V. Chow

Long-Term Cardiovascular and Noncardiovascular Mortality of 1023 Patients With Confirmed Acute Pulmonary Embolism

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.

Prognostic Impact of the Charlson Comorbidity Index on Mortality following Acute Pulmonary Embolism

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.

Risk Stratification in the Setting of Non-ST Elevation Acute Coronary Syndromes 1999-2007

It is unclear if clinician risk stratification has changed with time. The aim of this study was to assess the temporal change in the concordance between patient presenting risk and the intensity of evidence-based therapies received for non-ST-segment elevation acute coronary syndromes over a 9-year period. Data from 3,562 patients with non-ST-segment elevation acute coronary syndromes enrolled in the Australian and New Zealand population of the Global Registry of Acute Coronary Events (GRACE) from 1999 to 2007 were analyzed. Patients were stratified to risk groups on the basis of the GRACE risk score for in-hospital mortality. Main outcome measures included in-hospital use of widely accepted evidence-based medications, investigations, and procedures. Invasive management was consistently higher in low-risk patients than in intermediate- or high-risk patients (coronary angiography 66.7% vs 63.5% vs 35.3%, p <0.001; percutaneous coronary intervention 31.1% vs 22.0% vs 12.9%, p <0.001). Absolute rates of angiography and percutaneous coronary intervention in the high-risk group remained 24% and 15% lower compared to the low-risk group in the most recent time period (2005 to 2007). In-hospital use of thienopyridine, low-molecular weight heparin, and glycoprotein IIb/IIIa inhibitors showed a similar inverse relation with risk. Prescription of aspirin, β blockers, statins, and angiotensin receptor blockers was inversely related to risk before 2004, although this inverse relation was no longer present in the most recent time period (2005 to 2007). Only in-hospital use of unfractionated heparin showed use concordant with patient risk status. In conclusion, despite an overall increase in the uptake of evidence-based therapies, most investigations and treatments are not targeted on the basis of patient risk. Clinician risk stratification remains suboptimal compared to objective measures of patient risk.

Peri-procedural Anticoagulation and the Incidence of Haematoma Formation after Permanent Pacemaker Implantation in the Elderly

BACKGROUND Haematoma formation is a recognised complication after permanent pacemaker (PPM) implantation. The contribution of peri-procedural anticoagulation to the risk of haematoma formation is unclear. METHOD The records of 518 consecutive patients, mean age 76.9±9.8 years, receiving their first PPM (2004-2007) in a single tertiary referral centre were reviewed. Follow-up was complete for 506 patients (97.7%) up to six weeks. Haematomas were diagnosed clinically, and further subdivided according to the need for evacuation. RESULTS There were 27 instances of haematoma formation in 25 patients (4.9%) with 19 requiring drainage or evacuation. Twenty-one of the 25 patients who developed a haematoma had stopped warfarin and received bridging therapeutic anticoagulation pre- and post-PPM. The incidence of haematoma was significantly greater in those receiving peri-operative therapeutic anticoagulation (26.9% vs 0.9%, p<0.001), but was unaffected by the use of anti-platelet therapy. Most haematomas developed in patients whose heparin was recommenced within 24 hours of implantation. The development of haematoma post-PPM increased median hospital stay significantly (p<0.001). The main indication for anticoagulation in these patients was atrial fibrillation (79.5%) and most of these patients had a low to intermediate risk of peri-procedural thromboembolic events. CONCLUSION Peri-operative therapeutic anticoagulation is associated with more than 25-fold increase in haematoma formation post-pacemaker implantation. The risk-benefit ratio of therapeutic anticoagulation should be carefully considered, particularly in patients with a low risk of thromboembolic events.

Right atrial to left atrial area ratio on early echocardiography predicts long-term survival after acute pulmonary embolism.

BackgroundCurrent 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.MethodsA 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.ResultsIn 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.ConclusionA 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.

Acute coronary syndrome and stable coronary artery disease: Are they so different? Long-term outcomes in a contemporary PCI cohort

BACKGROUND Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are known to have poorer short-term prognosis compared to stable coronary artery (CAD) patients undergoing elective PCI. Few studies have made direct comparison of long-term mortality between ACS and stable CAD patients undergoing PCI. The aim of our study was to compare the long-term mortality following PCI between patients with ACS and those with stable CAD. METHODS We examined consecutive patients undergoing PCI with stenting at a tertiary referral hospital. Clinical, angiographic and biochemical data were collected and analysed. The primary outcome was all-cause mortality retrieved from the Statewide Death Registry database. RESULTS Included were 1923 consecutive PCI patients (970 stable CAD and 953 ACS). The mean follow-up time was 4.1 years ± 1.8 years. In-hospital mortality was 1.4% overall, seen exclusively in patients with ACS (n=28, 2.9%). Post-discharge mortality was 6.7% among patients with stable CAD and 10.5% for ACS (P<0.01). Multivariate predictors of post-discharge deaths for both groups included age (HR 1.08 per year, P<0.001) and impaired renal function (HR 2.49, P<0.001). Following adjustment for these factors, an ACS indication for PCI was not associated with greater post-discharge mortality (adjusted HR 1.18: 0.85-1.64, P=0.32). CONCLUSIONS Patients undergoing PCI following an ACS have higher long-term mortality to those with stable CAD, which is potentially explained by a greater prevalence of comorbidities. This suggests that for the ACS population, contemporary interventional and medical management strategies may effectively and specifically counter the adverse prognostic impact of coronary instability and myocardial damage.

Cardiac troponin-T and the prediction of acute and long-term mortality after acute pulmonary embolism

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.

Asymptomatic left ventricular dysfunction with long-term clozapine treatment for schizophrenia: a multicentre cross-sectional cohort study

Objectives Patients with schizophrenia treated with clozapine are at risk of acute myocarditis and dilated cardiomyopathy. However, there are no data on the prevalence of subclinical cardiomyopathy or its associations. Methods 100 consecutive patients with schizophrenia treated with clozapine for >1 year and without a history of cardiac pathology (group 1), 21 controls with a history of schizophrenia treated with non-clozapine antipsychotics for >1 year (group 2) and 20 controls without schizophrenia (group 3) were studied. Comprehensive evaluation by clinical examination, ECG, transthoracic echocardiography including left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) and biochemical profiles were performed. Results Patients with schizophrenia were of similar age, but had higher body mass index (BMI), rates of smoking and hyperlipidaemia than controls. Patients with schizophrenia had received clozapine or non-clozapine antipsychotics for a mean duration of 6.8±5.3 and 9.7±6.1 years, respectively. Patients taking clozapine demonstrated globally impaired LVEF (58.3%: group 1 vs 62.2%: group 2 vs 64.8%: group 3, p<0.001) and GLS (−16.7%: group 1 vs −18.6%: group 2 vs −20.2%: group 3, p<0.001). Moreover, LVEF was <50% in 9/100 (9%) patients receiving clozapine and in non-clozapine schizophrenia patients or healthy controls, but this was not statistically significantly different (analysis of covariance, p=0.19). Univariate analysis in patients taking clozapine found that impaired LV was not predicted by high-sensitivity troponin T, but was associated with features of the metabolic syndrome (including increased triglycerides, low high-density lipoprotein cholesterol (HDL-C), high-sensitivity C reactive protein and BMI), elevated neutrophil count, elevated heart rate, smoking and N-terminal probrain natriuretic peptide. In patients taking clozapine, multivariable analysis identified elevated neutrophil count and low HDL-C as the only independent predictors of impaired GLS. Conclusions Asymptomatic mild LV impairment is common in patients with schizophrenia receiving long-term clozapine treatment and is associated with neutrophilia and low HDL-C.

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.

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.