Hylton Miller

Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years

Abstract Objective: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. Design: Case control study over three years. Setting: An 800 bed general municipal hospital. Subjects: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. Interventions: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. Main outcome measure: Postprandial lipoprotein metabolism. Results: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) µmol/l.h; 95% confidence interval of difference 4.37 to 11.82). Conclusions: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease. Key messages Key messages The atherogenic effect of postprandial lipoproteins is hypothesised to be inversely related to their metabolic capacity Patients with coronary artery disease have decreased metabolic capacity of chylomicron remnants as compared with subjects with normal coronary arteries An ensuing postprandial dyslipidaemia may exist in patients with coronary artery disease who have normal fasting lipid values A vitamin A fat loading test may be useful in identifying these patients

Number and Adhesive Properties of Circulating Endothelial Progenitor Cells in Patients With In-Stent Restenosis

Objective—Intact endothelialization machinery is essential to facilitate vessel healing after stent placement and to prevent restenosis. Circulating endothelial progenitor cells (EPC) have been demonstrated in the peripheral blood and shown to display endothelial functional properties, along with the ability to traffic to damaged vasculature. We reasoned that robust in-stent intimal growth could be partially related to impaired endothelialization resulting from reduced circulating EPC number or function. Methods and Results—Sixteen patients with angiographically-demonstrated in-stent restenosis were compared with patients with a similar clinical presentation that exhibited patent stents (n=11). Groups were similar with respect to the use of drugs that could potentially influence EPC numbers. Circulating EPC numbers were determined by the colony-forming unit assay, and their phenotype was characterized by endothelial-cell markers. Adhesiveness of EPC from both groups to extracellular matrix and to endothelial cells was also assayed. Patients with in-stent restenosis and with patent stents displayed a similar number of circulating EPC. Fibronectin-binding was compromised in patients with in-stent restenosis as compared with their controls exhibiting patent stents. Patients with diffuse in-stent restenosis exhibited reduced numbers of EPC in comparison with subjects with focal in-stent lesions. Conclusion—Reduced numbers of circulating EPC in patients with diffuse in-stent restenosis and impaired adhesion of EPC from patients with restenosis provides a potential mechanism mediating the exuberant proliferative process. These markers, if further validated, could provide means of risk stratifying patients for likelihood of developing in-stent restenosis.

Analysis of Coronary Ultrasound Thrombolysis Endpoints in Acute Myocardial Infarction (ACUTE Trial) Results of the Feasibility Phase

BACKGROUNDnIt has been demonstrated that therapeutic ultrasound effects ultrasound thrombolysis by selectively disrupting the fibrin matrix of the thrombus. This study was conducted to evaluate the clinical feasibility of percutaneous transluminal coronary ultrasound thrombolysis in acute myocardial infarction (AMI).nnnMETHODS AND RESULTSnConsecutive patients (n = 15) with evidence of anterior AMI and Thrombolysis in Myocardial Infarction (TIMI) grade 0 or 1 flow in the left anterior descending artery underwent coronary ultrasound thrombolysis. Angiographic follow-up was performed after 10 minutes and 12 to 24 hours. Ultrasound induced successful reperfusion (TIMI grade 3 flow) in 87% of the patients. Adjunct percutaneous transluminal coronary angioplasty (PTCA) after ultrasound thrombolysis produced a final residual stenosis of 20 +/- 12% as determined by quantitative coronary angiographic analysis. There were no adverse angiographic signs or clinical effects during the procedure. There was no change in the degree of flow in any of the patients at the 12- to 24-hour angiograms. During hospitalization, 1 patient had recurrent ischemia on the fifth day after the procedure, and emergent catheterization revealed occlusion at the treatment site. The patient was successfully treated with PTCA.nnnCONCLUSIONSnThese results suggest that ultrasound thrombolysis has the potential to be a safe and effective catheter-based therapeutic modality in reperfusion therapy for patients with AMI and other clinical conditions associated with intracoronary thrombosis.

Effects of an acute dose of L-arginine during coronary angiography in patients with chronic renal failure: a randomized, parallel, double-blind clinical trial.

Background: Contrast media (CM) are nephrotoxic and might further worsen renal function in patients with chronic renal failure. L-Arginine, the substrate of nitric oxide, protects kidney function and may improve endothelial function in patients with coronary artery disease. Hypothesis: Acute administration of L-arginine in a subset of patients with combined coronary artery disease and impaired kidney function during coronary angiography might prevent superimposed acute renal failure. Methods: A double-blind study of patients with mild/moderate chronic renal failure (Cr >1.7 mg/dl) undergoing coronary angiography (meglumine ioxaglate) was conducted. Patients received either L-arginine (300 mg/kg) or placebo and were followed for 48 h. Cardiac hemodynamic parameters, renal function and nitric oxide production were sequentially recorded. Results – Primary and Secondary: Both groups experienced a decrease of creatinine clearance 48 h following the procedure (p < 0.05). Creatinine levels slightly increased following the administration of L-arginine (p < 0.05) but not in the placebo treated group. No changes of systemic and cardiac pressures, total peripheral resistance or cardiac output were recorded within and between the treatment and placebo groups. Conclusion: CM injection causes an impairment of renal function. Addition of intravenous L-arginine during cardiac catheterizations in patients with chronic renal failure does not prevent CM-induced nephrotoxicity and does not affect endothelial dysfunction in the particular population studied by the authors, i.e. patients with coronary artery disease (CAD) of various degrees, or suspicion of CAD and chronic mild renal failure.

Clinical value of 16‐slice multi‐detector CT compared to invasive coronary angiography

BACKGROUND: Multi‐detector row spiral CT (MDCT) can be applied as a noninvasive tool for the assessment of coronary artery stenoses. Few, confounding reports have been published using 16 detector rows. The aim of the present study was to determine the accuracy of 16‐detector row MDCT for the detection of significant stenoses in the coronary arteries, in comparison to conventional invasive coronary angiography. METHODS: Twenty‐two patients with suspected coronary artery disease, were prospectively evaluated by 16‐slice retrospectively ECG‐gated CT coronary angiography and quantitative invasive coronary angiography. The findings were compared for the detection of significant coronary artery stenoses (>50%) in all segments with diameter >1.5u2005mm. RESULTS: MDCT correctly classified all 14 patients (100%) that were found to have significant coronary artery disease on conventional angiography. Overall, 288 segments were included in the analysis, regardless of their image quality. Significant stenoses were detected in 24 segments by CT and in 28 segments by conventional angiography. Out of 260 segments that were negative for significant stenoses on conventional angiography, 255 were correctly identified on CT. The sensitivity, specificity, positive and negative predictive values were 86, 98, 83 and 98%, respectively. MDCT also revealed supplementary findings that invasive angiography was unable to visualize, including anomalous vessel course, the course of vessels filling via collaterals, intramyocardial course of vessels and non‐stenotic plaques. CONCLUSIONS: MDCT coronary angiography utilizing 16‐detector rows shows promising results for reliable detection of coronary artery stenoses and particularly for ruling out significant disease.

Serum lipids and restenosis after successful percutaneous transluminal coronary angioplasty

Abstract The effects of plasma lipids on the clinical and angiographic parameters of 134 patients, in whom coronary angioplasty was performed in 157 vessels, were prospectively examined. During a 6-month follow-up, restenosis was detected angiographically in 39 patients (29%; 45 vessels). None of the clinical, biochemical, or angiographic variables examined was predictive of stenosis and the tendency of a vessel to restenose was not patient-dependent but rather lesion-related. However, restenosis developed in 31 of 102 vessels (30%) in patients with high-density lipoprotein (HDL) cholesterol ⩽ 40 mg/dl, compared with restenosis in 10 of 55 vessels (19%) in patients with HDL cholesterol >40 mg/dl (p = 0.092). No significant differences were observed when restenosis rates were compared in patients with total cholesterol levels >250 mg/dl or 160 mg/dl and

Pulse transmission coefficient: A novel nonhyperemic parameter for assessing the physiological significance of coronary artery stenoses

OBJECTIVESnWe sought to test the hypothesis that the pulse transmission coefficient (PTC) can serve as a nonhyperemic physiologic marker for the severity of coronary artery stenosis in humans.nnnBACKGROUNDnCoronary lesions may impair the transmission of pressure waves across a stenosis, potentially acting as a low-pass filter. The PTC is a novel nonhyperemic parameter that calculates the transmission of high-frequency components of the pressure signal through a stenosis. Thus, it may reflect the severity of the coronary artery stenosis. This study was designed to examine the correlation between PTC and fractional flow reserve (FFR) in patients with coronary artery disease.nnnMETHODSnPressure signals were obtained by pressure guidewire in 56 lesions (49 patients) in the nonhyperemic state and were analyzed with a new algorithm that identifies the high-frequency components in the pressure signal. The PTC was calculated as the ratio between the distal and proximal high-frequency components of the pressure waveform across the lesion. The FFR measurements were assessed with intracoronary adenosine.nnnRESULTSnThere was a significant correlation between PTC and FFR (r = 0.81, p < 0.001). By using a receiver operating characteristic analysis, we identified a PTC < 0.60 (sensitivity 100%, specificity 98%) to be the optimal cutoff value for predicting an FFR < 0.75.nnnCONCLUSIONSnPulse transmission coefficient is a novel nonhyperemic parameter for the physiologic assessment of coronary artery stenoses. It correlates significantly with FFR and may predict an FFR < 0.75 with high accuracy. Pulse transmission coefficient may be useful as an adjunct measurement to FFR, especially in patients with microcirculatory disease and impaired maximal hyperemia.

Detection of Restenosis following Percutaneous Coronary Angioplasty in Single-Vessel Coronary Artery Disease: The Value of Clinical Assessment and Exercise Tolerance Testing

Chest pain and submaximal exercise testing were prospectively assessed over a 6-month period, for detecting the evolution of restenosis in patients undergoing percutaneous coronary angioplasty, following either acute myocardial infarction or treatment of an anginal syndrome. Seventy-eight patients with one-vessel coronary artery disease underwent a modified treadmill exercise test at the 1-week, 3-month and 6-month follow-up after angioplasty, when a final angiogram was also performed. Forty-four patients (group A) were examined after myocardial infarction; in 34 patients (group B) angioplasty was done for incapacitating angina. Both groups showed similar results with low sensitivity and relatively moderate specificity of both chest pain and exercise tests; this was also the case for the time of restenosis to occur. It is thus concluded that the parameters examined are somewhat limited markers of restenosis following coronary angioplasty.

Eptifibatide does not influence lymphocyte activation and CRP levels in patients with undergoing coronary angioplasty

Inhibitors of the IIB-IIIA integrin are widely used to prevent stent thrombosis. Abciximab has been shown to attenuate the inflammatory response in patients undergoing PCI. Herein, we tested the effect of eptifibatide infused during PCI on peripheral lymphocyte activation and CRP levels before, and one month after the procedure showing no noticeable effect. These results may explain the differences in clinical outcome following PCI by use of different IIB-IIIA agents. (Int J Cardiovasc Intervent 2004; 6: 107-109)