Neurological prognostication tools in out-of-hospital cardiac arrest patients in Danish intensive care units from 2005 to 2013.

BACKGROUND: Neurological prognostication is an essential part of post-resuscitation care in out-of-hospital cardiac arrest (OHCA). This study aims to assess the use of computed tomography (CT) and magnetic resonance imaging (MR) of the head, electroencephalography (EEG), and somatosensory evoked potentials (SSEP) in neurological prognostication in resuscitated OHCA patients and factors associated with their use in Danish tertiary and non-tertiary centers from 2005 to 2013 and associations with outcome. METHODS: We used the Danish Cardiac Arrest Registry to identify patients ≥18 years of age admitted to intensive care units due to OHCA of presumed cardiac etiology. CT 0-20 days and MR, SSEP, and EEG ≥2-20 days post OHCA were considered related to prognostication. Incidence and factors associated with procedures were assessed by multiple Cox regression with death as competing risk. RESULTS: Use of CT, MR, EEG, and SSEP increased during the study period (CT: 51%-67%, HRCT : 1.06, CI: 1.03-1.08, MR: 2%-5%, P = .08, EEG: 6%-33%, HREEG : 1.25, CI: 1.19-1.30, SSEP: 4%-15%, HRSSEP : 1.23, CI: 1.15-1.32). EEG and SSEP were more used in tertiary centers than non-tertiary (HREEG : 1.86, CI: 1.51-2.29, HRSSEP : 4.44, CI: 2.86-6.89). Use of CT, SSEP, and EEG were associated with higher 30-day mortality, and MR was associated with lower (HRCT : 1.15, CI: 1.01-1.30, HRMR : 0.53, CI: 0.37-0.77, HRSSEP : 1.90, CI: 1.57-2.32, HREEG : 1.75, CI: 1.49-2.05). CONCLUSION: Use of neurological prognostication procedures increased during the study period. EEG and SSEP were more used in tertiary centers. CT, EEG and SSEP were associated with increased mortality.

Left ventricular contractile function after distal protection in primary percutaneous coronary intervention: results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial.

BACKGROUND: Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function. METHODS: Patients with STEMI were randomly referred within 12 h for PCI with (N = 312) or without distal protection (N = 314). Left ventricular (LV) contractile function was assessed with echocardiography 8 months after PCI. Global LV myocardial wall motion index (WMI) was calculated as the average wall motion score of all myocardial segments. The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI were also recorded. RESULTS: The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI was 7.1% after distal protection and 5.7% after conventional treatment (p = 0.17). WMI improved by 4.1% at 8 months in patients treated with distal protection compared to patients receiving conventional PCI (p < 0.01). In myocardium supplied by a culprit artery treated by distal protection regional LV function was 9-11% higher than myocardial regions treated conventionally ( p < 0.02). CONCLUSIONS: Routine use of distal protection during primary PCI is associated with a significant improvement in LV contractile function, with no detectable impact on intermediate term clinical outcome.

Primary PCI as the preferred reperfusion therapy in STEMI: it is a matter of time.

There is a continuing controversy about the acceptable time-window for primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI). Recent American and European guidelines recommend PPCI if the delay in performing PPCI instead of administering fibrinolysis (PCI-related delay) is <60 min and the presentation delay is more than 3 h. Based on a review of the literature, this viewpoint recommends a revision of the guidelines. The evidence supports an acceptable PCI-related delay of 80-120 min and PPCI as the better reperfusion strategy also in the early incomers. Furthermore, the previous assumption that PPCI is less time-dependent than fibrinolysis is questioned. To maximise the number of patients with STEMI eligible for PPCI the optimal logistic may be to establish the diagnosis in the prehospital phase, to bypass local hospitals and re-route patients directly to catheterisation laboratories running 24/7.

Gains and losses of warfarin therapy as performed in an anticoagulation clinic.

BACKGROUND: Knowledge of the net benefit of warfarin therapy in routine care is needed to define realistic management recommendations, but lack of randomized controls precludes conventional risk-benefit analysis. OBJECTIVE: Assess risk and benefit of routine warfarin therapy in an anticoagulation clinic. DESIGN: Retrospective observational analysis. PATIENTS: A total of 1435 outpatients on warfarin for a total of 1613 patient years, treated to prevent the target events recurrent venous thromboembolism (VTE) or myocardial infarction (MI), and stroke in patients with atrial fibrillation (AF) or mechanical heart valves. MEASUREMENTS: Major bleeding and thromboembolic (TE) events and all deaths. CALCULATIONS: Expected annual target event rates without warfarin were from published data. Differences between combined major events observed with warfarin, and expected without warfarin were calculated. RESULTS: In the total material, annual rates were 3.0% major TE events, 1.1% major bleeding events, 0.12% fatal bleeding, and a benefit/risk ratio of 3.8. The net gain, expressed in reduced combined bleeding and target TE annual event rate, was 9.9% in secondary prophylaxis in AF, 4.4% in VTE patients, 2.7% in post-MI patients, 2.4% in primary prophylaxis in AF and 0.6 in patients with mechanical heart valves. The apparent benefit/risk ratio was 3.9 in VTE patients, 5.8 in AF patients and 1.1 in patients with mechanical heart valves. CONCLUSION: Net effects of prolonged warfarin therapy in patients with VTE and AF performed in an anticoagulation clinic have an acceptable risk/benefit ratio, comparable with what has been obtained in elective clinical trials.

Myocardial infarction centres: the way forward.

In the era of primary PCI, a strategy of admitting patients to the nearest hospital should be obsolete. Instead, a prehospital diagnostic strategy should be implemented in order to: (1) refer patients directly to interventional centres, thereby eliminating delay at local hospitals; (2) alert the interventional centre, thereby reducing door to balloon times; (3) initiate adjunctive medication in the prehospital phase.

The platelet polymorphism PlA2 is a genetic risk factor for myocardial infarction.

OBJECTIVES: Platelet glycoprotein (GP) receptor IIb/IIIa plays a key role in the development of myocardial infarction (MI), and Pl(A2) is a polymorphism in the gene encoding this receptor. The prevalence of Pl(A2) shows pronounced geographical variation and has to our knowledge not been presented for a Scandinavian population before. Platelets from Pl(A2)-positive individuals show increased aggregability compared with platelets from Pl(A2)-negative individuals, and Pl(A2) genotypes might be associated with MI. The purpose of this study was to investigate the relation between the Pl(A2) polymorphism and MI in a large Scandinavian population. DESIGN: Case-control study. We included patients with angiographically verified CAD with and without previous MI and a group of healthy individuals matched for age, race, and sex. RESULTS: We studied the frequency of Pl(A2) in 1191 healthy individuals and 1019 patients with coronary artery disease (CAD). Amongst these patients, 529 subjects had suffered an MI previously. Pl(A2) was present in 28% of healthy individuals, 28% of patients with CAD but no MI, and in 35% of patients with CAD and MI. The difference between healthy individuals and MI patients was significant (P = 0.002). Furthermore, a graded relationship between the number of Pl(A2) alleles and the risk of MI was seen (P = 0.011). Associations between Pl(A2) and traditional cardiovascular risk factors as well as mean platelet volume were investigated. We found a significant interaction between Pl(A2) and serum cholesterol. CONCLUSION: In our Scandinavian study population the common platelet polymorphism Pl(A2) is significantly associated with an increased risk of MI, but not of CAD. Clinically, typing for Pl(A2) might have implications for antiplatelet therapy of patients with MI.

Quality of lipid-lowering therapy in patients with ischaemic heart disease: a register-based study in 3477 patients.

OBJECTIVE: To develop a method to evaluate routine management practices concerning lipid-lowering treatment in patients with ischaemic heart disease (IHD) in a large geographic area. DESIGN: A register-based study linking information on IHD with cholesterol levels and prescriptions on lipid-lowering medications by personal registration number. Plasma cholesterol levels were collected from the electronic laboratory information system (LIS), and information on IHD from the Danish National Hospital Register (LPR). The extent of treatment was evaluated by information on prescriptions on lipid-lowering medications from the Danish National Health Service. SETTING: Evaluates treatment in both hospitals and primary care. SUBJECTS: Patients with IHD. RESULTS: In total 3477 patients <75 years were identified, and 43.7% had claimed prescriptions on lipid-lowering medications (01.01.2000-31.07.2000). In the whole population, 42% reached the goal for total cholesterol lower than 5 mmol L-1 set by European guidelines. In the 1521 patients treated with lipid-lowering medications 55% reached the goal. CONCLUSION: By use of registers it was possible to develop a method to evaluate and monitor current treatment practice for dyslipidaemia in a large geographic area. The method makes it possible to evaluate the impact of guidelines, changes in treatment procedures and to provide feedback to physicians. The study revealed that lipid-lowering treatment is still not sufficiently implemented in clinical practice even in patients with known IHD, and the used doses of statins are lower than those used in randomized clinical trials.

Are we underestimating the full potential of early thrombolytic treatment in patients with acute myocardial infarction?

Use of the Boersma curve in order to describe the beneficial effect of thrombolytic treatment at different treatment delays seems questionable, because the curve may underestimate the favourable prognostic effects of early thrombolysis in patients with acute myocardial infarction

A randomized controlled trial of shared care versus routine care for patients receiving oral anticoagulant therapy.

OBJECTIVES: To evaluate the effect of a shared care programme (SCP), defined as a scheme based on shared responsibility, enhanced information exchange, continues medical education and explicit clinical guidelines, between general practitioners (GPs) and a hospital outpatient clinic (HOC), on oral anticoagulant therapy (OAT). DESIGN: The study was a 2-year prospective, randomized, controlled trial, preceded by a 1-year period of observation. SETTING: The HOC, GPs, and OAT patients in the admission area of Aarhus University Hospital, Aarhus County, Denmark, covering 310 300 inhabitants. SUBJECTS: A total of 207 GPs, including their enlisted patients on OAT, were invited, and 61.4% accepted participation. They were randomized into an intervention group [group-INT: 64 GPs and 453 patients (170 patients on OAT throughout the study period, i.e. full follow-up)], and a control group [group-CON: 63 GPs and 422 patients (173 with full follow-up)]. The remaining 80 GPs served as a nonresponder group (group-NON) of 485 patients (184 with full follow-up). MAIN OUTCOME MEASURE: Therapeutic control of OAT in terms of time spent by the patients within the therapeutic interval (TI) of an international normalized ratio (INR) between 2.0 and 3.5. RESULTS: The groups did not differ significantly with regard to age, sex, OAT indication, anticoagulant drug used, or the therapeutic control at baseline. In a comparison based on intention-to-treat principles, the therapeutic control increased statistical significance amongst patients with full follow-up in group-INT compared with group-CON (median time within TI: group INT = 86.6% vs. 80.5%, P = 0.007). CONCLUSION: An SCP of anticoagulant management is effective in reducing patient time outside the therapeutic INR interval in OAT patients randomly assigned to an SCP, as compared with a control group.

Telemedicine used for remote prehospital diagnosing in patients suspected of acute myocardial infarction.

INTRODUCTION: In patients with acute myocardial infarction (AMI), considerable time elapses from symptom onset until initiation of thrombolytic therapy or primary percutaneous coronary intervention. Prehospital diagnosing can reduce time delays, and remote diagnosing using telemedicine may be appropriate in areas and countries where ambulances are not staffed with physicians. OBJECTIVES: To evaluate whether it was technically feasible for physicians at a remote university hospital to diagnose ST-segment-elevation-AMI (AMI(STelev)) in patients suspected of AMI, who were transported by ambulances to a local hospital. To determine associated prehospital delays and in-hospital treatment delays. METHODS: Patients carried in telemetry equipped ambulances had 12-lead electrocardiograms (ECGs) acquired as soon as possible. En route to the local hospital the ECGs were transmitted to a remote university hospital, by use of the GSM-system. The physician on call at the university hospital interviewed the patients, who were provided with cellular phone headsets, and alerted the local hospital if signs of AMI(STelev), bundle-branch-block-AMI or malignant arrhythmia were detected. Patients transported by traditional ambulances were included in a prospective control group. RESULTS: In 214 (86%) of 250 patients prehospital diagnosing was successful. Geographically related transmission problems were the primary reason for failure. Ninety-eight per cent of transmitted electrocardiograms and obtained history takings were technically acceptable for diagnostic purposes. Door-to-needle times were shorter amongst patients with AMI(STelev) who were subjected to prehospital diagnosing (n = 13) as compared with patients transported by traditional ambulances (n = 14) (38 vs. 81 min) (P = 0.004). CONCLUSIONS: It was technically feasible to use telemedicine for remote prehospital diagnosing of patients suspected of AMI. Patients subjected to prehospital diagnosing had shorter door-to-needle times compared with a prospective control group.

Intravenous magnesium does not influence the activity of the coagulation cascade.

Experimental arterial thrombus formation is reduced during intravenous magnesium infusion. It is well documented that magnesium reduces platelet reactivity, but the antithrombotic effect could also originate from anticoagulant properties or increased fibrinolysis. We therefore evaluated the effect of intravenous magnesium on prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III complex (TAT) concentrations, and fibrin degradation products (FbDP) in a randomized, cross-over study in 14 healthy volunteers. Citrated blood samples were collected at 0, 30, and 180 min. An additional in vitro study on magnesium's effect on the activity of different coagulation factors was carried out. A transient increase was seen in F1 + 2 and TAT after 30 min but without any significant difference between the placebo and magnesium period. FbDP did not change significantly between the two treatments. Increasing concentrations of magnesium dose-dependently decreased binding of activated factor X to activated factor VII (FVIIa), but the decrease was slight and probably without any significance for coagulation at the concentrations tested. No effect was observed on the activity of FVIIa or activated factor VIII. In conclusion, no significant differences were observed on markers of coagulation or fibrinolytic activity during intravenous magnesium infusion. These results indicate that the observed antithrombotic effect of magnesium is more likely to arise from the previously observed platelet inhibition.

Use and validation of public data files for identification of the diabetic population in a Danish county.

INTRODUCTION: This study aims to describe the process of identifying people known to have diabetes through public data files, to validate this method, and to describe models for optimization of such identification processes. PATIENTS AND METHODS: In a study population of 303,250 citizens, the diabetics were identified by combining information from public data files with information from general practitioners. Data validity was checked by comparing the results of data searches in public data files against information from general practitioners and a random sample of diabetics. Two models were defined to optimize the use of public data files for identification of diabetics. In model A the minimum number of parameters needed to obtain a sensitivity as high as possible was identified. In model B the optimal combination of parameters needed to obtain a high positive predictive value combined with a high sensitivity was identified. RESULTS: A total of 5449 diabetics were identified. Of those 4438 (81%) were classified as Type 2 diabetics and 1011 (19%) were classified as Type 1 diabetics. The data validation revealed that one person was misclassified as a diabetic and 93 persons were misclassified as non-diabetics. In model A the identification parameters included: "prescription", "HbA1c", "chiropodist service" and "glucose service". In model B the optimal combination of parameters was identified as: minimum two HbA1c measurements, minimum one visit to a chiropodist, minimum one prescription or minimum one abnormal HbA1c during one year. CONCLUSION: Public data files are suitable for identification of both Type 1 and Type 2 diabetics. Models have been developed to identify diabetics and to promote the possibilities of long-term follow-up and quality assessment in an unselected diabetic population in a region.

Electromechanical mapping for detection of myocardial viability in patients with ischemic cardiomyopathy.

BACKGROUND: We evaluated the ability of electromechanical mapping of the left ventricle to distinguish between nonviable and viable myocardium in patients with ischemic cardiomyopathy. METHODS AND RESULTS: Unipolar voltage amplitudes and local endocardial shortening were measured in 31 patients (mean+/-SD age, 62+/-8 years) with ischemic cardiomyopathy (ejection fraction, 30+/-9%). Dysfunctional regions, identified by 3D echocardiography, were characterized as nonviable when PET revealed matched reduction of perfusion and metabolism and as viable when perfusion was reduced or normal and metabolism was preserved. Mean unipolar voltage amplitudes and local shortening differed among normal, nonviable, and viable dysfunctional segments. Coefficient of variation for local shortening exceeded differences between groups and did not allow distinction between normal and dysfunctional myocardium. Optimum nominal discriminatory unipolar voltage amplitude between nonviable and viable dysfunctional myocardium was 6.5 mV, but we observed a great overlap between groups. Individual cutoff levels calculated as a percentage of electrical activity in normal segments were more accurate in the detection of viable dysfunctional myocardium than a general nominal cutoff level. The optimum normalized discriminatory value was 68%. Sensitivity and specificity were 78% for the normalized discriminatory value compared with 69% for the nominal value (P:<0.02). CONCLUSIONS: Endocardial ECG amplitudes in patients with ischemic cardiomyopathy display a wide scatter, complicating the establishment of exact nominal values that allow distinction between viable and nonviable areas. Individual normalization of unipolar voltage amplitudes improves diagnostic accuracy. Electroanatomic mapping may enable identification of myocardial viability.

[Examination and treatment of dyslipemia after myocardial infarction--are the goals achieved?]. / Udredning og behandling af dyslipidaemi efter akut myokardieinfarkt--opnås målene?

According to guidelines, medical treatment of dyslipidaemia in post-AMI patients should await assessment of underlying lipid disorders and the outcome of dietary treatment. The risk of patients not being treated with lipid-lowering therapy because of lack of follow-up has led to more aggressive guidelines recommending statin treatment even before discharge from hospital. In a study comprising 730 patients, we have shown that, although most patients were discharged from the coronary care unit without statin treatment, a traditional rehabilitation programme succeeded in assessing more than 95% of the patients for underlying lipid disorders, and more than 75% of patients with plasma cholesterol > or = 5.5 mmol/l received lipid-lowering therapy within the first year. Most patients were treated with statins. Statins, however, were given in smaller doses than those used in the clinical trials, and only 52% of the treated patients reached the recommended goal of plasma cholesterol lower than 5 mmol/l.

HbAlc in an unselected population of 4438 people with type 2 diabetes in a Danish county.

OBJECTIVE: To describe the use and level of HbA1c in a large unselected Type 2 diabetic population in Denmark. In addition, to describe the characteristics of the patients and the general practitioners in relation to the monitoring of HbA1c. DESIGN: Data were collected from public data files for the period January 1993 to December 1997. SETTING: The County of Vejle with a background population of 342,597 citizens, 303,250 of whom were listed with participating general practitioners. PATIENTS: The Type 2 diabetic population alive and resident in the county on 1 January 1997. RESULTS: In a population of 4438 Type 2 diabetics, 73% had a minimum of one annual HbA1c measurement in 1997. No HbA1c measurement was associated with a long history of diabetes, diet treatment or old age. Poor glycaemic regulation was found in 65% of the Type 2 diabetics in 1997. Poor glycaemic regulation was associated with tablet or insulin treatment, age under 70 years and long history of diabetes. The interpractice variation was huge. CONCLUSION: The quality of HbA1c monitoring of Type 2 diabetics needs to be improved. Possibilities for improvement seem to be present.

Pathophysiology of coronary thrombosis.

Detailed knowledge of the pathophysiology as well as the dynamic nature of coronary thrombus formation provides a valuable tool for correct management and proper adjunctive therapy in patients with acute coronary syndromes. Coronary thrombosis is in the majority of cases caused by disruption or fissuring of an atherosclerotic plaque. At the lesion thrombogenic material will be exposed to the flowing blood leading to activation of platelets and the formation of a platelet clot. Simultaneously, the coagulation system is activated resulting in increased thrombin formation. Thrombin is a key mediator in arterial thrombosis, due to its effect on both platelets and fibrin generation. Thrombin contributes to the stabilization of an initially loose platelet clot by generating cross-bound fibrin within the thrombus. During the course of an acute coronary syndrome, the patient presents changing chest pain and dynamic ischaemic ECG findings. This is likely to be related to the dynamic nature of the pathophysiology. The presence of a non-occlusive coronary thrombus may deprive the myocardium its normal blood flow and oxygen supply, leading to ischaemic pain. During lysis or embolization, blood supply may be restored, but the presence of thrombus fragments in the microcirculation holds the potential to sustained interference with myocardial metabolism. The emboli contain activated platelets which release vasoconstrictors that may compromise the microcirculation. Recurrent thrombus formation at the lesion site may result in occlusion of the artery adding to the dynamic nature of the clinical presentation. In conclusion, platelets, the coagulation system, and the endothelium cause a dynamic process of intermittent occlusion, vasospasm and embolization of thrombus material.

Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation.

Phenprocoumon, whose elimination half-time is 144 hours, has been the traditional oral anticoagulant of choice in Europe. However, today's most widely used drug is warfarin, whose elimination half-time is 40 hours. This study aims to evaluate a method for safe transition from phenprocoumon to warfarin, which is sometimes required. Hence, the large difference in their elimination rates may on occasion lead to serious overdosage upon transition from one drug to the other. According to average equipotent doses, a stepwise increase in warfarin dose was calculated based on the elimination half-times of the two drugs. The dosage scheme was subsequently tested in a pilot study including 35 patients. The conversion scheme was then adjusted based on the results from the pilot study. The new scheme was tested in 69 patients. The transition factor was 2.3, which implies that equipotency was achieved when the warfarin dose was 2.3 times larger than the phenprocoumon dose (in mg). This scheme proved optimal for 75% of the patients. However, the dose had to be adjusted individually in the remaining 25% of the patients to a level corresponding to the measured international normalised ratios. No patients experienced haemorrhages or thromboembolic complications during the period of changeover. In conclusion, the proposed scheme for changing medication from phenprocoumon to warfarin is safe and convenient.

[Anticoagulant treatment]. / Antikoagulationsbehandling.

In 1998, the sale of vitamin K antagonists (VKA) in Denmark corresponded to the amount used for treatment of more than 20,000 patients for one year. This is more than three times more than ten years earlier. The reasons for the increasing use of VKA are new indications for permanent anticoagulant treatment, especially chronic atrial fibrillation and venous thromboembolism associated with permanent thromboembolic risk factors. The risk of bleeding is higher in the introductory phase of anticoagulant treatment than later on. It is now recommended to commence anticoagulant therapy without a loading dose. This seems to hasten a good estimate of the maintenance dose. The metabolism of VKA depends on a number of genetic and acquired factors. Knowledge of these factors is crucial for optimal regulation of the treatment, and it is important that patients at start of treatment are thoroughly informed about these factors in order to minimize the risk of complications.