Gerald S. Werner

Angiographic Assessment of Collateral Connections in Comparison With Invasively Determined Collateral Function in Chronic Coronary Occlusions

Background—The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. Methods and Results—In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch–like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic location, the Rentrop, and the collateral connection grade showed only for the latter an independent and significant relation with RColl. CC2 collaterals preserved regional left ventricular function better than did CC1 collaterals and provided a higher collateral flow reserve during adenosine infusion. CC0 collaterals were predominantly observed in recent occlusions of 2 to 4 weeks’ duration, with the highest RColl. During balloon reocclusion, recruitable collateral function was best preserved with CC2 and least with CC0. Conclusions—The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.

Detection of Coronary Microembolization by Doppler Ultrasound in Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions

Background— Intracoronary Doppler guidewires can be used for real-time detection and quantification of microembolism during percutaneous coronary interventions (PCIs). We investigated whether the frequency of Doppler-detected microembolism is related to the incidence of myonecrosis during elective PCI. Methods and Results— The study population included 52 consecutive patients (aged 64±10 years; 36 men, 16 women) with coronary artery disease who underwent elective PCI of a single-vessel stenosis. Using intracoronary Doppler ultrasound, we compared the frequency of microembolism during PCI in 22 patients with periprocedural non–ST-segment elevation myocardial infarctions (pNSTEMI) and 30 patients without pNSTEMI. The 2 groups were comparable with regard to their clinical and procedural characteristics. In the group with pNSTEMI, the total number of coronary microemboli after PCI (27±10 versus 16±8, P<0.001) was higher than in the group without pNSTEMI. Although high-sensitivity C-reactive protein plasma levels were similar before PCI (2.9±2.2 versus 3.4±1.7 mg/L, P=NS), they were higher in the group with pNSTEMI after PCI (12.6±10.4 versus 6.1±5.1 mg/L, P<0.05). Microembolic count independently correlated to postprocedural cardiac troponin I elevation (r=0.565, P<0.001), coronary flow velocity reserve (r=−0.506, P<0.001), and baseline average peak velocity (r=0.499, P<0.001). Conclusions— Patients with pNSTEMI had a significantly higher frequency of coronary microembolization during PCI, and their systemic inflammatory response and microvascular impairment after PCI were more pronounced. Intracoronary Doppler ultrasound provides evidence that pNSTEMI in patients undergoing elective PCI is caused by microembolization during the procedure.

Safety of deferring angioplasty in patients with normal coronary flow velocity reserve

BACKGROUNDnIn the catheter laboratory there is a need for functional tests validating the hemodynamic significance of coronary artery stenosis.nnnOBJECTIVESnIt was the objective of our study to compare the long-term cardiac event rate and the clinical symptoms in patients with reduced coronary flow velocity reserve (CFVR) and standard PTCA with patients with normal CFVR and deferred angioplasty.nnnMETHODSnOur study included 70 patients with intermediate coronary artery stenoses (13 f, 57 m; diameter stenosis >50%, <90%) and an indication for PTCA due to stable angina pectoris and/or signs of ischemia in noninvasive stress tests. CFVR was measured distal to the lesion after intracoronary administration of adenosine using 0.014 inch Doppler-tipped guide wires.nnnRESULTSnIn 22 patients (31%), PTCA was deferred due to a CFVR > or = 2.0 (non-PTCA group). In the remaining 48 patients (69%) mean CFVR of 1.4+/-0.23 (p < 0.001) was measured (PTCA group). CFVR increased to 2.0+/-0.51 after angioplasty. During follow-up (average 15+/-6.0 months), the following major adverse cardiac events (MACE) occurred: in the PTCA group re-PTCA was performed in nine patients (18.8%) because of unstable angina, five patients (10.4%) suffered an acute myocardial infarction (MI) (two infarctions occurred during the angioplasty, three patients suffered an infarction during follow-up), two patients (4.2%) needed blood transfusions due to severe bleedings, two patients (4.2%) underwent bypass surgery and one patient (2.1%) died. In the non-PTCA group, angioplasty was necessary only in two cases (9.1%) during follow-up. We did not observe any MI in the non-PTCA group. The overall rate of MACE was significantly lower in the non-PTCA group compared to the PTCA group (9.1% vs. 33.3%, p < 0.01). However, only 40% of the patients of the non-PTCA group were free of angina pectoris at stress. In the PTCA group, 63% did not complain of any symptoms at follow-up (p < 0.05).nnnCONCLUSIONSnWe conclude that determination of the CFVR is a valuable parameter for stratifying the hemodynamic significance of coronary artery stenosis. PTCA can safely be deferred in patients with significant coronary stenosis but a CFVR > or = 2.0. The total rate of MACE at follow-up was below 10% among these patients. However, if PTCA was deferred the number of patients who are free of angina is lower compared to those patients who underwent angioplasty.

Immediate Changes of Collateral Function After Successful Recanalization of Chronic Total Coronary Occlusions

Background—Coronary collaterals are essential to maintain myocardial function in chronic total coronary occlusions (TCOs). The aim of the present study was to assess the collateral circulation in TCOs before coronary angioplasty and to determine the recruitable collateral perfusion after recanalization by use of intracoronary Doppler flow velocimetry. Methods and Results—In 21 patients with TCOs (duration >4 weeks), Doppler recordings of basal collateral flow were obtained before the first balloon inflation. Angioplasty was performed with stent implantation in all lesions. At the end of the procedure, recruitable collateral flow was measured during a repeat balloon inflation. The collateral flow index (CFI) was calculated from the velocity integral during the occlusion/velocity integral of antegrade flow. In 17 of 21 patients, angiography was repeated after 24 hours, and CFI was reassessed. Average peak velocity of collateral flow was 10.9±5.6 cm/s with a predominantly systolic flow (diastolic/systolic velocity ratio <0.5) compared with antegrade flow (diastolic/systolic velocity ratio >1.5). After recanalization, the average peak velocity of recruitable collateral flow dropped by >50% to 4.7±2.5 cm/s. CFI fell from 0.48±0.25 to 0.21±0.16 (P <0.001). There was no further change of CFI during the following 24 hours. CFI was higher in patients with preserved regional ventricular function than in those with akinetic myocardium (0.57±0.23 versus 0.38±0.12, P <0.05). Conclusions—Collateral circulation in TCO provided 50% of antegrade coronary flow. A considerable fraction of collateral flow was immediately lost after recanalization, indicating that TCO may not remain protected from future ischemic events by a well-developed collateral function.

Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction.

No‐reflow is a frequent observation during direct PTCA for acute myocardial infarction (AMI) and associated with a poor clinical outcome. This study assesses the value of verapamil for reversal of no‐reflow during PTCA for AMI. In a consecutive series of 212 direct or rescue PTCAs for AMI, a TIMI flow grade < 3 was observed in 23 patients (10.8%). Ten of these patients had received GP IIb/IIIa antagonists before PTCA. Seven patients with AMI and TIMI grade 3 flow served as controls. All lesions were treated by stents. In 18 patients with systolic blood pressure > 90 mm Hg, nitroglycerine (0.1 mg i.c.) was given. Verapamil (1 mg over 2 min) was given via an infusion catheter distal to the angioplasty site. Before and after nitroglycerine, after verapamil, and 15 min later coronary flow was assessed by the TIMI frame count method (TFC). Nitroglycerine had no effect on TFC. Verapamil reduced TFC from 56 ± 9 frames to 24 ± 4 (P < 0.001). In controls, TFC did not change significantly. The TIMI flow grade was restored to TIMI flow grade 3 in 65%. In two of seven right coronary and one of three circumflex arteries, intermittent AV block II occurred during verapamil injection, which disappeared after atropine. No‐reflow after PTCA for AMI can be reversed by intracoronary verapamil. This supports the hypothesis that no‐reflow is caused by acute microvascular dysfunction probably because of a disorder in calcium homeostasis or microvascular spasm. Cathet Cardiovasc Intervent 2002;57:444–451.

Regression of collateral function after recanalization of chronic total coronary occlusions: A serial assessment by intracoronary pressure and Doppler recordings

Background—Collaterals can maintain myocardial function or preserve viability in chronic total coronary occlusions (CTOs). It is unknown whether and to what extent collaterals regress after successful recanalization of a CTO. Methods and Results—In 103 patients with successful recanalization of a CTO collateral function was assessed by intracoronary Doppler and pressure recordings before and after recanalization, and again after 5.0±1.3 months. Doppler (CFI) and pressure-derived collateral function indexes (CPI) and collateral (RColl) and peripheral resistance indexes (RP) were calculated. In 10 patients with reocclusion, all without myocardial infarction during follow-up, collateral function had reached a similar level as before the first recanalization. In the other 93 patients with or without restenosis, collateral function was attenuated during follow-up. CPI had decreased by 23% immediately after recanalization (P <0.001) and decreased further by another 23% at follow-up (P <0.001). The RColl increased immediately after recanalization by 82% (P <0.001) and by a further 273% at follow-up (P <0.001). In contrast, RP increased only by 22% after recanalization (P <0.001) and by an additional 12% at follow-up (P <0.05). The initial size of the collaterals but not the incidence of a restenosis influenced the collateral regression. Only 18% of patients at follow-up had collaterals with a CPI >0.30, presumably sufficient to prevent ischemia during acute occlusion. Conclusions—Collateral function regresses during long-term follow-up, especially in collaterals with a small diameter. In the majority of patients, collaterals are not readily recruitable in the case of acute occlusion. However, collaterals have the potential to recover in the case of chronic reocclusion.

Direct assessment of coronary steal and associated changes of collateral hemodynamics in chronic total coronary occlusions

Background—Coronary steal can occur in collateral-dependent myocardium during pharmacologically induced vasodilation. This study assessed coronary steal invasively in chronic total coronary occlusions (TCOs). Methods and Results—In 35 consecutive patients with a percutaneous transluminal coronary angioplasty of a TCO (duration >4 weeks), coronary flow velocity (APV) by a Doppler wire and distal pressure (PD) by a pressure wire were assessed in the collateral-dependent vascular bed before dilatation. Indexes of peripheral resistance (RP) and for the collateral pathway, including the donor artery segment (RCP), were calculated. Changes of these parameters were assessed during intravenous adenosine (140 &mgr;g · kg−1 · min−1). Adenosine caused a decrease of APV, ie, coronary steal, in 13 patients (37%; group S), an increase in 11 patients (group R), and no change in 11 patients (group N). Angiographic analysis of collateral pathways showed no difference between the groups, except that in group S all collateral connections were continuously visible but no large collaterals (>0.5 mm) were found. In group N, collaterals were least developed. The increase of APV in group R was associated with a decrease of RP, whereas RCP remained unchanged. In contrast, group S showed no change in RP but a significant increase of RCP, indicating an increased resistance of the donor segment. Conclusions—Coronary steal is observed in about one third of TCOs and is associated with specific hemodynamic changes of RP and RCP. Steal occurred only with well-developed angiographically visible collaterals but not with very large collaterals.

Paclitaxel-eluting stents for the treatment of chronic total coronary occlusions: A strategy of extensive lesion coverage with drug-eluting stents

The recanalization of a chronic total coronary occlusion (CTO) is hampered by a high rate of lesion recurrence. The goal of the present study is to assess the effect of paclitaxel‐eluting stents in CTOs in a strategy of extensive stent coverage and the optional use of additional bare metal stents (BMSs). In 82 consecutive patients, a CTO (duration > 2 weeks) was successfully recanalized with implantation of one or more Taxus stents. These patients underwent a repeat angiography after 5.0 ± 1.5 months and were assessed by quantitative angiography. The patients were compared with 82 clinically and lesion‐matched patients from a consecutive series of 148 patients with CTOs treated by BMS in the preceding time period. In 21 of the 82 patients, additional lesions in the target artery not directly related to the original occlusion site were treated with BMSs (hybrid approach). The history of diabetes, extent of coronary artery disease, clinical symptoms, and angiographic features were similar in the Taxus and BMS group. Periprocedural adverse events were 3.3% with Taxus and 3.3% with BMS, but 12 months MACE was significantly lower in the group with exclusive use of Taxus (13.3% vs. 56.7%; P < 0.001), mainly due to a lower target lesion revascularization of 10.0% as compared to 53.4% (P < 0.001). There was only one late reocclusion with Taxus (1.7%) as compared to 21.7% with BMS (P < 0.05). However, in the hybrid group, the MACE rate was considerably higher, with 33.3%. Our data of a 80% reduction of target vessel failure as compared to BMS, with a lower risk of late reocclusions without increased acute adverse events, demonstrate the benefit of paclitaxel‐eluting stents in CTOs. However, diffuse atherosclerosis in CTOs should be covered completely by the drug‐eluting stents.

Growth Factors in the Collateral Circulation of Chronic Total Coronary Occlusions Relation to Duration of Occlusion and Collateral Function

Background—Despite extensive animal experimental evidence, there are few data on the relation of growth factors and collateral function in humans. Methods and Results—In 104 patients with a chronic total coronary occlusion (CTO; >2 weeks duration), collateral function was assessed invasively during recanalization by intracoronary Doppler and pressure recordings. A collateral resistance index, RColl, was calculated. Blood samples were drawn from the distal coronary bed supplied by the collaterals and from the aortic root to measure basic fibroblast growth factor (bFGF), monocytic chemotactic protein-1 (MCP-1), transforming growth factor-β (TGF-β), placenta growth factor (PlGF), and tumor necrosis factor-α (TNF-α). The bFGF concentration in the collateralized artery was higher than in the aortic root (34±20 versus 18±14 pg/mL; P<0.001). bFGF was highest in recent occlusions (2 to 12 weeks) with the highest RColl. Higher collateral concentrations were also observed for MCP-1, TGF-β, and PlGF, but without a close relation to the duration of occlusion. TNF-α was not increased in collaterals compared with the systemic circulation. MCP-1, PlGF, and TGF-β were significantly increased in small collaterals with the highest shear stress. Diabetic patients had lower bFGF and higher MCP-1 levels than nondiabetics. Conclusions—In CTOs, the continuous release of bFGF into collaterals showed a close relation to the duration of occlusion and collateral function, which underscores its therapeutic potential. Other factors influencing growth factor release appeared to be shear stress for MCP-1, TGF-β, and PlGF and the presence of diabetes.

Impaired acute collateral recruitment as a possible mechanism for increased cardiac adverse events in patients with diabetes mellitus

BACKGROUNDnThe mortality of coronary artery disease is increased in diabetic patients. An impaired collateral function is considered a possible explanation. This study should assess the influence of diabetes on collaterals by direct invasive assessment of collateral function.nnnMETHODSnIn 90 consecutive patients with a chronic coronary occlusion (TCO) of >2 weeks duration a recanalization was done. Thirty patients with diabetes (33%) were compared with 60 (67%) without diabetes. Blood flow velocity and pressure were measured distal to the occlusion by intracoronary Doppler and pressure wires before PTCA, and again after PTCA during a final balloon reocclusion to assess acute recruitment of collaterals. Resistance indexes for collaterals (R(Coll)) and peripheral microcirculation (R(P)) were calculated.nnnRESULTSnThe R(Coll)(diabetics: 8.1+/-6.8 vs nondiabetics: 8.7+/-6.7 mmHg cm(-1)s(-1); p=0.68) and R(P)(5.6+/-4.2 vs 6.6+/-3.8 mmHg cm(-1)s(-1); p=0.30) were similar in diabetic and nondiabetic patients before recanalization. During balloon reocclusion both R(Coll)and R(P)increased. This increase was significantly more pronounced in diabetic than in nondiabetic patients in TCOs <3 months duration. In TCOs of longer duration (> or =3 months) these differences were no longer detectable between both patient groups.nnnCONCLUSIONSnDiabetic patients with TCOs have similarly developed collaterals as nondiabetic patients. However, in TCOs <3 months duration the acute recruitment of collaterals in case of reocclusion is impaired. This could explain some of the higher complication rate and mortality after coronary interventions in diabetic patients.