冠状动脉微循环障碍及微血管型心绞痛的治疗现状

10%到30%的胸痛患者并无明显的冠状动脉病变(coronary artery disease,CAD),但50%到65%患者的细小冠状动脉血管舒张功能受损,发生冠状动脉微循环障碍(coronary microvascular dysfunction,CMD),即微血管型心绞痛(microvascular angina,MA),目前尚无针对MA的最佳治疗方案。本文综述了既往7篇微血管型心绞痛的治疗方案的临床研究结果,提示西地那非,喹那普利,雌激素和经皮脊髓电刺激对本病有一定的治疗效果,但并未发现L-精氨酸,多沙唑嗪,普伐他丁和地尔硫卓对本病有明确疗效。然而,这7篇研究对冠状动脉微循环障碍的定义不同、采用的治疗方案和效果评价指标存在较大差异,纳入的样本量较小,这些都严重影响了临床研究结果的可靠性。在将来的相关临床试验中需统一冠脉微循环障碍的定义,评估无阻塞性冠脉病变所致胸痛的冠脉微循环障碍以及相应的治疗效果。     

The importance of indicators of the initial phase of atherosclerosis in patients with microvascular angina

Endothelial dysfunction (ED) is generally considered to be the initial step in the progression to atherosclerosis but there is still much uncertainty about the role of the microvascular form of angina in patients with a normal coronary angiogram with regard to ED. The authors investigated the extent of endothelial perturbation and thereby whether the microvascular form of angina precedens macroscopic atherosclerosis by means of non-invasive ultrasound measurement of the intima-media thickening (IMT) in common carotid artery and flow mediated dilatation (FMD) in the brachial artery. 28 patients with stable angina with positive exercise test and ST segment depression (22 females, 6 males, average age 54 years) were compared with a control group consisting of 28 patients with no clinical signs of coronary artery disease (18 females, 10 males, average age 53 years). No significant difference in FMD% (7.3 vs. 10.8, p = 0.07) was found between the groups, though specific measurements (average dilatation of the brachial artery induced by ischemic insult, peak blood flow and peak hyperemic flow) differed considerably. Also IMT did not vary significantly between the groups (0.74 vs. 0.65, p = 0.08). In patients with IMT > 0.8 mm (6 patients in each group) a significant decrease of FMD was found as compared with patients with normal IMT (p < 0.05). It was concluded that in patients with increased IMT an inverse relationship between FMD and IMT exists both in patients with microvascular angina and in the healthy control subjects whereas in the group of patients with normal IMT no ED was demonstrated. This supports the hypothesis that the microvascular form of angina is the early stage of coronary artery atherosclerosis and this escapes angiographic recognition.     

低风险胸痛急性冠状动脉综合征患者心电图特征及其对诊断的价值研究

摘要 目的：分析低风险胸痛急性冠状动脉综合征(acute coronary syndrome,ACS)患者心电图特征及其对诊断的价值。方法：选择我院自2017年1月至2019年8月接诊的194例疑似低风险胸痛ACS患者,均采取心电图检查和冠状动脉造影检查;分析低风险胸痛ACS患者的心电图特征,观察心电图结果与冠状动脉病变支数、狭窄程度的关系,计算心电图诊断低风险胸痛ACS的特异性、敏感性等效能指标,使用受试者工作特征(receiver operating characteristic,ROC)曲线下面积(curve,AUC)定量分析ST段偏移值预测主要不良心血管事件的效能。结果：在194例疑似低风险胸痛ACS患者中,低风险胸痛ACS患者134例,低风险不稳定型心绞痛(UA)患者心电图表现以ST-T缺血性改变为主,发作时改变明显或呈现伪性改善;低风险非ST段抬高的心肌梗死(non-ST-segment elevation myocardial infarction,NSTEMI)患者心电图表现为肢体和胸导联ST段压低,T波低平、倒置,ST-T改变持续存在和呈动态衍变;低风险胸痛ACS患者心电图结果与冠状动脉病变支数无关(P＞0.05),与狭窄程度有关(P＜0.05);心电图诊断低风险胸痛ACS的特异性为71.67 %,敏感性为69.40 %,阳性预测值为84.55 %,阴性预测值为51.19 %,符合率为70.62 %;所有患者均获得随访,经ROC曲线分析,ST段偏移值预测低风险胸痛ACS患者发生主要不良心血管事件的最佳截值为1.85 mm,AUC为0.695,对比全球急性冠状动脉事件注册(GRACE)风险评分的0.675,差异无统计学意义(P＞0.05)。结论：低风险胸痛ACS患者心电图具有多样化,与冠状动脉狭窄程度有关,有助于初步诊断和风险评估,且ST段偏移值预测主要不良心血管事件的效能较好,值得进一步研究应用。     

Are coronary artery spasm and progressive damage to the heart associated with the hyperventilation syndrome?

A case of coronary artery vasospasm was studied in a man with a four year history of angina. He had evidence of symptomatic hyperventilation during a spontaneous episode of chest pain. When asked to hyperventilate the pain in his chest and ST elevation were reproduced in the same leads as occurred during the spontaneous attack. This may be the first reported case of spontaneous hyperventilation producing vasoconstriction, and the patient''s previous admissions to the coronary care unit may have been associated with coronary vasospasm induced by hyperventilation. When patients with variant angina report pains in the chest in association with dizziness and breathlessness hyperventilation should be considered to be a possible cause of the symptoms. As coronary vasospasm is increasingly implicated in angina after myocardial infarction the role of hyperventilation should be considered more often.     

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia.Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability.Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised.DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal.     

Chest pain in women: clinical,investigative, and prognostic features.

OBJECTIVE--To characterise clinical, investigative, and prognostic features of women referred with chest pain who subsequently underwent coronary angiography. DESIGN--Analysis of all women with angina referred to one consultant during 1987-91 who subsequently underwent coronary angiography, with follow up to present day. SETTING--Cardiothoracic centre. SUBJECTS--Women with normal coronary arteries; women with coronary artery disease shown on angiography; men with coronary artery disease matched for age; men referred with chest pain during the same period subsequently found to have normal coronary arteries. MAIN OUTCOME MEASURES--Risk factor analysis; results of exercise testing and coronary angiography; intervention; morbidity and mortality. RESULTS--Women comprised 23% (202/886) of patients referred with chest pain who subsequently underwent angiography. 83/202 women had normal coronary angiograms compared with 55/684 men (41% v 8%, P < 0.01). Diabetes mellitus was the only risk factor more frequently encountered in women with coronary artery disease (P = 0.001). The specificity and positive predictive value of exercise testing before angiography were significantly lower in women than men (71% v 93%, P < 0.001 and 76% v 95%, P < 0.001, respectively). Revascularisation procedures were as common in women with coronary artery disease as in men (81 (68%) v 70 (59%)), and there was no difference in event rate during follow up. Many patients with normal coronary arteries, irrespective of sex, had symptoms during follow up (61 (73%) women, 36 (65%) men) and continued to take antianginal drugs (27 (33%) women, 14 (28%) men); 14 (17%) women and six (11%) men required hospital readmission for severe symptoms. CONCLUSIONS--In this series, although women comprised the minority of patients referred with chest pain, a diagnosis of normal coronary arteries was five times more common in women than men. Risk factor analysis and exercise testing were of limited value in predicting coronary artery disease in women. There was no sex bias regarding revascularisation procedures, and outcome was similar. A diagnosis of non-cardiac chest pain in patients with normal coronary arteries was of little benefit to the patient with regard to morbidity.     

Duke Treadmill Score in prioritizing patients for coronary angiography: retrospective study of a Croatian regional hospital

Aim of the study was to determine the potential of Duke Treadmill Score (DTS) in prioritizing patients for coronary angiography in a transitional country clinical setting. We analyzed 114patients with suspected stable coronary artery disease who underwent exercise treadmill testing, and coronary angiography in Slavonski Brod General Hospital. DTS was calculated from treadmill test as: exercise time--(5 x ST deviation in mm)--(4 x exercise angina). Regarding the score, patients were grouped into three groups of risk for coronary artery disease: low risk, medium risk, and high risk patients. All patients underwent coronary angiography, and were grouped in accordance to the severity of the coronary artery disease into three groups: insignificant, significant, or severe coronary artery disease. All patients scored as high risk DTS had significant or severe coronary artery disease. Medium and low risk DTS patients had insignificant coronary artery disease in 50%, and 90% of cases, respectively. Medium risk patients with significant or severe coronary artery disease were significantly older, and had more frequent history of typical chest pain with higher number of episodes per week (P<0.05), whereas there were no differences regarding gender or presence of risk factors. There were no significant differences among medium risk patients regarding the severity of coronary artery disease in exercise time or ST deviation. However, the presence of limiting exercise angina in medium risk patients was significantly more related with significant and severe coronary artery disease (P<0.05). High risk DTS result showed great potential in stratifying patients for immediate coronary angiography. This scoring system may be used in prioritizing patients for coronary angiography in a transitional clinical setting.     

Toll-like receptor 4 expressions on peripheral blood monocytes were enhanced in coronary artery disease even in patients with low C-reactive protein

Toll-like receptors (TLRs) play important roles in the pathogenesis of atherosclerosis. On the other hand, serum high sensitivity C-reactive protein (hsCRP) is known as an independent coronary risk factor, but cardiovascular events do occur even in low hsCRP levels. We investigated whether the TLR4 expression levels on human peripheral blood monocytes were associated with serum hsCRP levels or the occurrence of coronary artery diseases (CAD). One hundred CAD patients and 100 non-CAD subjects were enrolled. There were 72 non-CAD subjects and 53 CAD patients with low serum hsCRP levels. Among the low-hsCRP subjects, the TLR4 expression levels were higher in CAD patients than in non-CAD subjects (P < 0.05, after being adjusted for other risk factors). Moreover, TLR4 expression levels in stable angina pectoris (SAP) patients were elevated compared with those in non-CAD subjects (P < 0.05), and those in acute coronary syndrome patients were higher than SAP patients even in low-hsCRP subjects (P < 0.01). In conclusion, the TLR4 expression levels on peripheral blood monocytes in CAD patients were higher than those in non-CAD subjects and correlated with disease activity, even in low-hsCRP subjects. The combined measurement of serum hsCRP and the TLR4 expression on peripheral blood monocytes, especially among low-hsCRP subjects, may become a new coronary risk marker.     

Plasma nociceptin/orphanin FQ levels rise after spontaneous episodes of angina, but not during induced myocardial ischemia

The aim of our study was to evaluate the effects of repeated episodes of angina and induced myocardial ischemia on plasma nociceptin/orphanin FQ (N/OFQ) levels. Patients with unstable angina (23 with new onset severe angina or accelerated angina and 18 with subacute angina at rest) who had had repeated spontaneous episodes of chest pain in the last week before the study underwent myocardial perfusion single-photon emission computed tomography using adenosine infusion. Twenty subjects without clinical symptoms of angina matched for age, sex and cardiac risk factors served as a control group. N/OFQ levels were significantly (P < 0.01) higher in the patients (15.2 ± 2.1 pg/ml) than in the control group (8.5 ± 2.6 pg/ml). Blood pressure and heart rate did not significantly differ. All patients showed transient adenosine infusion myocardial ischemia that did not induce chest pain or significantly modify plasma N/OFQ levels or hemodynamic parameters. Our findings show that unstable angina is associated with a significant increase in circulating N/OFQ levels unrelated to intervening transient myocardial ischemia or hemodynamic changes. This increase is probably related to the chest pain repeatedly occurring in the course of coronary artery disease, but absent during transient adenosine-induced myocardial ischemia.     

Prinzmetal's angina,normal coronary arteries and pericarditis.

A woman with Prinzmetal''s variant angina had spontaneous attacks of myocardial ischemia characterized by severe chest pain, hypotension, inferior ST-segment elevation, transient complete heart block and selective right ventricular dysfunction. Despite initial improvement following intravenous administration of atropine and sublingual administration of nitroglycerin she died of cardiogenic shock. Autopsy showed normal coronary arteries and acute pericarditis, more pronounced over the right side of the heart. It is postulated that the pericardial inflammation elicited severe spasm of the subjacent right coronary artery.     

Cocaine: its use in otolaryngology

A review of 120 patients who had a discharge diagnosis of intermediate coronary syndrome showed 12 patients with documented transient ST elevation during spontaneous rest pain consistent with Prinzmetal''s angina. Coronary arteriography showed severe proximal occlusive coronary atherosclerosis in nine of the patients, and normal or minimal disease in the other three patients. In two of these three, there was documented coronary arterial spasm with reproduction of symptoms during arteriography. Although a shorter history of chest pain, presence of an old myocardial infarction and a positive finding on electrocardiogram treadmill test tended to predict the patients with severe occlusive coronary artery disease, these methods were inadequate to select candidates for arteriography. All patients responded well to nitroglycerine while in the hospital. Five of the nine patients with coronary artery disease had coronary bypass operations, with two excellent, two fair and one poor result. One of the three patients with normal findings on coronary arteriograms died with refractory ventricular arrhythmia six months after study. The other two have had good-to-moderate relief of symptoms on long-acting vasodilators and propranolol. Current concepts of the syndrome of Prinzmetal''s angina and ST elevation are reviewed. It appears that this syndrome has a wide spectrum of clinical presentations and coronary arteriographic anatomies.     

Elderly and younger patients selected to undergo coronary angiography.

OBJECTIVE--To establish and compare the characteristics of older (greater than or equal to 70 years) and younger patients with chest pain selected to undergo coronary angiography and by analysis of their subsequent management to assess the value of coronary angiography for older patients with chest pain. DESIGN--Retrospective analysis of clinical case notes and coronary angiography reports. SETTING--Cardiology department with referral population of one million in an Edinburgh hospital. PATIENTS--134 consecutive patients with chest pain aged 70 years or over investigated by coronary angiography between 1978 and 1988; 134 randomly selected patients aged under 70 investigated over the same period. MAIN OUTCOME MEASURES--Clinical and angiographic features at time of angiography and management after angiography. RESULTS--Older patients represented a small, but increasing, proportion of those investigated. Older patients had more severe symptoms at the time of angiography, were taking more antianginal drugs, and had had their symptoms for longer than younger patients. At angiography more older patients had triple vessel coronary disease, left main stem stenosis, or left ventricular impairment. After angiography similar proportions of older and younger patients underwent coronary artery surgery, with more elderly patients requiring urgent operation; although operative mortality was higher for elderly patients, symptomatic benefit was similar to that in younger patients. CONCLUSIONS--Older patients with angina selected to undergo coronary angiography and subsequent coronary surgery have more severe symptoms and underlying cardiac disease. Earlier referral and investigation might yield a population with lower operative risk. Selection of patients for coronary angiography and coronary artery surgery should be based on the potential for benefit and should avoid "agism."     

Electrocardiographic chest wall mapping in the diagnosis of coronary artery disease.

Chest wall mapping of ST segment changes, inverted U waves, and Q waves using 16 electrocardiographic electrodes was performed at rest and during and after bicycle ergometry in 150 patients presenting with chest pain suggestive of angina. All patients underwent coronary angiography. The presence or absence of appreciable coronary artery disease (greater than or equal to 50% stenosis) was detected with a sensitivity of 98% and a specificity of 88%. The identification of lesions in individual coronary arteries was also possible with a sensitivity and specificity of 87% and 85% respectively for the territory of the left anterior descending and diagonal artery, 71% and 85% respectively for the right coronary artery, and 85% and 80% respectively for the circumflex artery. This test appears to be a reliable non-invasive screening method for selecting patients for angiography.     

Diagnostic re-classification and prognostic risk stratification of patients with acute chest pain

Unstable angina and myocardial infarction are prevalent manifestations of acute coronary artery disease, combined in the term ‘acute coronary syndromes’. The introduction of sensitive markers for myocardial necrosis has led to confusion regarding the distinction between small myocardial infarctions and ‘true’ unstable angina, and the application of ever more sensitive markers has accelerated the pace at which patients with unstable angina are being re-classified to non-ST-segment elevation myocardial infarction. But in how many patients with acute chest pain is myocardial ischaemia really the cause of their symptoms? Numerous studies have shown that most have <5 ng/l high-sensitivity cardiac troponin, and that their prognosis is excellent (event rate <0.5% per year), incompatible with ‘impending infarction’. This marginalisation of patients with unstable angina pectoris should lead to the demise of this diagnosis. Without unstable angina, the usefulness of the term acute coronary syndromes may be questioned next. It is better to abandon the term altogether and revert to the original diagnosis of thrombus-related acute coronary artery disease, myocardial infarction. A national register should be the next logical step to monitor and guide the application of effective therapeutic measures and clinical outcomes in patients with myocardial infarction.

     

A normal coronary arteriogram in a very young man with Prinzmetal's variant angina: Case report with review of the literature

The case of a very young man with Prinzmetal's variant angina and a normal coronary arteriogram is described. While in the hospital for diagnosis, he experienced severe chest pain accompanied by transient ST segment elevation. After intravenous administration of Ergonovine Maleate (0.4 mg), spastic obstruction of the right coronary artery was observed. He was treated successfully with nifedipine, and during 4 months of follow-up, he has had no symptoms. Because of the diagnostic interest in this type of angina in a young person, the literature on Prinzmetal's angina has also been reviewed.     

Likelihood of acute coronary syndrome in emergency department chest pain patients varies with time of presentation

ABSTRACT: BACKGROUND: There is a circadian and circaseptal (weekly) variation in the onset of acute coronary syndrome (ACS). The aim of this study was to elucidate whether the likelihood of ACS among emergency department (ED) chest pain patients varies with the time of presentation. METHODS: All patients presenting to the Lund ED at Skane University Hospital with chest pain or discomfort during 2006 and 2007 were retrospectively included. Age, sex, arrival time at the ED and discharge diagnose (ACS or not) were obtained from the electronic medical records. RESULTS: There was a clear but moderate circadian variation in the likelihood of ACS among presenting chest pain patients, the likelihood between 8 and 10 am being almost twice as high as between 6 and 8 pm. This was mainly explained by a variation in the ACS likelihood in females and patients under 65 years, with no significant variation in males and patients over 65 years. There was no significant circaseptal variation in the ACS likelihood. CONCLUSIONS: Our results indicate that there is a circadian variation in the likelihood of ACS among ED chest pain patients, and suggest that physicians should consider the time of presentation to the ED when determining the likelihood of ACS.     

Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease

Homogeneity of microvascular resistance in different perfusion areas of the same heart is generally assumed. We investigated the effect of the severity of an epicardial stenosis on microvascular resistance in 27 patients with coronary artery disease and stable angina. All patients had an angiographically normal coronary artery, an artery with an intermediate lesion, and an artery with a severe lesion; the latter was treated with angioplasty. In each patient, distal blood flow velocity and pressure were measured during baseline and maximal hyperemia (induced by intracoronary adenosine) using a Doppler and pressure guide wire, respectively. The ratio of mean distal pressure to average peak blood flow velocity was used as an index for the microvascular resistance (MRv). Within patients, the hyperemic MRv was higher in arteries with more severe stenosis (P = 0.021). After percutaneous transluminal coronary angioplasty (PTCA), the hyperemic MRv decreased (pre-PTCA, 2.6 vs. post-PTCA, 1.9 mmHg.cm(-1)s(-1), P < 0.01) toward the value of the reference artery (1.7 mmHg.cm(-1)s(-1); P = 0.67). We conclude that there is a positive association between coronary lesion severity and variability of distal microvascular resistance that normalizes after angioplasty. This study challenges the concept of uniform distribution of hyperemic MRv that is relevant for the interpretation of both noninvasive and invasive diagnostic tests.     

Diagnostic approach in patients with angina and no obstructive coronary artery disease: emphasising the role of the coronary function test

BackgroundMany patients with angina do not have obstructive coronary artery disease (CAD), also referred to as “Ischaemia with No Obstructive Coronary Arteries“ (INOCA). Coronary vascular dysfunction is the underlying cause of this ischaemic heart disease in as much as 59–89% of these patients, including the endotypes of coronary microvascular dysfunction and epicardial coronary vasospasm. Currently, a coronary function test (CFT) is the only comprehensive diagnostic modality to evaluate all endotypes of coronary vascular dysfunction in patients with INOCA.ObjectiveIn this paper we discuss the relevance of performing a CFT, provide considerations for patient selection, and present an overview of the procedure and its safety.MethodsWe reviewed the latest published data, guidelines and consensus documents, combined with a discussion of novel original data, to present this point of view.ResultsThe use of a CFT could lead to a more accurate and timely diagnosis of vascular dysfunction, identifies patients at risk for cardiovascular events, and enables stratified treatment which improves symptoms and quality of life. Current guidelines recommend considering a CFT in patients with INOCA and persistent symptoms. The safety of the procedure is comparable to that of a regular coronary angiography with physiological measurements. Non-invasive alternatives have limited diagnostic accuracy for the identification of coronary vascular dysfunction in patients with INOCA, and a regular coronary angiography and/or coronary computed tomography scan cannot establish the diagnosis.ConclusionsA complete CFT, including acetylcholine and adenosine tests, should be considered in patients with INOCA.Supplementary InformationThe online version of this article (10.1007/s12471-020-01532-9) contains supplementary material, which is available to authorized users.     

Cineangiography of the Coronary Arteries: Clinical,Functional and Anatomic Correlation in Patients with Chronic Chest Pain

Fifty French-Canadian patients presenting with typical or atypical anginal pain were studied by selective cinearteriography and coronary sinus catheterization, with measurement of myocardial function, oxygen and lactate extraction at rest and during isoproterenol infusion. In 28 of 42 patients all three coronary arteries were involved, but angina pectoris also occurred in patients with single mildly stenotic arterial lesions and even in eight patients with normal cinearteriograms. All patients with severe arterial lesions had typical angina, and the longer the duration of angina, the greater the extent, usually, of anatomic disease. Seventy-nine percent of resting electrocardiograms of patients with documented coronary artery disease were abnormal, with recognizable prior infarction in 18. Two-thirds of the patients experiencing pain during the stressful state had abnormal ventricular function. An abnormal arteriovenous lactate difference in response to isoproterenol occurred in patients in all groups.