Dale T. Ashby

Factors Influencing the Ability of HDL to Inhibit Expression of Vascular Cell Adhesion Molecule-1 in Endothelial Cells

We have previously reported that high density lipoproteins (HDLs) inhibit the cytokine-induced expression of adhesion molecules in endothelial cells. Here we investigate whether different preparations of HDLs vary in their ability to inhibit the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) activated by tumor necrosis factor-alpha (TNF-alpha). HDLs collected from a number of different human subjects all inhibited VCAM-1 expression in a concentration-dependent manner, although the extent of inhibition varied widely between subjects. The inhibitory activities of the HDL2 and HDL3 subfractions isolated from individual subjects also differed. Whether equated for concentrations of apolipoprotein (apo) A-I or cholesterol, the inhibitory activity of HDL3 was superior to that of HDL2. This difference remained apparent even when the HDL subfractions were present only during preincubations with the HUVECs and were removed before activation by TNF-alpha. To determine whether the inhibitory effect of HDL3 was influenced by apolipoprotein composition, preparations of HDL3 were modified by replacing all of their apo A-I with apo A-II. This change in apolipoprotein composition had no effect on the ability of the HDL3 to inhibit endothelial VCAM-1 expression. Thus, it has been shown that different preparations of HDLs differ markedly in their abilities to inhibit VCAM-1 expression in cytokine-activated HUVECs. The mechanism underlying the differences remains to be determined.

Coronary artery stenting

When Andreas Gruentzig performed the first percutaneous coronary angioplasty on an awake patient in 1977 (Zurich, Switzerland), he created the nascent field of interventional cardiology and ushered in a new era of coronary revascularization. Percutaneous coronary transluminal angioplasty (PTCA) was positioned to serve as an alternative and complement to coronary artery bypass grafting (CABG) and optimal medical therapy. As in many medical fields, the advancement of percutaneous coronary interventions (PCI) has been punctuated by innovations and pitfalls.

Safety of an Aspirin-Alone Regimen After Intracoronary Stenting With a Heparin-Coated Stent Final Results of the HOPE (HEPACOAT and an Antithrombotic Regimen of Aspirin Alone) Study

Background—Stent thrombosis is an infrequent complication of intracoronary stenting that often has devastating clinical consequences. This study assesses the additional benefit of heparin coating with the BX VELOCITY Balloon-Expandable Stent with HEPACOAT, Carmeda end-point attached heparin (HEPACOAT) in patients with de novo or restenotic native coronary artery lesions treated with aspirin monotherapy after optimal stenting. Methods and Results—This was a multicenter, prospective, nonrandomized, pilot study. Two hundred patients (69% men; mean age, 64.1±11.2 years) meeting the eligibility criteria were treated with the HEPACOAT stent and aspirin alone after stenting. Any other antiplatelet or anticoagulation therapy was not permitted. Procedural success was achieved in all patients. There were 3 postprocedural non–Q-wave myocardial infarctions. The primary end point of stent thrombosis at 30 days occurred in 2 of 200 patients (1%): in one after blunt chest trauma and in the other in the setting of essential thrombocytosis. Major adverse cardiac events (death, myocardial infarction, target lesion revascularization, and coronary artery bypass grafting) were observed at 30 days in 5 of 200 (2.5%) patients. Conclusions—The BX VELOCITY stent with HEPACOAT and aspirin alone after the procedure was safe in select patients with de novo or restenotic lesions in native coronary arteries. Heparin coating provides additional protection against stent thrombosis.

Lack of effect of serum amyloid A (SAA) on the ability of high-density lipoproteins to inhibit endothelial cell adhesion molecule expression.

Studies have been conducted to determine whether the ability of high density lipoproteins (HDL) to inhibit the cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells is altered by the presence in HDL of the acute phase reactant, serum amyloid-A (SAA). Preparations of HDL(3) were isolated on two separate occasions from the plasma of each of 19 patients: the first was collected before and the second 3 days after undergoing coronary artery bypass graft surgery. Whereas the preoperative HDL(3) sample contained no SAA, in the postoperative sample SAA accounted for an average of 42% of the HDL(3) protein. The preoperative HDL(3) and postoperative, SAA-enriched HDL(3) were identical in terms of their ability to inhibit the tumour necrosis factor-alpha (TNF-alpha)-induced expression of VCAM-1 in human umbilical vein endothelial cells (HUVECs). To assess the effect of having an even greater SAA enrichment of HDL(3), samples of HDL(3) were incubated with purified SAA, which displaced almost all of the apoAI and about 40% of the apoAII from the HDL(3). This in vitro SAA-enriched HDL(3) inhibited the TNF-alpha-induced expression of VCAM-1 in HUVECs in a concentration dependent manner, which was identical to that of the unmodified HDL(3). The presence of SAA did not alter the cell-surface binding of HDL(3) to endothelial cells. It has been concluded that the presence of SAA in HDL has no effect on the ability of these lipoproteins either to inhibit the expression of VCAM-1 in endothelial cells or to bind to proteins on the endothelial cell surface.

Effect of percutaneous coronary interventions for in-stent restenosis in degenerated saphenous vein grafts without distal embolic protection

OBJECTIVES This study was designed to investigate the impact of percutaneous coronary interventions (PCIs) in degenerated saphenous vein grafts (SVGs) without distal embolic protection. BACKGROUND Distal embolic protection devices have been shown to reduce the incidence of no reflow/slow flow during PCI of de novo lesions in degenerated SVGs. It is unclear whether PCI of in-stent restenosis (ISR) lesions in degenerated SVGs is associated with no reflow/slow flow and whether distal embolic protection is beneficial in these cases as well. METHODS We studied 54 consecutive patients with treated ISR lesions in degenerated SVGs who underwent PCI without distal embolic protection in a single center. Procedural and in-hospital outcomes were examined. The average age was 71 +/- 8 years; 32% of the patients had diabetes. The mean lesion length was 13 +/- 6 mm and the procedural success rate was 98% (53/54). Cutting balloon angioplasty was used in 46% (25/54) of cases, and a new stent was inserted in 46% (25/54) of patients. Gamma brachytherapy was performed in 19% (10/54) of patients. During the procedure there were no episodes of no reflow/slow flow, and there were no patients with in-hospital Q-wave or non-Q-wave myocardial infarction. There was one in-hospital noncardiac death. CONCLUSIONS In this consecutive series of patients with ISR of degenerated SVGs undergoing PCI without distal protection, there were no episodes of slow flow/no reflow and no procedure-related myocardial infarctions. It appears that distal embolic protection may not be necessary during PCI of ISR lesions in degenerated SVGs.

A retrospective case study to assess the value of the implantable loop recorder for the investigation of undiagnosed syncope.

ASHBY, D.T., et al.: A Retrospective Case Study to Assess the Value of the Implantable Loop Recorder for the Investigation of Undiagnosed Syncope. If not diagnosed by history, examination, or ECG, the diagnosis of syncope can be difficult with a low yield from echocardiography, ambulatory ECG recording, electrophysiological study, and tilt table testing. During 2 years, 48 patients with unexplained syncope or presyncope from three hospitals in one city underwent the implantation of a Medtronic Reveal implantable loop recorder capable of cardiac monitoring for 14 months. All patients had at least two prior episodes of syncope or presyncope. Fifty‐two percent of patients had electrophysiological studies, all of which were negative. The implantable loop recorder remained implanted until a diagnostic event was recorded, or until the end of the battery life. After a mean follow‐up of 5.6 ± 5.7 months, symptoms reoccurred in 25 (52.1%) patients at a mean of 2.8 ± 2.1 months after insertion of an implantable loop recorder. No further symptoms occurred in 23 (47.9%) patients. Of the 25 patients who had a symptom and recorded an event, an arrhythmia was seen in 10 (40%) patients. Seven patients had bradycardia; 4 with profound sinus bradycardia/sinus arrest, 1 with complete heart block, and 2 in association with the cardioinhibitory component of vasovagal syncope. Three patients had tachycardias; two with supraventricular tachycardia and one with atrial flutter. Fifteen (60%) of the 25 patients who activated their device due to syncope or presyncope were in sinus rhythm during the event. The implantable loop recorder was effective in making a cardiological or noncardiological diagnosis for unexplained syncope or presyncope in 52.1% of the patients.

Comparison of clinical outcomes using stents versus no stents after percutaneous coronary intervention for proximal left anterior descending versus proximal right and left circumflex coronary arteries.

Previous studies have demonstrated that proximal left anterior descending (LAD) stenoses have higher rates of restenosis after angioplasty than stenoses in other coronary segments. Stenting strategies may reduce this high rate of LAD restenosis. The study population included 1,289 patients with proximal coronary artery stenoses treated with percutaneous coronary interventions (PCI) with or without stents for single-vessel coronary disease between 1994 and 1999. Patients were divided into 4 groups: non-stent PCI in the proximal LAD artery (n = 168), non-stent PCI in proximal right/circumflex artery (n = 217), stent in the proximal LAD artery (n = 364), and stent to proximal right/circumflex artery (n = 540). Procedural success was higher in the stenting groups, but there were no significant differences in the major in-hospital events between the different lesion locations among the groups. At 1-year follow-up, there was no difference in mortality or myocardial infarction between the groups. There was no significant difference in the rate of target lesion revascularization (TLR) in the patients with proximal LAD stents compared with the patients with proximal right/circumflex coronary artery stents (10.1% vs 13.8%, p = 0.11). In the patients who did not receive stents with proximal narrowings, there was a significant increase in TLR in the LAD group compared with the right/circumflex group (21.1% vs 12.5%, p = 0.04). Thus, patients with proximal stenoses treated with non-stenting strategies have lower procedural success than those treated with stenting strategies; the patients with proximal LAD non-stent PCI have significantly higher rates of clinical restenosis than patients with proximal right and circumflex stenoses. A stenting strategy for proximal LAD stenoses appears to attenuate the differences of clinical restenosis noted after non-stent PCI.

Comparison of Outcomes in Men Versus Women Having Percutaneous Coronary Interventions in Small Coronary Arteries

Previous studies investigating the effect of gender on outcomes after percutaneous coronary intervention (PCI) have reported that women have higher in-hospital adverse event rates and a higher mortality rate than men. 1,2 This has been attributed to both the smaller size of women 3,4 and to the older age of women at the time of PCI. Older populations who undergo PCI are associated with increased rates of comorbid disease and an increased cardiac risk factor profi le. 5 Because women tend to have smaller coronary arteries than men, we hypothesized that the adverse outcomes may be partly due to the smaller coronary artery diameters. To test this hypothesis we compared men and women with small coronary arteries to evaluate whether gender remained a determinant

Long-term follow-up of patients after gamma intracoronary brachytherapy failure (from GAMMA-I, GAMMA-II, and SCRIPPS-III)

We report the long-term outcome of 225 patients who failed gamma-brachytherapy for in-stent restenosis. Total adverse events, target vessel revascularization, and myocardial infarction were higher after repeat percutaneous coronary intervention versus coronary artery bypass grafting. Therefore, coronary artery bypass grafting may be the preferable first-line therapy in these patients until other therapies (i.e., drug-eluting stents) are available. Shorter time from brachytherapy to radiation failure and late thrombosis after brachytherapy were independent predictors of adverse events.

Biventricular Pacing for Severe Mitral Reguritation Following Atrioventrgicular Nodal Ablation

DISNEY, P.J.S., et al.: Biventricular Pacing for Severe Mitral Regurgitation Following Atrioventricular Nodal Ablation. A 69‐year‐old woman developed acute pulmonary edema and severe mitral regurgitation (MR) 2 days following an uncomplicated AV nodal (AVN) ablation and insertion of VVI pacemaker for chronic atrial fibrillation. There was no history of significant mitral valve disease. Left ventricular function was normal and there was no evidence of an acute cardiac ischemic event. Transthoracic echo and right heart catheterization studies showed reduction in the severity of MR with biventricular pacing as opposed to RV pacing alone. A permanent pacemaker configured for biventricular pacing was implanted with complete resolution of symptoms and significant reduction in degree of MR. (PACE 2003; 26[Pt. I]:643–644)