High Bleeding Incidence in Unselected Hospitalized Suspected Non-ST-Segment Elevation Myocardial Infarction Patients Aged Under 65 Years.

High bleeding risk (HBR) is commonly encountered among patients with acute coronary syndrome (ACS), and bleeding complications are associated with worse prognosis. Data on bleeding events of patients with ACS are based almost exclusively on percutaneous coronary intervention registries. Enrolling only patients suitable for invasive procedures might have skewed the observed bleeding incidence. We sought to investigate bleeding incidence in unselected patients with ACS. Patients were retrospectively enrolled between January and June 2019 from the emergency department of a tertiary hospital. All consecutive hospitalized adults with suspected non-ST-segment elevation myocardial infarction were included. Data was gathered by a database search and verified using electronic patient records. Bleeding risk was assessed according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition. The primary end point was a composite of post- discharge Bleeding Academic Research Consortium type 2, 3, and 5 bleeding during 1-year follow-up. Of the 209 included patients, 15 (7.2%) suffered a bleeding event. There were more bleeding events among dual antiplatelet therapy (DAPT) users as compared with those without DAPT (10.7% vs 3.1%, p = 0.033). Among HBR patients, 6.1% and in non-HBR patients 8.1% suffered a bleeding event (p = 0.579). Notably, major bleeding (Bleeding Academic Research Consortium type 3) incidence was highest in patients <65 years and without DAPT use. In conclusion, unselected suspected non-ST-segment elevation myocardial infarction patients aged <65 years had surprisingly high bleeding incidence, regardless of ARC-HBR status or DAPT use.

Impact of Intraprocedural Pressure Changes on Hemodynamic Outcome During Self-Expanding TAVR.

INTRODUCTION: During the transcatheter aortic valve replacement (TAVR) procedure, hemodynamic measurements can be used to evaluate transcatheter heart valve (THV) performance. We hypothesized that the occurrence of a significant decrease in invasive aortic pressure immediately after annular contact by a self-expanding THV indicates effective annular sealing. This phenomenon could thus be used as a marker for the occurrence of paravalvular leak (PVL). METHODS: Thirty-eight patients undergoing TAVR procedure with a self-expandable Evolut R or Evolut Pro (Medtronic) valve prosthesis were included in the study. Drop in aortic pressure during valve expansion was defined as a decrease in systolic pressure of 30 mmHg immediately after annular contact. The primary endpoint was the occurrence of more than mild PVL immediately after valve implantation. RESULTS: A pressure drop was seen in 60.5% (23/38) of patients. More than mild PVL requiring balloon post-dilatation (BPD) was significantly more frequent in patients who did not have a systolic pressure decrease > 30 mmHg during valve implantation (46.7% [7/15] vs. 13.0% [3/23], respectively; p = 0.03). Patients without a systolic pressure decrease > 30 mmHg also had a lower mean cover index on computed tomography analysis (16.2% vs. 13.3%; p = 0.016). The 30-day outcomes were similar between the two groups, and echocardiography at 30 days demonstrated more than none/trace PVL in 21.1% (8/38) of patients, with no difference between the two groups. CONCLUSION: A decrease in aortic pressure after annular contact is associated with an increased probability of good hemodynamic outcome after self-expanding TAVR implantation. In addition to other methods, this parameter could be used as an additional marker for optimal valve positioning and hemodynamic outcome during the implantation procedure.

Prevalence of High Bleeding Risk among Hospitalized Suspected NSTEMI Patients.

In recent years, guidelines for the management of acute coronary syndromes (ACS) have placed more emphasis on identifying patients at high bleeding risk (HBR). We set out to investigate the prevalence of HBR patients according to the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in hospitalized patients with suspected non-ST-segment elevation myocardial infarction (NSTEMI). Consecutive patients were retrospectively enrolled between January and June 2019 from the emergency department (ED) of a tertiary hospital. The discharge diagnosis and baseline data were manually collected using electronic patient records and database searches. Patients with non-cardiac diagnoses were excluded. Overall, 212 patients were included in the study. A total of 146 (68.9%) patients were diagnosed with NSTEMI (Type 1), 47 (22.2%) with unstable angina pectoris (UAP) and 19 (9.0%) with "other." HBR was detected in 47.6% (n = 101) of all patients. Common criteria for HBR among ACS patients were age (40.4%), chronic kidney disease (33.7%), and the use of oral anticoagulation medicines (20.2%). In conclusion, nearly half of the patients hospitalized for ACS fulfilled HBR criteria. According to contemporary guidelines, the management of HBR patients differs from that of non-HBR patients, and thus, a more comprehensive screening for HBR may be considered in clinical practice.

Etiology of Minor Troponin Elevations in Patients with Atrial Fibrillation at Emergency Department-Tropo-AF Study.

Patients with atrial fibrillation (AF) presenting to the emergency department (ED) often have elevated cardiac troponin T (TnT) levels without evidence of type 1 myocardial infarction. We sought to explore the causes and significance of minor TnT elevations in patients with AF at the ED. All patients with AF admitted to the ED of Turku University Hospital between 1 March, 2013 and 11 April, 2016, and at least two TnT measurements, were screened. Overall, 2911 patients with a maximum TnT of 100 ng/L during hospitalization were analyzed. TnT was between 15 and 100 ng/L in 2116 patients. The most common primary discharge diagnoses in this group were AF (18.1%), infection (18.3%), ischemic stroke/transient ischemic attack (10.7%), and heart failure (5.0%). Acute coronary syndrome (ACS) was equally uncommon both in patients with normal TnT and elevated TnT (4.4% vs. 4.5%). Age ≥75 years, low estimated glomerular filtration rate (eGFR), high C-reactive protein (CRP), and hemoglobin <10.0 g/dL, were the most important predictors of elevated TnT. Importantly, TnT elevation was a very frequent (>93%) finding in elderly (≥75 years) AF patients with either low eGFR or high CRP. In conclusion, minor TnT elevations carry limited diagnostic value in elderly AF patients with comorbidities.

Trends in occurrence and 30-day mortality of infective endocarditis in adults: population-based registry study in Finland.

OBJECTIVES: Infective endocarditis (IE) is a life-threatening disease associated with significant mortality. We studied recent temporal trends and age and sex differences in the occurrence and short-term mortality of IE. DESIGN: Population based retrospective cohort study. SETTING: Data of IE hospital admissions in patients aged ≥18 years in Finland during 2005-2014 and 30-day all-cause mortality data were retrospectively collected from mandatory nationwide registries from 38 hospitals. OUTCOMES: Trends and age and sex differences in occurrence. Thirty-day mortality. RESULTS: There were 2611 cases of IE during the study period (68.2% men, mean age 60 years). Female patients were significantly older than males (62.0 vs 59.0 years, p=0.0004). Total standardised annual incidence rate of IE admission was 6.33/100 000 person-years. Men had significantly higher risk of IE compared with women (9.5 vs 3.7/100 000; incidence rate ratios [IRR] 2.49; p<0.0001) and difference was most prominent at age 40-59 years (IRR 4.49; p<0.0001). Incidence rate varied from 5.7/100 000 in 2005 to 7.1/100 000 in 2012 with estimated average 2.1% increase per year (p=0.036) and similar trends in both sexes. Significant increasing trend was observed in patients aged 18-29 years and 30-39 years (estimated annual increase 7.6% and 7.2%, p=0.002) and borderline in patients aged 40-49 years (annual increase 3.8%, p=0.08). In older population, IE incidence rate remained stable. The overall 30-day mortality after IE admission was 11.3%. Mortality was similar between sexes, increased with ageing, and remained similar during the study period. CONCLUSIONS: Occurrence of IE is increasing in young adults in Finland. Men, especially middle-aged, are at higher risk for IE compared with women. Thirty-day mortality has remained stable at 11%, increased with ageing, and was similar between sexes.

Direct Immunoassay for Free Pregnancy-Associated Plasma Protein A (PAPP-A).

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A), especially in its noncomplexed form (fPAPP-A), is linked to vulnerable atherosclerotic plaques and risk of cardiac events. An assay for sensitive detection of fPAPP-A has been lacking. Our aim was to develop and validate a direct fPAPP-A assay to meet this need. METHODS: Monoclonal antibodies binding exclusively fPAPP-A were produced by immunizing mice with recombinant PAPP-A. In the optimized immunoassay, we used an fPAPP-A-specific capture antibody together with a lanthanide-chelate-labeled monoclonal antibody recognizing all PAPP-A forms. The assay was evaluated with CLSI guidelines and compared to a 2-assay subtractive fPAPP-A approach. Clinical performance was assessed with acute coronary syndrome patients. RESULTS: The limits of detection and quantitation were 0.4 mIU/L and 1.3 mIU/L, respectively, and the assay was linear up to 1000 mIU/L (R2 = 0.999). Both serum and heparin plasma were suitable matrices, and the complexed form of PAPP-A caused no significant interference. Correlation between the developed assay and the 2-assay approach was fair (Pearson's r = 0.819). Median concentration in healthy individuals was 1.0 mIU/L. fPAPP-A concentration was higher in patients who had myocardial infarction or died during the 1-year follow-up period than in those who did not (1.13 mIU/L vs 0.82 mIU/L, P = 0.008, model adjusted with age and sex). fPAPP-A measured with this direct assay predicted this end point as well as (follow-up 1 year) or better (30 days) than the 2-assay fPAPP-A alone or in combination with cTnI. CONCLUSIONS: The new assay enables sensitive and reliable measurement of low cardiac-related fPAPP-A concentrations from blood samples.

[Update on Current Care Guidelines. Current Care Guideline: Stable Coronary Artery Disease]. / Kaypa Hoite-Suosituksen Paivitystiivistelma. Stabiili sepelvaltimotauti.

This guideline covers coronary heart disease symptoms, diagnosis and treatment. Stable coronary heart disease refers to a disease in, which patients have stable symptoms and evidence of ischemia or significant stenosis of coronary artery. Diagnosis is based on medical history and exercise test, which is the primary diagnostic test. Coronary angiography is in selected cases necessary to confirm the diagnosis and assess invasive treatment. Pharmacotherapy aims to improve the survival of the patient, relieve symptoms and improve quality of life. The guideline also deals with invasive treatment either with PCI or CABG.

Autoantibody prevalence with an improved immunoassay for detecting cardiac troponin-specific autoantibodies.

BACKGROUND: Cardiac troponin-specific autoantibodies (cTnAAb) can interfere with the measurement of cardiac troponin I (cTnI) by immunoassays used for the diagnosis of myocardial infarction (MI). Here, an improved version of a previous autoantibody assay was validated and used to evaluate the cTnAAb prevalence in a cohort of consecutive chest pain patients presenting to an emergency department. METHODS: Admission samples from 510 patients with suspected MI were analyzed in parallel with two sandwich-type cTnAAb assays based on different cTnI epitopes used to capture cardiac troponin-bound cTnAAbs. RESULTS: Sample-specific backgrounds were lower for the new assay than for the old assay (median 1225 vs. 2693 counts, p<0.001). Net signals of cTnAAb-positive samples were higher for the new assay than for the old assay (median 5076 vs. 3921 counts, p<0.001). Of all patients, 9.2% were cTnAAb-positive for the new assay and 7.3% for the old assay (p=0.013). Previous cardiac problems were not associated with cTnAAb status and cTnAAb status did not correlate with the 12-month outcome. CONCLUSIONS: With our new and more sensitive autoantibody assay, approximately one out of ten patients who presented to the initial cardiac triage had detectable amounts of cTnAAbs in the circulation. Because these cTnAAbs can interfere with state-of-the-art cTnI assays, their high prevalence should be acknowledged by clinical chemists, physicians, and kit manufacturers.

PR depression is useful in the differential diagnosis of myopericarditis and ST elevation myocardial infarction.

BACKGROUND: Deviation of the PR segment is a common but often ignored ECG finding in acute myopericarditis, but seems to be rare in the acute phase of ST elevation myocardial infarction (STEMI). Since rapid bedside differential diagnosis of acute myopericarditis and STEMI is essential, we decided to assess the diagnostic power of PR depressions in patients presenting with ST elevations in the emergency room. METHODS: Thirty-four consecutive patients with acute myopericarditis and 46 STEMI patients presenting with ST elevations fulfilling the criteria for STEMI were included. The first ECG recorded in the emergency room was analyzed with a focus on the PR segment. The diagnoses of myopericarditis and STEMI were ascertained with clinical follow-up together with rise in troponin levels, and in the STEMI patients also with coronary angiography. RESULTS: In myopericarditis, the most common location for PR depression was lead II (55.9%), while this ECG finding least likely appeared in lead aVL (2.9%). PR depression in any lead had a high sensitivity (88.2%), but fairly low specificity (78.3%) for myopericarditis. The combination of PR depressions in both precordial and limb leads had the most favorable predictive power to differentiate myopericarditis from STEMI (positive 96.7% and negative power 90%). CONCLUSIONS: Our present observations show that PR segment analysis is a powerful tool in the differential diagnosis of myopericarditis and STEMI. This simple information should be added to the diagnostic workup of patients presenting with ST elevations.

Cystatin C as a predictor of all-cause mortality and myocardial infarction in patients with non-ST-elevation acute coronary syndrome.

OBJECTIVES: To investigate the predictive value of cystatin C among patients diagnosed with non-ST-elevation acute coronary syndrome (nSTE-ACS). DESIGN AND METHODS: Admission serum samples from 245 nSTE-ACS patients were measured with a novel cystatin C immunoassay based on a dry-reagent, double monoclonal design. Creatinine concentrations, estimated glomerular filtration rates (eGFR) and one-year follow-up data were available for these patients. RESULTS: During the follow-up period, 34 (14%) of patients had myocardial infarction (MI) and 25 (11%) died. Increased serum cystatin C was an independent predictor of all-cause mortality and combined events (all-cause mortality and MI) after adjustment to non-biomarker baseline factors, hazard ratio (HR) 2.19 (per increase of 1 tertile; 95% Cl 1.28-3.78, p=0.0046) and 1.75 (1.22-2.51, p=0.0024), respectively. Corresponding values for eGFR were 2.56 (1.43-4.59, p=0.0016) and 1.76 (1.23-2.53, p=0.0022), respectively. Creatinine was not an independent predictor of endpoints (p>0.05). CONCLUSIONS: Cystatin C was associated with an increased risk of death and combined events in patients with nSTE-ACS.

Long-term safety of drug-eluting stents in patients on warfarin treatment.

BACKGROUND: The safety of drug-eluting stents (DES) in patients on long-term warfarin treatment has been questioned due to high risk of bleeding complications during prolonged triple (aspirin, clopidogrel, and warfarin) antithrombotic therapy. METHODS: We analysed the long-term outcome of 415 consecutive warfarin-treated patients who underwent DES (n = 191) or bare-metal (n = 224) stenting in six hospitals. RESULTS: The mean duration of triple therapy was longer (4.2 ± 3.1 versus 2.1 ± 1.8 months; P < 0.001) in the DES group. The incidence of major adverse cardiovascular and cerebrovascular events was comparable in the DES and bare-metal groups (39.8% versus 42.4%; P = 0.59) during a median follow-up of 3.5 years. Similarly, major bleeding events occurred equally often in both study groups (14.7% versus 12.9%). Six patients in the DES group and seven patients in the bare-metal group suffered stent thrombosis (3.1% versus 3.1%). In the propensity score analyses of 101 matched pairs, the outcome was similar in the two groups. CONCLUSION: Selective use of DES with a short triple therapy seems to be safe in patients with warfarin therapy. The prognosis of this fragile patient population is quite poor, and major bleeding events are common irrespective of stent type.

Safety of coronary artery bypass surgery during therapeutic oral anticoagulation.

INTRODUCTION: Therapeutic (international normalized ratio, INR 2.0-3.5) oral anticoagulation (TOAC) is assumed to increase perioperative bleeding complications and a standard recommendation is to discontinue warfarin before coronary bypass grafting (CABG). MATERIALS AND METHODS: To assess the safety of TOAC we retrospectively analyzed consecutive patients (n=270) with long-term warfarin therapy referred for CABG in two centers where TOAC strategy is employed. The main in-hospital outcomes of interest were death, stroke, acute myocardial infarction, new onset renal failure, resternotomy, and their composite. In the TOAC group of 103 patients CABG was performed during therapeutic oral anticoagulation and in the control group (81 patients) preoperative INR was lowered to a subtherapeutic (≤1.5) level. RESULTS: The patients in TOAC group were more often operated on an emergency basis (p=0.02) and their EuroSCORE was higher (p=0.02). There were no significant differences in the major outcome events or their composite (17.5 vs. 11.1%, p=0.30) between the groups. Patients in the TOAC group had more postoperative blood loss (941±615 vs. 754±610 ml, p<0.01) and received more fresh frozen plasma (2.8±3.0 vs. 1.3±2.4 units, p<0.001), but transfused red blood cells (2.1±2.8 vs. 2.1±3.4 units) were comparable in the groups. Preoperative clopidogrel (OR 4.8, 95% CI 1.4-16.2, p=0.01) and enoxaparin therapy (OR 2.6, 95% CI 1.1-6.5, p=0.04) were the only significant independent predictors for any major adverse event. CONCLUSIONS: Our study suggests that CABG is a safe procedure during TOAC with no excess bleeding or major complications. Prospective trials are needed to confirm this observation.

Postoperative stroke in patients on oral anticoagulation undergoing coronary artery bypass surgery.

OBJECTIVE: Patients on long-term warfarin treatment have an inherent high risk of stroke and here we aimed to identify the determinants of postoperative stroke after coronary artery bypass grafting (CABG) in these patients. METHODS: A consecutive series of 270 patients on long-term warfarin treatment who underwent isolated CABG in two university hospitals was assessed by logistic regression as well as classification and regression tree (CART) analysis. RESULTS: Postoperative stroke occurred in 10 patients during in-hospital stay (3.7%). Logistic regression showed that CHADS(2) > 2 (p = 0.036), recent thrombolysis (p < 0.0001) and history of deep vein thrombosis (p = 0.025) were independent predictors of postoperative stroke (area under the ROC curve 0.77). CART analysis showed that CHADS(2) > 2, history of stroke/TIA, no preoperative use of aspirin and preoperative use of low molecular weight heparins were associated with an increased risk of stroke (area under the ROC curve of 0.77). CONCLUSIONS: Both CART and logistic regression analyses showed that the patient characteristics included in CHADS(2) score are important also in the prediction of postoperative stroke risk. Preoperative antiplatelet treatment may be beneficial in the high risk patients and the preoperative bridging with low molecular weight heparins may even be harmful in this respect.

Studies on the effects of heparin products on pregnancy-associated plasma protein A.

BACKGROUND: Intravenous low molecular weight (LMWH) and unfractionated heparin (UFH) increase the circulating concentrations of pregnancy-associated plasma protein A (PAPP-A), a novel cardiac risk marker, in haemodialysis and coronary angiography patients. METHODS: To further investigate the mechanisms of heparin effects, free PAPP-A was analysed in serial serum samples collected during haemodialysis (intravenous LMWH), carotid endarterectomy or abdominal aortic aneurysm surgery (intravenous UFH), treatment at intensive care unit (subcutaneous LMWH), and coronary angiography (intravenous bivalirudin). PAPP-A was extracted from plaque tissue samples of endarterectomy and aneurysm patients. The interaction between heparin products and free PAPP-A was studied with gel filtration. RESULTS: After intravenous UFH and LMWH free PAPP-A increased significantly but bivalirudin had no effect. After LMWH bolus in haemodialysis patients 85% of free PAPP-A was cleared with a half-life of 13.1 min and the rest with a half-life of 96.6 min. Subcutaneous LMWH led to lower and slower free PAPP-A elevation. PAPP-A extracted from plaque tissues was in free form and extraction was strongly enhanced by LMWH. Heparin products increased the molecular size of free PAPP-A. CONCLUSIONS: The heparin-induced PAPP-A elevation is seen in various patients and should be taken into account when PAPP-A is studied as a biomarker.

Usefulness of outpatient bleeding risk index to predict bleeding complications in patients with long-term oral anticoagulation undergoing coronary stenting.

Long-term oral anticoagulation (OAC) prevents recurrent thrombosis, pulmonary embolism, and stroke, but it also increases bleeding risk. An outpatient bleeding risk index (OBRI) may help to identify patients at high risk of bleeding complications. The aim of this study was to evaluate the predictive value of OBRI in patients with OAC undergoing percutaneous coronary intervention (PCI). In addition, we analyzed the impact of OBRI on treatment choices in this patient group. Four hundred twenty-one patients with OAC underwent PCI at 6 centers in Finland. Complete follow-up was achieved in all patients (median 1,276 days). Sixty-four patients (15%) had a low bleeding risk (OBRI 0), 319 patients (76%) moderate bleeding risk (OBRI 1 to 2), and 38 (9%) high bleeding risk (OBRI 3 to 4). OBRI had no significant effect on periprocedural or long-term antithrombotic medications, choice of access site, or stent type. During follow-up, the incidence of major bleeding increased (p = 0.02) progressively with higher OBRI category (6.3%, 14.1%, and 26.3%, respectively). Similarly, mortality was highest in patients with high OBRI (14.1%, 20.7%, and 39.5%, p = 0.009, respectively), but rates of major adverse cardiovascular and cerebrovascular events were comparable in the OBRI categories. In conclusion, bleeding risk seems not to modify periprocedural or long-term treatment choices in patients after PCI on home warfarin. In contrast, patients with high OBRI often have major bleeding episodes and this simple index seems to be suitable for risk evaluation in this patient group.

Free vs total pregnancy-associated plasma protein A (PAPP-A) as a predictor of 1-year outcome in patients presenting with non-ST-elevation acute coronary syndrome.

BACKGROUND: The free fraction of pregnancy-associated plasma protein A (FPAPP-A) was found to be the PAPP-A form released to the circulation in acute coronary syndrome (ACS). We estimated the prognostic value of FPAPP-A vs total PAPP-A (TPAPP-A) concentrations in forecasting death and nonfatal myocardial infarction (combined endpoint) in patients with non-ST-elevation ACS. METHODS: We recruited 267 patients hospitalized for symptoms consistent with non-ST-elevation ACS and followed them for 12 months. FPAPP-A, TPAPP-A, C-reactive protein (CRP), and cardiac troponin I (cTnI) were measured at admission; cTnI was also measured at 6-12 h and 24 h. Because of the recently shown interaction between PAPP-A and heparin, we excluded patients treated with any heparin preparations before the admission blood sampling. RESULTS: During the follow-up, 57 (21.3%) patients met the endpoint (22 deaths and 35 nonfatal myocardial infarctions). According to FPAPP-A (<1.27, 1.27-1.74, >1.74 mIU/L) and TPAPP-A (<1.98, 1.98-2.99, >2.99 mIU/L) tertiles, this endpoint was met by 12 (13.5%), 18 (20.2%), 27 (30.3%) (P = 0.02), and 17 (19.1%), 17 (19.1%), 23 (25.8%) (P = 0.54) patients, respectively. After adjusting for age, sex, diabetes, previous myocardial infarction, and ischemic electrocardiogram (ECG) findings, FPAPP-A >1.74 mIU/L [risk ratio (RR) 2.0; 95% CI 1.0-4.1, P = 0.053), increased cTnI, and CRP >/=2.0 mg/L were independent predictors of an endpoint. The prognostic performance of TPAPP-A was inferior to that of FPAPP-A. CONCLUSIONS: FPAPP-A seems to be superior as a prognostic marker compared to TPAPP-A, giving independent and additive prognostic information when measured at the time of admission in patients hospitalized for non-ST-elevation ACS.

Preoperative warfarin treatment and outcome of coronary artery bypass graft surgery.

BACKGROUND: The aim of this case-control study was to evaluate the outcome of isolated coronary artery bypass grafting (CABG) when using a short (median, 2 days) preoperative pause in home warfarin treatment. METHODS: A consecutive series of 162 patients on long-term warfarin treatment (median international normalized ratio at the time of operation, 1.9) who underwent isolated CABG was compared with a matched control group of 162 patients with no oral anticoagulation. RESULTS: The operative risk of warfarin-treated patients was higher (p=0.001) than in the control patients. The in-hospital mortality was comparable in the warfarin and control groups (3.7% versus 2.5%; p=0.52), and there were no significant differences in the postoperative blood loss (818 versus 758 mL), transfused red blood cells (2.1 versus 1.8 units), or reoperations owing to bleeding (5.6% versus 7.4%) between the groups. The warfarin group received more (p<0.0001) fresh-frozen plasma (1.9 versus 0.5 units), needed longer treatment in the intensive care unit (4.1 versus 2.9 days; p<0.0001), and tended to have an increased risk of postoperative stroke (4.9% versus 1.2%; p=0.10). A CHADS2 score greater than 2, but not the international normalized ratio level, was associated with an increased risk of stroke when adjusted for other important comorbidities. Comparable results were observed also in 107 propensity-matched pairs. CONCLUSIONS: The risk of bleeding complications after isolated CABG is not increased when using a short preoperative pause in warfarin treatment. Better preventive strategies for stroke are needed, especially in patients with a high CHADS2 score.

The etiology and prognostic significance of cardiac troponin I elevation in unselected emergency department patients.

BACKGROUND: Cardiac troponin elevations are associated not only with acute coronary syndromes (ACS) but also with multiple other cardiac and non-cardiac conditions. STUDY OBJECTIVES: To investigate the etiology and clinical significance of cardiac troponin I elevations in an unselected Emergency Department (ED) patient cohort. METHODS: The study population consisted of 991 consecutive troponin-positive patients admitted to the ED of a university hospital with ACS as the presumptive diagnosis. Cardiac troponin I was measured on admission and a follow-up sample was obtained at 6-12 h. Clinical diagnosis was ascertained retrospectively using all the available information including electrocardiogram, clinical data, laboratory tests, and available coronary angiograms. RESULTS: At admission, 805 (81.2%) patients were already troponin positive; of these, the troponin elevation was related to myocardial infarction (MI) in 654 (81.2%) patients. Finally, 83.0% of the troponin elevations were due to MI, 7.9% were related to other cardiac causes, and 9.1% to non-cardiac diseases. The leading non-cardiac causes were pulmonary embolism, renal failure, pneumonia, and sepsis. Non-cardiac patients with elevated troponin I at admission showed significantly higher in-hospital mortality (26.7% vs. 13.4%, p = 0.002) compared to cardiac patients. CONCLUSION: Elevated troponin levels for reasons other than MI are common in the ED and are a marker of poor in-hospital prognosis.

Are glycoprotein inhibitors safe during percutaneous coronary intervention in patients on chronic warfarin treatment?

The aim of this study was to evaluate the safety of glycoprotein IIb/IIIa inhibitors (GPIs) during percutaneous coronary intervention (PCI) in patients on chronic warfarin therapy due to atrial fibrillation (AF). We analysed all consecutive AF patients (N = 377, mean age 70 years, male 71%) on warfarin therapy referred for PCI in seven centres. Major bleeding, access site complications and major adverse cardiovascular events were recorded during hospitalisation. A total of 111 patients (29%) received periprocedural GPIs with a wide inter-hospital variation in their use (range 3-68%). The use of GPIs increased with the severity of the disease presentation and 49% of patients with ST-elevation myocardial infarction received GPIs. Mean periprocedural international normalised ratio (INR) of patients who received GPIs was 1.89 (range 1.1-3.3). Major bleeding was more common in the patients treated with GPIs (9.0% vs. 1.5%, p = 0.001) than in those without GPIs, but there was no difference in major adverse cardiovascular events between the groups. In multivariable analysis, use of GPIs (odds ratio [OR] 5.1, 95% confidence interval [CI] 1.3-20.6, p = 0.02) and old age (OR 1.2, 95% CI 1.0-1.3, p= 0.02) remained as the only independent predictors of major bleeding. Also after adjusting for propensity score, GPIs remained as a significant predictor of major bleeding (OR 3.8, 95% CI 1.03-14.1, p = 0.045). In the GPI group, major bleeding was not predicted by INR level or warfarin pause. GPIs increase the risk of major bleeding events irrespective of periprocedural INR levels and should be used with caution in this fragile patient group.

Intravenous administration of low molecular weight and unfractionated heparin elicits a rapid increase in serum pregnancy-associated plasma protein A.

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a useful diagnostic and prognostic marker in acute coronary syndromes. Because low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are commonly used in these cases, we analyzed the effects of intravenous administration of these heparins on serum PAPP-A concentrations. METHODS: Serum concentrations of total and free PAPP-A were analyzed in 14 patients on chronic hemodialysis and in 10 coronary angiography patients. Ten of the dialysis patients received standard LMWH anticoagulation at the start of dialysis, and 4 were treated with a heparin-free method. Two of the patients on heparin-free hemodialysis received a reduced LMWH bolus 2 h after the start of dialysis. All angiography patients received UFH at the start of the procedure, and 1 patient received 2 extra boluses of UFH. Serum PAPP-A concentrations were analyzed before and during the dialysis session and during the coronary angiography examination. RESULTS: A rapid increase in total PAPP-A (median, 25-fold) was seen in all patients within 5 min of administration for both LMWH and UFH boluses. This response was due to an increase in free PAPP-A in the serum. PAPP-A did not increase significantly in the patients who underwent heparin-free hemodialysis. Repeated heparin boluses induced a new PAPP-A release. In vitro addition of heparins to samples of whole blood did not increase PAPP-A concentrations. CONCLUSIONS: Intravenous administration of heparin induces an intense and rapid increase in free PAPP-A in the serum. We recommend that this effect be considered when PAPP-A is assessed as a biomarker in acute coronary syndromes.