Huai Luo

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.

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.

Transcutaneous Ultrasound Augments Lysis of Arterial Thrombi In Vivo

BACKGROUND External ultrasound has a synergistic effect on thrombus disruption with thrombolytic agents in vitro. We hypothesized that transcutaneous ultrasound could augment thrombolysis in vivo. METHOD AND RESULTS Thrombus formation was induced electrically in 48 pairs of iliofemoral arteries of 24 rabbits; arterial occlusions were documented angiographically. In 17 of 24 rabbits, 25000 units/kg streptokinase was then administered intravenously. The pairs of iliofemoral arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Low-frequency (26 kHz) ultrasound (continuous wave, 18 W/cm2) was applied transcutaneously over the area of occlusion. In 7 of 24 rabbits, 14 thrombotically occluded iliofemoral arteries were exposed to ultrasound alone without streptokinase. The results were evaluated through the use of angiography (TIMI grade flow) and histopathology. After 30 +/- 10 minutes of activated sonication combined with intravenous streptokinase, 10 of 17 iliofemoral arteries (59%) treated with transcutaneous ultrasound were widely patent angiographically, with TIMI grade 3 flow. Histologically, the patent arteries had only minimal focal moral thrombus. The angiographic patency rate was significantly lower in the control groups: 1 of 17 arteries (6%) treated with streptokinase alone (P = .0012) and 1 of 14 arteries (7%) treated with ultrasound alone (P = .0036). CONCLUSIONS In vivo transcutaneous ultrasound significantly augments lysis of thrombi with streptokinase in rabbit iliofemoral arteries.

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. METHODS 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.

Noninvasive, Transthoracic, Low-Frequency Ultrasound Augments Thrombolysis in a Canine Model of Acute Myocardial Infarction

BACKGROUND Recently it has been demonstrated that transcutaneous delivery of ultrasound combined with tissue plasminogen activator (tPA) is more effective than tPA alone in recanalizing acutely thrombosed canine coronary arteries. In the present study, we investigated the incidence of partial (> or =50%) and complete (> or =70%) ST-segment elevation resolution in the precordial leads of dogs with experimental acute myocardial infarction that were treated with tissue plasminogen activator (tPA) alone or in combination with noninvasive transcutaneous delivery of high-intensity low frequency (27[emsp3 ]kHz) ultrasound. METHODS Thrombotic coronary occlusions were induced in the midportion of left anterior descending (LAD) coronary artery by electrical injury in 24 dogs. All dogs were given intravenous heparin and tPA. Dogs were randomized to tPA alone (n=12) or combined tPA and adjunctive transcutaneous ultrasound (US) delivery (n=12). Electrocardiograms were recorded at 1) baseline, 2) after coronary occlusion just before initiation of therapy, 3) when coronary angiography showed recanalization of the coronary artery (or at 90 minutes after initiation of therapy if reperfusion did not occur before then) and 4) 90 minutes later. ST amplitude was measured in all 6 precordial leads. RESULTS ST-segment amplitude at baseline was comparable between the tPA and the US group. Before initiation of therapy, sum of ST-segment elevation tended to be higher in the US group. At reperfusion and 90 minutes thereafter, sum of ST-segment amplitude tended to be smaller for the US group than in the tPA group (p<0.001 for the time effect; p=0.118 for the time x group interaction). Up to 90 minutes after initiation of therapy >/=50% resolution of the sum of precordial ST elevation was detected in 7 out of 11 dogs (63.6%) in the tPA group versus 10 out of 11 dogs (90.9%) in the US group. Ninety minutes thereafter, 3 out of 7 dogs in the tPA group (42.9%) versus 9 of 11 dogs in the US group (81.8%) had >/=50% resolution of the sum of precordial ST elevation. CONCLUSIONS The combination of tPA with noninvasive transcutaneous delivery of low frequency high-intensity ultrasound resulted in greater resolution of ST-segment elevation when reperfusion occurs and 90 minutes thereafter, as well as a higher rate of epicardial coronary artery reperfusion.

Assessment of aortic stenosis by three-dimensional echocardiography: an accurate and novel approach

Background: Accurate assessment of aortic valve area (AVA) is important for clinical decision-making in patients with aortic valve stenosis (AS). The role of three-dimensional echocardiography (3D) in the quantitative assessment of AS has not been evaluated so far. Objectives: To evaluate the reproducibility and accuracy of real-time three-dimensional echocardiography (RT3D) and 3D-guided two-dimensional planimetry (3D/2D) for assessment of AS, and compare these results with those of standard echocardiography and cardiac catheterisation (Cath). Methods: AVA was estimated by transthoracic echo-Doppler (TTE) and by direct planimetry using transoesophageal echocardiography (TEE) as well as RT3D and 3D/2D. 15 patients underwent assessment of AS by Cath. Results: 33 patients with AS were studied (20 men, mean (SD) age 70 (14) years). Bland–Altman analysis showed good agreement and small absolute differences in AVA between all planimetric methods (RT3D vs 3D/2D: −0.01 (0.15) cm2; 3D/2D vs TEE: 0.05 (0.22) cm2; RT3D vs TEE: 0.06 (0.26) cm2). The agreement between AVA assessment by 2D–TTE and planimetry was −0.01 (0.20) cm2 for 3D/2D; 0.00 (0.15) cm2 for RT3D; and −0.05 (0.30) cm2 for TEE. Correlation coefficient r for AVA assessment between each of 3D/2D, RT3D, TEE planimetry and Cath was 0.81, 0.86 and 0.71, respectively. The intraobserver variability was similar for all methods, but interobserver variability was better for 3D techniques than for TEE (p<0.05). Conclusions: The 3D echo methods for planimetry of the AVA showed good agreement with the standard TEE technique and flow-derived methods. Compared with AV planimetry by TEE, both 3D methods were at least as good as TEE and had better reproducibility. 3D aortic valve planimetry is a novel non-invasive technique, which provides an accurate and reliable quantitative assessment of AS.

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.

Enhancement of thrombolysis in vivo without skin and soft tissue damage by transcutaneous ultrasound

Previous studies have shown that transcutaneous ultrasound enhances thrombolysis by streptokinase in animals in vivo; however, skin and soft tissue damage induced by ultrasound energy has been a major limitation. The objective of this study was to examine the efficacy of thrombolysis and damage to skin and soft tissues using a newly designed concentrated ultrasound system with a cooling manifold. Using a rabbit model with iliofemoral arterial thrombotic occlusions, 15 pairs of arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Streptokinase (25,000 unit/kg) was given intravenously. Skin temperature was maintained at 25-33 degrees C when ultrasound energy was applied. The serum level of creatine kinase, lactate dehydrogenase, red blood cell counts, and platelet counts were checked at baseline, after thrombus induction, and after ultrasound treatment. Fifteen of fifteen (100%) iliofemoral arteries were angiographically recanalized after ultrasound treatment. In contrast, only 1/15 (6.7%) contralateral arteries were patent after 1 hour. After the subsequent hour with heparin the patency was 14/15 in the ultrasound treated group and 3/15 in the control group. Histologically, the patent arteries had only minimal focal mural thrombus, whereas the angiographically occluded arteries had occlusive thrombi. There was no histologic evidence of ultrasound induced damage to overlying skin, soft tissues, or arteries. In addition, there was no significant rise of creatine kinase, lactate dehydrogenase, or decrease in red blood cell counts and platelet counts induced by ultrasound. In conclusion, transcutaneous concentrated ultrasound which significantly enhances streptokinase induced thrombolysis in vivo can be delivered without concomitant tissue damage. This simple combination therapy has clinical potential for safely treating patients with arterial or venous thromboses.

Noninvasive Evaluation of Right Atrial Pressure

In current practice, right atrial pressure (RAP) is an essential component in the hemodynamic assessment of patients and a requisite for the noninvasive estimation of the pulmonary artery pressures. RAP provides an estimation of intravascular volume, which is a critical component for optimal patient care and management. Increased RAP is associated with adverse outcomes and is independently related to all-cause mortality in patients with cardiovascular disease. Although the gold standard for RAP evaluation is invasive monitoring, various techniques are available for the noninvasive evaluation of RAP. Various echocardiographic methods have been suggested for the evaluation of RAP, consisting of indices obtained from the inferior vena cava, systemic and hepatic veins, tissue Doppler parameters, and right atrial dimensions. Because the noninvasive evaluation of RAP involves indirect measurements, multiple factors must be taken into account to provide the most accurate estimate of RAP. The authors review the data supporting current guidelines, identifying areas of agreement, conflict, limitation, and uncertainty.

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age ≤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.