Anti-beta 2 glycoprotein I antibodies and the risk of myocardial infarction in young premenopausal women.

BACKGROUND: Contrasting data have been reported on the association between the presence of anti-phospholipid antibodies (aPL) and arterial thrombotic events, particularly those in coronary arteries. This discrepancy is perhaps related to the confounding effect of traditional risk factors. Among them, coronary atherosclerosis appears to be the most important in studies conducted in middle-aged and elderly patients. OBJECTIVE: To minimize such confounding effects, a multicenter case-control study on the association between aPL and myocardial infarction (MI) was carried out in a rare cohort of young premenopausal women. METHODS: We evaluated 172 cases hospitalized for a first MI before the age of 45 years and 172 controls individually matched with cases for age, sex and geographical origin. Clinical and laboratory data were collected and levels of anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) and anti-nuclear antibodies (ANA) were measured. RESULTS: A significant association between MI and IgG/IgM anti-beta2GPI antibodies was observed; the results were confirmed after adjusting for smoking and hypertension (anti-beta2GPI IgG OR = 2.47, 95% CI 1.81-3.38; anti-beta2GPI IgM 4th quartile OR 3.68, 95% CI 1.69-8.02). The association between anti-beta2GPI antibodies and MI was detected in both subgroups with and without coronary artery stenosis. Whereas the association of aCL IgG with MI was modest, ANA showed no significant association with MI. No aPL were found in unselected patients (mainly males) who recently developed acute MI. CONCLUSIONS: Anti-beta2GPI antibodies are a significant risk factor for MI in young premenopausal women independently of other risk factors, including the degree of coronary artery stenosis.

A 23bp insertion in the endothelial protein C receptor (EPCR) gene impairs EPCR function.

EPCR is a type I transmembrane protein, highly expressed on the endothelium of large vessels, that binds protein C and augments its activation. In this study, a 23bp insertion in the EPCR gene was found in 4/198 survivors of myocardial infarction and 3/194 patients with deep vein thrombosis. The EPCR gene with the insertion predicts a protein that lacks part of the extracellular domain, the transmembrane domain and the cytoplasmic tail. Expression studies showed that the truncated protein is not localized on the cell surface, cannot be secreted in the culture medium, and does not bind activated protein C. Since protein C activation depends on the concentration of EPCR, patients with the EPCR insertion could have a diminished protein C activation capacity. Further clinical studies of adequate samples size are necessary to establish whether or not the EPCR insertion predisposes to the development of thrombotic events.

Thrombogenic potential of human coronary atherosclerotic plaques.

Higher levels of tissue factor (the initiator of blood coagulation) have been found in coronary atherosclerotic plaques of patients with unstable coronary artery disease, but it is not established whether they are associated with a different thrombotic response to in vivo plaque rupture. In 40 patients undergoing directional coronary atherectomy, prothrombin fragment 1 + 2, a marker of thrombin generation, was measured in intracoronary blood samples obtained proximally and distally to the coronary atherosclerotic plaque before and after the procedure. Before the procedure, plasma prothrombin fragment 1 + 2 levels were significantly increased across the lesion in patients with unstable, but not in those with stable, coronary disease (unstable, median increase, 0.37 nM; range, -0.35-1.16 nM) (stable, median increase, -0.065 nM; range, -0.58-1.06 nM) (P =.0021). After plaque removal, an increase in prothrombin fragment 1 + 2 across the lesion was observed only in patients with unstable coronary disease (unstable, median increase, 0.25 nM; range, -1.04-4.9 nM) (stable, 0.01 nM; range, -0.48-3.59 nM) (P =.036)]. There was a correlation between the tissue factor content of the plaque and the increase in thrombin generation across the lesion (rho = 0.33; P =.038). The higher tissue factor content found in plaques obtained from patients with unstable coronary disease was associated with a local increase in thrombin generation, thus suggesting a link with the in vivo thrombogenicity of the plaque.

Tissue factor in human coronary atherosclerotic plaques.

The rupture or fissuring of a coronary atherosclerotic plaque and subsequent thrombosis is considered the key event in the pathogenesis of unstable angina and myocardial infarction. Although plaque disruption frequently occurs during the evolution of atherosclerosis, only a minority of ruptured plaques develop thrombosis. The content and procoagulant activity of tissue factor in human coronary atherosclerotic plaques varies widely, and different studies confirm that it is higher in the plaques extracted from patients with unstable angina, myocardial infarction or histologic/angiographic evidence of coronary thrombosis than in those taken from patients with stable angina or uncomplicated coronary lesions. Variations in tissue factor content and activity may be responsible for the different thrombotic responses to human coronary atherosclerotic plaque rupture.

Comparison of dobutamine stress echocardiography and exercise stress Thallium-201 SPECT for detection of myocardial ischemia after acute myocardial infarction treated with thrombolysis.

In order to compare the ability of dobutamine stress echocardiography (DSE) and exercise Thallium-201 SPECT to detect myocardial ischemia in patients with myocardial infarction (MI) treated with thrombolysis, 43 prospectively selected patients with MI treated with thrombolysis underwent within 1 month from MI DSE, stress-redistribution-reinjection Thallium-201 SPECT and coronary angiography. The echocardiographic and scintigraphic images were analyzed for the presence of myocardial ischemia using a 11-segment left ventricular model. DSE and exercise Thallium-201 SPECT detected myocardial ischemia in the infarct zone in 72% and 72% (31/43) of patients and ischemia at a distance in 12% (5/43) and 19% (8/43) of patients with a concordance of 67% and 88%, respectively. A significant agreement between DSE and exercise Thallium SPECT was found in the evaluation of the extent of both myocardial necrosis and stress-induced myocardial ischemia. DSE and exercise Thallium SPECT showed similar sensitivity (79 vs 76%), specificity (60 vs 60%) and accuracy (77 vs 74%) for detection of a critical stenosis of the infarct-related artery; there was also no significant difference between the tests in sensitivity, specificity and accuracy for detection of the multivessel disease. In conclusion, initially after thrombolyzed MI, DSE and exercise Thallium-201 SPECT detect myocardial ischemia in the infarct zone in a high proportion of patients and show a similar accuracy for the diagnosis of a critical stenosis of the infarct-related coronary artery and of the multivessel disease.

Prothrombotic genetic risk factors in young survivors of myocardial infarction.

It has long been thought that an individual thrombotic tendency increases the risk of myocardial infarction, especially in young adults. Several "prothrombotic" genetic factors that may influence the individual thrombotic risk have been identified. To investigate the association between the risk of myocardial infarction at a young age and genetic factors thought to be associated with an increased tendency to thrombosis (the polymorphisms 4G/5G of the PAI-1 gene, PIA1/PIA2 of the platelet glycoprotein IIIa, C3550T of the platelet glycoprotein Ib gene, G10976A of the factor VII gene, C677T of the methylenetetrahydrofolate reductase gene, G1691A of the factor V gene, and G20210A of the prothrombin gene), we performed a case-control study evaluating 200 survivors (185 men, 15 women) of myocardial infarction who had experienced the event before the age of 45 years and 200 healthy subjects with a negative exercise test, individually matched for sex, age, and geographic origin with the cases. The presence of the PIA2 polymorphic allele was the only prothrombotic genetic factor associated with the risk of myocardial infarction at a young age. The odds ratio for carriers of the PIA2 allele compared with those of the PIA1 allele was 1.84 (95% confidence intervals (CI) 1.12 to 3.03). There was a significant interaction between the presence of the PIA2 allele and smoking: with their simultaneous presence, 46% (95% confidence intervals 11% to 81%) of premature myocardial infarctions were attributable to the interaction between the two factors. In conclusion, carrying the PIA2 polymorphic allele of platelet glycoprotein IIIa was the only genetic prothrombotic factor associated with the risk of developing myocardial infarction at a young age. The clinical expression of this genetic predisposition seems to be enhanced by smoking.

Prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography early after acute myocardial infarction treated with thrombolysis.

OBJECTIVES: The aim of the study was to assess the prognostic value of myocardial viability and ischemia detected by dobutamine stress echocardiography (DSE) in patients with acute myocardial infarction (AMI) treated with thrombolysis. BACKGROUND: DSE can detect myocardial viability and ischemia early after AMI, but the prognostic importance of viability and ischemia in these patients has yet to be assessed. METHODS: DSE was performed in 152 patients at a mean of 9 +/- 5 days after a first AMI treated with thrombolysis to evaluate myocardial viability and ischemia. The patients were followed up for 15 +/- 19 months. RESULTS: On the basis of DSE results three groups of patients were identified: group 1 (95 patients, 62.5%) with myocardial viability and ischemia, group 2 with myocardial viability without ischemia (32 patients, 21%) and group 3 (25 patients, 16.5%) with no myocardial viability. During follow-up 10 patients (6.5%) had hard events, 53 (35%) developed unstable angina and 67 (44%) underwent myocardial revascularization. The rate of hard events was 10% in group 1 and 0% in group 2 and 3 patients (p < 0.05 group 1 versus group 2); group 1 patients with viability and ischemia showed a significantly higher rate of recurrence of unstable angina and myocardial revascularization procedures (40% and 60%) compared to group 2 (22% and 16%) and group 3 patients (20% and 20%). Using the Cox multivariate stepwise model, only the extent of ischemic myocardium (hazard ratio (HR) = 21.7, p = 0.02) and angina during DSE (HR = 4.45, p = 0.03) were significant predictors of hard events; an ischemic response to DSE (HR = 2.92, p = 0.001) was the most important predictor of spontaneous events, followed by ST-segment depression during DSE (HR = 1.71, p = 0.04), angina during DSE (HR = 1.53, p = 0.19) and age (HR = 0.96, p = 0.05). CONCLUSIONS: In patients with a first AMI treated with thrombolysis the presence and extent of myocardial ischemia during DSE is the most important predictor of both hard and spontaneous cardiac events, whereas myocardial viability does not have an independent prognostic value.

Dobutamine-induced ST-segment elevation in patients without myocardial infarction.

During dobutamine stress echocardiography, ST-segment elevation developed in 20 of 372 patients (5%) without previous myocardial infarction and was associated with a transient severe asynergy of the myocardial region corresponding to the site of ST elevation. In 17 of 19 patients, ST-segment elevation was associated with a critical stenosis of the ischemia-related coronary artery, whereas in 2 of 19 patients with no critical lesions of the ischemia-related artery, coronary vasospasm was the most likely mechanism of myocardial ischemia.

Significance of ST-segment elevation during dobutamine-stress echocardiography in patients with acute myocardial infarction treated with thrombolysis.

BACKGROUND: Stress-induced ST-segment elevation in patients with recent myocardial infarction treated with thrombolysis has not been extensively investigated. According to the results of previous studies it may represent residual myocardial ischaemia or dyskinesia in the infarcted region. The aim of the study was to analyse the significance of dobutamine-induced ST-segment elevation in the infarcted area in a consecutive group of patients (n = 42, 41 men, mean age 53 +/- 7 years) with a first acute myocardial infarction treated with thrombolysis within 6 h from symptoms onset. METHODS AND RESULTS: All patients underwent dobutamine-stress echocardiography (up to 40 micrograms.kg-1.min-1 + atropine) 7 +/- 3 days from the acute event and coronary arteriography within 1 month from the test. Significant ST-segment elevation was defined as a shift > or = 1 mm during dobutamine compared to baseline in at least two contiguous infarct-related leads; a correlation was made between the site of ST-segment elevation and wall motion changes during dobutamine. Dobutamine-induced ST-segment elevation in 23/42 (55%) patients (group 1) while no changes were observed in 19/23 (45%) patients (group 2). Compared to group 2, group 1 patients showed a higher asynergy score index (1.72 +/- 0.24 vs 1.50 +/- 0.32, P < 0.02) and a higher number of asynergic segments (5.04 +/- 1.9 vs 4.11 +/- 1.8), at baseline, a higher incidence of baseline and/or stress-induced dyskinesia (39 vs 10%, P < 0.05) in the infarct-related region and a higher percentage of occluded infarct-related arteries (48 vs 0%, P < 0.001). In the 42 patients studied, a significant correlation was found between baseline ST-segment elevation and baseline asynergy score index (RS = 0.56, P < 0.001) and between ST-segment elevation and asynergy score index at peak stress (RS = 0.55, P < 0.001). The incidence of reversible wall motion abnormalities indicative of myocardial viability and residual myocardial ischaemia was similar in the two groups (87 vs 84% and 74 vs 68%, respectively), while the number of segments with irreversible akinesia indicative of myocardial necrosis was higher in group 1 compared to group 2 (1.5 +/- 1.4 vs 0.9 +/- 1.4). Among the 23 patients of group 1 with dobutamine-induced ST-segment elevation, six had no reversible wall motion abnormalities indicative of myocardial ischaemia; of the 17 patients with myocardial ischaemia, 11 had > or = 50% and six had < or = 50% of basally asynergic segments showing reversible wall motion abnormalities. CONCLUSIONS: In patients with recent thrombolyzed myocardial infarction dobutamine-induced ST-segment elevation is associated with a larger akinetic area in basal conditions and either with reversible wall motion abnormalities indicative of myocardial ischaemia or with irreversible or minimally reversible wall motion abnormalities in the infarct area during the test. Thus, dobutamine echocardiography provides useful information for the interpretation of stress-induced ST-segment elevation and clinical management of these patients.

Dobutamine stress echocardiography early after myocardial infarction treated with thrombolysis. Identification of myocardial viability and ischemia and relation to spontaneous functional recovery.

The aim of the study was to assess the ability of dobutamine stress echocardiography to detect myocardial viability and ischemia in patients with acute myocardial infarction treated with thrombolysis and to correlate the acute response to dobutamine with late spontaneous functional recovery at follow-up. Forty-two consecutive patients with myocardial infarction treated with thrombolysis underwent low- (5 and 10 mcg/kg/min) and high-dose (20 to 40 mcg/kg/min) dobutamine stress echocardiography at a mean of 7 +/- 3 days of the acute phase. A follow-up 2D-echocardiogram was performed in all patients to evaluate the spontaneous recovery of function in the infarct area. On the basis of the response to the test, 3 groups of patients were identified: group 1 included 7 patients showing an improvement in left ventricular asynergy score index at low doses (from 1.5 +/- 0.3 to 1.3 +/- 0.2, p < 0.05) with no deterioration at high doses, indicative of myocardial viability without ischemia; group 2 (23 patients) showed a significant improvement in the asynergy index at low doses (from 1.58 +/- 0.3 to 1.32 +/- 0.32, p < 0.05) followed by a deterioration at high doses (1.68 +/- 0.4, p < 0.05 vs low-dose), suggestive of residual myocardial ischemia in the infarct zone; group 3 included 12 patients who showed no significant changes in the baseline asynergy score index (1.67 +/- 0.2) either at low or at high doses. The acute response to dobutamine stress echocardiography accurately predicted the spontaneous recovery of function in the infarct area at follow-up: both group 1 and group 2 patients showed a significant reduction in the asynergy score index (group 1: 1.16 +/- 0.3 vs 1.5 +/- 0.2, p < 0.001; group 2: 1.43 +/- 0.3 vs 1.58 +/- 0.3, p < 0.05), while group 3 had no recovery in the asynergy index (1.67 +/- 0.2 vs 1.67 +/- 0.2). Thus, in patients with acute myocardial infarction treated with thrombolysis dobutamine stress echocardiography can detect myocardial viability in 71% and ischemia in the infarct zone in 55% of patients; moreover, the response to the test during the acute phase is correlated with the degree of the late spontaneous recovery of function in the infarct area.

Thrombin activity and early outcome in unstable angina pectoris.

BACKGROUND: The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. METHODS AND RESULTS: Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038). CONCLUSIONS: Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Comparison of dobutamine stress echocardiography with dipyridamole stress echocardiography for detection of viable myocardium after myocardial infarction treated with thrombolysis.

OBJECTIVE: To compare the ability of dobutamine and dipyridamole stress echocardiography to detect functional recovery of stunned but viable myocardial regions early after acute myocardial infarction, and to predict late functional recovery of the reperfusion salvaged myocardium within the infarct area. METHODS: Within 10 d of acute myocardial infarction, 51 patients--30 anterior and 21 inferior, 44 Q wave and seven non-Q-wave infarction--were submitted to a dobutamine echocardiography test at low dose (5-10 micrograms/kg/min over 5 min) and high dose (20-40 micrograms/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) on different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at two months in 41 of 51 patients (80%). Regional wall motion of the left ventricle was analysed in a semiquantitative manner on a 14-segment model. Viability was defined as improvement of one grade or more of at least two basally asynergic segments in the infarcted area. RESULTS: Regional functional recovery was detected by low dose dobutamine in 38/51 patients (75%) and in 147/308 (48%) of basally asynergic segments, compared to 25/51 patients (49%; P < 0.001) and 78/308 segments (25%; P < 0.001) only identified by dipyridamole. Late spontaneous functional recovery was detected in 24/41 patients (59%) and in 78/254 basally asynergic segments (31%). The sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 72% and 51% respectively (P < 0.001), specificity 68% and 82% (P < 0.001), positive predictive value 50% and 56%, and negative predictive value 85% and 79%. CONCLUSIONS: In comparison with dipyridamole in patients with thrombolysed myocardial infarction, dobutamine induces regional functional recovery. This suggests that dobutamine is more sensitive in showing the presence of viable myocardium within the infarct zone, though it has a lower specificity in predicting delayed spontaneous functional recovery of non-contractile but still viable areas.

[Results and prognostic significance of echocardiography-dobutamine + atropine test in recent non-Q wave myocardial infarction]. / Risultati e significato prognostico del test eco-dobutamina + atropina nell'infarto miocardico non-Q recente.

BACKGROUND: Patients with non-Q wave myocardial infarction (NQ AMI) are usually considered to have an increased risk of recurrent ischemic events and reinfarction. We wished to assess whether dobutamine stress echocardiography with the addition of atropine (DOB-E + ATRO) can detect jeopardized myocardium after a recent NQ AMI and to assess the prognostic significance of this test in a group of patients with a first uncomplicated NQ AMI: METHODS AND RESULTS: Fourty-one consecutive patients (38 men, mean age 52 +/- 9 years, 31 anterior, 68% treated with thrombolysis) underwent low and high-dose DOB-E (from 5 to 40 mcg/kg/min); ATRO was added in 14/41 (34%) patients. A significant deterioration of wall motion in the infarcted region (IR) indicative of residual myocardial ischemia was present in 36/41 patients (88%). Significant electrocardiographic changes and angina developed in 61% and 32% of patients, respectively. Coronary angiography was performed in 30/41 patients (73%) and showed 1-vessel coronary artery disease (CAD) in 70% of cases, multivessel CAD in 23% of cases and no significant CAD in 7% of patients. Three patients were lost at follow-up and 10 other patients were excluded from the analysis because a revascularization procedure was performed during diagnostic angiography. On a mean follow-up period of 9.5 +/- 9 months, the incidence of coronary events (re-infarction, recurrent angina, revascularization procedures) was higher (15/36 vs 1/5, 42% vs 20%) in patients with a DOB-E + ATRO positive test (1 reinfarction, 9 recurrent angina, 5 revascularized) than in those with a negative test (1 recurrent angina). CONCLUSIONS: DOB-E + ATRO early after a first uncomplicated NQ AMI documents the presence of myocardial ischemia in the IR in the great majority of patients. A positive DOB-E + ATRO was found to be associated with a higher incidence of cardiac events at follow-up, but the results of this non prospective study (high sensitivity but low specificity and predictive value for cardiac events at follow-up) suggest to utilize with caution this test for risk stratification of patients with recent NQ AMI until prospective and larger studies are performed.

Results of dipyridamole plus atropine echo stress test for the diagnosis of coronary artery disease.

Sensitivity of dipyridamole stress echocardiography (DIP-E) has been reported to be less than ideal in particular subsets of patients such as those with less severe extent of coronary artery disease (CAD). To verify if sensitivity could be improved, ATRO (1 mg in 2 minutes) was added at the end of a negative high-dose (0.84 mg/kg over 10 minutes) DIP-E in 61 consecutive patients (58 men, aged 53 +/- 7 years) evaluated for chest pain (33%) or for detection of residual ischemia after acute myocardial infarction (AMI) or previous MI (67%). DIP-E was positive in 28/61 (46%) and negative in 33/61 (54%) patients. Additional echo positivity was obtained in 18/33 (54%) patients after ATRO. Coronary arteriography was normal in 6 patients (10%); 1-vessel CAD was diagnosed in 28 (46%), 2-vessel CAD in 16 (26%) and 3-vessel CAD in 11 (18%) cases. The sensitivity for CAD diagnosis was 49% (27/55) for DIP-E and 84% (46/55) for DIP-E+ATRO (p < 0.001). Specificity was 83% and 80%, respectively. Diagnostic accuracy increased from 52% to 83% (p < 0.001). The better diagnostic accuracy of DIP-E was mainly related to the significant increase in sensitivity of the combined test in patients with 1-vessel CAD (from 46% to 75%) (p < 0.005). At quantitative coronary evaluation, compared to patients with positive DIP-E+ATRO or negative DIP-E+ATRO test, patients with positive DIP-E had a higher mean % diameter stenosis: 80 +/- 13% vs 72 +/- 24% and 65 +/- 36%, respectively. Peak heart rate was significantly higher after the addition of ATRO vs basal and DIP alone in patients with a positive DIP-E+ATRO test. The addition of ATRO to DIP increases diagnostic accuracy of DIP-E particularly in patients with less severe extent of CAD; ATRO may be considered as a useful routine procedure for increasing diagnostic value of DIP-E test.

[The side effects and safety of the echo-dobutamine test. The experience with 373 patients]. / Effetti collaterali e sicurezza del test eco-dobutamina. Esperienza in 373 pazienti.

BACKGROUND: A potential limitation to the clinical utilization of dobutamine stress echocardiography is the higher incidence of side effects in respect to other noninvasive tests for the diagnosis of coronary artery disease reported by some authors. Due to the increased utilization of this test for the evaluation of chest pain and for prognostic stratification in patients with a recent myocardial infarction, we analyzed the results of 373 consecutive tests to evaluate the incidence and clinical significance of side effects induced by dobutamine. METHODS: Dobutamine stress echocardiography was performed in 256 patients (69%) for the evaluation of chest pain; 85 out of 256 (33%) suffered from a previous myocardial infarction. 117 patients (31%) were studied in the early phase after an acute myocardial infarction for prognostic purposes. Dobutamine was infused starting with the dose of 5 gamma/kg/min over 3 minutes with incremental steps of 10-20-30-40 gamma/kg/min over 3 minutes under 2D-echocardiographic and 12-lead electrocardiographic monitoring. RESULTS: In 95% of cases the test was stopped at the achievement of a target end point: wall motion abnormalities (60%), significant ECG changes (5%), 85% of the age-predicted maximal heart rate (13%), maximal dose (17%); only in 5% of cases a limiting side effect requiring a premature interruption of the test occurred: hypertension (systolic blood pressure over 240 mm Hg and/or diastolic over 120 mm Hg) (2%); symptomatic hypotension (0.5%); severe chest pain (1%); nausea (0.5%); cardiac arrhythmias (1%). Cardiac arrhythmias were the most frequently registered non limiting side effect. During the test 79 episodes of supraventricular arrhythmias and 211 episodes of ventricular arrhythmias occurred. Supraventricular arrhythmias consisted usually of benign sporadic premature beats; only 3 cases of self-limiting supraventricular tachycardia or atrial fibrillation were recorded. Sporadic ventricular premature beats were the most frequently recorded arrhythmias; 10 patients developed a ventricular tachycardia; however in no case this arrhythmia was sustained, associated with subjective symptoms and required the administration of a specific antiarrhythmic drug or the premature interruption of the test. Patients were divided according to the absence (Group 1, G1, n = 193, 52%) or the presence (Group 2, G2, n = 180, 48%) of cardiac arrhythmias during the test. Patients of G2 differed from patients of G1 only in respect of the maximal dose of dobutamine infused (33.5 vs 28.6 gamma/kg/min, p < 0.0005) and the incidence of a wall motion abnormality in the basal echocardiogram (66% vs 53%, p < .01). The second most recorded non limiting side effect (71/373 pts) (19%) was the occurrence of systolic hypotension, a drop of systolic blood pressure > or = 20 mm Hg in respect of the antecedent infusion step. In all cases no symptoms developed and the great majority of patients with this finding had a normal echocardiographic response to dobutamine at the time of his occurrence. CONCLUSIONS: Dobutamine echo stress test is limited by the occurrence of significant side effects only in a minority of patients (5%); however in all cases, including complex ventricular arrhythmias, these side effects were self limiting and promptly recovered after interruption of the drug infusion. Non limiting side effects, in particular cardiac arrhythmias and systolic hypotension, are usually well tolerated and not associated with the occurrence of myocardial ischemia or left ventricular disfunction; thus, dobutamine echo stress test may be considered a safe test for the evaluation of the presence and severity of coronary artery disease both in patients with a previous or recent myocardial infarction and in patients without myocardial infarction.

[Adding atropine improves the diagnostic accuracy of dipyridamole-echo test]. / L'aggiunta di atropina migliora l'accuratezza diagnostica del test eco-dipiridamolo.

BACKGROUND: The clinical experience with dipyridamole stress echocardiography for the diagnosis of coronary artery disease (CAD) revealed that patients with less severe extent of CAD and limited impairment of coronary reserve are frequently not recognized by the test. Increasing myocardial oxygen consumption adding atropine to dipyridamole may improve the diagnostic accuracy of dipyridamole for the detection of CAD. METHODS: Fifty-two patients (48 men, aged 53 +/- 7 years) underwent a high-dose dipyridamole-echo stress test (0.84 mg/kg over 10 minutes) and coronary arteriography within 15 days from the test. Eighteen out of 52 patients were referred for chest pain; 11 suffered from a previous myocardial infarction (MI) and 23 were studied in the early phase after a first acute MI. Starting after 4 minutes from the end of dipyridamole infusion, atropine was added, in 2 doses of 0.5 mg each, at 1-minute interval in those patients with no echocardiographic evidence of myocardial ischemia after dipyridamole alone. Left ventricular wall motion was analyzed on a 11-segment left ventricular model in a qualitative manner. RESULTS: Dipyridamole-echo stress test was positive in 23/52 (44%) and negative in 29/52 (56%) patients. In these patients atropine was added resulting in an additional echo positivity in 14/29 patients. Coronary arteriography was normal in 6 patients (12%); 1-vessel CAD was diagnosed in 23 (44%), 2-vessel CAD in 13 (25%) and 3-vessel CAD in 10 (19%) cases. The sensitivity for CAD diagnosis was 48% (22/46) for dipyridamole alone and 76% (35/46) for dipyridamole-atropine echo (p < .005), while the specificity was 83% (5/6) and 80% (4/5) respectively. Diagnostic accuracy increased from 52% (27/52) to 75% (39/52) (p < .001). The better diagnostic accuracy of dipyridamole-atropine echo stress test was mainly related to the increased sensitivity of the combined test in patients with 1-vessel CAD (from 39% to 70%) (p < .005). Peak heart rate was significantly higher after the addition of atropine (100 +/- 17 beats/min) compared to basal (64 +/- 10) and dipyridamole (85 +/- 12) in those patients with a positive dipyridamole-atropine echo stress test. No limiting side effects were elicited with the addition of atropine to dipyridamole. CONCLUSIONS: The combination of atropine and dipyridamole induces a chronotropic stress adjunctive to flow maldistribution phenomena that permits to increase diagnostic accuracy of dipyridamole-echo stress test particularly in patients with less severe extent of CAD; it is usually well tolerated and safe and may be considered as a useful procedure for optimizing diagnostic value of dipyridamole-echo stress test.

Hemodynamics of volume loading compared with dobutamine in severe right ventricular infarction.

To compare the hemodynamic effect of volume loading with that of dobutamine infusion in severe ischemic right ventricular (RV) dysfunction, 11 patients with inferior and RV infarction complicated by low cardiac output syndrome and important hemodynamic derangement (systolic blood pressure < 100 mm Hg, cardiac index < 2.0 liters/min/m2, right atrial pressure > 10 mm Hg) were prospectively studied within 48 hours of symptom onset. After right heart catheterization, volume loading (mean 400 ml saline solution) and dobutamine infusion (5 and 10 micrograms/kg/min over 10 minutes) were performed according to a randomized, crossover design. Volume loading resulted in increased right atrial (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) and pulmonary capillary (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) pressures, without increasing cardiac index, heart rate, aortic pressure, or right and left ventricular stroke work index. Dobutamine (5 micrograms/kg/min) increased cardiac index (from 1.5 +/- 0.3 to 1.9 +/- 0.5 liters/min/m2, p < 0.05), incrementing both heart rate (from 61 +/- 12 to 70 +/- 13 beats/min, p < 0.05) and stroke volume index (from 25 +/- 6 to 27 +/- 5 ml/beat/m2, p < 0.05), as well as right (from 1.4 +/- 1.6 to 2.3 +/- 2.2 g.m/m2, p < 0.05) and left (from 21 +/- 7 to 27 +/- 10 g.m/m2, p < 0.05) stroke work indexes; right and left ventricular filling pressures did not decrease. Dobutamine (10 micrograms/kg/min) significantly improved myocardial performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of dobutamine stress echocardiography in patients with syndrome X.

This study describes the results of Dobutamine stress echocardiography in 10 patients with Syndrome X. The diagnosis of Syndrome X was made on the basis of the presence of exertional angina, positive exercise stress test, negative ergonovine stress test and normal coronary arteries at angiography. All patients underwent Dobutamine stress echocardiography after interruption of any antianginal therapy. Dobutamine was infused starting with a dose of 5 mcg/kg/min over 3 minutes with incremental steps of 5 mcg/kg/min every 3 minutes up to a maximal dose of 40 mcg/kg/min. Two-dimensional echocardiography and 12-lead electrocardiography was monitored during the infusion of the drug. Nine patients received the maximal dose while one patient prematurely stopped the test for the occurrence of side effects. None of the ten patients developed segmental left ventricular wall motion abnormalities indicative of myocardial ischemia; ST-segment depression diagnostic for ischemia developed in 30% of patients; angina was elicited in one of these patients and in two additional patients. A hyperkinetic response to Dobutamine infusion involving all the segments of the left ventricle was observed both in patients with and without chest pain or electrocardiographic changes. In patients with Syndrome X Dobutamine induces a hyperkinetic left ventricular response indicative of normal contractile reserve despite the presence in some cases of angina and electrocardiographic signs of ischemia.

[Echocardiography-dobutamine test in the short-term evaluation of the results of coronary angioplasty]. / Il test eco-dobutamina nella valutazione a breve termine dei risultati dell'angioplastica coronarica.

BACKGROUND: Coronary angioplasty is commonly performed as a means of coronary revascularization, but at present no method has proven to be of definite value in assessing the functional result of a given angiographic procedure. OBJECTIVES: The purpose of this study was to evaluate whether dobutamine stress echocardiography can detect a reversal of ischemia-induced left ventricular regional wall motion abnormalities 15 days after an angiographically successful percutaneous transluminal coronary angioplasty (PTCA). METHODS: 25 patients underwent dobutamine stress echocardiography 24-48 hours before and 15 days after an elective angiographically successful PTCA. Twelve out of 25 patients (48%) suffered from a previous myocardial infarction. Symptomatic myocardial ischemia was documented before PTCA in 18/25 patients (72%) and asymptomatic ischemia in 7/25 (28%). Dobutamine was infused utilizing incremental steps of 5 mcg/kg/min over 3 minutes, up to a maximal dose of 40 mcg/kg/min. Echocardiographic images were stored on video tape and analyzed in a qualitative manner by two independent and experienced cardiologists without knowledge of the angiographic data. An asynergy score (from 0 = normal to 3 = dyskinesia) was calculated using a 14-segment left ventricular model in basal conditions and at peak stress, before and after PTCA. All tests were performed taking the patients off the antianginal therapy. RESULTS: One-vessel coronary artery disease was present in 18/25 (72%) patients, and two-vessel disease in 7/25 (28%) four of these 7 patients underwent PTCA on both involved vessels; mean diameter of the stenosis was 91 +/- 6% before PTCA, and was reduced to 22 +/- 8% after PTCA. Dobutamine stress echocardiography induced wall motion abnormalities in 24/25 patients before and in 4/25 after PTCA; the frequency of dobutamine-induced wall motion abnormalities significantly decreased from 96% to 12% before and after angioplasty (p < .01). All patients developed regional wall motion abnormalities in the region supplied by the dilated vessel. Wall motion score at peak dobutamine infusion improved from 8.5 +/- 4.8 before PTCA to 2.6 +/- 4.9 after PTCA (p < .001). There was a significant increase in the rate-pressure product achieved during the test after PTCA (21300 +/- 400 bts/min.mmHg) compared to the test performed before PTCA (19000 +/- 500 bts/min.mmHg) (p < .05). Dobutamine induced angina in 6/25 patients (24%) and ST-segment changes in 19/25 patients (76%) before PTCA, whereas angina occurred only once after PTCA and ST-segment changes 6 times only after PTCA. No major side effects occurred during dobutamine infusion both before and after PTCA. CONCLUSIONS: Our study indicates that dobutamine stress echocardiography is a feasible and safe method that accurately demonstrates an early improvement in stress-induced regional left ventricular dysfunction after an angiographically successful coronary angioplasty.