Hemoglobin, Frailty, and Long-term Cardiovascular Events in Community-Dwelling Older Men Aged ≥ 70 Years.

BACKGROUND: Anemia is associated with increased risk of all-cause mortality in older populations. However, the relationship between hemoglobin and major adverse cardiovascular events (MACE), and whether this is modulated by frailty, is unclear. METHODS: CHAMP (Concord Health and Ageing in Men Project) is a prospective study of community-dwelling men aged ≥ 70 years. The relationship between hemoglobin and 7-year MACE was analysed by means of Cox regression. The Youden index was used to determine the optimal hemoglobin cutoff point in predicting MACE. Frailty was assessed with the use of the Fried criteria. RESULTS: The cohort comprised 1604 men (mean ± SD age 76.9 ± 5.5 years). Decreasing hemoglobin was associated with increased comorbidity, frailty, and MACE (P < 0.001), with 140 g/L the optimal cutoff point for predicting MACE. Hemoglobin, age, and frailty independently predicted MACE (all P < 0.001). Each 10 g/L decrement in hemoglobin level was associated with increased risk of MACE (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.06-1.20; P < 0.001), all-cause mortality (HR 1.20, 95% CI 1.12-1.29; P < 0.001), cardiovascular mortality (HR 1.07, 95% CI 1.01-1.14; P = 0.025), myocardial infarction (HR 1.17, 95% CI 1.09-1.25; P < 0.001), and heart failure (HR 1.17, 95% CI 1.09-1.25; P < 0.001). When stratified into hemoglobin quintiles, men in the lowest 2 quintiles (Hb 133-140 g/L and < 132g/L, respectively) were at increased risk of MACE, cardiovascular mortality, myocardial infarction, and heart failure (all P < 0.05). This relationship for MACE was independent from frailty status, with the test for interaction between frailty and hemoglobin not reaching significance (P = 0.24). CONCLUSIONS: Low hemoglobin was associated with increased MACE in community-dwelling older men independently from frailty. A hemoglobin cutoff point of 140 g/L, a level that is above contemporary definitions of anemia, predicted long-term MACE.

A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention.

BACKGROUND: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort. METHODS AND RESULTS: All patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20-0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07-0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07-0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25-0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27-0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08-0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09-0.83, P = 0.02). CONCLUSIONS: In this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.

Incidentally identified coronary artery calcium on non-contrast CT scan of the chest predicts major adverse cardiac events among hospital inpatients.

BACKGROUND: Coronary artery calcium (CAC) identified on non-gated CT scan of the chest is predictive of major adverse cardiac events (MACE) in multiple studies with guidelines therefore recommending the routine reporting of incidental CAC. These studies have been limited however to the outpatient setting. We aimed to determine the prognostic utility of incidentally identified CAC on CT scan of the chest among hospital inpatients. METHODS AND RESULTS: Consecutive patients (n=740) referred for inpatient non-contrast CT scan of the chest at a tertiary referral hospital (January 2011 to March 2017) were included (n=280) if they had no known history of coronary artery disease, active malignancy or died within 30 days of admission. Scans were assessed for the presence of CAC by visual assessment and quantified by Agatston scoring. Median age was 69 years (IQR: 54-82) and 51% were male with a median CAC score of 7 (IQR 0-205). MACE occurred in 140 (50%) patients at 3.5 years median follow-up including 98 deaths. Half of all events occurred within 18 months. Visible CAC was associated with increased MACE (HR) 6.0 (95% CI: 3.7 to 9.7) compared with patients with no visible CAC. This finding persisted after adjusting for cardiovascular risk factors HR 2.4 (95% CI: 1.3 to 4.3) and with both absolute CAC score and CAC score ≥50th percentile. CONCLUSION: Incidental CAC identified on CT scan of the chest among hospital inpatients provides prognostic information that is independent of cardiovascular risk factors. These patients may benefit from aggressive risk factor modification given the high event rate in the short term.

Electrocardiographic QRS duration is influenced by body mass index and sex.

BACKGROUND: Electrocardiogram (ECG) measured QRS duration has been shown to influence cardiovascular outcomes. However, there is paucity of data on whether ECG QRS duration is influenced by obesity and sex in large populations. METHODS: All ECGs performed by a pathology provider over a 2-year period were included. ECGs with confounding factors and those not in sinus rhythm were excluded from the primary analysis. RESULTS: Of the 76,220 who met the inclusion criteria, 41,685 (55%) were females. The median age of the study cohort was 61 years (interquartile [IQR] range 48-71 years). The median QRS duration was 86 ms (IQR 80-94 ms). The median BMI was 27.6 kg/m2 (IQR 24.2-31.8 kg/m2). When stratified according to the World Health Organization classification of BMI < 18.50 kg/m2, 18.50-24.99 kg/m2, 25.00-29.99 kg/m2, and ≥ 30.00 kg/m2, the median QRS durations were 82 ms (IQR 76-88 ms), 86 ms (IQR 80-92 ms), 88 ms (IQR 80-94 ms) and 88 ms (IQR 82-94 ms), respectively (p < 0.001 for linear trend). Median QRS duration for females was 84 ms (IQR 78-88 ms); for males, it was 92 ms (IQR 86-98 ms), p < 0.001. Compared to males, females had narrower QRS complexes at similar age and similar BMI. In multiple linear regression analysis, BMI correlated positively with QRS duration (standardized beta 0.095, p < 0.001) independent of age, sex, and heart rate. CONCLUSIONS: In this large cohort there was a positive association between increasing BMI and QRS duration. Females had narrower QRS duration than males at similar age and similar BMI.

Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.

AIMS: Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone. METHODS AND RESULTS: Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74). CONCLUSION: RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.

Long-Term Outcomes Following Rapid Access Chest Pain Clinic Assessment: First Australian Data.

Australian guidelines recommend prompt evaluation of patients presenting to emergency departments with chest pain, found to be low risk for acute coronary syndromes, and cardiologist-led Rapid Access Chest Pain Clinics (RACPC) have been proposed as a model to provide such care. Initial Australian experience of RACPCs suggests excellent short-term outcomes, and that they are cost-beneficial, though little data exists examining longer-term outcomes. The present study therefore examines such longer-term outcomes to beyond 5 years following presentation to an RACPC in an Australian tertiary metropolitan centre.

Right ventricular speckle tracking strain echocardiography in patients with acute pulmonary embolism.

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 cm2 vs 14.5 ± 3.1 cm2) (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.

Low total cholesterol is associated with increased major adverse cardiovascular events in men aged ≥70 years not taking statins.

OBJECTIVE: Low levels of total cholesterol (TC) are associated with adverse outcomes in older populations. Whether this phenomenon is independent of statin use is unknown. We investigated the association between low TC levels and long-term major adverse cardiovascular events (MACE) in a prospective study of men aged ≥70 years without ischaemic heart disease (IHD) and whether this was influenced by statin use. METHODS: The CHAMP (Concord Health and Ageing in Men Project) cohort is a prospective cohort study of community-dwelling men aged ≥70 years. The relationship between TC and long-term MACE was analysed using Cox-regression modelling adjusted for comorbidities and stratified by statin use. RESULTS: The study cohort comprised 1289 men (mean (±SD) age, 77.0±5.5 years; mean follow-up, 6.4±2.7 years). Decreasing TC level was associated with increased comorbidity burden, frailty and MACE (linear trend p<0.001). In men not on statin therapy (n=731), each 1 mmol/L decrease in TC was associated with increased MACE (HR 1.27, 95% CI 1.10 to 1.45, p=0.001) and mortality (HR 1.22, 95% CI 1.03 to 1.44, p=0.02) adjusted for comorbidities. In contrast, low TC in men on statins (n=558) was not associated with MACE (HR 0.91, 95% CI 0.74 to 1.11) or mortality (HR 0.86, 95% CI 0.68 to 1.09). CONCLUSION: Low TC is associated with increased risk of MACE in older men without IHD who are not taking statin therapy but not in those on statins.

Falling hospital and postdischarge mortality following CABG in New South Wales from 2000 to 2013.

Objectives: To describe changes in mortality among patients undergoing coronary artery bypass grafting (CABG) in New South Wales (NSW) Australia from 2000 to 2013. Methods: Patients undergoing CABG were identified from the NSW Admission Patient Data Collection (APDC) registry, linked to the NSW state-wide death registry database. Changes in all-cause mortality over time were observed following stratification of the study cohort into two year groups. Results: We identified 54 767 patients undergoing CABG during the study period. The risk profile of patients increased over time with significant increases in age, comorbidities and concomitant valve surgery (all p < 0.0001). During a median follow-up period of 6 years, a total 12 161 (22.2%) of patients had died. Survival curves and adjusted analyses showed a steady fall in mortality rate: those operated on during 2012-2013 had 40 % lower mortality than those operated on during 2000-2001 (HR 0.61; 95% CI 0.53 to 0.69). This was contributed to both by a fall in mortality both in hospital (HR 0.48, 95% CI 0.37 to 0.62) and postdischarge (HR 0.73; 95% CI 0.61 to 0.86). Conclusions: We report a consistent reduction in medium-term mortality among a large unselected cohort of NSW patients undergoing CABG between 2000 and 2013. This fall is attributable both to an improvement in outcomes in hospital and in the postdischarge period.

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.

Echocardiographic Predictors of Long-Term Mortality in Patients Presenting With Acute Pulmonary Embolism.

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 cm2 (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.

Impact of Epicardial Adipose Tissue, Left Ventricular Myocardial Fat Content, and Interstitial Fibrosis on Myocardial Contractile Function.

Background Current understanding of metabolic heart disease consists of a myriad of different pathophysiological mechanisms. Epicardial adipose tissue (EAT) is increasingly recognized as metabolically active and associated with adverse cardiovascular outcomes. The present study aimed to investigate the effect of increased EAT volume index on left ventricular (LV) myocardial fat content and burden of interstitial myocardial fibrosis and their subsequent effects on LV myocardial contractile function. Methods and Results A total of 40 volunteers (mean age, 35±10 years; 26 males) of varying body mass index (25.0±4.1 kg/m2; range, 19.3-36.3 kg/m2) and without diabetes mellitus or hypertension were prospectively recruited. EAT volume index, LV myocardial fat content, and extracellular volume were quantified by magnetic resonance imaging. LV myocardial contractile function was quantified by speckle tracking echocardiography global longitudinal strain on the same day as magnetic resonance imaging examination. Mean total EAT volume index, LV myocardial fat content, and extracellular volume were 30.0±19.6 cm3/m2, 5.06%±1.18%, and 27.5%±0.5%, respectively. On multivariable analyses, increased EAT volume index and insulin resistance were independently associated with both increased LV myocardial fat content content and higher burden of interstitial myocardial fibrosis. Furthermore, increased EAT volume index was independently associated with LV global longitudinal strain. Conclusions Increased EAT volume index and insulin resistance were independently associated with increased myocardial fat accumulation and interstitial myocardial fibrosis. Increased EAT volume index was associated with detrimental effects on myocardial contractile function as evidenced by a reduction in LV global longitudinal strain.

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.].

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.

Right heart function during simulated altitude in patients with pulmonary arterial hypertension.

OBJECTIVE: Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. METHODS: Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. RESULTS: The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). CONCLUSIONS: Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function.

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.

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.

Iron Deficiency in Heart Failure: Looking Beyond Anaemia.

Iron is an essential micronutrient in many cellular processes. Iron deficiency, with or without anaemia, is common in patients with chronic heart failure. Observational studies have shown iron deficiency to be associated with worse clinical outcomes and mortality. The treatment of iron deficiency in chronic heart failure patients using intravenous iron alone has shown promise in several clinical trials, although further studies which include larger populations and longer follow-up times are needed.

Persistent global hypercoagulability in long-term survivors of acute pulmonary embolism.

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 ±â€Š1.4 years after pulmonary embolism) and 20 age (61.7 ±â€Š11.2 vs 56.6 ±â€Š6.4 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 ±â€Š13.0 vs 49.9 ±â€Š6.9, P = 0.03) and had impaired fibrinolysis with higher OHP (12.6 ±â€Š7.0 vs 5.9 ±â€Š2.0, P < 0.001) and lower OFP (78.1 ±â€Š9.4 vs 88.2 ±â€Š2.9, 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.

Global hypercoagulability in patients with schizophrenia receiving long-term antipsychotic therapy.

BACKGROUND: Patients with schizophrenia are at increased risk of venous thromboembolism. The mechanisms underlying this association are poorly understood. AIMS: We investigated whether there is a global hypercoagulable state in patients with schizophrenia utilising the overall haemostatic potential (OHP) assay which assesses overall coagulation potential (OCP), haemostatic potential (OHP) and fibrinolytic potential (OFP). METHOD: Citrated plasma was collected for OHP assays from patients with schizophrenia on long-term antipsychotic treatment and compared with healthy age- and sex-matched controls. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption of 405nm) after the addition of tissue factor and tissue plasminogen activator to plasma. RESULTS: Ninety patients with schizophrenia (antipsychotic treatment-15.9±9.7years) and 30 controls were recruited. Patients with schizophrenia had higher rates of smoking and levels of inflammatory markers (high-sensitivity C-reactive protein and neutrophil-to-lymphocyte ratio) than controls. Whilst D-dimer, fibrinogen and platelet count did not differ between patients with schizophrenia and controls, the OCP (54.0±12.6 vs 45.9±9.1, p=0.002) and OHP (12.6±5.8 vs 7.2±3.7, p<0.001) were higher, and OFP was lower (76.6±9.8% vs 84.9±6.4%, p<0.001) in patients with schizophrenia, implying both a hypercoagulable and hypofibrinolytic state in these patients. Importantly, abnormalities in overall coagulation were independently predicted by levels of plasminogen-activator-inhibitor-1, fibrinogen, platelet count, inflammatory markers and plasma triglycerides, suggesting a multifactorial aetiology. CONCLUSION: Patients with schizophrenia have evidence of a global hypercoagulable and hypofibrinolytic state which may contribute to their increased risk of venous thromboembolism.