Influence of smoking status on progression of endothelial dysfunction

Background: Cigarette smoking is a major risk factor for developing coronary artery disease and is associated with increased coronary morbidity and mortality in patients with established atherosclerosis. This report describes the influence of smoking on coronary endothelial function in normotensive patients with coronary artery disease, but without left ventricular dysfunction, severe hypercholesterolemia, or insulin-dependent diabetes mellitus. Methods: Placebo-treated patients (n = 54) from a larger study assessing coronary endothelial function were classified at baseline as smokers or nonsmokers for this subgroup analysis. Patients underwent coronary angiography at baseline and again after 6-month follow-up. Results: At baseline, there was a trend for a greater decrease in target segment diameter (n = 54) in smokers compared with nonsmokers (- 17.2 ± 5.3% vs. -8.0 ± 2.5%, acetylcholine 10^?4 mol/1). All measured coronary artery segments (n = 202) showed similar responses (- 7.3 ± 2.7% vs. - 3.8 ± 1.3%, acetylcholine 10^?4 mmol/1, for smokers vs. nonsmokers, respectively). After 6 months, smokers showed an even greater vasoconstrictor response to acetylcholine whereas nonsmokers did not (- 21.7 ± 5.3% vs. - 8.3 ± 2.5%, acetylcholine 10^?4 mmol/1). The vasodilatory response to nitroglycerin was similar in smokers and nonsmokers. Conclusions: In current smokers, a marked decline in endothelium-dependent vasomotor response was observed over a 6-month period.     

Thrombin generation test for evaluation of antiplatelet treatment in patients with coronary artery disease after percutaneous coronary intervention

To study the possibility of using thrombin generation tests in platelet-rich and platelet-poor plasma for evaluation of dual antiplatelet therapy efficacy in patients with coronary artery disease (CAD), following percutaneous coronary intervention. Venous blood was analyzed from CAD patients aged 53–75 years who had undergone percutaneous coronary intervention with stenting within one year and had been receiving standard doses of clopidogrel and aspirin (75 and 75–100 mg per day, respectively). The control group comprised age- and sex-matched subjects without clinical signs of CAD who were not receiving these drugs. Thrombin generation tests were performed in platelet-rich and platelet-poor plasma. Intravascular platelet activation, induced platelet aggregation, and routine coagulation were evaluated. Antiplatelet treatment did not influence results of routine coagulation tests or intravascular platelet activation. The dual antiplatelet therapy affects collagen-induced platelet aggregation (44 ± 2.5 vs. 7.9 ± 2.6%, р = 10^?7) and leads to decreases in endogenous thrombin potential (1900 ± 85 vs. 1740 ± 95 nM?min, p = 0.0045), maximum thrombin concentration (134 ± 9.5 vs. 106 ± 6.5 nM, p = 4?10^?6), and increases in time to peak thrombin (27 ± 1.5 vs. 31 ± 2 min, p = 0.0012). Decreases in thrombin generation rate showed the highest statistical significance (13 ± 2 vs. 7.9 ± 0.8 nM/min, p = 10^?8). Antiplatelet treatment did not alter thrombogram parameters for platelet-poor plasma.     

Mechanisms and immediate and long-term results of adjunct directional coronary atherectomy after rotational atherectomy

Objectives.The purpose of this study was to confirm the mechanisms and the immediate and long-term results of rotational atherectomy and adjunct directional coronaryatherectomy.Background.Rotational atherectomy is best suited for treating calcific stenoses, but the ability of rotational atherectomy alone to optimize lumen dimensions in large vessels is limited; this is only partly improved by adjunct balloon angioplasty.Methods.We treated 165 lesions in 163 patients by use of rotational atherectomy and adjunct directional coronary atherectomy. Quantitative angiography and intravascular ultrasond were used for lesion analysis. A matched comparison with 208 lesions treated with rotational atherectomy and adjunct coronary angioplasty was performed. Patients were then followed up for at least 9 months, and target-lesion revascularization was assessed.Results.In the 61 lesions imaged sequentially, lumen area increased from 1.7 ± 0.8 (mean ± 1 SD) to 3.9 ± 1.1 mm²after rotational atherectomy, owing to a decrease in plaque plus media area from 16.8 ± 5.0 to 15.2 ± 5.2 mm²(both p < 0.0001). After adjunct directional coronary atherectomy, lumen area increased even more to 6.7 ± 2.0 mm²(vs. 5.1 ± 1.4 mm²after adjunct coronary angioplasty, p < 0.0001) as a result of both vessel expansion (18.8 ± 5.3 to 20.8 ± 5.7 mm²) and additional plaque removal (to 14.1 ± 5.0 mm², all p < 0.0001). The total arcs of calcium decreased from 207 ± 107° to 166 ± 93° after rotational atherectomy and to 145 ± 87° after directional coronary atherectomy.Overall, procedural success was 96%, and final diameter stenosis was 15 ± 17%. Target-lesion revascularization was 23%. The only independent predictor of target-lesion revascularization was a larger overall atherectomy index (84% vs. 59%, p = 0.048).Conclusions.There is a synergistic relationship between rotational atherectomy and directional coronary atherectomy in the treatment of calcific lesions. The immediate results show a high procedural success—lumen dimensions were larger and late target-lesion revascularization was lower in lesions treated with rotational atherectomy and directional coronary atherectomy than in those treated with rotational atherectomy and adjunct balloon angioplasty.     

Insulin resistance and coronary artery disease

Summary The purpose of the present study was to quantitate insulin-mediated glucose disposal in normal glucose tolerant patients with angiographically documented coronary artery disease (CAD) and to define the pathways responsible for the insulin resistance. We studied 13 healthy, normal weight, normotensive subjects with angiographically documented CAD and 10 age-, weight-matched control subjects with an oral glucose tolerance test and a 2-h euglycaemic insulin (40 mU · m⁻²· min⁻¹) clamp with tritiated glucose and indirect calorimetry. Lean body mass was measured with tritiated water. All CAD and control subjects had a normal oral glucose tolerance test. Fasting plasma insulin concentration (66 ± 6 vs 42 ± 6 pmol/l, p < 0.05) and area under the plasma insulin curve following glucose ingestion (498 ± 54 vs 348 ± 42 pmol · l⁻¹· min⁻¹, p < 0.001) were increased in CAD vs control subjects. Insulin-mediated whole body glucose disposal (27.8 ± 3.9 vs 38.3 ± 4.4 μmol · kg fat free mass (FFM)⁻¹· min⁻¹, p < 0.01) was significantly decreased in CAD subjects and this was entirely due to diminished non-oxidative glucose disposal (8.9 ± 2.8 vs 20.0 ± 3.3 μmol · kg FFM⁻¹· min⁻¹, p < 0.001). The magnitude of insulin resistance was positively correlated with the severity of CAD (r = 0.480, p < 0.05). In the CAD subjects basal and insulin-mediated rates of glucose and lipid oxidation were normal and insulin caused a normal suppression of hepatic glucose production. In conclusion, subjects with angiographically documented CAD are characterized by moderate-severe insulin resistance and hyperinsulinaemia and should be included in the metabolic and cardiovascular cluster of disorders that comprise the insulin resistance syndrome or ’syndrome X'. [Diabetologia (1996) 39: 1345–1350] Received: 6 February 1996 and in revised form: 29 May 1996     

Determinants of coronary compliance in patients with coronary artery disease: An intravascular ultrasound study

Objectives. The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease.Background. Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance.Methods. Twenty-seven patients (mean age [±SD] 57 ± 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 dilferent coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (ΔA) and pressure (ΔP) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [ΔA/AJ/ΔP [mm Hg⁻¹×x 10³]).Results. Lumen area and plaque area were 12.6 ± 5.7 and 3 ± 3 mm², respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = −0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 ± 2.1 vs. 1.8 ± 1.2 mm Hg⁻¹, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 ± 1.9 vs. 1.6 ± 1.1 mm Hg⁻¹, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 ± 9.7 vs. 2.3 ± 1.6 mm Hg⁻¹, p < 0.01) but was similar in concentric and eccentric plaques (1.6 ± 1.5 vs. 1.6 ± 0.9 mm Hg⁻¹). Plaque area (r = − 0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance.Conclusions. Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.     

Alveolar Macrophage Release of Tumor Necrosis Factor-α in Chronic Alcoholics without Liver Disease

Alcohol is an immunosuppressive drug, and chronic abuse has been associated with increased susceptibility to a variety of infections, including bacterial pneumonia and tuberculosis. Alveolar macrophages are the resident phagocytes of the lung and play a central role in lung host defenses against infection ranging from direct antibacterial activity to the release of proinflammatory cytokines such as tumor necrosis factor-α (TNFα). TNFα, in particular, plays a key role in the development of the early inflammatory response. In this study, we investigated the effects of chronic alcohol consumption on alveolar macrophage release of TNFα in vitro. We prospectively studied lipopolysaccharide (LPS)-stimulated release of TNFα from alveolar macrophages obtained from bronchoalveolar lavage fluid (BALF) in 22 alcoholic (18 smokers, 4 nonsmokers) and 7 nondrinking healthy volunteers (3 smokers, 4 nonsmokers). The total number of cells recovered by bronchoalveolar lavage (BAL) and their differential distribution were not significantly different in alcoholics versus controls (43 ± 8 × 10⁶ and 39 ± 13 × 10⁶, respectively). However, the total number of cells recovered from BALF was significantly higher in smokers (51 ± 8 × 10⁶) than in nonsmokers (19 ± 5 × 10⁸). Spontaneous (basal) release of TNFα by alveolar macrophages was the same in alcoholics and controls. In contrast, LPS-stimulated release of TNFα was significantly suppressed in alcoholics compared with that of controls (1343 ± 271 vs. 3806 ± 926 U TNF/ml/10⁶ cells, respectively, p < 0.015). When controlled for smoking, LPS-stimulated TNFα production was suppressed in alcoholic nonsmokers (563 ± 413 U TNF/ml/10⁶) compared with control nonsmokers (5113 ± 1264 U TNF/ml/10⁶). LPS-stimulated TNFα production was also less in control smokers (2063 ± 386 U TNF/ml/10⁶ cells) than in control nonsmokers (5113 ± 1264 U TNF/ml/10⁶ cells). There was no difference in TNFα production between smoking alcoholics and smoking control subjects. We conclude that chronic alcohol consumption significantly suppresses LPS-stimulated alveolar macrophage production of TNFα. This effect is obscured if the subject also smokes. Because TNFα production is an important element in host defense, this may explain, in part, the susceptibility of chronic alcohol abusers to a variety of infections.     

Long-term histologic patency after percutaneous transluminal coronary angioplasty is predicted by the creation of a greater lumen area

Objectives. This study assessed the relation between histologic acute and long-term lumen size after coronary angioplasty.Background. Angiographic studies suggest that the creation of a larger acute lmmen is associated with a reduced incidence of restenosis. Histologic evaluation of the influence of the acute lumen on late outcome has not been previously reported.Methods. Detailed histologic examination and planimetry were performed in 28 postmortem coronary arteries subjected to angioplasty at an average of 71 weeks antemortem. The lumen area on each histologic segment was defined as the final lumen area. The lumen area immediately after angioplasty, the acute lumen area, was deined by the sum of the neointimal area plus final lumen. A final lumen area ≥ 25% of the arterial area was considered a long-term success; a final lumen area < 25% was considered a long-term failure.Results. Arterial size and neointimal area were similar in long-term successes aid failures. In successes, the mean (±SD) acute lumen area was greater than in failures (4.1 ± 1.9 vs. 2.7 ± 1.4 mm², respectively, p < 0.001). The acute lumen area as a percent of arterial area was 46 ± 10% in successes versus 27 ± 11% in failures (p < 0.0001). The corresponding estimated mean acute lumen diameter stenosis was 24 ± 8% in successes versus 42 ± 12% in failures (p < 0.0001). Plaque area was greater in failures (7.1 ± 3.2 mm²) than in successes (4.8 ± 2.4 mm², p < 0.002).Conclusions. Neointimal proliferation after angioplasty occurs in all dilated coronary arteries, and the amount of neointimal growth is independent of vessel size. The creation of a larger lumen and a larger lumen as a percent of vessel size were associated with an improved long-term histologic patency.     

Intravascular ultrasound and 3D angle measurements of coronary bifurcations

Objective: To standardize the intravascular ultrasound (IVUS) analysis of coronary bifurcations. Background: Percutaneous treatment of bifurcation lesions is difficult particularly at the side branch ostium. Imaging techniques may improve our understanding of treatment options. There is no established IVUS methodology to assess the bifurcation. The present study aims to develop standards for bifurcation imaging. Methods: Quantitative IVUS analysis and 3D bifurcation angle measurements were performed in 34 patients who were selected from the Washington Hospital Center Database. Patients were included if both left anterior descending (LAD) and first diagonal (DX) pullbacks in the same procedure were done. Angiograms were available in 27 patients to measure the 3D bifurcation angle using specialized software. Pullbacks were analyzed proximal and distal to the bifurcation, and at the bifurcation. Results: Prox_LAD versus Prox_LAD(DX) were similar for vessel area (15.5 ± 4.6 mm² vs. 15.9 ± 4.0 mm², P = 0.19), lumen area (8.3 ± 3.6 mm² vs. 8.6 ± 3.3 mm², P = 0.25), and plaque area (7.2 ± 2.0 mm² vs. 7.3 ± 1.9 mm², P = 0.55). However, Bifurcation_LAD was larger than Bifurcation_DX for vessel area (17.3 ± 4.0 mm² vs. 16.6 ± 3.9 mm², P = 0.0083). The 3D angiographic bifurcation angle was 50° ± 13° (range of 26°–84°), and did not affect the IVUS measurements. IVUS analysis showed that bifurcation lesions did obey Murray's Law, as Prox_LAD lumen area measured 36.7 ± 25.1 mm³ versus Dist_LAD/Dist_DX measured 38.0 ± 29.1 mm³, P = 0.56. Conclusions: Two IVUS pullbacks should be performed for a complete assessment of the bifurcation and comparison with Murray's Law. The proposed IVUS analysis was not influenced by the bifurcation angle. © 2009 Wiley‐Liss, Inc.     

Rotational vs. standard coronary angiography: An image content analysis

Objective : To evaluate the clinical utility of images acquired from rotational coronary angiographic (RA) acquisitions compared to standard “fixed” coronary angiography (SA). Background : RA is a novel angiographic modality that has been enabled by new gantry systems that allow calibrated automatic angiographic rotations and has been shown to reduce radiation and contrast exposure compared to SA. RA provides a dynamic multiple‐angle perspective of the coronaries during a single contrast injection. Methods : The screening adequacy, lesion assessment, and a quantitative coronary analysis (QCA) of both SA and RA were compared by independent blinded review in 100 patients with coronary artery disease (CAD). Results : SA and RA recognize a similar total number of lesions (P = 0.61). The qualitative assessment of lesion characteristics and severity between modalities was comparable and lead to similar clinical decisions. Visualization of several vessel segments (diagonal, distal RCA, postero‐lateral branches and posterior‐descending) was superior with RA when compared to SA (P < 0.05). A QCA comparison (MLD, MLA, LL, % DS) revealed no difference between SA and RA. The volume of contrast (23.5 ± 3.1 mL vs. 39.4 ± 4.1; P = 0.0001), total radiation exposure (27.1 ± 4 vs. 32.1 ± 3.8 Gycm²; P = 0.002) and image acquisition time (54.3 ± 36.8 vs. 77.67 ± 49.64 sec; P = 0.003) all favored RA. Conclusion : Coronary lesion assessment, coronary screening adequacy, and QCA evaluations are comparable in SA and RA acquisition modalities in the diagnosis of CAD however RA decreases contrast volume, image acquisition time, and radiation exposure. © 2009 Wiley‐Liss, Inc.     

Clinical pharmacology of the new beta-adrenergic blocking drugs. Part 6. A comparison of pindolol and propranolol in treatment of patients with angina pectoris. The role of intrinsic sympathomimetic activity.

Pindolol, a new beta-adrenergic blocking drug with intrinsic sympathomimetic activity, and propranolol were given in increasing equipotent doses (pindolol: 2.5 to 10 mg. every 6 hours; propranolol: 10 to 40 mg. every 6 hours) over 12 weeks in a double-blind randomized trial to 41 patients with angina pectoris. The drugs were then gradually withdrawn over a two week period. With maximum doses, both pindolol and propranolol increased exercise capacity, compared to control, on multistage treadmill testing (pindolol: 8.0 ± 0.4 to 9.7 ± 0.3 mets, p < 0.01; propranolol: 8.0 ± 0.4 to 9.6 ± 0.3 mets, p < 0.05). At each exercise level both pindolol and propranolol decreased the heart rate, systolic blood pressure, and rate-pressure product (HR × BP). At the 9 met exercise level, the HR × BP decreased from 17,420 ± 850 to 13,205 ± 510 mm. Hg min.^?1 with pindolol (p < 0.002); with propranolol; 18,106 ± 440 to 13,205 ± 480 mm. Hg min.^?1 (p < 0.01). At the same level the magnitude of exercise-induced ECG ST depression decreased from 1.3 ± 0.3 to 0.4 ± 0.15 mm. with pindolol (p < 0.05), and from 1.3 ± 0.3 to 0.8 ± 0.2 mm. with propranolol (p < 0.05). Both drugs reduced the number of spontaneous attacks of angina pectoris per week. Pindolol did not appreciably decrease the resting heart rate (66.8 ± 1.9 vs 64.6 ± 1.2) or HR × BP (8,254 ± 418 vs 7,651 ± 210 mm. Hg min.^?1 in contrast to propranolol, which reduced both (heart rate: 70.5 ± 2.2 to 62.2 ± 2.4, p < 0.01; HR × BP: 8,677 ± 423 to 7,338 ± 455 mm. Hg min.^?1, p < 0.005). In addition, pindolol slightly increased the echocardiographically estimated ejection fraction at rest (0.59 ± 0.02 to 0.62 ± 0.02, p < 0.02), while propranolol depressed it (0.57 ± 0.02 to 0.51 ± 0.01, p < 0.04). Both pindolol and propranolol could be safely withdrawn over a gradual two week withdrawal interval.     

Balloon angioplasty results in increased segmental coronary distensibiliy: A likely mechanism of percutaneous transluminal coronary angioplasty

Objectives. The purpose of this study was to evaluate the hypothesis that the increase in lumen area induced by percutaneous transluminal coronary angioplasty is secondary to a change in lesion (segmental) distensibility.Background. Despite the widespread use of coronary angioplasty, the precise mechanism (or mechanisms) of lumen area improvement remains poorly understood.Methods. Quantitative coronary angiography was used to measure the minimal (contrast agent filled) balloon diameters at 1 to 5 atm, inclusive, during the first and final balloon inflations in 24 lesions successfully treated with coronary angioplasty. To rule out possible confounding effects due to changes in balloon material distensibility during repeated inflations, five control balloons were studied ex vivo. In parallel, intravascular ultrasound imaging was utilized to compare the segmental distensibility (change in lumen area during the cardiac cycle) of eight disease-free and seven mildly diseased coronary segments and seven segments after successful balloon angioplasty.Results. Minimal balloon diameters increased significantly between the first and final inflations (46%, 33%, 26%, 14% and 10% at 1, 2, 3, 4 and 5 atm, respectively, all p < 0.0001), demonstrating an increase in arterial distensibility after successful coronary angioplasty. No significant changes in balloon diameters were observed during sequential initial inflations at 1 and 2 atm (n = 5). Minimal increases in Balloon diameters were observed during repeated balloon inflations in the ex vivo studies (4.9 ± 1% [mean ± SEM]). A distensibility index, derived from the intravascular ultrasound data, was not different between the balloon-dilated and the normal segments but was significantly lower in mildly diseased sites (14.7 ± 2.2 vs. 12.9 ± 1.2 vs. 6.9 ± 1.9, respectively, p < 0.05) despite a smaller plaque area (7.3 ± 1 vs. 11.3 ± 1 mm², proximal/nondilated vs. dilated segments, respectively, p < 0.05).Conclusions. Coronary distensibility is significantly impaired in atherosclerotically diseased coronary segments and increases significantly after balloon angioplasty. This increase in segmental coronary compliance after coronary angioplasty may create a larger lumen area by allowing the vessel to distend in response to normal intraarterial pressure.     

Influence of dual antiplatelet therapy on mean platelet volume in patients with coronary artery disease undergoing percutaneous coronary intervention

Mean platelet volume (MPV) is a well-established marker of platelet activation, and recent studies have shown that platelet activation is central to the processes in the pathophysiology of coronary artery disease (CAD). The study population consisted of 45 patients with stable CAD who underwent successful percutaneous coronary intervention (PCI) with drug-eluting stents. We selected 45 age- and sex-matched control subjects without cardiovascular diseases who did not require antiplatelet therapy. Hematological test was performed 3 times within 1 month before DAPT (baseline), at 2 weeks after PCI (post PCI) and at 9 months after PCI (follow-up). Compared to control subjects, MPV was significantly larger in patients with CAD (10.0 ± 0.6 vs 10.7 ± 0.8 fl, p < 0.01) although there was no significant difference in white blood cell count, hemoglobin, and platelet count between the 2 groups. In patients with CAD, DAPT did not affect platelet count (19.3 ± 4.8 × 10⁴–18.9 ± 4.6 × 10⁴/μl) or MPV (10.7 ± 0.8–10.5 ± 0.9 fl) during the follow-up period. MPV remained to be higher at follow-up in patients with CAD despite DAPT compared to control subjects (10.1 ± 0.7 vs 10.5 ± 0.9 fl, p < 0.05). Our data suggested that MPV might not be suitable for monitoring the effects of DAPT on platelet activity in patients with CAD undergoing PCI.     

Arm-crank ergometry: a new method for the evaluation of coronary artery disease

We have developed an electrocardiographic stress test to evaluate coronary heart disease using an arm-crank device (modified bicycle ergometer) in patients unable to perform leg exercise. With an initial work load of 200 kg-m/min at 40 revolutions/min for 3 minutes, followed by 100 kg-m/min increments every 3 minutes to a maximum of 700 kg-m/min at the same speed, a linear relation between the increase in heart rate and work load was observed. Twenty-one patients underwent both conventional treadmill exercise (modified Bruce protocol) and arm-crank exercise on separate days. Peak heart rate was slightly slower with arm-crank exercise (81 ± 4 [standard error] vs. 85 ± 3 percent of maximal predicted heart rate for age, P < 0.02) but peak systolic blood pressure and heart rate-systolic blood pressure product (double product) did not differ significantly (157 ± 7 vs. 154 ± 6 mm Hg, P > 0.5) and (22.0 ± 1.2 vs. 22.5 ± 1.2 × 10³, P > 0.1). Ten patients with documented coronary artery disease, including 7 with angina pectoris, had an ischemie S-T segment response (0.08 second depression greater than 1 mm) by both methods and 10 patients (7 with previous myocardial infarction and 3 with normal coronary arteriograms) had negative results by both techniques. One patient with normal coronary arteriograms had a negative arm-crank test and a positive treadmill test. In 26 patients unable to perform leg exercise the mean peak heart rate, systolic blood pressure and double product with arm-crank exercise were not significantly different (P > 0.05) from those achieved by the ambulatory patients (73.2 ± 1.9 vs. 81.0 ± 4.0 percent, 167 ± 8 vs. 157 ± 7 mm Hg and 22.4 ± 1.2 vs. 22.0 ± 1.4 × 10³, respectively). Six of 26 patients unable to perform leg exercise had a positive arm-crank test. Four of these six patients had angina pectoris and three had a previous myocardial infarction. We conclude that arm-crank exercise is comparable to treadmill exercise and is a reliable alternative method for the evaluation of suspected coronary artery disease in patients unable to perform leg exercise.     

Influence of left ventricular hypertrophy on left ventricular function during dynamic exercise in the presence or absence of coronary artery disease

Objectives. We investigated the influence of left ventricular hypertrophy in the presence or absence of coronary artery disease on hemodynamic characteristics during exercise in subjects without previous myocardial infarction.Background. Left ventricular hypertrophy has been found to increase the vulnerability of the myocardium to the development of ischemia. However, the independent influences of left ventricular hypertrophy and coronary artery disease have not been assessed in humans.Methods. Symptom-limited supine leg exercise tests were performed by 78 patients. They were classified into the following subgroups: no coronary artery disease or left ventricular hypertrophy (group I, n = 30), left ventricular hypertrophy only (group II, n = 12), coronary artery disease only (group III, n = 20) and both left ventricular hypertrophy and coronary artery disease (group IV, n = 16). Mean left ventricular mass index was 105, 158, 109 and 159 g/m²in groups I to IV, respectively.Results. Pulmonary artery wedge pressure increased from 6 ± 3 (mean ± SD) mm Hg at rest to 10 ± 5 mm Hg at peak exercise in group I, from 8 ± 2 to 18 ± 8 mm Hg in group II (p < 0.05 vs. group I), from 6 ± 3 to 23 ± 6 mm Hg in group III (p < 0.01 vs. group I) and from 8 ± 4 to 30 ± 7 mm Hg in group IV (p < 0.01 vs. group I; p < 0.01 vs. group II; p < 0.05 vs. group III). Multiple regression analysis showed that the number of diseased coronary vessels and left ventricular mass index were independent predictors of peak pulmonary artery wedge pressure (F = 59.2 and 19.1, respectively; multiple correlation coefficient r = 0.74, p < 0.0001).Conclusions. Left ventricular hypertrophy and coronary artery disease independently increased left ventricular filling pressure during supine leg exercise. Severe left ventricular dysfunction was induced by exercise when both conditions were present.     

Frequent red cell transfusions reduced vascular endothelial activation and thrombogenicity in children with sickle cell anemia and high stroke risk

Stroke is one of the most disabling complications of sickle cell anemia (SCA). The molecular mechanisms leading to stroke in SCA or by which packed red blood cell (PRBC) transfusion prevents strokes are not understood. We investigated the effects of PRBC transfusion on serum biomarkers in children with SCA who were at high‐risk for stroke. Serum samples from 80 subjects were analyzed, including baseline, study exit time point and 1 year after study exit. Forty of the 80 samples were from subjects randomized to standard care and 40 from transfusion arm. Samples were assayed for levels of BDNF, sVCAM‐1, sICAM‐1, MPO, Cathepsin‐D, PDGF‐AA, PDGF‐AB/BB, RANTES (CCL5), tPAI‐1, and NCAM‐1 using antibody immobilized bead assay. Significantly lower mean serum levels of sVCAM‐1 (2.2 × 10⁶ ± 0.8 × 10⁶ pg/mL vs. 3.1 × 10⁶ ± 0.9 × 10⁶ pg/mL, P < 0.0001), Cathepsin‐D (0.5 × 10⁶ ± 0.1 × 10⁶ pg/mL vs. 0.7 × 10⁶ ± 0.2 × 10⁶ pg/mL, P < 0.0001), PDGF‐AA (10556 ± 4033 pg/mL vs. 14173 ± 4631 pg/mL, P = 0.0008), RANTES (0.1 × 10⁶ ± 0.07 × 10⁶ pg/mL vs. 0.2 × 10⁶ ± 0.06 × 10⁶ pg/mL, P < 0.006), and NCAM‐1 (0.7 × 10⁶ ± 0.2 × 10⁶ pg/mL vs. 0.8 × 10⁶ ± 0.1 × 10⁶ pg/mL, P < 0.0006) were observed among participants who received PRBC transfusion, compared to those who received standard care. Twenty or more PRBC transfusion over 4 years was associated with lower serum levels of sVCAM‐1 (P < 0.001), PDGF‐AA (P = 0.025), and RANTES (P = 0.048). Low baseline level of BDNF (P = 0.025), sVCAM‐1 (P = 0.025), PDGF‐AA (P = 0.01), t‐PAI‐1 (P = 0.025) and sICAM‐1 (P = 0.022) was associated with higher probability of stroke free survival. Beyond improving hemoglobin levels, our results suggest that the protective effects of PRBC transfusion on reducing stroke in SCD may result from reduced thrombogenesis and vascular remodeling. Am. J. Hematol. 89:47–51, 2014. © 2013 Wiley Periodicals, Inc.     

Studies of Leukocyte Exudates in Cyanate-Treated Animals

Cyanate (NCO), which impedes sickling by increasing the oxygen affinity of sickle haemoglobin, may react with many proteins in the body and potentially interfere with many functional systems. Leukocyte glycogen was studied because elevated liver glycogen has been noted after high dose NCO treatment in rats. Leukocyte function was also studied in peritoneal exudates. In animals given NCO alone, blood leukocyte glycogen was 2.8 ± 0.3 (SE) mg per 10⁹ WBC while control values were 3.3 ± 0.6, a difference not statistically significant. In casein-induced peritoneal exudates, more WBC were recovered from NCO-treated animals (265 times 10⁶ WBC vs. 214 times 10⁶ WBC; P = 0.0009). Glycogen in blood leukocytes of casein-stimulated animals was not significantly different from NCO-treated animals. Leukocyte glycogen in peritoneal exudates was markedly increased over blood leukocyte glycogen in both controls (19.4 ± 0.6 vs. 2.7 ± 0.3 mg per 10⁹/WBC; P < 0.0001) and NCO-treated animals (17.5 ± 0.7 vs. 3.6 ± 0.5 mg per 10⁹ WBC; P < 0.001), although levels in exudates from control and NCO-treated animals did not significantly differ from each other. ¹⁴C-glucose incorporation into glycogen was significantly increased (P = 0.020) in exudate leukocytes of NCO-treated animals. Initial phagocytic rates were equal in exudate leukocytes of control and NCO-treated animals. Although NCO treatment has demonstrable effects on some aspects of leukocyte glycogen metabolism, exudation of leukocytes and phagocytic function are not impaired.     

Sex Differences in Coronary Computed Tomography Angiography–Derived Fractional Flow Reserve: Lessons From ADVANCE

ObjectivesThis study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)–derived fractional flow reserve (FFR_CT) according to sex.BackgroundWomen are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR_CT improves sex-based patient management decisions compared to CCTA alone is unknown.MethodsSubjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR_CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR_CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates.ResultsA total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR_CT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR_CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR_CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR_CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR_CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm³/g vs. 24.76 ± 7.22 mm³/g; p < 0.0001) that is associated with higher FFR_CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR_CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284).ConclusionsFFR_CT differs between the sexes, as women have a higher FFR_CT for the same degree of stenosis. In FFR_CT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR_CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)     

Alterations of the Architecture of Subendocardial Arterioles in Patients With Hypertrophic Cardiomyopathy and Impaired Coronary Vasodilator Reserve: A Possible Cause for Myocardial Ischemia

Objectives. The study was designed to investigate the architecture of subendocardial arterioles of patients with hypertrophic cardiomyopathy (HCM) and angina pectoris with respect to coronary vasodilator reserve.Background. There is growing evidence that the coronary microvasculature is abnormal in HCM. Arterioles, which mainly regulate intramyocardial blood flow, are especially suspect.Methods. Thirteen patients with HCM (50.1 ± 12.6 years old, mean value ± SD) were studied after exclusion of any relevant coronary stenoses. Subendocardial arterioles (density [n/mm²], wall area [μm²], percent lumen area [%lumen], periarteriolar collagen area [μm²]), myocyte diameter (μm) and interstitial collagen fraction (Vv%) were evaluated by means of stereologic morphometry of transvenous biopsy samples. Coronary blood flow was measured quantitatively with the inert chromatographic argon method at basal conditions and after dipyridamole (0.5 mg/kg body weight over 4 min intravenously), and coronary vasodilator reserve was calculated as the ratio of coronary resistance at basal conditions and after pharmacologic vasodilation. Data from five normotensive subjects (45.4 ± 11 years old, p = NS) served as control data.Results. Arteriolar density was diminished by 38% (p = 0.004) and %lumen by 13% (p = 0.009) in patients with HCM compared with control subjects. Coronary reserve was impaired in patients with HCM (2.28 ± 0.6 vs. 5.34 ± 1.49, p = 0.003) because of higher coronary resistance after vasodilation (0.48 ± 0.14 vs. 0.22 ± 0.06 mm Hg × min × 100 g/ml, p = 0.004). Coronary vasodilator reserve correlated with arteriolar density (r = +0.47, p = 0.045) and with %lumen (r = 0.65, p = 0.003).Conclusions. In HCM, the architecture of preterminal subendocardial arterioles is altered by a reduced total cross-sectional lumen area, corresponding to an impaired coronary vasodilator capacity that may predispose to myocardial ischemia.     

Framingham risk score and severity of coronary artery disease

Objectives

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Easy-to-perform and reliable parameters are needed to predict the presence and severity of CAD and to implement efficient diagnostic and therapeutic modalities. We aimed to examine whether the Framingham risk scoring system can be used for this purpose.

Methods

A total of 222 patients (96 women, 126 men; mean age, 59.1?±?11.9 years) who underwent coronary angiography were enrolled in the study. Presence of >?%50 stenosis in a coronary artery was assessed as critical CAD. The Framingham risk score (FRS) was calculated for each patient. CAD severity was assessed by the Gensini score. The relationship between the FRS and the Gensini score was analyzed by correlation and regression analyses.

Results

The mean Gensini score was 18.9?±?25.8, the median Gensini score was 7.5 (0–172), the mean FRS was 7.7?±?4.2, and the median FRS was 7 (0–21). Correlation analysis revealed a significant relationship between FRS and Gensini score (r?=?0.432, p?Conclusion Our work suggests that the FRS system is a simple and feasible method that can be used for prediction of CAD severity. As the sample size was small in our study, further large-scale studies are needed on this subject to draw solid conclusions.     

Cigarette smoking and arteriographically demonstrable coronary artery disease.

Patients undergoing selective coronary arteriography were studied to determine whether the extend of their coronary artery disease (CAD) was related to cigarette consumption. Those without demonstrable lesions averaged 29.0 pack years. Patients with single vessel disease, 38.3 pack years, those with double vessel disease 44.9 pack years and those with triple vessel disease 67.5 pack years. Nonsmokers with significant CAD were ten years older than their smoking counterparts (p less than 0.01). Forty-seven percent of patients with no demonstrable disease were nonsmokers whereas only 18 percnet of those with CAD were nonsmokers (p less than 0.001). Sixty-nine percent of nonsmoking normotensive patients had no CAD whereas only 23 percent of nonsmoking hypertensive patients fell in the no CAD category (p=0.01-0.005). This study demonstrates a correlation between the number of cigarettes consumed and the severity of CAD as well as the accelerating effect of cigarette consumption on the development of CAD. It also suggests that symptomatic CAD in a normotensive nonsmoker is unusual.