John C. Wynsen

Dobutamine Stress Echocardiography for Risk Stratification After Myocardial Infarction

BACKGROUND Because dobutamine stress echocardiography (DSE) provides assessment of left ventricular function and ischemia at a distance, the major determinants of adverse outcome after acute myocardial infarction (AMI), we undertook this study to determine the role of DSE in risk stratification after AMI. METHODS AND RESULTS A graded DSE in 5-minute stages was performed in 214 patients (age, 57 +/- 13 years [mean +/- SD]) at 2 to 7 days after AMI. Coronary angiography was performed in 193 patients. Follow-up data regarding major cardiac events were obtained through telephone interviews and chart reviews. All patients were followed for > or = 500 days or until a hard cardiac event occurred. The mean follow-up interval was 494 +/- 182 days after AMI. Peak heart rate and systolic blood pressure were 115 +/- 21 bpm and 135 +/- 29 mm Hg, respectively. An adverse outcome occurred in 80 of 214 patients; cardiac death occurred in 15, nonfatal AMI occurred in 15, sustained or symptomatic ventricular arrhythmia occurred in 5, congestive heart failure occurred in 14, and unstable angina occurred in 31. Significant predictors of adverse outcome by univariate analysis were prior myocardial infarction (P = .005), anterior infarction (P = .006), multivessel coronary artery disease (P < .0001), global resting left ventricular wall motion score index (P < .0001), infarction zone nonviability based on akinesis unresponsive to low-dose dobutamine (P < .0001), and ischemia/infarction at a distance (P < .0001). Furthermore, the extent of infarct zone and nonviability correlated with the severity of the cardiac event. Multivariate analysis of clinical, angiographic, and DSE variables revealed that the only independent predictors of adverse outcome were ischemia/infarction at a distance (P < .0001) and infarction zone nonviability (P < .0001). Multivessel disease identified through DSE was more predictive of adverse outcome than was angiographically determined multivessel disease. CONCLUSIONS DSE can be used to predict adverse outcomes after AMI.

Safety and Accuracy of Dobutamine-Atropine Stress Echocardiography for the Detection of Residual Stenosis of the Infarct-Related Artery and Multivessel Disease During the First Week After Acute Myocardial Infarction

BACKGROUND The safety of dobutamine-atropine echocardiography early after acute myocardial infarction is unknown. Its accuracy for the early detection of infarct artery stenosis and multivessel coronary artery disease is also unclear. The objective of the present study was to document its safety and accuracy during the first week after acute myocardial infarction. METHODS AND RESULTS Multistage dobutamine-atropine stress echocardiography was performed in 232 patients (age, 58 +/- 13 years; 58 women) at 5 +/- 2 days after acute myocardial infarction. The peak heart rate was 116 +/- 20 bpm. There were no episodes of sustained ventricular tachycardia, myocardial infarction, or death. Atropine with dobutamine was tolerated well. Coronary angiography was performed in 206 patients (89%). There were 171 patients (83%) with infarct artery stenosis of > or = 50% and 114 patients (55%) with multivessel disease. Ischemic or biphasic responses in the infarction zone were 82% (140 of 171) sensitive and 80% (28 of 35) specific for residual stenosis. Sensitivity was similar for occluded arteries (77%, 36 of 47) and patent but stenotic arteries (84%, 104 of 124). Wall motion abnormalities outside the infarction zone were specific (97%, 89 of 92) and moderately sensitive (68%, 77 of 114) for multivessel disease. The only determinant of sensitivity for residual infarct artery stenosis was improved wall motion at low dose (P < .01). The determinants of sensitivity for multivessel disease were peak heart rate and infarct size (P < .01). CONCLUSIONS Dobutamine-atropine stress echocardiography was safely used to detect residual infarct artery stenosis and multivessel disease during the first week after acute myocardial infarction. The test may be very effective for evaluating patients with acute myocardial infarction because sensitivity for residual stenosis and multivessel disease was maximal in the high-risk subsets of patients with viable, jeopardized myocardium and large infarct size.

Dobutamine-Atropine Stress Echocardiography for Reversible Dysfunction During the First Week After Acute Myocardial Infarction: Limitations and Determinants of Accuracy

OBJECTIVES We sought to compare the accuracy of biphasic and ischemic responses and sustained improvement for reversible dysfunction and to identify causes of false negative and false positive findings. BACKGROUND Previous studies have shown that low dose dobutamine echocardiography was accurate for detecting reversible dysfunction after acute myocardial infarction (MI) but did not determine whether accuracy was improved by peak dose findings or influenced by the test interval or clinical or angiographic factors. METHODS Dobutamine-atropine stress echocardiography (DASE) (baseline, low dose [5 and 10 microg/kg body weight per min] and peak dose) and coronary angiography were performed in 115 patients 2 to 7 days after MI (test interval). Segmental wall thickening was analyzed according to the 16-segment model. Sustained improvement and biphasic and ischemic responses included improved wall thickening at low and peak doses, improved wall thickening at the low dose with worsening at peak dose and no change in wall thickening at the low dose with worsening at peak dose, respectively. Follow-up echocardiography was performed at 4 to 8 weeks, and reversible dysfunction was defined as improved wall thickening. RESULTS Wall thickening improved at follow-up in 305 (44%) of 688 dysfunctional segments. The test interval was 2 days in 16 patients, 3 days in 24, 4 days in 24, 5 days in 12, 6 days in 16 and 7 days in 23. No change at low and peak doses accurately predicted fixed dysfunction (318 [88%] of 360 segments), especially in akinetic and dyskinetic segments (276 [91%] of 303), irrespective of the test interval or clinical and angiographic factors. Ischemic segmental responses also predicted fixed dysfunction (63% [12 of 19 patients]), especially in medically treated compared with revascularized patients (100% [8 of 8] vs. 36% [4 of 11], p = 0.013). Both biphasic responses and sustained improvement (77% [179 of 231 segments] vs. 87% [84 of 97], p = 0.082) were highly predictive of reversible dysfunction, especially in akinetic segments, irrespective of the test interval or clinical and angiographic factors. The only limitation was reduced accuracy (77% [177 of 222 segments], p < 0.001) due to false positive results (16%) in hypokinetic segments. CONCLUSIONS No change and ischemic responses during DASE were specific for fixed dysfunction. Improved wall thickening at the low dose, irrespective of changes at peak dose, was highly predictive of reversible dysfunction. Accuracy was only limited by false positive results in hypokinetic segments and not by the test interval or clinical or angiographic factors.

Low dose dobutamine echocardiography is more predictive of reversible dysfunction after acute myocardial infarction than resting single photon emission computed tomographic thallium-201 scintigraphy

To directly compare dobutamine echocardiography and resting single photon emission computed tomographic (SPECT) thallium-201 (Tl-201) scintigraphy for the detection of reversible dysfunction, 64 patients underwent dobutomine echocardiography (baseline, low dose 5 and 10 mg/kg/min, and peak dose), rest Tl-201 scintigraphy (3 mCi - 15 minute and 3- to 4-hour SPECT imaging), and coronary angiography during the first week after acute myocardial infarction. Follow-up echocardiography was performed 4 to 8 weeks after discharge. Wall thickening improved at follow-up in 52% (207 of 399) of the dysfunctional segments. By receiver operating characteristic analysis, biphasic responses and sustained improvement during dobutamine echocardiography were more accurate (p < 0.01) than Tl-201 uptake by SPECT scintigraphy for reversible dysfunction. The greater accuracy of dobutamine echocardiography resulted from higher accuracy in akinetic segments, Q wave infarction, and multivessel coronary artery disease. In conclusion, dobutamine echocardiography was more accurate than resting SPECT Tl-201 scintigraphy for reversible dysfunction after acute myocardial infarction.

Evolution of a Papillary Fibroelastoma

Papillary fibroelastoma is a rare primary tumor of the heart usually found incidentally at autopsy. Little is known about the natural history of this tumor, but an aggressive surgical approach is recommended because of the high incidence of embolization. We describe a patient whose tumor was found during transthoracic echocardiography and who had had a normal echo 10 years previously. This finding suggests that papillary fibroelastoma may be an acquired rather than a congenital lesion.

Zatebradine, a specific bradycardic agent, enhances the positive inotropic actions of dobutamine in ischemic myocardium

OBJECTIVES This investigation determined whether attenuation of the tachycardia produced by dobutamine administration would improve perfusion and function distal to a severe coronary artery stenosis. BACKGROUND Tachycardia adversely affects perfusion and function distal to a coronary artery stenosis. It is not known whether a specific bradycardic agent can improve blood flow and function in an ischemic zone during administration of dobutamine. METHODS The effects of dobutamine (2, 5 and 10 micrograms/kg body weight per min) alone and in combination with zatebradine (0.5 mg/kg), a specific bradycardic agent, on hemodynamic status, segment shortening (ultrasound length transducers) and myocardial perfusion (microspheres) were studied in anesthetized dogs with severe left circumflex coronary artery stenosis. RESULTS A 50% reduction in left circumflex coronary artery blood flow (58 +/- 4 to 29 +/- 2 ml/min [mean value +/- SEM]) produced a decrease in systolic shortening in the ischemic zone. Only a dose of dobutamine that did not elevate heart rate (2 micrograms/kg per min) produced an increase in segment shortening in the ischemic zone. High doses of dobutamine (10 micrograms/kg per min) caused an increase in heart rate without improvement in function and a reduction in the subendocardial/subepicardial flow ratio (0.74 +/- 0.06 to 0.48 +/- 0.05). Zatebradine administered in the presence of dobutamine caused a decrease in heart rate, an increase in subendocardial/subepicardial blood flow ratio (0.48 +/- 0.05 to 0.78 +/- 0.09) and allowed an increase in ischemic zone segment shortening. When normalized for changes in heart rate, ischemic zone subendocardial flow increased by 123 +/- 41% (0.39 +/- 0.09 to 0.71 +/- 0.12 ml/100 g per beat). Atrial pacing abolished the effects of zatebradine. CONCLUSIONS The present data suggest that the perfusion-contraction matching that accompanies a decrease in heart rate results in enhancement of inotropic stimulation of an ischemic zone. The actions of zatebradine are related to an increase in subendocardial blood flow per beat that allows improvement of regional contractile function.

Regional myocardial function after repetitive brief episodes of ischemia: Effect of altering the duration of the reperfusion period

How recovery of regional contractile function in myocardium is influenced by alterations in the duration of reperfusion after repetitive brief coronary artery occlusions was investigated in chronically instrumented, conscious dogs. All animals underwent five 5 minute left anterior descending coronary artery occlusions with a final 5-hour reperfusion period. Dogs were randomly assigned to one of three groups determined by the duration of reperfusion (5, 10, or 15 minutes) between successive 5-minute occlusion periods. A shortening of the duration of the reperfusion period between occlusions led to reduced recovery and progressive deterioration in systolic shortening after multiple occlusion-reperfusion sequences. With 15-minute reperfusion periods, the percentage of segment shortening (%SS) during the first through fourth reperfusion periods ranged from 17.1 +/- 2.6% to 18.2 +/- 1.8% and did not differ from the preocclusion control value (18.8 +/- 1.7%) by the end of the final reperfusion period. In contrast, in those dogs with 5-minute reperfusion periods, %SS was significantly reduced from the preocclusion control value (20.2 +/- 2.2%) at the completion of the final 5-hour reperfusion period (11.4 +/- 1.5%). Results of the present study indicate that after only a few brief periods of coronary artery occlusion, rapid and cumulative deterioration in regional contractile function can occur when the duration of intermittent reperfusion is sufficiently brief.

DIFFERENTIAL HEMODYNAMIC EFFECTS OF THE NITRIC OXIDE DONOR PIRSIDOMINE IN COMPARISON TO SIN-1, NITROPRUSSIDE AND NITROGLYCERIN

The systemic and coronary hemodynamic effects of the nitrovasodilator, pirsidomine, were compared with SIN-1, nitroprusside, and nitroglycerin. Four groups consisting of 32 experiments were performed in 17 conscious dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded during control conditions and after intravenous administration of pirsidomine (1.0, 2.0, and 4.0 mg.kg-1), SIN-1, (50, 100, and 200 micrograms.kg-1), nitroprusside (0.5, 1.0, and 2.0 micrograms.kg-1.min-1), or nitroglycerin (1.0, 2.0, and 4.0 micrograms.kg-1.min-1). Pirsidomine decreased mean arterial, left ventricular systolic and end-diastolic pressures, stroke volume and systemic vascular resistance. Diastolic coronary blood flow velocity and heart rate were increased and coronary vascular resistance decreased by pirsidomine. SIN-1, nitroprusside and nitroglycerin caused similar decreases in preload (evaluated by left ventricular end-diastolic pressure) and afterload (indirectly assessed by mean arterial pressure and systemic vascular resistance) as compared to pirsidomine. However, equihypotensive doses of SIN-1, nitroprusside, and nitroglycerin improved ventricular performance as assessed by increases in left ventricular dP/dtmax, cardiac output and segment shortening, in contrast to those findings during comparable doses of pirsidomine (4 mg.kg-1). Despite similar loading conditions, high doses of pirsidomine did not enhance left ventricular function, suggesting that pirsidomine may have direct negative inotropic effects.

Dipyridamole-induced decrement of functional recovery of postischemic reperfused myocardium in conscious dogs with well-developed coronary collateral circulation

The effects of dipyridamole (20 and 40 micrograms/kg/min intravenously) on the time course of functional recovery of myocardium after five 5-minute coronary artery occlusions and four 5-minute reperfusions and a subsequent 5-hour reperfusion period were studied in chronically instrumented, conscious dogs with well-developed coronary collateral circulation. In comparison with vehicle-treated control dogs, those given dipyridamole (20 and 40 micrograms/kg/min, respectively) 15 minutes before and during coronary occlusion had a greater depression of regional segment shortening (38 +/- 7% and 19 +/- 4%, respectively, vs control levels of 69 +/- 10% of preocclusion values) during acute coronary artery occlusion. After a 5-hour reperfusion period, segment shortening returned to preocclusion values in the control group but remained decreased in the dipyridamole groups (87 +/- 4% and 75%, respectively). These results suggest that dipyridamole in a dose-dependent manner exacerbates recovery of contractility of postischemic reperfused myocardium in dogs with well-developed coronary collateral circulation.

Comparative Effects of Inotropic Agents on Coronary and Systemic Hemodynamics of Conscious Dogs: Actions of Milrinone, Dopamine, Ouabain and MCI-154

The hemodynamic actions of a new inotropic agent, MCI-154, were compared to dopamine, ouabain and milrinone in conscious, chronically instrumented dogs. MCI-154 and milrinone produced similar hemodynamic changes: increases in heart rate, diastolic coronary blood flow velocity and peak positive dP/dt. Neither agent had significant effects on arterial pressure while both drugs reduced left ventricular end-diastolic pressure in a dose-related fashion and myocardial segment length, indicating a decrease in diastolic left-ventricular size. MCI-154 was found to be approximately twice as potent as milrinone. In contrast, dopamine and ouabain produced little change in left ventricular end-diastolic pressure or myocardial segment length during diastole, while both drugs produced increases in arterial and left ventricular systolic pressures. An increase in left ventricular afterload was not observed with either MCI-154 or milrinone, highlighting an important advantage of the latter compounds.