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Background:  Contemporary Australian epidemiological data on acute pulmonary embolism (PE) are lacking., Objectives:  To determine the admission rates of acute PE in Australia, and to assess the temporal trends in short- and medium-term mortality following acute PE., Methods:  Retrospective population-linkage study of all New South Wales residents admitted with a primary diagnosis of PE between January 1, 2002 and December 31, 2018 using data from the Centre for Health Record Linkage databases. Main outcome measures included temporal trends in total PE admissions and all-cause mortality at prespecified time points up to 1 year, stratified by gender., Results:  There were 61,607 total PE admissions between 2002 and 2018 (mean ± standard deviation: 3,624 ± 429 admissions per annum; 50.42 ± 3.70 admissions per 100,000 persons per annum). The mean admission rate per annum was higher for females than for males (54.85 ± 3.65 vs. 44.91 ± 4.34 admissions per 100,000 persons per annum, respectively) and remained relatively stable for both genders throughout the study period. The main study cohort, limited to index PE admission only, comprised 46,382 persons (mean age: 64.6 ± 17.3 years; 44.4% males). The cumulative in-hospital, 30-day, 3-month, and 1-year mortality rates were 3.7, 5.6, 9.6, and 16.8%, respectively. When compared with 2002 as the reference year, there was a significant reduction in in-hospital (odds ratio [OR] = 0.34; 95% confidence interval [CI] = 0.25-0.46), 30-day (OR = 0.58, 95% CI = 0.46-0.73), and 1-year (hazard ratio = 0.74, 95% CI = 0.66-0.84) (all p  < 0.001) mortality risk by 2017 after adjusting for age, gender, and relevant confounders. The survival improvements were seen in both genders and were greater for females than for males., Conclusion:  Mortality following PE has improved with reductions observed in both short- and medium-term follow-ups between 2002 and 2018 with greater reductions in females despite their higher admission rates over time., Competing Interests: None declared., (Thieme. All rights reserved.)

Right atrial (RA) and right ventricular (RV) parameters assessed by traditional echocardiography lack sensitivity to identify pulmonary embolism (PE). We sought to determine if alterations in RV free wall longitudinal strain (FWS) would be present in PE patients and improve evaluation. This retrospective study comprised of 84 consecutive PE patients from 2 centres, with adequate transthoracic echocardiography (TTE) images for RV FWS analysis. PE patients were compared to 66 healthy controls. Compared to controls, PE patients had increased RV parasternal long-axis diameter (RVPLAX) (33.4 ± 5.8 mm vs 39.9 ± 4.1 mm) and RA area (17.4 ± 5.6 cm 2 vs 14.5 ± 3.1 cm 2 ) (p < 0.001 for both). RV function was reduced in PE patients (RV fractional area change 31.1 ± 13.2% vs 41.7 ± 9.1%, TAPSE 17.0 ± 4.5 vs 21.3 ± 2.2 mm; p < 0.001 for both). RV FWS was reduced in PE patients (-14.4 ± 7.2% vs - 26.0 ± 4.4%, p < 0.001). RV FWS was the best discriminator for PE (AUC 0.912). In comparative multiple logistic regression models for PE, the model which included traditional measures of RV size and function and RV FWS, produced a powerful classifier (AUC 0.966, SE 0.013) with significantly better performance (p < 0.022) than the model without RV FWS (AUC 0.921, SE 0.024). RV FWS is a discriminator of PE patients; addition of RV FWS to existing parameters of RV size and function, significantly improves sensitivity and specificity for diagnosis of PE, and may play a role in diagnosis and guiding therapy. Validation in other PE groups is required to confirm these observations and its prognostic value needs evaluation.

Background: Clinical features and outcomes of patients with hypoalbuminaemia in acute pulmonary embolism (PE) have never been studied. The present study investigated the incidence and determined the prognostic significance of hypoalbuminaemia in patients with confirmed acute PE., Methods: From a dedicated tertiary-referral centre database involving 1,426 consecutive patients admitted with confirmed PE (2000-2012), 1,032 patients had serum albumin assessed on admission (day-1). Patients were stratified into hypoalbuminaemia (<35 g/L) or normal serum albumin (≥35 g/L). Multivariable logistic and Cox proportional-hazards regression methods were used to assess 30-day and 90-day all-cause mortality., Results: Hypoalbuminaemia was present in 160 (15.5%) patients at day-1 and was associated with higher mean (±SD) heart rate (94.4 ± 21.8 vs 87.8 ± 21.5 bpm), lower systolic blood pressure (131.0 ± 24.7 vs 142.3 ± 24.7 mmHg), lower arterial oxyhaemoglobin saturation (93.3 ± 6.1% vs 95.6 ± 4.0%), lower day-1 serum sodium (137.0 ± 4.7 vs 138.8 ± 3.8 mmol/L) and haemoglobin levels (114.4 ± 20.7 vs 131.5 ± 18.7 g/L). Patients with hypoalbuminaemia had higher incidence of malignancy (44.4% vs 18.8%) and chronic renal disease (9.4% vs 5.2%), and at admission were less likely to be taking aspirin/clopidogrel (19.3% vs 27.7%) and more likely to be using enoxaparin (6.7% vs 3.0%). During a mean follow-up of 5.0 ± 4.0 years, patients with hypoalbuminaemia had higher 30-day (16.3% vs 3.6%) and 90-day (26.3% vs 6.2%) mortality. Multivariable analyses showed hypoalbuminaemia independently predicted both 30-day (odds ratio 2.57, 95% confidence interval [CI] 1.03-6.41) and 90-day (hazard ratio 2.42 95% CI 1.38-4.22) mortality., Conclusion: Hypoalbuminaemia is an independent predictor of mortality following PE and may improve risk stratification of patients in risk prediction models., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Pulmonary embolism (PE) is associated with a high mortality; whether echocardiographic evaluation at presentation predicts long-term adverse outcomes is of importance. We sought to determine if a composite of routinely obtained echocardiographic parameters could determine long-term adverse events in PE patients. Right ventricular (RV) size and function and right atrial (RA) size were retrospectively evaluated in 233 consecutive PE patients with an inpatient echocardiogram, and compared with 70 healthy controls; mortality at 3 years was confirmed. PE patients had increased RV size (RV parasternal long-axis diameter [RVPLAX] and RV end-diastolic volume [p < 0.001 for both]) and RA area (p < 0.001). RV function was reduced in PE patients (RV fractional area change and RV ejection fraction [p <0.001 for both]). Peak tricuspid regurgitation (TR) velocity was higher in the PE group. At follow-up (3.0 ± 2.1 years), 61 patients died; multivariable analysis demonstrated RVPLAX diameter >37 mm (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.3 to 4.2; p = 0.005), RA area >20 cm 2 (HR 2.0, 95% CI 1.1 to 3.5; p = 0.016), and TR velocity >2.9 ms -1 (HR 1.9, 95% CI 1.1 to 3.4; p = 0.021), were independent echocardiographic predictors of mortality. Patients with all 3 "risk markers" had ∼17-fold increased mortality compared with those with no "risk markers" (HR 16.9, 95% CI 6.1 to 47.2; p < 0.001). In conclusion, a composite of routinely collected echocardiographic parameters, namely an enlarged RA and RV (RVPLAX diameter), and TR velocity, were independent predictors of mortality in PE patients, with an exponential increase in mortality when all 3 parameters were significantly altered. Prospective validation is required to confirm these preliminary observations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Anaemia is associated with increased mortality in acute pulmonary embolism (PE) patients. However, prior studies have not examined the prognostic impact of trends in plasma haemoglobin during admission. This study investigates the impact of changes in haemoglobin level on mortality during hospital stay in acute PE., Study Design: A retrospective observational study., Setting: Tertiary-referral centre in Australia., Participants: Consecutive patients from 2000 to 2012 admitted with confirmed acute PE were identified from a dedicated PE database. Haemoglobin levels on days 1, 3-4, 5-6 and 7 of admission were retrieved. Patients without both baseline haemoglobin and subsequent haemoglobin levels were excluded (n=327), leaving 1099 patients as the study cohort. Anaemia was defined as haemoglobin <130 g/L for men and <120 g/L for women. There were 576 patients without anaemia throughout admission, 65 with transient anaemia (anaemic on day 1, but subsequently normalised during admission), 122 with acquired anaemia (normal on day 1 but developed anaemia during admission) and 336 with persistent anaemia. A total of 71 patients received blood transfusion during admission., Main Outcome Measure: 6-month mortality was tracked from a state-wide death database and analysed using multivariable modelling., Results: After adjusting for transfusion, patietns with persistent anaemia had a significantly increased 6-month mortality risk (adjusted HR 1.97, 95% CI 1.26 to 3.09, p=0.003) compared with patients without anaemia. There was no difference in mortality between patients with transient or acquired anaemia and patients without anaemia., Conclusion: Among patients who had anaemia during their admission for acute PE, only the subgroup with persistent anaemia demonstrated worse outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Congestive heart failure (CHF) is a risk factor for pulmonary embolism (PE). PE is also an independent predictor of death or re-hospitalization among CHF patients. We assessed the incidence of CHF admission following acute PE using population-linkage analysis., Methods: Patients were identified from a comprehensive single-center PE database and CHF admissions or death after their PE were tracked from the statewide Admitted Patient Data Collection and Death registries respectively. Patients were divided into two groups: Group-1 were patients without a history of CHF and left ventricular ejection fraction (LVEF) ≥50%; Group-2 were patients with a history of CHF and/or LVEF <50%. Cox regression was used to identify independent predictors for post-PE CHF admission or death., Results: The study cohort comprised 515 patients (Group-1: n = 338 [65.6%]; Group-2: n = 177 [34.4%]). The incidence of first CHF hospitalization after discharge for acute PE over a mean (±SD) follow-up period of 4.7 ± 3.7 years for the total cohort was 71 (13.8%), with the rate significantly higher in Group-2 than Group-1 (Group-2: [n = 58] 9.11 per-100-patient-years vs Group-1: [n = 13] 0.73 per-100-patient-years). Independent predictors for CHF admission or death after acute PE were older age, male gender, history of CHF or malignancy, low day-1 serum hemoglobin, on diuretics during index PE admission, LVEF <50%, and elevated right ventricular-atrial pressure gradient on echocardiography., Conclusion: We report a high incidence of CHF requiring hospital admission after acute PE. Surveillance for new-onset heart failure and close monitoring for heart failure decompensation following acute PE particularly in at-risk groups may be warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Pulmonary embolism continues to be a significant cause of death. The aim was to derive and validate a risk prediction model for in-hospital death after acute pulmonary embolism to identify low risk patients suitable for outpatient management., Methods: A confirmed acute pulmonary embolism database of 1,426 consecutive patients admitted to a tertiary-center (2000-2012) was analyzed, with odd and even years as derivation and validation cohorts respectively. Risk stratification for in-hospital death was performed using multivariable logistic-regression modelling. Models were compared using receiver-operating characteristic-curve and decision curve analyses., Results: In-hospital mortality was 3.6% in the derivation cohort (n = 693). Adding day-1 sodium and bicarbonate to simplified Pulmonary Embolism Severity Index (sPESI) significantly increased the C-statistic for predicting in-hospital death (0.71 to 0.86, P = 0.001). The validation cohort yielded similar results (n = 733, C-statistic 0.85). The new model was associated with a net reclassification improvement of 0.613, and an integrated discrimination improvement of 0.067. The new model also increased the C-statistic for predicting 30-day mortality compared to sPESI alone (0.74 to 0.83, P = 0.002). Decision curve analysis demonstrated superior clinical benefit with the use of the new model to guide admission for pulmonary embolism, resulting in 43 fewer admissions per 100 presentations based on a risk threshold for admission of 2%., Conclusions: A risk model incorporating sodium, bicarbonate, and the sPESI provides accurate risk prediction of acute in-hospital mortality after pulmonary embolism. Our novel model identifies patients with pulmonary embolism who are at low risk and who may be suitable for outpatient management.

Background: Acute pulmonary embolism (PE) carries an increased risk of death. Using transthoracic echocardiography (TTE) to assist diagnosis and risk stratification is recommended in current guidelines. However, its utilization in real-world clinical practice is unknown. We conducted a retrospective observational study to delineate the prevalence of inpatient TTE use following confirmed acute PE, identify predictors for its use and its impact on patient's outcome., Methods: Clinical details of consecutive patients (2000 to 2012) from two tertiary-referral hospitals were retrieved from dedicated PE databases. All-cause and cause-specific mortality was tracked from a state-wide death registry., Results: In total, 2306 patients were admitted with confirmed PE, of whom 687 (29.8%) had inpatient TTE (39.3% vs 14.4% between sites, P<0.001). Site to which patient presented, older age, cardiac failure, atrial fibrillation and diabetes were independent predictors for inpatient TTE use, while malignancy was a negative predictor. Overall mortality was 41.4% (mean follow-up 66.5±49.5months). Though inpatient TTE use was not an independent predictor for all-cause or cardiovascular mortality in multivariable analysis, in the inpatient TTE subgroup, right ventricle-right atrial pressure gradient (hazard ratio [HR] 1.02 per-1mmHg increase, 95% confidence interval [CI] 1.01-1.03) and moderate/severe aortic stenosis (HR 2.26, 95% CI 1.20-4.27) independently predicted all-cause mortality., Conclusions: Inpatient TTE is used infrequently in real-world clinical settings following acute PE despite its usefulness in risk stratification, prognostication and assessing comorbid cardiac pathologies. Identifying patients that will benefit most from a TTE assessment following an acute PE episode and reducing barriers in accessing TTE should be explored., Competing Interests: The authors have declared that no competing interests exist.

Background: The prognostic influence of chest pain in patients presenting with pulmonary embolism has not been well defined. We investigated whether the presence of chest pain at presentation affected the mortality of patients with acute pulmonary embolism., Methods: Retrospective cohort study of consecutive patients admitted to a tertiary hospital with confirmed acute pulmonary embolism from 2000 to 2012, with study outcomes tracked using a state-wide death registry., Results: Of the 1306 patients included in the study, 771 (59%) had chest pain at presentation. These patients were younger with fewer comorbidities, and had lower 6-month mortality compared to patients without chest pain (5% vs 15%, P<0.001). Chest pain was consistently found to be an independent predictor of 6-month mortality in three separate multivariable models (range of hazard ratios 0.52-0.60, all with P<0.05). The addition of chest pain to a multivariable model that included the simplified pulmonary embolism severity index, haemoglobin, and sodium led to a significant net reclassification improvement of 18% (P<0.001)., Conclusions: Chest pain is a novel, favourable prognostic marker in patients with acute pulmonary embolism., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The prognostic significance of patients presenting with pulmonary embolism (PE) and elevated International Normalised Ratio (INR) not on anticoagulant therapy has not been described. We investigated whether these patients had higher mortality compared to patients with normal INR. A retrospective study of patients admitted to a tertiary hospital with acute PE from 2000 to 2012 was undertaken, with study outcomes tracked using a state-wide death registry. Patients were excluded if they were taking anticoagulants or had inadequate documentation of their INR and medication status. Of the 1,039 patients identified, 94 (9 %) had an elevated INR (> 1.2) in the absence of anticoagulant use. These patients had higher mortality at six months follow-up (26 % vs 6 %, p< 0.001) compared to controls (INR ≤ 1.2). An INR > 1.2 at diagnosis was an independent predictor of death at six months post-PE (hazard ratio [HR] 2.9, 95 % confidence interval [CI] 1.8-4.7, p< 0.001). The addition of INR to a multivariable model that included the simplified pulmonary embolism severity index (sPESI), chest pain, and serum sodium led to a significant net reclassification improvement estimated at 8.1 %. The final model's C statistic increased significantly by 0.04 (95 % CI 0.01-0.08, p=0.03) to 0.83 compared to sPESI alone (0.79). In summary, patients presenting with acute PE and elevated INR while not on anticoagulant therapy appear to be at high risk of death. Future validation studies in independent cohorts will clarify if this novel finding can be usefully incorporated into clinical decision making in patients with acute PE.

Background: Symptomatic pulmonary embolism (PE) is a major cause of cardiovascular death and morbidity. Estimated prevalence and incidence of atrial fibrillation (AF) in developed countries are between 388-661 per 100,000, and 90-123 per 100,000 person-years respectively. However, the prevalence and incidence of AF in patients presenting with an acute PE and its predictors are not clear., Methods: Individual patient clinical details were retrieved from a database containing all confirmed acute PE presentations to a tertiary institution from 2001-2012. Prevalence and incidence of AF was tracked from a population registry by systematically searching for AF during any hospital admission (2000-2013) based on International Classification of Disease (ICD-10) code., Results: Of the 1,142 patients included in this study, 935 (81.9%) had no AF during index PE admission whilst 207 patients had documented baseline AF (prevalence rate 18,126 per 100,000; age-adjusted 4,672 per 100,000). Of the 935 patients without AF, 126 developed AF post-PE (incidence rate 2,778 per 100,000 person-years; age-adjusted 984 per 100,000 person-years). Mean time from PE to subsequent AF was 3.4 ± 2.9 years. Total mortality (mean follow-up 5.0 ± 3.7 years) was 42% (n = 478): 35% (n = 283), 59% (n = 119) and 60% (n = 76) in the no AF, baseline AF and subsequent AF cohorts respectively. Independent predictors for subsequent AF after acute PE include age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.04-1.08, p<0.001), history of congestive cardiac failure (HR 1.88, 95% CI 1.12-3.16, p = 0.02), diabetes (HR 1.72, 95% CI 1.07-2.77, p = 0.02), obstructive sleep apnea (HR 4.83, 1.48-15.8, p = 0.009) and day-1 serum sodium level during index PE admission (HR 0.94, 95% CI 0.90-0.98, p = 0.002)., Conclusions: Patients presenting with acute PE have a markedly increased age-adjusted prevalence and subsequent incidence of AF. Screening for AF may be of importance post-PE.

Background: Long-term studies following acute pulmonary embolism (PE) remain limited in the current era. A recent study from our collaborative group, in a contemporary adult population, showed substantially increased cardiovascular mortality following PE. We sought to evaluate the contribution of cardiovascular mortality to long-term outcomes in a different demographic that comprised of a significantly younger PE cohort., Methods and Results: Demographic and clinical characteristics were retrospectively collected for this cohort, and similar methods and outcome measures were applied as detailed in the original study. We compared a population from a different metropolitan area (LH: Liverpool Hospital) to that from the original study (CRGH: Concord Hospital) over a similar time period. A total of 815 patients comprised this cohort with mean 5.3±3.8year follow-up. There were similar demographics between the two cohorts, though the mean age was significantly younger in LH group (60 vs 68years, p<0.001). Prior history of cardiovascular disease in the LH group was half of that present in the CRGH cohort. The overall mortality was 7.4% per patient-year. Patients with underlying cardiovascular disease when presenting with an acute PE had a 2.3-fold increased risk of death during follow-up compared to those without. Multivariate analysis showed that older age, male gender, malignancy, diabetes, cardiovascular disease and chronic pulmonary disease were independent predictors of post-discharge mortality., Conclusions: Despite our cohort being significantly younger with a lower incidence of pre-existing cardiovascular disease, cardiovascular disease was still a significant contributor to long-term outcomes and an important predictor of mortality following acute PE., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Hypercoagulable and/or hypofibrinolytic states are risk factors for venous thromboembolism (VTE) including acute pulmonary embolism. Current screening for thrombophilia is targeted towards identifying a specific defect and guidelines recommend a population-based rather than individualized strategy for anticoagulation treatment. We investigated whether there is a global hypercoagulable state in long-term survivors of pulmonary embolism no longer receiving therapeutic anticoagulation utilizing the overall haemostatic potential (OHP) assay, which assesses overall coagulation potential (OCP), OHP and overall fibrinolytic potential (OFP). Long-term survivors of acute pulmonary embolism were identified from a local registry and OHP assays were performed and compared with age and sex-matched controls without pulmonary embolism. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption 405 nm) after addition of tissue factor and tissue plasminogen activator to plasma. OHP assays were performed in 67 long-term survivors of single pulmonary embolism (7.9 ± 1.4 years after pulmonary embolism) and 20 age (61.7 ± 11.2 vs 56.6 ± 6.4 years, P = 0.06) and sex (P = 0.45)-matched controls. Survivors of pulmonary embolism were more hypercoagulable as reflected by significantly higher OCP (56.4 ± 13.0 vs 49.9 ± 6.9, P = 0.03) and had impaired fibrinolysis with higher OHP (12.6 ± 7.0 vs 5.9 ± 2.0, P < 0.001) and lower OFP (78.1 ± 9.4 vs 88.2 ± 2.9, P < 0.001) compared with controls. Importantly, these abnormalities in overall coagulation were independently predicted by levels of fibrinogen, platelet count, shortened activated partial thromboplastin time and inflammatory markers suggesting a multifactorial cause. Long-term survivors of pulmonary embolism demonstrate enhanced global coagulation and reduced fibrinolytic potential. Assessment of global coagulation may provide new insights into the aggregate effects of multiple prothombotic factors and long-term risk of VTE recurrence.

Background: The functional capacity of long-term survivors of submassive pulmonary embolism (PE) is unreported. A six-minute walk distance (6MWD) <350 m and reduced heart rate recovery (HRR) indicate adverse prognosis in various chronic diseases., Methods: Long-term survivors of acute PE (January 2000-June 2005) were invited to undergo prospectively planned six-minute walk test (6MWT), transthoracic echocardiogram (TTE), clinical and biochemical evaluation with cardiac biomarkers. HRR was calculated as the difference between heart rate at 6-min during and at 1-min post 6MWT., Results: 120 patients (52 males; mean age [±standard deviation] - 65 ± 14 years) were identified 7.7 ± 1.4 years after PE. 6MWD was significantly lower than that predicted after adjustment for age, sex, and height (448 ± 114 m vs 475 ± 89 m, p = 0.005), and 16% (17/104) had 6MWD <350 m. Among patients with no baseline comorbidities at follow-up (Charlson comorbidity index = 0), 8% (4/52) had 6MWD <350 m. Resting TTE identified 29% of patients had raised right ventricular (RV) pulmonary pressure (pulmonary arterial systolic pressure [PASP] >36 mmHg) and 13% had impaired RV function. Patients with 6MWD <85% predicted had significantly greater impairment of RV longitudinal function (p < 0.001), higher PASP (p < 0.001) and pulmonary vascular resistance (p < 0.001), elevated NT-proBNP (p = 0.03) and high-sensitivity troponin-T (HsTropT, p = 0.03), but similar left ventricular systolic and diastolic function, to those with normal 6MWT., Conclusions: Apparently well, long-term survivors of PE demonstrate impaired exercise capacity, heart rate recovery, mild pulmonary hypertension, raised PVR and right ventricular dysfunction associated with elevated NT-proBNP and HsTropT., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

The clinical characteristics and long-term outcomes of patients presenting with acute pulmonary embolism (PE) during treatment with warfarin have not been described. Clinical details of all patients admitted to a tertiary institution from 2000-2007 with acute PE were retrieved retrospectively, baseline warfarin status and the international normalised ratio (INR) were recorded, and their outcomes tracked using a statewide death registry. Of 923 patients with clearly documented warfarin status included in this study, 83 (9%) were taking warfarin. Mean (± standard deviation) day-1 INR of those taking warfarin was 2.3 ± 0.9, with 67% of patients therapeutically anti-coagulated (INR ≥2.0) at presentation (49 patients with INR <2.5 and 34 with INR ≥2.5). Patients taking warfarin on admission were more likely to have heart failure, atrial fibrillation and valvular heart disease, with similar prevalence of malignancy and ischaemic heart disease, compared to patients not on warfarin. Total mortality of the cohort (mean follow-up 4.0 ± 2.5 years) was 31.6% (in-hospital mortality 1.5%), and was similar between warfarin and no warfarin groups. There was however a greater than four-fold increased risk of post-discharge death due to recurrent PE for the patients taking warfarin on admission (hazard ratio [HR] 4.43, 95% confidence interval [CI] 1.36-14.42, p=0.01). Among patients taking warfarin on admission, day-1 INR <2.5 significantly increased long-term all-cause mortality compared to INR ≥2.5 (adjusted HR 2.51, 95% CI 1.08-5.86, p=0.03). In conclusion, patients presenting with PE during treatment with warfarin have an increased risk of death from recurrent PE. Admission INR appears to have independent long-term prognostic importance in these patients.

Background: Current guidelines recommend that transthoracic echocardiography (TTE) should be performed for acute risk stratification following acute pulmonary embolism (PE), but it is unclear whether the initial TTE can predict long-term outcome beyond six months. We sought to assess the potential of the initial right atrial (RA) to left atrial (LA) area ratio (RA/LA ratio) on TTE to predict long-term mortality in survivors of submassive PE., Methods: A derivation cohort comprised a previously reported group of 35 consecutive patients with acute PE who were intensively studied by serial TTE at 1, 2, 5 days, 2, 6, 12 and 26 weeks and RA/LA ratio related to long-term outcome. The Day 1 RA/LA ratio findings were then further related to long-term outcome in 158 patients followed for 3.6 ± 2.3 years., Results: In the derivation cohort, total mortality was 28.6% (n = 10) following a mean (±standard deviation) follow-up of 4.3 ± 1.9 years. The RA/LA ratio was highly dynamic, being increased at day 1, but normalised rapidly within 2-5 days of presentation and this was most marked amongst long-term non-survivors. A RA/LA ratio > 1.0 on day 1 was independently associated with a three-fold increase in long-term mortality on Kaplan-Meier analysis. Pooled analysis of 158 patient indicated that age, Charlson Comorbidity Index (CCI), simplified Pulmonary Embolism Severity Score (PESI), troponin T, day 1 RA/LA Ratio and pulmonary arterial systolic pressure (PASP) were univariate predictors of long-term mortality. Multivariate analysis identified Day 1 RA/LA Ratio (HR 1.7 per 10% increase, p = 0.002), CCI (HR 2.2 per 1 unit increase, p = 0.004) and age (HR 1.1, p = 0.03) as the only independent predictors of long-term mortality., Conclusion: A RA/LA Ratio >1.0 at presentation with acute PE was associated with a three-fold increased risk of long-term mortality. The RA/LA ratio on presentation with an acute PE is a simple, novel predictor of long-term survival.

Background: Although cardiac troponin elevation during acute pulmonary embolism (PE) predicts in-hospital death, its long-term prognostic significance, and the role of troponin-T concentration in this prediction, is unknown. Moreover, its use in acute PE in elderly populations with multiple comorbidities is not well described., Methods: Consecutive patients presenting with confirmed PE to a tertiary hospital between 2000 and 2007 with troponin-T measured were identified retrospectively and their outcomes tracked from a state-wide death registry., Results: There were 577 patients, (47% male) with a mean age (± standard deviation) of 70.1 ± 15.2 years, of whom 19 died during index admission. Of the 558 patients who survived to discharge, 186 patients died during a mean follow-up of 3.8 ± 2.4 years. There were 187 (32%) patients with elevated troponin-T (≥ 0.01 μg/L). Troponin-T concentration was significantly and independently associated with in-hospital and long-term mortality whether analyzed as a continuous or categorical variable (p<0.001). However, different cut-points were required to optimally predict in-hospital and post-discharge long-term mortality in multivariate analysis. Troponin-T ≥ 0.01 μg/L was not an independent predictor of in-hospital or post-discharge survival. A cut-point of troponin-T ≥ 0.03 μg/L was required to independently predict in-hospital death (p=0.03), and troponin-T ≥ 0.1 μg/L was required to independently predict long-term mortality (hazard ratio 2.3, 95% confidence interval 1.4-3.8, p=0.001)., Conclusions: Troponin-T elevation during acute PE shows a concentration-dependent relationship with acute and long-term outcome. Concentrations of troponin-T well above the threshold for detection may be required to independently contribute to prediction of outcome in elderly populations with acute PE., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Baseline hyponatremia predicts acute mortality following pulmonary embolism (PE). The natural history of serum sodium levels after PE and the relevance to acute and long-term mortality after the PE is unknown., Methods: Clinical details of all patients (n = 1023) admitted to a tertiary institution from 2000-2007 with acute PE were retrieved retrospectively. Serum sodium results from days 1, 3-4, 5-6, and 7 of admission were pre-specified and recorded. We excluded 250 patients without day-1 sodium or had <1 subsequent sodium assessment, leaving 773 patients as the studied cohort. There were 605 patients with normonatremia (sodium≥135 mmol/L throughout admission), 57 with corrected hyponatremia (day-1 sodium<135 mmol/L, then normalized), 54 with acquired hyponatremia and 57 with persistent hyponatremia. Patients' outcomes were tracked from a state-wide death registry and analyses performed using multivariate-regression modelling., Results: Mean (±standard deviation) day-1 sodium was 138.2±4.3 mmol/L. Total mortality (mean follow-up 3.6±2.5 years) was 38.8% (in-hospital mortality 3.2%). There was no survival difference between studied (n = 773) and excluded (n = 250) patients. Day-1 sodium (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.83-0.95, p = 0.001) predicted in-hospital death. Relative to normonatremia, corrected hyponatremia increased the risk of in-hospital death 3.6-fold (95% CI 1.20-10.9, p = 0.02) and persistent hyponatremia increased the risk 5.6-fold (95% CI 2.08-15.0, p = 0.001). Patients with either persisting or acquired hyponatremia had worse long-term survival than those who had corrected hyponatremia or had been normonatremic throughout (aHR 1.47, 95% CI 1.06-2.03, p = 0.02)., Conclusion: Sodium fluctuations after acute PE predict acute and long-term outcome. Factors mediating the correction of hyponatremia following acute PE warrant further investigation.

Objectives: It was the aim of this study to determine the prognostic significance of the Charlson Comorbidity Index (CCI) following acute pulmonary embolism (PE) and assess the prognosis of patients without comorbidities (defined as a CCI score of 0)., Methods: Outcomes of 1,023 consecutive patients admitted with confirmed PE were tracked after a median of 3.7 years (25-75th interquartile range 1.5-6.1 years). All were assigned a non-age-adjusted CCI score., Results: The median CCI score was 1.0 (interquartile range 0.0-3.0). Three hundred and fifty-one (34%) patients had a CCI score of 0. Only 1 (0.3%) of 31 in-hospital deaths occurred in patients with a CCI score of 0. Long-term mortality for these patients was similar to the population-derived age- and sex-matched mortality rate, and was significantly better than for those with a CCI score ≥1 (12.5 vs. 47.5%; p < 0.0001 adjusted for age and sex). In multivariate analysis, CCI (per 1-score increase) independently predicted in-hospital (hazard ratio 1.27, 95% confidence interval 1.09-1.49; p = 0.003) and post-discharge (hazard ratio 1.35, 95% confidence interval 1.29-1.42; p < 0.0001) death. The c statistics for the multivariate prediction models for in-hospital (incorporating CCI score and serum sodium level) and post-discharge death (age, CCI score, hyperlipidemia, serum sodium and hemoglobin) were 0.738 and 0.788, respectively (both p < 0.0001)., Conclusion: The CCI can be incorporated into risk models, with good discriminatory power, for predicting in-hospital and long-term outcomes following acute PE. Patients with a CCI score of 0 have a favorable long-term outcome following acute PE., (Copyright © 2012 S. Karger AG, Basel.)

Background: There are currently no guidelines advising long-term surveillance of patients following an acute pulmonary embolism (PE), because long-term outcome studies are rare. We investigated the long-term cardiovascular and all-cause mortality of a large patient cohort with confirmed PE in relation to baseline cardiovascular disease (CVD)., Methods and Results: Clinical details of all patients presenting with acute PE to a tertiary hospital were retrieved from medical records, and their survival tracked from a statewide death registry. There were 1023 (45% males) patients admitted with confirmed PE from 2000 to 2007. During a mean follow-up of 3.8±2.6 years, 363 patients died (35.5%), of whom only 31 (3.0%) died in-hospital during the index PE admission. The 3-month, 6-month, 1-year, 3-year, and 5-year cumulative mortality rates were 8.3%, 11.1%, 16.3%, 26.7%, and 31.6% respectively. Annual mortality did not improve over the 7-year period. The postdischarge mortality of 8.5%/patient-year was 2.5-fold that of an age- and sex-matched general population, being 12.6-fold in the youngest quintile (<55 years) and 1.9-fold in the oldest quintile (≥83 years). Patients with known CVD at baseline had 2.2-fold greater all-cause mortality than those without CVD, and this effect, although at a lower level of risk, remained significant after multivariate analysis. Of the 332 deaths occurring postdischarge, 40% were attributed to cardiovascular causes., Conclusions: In a contemporary adult population, PE is associated with a substantially increased long-term mortality, of which nearly half is cardiovascular. Our study highlights the urgent need to develop long-term surveillance strategies in this population.

Background: Acute pulmonary embolism (PE) associated with right ventricular (RV) dysfunction has an adverse prognosis. We investigated individual parameters of RV dysfunction after acute PE, assessing their correlation with the PE extent and recovery during 6 months., Methods: In all, 35 patients (age 63 +/- 18 years) with acute PE were prospectively investigated for 6 months with serial echocardiography, incorporating longitudinal myocardial-velocity and strain imaging. The extent of PE was quantified on day 1 by ventilation/perfusion pulmonary scintigraphy with PE defined as large when there was greater than 30% lung involvement., Results: PE extent correlated strongly with a number of parameters of RV function, and the strongest univariate correlates were tricuspid annular motion (TAM) (r = -0.65, P < .0001) and the ratio of RV apical to RV basal systolic velocity (r = 0.66, P < .0001). Multivariate analysis identified TAM (P < .0001) and RV basal late-diastolic velocity (P = .01) as independently predicting PE extent, with a combined correlation (R2 = 0.52, P < .0001). A TAM of less than 2.0 cm had sensitivity, specificity, and positive- and negative-predictive values of 75%, 84%, 75%, and 79%, respectively, in predicting large PE. Prospective follow-up identified that RV:left ventricular end-diastolic area ratio returned to normal within 6 weeks, whereas TAM and ratio of RV apical to RV basal systolic velocity normalized after 3 to 6 months., Conclusion: TAM and ratio of RV apical to RV basal systolic velocity are useful indicators of the extent of PE, and provide unique insights into the recovery of RV function after acute PE.

Background: Platelet activation is implicated in thrombotic disorders, but has not been described in acute clinical pulmonary embolism (PE)., Objectives: To investigate the natural history of platelet activation in PE and associated markers of inflammation, thrombosis and cardiac dysfunction., Methods: Thirty-five consecutive patients (age 62 +/-17 years) with acute PE were prospectively enrolled and followed for 6 months. Platelet activation was assessed by flow cytometry [measuring expression of platelet P-selectin, conformational activation of glycoprotein IIb/IIIa complex (PAC-1) and formation of platelet-leukocyte complexes] and by plasma soluble P-selectin. Platelet activation, right ventricular (RV) function (assessed as RV ejection area by transthoracic echocardiography), D-dimer and high-sensitivity C-reactive protein (hs-CRP) were measured at presentation and repeated over 6 months follow-up., Results: Soluble P-selectin (56 +/-19 ng mL(-1), anovaP < 0.0001) and PAC-1 (1.5 +/- 1.8%, anovaP = 0.005) were mildly but significantly increased in patients with acute PE relative to healthy young men (soluble P-selectin 33 +/- 13 ng mL(-1), P < 0.001; PAC-1 binding 0.5 +/- 0.6%, P < 0.01) and age-matched controls (soluble P-selectin 31 +/- 9 ng mL(-1), P < 0.001; PAC-1 binding 0.4 +/-0.4%, P < 0.05). Platelet P-selectin expression and platelet-leukocyte complexes were not increased during acute PE. Echocardiographic RV ejection area correlated inversely with soluble P-selectin (r = -0.47, P = 0.007) and positively with platelet P-selectin (r = 0.49, P = 0.0007), suggesting P-selectin is shed from activated platelets in proportion to the severity of RV dysfunction. Elevated soluble P-selectin, D-dimer and hs-CRP demonstrated a time-dependent return to normal during 6 months follow-up., Conclusion: Platelet activation is evident after acute PE. Platelet activation correlates with the severity of RV dysfunction, and can persist for several months after acute PE.

Background: Acute pulmonary thromboembolism (PTE) can be associated with right ventricular (RV) dysfunction. The relative importance of individual echocardiographic parameters, including those suggesting interdependence between right and left heart chambers, in predicting thromboembolic burden in elderly patients with acute PTE is unknown., Methods: We retrospectively studied the transthoracic echocardiograms of 63 elderly patients (age 71 +/- 16 years) with acute PTE, and assessed which individual echocardiographic parameters identified more than 30% pulmonary artery obstruction on the basis of quantitative ventilation/perfusion pulmonary scintigraphy., Results: RV hypokinesis (visual grade 0-3, P = .02), and the quantitative parameters RV end-systolic area (P = .005) and RV ejection area (P = .01) were associated with more extensive pulmonary artery obstruction. Although right atrial end-systolic area and RV end-diastolic area did not correlate with extent of PTE, the ratio of RV:left ventricular end-diastolic area (P = .003), and ratio of right:left atrial end-systolic area (P = .004), were strongly associated with the extent of pulmonary artery obstruction. These transthoracic echocardiographic parameters were independent of clinical variables such as prior chronic lung disease, congestive cardiac failure, or prior PTE., Conclusion: RV systolic dysfunction, RV end-systolic dilatation, right:left atrial end-systolic area ratio, and RV:left ventricular end-diastolic area ratio correlate with extent of PTE in the elderly.