Impaired acute collateral recruitment in patients with diabetes mellitus

From the Clinic for Internal Medicine I, Friedrich-Schiller-University, Jena, Germany

Diabetes mellitus adversely influences the clinical course of coronary artery disease.1-3 Impaired collateral development in diabetic patients has been considered a possible mechanism.4,5 A number of angiographic studies could not detect differences in collateral development between diabetic and non-

diabetic patients, however.6,7 In view of the higher cardiac event rate in diabetic patients with acute myocardial infarction (MI) and coronary inter-

ventions,2 the effect of a possibly impaired collateral circulation remains unknown.

Recent developments in microsensor technology make it possible to study collateral perfusion pressure and flow, and to calculate resistance indexes to quantify collateral vascular function better than with angiographic methods.8,9 We applied these techniques to study collateral function in chronic total coronary occlusions (TCOs) to test the hypothesis that diabetes mellitus impairs collateral function.

Methods

In 90 consecutive patients, we successfully recanalized a TCO (duration, 2 weeks—15 years; median, 5 months). We measured collateral function before recanalization and at the end of the procedure during a balloon reocclusion (recruitable collateral function) by a method described in detail elsewhere.10,11 In brief, we passed the occlusion with a dedicated guidewire and advanced a miniature probing catheter. Through this catheter, we advanced 0.014-inch Doppler and pressure wires to record the coronary flow velocity and pressure in the occluded arterial segment supplied by the collaterals. Using this approach, baseline collateral function can be assessed before the antegrade blood flow is reestablished by balloon angioplasty.

After the stent implantation was completed, the Doppler wire was reintroduced into the previously documented position to record the antegrade coronary flow. The recruitable flow was noted after reinflation of the stent balloon in the stent. The distal coronary pressure was also recorded with the pressure wire during balloon reocclusion.

To describe collateral function quantitatively, and incorporating information from flow velocity and pressure, we calculated a collateral resistance index as RColl = (aortic pressure — distal coronary pressure)/distal coronary flow velocity. In addition, the peripheral resistance index assessing the resistance of the microcirculation was calculated as RP = distal coronary pressure/distal coronary flow velocity, before recanalization and at the time of balloon reocclusion.11 Repeated measures analysis of variance (ANOVA) were used to compare changes of parameters of collateral function at baseline and during reocclusion between patients with and without diabetes mellitus.

Results

The study cohort consisted of 90 patients, 30 patients with type 2 diabetes and 60 patients without diabetes. The glycosylated hemoglobin (A1c) for patients with diabetes was 7.49% ± 1.19% (normal, 4.4%—6.2%), and hypertension was more prevalent in this group (table 1). The regional and global left ventricular ejection fraction, rate of prior MI, and duration of occlusion were the same for both groups. Although symptoms of angina pectoris were not as great in patients with diabetes, heart failure symptoms and left ventricular end diastolic pressure were increased. The vessel diameters of target arteries shown on angiography were similar between the two groups, but diabetes patients more often had multivessel disease.

The quantitative Doppler flow measurements of baseline collateral flow were similar for both groups, with a wide distribution of individual values of RColl and RP, but no significant difference in the mean values. Recruitable collateral function was assessed 36 ± 16 minutes after the baseline recording and was found to be reduced compared with the baseline. The RColl was significantly greater in patients with diabetes than in those without diabetes (table 2). A similar observation was made for RP, which was significantly higher in patients with diabetes during reocclusion.

Patients who had undergone a TCO within 3 months had greater changes in recruitable collateral function from baseline compared with patients with TCOs of 3 months or longer. Furthermore, diabetic patients with recent TCOs (< 3 months) had a greater increase of RColl after recanalization, showing impaired recruitability, compared with nondiabetic patients (figure). However, this difference between the two groups disappeared with TCOs of 3 months or longer. Also, with TCOs of 3 months or longer, the increase of RColl during reocclusion was not as great (figure).

Discussion

Our study assessed the hypothesis that collateral function is impaired in diabetic patients, possibly causing an increased cardiovascular event rate. We observed no difference in baseline collateral function between diabetic and nondiabetic patients, indicating a similar capacity for collateral development after an occlusion. The acute recruitment of collateral function during a balloon reocclusion, however, was impaired in diabetic patients with recent occlusions.

Whether diabetes leads to a deficiency in arteriogenesis despite increased angiogenesis has been debated.4 In our study, diabetic patients with chronic occlusions showed the same collateral development as patients without diabetes. Although multivessel disease was somewhat greater in patients with diabetes, there was no difference in the rate of prior MI and left ventricular function between patients with and without diabetes. In addition, in both groups, a similar percentage of patients with normal left ventricu-lar function showed that a slow development of the occlusion led to enough collateral development to avoid regional impairment.

Collateral development has been shown to occur within 2 weeks after acute MI, according to angiographic studies.12 We have previously shown that during the first 12 weeks following occlusion, collateral vessels continue to develop.11 In all patients, including those with documented MI, collateral circulation development was the same for patients with and without diabetes. In both diabetic and nondiabetic patients, RColl was greater immediately following the occlusion and dropped to a level similar to TCOs with a duration of

3 months or longer.

We have recently shown that after recanalization of a TCO, the collateral function is considerably attenuated during acute reocclusion,10 providing an explanation for the incidence of acute MI after percutaneous transluminal coronary angioplasty of previously well-collateralized lesions in cases of acute reocclusion.13 In the present study, RColl was higher during balloon reocclusion in diabetic patients compared with nondiabetic patients, indicating a greater immediate loss of collateral function. This difference was observed predominantly in recent TCOs, whereas recruitability improved in TCOs with a 3-month duration or longer. The difference between diabetic and nondiabetic patients in collateral recruitment may be due to impaired endothelial function in diabetics, which controls the adaptation of vascular conductance to acutely increased demands.14

In the patients with diabetes,reduced collateral development occurred in combination with an increase of RP, which would correspond to the diminished microvascular function known to occur in diabetic patients.14,15 Aside from the collateral supply, the microvascular resistance determines the blood flow distal to an occluded coronary segment. The impaired microvascular function in diabetic patients adds to the impaired collateral function and may further attenuate myocardial perfusion in case of a reocclusion.

There are some limitations in the present study related to the methods used and discussed in detail elsewhere.10,11 Our approach, however, is superior to the widely used classic angiographic studies in assessing collateral function. It is presently the only available way to directly assess collateral function in humans.

Conclusion

Our study showed that, during an acute coronary reocclusion, patients with diabetes have diminished recruitment of collateral vessels for the preservation of the myocardium. This, together with impaired microvascular function, may be the reason that diabetic patients with acute MI have higher complication and mortality rates after coronary interventions and a higher rate of recurrent ischemia and reinfarction.