Predictors of statin-induced regression of left anterior descending coronary artery wall thickness as measured by high-resolution transthoracic echocardiography

BACKGROUND: Statin therapy has been shown to reduce cardiovascular risk after myocardial infarction (MI). Using a novel technique of high-resolution transthoracic echocardiography (HRTTE), we sought to assess the statin-induced changes in left anterior descending coronary artery (LAD) wall thickness in previously statin naive patients over a 12-month period. METHOD AND RESULTS: Thirty subjects underwent HRTTE assessment of their LAD wall thickness predischarge post-MI (non-LAD territory) and at 3, 6, and 12 months. The LAD anterior and posterior wall thickness and vessel luminal diameter were measured. Blood lipid levels were also assessed at each study visit. All subjects were started on moderate lipid-lowering therapy (40 mg of atorvastatin or simvastatin). There was a sustained decrease in total cholesterol (-23%), triglycerides (-19%), and low-density lipoprotein (-41%) at the 3-month visit from the baseline, with no change in high-density lipoprotein level. Overall, there was no change in the LAD wall thickness and external or vessel lumen diameter over the 12-month period. Of those that demonstrated regression, the only predictor of percentage change in the LAD wall thickness was the baseline LAD wall thickness. Conclusion: Despite a favorable change in blood lipid profile, no overall change in the LAD wall thickness was detected over a 12-month period in subjects on moderate statin therapy using HRTTE. However, using case-based analysis, regression was able to be predicted by the baseline LAD wall thickness. HRTTE may be an instructive noninvasive modality to assess response to statin intervention.     

Quantitative evaluation of left ventricular regional wall motion using a real-time wall thickness curve system with two-dimensional echocardiography

The real-time wall thickness curve system was newly developed for recording left ventricular (LV) wall thickening (WT) on a 2-dimensional echocardiogram recorded in an arbitrary direction because of the scarcity of quantitative data on wall motion change during dobutamine-induced ischemia. This study tested the feasibility of this system for quantitative evaluation of wall motion. In normal subjects, accuracy and reproducibility of measurements were evaluated by comparison with measurements on a conventional M-mode echocardiogram and examination of inter- and intraobserver variability. In 28 patients with coronary artery disease, percent systolic wall thickening (%WT) was measured during dobutamine infusion in incremental doses of 6 microg/kg/min, from 6 to 30 microg/kg/min. Percent change in %WT by dobutamine was compared with percent coronary stenosis derived from quantitative coronary angiography. Analysis of the mean difference and 95% confidence intervals demonstrated good accuracy and reproducibility: 0.0 mm and intervals of -0.5 to 0.5 mm in diastolic wall thickening of LV posterior wall (PW) between both methods, -1% and -4% to 2% in %WT of IVS and LVPW between both observers, and -1% and -3% to 2% in that between both measurements. During dobutamine infusion, the percent change in %WT was significantly correlated with percent stenosis (r = 0.75, p<0.0001). The WT curve system enabled us to assess regional wall function as %WT and was available for quantitative observation of wall motion change during pharmacologic intervention. This system may reduce the effects of heart movement and may be of great clinical benefit in evaluating regional wall function.     

Diastolic changes in left ventricular wall thickness studied by echocardiography.

In order to study factors influencing posterior wall thickness during diastole, echocardiograms showing the septum, mitral valve and posterior wall endocardium and epicardium in 15 normal subjects and 49 patients with heart disease were digitized. Maximum wall thickness, minimum cavity dimension and the onset of mitral valve opening are normally synchronous, and an early period of rapid wall thinning, at a peak rate of 10.7 +/- 1.7 cm/sec corresponds closely to rapid filling. In patients with ischaemic heart disease the peak rate and duration of rapid thinning were normal, but thinning preceded mitral valve opening (mean 50 msec). In 11 of 17 patients with hypertrophic cardiomyopathy the peak rate of thinning was reduced and in 2 it was increased. There was a close correlation between the peak thinning rate in this group and the peak rate of increase in dimension. In mitral stenosis peak thinning rate was frequently reduced but in some patients was normal, with the reduced rate of increase in cavity dimension maintained by reversal of septal movement. We conclude that rapid thinning is an intrinsic property of the ventricular wall which is normally associated with rapid filling, but which may be dissociated from filling by asynchronous relaxation or inflow obstruction, or may be modified by myocardial disease.     

The effect of late patency of the infarct-related coronary artery on left ventricular morphology and regional function after thrombolysis.

The use of early coronary angiography to assess the benefits of coronary patency on left ventricular size and function fails to account for subsequent reocclusion or spontaneous reperfusion. To investigate the relationship between late vessel patency and changes in left ventricular structure and function after thrombolysis, echocardiography was performed within 48 hours and at 6 to 12 weeks in 30 patients treated with intravenous thrombolysis. Left ventricular endocardial surface area index (ESAj; cm2/m2) and extent of abnormal wall motion were quantitated in those with a patent (n = 20) and those with an occluded (n = 10) infarct-related artery on coronary angiography performed 8 +/- 6 days after thrombolysis. Mean ESAi increased from (53 +/- 7 to 61 +/- 10 cm2/m2; p less than 0.02) in the occluded group during the follow-up period but remained unchanged (60 +/- 11 to 62 +/- 11 cm2/m2; p = NS) in the patient group. Mean percentage of abnormal wall motion decreased in the patent group (27 +/- 16% to 18 +/- 16%; p less than 0.01), whereas no significant change was noted in the occluded group (20 +/- 13% to 23 +/- 17%; p = NS). Thus coronary patency at days after thrombolysis is associated with both improvement in regional left ventricular function and attenuated left ventricular dilatation.     

Serial analysis of regional left ventricular wall motion by two-dimensional echocardiography in patients with coronary artery enlargement after Kawasaki disease.

OBJECTIVES. This study was designed to assess the temporal relation between early coronary artery abnormalities and left ventricular function in Kawasaki disease. BACKGROUND. Although late segmental wall motion abnormalities may be seen in patients with Kawasaki disease who have coronary artery stenosis, the impact of early coronary artery abnormalities is unclear. METHODS. Regional left ventricular wall motion was assessed by two-dimensional echocardiography in 18 patients with Kawasaki disease and echocardiographic evidence of coronary artery enlargement at 3 weeks and 3 months and at either 6 or 12 months after the onset of fever. Four patients had a persistent left coronary artery aneurysm, four had regression of their aneurysm, two had persistent left coronary artery ectasia and eight had regression of ectasia. Left ventricular wall motion was assessed by measuring regional area change in parasternal and apical views. After planimetry of an end-systolic and an end-diastolic frame, the ventricle was divided into eight equal segments and the percent area change was calculated. A floating system correcting for translation and rotation was applied. The measurements in the patient group were compared with values previously obtained in 55 normal age-matched infants and children. RESULTS. A transient regional wall motion abnormality 3 and 6 months after the onset of fever was discovered in the inferolateral wall of one patient with a persistent left coronary artery aneurysm. One patient with regression of coronary artery ectasia had a persistent wall motion abnormality in the anterolateral left ventricular wall. There was no correlation between the extent of coronary artery enlargement and the presence or absence of wall motion abnormalities. CONCLUSIONS. These early changes are most likely secondary to associated myocarditis rather than coronary artery abnormalities.     

Right ventricular function in coronary artery disease as assessed by two-dimensional echocardiography

Two-dimensional echocardiography (2DE) was performed in 64 patients with coronary artery disease. There were 46 men and 18 women, aged 58.7 +/- 11.4 years. An apical four-chamber view, a two-chamber right ventricular (RV) view, and a subcostal four-chamber view were obtained in 58 of 64 (91%) patients. Regional wall motion abnormalities ( RWMA ) of the RV free or diaphragmatic wall were detected in 4 of 18 (22%) patients with acute inferior myocardial infarction (IMI) and in 3 of 14 (21%) patients with old IMI. All seven patients with RWMA by 2DE had two or more of the following findings: hypotension, second- or third-degree atrioventricular block, atrial arrhythmias, or ventricular tachycardia. The RV ejection fraction by first-pass radionuclide angiography was 19.7 +/- 8.3% in patients with IMI and RV RWMA by 2DE compared to 35.3 +/- 9.6% (p less than 0.005) in patients without. A hyperdynamic RV wall motion was seen in 12 of 15 (80%) patients with acute anterior MI (AMI). No RV RWMA was observed in 17 patients with greater than 75% obstruction of right coronary artery and absent infarction. Thus, RWMA of the right ventricle were detected by 2DE in 22% of patients with IMI and identified patients with clinically significant RV dysfunction, probably due to RV infarction; a compensatory hyperdynamic RV wall motion was observed in 80% of patients with acute AMI.     

Left anterior descending coronary artery wall thickness measured by high-frequency transthoracic and epicardial echocardiography includes adventitia

High-frequency, 2-dimensional transthoracic echocardiography (HR-2DTTE) measurements of the left anterior descending (LAD) coronary artery wall thickness are larger than measurements obtained by intravascular ultrasound. We hypothesize that this difference is due to inclusion of the third vascular layer, which may represent adventitia by HR-2DTTE, and that this layer must be increasing in thickness with the development of atherosclerosis. We evaluated the contribution of this third layer to the wall thickness of the normal and atherosclerotic LAD artery imaged by HR-2DTTE using high-frequency epicardial echocardiography (HFEE) as the reference standard. Eighteen patients (10 men, mean age 62 years), 13 with coronary atherosclerosis and 5 with normal coronary arteries, referred for open-heart surgery, underwent preoperative HR-2DTTE evaluation of the LAD artery (SONOS 5500; 3- to 8-MHz transducer) and intraoperative HFEE of the LAD artery (SONOS 5500; 6- to 15-MHz transducer). Wall thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries by both HR-2DTTE (1.9 +/- 0.3 vs 1.0 +/- 0.1 mm, p = <0.001) and HFEE (1.8 +/- 0.2 vs 1.0 +/- 0.2 mm, p = <0.001). On HFEE, the average intima plus media thickness was greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.78 +/- 0.3 vs 0.34 +/- 0.1 mm, p = 0.005). The average thickness of adventitia was also greater in patients with coronary atherosclerosis than in those with normal coronary arteries (0.92 +/- 0.2 vs 0.54 +/- 0.2 mm, p = 0.0005). HR-2DTTE and HFEE measurements of the wall thickness correlated well (r = 0.83 [reader 1], p <0.001; r = 0.61 [reader 2], p <0.01). A third vascular layer, which likely included adventitia, represents a significant portion of the LAD wall thickness imaged by HR-2DTTE and HFEE, and it significantly increases in thickness with the development of atherosclerosis.     

Prospective evaluation of the left main coronary artery using digital two-dimensional echocardiography

Recent clinical studies emphasize the importance of identification of patients with left main coronary artery obstruction. Although two-dimensional echocardiography can detect left main coronary artery disease, the technique requires frame by frame analysis, as no single frame provides all the necessary information. To determine if newly available computer-based digital processing techniques could overcome some of these technical difficulties, 119 consecutive patients were prospectively evaluated with two-dimensional echocardiography before coronary angiography. A continuous loop recording of the left main coronary artery was recorded as it passed through the ultrasonic beam in the short-axis view. Starting at a point when the vessel was first visualized, the ensuing eight consecutive fields, each 17 ms apart, were captured in digital format, thus providing a series of parallel, sequential, longitudinal slices of the left main coronary artery as it traversed the imaging plane. This was successfully accomplished in 100 (84%) of the 119 consecutive patients. By angiography, 16 patients (16%) had greater than 50% narrowing of the left main coronary artery. Digital echocardiography correctly identified 15 of these 16 patients (94% sensitivity) and accurately localized the lesion in 12 (80%) of 15. Of 84 patients without significant left main coronary artery obstruction, digital echocardiography correctly identified 78 (93% specificity). It was concluded that computer-based digital processing techniques can be applied to two-dimensional echocardiography to allow reliable visualization of the left main coronary artery. The technique provides more information than a single still frame and allows accurate noninvasive detection and possible localization of left main coronary artery lesions.     

Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy.

In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen.     

Changes in left anterior descending coronary artery wall thickness detected by high resolution transthoracic echocardiography

Recently, it has been demonstrated that high-resolution transthoracic echocardiography (HRTTE) is able to detect differences in the wall thickness of the left anterior descending coronary artery (LAD) between patients with coronary artery disease (CAD) and normal volunteers. The aim of this study was to further validate this technique. One hundred ten volunteers, 58 patients with angiographically proved CAD and 52 control subjects, underwent assessments of their LADs using HRTTE. Anterior and posterior wall thicknesses differed between subjects in the CAD group and controls (1.9 +/- 0.6 vs 1.2 +/- 0.3 mm, p <0.001, and 1.8 +/- 0.5 vs 1.2 +/- 0.3 mm, p <0.001, respectively). External LAD diameter was also greater in subjects in the CAD group compared with controls (5.2 +/- 1.9 vs 4.4 +/- 0.9 mm, respectively, p = 0.01). However, there was no difference in luminal diameter between subjects in the CAD group and the controls (1.9 +/- 0.9 vs 2.1 +/- 0.8 mm, respectively, p = 0.3). In conclusion, HRTTE demonstrated that LAD wall thicknesses and external diameters in patients with CAD were significantly larger than in normal volunteers. Luminal diameter, however, was maintained in the 2 groups, indicating that subjects in the CAD group had undergone positive remodeling at the site measured. This objectively visualized evidence of coronary atherosclerosis with HRTTE would likely be undetected during coronary angiography.     

Reperfusion of the infarct-related coronary artery limits left ventricular expansion beyond myocardial salvage.

Previous echocardiographic data from the Gruppo Italiano per lo Studio della Streptochinasi nell' Infarto Miocardico (GISSI 1) trial suggest that the relation between left ventricular end-systolic volume and infarct size could be altered by thrombolysis, which would exert a restraining effect on end-systolic volume beyond its reducing effect on infarct size. Thus in 63 patients with one-vessel disease and a recent anterior myocardial infarction, we tested at angiography (1) if perfusion of the anterior descending coronary artery exerts any restraining effect on end-systolic volume above and beyond infarct size reduction and (2) if ejection fraction reflects such an additional, beneficial difference in the ventricular remodeling process. End-systolic volume was calculated using the Dodge method and the right anterior oblique projection, while infarct size was quantified according to the number of ventricular radii whose percent shortening fell below the mean -2 SD of a group of normal individuals. Patients were then divided into two groups according to the perfusion status of the vessel using Thrombolysis in Myocardial infarction (TIMI) criteria (TIMI grade 0 to 1: nonperfused vessel, 27 patients; TIMI grade 2 to 3: perfused vessel, 36 patients). For both groups there was a significant linear relation (p less than 0.001) between end-systolic volume and infarct size; as in our echocardiographic data, the regression lines relating volume to infarct size showed a different slope in the two populations so that, for large and matched infarcts, end-systolic volume was smaller in patients with a perfused vessel (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early assessment of coronary artery bypass graft patency by high-dose dipyridamole echocardiography

To assess the role of high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiographic testing in the evaluation of coronary artery bypass graft patency early after surgery, 18 consecutive patients with angina underwent dipyridamole echocardiography and coronary angiography before and 7 to 10 days after bypass surgery. Coronary angiography showed 2- or 3-vessel disease in 7 and 11 patients, respectively. A total of 53 bypass grafts were performed. Before bypass surgery 14 patients had a positive and 4 a negative test result. No complication occurred during the test performed early after surgery. Of the 14 patients with positive dipyridamole echocardiographic results before surgery, 10 had negative and 4 had positive results after surgery. All 4 patients had negative results before and after surgery. In the 4 patients with positive results after dipyridamole echocardiographic testing before and after bypass surgery, dipyridamole time increased from 5.8 +/- 5 to 9.3 +/- 0.9 minutes (p = 0.3) after the procedure and wall motion score index at peak dipyridamole changed from 1.55 +/- 0.2 to 1.28 +/- 0.3 (p = 0.05). Forty-nine of 53 grafts were patent as seen on angiography. Dipyridamole echocardiographic results were positive in 4 of 5 patients who had at least 1 obstructed graft or native vessel obstructed distal to bypass graft insertion. The remaining patient had diagnostic electrocardiographic changes during dipyridamole infusion without wall motion abnormalities. Dipyridamole echocardiographic results were negative in all 13 patients who had complete revascularization. In the 4 patients with positive test results, the procedure correctly identified the localization of the diseased bypass graft.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limits of reproducibility of left ventricular wall thickness and mass by M-mode echocardiography

The present study describes the total intrinsic variability of both left ventricular wall thickness and left ventricular wall mass in a group of 11 normal volunteers with an echocardiographic follow-up of about 1 yr. Septal thickness, posterior wall thickness and left ventricular minor diameter were measured at end-diastole. From the parameters under investigation the left ventricular minor diameter showed the best reproducibility with a coefficient of variation of 4%. The coefficients of variation for septal thickness, posterior wall thickness and left ventricular wall mass by both the Penn and the ASE method were 10, 10, 15 and 13%, respectively. The left ventricular wall mass was better reproducible by the ASE method than by the Penn method.     

Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy

In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen.     

Patency of the infarct-related coronary artery and ventricular geometry.

The pathogenesis of acute myocardial infarction (AMI) involves a sudden thrombotic occlusion of a coronary artery. Spontaneous or pharmacologic thrombolysis may lead to myocardial salvage if patency is achieved within a narrow time window. However, patients in whom thrombolysis occurs late seem to demonstrate improved left ventricular (LV) function and prognosis, which may be independent of myocardial salvage. Preservation of normal LV geometry by reducing expansion of the infarcted segment is a likely mechanism for this benefit. Infarct expansion is most pronounced in patients with anterior wall AMI who have a persistently occluded infarct-related vessel. This process of expansion leads to early increases in LV volume and distortions of LV contour (abnormal LV geometry). Patients whose infarct segment is largest, patients who have manifested infarct expansion, and patients with a persistently occluded infarct-related artery are at highest risk for progressive LV dilation. Experimental data support the concept that reperfusion of occluded vessels that occurs too late for myocardial salvage will preserve LV geometry by limiting infarct expansion. Prospective clinical trials should address whether there is a late, "second time window" during which infarct expansion and distortions of LV geometry may be reduced by (1) therapy with thrombolytic agents applied late after infarction, (2) late mechanical reperfusion with percutaneous transluminal coronary angioplasty (PTCA) or related methods, and (3) load-reducing agents to decrease remodeling, such as angiotensin-converting enzyme inhibitors or nitroglycerin.