Denny D. Watson

Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography.

The ability of predischarge quantitative exercise thallium-201 (201T1) scintigraphy to predict future cardiac events was evaluated prospectively in 140 consecutive patients with uncomplicated acute myocardial infarction; the results were compared with those of submaximal exercise treadmill testing and coronary angiography. High risk was assigned if scintigraphy detected 201T1 defects in more than one discrete vascular region, redistribution, or increased lung uptake, if exercise testing caused ST segment depression greater than or equal to 1 mm or angina or if angiography revealed multivessel disease. Low risk was designated if scintigraphy detected a single-region defect, no redistribution, or no increase in lung uptake, if exercise testing caused no ST segment depression or angina, or if angiography revealed single-vessel disease or no disease. By 15 +/- 12 months, 50 patients had experienced a cardiac event; seven died (five suddenly), nine suffered recurrent myocardial infarction, and 34 developed severe class III or IV angina pectoris. Compared with that of patients at low risk, the cumulative probability of a cardiac event was greater in high-risk patients identified by scintigraphy (p less than .001), exercise testing (p = .011), or angiography (p = .007). Scintigraphy predicted low-risk status better than exercise testing (p = .01) or angiography (p = .05). Each predicted mortality with equal accuracy. However, scintigraphy was more sensitive in detecting patients who experienced reinfarction or who developed class III or IV angina. When all 50 patients with events were combined, scintigraphy identified 47 high-risk patients (94%), whereas exercise-induced ST segment depression or angina detected only 28 (56%) (p less than .001). The presence of multivessel disease as assessed by angiography identified nine more patients with events than exercise testing (p = .06). However, the overall sensitivity of angiography was lower than that of scintigraphy (71% vs 94%; p less than .01) because three patients who experienced reinfarction and 10 who developed class III or IV angina had single-vessel disease. Importantly, 12 (92%) of these 13 patients with single-vessel disease who had an event exhibited redistribution on scintigraphy. These results indicate that (1) submaximal exercise 201T1 scintigraphy can distinguish high- and low-risk groups after uncomplicated acute myocardial infarction before hospital discharge; (2) 201T1 defects in more than one discrete vascular region, presence of delayed redistribution, or increased lung thallium uptake are more sensitive predictors of subsequent cardiac events than ST segment depression, angina, or extent of angiographic disease; and (3) low-risk patients are best identified by a single-region 201T1 defect without redistribution and no increased lung uptake.

Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function.

BackgroundAlthough many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD. Methods and ResultsTwenty-one patients (mean LV ejection fraction, 0.27±0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic segments were classified with normal or mildly reduced viability. Among akinetic or dyskinetic segments, 20% had normal 201TI uptake, 53% had mildly reduced viability, and only 27% had severely reduced viability. 201TI viability criteria identified segments that improved function after CABG. Sixty-two percent of severely asynergic segments with normal viability and 54% with mildly reduced viability improved function after surgery, but only 23% with severely reduced viability improved function (p=0.002). When only adequately revascularized segments were considered, the predictive value of a positive preoperative viability scan for functional improvement was 73%. The greatest improvement in global LV function after CABG occurred in patients with the greatest number of asynergic segments classified as viable before surgery (p<0.01). In 10 patients with more than seven viable, asynergic segments, mean LV ejection fraction increased significantly after CABG (0.29±0.07 to 0.41±0.11, p=0.002). In 11 patients with seven or fewer viable, asynergic segments, mean LV ejection fraction remained unchanged after revascularization (0.27±0.05 to 0.30±0.08, p=NS). ConclusionsIn patients with CAD and severely depressed LV function, preoperative quantitative planar rest-redistribution 201TI imaging identifies viability in many asynergic myocardial segments, and these segments frequently improve function after CABG. The presence of numerous asynergic but viable myocardial segments before surgery correlated significantly with improvement in global LV function after bypass surgery.

Improved Outcome After Coronary Bypass Surgery in Patients With Ischemic Cardiomyopathy and Residual Myocardial Viability

BACKGROUND Although residual myocardial viability in patients with coronary artery disease and extensive regional asynergy is associated with improved ventricular function after coronary bypass surgery, the relationship between viability and clinical outcome after surgery is unclear. We hypothesized that patients with poor ventricular function and predominantly viable myocardium have a better outcome after bypass surgery compared with those with less viability. METHODS AND RESULTS Seventy patients with multivessel coronary artery disease and left ventricular ejection fractions < 40% who underwent preoperative quantitative 201Tl scintigraphy before coronary bypass surgery were analyzed retrospectively. 201Tl scintigrams were reviewed blindly, and each segment was assigned a score based on defect magnitude. Segmental viability scores were summed and divided by the number of segments visualized to determine a viability index. The viability index was significantly related to 3-year survival free of cardiac event (cardiac death or heart transplant) after bypass surgery (P=.011) and was independent of age, ejection fraction, and number of diseased coronary vessels. Patients with greater viability (group 1; viability index > 0.67; n=33) were similar to patients with less viability (group 2; viability index < or = 0.67; n=37) with respect to age, comorbidities, and extent of coronary artery disease. There were 6 cardiac deaths and no heart transplants in group 1 patients and 15 cardiac deaths and two transplants in group 2 patients. Survival free of cardiac death or transplantation was significantly better in group 1 patients on Kaplan-Meier analysis (P=.018). CONCLUSIONS We conclude that resting 201Tl scintigraphy may be useful in preoperative risk stratification for identification of patients more likely to benefit from surgical revascularization.

Tissue Heating During Radiofrequency Catheter Ablation: A Thermodynamic Model and Observations in Isolated Perfused and Superfused Canine Right Ventricular Free Wall

Thecharacteristics of radiofrequency catheter ablation induced injury in the heart are not well characterized. Since the mechanism of injury by radiofrequency energy is thermal, this study was performed to determine the temperature gradient in myocardial tissue during radiofrequency (RF) catheter ablation, and to validate a thermodynamic model derived to describe these observations. Lesions were created by RF heating in an experimental model of isolated perfused and superfused canine right ventricular (RV) free wall. RF power output was adjusted to maintain electrode tip temperature at 80°C for 120 seconds in 153 serial lesions and radial temperature gradients were measured. With increasing distance from the electrode, the temperature of the myocardium decreased in a hyperbolic form that was closely predicted by a derived thermodynamic model (P = 0.0001, r = 0.98). This gradient and resultant lesion sizes were unafected by the rate of coronary perfusion. The utility of tip temperature monitoring as a predictor of lesion size was tested in 104 serial lesions with tip temperatures that were varied between 50 and 85°C. The tip temperature correlated closely with lesion depth (P = 0.0001, r = 0.92) and width (P = 0.0001, r = 0.88), and was a better predictor of lesion size than measurements of power, current or energy. The temperature at the margin between viable and nonviable tissue was estimated to be 47.9°C. These data demonstrate that during radiofrequency catheter ablation, the radial temperature gradient is predictably hyperbolic and appears to be independent of intramyocardial perfusion if constant electrode temperature is maintained. The use of tip temperature monitoring can accurately predict the ultimate size of radiofrequency‐induced lesions.

Prospective assessment of regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy.

Because thallium-201 uptake relates directly to the amount of viable myocardium and nutrient blood flow, the potential for exercise scintigraphy to predict response to coronary revascularization surgery was investigated in 47 consecutive patients. All patients underwent thallium-201 scintigraphy and coronary angiography at a mean (+/- standard deviation) of 4.3 +/- 3.1 weeks before and 7.5 +/- 1.6 weeks after surgery. Thallium uptake and washout were computer-quantified and each of six segments was defined as normal, showing total or partial redistribution or a persistent defect. Persistent defects were further classified according to the percent reduction in regional thallium activity; PD25-50 denoted a 25 to 50% constant reduction in relative thallium activity and PD greater than 50 denoted a greater than 50% reduction. Of 82 segments with total redistribution before surgery, 76 (93%) showed normal thallium uptake and washout postoperatively, versus only 16 (73%) of 22 with partial redistribution (probability [p] = 0.01). Preoperative ventriculography revealed that 95% of the segments with total redistribution had preserved wall motion, versus only 74% of those with partial redistribution (p = 0.01). Of 42 persistent defects thought to represent myocardial scar before surgery, 19 (45%) demonstrated normal perfusion postoperatively. Of the persistent defects that showed improved thallium perfusion postoperatively, 75% had normal or hypokinetic wall motion before surgery, versus only 14% of those without improvement (p less than 0.001). Whereas 57% of the persistent defects that showed a 25 to 50% decrease in myocardial activity demonstrated normal thallium uptake and washout postoperatively, only 21% of the persistent defects with a decrease in myocardial activity greater than 50% demonstrated improved perfusion after surgery (p = 0.02). Thus, preoperative quantitative thallium-201 scintigraphy appears useful in predicting response to revascularization surgery, and some persistent defects may revert to normal thallium uptake after surgery. Importantly, the preoperative distinction between viable and nonviable myocardium can be reasonably established by quantitating the amount of persistent reduction in thallium uptake and correlating this with preoperative wall motion.

The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: a prospective natural history study.

Despite having smaller infarct size and better left ventricular function, patients with non-Q wave myocardial infarction (NQMI) appear to have an unexpectedly high long-term mortality that is ultimately comparable to that of patients with Q-wave myocardial infarction (QMI). Patients with NQMI may lose their initial prognostic advantage because there is more viable tissue in the perfusion zone of the infarct-related vessel, rendering myocardium more prone to reinfarction. We tested this hypothesis in a prospective study of 241 consecutive patients 65 years of age or younger with acute uncomplicated myocardial infarction confirmed by creatine kinase levels (MB fraction). All patients received customary care and none underwent thrombolytic therapy or emergency angioplasty. Predischarge coronary angiography, radionuclide ventriculography, 24 hr Holter monitoring, and quantitative thallium-201 (201T1) scintigraphy during treadmill exercise were performed 10 +/- 3 days after infarction. Infarcts were designated as QMI (n = 154) or NQMI (n = 87) by accepted criteria applied to serial electrocardiograms obtained on days 1, 2, 3, and 10. The baseline Norris coronary prognostic index, angiographic jeopardy scores, and prevalence of Lown grade ventricular arrhythmias were similar between groups despite evidence for less necrosis with NQMI vs QMI, reflected by lower peak creatine kinase levels (520 vs 1334 IU/liter; p = .0001, 4 hr sampling), higher resting left ventricular ejection fraction (53% vs 46%; p = .0001), fewer akinetic or dyskinetic segments (1.2 vs 2.4; p = .0001), and fewer persistent 201Tl defects in the infarct zone (0.9 vs 1.9; p = .0001). Patients with NQMI also had more patent infarct-related vessels (54% vs 25%; p less than .0001) and a shorter time from onset of infarction to peak creatine kinase level (16.9 vs 22.5 hr; p = .0001). Importantly, the prevalence and extent of quantitatively determined 201Tl redistribution within the infarct zone on exercise scintigraphy was greater in patients with NQMI vs those with QMI (60% vs 36%, p = .007; and 0.98 vs 0.53 myocardial segments, p = .0003); when the two groups were stratified on the basis of the infarct-related vessel, subset analysis revealed the same findings. During 30 months median follow-up, cardiac mortality was low, 8.4% in the QMI group and 9.2% in the NQMI group (p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Successful left ventricular opacification following peripheral venous injection of sonicated contrast agent: An experimental evaluation☆

A new agent for use in contrast echocardiography that is capable of passing through the pulmonary circulation and opacifying the left ventricular cavity after intravenous injection was evaluated in a canine model. Air-filled albumin microbubbles were produced by sonication. A Coulter counter was used to size and count the resultant microbubbles in vitro. The microbubbles had diameters sufficiently small (less than 9 micron) to permit transpulmonary passage. A total of 72 injections were made into the forepaw vein of five closed-chest dogs. Simultaneous two-dimensional echocardiographic images of the right ventricle and the left ventricle were recorded and digitized on an off-line computer. Of the 72 injections, 59 (82%) were suitable for digitization. Forty of the 59 digitized injections (68%) demonstrated left ventricular contrast enhancement. Indicator-dilution curves were generated from plots of intraventricular gray level VS time, and the curve widths and areas under the curves were determined. The ratio of total indicator curve area for left to right ventricular cavity was 0.39 for the 40 successful injections, indicating transpulmonary transmission of 39% of the contrast effect. Injection of bubbles with mean size less than 6 microns resulted in a larger median left ventricular curve area than those with bubbles averaging from 6 to 9 microns. Injections demonstrating successful left ventricular contrast opacification had larger right ventricular curve areas than those that were not successful. Blood pressure, heart rate, and arterial blood gases were not significantly altered by repeated intravascular contrast injections. Postmortem examination of hearts, lungs, livers, and kidneys revealed no histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of regional myocardial blood flow with myocardial contrast two-dimensional echocardiography

It was hypothesized that regional myocardial blood flow could be measured using myocardial contrast echocardiography. Accordingly, arterial blood was perfused into the coronary circulation in 16 dogs. In Group 1 dogs (n = 8), blood flow to the cannulated left circumflex artery was controlled with use of a roller pump, whereas in Group 2 dogs (n = 8) blood flow to the left anterior descending coronary artery was controlled by a hydraulic occluder placed around it. Sonicated microbubbles (mean size 4 microns) were used as the contrast agent. In Group 1 dogs the microbubbles were injected subselectively into the left circumflex artery, whereas in Group 2 dogs they were injected selectively into the left main coronary artery and two-dimensional echocardiographic images were recorded. Computer-generated time-intensity curves were derived from these images and variables of these curves correlated with transmural blood flow measured with radiolabeled microspheres. A gamma-variate function (y = Ate-alpha t) best described the curves, and alpha (a variable of curve width) correlated well with transmural blood flow at different flow rates in all Group 1 and Group 2 dogs (mean r = 0.81 and 0.97, respectively). Other variables of the curve width also correlated well with myocardial blood flow, but peak intensity had a poor correlation with myocardial blood flow in both groups of dogs (r = 0.39 and r = 0.63, respectively). When data from all dogs were pooled, Group 1 dogs still showed good correlation between variables of curve width and myocardial blood flow (r = 0.81); Group 2 dogs did not (r = 0.45). The difference between the two sets of dogs was related to the site of contrast agent injection. It is concluded that measurement of the transit time of microbubbles through the myocardium with two-dimensional echocardiography accurately reflects regional myocardial blood flow. Although injection of contrast agent selectively into the left main coronary artery only allows measurement of relative flow, it may be feasible to measure absolute flow by injecting contrast agent subselectively into a coronary artery. Myocardial contrast echocardiography may, therefore, offer the unique opportunity of simultaneously assessing regional myocardial perfusion and function in vivo.

Prognostic utility of the exercise thallium-201 test in ambulatory patients with chest pain: comparison with cardiac catheterization.

The goal of this study was to determine the prognostic utility of the exercise thallium-201 stress test in ambulatory patients with chest pain who were also referred for cardiac catheterization. Accordingly, 4 to 8 year (mean +/- 1SD, 4.6 +/- 2.6 years) follow-up data were obtained for all but one of 383 patients who underwent both exercise thallium-201 stress testing and cardiac catheterization from 1978 to 1981. Eighty-three patients had a revascularization procedure performed within 3 months of testing and were excluded from analysis. Of the remaining 299 patients, 210 had no events and 89 had events (41 deaths, nine nonfatal myocardial infarctions, and 39 revascularization procedures greater than or equal to 3 months after testing). When all clinical, exercise, thallium-201, and catheterization variables were analyzed by Cox regression analysis, the number of diseased vessels (when defined as greater than or equal to 50% luminal diameter narrowing) was the single most important predictor of future cardiac events (chi 2 = 38.1) followed by the number of segments demonstrating redistribution on delayed thallium-201 images (chi 2 = 16.3), except in the case of nonfatal myocardial infarction, for which redistribution was the most important predictor of future events. When coronary artery disease was defined as 70% or greater luminal diameter narrowing, the number of diseased vessels significantly (p less than .01) lost its power to predict events (chi 2 = 14.5). Other variables found to independently predict future events included change in heart rate from rest to exercise (chi 2 = 13.0), ST segment depression on exercise (chi 2 = 13.0), occurrence of ventricular arrhythmias on exercise (chi 2 = 5.9), and beta-blocker therapy (chi 2 = 4.3). The exclusion of myocardial revascularization procedures as an event did not change the results significantly. Although the number of diseased vessels was the single most important determinant of future events, the exercise thallium-201 stress test when considered as a whole (which included the number of segments demonstrating redistribution on delayed thallium-201 images, change in heart rate from rest to exercise, ST segment depression on the electrocardiogram, and ventricular premature beats on exercise) was equally powerful (chi 2 = 41.6). Combination of both catheterization and exercise thallium-201 data was superior to either alone (chi 2 = 57.5) for determining future events. Exercise stress test alone (without thallium-201 data) was inferior to the exercise thallium-201 stress test or cardiac catheterization for predicting future events (chi 2 = 30.6).(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201☆

The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.