Grzegorz L. Kaluza

Catastrophic Outcomes of Noncardiac Surgery Soon After Coronary Stenting

OBJECTIVES To assess the clinical course of patients who have undergone coronary stent placement less than six weeks before noncardiac surgery. BACKGROUND Surgical and percutaneous transluminal coronary angioplasty revascularization performed before high-risk noncardiac surgery is expected to reduce perioperative cardiac morbidity and mortality. Perioperative and postoperative complications in patients who have undergone coronary stenting before a noncardiac surgery have not been studied. METHODS Forty patients who underwent coronary stent placement less than six weeks before noncardiac surgery requiring a general anesthesia were included in the study (1-39 days, average: 13 days). The records were screened for the occurrence of adverse clinical events, including myocardial infarction, stent thrombosis, peri- and postoperative bleeding and death. RESULTS In 40 consecutive patients meeting the study criteria, there were seven myocardial infarctions (MIs), 11 major bleeding episodes and eight deaths. All deaths and MIs, as well as 8/11 bleeding episodes, occurred in patients subjected to surgery fewer than 14 days from stenting. Four patients expired after undergoing surgery one day after stenting. Based on electrocardiogram, enzymatic and angiographic evidence, stent thrombosis accounted for most of the fatal events. The time between stenting and surgery appeared to be the main determinant of outcome. CONCLUSIONS Postponing elective noncardiac surgery for two to four weeks after coronary stenting should permit completion of the mandatory antiplatelet regimen, thereby reducing the risk of stent thrombosis and bleeding complications.

Effects of SolCD39, a novel inhibitor of platelet aggregation, on platelet deposition and aggregation after PTCA in a porcine model

Introduction: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP.Methods and Results: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5–7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by > 90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7 ± 1.4 versus 11.7 ± 3.4) and fibrin (3.5 ± 0.4 versus 4.2 ± 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAPSFLLRN) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel.Conclusions: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study.Abbreviated Abstract. E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5–7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.

Clinical experience with a spiral balloon centering catheter for the delivery of intracoronary radiation therapy.

PURPOSE To develop and evaluate an intravascular radiation delivery catheter that incorporates a centering mechanism and that allows side branch and distal artery perfusion. METHODS AND MATERIALS The Galileo Centering Catheter (Guidant Vascular Interventions, Houston, TX) incorporates a rapid exchange tip design. A unique spiral balloon allows centering and facilitates perfusion to the distal artery and side branches. The catheter contains a dedicated dead-end lumen for source wire delivery to the lesion site. The treatment area is precisely defined by radiopaque markers. RESULTS In three clinical trials to date, radiation (or placebo) was delivered successfully to 300 of 312 patients (96%). With balloon inflation, TIMI grade 2 or 3 flow was achieved in side branches in 82% and in the distal artery in 77% of patients. Despite treatment (dwell) times ranging from 87 to 948 s (mean = 250 s), only 8% of patients required fractionation of treatment. CONCLUSION The Galileo Centering Catheter is a safe and highly effective method for delivering intracoronary radiation therapy. Its unique design provides centering of the source while allowing side branch and distal coronary perfusion during treatment. This catheter would facilitate intracoronary radiation therapy and allow uniform and reproducible dose delivery to the target in the artery wall.

Vulnerable plaque paradigm: Prediction of future clinical events based on a morphological definition

In the past, coronary atherosclerotic lesions were recognized only if they caused significant obstruction to flow, resulting in clinically manifest angina. However, angiographically obstructive atherosclerotic plaques are outnumbered by multiple nonobstructive lesions that are diffusely distributed along the coronary vasculature. These plaques display specific morphologic features [1], are usually multiple [2], and remain harbored predominately in positively remodeled vessels [3]. After many years of eluding detection by angiography, these plaques are now considered to be the most important substrate for plaque disruption, the leading cause of acute coronary syndromes (ACSs) [4]. Autopsy studies among patients with sudden cardiac death suggest that lesions responsible for the vast majority of acute coronary events possess specific morphologic features that make these plaques prone to disruption and thrombus formation [5,6], the so-called vulnerable plaque [7]. Recent technological developments have made remarkable progress in the accurate detection of different structural and metabolic substrates contained in these lesions. However, prevention of major adverse cardiovascular events will ultimately depend not only on the ability to detect these high-risk plaques before disruption, but also on the development of systemic and/or local therapies capable of preventing or containing plaque disruption. Only prospective longitudinal studies with multiple time points using perhaps complementary simultaneous imaging modalities will help us to understand and, most importantly, modify the natural history of the disease [8]. This review will discuss the concept, morphological features, and available data on the natural history of the plaques at the risk of rupture. Recent technological advances in plaque detection and their possible therapeutic implications for the future will also be addressed. CLINICAL VERSUS PATHOLOGICAL DEFINITION OF VULNERABLE PLAQUE

Targeting the adventitia with intracoronary beta-radiation: comparison of two dose prescriptions and the role of centering coronary arteries

PURPOSE To compare by intravascular ultrasound (IVUS) the efficacy of delivering the prescribed dose to the adventitia between two commonly used dose prescriptions for intracoronary radiotherapy. METHODS AND MATERIALS In 59 human postangioplasty coronary vessels, one IVUS cross-section (1 mm thick) with the highest plaque burden was used for creating dose-volume histograms with different hypothetical positions of the source. RESULTS On average, prescription to 1 mm beyond lumen surface resulted in delivery of the prescribed dose (20 Gy +/- 20%) to a higher fraction of adventitial volume than with the prescription to 2 mm from the source, with source placed in vessel center, lumen center, or in the IVUS catheter position. Source placement in the lumen center resulted in a low dose heterogeneity to the adventitia and the least dose heterogeneity to the intima. CONCLUSIONS Prescription to 1 mm beyond lumen surface appeared more effective in delivering the prescribed dose to the adventitia than the American Association of Physicists in Medicine (AAPM) recommended prescription to 2 mm from the source center. Moreover, centering the source in the lumen provides the better balance of effective adventitial targeting and intimal dose homogeneity. Modification of the current AAPM recommendation for dose prescription for intracoronary radiotherapy should be considered.

Novel technique for stent delivery in tortuous coronary arteries: Report of three cases

We present a novel technique for stent delivery across tortuous lesions. Gentle forward pressure was applied on the stent balloon while the balloon was inflated to 2–3 atm. This resulted in the balloon and stent crossing the impeding segment and settling in the target site where it was deployed with excellent angiographic outcome. Cathet Cardiovasc Intervent 2002;55:485–490.

Successful balloon valvuloplasty in an adult patient with severe pulmonic stenosis and aneurysmal poststenotic dilatation

We present a case of pulmonic stenosis with large aneurysmal poststenotic dilatation that was safely and effectively treated with balloon valvuloplasty. Though the poststenotic dilatation persists after the procedure, the risk of dissection and rupture is very low. Hence, balloon valvuloplasty should be considered the treatment of choice in this setting. Cathet Cardiovasc Intervent 2002;55:376–380.

The Proliferation REduction with Vascular ENergy Trial (PREVENT).

PREVENT was the first prospective, randomized placebo-controlled study of intracoronary beta radiotherapy with 32P. A total of 105 patients with de novo or restenotic lesions, treated by stenting or balloon angioplasty, received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm beyond the lumen surface. Rates of restenosis (50% diameter stenosis or more) were significantly lower in radiotherapy patients at the target site (8% compared with 39%, P = 0.012) and at the target site plus adjacent segments (22% compared with 50%, P = 0.018). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy.