A. V. G. Bruschke

Magnetic resonance imaging during dobutamine stress for detection and localization of coronary artery disease. Quantitative wall motion analysis using a modification of the centerline method.

Quantitative measurement of wall motion is essential to assess objectively the functional significance of coronary artery disease. We developed a quantitative wall thickening analysis on stress magnetic resonance images. This study was designed to assess the clinical value of magnetic resonance imaging (MRI) during dobutamine stress for detection and localization of myocardial ischemia in patients with suspected coronary artery disease. Methods and ResultsThirty-nine consecutive patients with clinically suspected coronary artery disease referred for coronary arteriography and 10 normal volunteers underwent gradient- echo MRI at rest and during peak dobutamine stress (infusion rate, 20 μg· kg−1· min−2). MRI was performed in the short-axis plane at four adjacent levels. Display in a cine loop provided a qualitative impression of regional wall motion (cine MRI). A modification of the centerline method was applied for quantitative wall motion analysis by means of calculation of percent systolic wall thickening. Short-axis cine MRI images were analyzed at 100 equally spaced chords constructed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours. Dobutamine MRI was considered positive for coronary artery disease if the percent systolic wall thickening of more than four adjacent chords was < 2 SD below the mean values obtained from the normal volunteers. The overall sensitivity of dobutamine MRI for the detection of significant coronary artery disease (diameter stenosis ≥ 50%) was 91% (30 of 33), specificity was 80% (5 of 6), and accuracy was 90% (35 of 39). The sensitivity for identifying one-vessel disease was 88% (15 of 17), for twovessel disease 91% (10 of 11), and for three-vessel disease 100% (5 of 5). The sensitivity for detection of individual coronary artery lesions was 75% for the left anterior descending coronary artery, 87% for the right coronary artery, and 63% for the left circumflex coronary artery. ConclusionsDobutamine MRI clearly identifies wall motion abnormalities by quantitative analysis using a modification of the centerline method. Dobutamine MRI is an accurate method for detection and localization of myocardial ischemia and may emerge as a new noninvasive approach for evaluation of patients with known or suspected coronary artery disease.

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful.

Reproducibility of left ventricular size, shape and mass with echocardiography, magnetic resonance imaging and radionuclide angiography in patients with anterior wall infarction : A plea for core laboratories

After myocardial infarction, left ventricular volume and ejection fraction can be assessed by echocardiography, magnetic resonance imaging and radionuclide angiography to guide therapy and determine prognosis. Whether a measured parameter gives the same results irrespective of the method used and the observer who performs the analysis is only partly known. Intra-observer and inter-observer variability were determined for echo and magnetic resonance imaging. Left ventricular ejection fraction measured by these techniques was related to radionuclide angiograms performed in the same period. Intra-observer variability for both echo and MRI was low and in most instances below 5%. Inter-observer variability for the echo and MRI measurements were substantially higher than intra-observer variability. Comparison of the three imaging modalities revealed systematic differences. Therefore, in clinical studies, left ventricular volume and function parameters have to be measured with the same technique and by the same observer in qualified core laboratories.

Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28 coronary bypass patients were divided into two groups: group A, 12 patients with, and group B, 16 patients without progression of coronary atherosclerosis. The lag time, reflecting the resistance of LDL to oxidative modification, was significantly smaller in group A as compared with group B (81 +/- 10 and 93 +/- 15 min, respectively). Besides differences in cholesterol and apolipoprotein B concentrations, the difference in susceptibility of LDL to oxidation significantly contributes to the differences between the progression and the non-progression group (P = 0.02). In the combined groups of patients, the lag phase of LDL for oxidation was positively correlated with LDL cholesterol ester to protein ratio (r = 0.53, P = 0.01). It is concluded that LDL samples obtained from coronary bypass patients differ with respect to their oxidizability depending on progression of atherosclerosis following coronary bypass surgery.

Increased risk for ischaemic events is related to combined RAS polymorphism

OBJECTIVE To determine whether the angiotensin converting enzyme (ACE) and the angiotensin II type 1 receptor (AT1R A1166C) gene polymorphism interact to increase the risk of ischaemic events, and whether this can be explained by the progression of angiographically defined coronary atherosclerosis. DESIGN Prospective defined substudy of the lipid lowering regression trial (REGRESS). SETTING University hospital. PATIENTS 885 male patients with stable coronary artery disease. MAIN OUTCOME MEASURES Incidence of ischaemic events during a two year follow up; serial quantitative coronary arteriography (mean segment diameter and minimum obstruction diameter) at baseline and after two years. RESULTS Patients who carried both the ACE-DD and AT1R-CC genotype had significantly more ischaemic events during the two year follow up than those carrying other genotype combinations (p = 0.035, Mantel-Haenszel test for linear association). There was no association between the two genotypes and mean segment diameter or minimum obstruction diameter at baseline or after two years. CONCLUSIONS The suggestion that ACE-DD and AT1R-CC genotypes interact to increase the risk of ischaemic events is confirmed. However, this increased risk was not accompanied by increased progression of angiographically defined coronary atherosclerosis.

Myocardial SPET imaging with 99Tcm-tetrofosmin in clinical practice : Comparison of a 1 day and a 2 day imaging protocol

99Tcm-tetrofosmin is a new myocardial perfusion agent with the advantage that it can be reconstituted at room temperature. Because two separate injections are required for rest and stress images, a separate-day imaging protocol with one injection each day would be optimal in terms of image quality. From the logistical point of view, a 1 day protocol may be more convenient for the majority of those referred as outpatients. The main aim of this study was to determine whether the detection of myocardial ischaemia would be impeded by the use of a 1 day protocol instead of a 2 day protocol. A secondary aim was to establish the relative diagnostic accuracy of the two imaging strategies. 99Tcm-tetrofosmin SPET imaging was performed in 157 patients. Sixty-nine (44%) patients were administered 250 MBq (7 mCi) 99Tcm-tetrofosmin at rest followed 4 h later by 750 MBq (21 mCi) during stress (the 1 day protocol), whereas 88 (56%) patients had rest and stress imaging studies on two separate days, receiving a 500 MBq (14 mCi) dose of 99Tcm-tetrofosmin on each occasion (the 2 day protocol). With the 1 day protocol, 135 of 621 (22%) abnormal segments (i.e. both reversible and persistent defects) were observed, compared with 195 of 792 (25%) segments with the 2 day protocol. Also, the occurrence of reversible defects only did not differ between the two protocols (both 9%). The sensitivity for the detection of coronary artery disease was 83 and 90% for the 1 and 2 day protocols respectively. We conclude that the 1 and 2 day protocols provide similar scintigraphic information and are equally sensitive and specific for the detection of coronary artery disease. Therefore, the imaging protocol can be adjusted as appropriate for the patient in question.

Proposed synergistic effect of calcium channel blockers with lipid-lowering therapy in retarding progression of coronary atherosclerosis

Lipid-lowering therapy now has undoubtedly proven to be an effective therapeutic modality to retard the progression of coronary atherosclerosis. An additional approach for prevention of the progression of atherosclerosis is calcium channel blocker (CCB) treatment. Evidence indicating that CCBs inhibit atherosclerosis is less unequivocal than the clear evidence for lipid-lowering therapy. Many investigations support the view that a number of key processes in atherosclerosis may be influenced by CCBs. From the “negative” and “positive” studies with CCBs performed in animals and humans we must conclude that apparently some, but not all, types or stages of the atherosclerotic process are inhibited by CCBs. To assess whether lipid-lowering therapy and CCB treatment may have an additive or synergistic beneficial effect on human atherosclerosis, which is conceivable because their anti-atherosclerotic properties differ, data from the angiographic lipid-lowering trial REGRESS (pravastatin vs. placebo) were reviewed. In REGRESS, patients in the pravastatin group had significantly less progression if cotreated with CCBs as compared with those with no CCB cotreatment, whereas in the placebo (no pravastatin) group no effect of CCB treatment was observed. With respect to angiographic new lesion formation, in the pravastatin group there were 50% less patients with new angiographic lesions if cotreated with CCBs as compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, again, no significant effect of CCB treatment was observed. No beneficial effects of CCB treatment on clinical events were observed during the 2-year study follow-up. In view of the correlation between angiographic progression and subsequent clinical events as demonstrated in several large trials, it is not unrealistic to also anticipate in this population, a beneficial effect on clinical events with longer follow-up. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest that addition of CCBs to HMG-CoA reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis. These results appear to warrant prospective randomized trials to determine in a more definitive manner the merits of this combination in the prevention of progression of coronary atherosclerosis. Currently a number of studies in these fields are being designed or are already underway.

Echocardiographic Parameters of the Freestyle Stentless Bioprosthesis in Aortic Position: The European Experience

The objective of this study was to determine normal Doppler and 2-dimensional characteristics of the Freestyle stentless aortic bioprosthesis. The Freestyle aortic bioprosthesis is a new type of aortic xenograft, and experience is limited. We therefore determined the normal range of echocardiographic and Doppler examinations of this valve. Three hundred thirty-nine consecutive patients with a Freestyle aortic bioprosthesis underwent an echocardiographic and Doppler examination according to a common protocol. Investigations were done within 4 weeks after operation, after 3 to 6 months, and after 1, 2, and 3 years. With a valve size from 19 to 27 mm, mean gradients decreased from 7.9 +/- 5.1 mm Hg at discharge to 5.5 +/- 3. 8 mm Hg after 3 to 6 months (P <.001). Thereafter, gradients remained stable. Effective orifice area 1 year after implantation was 1.59 +/- 0.58 cm(2) for the 21-mm valves, 1.92 +/- 0.74 cm(2) for the 23-mm valves, 2.03 +/- 0.64 cm(2) for the 25-mm valves, and 2.52 +/- 0.72 cm(2) for the 27-mm valves (P <.001). The performance index, the ratio of the measured effective orifice area in the patient divided by the effective orifice area measured in vitro, increased from 67% +/- 20% at discharge to 82% +/- 29% after 1, 2, and 3 years. Performance index was especially very high in the smaller-sized valves. After implantation with the subcoronary technique or root-inclusion technique, small cavities could be seen between the native aortic root and the Freestyle valve. Doppler values were evaluated for the Freestyle stentless porcine bioprostheses in the aortic root. Gradients appear to be close to those measured in native valves over a time period of 3 years.

Regional myocardial shape alterations in patients with anterior myocardial infarction

Objective: To assess the impact of regional left ventricular curvature in patients with an acute anterior myocardial infarction on ventricular volume.Methods: Left ventricular curvature was calculated at 100 points from apical four chamber echocardiograms of 68 patients with an acute anterior wall infarction. Curvature at any point of the contour was defined as the reciprocal of the radius of the circle that intersects that point tangentially and was independent of volume and geometric assumptions. Curvature, volume and shape of the patient group was compared with these measurements in 20 normal volunteers.Results: Diastolic curvature differed at the borderzone of the infarct and the apical area. In the basal septal area (point 9–18) mean curvature was lower in the patient group (0.1±2.7 versus 2.1±0.7; p<0.0001) as compared to the normal individuals. In the mid-septal area (point 22 to 27), mean curvature was more concave (− 0.1±2.6) in the patient group corresponding to in the normal population (− 0.4±1.3) p<0.005. In the apex point 52 and 53 diverged with a curvature of 9.9±1.9 in patients versus 9.4±2.9 p<0.005 in normal individuals. Systolic curvature diverged at the basal septum (point 1–4) with a mean curvature of 1.4±1.1 in patients compared to 3.5±2.5 in normal individuals p<0.01. Curvature differed also in the mid-septal region (point 9–29) with a curvature of − 1.7±1.2 in patients versus 0.4±0.9 (p<0.01) in normal individuals and in the apical septum (point 48–52) with a curvature of 16.6±5.2 in patients and 13.9±2.6 (p<0.0001) in healthy individuals. Separation of patients with the greatest curvature alteration to those with minor curvature change revealed, that baseline curvature analysis can discriminate patients at risk for left ventricular remodelling.Conclusion: Regional curvature analysis correctly identifies the geometric changes induced by myocardial infarction. Apical systolic curvature can distinguish those patients that are at risk for left ventricular remodelling from those who are not at risk.

Are enzymatic tests good indicators of coronary reperfusion

OBJECTIVE--To assess the accuracy of four enzymatic tests, including early release rates of creatine kinase and alpha-hydroxybutyrate dehydrogenase, in assessing coronary reperfusion after thrombolytic therapy. DESIGN--A prospective clinical trial identifying patients with a successful thrombolytic treatment. PATIENTS--Eighty nine patients with acute myocardial infarction were studied. Arteriography showed a closed infarct related artery in all of them. Reperfusion due to thrombolysis occurred in 74 patients and there was no reperfusion in 15 patients. RESULTS--The 74 patients showing coronary reperfusion had a significantly shorter time to peak creatine kinase activity, higher early release rates for creatine kinase and alpha-hydroxybutyrate dehydrogenase, and a more rapid release of alpha-hydroxybutyrate dehydrogenase (ratio of cumulative release of alpha-hydroxybutyrate dehydrogenase during the first 24 hours to that 72 hours after infarction). All these differences were statistically significant (p less than 0.001). Optimum cut off levels were determined with decision level plots and the accuracy of the four enzymatic tests was calculated. Accuracy was low for all four tests (73%, 70%, 70%, and 82%). CONCLUSION--None of the four enzymatic tests accurately predicted the perfusion state of the infarct related coronary artery after thrombolysis. These tests cannot be used reliably in routine clinical practice as non-angiographic markers of coronary reperfusion.