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Biomedical subjects

R J Siegel

Publications and source records attributed to R J Siegel.

At least 19 recordsLinked to original sources
PubMed2003

Mitral annular calcification: a marker of severe coronary artery disease in patients under 65 years old.

BACKGROUND: Mitral annular calcification has been associated with various systemic and cardiac diseases, with a higher prevalence in women and patients over 70. A possible association between mitral annular calcification and coronary artery disease has recently been suggested. OBJECTIVE: To determine the prevalence of severe coronary artery disease in younger patients with mitral annular calcification. METHODS: Consecutive patients aged or= 70% stenosis of at least one major epicardial coronary artery. PATIENTS: 17 735 patients were screened. Of these, 6207 (35%) had mitral annular calcification and 885 (5%) were also <or= 65 years old; coronary angiography was done in 100 of the latter (64 men; 36 women), mainly for anginal symptoms or a positive stress test. A control group (n = 121; 88 men, 33 women) was identified from 2840 consecutive patients screened. There was no significant difference between the groups in patient characteristics, indication for angiography, or atherosclerotic risk factors. RESULTS: Angiography showed a higher prevalence of severe coronary artery disease in patients with mitral annular calcification than in those without (88% v 68%, p = 0.0004), and a higher prevalence of left main coronary artery disease (14% v 4%, p = 0.009) and triple vessel disease (54% v 33%, p = 0.002). The positive predictive value of mitral annular calcification for finding severe coronary artery disease was 92%. CONCLUSIONS: In patients aged <or= 65 years, mitral annular calcification is associated with an increased prevalence of severe obstructive coronary artery disease. It may serve as a useful echocardiographic marker for the presence of obstructive coronary artery disease, especially when associated with anginal symptoms.

Adult↗
PubMed2001

There is synergism between high-intensity, low-frequency ultrasound and streptokinase but not with eptifibatide, heparin, and aspirin. Differential effects on fresh and aged blood clots. An in vitro study.

OBJECTIVE: Ultrasound is emerging as a promising modality for recanalization of acutely thrombosed blood vessels, especially when associated with fibrinolytics. We assessed the efficacy of ultrasound combined with saline, heparin, eptifibatide, aspirin, and streptokinase in disruption of fresh as well as aged human blood clots, using an in vitro model. METHODS: Blood clots from five donors, 2-4 or 48 hours old, were cut into 250-400 mg slices and immersed for 1, 15, or 30 min in 10 ml saline containing either heparin, eptifibatide, aspirin, streptokinase, or saline alone. Clots were then randomized to 10 s of 20 kHz ultrasound or immersion alone. After treatment, the percentage difference in weight was calculated. RESULTS: Immersion of fresh clots without ultrasound in eptifibatide and heparin resulted in significantly more clot lysis than immersion in saline, aspirin, and streptokinase. Immersion of aged thrombi without ultrasound in heparin, eptifibatide, and aspirin had no additive effect over immersion in saline. Ultrasound enhanced clot disruption in all five solutions, in each immersion time and both in fresh and aged clots. Heparin and aspirin had no additive effect, compared with saline, on ultrasound disruption of both fresh and aged clots, whereas eptifibatide was less effective than saline. In contrast, streptokinase greatly enhanced disruption of both fresh (P=.004) and aged (P<.001) thrombi by ultrasound. The combinations of ultrasound with saline, heparin, eptifibatide, and aspirin were less effective on aged than fresh thrombi, whereas the combination of ultrasound with streptokinase was equally effective on fresh and aged thrombi. CONCLUSIONS: Using a simple in vitro model, we found that the combination of streptokinase and low-frequency ultrasound had a synergistic effect on disruption of both fresh and aged blood clots. Further studies are needed to assess the role of heparin and antiplatelet agents in augmenting clot disruption by ultrasound in in vivo models of acute and subacute thrombosis.

Aspirin↗
PubMed2001

Coronary remodeling of proximal and distal stenotic atherosclerotic plaques within the same artery by intravascular ultrasound study.

The aim of this intravascular ultrasound study was to compare the type and the degree of vessel remodeling in proximal and distal de novo lesions within the same coronary artery in patients with stable angina pectoris. Seventy-six de novo coronary artery lesions in 38 coronary arteries of 38 patients were imaged by intravascular ultrasound. The vessel area (VA) within the external elastic lamina and the lumen area (LA) were measured, and the wall area (VA-LA) was calculated at the lesion site, and the proximal and distal reference sites. The VA ratio was defined as (lesion VA/average of the proximal and distal reference VAs) to represent the degree of vessel remodeling. The proximal coronary segments showed compensatory enlargement more often (68% vs 29%, p < 0.01) than the distal segments, and the VA ratio at the lesion site was significantly larger (1.1 +/- 0.3 vs 1.0 +/- 0.2, p <0 .01) in proximal segments than in distal segments. The type of coronary remodeling was discordant in 61% and concordant in only 39% of coronary arteries between the proximal and distal segments. The type of coronary remodeling of proximal and distal coronary lesions was inhomogeneous, even within the same vessel. Proximal coronary segments showed more prominent compensatory enlargement than distal segments, which have a similar degree of luminal narrowings.

Adult↗
PubMed2001

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.

Aged↗
PubMed2001

The effects of streptokinase and hydroxyethyl starch on in vitro clot disruption by ultrasound.

BACKGROUND: In vitro studies showed that low-frequency ultrasound (US) causes blood clot dissolution. This effect is augmented with thrombolytics, microbubbles and microparticles. However, in animal models of transcutaneous delivery, US alone is not effective, probably due to attenuation of US energy by overlying skin. When combined with thrombolytics or microbubbles, transcutaneous US is highly effective. PURPOSE: To assess the synergistic effect of low-intensity low-frequency US and saline, hydroxyethyl starch (HAES) (a non-gas filled microparticle containing solution), streptokinase (STK), and their combination on blood clot disruption. METHODS: Human blood clots from 4 healthy donors, 2-4 hours old, were immersed for 0, 15, or 30 min in 37 degrees C in 10 ml of the above-mentioned solutions, and then were randomized to 10 sec of 20 kHz US or no US. The % difference in weight was calculated. RESULTS: Immersion for 30 min without US resulted in 13.8 +/- 1.2% clot lysis in saline, and 22.0 +/- 1.3%, 21.7 +/- 2.1%, and 23.2 +/- 1.9% in STK, HAES, and STK + HAES, respectively (p = 0.002). US augmented clot lysis in all groups and at all time points. With low-intensity US, HAES was not better than saline. However, the combination of HAES + STK with US resulted in larger clot disruption at 15 sec incubation time (46.7 +/- 3.2%) than with saline (29.6 +/- 2.1%), HAES (29.6 +/- 2.5%), and STK (32.8 +/- 3.6%) (p < 0.001). CONCLUSION: low-frequency, low-intensity US combined with HAES and STK resulted in greater clot disruption at short incubation times. This combination may assist in achieving faster reperfusion in in vivo models.

Blood↗
PubMed2001

Augmentation of in-vitro clot dissolution by low frequency high-intensity ultrasound combined with antiplatelet and antithrombotic drugs.

BACKGROUND: Glycoprotein IIb/IIIa antagonists and heparin are increasingly used for treatment of acute coronary syndromes. There is no data on the effect of these drugs on clot dissolution when combined with low frequency high-intensity ultrasonic energy. We examined a possible additive effect of low frequency high-intensity ultrasound with an antithrombotic, an antiplatelet and a fibrinolytic agent alone or in combinations for in vitro blood clot dissolution. METHODS: Human blood clots were incubated for 10', 15' and 30' in normal saline containing commonly used concentrations of heparin, tirofiban, t-PA and Optison (echocardiographic contrast agent) alone and in combinations. Clots were then randomly exposed to low frequency high-intensity ultrasound (27[emsp3 ]kHz) for 5 minutes. The percent difference in clot weight and the incremental effect of ultrasound energy were calculated. RESULTS: The most significant additive effect of ultrasound energy was detected with the combination of tirofiban and heparin (39+/-2% augmentation after 10' of incubation, p<0.0001). The greatest magnitude of percent clot weight reduction was observed with ultrasound energy combined with either t-PA alone (72+/-1% after 30' incubation, p=0.0016) or with the combination of t-PA, tirofiban, heparin and Optison (68+/-4% after 30' incubation, p=0.015). CONCLUSIONS: Application of low frequency high-intensity ultrasound has an additive effect to antiplatelet, antithrombotic and fibrinolytic drugs, specifically with the combination of tirofiban and heparin or with t-PA; this effect is observed after a short incubation period.

Blood Coagulation↗
PubMed2001

Noninvasive transthoracic low frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction--evaluation of the extent of ST-segment resolution.

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.

Animals↗
PubMed2001

Influence of ejection fraction and valvular regurgitation on the accuracy of aortic valve area determination.

OBJECTIVE: To examine the influence of left ventricular dysfunction, aortic regurgitation, and mitral regurgitation on commonly used methods for aortic valve area (AVA) determination. BACKGROUND: Each method for AVA determination has its inherent limitations. METHODS: AVA determinations by transesophageal echocardiography (TEE) using planimetry, transthoracic echocardiography (TTE) with application of the continuity equation, and cardiac catheterization applying the Gorlin formula were performed in 74 patients with aortic stenosis. The severity of the aortic stenosis was defined by consensus of at least two methods. Over- or underestimation of AVA associated with ejection fraction, aortic regurgitation, mitral regurgitation, or severity of the aortic stenosis for each method in relation to the other two methods was assessed. RESULTS: Mean AVAs were 1.05 +/- 0.51 by TEE, 1.06 +/- 0.51 by TTE, and 1.08 +/- 0.53 by cardiac catheterization. An overestimation of the severity of the aortic stenosis by the Gorlin formula in patients with moderate-to-severe aortic regurgitation as compared to TEE-derived data was found (P = 0.014). A similar trend of overestimation by catheterization in comparison with the TTE data was found. In the context of moderate-to-severe mitral regurgitation, AVA determination by TTE overestimated the degree of aortic stenosis as compared to TEE (P = 0.011) and cardiac catheterization (P = 0.023). CONCLUSIONS: Overall mean AVA did not differ between methods, suggesting that these three methods are equally accurate in a nonselected clinical patient group. However, in the presence of significant aortic regurgitation, the two echocardiographic methods appear more accurate. Our observation of an overestimation of the severity of aortic stenosis by TTE in the presence of moderate-to-severe mitral regurgitation indicates that this possibility should be accounted for in clinical decisions based on TTE determinations of AVA.

Adult↗
PubMed2001

Ultrasound as treatment for coronary artery disease.

Therapeutic ultrasound is already established in the treatment of diverse surgical conditions, such as cataract, liver cancer, and stones, without danger to healthy tissue. Clinical trials of catheter-delivered, high energy, low frequency (kHz) ultrasound undertaken over the last decade have demonstrated the safety of ultrasound in the treatment of peripheral and coronary artery disease, and have identified a number of indications in which it may be particularly advantageous. The dispersal of thrombus, the recanalization of chronic total occlusions, and the favorable modification of the distensibility of small, atherosclerotic vessels are three promising areas. The authors review developments in these fields.

Angioplasty, Balloon, Coronary↗
PubMed2001

The use of transducer-tipped ultrasound catheter for recanalization of thrombotic arterial occlusions.

Ultrasound energy is currently being used and intensively investigated for recanalization of thrombotically occluded arteries. The ultrasonic energy is mainly applied either by a transcutaneous approach or by a percutaneous approach through a catheter with an external ultrasound transducer. Catheter-delivered transducer-tipped ultrasound thrombolysis is a new and innovative method. In this article we summarize the current available data on the use of this new type of catheter and discuss future directions and clinical applications.

Animals↗
PubMed2001

Noninvasive transcutaneous low frequency ultrasound enhances thrombolysis in peripheral and coronary arteries.

Previous studies have shown that external ultrasound with low frequencies and high intensities can enhance thrombolytic drug-induced clot dissolution during in vitro experiments. In this series of studies, we evaluated the efficacy of peripheral and coronary thrombolysis in vivo in animals by using noninvasive transcutaneous ultrasound combined with thrombolytic drugs (streptokinase and tPA) and/or microbubbles agents (dodecafluoropentane [DDFP] and perfluorocarbon-exposed sonicated dextrose albumin [PESDA]). Thrombotic occlusions were induced in 74 rabbit iliofemoral arteries and 24 canine left anterior descending (LAD) coronary arteries in this in vivo study. By using the combination of transcutaneous ultrasound and streptokinase, the angiographic patency rate in rabbit iliofemoral arteries was higher (56%-100%) than with ultrasound (6%; P < or = 0.0036) and streptokinase alone (6%; P < or = 0.0012). Also, with transcutaneous ultrasound and microbubbles, the angiographic patency rates were 76%-100% as compared with ultrasound alone (0%, P < or = 0.0003) or microbubbles alone (9%, P < or = 0.0001). In the canine study of acute myocardial infarction, thrombolysis in myocardial infarction (TIMI) grade flow at 90 minutes in the tPA alone group was 0.92 +/- 1.4 as compared with 2.42 +/- 1.9 in the tPA plus transthoracic ultrasound group (P = 0.006). There was much improved reperfusion with tPA plus ultrasound as compared with tPA alone. In vivo animal studies demonstrate that noninvasive transcutaneous ultrasound can greatly enhance the effect of clot dissolution with thrombolytic drugs and/or microbubbles, and has the potential for clinical application as an adjunctive method to improve arterial thrombolysis.

Animals↗
PubMed2001

Aortic root dilatation in patients with emphysema.

BACKGROUND: Abdominal aortic aneurysms have been recognized to occur more frequently in patients with emphysema. However, the prevalence of aortic root dilatation in patients with emphysema and its relationship to risk factors for aortic enlargement have not been previously described. METHODS: We studied 47 patients, past smokers (aged 67 +/- 6 years, 18 women) with severe emphysema diagnosed by a pulmonary function test and an ultrafast computed tomographic scan. Two-dimensional echocardiography was used to measure the aortic root at the aortic annulus, sinus of Valsalva, sinotubular junction and proximal part of the ascending aorta. Measured mean values were compared with published normal values and age- and sex-matched patients without emphysema. The relationship between aortic root size and cardiac risk factors (hypertension, hypercholesterolemia, and diabetes) was also examined. RESULTS: In patients with emphysema the mean aortic root dimensions were significantly larger than normal values at each measured site (P <.0001) and those of patients without emphysema (P <.05 to.0001). A substantial percentage of patients with emphysema had larger sinus of Valsalva (43%) and proximal ascending aorta (59%) than the upper limit of normal. In the multivariable regression model, emphysema was a significant determinant of aortic root size at all measured sites and hypertension was associated with additional dilatation at the sinus of Valsalva, sinotubular junction, and proximal ascending aorta. CONCLUSIONS: (1) In patients with emphysema the aortic root dimension is significantly larger than in patients without emphysema. (2) Systemic hypertension is associated with additional enlargement of the proximal ascending aorta, the sinus of Valsalva, and the sinotubular junction.

Aged↗