approved by the health research ethics board at the University of Calgary (REB17-2368) and followed the ethical research principles outlined by the 1964 Declaration of Helsinki. Demographics and clinical data We collected demographic and clinical data from the electronic medical records, including age, sex, height, weight, blood pressure, heart rate, and comorbidities. Acute pulmonary embolism was confirmed by CTPA and/or nuclear medicine ventilation-perfusion scan. Laboratory variables completed within 24 hours of admission were recorded including high sensitivity troponin T, N-terminal pro B-type natriuretic peptide, D-dimer, and serum lactate. Simplified pulmonary embolism severity index (sPESI) and Bova scores were calculated from hospital admission data [ 13 , 16 ]. Echocardiographic variables Comprehensive 2-dimensional and doppler echocardiogram imaging was performed as recommended by the American Society of Echocardiography using commercially available systems with a 1–5 MHz transducer (iE33; Philips Medical Systems) [ 17 – 19 ]. All measurements performed by a single reviewer were confirmed by a second reviewer who were both blinded to baseline patient data and outcomes with any discrepancies resolved by consensus. RV structure and function Using 2-D echocardiography, RV fractional area change (FAC) was calculated based on the RV end diastolic area minus the end systolic area divided by the end diastolic area. Tricuspid annular plane systolic excursion was measured using M-mode. Pulmonary artery systolic pressure (PASP) was estimated based on the sum of the right atrial pressure and the maximum systolic pressure gradient across the tricuspid valve in any view. Right atrial pressure was defined based on the size and collapsibility of the inferior vena cava [ 17 ]. Right to left ventricular diameter ratio (RV/LV) was determined by the ratio of the diameters of the basal RV and left ventricle. The stroke volume was calculated by the product of left ventricular outflow tract area and its corresponding pulsed wave doppler signal trace obtained from either of the standard 3-chamber or 5-chamber views. The overall subjective assessment of RVD (defined as none, mild, moderate, or severe) made by the interpreting echocardiographer at the time of the clinical study was collected to avoid bias introduced during quantitative measurements. The PEITHO trial definition of RVD was based on criteria outlined in the trial which included any of the following: right ventricular end-diastolic diameter > 30, right-to-left ventricular end-diastolic diameter > 0.9 (apical or subcostal 4-chamber view), hypokinesis of the right ventricular free wall (any view), or tricuspid systolic velocity > 2.6 m/s [ 4 ]. RV-PA coupling We evaluated RV-PA coupling using the TAPSE/PASP ratio, which has been shown to have prognostic value and to correlate with invasive pressure-volume catheter measurements in other conditions of RV overload [ 20 – 24 ]. We also calculated FAC/PASP as secondary measure of RV-PA coupling. We evaluated pulmonary artery capacitance using the ratio of stroke volume index SVI/PASP, which has been previously validated to correlate with invasive pulmonary artery capacitance during right heart catheterization [ 25 ]. Outcomes The primary composite outcome was in-hospital PE-related mortality or cardiopulmonary decompensation, defined as systolic blood pressure 15 minutes, administration of catecholamines for hypotension, endotracheal intubation, rescue thrombolysis or cardiopulmonary resuscitation. Secondary outcomes included PE-related mortality and all-cause mortality. All events were independently adjudicated by two authors and disagreements were resolved by consensus. Statistical analysis Continuous variables are reported as mean ± standard deviation if normally distributed or median (interquartile range (IQR)) if nonnormally distributed. The Shapiro-Wilk test was used to determine normality. Categoric variables are reported as absolute and relative frequencies. Continuous variables were compared using the t-test or Wilcoxon rank-sum test for normally and nonnormally distributed populations, respectively. Categorical variables were compared using the chi-squared test. The relationship between echocardiographic parameters and the primary outcome was evaluated using logistic regression analyses, unadjusted and adjusted for age and sex. A multivariate logistic regression analysis was performed to assess whether RV-PA coupling parameters had incremental value over other risk stratification methods including RVD determined by CTPA, the Bova score [ 13 ], and an echocardiographer’s subjective evaluation of RVD on TTE. The diagnostic performance of TAPSE/PASP, FAC/PASP, and SVI/PASP was examined using a receiver operating characteristic curve analysis. The Youden Index (value yielding the maximum sum of sensitivity and specificity) was determined for each RV-PA variable to calculate the diagnostic performance characteristics for each variable [26]. All statistical analyses were performed with Stata Statistical Software (version 17.0; StataCorp, College Station, TX). A two-tailed probability value of < 0.05 was deemed statistically significant. Results Study cohort A total of 2067 patients were diagnosed with normotensive pulmonary embolism during the study period. Of which, 820 of underwent TTE within 48 hours of diagnosis and were therefore included in the present analysis. No patients were lost to follow-up. The median age was 62 (50–74) years and 391 (47.7%) were female (Table 1 ). A total of 26 (3.2%) patients had a primary PE-related adverse event. Of these, 11 (42.3%) had PE-related mortality and 15 had hemodynamic decompensation (57.7%) of which 7 received rescue thrombolysis. An additional 10 (1.2%) patients died from non-PE related etiologies during hospitalization. Table 1 Baseline characteristics of patients with normotensive acute pulmonary embolism. All (n = 820) Free from PE-related event (n = 794) PE-related event (n = 26) p value Demographics Age, years; median (IQR) 62 (50–74) 62 (50–75) 56 (47–67) 0.12 Female sex 391 (47.7%) 383 (48.2%) 8 (30.8%) 0.08 Comorbidities Prior venous thromboembolism 158 (19.3%) 153 (19.3%) 5 (19.2%) 0.99 Lung disease 164 (20.0%) 156 (19.7%) 8 (30.8%) 0.16 Heart disease 145 (17.7%) 140 (17.6%) 5 (19.2%) 0.83 Malignancy 97 (11.8%) 93 (11.7%) 4 (15.4%) 0.57 Diabetes 126 (15.4%) 120 (15.1%) 6 (23.1%) 0.27 Chronic kidney disease 57 (7.0%) 55 (6.9%) 2 (7.7%) 0.88 Symptoms Dyspnea 671 (83.8%) 647 (83.5%) 24 (92.3%) 0.23 Chest pain 393 (47.9%) 380 (47.9%) 13 (50.0%) 0.83 Syncope 81 (9.9%) 79 (10.0%) 2 (7.7%) 0.70 DVT symptoms 10 (1.3%) 10 (1.4%) 0 (0.0%) 0.56 Clinical findings Heart rate, bpm; median (IQR) 96 (83–112) 96 (83–112) 94 (78–110) 0.48 Systolic blood pressure, mmHg; median (IQR) 128 (116–143) 128 (116–143) 120 (113–138) 0.08 Diastolic blood pressure, mmHg; median (IQR) 80 (70–89) 80 (70–89) 79 (68–86) 0.40 Supplemental oxygen 425 (51.8%) 411 (51.8%) 14 (53.8%) 0.83 Atrial fibrillation 49 (6.0%) 47 (5.9%) 2 (7.7%) 0.71 BSA, m 2 ; median (IQR) 2 (1.8–2.2) 2 (1.8–2.2) 2.2 (1.9–2.3) 0.10 Laboratory findings NT-proBNP, ng/L; median (IQR); n 1734 (407–4396); 187 1804 (407–4447); 183 739 (345–1774); 4 0.34 Troponin, ng/L; median (IQR); n 36 (12–95); 705 36 (12–95); 679 37 (8-101); 4 0.64 D-dimer, mg/L; median (IQR); n 4 (1.7–7.3); 475 4 (1.7–7.3); 458 2.8 (1.5–5.7); 17 0.67 Lactate, mmol/L; median (IQR); n 1.7 (1.2–2.4); 299 1.7 (1.2–2.3) 1.5 (0.9–7.2) 0.96 Diagnostic method CTPA 750 (91.5%) 724 (91.2%) 26 (100%) 0.28 Ventilation-perfusion scan 70 (8.5%) 70 (8.8%) 0 (0%) Diagnosis to echo, hours; median (IQR) 17 (8.1–25.6) 17 (8.8–26.0) 6.3 (1.0–15.0) < 0.001 Echo to event, hours; median (IQR) 23 (6–60) - 23 (6–60) - Risk stratification Simplified PESI 0 155 (18.9%) 155 (19.5%) 0 (0%) 0.01 ≥1 665 (81.1%) 639 (80.5%) 26 (100%) Bova score (IQR) 4 (2–4) 4 (2–4) 5 (4–5) 0.001 Bova stage 1 272 (41.8%) 271 (43.2%) 1 (4.2%) < 0.001 2 236 (36.3%) 227 (36.2%) 9 (37.5%) 3 143 (22.0%) 129 (20.6%) 14 (58.3%) BSA = body surface area, CTPA = computed tomography pulmonary angiography, DVT = deep vein thrombosis, IQR = interquartile range, n = number of patients with measurements; NT-proBNP = brain natriuretic peptide, PESI = pulmonary embolism severity index There were no differences in the patient age, sex, comorbidities, or symptoms between patients with and without an event. There was no difference in heart rate, blood pressure, or the need for supplemental oxygen between patients with and without an event. Most patients were diagnosed by CTPA. The sPESI score was ≥1 in 80.5% of those without an event and 100% in those with an event (p = 0.01). The Bova score and stages [ 13 ] were higher in patients with an event than those without (p < 0.001). Echocardiographic findings Echocardiographic findings are shown in Table 2 . Echocardiography was performed sooner for those who experienced a primary outcome event (6.3 hours, IQR 1.0–15.0 vs. 17 hours, IQR 8.1–25.6; p < 0.001). Tricuspid annular plane systolic excursion, SVI, and FAC were all lower in patients with an event compared to those without (all had p < 0.001). Pulmonary artery systolic pressure (p < 0.001) and RV/LV (p = 0.002) were greater in patients with an event compared to those without. Patients with an event had lower TAPSE/PASP, FAC/PASP, and SVI/PASP compared to those without an event (all had p < 0.001). Patients with an event were more likely to have subjective RVD determined by the initial clinical reading echocardiographer (p < 0.001) Table 2 Imaging findings of patients with normotensive acute pulmonary embolism. All (n = 820) Free from PE-related event (n = 794) PE-related event (n = 26) p value Computed Tomography Pulmonary Angiography RV/LV diameter ratio; median (IQR, n 1.2 (0.9–1.6); 753 1.2 (0.9–1.6); 729 1.9 (1.6–2.1); 24 < 0.001 RV structure RV/LV base diameter ratio; median (IQR), n 1.1 (0.9–1.3); 643 1.1 (0.9–1.3); 628 1.3 (1.1–1.4); 15 0.002 RV base diameter, cm; median (IQR), n 4.2 (3.7–4.9); 647 4.3 (3.7–4.8); 632 4.5 (4.2–5.2); 15 0.07 RV diastolic area, cm 2 ; median (IQR), n 27.9 (22.5–33.8); 632 27.8 (22.4–33.7); 616 31.7 (28.0-38.7); 16 0.02 RV systolic area, cm 2 ; median (IQR), n 18.4 (13.5–24.8); 632 18.3 (13.4–24.5); 616 26.0 (21.0-31.9); 16 < 0.001 RV function TAPSE, mm; median (IQR), n 18.7 (14.9–22.6); 763 18.8 (15-22.8); 740 13 (9.8–18.1); 23 < 0.001 FAC, %; median (IQR), n 33.9 (23.8–42.5); 632 34.2 (23.9–42.6); 616 26.1 (21.1–31.9); 16 < 0.001 Subjective right ventricular dysfunction None 345 (43.8%) 343 (44.8%) 2 (8.7%) < 0.001 Mild 158 (20.1%) 156 (20.4%) 2 (8.7%) Moderate 213 (27.0%) 205 (26.8%) 8 (34.8%) Severe 72 (9.1%) 61 (8.0%) 11 (47.8%) Additional findings McConnell’s sign 32 (3.9%) 29 (3.7%) 3 (11.5%) 0.04 Cardiac thrombus 19 (2.3%) 15 (1.9%) 4 (15.4%) < 0.01 PEITHO right ventricular dysfunction 636 (77.5%) 614 (77.3%) 22 (84.6%) 0.38 Pulmonary pressures RA pressure (mmHg) 3 265 (32.7%) 263 (33.5%) 2 (8.0%) 0.03 8 266 (32.8%) 260 (33.0%) 6 (24.0%) 15 237 (29.2%) 222 (28.3%) 15 (60.0%) Indeterminate 42 (5.2%) 40 (5.1%) 2 (8.0%) PASP, mmHg; median (IQR), n 44 (33.8–55.7); 603 43.1 (33.7–55.1); 585 60.9 (50.2–68.7); 18 < 0.001 Cardiac output Stroke volume, mL; median (IQR), n 57.4 (45.4–69.4); 723 57.9 (46.3–69.7); 705 34.4 (30.1–41.6); 18 < 0.001 SVI, mL/m 2 ; median (IQR), n 28.2 (22.8–34.7); 723 28.5 (22.9–35.5); 705 17.6 (15.5–20.0); 18 < 0.001 RV-PA Coupling TAPSE/PASP, mm/mmHg; median (IQR), n 0.40 (0.28–0.59); 572 0.41 (0.28–0.59); 556 0.21 (0.17–0.31); 16 < 0.001 FAC/PASP, %/mmHg; median (IQR), n 0.67 (0.45–1.09); 493 0.68 (0.46–1.10); 480 0.34 (0.27–0.65); 13 < 0.001 SVI/PASP, mL/mmHg; median (IQR), n 0.63 (0.43–0.93); 583 0.65 (0.44–0.92); 566 0.26 (0.23–0.35); 17 < 0.001 FAC = fractional area change; IQR = interquartile range; n = number of patients with measurement PASP = pulmonary artery systolic pressure; RV = right ventricle; RV/LV = right to left ventricular diameter ratio, SVI = stroke volume index; TAPSE = tricuspid annular plane systolic excursion; TR = tricuspid regurgitation; TTE = transthoracic echocardiogram Ventricular-arterial coupling Echocardiography-derived RV-PA coupling parameters were strongly associated with PE-related adverse events, PE-related mortality, and all-cause mortality (Table 3 ). Neither the PEITHO trial definition of RVD (OR 1.61, 95% CI 0.55–4.74; p = 0.385; n = 813) nor high sensitivity troponin T (OR 1.00, 95% CI 0.997–1.002; n = 705) were associated with PE-related adverse events. In multivariate analysis with subjective TTE-derived RVD, CTPA RV/LV ratio, and the Bova score, only TAPSE/RVSP (p = 0.044) and SVI/RVSP (p = 0.002) were independently associated with PE-related adverse events while FAC/RVSP was not (p = 0.308) (Table 4 ). Table 3 Logistic regression analysis of ventricular-arterial coupling parameters for composite PE-related adverse events, PE-related mortality, and all-cause mortality Number of Patients Crude OR 95% CI P value Adjusted OR* 95% CI P value Composite PE-related event TAPSE/PASP (per 0.1 mm/mmHg decrease) 572 2.47 1.47–4.14 0.001 2.49 1.46–4.24 0.001 SVI/PASP (per 0.1 mL/mmHg•m 2 decrease) 583 2.77 1.73–4.43 < 0.001 2.78 1.72–4.50 < 0.001 FAC/PASP (per 0.1%/mmHg decrease) 493 1.43 1.10–1.87 0.008 1.42 1.09–1.86 0.010 PE-related mortality TAPSE/PASP (per 0.1 mm/mmHg decrease) 572 2.97 1.18–7.49 0.021 2.88 1.16–7.12 0.022 SVI/PASP (per 0.1 mL/mmHg•m 2 decrease) 583 2.96 1.32–6.64 0.008 2.98 1.32–6.70 0.008 FAC/PASP (per 0.1%/mmHg decrease) 493 1.27 1.00-1.61 0.016 1.28 1.00-1.64 0.052 All-cause mortality TAPSE/PASP (per 0.1 mm/mmHg decrease) 572 1.87 1.19–2.92 0.007 1.84 1.18–2.86 0.007 SVI/PASP (per 0.1 mL/mmHg•m 2 decrease) 583 1.44 1.11–1.89 0.007 1.46 1.12–1.92 0.006 FAC/PASP (per 0.1%/mmHg decrease) 493 1.31 1.01–1.71 0.039 1.33 1.01–1.75 0.039 *Adjusted for age and sex. CI = confidence interval; FAC = fractional area change; OR = odds ratio; PE = pulmonary embolism; PASP = pulmonary artery systolic pressure; SVI = stroke volume index; TAPSE = tricuspid annular plane systolic excursion Table 4 Univariate and multivariate logistic regression analysis for PE-related of RV-PA coupling parameters compared to subjective assessment of RVD, the Bova score, and the CR RV/LV ratio. Number of Patients OR 95% CI P value Univariate Subjective right ventricular dysfunction (per unit increase) 788 3.41 2.07–5.60 < 0.001 Bova Score (per unit increase) 650 1.92 1.39–2.66 < 0.001 CTPA RV/LV ratio (per unit increase) 755 8.88 3.58–22.03 < 0.001 Multivariate TAPSE/PASP (per 0.1 mm/mmHg decrease) 448 1.91 1.02–3.58 0.044 Subjective right ventricular dysfunction (per unit increase) 1.70 0.72–4.04 0.226 Bova Score (per unit increase) 1.17 0.68–4.04 0.226 CTPA RV/LV ratio (per unit increase) 2.18 0.41–11.63 0.361 SVI/PASP (per 0.1 mL/mmHg•m 2 decrease) 457 2.21 1.35–3.61 0.002 Subjective right ventricular dysfunction (per unit increase) 1.64 0.71–3.80 0.248 Bova Score (per unit increase) 1.12 0.65–1.93 0.673 CTPA RV/LV ratio (per unit increase) 2.10 0.37-12.00 0.405 FAC/PASP (per 0.1%/mmHg decrease) 386 1.17 0.87–1.58 0.308 Subjective right ventricular dysfunction (per unit increase) 1.73 0.69–4.34 0.240 Bova Score (per unit increase) 1.11 0.63–1.94 0.717 CTPA RV/LV ratio (per unit increase) 2.66 0.45–15.68 0.280 CTPA RV/LV = computed tomography right to left ventricular diameter ratio; FAC = fractional area change; OR = odds ratio; PE = pulmonary embolism; PASP = pulmonary artery systolic pressure; RVD = right ventricular dysfunction; SVI = stroke volume index; TAPSE = tricuspid annular plane systolic excursion. Receiver operating characteristic analysis was performed to assess the diagnostic performances of TAPSE/PASP, SVI/PASP, FAC/PASP (Fig. 1 ). The area under curve (AUC) for TAPSE/PASP was 0.81 (CI 0.68–0.87), SVI/PASP was 0.89 (CI 0.83–0.96), and FAC/PASP 0.77 (CI 0.64–0.90). While SVI/PASP had a higher AUC compared to FAC/PASP (p < 0.01) it only trended towards being greater than TAPSE/PASP (p = 0.13). There was no difference between FAC/PASP and TAPSE/PASP (p = 0.678). The diagnostic performance indices for each RV-PA variable are shown in Table 5 . There was no difference in the diagnostic performance indices between each RV-PA variable although confidence intervals were large. Table 5 Diagnostic performance characteristics for TTE-derived measures of right ventricular dysfunction. TTE Parameter and Youden Index Sensitivity (%) (95% CI) Specificity (%) (95% CI) PPV (%) (95% CI) NPV (%) (95% CI) Positive LR (95% CI) Negative LR (95% CI) TAPSE/PASP < 0.29 mm/mmHg 75.0 (47.6–92.7) 72.1 (68.2–75.8) 7.2 (3.8–12.2) 99.0 (97.5–99.7) 2.7 (2.0-3.7) 0.3 (0.1–0.8) SVI/PASP < 0.36 mL/m 2 82.4 (56.6–96.2) 78.8 (75.4–82.0) 9.7 (5.4–15.7) 99.4 (98.2–99.9) 3.9 (3.0-5.1) 0.2 (0.1–0.6) FAC/PASP < 0.35%/mmHg 69.2 (38.6–90.9) 86.3 (82.8–89.2) 12.0 (5.6–21.6) 99.0 (97.6–99.7) 5.0 (3.3–7.7) 0.4 (0.2–0.8) FAC = fractional area change; LR = likelihood ratio; NPV = negative predictive value; PPV = positive predictive value; PASP = pulmonary artery systolic pressure; SVI = stroke volume index; TTE = transthoracic echocardiogram Discussion This study showed that TTE-derived estimates of RV-PA coupling including FAC/PASP, and TAPSE/PASP and SVI/PASP were associated with PE-related adverse events in 820 normotensive patients with PE. The TAPSE/PASP and SVI/PASP had incremental value to the Bova score and CTPA RV/LV ratio, and subjective assessment of TTE-derived RVD in discriminating PE-related adverse events. These findings provide important insights into the importance of RV-PA coupling in the pathophysiology of hemodynamic decompensation in PE. Additionally, it underscores the challenges in identifying a universal TTE-derived prognostic marker to risk stratify normotensive patients, who represent a significant proportion of patients with PE. Lastly This is the first study to assess the association of multiple parameters of RV-PA coupling with PE-related adverse events in the same cohort of patients and directly compare its utility against other markers RVD and risk stratification tools. Importantly, this study showed that in multivariate analysis with CTPA-derived RV/LV, the Bova score and subjective TTE assessment of RVD, SVI/PASP and TAPSE/PASP were both independently associated with PE-related adverse events. This suggests that RV-PA coupling has additive prognostic value beyond RVD identified by CTPA or clinical risk prediction scores, and it underscores the importance of quantitative assessment of RVD over subjective assessment alone. We also demonstrated that the conventional definition of RVD used in the PEITHO trial was not associated with adverse PE-related events in our population, while quantitative TTE measures including RV-PA coupling indices were strongly associated. Conventional definitions of RVD are ubiquitous in this population being present in 37% of patients with normotensive PE emphasizing the importance of more specific tools for identifying patients at heightened risk of adverse events [ 2 ]. This may be one reason that the PEITHO trial was unable to show a net benefit from systemic thrombolysis [ 4 ]. It suggests that future trials of thrombolysis or invasive catheter directed therapies may need to use a different definition for TTE-derived RVD that is more strongly associated with adverse events. Ciurzyński et al. was the first to evaluate an RV-PA coupling parameter in PE using a stepwise approach to risk stratification with tricuspid annular plane systolic excursion (TAPSE) < 20mm followed by the ratio of tricuspid regurgitation peak gradient divided by TAPSE [ 7 ]. More recently, studies by Kamran et al. evaluated pulmonary artery systolic pressure (PASP) divided by left ventricular stroke volume and Lyhne et al. and Falsetti et al. evaluated TAPSE/PASP showing that these markers were associated with adverse outcomes in PE [ 8 – 10 ]. Kamran et al. concluded that PASP/left ventricular stroke volume was superior to the velocity time integral (VTI) although this was done comparing continuous odds ratios with different units [ 9 ]. However, Falsetti et al . found no difference in the association with adverse outcomes between TAPSE/PASP and VTI when comparing categorical odds ratios. Echocardiographic markers of RV-PA coupling and stroke volume all seem to have competitive risk stratification potential. However, it is unlikely that identifying an incrementally superior single TTE-derived markers of RVD will dramatically change outcomes of risk stratification. Instead, current guidelines appropriately promote a multimodality approach using clinical, biochemical, and radiologic markers of risk [ 6 ]. We did not directly compare markers of RV-PA coupling directly with other quantitative measures of RVD due to lack of statistical power for meaningful comparisons and because most of the quantitative measures of RVD in this study are components of the RV-PA parameters. As pulmonary vascular resistance increases, there is an inverse nonlinear relationship in the compliance [ 27 ]. In turn, this results in an exaggerated RV pulsatile load, RV ejection pressure, and increased RV stroke work, all of which contribute to RV failure [ 28 , 29 ]. The cardiovascular system operates in dynamic state whereby ventricular contractility is coupled with arterial afterload, otherwise known as ventricular-arterial coupling. Accordingly, in response to increased pulmonary artery pressures, the RV undergoes adaptive changes to increase contractility and preserve RV-PA coupling. RV-PA decoupling occurs when the RV contractility fails to match arterial afterload resulting in RV failure and hemodynamic decompensation thereafter. In the case of PE, this may result from excessive arterial elastance, direct impairment of RV contractility by cardiac ischemia, and the harmful RV-LV interaction whereby abnormal septal motion impairs left ventricular filling and resulting left sided stroke volume [ 14 ]. The fact that TAPSE/PASP, FAC/PASP, and SVI/PASP were all strongly associated with PE-related adverse events strengthens the finding that RV-PA decoupling is implicated in the pathophysiology of hemodynamic decompensation. SVI uniquely measures the most downstream hemodynamic effect of a PE, which not only decreases during RV-PA decoupling but also when left ventricular filling is impaired due to abnormal septal movement towards the left ventricle. Indices of RV-PA coupling including SVI/PASP, FAC/PASP, and TAPSE/PASP were strongly associated with adverse in-hospital PE-related events in patients with normotensive PE. Stroke volume index, TAPSE and PASP are simple measurements that are easily obtainable during standard TTE. While FAC/PASP was associated with adverse PE-related events, FAC requires accurate RV endocardial contouring in both systole and diastole which may be difficult to perform reliably in clinical practice. The RV can be particularly challenging to accurately image due to its asymmetric shape and is prone to off axis imaging which may falsely estimate its function. The utility of direct assessment of RV size and function may be more limited due to these factors. Another challenge can be in obtaining a complete doppler signal to calculate the PASP. In this study, PASP could be determined in only 603 patients, FAC was only possible in 632 patients compared to TAPSE that was measurable in 763 patients and SVI that was measurable in 795 patients. These RV-PA coupling parameters represent multiple potential measurements that can be obtained during a standard TTE to identify normotensive patients at higher risk of PE-related mortality or hemodynamic decompensation. These parameters could have the potential to enrich future clinical trials of invasive therapies (i.e. thrombolytic therapy or catheter directed therapies) with truly intermediate-high risk patients. Future prospective prognostic studies are required to determine the feasibility of performing these measurements and validate these retrospective findings. This study has several limitations. Our cohort had only 26 adverse PE-related events (3.2%). This is in part due to the more stringent definition of PE-related mortality rather than all-cause mortality. In our study, markers of RV-PA coupling were less associated with all-cause mortality than PE-related mortality. This is because all-cause mortality is less related to the underlying pathophysiologic mechanism of mortality in PE and is therefore likely of less suitable outcome than PE-related mortality when evaluating echocardiographic measurements. However, our event rates are similar to other unselected PE populations assessing RV-PA coupling such as Ciurzyński et al . where 8/400 (2%) PE-related death or hemodynamic decompensation [ 7 ] and Falsetti et al. where 10/256 (3.9%) had in-hospital mortality [ 10 ]. Data collection was retrospective and some TTE parameters were unavailable as they were not recorded routinely but at the discretion of the echocardiography technologist. At least one of FAC/PASP, TAPSE/PASP, or SVI/PASP was only possible in 599/820 (73%) of patients. This means that in 27% of patients another simpler marker of TTE-derived RVD must be used. This seems consistent with Kamran et al. who reported that only 215/343 (63%) patients that met inclusion had complete data for analysis, and Falsetti et al. who reported that only 270/326 (83%) patients had complete data [ 9 , 10 ]. Lastly, because performing a TTE was at the discretion of the attending physician, there have been some selection bias in this cohort (only 820/2067 patients had a TTE within 48 hours of diagnosis). Despite this, we saw similar event rates compared to other contemporary studies assessing RV-PA coupling parameters. Conclusion In patients with normotensive acute pulmonary embolism, TTE-derived RV-PA coupling parameters including TAPSE/PASP and FAC/PASP and SVI/PASP were associated with adverse in-hospital PE-related events with TAPSE/PASP and SVI/PASP being independent of CTPA-derived RV/LV, the Bova score, and subjective TTE assessment of RVD. Future prospective studies evaluating TTE-derived RVD including markers of RV-PA coupling are required to validate these findings and identify whether a single or multivariable approach is most valuable for prognostication of PE-related adverse events using TTE. Declarations Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Omid Kiamanesh, Kevin Solverson, Graeme Prosperi-Porta, and Jason Weatherald. The first draft of the manuscript was written by Omid Kiamanesh and Graeme Prosperi-Porta and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Goldhaber SZ, Elliott CG. Acute pulmonary embolism: part I: epidemiology, pathophysiology, and diagnosis. Circulation. 2003;108:2726-9.https://doi.org/10.1161/01.Cir.0000097829.89204.0c Cho JH, Kutti Sridharan G, Kim SH, Kaw R, Abburi T, Irfan A, et al. Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis. BMC Cardiovasc Disord. 2014;14:64.https://doi.org/10.1186/1471-2261-14-64 Barco S, Mahmoudpour SH, Planquette B, Sanchez O, Konstantinides SV, Meyer G. Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis. European Heart Journal. 2019;40:902-10.https://doi.org/10.1093/eurheartj/ehy873 Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. New England Journal of Medicine. 2014;370:1402-11.https://doi.org/10.1056/NEJMoa1302097 Jentzer JC, Anavekar NS, Reddy YNV, Murphree DH, Wiley BM, Oh JK, et al. Right Ventricular Pulmonary Artery Coupling and Mortality in Cardiac Intensive Care Unit Patients. Journal of the American Heart Association. 2021;10:e019015.https://doi.org/10.1161/JAHA.120.019015 Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing G-J, Harjola V-P, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European Heart Journal. 2019;41:543-603.https://doi.org/10.1093/eurheartj/ehz405 Ciurzyński M, Kurnicka K, Lichodziejewska B, Kozłowska M, Pływaczewska M, Sobieraj P, et al. Tricuspid Regurgitation Peak Gradient (TRPG)/Tricuspid Annulus Plane Systolic Excursion (TAPSE) - A Novel Parameter for Stepwise Echocardiographic Risk Stratification in Normotensive Patients With Acute Pulmonary Embolism. Circ J. 2018;82:1179-85.https://doi.org/10.1253/circj.CJ-17-0940 Lyhne MD, Kabrhel C, Giordano N, Andersen A, Nielsen-Kudsk JE, Zheng H, et al. The echocardiographic ratio tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure predicts short-term adverse outcomes in acute pulmonary embolism. Eur Heart J Cardiovasc Imaging. 2021;22:285-94.https://doi.org/10.1093/ehjci/jeaa243 Kamran H, Hariri EH, Iskandar JP, Sahai A, Haddadin I, Harb SC, et al. Simultaneous Pulmonary Artery Pressure and Left Ventricle Stroke Volume Assessment Predicts Adverse Events in Patients With Pulmonary Embolism. J Am Heart Assoc. 2021;10:e019849.https://doi.org/10.1161/JAHA.120.019849 Falsetti L, Marra AM, Zaccone V, Sampaolesi M, Riccomi F, Giovenali L, et al. Echocardiographic predictors of mortality in intermediate-risk pulmonary embolism. Internal and Emergency Medicine. 2022.https://doi.org/10.1007/s11739-021-02910-w Bajaj A, Rathor P, Sehgal V, Kabak B, Shetty A, Al Masalmeh O, et al. Prognostic Value of Biomarkers in Acute Non-massive Pulmonary Embolism: A Systematic Review and Meta-analysis. Lung. 2015;193:639-51.https://doi.org/10.1007/s00408-015-9752-4 Meinel FG, Nance JW, Jr., Schoepf UJ, Hoffmann VS, Thierfelder KM, Costello P, et al. Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis. Am J Med. 2015;128:747-59.e2.https://doi.org/10.1016/j.amjmed.2015.01.023 Bova C, Sanchez O, Prandoni P, Lankeit M, Konstantinides S, Vanni S, et al. Identification of intermediate-risk patients with acute symptomatic pulmonary embolism. Eur Respir J. 2014;44:694-703.https://doi.org/10.1183/09031936.00006114 Prosperi-Porta G, Solverson K, Fine N, Humphreys CJ, Ferland A, Weatherald J. Echocardiography-Derived Stroke Volume Index Is Associated With Adverse In-Hospital Outcomes in Intermediate-Risk Acute Pulmonary Embolism: A Retrospective Cohort Study. Chest. 2020;158:1132-42.https://doi.org/10.1016/j.chest.2020.02.066 Solverson K, Humphreys C, Liang Z, Prosperi-Porta G, Andruchow JE, Boiteau P, et al. Rapid prediction of adverse outcomes for acute normotensive pulmonary embolism: derivation of the Calgary Acute Pulmonary Embolism (CAPE) score. ERJ Open Research. 2021:00879-2020.https://doi.org/10.1183/23120541.00879-2020 Jiménez D, Aujesky D, Moores L, Gómez V, Lobo JL, Uresandi F, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170:1383-9.https://doi.org/10.1001/archinternmed.2010.199 Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, et al. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography. Journal of the American Society of Echocardiography. 2019;32:1-64.https://doi.org/10.1016/j.echo.2018.06.004 Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1-39.e14.https://doi.org/10.1016/j.echo.2014.10.003 Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685-713; quiz 86-8.https://doi.org/10.1016/j.echo.2010.05.010 Schmeisser A, Rauwolf T, Groscheck T, Kropf S, Luani B, Tanev I, et al. Pressure-volume loop validation of TAPSE/PASP for right ventricular arterial coupling in heart failure with pulmonary hypertension. Eur Heart J Cardiovasc Imaging. 2021;22:168-76.https://doi.org/10.1093/ehjci/jeaa285 Tello K, Wan J, Dalmer A, Vanderpool R, Ghofrani HA, Naeije R, et al. Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension. Circ Cardiovasc Imaging. 2019;12:e009047.https://doi.org/10.1161/circimaging.119.009047 Guazzi M, Dixon D, Labate V, Beussink-Nelson L, Bandera F, Cuttica MJ, et al. RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes and Outcomes. JACC Cardiovasc Imaging. 2017;10:1211-21.https://doi.org/10.1016/j.jcmg.2016.12.024 Tello K, Ghofrani HA, Heinze C, Krueger K, Naeije R, Raubach C, et al. A simple echocardiographic estimate of right ventricular-arterial coupling to assess severity and outcome in pulmonary hypertension on chronic lung disease. Eur Respir J. 2019;54.https://doi.org/10.1183/13993003.02435-2018 Tello K, Axmann J, Ghofrani HA, Naeije R, Narcin N, Rieth A, et al. Relevance of the TAPSE/PASP ratio in pulmonary arterial hypertension. Int J Cardiol. 2018;266:229-35.https://doi.org/10.1016/j.ijcard.2018.01.053 Papolos A, Fan E, Wagle RR, Foster E, Boyle AJ, Yeghiazarians Y, et al. Echocardiographic determination of pulmonary arterial capacitance. Int J Cardiovasc Imaging. 2019;35:1581-6.https://doi.org/10.1007/s10554-019-01595-9 Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32-5.https://doi.org/10.1002/1097-0142(1950)3:13.0.co;2-3 Tedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, et al. Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading. Circulation. 2012;125:289-97.https://doi.org/10.1161/CIRCULATIONAHA.111.051540 Vonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62:D22-33.https://doi.org/10.1016/j.jacc.2013.10.027 Wang Z, Chesler NC. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulm Circ. 2011;1:212-23.https://doi.org/10.4103/2045-8932.83453 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 15 May, 2022 Reviews received at journal 11 May, 2022 Reviews received at journal 10 May, 2022 Reviewers agreed at journal 30 Apr, 2022 Reviewers agreed at journal 30 Apr, 2022 Reviewers invited by journal 27 Apr, 2022 Editor assigned by journal 27 Apr, 2022 Submission checks completed at journal 27 Apr, 2022 First submitted to journal 26 Apr, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1598950","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":101750391,"identity":"44d6a497-7b09-4c79-9ba6-3de3e921bdb8","order_by":0,"name":"Omid Kiamanesh","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Omid","middleName":"","lastName":"Kiamanesh","suffix":""},{"id":101750392,"identity":"6b548e55-b528-43ba-9e71-c95b4f15c5fc","order_by":1,"name":"Graeme Prosperi-Porta","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Graeme","middleName":"","lastName":"Prosperi-Porta","suffix":""},{"id":101750393,"identity":"731a1e0e-e77f-4ee8-a058-9b914f87205b","order_by":2,"name":"Lea Harper","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lea","middleName":"","lastName":"Harper","suffix":""},{"id":101750394,"identity":"e3ee298c-22b6-4670-8265-20dfc7d97108","order_by":3,"name":"Kevin Solverson","email":"","orcid":"","institution":"University of Calgary","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Solverson","suffix":""},{"id":101750395,"identity":"7dab6001-9a55-4b69-9cd3-4f29f5b0af27","order_by":4,"name":"Paul Boiteau","email":"","orcid":"","institution":"University of 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Calgary","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jason","middleName":"","lastName":"Weatherald","suffix":""}],"badges":[],"createdAt":"2022-04-27 01:29:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1598950/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1598950/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":20928697,"identity":"63cbf6bc-4321-4d54-9474-cc2d4f831e65","added_by":"auto","created_at":"2022-04-29 16:29:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":54244,"visible":true,"origin":"","legend":"\u003cp\u003eReceiver-operating-characteristic (ROC) curves describing the diagnostic performance of FAC/PASP, TAPSE/PASP, and SVI/PASP to identify a pulmonary embolism-related mortality or hemodynamic decompensation among patients with normotensive PE.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1598950/v1/dc6a0670ec60cb296d5f52d0.png"},{"id":20928711,"identity":"1eedd8d6-0776-41f0-9bc9-f82ec6ab5bf6","added_by":"auto","created_at":"2022-04-29 16:29:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":516601,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1598950/v1/319c3c06-9cc6-432e-adbd-968e1d33520c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute pulmonary embolism (PE) is a common cardiopulmonary disorder with a high morbidity and mortality [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. While the presence of right ventricular dysfunction (RVD) is associated with poor outcomes in normotensive patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], upfront thrombolytic therapy in the PEITHO trial demonstrated an unfavourable risk-benefit profile whereby it improves hemodynamic outcomes at the expense of major intracranial bleeding [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In PE, the primary physiologic abnormality is an acute increase in pulmonary arterial pressure and right ventricular (RV) afterload, hypoxic vasoconstriction, and neurohormonal activation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. A compensatory increase in RV contractility is required to match increased RV afterload and maintain right ventricular-pulmonary arterial (RV-PA) coupling. If the RV is unable to match the increased afterload, RV-PA decoupling occurs with resultant reduction of cardiac output and RV failure [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrent international guidelines on the diagnosis and management of PE recommend consideration of transthoracic echocardiography (TTE) for risk stratification although there are no standardized echocardiographic measures to define the presence or absence of RVD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The prognostic importance of TTE-derived RV-PA coupling indices such as tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and stroke volume/PASP have been recently reported [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, questions regarding the role of RV-PA coupling in PE still exist. First, multiple TTE markers of RV-PA coupling exist which have not been directly compared to determine which is most accurate or reliable. Second, for clinical use, RV-PA coupling indices should have incremental value over other common and proven methods of risk stratification such as cardiac biomarkers [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], RVD determined by computed tomography pulmonary angiography (CTPA) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], the conventional definition of RVD used in the PEITHO trial [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], the Bova score [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and an echocardiographer\u0026rsquo;s subjective evaluation of RVD on TTE.\u003c/p\u003e \u003cp\u003eTherefore, we aimed to evaluate the association between several candidate markers of RV-PA coupling assessed by TTE and adverse outcomes in a large cohort of normotensive patients with PE. We hypothesized that TTE markers of RV-PA decoupling would be associated with PE-related outcomes and would have incremental value when added to conventional tools used in guideline-based risk stratification.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eThis retrospective multi-site cohort study was performed at 4 academic hospitals in Calgary, Alberta, Canada. The methods of the study are previously reported [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Briefly, we included all normotensive patients age\u0026thinsp;\u0026ge;\u0026thinsp;18 years admitted to hospital with PE between January 1, 2012 - March 31, 2017 who underwent TTE within 48 hours of admission. We excluded patients who had: (1) hemodynamic instability on presentation, (2) diagnosis of PE\u0026thinsp;\u0026gt;\u0026thinsp;24 hours after admission, (3) no imaging confirmation of PE, (4) recurrent PE within 6 months, (5) incidental or asymptomatic PE, (6) reperfusion therapy at presentation, or (7) a palliative approach to care. The research study was approved by the health research ethics board at the University of Calgary (REB17-2368) and followed the ethical research principles outlined by the 1964 Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDemographics and clinical data\u003c/h2\u003e \u003cp\u003eWe collected demographic and clinical data from the electronic medical records, including age, sex, height, weight, blood pressure, heart rate, and comorbidities. Acute pulmonary embolism was confirmed by CTPA and/or nuclear medicine ventilation-perfusion scan. Laboratory variables completed within 24 hours of admission were recorded including high sensitivity troponin T, N-terminal pro B-type natriuretic peptide, D-dimer, and serum lactate. Simplified pulmonary embolism severity index (sPESI) and Bova scores were calculated from hospital admission data [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eEchocardiographic variables\u003c/h2\u003e \u003cp\u003eComprehensive 2-dimensional and doppler echocardiogram imaging was performed as recommended by the American Society of Echocardiography using commercially available systems with a 1\u0026ndash;5 MHz transducer (iE33; Philips Medical Systems) [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. All measurements performed by a single reviewer were confirmed by a second reviewer who were both blinded to baseline patient data and outcomes with any discrepancies resolved by consensus.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eRV structure and function\u003c/h2\u003e \u003cp\u003eUsing 2-D echocardiography, RV fractional area change (FAC) was calculated based on the RV end diastolic area minus the end systolic area divided by the end diastolic area. Tricuspid annular plane systolic excursion was measured using M-mode. Pulmonary artery systolic pressure (PASP) was estimated based on the sum of the right atrial pressure and the maximum systolic pressure gradient across the tricuspid valve in any view. Right atrial pressure was defined based on the size and collapsibility of the inferior vena cava [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Right to left ventricular diameter ratio (RV/LV) was determined by the ratio of the diameters of the basal RV and left ventricle. The stroke volume was calculated by the product of left ventricular outflow tract area and its corresponding pulsed wave doppler signal trace obtained from either of the standard 3-chamber or 5-chamber views. The overall subjective assessment of RVD (defined as none, mild, moderate, or severe) made by the interpreting echocardiographer at the time of the clinical study was collected to avoid bias introduced during quantitative measurements. The PEITHO trial definition of RVD was based on criteria outlined in the trial which included any of the following: right ventricular end-diastolic diameter\u0026thinsp;\u0026gt;\u0026thinsp;30, right-to-left ventricular end-diastolic diameter\u0026thinsp;\u0026gt;\u0026thinsp;0.9 (apical or subcostal 4-chamber view), hypokinesis of the right ventricular free wall (any view), or tricuspid systolic velocity\u0026thinsp;\u0026gt;\u0026thinsp;2.6 m/s [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eRV-PA coupling\u003c/h2\u003e \u003cp\u003eWe evaluated RV-PA coupling using the TAPSE/PASP ratio, which has been shown to have prognostic value and to correlate with invasive pressure-volume catheter measurements in other conditions of RV overload [\u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. We also calculated FAC/PASP as secondary measure of RV-PA coupling. We evaluated pulmonary artery capacitance using the ratio of stroke volume index SVI/PASP, which has been previously validated to correlate with invasive pulmonary artery capacitance during right heart catheterization [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary composite outcome was in-hospital PE-related mortality or cardiopulmonary decompensation, defined as systolic blood pressure\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg for \u0026gt;\u0026thinsp;15 minutes, administration of catecholamines for hypotension, endotracheal intubation, rescue thrombolysis or cardiopulmonary resuscitation. Secondary outcomes included PE-related mortality and all-cause mortality. All events were independently adjudicated by two authors and disagreements were resolved by consensus.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables are reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation if normally distributed or median (interquartile range (IQR)) if nonnormally distributed. The Shapiro-Wilk test was used to determine normality. Categoric variables are reported as absolute and relative frequencies. Continuous variables were compared using the t-test or Wilcoxon rank-sum test for normally and nonnormally distributed populations, respectively. Categorical variables were compared using the chi-squared test. The relationship between echocardiographic parameters and the primary outcome was evaluated using logistic regression analyses, unadjusted and adjusted for age and sex. A multivariate logistic regression analysis was performed to assess whether RV-PA coupling parameters had incremental value over other risk stratification methods including RVD determined by CTPA, the Bova score [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and an echocardiographer\u0026rsquo;s subjective evaluation of RVD on TTE. The diagnostic performance of TAPSE/PASP, FAC/PASP, and SVI/PASP was examined using a receiver operating characteristic curve analysis. The Youden Index (value yielding the maximum sum of sensitivity and specificity) was determined for each RV-PA variable to calculate the diagnostic performance characteristics for each variable [26]. All statistical analyses were performed with Stata Statistical Software (version 17.0; StataCorp, College Station, TX). A two-tailed probability value of \u0026lt;\u0026thinsp;0.05 was deemed statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec11\"\u003e\n \u003ch2\u003eStudy cohort\u003c/h2\u003e\n \u003cp\u003eA total of 2067 patients were diagnosed with normotensive pulmonary embolism during the study period. Of which, 820 of underwent TTE within 48 hours of diagnosis and were therefore included in the present analysis. No patients were lost to follow-up. The median age was 62 (50\u0026ndash;74) years and 391 (47.7%) were female (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). A total of 26 (3.2%) patients had a primary PE-related adverse event. Of these, 11 (42.3%) had PE-related mortality and 15 had hemodynamic decompensation (57.7%) of which 7 received rescue thrombolysis. An additional 10 (1.2%) patients died from non-PE related etiologies during hospitalization.\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of patients with normotensive acute pulmonary embolism.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 32.361%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;820)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003eFree from PE-related event (n\u0026thinsp;=\u0026thinsp;794)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003ePE-related event\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eAge, years; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e62 (50\u0026ndash;74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e62 (50\u0026ndash;75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e56 (47\u0026ndash;67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eFemale sex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e391 (47.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e383 (48.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e8 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003ePrior venous thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e158 (19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e153 (19.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e5 (19.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eLung disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e164 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e156 (19.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e8 (30.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eHeart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e145 (17.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e140 (17.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e5 (19.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eMalignancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e97 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e93 (11.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e4 (15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e126 (15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e120 (15.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e6 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eChronic kidney disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e57 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e55 (6.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e2 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymptoms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eDyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e671 (83.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e647 (83.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e24 (92.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eChest pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e393 (47.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e380 (47.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e13 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eSyncope\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e81 (9.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e79 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e2 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eDVT symptoms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e10 (1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e10 (1.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eHeart rate, bpm; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e96 (83\u0026ndash;112)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e96 (83\u0026ndash;112)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e94 (78\u0026ndash;110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eSystolic blood pressure, mmHg; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e128 (116\u0026ndash;143)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e128 (116\u0026ndash;143)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e120 (113\u0026ndash;138)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eDiastolic blood pressure, mmHg; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e80 (70\u0026ndash;89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e80 (70\u0026ndash;89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e79 (68\u0026ndash;86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eSupplemental oxygen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e425 (51.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e411 (51.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e14 (53.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eAtrial fibrillation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e49 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e47 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e2 (7.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eBSA, m\u003csup\u003e2\u003c/sup\u003e; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e2 (1.8\u0026ndash;2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e2 (1.8\u0026ndash;2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e2.2 (1.9\u0026ndash;2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eNT-proBNP, ng/L; median (IQR); n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e1734 (407\u0026ndash;4396); 187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e1804 (407\u0026ndash;4447); 183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e739 (345\u0026ndash;1774); 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eTroponin, ng/L; median (IQR); n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e36 (12\u0026ndash;95); 705\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e36 (12\u0026ndash;95); 679\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e37 (8-101); 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eD-dimer, mg/L; median (IQR); n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e4 (1.7\u0026ndash;7.3); 475\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e4 (1.7\u0026ndash;7.3); 458\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e2.8 (1.5\u0026ndash;5.7); 17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eLactate, mmol/L; median (IQR); n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e1.7 (1.2\u0026ndash;2.4); 299\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e1.7 (1.2\u0026ndash;2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e1.5 (0.9\u0026ndash;7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnostic method\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eCTPA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e750 (91.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e724 (91.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e26 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eVentilation-perfusion scan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e70 (8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e70 (8.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eDiagnosis to echo, hours; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e17 (8.1\u0026ndash;25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e17 (8.8\u0026ndash;26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e6.3 (1.0\u0026ndash;15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eEcho to event, hours; median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e23 (6\u0026ndash;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e23 (6\u0026ndash;60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRisk stratification\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eSimplified PESI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e155 (18.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e155 (19.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e\u0026ge;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e665 (81.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e639 (80.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e26 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eBova score (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e4 (2\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e4 (2\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e5 (4\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003eBova stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.6125%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e272 (41.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e271 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e1 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\" style=\"width: 6.6125%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e236 (36.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e227 (36.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e9 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 32.361%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 15.2287%;\"\u003e\n \u003cp\u003e143 (22.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 23.9451%;\"\u003e\n \u003cp\u003e129 (20.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.2249%;\"\u003e\n \u003cp\u003e14 (58.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\" style=\"width: 92.4742%;\"\u003e\n \u003cp\u003eBSA\u0026thinsp;=\u0026thinsp;body surface area, CTPA\u0026thinsp;=\u0026thinsp;computed tomography pulmonary angiography, DVT\u0026thinsp;=\u0026thinsp;deep vein thrombosis, IQR\u0026thinsp;=\u0026thinsp;interquartile range, n\u0026thinsp;=\u0026thinsp;number of patients with measurements; NT-proBNP\u0026thinsp;=\u0026thinsp;brain natriuretic peptide, PESI\u0026thinsp;=\u0026thinsp;pulmonary embolism severity index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eThere were no differences in the patient age, sex, comorbidities, or symptoms between patients with and without an event. There was no difference in heart rate, blood pressure, or the need for supplemental oxygen between patients with and without an event. Most patients were diagnosed by CTPA. The sPESI score was \u0026ge;1 in 80.5% of those without an event and 100% in those with an event (p\u0026thinsp;=\u0026thinsp;0.01). The Bova score and stages [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e] were higher in patients with an event than those without (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec12\"\u003e\n \u003ch2\u003eEchocardiographic findings\u003c/h2\u003e\n \u003cp\u003eEchocardiographic findings are shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Echocardiography was performed sooner for those who experienced a primary outcome event (6.3 hours, IQR 1.0\u0026ndash;15.0 vs. 17 hours, IQR 8.1\u0026ndash;25.6; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Tricuspid annular plane systolic excursion, SVI, and FAC were all lower in patients with an event compared to those without (all had p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Pulmonary artery systolic pressure (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and RV/LV (p\u0026thinsp;=\u0026thinsp;0.002) were greater in patients with an event compared to those without. Patients with an event had lower TAPSE/PASP, FAC/PASP, and SVI/PASP compared to those without an event (all had p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Patients with an event were more likely to have subjective RVD determined by the initial clinical reading echocardiographer (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u0026nbsp;\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eImaging findings of patients with normotensive acute pulmonary embolism.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 31.9621%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003eAll\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;820)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003eFree from PE-related event (n\u0026thinsp;=\u0026thinsp;794)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003ePE-related event\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComputed Tomography Pulmonary Angiography\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eRV/LV diameter ratio; median (IQR, n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e1.2 (0.9\u0026ndash;1.6); 753\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e1.2 (0.9\u0026ndash;1.6); 729\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e1.9 (1.6\u0026ndash;2.1); 24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRV structure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eRV/LV base diameter ratio; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e1.1 (0.9\u0026ndash;1.3); 643\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e1.1 (0.9\u0026ndash;1.3); 628\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e1.3 (1.1\u0026ndash;1.4); 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eRV base diameter, cm; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e4.2 (3.7\u0026ndash;4.9); 647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e4.3 (3.7\u0026ndash;4.8); 632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e4.5 (4.2\u0026ndash;5.2); 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eRV diastolic area, cm\u003csup\u003e2\u003c/sup\u003e; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e27.9 (22.5\u0026ndash;33.8); 632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e27.8 (22.4\u0026ndash;33.7); 616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e31.7 (28.0-38.7); 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eRV systolic area, cm\u003csup\u003e2\u003c/sup\u003e; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e18.4 (13.5\u0026ndash;24.8); 632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e18.3 (13.4\u0026ndash;24.5); 616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e26.0 (21.0-31.9); 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRV function\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eTAPSE, mm; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e18.7 (14.9\u0026ndash;22.6); 763\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e18.8 (15-22.8); 740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e13 (9.8\u0026ndash;18.1); 23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eFAC, %; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e33.9 (23.8\u0026ndash;42.5); 632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e34.2 (23.9\u0026ndash;42.6); 616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e26.1 (21.1\u0026ndash;31.9); 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubjective right ventricular dysfunction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e345 (43.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e343 (44.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e158 (20.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e156 (20.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e2 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e213 (27.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e205 (26.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e8 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e72 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e61 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e11 (47.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdditional findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eMcConnell\u0026rsquo;s sign\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e32 (3.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e29 (3.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e3 (11.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eCardiac thrombus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e19 (2.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e15 (1.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e4 (15.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003ePEITHO right ventricular dysfunction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e636 (77.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e614 (77.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e22 (84.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary pressures\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eRA pressure (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e265 (32.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e263 (33.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e2 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"3\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e266 (32.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e260 (33.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e6 (24.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e237 (29.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e222 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e15 (60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eIndeterminate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e42 (5.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e40 (5.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e2 (8.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003ePASP, mmHg; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e44 (33.8\u0026ndash;55.7); 603\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e43.1 (33.7\u0026ndash;55.1); 585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e60.9 (50.2\u0026ndash;68.7); 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac output\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eStroke volume, mL; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e57.4 (45.4\u0026ndash;69.4); 723\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e57.9 (46.3\u0026ndash;69.7); 705\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e34.4 (30.1\u0026ndash;41.6); 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eSVI, mL/m\u003csup\u003e2\u003c/sup\u003e; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e28.2 (22.8\u0026ndash;34.7); 723\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e28.5 (22.9\u0026ndash;35.5); 705\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e17.6 (15.5\u0026ndash;20.0); 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRV-PA Coupling\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eTAPSE/PASP, mm/mmHg; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e0.40 (0.28\u0026ndash;0.59); 572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e0.41 (0.28\u0026ndash;0.59); 556\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e0.21 (0.17\u0026ndash;0.31); 16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eFAC/PASP, %/mmHg; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e0.67 (0.45\u0026ndash;1.09); 493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e0.68 (0.46\u0026ndash;1.10); 480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e0.34 (0.27\u0026ndash;0.65); 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 31.9621%;\"\u003e\n \u003cp\u003eSVI/PASP, mL/mmHg; median (IQR), n\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 14.4567%;\"\u003e\n \u003cp\u003e0.63 (0.43\u0026ndash;0.93); 583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 22.7177%;\"\u003e\n \u003cp\u003e0.65 (0.44\u0026ndash;0.92); 566\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 13.8666%;\"\u003e\n \u003cp\u003e0.26 (0.23\u0026ndash;0.35); 17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.5891%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\" style=\"width: 90.7724%;\"\u003e\n \u003cp\u003eFAC\u0026thinsp;=\u0026thinsp;fractional area change; IQR\u0026thinsp;=\u0026thinsp;interquartile range; n\u0026thinsp;=\u0026thinsp;number of patients with measurement PASP\u0026thinsp;=\u0026thinsp;pulmonary artery systolic pressure; RV\u0026thinsp;=\u0026thinsp;right ventricle; RV/LV\u0026thinsp;=\u0026thinsp;right to left ventricular diameter ratio, SVI\u0026thinsp;=\u0026thinsp;stroke volume index; TAPSE\u0026thinsp;=\u0026thinsp;tricuspid annular plane systolic excursion; TR\u0026thinsp;=\u0026thinsp;tricuspid regurgitation; TTE\u0026thinsp;=\u0026thinsp;transthoracic echocardiogram\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec13\"\u003e\n \u003ch2\u003eVentricular-arterial coupling\u003c/h2\u003e\n \u003cp\u003eEchocardiography-derived RV-PA coupling parameters were strongly associated with PE-related adverse events, PE-related mortality, and all-cause mortality (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Neither the PEITHO trial definition of RVD (OR 1.61, 95% CI 0.55\u0026ndash;4.74; p\u0026thinsp;=\u0026thinsp;0.385; n\u0026thinsp;=\u0026thinsp;813) nor high sensitivity troponin T (OR 1.00, 95% CI 0.997\u0026ndash;1.002; n\u0026thinsp;=\u0026thinsp;705) were associated with PE-related adverse events. In multivariate analysis with subjective TTE-derived RVD, CTPA RV/LV ratio, and the Bova score, only TAPSE/RVSP (p\u0026thinsp;=\u0026thinsp;0.044) and SVI/RVSP (p\u0026thinsp;=\u0026thinsp;0.002) were independently associated with PE-related adverse events while FAC/RVSP was not (p\u0026thinsp;=\u0026thinsp;0.308) (Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eLogistic regression analysis of ventricular-arterial coupling parameters for composite PE-related adverse events, PE-related mortality, and all-cause mortality\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 20.7521%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003eNumber of Patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003eCrude OR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003eAdjusted OR*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eComposite PE-related event\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eTAPSE/PASP (per 0.1 mm/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e2.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.47\u0026ndash;4.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.46\u0026ndash;4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eSVI/PASP (per 0.1 mL/mmHg\u0026bull;m\u003csup\u003e2\u003c/sup\u003e decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e2.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.73\u0026ndash;4.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e2.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.72\u0026ndash;4.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eFAC/PASP (per 0.1%/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.10\u0026ndash;1.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.09\u0026ndash;1.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePE-related mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eTAPSE/PASP (per 0.1 mm/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e2.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.18\u0026ndash;7.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e2.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.16\u0026ndash;7.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eSVI/PASP (per 0.1 mL/mmHg\u0026bull;m\u003csup\u003e2\u003c/sup\u003e decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e2.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.32\u0026ndash;6.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e2.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.32\u0026ndash;6.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eFAC/PASP (per 0.1%/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.00-1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e1.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.00-1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAll-cause mortality\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eTAPSE/PASP (per 0.1 mm/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e572\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e1.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.19\u0026ndash;2.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e1.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.18\u0026ndash;2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eSVI/PASP (per 0.1 mL/mmHg\u0026bull;m\u003csup\u003e2\u003c/sup\u003e decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.11\u0026ndash;1.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.12\u0026ndash;1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 20.7521%;\"\u003e\n \u003cp\u003eFAC/PASP (per 0.1%/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.3396%;\"\u003e\n \u003cp\u003e493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.262%;\"\u003e\n \u003cp\u003e1.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.01\u0026ndash;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 8.5921%;\"\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5339%;\"\u003e\n \u003cp\u003e1.01\u0026ndash;1.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6601%;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\" style=\"width: 67.2076%;\"\u003e\n \u003cp\u003e*Adjusted for age and sex. CI\u0026thinsp;=\u0026thinsp;confidence interval; FAC\u0026thinsp;=\u0026thinsp;fractional area change; OR\u0026thinsp;=\u0026thinsp;odds ratio; PE\u0026thinsp;=\u0026thinsp;pulmonary embolism; PASP\u0026thinsp;=\u0026thinsp;pulmonary artery systolic pressure; SVI\u0026thinsp;=\u0026thinsp;stroke volume index; TAPSE\u0026thinsp;=\u0026thinsp;tricuspid annular plane systolic excursion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate and multivariate logistic regression analysis for PE-related of RV-PA coupling parameters compared to subjective assessment of RVD, the Bova score, and the CR RV/LV ratio.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of Patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSubjective right ventricular dysfunction (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.07\u0026ndash;5.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBova Score (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e650\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.39\u0026ndash;2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCTPA RV/LV ratio (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e755\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.58\u0026ndash;22.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTAPSE/PASP (per 0.1 mm/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.02\u0026ndash;3.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSubjective right ventricular dysfunction (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u0026ndash;4.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBova Score (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u0026ndash;4.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCTPA RV/LV ratio (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u0026ndash;11.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSVI/PASP (per 0.1 mL/mmHg\u0026bull;m\u003csup\u003e2\u003c/sup\u003e decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e457\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.35\u0026ndash;3.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSubjective right ventricular dysfunction (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71\u0026ndash;3.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBova Score (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65\u0026ndash;1.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.673\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCTPA RV/LV ratio (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37-12.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFAC/PASP (per 0.1%/mmHg decrease)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"4\"\u003e\n \u003cp\u003e386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87\u0026ndash;1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSubjective right ventricular dysfunction (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u0026ndash;4.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBova Score (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63\u0026ndash;1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.717\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCTPA RV/LV ratio (per unit increase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u0026ndash;15.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eCTPA RV/LV\u0026thinsp;=\u0026thinsp;computed tomography right to left ventricular diameter ratio; FAC\u0026thinsp;=\u0026thinsp;fractional area change; OR\u0026thinsp;=\u0026thinsp;odds ratio; PE\u0026thinsp;=\u0026thinsp;pulmonary embolism; PASP\u0026thinsp;=\u0026thinsp;pulmonary artery systolic pressure; RVD\u0026thinsp;=\u0026thinsp;right ventricular dysfunction; SVI\u0026thinsp;=\u0026thinsp;stroke volume index; TAPSE\u0026thinsp;=\u0026thinsp;tricuspid annular plane systolic excursion.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eReceiver operating characteristic analysis was performed to assess the diagnostic performances of TAPSE/PASP, SVI/PASP, FAC/PASP (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The area under curve (AUC) for TAPSE/PASP was 0.81 (CI 0.68\u0026ndash;0.87), SVI/PASP was 0.89 (CI 0.83\u0026ndash;0.96), and FAC/PASP 0.77 (CI 0.64\u0026ndash;0.90). While SVI/PASP had a higher AUC compared to FAC/PASP (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) it only trended towards being greater than TAPSE/PASP (p\u0026thinsp;=\u0026thinsp;0.13). There was no difference between FAC/PASP and TAPSE/PASP (p\u0026thinsp;=\u0026thinsp;0.678). The diagnostic performance indices for each RV-PA variable are shown in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. There was no difference in the diagnostic performance indices between each RV-PA variable although confidence intervals were large.\u003c/p\u003e\n \u003ctable border=\"1\" id=\"Tab5\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDiagnostic performance characteristics for TTE-derived measures of right ventricular dysfunction.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTTE Parameter and Youden Index\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity (%)\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpecificity (%)\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePPV (%)\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNPV (%)\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePositive LR\u003c/p\u003e\n \u003cp\u003e(95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNegative LR (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTAPSE/PASP\u0026thinsp;\u0026lt;\u0026thinsp;0.29 mm/mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.0 (47.6\u0026ndash;92.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e72.1 (68.2\u0026ndash;75.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.2 (3.8\u0026ndash;12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.0 (97.5\u0026ndash;99.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7 (2.0-3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.3 (0.1\u0026ndash;0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSVI/PASP\u0026thinsp;\u0026lt;\u0026thinsp;0.36 mL/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82.4 (56.6\u0026ndash;96.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.8 (75.4\u0026ndash;82.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.7 (5.4\u0026ndash;15.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.4 (98.2\u0026ndash;99.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.9 (3.0-5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2 (0.1\u0026ndash;0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFAC/PASP\u0026thinsp;\u0026lt;\u0026thinsp;0.35%/mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69.2 (38.6\u0026ndash;90.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.3 (82.8\u0026ndash;89.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.0 (5.6\u0026ndash;21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99.0 (97.6\u0026ndash;99.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0 (3.3\u0026ndash;7.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.4 (0.2\u0026ndash;0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eFAC\u0026thinsp;=\u0026thinsp;fractional area change; LR\u0026thinsp;=\u0026thinsp;likelihood ratio; NPV\u0026thinsp;=\u0026thinsp;negative predictive value; PPV\u0026thinsp;=\u0026thinsp;positive predictive value; PASP\u0026thinsp;=\u0026thinsp;pulmonary artery systolic pressure; SVI\u0026thinsp;=\u0026thinsp;stroke volume index; TTE\u0026thinsp;=\u0026thinsp;transthoracic echocardiogram\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study showed that TTE-derived estimates of RV-PA coupling including FAC/PASP, and TAPSE/PASP and SVI/PASP were associated with PE-related adverse events in 820 normotensive patients with PE. The TAPSE/PASP and SVI/PASP had incremental value to the Bova score and CTPA RV/LV ratio, and subjective assessment of TTE-derived RVD in discriminating PE-related adverse events. These findings provide important insights into the importance of RV-PA coupling in the pathophysiology of hemodynamic decompensation in PE. Additionally, it underscores the challenges in identifying a universal TTE-derived prognostic marker to risk stratify normotensive patients, who represent a significant proportion of patients with PE. Lastly\u003c/p\u003e \u003cp\u003eThis is the first study to assess the association of multiple parameters of RV-PA coupling with PE-related adverse events in the same cohort of patients and directly compare its utility against other markers RVD and risk stratification tools. Importantly, this study showed that in multivariate analysis with CTPA-derived RV/LV, the Bova score and subjective TTE assessment of RVD, SVI/PASP and TAPSE/PASP were both independently associated with PE-related adverse events. This suggests that RV-PA coupling has additive prognostic value beyond RVD identified by CTPA or clinical risk prediction scores, and it underscores the importance of quantitative assessment of RVD over subjective assessment alone. We also demonstrated that the conventional definition of RVD used in the PEITHO trial was not associated with adverse PE-related events in our population, while quantitative TTE measures including RV-PA coupling indices were strongly associated. Conventional definitions of RVD are ubiquitous in this population being present in 37% of patients with normotensive PE emphasizing the importance of more specific tools for identifying patients at heightened risk of adverse events [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. This may be one reason that the PEITHO trial was unable to show a net benefit from systemic thrombolysis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It suggests that future trials of thrombolysis or invasive catheter directed therapies may need to use a different definition for TTE-derived RVD that is more strongly associated with adverse events.\u003c/p\u003e \u003cp\u003e\u003cem\u003eCiurzyński et al.\u003c/em\u003e was the first to evaluate an RV-PA coupling parameter in PE using a stepwise approach to risk stratification with tricuspid annular plane systolic excursion (TAPSE)\u0026thinsp;\u0026lt;\u0026thinsp;20mm followed by the ratio of tricuspid regurgitation peak gradient divided by TAPSE [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. More recently, studies by \u003cem\u003eKamran et al.\u003c/em\u003e evaluated pulmonary artery systolic pressure (PASP) divided by left ventricular stroke volume and \u003cem\u003eLyhne et al.\u003c/em\u003e and \u003cem\u003eFalsetti et al.\u003c/em\u003e evaluated TAPSE/PASP showing that these markers were associated with adverse outcomes in PE [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. \u003cem\u003eKamran et al.\u003c/em\u003e concluded that PASP/left ventricular stroke volume was superior to the velocity time integral (VTI) although this was done comparing continuous odds ratios with different units [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, \u003cem\u003eFalsetti et al\u003c/em\u003e. found no difference in the association with adverse outcomes between TAPSE/PASP and VTI when comparing categorical odds ratios. Echocardiographic markers of RV-PA coupling and stroke volume all seem to have competitive risk stratification potential. However, it is unlikely that identifying an incrementally superior single TTE-derived markers of RVD will dramatically change outcomes of risk stratification. Instead, current guidelines appropriately promote a multimodality approach using clinical, biochemical, and radiologic markers of risk [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. We did not directly compare markers of RV-PA coupling directly with other quantitative measures of RVD due to lack of statistical power for meaningful comparisons and because most of the quantitative measures of RVD in this study are components of the RV-PA parameters.\u003c/p\u003e \u003cp\u003eAs pulmonary vascular resistance increases, there is an inverse nonlinear relationship in the compliance [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In turn, this results in an exaggerated RV pulsatile load, RV ejection pressure, and increased RV stroke work, all of which contribute to RV failure [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The cardiovascular system operates in dynamic state whereby ventricular contractility is coupled with arterial afterload, otherwise known as ventricular-arterial coupling. Accordingly, in response to increased pulmonary artery pressures, the RV undergoes adaptive changes to increase contractility and preserve RV-PA coupling. RV-PA decoupling occurs when the RV contractility fails to match arterial afterload resulting in RV failure and hemodynamic decompensation thereafter. In the case of PE, this may result from excessive arterial elastance, direct impairment of RV contractility by cardiac ischemia, and the harmful RV-LV interaction whereby abnormal septal motion impairs left ventricular filling and resulting left sided stroke volume [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The fact that TAPSE/PASP, FAC/PASP, and SVI/PASP were all strongly associated with PE-related adverse events strengthens the finding that RV-PA decoupling is implicated in the pathophysiology of hemodynamic decompensation. SVI uniquely measures the most downstream hemodynamic effect of a PE, which not only decreases during RV-PA decoupling but also when left ventricular filling is impaired due to abnormal septal movement towards the left ventricle.\u003c/p\u003e \u003cp\u003eIndices of RV-PA coupling including SVI/PASP, FAC/PASP, and TAPSE/PASP were strongly associated with adverse in-hospital PE-related events in patients with normotensive PE. Stroke volume index, TAPSE and PASP are simple measurements that are easily obtainable during standard TTE. While FAC/PASP was associated with adverse PE-related events, FAC requires accurate RV endocardial contouring in both systole and diastole which may be difficult to perform reliably in clinical practice. The RV can be particularly challenging to accurately image due to its asymmetric shape and is prone to off axis imaging which may falsely estimate its function. The utility of direct assessment of RV size and function may be more limited due to these factors. Another challenge can be in obtaining a complete doppler signal to calculate the PASP. In this study, PASP could be determined in only 603 patients, FAC was only possible in 632 patients compared to TAPSE that was measurable in 763 patients and SVI that was measurable in 795 patients. These RV-PA coupling parameters represent multiple potential measurements that can be obtained during a standard TTE to identify normotensive patients at higher risk of PE-related mortality or hemodynamic decompensation. These parameters could have the potential to enrich future clinical trials of invasive therapies (i.e. thrombolytic therapy or catheter directed therapies) with truly intermediate-high risk patients. Future prospective prognostic studies are required to determine the feasibility of performing these measurements and validate these retrospective findings.\u003c/p\u003e \u003cp\u003eThis study has several limitations. Our cohort had only 26 adverse PE-related events (3.2%). This is in part due to the more stringent definition of PE-related mortality rather than all-cause mortality. In our study, markers of RV-PA coupling were less associated with all-cause mortality than PE-related mortality. This is because all-cause mortality is less related to the underlying pathophysiologic mechanism of mortality in PE and is therefore likely of less suitable outcome than PE-related mortality when evaluating echocardiographic measurements. However, our event rates are similar to other unselected PE populations assessing RV-PA coupling such as \u003cem\u003eCiurzyński et al\u003c/em\u003e. where 8/400 (2%) PE-related death or hemodynamic decompensation [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and \u003cem\u003eFalsetti et al.\u003c/em\u003e where 10/256 (3.9%) had in-hospital mortality [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Data collection was retrospective and some TTE parameters were unavailable as they were not recorded routinely but at the discretion of the echocardiography technologist. At least one of FAC/PASP, TAPSE/PASP, or SVI/PASP was only possible in 599/820 (73%) of patients. This means that in 27% of patients another simpler marker of TTE-derived RVD must be used. This seems consistent with \u003cem\u003eKamran et al.\u003c/em\u003e who reported that only 215/343 (63%) patients that met inclusion had complete data for analysis, and \u003cem\u003eFalsetti et al.\u003c/em\u003e who reported that only 270/326 (83%) patients had complete data [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Lastly, because performing a TTE was at the discretion of the attending physician, there have been some selection bias in this cohort (only 820/2067 patients had a TTE within 48 hours of diagnosis). Despite this, we saw similar event rates compared to other contemporary studies assessing RV-PA coupling parameters.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn patients with normotensive acute pulmonary embolism, TTE-derived RV-PA coupling parameters including TAPSE/PASP and FAC/PASP and SVI/PASP were associated with adverse in-hospital PE-related events with TAPSE/PASP and SVI/PASP being independent of CTPA-derived RV/LV, the Bova score, and subjective TTE assessment of RVD. Future prospective studies evaluating TTE-derived RVD including markers of RV-PA coupling are required to validate these findings and identify whether a single or multivariable approach is most valuable for prognostication of PE-related adverse events using TTE.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Omid Kiamanesh, Kevin Solverson, Graeme Prosperi-Porta, and Jason Weatherald. The first draft of the manuscript was written by Omid Kiamanesh and Graeme Prosperi-Porta and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGoldhaber SZ, Elliott CG. Acute pulmonary embolism: part I: epidemiology, pathophysiology, and diagnosis. Circulation. 2003;108:2726-9.https://doi.org/10.1161/01.Cir.0000097829.89204.0c\u003c/li\u003e\n\u003cli\u003eCho JH, Kutti Sridharan G, Kim SH, Kaw R, Abburi T, Irfan A, et al. Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis. BMC Cardiovasc Disord. 2014;14:64.https://doi.org/10.1186/1471-2261-14-64\u003c/li\u003e\n\u003cli\u003eBarco S, Mahmoudpour SH, Planquette B, Sanchez O, Konstantinides SV, Meyer G. Prognostic value of right ventricular dysfunction or elevated cardiac biomarkers in patients with low-risk pulmonary embolism: a systematic review and meta-analysis. European Heart Journal. 2019;40:902-10.https://doi.org/10.1093/eurheartj/ehy873\u003c/li\u003e\n\u003cli\u003eMeyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J, et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. New England Journal of Medicine. 2014;370:1402-11.https://doi.org/10.1056/NEJMoa1302097\u003c/li\u003e\n\u003cli\u003eJentzer JC, Anavekar NS, Reddy YNV, Murphree DH, Wiley BM, Oh JK, et al. Right Ventricular Pulmonary Artery Coupling and Mortality in Cardiac Intensive Care Unit Patients. Journal of the American Heart Association. 2021;10:e019015.https://doi.org/10.1161/JAHA.120.019015\u003c/li\u003e\n\u003cli\u003eKonstantinides SV, Meyer G, Becattini C, Bueno H, Geersing G-J, Harjola V-P, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). European Heart Journal. 2019;41:543-603.https://doi.org/10.1093/eurheartj/ehz405\u003c/li\u003e\n\u003cli\u003eCiurzyński M, Kurnicka K, Lichodziejewska B, Kozłowska M, Pływaczewska M, Sobieraj P, et al. Tricuspid Regurgitation Peak Gradient (TRPG)/Tricuspid Annulus Plane Systolic Excursion (TAPSE) - A Novel Parameter for Stepwise Echocardiographic Risk Stratification in Normotensive Patients With Acute Pulmonary Embolism. Circ J. 2018;82:1179-85.https://doi.org/10.1253/circj.CJ-17-0940\u003c/li\u003e\n\u003cli\u003eLyhne MD, Kabrhel C, Giordano N, Andersen A, Nielsen-Kudsk JE, Zheng H, et al. The echocardiographic ratio tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure predicts short-term adverse outcomes in acute pulmonary embolism. Eur Heart J Cardiovasc Imaging. 2021;22:285-94.https://doi.org/10.1093/ehjci/jeaa243\u003c/li\u003e\n\u003cli\u003eKamran H, Hariri EH, Iskandar JP, Sahai A, Haddadin I, Harb SC, et al. Simultaneous Pulmonary Artery Pressure and Left Ventricle Stroke Volume Assessment Predicts Adverse Events in Patients With Pulmonary Embolism. J Am Heart Assoc. 2021;10:e019849.https://doi.org/10.1161/JAHA.120.019849\u003c/li\u003e\n\u003cli\u003eFalsetti L, Marra AM, Zaccone V, Sampaolesi M, Riccomi F, Giovenali L, et al. Echocardiographic predictors of mortality in intermediate-risk pulmonary embolism. Internal and Emergency Medicine. 2022.https://doi.org/10.1007/s11739-021-02910-w\u003c/li\u003e\n\u003cli\u003eBajaj A, Rathor P, Sehgal V, Kabak B, Shetty A, Al Masalmeh O, et al. Prognostic Value of Biomarkers in Acute Non-massive Pulmonary Embolism: A Systematic Review and Meta-analysis. Lung. 2015;193:639-51.https://doi.org/10.1007/s00408-015-9752-4\u003c/li\u003e\n\u003cli\u003eMeinel FG, Nance JW, Jr., Schoepf UJ, Hoffmann VS, Thierfelder KM, Costello P, et al. Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis. Am J Med. 2015;128:747-59.e2.https://doi.org/10.1016/j.amjmed.2015.01.023\u003c/li\u003e\n\u003cli\u003eBova C, Sanchez O, Prandoni P, Lankeit M, Konstantinides S, Vanni S, et al. Identification of intermediate-risk patients with acute symptomatic pulmonary embolism. Eur Respir J. 2014;44:694-703.https://doi.org/10.1183/09031936.00006114\u003c/li\u003e\n\u003cli\u003eProsperi-Porta G, Solverson K, Fine N, Humphreys CJ, Ferland A, Weatherald J. Echocardiography-Derived Stroke Volume Index Is Associated With Adverse In-Hospital Outcomes in Intermediate-Risk Acute Pulmonary Embolism: A Retrospective Cohort Study. Chest. 2020;158:1132-42.https://doi.org/10.1016/j.chest.2020.02.066\u003c/li\u003e\n\u003cli\u003eSolverson K, Humphreys C, Liang Z, Prosperi-Porta G, Andruchow JE, Boiteau P, et al. Rapid prediction of adverse outcomes for acute normotensive pulmonary embolism: derivation of the Calgary Acute Pulmonary Embolism (CAPE) score. ERJ Open Research. 2021:00879-2020.https://doi.org/10.1183/23120541.00879-2020\u003c/li\u003e\n\u003cli\u003eJiménez D, Aujesky D, Moores L, Gómez V, Lobo JL, Uresandi F, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170:1383-9.https://doi.org/10.1001/archinternmed.2010.199\u003c/li\u003e\n\u003cli\u003eMitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, et al. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography. Journal of the American Society of Echocardiography. 2019;32:1-64.https://doi.org/10.1016/j.echo.2018.06.004\u003c/li\u003e\n\u003cli\u003eLang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1-39.e14.https://doi.org/10.1016/j.echo.2014.10.003\u003c/li\u003e\n\u003cli\u003eRudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23:685-713; quiz 86-8.https://doi.org/10.1016/j.echo.2010.05.010\u003c/li\u003e\n\u003cli\u003eSchmeisser A, Rauwolf T, Groscheck T, Kropf S, Luani B, Tanev I, et al. Pressure-volume loop validation of TAPSE/PASP for right ventricular arterial coupling in heart failure with pulmonary hypertension. Eur Heart J Cardiovasc Imaging. 2021;22:168-76.https://doi.org/10.1093/ehjci/jeaa285\u003c/li\u003e\n\u003cli\u003eTello K, Wan J, Dalmer A, Vanderpool R, Ghofrani HA, Naeije R, et al. Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension. Circ Cardiovasc Imaging. 2019;12:e009047.https://doi.org/10.1161/circimaging.119.009047\u003c/li\u003e\n\u003cli\u003eGuazzi M, Dixon D, Labate V, Beussink-Nelson L, Bandera F, Cuttica MJ, et al. RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes and Outcomes. JACC Cardiovasc Imaging. 2017;10:1211-21.https://doi.org/10.1016/j.jcmg.2016.12.024\u003c/li\u003e\n\u003cli\u003eTello K, Ghofrani HA, Heinze C, Krueger K, Naeije R, Raubach C, et al. A simple echocardiographic estimate of right ventricular-arterial coupling to assess severity and outcome in pulmonary hypertension on chronic lung disease. Eur Respir J. 2019;54.https://doi.org/10.1183/13993003.02435-2018\u003c/li\u003e\n\u003cli\u003eTello K, Axmann J, Ghofrani HA, Naeije R, Narcin N, Rieth A, et al. Relevance of the TAPSE/PASP ratio in pulmonary arterial hypertension. Int J Cardiol. 2018;266:229-35.https://doi.org/10.1016/j.ijcard.2018.01.053\u003c/li\u003e\n\u003cli\u003ePapolos A, Fan E, Wagle RR, Foster E, Boyle AJ, Yeghiazarians Y, et al. Echocardiographic determination of pulmonary arterial capacitance. Int J Cardiovasc Imaging. 2019;35:1581-6.https://doi.org/10.1007/s10554-019-01595-9\u003c/li\u003e\n\u003cli\u003eYouden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32-5.https://doi.org/10.1002/1097-0142(1950)3:1\u0026lt;32::aid-cncr2820030106\u0026gt;3.0.co;2-3\u003c/li\u003e\n\u003cli\u003eTedford RJ, Hassoun PM, Mathai SC, Girgis RE, Russell SD, Thiemann DR, et al. Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading. Circulation. 2012;125:289-97.https://doi.org/10.1161/CIRCULATIONAHA.111.051540\u003c/li\u003e\n\u003cli\u003eVonk-Noordegraaf A, Haddad F, Chin KM, Forfia PR, Kawut SM, Lumens J, et al. Right heart adaptation to pulmonary arterial hypertension: physiology and pathobiology. J Am Coll Cardiol. 2013;62:D22-33.https://doi.org/10.1016/j.jacc.2013.10.027\u003c/li\u003e\n\u003cli\u003eWang Z, Chesler NC. Pulmonary vascular wall stiffness: An important contributor to the increased right ventricular afterload with pulmonary hypertension. Pulm Circ. 2011;1:212-23.https://doi.org/10.4103/2045-8932.83453\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-international-journal-of-cardiovascular-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caim","sideBox":"Learn more about [The International Journal of Cardiovascular Imaging](https://www.springer.com/journal/10554)","snPcode":"10554","submissionUrl":"https://submission.nature.com/new-submission/10554/3","title":"The International Journal of Cardiovascular Imaging","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pulmonary embolism, transthoracic echocardiography, right ventricular dysfunction, right ventricle-pulmonary artery coupling","lastPublishedDoi":"10.21203/rs.3.rs-1598950/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1598950/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eDuring acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and right ventricular fractional area change (FAC)/PASP as well as stroke volume index (SVI)/PASP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1mm/mmHg decrease in TAPSE/PASP the odds of an adverse event increased by 2.5-fold (adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46\u0026ndash;4.24, p\u0026thinsp;=\u0026thinsp;0.001), for every 0.1%/mmHg decrease in FAC/PASP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09\u0026ndash;1.86, p\u0026thinsp;=\u0026thinsp;0.010), and for every 0.1mL/mmHg\u0026bull;m\u003csup\u003e2\u003c/sup\u003e decrease in SVI/PASP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72\u0026ndash;4.50, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In multivariate analysis, TAPSE/PASP and SVI/PASP were independent of other risk stratification methods including computed tomography-derived RVD, the Bova score, and subjective assessment of TTE-derived RVD.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eIn patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are strongly associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD.\u003c/p\u003e","manuscriptTitle":"Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-04-29 16:29:13","doi":"10.21203/rs.3.rs-1598950/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-05-15T18:00:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-05-11T22:58:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-05-10T20:46:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"cf61f616-83ea-441c-b7ae-6608cc59a90e","date":"2022-04-30T13:58:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"311f377f-04b9-4482-9109-f2205cfe01f6","date":"2022-04-30T12:26:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-04-27T12:06:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-04-27T06:49:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-04-27T06:49:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"The International Journal of Cardiovascular Imaging","date":"2022-04-27T01:28:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-international-journal-of-cardiovascular-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caim","sideBox":"Learn more about [The International Journal of Cardiovascular Imaging](https://www.springer.com/journal/10554)","snPcode":"10554","submissionUrl":"https://submission.nature.com/new-submission/10554/3","title":"The International Journal of Cardiovascular Imaging","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5476e4d2-bf02-430a-a951-634d6f98968c","owner":[],"postedDate":"April 29th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-06-16T06:59:26+00:00","versionOfRecord":[],"versionCreatedAt":"2022-04-29 16:29:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1598950","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1598950","identity":"rs-1598950","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}