Functional status and quality of life in patients with heart failure undergoing coronary bypass surgery after assessment of myocardial viability.

OBJECTIVES: The aim of this study was to evaluate whether preoperative clinical and test data could be used to predict the effects of myocardial revascularization on functional status and quality of life in patients with heart failure and ischemic LV dysfunction. BACKGROUND: Revascularization of viable myocardial segments has been shown to improve regional and global LV function. The effects of revascularization on exercise capacity and quality of life (QOL) are not well defined. METHODS: Sixty three patients (51 men, age 66+/-9 years) with moderate or worse LV dysfunction (LVEF 0.28+/-0.07) and symptomatic heart failure were studied before and after coronary artery bypass surgery. All patients underwent preoperative positron emission tomography (PET) using FDG and Rb-82 before and after dipyridamole stress; the extent of viable myocardium by PET was defined by the number of segments with metabolism-perfusion mismatch or ischemia. Dobutamine echocardiography (DbE) was performed in 47 patients; viability was defined by augmentation at low dose or the development of new or worsening wall motion abnormalities. Functional class, exercise testing and a QOL score (Nottingham Health Profile) were obtained at baseline and follow-up. RESULTS: Patients had wall motion abnormalities in 83+/-18% of LV segments. A mismatch pattern was identified in 12+/-15% of LV segments, and PET evidence of viability was detected in 30+/-21% of the LV. Viability was reported in 43+/-18% of the LV by DbE. The difference between pre- and postoperative exercise capacity ranged from a reduction of 2.8 to an augmentation of 5.2 METS. The degree of improvement of exercise capacity correlated with the extent of viability by PET (r = 0.54, p = 0.0001) but not the extent of viable myocardium by DbE (r = 0.02, p = 0.92). The area under the ROC curve for PET (0.76) exceeded that for DbE (0.66). In a multiple linear regression, the extent of viability by PET and nitrate use were the only independent predictors of improvement of exercise capacity (model r = 0.63, p = 0.0001). Change in Functional Class correlated weakly with the change in exercise capacity (r = 0.25), extent of viable myocardium by PET (r = 0.23) and extent of viability by DbE (r = 0.31). Four components of the quality of life score (energy, pain, emotion and mobility status) significantly improved over follow-up, but no correlations could be identified between quality of life scores and the results of preoperative testing or changes in exercise capacity. CONCLUSIONS: In patients with LV dysfunction, improvement of exercise capacity correlates with the extent of viable myocardium. Quality of life improves in most patients undergoing revascularization. However, its measurement by this index does not correlate with changes in other parameters nor is it readily predictable.

Correlation of preoperative myocardial function, perfusion, and metabolism with postoperative function at rest and stress after bypass surgery in severe left ventricular dysfunction.

Previous studies of dobutamine echocardiography (DE) and positron emission tomography (PET) showed similar accuracy for predicting improvement in resting wall motion after revascularization, although limited direct comparative data are available. We sought to compare the relative accuracy of detecting contractile reserve, ischemia, perfusion, and myocardial metabolism for predicting functional recovery after coronary bypass surgery in 94 consecutive patients (aged 63+/-11 years) with chronic coronary disease and depressed left ventricular function (ejection fraction 28+/-5%). PET imaging comprised rest and dipyridamole stress myocardial perfusion images, with fluorodeoxyglucose to define metabolism-perfusion mismatch. A standard dobutamine-atropine stress was used, with evaluation of low- and peak-dose echocardiographic responses. Regional function was assessed after 13+/-16 weeks at rest in 68 patients who underwent isolated coronary bypass operation without evidence of perioperative infarction, and at rest and stress in a subgroup of 29 patients. Concordance between methods for evaluating abnormal segments (ischemic, viable, and scar) and accuracy of both tests for predicting improvement in regional function were identified. Concordance between PET and DE for identifying viable or nonviable myocardium was 63% using a 16-segment model. For predicting improved resting function after surgery, the sensitivity of PET (84%) was superior to DE (69%, p<0.001), but DE was more specific (78% vs. 37%, p<0.0001) and more accurate (75% vs. 53%, p<0.001) in predicting recovery at rest. Analysis of postoperative recovery of segmental function during stress also showed the specificity of DE to exceed that of PET (89% vs. 32%, p<0.001). The accuracy of DE was enhanced by evaluation of function during stress (86%, p<0.001), but this was not altered with PET (52%, p = NS). Thus, PET is more sensitive than DE in predicting functional recovery, but DE is more specific than PET. Evaluation of left ventricular functional recovery during stress may be preferable to assessment at rest.

Phospholipid turnover during the division cycle of Escherichia coli.

The turnover of phospholipids in Escherichia coli B/r was analyzed in synchronously growing populations. The turnover of presynthesized phosphatidyl-glycerol and cardiolipin continued at a constant exponential rate throughout the division cycle.

Ribosomal genes not integrated into chromosomal DNA in Drosophila melanogaster.

DNA obtained by a gentle lysis procedure from adult Drosophila melanogaster was analyzed by sucrose gradient sedimentation. The major portion of the DNA has an estimated weight of at least 5--10 X 10(9) daltons. All of the ribosomal genes are present in this high molecular weight DNA in adult males with one nucleolus organizer or in adult females with two nucleolus organizers as shown by hybridizing fractions of the gradient with ribosomal RNA. In female adults with one nucleolus organizer instead of the usual two, 68% of the ribosomal genes are found in high molecular weight DNA and 32% are found in DNA of smaller size (approximately 3 X 10(8) daltons). We propose that these latter genes are not integrated into the DNA of the chromosome.

Unintegrated ribosomal genes in diploid and polytene tissues of Drosophila melanogaster.

We have examined DNA from polytene salivary glands and diploid brains and imaginal discs of male and female larvae having one or two nucleolus organizers. DNA having an estimated molecular weight of 5 X 10(9) or greater was obtained by sucrose gradient sedimentation of gently prepared lysates. Hybridization of the gradient fractions with 3H-ribosomal RNA REVEALS THAT 42% OF THE RIBOSOMAL GENES ARE FOUND IN DNA of lower molecular weight (approximately 3 X 10(8) daltons) in the salivary glands of every genotype examined. In the brains and imaginal discs, by contrast, all of the ribosomal genes are found in the high molecular weight peak except in females with one nucleolus organizer where 42% are found in lower molecular weight DNA, as in the salivary gland. Thus unintegrated genes are not an exclusive feature of polytene tissue, but can occur in diploid tissue as well in at least one genotype.

Chromosomal rearrangements which affect the chromosomal integration of the ribosomal genes in Drosophila melanogaster.

Sucrose gradient analysis of DNA from detergent-pronase lysates of whole adult flies has been used to examine a variety of genotypes for the presence of ribosomal genes not integrated into the DNA of the chromosome. Such genes were found in females in which one X chromosome carries an inversion, having one of its breakpoints between the nucleolus organizer and the centromere. These inversions move the nucleolus organizer to the distal end of the X chromosome. Other inversions which do not move the nucleolus organizer, as well as a series of bobbed deficiencies, did not induce unintegrated genes. The same inversions which induce unintegrated genes in adults also produce them in the diploid brain and imaginal discs of larvae. On the other hand, in the polytene salivary glands, unintegrated genes were found in every genotype examined.

The effect of X chromosome heterozygosity on the structure of the ribosomal genes in Drosophila melanogaster.

Sucrose gradient analysis of DNA isolated from detergent-pronase lysates of adult flies has been used to look for ribosomal genes not integrated into the DNA of the chromosome in genotypes containing various combinations of inversions having breakpoints in the proximal heterochromatin of the X chromosome. Unintegrated genes are found in females heterozygous for inversions which have one breakpoint between the nucleolus organizer and the centromere. Homozygotes and males do not have unintegrated genes. The results suggest that unintegrated ribosomal genes result from an interaction between homologues having different arrangements of the proximal heterochromatin. In addition, data from a series of stocks carrying duplications of the X heterochromatin provide independent evidence for the size of the DNA on our gradients.