G.B.John Mancini

Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): Reduction in atherosclerosis progression and clinical events

OBJECTIVESnThis study was designed to evaluate the effect of pravastatin on progression of coronary atherosclerosis and ischemic events in patients with coronary artery disease and mild to moderate hyperlipidemia.nnnBACKGROUNDnFew clinical trial data support the use of lipid-lowering therapy in patients with coronary artery disease and mild to moderate elevations in cholesterol levels.nnnMETHODSnFour hundred eight patients (mean age 57 years) with coronary artery disease and low density lipoprotein (LDL) cholesterol > or = 130 mg/dl (3.36 mmol/liter) but < 190 mg/dl ([4.91 mmol/liter]) despite diet were randomized in a 3-year study to receive pravastatin or placebo. Atherosclerosis progression was evaluated by quantitative coronary arteriography.nnnRESULTSnBaseline mean LDL cholesterol was 164 mg/dl (4.24 mmol/liter). Pravastatin decreased total and LDL cholesterol and triglyceride levels by 19%, 28% and 8%, respectively, and increased high density lipoprotein cholesterol by 7% (p < or = 0.001 vs. placebo for all lipid variables). Progression of atherosclerosis was reduced by 40% for minimal vessel diameter (p = 0.04), particularly in lesions < 50% stenosis at baseline. There was a consistent although not statistically significant effect on mean diameter and percent diameter stenosis. There were also fewer new lesions in those assigned pravastatin (p < or = 0.03). Myocardial infarction was reduced during active treatment (8 in the pravastatin group, 17 in the placebo group; log-rank test, p < or = 0.05; 60% risk reduction), with the benefit beginning to emerge after 1 year.nnnCONCLUSIONSnIn patients with coronary artery disease and mild to moderate cholesterol elevations, pravastatin reduces progression of coronary atherosclerosis and myocardial infarction. The time course of event reduction increases the potential for a relatively rapid decrease in the clinical manifestations of coronary artery disease with lipid lowering.

Anticoagulation for cardioversion of atrial fibrillation

A trial fibrillation (AF) is a common arrhythmia associated with a broad spectrum of underlying diseases that include systemic hypertension, rheumatic heart disease and coronary artery disease.1 Several studies have documented the strong relation between chronic AF and emboli.2,3 In addition, an increased risk of embolism exists in the setting of cardioversion of AF to sinus rhythm.4,5 In the best study to date, Bjerkelund and Orning6 reported on 572 attempted cardioversions in 437 patients and observed a 0.8% incidence of embolization in long-term anticoagulated patients compared with 5.3% in a nonanticoagulated group. Shortcomings of this study included lack of randomization, no evaluation of shortterm therapy and inclusion of arrhythmias such as atrial flutter and atrial tachycardia. Based on such work, current recommendations include anticoagulation for 2 to 4 weeks before cardioversion to allow adherence and endothelialization of existing thrombus and 1 to 4 weeks after cardioversion to provide coverage for late resumption of atrial activity.7,8 The present report evaluates these recommendations in light of our experience over the past 10 years.

Variability of quantitative digital subtraction coronary angiography before and after percutaneous transluminal coronary angioplasty

Quantitative coronary angiography has been proposed as a means of reducing observer variability in the interpretation of coronary angiograms, especially before and after percutaneous transluminal coronary angioplasty (PTCA). Analysis of 13 consecutively acquired biplane digital subtraction angiograms before and after PTCA was undertaken to determine intra- and interobserver variability of absolute lesion diameter, relative videodensitometric cross-sectional area, automated percent diameter stenosis and visual percent diameter stenosis using a new fully automated quantitative computer program. The reliability of single-view measurements was also assessed. Both before and after PTCA, measures of absolute diameter showed less interobserver variability than densitometry, percent automated diameter stenosis and percent visual diameter stenosis measurements (before, r = 0.95, 0.83, 0.86, 0.70; after, 0.95, 0.88, 0.81, 0.62, respectively). Relative videodensitometric cross-sectional area correlated poorly with images from the orthogonal view (r = 0.46). These data suggest that quantitative angiography reduces variability from visual estimates; of all quantitative angiographic measurements, the highest interobserver reproducibility is achieved using absolute lesion diameter both before and after PTCA, probably because no operator interaction is needed to identify a normal segment. Unselected, single-view quantitative arteriography is poorly reproducible using videodensitometry. Therefore, automated determination of absolute lesion diameter in at least 2 projections provides the most reproducible evaluation of coronary lesions both before and after PTCA.

Value of percutaneous transluminal coronary angioplasty after unsuccessful intravenous streptokinase therapy in acute myocardial infarction

The effect of sequential high-dose intravenous streptokinase (SK) (1.5 million units) followed by emergency percutaneous transluminal coronary angioplasty (PTCA) on preserving left ventricular function was assessed prospectively in 34 patients with acute myocardial infarction (AMI). Intravenous SK therapy was initiated 2.6 +/- 1.3 hours (mean +/- standard deviation) after the onset of chest pain. Urgent coronary angiography showed persistent total occlusion in 13 patients, significant diameter stenosis (70 to 99%) in 18 patients and a widely patent artery (less than 50% stenosis) in 3 patients. Emergency PTCA was performed in 29 patients 5.0 +/- 2.1 hours after symptom onset. Successful recanalization was achieved in 33 of the 34 patients (97%) treated with sequential therapy. Repeat contrast ventriculograms recorded 7 to 10 days after intervention in 23 patients showed that the left ventricular ejection fraction increased from 53 +/- 12% to 59 +/- 13% (area-length method, p less than 0.002). Regional wall motion of the infarcted segments improved from -2.7 +/- 1.1 to -1.5 +/- 1.7 SD/chord (centerline method, p less than 0.003). In the subgroup of patients with an occluded artery on initial angiography (group A, n = 10), both global left ventricular ejection fraction (49 +/- 12% vs 59 +/- 12%, p less than 0.002) and regional wall motion (-3.2 +/- 1.0 vs -1.9 +/- 1.7 SD/chord, p less than 0.002) improved significantly. In contrast, no significant improvement was seen in patients with a patent artery on initial angiography (n = 13). Thus, sequential intravenous SK and emergency PTCA is efficacious in achieving coronary reperfusion and in improving both global and regional left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative regional curvature analysis: An application of shape determination for the assessment of segmental left ventricular function in man

All traditional techniques of regional ventricular function analysis depend upon one or more assumptions about coordinate, reference, or indexing systems, idealized ventricular geometry, and the uniformity of ventricular contraction. Therefore, a method of shape analysis was developed that allows the quantitation of regional curvature and is independent of the assumptions outlined. This was implemented on a commercial image processing unit and applied to silhouettes of 30-degree right anterior oblique left ventriculograms. Three groups with abnormal wall motion (anterior abnormality, n = 23; inferior abnormality, n = 23; anterior and inferior abnormalities, n = 22) were analyzed and compared to a group with normal regional function (n = 22). Relatively few significant quantitative curvature differences were noted at end diastole among the groups. These few abnormalities described a slight increase in curvature or globularity of the anterior and inferior walls. More marked and extensive aberrations were detected at end systole. The group with anterior wall motion disturbances showed four distinct areas of curvature abnormality. Excessive curvature was present on either side of the apex (anterior and inferoapical regions) and apical curvature was less than normal. The fourth region was in the inferior zone, which showed curvature values that were less than normal, suggesting increased inward motion contralateral to the anterior abnormality. The group with inferior wall motion abnormalities also showed excessive end-systolic curvature on either side of the apex (diaphragmatic and anteroapical zones) and deficient curvature at the apex. A combination of these regional morphologic abnormalities was noted in the group with both anterior and inferior dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of automated quantitative coronary angiography with caliper measurements of percent diameter stenosis

Measurement of coronary artery stenosis is an invaluable tool in the study of coronary artery disease. Clinical trials and even day-to-day decision making should ideally be based on accurate and reproducible quantitative methods. Quantitative coronary angiography (QCA) using digital angiographic techniques has been shown to fulfill these requirements. Yet many laboratories have abandoned visual analysis in favor of the intermediate quantitative approach involving hand-held calipers. Thus, the purpose of this study was to determine the relation between QCA and the commonly used caliper measurements. Percent stenosis was assessed in 155 lesions using 3 techniques: QCA, caliper measures from a 35-mm cine viewer (cine) and caliper measures from a video display (CRT). Good overall correlation was noted among the 3 different techniques (r greater than or equal to 0.72). Both of the caliper methods underestimated QCA for stenosis greater than or equal to 75% (p less than or equal to 0.001) and overestimated stenosis less than 75% (p less than 0.05). Reproducibility assessed in 52 lesions by independent observers showed QCA to be superior (r = 0.95) to either of the caliper measurements (cine: r = 0.63; CRT: r = 0.73). Therefore, the commonly used caliper method is not an adequate substitute for QCA because overestimation of noncritical stenoses and underestimation of severe stenoses may occur and the measurements have poor reproducibility. These factors definitely preclude its use in rigorous clinical trials. Moreover, since they do not appear to overcome known deficiencies of visual analysis, caliper measurements for day-to-day clinical use must also be seriously questioned.

Determination of left ventricular volumes and ejection fraction by nuclear magnetic resonance imaging

To determine the ability of nuclear magnetic resonance (NMR) imaging to assess left ventricular (LV) volumes and ejection fraction (EF), we studied 24 patients within 48 hours of single-plane LV angiography. In all patients, a transverse, single-plane NMR acquisition technique was employed with LV end-diastolic (ED) and end-systolic (ES) volumes (V) calculated by a modified area-length algorithm. In nine patients, a multislice acquisition technique was employed with LVEDV and LVESV calculated by a Simpsons rule algorithm. NMR-determined LVV and EF correlated reasonably well with angiographic values (LVEDV: r = 0.75; LVESV: r = 0.90; and LVEF: r = 0.76). The single-plane NMR technique significantly underestimated LVEDV (p less than 0.01), whereas no significant difference was demonstrated for LVESV. As a result, angiographic LVEF was significantly underestimated (p less than 0.05). This underestimation is likely related to off-axis imaging and to the geometric constraints of a single-plane algorithm. In comparing multislice NMR to angiographic data, no significant difference was demonstrated for LVEDV, LVESV, or LVEF. Thus, quantitation of LVV and EF with NMR is feasible, and comparison to angiographic volumes is similar to results reported from other noninvasive imaging modalities. Improvement in current acquisition techniques and software should result in further quantitative potential.

Tachycardia, contractility and volume loading alter conventional indexes of coronary flow reserve, but not the instantaneous hyperemic flow versus pressure slope index

OBJECTIVES AND BACKGROUNDnBecause measurements of flow reserve are often made in the setting of fluctuating hemodynamic variables that cause alterations in basal or hyperemic coronary blood flow, traditional flow reserve indexes may be difficult to interpret. Prior work in this laboratory has suggested that the instantaneous hyperemic flow versus pressure slope index is a more hemodynamically stable alternative to measures of flow reserve. Although this index has no hemodynamic dependence on changes in aortic pressure, the extent to which it is affected by other factors that alter myocardial work is unknown. Therefore, the purpose of this investigation was to analyze the effects of tachycardia (induced by atrial pacing at 10 beats/min above the basal heart rate), dobutamine infusion (10 micrograms/kg per min) and saline solution volume loading (500 ml) on measurements of traditional coronary flow reserve, the resistance reserve ratio and the instantaneous hyperemic flow versus pressure slope index.nnnMETHODSnTwenty-nine open chest anesthetized dogs were studied in four sequential stages: baseline, tachycardia, dobutamine infusion and saline solution volume loading. Traditional coronary flow reserve was defined as the ratio of hyperemic coronary blood flow to basal coronary blood flow, the resistance reserve ratio as the ratio of basal coronary resistance to hyperemic coronary resistance and the instantaneous hyperemic flow versus pressure slope index as the slope of the instantaneous relation between diastolic hyperemic coronary blood flow and diastolic aortic pressure normalized by perfusion bed weight. Hyperemia was induced by intravenous adenosine infusion (1 mg/kg per min). Mean aortic pressure was kept nearly constant during the interventions by manipulation of an aortic clamp or a vena caval snare.nnnRESULTSnThe final study group comprised 18 open chest dogs. Coronary flow reserve was significantly decreased by tachycardia (3.7 +/- 1.2 to 3.0 +/- 1.2, p < 0.0001), decreased by saline solution volume loading (3.2 +/- 1.3 vs. 2.7 +/- 0.8, p = 0.06) and significantly increased by dobutamine infusion (3.2 +/- 1.3 to 4.3 +/- 1.5, p < 0.0005). In contrast, the instantaneous hyperemic flow versus pressure slope index was not affected by the three interventions (7.4 +/- 3.1 vs. 7.3 +/- 3.3, 7.4 +/- 3.2 vs. 7.4 +/- 3.4 and 7.5 +/- 3.1 vs. 7.3 +/- 3.4, respectively, all p = NS). The changes observed in the resistance reserve ratio were of similar or greater magnitude and significance to the changes in coronary flow reserve.nnnCONCLUSIONSnThe instantaneous hyperemic flow versus pressure slope index offers a hemodynamically stable alternative to measures of vascular reserve because it is independent of moderate changes in heart rate, contractility and volume loading that may occur commonly in clinical situations.

Quantitative coronary arteriographic methods in the interventional catheterization laboratory: An update and perspective☆

Recent research advances in the area of quantitative coronary arteriography are described with respect to their potential role in assessing the effects of interventional therapy and monitoring the restenosis process. Specific areas emphasized are the importance of quantitative arteriography and absolute measures of arterial dimension in monitoring restenosis, the development of a computerized method for measuring lesion roughness, the potential role of measuring stenosis flow reserve based on component analysis principles, limitations of direct measures of myocardial flow reserve using a digital angiographic method and cautionary notes about clinical applications of videodensitometry. The current use of radiography and quantitative measures in limiting arterial injury are briefly reviewed. Finally, a perspective is put forth on the need to develop complementary roles for endovascular echocardiography and angioscopy with existing radiographic imaging technology.

A comparison of 35 mm cine film and digital radiographic image recording: implications for quantitative coronary arteriography. Film vs. digital coronary quantification.

To assess potential differences in the intrinsic properties of image recording media and their impact on quantitative coronary arteriography, we used an automatic quantitative arteriography computer program to analyze cine film and digital radiographic images of a radiographic arterial phantom. The phantom consisted of a lucite plate with precision-drilled lumena ranging from 0.5 to 5.0 mm in diameter. Film images were digitized at 2048 X 2048 pixel resolution, and digital radiographic images were acquired at 512 X 512 and 1024 X 1024 resolution. Arterial geometric diameter, percent diameter stenosis, densitometric relative cross-sectional area, and densitometric percent area stenosis were measured. All three techniques were equivalent in measuring diameters with a high degree of overall accuracy (R greater than .992). All methods overestimated diameters below 1.0 mm. Both 512 X 512 and 1024 X 1024 digital images were superior to film for densitometric measurement of relative area (R = .995 vs. R = .940, P = .0032). We conclude that automated analysis of digital radiographic images yields results that are similar in geometric precision but greater in densitometric precision than film analysis.