Baseline findings of the population-based, randomized, multifaceted Danish cardiovascular screening trial (DANCAVAS) of men aged 65-74 years.

BACKGROUND: The challenge of managing age-related diseases is increasing; routine checks by the general practitioner do not reduce cardiovascular mortality. The aim here was to reduce cardiovascular mortality by advanced population-based cardiovascular screening. The present article reports the organization of the study, the acceptability of the screening offer, and the relevance of multifaceted screening for prevention and management of cardiovascular disease. METHODS: Danish men aged 65-74 years were invited randomly (1 : 2) to a cardiovascular screening examination using low-dose non-contrast CT, ankle and brachial BP measurements, and blood tests. RESULTS: In all, 16 768 of 47 322 men aged 65-74 years were invited and 10 471 attended (uptake 62·4 per cent). Of these, 3481 (33·2 per cent) had a coronary artery calcium score above 400 units. Thoracic aortic aneurysm was diagnosed in the ascending aorta (diameter 45 mm or greater) in 468 men (4·5 per cent), in the arch (at least 40 mm) in 48 (0·5 per cent) and in the descending aorta (35 mm or more) in 233 (2·2 per cent). Abdominal aortic aneurysm (at least 30 mm) and iliac aneurysm (20 mm or greater) were diagnosed in 533 (5·1 per cent) and 239 (2·3 per cent) men respectively. Peripheral artery disease was diagnosed in 1147 men (11·0 per cent), potentially uncontrolled hypertension (at least 160/100 mmHg) in 835 (8·0 per cent), previously unknown atrial fibrillation confirmed by ECG in 50 (0·5 per cent), previously unknown diabetes mellitus in 180 (1·7 per cent) and isolated severe hyperlipidaemia in 48 men (0·5 per cent). In all, 4387 men (41·9 per cent), excluding those with potentially uncontrolled hypertension, were referred for additional cardiovascular prevention. Of these, 3712 (35·5 per cent of all screened men, but 84·6 per cent of those referred) consented and were started on medication. CONCLUSION: Multifaceted cardiovascular screening is feasible and may optimize cardiovascular disease prevention in men aged 65-74 years. Uptake is lower than in aortic aneurysm screening.

The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65-74 Years.

OBJECTIVE/BACKGROUND: This pilot study of a large population based randomised screening trial investigated feasibility, acceptability, and relevance (prevalence of clinical and subclinical cardiovascular disease [CVD] and proportion receiving insufficient prevention) of a multifaceted screening for CVD. METHODS: In total, 2060 randomly selected Danish men and women aged 65-74 years were offered (i) low dose non-contrast computed tomography to detect coronary artery calcification (CAC) and aortic/iliac aneurysms; (ii) detection of atrial fibrillation (AF); (iii) brachial and ankle blood pressure measurements; and (iv) blood levels of cholesterol and hemoglobin A1c. Web based self booking and data management was used to reduce the administrative burden. RESULTS: Attendance rates were 64.9% (n = 678) and 63.0% (n = 640) for men and women, respectively. In total, 39.7% received a recommendation for medical preventive actions. Prevalence of aneurysms was 12.4% (95% confidence interval [CI] 9.9-14.9) in men and 1.1% (95% CI 0.3-1.9) in women, respectively (p < .001). A CAC score > 400 was found in 37.8% of men and 11.3% of women (p < .001), along with a significant increase in median CAC score with age (p = .03). Peripheral arterial disease was more prevalent in men (18.8%, 95% CI 15.8-21.8) than in women (11.2%, 95% CI 8.7-13.6). No significant differences between the sexes were found with regard to newly discovered AF (men 1.3%, women 0.5%), potential hypertension (men 9.7%, women 11.5%), hypercholesterolemia (men 0.9%, women 1.1%) or diabetes mellitus (men 2.1%, women 1.3%). CONCLUSION: Owing to the higher prevalence of severe conditions, such as aneurysms and CAC ≥ 400, screening for CVD seemed more prudent in men than women. The attendance rates were acceptable compared with other screening programs and the logistical structure of the screening program proved successful.

Pre-treatment with a sinus node blockade, ivabradine, before coronary CT angiography: a retrospective audit.

AIM: To evaluate whether a simple pre-treatment regimen of sinus node inhibition by ivabradine taken at home for only 1 day resulted in a lower pre-scanning heart rate (HR) and reduced the need for intravenous beta-blockers (BB) prior to coronary computed tomography angiography (CTA). MATERIALS AND METHODS: The pre-treatment regimen for coronary CTA changed from using no medication at home (group 1 patients) to the use of 5 mg ivabradine twice a day (group 2 patients), to using 7.5 mg ivabradine twice a day (group 3 patients). The target HR was the same for groups 1 and 2, but lower for group 3. HRs and the use of intravenous BB before coronary CTA was performed were compared between the study groups. RESULTS: The mean HR immediately before the planned CTA procedure was significantly lower throughout groups 1-3 with values of 70 ± 12.9, 64.9 ± 9.8, and 63.2 ± 10.6 beats/min in groups 1, 2, and 3, respectively (p < 0.001). This resulted in a significantly diminished use of intravenous BB in group 2 (mean 5.1 ± 5.8 mg) compared to group 1 (mean 9 ± 7.6 mg; p = 0.002). The target HR of 65 beats/min was achieved in 37%, 47%, and 61% of groups 1, 2, and 3, respectively (p < 0.0001). CONCLUSION: In conclusion, the administration of ivabradine tablets at home for only 1 day to patients scheduled for coronary CTA resulted in a significantly lower in-clinic HR and a significantly lower mean use of intravenous BB.

The relation between coronary artery calcification in asymptomatic subjects and both traditional risk factors and living in the city centre: a DanRisk substudy.

OBJECTIVE: To evaluate the association between the risk factor for living in the city centre as a surrogate for air pollution and the presence of coronary artery calcification (CAC) in a population of asymptomatic Danish subjects. DESIGN AND SUBJECTS: A random sample of 1825 men and women of either 50 or 60 years of age were invited to take part in a screening project designed to assess risk factors for cardiovascular disease (CVD). Noncontrast cardiac computed tomography was performed on all subjects, and their Agatston scores were calculated to evaluate the presence of subclinical coronary atherosclerosis. The relationship between CAC and several demographic and clinical parameters was evaluated using multivariate logistic regression. RESULTS: A total of 1225 individuals participated in the study, of whom 250 (20%) were living in the centres of major Danish cities. Gender and age showed the greatest association with the presence of CAC: the odds ratio (OR) for men compared with women was 3.2 [95% confidence interval (CI) 2.5-4.2; P < 0.0001], and the OR for subjects aged 60 versus those aged 50 years was 2.2 (95% CI 1.7-2.8; P < 0.0001). Other variables independently associated with the presence of CAC were diabetes and smoking with ORs of 2.0 (95% CI 1.1-3.5; P = 0.03) and 1.9 (95% CI 1.4-2.5, P < 0.0001), respectively. The adjusted OR for subjects living in city centres compared to those living outside was 1.8 (95% CI 1.3-2.4; P = 0.0003). CONCLUSION: Both conventional risk factors for CVD and living in a city centre are independently associated with the presence of CAC in asymptomatic middle-aged subjects.

First experiences with model based iterative reconstructions influence on quantitative plaque volume and intensity measurements in coronary computed tomography angiography.

PURPOSE: Investigate the influence of adaptive statistical iterative reconstruction (ASIR) and the model-based IR (Veo) reconstruction algorithm in coronary computed tomography angiography (CCTA) images on quantitative measurements in coronary arteries for plaque volumes and intensities. METHODS: Three patients had three independent dose reduced CCTA performed and reconstructed with 30% ASIR (CTDIvol at 6.7 mGy), 60% ASIR (CTDIvol 4.3 mGy) and Veo (CTDIvol at 1.9 mGy). Coronary plaque analysis was performed for each measured CCTA volumes, plaque burden and intensities. RESULTS: Plaque volume and plaque burden show a decreasing tendency from ASIR to Veo as median volume for ASIR is 314 mm3 and 337 mm3-252 mm3 for Veo and plaque burden is 42% and 44% for ASIR to 39% for Veo. The lumen and vessel volume decrease slightly from 30% ASIR to 60% ASIR with 498 mm3-391 mm3 for lumen volume and vessel volume from 939 mm3 to 830 mm3. The intensities did not change overall between the different reconstructions for either lumen or plaque. CONCLUSION: We found a tendency of decreasing plaque volumes and plaque burden but no change in intensities with the use of low dose Veo CCTA (1.9 mGy) compared to dose reduced ASIR CCTA (6.7 mGy & 4.3 mGy), although more studies are warranted.

Relationship between serum amino-terminal propeptide of type III procollagen and changes of left ventricular function after acute myocardial infarction.

BACKGROUND: The amino-terminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen synthesis, which has previously been shown to correlate with infarct size in nonthrombolyzed myocardial infarction (MI) and to provide prognostic information after MI. METHODS AND RESULTS: The relationship between PIIINP and changes of left ventricular (LV) function was studied in 47 consecutive patients with first acute MI and 16 control subjects. Serum PIIINP analysis was measured daily during hospitalization and on days 90, 180, and 360. LV function was assessed by echocardiography on days 1, 5, 90, and 360. Patients with MI were stratified according to their serum PIIINP value at day 4 (group A, 5.0 microg/L). On arrival, LV function and size were comparable between groups A (n=31) and B (n=16). LV ejection fraction, initially depressed (day 1: group A, 47+/-7% versus group B, 47+/-8%; P=NS), increased significantly in group A (day 360: 54+/-8%, P<0.001) but was unchanged in group B (day 360: 43+/-8%, P=NS). LV volumes increased significantly in group B (P<0. 05) but not in group A. Furthermore, patients in group B developed signs of restrictive LV diastolic filling. Multivariate regression analysis identified PIIINP >5.0 microg/L and deceleration

Pseudonormal and restrictive filling patterns predict left ventricular dilation and cardiac death after a first myocardial infarction: a serial color M-mode Doppler echocardiographic study.

OBJECTIVES: We sought to assess the prognostic value of left ventricular (LV) filling patterns, as determined by mitral E-wave deceleration time (DT) and color M-mode flow propagation velocity (Vp), on cardiac death and serial changes in LV volumes after a first myocardial infarction (MI). BACKGROUND: Combined assessment of DT and Vp allows separation of the effects of compliance and relaxation on LV filling, thereby allowing identification of pseudonormal filling. This may be valuable after MI, where abnormal LV filling is frequently present. METHODS: Echocardiography was performed within 24 h, five days and one and three months after MI in 125 unselected consecutive patients. Normal filling was defined as DT 140 to 240 ms and Vp > or =45 cm/s; impaired relaxation as DT > or =240 ms; pseudonormal filling as DT 140 to 240 ms and Vp <45 cm/s; and restrictive filling as DT <140 ms. RESULTS: Left ventricular filling was normal in 38 patients; impaired relaxation in 38; pseudonormal in 23; and restrictive in 26. End-systolic and end-diastolic volume indexes were significantly increased during the first three months after MI in patients with pseudonormal or restrictive filling (37+/-15 vs. 47+/-19 ml/m2, p<0.0005 and 71+/-20 vs. 88+/-24 ml/m2, p<0.0005, respectively). During a follow-up period of 12+/-7 months, 33 patients died. Mortality was significantly higher in patients with impaired relaxation (p = 0.02), pseudonormal filling (p<0.00005) and restrictive filling (p<0.00005), compared with patients with normal filling. On Cox analysis, restrictive filling (p = 0.003), pseudonormal filling (p = 0.006) and Killip class > or =II (p = 0.008) independently predicted cardiac death, compared with clinical and echocardiographic variables. CONCLUSIONS: Pseudonormal or restrictive filling patterns are related to progressive LV dilation and predict cardiac death after a first MI.

Ratio of left ventricular peak E-wave velocity to flow propagation velocity assessed by color M-mode Doppler echocardiography in first myocardial infarction: prognostic and clinical implications.

OBJECTIVES: To determine the ability of the ratio of peak E-wave velocity to flow propagation velocity (E/Vp) measured with color M-mode Doppler echocardiography to predict in-hospital heart failure and cardiac mortality in an unselected consecutive population with first myocardial infarction (MI). BACKGROUND: Several experimental studies indicate color M-mode echocardiography to be a valuable tool in the evaluation of diastolic function, but data regarding the clinical value are lacking. METHODS: Echocardiography was performed within 24 h of arrival at the coronary care unit in 110 consecutive patients with first MI. Highest Killip class was determined during hospitalization. Patients were divided into groups according to E/Vp <1.5 and > or =1.5. RESULTS: During hospitalization 53 patients were in Killip class > or =II. In patients with E/Vp > or =1.5, Killip class was significantly higher compared with patients with E/Vp <1.5 (p < 0.0001). Multivariate logistic regression analysis identified E/Vp > or =1.5 to be the single best predictor of in-hospital clinical heart failure when compared with age, heart rate, E-wave deceleration time (Dt), left ventricular (LV) ejection fraction, wall motion index, enzymatic infarct size and Q-wave MI. At day 35 survival in patients with E/Vp <1.5 was 98%, while for patients with E/Vp > or =1.5, it was 58% (p < 0.0001). Cox proportional hazards model identified Dt <140 ms, E/Vp > or =1.5 and age to be independent predictors of cardiac death, with Dt < 140 ms being superior to age and E/Vp. CONCLUSIONS: In the acute phase of MI, E/Vp > or =1.5 measured with color M-mode echocardiography is a strong predictor of in-hospital heart failure. Furthermore, E/Vp is superior to systolic measurements in predicting 35 day survival although Dt <140 ms is the most powerful predictor of cardiac death.

Selection of medical treatment in stable angina pectoris: results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. METHODS: In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS: Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.

Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study.

OBJECTIVES: This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. BACKGROUND: Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. METHODS: Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. RESULTS: At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. CONCLUSIONS: The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.

Asymptomatic myocardial ischemia as a predictor of cardiac events after coronary artery bypass grafting for stable angina pectoris.

Thirty-six patients with chronic stable angina were studied before and after coronary artery bypass grafting (CABG) to assess the prevalence and prognostic implications of asymptomatic myocardial ischemia obtained by ambulatory monitoring. Ambulatory monitoring performed during medical therapy before CABG detected 66 episodes of transient ischemia, 54 (82%) being asymptomatic. All patients were asymptomatic or with minimal symptoms 3 months after CABG. Additional ambulatory monitoring was performed for 36 hours. There were 39 episodes of silent ischemia detected in the 12 patients of group 1, whereas no episodes of ST-segment shift occurred in the 24 patients of group 2. Coronary artery bypass grafting reduced the frequency of transient ischemia by 41% (p less than 0.05) compared with medical therapy, whereas the number of ischemic episodes in group 1 increased from 23 during medical therapy to 39 episodes after CABG (41%, p less than 0.05). During a follow-up of 9 months, 8 cardiac events occurred: 6 in group 1 comprising sudden death (1), revascularization (2), and angina (3) and 2 in group 2, including revascularization (1) and angina (1) (p = 0.005). Kaplan-Meier analysis demonstrated that asymptomatic myocardial ischemia was correlated with a significant cumulative probability of cardiac events (p less than 0.025) and multivariate analysis of 11 variables showed that silent ischemia was the most powerful predictor of cardiac events (p less than 0.005). Silent ischemia was a forerunner for angina pectoris in some patients, whereas angina did not occur during the follow-up period in others. This study does not reveal whether or not these patients are at higher risk for cardiac events during long-term follow-up.

Transient myocardial ischemia after abrupt withdrawal of antianginal therapy in chronic stable angina.

In 47 patients with chronic stable angina and proven coronary artery disease, abrupt withdrawal of beta-adrenoceptor blocking agents either as monotherapy or in combination with calcium antagonists (group 1, n = 25) was compared with abrupt withdrawal of calcium antagonist monotherapy (group 2, n = 22) as regards the occurrence of cardiac events and total ischemic activity detected by ambulatory monitoring. Reinstitution of medical therapy was required in 6 patients (4 in group 1 and 2 in group 2). Ambulatory monitoring was initiated for 36 hours on 3 occasions: before withdrawal, and again 2 and 5 days after withdrawal. The first 2 monitorings were performed in the hospital and the last during daily activity. In group 1, the frequency of total ischemia increased by 64 and 148% from monitoring occasions 1 to 2 and 1 to 3, respectively (p less than 0.01), and silent ischemia increased by 100 and 129%, respectively (p less than 0.01). However, no significant change in transient myocardial ischemia was noted in group 2. Heart rate at onset of ischemia increased significantly in group 1 (p less than 0.01), in contrast to group 2 which had significant increases only in out-of-hospital values (p less than 0.05). These results indicate that a rebound increase in ischemic activity (mainly silent) occurs after abrupt withdrawal of beta-receptor blockade in patients with chronic stable angina. This increase in ischemic activity may be caused by increased myocardial oxygen demand.

Transient myocardial ischemia during nifedipine therapy in stable angina pectoris, and its relation to coronary collateral flow and comparison with metoprolol.

There are conflicting results concerning the anti-ischemic effect of nifedipine in patients with chronic stable angina. Therefore, the purpose of this study was to assess whether the anti-ischemic effect of nifedipine may be related to coronary collateral circulation. Forty-one patients with stable angina and coronary artery disease were randomized to a parallel double-blind study with nifedipine and metoprolol, and compared for effects on transient ischemic episodes during ambulatory electrocardiographic monitoring and exercise-induced ischemia. The effects were correlated to the presence of collateral circulation. In 17 patients, angiographically poor or no collateral flow was observed (group 1), and 24 had good collateral flow (group 2). Nifedipine was administered to 20 patients (8 in group 1, and 12 in group 2). In group 1, nifedipine reduced the frequency of total and asymptomatic ischemic episodes (p < 0.05), whereas significant increases in both total (p < 0.05) and silent (p < 0.01) ischemia were observed in group 2. Exercise variables were slightly improved (p = NS) during nifedipine therapy in group 1, and slightly worsened (p = NS) in group 2. Reflex tachycardia was not observed at either the onset of transient ischemia out of the hospital or exercise-induced ischemia. This was in contrast with the effect in 21 patients treated with metoprolol (9 in group 1, and 12 in group 2) where significant reductions were observed in the frequency of both total (p < 0.01) and silent (p < 0.01) ischemia in both groups. Furthermore, a beneficial effect was observed on all exercise variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial changes and prognostic implications of a Doppler-derived index of combined left ventricular systolic and diastolic myocardial performance in acute myocardial infarction.

The purpose of this study was to investigate the serial changes and prognostic value of a nongeometric Doppler-derived index of myocardial function that combines systolic and diastolic time intervals of the left ventricle in acute myocardial infarction (AMI). The Doppler index was measured in 60 consecutive patients with AMI and in 30 patients admitted to hospital with suspected but disproved AMI who served as controls. The patients were studied at days 1, 5, 90, and 360 after arrival in the coronary care unit. The index was defined as the sum of isovolumetric contraction time, and isovolumetric relaxation time divided by ejection time was measured from mitral inflow and left ventricular outflow Doppler velocity profiles. The index was significantly higher in patients with AMI than in control subjects at days 1 and 360 (day 1, 0.58 +/- 0.09 vs 0.41 +/- 0.08, p <0.0001; day 360, 0.50 +/- 0.09 vs 0.39 +/- 0.07, p <0.01, respectively). The index decreased significantly in patients with AMI during follow-up (p <0.01). The index was significantly higher in patients who developed congestive heart failure or died compared with survivors who were free of congestive heart failure (day 1, 0.63 +/- 0.10 vs 0.53 +/- 0.10, p <0.01; day 360, 0.56 +/- 0.08 vs 0.48 +/- 0.10, p <0.01, respectively). During 20.2 +/- 8.5 months' follow-up, 10 patients died of cardiac causes and 13 developed congestive heart failure. Univariate analyses demonstrated that the Doppler index > or =0.60 (chi-square 8.3, p <0.0001), deceleration time < or =140 ms (chi-square 8.5, p <0.0001), ejection fraction < or =0.40% (chi-square 3.3, p <0.005), anterior wall AMI (chi-square 3.2, p <0.01), and age (chi-square 1.06/ year increase, p <0.01) were significant predictors of outcome. Multivariate stepwise analysis showed that the index < or =0.60 (chi-square 3.4, p <0.05), deceleration time < or =140 ms (chi-square 4.2, p <0.02), and age (chi-square 1.06/year increase, p <0.02) were independent predictors of outcome. The Doppler index reflects severity of left ventricular function and has incremental prognostic value in patients with AMI.

Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine.

The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve.(ABSTRACT TRUNCATED AT 250 WORDS)

Potassium and magnesium distribution, ECG changes, and ventricular ectopic beats during beta 2-adrenergic stimulation with terbutaline in healthy subjects.

OBJECTIVE: To study the effect of intravenous (i.v.) terbutaline on potassium (K) and magnesium (Mg) distribution, ECG changes, and prevalence of ventricular ectopic beats in healthy subjects. DESIGN: Randomized double-blind, placebo-controlled crossover. Subjects received either placebo or terbutaline (bolus, 0.25 mg; maintenance dose, 5 micrograms/min). SETTING: University Department of Clinical Chemistry. PARTICIPANTS: Ten healthy male volunteers. Mean age was 24.1 (range, 20 to 31) years. MAIN OUTCOME MEASURES: Serum potassium and magnesium muscle potassium and magnesium, and muscle sodium-potassium pump number. Urinary excretion of potassium and magnesium. ECG changes (T-wave and QTC interval) and the number of ventricular ectopic beats. MAIN RESULTS: Terbutaline produced an immediate decrease in serum potassium level from 4.17 (4.04 to 4.30) mmol/L to a nadir of 3.32 (3.06 to 3.58) mmol/L (p < 0.001). The urinary excretion of potassium decreased from 0.077 mmol/min (0.052 to 0.102) to 0.038 mmol/min (0.025 to 0.051) (p < 0.01). There was an increase in the number of sodium potassium pumps from 1,104.1 nmol/kg dry weight (1,030.6 to 1,177.5) to 1,273.3 nmol/kg dry weight (1,193.5 to 1,353.2) (p < 0.01), but no measurable change in muscle potassium. The QTC interval increased from 395 (385 to 405)ms to 449 (432 to 466) ms (p < 0.003). There was no change in the number of ventricular ectopic beats. CONCLUSIONS: Short-term i.v. administration of terbutaline produced hypokalemia partly due to an increase in the number of sodium-potassium pumps. Furthermore, terbutaline induced changes in ECG with a highly significant lengthening of the QTc interval but with an unchanged number of ventricular ectopic beats in healthy subjects.

Effect of preload alternations on a new Doppler echocardiographic index of combined systolic and diastolic performance.

The objective of the study was to assess the effect of preload alternations on a nongeometric Doppler index of combined systolic and diastolic myocardial performance (MPI). Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after sublingual administration of nitroglycerin in 50 healthy volunteers (group 1) and 25 patients (group 2) with previous myocardial infarction. MPI was significantly lower in group 1 (0.34 +/- 0.04) compared with group 2 (0.52 +/- 0.14), P <.0005. In group 1 MPI was significantly increased during preload manipulations (P =. 001). The largest change in MPI was induced by nitroglycerin (0.034 +/- 0.05). In group 2 no significant changes in MPI were found. In both groups peak E-wave velocity (P <.0005), E/A-ratio (P <.0005), and E-wave deceleration time (P <.0005) were found to change during preload alternations. In conclusion, we found in normal subjects and to a lesser extent in patients with previous myocardial infarction that MPI is influenced by preload.

Preload dependence of color M-mode Doppler flow propagation velocity in controls and in patients with left ventricular dysfunction.

The purpose of this study was to assess the effects of preload alterations on color M-mode flow propagation velocity (Vp) in volunteers with normal left ventricular (LV) function and in patients with depressed LV function. Color M-mode Doppler echocardiography was performed during Valsalva maneuver, passive leg lifting, and after administration of nitroglycerin in 30 healthy volunteers and in 30 age- and sex-matched patients with previous myocardial infarction (MI). Mean Vp in controls was 74 +/- 15 cm/s at baseline and 46 +/- 15 cm/s in MI patients (P <.0005). In both groups, minor changes in Vp were seen during preload alterations; however, these were not significant (control P =.72, MI P =.31). In both groups, peak E-wave velocity (P <.0005), ratio of early-to-late peak velocities (P <.0005), and E-wave deceleration time (P <.0005) were found to change during preload alterations. In conclusion, we found that in controls and patients with previous MI, the color M-mode flow propagation velocity is not affected significantly by preload.

Color M-mode and pulsed wave tissue Doppler echocardiography: powerful predictors of cardiac events after first myocardial infarction.

To assess the association between color M-mode flow propagation velocity and the early diastolic mitral annular velocity (E(m)) obtained with tissue Doppler echocardiography and to assess the prognostic implications of the indexes, echocardiography was performed on days 1 and 5, and 1 and 3 months after a first myocardial infarction in 67 consecutive patients. Flow propagation velocity correlated well with E(m) (r = 0.72, P <.0001). The ratio of peak E-wave velocity (E) to flow propagation velocity also correlated well with E/E(m) (r = 0.87, P <.0001). The positive predictive value of E/FPV > or =1.5 to identify patients with Killip class > or =II was 90%, and the negative predictive value 92%. The corresponding values for E/E(m) > or =10 were 70% and 90%. Cox proportional hazards analysis identified E/flow propagation velocity > or =1.5 (relative risk, 12.4 [95% confidence interval, 4.1-37.3]), E/E(m) > or =10 (relative risk, 11.5 [95% confidence interval, 3.8-34.7]), and Killip class > or =II (relative risk, 7.8 [95% confidence interval, 1.6-40.4]) to be predictors of the composite end point of cardiac death and readmission because of heart failure. Thus flow propagation velocity and E(m) are closely related after myocardial infarction and appear to have similar prognostic information.

Serial Doppler echocardiographic assessment of left and right ventricular performance after a first myocardial infarction.

We sought to investigate the relation between left ventricular (LV) and right ventricular (RV) function assessed with the Doppler-derived myocardial performance index (MPI), to assess serial changes, and to investigate the prognostic value of biventricular assessment of cardiac function after a first myocardial infarction (MI). To do so, serial Doppler echocardiography was performed in 77 consecutive patients with a first MI. Right ventricular MPI correlated significantly with LV MPI (r = 0.51, P <.0001). In patients with echocardiographic signs of RV MI, the RV MPI was significantly higher (0.59 +/- 0.18 versus 0.44 +/- 0.19, P =.001), whereas no difference in LV MPI was seen (0.55 +/- 0.19 versus 0.56 +/- 0.13, P = not significant). Right ventricular MPI showed a rapid normalization during follow-up, whereas LV MPI did not decrease. During follow-up, 23 patients died of cardiac causes or were readmitted because of worsening heart failure. Multivariate Cox analysis indicated LV MPI (relative risk 4.9 [95% CI 1.8-13.5], P =.002) and RV MPI (relative risk 3.8 [1.3-17.0], P =.01) to be predictors of cardiac events. Thus the RV MPI is frequently abnormal after a first MI but normalizes rapidly on follow-up, and biventricular assessment of cardiac function may improve the prognostic accuracy compared with LV assessment alone.