Charles Chan

Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty : a prospective study

OBJECTIVES The goal of the study was to evaluate the progressive increase in ischemic threshold with multiple sequential transient coronary occlusions and to assess the role of the collateral circulation in adaptation to ischemia. BACKGROUND It has been observed that the duration of balloon inflations during coronary angioplasty can be gradually prolonged during subsequent dilations with a reduction in patient symptoms and diminished ischemic electrocardiographic (ECG) changes. Although the mechanism has not been fully explained, recruitment of coronary collateral circulation induced by repeated coronary occlusion has been reported. The stimuli for recruitment and the natural history of coronary collateral circulation are not understood. METHODS Seventeen patients with isolated stenosis of the left anterior descending coronary artery and a normal left ventricle were enrolled. Angioplasty consisted of five successive prolonged inflations. Sequential changes in clinical, intracoronary ECG and left ventricular indexes of myocardial ischemia were examined. Coronary collateral channels were evaluated during balloon inflations by ipsilateral and contralateral injections of contrast medium and hemodynamically by occlusion pressure. RESULTS An improved tolerance to myocardial ischemia with repetitive coronary occlusions was demonstrated by a significant reduction of angina, ST segment deviation, left ventricular filling pressure and less impairment of ejection fraction. Left ventricular wall motion abnormalities remained unchanged. Collateral angiographic grade did not change in 7 patients and increased in 10. CONCLUSIONS This study confirms a progressive adaptation of myocardial ischemia to repetitive coronary occlusions and supports the concept that sequential episodes of myocardial ischemia are a stimulating factor for the recruitment of collateral channels in humans. These results also suggest that enhancement of recruitable collateral circulation might be an underlying mechanism of myocardial ischemic preconditioning.

Six- and Twelve-Month Results From First Human Experience Using Everolimus-Eluting Stents With Bioabsorbable Polymer

Background—Everolimus, an active immunosuppressive and antiproliferative agent of the same family as sirolimus (rapamycin), has demonstrated significant reduction of neointimal proliferation in animal studies. The First Use To Underscore restenosis Reduction with Everolimus (FUTURE) I trial was the first in-human experience to evaluate the safety and efficacy of everolimus-eluting stents (EES), coated with a bioabsorbable polymer, compared with bare metal stents (BMS). Methods and Results—FUTURE I was a prospective, single-blind, randomized trial that enrolled 42 patients with de novo coronary lesions (EES 27, BMS 15). Patient and lesion characteristics were comparable between the groups. Major adverse cardiac event rates were low at 30 days and 6 months, without any early or late stent thrombosis for either group (P =NS). Between 6 and 12 months, there were no additional reports of major adverse cardiac events. The 6-month angiographic in-stent restenosis rate was 0% versus 9.1% (1 patient) (P =NS), with an associated late loss of 0.11 mm versus 0.85 mm (P <0.001), and the in-segment restenosis rate was 4% (1 patient) and 9.1% (1 patient) (P =NS) for EES and BMS, respectively. Intravascular ultrasound analysis revealed a significant reduction of percent neointimal volume in EES compared with BMS (2.9±1.9 mm3 /mm versus 22.4±9.4 mm3 /mm, P <0.001). There was no late stent malapposition in either group. The safety and efficacy of the EES appeared to be sustained at 12 months. Conclusions—In this initial clinical experience, EES with bioabsorbable polymer demonstrated a safe and efficacious method to reduce in-stent neointimal hyperplasia and restenosis.

A randomized comparison of sirolimus-eluting versus bare metal stents in the treatment of diabetic patients with native coronary artery lesions: The DECODE study†

Objective: To compare the effects of sirolimus‐eluting (SES) versus bare metal stents (BMS) on 6‐month in‐stent late luminal loss (LLL) and 1‐year major adverse cardiac events (MACE) in diabetics undergoing percutaneous coronary interventions. Background: In studies of unselected patients, coronary restenosis rates have been lower with SES than with BMS. Comparisons of SES versus BMS in diabetics with more than one stenosis or more than one vessel disease are few. Methods: This open‐label trial randomly assigned 200 diabetics with de novo coronary artery stenoses to receive up to three SES versus BMS in a 2:1 ratio. The patients underwent repeat coronary angiography at 6 months after the index procedure and were followed‐up for 1 year. The primary study endpoint was in‐stent LLL at 6 months. Results: Between August 2002 and May 2004, 83 patients (mean age = 60 years) with 128 lesions (mean = 1.5 per patient) were enrolled at four U.S. and seven Asian medical centers. Enrollment was terminated early by the Safety Monitoring Board because of a statistically significant difference in rates of clinical endpoints. The mean in‐stent LLL at 6 months was 0.23 mm in SES versus 1.10 mm in BMS recipients (P < 0.001). At 12 months, 8 patients (15%) assigned to SES had experienced MACE versus 12 patients (41%) assigned to BMS (P = 0.006). Conclusions: In diabetics, the mean 6‐month in‐stent LLL was significantly smaller, and 12‐month MACE rate significantly lower, after myocardial revascularization with SES than with BMS.

Primary stenting of de novo lesions in small coronary arteries: a prospective, pilot study.

Technical advancement and new anti-thrombotic regimens have recently shown so much improvement in the results of coronary stenting that the conventional contra-indication for stenting in small coronary arteries (<3 mm) needs to be revised. We undertook a prospective pilot study of elective Palmaz-Schatz stenting in de novo lesions located in coronary arteries of less than 3 mm diameter. Fifty consecutive patients (63 +/- 9 years) with stable (n = 38) and unstable angina (n = 12) were included. Philips-DCI quantitative coronary analysis was used to measure reference diameter, minimal lumen diameter and percent diameter stenosis before PTCA, after stenting and at 6-month angiographic follow-up study. All measurements were performed after intracoronary injection of nitroglycerin (300 microg). All patients received ticlopidine (250 mg/day) and aspirin (100 mg/day). The mean lesion length was 9 +/- 3 mm. The balloon size used for stent delivery was 2.75 mm in 30 patients and 2.5 mm in 20 patients and the mean balloon inflation pressure used for stent deployment was 12 +/- 2 atm. All stents were deployed successfully. In-hospital complications occurred in two patients, diagonal branch occlusion at day 2 requiring emergency PTCA in one and a hematoma at the femoral puncture site requiring surgery in the other. Major adverse cardiac event (MACE) rate remained 2% (nonfatal infarct in one). Follow-up angiography (n = 46, 92%) at 6 +/- 3 months showed a 30% restenosis rate. Target vessel revascularization (TVR) rate was 13%. We conclude that elective stenting in small coronary arteries is feasible and involves an acceptable risk of restenosis.

Combined fibrinolysis using reduced-dose alteplase plus abciximab with immediate rescue angioplasty versus primary angioplasty with adjunct use of abciximab for the treatment of acute myocardial infarction: Asia-Pacific Acute Myocardial Infarction Trial (APAMIT) pilot study.

We conducted a randomized feasibility pilot study comparing combined fibrinolysis with immediate rescue angioplasty vs. primary angioplasty with adjunctive abciximab in patients with acute myocardial infarction (AMI). Seventy patients with ST segment elevation AMI of ≤ 6 hr were randomized to either 50 mg of alteplase and abciximab (n = 34) or primary angioplasty with adjunctive abciximab (n = 36). Coronary angiography was performed at 60 min in the combined lytic group and TIMI 3 flow was present in 65% of patients as compared to 25% (P = 0.001) in the primary angioplasty group prior to intervention. Treatment success, defined as TIMI 3 flow, was achieved in 83% of patients in the primary angioplasty group (P = 0.075 compared to 65% in combined lytic group before rescue angioplasty). There was no difference in overall treatment success between primary angioplasty and combined lytic group with rescue angioplasty (83% vs. 94%; P = NS). Major adverse cardiac events at 1 month were not significant (15% vs. 11%; P = NS), but there was a trend toward more events in the combined lytic group at 6 months (32% vs. 14%; P = 0.066), particularly in target vessel revascularization. In this feasibility pilot study, high rate of TIMI 3 flow was attained in patients with AMI with both combined fibrinolysis and primary angioplasty with adjunctive abciximab. A larger randomized trial is currently ongoing to compare these two strategies. Cathet Cardiovasc Intervent 2004;62:445–452.

The effect of rod diameter on correction of adolescent idiopathic scoliosis at two years follow-up.

Study Design: The review of multicenter national pediatric scoliosis database. Objective: The purpose of this study was to compare the radiographic outcomes of patients who underwent scoliosis surgery utilizing different rod diameter constructs by the posterior approach. Background: Little attention has specifically been focused on the effect of rod diameter on correction of spinal deformity after posterior spinal instrumentation and fusion in children with adolescent idiopathic scoliosis (AIS). Methods: The review of national database comprised of 1125 patients, of which 352 patients had a minimum follow-up of 2 years. Of these, 163 patients received 5.5 mm and 189 patients received 6.35 mm diameter rods for posterior spinal instrumentation. Results: The 6.35 mm rods were used more often for patients who were male, taller, heavier, with larger coronal curves, and more flexible curves. Larger diameter rods were also more likely to be stainless steel, implanted with an increased number of implants per level, and an increased number of pedicle screws used on the concavity of the curve. Univariate analysis of coronal curve showed a significant difference between 5.5 and 6.35 mm rods in correction (67.0% vs. 57.3%) at 2 years. Multivariate analysis revealed that the most significant factors affecting coronal curve correction at 2 years were rod diameter, the patient’s preoperative coronal major curve and flexibility, and the implant density. In the sagittal plane, preoperative sagittal curve and rod diameter are the predictors of sagittal correction at 2 years. Conclusions: The study did not support our hypothesis that larger rods would be associated with a greater correction of frontal and sagittal plane in patients with AIS. In addition to rod diameter, implant density and the inherent flexibility and deformity of the patient were found to be influential factors contributing for the correction and maintenance of coronal and sagittal curves in AIS.

Thrombin generation and fibrinolytic activities among patients receiving reduced-dose alteplase plus abciximab or undergoing direct angioplasty plus abciximab for acute myocardial infarction

The purpose of this study was to determine the impact of these 2 reperfusion strategies (reduced-dose alteplase plus abciximab or direct angioplasty plus abciximab) on fibrinolytic and thrombin generation activities. The effect of reduced-dose alteplase plus abciximab and direct angioplasty plus abciximab on hemostatic factors is unknown. Of 70 patients with acute myocardial infarction of < or = 6 hours, 34 were randomized to reduced-dose alteplase (35 to 50 mg in 1 hour) and 36 to direct angioplasty. A standard bolus and infusion dose of abciximab was administered to all patients. Blood specimens were collected at baseline, and at 1, 4, 12, and 24 hours. The following parameters were assayed: fibrinogen, plasminogen and antiplasmin activities, tissue plasminogen activator antigen, D-dimer, prothrombin fragments F1 + 2, and thrombin/antithrombin III complexes. Among patients treated with reduced-dose alteplase plus abciximab, the fibrinogen level decreased by 28.4% in the first hour (11.7 +/- 3.4 vs 7.8 +/- 2.5 micromol/L, p <0.001). Correspondingly, plasminogen and antiplasmin activities decreased by 43.8% (p <0.001) and 59.1% (p <0.001), respectively. Prothrombin fragments F1 + 2 increased from 2.2 +/- 1.7 to 4.2 +/- 1.6 nmol/L (1 hour) (p <0.001) and thrombin/antithrombin III increased from 16.3 +/- 15.0 to 33.5 +/- 19.9 microg/L (1 hour) (p <0.001). Conversely, in the direct angioplasty group, there was a marginal elevation in fibrinogen level at 1 hour (10.2 +/- 2.4 vs 10.6 +/- 2.0 micromol/L, p = 0.064) despite a significant reduction in plasminogen and an increase in tissue plasminogen activator levels. There was no significant change in prothrombin fragments F1 + 2 and thrombin/antithrombin III levels. Thus, there was considerable fibrinolytic activity with reduced-dose alteplase plus abciximab; thrombin generation was not prevented. Among patients treated with direct angioplasty, there was some endogenous fibrinolytic activity, but there was no significant thrombin generation.

Giant coronary aneurysms with multiple vascular aneurysms : A rare manifestation of hyperhomocysteinemia

Hyperhomocysteinemia is associated with accelerated atherosclerosis, which leads to an increased incidence of premature vascular disease. Although multiple vascular aneurysms have been linked to hyperhomocysteinemia, coronary artery aneurysms have not. We report a case of giant coronary artery aneurysm associated with multiple peripheral vascular aneurysms in a patient with hyperhomocysteinemia. Cathet Cardiovasc Intervent 2001;52:116–119.

Unilateral Meniscomeniscal Ligament

Four normal variants of meniscomeniscal ligaments have been previously reported in the anatomy, arthroscopy, and radiology literature. The anterior and posterior transverse meniscal ligaments are the 2 most commonly observed, with a reported frequency of 58% and 1% to 4%, respectively. The last 2 variants include the medial and lateral oblique meniscomeniscal ligaments and account for a combined frequency of 1% to 4%.This article describes 2 patients with unilateral meniscomeniscal ligaments observed on magnetic resonance imaging. One patient had a unilateral lateral meniscomeniscal ligament extending from the anterior horn of the lateral meniscus to the posterior horn of the lateral meniscus and underwent conservative management. The second patient had a unilateral medial meniscomeniscal ligament with a concomitant medial meniscus tear and underwent arthroscopic intervention. The ligament was stable intraoperatively and, therefore, was not resected. Both patients had resolution of their symptoms.These 2 variants are additions to the previously described 4 normal intermeniscal ligament variants. The functions of the 2 new variants described in this article are poorly understood but are thought to involve meniscal stability. Accurate descriptions of normal variants can lead to the proper management of anomalous rare structures and prevent false imaging interpretations because these structures can closely mimic a double posterior cruciate ligament sign. Furthermore, an understanding of the various normal variants of intermeniscal ligaments can prevent unnecessary surgery that could result in further iatrogenic meniscus injury.

Musashi1 antigen expression in human fetal germinal matrix development

Musashi1 is a highly conserved protein found in neural progenitor cells. We examined the expression dynamics of Musashi1 in conjunction with other representative neural progenitor antigenic determinants (Ki-67 and nestin) during 8 different stages of the developing human fetal germinal matrix. Our results indicate that Musashi1 is a useful marker for immature cells in periventricular areas inhabited by stem cells, progenitor cells, and differentiating cells.