Hyperventilation-echocardiography test for the diagnosis of myocardial ischaemia at rest

The purpose of this study was to assess the feasibility, safety,specificity and sensitivity of the hyperventilation test performedunder echocardiographic monitoring for the provocation of vasospasticischaemia. Hyperventilation (approximately 30 cycles.min^–1for 5 min) was performed in 104 hospitalized patients, referredfor pain typical of angina at rest, under 2-D echocardiographicand 12-lead electrocardiographic monitoring. All the tests werecompleted and no significant side effect was observed. In-hospitaldocumentation of spontaneous myocardial ischaemia and/or ergonovine-inducedischaemia was achieved in 38 patients (group I). A positivehyperventilation–echocardiography test (occurrence ofnew transient asynergies or worsening of basal ones) was obtainedin 32/38 patients. Among the group I patients, only 23 had diagnosticST-T changes and only 16 experienced chest pain during the hyperventilation-echotest. Of the 66 patients without evidence of myocardial ischaemiaat rest (negative ECG monitoring during hospitalization and/ornegative ergonovine maleate-echo test)—Group II, noneshowed echocardiographic changes, seven presented ST-T changesand six complained of typical chest pain during the test. Thus,in relation to in-hospital documentation of myocardial ischaemiaat rest, both spontaneous and/or ergonovine-induced episodes,the hyperventilation–echo test showed a specificity of100%, a sensitivity of 84%, a positive predictive value of 100%and a negative predictive value of 92%. In conclusion, hyperventilation performed under echocardiographicmonitoring is feasible and safe; it can be proposed as a screeningtest to unmask vasospastic myocardial ischaemia in patientswith angina at rest, in whom documentation of spontaneous episodesis not available.     

Exercise testing for detection of myocardial ischemia in patients with abnormal electrocardiograms at rest.

This review consists of two parts: (1) discussion of the electrophysiologic mechanisms that are believed to produce ventricular repolarization changes during the electrocardiographic stress test, and (2) clinical assessment of the electrocardiographic changes with stress in patients with an abnormal electrocardiogram at rest. In the first part, the mechanisms of S-T segment elevation, S-T segment depression, T wave changes and linked S-T and T wave changes are reviewed. In the second part, all electrocardiographic abnormalities at rest are grouped into four categories: (1) changes that mask the manifestations of ischemia, (2) changes that stimulate or exaggerate the manifestations of ischemia, (3) changes that have no important effect on the manifestations of ischemia, and (4) changes that reproduce the patterns of acute myocardial infarction after an apparent healing. The reported studies of electrocardiographic stress testing in patients who have abnormal electrocardiogram at rest are summarized.     

Long-term prognosis of transient acute myocardial ischemia at rest

A medical approach to treatment was adopted in 652 patients with documented myocardial ischemia at rest during both the acute and follow-up phases. No patient underwent coronary revascularization during hospitalization and only 86 patients (13%) underwent coronary bypass surgery within 8 months from discharge. During hospitalization 13 patients died. In the remaining group (639 patients), the likelihood of death in the 10-year period after discharge was 28% for all patients and 20% for cardiac causes only. A series of factors studied during the acute stage were assessed in an effort to predict long-term outcome. The following noninvasive characteristics, listed in decreasing order of statistical significance, were found to be significant univariate predictors of survival: abnormal basal electrocardiogram, duration of coronary artery disease, previous myocardial infarction, pattern of ST-T changes during episodes of ischemia at rest, age and systemic hypertension. The average annual mortality rate for patients with T-wave changes, ST-segment elevation and ST-segment depression was 0.9, 1.8 and 3%, respectively. The Cox survival analysis identified abnormal basal electrocardiogram, duration of coronary artery disease and pattern of ST-T changes as significant, independent predictors of death. When invasive characteristics were entered in the model, number of greater than or equal to 50% narrowed coronary arteries, left ventricular ejection fraction, abnormal basal electrocardiogram and smoking habit were found to be independent and additive prognostic variables. Thus, long-term prognosis of patients with ischemia at rest is related to the severity of anatomic impairment, independent of the pattern of ST-T changes observed during the acute phase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between left ventricular function at rest and with exercise and silent myocardial ischemia.

The prognostic value of radionuclide measures of left ventricular function at rest and exercise is well established. Some studies have suggested that the frequency and duration of silent ischemia during ambulatory monitoring provide similar prognostic information; however, studies comparing these two techniques have not been performed. This study examines the relation between left ventricular function at rest and exercise-induced ischemia assessed by radionuclide ventriculography with myocardial ischemia during ambulatory electrocardiographic (ECG) monitoring. Of the 155 patients with coronary artery disease studied, 88% had left ventricular dysfunction with exercise, defined as failure of the ejection fraction to increase by greater than 4% with exercise, and 33% of patients had left ventricular dysfunction at rest (ejection fraction less than 45%); 52% had transient episodes of ST segment depression during 48-h ambulatory ECG monitoring. Exercise-induced left ventricular dysfunction during radionuclide ventriculography was extremely sensitive (94%) in detecting patients with ischemic episodes during ambulatory ECG monitoring; however, only 55% of patients with exercise-induced left ventricular dysfunction had ST segment depression during ambulatory monitoring. Moreover, patients with left ventricular dysfunction at rest had a lower prevalence of transient episodes of ST segment depression (31%) than did patients with normal left ventricular function at rest (62%) (p = 0.008). The relation between prognostically important variables during exercise radionuclide ventriculography and the number and duration of transient episodes of ST depression was examined.(ABSTRACT TRUNCATED AT 250 WORDS)     

腺苷负荷心肌灌注显像正常女性中心电图呈缺血改变35例分析

目的:探讨腺苷负荷心电图(ECG)呈缺血性改变而核素心肌灌注显像(MPI)正常的女性患者,MPI和冠状动脉CT(CTCA)结果对冠心病(CAD)诊断的临床价值。方法:回顾性分析2008年5月至2011年11月疑诊冠心病行腺苷负荷/静息MPI的4 142例女性患者资料,将其中35例〔年龄39～76岁,平均年龄(55.74±9.43)岁〕腺苷负荷ECG呈缺血改变,但MPI正常者作为研究对象,35例患者均利用SPECT/CT行MPI和同机CTCA检查,其中1例患者在1个月内行冠状动脉造影(CAG)检查。结果:35例患者静息状态ECG均正常,腺苷负荷ECG则出现ST段水平或下斜型下移≥0.1 mV,停止负荷1 min后ECG恢复正常,提示心肌缺血改变,随后的负荷/静息MPI均未见心肌缺血改变。同机CTCA结果示:27例冠状动脉正常(27/35,77.1%),7例冠状动脉粥样硬化性改变(7/35,20.0%),1例(2.9%)为3支冠状动脉狭窄性病变,程度均≥50%,其CAG显示:LAD近段狭窄75%,LCX中段狭窄90%,RCA近中段狭窄95%。结果提示:此组患者中97.1%的冠状动脉是正常或仅呈硬化性改变,而无心肌缺血存在。结论:女性患者易出现负荷ECG"假阳性";负荷MPI是评价此类患者有无冠心病的重要手段;同机CTCA则是避免冠状动脉3支病变而MPI"假阴性"的弥补手段,因此,利用SPECT/CT施行同机MPI/CTCA是对此类患者进行冠心病筛查的准确性较高的无创性评价手段。     

Electrocardiographic manifestations and in-hospital prognosis of transient acute myocardial ischemia at rest

From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.     

Increased myocardial perfusion at rest and diminished perfusion reserve in patients with angina and angiographically normal coronary arteries

Angiographically normal coronary arteries are found in a substantial number of patients evaluated for angina pectoris. One third to one half of such patients demonstrate abnormalities of myocardial perfusion or metabolism when evaluated with invasive techniques. This study was designed to determine whether angina in such patients is attributable to abnormalities of perfusion at rest, maximal perfusion or vasodilator reserve and whether any identified abnormalities were global or regional in nature. Positron emission tomography was performed with oxygen-15-labeled water (H2(15)O) and oxygen-15-labeled carbon monoxide (C15O) before and after intravenous dipyridamole to assess regional myocardial perfusion and perfusion reserve in absolute terms in 16 normal subjects and 17 patients with chest pain and angiographically normal coronary arteries. Eight of the 17 patients had a myocardial perfusion reserve less than 2.5 (the lower limit of normal in studies with positron emission tomography, as well as with other techniques) and 9 of 17 patients had a normal response. In the patients with an impaired perfusion reserve, perfusion at rest was significantly higher than that measured in normal subjects (1.61 +/- 0.38 versus 1.25 +/- 0.28 ml/g per min, p less than 0.02) and maximal flow and perfusion reserve were significantly reduced (2.26 +/- 0.92 versus 4.62 +/- 1.58 ml/g per min and 1.4 +/- 0.5 versus 3.8 +/- 1.1, respectively; p less than 0.001 for both comparisons). Abnormalities of perfusion and perfusion reserve were spatially homogeneous without detectable regional disparities. Thus, nearly half of patients with chest pain and normal coronary arteries have abnormalities of myocardial perfusion that are detectable noninvasively with positron emission tomography and H2(15)O.     

The effect of digoxin on the electrocardiogram of healthy middle-aged and elderly patients at rest and during exercise--a comparison with the ECG reaction induced by myocardial ischemia

The effect of digoxin on electrocardiogram (ECG) at rest and during exercise, and on QRS amplitude variability (variance ECG) was studied in 20 healthy, middle-aged men and women. Exercise test and variance ECG were performed before and after pretreatment with digoxin orally. Plots of ST-segment level vergus heart rate (HR) were constructed from the rest and exercise ECG recordings. Thus obtained ST/HR loops were compared with loops from 10 male patients with angiographically verified ischemic heart disease (IHD). Pretreatment with digoxin caused a significant (P <.001) ST depression in precordial leads, which was similar in men and women and returned promptly to the isoelectric level after exercise resulting in a counterclockwise rotation of the ST/HR loop. In IHD patients, the exercise-induced ST-segment depression was significantly more pronounced (P <.01) and the ST-segment recovery slower, resulting in clockwise rotated ST/HR loops. The results of variance ECG were not influenced by digoxin. The digoxin-induced ST-reaction during exercise mimics exercise-induced ischemic ST-reaction in patients with IHD, but can still be discerned by the analysis of ST/HR loops.     

Prognostic value of an electrocardiogram at rest and exercise test in patients admitted with suspected acute myocardial infarction, in whom the diagnosis is not confirmed

The prognosis following discharge in 217 patients admitted with suspected acute myocardial infarction (AMI) due to chest pain, but in whom AMI was not confirmed, was related to the electrocardiogram (ECG) at rest and a symptom-limited exercise test. The patients were followed for 12 to 24 months, (median 14 months). The end-point was a cardiac event, i.e. non-fatal AMI or cardiac death. The prognosis after discharge was only slightly better than in a comparable group of patients with confirmed AMI (P = 0.05). The percentages without a cardiac event after one year were 91.3 and 86.1, respectively. Impaired prognosis was found in patients with negative T waves or ST depression at rest or with ST--T abnormalities or angina pectoris during exercise. Patients with ST depression or elevation, Q wave or intraventricular block at rest. ST abnormalities during exercise or both constituted a high-risk group. The prognosis was significantly better for patients without these entities. The percentage without a cardiac event after one year was 86.9 and 97.6, respectively. It is concluded that patients in whom AMI is not confirmed have a high risk of cardiac events following discharge. Signs of ischaemic heart disease in the ECG at rest and during exercise can be used to identify high and low risk patients.     

Surface 12-lead electrocardiographic findings and plasma markers of thrombin activity and generation in patients with myocardial ischemia at rest

Background: Myocardial ischemia at rest is typically associated with atherosclerotic coronary artery disease, atheromatous plaque rupture, and intracoronary thrombosis. In areas of advanced disease and vascular injury, the extent of thrombus is influenced largely by a delicate balance of procoagulant factors, favoring thrombus initiation, growth, and development, and anticoagulant factors, attempting to limit potentially flow-limiting coronary thrombosis. Thrombin, a 308 amino acid serine protease, is considered the most potent procoagulant factor in the setting of acute vessel wall injury, playing an essential role in the conversion of fibrinogen to fibrin, accelerating the prothrombinase complex, activating platelets, and stabilizing fibrin polymers. The purpose of this study was to determine the relationship between electrocardiographic abnormalities and markers of thrombin activity and generation among patients with unstable angina and non-Q-wave myocardial infarction.Methods and Results: In a study of 36 patients (59.1 ± 11.0 years) with myocardial ischemia at rest participating in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB trial, thrombin activity in plasma, as determined by fibrinopeptide A (FPA), prothrombin fragment 1.2 (F 1.2), and thrombin-antithrombin III complexes (TAT) concentrations, were found to be increased significantly when compared with healthy volunteers (p < 0.004). Thrombin generation was also increased modestly compared with age-matched patients with stable coronary artery disease undergoing elective cardiac catheterization. Given that the surface 12-lead electrocardiogram (ECG) is frequently abnormal in patients with ischemic chest pain at rest and represents a readily available, first-line diagnostic test for assessing disease activity and treatment response, we investigated whether ECG abnormalities and thrombin activity/ generation in plasma were correlated. Twenty-six patients (72%) had ECG changes compatible with myocardial ischemia at the time of study entry, including 18 (50%) with newly inverted T waves (or pseudonormalization), 14 (39%) with reversible ST-segment depression, and 4 (11%) with transient (<30 minutes) ST-segment elevation. Within the predefined ECG groups there were no differences in plasma thrombin activity between patients with and those without confirmed abnormalities. Similarly, there were no differences in either plasma thrombin activity or generation between the predefined ECG groups.Conclusion: Although ECG abnormalities supporting the presence of myocardial ischemia occur commonly in patients with chest pain at rest, they do not correlate closely with markers of thrombin activity and generation in plasma. The diagnostic and prognostic capabilities of these diagnostic tools, considered either alone or together, require further investigation.Presented in part at the American College of Cardiology 42nd annual Scientific Session, Anaheim, CA, March 14–18, 1993.     

Painless myocardial ischemia. Comparison of 2 groups of patients with a positive exercise test after myocardial infarction

Myocardial ischemia usually presents with chest pain, the characteristics of which are well known. However, anginal pain may be absent during true ischemia, an entity known as painless or silent myocardial ischemia. Does this type of ischemia have special clinical, angiographic or ergometric characteristics after posterior myocardial infarction (MI)? In order to answer this question 183 consecutive patients with recent posterior MI who had undergone coronary angiography and who had positive exercise stress tests on bicycle ergometers were separated into two groups depending on whether they had experienced at least one episode of pain after the acute phase of myocardial infarction or during the exercise stress test (Group S: 83 patients, average age 54 +/- 10 years) or not (Group A: 100 patients, average 54 +/- 8 years). The following parameters were commoner in Group A: cigarette smoking, heart rate and load developed during exercise stress testing provoking electrical signs of ischemia, single vessel disease on coronary angiography, long-term medical treatment. On the other hand, the following parameters were statistically more frequent in Group S: hypercholesterolemia, preinfarction angina, degree of ST depression during exercise testing, reperfusion of the distal vessels of the occluded artery responsible for the infarct by a collateral circulation, triple vessel disease and surgical treatment. However long-term follow-up (average 3 years) shows that mortality and recurrence of MI are similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thallium-201 myocardial scintigraphy and left ventricular function at rest in patients with rest angina pectoris

The purpose of this study was to examine the rest thallium-201 perfusion pattern during angina-free periods in 40 patients with rest angina pectoris secondary to coronary artery disease (greater than or equal to 70% diameter narrowing). Seventeen patients had previous Q wave myocardial infarction. The perfusion defects were considered fixed or reversible, depending on the absence or presence of redistribution in the 4-hour delayed images. There were 40 perfusion defects (26 fixed and 14 reversible) in 27 patients whereas 13 patients had normal scans. Reversible perfusion defects were present in 10 patients (25%). Of the 26 fixed perfusion defects, 17 did not have corresponding Q waves. Occluded vessels (63%) had more perfusion defects than vessels with subtotal occlusion (30%) (p less than 0.01). The perfusion defect size was larger in patients with lower ejection fraction than in patients with higher ejection fraction. We conclude: (1) perfusion defects are common in patients with rest angina and are reversible in 25% of patients indicating reduced regional coronary blood flow; (2) the degree of stenosis affects the presence of perfusion defect; (3) fixed defects may be present without corresponding Q waves; and (4) global left ventricular function is related to the size of perfusion defects.     

总胆固醇正常的冠心病患者心肌缺血预警指标的临床研究

目的探讨高敏C-反应蛋白(hs-CRP)和心型脂肪酸结合蛋白(h-FABP)对总胆固醇正常的冠心病(CHD)患者心肌缺血的预警作用。方法将住院的总胆固醇正常的CHD患者分成稳定型、不稳定型心绞痛和急性心肌梗死三组。其中,稳定型心绞痛(SAP)住院患者63例,男39例,女24例;同期住院的不稳定型心绞痛(UAP)患者58例,男31例,女27例;急性心肌梗死患者23例,男14例,女9例。分别检测其血清hs-CRP、h-FABP、cTn-I和CK-MB的含量。同时,抽取同期门诊47例健康体检者作为对照组。结果SAP和UAP组患者血清hs-CRP的含量分别为(1.63±0.53)mg/L和(6.34±1.97)mg/L,高于对照组的(0.71±0.32)mg/L(P<0.05,P<0.01)。SAP和UAP组患者血清h-FABP的含量分别为(2.89±0.76)μg/L和(17.14±5.69)μg/L,高于对照组的(1.76±0.68)μg/L(P<0.05,P<0.01)。结论hs-CRP、h-FABP联合检测与传统心肌损伤检测指标cTn-I、CK-MB相比,对总胆固醇正常的CHD患者发生心肌缺血的可能性具有更高的预测价值。     

Handgrip-apexcardiographic test: a new mode of detecting patients with silent exercise-induced myocardial ischemia.

There are no simple noninvasive stress tests for detecting silent myocardial ischemia by assessing left ventricular (LV) diastolic abnormalities which are known to occur early on the onset of every ischemic episode. It has been proved that the LV apexcardiogram (ACG) reflects the LV pressure curve in early and late diastole and can be recorded during isometric handgrip (HG) exercise. To determine the clinical validity of HG-ACG-Test (HAT) in identifying patients with silent ischemia, 16 patients (8 with prior infarction) with angiographically documented coronary artery disease, positive treadmill electrocardiographic test and without symptoms were examined. According to the largest and lowest individual values in 253 healthy volunteers, the positivity of HAT was defined by the presence of at least one of the criteria: 1) The relative A-wave to total height of ACG during or/and after HG greater than 21%. 2) The total ACG relaxation time (TART) during HG longer than at rest and also longer than 143 ms or/and the heart rate corrected TART during HG less than 0.14, or 3) the combined index of overall diastolic function DATI (= diastolic amplitude time index) during HG less than 0.27. Based on this definition 14/16 (sensitivity: 88%) patients showed a positive test result. It is concluded that, using new definitions of positivity, HAT shows a high sensitivity for detecting patients with proved silent ischemia providing, thus, providing a new simple clinical tool for the identification of these patients.     

The effect of coronary artery bypass grafting on left ventricular systolic function at rest: evidence for preoperative subclinical myocardial ischemia

Successful coronary artery bypass grafting (CABG) improves exercise-induced left ventricular (LV) dysfunction in patients with coronary artery disease (CAD), but its potential for improving resting LV function remains controversial. To assess the influence of CABG on LV function at rest, 31 CAD patients without previous myocardial infarction were studied before and 6 months after CABG by radionuclide angiography after all cardiac medicines were withdrawn. No patient had angina or ischemic electrocardiographic changes at rest. In 27 patients with patent bypass grafts, CABG significantly increased LV ejection fraction during exercise (47 +/- 11% before to 63 +/- 9% after operation, p less than 0.001), indicating reduction in exercise-induced LV ischemia. Moreover, LV ejection fraction at rest also increased (55 +/- 9 to 60 +/- 8%, p less than 0.001), with 20 of 27 patients manifesting an increase compared with preoperative values. Eleven of these 20 patients had apparently normal LV function at rest (ejection fraction and regional wall motion) before CABG. LV regional ejection fraction was computed by dividing the LV region of interest into 20 sectors. Regional analysis indicated that improved ejection fraction at rest after CABG occurred in regions developing ischemia during exercise before CABG. In 4 patients with occluded grafts, the ejection fraction at rest was unchanged by CABG globally (59 +/- 8 to 58 +/- 9%, difference not significant) and regionally. Thus, LV global and regional function at rest improved after successful CABG, even in patients with normal global LV ejection fraction and no visually detectable wall motion abnormality before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noninvasive assessment of myocardial contractility in asymptomatic patients with severe aortic regurgitation and normal left ventricular ejection fraction at rest

In 14 asymptomatic patients with isolated aortic insufficiency the slope k of the end-systolic pressure-volume relation was determined noninvasively with equilibrium radionuclide angiography. The results were compared with changes in left ventricular ejection fraction during maximal physical stress. Nine normal volunteers served as a control group. Patients with aortic insufficiency did not differ significantly from the control group with respect to left ventricular ejection fraction at rest (aortic insufficiency 62 + 8 percent, control 65 ± 6; probability [p] = not significant [NS]), physical work capacity (aortic insufficiency 113 ± 31 watts, control 117 ± 25; p = NS) or age (aortic insufficiency 40 ± 10 years, control 47 ± 7; p = NS).The slope (k) of the end-systolic pressure-volume relation was found to be significantly lower in the group with aortic insufficiency (3.1 ± 1.1) than in the control group (4.1 ± 0.5; p < 0.05). Patients with aortic insufficiency could be classified into two subgroups with respect to the slope k. In subgroup A (n = 7) the slope fell within the normal range (4.0 ± 0.6) as defined by the control group, and the left ventricular exercise reserve was normal (6 percent ± 1). In subgroup B (n = 7) the slope was significantly lower (2.2 ± 0.6, p < 0.01), indicating depressed myocardial contractility, and all patients experienced left ventricular dysfunction during exercise (left ventricular exercise reserve ?5 ± 5 percent). Thus, noninvasive determination of the end-systolic pressure-volume relation identified two subsets of asymptomatic patients with aortic insufficiency, one with impaired myocardial contractility and normal left ventricular exercise reserve and a second group with depressed myocardial contractility and left ventricular dysfunction during exercise.Therefore, an abnormal baseline contractile state in asymptomatic patients with aortic insufficiency may be uncovered by noninvasive determination of the end-systolic pressure-volume relation or by assessing the left ventricular exercise reserve. Serial studies in a larger group of patients undergoing surgical correction of the valve lesion are indicated to determine whether this information will be helpful in evaluating when to operate on asymptomatic patients with aortic insufficiency.