Allan Iversen

Field Triage Reduces Treatment Delay and Improves Long-Term Clinical Outcome in Patients With Acute ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

OBJECTIVES We evaluated the independent impact of field triage on treatment delay and long-term clinical outcome in a large contemporary, consecutive population of ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND Reduction of treatment delay is crucial for patients with STEMI. METHODS From January 2005 to July 2008, 1,437 STEMI patients were treated with pPCI at a single high-volume invasive center. We present the 1-year outcome in this observational registry study. RESULTS A total of 616 patients were admitted by field triage and 821 by emergency departments. Baseline and angiographic variables were similar in the 2 populations. Patients admitted by field triage had a significantly shorter median door-to-balloon time compared with patients admitted by emergency department triage (83 min, interquartile range 67 to 100 min vs. 103 min, interquartile range 80 to 135 min; p<0.001). Door-to-balloon times of less than the recommended 90 min were achieved in 61% of field triage patients, but only in 36% of nonfield-triage patients (p<0.001). After adjustment for relevant baseline variables, patients admitted by field triage had a reduced risk of reaching the combined end point of all-cause mortality or nonfatal myocardial infarction (hazard ratio: 0.67; 95% confidence interval: 0.46 to 0.97; p=0.035). CONCLUSIONS This study shows that field triage of STEMI patients to pPCI significantly reduces treatment delay and improves outcome. These results emphasize the value of field triage as an important tool in the quest to improve clinical outcomes in STEMI patients undergoing pPCI.

Myocardial Strain Analysis by 2-Dimensional Speckle Tracking Echocardiography Improves Diagnostics of Coronary Artery Stenosis in Stable Angina Pectoris

Background—Two-dimensional strain echocardiography detects early signs of left ventricular dysfunction; however, it is unknown whether myocardial strain analysis at rest in patients with suspected stable angina pectoris predicts the presence of coronary artery disease (CAD). Methods and Results—In total, 296 consecutive patients with clinically suspected stable angina pectoris, no previous cardiac history, and normal left ventricular ejection fraction were included. All patients were examined by 2-dimensional strain echocardiography, exercise ECG, and coronary angiography. Two-dimensional strain echocardiography was performed in the 3 apical projections. Peak regional longitudinal systolic strain was measured in 18 myocardial sites and averaged to provide global longitudinal peak systolic strain. Duke score, including ST-segment depression, chest pain, and exercise capacity, was used as the outcome of the exercise test. Patients with an area stenosis ≥70% in ≥1 epicardial coronary artery were categorized as having significant CAD (n=107). Global longitudinal peak systolic strain was significantly lower in patients with CAD compared with patients without (17.1±2.5% versus 18.8±2.6%; P<0.001) and remained an independent predictor of CAD after multivariable adjustment for baseline data, exercise test, and conventional echocardiography (odds ratio, 1.25 [P=0.016] per 1% decrease). Area under receiver operating characteristic curve for exercise test and global longitudinal peak systolic strain in combination was significantly higher than that for exercise test alone (0.84 versus 0.78; P=0.007). Furthermore, impaired regional longitudinal systolic strain identifies which coronary artery is stenotic. Conclusions—In patients with suspected stable angina pectoris, global longitudinal peak systolic strain assessed at rest is an independent predictor of significant CAD and significantly improves the diagnostic performance of exercise test. Furthermore, 2-dimensional strain echocardiography seems capable of identifying high-risk patients.

High-degree atrioventricular block complicating ST-segment elevation myocardial infarction in the era of primary percutaneous coronary intervention

AIMS Primary percutaneous coronary intervention (pPCI) has replaced thrombolysis as treatment-of-choice for ST-segment elevation myocardial infarction (STEMI). However, the incidence and prognostic significance of high-degree atrioventricular block (HAVB) in STEMI patients in the pPCI era has been only sparsely investigated. The objective of this study was to assess the incidence, predictors and prognostic significance of HAVB in STEMI patients treated with pPCI. METHODS AND RESULTS This study included 2073 STEMI patients treated with pPCI. The patients were identified through a hospital register and the Danish National Patient Register. Both registers were also used to establish the diagnosis of HAVB. All-cause mortality was the primary endpoint. During a median follow-up of 2.9 years [interquartile range (IQR) 1.8-4.0] 266 patients died. High-degree atrioventricular block was documented in 67 (3.2%) patients of whom 25 died. Significant independent predictors of HAVB included right coronary artery occlusion, age >65 years, female gender, hypertension, and diabetes. The adjusted mortality rate was significantly increased in patients with HAVB compared to patients without HAVB [hazard ratio = 3.14 (95% confidence interval 2.04-4.84), P< 0.001]. A landmark-analysis 30 days post-STEMI showed equal mortality rates in the two groups. CONCLUSION The incidence of HAVB in STEMI patients treated with pPCI has been reduced compared with reports from the thrombolytic era. However, despite this improvement high-degree AV block remains a severe prognostic marker in the pPCI era. The mortality rate was only increased within the first 30 days. High-degree atrioventricular block patients who survived beyond this time-point thus had a prognosis equal to patients without HAVB.

Comparison of Osteoprotegerin to Traditional Atherosclerotic Risk Factors and High-Sensitivity C-Reactive Protein for Diagnosis of Atherosclerosis

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic stroke, and compared to controls, this group with clinical atherosclerosis had higher mean OPG (1,773 vs 1,337 ng/L, p <0.001) and high-sensitivity C-reactive protein (2.3 vs 1.6 mg/L, p <0.001). In a multivariate model with age, gender, body mass index, hypertension, diabetes, hypercholesterolemia, smoking status, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and OPG, OPG remained significantly associated with clinical atherosclerosis (p <0.01); high-sensitivity C-reactive protein, in contrast, did not (p = 0.74). In the control group without clinical atherosclerosis, OPG was independently associated with hypertension, diabetes, hypercholesterolemia, smoking, and subclinical peripheral atherosclerosis as measured by ankle brachial index. For each doubling of the plasma OPG concentration, the risk for subclinical peripheral atherosclerosis increased by 50% (p <0.001) after multivariate adjustment. In conclusion, OPG appears to be a promising biomarker of atherosclerosis that is independently associated with traditional risk factors of atherosclerosis, subclinical peripheral atherosclerosis, and clinical atherosclerotic disease such as ischemic heart disease and ischemic stroke.

Intracoronary Compared to Intravenous Bolus Abciximab during Primary Percutaneous Coronary Intervention in ST-segment Elevation Myocardial Infarction (STEMI) Patients Reduces 30-day Mortality and Target Vessel Revascularization: A Randomized Trial

BACKGROUND  Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has been questioned. Preliminary studies suggest that IC-bolus is superior, probably due to high local concentration. In this study, we assess the short-term efficacy and safety of IC compared to IV bolus of abciximab in patients with STEMI during pPCI. METHODS  In 2006-2008, we randomized 355 STEMI patients who underwent pPCI and had indication for abciximab to either IV or IC bolus followed by a 12-hour IV infusion. Primary end-points at 30 days were target vessel revascularization (TVR), recurrent myocardial infarction (MI) or death, and the composite of the three. Secondary end-points were bleeding complications. RESULTS  The two groups (IV n = 170;IC n = 185) were similar with respect to baseline characteristics. Mortality at 30 days was 5.3% in the IV group compared to only 1.1% in the IC group (P = 0.02). TVR was performed in 9.4% in the IV group compared to 3.8% in the IC group (P = 0.03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). CONCLUSION  IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus.

Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP

Objective To evaluate the association of plasma osteoprotegerin (OPG) to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP). Design OPG and hsCRP concentrations were measured at baseline in a large Danish prospective community-based population study. Setting The 4th Copenhagen City Heart Study. Participants 5863 men and women aged 20–95 were recruited from the general population. Main outcome measures Combined end-point of IHD, ischaemic stroke or all-cause mortality. Results During a median follow-up of 7.8 years (IQR 7.3–8.3), 1270 subjects (21.7%) reached the combined end-point. A twofold increase in plasma OPG was a significant predictor of the combined end-point (univariable HR 1.85, 95% CI 1.75 to 1.96; p<0.001). In a multivariable Cox-regression model containing age, male sex, hypertension, diabetes, hypercholesterolaemia, present or former smoking, glomerular filtration rate, prior IHD, prior ischaemic stroke, hsCRP and plasma OPG, high concentrations of hsCRP and plasma OPG were independent predictors of the combined end-point. The two biomarkers interacted statistically (p<0.001). Compared to low hsCRP and low OPG (n=1927), either high hsCRP or high OPG (univariable HR 2.38, 95% CI 2.02 to 2.80, p<0.001; n=2816), or both high hsCRP and high OPG (univariable HR 5.13, 95% CI 4.29 to 6.13, p<0.001; n=775) conferred increased risk of the combined end-point. Conclusions OPG is an independent predictor of the combined end-point of hospitalisation of IHD, ischaemic stroke and all-cause mortality. The combination of plasma OPG and hsCRP provides more prognostic information than the individual effect of the two biomarkers.

Hypercholesterolaemia and risk of coronary heart disease in the elderly: Impact of age: The Copenhagen City Heart Study

BACKGROUND Population and interventional studies have shown that high plasma-cholesterol is a risk factor of coronary heart disease (CHD). However, in most of the studies elderly people were excluded. AIM This paper assesses whether the effect of total plasma-cholesterol on the risk of incident CHD decreases with age in a healthy population. METHODS Within the Copenhagen City Heart Study in 1981-1983, 4647 men and 5829 women, aged 40-93 years, underwent a cardiovascular health examination including measurement of plasma-cholesterol. The cohort was followed with respect to incident CHD until 1994, i.e. before statins were introduced in Denmark. RESULTS In people below 60 years of age plasma-cholesterol levels on 5-6; 6-8; and >8 mmol/L were associated with relative risks of CHD on 2.0 (95% confidence interval (CI) 1.2-3.2, P=0.004); 3.1 (CI 2.0-5.0, P<0.001); and 5.1 (CI 2.8-9.3, P<0.001), respectively (reference group: plasma-cholesterol <5 mmol/L). In people aged 60-70 years a plasma-cholesterol level on 5-6 mmol/L was not associated with increased risk, whereas plasma-cholesterol on 6-8 mmol/L and >8 mmol/L was associated with relative risks on 1.3 (CI 1.0-1.8, P=0.03), and 2.3 (CI 1.6-3.4, P<0.001), respectively. In people aged 70-80 years only plasma-cholesterol >8 mmol/L conferred increased relative risk on 1.6 (CI 1.2-2.4, P=0.007). In people above 80 years of age increased plasma-cholesterol was not associated with increased risk of incident CHD. CONCLUSION The risk of incident CHD associated with high plasma-cholesterol declines with age. This finding should be considered in future recommendations of plasma-cholesterol levels in elderly people without atherosclerotic cardiovascular disease.

The Optimal Route of Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Abciximab During Percutaneous Coronary Intervention; Intravenous Versus Intracoronary

The use of the glycoprotein (GP) IIb/IIIa receptor antagonist Abciximab has over the years become an important part of the anticoagulant regimen in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Abciximab is a potent inhibitor of platelet aggregation and thrombus formation, but other mechanisms, such as suppression of the inflammatory pathways, have also been proposed to contribute to the benefits of Abciximab. The optimal route of administration, i.e. intravenous versus intracoronary, of the first dose has been questioned, but only tested in small, non-randomised and retrospective studies or studies with short follow-up. No definite conclusion can be made based on these studies. In this review we present the current knowledge published about the intracoronary administration of Abciximab including the mechanisms behind the potential beneficial effects, and the safety. The emphasis will be on clinical trials rather than on studies on the pharmacological mechanisms, as the latter have been reviewed thoroughly elsewhere. Our conclusion from this present review is that randomized trials of intracoronary versus intravenous bolus of Abciximab are needed.

Osteoprotegerin predicts long-term outcome in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

Background: Osteoprotegerin (OPG) is a glycoprotein with a regulatory role in immune, skeletal and vascular systems. Data suggest that high circulating OPG levels are associated with an increased risk of cardiovascular disease. We analyzed the association between OPG and long-term outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods: We included 716 consecutive STEMI patients admitted to a single high-volume invasive heart center from September 2006 to December 2008. Endpoints were all-cause mortality, repeat myocardial infarction, admission due to heart failure and combinations thereof. Median follow-up lasted 27 months (interquartile range: 22–33). Results: OPG levels exhibited a non-Gaussian distribution and were therefore divided into quartiles. High levels of OPG were significantly associated with a worse outcome. After adjustment for conventional risk factors (e.g. C-reactive protein, estimated glomerular filtration rate, symptom-to-balloon time and troponin I) using Cox regression, OPG remained a significantly independent predictor of death (HR per increase in OPG quartile: 1.28; CI: 1.03–1.59; p = 0.03), repeat myocardial infarction (HR: 1.30; CI: 1.00–1.68; p = 0.05) and admission with heart failure (HR: 1.50; CI: 1.18–1.90; p = 0.001). Conclusion: This study shows that OPG independently predicts long-term outcome in STEMI patients treated with pPCI. Eventually, this knowledge could improve risk stratification and overall outcome.

Intracoronary versus intravenous bolus abciximab administration in patients undergoing primary percutaneous coronary intervention with acute ST-elevation myocardial infarction: a pooled analysis of individual patient data from five randomised controlled trials

AIMS In recent years, intracoronary bolus abciximab has emerged as an alternative to the standard intravenous route in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The aim of the current study was to perform an individual patient-level pooled analysis of randomised trials, comparing intracoronary versus intravenous abciximab bolus use in STEMI patients undergoing primary PCI. METHODS AND RESULTS Individual data of 3,158 patients enrolled in five trials were analysed. Reperfusion endpoints were: post-procedural Thrombolysis in Myocardial Infarction (TIMI) 3 flow, myocardial blush grade (MBG) 2/3 and complete ST-segment resolution. The primary clinical endpoint of interest was the composite of death and reinfarction at 30 days. Compared with the intravenous route, intracoronary abciximab bolus administration did not improve TIMI 3 flow (odds ratio [OR] 1.19; 95% confidence interval [CI]: 0.90-1.59; p=0.23) and complete ST-segment resolution (OR 1.22, 95% CI: 0.92-1.63, p=0.17), but increased MBG 2/3 occurrence (OR 1.83, 95% CI: 1.05-3.18, p=0.03). At 30-day follow-up, intracoronary bolus abciximab did not reduce the risk of death and reinfarction (OR 0.78, 95% CI: 0.55-1.10, p=0.16), death (OR 0.77, 95% CI: 0.51-1.17, p=0.22), reinfarction (OR 0.79, 95% CI: 0.46-1.33, p=0.38) and stent thrombosis (OR 0.77, 95% CI: 0.43-1.35, p=0.36) as compared with intravenous administration. CONCLUSIONS In STEMI patients undergoing primary PCI, intracoronary abciximab does not provide additional benefits as compared with standard intravenous treatment and, therefore, it should not be recommended as the default route of administration in this setting.