Is myocardial contrast echocardiography ready to assume 'gold standard' status for quantification of collateral flow in humans?

Quantification of collateral flow in humans is most important and we recognize the valuable contribution by Vogel et al.1 towards this aim. However, some methodological issues related to the promising ultrasound-based method described should be resolved before it is pronounced the gold standard. A fundamental source of error is the assumption that blood vessels are rigid tubes and that relative blood volume (rBV) is constant during a coronary occlusion despite a substantial drop in perfusion pressure. Experimental findings demonstrated that blood volume dynamically varies with pressure.2 This is in line with earlier observations by this group3 showing a significant increase in rBV in healthy volunteers upon adenosine-induced vasodilation, which raises pressure in the microcirculation downstream of the resistance vessels. An erroneous assumption of constant myocardial blood volume during coronary occlusion critically affects calculated collateral flow. The relationship with the pressure-derived collateral flow index (CFIp) is a function of the filling volume during proximal occlusion (represented by myocardial plateau intensity A). If the filling volume used in the fitting procedure is too high, the exchange frequency β is more than proportionally too small and, consequently, collateral blood flow is underestimated. In contrast, a smaller filling volume would lead to further underestimation of the relative perfusion index, CPI, by CFIp. Information on the period between coronary occlusion and start of the perfusion-refill sequence or on changes in filling volume of the collateral-dependent region with declining perfusion pressure is therefore essential to ascertain steady state after onset of the acute occlusion. In our opinion, this fundamental issue at present precludes reliable application of this method to quantify collateral flow in humans or to validate pressure-derived CFI. Additionally, heart contraction has a strong effect on coronary and collateral pressure-flow relations,4 especially on subendocardial perfusion.5 It would be a valuable contribution of myocardial contrast echocardiography if a distinction could be made between subendocardial and subepicardial perfusion, especially when investigating collateral flow. Although collateral flow may be measurable to a certain region, it may not help the subendocardium where it is needed most.