Psoas Muscle Area as a Predictor of Transcatheter Aortic Valve Implantation Outcomes.

BACKGROUND: Frailty is a well-recognised predictor of outcomes after transcatheter aortic valve implantation (TAVI). Psoas muscle area (PMA) is a surrogate marker for sarcopaenia and is a validated assessment tool for frailty. The objective of this study was to examine frailty as a predictor of outcomes in TAVI patients and assess the prognostic usefulness of adding PMA to established frailty assessments. METHODS: Frailty assessments were performed on 220 consecutive patients undergoing TAVI. These assessments used four markers (serum albumin, handgrip strength, gait speed, and a cognitive assessment), which were combined to form a composite frailty score. Preprocedural computed tomography scans were used to calculate cross-sectional PMA for each patient. The primary outcomes were all-cause mortality at 1-year and post-procedure length of hospital stay. RESULTS: Frailty status, as defined by the composite frailty score, was independently predictive of length of hospital stay (p=0.001), but not predictive of 1-year mortality (p=0.161). Albumin (p=0.036) and 5-metre walk test (p=0.003) were independently predictive of 1-year mortality. The PMA, when adjusted for gender, and normalised according to body surface area, was not predictive of 1-year mortality. Normalised PMA was associated with increased post-procedure length of stay within the female population (p=0.031). CONCLUSIONS: A low PMA is associated with increased length of hospital stay in female TAVI patients but does not provide additional predictive value over traditional frailty scores. The PMA was not shown to correlate with TAVI-related complications or 1-year mortality.

30-Day Outcomes With the Portico Transcatheter Heart Valve: Insights From a Multi-Centre Australian Observational Study.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established therapy for the treatment of aortic valve disease in appropriately selected patients. Previous studies using the self-expanding Portico transcatheter heart valve (THV), (Abbott Structural Heart, St Paul, MN, USA) have demonstrated the technical feasibility of this system albeit in the hands of relatively inexperienced Portico users. The objective of this study was to assess the real-world safety and efficacy of the Portico THV (with and without the FlexNav delivery system, Abbott Structural Heart) at the 30-day timepoint in an Australian cohort. METHODS AND RESULTS: This study was a retrospective real-world cohort analysis of 269 consecutive patients with severe aortic valve disease who underwent TAVI at multiple centres within Australia between February 2015 and April 2021. Of the 269 patients, 51.7% were female, mean Society of Thoracic Surgeons (STS) score was 5.2 (±6.8) and 98.5% had successful implantations. Thirty (30)-day post-implantation all-cause mortality was observed in one (0.4%) patient, major vascular complications in two (0.7%) patients, more-than-mild paravalvular leak in six (2.2%) patients and requirement for new permanent pacemaker implantation in 27 (10.2%) patients. Haemodynamic parameters at 30 days included mean effective orifice area (EOA) of 2.3 (±0.9) cm2 and mean aortic valve gradient (AVG) of 9.6 (±6.2) mmHg. CONCLUSION: This analysis of the Portico THV in a real-world setting suggested that the system is associated with satisfactory safety and efficacy parameters. Previously published datasets may not have found similar findings owing to lower operator experience with the Portico THV system.

Fractional Flow Reserve and Instantaneous Wave-Free Ratio Predict Pathological Wall Shear Stress in Coronary Arteries: Implications for Understanding the Pathophysiological Impact of Functionally Significant Coronary Stenoses.

Background The pathophysiological mechanism behind adverse outcomes associated with ischemia-inducing epicardial coronary stenoses and microcirculatory dysfunction remains unclear. Wall shear stress (WSS) plays an important role in atherosclerotic plaque progression and vulnerability. We aimed to evaluate the relationship between WSS, functionally significant epicardial coronary stenoses, and microcirculatory dysfunction. Methods and Results Patients undergoing invasive coronary physiology testing were included. Fractional flow reserve, instantaneous wave-free ratio, and the index of microcirculatory resistance were measured. Quantitative coronary angiography was used to obtain the lesion percentage diameter stenosis. Computational fluid dynamics analysis was performed to calculate WSS parameters. Multiple regression analysis was performed to calculate the standardized regression coefficient (ß) for the coronary physiology indices. A total of 107 vessels from 88 patients were included. Fractional flow reserve independently predicted the total area of low WSS (ß=-0.44; 95% CI, -0.62 to -0.25; P<0.001) and maximum lesion WSS (ß=-0.53; 95% CI, -0.70 to -0.36; P<0.001) after adjusting for percentage diameter stenosis and index of microcirculatory resistance. Similarly, instantaneous wave-free ratio also independently predicted the total area of low WSS (ß=-0.45; 95% CI, -0.62 to -0.28; P<0.001) and maximum lesion WSS (ß=-0.58; 95% CI, -0.73 to -0.43; P<0.001). The index of microcirculatory resistance did not predict either low or high WSS. Conclusions Fractional flow reserve and instantaneous wave-free ratio independently predicted the total burden of low WSS and maximum lesion WSS in coronary arteries. No relationship was found between microcirculatory dysfunction and WSS.

Identifying New Factors Associated With Cognitive Decline and Delirium After Transcatheter Aortic Valve Implantation: A Study Protocol.

Background: Transcatheter aortic valve implantation (TAVI) has become the standard-of-care for treatment of severe symptomatic aortic stenosis and is also being increasingly recommended for low-risk patients. While TAVI boasts positive post-procedural outcomes, it is also associated with cognitive complications, namely delirium and cognitive decline. There is a pressing need for accurate risk tools which can identify TAVI patients at risk of delirium and cognitive decline, as risk scores designed for general cardiovascular surgery fall short. The present effect-finding exploratory study will assess the utility of various measures in the context of aging and frailty in predicting who will and who will not develop delirium or cognitive impairment following TAVI. The measures we propose include gait, visual symptoms, voice, swallowing, mood and sleep. Methods: This is an observational prospective cohort study focused on identifying pre-procedural risk factors for the development of delirium and cognitive decline following TAVI. Potential risk factors will be measured prior to TAVI. Primary outcomes will be post-procedure cognitive decline and delirium. Secondary outcomes include activities of daily living, quality of life, and mortality. Delirium presence will be measured on each of the first 2 days following TAVI. All other outcomes will be assessed at 3-, 6-, and 12-months post-operatively. A series of logistic regressions will be run to investigate the relationship between potential predictors and outcomes (presence vs. absence of either delirium or cognitive decline). Discussion: This study will assess the strengths of associations between a range of measures drawn from frailty and aging literature in terms of association with cognitive decline and delirium following TAVI. Identified measures can be used in future development of TAVI risk prediction models, which are essential for the accurate identification of cognitive at-risk patients and successful application of pre-procedural interventions. Clinical Trial Registration: This trial is registered with the Australian New Zealand Clinical Trials Registry. [https://bit.ly/2PAotP5], [ACTRN12618001114235].

Circulating platelet-derived extracellular vesicles are decreased after remote ischemic preconditioning in patients with coronary disease: A randomized controlled trial.

BACKGROUND: Brief nonharmful ischemia, remote ischemic preconditioning (RIPC) has been proposed to confer benefit to patients with coronary artery disease via unknown mechanisms. OBJECTIVES: We aimed to investigate the effect of RIPC on circulating levels of extracellular vesicles (EVs) and global coagulation and fibrinolytic factors in patients with coronary disease. PATIENTS/METHODS: Blood samples were taken from 60 patients presenting for coronary angiography enrolled in a randomized, controlled trial before and after RIPC (3 × 5 min administration of 200 mmHg sphygmomanometer on the arm, n = 31) or sham (n = 29) treatment. Most patients (n = 48) had significant coronary artery disease and all were taking at least one antiplatelet agent. RESULTS: Remote ischemic preconditioning significantly decreased circulating levels of EVs expressing platelet markers CD41 and CD61 detected by flow cytometry in plasma, whereas no such effect was found on EVs expressing phosphatidylserine, CD62P, CD45, CD11b, CD144, CD31+ /CD41- , or CD235a. RIPC had no effect on the overall hemostatic potential assay or circulating antigen levels of tissue plasminogen activator, urokinase, plasminogen activator inhibitor-1, or plasminogen. Sham treatment had no effect on any studied parameter. Statin use inhibited the effect of RIPC on CD61+ EVs, diabetes modified the effect of RIPC on CD45+ and CD11b+ EVs, and hypertension modified the effect of RIPC on CD235a+ EVs. CONCLUSIONS: Remote ischemic preconditioning decreased circulating levels of platelet-derived EVs in patients with coronary disease taking conventional antiplatelet therapy. This may reflect increased EV clearance/uptake or change in production. Clinical variables may alter the effectiveness of RIPC.

Remote ischemic preconditioning inhibits platelet αIIb ß3 activation in coronary artery disease patients receiving dual antiplatelet therapy: A randomized trial.

OBJECTIVES: We investigated whether remote ischemic preconditioning (RIPC) inhibits agonist-induced conformational activation of platelet αIIb ß3 in patients with coronary artery disease already receiving conventional antiplatelet therapy. PATIENTS/METHODS: Consecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham. Platelet aggregometry (ADP, arachidonic acid) and whole blood platelet flow cytometry was performed for CD62P, CD63, active αIIb ß3 (PAC-1 binding) before and after stimulation with ADP, thrombin ± collagen, or PAR-1 thrombin receptor agonist. RESULTS: Patients (25 RIPC, 23 sham) were well matched, 83% male, age (mean ± standard deviation) 63.3 ± 13.2 years, 95% aspirin, 81% P2Y12 inhibitor. RIPC did not affect platelet aggregation, nor agonist-induced expression of CD62P, but selectively and significantly decreased αIIb ß3 activation after stimulation with either PAR-1 agonist peptide or the combination of thrombin + collagen, but not after ADP nor thrombin alone. The effect of RIPC on platelet αIIb ß3 activation was evident in patients receiving both aspirin and P2Y12 inhibitor, and was not associated with an increase in vasodilator-stimulated phosphoprotein phosphorylation. CONCLUSIONS: Remote ischemic preconditioning inhibits conformational activation of platelet αIIb ß3 in response to exposure to thrombin and collagen in patients with coronary artery disease receiving dual antiplatelet therapy. These findings indicate agonist-specific inhibition of platelet activation by RIPC in coronary artery disease that is not obviated by the prior use of P2Y12 inhibitors.

Impact of persistent anaemia on mortality in patients hospitalised with acute pulmonary embolism: an Australian retrospective observational study.

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.

Remote Ischemic Preconditioning Acutely Improves Coronary Microcirculatory Function.

Background Remote ischemic preconditioning (RIPC) attenuates myocardial damage during elective and primary percutaneous coronary intervention. Recent studies suggest that coronary microcirculatory function is an important determinant of clinical outcome. The aim of this study was to assess the effect of RIPC on markers of microcirculatory function. Methods and Results Patients referred for cardiac catheterization and fractional flow reserve measurement were randomized to RIPC or sham. Operators and patients were blinded to treatment allocation. Comprehensive physiological assessments were performed before and after RIPC/sham including the index of microcirculatory resistance and coronary flow reserve after intracoronary glyceryl trinitrate and during the infusion of intravenous adenosine. Thirty patients were included (87% male; mean age: 63.1±10.0 years). RIPC and sham groups were similar with respect to baseline characteristics. RIPC decreased the calculated index of microcirculatory resistance (median, before RIPC: 22.6 [interquartile range [IQR]: 17.9-25.6]; after RIPC: 17.5 [IQR: 14.5-21.3]; P=0.007) and increased coronary flow reserve (2.6±0.9 versus 3.8±1.7, P=0.001). These RIPC-mediated changes were associated with a reduction in hyperemic transit time (median: 0.33 [IQR: 0.26-0.40] versus 0.25 [IQR: 0.20-0.30]; P=0.010). RIPC resulted in a significant decrease in the calculated index of microcirculatory resistance compared with sham (relative change with treatment [mean±SD] was -18.1±24.8% versus +6.1±37.5; P=0.047) and a significant increase in coronary flow reserve (+41.2% [IQR: 20.0-61.7] versus -7.8% [IQR: -19.1 to 10.3]; P<0.001). Conclusions The index of microcirculatory resistance and coronary flow reserve are acutely improved by remote ischemic preconditioning. This raises the possibility that RIPC confers cardioprotection during percutaneous coronary intervention as a result of an improvement in coronary microcirculatory function. Clinical Trial Registration URL: www.anzctr.org.au/ . Unique identifier: CTRN12616000486426.

Outcomes of 4838 patients requiring temporary transvenous cardiac pacing: A statewide cohort study.

BACKGROUND: Temporary-transvenous-cardiac-pacing (TTCP) is a potentially lifesaving procedure, however trends in its utilization and outcomes in unselected contemporary populations are all unknown. METHODS: Consecutive patients requiring TTCP between July-1, 2000 and December-31, 2013 were identified from a statewide registry of admitted patients. In addition, all patients who underwent other cardiac procedures including permanent-pacemaker (PPM) implantation, automated-implantable-cardiac-defibrillator (AICD) implantation, percutaneous-coronary-intervention (PCI), or coronary-artery-bypass-graft (CABG) surgery were identified for comparative outcome analyses. Survival was tracked from a statewide death registry. RESULTS: A total of 4838 patients (mean age [±standard deviation] 74.7 ±â€¯12.7 years; 58.0% males) requiring TTCP were identified. The incidence for TTCP was 5.86 ±â€¯1.06 cases per-100,000-persons-per-annum, declining by 46% between 2003 and 2013. During 4.2 ±â€¯3.7 years of follow-up, 2594 (53.6%) patients died, of whom 569 (11.8%) died during the index admission. Weekend admission was associated with increased mortality compared to weekdays (hazard ratio: 1.15, 95% confidence interval [CI] 1.06-1.26, p = 0.002) and independently predicted all-cause death. After adjusting for age, gender, comorbidities, and referral source for admission, patients requiring TTCP had worse survival than those undergoing PPM (n = 17,988) or AICD (n = 5264) implantation, PCI (n = 46,859), or CABG surgery (n = 50,992) (adjusted hazard ratio [aHR]: 2.14, 95% CI 1.94-2.37; aHR: 1.61, 95% CI 1.41-1.83; aHR: 1.76, 95% CI 1.61-1.93; aHR: 2.09, 95% CI 1.98-2.21 respectively, all p < 0.001). CONCLUSION: TTCP utilization is decreasing and is associated with substantial in-hospital and long-term mortality with weekend-weekday variation in outcome. Further studies are needed to develop strategies to better understand the determinants of adverse outcomes of these patients, as well as appropriate strategies for outcome improvement.

Red blood cell transfusion and outcomes in acute pulmonary embolism.

BACKGROUND AND OBJECTIVE: Blood transfusion has been associated with adverse outcomes in certain conditions. This study investigates the prevalence and outcomes of red blood cell (RBC) transfusion in patients with acute pulmonary embolism (PE). METHODS: Retrospective study of consecutive patients from 2000 to 2012 admitted to a tertiary hospital with a primary diagnosis of acute PE. Transfusion status during the hospital admission was ascertained. Mortality was tracked from a state-wide death database and analysed using multivariable modelling. RESULTS: A total of 73 patients (5% of all patients admitted with PE) received RBC transfusion during their admission. These patients were significantly older, had more co-morbidities, worse haemodynamics, higher simplified pulmonary embolism severity index scores, and lower plasma sodium and haemoglobin (Hb) levels at admission. Unadjusted mortality for the transfused group was significantly higher at 30-day (19% vs 4%, P < 0.001) and 6-month (40% vs 10%, P < 0.001) follow-up. Multivariable modelling showed RBC transfusion to be a significant independent predictor of mortality at 30-day (odds ratio 3.06, 95% CI: 1.17-8.01, P = 0.02) and 6-month (hazard ratio (HR) 1.97, 95% CI: 1.12-3.46, P = 0.02). Sensitivity analysis confirmed that transfused patients had higher mortality than non-transfused patients in the subgroup of patients with Hb <100 g/L. CONCLUSION: RBC transfusion in patients hospitalized with acute PE is rare and appears to be associated with increased risk of short- and long-term mortality, independent of Hb level on admission. This finding underscores the need for future randomized controlled studies on the impact of RBC transfusion in the management of patients admitted with acute PE. [Correction added on 4 May 2018, after first online publication: the word 'serum' was changed to 'plasma' throughout the article where appropriate.].

A Time to Act and a Time to Watch: Severe Guide-Catheter Induced Proximal Coronary Dissection With Extensive Ascending Aorta and Arch Dissection, Managed by Immediate Coronary Stenting and Watchful Waiting.

In this case, prompt stenting of the dissection entry flap allowed for stabilization and eventual healing of a severe catheter-induced aortic dissection, without resort to surgical intervention.

The relationship between coronary artery distensibility and fractional flow reserve.

Discordance between angiography-based anatomical assessment of coronary stenosis severity and fractional flow reserve (FFR) has been attributed to several factors including lesion length and irregularity, and the myocardial territory supplied by the target vessel. We sought to examine if coronary arterial distensibility is an independent contributor to this discordance. There were two parts to this study. The first consisted of "in silico" models of 26 human coronary arteries. Computational fluid dynamics-derived FFR was calculated for fully rigid, partially distensible and fully distensible models of the 26 arteries. The second part of the study consisted of 104 patients who underwent coronary angiography and FFR measurement. Distensibility at the lesion site (DistensibilityMLA) and for the reference vessel (DistensibilityRef) was determined by analysing three-dimensional angiography images during end-systole and end-diastole. Computational fluid dynamics-derived FFR was 0.67±0.19, 0.70±0.18 and 0.75±0.17 (P<0.001) in the fully rigid, partially distensible and fully distensible models respectively. FFR correlated with both DistensibilityMLA (r = 0.36, P<0.001) and DistensibilityRef (r = 0.44, P<0.001). Two-way ANCOVA analysis revealed that DistensibilityMLA (F (1, 100) = 4.17, p = 0.031) and percentage diameter stenosis (F (1, 100) = 60.30, p < 0.01) were both independent predictors of FFR. Coronary arterial distensibility is a novel, independent determinant of FFR, and an important factor contributing to the discordance between anatomical and functional assessment of stenosis severity.

Predicting in-hospital death during acute presentation with pulmonary embolism to facilitate early discharge and outpatient management.

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.

The underutilisation of dual antiplatelet therapy in acute coronary syndrome.

BACKGROUND: Despite guideline recommendation of dual antiplatelet therapy (DAPT) in treating ACS, DAPT is underutilized. Our objective was to determine independent predictors of DAPT non-prescription in ACS and describe pattern of DAPT prescription over time. METHODS: Patients presenting to 41 Australian hospitals with an ACS diagnosis between 2009 and 2016 were stratified according to discharge prescription with DAPT and single antiplatelet therapy (SAPT) or no antiplatelet therapy. Multiple stepwise logistic regression, accounting for within hospital clustering, was used to determine the independent predictors of DAPT non-prescription, defined as discharge with SAPT alone or no antiplatelet agent. RESULTS: 8939 patients survived to discharge with an ACS diagnosis. Of these, 6294 (70.4%) patients were discharged on DAPT, 2154 (24.1%) on SAPT and 491 (5.5%) on no antiplatelet agent. Independent predictors of DAPT non-prescription in the overall cohort were: in-hospital CABG (OR 0.09, 95%CI 0.05-0.14), discharge with warfarin (0.10 (0.07-0.14)), in hospital major bleeding (0.48 (0.34-0.67), diagnosis of unstable angina (0.35, (0.27-0.45)), non-ST-elevation myocardial infarction (0.67 (0.57-0.78)) [both vs. ST-segment elevation myocardial infarction], in hospital atrial arrhythmia (0.72 (0.60-0.86)), history of hypertension (0.83 (0.73-0.94)) and GRACE high risk (0.83 (0.71-0.98)). There was an increase in prescription of DAPT and a shift towards ticagrelor over clopidogrel for ACS from 2013 to 2016 (p<0.0001), but no overall change in the frequency of DAPT prescription over the entire study period. CONCLUSION: This study revealed high-risk ACS subgroups who do not receive optimal DAPT. Strategies are necessary to bridge the treatment gap in ACS antiplatelet management.

Cardiac Remote Ischaemic Preconditioning: Mechanistic and Clinical Considerations.

Brief, non-harmful ischaemic insults to an organ remote from the heart, remote ischaemic preconditioning (RIPC), has been proposed to confer protection to the heart against ischaemia-reperfusion injury. While most clinical trials of RIPC during coronary interventions (PCI) suggest benefit, recent large, multicentre trials in coronary artery bypass surgery suggest a lack of efficacy. Mechanistically, RIPC most likely promotes the release of circulating factors which modulate multiple cellular pathways in the heart, promoting cell survival. This review explores potential mechanisms underlying RIPC and includes a contemporary evaluation of clinical studies in PCI and cardiac surgery, highlighting methodological differences which may explain discrepant findings between these two clinical groups.

Prevalence of Echocardiography Use in Patients Hospitalized with Confirmed Acute Pulmonary Embolism: A Real-World Observational Multicenter Study.

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.

The prognostic impact of chest pain in 1306 patients presenting with confirmed acute pulmonary embolism.

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.

The Prevalence and Incidence of Atrial Fibrillation in Patients with Acute Pulmonary Embolism.

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.

High mortality in patients presenting with acute pulmonary embolism and elevated INR not on anticoagulant therapy.

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.

Evidence-based care in a population with chronic kidney disease and acute coronary syndrome. Findings from the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE).

BACKGROUND: Acute coronary syndrome (ACS) guidelines recommend that patients with chronic kidney disease (CKD) be offered the same therapies as other high-risk ACS patients with normal renal function. Our objective was to describe the gaps in evidence-based care offered to patients with ACS and concomitant CKD. METHODS: Patients presenting to 41 Australian hospitals with suspected ACS were stratified by presence of CKD (glomerular filtration rate <60 mL/min). Receipt of evidence-based care including, coronary angiography (CA), evidence-based discharge medications (EBMs), and cardiac rehabilitation (CR) referral, were compared between patients with and without CKD. Hospital and clinical factors that predicted receipt of care were determined using multilevel multivariable stepwise logistic regression models. RESULTS: Of the 4,778 patients admitted with suspected ACS, 1,227 had CKD. On univariate analyses, patients with CKD were less likely to undergo CA (59.1% vs 85.0%, P < .0001) or receive EBM (69.4% vs 78.7%, P < .0001), or were offered CR (49.5% vs 68.0%, P < .0001). After adjusting for patient characteristics and clustering by hospital, CKD remained an independent predictor of not undergoing CA only (odds ratio 0.48, 95% CI 0.37-0.61). Within the CKD cohort, presenting to a hospital with a catheterization laboratory was the strongest predictor of undergoing CA (odds ratio 3.07, 95% CI 1.91-4.93). CONCLUSION: The presence of CKD independently predicts failure to undergo CA but not failure to receive EBM or CR, which is predicted by comorbidities. Among the CKD population, performance of CA is largely determined by admission to a catheterization capable hospital. Targeting these patients through standardization of care across institutions offers opportunities to improve outcomes in this high-risk population.