Congenital coronary artery anomalies in adults: non-invasive assessment with multidetector CT.

Congenital coronary anomalies (CCAs) are uncommon but can cause sudden cardiac death or other symptoms of myocardial ischaemia, especially in young healthy subjects. Conventional coronary angiography (CA) is an invasive and expensive procedure, and cannot provide three-dimensional data on the anomalous vessel. Electrocardiographic gated multidetector CT (MDCT) has been reported to be useful for non-invasive evaluation of CCAs. The purpose of this pictorial review is to discuss and illustrate different CCAs in terms of clinical importance, type and manifestations using MDCT. Knowledge of the CT appearances and an understanding of the clinical significance of these anomalies are essential for making the correct diagnosis and planning patient treatment.

Acute myocardial infarction in a young woman with normal coronary arteries and myocardial bridging.

Myocardial bridging (MB) is defined as an intramural segment of a coronary artery that normally courses epicardially. MB is usually a benign condition; however, some cases resulting in myocardial ischaemia, infarction and sudden death have been reported. We describe a case of myocardial infarction related to MB in a young healthy woman with no risk factors for coronary artery disease. The bridge was demonstrated in detail by coronary CT angiography using multiplanar reconstruction and three-dimensional volume-rendered techniques.

Diagnostic accuracy of serum B-type natriuretic peptide for myocardial ischemia detection during exercise testing with spect perfusion imaging.

OBJECTIVE: To determine whether serum B-type natriuretic peptide measured at rest and peak exercise and DeltaBNP contribute to the predictive value and diagnostic accuracy of exercise test in the diagnosis of myocardial ischemia. BACKGROUND: Ventricular myocytes release BNP in response to increased wall stress that occurs in acute ischemia. During exercise testing, transient myocardial ischemia could also cause acute myocardial stress and changes in circulating BNP. METHODS: BNP was measured before and immediately after exercise testing with radionuclide imaging in 203 consecutive subjects referred for chest pain evaluation. Tested subjects were classified as ischemic and non-ischemic based on exercise results, and no ischemia, mild-moderate, and severe ischemia according to perfusion scan results. A logistic regression model, constructed of an ROC and an AUC (area under the curve), was used. RESULTS: Ischemic ECG changes (> or =1 mm, horizontal S-T shift) were detected in the treadmill exercise test in 127 subjects (62.6%), and 76 (37.4%) had neither ST segment shift nor chest pain. Baseline BNP was higher in the ischemic group compared to the non-ischemic group (p=0.044); peak BNP was also higher in the ischemic group (p=0.025), as was DeltaBNP (p=0.0126). Of these 127 subjects, 106 (52% of all) had abnormal perfusion scan results. In the ischemic group, the median baseline, peak exercise BNP, and DeltaBNP values from baseline to peak were higher than in the non-ischemic group. In the severe ischemic group these variables were approximately three-fold higher than in the mild-moderate ischemic group (p<0.0001 for baseline; p<0.0001 for peak; and p<0.0001 for DeltaBNP). Rest, peak exercise, and DeltaBNP values were significantly higher in patients with previous myocardial infarction (p<0.001) and in patients treated with beta blockers; peak exercise BNP was higher in hypertensives and diabetics (p<0.05). The ROC convergence model showed that the AUC for peak-exercise BNP was best able to discriminate and predict severe ischemia and no ischemia, while DeltaBNP from rest to peak exercise discriminated best between mild-moderate and severe ischemia. CONCLUSIONS: Peak exercise BNP and DeltaBNP improved the sensitivity, specificity, positive likelihood ratio, predictive value, and diagnostic accuracy of severe ischemia detection during an exercise test. The contribution of BNP determination during exercise was, however, less impressive than previously reported by others.

Coronary-pulmonary artery fistula diagnosed by multidetector computed tomography.

Coronary-pulmonary artery fistula is an uncommon cardiac anomaly, usually congenital. Most coronary-pulmonary artery fistulas are clinically and haemodynamically insignificant and are usually found incidentally. This report describes a case of complex coronary-pulmonary artery fistula with two feeding vessels of separate origins: one from the proximal part of the left anterior descending artery and another arising from the right aortic cusp. The complex anatomy of the fistula was shown in detail by multidetector computed tomography using multiplanar reconstruction and 3D volume rendering techniques.

Induction of apoptosis by ultrasound application in human malignant lymphoid cells: role of mitochondria-caspase pathway activation.

In the present study, we have focused on the specific question of whether ultrasound application (ULS) delivered with optimized parameters for cavitation generation can stimulate apoptosis in lymphoid cell lines. Suspended T and B lymphoid cell lines (Jurkat and Raji, respectively) were exposed to low frequency ULS (750 KHz) at an intensity level of 54.6 W/cm(2) spatial peak temporal average (SPTA) at focal area, which was found to be the optimal physical parameter to induce apoptosis in these malignant cell lines. Unsonicated cells and cells exposed to gamma-radiation (20 Gy) using (137)Cs source were used as control. Apoptosis was evaluated by cell morphology changes, cell-cycle analysis, and phosphatidylserine exposure. Fraction of cells with low mitochondria membrane potential was observed 1 h after sonication, accompanied by cytochrome c release from mitochondria to the cytosol and caspase-3 activation. Here we present evidence that ULS exposure with cavitation formation on malignant lymphoid cell lines differs from gamma-radiation and is associated with time-dependent apoptosis, which is mitochondria-caspase dependent.

Catheter-delivered ultrasound therapy for native coronary arterial thrombosis and occluded saphenous vein grafts.

Acute coronary thrombosis, overlying ruptured atherosclerotic plaque, is the hallmark of myocardial infarction and unstable angina. Despite use of modern therapeutic modalities, including glycoprotein IIb/IIIa antagonists and stenting, intracoronary thrombus heralds an increased risk of serious complications following percutaneous coronary interventions (PCI). Abundant in vitro and in vivo experimental data have proven that ultrasound energy is capable of lysing intravascular thrombus without injuring the vessel wall. Expanding experience and technological advancements now allow us to use this tool in clinical practice. In this article we review the emergence of percutaneous ultrasonic thrombolysis as a safe and effective tool for treatment of patients in various clinical settings associated with coronary thrombosis.

Ultrasound thrombolysis in stent thrombosis.

Recent refinement in stent implantation technique and peri-procedural pharmacological treatment has lowered the incidence of stent thrombosis significantly. Still, all stent thromboses are associated with major adverse events. In previous studies it has been suggested that intravascular ultrasound fibrinolysis is safe and effective. In this report, ultrasound successfully reperfused thrombotically occluded stents. These observations suggest that ultrasound may dissolve occlusive platelet-rich thrombus effectively and safely. Cathet. Cardiovasc. Intervent. 51:332-334, 2000.

Catheter-based ultrasound thrombolysis--a new promising thrombus-debulking device for the treatment of intracoronary thrombosis.

Angiographic suggestion of intercoronary thrombus is often seen in patients sustaining acute coronary syndromes (ACS). Even in the era of stenting and glycoprotein IIb/IIIa antagonists, the presence of thrombus-rich lesion during percutaneous coronary interventions portends an increased risk of adverse events. It has been hypothesized that reduction of clot-burden prior to PCI may reduce complications and enhance efficacy. Experimental and clinical data have shown that catheter-based ultrasound thrombolysis is capable of inducing an efficacious and safe thrombus-debulking. This article reviews the collective experience with this promising device solution for the treatment of thrombotic lesions in the setting of ACS.

Treatment of lesions with thrombus: beyond stents and GP IIb/IIIa inhibitors.

In the presence of an intracoronary thrombus, percutaneous coronary intervention (PCI) will frequently lead to complications. Glycoprotein IIb/IIIa blockade as adjunct to PCI is very effective in patients with non-occlusive clots and biochemical evidence of platelet micro-embolization. Thrombotically-occluded vessels still remain a major clinical problem. This provides a rationale for thrombus debulking prior to PCI. A powerful antiplatelet agent used in combination with a thrombus debulking strategy and stenting of the underlying ruptured plaque offers the potential for further enhancement of PCI. Protection against embolization could potentially be optimized with the use of anti-embolization devices and covered stents.

Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results.

BACKGROUND: Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. METHODS AND RESULTS: A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency (r(2)=0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-micros pulse length) at an intensity (I(spta)) of >35+/-5 W/cm(2). Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93+/-1% of the lysed clot became subcapillary in size (<8 microm). In vitro safety studies, however, showed arterial damage when an I(spta) of 45 W/cm(2) was used for periods of >/=300 seconds. CONCLUSIONS: External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of

Apoptosis induction of human myeloid leukemic cells by ultrasound exposure.

Therapeutic ultrasound (ULS) and the resulting cavitation process has been shown to induce irreversible cell damage. In this study, we wanted to further investigate the mechanism of ULS-induced cell death and to determine whether apoptosis is involved. High intensity focused pulsed ULS sonication at a frequency of 750 KHz was delivered to HL-60, K562, U937, and M1/2 leukemia cell line cultures. ULS exposure used with induction of transient cavitation in the focal area was delivered with an intensity level of 103.7 W/cm2 and 54.6 W/cm2 spatial-peak temporal-average intensity. As a control, ULS of lower intensity was delivered at 22.4 W/cm2 spatial-peak temporal-average intensity, presumably without generation of cavitation. Our results indicated that DNA damage induced by ULS cavitation did not involve generation of free radicals in the culture media. Morphological alterations observed in cells after exposure to ULS included: cell shrinkage, membrane blebbing, chromatin condensation, nuclear fragmentation, and apoptotic body formation. Apoptotic cells were evaluated by fluorescence microscopy and detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, which identifies DNA breaks, and by the leakage of phosphatidylserine from the inner to the outer side of the membrane layer of treated cells. Some bioeffects induced on sonicated HL-60 cells, such as inhibition of cell proliferation, DNA repair, and cell-dependent apoptosis, were found to be similar to those produced by gamma-irradiation. Thus, much of the cell damage induced by therapeutic ULS in leukemia cells surviving ULS exposure appears to occur through an apoptotic mechanism.

Clinical and inflammatory effects of dietary L-arginine in patients with intractable angina pectoris.

We evaluated the effects of oral L-arginine on the clinical outcome and the inflammatory markers of patients with intractable angina pectoris. Our findings demonstrated a significant clinical improvement in 7 of 10 patients, which was associated with a significant decrease in cell adhesion molecule and proinflammatory cytokine levels. Dietary L-arginine may have clinical beneficial effects in patients with intractable angina pectoris, and may have anti-inflammatory properties.

Percutaneous transluminal therapy of occluded saphenous vein grafts: can the challenge be met with ultrasound thrombolysis?

BACKGROUND: Percutaneous transluminal treatment of a thrombotic vein graft yields poor results. We have previously reported our experience with transluminal percutaneous coronary ultrasound thrombolysis (CUT) in the setting of acute myocardial infarction (AMI). This report describes the first experience with ultrasound thrombolysis in thrombus-rich lesions in saphenous vein grafts (SVGs), most of which were occluded. METHODS AND RESULTS: The patients (n=20) were mostly male (85%), aged 64+/-4 years old. The presenting symptom was AMI in 2 patients (10%) and unstable angina in the rest. Fifteen patients (75%) had totally occluded SVGs. The median age of clots was 6 days (range, 0 to 100 days). The ultrasound thrombolysis device has a 1.6-mm-long tip and fits into a 7F guiding catheter over a 0.014-in guidewire in a "rapid-exchange" system. CUT (41 kHz, 18 W,

Ultrasound inhibits the adhesion and migration of smooth muscle cells in vitro.

This study investigated in vitro the effect of therapeutic ultrasound (ULS) on smooth muscle cell (SMC) function as adhesion, migration and proliferation. Experiments were conducted on aortic SMC in culture. The LD50 was established (1.5 W for 15 s at a frequency of 20 kHz) and used as standard dose in all experiments. Control SMC and viable sonicated SMC were compared in each experiment. Migratory capacity decreased 2.4-fold after sonication and stayed reduced for up to 24 h. Adhesion capacity decreased 5.5-fold after ULS. The proliferative capacity was similar to that of nonsonicated SMC. Sonication was accompanied by the disorganization of alpha-SM actin fibers and diminished distribution of vinculin; tyrosinated alpha tubulin and vimentin appeared unaffected. These changes might be responsible for the observed inhibition of SMC adhesion and migration. Sonicated cells exhibited less lamellipodia, membrane collapse and bleb formation. The signal transduction cascade, which involves activation of the phospholipase-C pathway, was unaffected by ULS.

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase.

BACKGROUND: It has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI). METHODS AND RESULTS: Consecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA. CONCLUSIONS: These results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.

[Ultrasound coronary angioplasty: state of the art and new clinical aspects]. / Koronare Ultraschallangioplastie: Standpunkt und neue klinische Aspekte.

Therapeutic ultrasound was shown to ablate thrombi and to disrupt atherosclerotic plaques in vitro and recently to recanalize occluded coronary arteries in acute myocardial infarction (AMI). The goal of this article is to update collective experience and to weigh the promising and unresolved aspects of this newly developed technology and its clinical results. As therapeutic ultrasound was for long known a synonym for lithotripsy of calculi diseases, it lastly received high attention as a catheter-based ultrasound method to ablate thrombi and disrupt atherosclerotic plaques in interventional cardiology (Figure 1). The effect of therapeutic ultrasound to ablate selectively pathological tissue depends on its bioselectivity for elastic fibers: After ultrasound sonication, healthy tissue-rich in elastin and collagen-including arterial wall remains intact whereas thrombus and plaque with their minimal elastic support are found to be highly susceptible to ablation. Our catheter for coronary ultrasound thrombolysis (Figure 2) consists of a solid metal probe and is connected to a piezo-electric transducer at its proximal end. The distal part ends in a three-wire flexible segment with a 1.6 mm tip ball to guarantee maximal wire flexibility and optimal transmission of ultrasound energy. The initial in vitro studies resulted in a fundamental understanding of the destructive effect of ultrasound on tissue based on 4 factors: mechanical vibration, thermal effects, microcurrents, and cavitation. The first studies on human peripheral vessels were published in 1991 being performed during femoral bypass surgery on occluded and partially obstructed arteries. The procedure was performed without perforation, no adverse side effects emerged, restenosis rate was 20%. The clinical application of coronary ultrasound angioplasty was initiated in 1991; Siegel published his data on 44 patients. In his study, 30 patients with chronic atherosclerotic occlusive lesions and 14 with unstable or stable angina or AMI were treated by ultrasound angioplasty. Residual stenosis after ultrasound treatment was 71%, after balloon dilation reduced to 34%. In the 6-month follow-up angiograms showed no major adverse effect or restenosis. Our experience with coronary ultrasound thrombolysis (CUT) is based on the analysis of 33 patients' data in the feasibility (Table 1) plus multicenter phase of the ACUTE trial (Analysis of Coronary Ultrasound Thrombolysis Endpoints) (Figure 3). Our patients were exclusively treated for AMI by ultrasound angioplasty and afterwards by PTCA if required (Figure 4). The average final percent stenosis was 20% (Figure 5). The main efficacy parameters, device success and angiographic success rates were 100%, clinical success rate was 91.7% (Figure 6 and Table 2). The adverse clinical events of CUT are limited--at least in our studies--to reocclusion of infarct-related artery and ischemia and could be reversed by additional PTCA. No adverse clinical side effects were observed during sonication of the coronary tree. Final angiography revealed residual stenosis of 20% without morphological signs. These excellent results suggest that bioselectivity of ultrasound together with the developed skills of the catheter system induces rapid and selective thrombolysis with no need to cross the target lesion before sonication. But what is the better solution for thrombosis and which for plaque disruption? The development of transluminal balloon catheter really modified therapeutic approach to obstructive coronary and peripheral arterial disease but it is still accompanied by a high rate of abrupt closure, AMI and death. Although the use of intravenous thrombolytic agents is well established in the treatment of AMI and these agents are widely used, a large patient collective remains (up to 33% and more) in whom their use is inadvisable due to recent stroke, surgery, trauma or other contraindications. (ABSTRACT TRUNCATED)