Intracoronary artery thrombus formation in unstable angina: a clinical, biochemical and angiographic correlation

OBJECTIVES: We examined the relation between the level of urinary fibrinopeptide A and the presence of angiographic intracoronary thrombus in patients with unstable angina to determine whether this marker predicts active thrombus formation. BACKGROUND: Although it is known that thrombus plays a role in acute ischemic syndromes, a noninvasive method to predict its presence in individual patients with unstable angina has not been determined. Fibrinopeptide A is a polypeptide cleaved from fibrinogen by thrombin and thus is a sensitive marker of thrombin activity and fibrin generation. METHODS: Angiographic thrombus, graded 0 to 4, and the presence of ST segment depression or T wave inversions, or both, on the electrocardiogram (ECG) were related to fibrinopeptide A levels in 24 patients with rest angina of new onset, 18 with crescendo angina, 19 with stable angina and 9 with chest pain but without coronary artery disease. All patients had chest pain within the 24 h of sample acquisition. RESULTS: The angiographic incidence of thrombus was significantly higher in patients with new onset of rest angina (67%, p < 0.001) and crescendo angina (50%, p < 0.001) as were fibrinopeptide A levels (p = 0.002). Fibrinopeptide A levels correlated significantly (p < 0.001) with the presence of a filling defect (grade 4 intracoronary thrombus) or contrast staining (grade 3). All patients with fibrinopeptide A > or = 8 ng/mg creatinine showed grade 3 to 4 thrombus and 15 of 16 patients with levels > or = 6.0 ng/mg creatinine exhibited angiographic evidence of thrombus (13 with grades 3 to 4). Patients with reversible ST changes on the ECG had significantly higher levels of fibrinopeptide A (p < 0.001), and ST changes correlated significantly with the presence of angiographic thrombus (p < 0.001). Nonetheless, a significant minority of patients with unstable angina had neither angiographic nor biochemical evidence of thrombus. CONCLUSIONS: Elevated fibrinopeptide A levels in unstable angina reflected active intracoronary thrombus formation and were present in patients with angina of new onset as well as crescendo angina. Reversible ST changes are accompanied by thrombin activity and angiographic thrombus formation. However, a sizable percentage of patients with unstable angina had no evidence of thrombus and these patients may have had transient platelet aggregation without fibrin thrombus formation.     

Comparison of the effects of Ca2+ and those of Mg2+ and La3+ on endplate currents in mouse interosseus muscles

Intravascular ultrasound imaging (IVUS) is a new method that permits in vivo visualization of central venous catheters with hitherto unknown image resolution. It provides information not only about thrombus formation, but also about catheter movement, catheter malposition, and vessel wall injuries. In the present investigation the method was applied to evaluate the frequency of thrombus formation on double-lumen hemodialysis catheters and its significance for catheter malfunction. In 14 patients who had a double-lumen hemodialysis catheter for temporary or long-term vascular access, IVUS of the catheter and the mediastinal vein stems was performed. Mean indwelling duration at the time of the ultrasound investigation was 101 days (range. 3 to 730 days; median, 58 days). Four patients had catheter-related thrombotic complications: IVUS failed to detect an intracatheter thrombus in one case; a catheter thrombus and superior vena cava stenosis were found in a catheter with normal function in one case; in one case with catheter malfunction, a combined catheter-mural thrombus was found; and in the remaining case, a catheter thrombus and a mural superior vena cava thrombus were found in a patient with normal catheter function and pulmonary emboli. Thus, two of 12 patients with well-functioning catheters (16%) had thrombotic complications demonstrated by IVUS, and one of two patients with catheter malfunction had thrombus identified by IVUS. It is concluded that thrombus formation is less likely in patients without signs of catheter malfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Medullary mechanism of the inhibition on renal sympathetic efferent activities by stimulation of the cervical vagal afferent nerve in rabbits

The presence of angiographic evidence of thrombus is generally thought to be a contraindication to coronary stent placement. This report describes four patients in whom angiographic thrombus was lysed using the Dispatch infusion catheter prior to coronary stenting. Urokinase was infused via the Dispatch catheter with resolution of angiographic evidence of thrombus in all cases. No complications were encountered using this technique, and all patients had excellent angiographic results after stenting. We conclude that lysis of intracoronary thrombus using the Dispatch infusion catheter is feasible and appears safe in this small study. Further trials are needed to determine if this technique reduces the acute stent thrombosis rate compared to other techniques for stent deployment in the presence of angiographic evidence of thrombus.     

Predictors for the massive thrombi occurring in the right coronary artery related to acute myocardial infarction

Acute myocardial infarction (AMI) related to the right coronary artery (RCA) is associated with a lower reperfusion rate and higher reocclusion rate in the acute phase than AMI related to the left coronary artery. The greater susceptibility of the RCA to development of large thrombi makes successful reperfusion more difficult to achieve. This study investigated predictive factors for massive thrombus in the RCA before the selection of the treatment to achieve better rates of reperfusion. We classified 51 patients with AMI related to RCA into the massive (linear intraluminal radiolucency > 3 cm) thrombus group (9 patients) and the non-massive thrombus group (42 patients). 1) History: Patients in the massive thrombus group had a greater incidence of hypertension than the non-massive thrombus group, with more left ventricular hypertrophy (p < 0.05). There were no significant differences in other coronary risk factors. 2) RCA morphology: The maximum RCA diameter was significantly greater in the massive thrombus group than that in the non-massive thrombus group [proximal to the right ventricular branch, 4.2 vs 3.2 mm (median); distal to the right ventricular branch, 4.2 vs 3.4 mm, p < 0.05]. 3) Conditions of onset: The elapsed time was significantly longer in the massive thrombus group (15 hours) than that in the non-massive thrombus group (2.5 hours, p < 0.05). More massive thrombus cases were observed in summer (p < 0.05), but there was no evident correlation between massive thrombus formation and the onset time of day, weather, Hct and coagulation factor at the onset, left ventricular ejection fraction or left ventricular end-diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of depressive symptoms and depressive disorder in primary care patients over 65 years of age

Several reports suggest that pretreatment of intracoronary thrombus with fibrinolytic agents may reduce the risk for complications during subsequent balloon angioplasty. We report a case, for the first time, of successful lysis of an extensive thrombus in a native coronary artery by administering a prolonged intracoronary infusion of streptokinase to facilitate subsequent angioplasty and discuss the management strategy when intracoronary thrombus is encountered.     

Predictors of left atrial thrombus and spontaneous echo contrast in rheumatic valve disease before and after mitral valve replacement

In this study we aimed to analyze, with reference to mitral regurgitation (MR), the incidence and predictors of left atrial (LA) thrombus and spontaneous echo contrast in patients with rheumatic valve disease before and after mitral valve replacement. The incidence of LA thrombus is known to be less in patients with MR. The impact of mitral valve replacement on this beneficial effect has not been studied in detail. The study included 169 consecutive patients (59 men and 110 women, average age 40 +/- 13 years) with rheumatic mitral valve disease who underwent transesophageal echocardiographic examination 1 to 3 days before and within 7 days (mean 4.0 +/- 1.3) after mitral valve replacement using mechanical prostheses in a single institution. The preoperative incidence of echocardiographic LA spontaneous echo contrast (SEC) was 1.1%, 30%, and 54%, and the incidence of thrombus was 1.1%, 13%, and 17% in the groups with MR, combined mitral stenosis + MR, and isolated mitral stenosis, respectively. In the MR group, SEC and thrombus incidence increased significantly after surgery. The independent predictors for postoperative thrombus development were atrial fibrillation, postoperative SEC, and preoperative thrombus. Thrombus recurred after surgery in 64% of 14 patients who had surgical thrombectomy. The presence of postoperative MR was associated with decreased risk of postoperative SEC and thrombus development. The interaction between MR and SEC and thrombus both before and after surgery provides further support for the protective effect of MR against LA thrombus formation.     

First report of a human isolate of Erwinia persicinus

Left ventricular thrombus is a complication of myocardial infarction, ventricular aneurysm, cardiomyopathy, and myocarditis. Left ventriculotomy has been the standard approach for removal of left ventricular thrombus. This approach has produced an unacceptable incidence of ventricular dysfunction, arrhythmias, and aneurysm formation. We describe a case of left ventricular thrombus with systemic embolization in a patient with myocarditis. Video-assisted cardioscopy allowed visualization and removal of the thrombus via an aortotomy, thereby avoiding a left ventriculotomy.     

Thrombosis, antithrombotic agents, and the antithrombotic approach in cardiac disease

To develop a rational approach to antithrombotic therapy, in cardiac disease, a sound understanding is required (1) of the hemostatic processes leading to thrombosis, (2) of the various antithrombotic agents, and (3) of the relative risks of thrombosis and thromboembolism in the various cardiac disease entities. With the understanding of pathogenesis and risk of thrombus formation, a rational approach to the use of antiplatelet and anticoagulant agents can be formulated. Those at high risk of thrombus formation should generally receive a high degree of antithrombotics and, depending on the pathophysiology of the thrombus, may benefit from the concomitant use of antiplatelet and anticoagulant agents. Those with a medium risk of thrombus formation may benefit with the use of an antiplatelet agent alone or anticoagulants alone. Patients at low risk of thrombus formation should not receive antithrombotics. Such rational approach to antithrombotic therapy serves as the basis of this article.     

Superimposition of In-111 platelet SPECT and CT/MR imaging in intracardiac thrombus

An initial attempt to superimpose in-111-labeled platelet SPECT over CT/MRI in two patients with intracardiac thrombus is presented. One patient was a 65-year-old woman with a history of mitral and tricuspid valve replacement. This patient had a large thrombus measuring 74 x 43 x 34 mm in the right atrium. Fusion imaging with CT showed increased in-111 activity on the surface of the thrombus, which was visualized as circular activity on a planar image. The other patient was a 72-year-old woman who had a thrombus measuring 17 x 14 x 12 mm at the cardiac apex. Planar imaging showed two discrete areas of abnormal in-111 activity. Superimposition of the SPECT image over MR revealed that one of these areas corresponded to the small thrombus, whereas the other related to a previous subendomyocardial biopsy. In both patients, the activity ratio of the abnormal in-111 accumulation versus the cardiac chamber on SPECT was greater than that on planar images. The correlation of in-111 platelet SPECT and CT/MRI was useful in accurately localizing the intracardiac thrombus.     

Observations on detecting left ventricular thrombus with two dimensional echocardiography: emphasis on avoidance of false positive diagnoses

Observations made in detecting left ventricular thrombus with two dimensional echocardiography in 25 patients are reviewed. In 20 patients thrombus was documented on angiography, surgery postmortem examination or serial two dimensional echocardiographic findings; in the remaining five patients two dimensional echocardiographic findings of thrombus were unequivocal. In all 25 patients wall motion abnormalities ranging from hypokinesia to frank dyskinesia were present at the site of the thrombus. Twenty-three patients had an apical thrombus; two had thrombus adjacent to the inferior wall. Clear delineation of the endocardium and thrombus margin was considered essential to the correct diagnosis of thrombus. Both intracavitary motion of the thrombus margin and a layering effect were noted infrequently although they were of benefit in identifying an intracardiac mass as thrombus. In addition, serial evaluations were helpful in establishing the correct diagnosis. False positive diagnoses can be minimized if one understands certain technical limitations of this method and correctly identifies apical structures that are not thrombi. Axial and lateral resolution problems inherent with this technique can produce intracavitary echoes that may simulate thrombi. In addition, normal or pathologic structures at the apex may also simulate thrombi. These structures include the papillary muscles, muscular trabeculae, chordal structures and tangential information from normal myocardium. Varying the sector orientation or acoustic window, or both, will aid in correctly identifying these structures and distinguishing them from left ventricular thrombi.     

Differentiating thrombus from pannus formation in obstructed mechanical prosthetic valves: an evaluation of clinical, transthoracic and transesophageal echocardiographic parameters

OBJECTIVES: We sought to determine the clinical and echocardiographic parameters that differentiate thrombus from pannus formation as the etiology of obstructed mechanical prosthetic valves. BACKGROUND: Distinction of thrombus from pannus on obstructed prosthetic valves is essential because thrombolytic therapy has emerged as an alternative to reoperation. METHODS: We analyzed clinical, transthoracic and transesophageal echocardiography (TEE) data in 23 patients presenting with 24 obstructed prosthetic valves and compared the findings to pathology at surgery. RESULTS: Fourteen valves had thrombus and 10 had pannus formation. Patients with thrombus had a shorter duration from time of valve insertion to malfunction, shorter duration of symptoms, but similar New York Heart Association functional class at the time of operation. Patients with thrombus had a lower rate of adequate anticoagulation (21% vs. 89%; p=0.0028). Pannus formation was more common in the aortic position (70% vs. 21%; p=0.035). Abnormal prosthetic valve motion was detected by TEE in all cases with thrombus formation but in 60% with pannus (p=0.0198). Thrombi were larger than pannuses (total length 2.8+/-2.47 cm vs. 1.17+/-0.43 cm; p=0.038). This was mostly due to extension of thrombi into the left atrium in prosthetic mitral valves. Thrombi appeared as a soft mass on the valve in 92% of cases, whereas 29% of pannuses had a soft echo density (p= 0.007). Ultrasound video intensity ratio, derived as the videointensity of the mass to that of the prosthetic valve, was lower in the thrombus group (0.46+/-0.14 vs. 0.71+/-0.17, p=0.006). A videointensity ratio of <0.70 had a positive predictive value of 87% and a negative predictive value of 89% for thrombus. Duration from onset of symptoms to reoperation of <1 month separated thrombus from pannus formation. The best objective clinical parameter for prediction of thrombus was inadequate anticoagulation, whereas the best TEE parameters were qualitative and quantitative ultrasound intensity of the mass. The presence of either inadequate anticoagulation or a soft mass by TEE improved the predictive power of either parameter alone and was similar to that of ultrasound videointensity ratio. CONCLUSIONS: Duration of symptoms, anticoagulation status and qualitative and quantitative ultrasound intensity of the mass obstructing a mechanical prosthetic valve can help differentiate pannus formation from thrombus and may therefore be of value in refining the selection of patients for thrombolytic therapy of prosthetic valve obstruction.     

Anesthetic management for renal tumor extending to the inferior vena cava

A 58 year-old woman underwent radical nephrectomy, thrombectomy and ileo-cecal resection for renal tumor with thrombus involving the inferior vena cava and ascending colon cancer. In a patient having tumor thrombus extending to the vena cava, recognition of the position of the thrombus is important for surgical and anesthetic management in pre- and intra-operative periods. Transesophageal echocardiography (TEE) enabled us to visualize the real-time movement and deformity of thrombus by surgical manipulation and compression during operation. TEE seemed also very useful not only in understanding the hemodynamics during operation but also in detecting the residual tumor and the blood flow in liver and the inferior vena cava after operation.     

Primary prevention of malignant melanoma in the Stockholm Cancer Prevention Programme

The relation between intracoronary thrombus and endothelin-1 (ET-1) was studied. In a canine model, acute myocardial infarction (MI) was induced by coronary occlusive thrombus produced at a mock atheromatous plaque. Blood samples were collected from the aorta (A) and coronary vein (V). Twenty-eight open-chest dogs divided into three groups were studied. Group I (n = 15): acute MI was induced by coronary occlusive thrombus, and thrombolysis was obtained by urokinase two hours after MI. Group II (n = 8): nonocclusive thrombus was produced without inducing MI. Group III (n = 5): coronary artery was ligated for two hours and reperfused by release of ligation. In Group I, ET-1 was significantly increased after MI in A and V, and ET-1 in V was significantly more elevated than in A during thrombolysis, suggesting ET-1 production in the coronary vessels by thrombolysis. In Group II, ET-1 increased slightly during thrombus formation, but there was no difference in A and V. In Group III, ET-1 was elevated significantly after MI without A and V difference. These results indicate that there is no detectable ET-1 production with coronary thrombus formation, whereas coronary ET-1 production is detected during thrombolysis, most probably because resolved thrombus releases a more potent stimulus to ET-1 production.     

A case of left atrial free-floating ball thrombus

A rare case of left atrial free floating ball thrombus with mitral stenosis is reported. A 66-year-old woman was admitted for epigastralgia and acute heart failure without atrial fibrillation and previous embolization. The patient was treated successfully with removal of ball thrombus and mitral valve replacement. Intraoperative transesophageal echocardiography was effective for monitoring of mobile left atrial thrombus.     

Potential influence of intraluminal thrombus on abdominal aortic aneurysm as assessed by a new non-invasive method

Intraluminal thrombus may play a role in abdominal aortic aneurysm pathogenesis and rupture. The purpose of this work was to demonstrate the feasibility of a new non-invasive method for the determination of the biomechanical features of the aortic wall and luminal boundary in abdominal aortic aneurysm containing intraluminal thrombus. Automated ultrasonographic measures of infrarenal aortic cross-sectional area (A) were obtained on-line along with non-invasive arterial pressure (p) from eight patients of mean (s.e.m.) age 74(3) years, with abdominal aortic aneurysm (mean dimensions 5.9(0.4) x 5.3(0.5) cm) containing intraluminal thrombus. Luminal boundary and abdominal aortic aneurysm wall were scanned separately. Compliance (C) was computed as C = (Amax - Amin)/[Amax(Pmax - Pmin)], where 'max and 'min' represent maximum and minimum values, respectively. Mean compliance was lower for the abdominal aortic aneurysm wall alone than for the luminal surface enclosed by intraluminal thrombus: 4.0(0.9) x 10(-4)/mmHg versus 9.8(1.7) x 10(-4)/mmHg (P < 0.01). Intraluminal thrombus area was nearly constant over the cardiac cycle, indicating that the thrombus is virtually incompressible. This noninvasive method to assess biomechanical features of abdominal aortic aneurysm has potential to further the understanding of the influences of intraluminal thrombus on aneurysm disease.     

Profibrillatory effects of intracoronary thrombus in acute regional ischemia of the in situ porcine heart

BACKGROUND: An intracoronary thrombus during regional ischemia is related to life-threatening arrhythmias. The electrophysiological consequences of a thrombus are unknown. METHODS AND RESULTS: In open chest pigs, regional ischemia was induced by intracoronary injection of a thrombus (protocol 1). In protocol 2, coronary ligation was followed by injection of heparinized blood. Three consecutive episodes of ischemia (10 minutes) and reperfusion (20 minutes) were studied in protocols 3 and 4 (ligation). During the former, an intracoronary thrombus started the third period of ischemia. Multiple (78) local electrograms were recorded simultaneously, and activation patterns were determined. In a first period of ischemia, ventricular fibrillation (during the first 10 minutes) occurred more often after intracoronary thrombosis than during the other protocols (4/7 versus 2/19, P<.05) despite similar size of the ischemic tissue. The incidence of delayed arrhythmias (between 15 and 30 minutes) was not different. Epicardial activation delay was larger 2 to 4 minutes after intracoronary thrombosis compared with ligation. ST elevation was larger with than without a thrombus (2 minutes of ischemia, 12.9+/-4.1 versus 8.2+/-3.0 mV; +/-SD, P<.05). In protocols 3 and 4 the second period and third period of ischemia were similar irrespective of the presence of an intracoronary thrombus. CONCLUSIONS: More conduction slowing underlies the profibrillatory effect of an intracoronary thrombus relative to coronary ligation. After preconditioning with ischemia, the profibrillatory effects are no longer detectable.     

The Fab-fragment of a PAI-1 inhibiting antibody reduces thrombus size and restores blood flow in a rat model of arterial thrombosis

The effect of PRAP-1, a Fab-fragment of a PAI-1-inhibiting polyclonal antibody, on thrombus size and arterial blood flow was studied in a rat model of arterial thrombosis. It was shown that exposure of the carotid artery to FeCl3 led to the rapid formation of an occlusive thrombus with a morphology similar to that of arterial thrombi found in humans. Tranexamic acid (50 mg/kg), an inhibitor of fibrinolysis, increased thrombus size (p = 0.014) when given intravenously (i.v.) prior to the FeCl3-exposure. Heparin (1000 U), when given i.v. after FeCl3, did not affect the thrombus size per se, but caused a reduction in the interindividual variation of the size of the thrombus (p < 0.05). Thus, heparin was included in all the subsequent experiments. An i.v. infusion of t-PA (1 mg/kg/h), starting before thrombus formation, induced a 3.3 fold increase in the perfusion rate (p = 0.006) and a 67% reduction in the thrombus size (P < 0.001). PRAP-1, an inhibitor of rat PAI-1 activity, was given i.v. as a bolus followed by an infusion. Two doses of PRAP-1 were studied (7.5 and 15 mg/kg/h), and the administration of the PAI-1 inhibitor was started 10 min before FeCl3. The lower PRAP-1 dose caused a 3.8 fold increase in perfusion rate (p = 0.036), a 1.44 fold increase in the time to occlusion (p = 0.034), and the thrombus size was decreased by 18% (p = 0.104). The corresponding effects of the high PRAP-1 dose were a 6.5 fold increase in perfusion rate (p < 0.001), a 1.6 fold increase in time to occlusion (p = 0.038) and a 32% reduction in thrombus size (p = 0.016). It is concluded that an inhibitor of PAI-1 activity, PRAP-1, caused a moderate decrease in thrombus size and partly restores blood flow in a rat model of arterial thrombus. This finding suggests a potential role for an inhibitor of PAI-1 in the treatment of arterial thrombosis.     

Two rare cases of neovascularity on coronary angiography (author's transl)

The appearance of neovascularity on coronary angiography is described in two patients. A large thrombus was documented in one case at autopsy, whilst in the second case the presence of a thrombus was confirmed by two subsequent coronary arteriographic and ventriculographic studies. Thus, the observation of neovascularity of the left ventricle on angiography is indicative of thrombus formation rather than the presence of a neoplasm.     

Coronary angiographic finding of thrombus in the left atrial appendage

PURPOSE: The value of coronary angiography in the diagnosis of thrombus in the left atrial appendage (LAA) was retrospectively analyzed. MATERIAL AND METHODS: The study covers 34 patients in whom coronary angiography showed coronary neovascularity in LAA with coronary artery-left atrial fistula indicating LAA thrombus. All 34 patients underwent transthoracic echocardiography within one week of coronary angiography. Open-heart surgery was undertaken 2-31 months after angiography in 28 patients. RESULTS: Coronary neovascularity and coronary artery-left atrial fistula arose from the left circumflex artery in 28 patients, and from the left circumflex artery and the right coronary artery in the remaining 6 patients. By echocardiography, LAA thrombus was detected in only one of the 34 patients. In 18 of the 28 patients who underwent open-heart surgery, LAA thrombus was found at surgery to have resolved. CONCLUSION: Coronary angiography is useful in the diagnosis of LAA thrombus, and coronary neovascularity and fistula formation may indicate that the thrombus can spontaneously resolve.     

Right atrial thrombus in a patient with stage IV carcinoma of the lung: is the surgical treatment the correct choice?

Thrombus in the right atrium or ventricle is rare and carries a mortality rate of 40%. Death frequently occurs when the thrombus moves toward the pulmonary arteries. Emergent treatment is therefore required. However there is no clear consensus regarding therapeutic management. We present here a patient with right atrial thrombus who underwent surgical exploration of the right atrium and successful thrombectomy.