Prediction by postexercise fluoro-18 deoxyglucose positron emission tomography of improvement in exercise capacity after revascularization.

The extent of ischemic and hibernating myocardium, which may be detected by increased postexercise uptake of fluoro-18 deoxyglucose (FDG) using positron emission tomography, may determine the degree of functional benefit after revascularization. This study examined the influence of the amount of this FDG-avid myocardium on changes in left ventricular function and exercise parameters after revascularization. Echocardiography and exercise testing were performed before and after intervention in 23 patients who had undergone positron emission tomography for the evaluation of myocardial perfusion (using rubidium-82), and postexercise FDG imaging in the fasting state. Follow-up echocardiography (22 +/- 14 weeks after revascularization) was compared with preoperative FDG activity in 7 myocardial regions per patient. Systolic function improved after intervention in 19 of 26 malperfused, dysfunctional FDG-avid regions (73%), and did not improve in 35 of 47 dysfunctional regions without increased FDG uptake (74%). The influence of the amount of FDG-avid tissue on changes in functional state was examined by comparing 9 patients with multiple (greater than or equal to 2) FDG-avid regions with the remainder. Those with multiple FDG-avid regions demonstrated improvement in peak rate-pressure product (20 +/- 4 to 26 +/- 4 x 10(3), p less than 0.02), and percentage of maximal heart rate achieved at peak (84 +/- 10% to 93 +/- 6%, p = 0.04), neither of which changed significantly in the remaining patients. Exercise capacity increased from 5.6 +/- 2.7 to 7.5 +/- 1.7 METS in the group with multiple FDG-avid regions; this increase of 55 +/- 18% exceeded the increase of 13 +/- 10% in the remainder (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

The value of 2-D Doppler echocardiography in the evaluation of asymptomatic patients with Mustard operation for transposition of the great arteries

2-D Doppler echocardiography was used to assess the occurrenceof haemodynamic abnormalities in 45 asymptomatic patients, aged4 to 16 years (median 7·4) after a Mustard operationfor transposition of the great arteries. The findings were comparedwith those derived from cardiac catheterization. Thirty-fivecardiac lesions were correctly diagnosed by 2-D Doppler echocardiographyin 23 patients, but on six occasions, minor abnormalities weremissed. 2-D Doppler echocardiography demonstrated systemic venouspathway obstruction of more than 3 mmHg at cardiac catheterizationin nine patients, and in five of the six patients with pulmonaryvenous channel obstruction. A left ventricular outflow tractobstruction (pressure difference > 15 mmHg) was diagnosedcorrectly by Doppler echocardiography in seven patients. Baffleleakage was found in two patients with a left to right shuntof 25% or more of pulmonary bloodflow, but was missed in fiveout of nine patients with small shunts. Tricuspid regurgitationwas well defined in eight patients, The absence of symptomsand a routine examination after a Mustard operation do not ruleout haemodynamic abnormalities. However, these, with the possibleexception of minor baffle leakage, can be detected by 2-D Dopplerechocardiography.     

Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as ≥1 stenosis of ≥50% in a major epicardial artery or its main branches; severe coronary disease was defined as ≥50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with ≥70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.     

Prediction of outcomes in hypertensive patients with suspected coronary disease

Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0+/-1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%, P< 0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43, P=0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75, P=0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.     

Identification of recurrent ischemia after coronary artery bypass surgery: a comparison of positron emission tomography and single photon emission computed tomography.

Current techniques for the detection of recurrent coronary stenoses following bypass grafting have shown disappointing diagnostic accuracy. This study used the same dipyridamole-handgrip stress to compare the accuracy of rubidium-82 positron emission tomography and thallium-201 single photon emission computed tomography, in 50 consecutive post-bypass patients undergoing coronary arteriography at a mean interval of 6.5 years after surgery. Significant stenoses in native coronary vessels (greater than 50% diameter) or grafts (greater than 70% diameter) were defined by quantitative angiography. Forty-six patients had recurrent or residual stenoses, 43 (93%) had a perfusion defect identified by positron emission tomography, and 35 (76%) were identified by single photon emission computed tomography (P = 0.04). Fourteen of the 17 patients (82%) without previous Q-wave myocardial infarction were identified by positron emission tomography; 10 of the 17 (59%) were detected by single photon emission computed tomography (P = NS). Stress-induced perfusion defects were demonstrated by positron emission tomography in 19 patients; of this group, thallium imaging identified reversible defects in 11, showed no perfusion defect in 1, and portrayed a persistent defect in 7 patients. Significant graft disease was present in 33 patients; perfusion defects were identified by positron emission tomography in 30 (91%), and by single photon emission computed tomography in 24 (73%, P = NS). Four patients were fully revascularized, without significant recurrent coronary disease; normal perfusion was present in 3 (75%) by positron emission tomography, and 4 (100%) by single photon emission computed tomography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cell cycle progression of B-chronic lymphocytic leukemia cells induced to differentiate by TPA

The cell cycle transition and differentiation-associated surface antigen expression was studied in a clone of B cell chronic lymphocytic leukemia (B-CLL) with phenotypic properties similar to those of resting B lymphocytes. Differentiation was induced with TPA (12-O-tetradecanoyl- phorbol-13-acetate) and defined and quantitated by morphological and functional markers. Changes in the cell cycle position were determined by flow cytometry of acridine orange-stained cells. The uninduced B-CLL cells represented a homogeneous population with the same cell cycle position (GO) as resting normal peripheral blood lymphocytes. After five days of TPA stimulation, 56% of the B-CLL cells were found in G1A, 9% in G1B, and 3% in the S + G2/M phase, of which 2% was accounted to proliferating T cells. The cell cycle transition of the differentiating B-CLL cells was also examined using cell cycle-associated surface antigens as markers. HLA-DR and CD23 antigens were present already on noninduced cells. The former had a high constant expression, while the amount of CD23 increased upon induction. The 4F2 antigen was absent on noninduced cells but present on 86% of the induced cells. HH1 (CD37) was expressed by the majority of the cells before TPA treatment and decreased to almost undetectable levels within 24 hours. Two antigens related to late stages of the cell cycle, the interleukin 2 (IL 2; CD25) and the transferrin receptor, were present on about 20% of the induced cells. Experiments with enriched T cells showed that T but not B cells incorporated 3H-thymidine. Taken together these results and previous work on the induction of the protooncogene c-myc and c-fos suggest that this B-CLL clone represents GO cells that undergo differentiation without concomitant proliferation when exposed to TPA.