Sonothrombolysis in the ambulance for ST-elevation myocardial infarction: rationale and protocol.

BACKGROUND: Treatment of ST-elevation myocardial infarction (STEMI) has improved over the years. Current challenges in the management of STEMI are achievement of early reperfusion and the prevention of microvascular injury. Sonothrombolysis has emerged as a potential treatment for acute myocardial infarction, both for epicardial recanalisation as well as improving microvascular perfusion. This study aims to determine safety and feasibility of sonothrombolysis application in STEMI patients in the ambulance. METHODS: Ten patients with STEMI will be included and treated with sonothrombolysis in the ambulance during transfer to the PCI centre. Safety will be assessed by the occurrence of ventricular arrhythmias and shock during sonothrombolysis intervention. Feasibility will be assessed by the extent of protocol completion and myocardial visibility. Efficacy will be determined by angiographic patency rate, ST-elevation resolution, infarct size and left ventricular volumes, and function measured with cardiovascular magnetic resonance imaging, and contrast and strain echocardiography. A comparison will be made with matched controls using an existing STEMI database. DISCUSSION: Sonothrombolysis is a novel technique for the treatment of cardiovascular thromboembolic disease. The first clinical trials on its use for STEMI have demonstrated promising results. This study will be the first to examine the feasibility of in-ambulance sonothrombolysis for STEMI. TRIAL REGISTRATION: EU Clinical Trials Register (identifier: 2019-001883-31), registered 2020-02-25.

Long-term prognostic value of stress myocardial perfusion echocardiography in patients with coronary artery disease: a meta-analysis.

AIMS: To evaluate the prognostic value of myocardial perfusion (MP) imaging during contrast stress echocardiography (cSE) in patients with known or suspected coronary artery disease (CAD). METHODS AND RESULTS: A search in PubMed, Embase databases, and the Cochrane library was conducted through May 2019. The Cochran Q statistic and the I2 statistic were used to assess heterogeneity, and the results were analysed by RevMan V5.3 and Stata V15.1 software. Twelve studies (seven dipyridamole and five exercise/dobutamine) without evidence of patient overlap (same institution publishing results over a similar time period) enrolling 5953 subjects (47% female, 8-80 months of follow-up) were included in the analysis. In all studies, total adverse cardiovascular events were defined as either cardiac death, non-fatal myocardial infarction (NFMI), or need for urgent revascularization. Hazard ratios (HRs) revealed that a MP abnormality [pooled HR 4.75; 95% confidence interval (CI) 2.47-9.14] was a higher independent predictor of total events than abnormal wall motion (WM, pooled HR 2.39; 95% CI 1.58-3.61) and resting left ventricular ejection fraction (LVEF, pooled HR 1.92; 95% CI 1.44-2.55) with significant subgroup differences (P = 0.002 compared with abnormal WM and 0.01 compared with abnormal LVEF). Abnormal MP was associated with higher risks for death [Risk ratio (RR) 5.24; 95% CI 2.91-9.43], NFMI (RR 3.09; 95% CI 1.84-5.21), and need for coronary revascularization (RR 16.44; 95% CI 6.14-43.99). CONCLUSION: MP analysis during stress echocardiography is an effective prognostic tool in patients with known or suspected CAD and provides incremental value over LVEF and WM in predicting clinical outcomes.

Autonomic pathophysiology in heart failure patients. Sympathetic-cholinergic interrelations.

We conducted this study in an effort to characterize and understand vagal abnormalities in heart failure patients whose sympathetic activity is known. We measured sympathetic (peroneal nerve muscle sympathetic recordings and antecubital vein plasma norepinephrine levels) and vagal (R-R intervals and their standard deviations) activities in eight heart failure patients and eight age-matched healthy volunteers, before and after parasympathomimetic and parasympatholytic intravenous doses of atropine sulfate. At rest, sympathetic and parasympathetic outflows were related reciprocally: heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows. Low dose atropine, which is known to increase the activity of central vagal-cardiac motoneurons, significantly increased R-R intervals in healthy subjects, but did not alter R-R intervals in heart failure patients. Thus, our data document reciprocal supranormal sympathetic and subnormal parasympathetic outflows in heart failure patients and suggest that these abnormalities result in part from abnormalities within the central nervous system.

Visually discernible myocardial echocardiographic contrast after intravenous injection of sonicated dextrose albumin microbubbles containing high molecular weight, less soluble gases.

OBJECTIVES: The central hypothesis of this study was that microbubble survival, and subsequent left ventricular and myocardial ultrasound contrast, could be improved by altering microbubble gas to consist of a higher molecular weight (less diffusible) and less soluble gas. BACKGROUND: Microbubble survival after intravenous injection is shortened because of rapid diffusion of blood-soluble room air gases (nitrogen and oxygen) across the permeable bubble membrane into blood. METHODS: Thirteen open chest dogs received intravenous injections of a constant dose of sonicated dextrose albumin that was incubated with either room air or 100% nitrogen, 100% helium or 100% sulfur hexafluoride. Nitrogen (100%) is less blood soluble than room air, whereas helium and sulfur hexafluoride are the least soluble. Sulfur hexafluoride has the slowest diffusion rate. To further decrease the diffusion rate, each sample was administered during inhalation of room air and again during brief inhalation of the same gas with which it had been incubated. RESULTS: The highest peak videointensity in the left ventricular cavity was produced by the sonicated dextrose albumin incubated with sulfur hexafluoride, the gas having lowest blood solubility and diffusion rate, while sulfur hexafluoride was briefly inhaled during the period of intravenous injection (peak videointensity 139 +/- 10 vs. 54 +/- 11 for room air-exposed sonicated dextrose albumin, p < 0.001). Myocardial contrast was visually evident in > 80% of the intravenous injections of sulfur hexafluoride-exposed sonicated dextrose albumin when the agent was given as an 8-fold concentrated sample during brief inhalation of sulfur hexafluoride. CONCLUSIONS: Visual myocardial echocardiographic contrast is possible after intravenous injection of sonicated dextrose albumin if the microbubbles contain a gas with low blood solubility and diffusivity.

Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropropane-exposed sonicated dextrose albumin.

OBJECTIVES: The purpose of this study was to determine whether intravenous dextrose albumin sonicated with a commonly used gas of low blood solubility and diffusivity (perfluoropropane) could identify acute myocardial ischemia and reperfusion. BACKGROUND: Recently, it has been demonstrated that dextrose albumin sonicated with gases that have low blood solubility and diffusivity results in microbubbles capable of consistently producing myocardial ultrasound contrast after intravenous injection. It remains to be determined, however, whether this contrast agent can visually detect the myocardial blood flow abnormalities seen with acute ischemia or stunned myocardium after reperfusion. METHODS: We gave intravenous injections (0.06 ml/kg body weight) of perfluoropropane-exposed sonicated dextrose albumin to 10 open chest dogs. The measured degree of myocardial contrast (0+ to 2+) and background-subtracted peak anterior myocardial videointensity produced from each injection were measured at three stages: 1) under baseline conditions, 2) during acute ischemia produced by a proximal left anterior descending coronary artery ligation lasting 10 to 120 min, and 3) after reflow was established. Coronary blood flow was monitored during all injections by using an ultrasound flow probe placed around the left anterior descending artery. RESULTS: Coronary blood flow ranged from 0 to 137 ml/min, and peak myocardial videointensity after intravenous administration of perfluoropropane-exposed sonicated dextrose albumin ranged from 0 to 70 gray scale U. There was consistent visual myocardial opacification in all dogs during baseline conditions and a visually evident decrease in myocardial contrast in the left anterior descending artery distribution after ligation. A relative increase in contrast in this same distribution after intravenous contrast agent administration occurred in 7 of the 10 dogs during reflow. Quantitatively, there was an excellent correlation in individual dogs between peak myocardial videointensity and coronary flow at all stages (mean correlation coefficient 0.95 +/- 0.04, range 0.87 to 0.99). CONCLUSIONS: Perfluoropropane-exposed sonicated dextrose albumin is an ultrasound contrast agent that can visually identify myocardial perfusion abnormalities from a peripheral venous injection.

Improved myocardial contrast with second harmonic transient ultrasound response imaging in humans using intravenous perfluorocarbon-exposed sonicated dextrose albumin.

OBJECTIVES: The objectives of this study were to determine whether a new method of ultrasound imaging (transient response imaging) could improve the myocardial contrast after intravenous injections of perfluorocarbon-exposed sonicated dextrose albumin microbubble contrast medium in humans. BACKGROUND: We have shown in animals that very low doses of intravenous contrast medium can produce transient but significantly better myocardial contrast when diagnostic ultrasound pulses are interrupted (delivered only once per cardiac cycle) instead of conventional 25- to 30-Hz frame rate imaging. METHODS: In 14 patients with normal rest wall motion, the peak myocardial contrast produced by transient response imaging was compared with that produced by conventional harmonic ultrasound imaging after injections of low doses (0.0025 to 0.01 ml/kg) of intravenous contrast medium. All studies were performed with second harmonic imaging (2.0 to 2.5 MHz-transmitted frequency). Blood pressure, oxygen saturation, respiratory rate and pulse were monitored before and after each injection. RESULTS: The intravenous contrast medium in the doses given produced no hemodynamic changes and no significant side effects in any patients. Overall, the mean (+/-SD) anterior and posterior myocardial contrast produced was significantly greater with transient response imaging than with conventional harmonic ultrasound imaging (anterior: 37 +/- 20 U transient response imaging vs. 18 +/- 14 U conventional harmonic imaging; posterior: 17 +/- 14 U transient response imaging vs. 5 +/- 5 U conventional; p< 0.01). With the sample size of 14 patients, the study had 80% power to detect a true difference of 18 U for anterior myocardial contrast and 90% power to detect a difference of 12 U for posterior contrast. Visually evident anterior or apical myocardial contrast was observed in 14 of 15 patients with transient response imaging but in only 7 patients with conventional harmonic imaging. Posterior or basal myocardial contrast was evident in 10 patients with transient response imaging but in only 1 patient with conventional harmonic imaging. CONCLUSIONS: Transient response imaging produces significantly better myocardial contrast than conventional harmonic imaging in humans and can be produced safely with minute quantities of intravenous perfluorocarbon.

Effect of significant two-vessel versus one-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging after intravenous contrast injection during dobutamine stress echocardiography.

OBJECTIVES: We sought to determine the effect of multivessel as opposed to single-vessel coronary artery stenosis on myocardial contrast defects observed with intermittent harmonic imaging and intravenous perfluorocarbon-exposed sonicated dextrose albumin contrast injection. BACKGROUND: Intermittent harmonic imaging has permitted the detection of myocardial perfusion abnormalities with an intravenous ultrasound contrast agent. The effect of multivessel disease on inducibility of these perfusion abnormalities is unknown. METHODS: In 10 dogs, intravenous injections of contrast agent were given at rest and during dobutamine stress echocardiography when a single coronary artery stenosis was present (> or = 50% diameter by quantitative angiography) and again when a second stenosis (range 44% to 92% diameter) was present in the vessel supplying the adjacent perfusion bed. The peak myocardial contrast was visually and quantitatively assessed in the mid and lateral regions of the perfusion bed of the first stenosis (original stenosis zone) in the presence of one- and two-vessel stenosis. RESULTS: Peak myocardial contrast defects in both the mid and lateral segments of the original stenosis zone during dobutamine stress echocardiography was significantly lower when two-vessel stenosis was present (p = 0.015), especially in the lateral segment. The spatial extent of the perfusion defect in the original stenosis zone risk area increased significantly when two-vessel stenosis was present, and correlated closely with actual risk area (r = 0.99). Previous total occlusion followed by reperfusion of the vessel supplying the original stenosis zone significantly increased the amount of collateral activity between perfusion beds. CONCLUSIONS: Collateral flow limits the spatial extent of inducible ischemia within the risk area of single-vessel stenosis. Restoring blood flow to one perfusion bed reduces the extent of a perfusion abnormality that can be induced in an adjacent stenosed bed.

Improved endocardial border resolution during dobutamine stress echocardiography with intravenous sonicated dextrose albumin.

OBJECTIVES: The purpose of this study was to determine whether intravenous sonicated dextrose albumin could improve endocardial border resolution during dobutamine stress echocardiography. BACKGROUND: Sonicated albumin improves endocardial border resolution in patients undergoing exercise stress echocardiography. Because a sonicated mixture of albumin with dextrose results in better transpulmonary passage than sonicated albumin alone, this agent could be utilized to further improve endocardial border resolution during dobutamine stress echocardiography. METHODS: We gave intravenous injections of sonicated dextrose and albumin to 50 patients undergoing dobutamine stress echocardiography. Left ventricular video intensity, contrast agent persistence (in seconds), number of contrast agent-enhanced cardiac cycles and improvement in endocardial border resolution were assessed from the apical four-chamber view at baseline, low dose (10 micrograms/kg body weight per min) and peak dobutamine infusion. RESULTS: There was significantly better left ventricular peak video intensity at peak dobutamine infusion than after the same injection at baseline (p < 0.005, analysis of variance). The number of contrast agent-enhanced cardiac cycles in the left ventricular cavity was also significantly longer at peak infusion. Endocardial border resolution was improved (mainly in lateral segments) in 93% of patients at low dose and 95% of patients at peak infusion. CONCLUSIONS: Intravenous sonicated dextrose albumin improves endocardial border resolution during dobutamine stress echocardiography.

Detection of myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles using transient response second harmonic imaging.

OBJECTIVES: The purpose of this study was to prove that transient response harmonic imaging could detect normal and abnormal myocardial perfusion in multiple echocardiographic windows with one intravenous injection of microbubbles in humans. BACKGROUND: Myocardial ultrasound contrast can be produced from intravenous perfluorocarbon-exposed sonicated dextrose albumin, and ultrasound can be significantly improved by briefly suspending the interval between frame rates. Whether this contrast can noninvasively quantify myocardial perfusion in humans is unknown. METHODS: In 28 patients, harmonic transient response imaging was used to image the heart in multiple different imaging planes after one intravenous injection of ultrasound contrast agent. Twenty-five of these 28 patients had a repeat injection during dipyridamole stress. In the primary view, the ultrasound transmission rate was one frame per cardiac cycle; in secondary and tertiary views, the transmission rate was once every multiple cardiac cycles. Regional myocardial contrast was visually assessed and quantified off-line. Quantitative rest thallium and dipyridamole stress sestamibi imaging was also performed. RESULTS: Perfusion abnormalities were evident in the secondary and tertiary views only with one frame every multiple cardiac cycles. Regional peak myocardial videointensity (PMVI) correlated closely with regional tracer uptake in individual patients both at rest (r = 0.84) and during stress (r = 0.88). A PMVI ratio (abnormal region divided by the region with highest nuclear uptake) < 0.6 in any view had a 92% sensitivity and a 84% specificity in identifying a regional nuclear perfusion abnormality. CONCLUSIONS: Transient response imaging produces myocardial contrast in multiple views with one intravenous injection of contrast agent and can accurately identify regional myocardial perfusion abnormalities.

Real-time perfusion imaging with low mechanical index pulse inversion Doppler imaging.

OBJECTIVES: We sought to determine how successful pulse inversion Doppler (PID) imaging would be in detecting myocardial perfusion defects during dobutamine stress echocardiography. BACKGROUND: By transmitting multiple pulses of alternating polarity (PID) at a low mechanical index, myocardial contrast enhancement from intravenously injected microbubbles can be detected using real-time frame rates. Pulse inversion Doppler imaging was performed in 117 patients during dobutamine stress echocardiography by using an intravenous bolus of a perfluorocarbon-filled, albumin-(Optison: n = 98) or liposome- (Definity: n = 19) encapsulated microbubble and a mechanical index of <0.3. The visual identification of myocardial contrast defects and wall motion abnormalities was determined by blinded review. Forty of the patients had quantitative angiography (QA) performed to correlate territorial contrast defects with stenosis diameter >50%. RESULTS: There was a virtual absence of signal from the myocardium before contrast injections in all patients. Bright myocardial opacification at peak stress was observed in at least one coronary artery territory at frame rates up to 25 Hz in 114 of the 117 patients during dobutamine stress echocardiography. Regional myocardial contrast defects at peak stress were observed in all 30 patients with >50% stenosis in at least one vessel (13 with single-vessel and 17 with multivessel disease). Contrast defects were observed in 17 territories subtended by >50% diameter stenosis that had normal wall motion at peak stress. Overall agreement between QA and myocardial contrast enhancement on a territorial basis was 83%, as compared with 72% for wall motion. CONCLUSIONS: Pulse inversion Doppler imaging allows the detection of myocardial perfusion abnormalities in real-time during stress echocardiography and will further add to the quality and sensitivity of this test.

Intravascular ultrasound study of angiographically mildly diseased coronary arteries.

OBJECTIVES: We hypothesized that intravascular ultrasound may identify significant coronary artery narrowing in the mildly diseased coronary artery of patients with insignificant or one- or two-vessel coronary artery disease. BACKGROUND: Necropsy studies have revealed that coronary angiography may underestimate stenosis severity in vessels that appear mildly diseased. Intravascular ultrasound has been shown to detect atherosclerotic changes in angiographically normal coronary arteries and to correlate better with histologic findings. METHODS: In 20 patients, we performed intravascular ultrasound imaging (3.5F catheter, 30-MHz transducer) in 37 coronary arteries that were considered mildly diseased (<50% diameter narrowing) by qualitative angiography. The angiographic diagnosis was no significant coronary artery disease in eight patients, one-vessel disease in seven and two-vessel disease in five. Each vessel, except for the left main coronary artery, was divided into proximal, mid and distal segments. Percent area narrowing and minimal lumen diameter were subsequently quantified by both ultrasound and quantitative angiography. RESULTS: Mean maximal arterial area narrowing by ultrasound in the 67 segments studied was 36 +/- 20% (range 0% to 80.2%) and 19 +/- 23% (range 0% to 82%) by quantitative angiography of these same segments (p < 0.001, paired t test). Mean minimal lumen diameter of the segment was 3.3 +/- 0.9 mm by ultrasound and 2.7 +/- 0.8 mm by quantitative angiography. In 10 patients there were 19 angiographically mildly diseased segments where the percent arterial area narrowing by ultrasound was > or = 50%. Intravascular ultrasound revealed that the more proximal (reference) segment had > 25% intimal thickening in 12 of the 19 underestimated segments. In six stenosed segments (32%), total vessel area increased compared with that of the adjacent proximal vessel segment because of compensatory dilation. CONCLUSIONS: Intravascular ultrasound identifies potentially significant coronary artery disease in vessels that appear to be only mildly diseased by angiography.

Ischemia-induced regional wall motion abnormality is improved after coronary angioplasty: demonstration by dobutamine stress echocardiography.

OBJECTIVES: The purpose of this study was to examine whether dobutamine stress echocardiography can detect reversal of ischemia-induced left ventricular regional wall motion abnormality immediately after percutaneous transluminal coronary angioplasty. BACKGROUND: Although angioplasty is routinely performed as a means of coronary revascularization, at present there is a question whether this results in an immediate improvement in ischemia-induced left ventricular regional function. METHODS: Thirty-five patients underwent dobutamine stress echocardiography 24 h before and 24 to 48 h after angiographically successful coronary angioplasty. Only patients with normal wall motion at rest were included. Dobutamine infusion was begun at 5 micrograms/kg per min and increased at 5-min intervals (10, 20, 30, 40 micrograms/kg per min). Echocardiographic images were stored into cine loops and analyzed off line with simultaneous comparison of images acquired at baseline, 5 micrograms/kg per min, peak infusion and recovery. Echocardiographic images were interpreted independently, without knowledge of other data, by two experienced cardiologists using the 16-myocardial segment model. RESULTS: Before angioplasty, dobutamine stress echocardiography induced wall motion abnormalities in 31 patients (88%). Wall motion score at peak dobutamine infusion improved in 28 (90%) of the 31 patients after angioplasty. Wall motion score at peak dobutamine infusion for the group improved from 20 +/- 3 before angioplasty to 17 +/- 2 after angioplasty (p < 0.001). There was no change in the rate-pressure product achieved for the group before and after angioplasty (20,038 +/- 6,415 beats/min x mm Hg before versus 20,775 +/- 5,435 after angioplasty, p = NS). Before angioplasty, dobutamine stress echocardiography induced angina in 13 patients (37%), whereas angina occurred only once after angioplasty. Electrocardiographic changes diagnostic of ischemia occurred seven times, all before angioplasty. CONCLUSIONS: We conclude that dobutamine stress echocardiography is an excellent method to demonstrate an immediate improvement in stress-induced regional left ventricular dysfunction in the distribution of the vessel undergoing successful angioplasty.

Left ventricular volume changes during dobutamine stress echocardiography identify patients with more extensive coronary artery disease.

OBJECTIVES: We hypothesized that patients with more extensive coronary artery disease could be identified by abnormal left ventricular volume changes during dobutamine stress echocardiography. BACKGROUND: In patients with more than one significant coronary artery stenosis, the typical hypercontractile function during dobutamine infusion may not occur. This may result in a smaller decrease or even an increase in left ventricular volumes at peak dobutamine infusion. METHODS: We measured end-diastolic and end-systolic volumes in 61 patients undergoing dobutamine stress echocardiography and quantitative coronary analysis. Stress echocardiographic findings were positive in 39 patients (Group I) and negative in 22 (Group II). The percent change in these volume measurements from baseline to peak infusion were compared with quantitative coronary analysis jeopardy scores and incidence of two- or three-vessel coronary artery disease. An abnormal response was defined as < 15% decrease in end-diastolic or end-systolic volume. RESULTS: Among the 39 patients with positive findings on dobutamine stress echocardiography (Group I), 11 had an abnormal end-diastolic volume response (< 15% decrease). Nine of these patients had two- or three-vessel coronary artery disease compared with 11 of 28 patients with a normal volume response (p < 0.05). In the 22 patients with negative findings on dobutamine stress echocardiography (Group II), an abnormal end-diastolic volume response was seen in 12 patients, 8 of whom had two- or three-vessel coronary artery disease, whereas none of the 10 patients with a normal volume response had two- or three-vessel coronary disease (p < 0.005; sensitivity 100%, specificity 68%). In the 12 patients with no significant coronary artery disease, end-diastolic and end-systolic volumes decreased by > 15% in all but 1. CONCLUSIONS: Failure of end-diastolic volume to significantly decrease during dobutamine stress echocardiography identifies a group of patients with more extensive significant coronary artery disease.

Composition of coronary atherosclerotic plaque in the intima and media affects intravascular ultrasound measurements of intimal thickness.

OBJECTIVES: The purpose of this study was to evaluate how intravascular ultrasound-determined thickness and reflectivity of the inner echogenic layer of coronary artery plaque is affected by changes in collagen, elastin, proteoglycan, calcium and lipid content in the intima and media. BACKGROUND: Coronary artery plaque often results in disruption of the internal elastic lamina and in increased collagen in the media as well as increased intimal lipid, calcium and proteoglycan content. How these factors affect intravascular ultrasound-derived measurements of intimal thickness are unknown. METHODS: Twenty-one coronary artery segments from 10 patients with varying degrees of coronary artery disease were obtained fresh and unfixed at autopsy. Intravascular ultrasound (30-MHz, 3.5F catheter) was performed at regions in the vessel where a three-layered region was evident. Quantitative measurements of inner echogenic and deeper echolucent layer thickness were determined as well as estimates of ultrasound reflectivity and compared with histologic measurements of intimal and medial thickness and collagen, proteoglycan, lipid and calcium content. RESULTS: In plaque > 300 microns thick and equivalent histologic levels of collagen, inner echogenic layer reflectivity was greater in regions with a greater amount of calcium and proteoglycan and lesser amounts of lipid. Inner echogenic layer thickness correlated well with intimal thickness but had the best correlation with intimal and medial thickness when medial collagen content was increased (r = 0.89). The median observed difference between intimal and inner echogenic thickness was 160 (p < 0.05 compared with zero), whereas the median observed difference between inner echogenic thickness and intimal plus medial thickness when medial collagen content was increased was 60 (not significantly different from zero). CONCLUSIONS: The inner echogenic layer of human coronary artery plaque may represent both intima and media. The echolucent layer by ultrasound may represent only the basal section of the media that does not contain high collagen content.

Endothelium-dependent pulmonary artery responses in chronic heart failure: influence of pulmonary hypertension.

OBJECTIVES: The purpose of this study was to determine whether pulmonary artery responses to acetylcholine are abnormal in patients with chronic heart failure. BACKGROUND: Defective pulmonary artery endothelium-dependent responses have been observed in chronic heart failure models in animals. However, pulmonary artery endothelial responses in humans with chronic heart failure are unknown. METHODS: Twenty-two patients with chronic treated heart failure (12 with secondary pulmonary hypertension, Group I; 10 with normal pulmonary artery pressure, Group II) and 8 control patients constituted the study groups. Intravascular ultrasound measurements of pulmonary artery area just beyond the tip of an 8F infusion sheath were obtained in response to acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter). The 10(-6) mol/liter infusion was repeated after methylene blue infusion. Indomethacin (5 micrograms/ml) was sequentially added to this combination in 17 patients. RESULTS: There were no significant differences among the three groups in vascular area responses to the lowest concentration (10(-6) and 10(-5) mol/liter) of acetylcholine, but the 10(-4) mol/liter infusion resulted in significant constriction in Group II patients (p < 0.05, analysis of variance [ANOVA]). Pretreatment with methylene blue in Group II also resulted in significant pulmonary artery vasoconstriction to even the 10(-6) mol/liter acetylcholine infusion (10.4 +/- 7.8% in Group II vs. 1.7 +/- 3.9% in the control group and 0.1 +/- 4.3% in Group I, p < 0.05, ANOVA). The addition of indomethacin resulted in reversal of the constriction in Group II patients. CONCLUSIONS: These responses indicate that the pulmonary artery endothelium may play a significant role in inhibiting vasoconstriction in patients with chronic heart failure who maintain normal pulmonary artery pressure.

Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: validation in humans.

OBJECTIVES: The aim of this study was to validate the use of myocardial contrast echocardiography to determine coronary blood flow reserve in humans. BACKGROUND: Although myocardial contrast echocardiography has been used to accurately quantify coronary flow reserve in animals, validation for its use in humans to measure flow reserve is lacking. METHODS: We analyzed the time-intensity curve from the anteroseptal region of the left ventricular short axis produced after a left main coronary artery injection of sonicated albumin before and after intracoronary administration of papaverine in 16 patients without angiographically significant coronary artery disease. The ratio of half-time of video intensity disappearance from peak intensity, variable of curve width, area under the time-intensity curve and corrected peak contrast intensity after papaverine compared with baseline were correlated with coronary flow reserve measured simultaneously with an intracoronary Doppler probe in the left anterior descending coronary artery. RESULTS: There was a strong inverse correlation with half-time of contrast washout and coronary flow reserve (r = -0.76, p = 0.0007) and a strong positive correlation between the variable of curve width (which is inversely proportional to curve width) and coronary flow reserve (r = 0.71, p = 0.002). There was a weak but significant inverse correlation between area under the time-intensity curve and coronary flow reserve (r = -0.54, p = 0.03) but no correlation between corrected peak contrast intensity and coronary flow reserve (r = -0.36, p = NS). Despite the strong correlation for the ratios for half-time of contrast washout and variable of curve width and actual coronary flow reserve measured with intracoronary Doppler probe, the transit time ratios consistently underestimated coronary flow reserve. CONCLUSIONS: Myocardial contrast echocardiography performed with left main coronary artery injections of sonicated albumin can be utilized to measure coronary flow reserve in humans. Transit time variable ratios (half-time of contrast washout and variable of curve width) derived from the time-intensity curve correlate most strongly with coronary flow reserve.

Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography.

OBJECTIVES: We sought to determine the feasibility and accuracy of real-time imaging of myocardial contrast echocardiography (MCE) in detecting myocardial perfusion defects during exercise echocardiography compared with radionuclide tomography. BACKGROUND: Ultrasound imaging at a low mechanical index and frame rate (10 to 20 Hz) after intravenous injections of perfluorocarbon containing microbubbles has the potential to evaluate myocardial perfusion and wall motion (WVM) simultaneously and in real time. METHODS: One hundred consecutive patients with intermediate-to-high probability of coronary artery disease underwent treadmill (n = 50) or supine bicycle (n = 50) exercise echocardiography. Segmental perfusion with MCE and WM w ere assessed in real time before and at peak exercise using low mechanical index (0.3) and frame rates of 10 to 20 Hz after 0.3 ml bolus injections of intravenous Optison (Mallinckrodt Inc., San Diego, California). All patients had a dual isotope (rest thallium-201, stress sestamibi) study performed during the same exercise session, and 44 patients had subsequent quantitative coronary angiography. RESULTS: In the 100 patients, agreement between MCE and single photon emission computed tomography (SPECT) was 76%, while it was 88% between MCE and WM assessment. Compared with quantitative angiography, sensitivity of MCE, SPECT and WM was comparable (75%), with a specificity ranging from 81% to 100%. The combination of MCE and WM had the best balance between sensitivity and specificity (86% and 88%,respectively) with the highest accuracy (86%). CONCLUSIONS: The real-time assessment of myocardial perfusion during exercise stress echocardiography can be achieved with imaging at low mechanical index and frame rates. The combination of WM and MCE correlates well with SPECT and is a promising important addition to conventional stress echocardiography.

Segmental analysis of coronary arteries with equivalent plaque burden by intravascular ultrasound in patients with and without angiographically significant coronary artery disease.

These IVUS-derived data indicate that failure of compensatory dilation is an important factor in the development of clinically and angiographically significant coronary artery disease independent of plaque burden. We observed an actual reduction in total vessel area at the most stenotic site in coronary arteries that had a quantitatively significant angiographic lesion.

The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction.

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function.

Effects of exercise on left ventricular diastolic performance in trained athletes.

Dynamically trained athletes develop increased left ventricular (LV) wall mass. To determine whether this increased wall mass impaired characteristics of LV diastolic filling, serial Doppler echocardiograms were obtained from 10 trained athletes (mean age 21 years) at rest, during supine graded bicycle exercise and during recovery at heart rates of 80, 120 and 140 beats/min, respectively. Similar studies were obtained in 10 age-matched control subjects. Studies at rest showed significant increases in athletes in LV end-diastolic dimension and indexed LV wall mass. Differences in peak filling rates and in normalized peak lengthening rates between athletes and control subjects were seen at heart rates of 140 beats/min during exercise and recovery. Differences in Doppler-derived variables between athletes and control subjects were seen in total time-velocity integral, early peak filling velocity and E/A ratio. In athletes, time-velocity integral was increased during recovery at heart rates of 120 beats/min and 80 beats/min, early peak filling velocity was increased during exercise at 120 beats/min and during recovery at 120 beats/min and 80 beats/min, and E/A ratio was higher at all heart rates during both exercise and recovery. Although no significant differences were found in LV diastolic filling indexes at rest, a significant enhancement was found in these parameters in dynamically trained athletes during exercise, particularly at higher levels of dynamic exercise.