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Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: Results from the NHLBI WISE study

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AMERICAN HEART JOURNAL 2001年第5期141卷 735-741页

作者： Reis, SE Holubkov, R Smith, AJC Kelsey, SF Sharaf, BL Reichek, N Rogers, WJ Merz, CNB Sopko, G Pepine, CJ Univ Pittsburgh Cardiovasc Inst Pittsburgh PA USA Univ Pittsburgh Dept Epidemiol Pittsburgh PA 15261 USA Rhode Isl Hosp Dept Med Div Cardiol Providence RI 02903 USA Allegheny Gen Hosp Dept Med Div Cardiol Pittsburgh PA 15212 USA Univ Alabama Dept Med Div Cardiol Birmingham AL 35294 USA Cedars Sinai Med Ctr Dept Med Div Cardiol Los Angeles CA 90048 USA NHLBI Div Heart & Vasc Dis Bethesda MD 20892 USA Univ Florida Dept Med Div Cardiol Gainesville FL USA

Background Chest pain in the absence of obstructive coronary artery disease (CAD) is common in women;it is Frequently associated with debilitating symptoms and repeated evaluations and may be caused by coronary microvascular dysfunction. However, the prevalence and determinants of microvascular dysfunction in these women are uncertain. Methods We measured coronary flow velocity reserve (coronary velocity response to intracoronary adenosine) to evaluate the coronary microvasculature and risk factors for atherosclerosis in 159 women (mean age, 52.9 years) with chest pain and no obstructive CAD. All women were referred for coronary angiography to evaluate their chest pain as part of the Women's Ischemia Syndrome Evaluation (WISE) study. Results Seventy-four (47%) women had subnormal (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction (mean, 2.02 +/- 0.38): 85 (53%) had normal reserve (mean, 3.13 +/- 0.64). Demographic characteristics, blood pressure, ventricular function, lipid levels, and reproductive hormone levels were not significantly different between women with normal and those with abnormal microvascular function. Postmenopausal hormone use within 3 months was significantly less prevalent among those with microvascular dysfunction (40% vs 60%, P = .032). Age and number of years past menopause correlated with flow velocity reserve (r = -0.18, P = .02, and r = -0.30, P < .001, respectively). No significant associations were identified between flow velocity reserve and lipid and hormone levels, blood pressure, and left ventricular ejection fraction. Conclusions Coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of obstructive CAD and cannot be predicted by risk factors for atherosclerosis and hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction should be considered in women with chest pain not attributable to obstructive CAD.

关键词：血流速度强心药/诊断应用胸痛/血液胸痛/诊断胸痛/流行病学胸痛/病理生理学胆固醇/血液冠状血管造影术冠状动脉循环冠状血管/病理生理学诊断鉴别多巴酚丁胺/诊断应用超声心动描记术性腺甾类激素/血液心脏导管插入术微循环/病理生理学绝经后期/血液患病率危险因素女(雌)性人类

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Coronary microcirculatory vasoconstriction during ischemia in patients with unstable angina

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第2期35卷 327-334页

作者： Marzilli, M Sambuceti, G Fedele, S L'Abbate, A CNR Inst Clin Physiol I-56100 Pisa Italy

OBJECTIVE To verify the behavior of coronary microvascular tone during spontaneous ischemia in patients with unstable angina (UA). BACKGROUND In UA, the pathogenetic role of vasoconstriction is classically confined at the stenotic coronary segment. However, microcirculatory vasoconstriction has been also suggested by previous experimental and clinical studies. METHODS The study included 10 patients with UA (recent worsening of anginal threshold and appearance of angina at rest) and single-vessel CAD. Blood flow velocity was monitored by a Doppler catheter in the diseased artery. Transstenotic pressure gradient was monitored by aortic and distal coronary pressure monitoring. Stenosis resistance was calculated as the ratio between pressure gradient and blood flow, microvascular resistance as the ratio between distal pressure and blood flow. Measurements were obtained at baseline, following intracoronary adenosine (2 mg) and during transient ischemia. Aortic and distal coronary pressures were also measured during balloon coronary occlusion. RESULTS Adenosine did not affect stenosis resistance, while it decreased (p < 0.05) microvascular resistance to 52 +/- 22% of baseline. Angina and ischemic ST segment shift were associated with transient angiographic coronary occlusion in 7 of 10 patients;however, in no case was ischemia associated with interruption of flow. Despite markedly different flow values, distal coronary pressure was similar during adenosine and during spontaneous ischemia (48 +/- 15 vs. 46 +/- 20 mm Hg, respectively, NS). During ischemia, a marked increase in the resistance of both coronary stenosis and coronary microcirculation was observed (to 1,233% +/- 1,298% and 671% +/- 652% of baseline, respectively, p < 0.05). Distal coronary pressure was markedly reduced during balloon coronary occlusion (14 +/- 7 mm Hg, p < 0.05 vs, both adenosine and ischemia), suggesting the absence of significant collateral circulation. CONCLUSIONS In patients with UA, transie

关键词：腺苷/投药和剂量心绞痛不稳定型/诊断显像心绞痛不稳定型/病理生理学血流速度血压冠状血管造影术冠状动脉循环/药物作用冠状动脉循环/生理学冠状血管/诊断显像冠状血管/药物作用冠状血管/病理生理学心电描记术注射动脉内心肌缺血/诊断显像心肌缺血/病理生理学疾病严重程度指数超声检查多普勒超声检查介入性血管阻力/药物作用血管收缩/药物作用血管舒张药/投药和剂量人类中年人

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Functional significance of recruitable collaterals during temporary coronary occlusion evaluated by ^99mTc-sestamibi single-photon emission computerized tomography

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第3期35卷 624-632页

作者： Sand, NPR Rehling, M Bagger, JP Thuesen, L Flo, C Nielsen, TT Aarhus Univ Hosp Dept Nucl Med Skejby Sygehus DK-8200 Aarhus N Denmark Aarhus Univ Hosp Dept Cardiol Skejby Sygehus DK-8000 Aarhus Denmark

Objectives. The present study evaluated the impact of recruitable collaterals on regional myocardial perfusion measured by (99m)technetium (Tc)-sestamibi single-photon emission computerized tomography (SPECT) during temporary coronary occlusion and related these estimates to the coronary wedge pressure and electrocardiographic (ECG) ST-segment changes. Background. Clinical variables (angina and ECG changes) and intracoronary flow and pressure recordings have indicated a protective role of recruitable collaterals on myocardial perfusion during percutaneous transluminal coronary angioplasty (PTCA). Methods. Thirty patients (mean age 55 years, SD 9;20 men) with stable angina pectoris and proximal nonoccluding single-vessel left anterior descending coronary artery (LAD)-stenosis scheduled for PTCA were included. Visualization of recruitable collaterals by ipsilateral and contralateral contrast injection, registration of coronary wedge pressure and injection of Tc-99m-sestamibi during 90-s LAD occlusions were undertaken. A rest perfusion study was performed within four days before PTCA. As an estimate of the severity of regional hypoperfusion during occlusion, an occlusion/rest count ratio was calculated (mean defect pixel count during occlusion divided by mean pixel count in identical regions at rest). Results. The scintigraphic occlusion/rest count ratio was higher in patients with recruitable collaterals (n = 16), 67 +/- 11%, compared to patients without collaterals (n = 14), 60 +/- 6% (p < 0.05). The occlusion/rest count ratio correlated with the coronary wedge pressure (R-2 = 0.34;p < 0.001). The occlusion/rest count ratio was lower, 61 +/- 6%, in patients with ST-segment elevation (n = 23) versus 74 +/- 9% in patients without ST-segment elevation (n = 7) (p < 0.0001). Conclusions. Using Tc-99m-sestamibi SPECT imaging during brief episodes of coronary occlusion, the severity of regional myocardial hypoperfusion was reduced by the presence of recruitable collaterals

关键词：心绞痛/并发症血管成形术气囊冠状动脉侧支循环/生理学冠状动脉循环/生理学冠心病/诊断显像冠心病/病理生理学冠心病/治疗冠状血管/诊断显像冠状血管/病理生理学心电描记术血流动力学注射静脉内预后前瞻性研究放射性药物/投药和剂量结果可重复性 99m锝甲氧基异丁基异腈/投药和剂量体层摄影术发射型计算机单光子女(雌)性人类男(雄)性中年人

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EXERTIONAL ANGINA-PECTORIS CAUSED BY CORONARY ARTERIAL SPASM - EFFECTS OF VARIOUS DRUGS

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AMERICAN JOURNAL OF CARDIOLOGY 1979年第3期43卷 647-652页

作者： YASUE, H OMOTE, S TAKIZAWA, A NAGAO, M MIWA, K TANAKA, S From the Division of Internal Medicine Shizuoka City Hospital Shizuoka City Japan

In four patients with exertional angina induced by arm exercise, coronary arteriograms taken before, during and after the attack demonstrated that spasm appeared in the large coronary artery supplying the area of myocardium shown to be ischemic in the electrocardiogram during the attack. The spasm disappeared with subsidence of the attack after administration of nitroglycerin. Anginal attacks induced by treadmill exercise were not suppressed by propranolol, 60 mg orally, in two of the four patients. However, such attacks were suppressed in all patients by oral administration of diltiazem (90 mg, four patients) or nifedipine (20 mg, three patients) or intramuscular injection of phentolamine (0.2 mg/kg body weight, three patients). It is concluded that coronary arterial spasm can be induced by exercise and can cause exertional angina in some patients. Diltiazem and nifedipine, calcium antagonistic drugs, prevent spasm.

关键词：心绞痛/药物疗法心绞痛/病因学缩窄病理性/并发症缩窄病理性/药物疗法冠状血管造影术冠状血管/病理生理学地尔硫|艹卓|/治疗应用运动试验硝苯地平/治疗应用硝酸甘油/治疗应用酚妥拉明/治疗应用普萘洛尔成年人女(雌)性人类男(雄)性中年人

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THE USE OF ANGIOSCOPY IN PERCUTANEOUS CORONARY INTERVENTIONS

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JOURNAL OF INTERVENTIONAL CARDIOLOGY 1994年第1期7卷 65-75页

作者： ESCANED, J DIMARIO, C BAPTISTA, J FOLEY, DP OOMEN, J DEJAEGERE, P DEFEYTER, P SERRUYS, PW ERASMUS UNIV ROTERDAM THORAXCTRCATHETERIZAT & INTRACORONARY IMAGING LABS3000 DR ROTTERDAMNETHERLANDS

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Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans - A sympathoexcitatory response to myocardial ischemia

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 1999年第7期34卷 1924-1931页

作者： Joho, S Asanoi, H Remah, HA Igawa, A Kameyama, T Nozawa, T Umeno, K Inoue, H Toyama Med & Pharmaceut Univ Dept Internal Med 2 Toyama 9300194 Japan Toyama Med & Pharmaceut Univ Dept Physiol 1 Toyama 9300194 Japan

OBJECTIVES We assessed time-varying spectral components of heart rate and left ventricular (LV) pressure variability during coronary angioplasty to elucidate dynamic autonomic responses to transient myocardial ischemia. BACKGROUND Sympathoexcitatory reflexes elicited by acute coronary occlusion are rarely addressed in the clinical settings because of a lack of technique to monitor transient changes in sympathetic activation. METHODS RR interval and LV pressure and volume were serially recorded in 14 patients with effort angina during balloon coronary angioplasty. Wavelet analysis was applied for determination of nonstationary spectral components of RR interval and LV peak pressure variability. RESULTS The wavelet analysis revealed that coronary occlusion provoked low-frequency (LF) fluctuations of RR interval (seven patients) and LV peak pressure (six patients) at 0.06 +/- 0.01 Hz, but not in the remaining patients. Following the balloon inflation, the LF component of RR interval began to increase after the onset of myocardial ischemia, peaked at about 80 s, and then declined in the: late phase of inflation. Consequently, the ratio of low to high frequency component rose to be significantly greater in the LF augmentation group than in the no LF augmentation group in the middle phase of coronary occlusion. The patients with no LF augmentation had little evidence of myocardial ischemia as reflected by changes in ST segment and LV systolic function during coronary occlusion. CONCLUSIONS The wavelet analysis of RR interval and LV pressure variability clearly showed a dynamic profile of spectral components in response to transient coronary artery occlusion. The resultant regional myocardial ischemia elicited a profound sympathoexcitatory response followed by a gradual suppression. This method provides a useful tool to gain a new insight into the nonstationary autonomic influence on the cardiovascular system. (C) 1999 by the American College of Cardiology.

关键词：血管成形术气囊冠状动脉收缩冠心病/病理生理学冠心病/治疗冠状血管/神经支配冠状血管/病理生理学心电描记术兴奋性突触后电位/生理学心率/生理学测压法心肌缺血/病理生理学反射时间因素迷走神经/病理生理学心室压/生理学成年人老年人女(雌)性人类男(雄)性中年人

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Assessment of resting perfusion with myocardial contrast echocardiography: Theoretical and practical considerations

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AMERICAN HEART JOURNAL 2000年第2期139卷 231-240页

作者： Lindner, JR Villanueva, FS Dent, JM Wei, K Sklenar, J Kaul, S Univ Virginia Med Ctr Div Cardiovasc Charlottesville VA 22908 USA Univ Pittsburgh Div Cardiovasc Pittsburgh PA 15260 USA

Background The aim of this study was to perform a quantitative comparison between myocardial contrast echocardiography (MCE) and single-photon emission computed tomography (SPECT) in patients with prior myocardial infarction (MI). We also wanted to determine the optimal method for the intravenous administration of an ultrasound contrast agent in the clinical setting. Methods and Results Seventeen patients with resting perfusion defects in a single vascular territory on SPECT were-studied. MCE was performed with intermittent harmonic imaging during continuous infusions of a second-generation ultrasound contrast agent (Sonovue, Bracco Diagnostics) in all 17 patients and after bolus injection in 8 of them. During continuous infusions, the video intensity (VI) ratio between the abnormal and normal myocardium at a pulsing interval (PI) of 8 cardiac cycles correlated well with the activity ratio between these segments:on SPECT (r = 0.73, P < .01). When information regarding microbubble velocity (MV) denoted as change in VI with increasing PIs was added, the correlation with SPECT activity ratio improved (P < .05) significantly (r = 0.87, P < .0001). Higher microbubble doses resulted in higher VI during Continuous infusions with good myocardial opacification:and no Far-field attenuation until the highest dose was reached. With bolus injections, the VI ratio between the abnormal and normal myocardium at PI of 1 and 5 cardiac cycles showed a modest correlation (r = 0.46 and r = 0.48, respectively,: P < .05) with activity ratios between these regions on SPECT. When a dose of microbubbles administered as a bolus produced adequate myocardial opacification, it invariably resulted in far-field attenuation. Conclusions In patients with prior MI, quantitative assessment of resting perfusion defects on MCE correlates well with regional activity on SPECT. Continuous infusions offer an advantage over:bolus injections because they can provide an assessment of both relative VI and MV. A

关键词：冠状动脉循环/生理学冠状血管/生理学冠状血管/病理生理学冠状血管/超声检查心脏/生理学输注静脉内微球体心肌梗死/病理生理学心肌梗死/超声检查体层摄影术发射型计算机单光子女(雌)性人类男(雄)性

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Abnormal coronary microvascular endothelial function in humans with asymptomatic left ventricular dysfunction

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AMERICAN HEART JOURNAL 2003年第3期146卷 549-554页

作者： Prasad, A Higano, ST Al Suwaidi, J Holmes, DR Mathew, V Pumper, G Lennon, RJ Lerman, A Mayo Clin & Mayo Fdn Div Cardiovasc Dis Rochester MN 55905 USA Mayo Clin & Mayo Fdn Dept Internal Med Rochester MN 55905 USA Mayo Clin & Mayo Fdn Biostat Sect Ctr Coronary Physiol & Imaging Rochester MN 55905 USA

Background Coronary endothelial dysfunction may potentially lead to myocardial ischemia and to the progression of heart failure. Though endothelial dysfunction is associated with advanced heart failure in humans, relatively little is known regarding their temporal relationship. Thus, the current study was designed to test the hypothesis that coronary endothelial dysfunction is present in patients with asymptomatic left ventricular dysfunction. Methods and Results Three hundred patients without symptoms of heart failure, with normal or mildly diseased coronary arteries at angiography underwent coronary vascular reactivity evaluation using intracoronary adenosine, acetylcholine (ACH) and nitroglycerin. Patients were divided into 2 groups based on the left ventricular ejection fraction (EF): patients with asymptomatic left ventricular dysfunction (ALVD), EF <45% (n = 11);and patients with EF ≥45% (n 289, controls). Except for a lower high-density lipoprotein level in patients with ALVD, there were no significant differences between the groups in regards to conventional cardiovascular risk factors. There was no difference in the change (mean ± SE) in epicardial diameter in response to ACH (-21.7% ± 7.2% vs -13.8% ± 1.5%, P = .3). The change in coronary blood flow in response to ACH was significantly attenuated in the patients with ALVD when compared to the controls (-18.5% ± 14.9% vs 74.0% ± 7.2%, P < .013). By multivariate analysis, EF was an independent predictor of coronary microvascular dilation with ACH (P < .001). Conclusion The current study demonstrates that coronary microvascular endothelial dysfunction is present in ALVD. Thus, coronary endothelial dysfunction may be an early event in the pathophysiology of heart failure.

关键词：冠状动脉循环冠心病/病理生理学冠状血管/病理生理学内皮血管/生理学微循环统计数据每搏输出量/生理学心室功能障碍左/病理生理学成年人老年人女(雌)性人类男(雄)性中年人

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Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第5期36卷 1467-1473页

作者： Prasad, A Husain, S Schenke, W Mincemoyer, R Epstein, N Quyyumi, AA NHLBI NIH Cardiol Branch Bethesda MD 20892 USA

OBJECTIVES The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 mug/min) and BK (62.5 ng/min and 4 mug/min), and endothelium independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS There was progressive impairment in AGH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK;segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype. (C) 2000 by the American College of Cardiology.

关键词：乙酰胆碱/药理学腺苷/药理学动脉硬化/病理生理学缓激肽/药理学冠状血管/药物作用冠状血管/病理生理学血流动力学一氧化氮/生理学硝普钠/药理学肽基二肽酶A/血液肽基二肽酶A/遗传学多态现象遗传受体缓激肽/药物作用受体缓激肽/生理学危险因素血管舒缩系统/药物作用血管舒缩系统/病理生理学 ωN-甲基精氨酸/药理学女(雌)性人类男(雄)性中年人

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Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy

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JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2000年第6期35卷 1654-1660页

作者： Hamasaki, S Al Suwaidi, J Higano, ST Miyauchi, K Holmes, DR Lerman, A Mayo Clin & Mayo Fdn Ctr Coronary Physiol & Imaging Div Cardiovasc Dis Dept Internal Med Rochester MN 55905 USA

OBJECTIVES The purpose of this study was to evaluate the association between hypertension and left ventricular hypertrophy (LVH) with both coronary vascular remodeling and endothelial function. BACKGROUND The association between endothelial and nonendothelial coronary flow reserve with vascular remodeling in patients with hypertension and LVI-I is still unclear. METHODS One hundred and eleven patients with normal or mildly diseased coronary arteries at angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Patients were divided into three groups: group I: n = 13, hypertensive patients with LVH;group 2: n 30, hypertensive patients without LVH;group 3: n 68, normotensive patients. Vessel and lumen area and atherosclerotic plaque area were evaluated. Vascular reactivity was examined using intracoronary adenosine and acetylcholine. RESULTS Vessel area in group 1 (with LVH) was significantly (p < 0.01) greater than that in group 2 (without LVH), whereas, vessel area in both groups 1 and 3 was similar (12.8 +/- 0.8 mm(2), 10.7 +/- 0.4 mm(2) and 11.5 +/- 0.3 mm(2)). Coronary blood flow at baseline for patients in group 1 (with LVH) was significantly greater than it was for patients in groups 2 and 3 (81.1 +/- 9.9 ml/min, 56.5 +/- 6.2 ml/min and 48.1 +/- 3.2 ml/min, both p < 0.05). In comparison with groups 2 and 3, the response to both acetylcholine and adenosine was significantly impaired in patients with LVH. CONCLUSIONS The current study demonstrates that hypertension with LVH is associated with both coronary vascular remodeling and attenuated endothelial and nonendothelial coronary flow reserve. (C) 2000 by the American College of Cardiology.

关键词：乙酰胆碱腺苷冠状血管造影术冠状动脉疾病/诊断冠状动脉疾病/病理生理学冠状动脉循环/生理学冠状血管/病理生理学腔内超声检查内皮血管/病理生理学高血压/诊断高血压/病理生理学肥大左心室/诊断肥大左心室/病理生理学前瞻性研究血管舒张/生理学心室功能左/生理学女(雌)性人类男(雄)性中年人

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