A prospective validation of the HEART score for chest pain patients at the emergency department.

BACKGROUND: The focus of the diagnostic process in chest pain patients at the emergency department is to identify both low and high risk patients for an acute coronary syndrome (ACS). The HEART score was designed to facilitate this process. This study is a prospective validation of the HEART score. METHODS: A total of 2440 unselected patients presented with chest pain at the cardiac emergency department of ten participating hospitals in The Netherlands. The HEART score was assessed as soon as the first lab results and ECG were obtained. Primary endpoint was the occurrence of major adverse cardiac events (MACE) within 6 weeks. Secondary endpoints were (i) the occurrence of AMI and death, (ii) ACS and (iii) the performance of a coronary angiogram. The performance of the HEART score was compared with the TIMI and GRACE scores. RESULTS: Low HEART scores (values 0-3) were calculated in 36.4% of the patients. MACE occurred in 1.7%. In patients with HEART scores 4-6, MACE was diagnosed in 16.6%. In patients with high HEART scores (values 7-10), MACE occurred in 50.1%. The c-statistic of the HEART score (0.83) is significantly higher than the c-statistic of TIMI (0.75)and GRACE (0.70) respectively (p<0.0001). CONCLUSION: The HEART score provides the clinician with a quick and reliable predictor of outcome, without computer-required calculating. Low HEART scores (0-3), exclude short-term MACE with >98% certainty. In these patients one might consider reserved policies. In patients with high HEART scores (7-10) the high risk of MACE may indicate more aggressive policies.

The predictive value of the exercise ECG for major adverse cardiac events in patients who presented with chest pain in the emergency department.

BACKGROUND: To improve early diagnostic and therapeutic decision making, we designed the HEART score for chest pain patients in the emergency department (ED). HEART is an acronym of its components: History, ECG, Age, Risk factors and Troponin. Currently, many chest pain patients undergo exercise testing on the consecutive days after presentation. However, it may be questioned how much diagnostic value the exercise ECG adds when the HEART score is already known. METHODS: A subanalysis was performed of a multicenter prospective validation study of the HEART score, consisting of 248 patients who underwent exercise testing within 7 days after presentation in the ED. Outcome is the predictive value of exercise testing in terms of major adverse cardiac events (MACE) within 6 weeks after presentation. RESULTS: In low-risk patients (HEART score ≤ 3), 63.1 % were negative tests, 28.6 % non-conclusive and 8.3 % positive; the latter were all false positives. In the intermediate-risk group (HEART score 4-6), 30.9 % were negative tests, 60.3 % non-conclusive and 8.8 % positive, half of these positives were false positives. In the high-risk patients (HEART score ≥ 7), 14.3 % were negative tests, 57.1 % non-conclusive and 28.6 % positive, of which half were false positives. CONCLUSION: In a chest pain population risk stratified with HEART, exercise testing has only a modest contribution to clinical decision making. 50 % of all tests are non-conclusive, with high rates of false positive tests in all three risk groups. In intermediate-risk patients, negative exercise tests may contribute to the exclusion of disease. Clinicians should rather go for sensitive tests, in particular in patients with low HEART scores.

Diagnostic value of a heart-type fatty acid-binding protein (H-FABP) bedside test in suspected acute coronary syndrome in primary care.

BACKGROUND: To determine the diagnostic accuracy of a rapid heart-type fatty acid-binding protein (H-FABP) test in patients suspected of acute coronary syndrome (ACS) in primary care. METHODS: General practitioners included 298 patients suspected of ACS. In all patients, whether referred to hospital or not, ECG and cardiac biomarker testing was performed. ACS was determined in accordance with international guidelines. Multivariate analysis was used to determine the value of H-FABP in addition to clinical findings. RESULTS: Mean patient age was 66 years (SD 14), 52% was female and 66 patients (22%) were diagnosed with ACS. The H-FABP bedside test was performed within 24h (median 3.1, IQR 1.5 to 7.1) after symptom onset. The positive predictive value (PPV) of H-FABP was 65% (95% confidence interval (CI) 50-78). The negative predictive value (NPV) was 85% (95% CI 80-88). Sensitivity was 39% (29-51%) and specificity 94% (90-96%). Within 6h after symptom onset, the PPV was 72% (55-84) and the NPV was 83% (77-88), sensitivity 43% (31-57%) and specificity 94% (89-97%). Adding the H-FABP test to a diagnostic model for ACS led to an increase in the area under the receiver operating curve from 0.66 (95% CI 0.58-0.73) to 0.75 (95% CI 0.68-0.82). CONCLUSION: The H-FABP rapid test provides modest additional diagnostic certainty in primary care. It cannot be used to safely exclude rule out ACS. The test can only be used safely in patients otherwise NOT referred to hospital by the GP, as an extra precaution not to miss ACS ('rule in').

Gender differences in pre-hospital time delay and symptom presentation in patients suspected of acute coronary syndrome in primary care.

OBJECTIVE: To describe gender differences in pre-hospital delay times and symptom presentation in patients suspected of acute coronary syndrome (ACS) in a primary care setting. METHODS: Over 150 participating GPs included 298 consecutive patients suspected of ACS (52% female, mean age 66 years, 22% eventually diagnosed with ACS according to international guidelines) in a 28-month time period. Data on time from call for help until GP consultation (doctor delay) were prospectively collected, while the time from onset of symptoms until call for help (patient delay) was recorded by the GP at the time of arrival at the patient, together with patient characteristics, including age, sex, previous medical history, chest pain, radiation of chest pain and nausea/sweating. RESULTS: Median doctor delay was 45 [interquartile range (IQR) 20-55] minutes in women and 33 (IQR 26-72) minutes in men (P = 0.01). Median patient delay was 108 (IQR 39-348) minutes in women and 180 (IQR 48-396) minutes in men (P = 0.20). Women reported spreading chest pain more often than men (68% versus 57%, P = 0.06). Women diagnosed with ACS were older than men (mean 75 years versus 65 years, P < 0.001). CONCLUSIONS: In patients suspected of ACS in primary care, no differences were found in patient delay, but doctor delay was longer in women than in men. Symptom presentation was largely similar between men and women, although women tended to report 'spreading' chest pain more often.

Chest pain in the emergency room: a multicenter validation of the HEART Score.

OBJECTIVE: Decision-making in chest pain patients is hampered by poor diagnostic power of patient's history, electrocardiogram, age, risk factors, and troponin. Each of these findings may be qualified with 0, 1, or 2 points. Together they compose the HEART score. We tested the hypothesis that the HEART score predicts major adverse cardiac events. DESIGN: Retrospective multicenter analysis in patients presenting at the cardiology emergency room. SETTING: Patient inclusion between January 1 and March 31, 2006. PATIENTS: A total of 2161 patients were admitted, of which 910 patients (42%) presented with chest pain. Analysis was performed in 880 cases (96.7%). MAIN OUTCOME MEASURES: The primary endpoint was a composite of acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery and death, within 6 weeks after presentation, together called major adverse cardiac events. RESULTS: A total of 158 patients (17.95%) reached the primary endpoint. Ninety-two patients had an acute myocardial infarction (10.45%), 82 a percutaneous coronary intervention (9.32%), 36 a coronary artery bypass graft (4.09%), and 13 died (1.48%). Of 303 patients with HEART score 0 to 3, three (0.99%) had an endpoint. In 413 patients with HEART score 4 to 6, 48 cases (11.6%) reached an endpoint. In case of a HEART score of 7 to 10, an endpoint was reached in 107/164 cases (65.2%). CONCLUSIONS: The HEART score helps in making accurate diagnostic and therapeutic decisions without the use of radiation or invasive procedures. The HEART score is an easy, quick, and reliable predictor of outcome in chest pain patients and can be used for triage.

Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): background and design of a diagnostic study in primary care.

BACKGROUND: Currently used biomarkers for cardiac ischemia are elevated in blood plasma after a delay of several hours and therefore unable to detect acute coronary syndrome (ACS) in a very early stage. General practitioners (GPs), however, are often confronted with patients suspected of ACS within hours after onset of complaints. This ongoing study aims to evaluate the added diagnostic value beyond clinical assessment for a rapid bedside test for heart-type fatty-acid binding protein (H-FABP), a biomarker that is detectable as soon as one hour after onset of ischemia. METHODS: Participating GPs perform a blinded H-FABP rapid bedside test (Cardiodetect) in patients with symptoms suggestive of ACS such as chest pain or discomfort at rest. All patients, whether referred to hospital or not, undergo electrocardiography (ECG) and venapunction for a plasma troponin test within 12-36 hours after onset of complaints. A final diagnosis will be established by an expert panel consisting of two cardiologists and one general practitioner (blinded to the H-FABP test result), using all available patient information, also including signs and symptoms. The added diagnostic value of the H-FABP test beyond history taking and physical examination will be determined with receiver operating characteristic curves derived from multivariate regression analysis. CONCLUSION: Reasons for presenting the design of our study include the prevention of publication bias and unacknowledged alterations in the study aim, design or data-analysis. To our knowledge this study is the first to assess the diagnostic value of H-FABP outside a hospital-setting. Several previous hospital-based studies showed the potential value of H-FABP in diagnosing ACS. Up to now however it is unclear whether these results are equally promising when the test is used in primary care. The first results are expected in the end of 2008.

Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISON II): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation for the treatment of total coronary occlusions.

BACKGROUND: Sirolimus-eluting stents markedly reduce the risk of restenosis compared with bare metal stents. However, it is not known whether there are differences in effectiveness between bare metal and sirolimus-eluting stents in patients with total coronary occlusions. METHODS AND RESULTS: In a prospective, randomized, single-blind, 2-center trial, we enrolled 200 patients with total coronary occlusions: Half (n = 100) were randomly assigned to receive bare metal BxVelocity stents and half (n = 100) to receive sirolimus-eluting Cypher stents. The primary end point was angiographic binary in-segment restenosis rate at 6-month follow-up. Secondary end points were a composite of major adverse cardiac events, target vessel failure, binary in-stent restenosis rate, in-stent and in-segment minimal lumen diameter, percent diameter stenosis, and late luminal loss at 6-month follow-up. The sirolimus stent group showed a significantly lower in-stent binary restenosis rate of 7% compared with 36% in the bare metal stent group (P < 0.001). The in-segment binary restenosis rate was 11% in the group receiving a sirolimus stent versus 41% in the bare metal stent group (P < 0.0001), resulting in a target lesion revascularization rate of 4% in the sirolimus group versus 19% in the bare metal group (P < 0.001). Patients who received the drug-eluting stent also had significantly lower rates of target vessel revascularization, target vessel failure, and all major adverse cardiac events. CONCLUSIONS: In patients with total coronary occlusions, use of the sirolimus-eluting stents are superior to the bare metal stents with significant reduction in angiographic binary restenosis, resulting in significantly less need for target lesion and target vessel revascularization.

Long-term follow-up of coronary angioplasty in patients with diabetes compared with nondiabetics.

BACKGROUND: Some reports have indicated that in patients with diabetes mellitus and multivessel disease, coronary artery bypass surgery is preferred over percutaneous coronary intervention (PCI). We retrospectively compared outcome PCI in diabetic and nondiabetic patients. METHODS: Ninety-seven diabetics and 971 nondiabetics were included and randomised before PCI to aspirin alone or aspirin plus coumadin. Fifty diabetics and 481 nondiabetics underwent follow-up angiography. The primary endpoint comprised all-cause mortality, myocardial infarction or targetvessel revascularisation. RESULTS: Baseline characteristics were similar between the groups except for significantly more males and smokers among the nondiabetics. The diabetics had significantly more previous strokes, more left anterior descending coronary artery disease as well as more restenotic lesions and multivessel disease. At 30 days, the primary endpoint had occurred in five diabetics (5.2%) and 47 nondiabetics (4.9%), (p=0.8) and at one year in 17 (17.5%) and in 165 (17.1%), respectively (p=0.9). Event-free survival remained comparable during long-term follow-up (four years). Multivariate analysis showed no differences for the occurrence of any event (p=0.9, 95% CI 0.6-1.7). At six months, the minimal luminal diameter was significantly smaller in the diabetics (1.55±0.76 mm vs. 1.78±0.66 mm, p=0.01). Diabetics also had more restenosis (41% vs. 23%, p=0.003). CONCLUSION: Despite angiographical differences at six months between the diabetics and nondiabetics, both short-term and long-term clinical follow-up appeared to be similar.

Long term follow up after elective percutaneous coronary intervention for unprotected non-bifurcational left main stenosis: is it time to change the guidelines?

BACKGROUND: According to the American College of Cardiology/American Heart Association guidelines, percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) stenosis is contraindicated and coronary artery bypass graft surgery (CABG) is preferred. However, PCI of the LMCA is performed under exceptional circumstances. OBJECTIVE: To analyse the data of patients who underwent PCI of the unprotected LMCA in St Antonius Hospital, Nieuwegein, Netherlands. RESULTS: In a database of 17 683 PCI procedures, 71 patients (0.4%) were found with non-bifurcational LMCA stenosis who underwent an elective PCI between 1991 and 2001. Ages ranged from 26.7-86.5 years. Severe concomitant disease was the most frequent argument in favour of PCI instead of CABG. PCI consisted of only balloon angioplasty in 23 cases (32.4%). A stent was used in 46 cases (64.4%). Average follow up was 43 months (range 0-121 months). One patient died one day after the procedure. The total one year survival rate was 98.6% (70/71). Seven patients died during the follow up period, mostly because of non-cardiac reasons. The annual mortality rate was 2.5%. Recurrent elective percutaneous transluminal coronary angioplasty for restenosis of the LMCA was performed in one patient (1.4%) six weeks after the initial procedure. CABG was required in 13 patients (18.3%) throughout the follow up period. CONCLUSION: These results suggest that at highly experienced centres, elective PCI of the non-bifurcational LMCA can be performed safely where the anatomy is suitable.

Stenting for restenotic lesions with the BARD XT stent.

BACKGROUND: Conventional PTCA for the treatment of restenotic lesions is associated with a high rate of recurrence (30-50%). Primary stenting decreases the restenosis rate at long-term follow-up. METHODS: One-hundred consecutive patients with restenosis received a Bard XT stent. Follow-up angiography was performed after 6 months. Angiograms were compared by means of computed quantitative analysis. RESULTS: The mean pretreatment reference diameter was 2.88 +/- 0.51 mm. The mean minimal luminal diameter (MLD) increased from 1.09 +/- 0.57 mm to 2.70 +/- 0.44 mm. The percent diameter stenosis decreased from 66 +/- 13% to 15 +/- 10%. The procedural success rate was 99%. At 6 month follow-up repeat angiography was performed in 86 patients. The mean MLD was 1.74 +/- 0.67 mm with a mean diameter stenosis of 41 +/- 20%. Residual anginal complaints were reported in 29% of patients. In-stent restenosis (defined as diameter stenosis of more than 50%) occurred in 18% of the patients. CONCLUSION: Placement of the Bard XT stent in restenotic lesions is feasible, has an excellent short term outcome and yields a favorable result at 6 month follow-up angiography.

Is direct stent implantation without predilatation safe? Acute and long-term outcome.

Direct stenting could potentially lead to a reduction in dissections, time, and restenosis at 6-month follow-up. Using the premounted Palmaz-Schatz Crown stent elective stenting was performed without predilatation in 61 consecutive patients who were compared with a control group of provisional stenting. All patients underwent clinical and angiographic follow-up at 6 months. Direct stenting was successful in 81% of patients. In 16% of the patients predilatation was needed. In 3% the stent could not be implanted despite predilatation. Stent dislodgment occurred in 2% of patients, without embolization. Six-month angiographic follow-up was performed in 51 (84%) of 61 patients. In the direct stenting group the mean preprocedural minimal luminal diameter (MLD) increased from 0.96 +/- 0.47 to 3.09 +/- 0.54 mm directly after the procedure. At 6-month follow-up the MLD measured 2.32 +/- 0.79 mm. In the provisional stenting group the mean MLD increased from 0.92 +/- 0.51 to 2.44 +/- 0.58 mm and was 1.84 +/- 0.70 mm at 6-month follow-up. Restenosis, defined as a diameter stenosis > 50%, occurred in 8% of the direct stenting group compared with 28% in the provisional stenting group (P < 0.001). Direct coronary stent implantation can be attempted safely and efficaciously. The risk of stent loss is low. The initial and long-term angiographic results are significantly better as compared with provisional stenting. The risk of restenosis is significantly lower.

How good are experienced cardiologists at predicting the hemodynamic severity of coronary stenoses when taking fractional flow reserve as the gold standard.

BACKGROUND: Coronary angioplasty should be based on documented ischemia. However, in daily clinical practice the indication for angioplasty is often based on eyeball assessment of the severity of the stenosis. This study was performed to assess the accuracy of eyeball estimation of coronary stenosis when taking functional flow reserve (FFR) as gold standard. METHODS: Study lesions were where no mutual agreement on the severity of the stenosis was obtained. The procedure consisted of a repeat control angiogram, FFR measurement and in case of FFR<75% percutaneous coronary intervention. The eyeball assessment of the stenosis was written down before further execution of the procedure. FFR was measured with a pressure monitoring guide. Maximal myocardial hyperemia was induced by intravenous adenosine infusion. RESULTS: Fifty-two patients were studied. Agreement between eyeball assessment and FFR existed in a total of 36 cases (69.2%). Over estimation of hemodynamic severity occurred in six cases (11.5%) and under estimation in 10 cases (19.2%). Consequently, the positive predictive value of eyeball assessment for pressure-derived FFR was 63% and the negative predictive value 76%. CONCLUSION: The assessment of the hemodynamic severity of intermediate coronary stenosis should not be based on eyeball assessment even by experienced interventional cardiologists.

Early and late effects of coumarin therapy started before percutaneous coronary intervention: Clinical, angiographic and cost-effective outcome of the Balloon Angioplasty and Anticoagulation Study (BAAS).

BACKGROUND: Coronary angioplasty frequently creates a thrombogenic surface with subsequent mural thrombosis that may lead to acute complications and possibly stimulates the development of restenosis. Whether coumarins can prevent these complications is unclear. METHODS: In the Balloon Angioplasty and Anticoagulation Study (BAAS), the effect of coumarins started before the procedure on early and late outcome was studied. Patients were randomised to aspirin only or to aspirin plus coumarins. Half of the patients were randomised to undergo six-month angiographic follow-up. Study medication was started one week before coronary angioplasty and the target international normalised ratio (INR) was 2.1-4.8 during angioplasty and six-month follow-up. 'Optimal' anticoagulation was defined as an INR in the target range for at least 70% of the follow-up time. In addition, cost-effectiveness of coumarin treatment was measured. RESULTS: At one year death, myocardial infarction, target-lesion revascularisation and stroke were observed in 14.3% of the 530 patients randomised to aspirin plus coumarin versus in 20.3% of the 528 patients randomised to aspirin alone (relative risk 0.71; 95% CI 0.54-0.93). The incidence of major bleedings and false aneurysms during hospitalisation was 3.2% and 1.0%, respectively, (relative risk 3.39; 95% CI 1.26-9.11). Optimal anticoagulation was an independent predictor of late thrombotic events (relative risk, 0.33; 95% CI, 0.19-0.57). Quantitative coronary analysis was performed of 301 lesions in the ASA group and of 297 lesions in the coumarin group. At six months, the minimal luminal diameter was similar in the ASA and coumarin group. However, optimal anticoagulation was an independent predictor of angiographic outcome at six months. Optimal anticoagulation led to a 0.21 mm (95% CI: 0.05-0.37) larger MLD as compared with suboptimal anticoagulation whereas aspirin use led to a 0.12 mm (95% CI -0.28-0.04) smaller MLD. When including all costs, the savings associated with coumarin treatment were estimated at € 235 per patient after one year. CONCLUSIONS: Coumarin pretreatment reduces early and late events in patients undergoing percutaneous coronary intervention at the expense of a small increase in nonfatal bleeding complications. Furthermore, an optimal level of anticoagulation is associated with a significantly better outcome as compared with a suboptimal level of anticoagulation. In addition, coumarin treatment reduces costs.

Hepatitis E virus antibody prevalence among persons who work with swine.

Prevalence of antibody and risk factors to hepatitis E virus (HEV) infection were determined in a cross-sectional study of 2 group-matched populations: swine farmers (n=264) and persons without occupational exposure to swine (n=255) in Moldova, a country without reported cases of hepatitis E. The prevalence of HEV infection was higher among swine farmers than among the comparison group (51.1% vs. 24.7%; prevalence ratio, 2.07; 95% confidence interval [CI], 1.62-2.64). In multivariate analysis, HEV infection was associated with an occupational history of cleaning barns or assisting sows at birth (odds ratio [OR], 2.46; 95% CI, 1.52-4.01), years of occupational exposure (OR, 1.04 per year; 95% CI, 1.01-1.07), and a history of drinking raw milk (OR, 1.61; 95% CI, 1.08-2.40). HEV infection was not associated with civilian travel abroad or having piped water in the household. The increased prevalence of HEV infection among persons with occupational exposure to swine suggests animal-to-human transmission of this infection.

Childhood hepatitis B virus infections in the United States before hepatitis B immunization.

OBJECTIVE: To estimate the number of hepatitis B virus (HBV) infections among US children younger than 10 years before implementation of routine childhood hepatitis B immunization. METHODS: Incidence of HBV infection in children was modeled from existing prevalence data by means of regression analysis. Sources of data for the models included published and unpublished surveys that determined the prevalence of HBV infection in US-born children. The number of nonperinatal HBV infections in children younger than 10 years was estimated by applying these infection rates to 1991 population data according to maternal race, ethnicity, and birthplace. RESULTS: Estimated annual rates of infection ranged from 24 per 100 000 in non-Asian children to 2580 per 100 000 in children of Southeast Asian immigrant mothers. These rates indicate that by the early 1990s, HBV was infecting 16 000 children who were younger than 10 years (8700 non-Asian children and 7300 Asian-American children) annually. The total estimate, not including perinatal infections, ranged from 12 000 (95% confidence interval: 5500-27 700) to 24 900 (95% confidence interval: 16 700-42 300) infections and depended on how the estimated rates were applied to the population data. CONCLUSION: Thousands of US children were infected each year with HBV before routine infant hepatitis B immunization, placing them at high risk of death from cirrhosis or hepatocellular carcinoma later in life.