Identification of asymptomatic type 2 diabetes mellitus patients with a low, intermediate and high risk of ischaemic heart disease: is there an algorithm?

AIMS/HYPOTHESIS: The leading cause of death in type 2 diabetes is cardiovascular disease (CVD). We examined the prevalence of myocardial ischaemia in type 2 diabetes patients and tried to establish an algorithm to identify patients with a high risk of ischaemic heart disease. METHODS: Type 2 diabetes patients who had no known or suspected CVD, and had been referred consecutively to a diabetes clinic for the first time (n=305; age 58.6+/-11.3 years; diabetes duration 4.5+/-5.3 years) were screened for myocardial ischaemia using myocardial perfusion scintigraphy (MPS). RESULTS: The univariate predictors of myocardial ischaemia were: atypical or typical angina pectoris, two or more traditional risk factors for CVD, BMI >32 kg/m2, systolic blood pressure >140 mmHg, HbA1c >8.5%, high-sensitivity C-reactive protein >4.0 mg/l, N-terminal pro-brain natriuretic peptide >300 pg/ml, left atrial volume index >32 ml/m2, left ventricular ejection fraction <50%, and carotid and peripheral arterial disease. The algorithm identified low (n=96), intermediate (n=65) and high risk groups (n=115), in which the prevalence of myocardial ischaemia was 15%,23% and 43%, respectively. Overall the algorithm reduced the number of patients referred to MPS from 305 to 144.However, the sensitivity and specificity of the algorithm was just 68% and 62%, respectively. CONCLUSIONS/INTERPRETATION: Our algorithm was able to stratify which patients had a low, intermediate or high risk of myocardial ischaemia based on MPS. However, the algorithm had low sensitivity and specificity, combined with high cost and time requirements. TRIAL REGISTRATION: clinicaltrials.gov NCT00298844 FUNDING: The study was funded by the Danish Cardio vascular Research Academy (DaCRA), The Danish Diabetes Association and The Danish Heart Foundation.

Depression assessed over 1-year survival in patients with myocardial infarction.

OBJECTIVE: To estimate the prevalence of ICD-10 depression using a self-reported questionnaire and to examine if depression is associated with increased 1-year mortality in patients with myocardial infarction (MI). METHOD: In total, 763 MI-patients completed the Major Depression Inventory at discharge. Information from hospital notes was collected and patients were followed 1 year for re-admission and mortality through national registries. RESULTS: Seventy-three patients (9.6%) were depressed at discharge. Depression was not a significant independent predictor of mortality; however, there was a significant trend for increasing mortality with increasing severity of the depressive state (P = 0.028). All mortality among depressed patients was in patients with non-Q-wave infarction. CONCLUSION: Ten per cent of MI-patients fulfilled diagnostic criteria for depression at discharge. There was a significant trend for increasing mortality with increasing severity of the depressive episode. All mortality among depressed patients was seen in patients with non-Q-wave infarction. These findings indicate future studies in selected subgroups of MI-patients.

Diagnostic accuracy of plasma brain natriuretic peptide and aminoterminal-proBNP in mild heart failure depends on assay and introduction of therapy.

OBJECTIVE: A reliable biochemical marker of left ventricular dysfunction (LVD) could improve diagnostic accuracy. The aim of this study was to compare the correlation of measurements of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays. The diagnostic accuracy of the tests in mild heart failure (HF) was estimated before and after the start of therapy. MATERIAL AND METHODS: Doppler echocardiography and measurements of plasma BNP and NT-proBNP were performed in 150 patients. RESULTS: Systolic dysfunction (LV ejection fraction 0.45) was present in 22 patients, and 58 had only abnormalities in LV filling. P-NT-proBNP based on two different assays demonstrated a moderate correlation (r = 0.57, p<0.0001) and a concentration-dependent systematic difference. Excellent correlation (r = 0.95, p<0.0001) was found between BNP and NT-proBNP based on two-site antibody assays, but was moderate between BNP and a one-site antibody NT-proBNP assay (r = 0.58, p<0.0001). Areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.93 (95 % CI, 0.90-0.98) for BNP, 0.95 (0.91-0.99) for NT-proBNP (two-site antibody assay) and 0.77 (0.70-0.85) for the one-site antibody NT-proBNP assay (p = 0.0001). At re-evaluation of LVD at 6 and 12 months, AUCs of BNP were 0.81 (0.74-0.99) and 0.83 (0.76-0.89), respectively, and AUCs of NT-proBNP (two-site) were 0.84 (0.77-0.91) and 0.87 (0.81-0.93), respectively. Using the baseline threshold reduced the sensitivity and specificity of BNP and NT-proBNP measurements. CONCLUSIONS: BNP and NT-proBNP measurements demonstrated assay-dependent correlations. Measurement of p-BNP or p-NT-proBNP by a two-site antibody assay demonstrated potential as an indicator of mild, incident HF, but the applicability of the index tests was limited over time and was likely influenced by therapeutic interventions.

Psychosocial predictors of depression in patients with acute coronary syndrome.

OBJECTIVE: To describe the prevalence of depression according to ICD-10 criteria using a self-completed questionnaire and to identify psychosocial predictors of depression at discharge in patients with acute coronary syndrome. METHOD: A total of 899 patients with acute coronary syndrome completed the Major Depression Inventory at discharge and a questionnaire regarding previous depression and family history of depression. Information concerning civil status was obtained from the Civil Person Registry. RESULTS: Ninety patients (10%) were depressed according to ICD-10 criteria at discharge with 7.2% having a moderate to severe depression at discharge. Women were significantly more frequently and severely depressed than men. Patients with and without depression reported primarily somatic symptoms of depression. Cardiovascular risk factors or treatment did not differ between patients with and without depression. Previous depression (OR 2.9, 95% CI 1.4-6.0 adjusted) and female gender (OR 2.5, 95% CI 1.5-4.3 adjusted) predicted depression at discharge in a logistic regression model. CONCLUSION: Somatic symptoms of depression are prevalent in patients with acute coronary syndrome. The use of self-completed non-diagnostic questionnaires assessing symptoms of depression therefore is cautioned as patients may wrongly be identified as depressed. In patients with acute coronary syndrome depression is predicted by well-known psychosocial risk factors.

Continued improvement of clinical outcome and cost effectiveness following intravascular ultrasound guided PCI: insights from a prospective, randomised study.

OBJECTIVE: To investigate in a prospective randomised study both long term clinical effects and cost effectiveness of percutaneous coronary interventions (PCI) with or without intravascular ultrasound (IVUS) guidance. METHODS: 108 male patients with stable angina referred for PCI of a significant coronary lesion were randomly assigned to IVUS guided PCI or conventional PCI. Individual accumulated costs of the entire follow up period were calculated and compared in the randomisation groups. Effectiveness of treatment was measured by freedom from major adverse cardiac events. RESULTS: Cost effectiveness of IVUS guided PCI that was noted at six months was maintained and even accentuated at long term follow up (median 2.5 years). The cumulated cost level was found to be lower for the IVUS guided group, with a cumulated cost of &163 672 in the IVUS guided group versus &313 706 in the coronary angiography group (p = 0.01). Throughout the study, mean cost per day was lower in the IVUS guided PCI group (&2.7 v & 5.2; p = 0.01). In the IVUS group, 78% were free from major adverse cardiac events versus 59% in the coronary angiography group (p = 0.04) with an odds ratio of 2.5 in favour of IVUS guidance. CONCLUSION: IVUS guidance results in continued improvement of long term clinical outcome and cost effectiveness. The results of this study suggest that IVUS guidance may be used more liberally in PCI.

Patient delay from onset of chest pain suggesting acute coronary syndrome to hospital admission.

OBJECTIVE: The aim of the study was to examine patient delay (time from onset of chest pain to patient seeking medical care) among patients who were admitted to hospital with suspected acute coronary syndrome (ACS). DESIGN AND RESULTS: For 337 patients acutely admitted to the Cardiology Department, Odense University Hospital, during a 3-month period in 1998 with suspected ACS, patient delay and the total pre-hospital delay were registered. In addition, information on patient characteristics, patient behaviour and symptom perception was obtained. The median patient delay was 2.85 h (range 0.2-91 h), of this the "silent" patient delay represented 1 h (range 1 min-11.3 h). The total pre-hospital delay was median 3.88 h. Thirty-one per cent of the patients had confirmed acute myocardial infarction (AMI), and this patient group had a significantly shorter patient delay compared with the group without AMI, 2.05 h vs 3.12 h, p = 0.01. Patient delay of more than 2 h was associated with the factors "self-medication" and "wanted to wait and see if the symptoms went away". A smaller than average risk of patient delay was found in the case of "suspicion of heart attack" and "suspicion of a serious condition". CONCLUSION: Patient delay is considered to be a serious impediment to markedly improving the prognosis in the case of ACS.

[Coronary atherosclerosis assessed by coronary angiography or intravascular ultrasound]. / Koronar aterosklerose vurderet ved koronarangiografi eller intravaskulaer ultralyd.

Intensive lowering of serum cholesterol in patients with ischaemic heart disease may retard atherosclerotic progression, and may even cause a limited regression in some patients and partly restore endothelial function. Coronary angiography has been the standard method to evaluate coronary anatomy. However, coronary angiography delineates only the vessel lumen as a silhouette, a perspective that is incapable of reflecting the irregular nature of the atherosclerotic vessel wall changes. Three-dimensional intravascular ultrasound provides cross-sectional and longitudinal images of both the vessel lumen and wall and the plaque volume can be measured in entire arterial segments. Three-dimensional intravascular ultrasound is a reliable technique to measure progression and regression of atherosclerosis in coronary arteries.

Reproducibility of intravascular ultrasound and intracoronary Doppler measurements.

The aim of this study was to evaluate the reproducibility of intravascular ultrasound (IVUS) and intracoronary (IC) Doppler flow velocity measurements. The use of IVUS and IC Doppler has been suggested as a means for percutaneous coronary intervention (PCI) guidance in a series of studies. This would require an acceptable level of accuracy and reproducibility of these two methods for lesion evaluation. In this study, the main focus was on the issue of reproducibility. One hundred and eight patients referred for PCI entered into the study. Inter- and intraobserver variability was measured. Catheter difference was assessed. On-line and off-line measurements were compared. MUSIC criteria were assessed off-line, twice. Calculated and measured diameters were compared. After having obtained initial IC Doppler measurements, the Doppler wire was immediately withdrawn and repositioned for reacquisition of Doppler measurements. IVUS measurements are reproducible and reliable off-line and, to a slightly lesser degree, on-line. Area measurements should be performed more than once and the mean used for vessel description. Lumen diameters should be calculated from the mean of the area measurements. A measuring technique consensus should be reached and adhered to. CFR measurements can be used to determine reduced vs. normal flow reserve. In this study, it was found that proximal to distal velocity ratio and diastolic to systolic velocity ratio variability made these parameters unsuitable for PCI guidance.

Cost-effectiveness analysis of intravascular ultrasound guided percutaneous coronary intervention versus conventional percutaneous coronary intervention.

OBJECTIVE: Investigation of the cost-effectiveness of intravascular ultrasound (IVUS) guided percutaneous coronary intervention (PCI) compared to PCI guided by coronary angiography (CAG). METHODS: One hundred and eight men referred for PCI, were randomized to IVUS or CAG guided PCI. After 6 months, the patients were subjected to a study related clinical and invasive follow-up investigation by CAG, IVUS and intracoronary Doppler flow measurements. Incremental costs of IVUS guided procedures and costs of re-interventions were estimated using the Activity Based Costing (ABC) method. RESULTS: Patients randomized to IVUS guided PCI experienced an improved clinical outcome, with lower angina levels than patients in the CAG guided group. The initial cost of performing IVUS guidance was increased due to extra procedure time, IVUS catheters and slightly more balloons and stents, but fewer patients in the IVUS guided group needed re-intervention. Overall, these savings outweighed the initial cost increase. CONCLUSION: Our data suggest that when performing IVUS guided PCI, costs as well as benefits increase. The increased benefits measured as cost savings resulting from less restenosis outweigh the cost increase from performing the IVUS guided PCI as opposed to CAG guided PCI.

Myocardial perfusion imaging and coronary angiography in patients with known or suspected stable angina pectoris.

INTRODUCTION: The patho-physiological cause of angina pectoris is myocardial ischaemia, which can be objectified by myocardial perfusion imaging (MPI). METHODOLOGY: MPI was undertaken prior to coronary angiography (CAG) in 86 randomly selected patients with known or suspected stable angina pectoris. RESULTS: Among 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single and 34 with multi vessel disease). Using angiography as a reference, the sensitivity and specificity of MPI in detecting coronary artery disease was 88% and 93%, respectively. DISCUSSION: MPI demonstrates regional hypoperfusion whereas CAG depicts anatomical stenosis in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. The functional significance of coronary artery lesions is, however, variable and MPI can demonstrate normal myocardial perfusion in the presence of moderate lesions. MPI exhibited a high sensitivity and specificity regarding significant lesions. More than one third of the subjects had a normal MPI and a normal CAG. Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do usually not require further invasive investigation or therapy. Reversible ischaemia and irreversible ischaemia with demonstration of viable tissue call for coronary revascularisation.

Interpretive intra- and interobserver reproducibility of rest/stress 99Tcm-sestamibi myocardial perfusion SPECT in a consecutive group of male patients with stable angina pectoris before and after percutaneous transluminal angioplasty.

BACKGROUND: Observer variability of 99Tcm-sestamibi myocardial perfusion imaging (MPI) has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. PATIENTS: We report on 108 consecutive male patients with stable angina pectoris, investigated before and after percutaneous transluminal angioplasty (PTCA). METHODS: A 2-day rest/stress 99Tcm-sestamibi gated single photon emission computed tomography (SPECT) protocol was used. MPI was interpreted by two independent observers without knowledge of clinical data, using a 20-segment scoring model. RESULTS: Intra- and interobserver agreement was found to be good to excellent (kappa = 0.71-0.85) with regard to the overall diagnosis as well as the individual vessel diagnosis (kappa = 0.60-0.87). However, agreement was higher for left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) vascular territories than for the right coronary artery (RCA) territory. Moderate to good intraobserver agreement (kappa = 00.54-0.68) and slightly lower interobserver agreement (kappa = 0.52-0.56) was found for segmental score interpretation. When comparing the interpretive reproducibility before and after PTCA intra- and interobserver agreement was better after PTCA, probably reflecting the increase in normal scans after revascularization. CONCLUSIONS: In a group of consecutive male patients with stable angina pectoris interpretive reproducibility (overall and individual vessel diagnosis) was good to excellent. However, segmental scoring reproducibility was moderate to good.

[Myocardial scintigraphy and coronary arteriography in patients with known or suspected stable angina pectoris]. / Myokardiescintigrafi og koronararteriografi hos patienter med kendt eller formodet stabil angina pectoris.

INTRODUCTION: Myocardial perfusion imaging (MPI) demonstrates regional hypoperfusion, whereas coronary angiography shows anatomical stenoses in epicardial arteries. Both modalities are potentially relevant in patients with stable angina pectoris. MATERIALS AND METHODS: MPI was undertaken before angiography in 86 randomly selected patients with stable angina pectoris. RESULTS: Of 78 adequately stressed patients, MPI was normal in 28 (36%) and showed reversible and irreversible perfusion abnormalities in 30 (38%) and 20 patients (26%), respectively. Coronary angiograms were normal in 28 (36%) and revealed at least one > or = 50% stenosis in 50 patients (64%) (16 with single vessel and 34 with multivessel disease). With angiography as reference, the sensitivity and specificity of MPI in the detection of coronary artery disease were 88% and 93%, respectively. DISCUSSION: Patients with stable angina pectoris and a normal MPI have a very low risk of cardiac events and do not usually require invasive investigation and therapy. Reversible ischaemia and irreversible ischaemia with viable tissue call for coronary revascularisation.

Saturated fat intake is reduced in patients with ischemic heart disease 1 year after comprehensive counseling but not after brief counseling.

OBJECTIVE: To examine the dietary habits of patients with ischemic heart disease 1 year after they received either dietary advice on using the Plate Model and how to increase intakes of fruits and vegetables in a 10-minute session (brief counseling group, BCG) or dietary advice primarily based on the National Cholesterol Education Program Step I diet provided in 2 individually tailored 50-minute sessions held 3 months apart (comprehensive counseling group, CCG). DESIGN: A randomized study that included dietary intake evaluation on basis of 7-day weighed food records completed at 3 occasions: immediately before counseling (week zero), 12 weeks after counseling, and 52 weeks after counseling. SUBJECTS: BCG was composed of 15 men and 2 women and CCG was composed of 16 men and 3 women with ischemic heart disease age 70 years or younger recruited from the Department of Cardiology, Odense University Hospital, Odense, Denmark. STATISTICAL ANALYSES PERFORMED: ANOVA, unpaired t tests, and multiple regression analysis, as well as nonparametric statistical analyses were carried out. RESULTS: The comprehensive counseling resulted in significant improvements from week 0 to 52 in the percent of energy from fat (33% to 28%), saturated fat (12% to 9%) and carbohydrate (51% to 54%) consumed by the subjects. The corresponding values in BCG did not differ significantly (31% to 32%, 11% to 12%, 53% to 52% respectively). Differences from week 0 to 52 between groups were significant for fat, saturated fat, and carbohydrate intake. In CCG, median intakes of fish, fruits, and vegetables were 44 g/day, 172 g/day, and 315 g/day, respectively, at week 52. The corresponding values in BCG were 44 g/day, 129 g/day, and 224 g/day. There was no significant difference either within or between the groups. CONCLUSION: This study suggests that sustained improvements in dietary behavior require individualized and reinforced counseling in patients with ischemic heart disease. Changes in intakes of fish, fruits, and vegetables need to be specifically targeted.

Early reperfusion assessment and repeated thrombolysis in acute myocardial infarction estimated by repeated standard electrocardiography. A randomised, double-blind, placebo-controlled pilot study.

Thrombolytic therapy with streptokinase (SK) in acute myocardial infarction (AMI) does not result in early reperfusion in approximately 25% of patients. We hypothesized that early repeated thrombolysis with rt-PA in patients with early failed reperfusion would result in myocardial reperfusion. Fifty-nine AMI patients with a symptom delay of <6 h, treated with SK were included. ECG was taken on admission and after 90 and 180 min. An ST recovery of > or =25% at 90 min was interpreted as successful reperfusion. Sixteen patients had failed reperfusion at 90 min and were randomized to repeated thrombolysis with rt-PA or placebo. At 180 min from SK start, ST recovery was higher in the placebo group than in the rt-PA group (71 vs. 40%, p = 0.05). No serious bleeding complications were observed. Due to the limited sample size it was not possible to draw prominent conclusions.

[DANAMI. A Danish study of invasive versus conservative treatment of patients with post-infarction ischemia who had received thrombolytic therapy]. / DANAMI. En dansk undersøgelse af invasiv versus medicinsk behandling af trombolysebehandlede patienter med postinfarkt iskaemi.

INTRODUCTION: To compare an invasive strategy employing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG) with a medical strategy in patients who had received thrombolytic treatment for first acute myocardial infarction (AMI), and with signs of inducible ischaemia. METHODS: In a prospective study 1008 patients were randomized, 503 to invasive treatment, of whom 266 (52.9%) had PTCA, and 147 (29.2%) CABG, 505 to conservative treatment, of whom eight (1.6%) were revascularized within two months. RESULTS: After a median follow-up of 2.4 years the mortality in the invasive group was 3.6% vs. 4.4% (p = 0.45) in the conservative group, re-infarction incidence was 5.6% vs. 10.5% (p = 0.0038) and percentage of admissions with unstable angina was 17.9% vs. 29.5% (p < 0.00001). DISCUSSION: We conclude that post-infarct patients with inducible ischaemia should be referred to coronary angiography and revascularised accordingly.

Health related quality of life after conservative or invasive treatment of inducible postinfarction ischaemia. DANAMI study group.

OBJECTIVE: To assess health related quality of life in patients with inducible postinfarction ischaemia. DESIGN: A questionnaire based follow up study on patients randomised to conservative or invasive treatment because of postinfarction ischaemia. SETTING: Seven county hospitals in eastern Denmark and the Heart Centre, National University Hospital, Copenhagen, Denmark. PATIENTS: 113 patients with inducible postinfarction ischaemia: 51 were randomised to conservative treatment and 62 to invasive treatment. Average follow up time was three years (19-57 months). MAIN OUTCOME MEASURES: SF-36, Rose angina and dyspnoea questionnaire, drug use, lifestyle, and cognitive function. RESULTS: Invasively treated patients scored better on the SF-36 scales of physical functioning (p = 0.03) and on role-physical (p = 0.04) and physical component scales (p = 0.05) and took significantly less anti-ischaemic drug treatment. Angina occurred in 18% of the invasively treated patients and 31% of the conservatively treated patients (p = 0.09). However, more invasively treated patients suffered from concentration difficulties (18% v 4%; p = 0.04). CONCLUSIONS: Patients who were treated invasively had better health related quality of life scores in the physical variables compared with conservatively treated patients. However, a larger proportion of invasively treated patients had concentration difficulties.