Gustavo Camarano

Microvascular integrity indicates myocellular viability in patients with recent myocardial infarction. New insights using myocardial contrast echocardiography.

BACKGROUND Patency of the infarct-related artery (IRA) after acute myocardial infarction (AMI) may not reflect the magnitude of tissue perfusion. In animal models of AMI, myocardial cellular necrosis has been associated with extensive capillary damage. Because myocardial contrast echocardiography (MCE) can define the spatial distribution of microvascular perfusion, we hypothesized that it could be used in patients after recent AMI to distinguish myocardial regions that have an intact microvasculature and thus are viable from those without an intact microvasculature and thus are not viable. METHODS AND RESULTS One hundred five patients with a recent AMI (range, 1 day to 4 weeks; median, 8 days) who were undergoing cardiac catheterization were included in the study. Two-dimensional echocardiography was performed at baseline and repeated 1 month later to assess regional function within the infarct zone (scores of 1 to 5 indicating normal to dyskinetic segments, respectively). MCE was performed in the cardiac catheterization laboratory to assess microvascular perfusion within the infarct bed. A contrast score index was derived by assigning scores to individual segments within the infarct zone (0, 0.5, and 1 denoting no, intermediate, and homogeneous contrast effect, respectively) and deriving the average score within the infarct bed. Revascularization was performed as clinically indicated. Although the baseline wall motion score and the contrast score index were similar in the 90 patients with a patent IRA and the 15 patients with an occluded IRA (median +/- 1 interquartile range, 3 +/- 1 versus 3.5 +/- 1; P = .41), wall motion score 1 month later was significantly better in those with open IRAs compared with those with closed IRAs (2 +/- 2 versus 3 +/- 2, P = .05). In the 90 patients with an open IRA, a strong correlation was noted between wall motion score 1 month later and the contrast score index (rho = -.64, P < .001). On multivariate analysis, the best correlate of the 1-month wall motion score was the contrast score index. CONCLUSIONS In patients studied in the cardiac catheterization laboratory between 1 day and 4 weeks after AMI, an intact microvasculature as identified by MCE indicates myocardial regions that improve function 1 month later. This study demonstrates that microvascular patency is closely associated with myocardial cellular viability after AMI in humans.

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection

OBJECTIVES We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.

Quantification of myocardial perfusion with myocardial contrast echocardiography during left atrial injection of contrast. Implications for venous injection.

BackgroundThe purpose of this study was to determine whether myocardial perfusion can be quantified with myocardial contrast echocardiography using left atrial (LA) injection of contrast. Methods and ResultsBased on a series of in vitro and in vivo experiments, the optimal dose of sonicated albumin microbubbles injected into the LA for establishing a linear relation between video intensity and blood volume in the anterior myocardium was determined. In 10 open-chest dogs, myocardial blood flow (MBF) was augmented by increasing myocardial blood volume (MBV) with an intravenous infusion of phenylephrine HCl. In the presence of this drug, left anterior descending artery stenosis was produced, followed by release of stenosis, to change MBF within the anterior myocardium. MBV was calculated by dividing radiolabeled microsphere-derived MBF by microbubble transit rate. There was close coupling between MBF and MBV in the anterior myocardium during LA injection of contrast (y=1.0x−0.03, SEE=1.07, r=.92, P<.001). An excellent correlation was also noted between background-subtracted peak video intensity and MBV (y=0.24x+0.73, SEE=0.36, r=.88, P<.001). On multivariate analysis, background-subtracted peak video intensity correlated best with MBV. ConclusionsMyocardial perfusion can be quantified from time-intensity curves derived from the anterior myocardium after LA injection of contrast. Background-subtracted peak video intensity in this situation correlates closely with MBV. When MBV and MBF are closely coupled, such as during inotropic stimulation of the heart, background-subtracted peak video intensity also correlates closely with MBF. Since there are similarities in the models of LA and venous injections, these data indicate that it may be feasible to quantify myocardial perfusion with myocardial contrast echocardiography after venous injection of contrast.

Coronary Reserve Abnormalities in the Infarcted Myocardium Assessment of Myocardial Viability Immediately Versus Late After Reflow by Contrast Echocardiography

BACKGROUND The aim of this study was to determine whether myocardial contrast echocardiography (MCE) during exogenous vasodilation can accurately delineate infarct size, and hence the extent of myocardial viability, both immediately (15 minutes) and late (3 hours) after reperfusion when postreflow coronary hyperema is still present. METHODS AND RESULTS Twenty-one open-chest anesthetized dogs underwent 3 to 6 hours of coronary occlusion followed by reperfusion. MCE was performed 15 minutes after reflow before and during infusion of 0.2 mg.kg-1.min-1 adenosine i.v.. In 12 dogs, infarct size was measured at this time. In the remaining 9 dogs, reperfusion was continued for 3 hours, when MCE was repeated before and after an infusion of 0.56 mg.kg-1.min-1 dipyridamole i.v. and infarct size was measured. In the absence of adenosine, MCE perfusion defect at 15 minutes underestimated infarct sizes at both 15 minutes and 3 hours, whereas in the presence of adenosine, the estimate of infarct size was more accurate. Similarly, in the absence of dipyridamole, although MCE perfusion defect underestimated infarct size (both measured 3 hours after reflow), in the presence of dipyridamole, the estimate of infarct size was more accurate. CONCLUSIONS By unmasking abnormalities in flow reserve within the infarct bed, MCE in conjunction with coronary vasodilators can accurately predict infarct size both 15 minutes and 3 hours after reperfusion. Thus, MCE can be used for assessing the extent of myocardial viability both immediately and late after reperfusion when postreflow coronary hyperemia is still present.

Identification of viable myocardium with contrast echocardiography in patients with poor left ventricular systolic function caused by recent or remote myocardial infarction

We hypothesized that viable myocardium can be identified in patients with poor left ventricular (LV) systolic function caused by recent or prior infarction using myocardial contrast echocardiography. Accordingly, 39 patients with reduced LV ejection fraction (range 0.10 to 0.40) and recent (n = 30) or remote (n = 9) myocardial infarction were studied. Echocardiography was performed at baseline and at 1 month to assess regional function (1 = normal, 5 = dyskinesia) in 12 segments/patient; the segments were also scored for contrast effect (1 = homogenous, 0.5 = partial, 0 = none) during contrast echocardiography performed in the cardiac catheterization laboratory. Four patients had unsuccessful angioplasty of occluded arteries and were treated medically, 9 were treated medically because of noncritical coronary stenoses (< 80%), and 26 underwent revascularization (16 angioplasty and 10 bypass operation). Twelve segments could not be visualized (2 each in 6 patients), and 30 segments continued to be subserved by totally occluded arteries because of unsuccessful angioplasty in 4 patients. Of the remaining 426 segments, 186 (44%) demonstrated baseline wall motion scores of > or = 3. The best correlate of 1-month wall motion score in these segments was the contrast score (p = -0.62), with better 1-month function noted in segments with more contrast. The overall perfusion status of LV myocardium also correlated (p = -0.59) with global LV systolic function at 1 month. We conclude that myocardial contrast echocardiography can be used during cardiac catheterization to define myocardial segments that are viable in patients with poor LV systolic function caused by recent or remote myocardial infarction.

Relation Between Air-Filled Albumin Microbubble and Red Blood Cell Rheology in the Human Myocardium Influence of Echocardiographic Systems and Chest Wall Attenuation

BACKGROUND We have previously shown that the intravascular rheology of sonicated air-filled albumin microbubbles is similar to that of red blood cells (RBCs) and that their myocardial transit rate is also similar to that of RBCs in the beating canine heart. In the present study, we tested the hypothesis that the myocardial transit rates of these microbubbles reflect those of RBCs in humans at different coronary flow rates. METHODS AND RESULTS RBC and microbubble transit rates were measured in 17 patients undergoing coronary angiography: in 8, measurements were made only at rest, whereas in 9, they were performed both at rest and during a pacing-induced increase in coronary blood flow. A gamma-variate function was used to derive mean RBC and microbubble transit rates from the time-activity and time-intensity plots after the left main injection of RBCs and microbubbles, respectively. There was linear correlation between the myocardial transit rates with both tracers with the slope of the correlation determined by the specific echocardiographic system that was used. Microbubble transit rate consistently overestimated RBC transit rate due to artificial narrowing of the time-intensity curves caused by chest wall attenuation of the echocardiographic signal, which was confirmed through in vitro experiments. CONCLUSIONS There is close correlation between air-filled albumin microbubbles and RBC rheology in the human myocardium. The use of these microbubbles in the cardiac catheterization laboratory could, therefore, provide further insights into myocardial blood flow/myocardial blood volume relations in humans.

Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans

BACKGROUND Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.

Contractile Versus Microvascular Reserve for the Determination of the Extent of Myocardial Salvage After Reperfusion

Background We hypothesized that microvascular reserve is a better indicator of the extent of viable myocardium postinfarction than contractile reserve, especially in the presence of a residual stenosis of the infarct-related artery. Methods and Results Fifteen dogs with various infarct sizes were studied after reperfusion. Contractile reserve, studied by use of dobutamine echocardiography, and microvascular reserve, studied by use of myocardial contrast echocardiography, were measured both before and after creation of a stenosis. In the absence of a stenosis, the relation between infarct size, expressed as percent of risk area, and wall thickening improved with increasing doses of dobutamine (r=.41, .71, and .90 for 5, 10, and 15 μg·kg−1·min−1, respectively; P<.01 for dobutamine 15 μg·kg−1·min−1). In the presence of a stenosis, however, the relation was poor for all doses of dobutamine (r=.22, .57, and .32 for 5, 10, and 15 μg·kg−1·min−1, respectively; P<.01 for 15 μg·kg−1·min−1 dobutamine in the absence ...

Myocardial Contrast Echocardiography Demonstrates That Collateral Flow Can Preserve Myocardial Function Beyond a Chronically Occluded Coronary Artery

Myocardial contrast echocardiography, unlike coronary angiography, can define collateral perfusion. This study shows that collateral blood flow can preserve myocardial function beyond a chronically occluded coronary artery.

Myocardial viability in patients with chronic coronary artery disease and previous myocardial infarction: comparison of myocardial contrast echocardiography and myocardial perfusion scintigraphy.

The aim of this study was to compare perfusion patterns on myocardial contrast echocardiography with those on myocardial perfusion scintigraphy for the assessment of myocardial viability in patients with previous myocardial infarction. Accordingly, perfusion scores with the two techniques were compared in 91 ventricular regions in 21 patients with previous (>6 weeks old) myocardial infarction. Complete concordance between the two techniques was found in 63 (69%) regions; 25 (27%) regions were discordant by only 1 grade, and complete discordance (2 grades) was found in only 3 (3%) regions. A kappa statistic of 0.65 indicated good concordance between the two techniques. Although the scores on both techniques demonstrated a relation with the wall motion score, the correlation between the myocardial contrast echocardiography and wall motion scores was closer (r = -0.63 vs r = -0.50, p = 0.05). It is concluded that myocardial contrast echocardiography provides similar information regarding myocardial viability as myocardial perfusion scintigraphy in patients with coronary artery disease and previous myocardial infarction.