Revascularization of the Dysfunctional Left Ventricle
ABSTRACTS & COMMENTARY
Synopsis: Cardiologists need to be more attentive to the patient with severe CAD who has depressed LV function.
Sources: Williams J, et al. Am Heart J 1998;136:57-62; Wijns W, et al. N Engl J Med 1998;339:173-181; Fath-Ordoubadi F, et al. Am J Cardiol 1998;82:26-31.
Two studies indicate that in selected subjects with multi-vessel coronary artery disease (CAD) and marked depression of left ventricular (LV) systolic function, revascularization with bypass surgery may substantially improve LV function as well as improving exercise capacity. Williams and associates studied a non-randomized cohort of 52 individuals with LV dysfunction and CAD from the Cleveland Clinic. They were assessed with baseline metabolic stress testing and LV function evaluation before and six months after bypass grafting or intensive medical treatment, compared to a control group of dilated cardiomyopathy patients with comparable baseline systolic function who received maximum medical therapy. The subjects with ischemic heart disease had an average ejection fraction of 25% and were divided into two groups-the bypass cohort (group A) consisting of 20 patients and an aggressive medical therapy group (B) of 16 individuals with comparable LV function who were not considered to be candidates for revascularization. A significant number in Group A had angina pectoris. Controls consisted of 16 patients with dilated cardiomyopathy. All individuals underwent baseline metabolic stress testing with on-line collection of expired air and assessment of CO2 consumption and CO2 production. Baseline LV function was measured by quantitative echocardiography or radionuclide angiograms. The bypass subjects received an average of three grafts; the optimal medical treatment group was treated with an increase in ACE inhibitors, as well as the addition of nitrates, digitalis, and diuretics when appropriate. Presumably, the dilated cardiomyopathy patients received similar therapy. Following revascularization, Group A individuals increased baseline exercise performance from 4.7 to 5.6 mets (P = 0.02), whereas Group B and C individuals did not significantly increase exercise performance (B: 4.7-5.0 mets, C: 5.2-5.2 mets, both NS) at follow-up. Follow-up metabolic exercise testing was carried out 8 ± 6 months after baseline. When the six bypass patients with angina were excluded, a comparable increase in exercise performance remained. Ejection fraction rose only in Group A, 26 ± 5% increasing to 31 ± 6% post op; Group B and C had no augmentation of ejection fraction (25% and 23% at baseline, respectively). Williams et al conclude that selective revascularization in appropriate patients resulted in improvement in exercise performance as well as systolic function, and they suggest that this is the first study to show concordance between these two parameters. They believe that the revascularization improved zones of viable myocardium with depressed myocardial function, although viability studies were not performed.
In a study from London and the Cyclotron Unit at Hammersmith Hospital, a comparable group of individuals with CAD and abnormal LV function were subjected to positron emission tomography (PET) during euglycemic hyperinsulinemic clamp with (18F)2-fluoro-2-deoxy-D-glucose (FDG) PET imaging. Global and regional left ventricular function was assessed before and 4-6 months after bypass surgery in 47 patients with CAD and LV dysfunction. Patients were arbitrarily divided into two groups with moderate or severe left ventricular dysfunction. Group 1 consisted of 26 patients with a mean ejection fraction of less than 30%, whereas Group 2 included 21 subjects with an ejection fraction of more than 30%. Following revascularization, ejection fraction improved substantially in Group 1 (22 ± 6% to 31 ± 10%, P = < 0.0001), with a concordant improvement in wall motion score. In the patients with better baseline ejection fraction, there was no change in global ejection fraction (43 ± 9% vs 43 ± 12%), although wall motion scored tended to improve somewhat. FDG uptake was able to predict improvement. Those segments that were dysfunctional at baseline and had a higher FDG uptake improved the greatest. Of all segments analyzed 4-6 months after bypass surgery, 46% were normal and 54% were pre-operatively dysfunctional. Of the latter, 60% improved following revascularization, particularly in Group 1 subjects. The metabolic rate of glucose uptake (MRG) on PET imaging was proportional to depression of baseline LV function. Those segments that improved had a higher baseline MRG on a regional and global basis as well as substantially more dysfunctional segments. Thus, the segments with worst function at baseline that were shown to be viable on PET imaging improved the most. The predictive accuracy of PET was related to baseline LV function; glucose use at baseline was greater in those who improved the most. The low ejection fraction group would appear to have had a greater potential recovery of myocardial tissue than those with higher ejection fraction.
COMMENT BY JONATHAN ABRAMS, MD
These two small studies are observational at best, but confirm that dysfunctional LV myocardium that is viable will improve following revascularization, and that improvement can be substantial in appropriately selected individuals. The Cleveland Clinic study did not use viability studies, but the presence of angina and ischemia was higher in the patients selected for bypass surgery. Bias in physician decision making for medical or surgical therapy clearly influences this report, as does the small sample size. Nevertheless, the data are not surprising. What appears to be new is the demonstration that metabolic exercise test performance was shown to be enhanced in the revascularization patients but not in medically treated individuals. The London study indicates that detection of viable myocardium, with a highly sophisticated PET technique, is predictive of both regional and global improvement in LV function following revascularization. A recent review article of the subject of hibernating myocardium has just appeared. This overview argues strongly for an enhanced use of techniques to assess viable myocardium in patients with CAD and depressed regional and/or global LV function. Based on literature review, these authors estimate that hibernating myocardium may exist in one-third to one-half of individuals with prior infarction, and that functional recovery is possible in a large number of dysfunctional segments. They stress that the latest research in animals and humans appears to reject the well-known hypothesis that hibernation is due to marked reduction of baseline blood flow. The authors discuss recent data indicating that blood flow is actually normal or slightly below normal in zones of depressed LV function that remain viable, and suggest that myocardial stunning due to recurrent ischemia may be an important mechanism in hibernation. There is a specific pathophysiology in hibernating myocardium characterized by severely reduced myocardial function and normal or moderately reduced blood flow. Techniques to detect myocardial viability are discussed in detail and include low-dose dobutamine echocardiography, nuclear imaging with technetium-99m sestamibi or thallium-201, as well as PET imaging with FDG. Thallium imaging may be done with stress-redistribution or with rest-redistribution techniques, both having rather low specificities. All techniques demonstrate a high sensitivity.
In conclusion, cardiologists need to be more attentive to the patient with severe CAD who has depressed LV function, and not necessarily conclude that the depressed LV systolic function must be due to scar. This is particularly an issue in individuals who do not have extensive Q waves in the electrocardiogram. Nevertheless, it is often difficult to predict which dysfunctional zones will or will not be viable without testing. It appears that PET imaging is the best technique for the detection of viable-hibernating muscle, but this is available only in a small percentage of institutions, and physicians must rely on and learn to use dobutamine or nuclear techniques. Much older data, including those from the CASS Trial, indicate that the poor prognosis of individuals of CAD and a bad ventricle can be substantially improved with revascularization. It is now well established that many segments that are hypokinetic, akinetic, and even dyskinetic at baseline may improve substantially when blood flow is restored. This will often result in improved clinical outcomes as well.
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