Bivalirudin in Percutaneous Coronary Interventions and Acute Coronary Syndromes: New Concepts, New Directions.

Inhibition of thrombin and platelets during percutaneous coronary intervention (PCI), using a combination of unfractionated heparin and aspirin, is designed primarily to minimize the rare but devastating potential acute thrombotic complications of the procedure. Direct thrombin inhibitors, such as bivalirudin (formerly Hirulog, The Medicines Company, Cambridge, MA), offer specific theoretic advantages over unfractionated heparin as antithrombin therapy. This review focuses on the pharmacologic promise and the clinical performance of bivalirudin in PCI, and in the pharmacologic management of acute coronary syndromes. Clinical experience with bivalirudin in PCI preceded recent dramatic advances in mechanical interventional techniques and the emergence of novel potent platelet inhibitors. The role of bivalirudin and other direct thrombin inhibitors in the modern era of coronary intervention therefore requires further elucidation.

Coronary Revascularization in Patients with Acute Coronary Syndromes.

Non-Q wave myocardial infarction and unstable angina remain major causes of morbidity and mortality in patients with atherosclerotic coronary artery disease. Judicious use of cardiac catheterization and coronary revascularization may further improve the prognosis of patients with these acute coronary syndromes (ACS). Patients with ACS at high risk for further cardiac events include those patients with electrocardiographic ST-segment depression, left bundle branch block, and, to a lesser extent, T-wave inversion, and those patients with recurrent pain, cardiac enzyme elevation, or exercise-induced ischemia after hospitalization. While these patient subgroups may benefit from early cardiac catheterization and revascularization, the role of routine coronary revascularization is less well established. Whereas one study has demonstrated reduced recurrent hospitalizations in patients treated with routine invasiveive strategy, another has suggested that outcomes are not different with the two approaches. Pending the results of a third ongoing study Ñ the Thrombolysis in Myocardial Infarction (TIMI)-18 trial Ñ a judicious approach to revascularization in patients presenting with ACS is warranted.

Intravascular Ultrasound Assessment of the Mechanisms and Predictors of Restenosis Following Coronary Angioplasty.

Restenosis occurs after 30% to 50% of transcatheter coronary procedures; its mechanisms remain incompletely understood. Intravascular ultrasound (IVUS) studies were analyzed in 360 nonstented native coronary artery lesions in which follow-up quantitative angiographic and/or IVUS data was available. Pre-intervention, post-intervention, and follow-up, the external elastic membrane (EEM) and lumen cross-sectional areas (CSA) were measured; plaque+media (P+M=EEM Ð lumen CSA), and cross-sectional narrowing (CSN=P+M/EEM CSA) were calculated. The anatomic slice selected for serial analysis had an axial location within the lesion at the smallest follow-up lumen CSA. At follow-up, 73% of the decrease in lumen CSA was due to a decrease in EEM CSA; 27% was due to an increase in P+M CSA. The change in lumen CSA correlated more strongly with the change in EEM CSA than with the change in P+M CSA. The change in EEM CSA was bidirectional; 47 lesions (22%) showed an increase in EEM CSA. Despite a greater increase in P+M CSA, lesions exhibiting an increase in EEM CSA had (1) no change in lumen CSA, (2) decreased restenosis, and (3) a 49% frequency of late lumen gain. The independent clinical, angiographic, and IVUS predictors of angiographic restenosis (³ 50% diameter stenosis at follow-up) were the IVUS reference lumen CSA, angiographic pre-intervention diameter stenosis, and post-intervention IVUS CSN. Restenosis appeared to be determined primarily by the direction and magnitude of the change in EEM CSA. An increase in EEM CSA was adaptive while a decrease in EEM CSA contributed to restenosis. The most powerful predictor of restenosis was the IVUS post-procedural CSN. The importance of the post-procedural CSN was related to the change in EEM CSA as a mechanism of restenosis.

Intravascular Ultrasound Assessment of the Mechanisms and Predictors of Restenosis Following Coronary Angioplasty.

Restenosis occurs after 30% to 50% of transcatheter coronary procedures; its mechanisms remain incompletely understood. Intravascular ultrasound (IVUS) studies were analyzed in 360 non-stented native coronary artery lesions in which follow-up quantitative angiographic and/or IVUS data was available. Pre-intervention, post-intervention, and follow-up, the external elastic membrane (EEM) and lumen cross-sectional areas (CSA) were measured; plaque + media (P + M = EEM - lumen CSA), and cross-sectional narrowing (CSN = P + M/EEM CSA) were calculated. The anatomic slice selected for serial analysis had an axial location within the lesion at the smallest follow-up lumen CSA. At follow-up, 73% of the decrease in lumen CSA was due to a decrease in EEM CSA; 27% was due to an increase in P+M CSA. The change in lumen CSA correlated more strongly with the change in EEM CSA than with the change in P + M CSA. The change in EEM CSA was bidirectional; 47 lesions (22%) showed an increase in EEM CSA. Despite a greater increase in P + M CSA, lesions exhibiting an increase in EEM CSA had (1) no change in lumen CSA, (2) decreased restenosis, and (3) a 49% frequency of late lumen gain. The independent clinical, angiographic, and IVUS predictors of angiographic restenosis (³ 50% diameter stenosis at follow-up) were the IVUS reference lumen CSA, angiographic pre-intervention diameter stenosis, and post-intervention IVUS CSN. Restenosis appeared to be determined primarily by the direction and magnitude of the change in EEM CSA. An increase in EEM CSA was adaptive while a decrease in EEM CSA contributed to restenosis. The most powerful predictor of restenosis was the IVUS post-procedural CSN. The importance of the post-procedural CSN was related to the change in EEM CSA as a mechanism of restenosis.

Angiographic Results and Late Clinical Outcomes Utilizing a Stent Synergy (Pre-Stent Atheroablation) Approach in Complex Lesion Subsets.

To investigate the strategy of ÒdebulkingÓ in complex lesions before stent implantation (stent synergy) to improve procedural safety and achieve optimal acute and long-term results, we reviewed our experience in 389 patients with 504 lesions undergoing a combined stent procedure (45% rotational atherectomy, 24% laser angioplasty, 20% directional atherectomy, and 11% transluminal extraction atherectomy before stent implantation). Procedural success was achieved in 94.5%, with 4% major ischemic complications (1.1% death, 1.9% Q-wave myocardial infarction, and 2.3% emergency coronary artery bypass surgery). Overall, subacute stent thrombosis occurred in 1.5% of patients. Target-lesion revascularization during follow-up was required in 9.8% of the patients. We conclude that a strategy of selective pre-stent atheroablation in complex lesion subsets results in excellent procedural outcomes with acceptable complications and favorable long-term results.

Carotid Stent-Assisted Angioplasty: Preliminary Technique, Angiography, and Intravascular Ultrasound Observations.

Currently, surgical carotid endarterectomy has been the standard therapy for symptomatic and asymptomatic patients with significant carotid artery stenoses. However, there are high surgical risk and other patient subsets, wherein a Òlesser invasiveÓ catheter-based procedure may be worthwhile. Carotid stent-assisted angioplasty (CSSA) is a percutaneous interventional treatment approach for appropriately selected patients with common and internal carotid artery lesions. The present report discusses preliminary technique-related, angiographic, and intravascular ultrasound observations of CSSA. Five symptomatic patients (with six carotid stenoses) with other co-morbid states were treated by a multidisciplinary team under the aegis of an approved protocol using conventional equipment and available Palmaz tubular slotted stents. On-line quantitative angiography and intravascular ultrasound imaging was performed to guide stent insertion and monitor results. There were no procedure-related complications and angiographic results were excellent (final mean diameter stenosis 5%). Intravascular ultrasound imaging was feasible and safe. In two cases, the findings obtained from ultrasound images assisted in subsequent operator decisions. Thus far, there have been no additional clinical sequelae in these patients (@ 30 days). This preliminary experience with CSSA indicates that interventional neurovascular therapies may provide a useful alternative for selected patients requiring endoluminal reconstruction of carotid stenoses. Extensive additional studies are required to establish the appropriate clinical application of this technique.

Angiographic and Clinical Outcome after Cutting Balloon Angioplasty.

To evaluate the safety and efficacy of cutting balloon angioplasty, we reviewed the early angiographic and clinical outcomes of 160 consecutive patients with 173 lesions undergoing this procedure. Angiographic core laboratory analysis was available in 150 of these lesions. Eccentricity was the most common (49%) unfavorable pre-procedural morphologic feature; other morphologic findings included length ³ 10 mm (28%), calcification (23%), angulation ³ 45 degrees (13%), irregularity (7%), ostial location (3%), and thrombus (1%). ÒStand-aloneÓ cutting balloon angioplasty was performed in 106 (71%) lesions and an adjunct balloon or new device was used in 44 (29%) lesions to treat a residual stenosis > 40% after cutting balloon angioplasty. The reference artery size was 2.80 +/- 0.42 mm. The minimal lumen diameter increased from 1.02 +/- 0.30 mm to 2.01 +/- 0.42 mm (p < 0.001) and the % diameter stenosis was reduced from 64 +/- 9% to 29 +/- 12% (p < 0.001). Angiographic success (< 50% diameter stenosis ) was obtained in 145 (97%) lesions. The residual stenosis was higher in lesions treated with stand-alone cutting balloon angioplasty than in those undergoing adjunct balloon or new device angioplasty (31 +/- 10 versus 24 +/- 14; p = 0.0006). The average cutting balloon:artery ratios in those lesions with and without dissections after cutting balloon use (1.00 +/- 0.11 versus 0.97 +/- 0.13, respectively; p = 0.29). A significant inverse relationship between the cutting balloon:artery ratio and the final % diameter stenosis was noted (R = 0.33; p = 0.0003). There were no major in-hospital complications after cutting balloon use. This series demonstrates the safety and efficacy of cutting balloon angioplasty as an alternative to conventional balloon angioplasty in patients with non complex coronary artery disease. A multicenter, randomized comparison of cutting balloon angioplasty with conventional balloon angioplasty for prevention of restenosis is currently underway.

Frequency and Prognostic Importance of Creatine Phosphokinase Myocardial Isoforms after Successful Balloon and New Device Coronary Angioplasty.

The frequency and prognostic importance of subclinical myocardial necrosis after new device coronary intervention is not known. To identify the frequency of CPK-MB release after balloon and single new device angioplasty in native coronary arteries, we reviewed the course of 810 patients who underwent successful single lesion, native vessel angioplasty using balloon angioplasty (N=174), Gianturco-Roubin stent placement for suboptimal angioplasty results (N=31), Palmaz-Schatz stent deployment (N=320), directional coronary atherectomy (N=102), or rotational atherectomy (N=183). All patients had serial measurements of CPK-MB isoenzymes 6 and 18Ð24 hours after coronary intervention; absolute CPK-MB levels were determined by radioimmunoassay (normal assay < 4 ng/ml). CPK-MB isoenzymes were > 2 times normal (> 8 ng/dl) in 15.6% of procedures, > 3 times normal (³ 12 ng/ml) in 11.5% of procedures, > 4 times normal (³ 16 ng/ml) in 8.6% of procedures, and > 5 times normal (³ 20 ng/ml) in 7.7% of procedures. CPK-MB elevation > 2 times normal was more common in those undergoing directional atherectomy (20.8%) and Gianturco-Roubin stent placement (34,4%) than in those undergoing balloon angioplasty (11.7%). No significant differences were noted in patients undergoing rotational atherectomy (13.2%) or Palmaz-Schatz stent placement (15.6%) than in those undergoing balloon angioplasty. CPK-MB > 5 times normal occurred after 7.7% of procedures, but did not vary significantly among the devices used in this study. We conclude that CPK-MB elevations > 2 times normal are highest in patients undergoing directional coronary atherectomy and ÒbailoutÓ use of the Gianturco-Roubin stent. No significant differences in CPK-MB elevation were seen in patients undergoing balloon angioplasty, Palmaz-Schatz stent deployment, or rotational atherectomy. Identification of the prognostic importance of these CPK-MB elevations is currently under study.