Henri Kulbertus

Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: Comparison with positron emission tomography☆

To assess the presence of viable myocardium salvaged by coronary artery reperfusion, 17 patients with acute anterior myocardial infarction were studied. Each received intravenous thrombolysis within the first 3 h of symptoms and underwent two-dimensional echocardiography before and during dobutamine infusion (10 micrograms/kg per min) 7 +/- 4 days after admission and positron emission tomography 9 +/- 5 days after admission. Echocardiography and positron emission tomography were again performed 9 +/- 7 months later. Six comparable segments specific for the territory of the left anterior descending artery were selected for comparison of the two techniques. Wall thickening was evaluated by using an echocardiographic score index. Segmental perfusion and glucose uptake were measured and normalized to the peak activity. A ratio of glucose uptake to perfusion was calculated for each segment. Concordant interpretation of the two techniques was found in 79% of affected segments for both acute and follow-up studies. Positron emission tomography revealed the presence of viable myocardium in 11 patients (group 1); perfusion was within normal limits in 5 of these (group 1A). Myocardial thickening improved with dobutamine infusion in these five patients, the echocardiographic score index decreasing from 12 +/- 2 at rest to 7.8 +/- 1.3 during dobutamine infusion (p = 0.003). Functional recovery was demonstrated in all five patients (follow-up score index 7.4 +/- 1.7). Six patients exhibited decreased perfusion but an abnormally high glucose to perfusion ratio (group 1B); their score index improved with dobutamine from 14.8 +/- 2.2 to 12 +/- 2.1 (p = 0.05), but late functional recovery was found in only one of the six patients (mean follow-up score index in group 1B 16 +/- 1.7). In the six remaining patients in whom no viable myocardium was detected with positron emission tomography (group 2), the echocardiographic score index did not change with dobutamine (15 +/- 0.9 to 14.7 +/- 0.8, p = NS) and there was no functional recovery (follow-up score index 15.5 +/- 1.0). Echocardiography during dobutamine infusion is a promising method to unmask viable myocardium in acute myocardial infarction. Early recovery of perfusion in the area at risk is associated with a good functional outcome, whereas a high glucose to perfusion ratio indicates jeopardized myocardium that frequently loses viability.

Predicting the extent and location of coronary artery disease in acute myocardial infarction by echocardiography during dobutamine infusion

The feasibility, safety and usefulness of 2-dimensional echocardiography (2-D echo) during dobutamine infusion for identifying patients with multivessel coronary artery disease (CAD) after acute myocardial infarction (AMI) were evaluated in 30 patients 5 to 10 days after AMI. Patients underwent 2-D echo under basal conditions and during dobutamine infusion at each dose from 5 to a maximum of 40 micrograms/kg/min, limited multilead submaximal bicycle exercise testing and coronary and left ventricular angiography. Echocardiograms were analyzed independently by 2 observers. The test response was considered positive if abnormal wall motion and reduced myocardial thickening were observed during dobutamine infusion in vascular distributions other than the area of infarction identified during basal conditions. Exercise testing was considered positive when more than 1 mm of ST depression occurred 80 ms after the J point. Dobutamine stress testing was well tolerated; no complications and no significant arrhythmia were observed. Echocardiographic recordings were adequate in all patients during the entire test; the concordance in interpretation between the 2 observers was perfect for the prediction and location of ischemic segments during dobutamine infusion. In 15 of 17 patients without multivessel CAD, no asynergy was observed outside the infarct zone during dobutamine infusion (specificity 88%). In 11 of 13 patients with multivessel CAD, new wall motion abnormalities were identified in the segments corresponding to the arterial lesions diagnosed by angiography (sensitivity 85%).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of spinal cord stimulation on regional myocardial perfusion assessed by positron emission tomography

Spinal cord stimulation (SCS) can relieve symptoms in patients with severe angina pectoris refractory to conventional medical or surgical therapy. This symptomatic improvement may result from decreased myocardial ischemia. To test this hypothesis, positron emission tomography (PET) and potassium-38 as a flow tracer were used in 8 patients for the quantitative evaluation of regional myocardial perfusion at rest and after exercise, before and during SCS. Potassium uptake was evaluated as myocardial clearance (flow times net extraction) in ml/min/100 g. Tomographic segments were categorized as nonaffected and affected on the basis of the absence or presence of arterial stenosis on coronary angiography and on the basis of thallium scintigraphic data. In nonaffected segments, before SCS, regional myocardial clearance significantly increased from rest (28 +/- 4) to exercise (47 +/- 13 clearance units; p less than 0.004). A similar increase occurred after SCS. In affected segments, before SCS, regional myocardial clearance barely increased (p = 0.065) from rest (26 +/- 6) to exercise (33 less than or equal to 12). In comparison, after SCS, the resting regional myocardial clearance was slightly elevated (29 +/- 8) reflecting an increased double product, but did not increase (p = 0.192) with exercise (34 +/- 12). However, the magnitude and duration of ST-segment depression decreased during treatment with SCS. Anginal pain occurred in all patients during control exercise, but was attenuated in all but one with SCS. These results indicate that SCS improves exercise-induced angina and electrocardiographic signs of ischemia but this influence does not appear to be mediated by changes in regional myocardial perfusion.

Effect of the haptoglobin phenotype on the size of a myocardial infarct.

We investigated the relation between haptoglobin (Hp) phenotypes and serum levels of various biochemical markers after myocardial infarction in 496 patients. In 122 subjects selected on the basis of short delays until hospitalization, patients with Hp 2-2 had higher cumulated creatine kinase activity than patients with Hp 1-1, or Hp 2-1 (P less than 0.05), as well as higher myoglobin concentrations (P less than 0.02) 12 to 28 hours after admission. Comparison of serum enzyme activities in the remaining 374 patients confirmed that Hp 2-2 patients had significantly higher total creatine kinase, creatine kinase isoenzyme MB fraction, aspartate aminotransferase, and lactate dehydrogenase peak levels. Complications of left ventricular failure were more frequent in these patients (P = 0.05). Our results suggest that Hp 2-2 patients have more severe myocardial infarctions than Hp 1-1 and Hp 2-1 patients, However, no difference in the distribution of haptoglobin phenotype was found between patients who had a myocardial infarction and healthy subjects, indicating that Hp 2-2 does not predispose to the occurrence of infarction.

Relation Between Contractile Reserve and Positron Emission Tomographic Patterns of Perfusion and Glucose Utilization in Chronic Ischemic Left Ventricular Dysfunction: Implications for Identification of Myocardial Viability

OBJECTIVES This study sought to determine the incidence and extent of dobutamine-induced contractile reserve in myocardial regions characterized by classical and new positron emission tomographic (PET) patterns in patients with chronic ischemic left ventricular dysfunction. BACKGROUND PET is considered the most accurate method for assessment of myocardial viability, which is traditionally identified by perfusion-metabolism mismatch. METHODS In 23 patients, segmental wall thickening expressed by four echocardiographic scores at rest and during low dose (5 and 10 microg/kg body weight per min) dobutamine infusion and regional myocardial uptake of potassium-38 and fluorine-18 fluorodeoxyglucose (F-18 FDG) during glucose clamp were compared in 16 corresponding segments. RESULTS Of a total of 368 segments, data analysis focused on 214 (58%) dyssynergic segments at baseline. Contractile reserve was identified with increasing incidence according to the six following PET patterns: 1) diminished perfusion and moderate reduction of F-18 FDG uptake (3 [11%] of 28 segments); 2) proportional reduction of perfusion and F-18 FDG uptake (10 [23%] of 43 segments); 3) perfusion-metabolism mismatch (19 [46%] of 41 segments); 4) preserved perfusion but moderate reduction of F-18 FDG uptake (13 [46%] of 27 segments); 5) preserved perfusion and F-18 FDG uptake (37 [59%] of 63 segments) compared with our normal database; and 6) normal perfusion but absolute increased F-18 FDG uptake (8 [73%] of 11 segments). In the latter category, only 7 of 24 segments had normal rest function. In dyssynergic segments with F-18 FDG uptake > or = 50% supplied by vessels with > or = 75% stenosis, improvement in contractility during dobutamine correlated with the presence of collateral channels. CONCLUSIONS Myocardial regions with the traditional mismatch pattern of viability show contractile reserve in slightly < 50%. In segments with moderate reduction of F-18 FDG uptake, the contractile response to dobutamine is linked to the level of rest perfusion. Most segments with preserved perfusion and increased F-18 FDG uptake have impaired rest function, but contractile reserve is still present. These data suggest that in chronic ischemic left ventricular dysfunction, myocardial hibernation is a heterogeneous condition.

Prognostic significance of angina pectoris before first acute myocardial infarction

To delineate the clinical significance and prognostic importance of a history of chronic or new onset angina pectoris before acute myocardial infarction (AMI), 732 consecutive patients admitted for a first AMI were studied and divided into 3 groups. Two hundred patients (27%) had chronic angina before AMI (greater than 1 month); 247 patients (34%) had new onset angina before AMI (less than 1 month) and the 285 remaining patients (39%) never had angina before AMI. All clinical characteristics were similar in the group of patients with chronic angina and in the group of patients with new onset angina, including in-hospital mortality (10 vs 9%) and 3-year post-hospital mortality (16 vs 16%). Compared to the 285 patients without angina, the 447 patients with angina before AMI were older, more likely to be women, and had a higher frequency of anterior AMI and early post-infarction angina. Both groups had a similar in-hospital mortality (10 vs 8%, not significant), but patients with angina had a higher 3-year post-hospital mortality (16 vs 7%, p less than 0.001). In the group of patients with angina before AMI who were discharged from the hospital, the comparison of nonsurvivors and survivors showed that the patients who died were older, presented more frequently with a non-Q-wave myocardial infarct and more often had left ventricular failure and complete bundle branch block during hospital stay. Chronic and new onset angina before AMI have the same clinical characteristics and deleterious long-term prognostic significance.

Combined mexiletine and amiodarone treatment of refractory recurrent ventricular tachycardia.

A combined mexiletine and amiodarone treatment was applied in nine cases with recurrent refractory ventricular tachycardia. During the first two days of treatment, mexiletine and amiodarone were perfused intravenously at a dose of 1,000 mg. and 1,500 mg. per 24 hours, respectively. Simultaneously amiodarone was also given orally at a dose of 600 mg. per 24 hours. From the third day onwards, the intravenous administration was interrupted and both drugs were continued orally at a dose of 600 mg. daily. The first three patients were very critically ill and had had at least five episodes of ventricular tachycardia per 24 hours during the last 10 days in the intensive care unit. The treatment resulted in total suppression of the tachycardic episodes within three days after initiation of therapy. In the remaining six cases, ventricular tachycardia was easily initiated by programmed electrical stimulation of the heart. No arrhythmia could be elicited by repeated testing on the seventh day of treatment. The mean follow-up period was 6 months. Two patients with poor left ventricular function died in intractable heart failure. Another one died suddenly 4-1/2 months after his release from the hospital. He had a large aneurysm and whether he continued his treatment is unknown. A fourth patient had an aneurysmectomy; he suffered a recurrence, and died at his second operation. All the others presently remain asymptomatic. The association of a class I (mexiletine) with a class III (amiodarone) agent is theoretically attractive for the treatment of refractory ventricular arrhythmias. The present findings corroborate this hypothesis, but show that this association is not able to protect individuals with severe underlying myocardial damage.

Short-term risk stratification at admission based on simple clinical data in acute myocardial infarction

Abstract Simple clinical data, available in all coronary care units, were recorded in 1,013 consecutive patients with acute myocardial infarction (AMI). In order to identify the patients at highest and lowest risk of mortality during hospital stay, a prognostic index was established from a stepwise logistic discriminant analysis of 10 clinical variables obtained at admission in a consecutive series of 477 patients hospitalized in 1 of 2 coronary care units admitting new patients on alternate days and treating them similarly. This prognostic index was applied to a comparison group of 536 consecutive patients admitted to the other coronary care unit. In the experimental group, 57 of the 477 patients (12%) died (during hospital stay; 60 of the 536 patients (11%) died in the comparison group. As individual variables, age, previous history of AMI, anterior site and left ventricular function on admission were associated witincreased mortality. Three variables were selected from the stepwise logistic discriminant analysis of the experimental group: age; site (anterior = 1, other = 0); and grade of left ventricular function (0 to 4). Prognostic index = 5.9019 − 0.8961 function −0.5708 location −0.0369 age. This index was validated in the comparison group. Patients were allocated into different classes with increasing index values associated with decreasing risk. Three subgroups of patients were identified: high risk of hospital mortality (index ≤1; mortality: 51%), intermediate risk (index 1 to 3; mortality: 18%) and low risk (index >3; mortality: 4%). The use of this simple prognostic index may improve clinical management and selection of patients for intervention trials.

Hemodynamic effects of a new antiarrhythmic agent, flecainide (R-818), in coronary heart disease.

The hemodynamic effects of flecainide acetate, a new class I antiarrhythmic agent, were studied in 10 patients with coronary heart disease. The drug was injected intravenously at a dose of 2 mg/kg over 30 minutes. The mean drug plasma level achieved was 394 ng/ml (range 329 to 470). The heart rate did not change, but a significant increase (p less than 0.001) in P-R (+17%), QRS (+15%), and Q-T (+7%) duration occurred after drug administration. Negative inotropic effects also were observed and consisted of an increase (p less than 0.01) in pulmonary wedge pressure (+27%) and a decrease (p less than 0.01) in stroke index (-10%), left ventricular stroke work index (-12%), and left ventricular ejection rate (-11%). No significant change in mean aortic pressure or systemic and pulmonary vascular resistance occurred. Left ventriculography performed after drug infusion revealed a significant increase (p less than 0.01) in systolic volume (+9%) and a decrease in ejection fraction (-9%) and mean velocity of circumferential fiber shortening (Vcf) (-13%). A progressive and significant decrease of dP/dt was observed during drug infusion, but 15 minutes after the injection, dP/dt had returned to near basal values. Thus, flecainide acetate has slight, but significant negative inotropic effects, particularly conspicuous during drug infusion. The drug should be administered with caution in patients with poorly compensated heart.

Incidence and significance of pericardial effusion in acute myocardial infarction as determined by two-dimensional echocardiography

To determine the incidence and clinical significance of pericardial effusion after acute myocardial infarction, two-dimensional echocardiography was serially performed in 66 consecutive patients. Pericardial effusion was observed in 17 (26%); the effusion was small in 13 patients, moderate in 3 and large with signs of cardiac tamponade in 1. In this patient, two-dimensional echocardiography strongly suggested myocardial rupture. The observation of pericardial effusion was not associated with age, sex, previous myocardial infarction, atrial fibrillation or treatment with heparin. It was more often a complication of anterior than of inferior acute infarction. Patients with pericardial effusion had higher peak levels of creatine kinase and lactic dehydrogenase and a higher wall motion score index. More patients with pericardial effusion had congestive heart failure or ventricular arrhythmias, developed a ventricular aneurysm or died within 1 year after their infarction. In conclusion, pericardial effusion is frequently visualized by two-dimensional echocardiography after acute myocardial infarction and its presence is associated with an increased occurrence of complications and cardiac death.