Blood viscosity changes in slow coronary flow patients

Microvascular dysfunction is implicated in the pathogenesis of slow coronary flow (SCF), but less attention has been paid to intrinsic properties of blood that can also impair the microcirculatory flow. In this study we aimed to evaluate the blood viscosity focusing on erythrocyte aggregation, erythrocyte deformability and plasma viscosity in SCF. Thirty-three patients with SCF (21 male, 54 ± 12.8 years) and 23 subjects with normal coronary arteries (13 male, 59 ± 10.3 years) were included in the study. Coronary flow was quantified by means of thrombolysis in myocardial infarction (TIMI) frame count and aggregation and deformability of erythrocytes were measured by an ektacytometer. Plasma viscosity was measured by a cone-plate viscometer. Aggregation amplitude (23 ± 3.8 au vs. 15.7 ± 6.1 au, respectively, p < 0.001) and area A index (area above syllectogram) (153.2 ± 30.7 au.s vs. 124.9 ± 49.3 au.s, respectively, p < 0.01) were higher in SCF patients. Aggregation half-time, aggregation index, elongation index and plasma viscosity values were similar between two groups. Correlation analysis revealed a significant relationship between the TIMI frame count for left anterior descending artery and aggregation amplitude in SCF patients (r = 0.679, p < 0.0001). The result of this study reveals changes in erythrocyte aggregation which may contribute to the pathophysiology of SCF. Larger studies are needed to make more robust conclusions on this issue.     

Left ventricular function and exercise capacity in patients with slow coronary flow

Background: Endothelial and microvascular dysfunction have been implicated in slow coronary flow (SCF). How and to what extent do these etiological factors affect left ventricular (LV) function and exercise capacity? Aim: The aim of the study was to evaluate LV systolic and diastolic function by pulsed tissue Doppler imaging (TDI) in SCF patients and their effects on exercise capacity. Subjects and methods: Sixty SCF patients and 20 control subjects were included in the study. Echocardiographic examination, treadmill exercise test, and TDI were performed. Isovolumic myocardial acceleration (IVA) and myocardial performance index (MPI) were measured. Results: TDI mean parameters for systolic and diastolic LV function were significantly impaired in SCF group with decreased Sa, IVA, Ea/Aa, and increased MPI (0.31 ± 0.06 vs. 0.26 ± 0.04, P < 0.01) compared to control. There was significant correlation between thrombolysis in myocardial infarction (TIMI) frame count and TDI mean parameters for LV systolic function (Sa & IVA, r =?0.53, P < 0.01 & r =?0.36, P < 0.05, respectively). Mean TIMI frame count was correlated with MPI and E/Ea. SCF patients had poorer peak exercise capacity than the controls (9.9 ± 1.9 METs vs. 12.7 ± 2.3, P < 0.01) with significant negative correlation with mean TIMI frame count (r =?0.46, P < 0.01). Conclusion: There is impairment of LV systolic and diastolic function in SCF patients with clinical impact on exercise capacity which emphasizes the importance of close follow‐up of these patients for risk stratification. (Echocardiography 2012;29:158‐164)     

经胸多普勒超声冠状动脉血流储备检查诊断左前降支显著狭窄

目的比较经胸多普勒超声冠状动脉血流储备（CFR）指标诊断左前降支（LAD）显著狭窄的临床价值。方法连续120例怀疑冠心病的患者于冠状动脉造影（CAG）前一天进行双嘧达莫（0．56mg／kg）负荷试验，测定LAD的CFR指标，包括收缩期最大冠状动脉血流储备（SCFRpeak）、收缩期平均冠状动脉血流储备（SCF Rmean）、收缩期流速时间积分储备（SCFRVTI）、舒张期最大冠状动脉血流储备（DCFRpeak）、舒张期平均冠状动脉血流储备（DCFRmean）和舒张期流速时间积分储备（DCFRVTI）。结果82例获得LAD血流频谱，按照CAG结果分为LAD显著狭窄组（A组，≥70％狭窄，n=16）和LAD非显著狭窄组（B组，〈70％狭窄，n=66）。A组患者各项CFR指标均显著低于B组。ROC曲线法分析显示，DCFRmean〈1．825诊断LAD显著狭窄的敏感性和特异性相对较高。结论经胸多普勒超声评价CFR有助于检出LAD显著狭窄，DCFRmean〈1．825是较好的判别指标。     

阿托伐他汀对冠状动脉血流缓慢患者冠状动脉血流储备的影响

目的 探讨冠状动脉血流缓慢患者冠状动脉血流储备(CFR)的改变以及阿托伐他汀对这类患者CFR的影响.方法 入选有胸痛症状但冠状动脉造影结构正常的冠状动脉血流缓慢患者91例,分为治疗组(51例)和无治疗组(40例).治疗组给予阿托伐他汀20 mg治疗8周.另选26例冠状动脉造影正常且运动试验阴性的无心脏疾患者为正常对照组.治疗前后测定治疗组和无治疗组的血脂以及利用腺苷负荷超声记录左前降支远端血流频谱,并评价CFR.结果 (1)冠状动脉血流缓慢者接受阿托伐他汀8周治疗后总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)较无治疗组及正常对照组明显减低[TC:(3.83±0.80)mmol/L比(5.30±1.18)mmol/L和(5.32±1.17)mmol/L,均P＜0.05:LDL=C:(2.26±0.64)mmol/L比(3.28±0.85)mmol/L和(3.30±0.82)mmol/L,均P＜0.05].(2)给予阿托伐他汀前,治疗组与无治疗组CFR(分别为2.32±0.30和2.25±0.33)均低于正常对照组(3.15±0.34,P＜0.05);8周后,治疗组冠状动脉血流速度(CFV)[(26.06±3.22)cm/s]较无治疗组[(29.02±3.36)cm/s]及治疗前静息状态[(28.43±3.40)cm/s]低(均P＜0.05),最大冠状动脉扩张状态CFV高于无治疗组和对照组[分别为(77.63±8.96)、(65.17±7.22)和(64.58±6.26)cm/s,P＜0.05],CFR低于治疗前和无治疗组(分别为3.07±0.29、2.28±0.35和2.32±0.30,P＜0.05),且与正常对照组差异均无统计学意义.结论 冠状动脉血流缓慢患者CFR明显减低,短期阿托伐他汀在调脂的同时可以有效改善其CFR.     

Plasma homocysteine is associated with ischemic findings without organic stenosis in patients with slow coronary flow

AimTo investigate the plasma concentrations of homocysteine (Hcy) in slow coronary flow (SCF) patients before and at the end of the exercise test and compare with the values of healthy controls.MethodsStudy population consisted of 41 patients with SCF [68% men, aged 49 ± 8 years], and 41 subjects with normal epicardial coronary arteries [56% men, aged 50 ± 9 years]. Exercise test was performed in all study participants. Blood samples were drawn at rest and immediately at the end of exercise testing after 12 h of overnight fasting.ResultsThe baseline Hcy value of the SCF patients was higher than that of the control subjects (p < 0.0001), and this difference continued after exercise test between the groups (p < 0.0001). Median post-exercise increases in Hcy levels were higher in the SCF group than in the control group, without a significant difference (p = 0.088). In the SCF group after exercise, Hcy levels in 17 patients with angina and 18 patients with ST depression were higher than those without angina and ST depression (p < 0.0001 and p < 0.0001, respectively). In addition, Hcy values in patients with both angina and ST depression were greater than those with either angina (p < 0.05) or ST depression (p < 0.05).ConclusionThe results of this study show that there is an important pathophysiologic link between the increased levels of plasma Hcy, the degree of ischemic findings, and the severity of slow flow in SCF patients.     

Outcome of patients with significant coronary stenosis but without ischemic evidence on exercise myocardial perfusion scintigraphy

OBJECTIVES: The rates of cardiac events and coronary revascularization were evaluated in patients with significant coronary stenosis of more than 75% by the American Heart Association (AHA) classification but no ischemic evidence by exercise myocardial perfusion scintigraphy. METHODS: Subjects were 171 patients (113 males, 58 females, mean age 66 +/- 9 years) undergoing coronary angiography and without scintigraphic evidence of myocardial ischemia. They were divided into two groups according to the severity of coronary artery stenosis based on AHA classification. Group A was composed of 139 patients with more than 75% stenosis (101 patients with 75% stenosis and 38 patients with more than 90% stenosis), and Group B was composed of 32 patients with 50% stenosis. Cardiac events including angina pectoris (n = 63), myocardial infarction (n = 1), heart failure (n = 2) and cardiac death (n = 0), coronary revascularization and predictive factors were evaluated during follow-up of 34 +/- 21 months. Furthermore, the interval between coronary revascularization and exercise myocardial perfusion scintigraphy was estimated. RESULTS: The rates of cardiac events (45%) and coronary revascularization (29%) in Group A were significantly higher than the rate of cardiac events (9%, p < 0.05) and coronary revascularization (6%, p < 0.05) in Group B. Only percentage stenosis and the number of diseased vessels affected the rates of cardiac event and coronary revascularization. CONCLUSIONS: Patients with significant coronary stenosis, but without ischemic evidence by exercise myocardial perfusion scintigraphy, have a relatively high rate of cardiac event and coronary revascularization, especially in patients with severe stenosis or multivessel disease. However, coronary revascularization should not be performed in all patients with significant coronary stenosis.     

Effects of atorvastatin on coronary flow reserve in patients with slow coronary flow

BACKGROUND: Statins improve endothelial functioning in patients with coronary artery disease and hypercholesterolemia, while substantially little is known about induced changes in myocardial microcirculation. However, although previous studies have suggested that microvascular abnormalities and endothelial dysfunction is responsible for slow coronary flow (SCF), there is no study investigating possible effects of statins on coronary microvascular function in patients with SCF. HYPOTHESIS: We prospectively investigated the effects of short-term lipid-lowering therapy with atorvastatin on coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SCF assessed by transthoracic Doppler echocardiography (TTDE). METHODS: In an open clinical trial, CFR was studied in 20 subjects with SCF. TTDE was used to assess CFR at baseline as well as after 8 weeks of atorvastatin therapy. Coronary flow was quantified according to TIMI frame count (TFC). Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. RESULTS: CFR was independently correlated with TFC. After 8 weeks of atorvastatin therapy, CFR values increased significantly (1.95 +/- 0.38 vs. 2.54 +/- 0.56, (p < 0.001). No change in hemodynamic parameters was noted during the entire study. The improvement in CFR was not correlated to the amount of lipid-lowering effect of atorvastatin. CONCLUSIONS: These findings suggest that short-term lipid-lowering therapy with atorvastatin improved CFR, which reflects coronary microvascular functioning in patients with SCF.     

Factors affecting ST depression during cardiopulmonary exercise testing in patients with mitral stenosis without significant coronary lesions

Symptom-limited cardiopulmonary exercise testing was performed in 37 patients with mitral stenosis (MS) without significant coronary artery stenosis to evaluate factors affecting ST depression in exercise electrocardiograms. The degree of ST depression was not associated with gender or exercise tolerance. The incidence of significant ST depression was higher in the patients receiving than in those not receiving digitalis (P < 0.05). In addition, the patients with atrial fibrillation and a higher heart rate response were more likely to have a high prevalence of significant ST depression than those with sinus rhythm and a lower response (P < 0.05). We concluded that atrial fibrillation, a higher maximum heart rate, and oral digitalis administration were involved in ST depression during exercise testing in patients with mitral stenosis without coronary heart disease.     

Decreased aortic distensibility and coronary flow velocity reserve in patients with significant aortic valve stenosis with normal epicardial coronary arteries

BACKGROUND AND AIM OF THE STUDY: A number of clinical and experimental studies have suggested that aortic valve stenosis (AS) is a manifestation of atherosclerotic process. Previous studies have revealed a decreased coronary flow velocity reserve (CFR) in AS patients in consequence of left ventricular hypertrophy. The hypothesis was tested that the elastic properties of the descending aorta of AS patients might indicate signs of stiffness of the aorta. METHODS: The CFR and indices of aortic distensibility as functional markers of the descending aorta were compared in three different patient populations: (i) control subjects without valvular and coronary artery disease; (ii) patients with AS with normal epicardial coronary arteries; and (iii) patients with significant left anterior descending coronary artery (LAD) stenosis. CFR measurements were carried out according to a standard protocol, using vasodilatory stimulation with dipyridamole (0.56 mg/kg for 4 min), and peak diastolic velocity measurements at 6 min. The elastic properties of the aorta were calculated from echocardiographic parameters and blood pressure data. RESULTS: The CFR in AS patients was decreased to a similar extent as in patients with LAD stenosis. The aortic distensibility indices were similarly significantly increased in patients with AS and normal epicardial coronary arteries and with LAD stenosis, as compared with controls. CONCLUSION: These results indicate that the descending aorta exhibits appreciable increased stiffness in AS patients with normal epicardial coronary arteries.     

The decrease in QRS amplitude after aortic valve replacement in patients with aortic valve stenosis

Purpose

The purpose of this study was to evaluate the effect of aortic valve replacement on electrocardiogram (ECG) in patients with aortic valve stenosis.

Methods

Serial 12-lead ECGs were obtained in 15 patients with aortic valve stenosis who underwent aortic valve replacement. Three ECG indexes for left ventricular hypertrophy were manually measured in each ECG: Sokolow-Lyon index (sum of S wave in V₁ and R wave in V₅), Cornell voltage index (sum of R wave in aVL and S wave in V₃), and Gubner index (sum of R wave in I and S wave in III).

Results

After aortic valve replacement, Sokolow-Lyon index gradually decreased during 2 years (51.1 ± 17.9 to 34.8 ± 12.5 mm, P < .01). Cornell voltage index (25.6 ± 7.0 to 15.0 ± 4.8 mm, P < .01) and Gubner index (15.8 ± 7.6 to 10.3 ± 5.5 mm, P < .01) also gradually decreased during 2 years. ST depression in V₆ was found in 14 patients (93%) before aortic valve replacement. It resolved in 9 of 14 patients during 2 years.

Conclusions

Electrocardiographic evidence of left ventricular hypertrophy gradually resolved after aortic valve replacement in patients with aortic valve stenosis.     

Increased platelet activation in patients with slow coronary flow

We tested the hypothesis that increased platelet activation may be present in patients with slow coronary flow (SCF) and may contribute to the pathogenesis of slow coronary flow phenomenon (SCFP). Fifty patients angiographically proven normal coronary flow (control group; mean age = 61.3 ± 7.0 years, 43 male) and 50 patients with angiographically proven SCF in all coronary arteries (patient group; man age = 62.7 ± 6.7 years, 38 male) were included in the present study. Coronary flow rates of all subjects were documented by Thrombolysis In Myocardial Infarction frame count (TIMI frame count). Patients with a corrected TIMI frame count greater than two standard deviations from normal published range for the particular vessel were considered as having SCF. Complete blood count and mean platelet volume (MPV) was measured from whole blood sample with Abbott Cell-Dyne 4000 cell counter. Plasma sP-selectin concentrations were analyzed with sP-Selectin ELISA kit. There were no statistically significant differences between the two groups with respect to baseline demographic, clinical and lipid parameters. Not only MPV values but also plasma sP-selectin levels were significantly higher in patients with the patients with SCF compared to those of controls (for MPV; 8.2 ± 0.7 vs. 7.2 ± 0.6 fl, P < 0.001, for sP-Selectin; 1.5 ± 0.3 vs. 1.0 ± 0.2 ng/ml, P < 0.001). Interestingly, significant positive correlations were detected between mean TIMI frame counts and MPV and sP-selectin levels (for MPV; r = 0.56, P < 0.001, for sP-selectin r = 0.67, P < 0.001). The current study demonstrates that platelet activity is increased in the patients with SCF compared to that of the patients with normal coronary flow.     

Coronary flow reserve is impaired in patients with slow coronary flow

BACKGROUND: Slow coronary flow (SCF) in a normal coronary angiogram is a well-recognized clinical entity, but its etiopathogenesis remains unclear. However, previous studies have suggested that microvascular abnormalities and endothelial dysfunction responsible for SCF. Accordingly, we hypothesized that SCF phenomenon may be a form, at least early phase, of atherosclerosis that involve both small vessels and epicardial coronary arteries, and therefore we investigated coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SCF. METHODS: Twenty subjects with SCF and 15 control subjects with normal coronary flow were studied. Coronary flow was quantified according to TIMI frame count (TFC). Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. RESULTS: Demographic features, coronary risk factors, echocardiographic measurements except diastolic function parameters, and biochemical measurements were similar between the groups. CFR values were significantly lower in subjects with SCF than in the control group (1.99+/-0.38 versus 2.99+/-0.47, P<0.0001). In addition, TIMI frame count independently correlated with CFR. CONCLUSION: These findings suggest that CFR, which reflects coronary microvascular function, is impaired in patients with SCF, and corrected TFC well correlates with CFR.     

Platelet function disorder in patients with coronary slow flow

BACKGROUND: Some patients evaluated for chest pain with angiographically normal coronary arteries show coronary slow flow phenomenon (CSFP) on angiography. Slow flow of dye in epicardial coronary arteries is also not an infrequent finding in patients during routine coronary angiography. The precise pathophysiology of CSFP is not known yet. HYPOTHESIS: This study investigates the presence of platelet function disorders in patients with CSFP. METHODS: The patient group included 24 patients with CSFP detected by coronary angiography via the TIMI "frame count" method, and a control group included 23 patients with normal coronary flow. Platelet aggregability induced by use of ristocetin, collagen, and adenosine diphosphate (ADP), was measured from all blood samples in both control and patient groups. RESULTS: The ratio of platelet aggregability increased significantly in patients with CSFP compared with patients with normal coronary flow (ristocetin 57.6 +/- 15 vs. 45.4 +/- 17.1, collagen 62.9 +/- 16.4 vs. 48.9 +/- 25.3, ADP 59.4 +/- 18 vs. 42.4 +/- 15.2, p < 0.05). CONCLUSION: Platelet aggregability is increased in patients with CSFP.     

Vascular endothelial function in patients with slow coronary flow

BACKGROUND: Slow coronary flow (SCF) in a normal coronary angiogram is a well-recognized clinical entity, but its etiopathogenesis remains unclear. DESIGN: The aim of the study was to determine endothelial function in patients with SCF using a flow-mediated dilatation (FMD) technique in the brachial artery. METHODS: Coronary flow was quantified using the corrected thrombosis in myocardial infarction (TIMI) frame count (CTFC) method. Endothelial function was studied in 27 patients with SCF (23 men, four women, mean age 47.6+/-8.7 years) and in 30 people with normal coronary flow (NCF) (22 men and eight women, mean age 47.5+/-7.4 years). RESULTS: The flow-mediated diameter increase in the SCF group was significantly smaller than that in the NCF group (3.48+/-0.10% compared with 9.11+/-0.10%, P < 0.001). The percentage of nitroglycerine (NTG)-induced dilatation was not significantly different between patients with SCF and people with NCF (16.8+/-1.1% compared with 17.1+/-1.1%, P = 0.87). Simple regression analysis showed that mean CTFC (CTFC(m)) was strongly and inversely related to the percentage of FMD (r = -0.29, P < 0.01) in all participants. When the patients with SCF were excluded, CTFC(m) was still inversely related to the percentage of FMD (r = -0.36, P < 0.05). CTFC(m) was also inversely related to NTG-induced dilatation in the 57 participants (r = -0.23, P < 0.05). Multiple regression analysis showed that CTFC(m) was inversely related to the percentage of FMD only (r = -0.37, P < 0.05). CONCLUSIONS: These findings suggest that endothelial function is impaired in people with SCF and that CTFC correlates well with endothelial dysfunction.     

冠心病患者运动试验中QRS波时间变化

观察了42例踏车试验阳性的冠心病人及20例踏车试验阴性的正常人踏车运动试验前后QRS波时间的变化，结果显示，正常人踏车即刻2、4、分钟QRS波时间较踏车前明显缩短（P均＜0．05）。冠心病组踏车后即刻、2、4、6分钟较踏车前显著延长（P均＜0．05），ST段明显压低者，QRS波时间延长更显著，提示冠心病患者运动致QRS时间延长是心肌缺血的一个标志。     

Endothelial nitric oxide synthase levels and their response to exercise in patients with slow coronary flow

Slow coronary flow (SCF), described for the first time by Tambe and his colleagues in 1972, is an angiographic diagnosis characterised by a low rate of flow of contrast agent in the epicardial coronary arteries, together with typical angina pectoris and normal coronary arteries.1 Even though micro- and macrovascular disease findings have been identified, such as myofibrillar hypertrophy, myofibrillar degeneration, hyperplastic fibromuscular thickening, luminal narrowing, endothelial degeneration, endothelial dysfunction and diffuse atherosclerosis, which may lead to reduced coronary flow reserve, uncertainties still exist in the aetiopathogenesis.2,3Coronary blood flow and oxygen transport to the myocardium are increased by autoregulatory mechanisms for the increased metabolic needs associated with effort. The amount of oxygen extracted from the blood also increases, which leads to a decrease in the concentration of oxygen in the blood. Mitochondrial metabolism is altered by coronary endothelium-derived nitric oxide (NO) in an attempt to reduce the growing energy requirements.4,5Vascular endothelium exhibits a number of haemostatic functions in normal blood vessels. NO is a key molecule for normal autoregulatory mechanisms, such as modulating the vasodilator response to tachycardia and exercise,6 and it has also been found to be essential for flow-mediated dilatation of large human arteries in vivo.7 Endothelial nitric oxide synthase (eNOS) is an enzyme involved in the synthesis of NO.8 Decreased plasma eNOS level is an important indicator of endothelial dysfunction.9To our knowledge, there has been no study evaluating plasma eNOS levels and their response to exercise in SCF patients. Therefore we aimed to investigate the plasma levels of eNOS before and after exercise in patients with SCF.