Noninvasive, transthoracic, low-frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction.

BACKGROUND: Limitations of coronary thrombolysis include the time to reperfusion, patency rate, and bleeding. We evaluated the use of noninvasive transcutaneous ultrasound to augment coronary thrombolysis. METHODS AND RESULTS: In 24 dogs, a thrombotic occlusion of the left anterior descending coronary artery was induced and documented by 12-lead ECG and coronary angiography. After >/=60 minutes of occlusion, tissue-type plasminogen activator (t-PA; 1.42 mg/kg) was given intravenously over 90 minutes. A total of 12 of the 24 dogs had concomitant transcutaneous application of low-frequency ultrasound (27 kHz) over the chest. At 90 minutes, the mean TIMI grade flow in the t-PA alone group was 0.92+/-1.4 compared with 2. 42+/-1.9 in the t-PA plus ultrasound group (P=0.006). TIMI 2 to 3 flow was present in 4 of 12 cases receiving t-PA alone compared with 10 of 12 cases receiving t-PA plus ultrasound (P=0.003). At 180 minutes, mean TIMI grade flow was 0.75+/-1.4 in the t-PA alone group versus 2.58+/-0.9 in the t-PA plus ultrasound group (P=0.001). Pathological examination confirmed the angiographic patency rate and did not reveal injury secondary to ultrasound in the skin, soft tissues, heart, or lungs. CONCLUSIONS: In vivo, the noninvasive transthoracic application of low-frequency ultrasound (1) greatly augments the efficacy of t-PA-mediated thrombolysis, (2) seems safe, and (3) has substantial potential as a noninvasive adjunct to improve coronary patency without increasing the risk of bleeding.

Intravascular ultrasound imaging: a current perspective.

Catheter-based intravascular ultrasound imaging has evolved from a research tool to a device that has received Food and Drug Administration approval. Although it is currently employed as an adjunct to contrast angiography in both the peripheral and the coronary circulation, the indications for its use and its clinical utility have yet to be defined. Much of the research on the technique has explored its qualitative and quantitative capabilities to improve the assessment of atherosclerotic vascular disease. There is the hope that this imaging technique may ultimately improve the performance of endovascular interventions. This review describes the development of the technology from early in vitro validation studies to its present use in human subjects. Wherever possible, studies that validate the findings (that is, by comparison with histopathology results) of intravascular ultrasound are emphasized. Although there is great promise for this technology, limitations such as loss of image quality in severely diseased or heavily calcified vessels hinder its use. The application of imaging with endovascular intervention, imaging of intracardiac structures and the pulmonary circulation and new techniques such as computer image analysis are discussed.

High intensity ultrasound increases distensibility of calcific atherosclerotic arteries.

To assess the effect of high intensity ultrasound energy on atherosclerotic arteries, the pressure-volume relation of stenoses in 14 atherosclerotic human cadaver arteries was measured before and after intraarterial application of ultrasound energy. The pressure-volume relation was measured by inflating a 3-mm angioplasty balloon within each artery with use of a syringe equipped with pressure and volume transducers. To minimize potential effects of balloon inflations on compliance, balloon inflation pressure was set at less than or equal to 3 atm before ultrasound application. Ultrasound energy was applied by using a titanium wire probe at a frequency of 20 kHz for 2 min. After exposure to ultrasound, arterial distensibility (measured as volume at 1 atm of balloon pressure) increased by a mean value of 82 +/- 60 microliters. These data suggest that ultrasound energy probably increases the pliability of atherosclerotic lesions by interrupting calcified plaque. This effect may enhance in vivo distensibility and render calcified atherosclerotic lesions more amenable to balloon angioplasty.

Limitations of postmortem assessment of human coronary artery size and luminal narrowing: differential effects of tissue fixation and processing on vessels with different degrees of atherosclerosis.

Numerous studies have utilized histologic sections of coronary arteries as the standard for testing the validity of the angiographic determination of coronary artery dimensions. However, little attention has been given to artifactual dimensional changes that occur during fixation and histologic processing of tissues (dehydration, clearing, embedding, sectioning and staining). Using planimetric techniques, the dimensional changes that occurred with fixation and processing were quantitated in 61 coronary artery segments with minimal or moderate to severe atherosclerosis obtained from 12 patients studied at autopsy. In vessels with minimal atherosclerotic narrowing, fixation and processing resulted in a decrease in total vessel cross-sectional area and luminal cross-sectional area (p less than or equal to 0.05), whereas absolute wall area (total vessel cross-sectional area minus luminal cross-sectional area) did not change (p = NS). These disproportionate changes resulted in an alteration in the relation between lumen and wall areas so that luminal cross-sectional area decreased from 47.6 +/- 8.5% of the total vessel cross-sectional area observed before fixation to 36.2 +/- 7% after processing (p less than or equal to 0.05). In vessels with moderate to severe atherosclerosis, both the total cross-sectional area and wall area decreased after fixation and processing (p less than or equal to 0.05), but luminal area did not change (p = NS). As a result, the percent luminal cross-sectional area in these vessels increased from 21.1 +/- 10.1% before fixation to 28.7 +/- 9.7% after processing (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical trial of percutaneous peripheral ultrasound angioplasty.

OBJECTIVES: The purpose of this study was to present follow-up data as well as short-term results on a larger clinical series of patients undergoing ultrasound angioplasty. BACKGROUND: Previous pilot studies have demonstrated the feasibility of peripheral arterial ultrasound angioplasty. METHODS: We performed percutaneous ultrasound angioplasty on 50 arterial lesions in 45 patients. Our ultrasound ablation system had a frequency of 19.5 kHz. A fixed-wire probe with 2- or 3-mm ball tips and a 3-mm over-the-wire probe were used to treat 40 femoral, 7 popliteal and 3 tibioperoneal lesions. Seventeen (34%) of the lesions were calcific. Thirty (86%) of 35 occluded segments, 0.5 to 28 cm long (mean 6.2 +/- 5.7), were recanalized. RESULTS: In the 45 patent arteries, the stenosis decreased from 94 +/- 10% to 55 +/- 23% after ultrasound angioplasty and to 12 +/- 8% after balloon angioplasty. Mechanical arterial dissections (n = 4) and perforations (n = 4) without clinical consequence occurred only with the fixed non-over-the-wire probes. No evidence of embolism or vasospasm was detected; in fact, vasodilation occurred. There were no clinical manifestations of acute reocclusion. At 24 h, ankle-brachial indexes increased by 0.23 +/- 0.21 (range -0.27 to 0.72). Six- to 12-month clinical and ankle-brachial index follow-up data for 35 patients treated with ultrasound and adjunctive balloon angioplasty were indicative of restenosis in 7 patients (20%). CONCLUSIONS: Our findings indicate that percutaneous peripheral ultrasound angioplasty 1) is useful for recanalization of fibrous, calcific and thrombotic arterial occlusions; 2) reduces arterial stenoses; and 3) has clinical and ankle-brachial index data indicative of a restenosis rate of 20% at 6 to 12 months in a small cohort of patients. A larger randomized series of patients will need to be studied to assess the impact of ultrasound ablation on restenosis.

Regional remodeling of atherosclerotic arteries: a major determinant of clinical manifestations of disease.

In this review we present the current data on remodeling, based on in vivo ultrasound imaging or postmortem histologic analysis of native peripheral and coronary arteries from animal models and studies in patients (coronary artery saphenous vein bypass grafts, lesions of restenosis after balloon angioplasty and other catheter-based interventions). Histologic and ultrasound imaging studies of arteries with atherosclerosis and after vascular injury reveal that arterial remodeling is common and that the cross-sectional area of the vessel is not constant. Compensatory enlargement, inadequate compensatory enlargement and shrinkage at the site of atherosclerotic lesions occurs in coronary and peripheral arteries. Current studies demonstrate that arterial remodeling is a major determinant of vessel lumen size.

Myocardial contractile reserve on dobutamine echocardiography predicts late spontaneous improvement in cardiac function in patients with recent onset idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether identification of contractile reserve with dobutamine would predict recovery of myocardial function during follow-up in patients with recent onset idiopathic dilated cardiomyopathy (IDC). BACKGROUND: The prognosis of patients presenting with new onset IDC is variable and difficult to predict. METHODS: Twenty-two patients (17 men, 5 women, 46 +/- 14 years) with recently diagnosed IDC (4 +/- 3 months) underwent dobutamine echocardiography. Left ventricular ejection fraction (LVEF) and LV sphericity before and at peak dobutamine infusion (30 +/- 11 microg/kg/min) were determined. A follow-up echocardiographic assessment was done at 6 +/- 4 months. RESULTS: The LVEF on dobutamine was directly related to baseline LV mass expressed as g/ml (Pearson r = 0.65, p = 0.0003). Baseline variables that were significantly predictive of follow-up LVEF were deceleration time (r = 0.69, p = 0.0006), wall motion score index (WMSI) (r = -0.63, p = 0.002), LV mass (r = 0.56, p = 0.008) and LVEF on dobutamine (r = 0.84, p = 0.0001). When either deceleration time or WMSI or LV mass was entered into a regression equation to predict follow-up LVEF, the LVEF on dobutamine added significantly to predictive power. However, if LVEF on dobutamine was entered first, none of the other three variables added significantly to prediction. Baseline LV sphericity at end diastole (ED) (r = 0.13, p = 0.6) did not correlate with follow-up LV sphericity in ED, whereas LV sphericity in ED on dobutamine (ED [r = 0.70, p = 0.0004]) correlated with LV sphericity in ED on follow up. CONCLUSIONS: This study demonstrates that dobutamine-induced improvement in baseline LVEF and LV sphericity identifies patients with IDC who exhibit substantial improvement in LV function and geometry over time.

Clinical demonstration that catheter-delivered ultrasound energy reverses arterial vasoconstriction.

OBJECTIVES: This study was designed to describe the clinical effects of ultrasound energy on guide-wire-induced arterial vasoconstriction. BACKGROUND: We have previously shown that ultrasound energy (20 kHz) delivered by a wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. METHODS: A high intensity, low frequency ultrasound catheter system was used to recanalize total occlusions in the superficial femoral arteries of two patients. After recanalization, the proximal residual stenoses were each less than 15%. However, distal arterial vasospasm was found angiographically in a popliteal artery of one patient and in an anterior tibial artery of another. Subsequently, the ultrasound catheter probe was advanced to the sites of arterial vasospasm (diffuse in one, focal in one). RESULTS: After 30 and 90 s, respectively, of exposure to ultrasound energy with a frequency of 19.5 kHz, peak tip amplitude of 111 microns and power output at the transducer of 25 W, the vasospasm resolved in each arterial segment. CONCLUSIONS: Our findings are the first reported clinical cases documenting that catheter-delivered low frequency, high intensity ultrasound induces arterial vasodilation at the site of vasoconstriction. These biologic effects appear to be relatively unique for an angioplasty device and may have potential clinical importance.

Pacing stress echocardiography: an alternative to pharmacologic stress testing.

OBJECTIVES: We sought to evaluate the diagnostic accuracy and feasibility of bedside pacing stress echocardiography (PASE) as a potential substitute for pharmacologic stress echocardiography in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris. BACKGROUND: Accurate and rapid noninvasive identification and evaluation of the extent of coronary artery disease (CAD) is essential for optimal management of these patients. METHODS: Bedside transthoracic stress echocardiography was performed in 54 consecutive patients admitted to a community hospital with new-onset chest pain, after acute myocardial infarction had been excluded. We used 10F transesophageal pacing catheters and a rapid and modified pacing protocol. The PASE results were validated in all patients by coronary angiography performed within 24 h of the test. Significant CAD was defined as > or =75% stenosis in at least one major epicardial coronary artery. RESULTS: The sensitivity of PASE for identifying patients with significant CAD was 95%, specificity was 87% and accuracy was 92%. The extent of significant CAD (single- or multivessel disease) was highly concordant with coronary angiography (kappa = 0.73, p<0.001). Pacing stress echocardiography was well tolerated, and only 4% of the patients had minor adverse events. The mean rate-pressure product at peak pacing was 22,313+/-5,357 beats/min per mm Hg, and heart rate >85% of the age-predicted target was achieved in 94% of patients. The average duration of the bedside PASE test, including image interpretation, was 38+/-6 min. CONCLUSIONS: Bedside PASE is rapid, tolerable and accurate for identification of significant CAD in patients admitted to the hospital with new-onset chest pain or worsening angina pectoris.

Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study.

OBJECTIVES: This intravascular ultrasound study sought to examine to what extent native coronary artery stenosis is accompanied by vessel wall thickening or inadequate compensatory enlargement (relative vessel constriction), or both. BACKGROUND: In human femoral arteries, inadequate compensatory enlargement is reported to be a paradoxic mechanism for the development of severe arterial lumen narrowing. However, it is unclear in human coronary arteries whether inadequate compensatory enlargement contributes to the development of critical arterial stenosis. METHODS: Thirty-five primary coronary artery lesions from 30 patients (19 men, 11 women; mean [+/- SD] age 65 +/- 13 years) were imaged by intravascular ultrasound. The vessel cross-sectional area and lumen area were measured, and the wall area (vessel cross-sectional area minus lumen area) was calculated at the lesion site and at the proximal and distal reference sites. We defined compensatory enlargement to be present when the vessel cross-sectional area at the lesion site was larger than that at the proximal reference site, inadequate compensatory enlargement when the vessel cross-sectional area at the lesion site was smaller than that at the distal reference site and intermediate remodeling when the vessel cross-sectional area at the lesion site was intermediate between the two reference sites. RESULTS: Compensatory enlargement was observed in 19 (54%) of 35 lesions, inadequate compensatory enlargement in 9 (26%) of 35 and intermediate remodeling in 7 (20%) of 35. In the inadequate compensatory enlargement group, reduction of the vessel cross-sectional area contributed to 39% of lumen reduction. CONCLUSIONS: Compensatory enlargement commonly (54%) occurs at stenotic coronary lesions. However inadequate compensatory enlargement results in a substantial amount (39%) of the lumen area reduction in 26% of primary coronary artery lesions.

Correspondence of left ventricular ejection fraction determinations from two-dimensional echocardiography, radionuclide angiography and contrast cineangiography.

OBJECTIVES: This study assessed the agreement of left ventricular ejection fraction determinations from two-dimensional echocardiography, radionuclide angiography and contrast cineangiography. BACKGROUND: Previously published reports suggest that two-dimensional echocardiography, radionuclide angiography and contrast cineangiography are equally acceptable methods of assessing left ventricular ejection fraction on the basis of high coefficients of correlation. However, correlation of methods does not necessarily imply agreement. METHODS: In a prospective analysis, 25 consecutive subjects all had two-dimensional echocardiography and radionuclide angiography performed within 10 days of each other in the cardiology department of metropolitan community hospital. A retrospective computer search (Medline) revealed seven studies, using the coefficient of correlation (r), comparing two-dimensional echocardiographic left ventricular ejection fraction (n = 268) with radionuclide angiographic (n = 174) or contrast cineangiographic (n = 119) left ventricular ejection fractions. RESULTS: The eight individual studies (n = 293) comparing two-dimensional echocardiography with either radionuclide angiography or contrast cineangiography exhibited coefficients of correlation ranging from 0.78 to 0.93. Agreement analysis using the method of Bland and Altman was performed by averaging the results obtained from the two techniques and determining how disparate any single ejection fraction was (with 95% confidence limits) from the mean value. Agreement ranged from 23% to 42% around the mean ejection fraction. The average lack of agreement between the two methods for all studies involved was 17%, with an average r value of 0.86. CONCLUSIONS: Left ventricular ejection fraction determinations by means of two-dimensional echocardiography, radionuclide angiography and contrast cineangiography exhibit high correlation and only moderate agreement. High correlation does not always imply high agreement. These results suggest that, when validated by agreement analysis, multiple studies may not be necessary in appropriate clinical situations, potentially reducing costs.

In vivo ultrasound arterial recanalization of atherosclerotic total occlusions.

The purpose of this study was to assess the potential of intraarterial ultrasound for in vivo recanalization of atherosclerotic total occlusions. Ultrasound energy at a frequency of 20 kHz was applied with a prototype solid wire probe to 12 surgically implanted occluded human atherosclerotic arterial xenografts, 9 of which were calcified, as well as to the intimal surface of 12 normal canine arteries. In both the normal canine arteries and the atherosclerotic occluded xenografts, there was no angiographic evidence of vasospasm, thrombosis or arterial dissection. Eleven of the 12 atherosclerotic complete arterial occlusions were resistant to passage of a conventional guide wire or probe without ultrasound energy. However, the occlusions were recanalized after administration of 15 s to 4 min (mean 1.5 +/- 1.3 min) of intermittent ultrasound energy. After ultrasound, 8 of the 12 vessels underwent balloon angioplasty. Angiographic residual stenosis after ultrasound alone was 62 +/- 24% and after combined ultrasound and balloon angioplasty, 29 +/- 13%. Although routine angiography did not reveal arterial emboli, high resolution cut films did demonstrate a few distal nonocclusive thrombi of a size similar to that reported with other recanalization methods. Histologic studies demonstrated changes similar to those after balloon angioplasty, with focal cracking of the fibrotic and calcified plaque. The findings demonstrate that ultrasound energy applied through a catheter delivery system can be used in vivo to open completely obstructed atherosclerotic vessels. These studies suggest that it might be clinically feasible to use the ultrasound probe to create a lumen, allowing subsequent balloon dilation.

High intensity, low frequency catheter-delivered ultrasound dissolution of occlusive coronary artery thrombi: an in vitro and in vivo study.

OBJECTIVES: This study assessed the efficacy of a new high intensity, low frequency therapeutic coronary ultrasound catheter for thrombus dissolution in vitro and in vivo in canine coronary arteries. BACKGROUND: Therapeutic ultrasound has been shown to dissolve thrombi in vitro and in peripheral arteries in vivo. There have been no previous studies on in vivo coronary thrombus dissolution by ultrasound. METHODS: In vitro, we exposed 1- to 4-h old human blood clots for 3 min to pulsed-wave ultrasound. Clot dissolution under various conditions was evaluated. In vivo occlusive coronary thrombi were induced in 18 dogs. RESULTS: In vitro irrigation alone (10 ml/min of normal saline solution) and ultrasound alone each contributed to a reduction of clot weight by 47.1 +/- 11.4 mg and 84.6 +/- 25.6 mg, respectively, after 3 min (p < 0.001). Ultrasound plus irrigation resulted in a reduction of clot weight by 216.5 +/- 31.5 mg after 3 min (p < 0.001). The magnitude of clot dissolution was considerably amplified when ultrasound energy was combined with irrigation, probably because of cavitational effects. In vivo, in three dogs mechanical passage of the unactivated probe failed to recanalize the artery, and the arteries remained thrombotically occluded. After passage of the activated ultrasound probe, angiography revealed widely patent coronary arteries in 13 of 15 dogs and partial recanalization with filling defects indicative of residual thrombus in 2 of 15 dogs. Three of 15 coronary arteries were histologically free of residual thrombi. Mural thrombi extending to < or = 10% of the vessel circumference were seen in 10 of 15 dogs. Residual thrombi > or = 50% of the vessel circumference were found in two cases. There was no histologic evidence of ultrasound-mediated vessel damage. CONCLUSIONS: Catheter-delivered therapeutic ultrasound effectively dissolves clots in vitro and in canine coronary arteries in vivo. Thus, therapeutic catheter-delivered ultrasound has the potential to serve as an adjunct or alternative treatment for thrombus-mediated coronary ischemic syndromes or myocardial infarction.

In vitro validation of three-dimensional intravascular ultrasound for the evaluation of arterial injury after balloon angioplasty.

OBJECTIVES: The hypothesis of this study was that three-dimensional ultrasound imaging would facilitate the evaluation of arterial dissection after balloon angioplasty. BACKGROUND: The presence and extent of arterial dissection occurring at the time of balloon angioplasty may be important predictors of abrupt vessel closure or late restenosis. METHODS: Forty-one human arterial segments obtained after death were imaged in an in vitro system at physiologic pressure (80 to 100 mm Hg) before and after balloon angioplasty. Images were acquired with a 20- to 30-MHz mechanical intravascular ultrasound imaging system (Cardiovascular Imaging Systems) with a constant pullback technique (1 mm/s). Standard 0.5-in. (1.27-cm) video tapes were used for data storage and later playback for analog to digital conversion. Digitized data were reconstructed to three-dimensional images with use of voxel space modeling. The vessels were opened longitudinally and subjected to pathologic examination, photographed and classified histologically as normal, fibrous or calcified. Dissection was defined as a disruption and separation of components of the arterial wall. The length and depth of arterial dissection were evaluated grossly and microscopically. RESULTS: Of the 41 arteries studied, 36 (88%) exhibited dissection on pathologic examination after balloon angioplasty. Three-dimensional reconstruction of intravascular ultrasound images identified dissection in 11 (92%) of 12 normal, 8 (100%) of 8 fibrous and 11 (69%) of 16 calcified arteries. Excellent agreement between ultrasound and pathologic findings was achieved in the evaluation of length and depth of dissection for histologically normal and fibrous arteries (kappa = 0.72 to 1.0). When the vessels were severely calcified, the agreement was not as good (kappa = 0.27 to 0.56), particularly in detection of small, non-raised intimal flaps. CONCLUSIONS: This histopathologic validation study suggests that three-dimensional intravascular ultrasound imaging facilitates the evaluation of both quantitative and morphologic features of arterial dissection induced by balloon angioplasty. The advantage of three-dimensional intravascular ultrasound is its ability to assess the length and morphology of arterial injury over an entire vessel segment.

Dissolution of thrombotic arterial occlusion by high intensity, low frequency ultrasound and dodecafluoropentane emulsion: an in vitro and in vivo study.

OBJECTIVES: We examined the effectiveness of the microbubbles of an echo contrast agent, dodecafluoropentane (DDFP) emulsion, to enhance low frequency ultrasound clot disruption in vitro and in vivo. BACKGROUND: Ultrasound is reported to facilitate clot dissolution, and microbubbles could theoretically enhance ultrasound clot dissolution by augmenting cavitational effects. IN VITRO STUDIES: The disruption rate of fresh human clots by ultrasound (24 kHz, 2.9 W/cm2) was examined in saline and DDFP emulsion. In vivo studies: Using a rabbit iliofemoral thrombotic occlusion model, recanalization rate and histopathologic findings were compared among groups treated with DDFP emulsion alone, transcutaneous ultrasound (20 kHz, 1.5 W/cm2) alone and with DDFP emulsion and ultrasound combined. RESULTS: The ultrasound clot disruption rate was significantly (p < 0.01) increased, from 72 +/- 18% (mean +/- SD) in saline to 98 +/- 4% in DDFP emulsion in 3 min in vitro. No vessel was recanalized by DDFP emulsion alone (0%), and only a single artery was patent after ultrasound treatment alone (9%). In contrast, 82% of iliofemoral arteries were angiographically recanalized after ultrasound treatment with DDFP emulsion. Histologically, the patent arteries had only minimal focal mural thrombus, with no evidence of vessel wall damage. However, substantial damage was observed in rabbit dermis and subcutaneous tissue. CONCLUSIONS: 1) DDFP emulsion, an echo contrast agent, significantly enhances the clot-disrupting effect of low frequency ultrasound in vitro and in an in vivo rabbit iliofemoral occlusion model. 2) This simple combination therapy has potential for clinical application in patients with thrombotic arterial occlusions.

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age < or =65 years old.

OBJECTIVES: We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age < or =65 years. BACKGROUND: Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly. METHODS: We studied 338 subjects age < or =65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses. RESULTS: Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (> or =2) calcium (or sclerosis) deposits with diabetes or multiple (> or =2) coronary risk factors were significantly associated with abnormal SPECT in women age < or =55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age < or =55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age < or =55 years (p < 0.05) and the total group of subjects (p < 0.01). CONCLUSIONS: When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men < or =55 years old and women.

Clinical validation of intravascular ultrasound imaging for assessment of coronary stenosis severity: comparison with stress myocardial perfusion imaging.

OBJECTIVES: To validate intravascular ultrasound (IVUS) measurements for differentiating functionally significant from nonsignificant coronary stenosis. BACKGROUND: To date, there are no validated criteria for the definition of a flow-limiting coronary artery stenosis by IVUS. METHODS: Preinterventional IVUS imaging (30-MHz imaging catheter) of 70 de novo coronary lesions was performed. The lesion lumen area and three IVUS-derived stenosis indixes comparing lesion lumen area with the lesion external elastic lamina (EEL) area, the mean reference lumen area and the mean reference EEL area were compared with the results of stress myocardial perfusion imaging. RESULTS: The lesion lumen area and three IVUS-derived stenosis indexes showed sensitivities and specificities ranging between 80% and 90% using stress myocardial perfusion imaging as the gold standard. The lesion lumen area < or =4 mm2 is a simple and highly accurate criterion for significant coronary narrowing. CONCLUSIONS: Quantitative IVUS indices can be reliably used for identifying significant epicardial coronary artery stenoses.

Assessment of myocardial viability by dobutamine echocardiography, positron emission tomography and thallium-201 SPECT: correlation with histopathology in explanted hearts.

OBJECTIVES: We examined the relationship among viability assessment by dobutamine echocardiography (DE), positron emission tomography (PET) and thallium-201 single-photon emission computed tomography (TI-SPECT) to the degree of fibrosis. BACKGROUND: DE, PET and TI-SPECT have been shown to be sensitive in identifying viability of asynergic myocardium. However, PET and TI-SPECT indicated viability in a significant percentage of segments without dobutamine response or functional improvement after revascularization. METHODS: Twelve patients with coronary artery disease and severely reduced left ventricular function (EF 14.5+/-5.2%) were studied with DE prior to cardiac transplantation: 5 had additional PET and 7 had TI-SPECT studies. Results of the three techniques were compared to histologic findings of the explanted hearts. RESULTS: Segments with >75% viable myocytes by histology were determined to be viable in 78%, 89% and 87% by DE, PET and TI-SPECT; those with 50-75% viable myocytes in 71%, 50% and 87%, respectively. Segments with 25-50% viable myocytes showed response to dobutamine in only 15%, but were viable in 60% by PET and 82% by TI-SPECT. Segments with <25% viable myocytes responded to dobutamine in 19%; however, PET and TI-SPECT demonstrated viability in 33% and 38%, respectively. Discrepant segments without dobutamine response but viability by PET and SPECT had significantly more viable myocytes by pathology than did those classified in agreement to be nonviable but had significantly less viable myocytes than those classified in agreement to be viable (p < .001). CONCLUSIONS: These findings suggest that contractile reserve as evidenced by a positive dobutamine response requires at least 50% viable myocytes in a given segment whereas scintigraphic methods also identify segments with less viable myocytes. Thus, the methods may provide complementary information: Nuclear techniques appear to be highly sensitive for the detection of myocardial viability, and negative tests make it highly unlikely that a significant number of viable myocytes are present in a given segment. Conversely, dobutamine echo may be particularly useful for predicting recovery of systolic function after revascularization.

Subaortic stenosis revisited: the importance of the dynamic pressure gradient.

Brachfeld and Gorlin's revised concept of subaortic stenosis derived from their recognition that the large magnitudes of the pressure gradients were incompatible with the relatively mild anatomic lesions found at surgery in 3 of their patients, and the rapidity of their arterial pulse upstroke. They proposed that a gradient caused by a superimposed systolic stenosis was responsible for the large pressure gradients and the overestimation of the severity of the discrete subaortic stenosis (DSAS). A fourth patient had no anatomic cause for the pressure gradient, and findings compatible with hypertrophic cardiomyopathy (HCM). All 4 patients had septal hypertrophy which they felt was instrumental in the brisk pulse contour and dynamic gradients across the outflow tract. In the ensuing decades, imaging techniques have been developed which permit detailed studies of ventricular ejection patterns in dynamic gradients associated with HCM and DSAS. These studies have been interpreted variously. The prevailing view is that there is a dynamic obstruction that increases progressively in severity during systole, as proposed by Brachfeld and Gorlin. An opposing view is that dynamic gradients can occur in the absence of any hindrance to ejection, and that these gradients instead result from rapid and complete emptying of the ventricle. Regardless of their cause, dynamic gradients are often superimposed upon gradients caused by DSAS and valvar aortic stenosis, leading to exaggerated estimates of severity. These dynamic gradients are uncovered when the anatomic cause of stenosis is removed, and seemingly increase the postoperative morbidity. A greater understanding of the significance of dynamic gradients and the mechanism(s) responsible for them should lead to more rational management of DSAS and HCM in the future.

Marine lipid concentrate and atherosclerosis in the rabbit model.

Twenty-seven New Zealand white rabbits underwent balloon de-endothelialization of the aorta and iliac arteries while consuming a 2% cholesterol, 10% peanut oil rabbit chow. Ten of these rabbits were fed 1 ml of concentrated marine fish lipid (MaxEpaTm) daily. Six weeks after de-endothelialization, angiography of the treated arteries was performed and histologic cross-sections of the terminal aorta were measured with a planimeter. Iliac artery luminal diameters were also measured at consecutive 3-mm divisions from the aortic bifurcation and found to have a mean lumen diameter of 1.60 +/- 0.08 mm in the marine lipid-supplemented group (M) and 1.38 +/- 0.12 mm in the control group (C) (P less than 0.001). Analysis of variance on individual segmental diameters confirmed this difference. However, neither the angiographic diameters nor histologic, cross-sectional, luminal areas of the terminal aorta were different between groups. Instead, the mean cross-sectional area of the terminal aortic wall was significantly greater in the marine lipid-fed group (4.4 +/- 1.2 mm2 in M and 3.1 +/- 0.6 mm2 in C, P less than 0.01). In addition, the vessel wall area showed a positive correlation with red blood cell (RBC) incorporation of docosahexaenoic acid (r = 0.82, P less than 0.005) in both groups. In the M group, RBC eicosapentaenoic acid and docosahexaenoic acids increased 100% and 650%, respectively, over baseline.(ABSTRACT TRUNCATED AT 250 WORDS)