We have read the report by Desch et al with great interest. The investigators evaluated the impact of the coronary collateral circulation in patients with acute ST-segment elevation myocardial infarctions who underwent primary percutaneous intervention. They found that patients with well-developed coronary collaterals had smaller infarctions, lower microvascular obstruction, and a tendency toward better clinical outcomes. Certainly, this is a highly important topic. The relevance of the collateral circulation has been debated for decades. However, the study by Desch et al adds to the increasing evidence that the coronary collateral system has an important protective effect. Of note, this protection is most important during an acute vessel occlusion, such as in the investigators’ study setting. Desch et al raised an essential question and in general, they addressed this question using sound methods and analyses.

Nevertheless, we think that there is a relevant caveat to be considered when interpreting Desch et al’s results. Although they claim to have used “the reference method” (magnetic resonance imaging) to assess the dependent variables of the study (infarct size and microvascular obstruction), they failed to do so for their predictor variable (i.e., the coronary collateral circulation). The predictor variable is especially critical; although some (random) measurement error is less problematic for the dependent variable, standard statistical regression models assume the predictor variable to be measured error free. Far from being error free is the method Desch et al chose to “quantify” coronary collaterals, Rentrop scoring. This method is a “guesstimate” and shows poor agreement with the gold standard, the hemodynamic assessment of collaterals (collateral flow index).

Furthermore, the fact that Desch et al even included patients without total coronary occlusion (Thrombolysis In Myocardial Infarction flow grade 1) represents a major limitation. Rentrop et al originally described this method by estimating vessel filling in a balloon-occluded vessel while injecting the contralateral vessel through a second catheter. Desch et al did not describe whether they actually used a second guide catheter. Even if performed in this strict sense, other important limitations of this approach cannot be overcome, such as its dependence on injection force and on projection angles, the lack of functional information, and so on.

In the end, the results of Desch et al’s study appear clinically plausible but must be interpreted in the context of these limitations. The findings indicate the importance of finding means for the therapeutic induction of collateral growth; in fact, first phase I and II trials have shown that collateral induction in human is feasible.