Left Ventricular Thrombosis, Wall Motion Abnormalities, and Blood Viscosity Changes after First Transmural Anterior Myocardi81lnfarction*

Transcription

1 Left Ventricular Thrombosis, Wall Motion Abnormalities, and Blood Viscosity Changes after First Transmural Anterior Myocardi81lnfarction* Sudhir K. Bhatnagar, M.R.C.P.; Aranka Hudak, M.D.; and Abdul Razzak Al-Yusuf, F.R. C. P. Sixty-three consecutive patients with a first transmural anterior myocardial infarction (MI) were studied by serial two-dimensional echocardiography (2D echo) to relate left venbicular (LV) thrombosis with (1) serial changes in blood and plasma viscosity and 6brinogen levels, and (2) wall motion abnormalities at the thrombus site, in order to identify those prone to this complication. The results suggest that an early 2D echo be performed in all patients with acute transmural anterior MI to detect LV thrombi and to identify those at risk of thrombosis. The incidence of left ventricular (LV) thrombosis after acute myocardial infarction (MI) determined by two-dimensional echocardiography (2D echo) varies from 14 to 17 percent. L2 In these studies, LV thrombi were found to be presentalmostexclusively in patients with transmural anterior MI. The association of LV thrombosis with the presence ofsignificant wall motion abnormalities at that site is well confirmed, 1-3 but the presence ofcongestive cardiac failure in patients with acute MI, although reported to be a factor in the development of LV thrombus, 4 was not confirmed by others. L2 The changes in the circulating blood and rate of blood fl~ and changes in the vessel wall are the primary factors for thrombus formation. The interaction among these factors in the development ofthrombus in arteries and veins has been well reviewed. 5 Hence, in one study, an association between high blood viscosity and extensive coronary artery disease, perhaps due to an increased tendency for arterial thrombosis, has been reported. 6 In the setting ofacute MI, a rise in blood viscosity7 and fibrinogen7.8 is known to occur and an increased risk of intracardiac clotting and thromboembolism in these patients was also shown. Whether increased blood viscosity and its constituents also favors the development ofa LV thrombus has not yet been investigated. In this context, utilizing 2D echo, we report a prospective study of consecutive patients admitted with a first transmural anterior MI. The purpose ofthis study was (1) to relate the development oflv thrombus with changes in blood and plasma viscosity and fibrinogen levels ifany, in order to identify patients prone to -From the Faculty of Medicine, Kuwait University, Kuwait. Manuscript received October 15; revision accepted Jan~ 3. Reprint request8: Dr. Bhatnagar, A,sUtant &e'8or of Medicine, PO BO% HawaUi, Kuwait (Arabian Gulf) 40 this complication, and (2) to correlate 2D echo wall motion abnormalities with LV thrombosis in these patients. METHODS During a nine-month period, 63 consecutive patients admitted to the coronary care unit with a first transmural anterior MI were studied. Patients with history and/or ECG evidence ofprevious infarction were not included in the study. Diagnosis oftransmural anterior MI was based on the following: (1) the presence oftypical prolonged cardiac pain; (2) development ofnewqwaves ~o. 04 s in leads V 1 -V 4 (anteroseptal MI) and leads 1, avl, Vs-V s (anterolateral MI); and (3) greaterthan twofold elevation ofserum creatine kinase (CK) with positive MB fraction (normal levels: total CIC: 35 to 232 lull, CK-MB 0 to 8 lull). Total serum CK was performed every eight hours for the first 24 hours and then daily for the next two days using a commerciallyavailable kit. The CK-MB was performedbyagarose electrophoretic determination with fluorometric evaluation. Assessment of LV failure was made clinically by Killip classification g on admission, and theworst Killip class attained during the stay in the coronary care unit was recorded. In all patients, venous blood samples were obtained and anticoagulated with EDTA for measurement of hematocrit (Gelman-Hawksley microhematocrit method), and high shear rate blood and plasmaviscosityat 23 to25 C (Ostwald type capillaryviscometer, diameter: O.8mm; flow rate: 0.04 mils) on admission, and thereafter daily until the highest (peak) levels had begun tofall. In 27 consecutive patients, plasmafibrinogen was also determined daily by means ofcommercially available fibrinogen kit for at least six days after their admission, and the peak level was recorded. Ifthe fibrinogen levels continued to rise, more samples were obtained to record the peak level. Ninety seven male patients admitted to the coronary care unit in whom MI was excluded constituted an age-matched control group. These subjects were nondiabetic, free from any hepatic, renal, or overt cardiac failure, and were not receiving treatmentwith diuretics orclofibrate which effect the above measurements. A total of38 ofthese men formed a control group for plasma fibrinogen levels. Patients received anticoagulation therapy initially with intravenous heparin only ifa LV thrombus was detected by 2D echo and were not receiving any other drugs. Patients who smoked regularly and those with diabetes mellitus were included, but none had any hepatic or renal disease due to any cause. Ctwlges after Rrst Transmural AnterIor MI (Bhatnagar, Hudak, AI-Yuauf)

2 planes and agreement oftwo independent observers was required. Wall motion abnormality at the site of thrombosis was classified as normal, hypokinetic, akinetic, and dyskinetic, according to previous reports. U Thirteen patients were excluded; six had unsatisfactory 20 echo /Or analysis, three died before a second 20 echo, and four did not have satisfactory samples for analysis of blood and plasma viscosity. Thus, the study group was comprised of 50 patients (43 men, seven women) whose mean age was 52 years (range 30 to 73 yrs). Nine patients had a LV thrombus (group 1) and 41 did not (group 2). Statistical Methods Comparisonsofthe average ofcontinuous variables in the clinical groups were made by the Students' t-test /Or unpaired data, and the nonparametric Mann-Whitney V-test was used to compare the medians ofdiscrete variables. The normal z-test was used to assess the differences between proportions. FIGURE 1A (upper). Apical four-chamber view 0(a patient showing an apical thrombus (arrows) protruding into the left ventricle (LV), LA is left atrium; RV, right ventricle; RA, right atrium. B (lower). Parasternal short axis view of the LV apex in the same patient showing the thrombus (lj in the center. Echocardiography A 20 echo was performed with a wide angle (90") phased array sector scanner (3.5 mhz, Aloka SSO-810). All patients were examined on day 3 and day 10 after the acute Ml. Standard LV 20 echo views from left parasternal (multiple long and short axis views) and apical (two and /Our chamber views) transducer positions were recorded on videotape for analysis. Apical views were obtained utilizing shallow depth of field settings of 7.5 or 10 cm in order to avoid near field artifacts, and multiple gain settings and reject controls were used to avoid misinterpretations of apical anatomy (Fig 1 and 2). Athrombus was defined as an echo-dense mass in the left ventricle that had distinct margins clearly delineated from the underlying endocardial echoes and associated with an adjacent wall motion abnormality.3.1. The diagnosis oflv thrombosis had to be confirmed in at least two RESUITS Clinical characteristics of the patients studied are shown in 'Thble 1. There was no significant difference between the two groups. The laboratory measurements of the patients with and without LV thrombosis are shown in Table 2. There was no significant difference between the two groups with respect to any of the measurements performed. Exceptfur admission plasmaviscosity in both groupsof patientsand admission hematocrit in group2 patients, all measurements were significantly higherwhen compared to the controls. As serial plasma fibrinogen was estimated in only 27 patients (six with and 21 without a thrombus), its peak level and other laboratory measurement data are shown in 'Thble 3. The average admission plasma fibrinogen level in 38 male control subjects was 2.7 ± 0.4 gil. The fibrinogen level peaked on the fifth post MI day in almost all patients and averaged 5.2 (±1.6) gil. Although there was a significant difference between the level ofpeak fibrinogen between patients with and without LV thrombosis (p<o.oo5), neither the admission nor the peak hematocrit, blood and plasma viscosity differed among these patients. Table l-cunical ChtJracteriatica of Acute Anterior :&ammural Ml Patients with and without Left Ventricular Thrombua (LVT) Characteristics Sex Mean age (:t SO) (years) No. of smokerst No. of patients with diabetes mellitus No. of patients in Killip class Admission Worst Creatine kinase (lull) (mean:tso) Group 1 LVT (n=9)* All males 51:t K1 K O:t2452 *Differences not significant. tsmoked cigarettes regularly ;;!o20/day. Group 2 No LVT (n =41)* Males 34, Females 7 52:t K1 K2 K :t 1601 CHEST I 88 I 1 I JULY,

3 All thrombi detected in the nine patients were along the LV apex (Fig 1 and 2 shown as examples). In five patients, these LV thrombi were detected on day 3 and in four, on day 10 after the acute MI. The LV apical wall motion during the initial2d echo study in all patients with and without LV thrombi is compared in Table 4. These results remained unchanged at the timeofsecond 2Decho study. Theassociation of wall motion abnormality with the development of apical thrombosis was significant. Of all 23 patients who had an akinetic/dyskinetic apex, seven (30 percent) developed a LV thrombus (p<0.05 for group 1 vs 2). Of those 18 patients who had hypokinesis ofthis site, two (11 percent) had thrombosis (p = for patients with and without thrombosis). No patient with a LV thrombosis had a normal apical wall motion. DISCUSSION FIGURE 2. Apical two-charnber view (slightly modified) showing a large thrombus (arrows) filling up the apex in another patient. Abbreviations same as in Figure 1. cent and the incidence of LV thrombosis in transmural anterior MI was 18 percent, confirming our previous observation.' Our results did not indicate that hematocrit, and blood and plasma viscosity measured in patients with acute MI soon after their admission could identify those prone to develop subsequent LV thrombosis. We deduce this because, although the admission and peak values ofthese measurements were higher in patients who developed LV thrombi compared with those who did not, the difference was not significant. These results remained unchanged whether or not women were included in the comparative analysis of the two groups of patients. Plasma fibrinogen levels have been found to rise around thefourth to fifth day following acute MI We measured fibrinogen in 54 percent ofour patients, and its average admission and peak concentration in them was significantly higher compared to the control values. Its mean peak level in patients with LV thrombi In the current study, the success rate of obtaining 2D echo images to diagnose LV thrombosis was 90 per- Table 2-Laboratory MetJIUnmaenU Data (Ezprnud as Meam±SD) Controls Group 1- Group 2- (Range) LVT Present No LVT All males All males Male & Females, n=41 n=97 n=9 pt (only males, n = 34) pi Hematocrit Admission 45: :5.5 < :5.7 (%) (40-51%) (47.h5.6) «0.025) Peak 51.2:5.1 < :5.6 <0.005 (49.0:5.3) «0.001) Blood Viscosity Admission 5.8: : 1.7 < :1.8 <0.025 (mpas) ( } (6.h2.0) «0.025) Peak 8.1:1.8 < : 1.9 <0.001 (7.5:2.1) «0.001) Plasma viscosity Admission 1.75: : :0.15 (mpa s) ( } Peak 2.17:0.13 < :0.20 < p= for group 1 vs 2. tp= group 1 vs control subjects. ip = group 2 vs control subjects. LVT is left ventricular thrombus; conversion: SI to traditional units = viscosity; 1 mpas = Icp. Values for only males (n = 34) in group 2 and their comparison with control subjects are shown in parentheses. 42 Changes after First ltansmural Anterior MI (Bhatneg8T, Hudllk, AI-Yusuf)

4 Table 3-Peak Fibrinogen ~,. Gnd Other laboratory Meaurernenta in 27 Male PatientI with andtdithout Left Ventricultlr Thrombua (LVT) Plasma fibrinogen Admission (gil) Peak Hematocrit Admission ('II) Peak Blood viscosity Admission (mpa s) Peak Plasma viscosity Admission (mpa s) Peak (LVf present) (n=6) 3.7± ±0.9 49±5.7 5O± ± ± ± ±0.15 p<o.ooi when compared to control subjects in both groups. tp=comparison between patients with and without LVI: Plasma fibrinogen level in male controls =2.7± 0.4 vll. was also significantly higher when compared to those without this complication, and in almost all patients, the recorded peak was around the fifth day after the acute MI. However, the expected difference between the peakplasmaviscosity ofthese patients as a result of higher fibrinogen levels in patients with thrombi was not seen, probablyowing todifferences in otherplasma proteins and/or comparison between small numbers of patients. Peak blood viscosity was similarly no different among these patients. This could be because unlike plasma viscosity, in these patients we have compared only the highest levels ofblood viscosity and not its level atthe timeofpeak fibrinogen concentrations. Fulton et al 8 have reported nonfatal thromboembolism in those patients with acute MI whose plasmafibrinogen exceeded 750 mg/dl and suggested that these patients may have intracardiac clotting. HoweveJ; they did not use any method to demonstrate LV thrombi in their patients, as in our study. Significant apical wall motion abnormality detected by 2D echo seemed to be an important predisposing factor for LV thrombosis at this site. These abnormalities were present initially at the time the thrombus was visualized on day 3 after the acute MI in five patients and preceded the thrombosis diagnosed on day 10 in the other four patients. No patient with a LV thrombus had a normal apical wall motion. Thus, the difference Table 4-ComptJrUon ofleft VentricultJr Apical Wall Motion in Patten" with and without Left Ventricultlr Thrombua (LVT) during Initw2D Echo Study Type ofwall Motion Normal Hypokinesis Akinesis Dyskinesis No. of Patients Group 1 (LVf present) o (No LVT) (n=21) 3.8± ± ±3.9 5O± ± ± ± ±0.13 Group 2 (No LVT) o Akinesis and dyskinesis considered together for statistical analysis. pt <0.005 p <0.01 <0.05 between patients with and without LV thrombi with regard to the association ofakinesis and dyskinesis of the apex and LV thrombosis was very cleat: Neither the peak serum CK nor the Killip class assigned to the patients on admission or during their stay in the coronary care unit was significantly different between patients who did and did not develop thrombi. This probably indicated that clinical LV failure and cardiac enzymes have a limited predictive value for the selection of patients at high risk of LV thrombosis and confirms results ofprevious studies. 1.2 Thrombi in blood vessels seem to develop in the presence ofstasis ofblood, vessel injury, 5 and perhaps due to increased blood viscosity and fibrinogen. 6 Wilhelmsen et al lj have recently reported a significant relation between the high plasma fibrinogen levels and incidence of MI in men by univariate analysis. In this study, the authors have suggested the increased risk of early thrombosis at an atherosclerotic plaque in the presence of high fibrinogen levels, in addition to the interaction of local disturbances in prostaglandin balance, catecholamine concentration and ph, with the fibrinolytic processes. Endocardial injury occurs during the acute MI and stasis ofblood at the LV apex due to akinesis together with the forme!; probably contributes towards thrombus development at this site as shown in previous studies..13 Whether changes in blood constituents could also playa role in LV thrombus formation is not clear, but results of the current study did not support this idea. Although increased plasma fibrinogen concentrations did appear to be important in this context, the number of patients thus studiedwas small, andfurther studies are necessary for a definite conclusion. We undertook this study in patients with acute MI to see ifsimple measurements of hematocrit, blood and plasma viscosity, and fibrinogen could be related to the subsequent LV thrombosis. Hence, complex platelet functions and tests for red blood cell aggregation, rigidity, and deformibility were not undertaken. Patients with diabetes mellitus and those who smoked were included in the study, although changes in hematocrit blood and plasmaviscosity, and fibrinogen are known to occur in them Exclusion ofsuch patients is not meaningful, as a considerable numberofpatients with acute MI could be smokers and have diabetes mellitus. These factors, however, did not seem to affect the analysis of our patients' results. Fresh mural thrombi induced experimentally in dogs were reported to be comprised predominantly ofplatelets and red blood cells entrapped in fibrin. 16 This could possibly mean that the role ofplatelets and red blood cells may be important and needs to be studied more carefully in order to identify patients likely to develop a LV thrombus. CHEST I 88 I 1 I JULY,

5 CLINICAL IMPLICATIO AND CONCLUSIO. Whole blood viscosity is elevated and remains so for a period ofabout three weeks after the acute MI in a majorityofpatients.7 Plasma fibrinogen also rises, but at a later date after the MI. 8.ll Hence, both these measurements do not seem to be of much help for an early identification ofpatients prone to develop subsequent LV thrombosis. In the current study, neither the admission nor the peak hematocrit, and blood and plasma viscosity were significantly different between patients with and without LV thrombosis, although the peak fibrinogen concentrations were significantly higher in those who developed LV thrombi. On the other hand, 2D echo wall motion abnormality at the site oflv thrombosis was significantly related to this complication in all patients and precededthe diagnosis in about one half of them. It is therefore desirable to undertake 2D echo in all patients with acute transmural anterior MI as early as the third day not only to diagnose LV thrombi, but to identify patients at high risk for LV thrombosis. Meanwhile, further studies are clearly indicated to define the role offibrinogen in the development of LV thrombi after acute MI. REFERENCES 1 Bbatnagar SK, Al-Yusuf AR. Left ventricular thrombi after myocardial infarction. Postgrad Med J 1983; 59: Asinger R~ Mikell FL, ElspergerJ, Hodges M. Incidence ofleft ventricular thrombosis after acute transmural myocardial infarction: serial evaluation by two dimensional echocardiography. N Eng} J Med 1981; 305: Asinger R~ Mikell FL, Sharma B, Hodges M. Observations on detecting left ventricular thrombus with two dimensional echocardiography: emphasis on avoidance offalse positive diagnosis. Am J Cardioll981; 47: Jordan RA, Miller RD, Edwards JE, Parker RL. Thromboembolism in acute and in healed myocardial infarction. Circulation 1952; 6,1-6 5 Mustard JF, Packham MA, Kinlough-Rathbone RL. Mechanisms in thrombosis. In: Bloom AL, Thomas D~ Haemostasis and thrombosis. 1st ed. New York: Churchill Livingstone, 1981: Lowe GOO, Drummond MM, Lorimer AR, Hutton I, Forbes CD, Prentice CRM, et ale Relation between extent ofcoronary artery disease and blood viscosity. Br Med J 1980; 280: Jan Kung-Ming, Chen Shu, Bigger1: Observations on blood viscosity changes after acute myocardial infarction. Circulation 1975; 51: Fulton RM, Duckett K. Plasma fibrinogen and thromboembolism after myocardial infarction. Lancet 1976; 2: Killip TIn, Kimbell.n: Ueatment ofmyocardial infarction in a coronary care unit: a two year experience with 250 patients. Am J Cardiol 1967;20: Meltzer RS, Guthaner D, Rakowski H, Popp RL, Martin ~ Diagnosis ofleftventricularthrombi bytwo dimensional echocardiography. Br Heart J1979; 42: Dormandy J, Ernst E, Mataria A, Flute P1: Hemorrheologic changes following acute myocardial infarction. Prog Cardiol 1982; 104: Wtlhelmsen L, Svardsudd K, Bengsten KK, Larsson B, Welin L, libblin G. N Eng} J Med 1984; 311: Solandt DY, Nassim R, Bett CH. Production and prevention of cardiac mural thrombosis in dogs. Lancet 1939; 2: Dintefass L. The clinical impact ofthe newer research in blood rheology: an overview. Angiology 1981; 32: DintefassL. Elevationofbloodviscosity, aggregationofred cells, haematocrit values and fibrinogen levels in cigarette smokers. Med J Aust 1975; 1: Mikell FL, Asinger R~ Elsperger KJ, Anderson WR, Hodges M. TIssue acoustic properties of fresh left ventricular thrombi and visualization bytwo-dimensionalechocardiography-experimental observations. Am J Cardioll982; 49: Ch8ngee after RratlransmuralAnterior MI (BMlnagar, Hudelc, AJ-YusuI)