Meta-analysis: Coronary Collateral Flow Linked to Reduced CAD Mortality

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In patients with coronary artery disease (CAD), a high level of coronary collateralization reduces the risk of death by more than one-third compared with patients with no or only faintly visible coronary collateral circulation on angiography, researchers conclude in a study published online October 3, 2011, ahead of print in the European Heart Journal.

Christian Seiler, MD, of University Hospital Bern (Bern, Switzerland), and colleagues conducted a meta-analysis of 12 studies involving a total of 6,529 patients. Most studies included a visual assessment and classified patients as having high or low collateral circulation.

Patients with high collateralization had a lower mortality risk compared with patients with low collateral flow in a random effects model (RR 0.64; 95% CI 0.45-0.91; P = 0.012). Reductions in mortality were seen regardless of disease state, although the difference was only statistically significant for stable CAD (table 1). Overall, though, the differences in relative risk were not statistically significant (interaction P = 0.149).

 Table 1. Risk for Mortality by Disease Type

The beneficial effect of collaterals was even more pronounced in studies where most patients underwent PCI (RR 0.42; 95% CI 0.32-0.56; P < 0.001) compared with non-PCI studies (RR 0.70; 95% CI 0.51-0.97; P = 0.035). However, in 1 study where patients underwent thrombolysis, those with high collateralization had increased mortality (RR 1.82; 95% CI 1.12-2.96; P = 0.015). These differences in relative risk were statistically significant (interaction P < 0.001).

The predictive role of collaterals was significant in studies where visual assessment was used, and was even more pronounced when collaterals were measured by collateral flow index (RR 0.38; 95% CI 0.26-0.56; P < 0.001). This difference also was statistically significant (interaction P = 0.015).

Although the studies in the meta-analysis ranged widely by date—from 1971 to2010—the authors found that year of publication had no influence on the reported effect of collaterals on survival and no effect on duration of follow-up, which ranged from a median of 5 days to 60 months.

Exact Mechanism Unclear

The study authors say the exact underlying mechanism for the protective role of collaterals

is unclear. One possibility is that high coronary collateral circulation reduces mortality risk by decreasing QT prolongation during vessel occlusion. Collateral circulation also has demonstrated clinical benefit with regard to smaller infarct size, preservation of cardiac function after acute infarctions, and reduction in post-infarct ventricular dilatation—all of which are likely to contribute to reductions in mortality in the long term, Dr. Seiler and colleagues conclude.

Importantly, the study authors assert that coronary collaterals may represent a useful prognostic marker. Patients with known low collateral flow should be considered to have an increased mortality risk and be monitored more closely.

“Diagnostic angiography in patients with suspected CAD remains important to define the coronary anatomy and the degree of collateralization,” they write. “This is optimally being done by measuring the [collateral flow index], while the Rentrop score [based on visual assessment] is easier and cheaper to assess but has significant limitations. Alternatively, an intracoronary ECG could be used as an objective and simple method.”

The study findings highlight the importance of finding ways to induce coronary collateral growth, the authors say. While a few studies have demonstrated that it is possible to promote arteriogenesis with growth factors such as GM-CSF, G-CSF or with external counterpulsation, the studies were too small to evaluate whether this improvement in collateral function translates into improved survival. To this end, larger-scale interventional studies are needed to test specific therapeutic promotion of collaterals, they conclude.

Clinical Usefulness Questioned

In a telephone interview with TCTMD, Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), said the meta-analysis presents good evidence that coronary collaterals are protective in CAD patients, which is somewhat intuitive from a physiologic perspective. But he added that there are still many unanswered questions about how and why some patients compensate for arterial blockages with high collateralization while others do not.

“There are certain patients in whom even though the blockage in the main artery happens slowly, they still don’t have the ability to form collaterals and we don’t really understand why some people do it better than other people,” he said.

Dr. Kirtane added that to suggest collaterals can act as prognostic markers is a bit of a stretch.

“There are some data that show that collaterals don’t supply as much flow, particularly during stress, as do open native arteries,” he explained. “That would suggest that just having collaterals shouldn’t give a false sense of security that you are protected from bad events. The bottom line is it’s too early to say that we should change our treatment paradigm based on presence or absence of collaterals.”

 

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Source:
Meier P, Hemingway H, Lansky AJ, et al. The impact of the coronary collateral circulation on mortality: A meta-analysis. Eur Heart J. 2011;Epub ahead of print.

 

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