REPLY:

We appreciate the comments on our article (1) and the article by Sciagra (2). As Dr. Bianco mentions, viability assessment is of paramount clinical importance, especially in patients with severe left ventricular dysfunction in whom the outcome without intervention is poor but the risk of revascularization is high. It is interesting that the regional thickening of myocardial segments with severely reduced coronary blood flow reserve can improve in response to low-dose dobutamine. Lee et al., using PET, reported that myocardial blood flow increased more in contractile reserve-positive segments than in contractile reserve-negative segments in patients with left ventricular dysfunction (3). Thus, low-dose dobutamine is considered able to improve myocardial blood flow and contractile function, even in segments with impaired flow reserve of severe left ventricular dysfunction.

In our study (1), nitroglycerin preferentially reduced coronary vascular resistance (CVR) without significantly changing it in the nonischemic or nonviable myocardium. The reduction in CVR in viable myocardium with ischemia could be caused by dilatation of epicardial coronary stenosis and collateral vessels. The lack of reduction in CVR in nonviable myocardium may be because of damage in the myocardium itself or in the microcirculation, despite the dilatation of these vessels. CVR in nonischemic myocardium may be determined by the small microvessels, on which nitroglycerin has little effect. This change in CVR apparently makes coronary blood flow redistribute from the nonischemic to the ischemic myocardium with viability. From the teleologic point of view, apparent redistribution of flow from the nonischemic to the ischemic myocardium with viability effectively relieves regional ischemia and anginal pain, if present. Further studies are needed to evaluate myocardial perfusion induced by nitroglycerin and by low-dose dobutamine in the various myocardial segments. Studies of coronary circulation have demonstrated that the control of CVR is interesting but complex. Mechanisms responsible for these heterogeneous responses need further examination. The difference in flow responsiveness to nitrate and dobutamine will offer new insights into the pathophysiology of dysfunctional myocardium and may be useful for better tissue characterization.

REPLY:

I am grateful to Dr. Bianco for the kind attention to my commentary on the article by Tadamura et al. (1,2). In my opinion, the equation between hibernating myocardium and reduced resting blood flow is somewhat simplistic, and the concept that viable dysfunctional myocardium is always the result of repetitive stunning is oversimplified as well (3). As Bianco correctly remarks, it is difficult to explain the contractile response elicited by low-dose dobutamine in the absence of any change in coronary blood flow. Sun et al., measuring myocardial blood flow with PET and ¹³NH₃, observed a slightly reduced baseline flow in dysfunctional viable regions, and during low-dose dobutamine there was an increase that was more limited than in normal segments (4). In an experimental model of chronic regional dysfunction in dogs, Gerber et al., using PET and ¹³NH₃, demonstrated a preserved baseline myocardial blood flow with a reduced coronary reserve as compared with normally contracting segments (5). Thus, it could be concluded that a preserved although reduced coronary reserve must be present to support the contractile response to low-dose dobutamine stimulation, independently of the level of baseline blood flow (6). To return to the clinical issues raised by Bianco, it is important to remember, as for instance demonstrated by Bax et al. (7), that myocardial perfusion imaging is more sensitive (but less specific) than dobutamine echocardiography in detecting viable myocardium. The extent of ultrastructural damage in the dysfunctional region has been advocated to explain the discrepancy between preserved uptake of perfusion agents and maintained contractile reserve (8). To overcome the intrinsic limitation of each diagnostic modality and as correctly suggested by Bianco, the combined evaluation of different viability markers could be helpful to optimize the recognition of segments likely to recover after revascularization (9). This is most important in the current clinical scenario, in which population aging dramatically increases the number of patients with heart failure symptoms and consequently the need for methods able to identify at a reasonable cost the presence of reversible left ventricular dysfunction.