Prognostic role of heart rate in patients referred for coronary angiography: age and sex differences.

UNLABELLED: OBJECTIVE To evaluate the predictive value of resting heart rate (RHR) for cardiac and total mortality in a large population of patients referred for coronary angiography with an extended follow-up, stratified in four subpopulations according to gender and age (50th percentile corresponding to 67 years). METHODS: We studied 3559 subjects (2603 males, age: 66 ± 11 years, mean ± SD), obtaining patient data from the Institute electronic databank which saves demographic, clinical, instrumental and follow-up data of patients admitted to our department. RESULTS: During a mean follow-up period of 35 ± 25 months, 296 (8%) patients died; there were 173 (5%) cardiac deaths. In female patients irrespective of age, RHR (≥ 76 bpm, 75th percentile) did not appear predictive for cardiac death. In females, RHR was predictive for overall mortality after multivariate adjustment only in those aged ≥ 67 years (hazard ratio (HR) 1.7, 95% confidence interval (CI) 1-2.8, p ≤ 0.05). In male patients aged < 67 years, RHR remained as an independent predictive factor for overall mortality at the multivariate analysis (HR 2.5, 95% CI 1.5-4.2, p < 0.001), and as an independent predictor for both cardiac mortality (HR 1.8, 95% CI 1.2-2.7, p < 0.01) and total mortality (HR 1.6, 95% CI 1.2-2.3, p < 0.01) in male patients over 67 years. CONCLUSION: The current study suggests that the prognostic importance of RHR may differ according to the patient's gender and age, suggesting significant differences in cardiovascular physiopathology between female and male patients.

Monthly Intramuscular Neridronate for the Treatment of Postmenopausal Osteoporosis: Results of a 6-Year Prospective Italian Study.

PURPOSE: Oral bisphosphonates (BPs) are the most commonly used medications for osteoporosis (OP), but their poor gastrointestinal (GI) absorption and tolerance hamper compliance. Intramuscular (IM) neridronate (NE), an amino-BP, is an easy-to-administer, effective, and safe alternative to oral BPs. We assessed the 6-year effects of monthly IM NE on bone mineral density (BMD) and bone turnover biomarkers (BMs) in postmenopausal OP. METHODS: This single-center, prospective study enrolled postmenopausal osteoporotic outpatients with gastric intolerance to BPs (based on Tuscany Region's law GRT n. 836 20/10/2008). They received 25 mg IM NE once a month (with vitamin D and calcium if necessary) for 6 years. BMD was evaluated at lumbar spine (L1-L4), femoral neck (FN), and total femur (TF) at baseline (BL) and every 12 months afterwards. At BL, month 3, and every 12 months after BL, total and ionized calcium, vitamin D, parathyroid hormone 1-84, bone alkaline phosphatase (BALP), osteocalcin, and N- and C-terminal telopeptides were assayed. RESULTS: Overall, 60 women (mean age: 62.3 ± 7.5 years) received monthly IM NE for 6 years, with vitamin D and calcium supplementation in 81.3% of cases. Compared to BL, BMD increased significantly already after 1 year at all sites (4.5 ± 0.9% for L1-L4, 4.5 ± 0.8% for TF, and 2.1 ± 0.6% for FN, P ≤ 0.05), and the changes were maintained over time, whereas FN further improved up to year 3 and remained stable afterwards (P ≤ 0.05). All BMs, except for total calcium and BALP, progressively decreased over time (P ≤ 0.05). No fractures and significant adverse events were reported. CONCLUSION: The monthly administration of IM NE represents a manageable and effective option, in terms of BMD and bone BM improvement, for the long-term treatment of postmenopausal OP women with gastric intolerance to BPs. This trial is registered with ClinicalTrials.gov Identifier: NCT03699150.

Antioxidants in the Diet and Cognitive Function: Which Role for the Mediterranean Life-style?

This review aims to focus on main antioxidants- abundantly contained in the diet- as well as of the whole Mediterranean diet and life-style and their relationship with cognitive function, especially critical in two phases of life, in children until adolescence and oldness. The role of emerging biochemical and molecular biomarkers as opportunity to estimate more accurately nutritional assumption and requirement, in terms of cognitive preservation and disease risk, will be also discussed. The cluster of factors within the Mediterranean pattern -which include not only nutritional, but also physical, social, and stimulating aspects- is still largely understudied as a whole, but it is proposed as attractive research area and tool for public health planning of prevention and intervention.

Higher uric acid serum levels are associated with better muscle function in the oldest old: Results from the Mugello Study.

BACKGROUND: Sarcopenia is the progressive loss of muscle mass and strength that occurs with advancing age and plays a pivotal role in the causal pathway leading to frailty, disability and, eventually, to death among older persons. As oxidative damage of muscle proteins has been shown to be a relevant contributory factor, in this study we hypothesized that uric acid (UA), a powerful endogenous antioxidant, might exert a protective effect on muscle function in the oldest old and we tested our hypothesis in a group of nonagenarians who participated in the Mugello Study. METHODS: 239 subjects, 73 men and 166 women, mean age 92.8years±SD 3.1, underwent the assessment of UA serum level and isometric handgrip strength, a widely used clinical measure of sarcopenia. RESULTS: Mean UA serum level was 5.69mg/dL±SD 1.70 and mean handgrip strength was 15.0kg±SD 6.9. After adjusting for relevant confounders, higher UA serum levels remained independent positive predictors of isometric handgrip strength (ß 1.24±SE(ß) 0.43, p=0.005). CONCLUSION: Our results show that higher UA serum levels are associated with better muscle function in the oldest old and, accordingly, might slow down the progression of sarcopenia.

Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: I. Contribution of methodological factors.

The influence of several methodological factors on mean values of sister chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes of 1,650 subjects was analyzed. Donors belonged to a general healthy population living in Pisa and in two nearby small cities: Cascina and Navacchio (Ca-Na). Blood samples were collected over a period of 29 months and processed in three different laboratories of the some institute. Slides were analyzed by several scorers. Our data showed that lymphocyte proliferation indexes (PIs) and baseline mean values of SCEs were affected mainly by sampling period. This factor accounted for a percentage ranging from roughly 10% (Pisa) to 20% (Ca-Na) of total SCE variance and from roughly 10% (Pisa) to 13% (Ca-Na) of total PIs variance. A marginal effect was attributable to the different laboratories involved (maximum 3% for SCEs and 7% for PIs). The sampling period variable included many sources of variability such as culture media batches, fetal calf serum, PHA, BrdUrd, and seasonality. MN counts revealed a more marked dependence on processing laboratories. This factor accounted for a percentage of roughly 10% (Pisa and Ca-Na) of total variance, while the sampling period was marginally effective (about 1-4% of total variability). Because laboratories were equipped and supplied with the same materials and consumables and technicians were rotated constantly, the only variable ascertained was represented by the three different models of CO2 incubators used for lymphocyte culturing. When "month" and "incubator" variables were considered jointly, experimental variability accounted for 15-20% of total variance, both for PIs and mean values SCEs and MN. The variability due to slide scoring was reduced by assigning each slide to five different scorers and matching low with high scorers in each group. Present data show that when the study is performed under these controlled conditions, about 20% of total interdonor variability can be explained by experimental or seasonal factors.

Detection of perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis by intravenous administration of the echo-enhancing agent BR1.

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.

Vasoactive biomarkers and oxidative stress in healthy recently postmenopausal women treated with hormone replacement therapy.

BACKGROUND: Despite biologically plausible mechanisms for cardiac protection from estrogen therapy, recent clinical trials have suggested possible cardiovascular risk rather than benefit. However, it has been speculated that cardioprotective benefits from hormone replacement therapy (HRT) may be more evident in the early postmenopausal period. We have previously reported early beneficial effects on biochemical markers of endothelial function in healthy women after short-term estradiol replacement therapy. In this study we aimed to evaluate the effect of long-term HRT on different vasoactive factors and oxidative stress in healthy recently postmenopausal women. METHODS: Fifteen women (age 50 +/- 1 years, time since menopause 1.6 +/- 0.1 years) were randomized to a sequential oral and transdermal estradiol regimen (2 mg oral micronized 17beta-estradiol/day or 1.5 mg 17beta-estradiol gel/day). Oral dydrogesterone (10 mg/day, 12 days/month) was then cyclically combined with either of the estrogen therapies for 1 year. Blood samples were collected at baseline and after 1, 2, 6 and 12 months of therapy to evaluate levels of follicle stimulating hormone (FSH), estradiol, 6-keto PGF1alpha (prostacyclin metabolite), nitrite/nitrate, epinephrine, norepinephrine, 8-isoprostane (8-epi PGF2alpha) and lipid profile values. RESULTS: FSH levels decreased (p < 0.001) while estradiol levels increased (p < 0.001) during HRT. Levels of epinephrine (p < 0.001), norepinephrine (p < 0.01), mean blood pressure (p < 0.01) and low density lipoprotein (LDL) cholesterol (p < 0.01) decreased, and nitrite/nitrate levels increased (p < 0.01) during HRT, which did not significantly affect 8-epi PGF2alpha levels. CONCLUSIONS: One-year HRT significantly reduced the levels of catecholamines, mean blood pressure and LDL cholesterol while it increased levels of nitrite/nitrate, indicating cardiovascular benefit in healthy recent postmenopausal women. Levels of 8-epi PGF2alpha did not change, suggesting no evident relationship between HRT and oxidative stress.

Endothelial cell function on 2D and 3D micro-fabricated polymer scaffolds: applications in cardiovascular tissue engineering.

Polymeric structures of a polylactide-polycaprolactone blend were micro-fabricated using the Pressure Assisted Microsyringe (PAM) system. Human umbilical vein endothelial cells were cultured on the scaffolds, and apoptosis, cell adhesion, proliferation and metabolism were evaluated. In addition, more specific indicators of endothelial cell function, namely nitric oxide and endothelin production, were also assessed. Thin films of the blend, as well as gelatine-coated glass slides (as controls) were used. The results show that as far as adhesion, apoptosis and metabolism are concerned, the scaffolds do not interfere with cell function compared with gelatin controls. However, the nitric oxide/endothelin ratio was higher than that observed on the gelatin films, suggesting that the scaffolds could be used for engineering small diameter blood vessels without risk of occlusion.

Influence of chronic aerobic exercise on microcirculatory flow and nitric oxide in humans.

In the present study we assessed the effect of physical training on Laser Doppler skin flux (LDF) and nitric oxide (NO) release, before and after 3 min of brachial artery occlusion. To this end we performed laser Doppler measurements and the venous plasma assay of nitrite/nitrate (NOx) on 10 sedentary healthy subjects and 10 endurance athletes. The sedentary control subjects had lower basal and post reperfusion levels of NOx as compared to athletes (mean +/- SE: 27.8 +/- 3.5 vs. 33.2 +/- 3.4, 48.6 +/- 7.9 vs. 60.1 +/- 10.1 micromol/L; p < 0.05). LDF at baseline was not significantly different in the two groups (157.5 +/- 7.9 and 176.64 +/- 26.7 PU for sedentary subjects and athletes, respectively) while post ischemic LDF was significantly lower in nonathletic subjects than in athletes (209.9 +/- 13 and 343.8 +/- 21.3 PU, p < 0.001). In both groups the hyperaemic stimulus significantly increased LDF and NOx levels (p < 0.01 and p < 0.05, respectively). The flow reserve, estimated as peak/basal LDF, was significantly lower in control subjects than in athletes (1.34 +/- 0.2 and 2.32 +/- 0.9, respectively, p < 0.01). In athletes, as opposed to sedentary subjects, a direct correlation was found between plasma NOx concentration and LDF both in basal conditions (r = 0.92; p < 0.001), and during hyperaemia (r = 0.84; p < 0.01). In conclusion, compared to sedentary subjects, athletes had an enhanced nitric oxide release. Hyperaemia increased LDF and nitric oxide levels both in sedentary subjects and in athletes.

Oxidative stress and its association with coronary artery disease and different atherogenic risk factors.

OBJECTIVE: It is well known that free radicals contribute to endothelial dysfunction and are involved in the pathogenesis and development of cardiovascular diseases, such as atherosclerosis. The aim of this study was to provide evidence for enhanced oxidative stress in coronary artery disease (CAD). METHODS: Plasma levels of 8-isoprostane (8-epiPGF(2alpha)), marker of lipid peroxidation, were measured in 68 subjects (age: 60 +/- 2 years, mean +/- SEM). Subjects included 30 healthy control subjects and 38 patients with angiographically proven CAD. In addition, the total antioxidant power (PAO) was evaluated in a subgroup (40 subjects, 12 healthy and 28 CAD). RESULTS: Levels of 8-epiPGF(2alpha) increased with the number of affected vessels (one- and multi-vessel disease versus control subjects, P < 0.001) and considering different risk determinants for atherosclerosis (i.e. hypertension, gender, hypercholesterolaemia, P < 0.01). In multivariate regression models the number of affected vessels was independently correlated with 8-epiPGF(2alpha) (P < 0.05). PAO values significantly decreased with increased number of affected vessels (P < 0.05) and in hypertensive patients when compared with those without hypertension (P < 0.05). In multivariate regression models the number of affected vessels resulted an independent determinant for PAO (P < 0.05). Concentration of 8-epiPGF(2alpha) and PAO also correlated with the number of cardiovascular risk factors (P < 0.01 and P = 0.07, respectively). CONCLUSION: These findings indicate that elevated levels of plasma 8-epiPGF(2alpha) and reduced antioxidant capacity are associated with the extent and the severity of CAD and with the occurrence and number of different atherogenic risk factors. This observation may assist in providing more information as to how oxidative stress may predispose to atherogenesis and suggest attractive therapeutic strategies in the prevention and treatment of cardiovascular disease.

Quantitative aspects in myocardial contrast echocardiography.

Myocardial tissue perfusion is not currently quantified in the clinical setting. Thus the aim of this paper is to review the quantitative information on myocardial perfusion provided by contrast echocardiography. In a circulatory model-without the capillary network interposed between injection and sampling point of contrast-the transit time of microbubbles (source of the echo contrast effect) is inversely related to absolute flow, thus providing accurate quantitation. A similar situation is represented by blood flow inside a vessel or a cardiac cavity, where, if the prerequisites for quantitation are respected, it is possible to measure blood flow by contrast echocardiography. In the coronary circulation, the transit time of contrast microbubbles varies according to their interaction with coronary microcirculation, and to the characteristics of contrast agents as flow tracers. Echo contrast agents with small microbubbles have been injected into the coronary branches of experimental animals, under both coronary autoregulation and maximal coronary dilation, providing good estimates of coronary blood flow. The accuracy of these measurements might improve when new contrast agents, with characteristics closer to those of a flow tracer, are available. If a tracer is injected before a bifurcation, and provided it mixes adequately, the amount of tracer distributed to each branch is proportional to the corresponding blood flow. A similar situation is encountered when an echo contrast agent is injected into the aortic root or into the left main coronary artery. Here, the ratio between myocardial signal intensity in the different perfusion territories reflects the corresponding ratio of blood flows. The validity of this approach has been previously demonstrated in experimental animals and validated in patients with coronary stenoses. The injection of contrast agents into the coronary circulation at baseline and under coronary hyperaemia has the potential for measuring coronary blood flow reserve. However, what is still unclear is whether contrast echo changes reflect changes in coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary recruitment) or both, and also whether they influence the different types of contrast agent. Finally, myocardial contrast echocardiography can provide information on the spatial distribution of myocardial perfusion, i.e. the presence, site and extent of perfused myocardium. Thus, in models where myocardial perfusion may be either present or absent, contrast echo can provide an accurate estimate of perfusion abnormalities.

The effect of lipoproteins on endothelial nitric oxide synthase is modulated by lipoperoxides.

BACKGROUND AND AIM: The effect of low-density lipoproteins (LDLs) on endothelial nitric oxide synthase (eNOS) is debated. By coupling in vivo and in vitro experiments we evaluated the role of oxidized lipid substrates in the modulation of eNOS activity by LDLs. MATERIALS AND METHODS: Plasma lipids, nitrite/nitrates (NO2/NO3), and malondialdehyde (MDA) were measured in 14 controls, and in 13 patients with familial hypercholesterolemia (FH) before and after 12 weeks of treatment with atorvastatin (20 mg u.i.d.). Nitric oxide synthase in cell lysate and NO2/NO3 into the medium were measured in human microvascular (HMEC-1) and umbilical vein (HUVEC) endothelial cells after 24 h of incubation with increasing concentrations of mildly oxidized LDLs with and without atorvastatin and in HMEC-1 with and without vitamin C. In HMEC-1, NO2/NO3 was also determined after exposure to more intensively oxidized LDLs. RESULTS: At baseline, plasma NO2/NO3 (56 +/- 7 vs. 35 +/- 3 micro M) and MDA (5.6 +/- 0.7 vs. 2.9 +/- 0.3 micro M), were significantly (P < 0.02 for both) higher in the FH patients. In the whole study group, NO2/NO3 was more strongly correlated with plasma MDA (Rho = 0.70) than LDL-cholesterol (Rho = 0.57). In the FH patients, atorvastatin induced a significant decline in plasma total and LDL-cholesterol (-3.1 +/- 0.5 and -2.9 +/- 0.5 mM, respectively), NO2/NO3 (-35 +/- 8 microM) and MDA (-3.4 +/- 0.7 microM) (P < 0.001 for all). Changes in plasma NO2/NO3 were related to the concomitant changes in plasma MDA (Rho = 0.79, P < 0.006) and not to changes in LDL-cholesterol. In HMEC-1 and in HUVEC, mildly oxidized LDLs stimulated both e-NOS and NO2/NO3 accumulation; the effect on e-NOS was potentiated by vitamin C in HMEC-1. Atorvastatin had no effect in HMEC-1 while it stimulated eNOS but not NO2/NO3 in HUVEC. The accumulation of NO2/NO3 in HMEC exposed to increasing concentrations of more intensively oxidized-LDLs showed a nonlinear dose-response curve. CONCLUSIONS: In uncomplicated patients with FH, plasma NO2/NO3 concentrations are elevated; the cross-sectional data, intervention study and in vitro experiments indicate that oxidized lipids exert a tonic stimulatory action on e-NOS and NO2/NO3 generation not mediated through superoxide anion formation. Atorvastatin amplify this eNOS response in HUVEC, but not in HMEC, and this effect is not associated with a parallel increased NO2/NO3 generation.

The multicentre trial philosophy in stress echocardiography: lessons learned from the EPIC study. EPIC-EDIC Study Project. Echo Persantine International Cooperative Study. Echo-Dobutamine International Cooperative Study.

The scientific assessment of diagnostic tests should not be based upon a small series of results published by the best academic institutions, but ought to require large scale, multicentre validation founded on grass roots institutions with real doctors, real patients and real problems. To this purpose, an international network of stress echo laboratories has been organized, and within a few years has collected data from thousands of studies using pharmacological stress echocardiography, performed with either dipyridamole (EPIC: Echo Persantine International Cooperative Study) or dobutamine (EDIC: Echo Dobutamine International Cooperative Study) stresses. In a widely deregulated field, all network laboratories have agreed: to pass a quality control examination on stress echo reading before entering the study; to adopt an identical drug infusion protocol; to code similarly the LV segments; and to adopt a common scoring system for wall motion analysis. A minimum amount of historical, clinical, and-when available-stress electrocardiographic, angiographic and follow-up data have been collected on each patient, and disseminated in the various centres, facilitating the creation of an international stress echo language that will help, not only the production of high quality scientific data, but also the build up of a common stress echo lab, with a standardized way of making the studies, unifying the methods and terminology, and archiving data. To date, we have 50 echo laboratories from 15 nations across four continents (Europe, America, Asia and Africa) actively involved in this project. These data will ultimately fill the gap between the academic theory of journals and the pragmatic experience of daily life in a busy echocardiographic laboratory.

Airway inflammation in nonasthmatic amateur runners.

Elite athletes show a high prevalence of symptoms and signs of asthma, but no study has assessed the acute effects of endurance exercise on airway cells in nonasthmatic athletes. We measured exhaled nitric oxide (NO) and collected samples of induced sputum after 3% NaCl aerosol administration for 20 min in nonasthmatic middle-aged amateur runners after the Fourth Palermo International Marathon and 6--9 wk later (habitual training period) at baseline. After the marathon, exhaled NO (n = 9 subjects) was higher [27 +/- 9 parts/billion (ppb)] than at baseline (12 +/- 4 ppb; P < 0.0005). Polymorphonuclear neutrophil (PMN) counts in induced sputum were much higher in runners (91.2 +/- 3.6% of total cells postmarathon and 78.7 +/- 9.1% at baseline) than in sedentary control subjects (9.9 +/- 5.9%; P < 0.001). Expression of L-selectin and CD11b/CD18 in sputum PMNs was lower after the race than at baseline and inversely related to the amount of exhaled NO (r = -0.66 and -0.69, respectively; P < 0.05). Our data indicate that sputum PMNs are increased in nonasthmatic runners both after a marathon and at baseline and suggest that NO may modulate exercise-associated inflammatory airway changes.

Chronic long-term nitrate therapy: possible cytogenetic effect in humans?

Nitrates act as donors of nitric oxide (NO), a molecule with a recognized potential for genotoxicity. In order to assess whether chronic long-term nitrate therapy may increase genotoxicity, we evaluated chromosomal damage in peripheral lymphocytes of 27 ischaemic patients undergoing chronic nitrate treatment for vertical line4 years (7.9 +/- 3.1, mean +/- SD) and 18 age- and sex-matched subjects without any previous nitrate treatment. At the same time, after treatment in vitro with 0-20 microM sodium nitroprusside as NO donor, micronucleus induction and cell proliferation were also evaluated using blood from six different healthy donors. The results showed that the frequency of structural chromosomal aberrations was not significantly higher in the drug-treated group than the control [2.1 +/- 1.4 versus 1.6 +/- 1.2 (mean +/- SD); P = 0.23]. The frequency of micronucleated lymphocytes was higher in the nitrate group than in the control group (6.5 +/- 4.6 versus 3.5 +/- 2.9, P=0.01). In vitro treatment indicated a dose-dependent increase in the frequency of micronucleated lymphocytes with increasing SNP concentrations. Cytotoxicity and cell cycle delay, with a statistically significant difference with respect to control culture, were also observed. Our results suggest a possible genotoxic activity of nitrate therapy. Further studies focusing on the possible link between nitrate therapy and genotoxicity are warranted at this point.

The relative value of exercise-electrocardiography and dipyridamole stress echocardiography for risk stratification early after uncomplicated myocardial infarction. The EPIC (Echo Persantine International Cooperative) Study Group.

BACKGROUND: Rational prognostic algorithm should be developed considering the logical progression of the information as it becomes available to the physician, with clinical data first, ECG data second and stress imaging data last. The aim of the present study was to assess in a clinically realistic fashion the relative prognostic value of exercise electrocardiography test (EET) and dipyridamole-echocardiography test (DET) early after first acute uncomplicated myocardial infarction. METHODS AND RESULTS: Five hundred and forty-seven in-hospital patients (age = 56 +/- 9 years) with recent clinically uncomplicated first myocardial infarction, baseline echocardiographic findings of satisfactory quality, interpretable ECG and capability to exercise underwent a resting 2D echocardiogram, a DET and an EET at a mean of 10 days from the infarction and were followed up for 16.2 +/- 11 months. During the follow-up, there were 17 cardiac deaths, 19 non-fatal myocardial infarctions and 49 unstable angina. When cardiac death was considered as the only significant event, with multivariate analysis, peak dipyridamole Wall Motion Score Index was the only significant predictor (chi 2 = 5.66; p = 0.013; relative risk estimate = 4.7; confidence intervals = 1.35-16.08). In presence of a negative exercise electrocardiography test for both chest pain and electrocardiographic criteria, the death rate was 2%. CONCLUSION: DET provides stronger information in comparison with historical and EET variables. However, a negative maximal EET is sufficient to identify a very low risk subset in whom additional testing may not be warranted.