Revascularization of a Dysfunctional LV
abstracts & commentary
Synopsis: Meluzin et al and Afridi et al conclude that the identification of a large amount of dysfunctional but viable myocardium in coronary artery disease (CAD) patients predicts a favorable outcome following revascularization.
Sources: Meluzin J, et al. J Am Coll Cardiol 1998;32: 912-920. Afridi I, et al. J Am Coll Cardiol 1998;32: 921-926.
In patients with ischemic left ventricular (lv) dysfunction, revascularization can improve LV function. However, whether revascularization or the improved LV function will affect survival is unclear. Thus, two recent studies are of interest. Meluzin et al studied 274 patients referred for coronary angiography and possible revascularization with a left ventricular ejection fraction (EF) of 40% or less, at least one vessel coronary artery disease, a technically good dobutamine stress echocardiogram (DSE), and no other confounding diseases. Of these patients, 139 were revascularized based on clinical criteria using bypass surgery in 118 and angioplasty in 15. The patients were followed for an average of 20 months for cardiac events including death, myocardial infarction, hospitalization for unstable angina, and heart failure. Resting echocardiograms were done 3-6 months following revascularization. Based on the DSE results, three groups were established: group A, 29 patients with a large amount of dysfunctional but viable myocardium; group B, 60 patients with a small amount of viable myocardium; and group C, 44 patients with nonviable damaged myocardia. Following revascularization, LVEF increased in the patients in group A from 35 to 47% (P < 0.01), in group B from 34 to 40% (P < 0.01), and group C showed no change (36-37%). Cardiac events were much lower in group A as compared to groups B and C (2 vs 18 vs 17%; P < 0.05). Event-free survival was higher in group A vs. groups B and C, but survival alone was not significantly different between groups. Meluzin et al and Afridi et al conclude that the identification of a large amount of dysfunctional but viable myocardium in coronary artery disease (CAD) patients predicts a favorable outcome following revascularization.
Comment by Michael H. Crawford, MD
The important finding in Meluzin et al’s study is that in the patients with a large amount of dysfunctional but viable myocardium who underwent revascularization, there was only one early death, there were no late deaths, and no late events. In addition, these patients experienced the greatest improvement in LVEF. These results are compelling but there are some limitations to this study. First, it is a small study population that was underpowered to look at survival alone. Also, it’s unclear how many patients were screened to arrive at this group of subjects who all were suitable for revascularization, all had excellent echocardiograms, and had no myocardial infarction or unstable angina episodes in the last two months. Finally, we don’t know the extent of revascularization in these patients since there were no follow-up catheterization data. However, if angina is used as a surrogate for the extent of revascularization, it decreased significantly postoperatively.
The second study is based on the concept that there are little data in patients with CAD and severe LV systolic dysfunction about whether myocardial viability affects outcome. Thus, Afridi et al studied 318 patients with CAD and LVEF of 35% or less who had DSE and were followed for an average of 18 months. The specific aim of the study was to test whether viability as determined by DSE was predictive of survival. This observational study divided patients into four groups: group 1, 85 patients with viability who underwent revascularization; group 2, 119 patients with viability who did not undergo revascularization; group 3, 30 patients who had no viability but underwent revascularization; and group 4, 84 patients who had neither viability nor revascularization. The mean age of the patients was 64 years, average LVEF was 27%, and 54% of the patients had three-vessel disease. Among 204 patients with viability by DSE, there was no difference in LVEF between groups 1 and 2(27 vs 28%). Viability was defined using a 16-segment echocardiographic LV model where four or more segments either needed to improve or show a biphasic response. Within three months of DSE, 115 patients underwent revascularization (79 bypass surgery, 36 angioplasty). Among the total population of 318 patients, there were 51 deaths during follow-up (16%). Early mortality associated with revascularization was not different between surgery and angioplasty (8 vs 11%). Survival was best in group 1 compared to the other three groups and the difference in survival increased over time: at six months, survival in group 1 was 99% vs. 94% in the other three groups; at 12 months, 96 vs. 89%; at 18 months, 92 vs. 83%; and at two years, 92 vs. 78% (P = 0.01). Multivariate analysis adjusting for age, LVEF and CAD severity showed that the best predictor of survival was group 1 characteristics. Among the patients who did not undergo revascularization, age, LVEF, and a lack of viability predicted mortality. Afridi et al conclude that patients with CAD and severe LV dysfunction who had DSE evidence of myocardial viability and underwent revascularization had improved survival compared to those medically treated .
The important results of the Meluzin study are that patients with severe LV dysfunction and evidence of myocardial viability had a much better prognosis with revascularization. Interestingly, there was no difference in outcome among those who had an absence of myocardial viability and who were either treated medically or with revascularization, nor was there any difference between these two groups and those with evidence of viability who were treated medically. Patients with myocardial viability treated medically had the same prognosis as patients without myocardial viability no matter how the latter group was treated. Also of interest was that the differences in mortality took time to be manifest. Biologically significant differences were not observed until after one year of follow-up. The reason for this is not known from the study, but it may be that there needs to be time to overcome the initial effect of the somewhat higher surgical mortality in patients with severely depressed LVEF. However, there may be myocardial stunning or hibernation that takes time to recover after revascularization. Also, the mechanism of increased survival is not known from the data. It could be the improvement in LVEF since this measure is a powerful predictor of survival in most studies of patients with CAD. On the other hand, even patients whose LVEF did not improve seem to have better survival and this may be due to a cessation of remodeling, which would tend to reduce LVEF further, or a change in the susceptibility of the heart to lethal ventricular arrhythmias.
Although this study presents compelling data, there were some limitations. First, the DSE results were available to the treating physicians and this may have influenced their referrals for revascularization. Since patients were not randomized to revascularization, definitive conclusions about the value of medical vs. surgical therapy could not be derived from this study. Also, the group of patients without evidence of viability who underwent revascularization was a small group. Although they appeared not to benefit, their mortality was no higher than those with no viability who were not revascularized. It would probably take a randomized trial to clarify this issue.
These two studies, although imperfect, present strong observational data for the revascularization of patients with CAD, severe LV dysfunction, and evidence of myocardial viability. As Meluzin et al and Afridi et al suggest, this may be a way to distinguish revascularization from transplant candidates. Thus, Meluzin et al and Afridi et al suggest that such patients always need a viability study, although these two studies used DSE, there is no reason to think that thallium imaging or PET scanning could not produce similar results based on previous comparative trials showing similar ability to detect viable myocardium with these three techniques. When the gold standard of improved segmental myocardial function following revascularization has been applied to all three techniques, none are perfect at detecting viable myocardium. In fact, as much as 15% of patients with viable myocardium based on this clinical definition may be missed by all three techniques used singly. Given the high mortality in patients with viability and medical treatment demonstrated in the Afridi study, an argument can be made to revascularize all suitable patients with CAD and severe LV dysfunction. In support of this argument is that patients with no viability who are revascularized did not fare any worse than patients with no viability who are not revascularized. So the erroneous revascularization of patients with non-viable myocardium may not worsen survival. Thus, the argument could be made that you have nothing to lose revascularizing all CAD patient with severe LV dysfunction, as long as it’s anatomically feasible to accomplish revascularization. This approach would mean that no one needs a viability study. This has been our approach but we do use viability studies when the surgeons are reluctant to operate because of co-morbidity. If extensive viable myocardium is discovered, it makes the patient more attractive to the surgeons despite the increased risk of the co-morbid conditions. No matter what approach is used to identify appropriate revascularization candidates, it is clear that patients with CAD and severe LV dysfunction should be seriously considered for revascularization prior to any other form of treatment.
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