Factor V Leiden and its relation to left ventricular thrombus in acute myocardial infarction

OBJECTIVE: The genetic defect of coagulation factor V, known as factor V Leiden, produces a resistance to degradation by activated protein C (APC) and increases the risk of venous thrombosis. However, the role of factor V Leiden in the formation of left ventricular (LV) thrombus has not been studied. We investigated whether factor V Leiden is a risk factor for LV thrombus in patients with acute myocardial infarction (AMI). METHODS and RESULTS: We have analyzed clinical, echocardiographic and biochemical data in 135 consecutive patients (aged 58 +/- 13 years; 31 women) with first anterior AMI. Two-dimensional echocardiographic examination was performed on days 1, 3, 7, 15 and 30; LV thrombus was detected in 33 (24.4%) of 135 patients with AMI. The study also included 95 control subjects. Healthy age and sex-matched subjects without a personal or family history of ischaemic heart disease, stroke or thromboembolic disease served as a control group. Blood samples from the patients and controls were analyzed for the factor V Leiden mutation by DNA analysis, using the polymerase chain reaction. In addition, concentrations of fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and D-dimer were measured in 135 patients. There was no significant difference in the prevalence of factor V Leiden between patients and control subjects. The prevalence of the factor V mutation was 9% (3/33) in patients with thrombus, and 7.7% (8/103) in patients without thrombus. The prevalence of factor V Leiden was 7.3% (7/95) in control subjects. No significant differences in plasma fibrinogen (480 +/- 195 vs. 444 +/- 179 mg/dl, p = 0.6), D-dimer (471 +/- 256 vs. 497 +/- 293 ng/dl, p = 0.7), vWF (112 +/- 18 vs. 103 +/- 15%, p=0.5), PAI-1 (26.7+/- 9.8 vs. 28.1 +/- 10.2 ng/dl, p = 0.6), and t-PA (19.8 +/- 8.7 vs. 17.2 +/- 9.1 ng/dl, p = 0.7), levels are found in patients with LV thrombus when compared with those without LV thrombus. Multivariate analyses showed that peak creatine kinase level (p = 0.002) and LV wall motion score index (p = 0.003) were independent predictors of LV thrombus formation. CONCLUSION: Factor V Leiden mutation is not a risk factor for LV thrombus formation in patients with AMI.     

Serum lipoprotein(a) and its relation to left ventricular thrombus in patients with acute myocardial infarction

It is well known that the incidence of left ventricular (LV) thrombosis is high in patients with acute myocardial infarction (AMI). Due to the high degree of structural homology with plasminogen, lipoprotein(a) may produce thrombogenic effects by modulating the fibrinolytic system. However, the role of Lp(a) level in the formation of LV thrombus has not been studied. This study sought to determine whether Lp(a) is a risk factor for LV thrombus in patients with AMI. We have analyzed clinical, echocardiographic and biochemical data in 102 consecutive patients (aged 58+/-12 years, 92 men / 10 women) with first anterior AMI. Two-dimensional examination was performed on days 1, 3, 7, 15, and 30. Blood samples were obtained within 12 h after the onset of symptoms and before beginning the therapy. Plasma levels of fibrinogen and Lp(a) were measured using enzyme-linked immunosorbent assay and immunonephelometric methods, respectively. LV thrombus was detected in 20 (20.3%) patients. No significant difference was found for admission Lp(a) levels between patients with or without thrombus (30.5+/-17.2 vs 32.3+/-22.4 mg/dl, p = 0.7). Univariate analysis showed that patients with LV thrombus had a higher wall motion score index (1.8+/-0.3 vs 1.4+/-0.3, p = 0.002), a higher peak creatine kinase level (2945+/-898 vs 1805+/-1336, I / U p = 0.004), a larger end-diastolic volume (139.7+/-38.6 vs 114.1+/-41.8 ml, p = 0.04), a larger end-systolic volume (83.1+/-34.3 vs 59.2+/-30.6 ml, p = 0.02 ), and a lower ejection fraction (38+/-12 vs 47+/-11, p = 0.04). In multivariate analyses, only peak creatine kinase level (p = 0.04) and LV wall motion score index (p = 0.002) were independent predictors of left ventricular thrombus formation. These results suggest that Lp (a) is not a risk factor for LV thrombus in patients with AMI. Our data demonstrate that the best predictors of LV thrombus formation after AMI are a high peak creatine kinase level and a high LV wall motion score index.     

急性心肌梗死后左室重构的临床危险因素探讨

目的对急性心肌梗死后左室重构的临床危险因素进行评估。方法将进入本观察的５１例病人,按溶栓治疗后,有无Ｑ波形成,分为Ｑ波组和非Ｑ波组,全部病人入住ＣＣＵ,并在入院即刻及入院后８、１６、２４、４８和７２小时分别进行血清心肌酶学检查。对其中３４例病人在心梗后１周和６周行超声心动图检查,并测定左室质量指数。结果Ｑ波组血清ＣＰＫ峰值（１３４７５８±２２０３３）ＩＵ,左室质量指数在心梗后１周和６周分别为（２３４２８±９２３６）ｇ·ｍ－２、（２７１５２±９３１２）ｇ·ｍ－２,均明显高于非Ｑ波组,随访半年表明新近出现心衰亦明显高于非Ｑ波组。结论溶栓后的有Ｑ波出现,血清ＣＰＫ峰值高于５００ＩＵ,左室质量指数＞２２０ｇ·ｍ－２,是急性心肌梗死后左室重构的危险因素。     

Magnesium dynamics and relation to left ventricular function in acute myocardial infarction

The present study investigated the serial changes in serum magnesium (Mg) and erythrocyte concentration of Mg in patients with acute myocardial infarction (AMI) and the relationship between these changes and left ventricular ejection fraction (LVEF) at 1 month after the onset of infarction. The study group comprised 26 patients with AMI (mean age, 57.9+/-8.9 years). Serum Mg and erythrocyte Mg were measured on hospital days 1, 2, 4, 7 and 21. The change in erythrocyte Mg during the acute phase was calculated as a ratio: [(erythrocyte Mg at day 2)-(erythrocyte Mg at day 1)]/(erythrocyte Mg at day 1). The change in serum Mg was calculated similarly. The following results were obtained. (1) Serum Mg tended to increase from the onset of myocardial infarction (day 1: 1.86+/-0.19, day 2: 1.93+/-0.22, day 4: 2.17+/-0.23; day 7: 2.25+/-0.20; day 21: 2.12+/-0.15 mg/dl). (2) Erythrocyte Mg on day 2 and day 4 showed a significant decrease compared with day 1 (day 1: 2.45+/-0.40, day 2: 2.09+/-0.41, day 4: 2.07+/-0.37, day 7: 2.22+/-0.33, day 7: 2.34+/-0.28 mg/dl per 400x10(4)/mm3 cells). (3) A significant positive correlation was observed between the change in serum Mg and LVEF (r=0.55, p<0.05), and a significant negative correlation was observed between the change in erythrocyte Mg and LVEF (r=-0.57, p<0.05). Thus, it was concluded that an extracellular shift in intracellular Mg occurred during the first 2 days after the onset of myocardial infarction. This responsive increase in the extracellular Mg level may be an important factor for maintaining left ventricular function in patients 1 month after the onset of AMI.     

Clinical predictors of early left ventricular thrombus formation in acute myocardial infarction

OBJECTIVE: Clinical epidemiological and echocardiographic risk factors relating to the development of a left ventricular thrombus were studied retrospectively in patients with acute myocardial infarction. METHODS AND RESULTS: The data on 1833 consecutive patients treated for acute myocardial infarction during a 10-year period were processed retrospectively. Transthoracic echocardiography was performed on each patient 65.0 +/- 5.5 hours after hospital admission. A left ventricular thrombus was detected in 145 patients (7.9%). The patients with acute myocardial infarction and a left ventricular thrombus had significantly lower frequencies of 1) myocardial infarction in their family history (3% versus 11%, respectively), 2) hospital admission within 24 hours from the onset of chest pain (17% versus 50%, respectively), 3) thrombolytic therapy (8% versus 23%, respectively) and 4) current smoking (24% and 35%, respectively) than those without a left ventricular thrombus. In contrast, anterior infarction (81% versus 38%, respectively), left ventricular dilatation (30% versus 19%, respectively), dyskinesis of the left ventricular wall (23% versus 10%, respectively), an aneurysm (22% versus 7%, respectively) and a reduced systolic left ventricular function (ejection fraction < 40%) (28% versus 17%, respectively) were more frequent in the presence of a left ventricular thrombus after myocardial infarction. Multivariate analysis of the results revealed that the presence of anterior myocardial infarction and an aneurysm is associated with significantly increased hazard ratios. On the other hand, early hospitalization and a positive family history of infarction significantly lowered the hazard ratio. The frequency of a left ventricular thrombus was significantly higher in spring and winter. CONCLUSIONS: The results presented in this paper confirm the significant hazard of certain parameters [location of infarction (anterior) and aneurysm] as concerns left ventricular thrombus formation among patients with acute myocardial infarction. Early hospitalization was found to lower the risk of thrombus formation.These echocardiographic and clinical parameters may be useful in the establishment of the individual risk of intracavital thrombus formation and may be of help in everyday medical practice.     

C-Reactive protein as a risk factor for left ventricular thrombus in patients with acute myocardial infarction

BACKGROUND: Elevated C-reactive protein (CRP) has been found to correlate with higher risk for cardiac events in patients with acute myocardial infarction (AMI). It has been suggested that CRP may be involved in initiation process of coagulation; however, the role of CRP level in the formation of left ventricular (LV) thrombus has not been studied. HYPOTHESIS: This study investigated whether CRP is a risk factor for LV thrombus in patients with AMI. METHODS: Clinical, echocardiographic, and biochemical data were analyzed in 141 consecutive patients (aged 57 +/- 13 years; 33 women) with first anterior AMI. Two-dimensional and Doppler echocardiographic examinations were performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained every day during hospitalization. Serum CRP concentrations were measured by an ultrasensitive immunonephelometry method. RESULTS: Left ventricular thrombus was detected in 33 (23.4%) patients. Univariate analysis showed that patients with LV thrombus had a higher peak creatine kinase (CK) level (2,879 +/- 742 vs. 1,693 +/- 1,210 I/U, p = 0.001), higher peak CRP level (14.9 +/- 7.1 vs. 9.2 +/- 6.8 mg/dl, p = 0.001), higher wall motion score index (1.8 +/- 0.2 vs. 1.5 +/- 0.3, p = 0.002), higher apical wall motion score index (2.35 +/- 0.72 vs. 2.07 +/- 0.70, p = 0.001), larger end-diastolic volume (145.2 +/- 43.7 vs. 116.5 +/- 44.2 ml, p = 0.002), larger end-systolic volume (85.4 +/- 37.2 vs. 62.9 +/- 31.6 ml, p = 0.003), and lower ejection fraction (42.1 +/- 12 vs. 47.3 +/- 13, p = 0.04). In multivariate analyses, only peak CK level (p = 0.0001), LV apical wall motion score index (p = 0.001), and CRP levels (p = 0.001) were independent predictors of LV thrombus formation. CONCLUSIONS: These results suggest that CRP is a risk factor for LV thrombus in patients with AMI.     

Usefulness of high-dose anticoagulants in preventing left ventricular thrombus in acute myocardial infarction

Fifty-three patients with a suspected first anterior wall acute myocardial infarction (AMI) were randomized to intervention with intravenous heparin followed by oral warfarin (26 patients) or matching placebo (27 patients). The regimen was started within 12 hours after the onset of AMI. Anticoagulation was maintained at a therapeutic level (for heparin, activated partial thromboplastin time 70 to 140 seconds; for warfarin, thrombotest 5 to 10%) for 10 days, and no bleeding episodes occurred. The baseline characteristics of the 2 study groups were well matched. In 7 patients in the placebo group and in none in the anticoagulant group, left ventricular thrombus developed during the study, as detected by serial 2-dimensional echocardiography. Early intervention with high-dose anticoagulant drugs may prevent the development of left ventricular thrombus in anterior wall AMI.     

Influence of coronary arterial thrombus location on left ventricular function in acute myocardial infarction

In 238 patients with acute myocardial infarction studied during intracoronary streptokinase therapy, the circumferential extent of left ventricular hypokinesis was measured by 5 methods and correlated with the location of the infarct-related coronary artery segment and with 1-year survival. Of the 5 methods, 1 focused only on the infarct region, and 4 varied in the complexity of the noise filter. Hypokinetic segment length measurements by all 5 methods correlated significantly with the location of occlusion along the left anterior descending coronary artery. No method yielded measurements that correlated with occlusion location along the right coronary artery. Measurements by all methods correlated significantly with survival, but the method that focused on the infarct region performed least well. Thus, the circumferential extent of hypokinesis in patients with acute myocardial infarction is greater for proximal than mid- or distal occlusions of the left anterior descending but not the right coronary artery. Survival is influenced by the function of periinfarct and noninfarct regions and by the function of the infarct region. Complex noise filters provide no advantage over simpler filters in measuring the extent of hypokinesis.     

Usefulness of mitral regurgitation in protecting against left ventricular thrombus after acute myocardial infarction

In conclusion, we documented an increased incidence of LV thrombus in patients with MR after AMI.     

Prospective two-dimensional echocardiographic evaluation of left ventricular thrombus and embolism after acute myocardial infarction

To determine whether two-dimensional echocardiography can identify patients with left ventricular thrombus after myocardial infarction who are prone to embolism, clinical and echocardiographic variables in 541 patients with a first infarction between 1979 and 1983 were studied prospectively. The first echocardiogram showed definite thrombus in 115 patients (Group 1, 21%) and no thrombus in 426 (Group 2, control). In Group 1, 27 patients (23%) had clinical evidence of systemic embolism related to the thrombus before referral (Group 1a) and 88 did not (Group 1b); these two groups were similar in age, gender and infarct location, but more Group 1a patients were within 1 month of the acute infarction. In both Groups 1a and 1b, the thrombus was found in apical views over asynergic zones, with no difference (p greater than 0.05) between the two groups in the size (average area from two views being 5.3 versus 4.5 cm2), type (protruding in apical views 30% versus 27%), location (apical 83% versus 86%; septal 11% versus 11%; posterior 4% versus 2%), extent of asynergy (31% versus 33%) and ejection fraction (33% versus 34%). However, the frequency of anticoagulant therapy was less (26% versus 63%, p less than 0.005), adjacent hyperkinesia greater (100% versus 49%, p less than 0.005) and thrombus mobility greater (81% versus 19%, p less than 0.005) in Group 1a than in Group 1b. Serial echocardiograms revealed a decreased size of the thrombus by 6 months in both Groups 1a and 1b, and little or no trace in 85% by 24 months. Thus, ventricular thrombus size, location and protrusion in apical views on echocardiography did not correlate with embolism. In contrast, thrombus mobility, the presence of adjacent hyperkinesia and thrombus protrusion assessed in multiple views appeared to be strong discriminators of thrombus prone to embolism. These echocardiographic features might provide a guide for the duration of anticoagulant therapy.     

Lactate metabolism in acute myocardial infarction and its relation to regional ventricular performance

Myocardial metabolism was assessed in 20 patients with acute anterior myocardial infarction using lactate uptake (defined as (aortic lactate - great cardiac venous lactate)/aortic lactate X 100) as an index. The regional ejection fraction of the anterior wall was obtained from left ventriculography. There was a linear relation between lactate uptake and regional ejection fraction (r = 0.79, p less than 0.001). Four patients without total occlusion in the infarct vessel had a higher lactate uptake (19.6 +/- 6.7 versus 4.2 +/- 13.4%, p less than 0.05) and regional ejection fraction (26.3 +/- 7.9 versus 14.9 +/- 7.0%, p less than 0.05) than did 16 patients with total occlusion. The latter group of patients underwent intracoronary infusion of urokinase, which resulted in reperfusion in 13 patients. Lactate uptake before urokinase infusion (sample I), just after reperfusion (sample II), 30 minutes after reperfusion (sample III) and 4 weeks after reperfusion (sample IV) was 5.7 +/- 13.2, -13.9 +/- 14.7, 2.9 +/- 15.2 and 20.2 +/- 11.0%, respectively (sample I versus II and II versus III, p less than 0.01; sample I versus IV and III versus IV, p less than 0.05). The decrease in lactate uptake immediately after reperfusion, which was accompanied by an increase in creatine kinase-MB isoenzyme release into the blood, was considered to be the result of a "washout" effect. Lactate uptake was ameliorated 4 weeks later, accompanied by an improvement (from 15.1 +/- 7.1 to 23.4 +/- 7.2%, p less than 0.01) in the regional ejection fraction. It is concluded that the degree of asynergy was closely related to the extent of metabolic deterioration in myocardial infarction.     

Pulsed wave tissue Doppler-derived myocardial performance index for the assessment of left ventricular thrombus formation risk after acute myocardial infarction

Background

Assessment of left ventricular (LV) thrombosis risk after acute myocardial infarction (AMI) is important because of potential embolic sequelae that are reduced by oral anticoagulant agents. The goal of this study was to investigate whether early assessment of LV systolic and diastolic performance with pulsed wave tissue Doppler ultrasound scanning (PWTD) predicts LV thrombosis after AMI.

Methods

Two-dimensional and Doppler ultrasound scanning echocardiographic examinations were performed in 92 consecutive patients (age, 58 ± 10 years; 11 women) with first anterior AMI within 24 hours after arrival to the coronary care unit. From the apical 4-chamber view, the mitral annular velocities were recorded at the lateral corner of the mitral annulus with PWTD. The myocardial performance index (MPI), which combines parameters of both systolic and diastolic ventricular function, was calculated from the PWTD recordings. To analyze LV thrombus formation, the 2-dimensional echocardiographic examination was repeated on days 3, 7, 15, and 30. The patients were divided in 2 groups according to LV thrombus formation.

Results

LV thrombus was found in 32 of 92 patients (35%; group 1) and was not found in 60 patients (65%; group 2). The MPI was significantly higher in group 1 than in group 2 (0.73 ± 0.20 vs 0.53 ± 0.14; P <.001). When an MPI >0.6 was used as the cutoff, LV thrombus formation could be predicted with a sensitivity rate of 81%, a specificity rate of 73%, a positive predictive value of 62%, and a negative predictive value of 88%. In multivariate analyses, only MPI and LV wall motion score index were independent predictors of LV thrombus formation (P = .038 and P = .047, respectively).

Conclusions

The MPI derived with PWTD soon after admission appears to be a useful parameter for assessing the risk of LV thrombosis after AMI. Patients with an MPI >0.6 after AMI seem to be at a higher risk for thrombus formation.     

急性心肌梗死后左室重构的临床危险因素

目的对急性心肌梗死后左室重构的临床危险因素进行评估。方法将进入本观察的51例患者,按溶栓治疗后有无Q波形成,分为Q波组和非Q波组,全部患者入住CCU,并在入院即刻,入院后8、16、24、48、72h分别进行血清心肌酶学检查。对其中34例患者在心梗后1周、6周行超声心动图检查,并测定左室质量指数。结果Q波组血清CPK峰值(1347.58±220.33)IU,左室质量指数分别为234.82±92.36(1周),271.52±93.12(6周)均明显高于非Q波组,随访半年表明新近出现心衰明显高于非Q波组。结论溶栓后的有Q波出现,血清CPK峰值高于500IU,左室质量指数>220g/m3,是急性心肌梗死后左室重构的危险因素。     

Catecholaminergic activation in acute myocardial infarction: time course and relation to left ventricular performance

AIM: The study was designed to assess (1) the time course of catecholaminergic activation in acute myocardial infarction (AMI) as estimated by adrenaline (ADR) and noradrenaline (NOR) concentrations, and (2) to relate activation of these hormones to predict the outcome of cardiac performance. PATIENTS AND METHODS: Eighteen patients with first AMI were studied. Blood samples were drawn within the first 4-18 h, after 18-24 h, on day 2, day 3 and on day 6 as well as after 1 year. Radionuclide ventriculography was performed on the day of discharge and after 1 year to determine left-ventricular ejection fraction (LVEF). RESULTS: In the study group as a whole, the concentrations of ADR decreased from (mean +/- SEM) 0.80 +/- 0.12 nmol/l on admission to 0.33 +/- 0.03 nmol/l at discharge (p < 0.05). NOR decreased from 4.19 +/- 0.78 to 2.44 +/- 0.33 nmol/l (p < 0.05). Initial peak concentrations of both ADR and NOR on admission were correlated to LVEF at discharge (r = -0.56, p < 0.05 and r = -0.72, p < 0.05, respectively). If NOR was normal (<3 nmol/l) at admission, the LVEF was normal or almost normal (= 0.46) at discharge. The mean plasma level of ADR and NOR after 1 year follow-up was 0.34 +/- 0.04 and 1.95 +/- 0.25 nmol/l, respectively. The values after 1 year were unchanged compared to values at discharge, at day 6 (n.s.). Mean LVEF was 0.50 +/- 0.03 (range: 0.23-0.69) at discharge and unchanged 0.46 +/- 0.05 (range: 0.18-0.72) at 1 year follow-up (n.s.). During hospitalisation, the group with LVEF <0.50 had an 86% higher initial ADR and an 82% higher initial NOR concentration compared to values in patients with LVEF >0.50 (p < 0.05). CONCLUSION: (1) Catecholaminergic activation, as measured by plasma ADR and NOR in AMI, is acute and restricted to the first 5 days. Thereafter, the hormone levels are normal and stable. (2) The magnitude of the early catecholaminergic activation correlates with left ventricular systolic performance. (3) Normal NOR values at admittance predicts normal or almost normal LVEF at discharge.     

Usefulness of contrast echocardiography for assessment of left ventricular thrombus after acute myocardial infarction

Fifty consecutive patients referred to a coronary care unit for acute anterior myocardial infarction with ST-segment elevation underwent coronary arteriography, left ventricular (LV) angiography, and revascularization. Transthoracic echocardiography was systematically performed using fundamental imaging, second harmonic imaging, and contrast agents to assess the LV chamber. Six patients (12%) presented with a confirmed LV mural thrombus. Thirty-five percent of patients with time to revascularization>3 hours presented with an LV mural thrombus versus 0 patients with time to revascularization3 hours.     

Long-term prospective assessment of left ventricular thrombus in anterior wall acute myocardial infarction and implications for a rational approach to embolic risk

To prospectively assess the predictive value of left ventricular (LV) thrombus anatomy for defining the embolic risk after acute myocardial infarction (AMI), 2 comparable groups of patients with a first anterior AMI (group A, 97 thrombolysed patients; group B, 125 patients untreated with antithrombotic drugs [total 222]) underwent prospective serial echocardiography (follow-up 39 +/- 13 months) at different time periods. LV thrombi were detected in 26 patients in group A (27%) and in 71 in group B (57%; p <0.005). Embolism occurred in 12 patients (5.4%; 1 in group A [1%] vs 11% in group B [9%], p < 0.04). At multivariate analysis, thrombus morphologic changes were the most powerful predictor of embolism (p <0.001), followed by protruding shape (p <0.01) and mobility (p <0.02). In patients untreated with thrombolysis, a higher occurrence of thrombus morphologic changes (48% vs 8%, p <0.002) and protruding shape (69% vs 31%, p <0.002) were observed, whereas thrombus mobility was similar in the 2 groups (18% vs 8%, p = NS). Thrombus resolution occurred more frequently in thrombolysed patients (85% vs 56%, p <0.002). Thus, after anterior AMI, changes in LV thrombus anatomy frequently occur and appear the most powerful predictor of embolization. A minor prevalence of thrombus, a more favorable thrombus anatomy, and a higher resolution rate may contribute to reduce embolic risk after thrombolysis.