Clinical and angiographic correlates of dobutamine-induced wall motion patterns after myocardial infarction.

The ability of different dobutamine-induced wall motion patterns to define the anatomic status of the infarct-related artery (IRA) was evaluated in 159 patients who underwent dobutamine stress echocardiography (DSE) and coronary angiography 10 +/- 2 and 18 +/- 3 days, respectively, after hospital admission. The DSE result was classified as: (1) biphasic: improvement with a low dose followed by deterioration with a high dose; (2) worsening: direct deterioration at low or high doses; (3) sustained improvement: improvement with a low dose that was maintained at high dose; and (4) no change: no change during the entire protocol. A diameter narrowing >70% (50% for the left main stem) of major coronary arteries indicated a severe lesion. Angiograms were classified according to the jeopardy score and collateral circulation graded according to Rentrop's classification. DSE was positive in 92 patients (22 had biphasic results and 70 had worsening results) and negative in 67 patients (14 had sustained improvement and 53 had no changes). Biphasic response was associated with more frequent anterior infarction (p <0.05) and higher resting (p <0.001) and peak (p <0.01) wall motion score indexes. The IRA was totally occluded in 4 of the 92 patients (4%) with positive (worsening pattern) and 12 of the 67 patients (18%) with negative (no change pattern) tests. The biphasic pattern was associated with the highest jeopardy score and was significantly (p <0.05) more specific (100%) compared with worsening (78%) in identifying a severe stenosis of the IRA. The combination of ischemic patterns provided a significantly superior sensitivity (p <0.0001). Logistic regression analysis identified the biphasic pattern as the only significant predictor. Conversely, the prediction of total occlusion of the IRA was poor. Sustained improvement was the most specific (100%) predictor of absence of severe stenosis of the IRA, whereas the combination with no change pattern provided a significantly superior sensitivity (p <0.0001). Thus, DSE effectively predicts the residual stenosis of the IRA. In particular, the biphasic response has an excellent specificity and positive predictive value and is the only significant predictor among clinical and echocardiographic variables.

Angiographic and prognostic correlates of cardiac output by cardiopulmonary exercise testing in patients with anterior myocardial infarction.

STUDY OBJECTIVE: To assess the diagnostic and prognostic value of cardiac output assessed by cardiopulmonary exercise testing in patients with anterior acute myocardial infarction (AMI) and left ventricular dysfunction. PATIENTS AND SETTING: Forty-six patients with AMI (7 female patients; mean +/- SD age, 55 +/- 8 years; ejection fraction, 39 +/- 7%) underwent cardiopulmonary exercise testing and coronary angiography following hospital discharge. MEASUREMENT AND RESULTS: Cardiac output was estimated from oxygen uptake (VO(2)) during exercise according to a method based on the linear regression between arteriovenous oxygen content difference and percent maximum VO(2). Angiograms were scored using Gensini and Duke "jeopardy" scores. Cardiac output at anaerobic threshold (COAT) < or = 7.3 L/min was the best cutoff value for identifying multivessel coronary artery disease (relative risk, 3.1). Angiographic scores were significantly higher in patients with COAT < 7.3 L/min as compared to those with COAT > 7.3 L/min (82 +/- 8 vs 53 +/- 7 and 6 +/- 2 vs 4 +/- 3, respectively; p < 0.05) and were inversely and significantly correlated to COAT. Conversely, no correlation was found with ECG changes. COAT, VO(2) at anaerobic threshold, and peak VO(2) were univariate prognostic indicators. However, using Cox's model, COAT was the only multivariate predictor of outcome (odds ratio, 0.28; 95% confidence interval [CI], 0.09 to 0.9). Moreover, COAT < 7.3 L/min was associated to an increased risk of further cardiac events (odds ratio, 5; 95% CI, 1.4 to 17) and provided a significant discrimination of survival for the combined end point of cardiac death, reinfarction, and clinically driven revascularization. CONCLUSIONS: COAT is a safe and feasible tool providing additional diagnostic and prognostic information in patients with AMI.

Myocardial viability assessment after acute myocardial infarction: low-dose dobutamine echocardiography versus rest-redistribution thallium-201 SPECT.

BACKGROUND: The presence of tissue viability is of great importance in the prognostic work-up of patients recovering from acute myocardial infarction. However, uncertainty still exists concerning the optimal tool for its assessment. The present study was undertaken in order to compare low-dose dobutamine echocardiography and rest-redistribution thallium SPECT for predicting late improvement of regional left ventricular function after acute myocardial infarction. METHODS: Fifteen patients undergoing coronary angiography, low-dose dobutamine echocardiography and rest-redistribution thallium SPECT after thrombolyzed anterior acute myocardial infarction were studied. A 3 month follow-up echocardiogram was performed in all patients and 9 underwent coronary revascularization. RESULTS: A significant (> or = 70%) residual stenosis of the infarct-related artery was present in 14 patients, whilst a total occlusion was observed in 1. At 3 month follow-up, 41% of the dyssynergic segments improved. The sensitivity, specificity and accuracy for late wall motion improvement was 61, 89 and 77% for low-dose dobutamine echocardiography and, respectively, 76, 45 and 58% for rest-redistribution thallium SPECT. Tissue viability was detected in 65 and 31% of dyssynergic segments by rest-redistribution thallium SPECT and low-dose dobutamine echocardiography, respectively (p < 0.001). The agreement between the two techniques was 48%. CONCLUSIONS: Low-dose dobutamine echocardiography is more accurate than rest-redistribution thallium SPECT for predicting 3 month wall motion improvement in patients with acute anterior myocardial infarction, mainly due to its significantly better specificity.

Early assessment of viable myocardium after acute myocardial infarction by low-dose echo-dobutamine.

BACKGROUND: The aim of the study was to evaluate the usefulness of low-dose dobutamine echocardiographic testing performed within 48 hours from anterior AMI in order to identify the extent of viable myocardium and predict its functional outcome. The early echo-dobutamine test was also compared with a predischarge test in order to evaluate the effects of different timing on the accuracy of the test. METHODS: Nineteen consecutive patients, aged 54 +/- 11 years, with a first anterior AMI entered the study. All patients underwent a low-dose dobutamine echocardiographic test within 48 hours from hospital admission and at predischarge. In all the patients, a rest follow-up echocardiogram was performed three months after hospital discharge. Eleven patients underwent a revascularization procedure (7 underwent PTCA and 4 CABG). RESULTS: Of the 159 dyssynergic segments, 26% improved spontaneously at predischarge and 51% improved at the three-month follow-up. Of the 145 predischarge dyssynergic segments, 38% improved at three months. Considering the results on a segmental basis, early low-dose dobutamine echocardiography showed a sensitivity of 52%, a specificity of 87%, a positive predictive value of 81%, a negative predictive value of 64% and a diagnostic accuracy of 69% for wall-motion improvement at three months. The predischarge test showed very similar values. A slight enhancement of the sensitivity of both tests was observed considering the akinetic segments only. Finally, considering the amount of segmental reversible dysfunction inside the infarct area in the single patients, early low-dose dobutamine echocardiography showed a sensitivity of 86% and a specificity of 80%. CONCLUSIONS: Our results indicate that: 1) recovery of regional wall motion after AMI is slow and progressive, with substantial improvement ensuing within the first days after infarction; 2) considering results on a segmental basis, low-dose dobutamine echocardiography performed within 48 hours of AMI shows a high specificity but a low sensitivity for late recovery of regional function, although it gave information similar to what was obtained performing the test at predischarge; 3) the efficiency of test can be improved by considering the amount of reversible segmental dysfunction inside the infarct area in the single patients.

Time-course of dobutamine-induced wall motion abnormalities in the infarct area following thrombolytic therapy.

Stress-induced asynergies in the infarct area following thrombolytic therapy are considered to reflect incomplete recanalization of the culprit vessel. However, reperfusion is a dynamic process with successive pathophysiological phases, so that the timing of assessment of residual ischemia may have relevant clinical implications. We studied the time-course of dobutamine-induced homozonal asynergies in 61 (group B) survivors of uncomplicated infarction as compared to 54 (group A) control subjects showing normal response to dobutamine stress echocardiography within 10 days of acute myocardial infarction. The 79 (43 of group A and 36 of group B) patients not presenting new cardiac events underwent further dobutamine stress echo within 90 +/- 17 days, which was positive in 20 and negative in 59. Persistence of test positivity was observed in just 17/36 (47%) patients, who showed significantly more extensive dobutamine-induced asynergies as compared to pre-discharge evaluation and less frequent (p < 0.01) evidence of viable myocardium. These results arise question about the decisional impact of stress-induced wall motion abnormalities in the culprit vessel area early after thrombolysis in low-risk patients and emphasize the need to further clarify the time factor role in this setting.

Dobutamine stress echocardiography for the identification of multivessel coronary artery disease after uncomplicated myocardial infarction: the importance of test end-point.

Our aim was to verify whether the sensitivity of pharmachological stress echocardiography for multivessel disease after acute myocardial infarction may be improved by a more aggressive protocol, i.e. not considering the appearance of the first wall motion abnormality as the absolute end-point if it occurs in the infarcted area without clinical or instrumental markers of extensive ischemia or left ventricular dysfunction. One-hundred twenty-one consecutive patients (age 32-71 years) prospectively underwent dobutamine-atropine stress echo (dobutamine infusion up to 40 micrograms/kg/min with additional atropine 1 mg) 11.8 +/- 4.8 days after uncomplicated myocardial infarction and coronary angiography within 6 weeks. Criteria for stopping the test were: significant ST depression or elevation, typical chest pain, major arrhythmias and left ventricular dysfunction. The test was considered as positive if a deterioration of basal wall motion pattern was observed: it was defined homozonally positive (the deterioration occurred in the myocardial area fed by the culprit vessel) or heterozonally positive (the deterioration occurred in a different vascular area). A coronary stenosis > 70% of vessel lumen was defined as critical. Thirty-four patients showed a negative test result. Among the 87 patients with positive test, 65 had no further wall motion deterioration from the first-induced wall motion abnormality (WMA) to peak test (Group A), whereas nine patients showed further homozonal (Group B) and 13 further heterozonal (Group C) asynergies. Sensitivity, specificity and accuracy of dobutamine stress echocardiography for multivessel disease were, respectively, 63%, 96% and 82% using the first-induced wall motion abnormality as test end-point, whilst they were 84% (P < 0.01), 93% and 89% according to the aggressive approach previously described. Dobutamine stress time of patients with multivessel disease was higher in Groups B and C (13.1 +/- 3.6 min) than in Group A (9.8 +/- 3.7 min, P < 0.01) and, finally, the mean obstruction of non-culprit vessel was higher in Group A (62.2%) than in Group C (47.4%, P < 0.05). No major complications were found. We conclude that the sensitivity of dobutamine stress echocardiography for multivessel disease following recent myocardial infarction is critically dependent on the test end-point. It may be improved by a more aggressive approach capable to identify less severe heterozonal coronary lesions.

Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction. A comparison between streptokinase and recombinant tissue-type plasminogen activator.

BACKGROUND: We have previously shown that treatment with streptokinase induces abrupt complement activation and transient neutropenia in patients with acute myocardial infarction (AMI). The purpose of this study was to compare the effects of two different thrombolytic agents--streptokinase (SK) and recombinant tissue-type plasminogen activator (rTPA)--on activation of the complement and kinin systems in plasma of patients with AMI. METHODS AND RESULTS: Forty-one patients with AMI who were eligible for thrombolytic therapy were studied. Twenty-three patients were treated with streptokinase (1.5 million IU IV over 60 minutes) and 18 were treated with rTPA (8 with bolus of 10 mg IV, followed by 50 mg infused over 60 minutes and then 40 mg infused over 120 minutes; 10 patients were administered rTPA and heparin according to the accelerated infusion protocol indicated by the GUSTO study). C4a and C3a were measured by radioimmunoassay, soluble terminal complement components (SC5b-9) and anti-SK IgG antibodies were measured by ELISA. Cleaved high molecular weight kininogen (HK) was quantitated in plasma by SDS-PAGE and immunoblotting analysis. C4a levels were significantly and similarly increased in both groups, whereas the levels of C3a and SC5b-9 after rTPA infusion were only slightly elevated and were significantly lower than after SK. No differences were observed between patients treated with slow or accelerated rTPA regimens. The titer of antibodies to SK was highly correlated with the levels of C3a and SC5b-9, whereas a lesser correlation was observed with C4a. Treatment with rTPA did not induce the transient neutropenia observed after SK infusion. The cleavage products of HK were significantly greater after SK than after rTPA infusion. CONCLUSIONS: Our results show that both thrombolytic agents activate the classic complement pathway and that plasmin could be the common trigger for this phenomenon. A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections. The minimal activation of C5 component of the common pathway explains the absence of leukopenia in patients treated with rTPA. Cleavage of HK, larger after SK than after rTPA infusion, represents a condition enhancing the generation of bradykinin by kallikrein. The recent experimental data that indicate a damaging effect of complement activation on the infarcted zone and the contrasting favorable effect consequent to bradykinin formation raise some questions about the clinical importance of the different biological consequences of SK versus rTPA.

Thrombolytic treatment and complement activation.

Details of possible complement activation in acute myocardial infarction (AMI) and the in vivo effects of fibrinolytic agents on this activation are not yet known. We measured complement activation in 40 patients with AMI: 20 were treated with streptokinase, and 20 did not receive any fibrinolytic agent. Anaphylatoxin C4a, C3a and membrane attack complexes SC5b-9 increased about 10-fold (p < 0.0001) during streptokinase infusion. There were no increases in complement catabolic products in AMI patients not treated with streptokinase. Significant transient leukopenia (-29.5%, 7.0 SEM, p = 0.001) and a drop in systolic pressure (-29%, 3.4 SEM, p < 0.0001) occurred after 15 min of streptokinase infusion simultaneously with the peak of anaphylatoxins in plasma.

Effects of posture, effort and psychophysiological activation on atrio-ventricular node and Kent bundle refractoriness.

A new protocol is described for non-invasive evaluation of electrophysiological effects of autonomic nervous system on both normal and abnormal atrio-ventricular conduction in patients with Wolff-Parkinson-White (WPW) syndrome. In 64 WPW patients with stable Kent-type ventricular preexcitation transoesophageal atrial pacing has been carried out to quantify changes in both atrioventricular (AV) node and Kent bundle refractoriness and maximal conductive capability induced by posture, physical exercise and psychophysiological activation. A significant shortening of AV nodal and accessory pathway refractory periods was found, induced by manoeuvres enhancing the sympathetic outflow, being the AV node the most sensitive structure. This finding suggests that an exhaustive investigation protocol of WPW patients should include the evaluation of the neurovegetative effects on cardiac electrophysiological parameters, under conditions which can reproduce as close as possible the individual situations a patient has to face in his real life.

A randomized dose-ranging study of rt-PA in acute myocardial infarction. Effects on coronary patency and fibrinolytic parameters.

This study was designed to examine the relationships between dose of Wellcome two-chain recombinant tissue type-plasminogen activator (BW rt-PA) and coronary patency and fibrinolytic parameters in acute myocardial infarction (AMI). In an open randomized study, patients with AMI (determined by ECG) and symptoms of less than 4 h duration without contraindications for fibrinolytic therapy were treated with rt-PA in nominal doses of 20 (7.7 MU), 50 (14.8-29.6 MU) or 100 mg (29.6-48.2 MU) administered over 90 min followed by intravenous heparin. Coronary patency was determined by coronary arteriography of the infarct-related artery and haematological parameters (fibrinogen, plasminogen, alpha 2-antiplasmin and fibrin(ogen) degradation products) measured at 90 min. Coronary patency increased in a dose-related manner to 53% (95% C.I. 37-69%) in the 100 mg/90 min group. Logistic regression demonstrated a relationship between dose (in MU kg-1) and coronary patency. Fibrinogen at 90 m was reduced to 74 (61.5-86.4%) of the pooled plasma standard in the nominal 100 mg group. Patients with a higher predose fibrinogen had higher reductions of fibrinogen. Serious bleeding occurred in three (3%) patients, and no intracranial bleeds were reported. BW rt-PA produces dose-related patency of the coronary arteries with moderate, dose-related reduction in fibrinogen.

Vectorcardiographic evaluation of diabetic cardiomyopathy and of its contributing factors.

In order to investigate the prevalence of vectorcardiographic bites, expression of small areas of fibrosis, atrophy or degeneration of the myocardium, we studied, using the vectorcardiograms (VCG) of 101 diabetic patients (35 with insulin-dependent and 66 with non-insulin-dependent diabetes mellitus, aged from 25 to 60 years, without hypertension, coronary artery disease, or intraventricular conduction defects) and 228 normal control subjects, matched for age and sex. The prevalence of bites was 38.6% in diabetic patients and 10.0% in the control group (p less than 0.001). Diabetic patients were also subdivided into groups according to age, sex, metabolic control, risk factors for coronary heart disease, type of diabetes, duration of diabetes and diabetic microangiopathy. No correlation was found between any of the variables investigated nor of a combination of these, and the presence of bites. We conclude that VCG is a sensitive test for cardiac involvement in diabetic patients but that it cannot be used to identify any specific factor able to influence the onset and evolution of this involvement.

Relationship between changes in R wave voltage and cardiac volumes. A vectorcardiographic study during hemodialysis.

The effects of acute changes in cardiac volumes determined by hemodialysis on cardiac voltages were assessed in 18 chronically uremic patients by means of a vectorcardiographic and scalar Frank leads recording, immediately before, at the 90th and 180th minute, and immediately after hemodialysis. The following parameters were simultaneously monitored: body weight, systolic and diastolic blood pressure, heart rate, hematocrit and, in eight patients, echocardiographic systolic and diastolic diameters of the left ventricle. During hemodialysis all voltages considered except R wave in X lead increased significantly. They were inversely correlated with body weight, blood pressure, and systolic and diastolic diameters and directly with hematocrit (volemia-dependent parameters). The maximal vector on the left sagittal plane and the R wave amplitude in Z lead, representing left ventricular posterolateral wall activation, showed the greatest increase. When, at the end of hemodialysis, an amount of fluids ranging from 300 to 800 ml was restored, these cardiac voltages decreased paralleling the increase of left ventricular diameters. In conclusion, these results demonstrate that cardiac voltage and volumes are inversely related.

Positive inotropic effect of K-canrenoate: an investigation in anaesthetized dogs, untreated or treated with digitalis.

Potassium canrenoate (KCR) is widely used in cardiac patients as an aldosterone antagonist, antiarrhythmic and diuretic drug. According to experimental and clinical studies it can also elicit an inotropic action. It is not clear, however, whether this inotropic activity occurs in the absence of any treatment or after the myocardial contractility has already been improved with digitalis. In order to evaluate a possible interaction of this drug with digitalis we administered KCR intravenously to 41 anaesthetized dogs either untreated or treated with digitalis, in which aortic and left ventricular pressures were recorded and myocardial contractility was evaluated by calculating in real time the first derivative of ventricular pressure (Formula: see text) max and two other contractility indexes (Formula: see text) max and V.max. The results obtained showed that KCR given at doses of 10, 20 and 30 mg/kg i.v. did not elicit any inotropic effect in dogs not previously digitalized. 100 mg/kg i.v. first depressed cardiac contractility and then increased it. After cardiac performance had been improved by digitalis, KCR further increased all contractility indexes significantly. These results could explain previous observations that no inotropic effect was observed in human subjects not treated with digitalis after treatment with KCR.