Verghese Mathew

Smoking Is Associated With Epicardial Coronary Endothelial Dysfunction and Elevated White Blood Cell Count in Patients With Chest Pain and Early Coronary Artery Disease

Background— Smoking is a major risk factor for cardiovascular events. One of the potential mechanisms may be related to both coronary endothelial dysfunction and increased inflammatory response. The present study was designed to test the hypothesis that smoking is associated with epicardial coronary endothelial dysfunction and inflammation. Methods and Results— Coronary endothelial function in response to acetylcholine was assessed in 881 patients (115 current smokers and 766 nonsmokers, including 314 previous smokers). Smokers were significantly younger than nonsmokers (43±1 versus 51±1 years, P<0.0001), had more epicardial vasoconstriction in response to intracoronary acetylcholine (−19±2% versus −14±1% change in coronary artery diameter, P=0.03), and were more likely than nonsmokers to have epicardial endothelial dysfunction (46% versus 35%, P=0.005), but their microvascular endothelial function was intact. Smokers had higher white blood cell counts than nonsmokers (7.7±0.2 versus 6.6±0.1×109/L, P<0.0001), higher myeloperoxidase (156±19 versus 89±8 ng/mL), higher lipoprotein-associated phospholipase A2 (242±12 versus 215±5 ng/mL), and higher levels of intracellular adhesion molecule (283±14 versus 252±5 ng/mL). There were no differences in the levels of C-reactive protein, fibrinogen, or vascular cell adhesion molecule between the groups. Conclusion— Young smokers are characterized by epicardial coronary endothelial dysfunction, preserved microvascular endothelial function, and increased levels of inflammatory biomarkers and oxidative stress. The present study provides further information regarding the potential mechanisms by which smoking contributes to cardiovascular events.

Enhanced Endothelin-Mediated Coronary Vasoconstriction and Attenuated Basal Nitric Oxide Activity in Experimental Hypercholesterolemia

BACKGROUND Experimental hypercholesterolemia is associated with coronary vasomotor dysfunction. This study was designed to test the hypothesis that experimental hypercholesterolemia is characterized by altered coronary vasomotor responses to endothelin and inhibition of the endogenous NO pathway. METHODS AND RESULTS Endothelin-1 (ET-1) at 5 ng x kg(-1) x min(-1) or N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of nitric oxide synthase (NOS), at 50 microg x kg(-1) x min(-1) was infused into the left anterior descending coronary artery in pigs before and after 10 weeks of cholesterol diet. There was a significant increase in serum cholesterol. At 10 weeks, ET-1 resulted in an accentuated decrease in coronary blood flow (CBF) and coronary artery diameter (CAD) compared with baseline (-88+/-6% versus -45+/-9%, P<.05, and -77+/-14% versus -18+/-8%, P<.05, respectively) and an increase in coronary vascular resistance (CVR) (242+/-18% versus 110+/-17%, P<.05); ET receptor density and binding affinity in epicardial coronary arteries were unchanged. The effect of L-NMMA on CBF, CAD, and CVR was attenuated at 10 weeks (-7+/-8% versus -48+/-4%, -2+/-3% versus -17+/-5%, and 16+/-10% versus 125+/-32%; each P<.05). Immunohistochemistry staining for constitutive NOS revealed a decrease in immunoreactivity in the coronary arteries of hypercholesterolemic pigs. CONCLUSIONS The present study demonstrates an enhanced coronary vasoconstrictive response to pathophysiological doses of endothelin and an attenuated response to the inhibition of endogenous NO activity, suggesting an alteration in coronary vascular reactivity in experimental hypercholesterolemia.

Evaluation of long-term survival after successful percutaneous coronary intervention among patients with chronic renal failure ∗

We studied the long-term outcomes after percutaneous coronary intervention in dialysis patients and in patients with chronic renal failure (CRF) (serum creatinine > or = 3.0 mg/dl). All-cause mortality at 1 year was 2.9% for the control group, 16.2% for the group with CRF, and 14.1% for dialysis patients. Cardiac mortality at 1 year was 1.9% for ther control group, 15.2% for the group with CRF, and 10.0% for dialysis patients.

Symptomatic conduction system disease in cardiac amyloidosis

Symptomatic conduction system disease in cardiac amyloidosis and its management has been reported infrequently. We report our experience of patients with amyloidosis having symptomatic conduction system disease requiring permanent pacemaker implantation.

Clinical Risk Stratification Correlates With the Angiographic Extent of Coronary Artery Disease in Unstable Angina

OBJECTIVES We sought to determine whether clinical risk stratification correlates with the angiographic extent of coronary artery disease (CAD) in patient with unstable angina. BACKGROUND The Agency for Health Care Policy and Research (AHCPR) guidelines stratify patients with unstable angina according to short-term risk of myocardial infarction or death. Whether these guidelines are useful in predicting the extent of CAD is unknown. METHODS All residents of Olmsted County, Minnesota, undergoing emergency department evaluation from January 1, 1985 through December 31, 1992 for unstable angina without a history of prior coronary artery bypass grafting, and who underwent early angiography (within seven days of presentation) were classified into low, intermediate and high risk subgroups based on AHCPR criteria. RESULTS Seven hundred ninety-five patients underwent early angiography: 159 high risk, 572 intermediate risk and 64 low risk patients. Logistic regression analysis demonstrated that low risk patients had a greater likelihood of normal or mild CAD relative to intermediate risk (odds ratio [OR], 4.67; 95% confidence interval [CI], 2.70-8.06; p < 0.001) and high risk (OR, 11.1; 95% CI, 5.71-22.2; p < 0.001). Significant 1-, 2-, 3-vessel coronary disease or left main coronary disease was more likely in high relative to low risk (OR, 8.09; 95% CI, 4.22-15.5; p < 0.001), intermediate relative to low risk (OR, 4.11; 95% CI, 2.34-7.22; p < 0.001), and high relative to intermediate risk (OR, 1.97; 95% CI, 1.31-2.96; p = 0.0012). CONCLUSIONS Among patients with unstable angina undergoing early coronary angiography, risk stratification according to the AHCPR guidelines correlates with the angiographic extent of CAD.

Stent Designs and Implantation Techniques

The introduction of intracoronary stents has significantly influenced the current practice of interventional cardiology. The increase in the use of stents began with the publication of results of the BENESTENT (Belgium Netherlands Stent) and STRESS (Stent Restenosis Study) trials, which demonstrated significant reduction in restenosis rates in patients with discrete stenosis in large native arteries [1,2]. Acute complications of angioplasty, including abrupt vessel closure and emergency coronary bypass surgery, have also been reduced with the use of stents [3]. Similar success with stents has been noted in angiographic subsets of complex lesions (eg, diffuse, tandem, severely calcified, restenotic, thrombotic, or ostial); in total occlusions, bifurcation lesions, saphenous vein grafts, and multivessel interventions, the combination of stenting and abciximab conferred additive long-term benefit with respect to death, myocardial infarction, and target vessel revascularization [4].

Rotational Coronary Atherectomy

Rotational atherectomy uses the principle of high-speed abrasive differential cutting to ablate atheromatous plaque. This system, developed by David Auth, was approved for coronary use in 1993. Rotational atherectomy and other newer devices were designed principally to aid in the procedural success of percutaneous coronary intervention and potentially to reduce the occurrence of restenosis compared with that achieved with balloon angioplasty. Obviously, none of the newer devices (except for stents) have reduced the rates of restenosis, but rotational atherectomy may indeed be useful in certain lesion subsets in clinical practice. This chapter discusses the principles of operation, system and design characteristics, relevant clinical data, technical and procedural issues, and management of complications associated with rotational atherectomy.

Atlas of interventional cardiology

Coronary Arterial Response to Injury.- Lesion Assessment.- Equipment Selection and Techniques of Percutaneous Coronary Intervention.- Guide Selection.-Stent Designs and Implantation Techniques.- In-stent Restenosis.- Directional Coronary Atherectomy.- Rotational Coronary Atherectomy.- Cutting Balloon Angioplasty.- Specific Lesion Subsets.- Drug-eluting Stents.- Distal Protection Devices.- Complications of Percutaneou.- Coronary Artery Intervention.- Peripheral Interventions.