Coronary reserve, extent of coronary disease, recurrent angina and ECG changes during pain in the in-hospital prognosis of acute coronary syndromes

The prognostic value of recurrent angina, severity of coronarydisease, ECG changes during pain and coronary reserve (ischaemicthreshold measured by atrial pacing: heart rate with ST segmentshift = 1 mm), was evaluated in 383 consecutive patients withacute coronary syndromes. Univariate analysis showed a significantrelationship between occurrence of complications (death, infarctionor coronary surgery) and number of anginal episodes, extentof coronary disease, ischaemic threshold and ST depression withpain. A multivariate analysis indicated that the first threeparameters were the main independent predictors. Coronary reservewas reduced (threshold 150 beats. min^–1) in 83% of patientswho had a myocardial infarction (40), in 91% of those who died(11), in 87% of those who underwent coronary surgery (52) andin 47% of uncomplicated cases (301). Also, a low ischaemic thresholdwas associated with a larger number of anginal episodes thana high threshold ( 130 beats. min^–1, 6.1 ± 5.6vs > 150 beats. min^–1, 2.9± 4.1, P<0.0001),and in complicated patients with one-, two- or three-vesseldisease ischaemic threshold (137.3± 21.2, 133.3 ±18.9, and 135.1 ± 21.2 beats. min^–1, respectively)was lower than in the uncomplicated ones (153.4±20.1,P < 0.005; 148.2± 19.1 P < 0.005; and 139.2 ±23.0 ns, beats, min^–1). A threshold <150 beats. min^–1and ECG changes during pain identified the subset with the highestrisk for complications (59/137, 45%), whereas a threshold >150 beats. Min^–1 and absence of pain or ECG changes duringpain identified those with the lowest risk (5/109, 5%, p <0.001). Thus, our findings document the prognostic significance of coronaryreserve for in-hospital complications in patients with acutecoronary syndromes and confirm the prognostic value of previouslyknown risk markers. They also indicate that some of them maybe significantly influenced by the status of coronary reserve.     

Nocturnal angina in patients with fixed coronary stenosis. Increased coronary vasoconstrictive sensitivity with independence of pacing ischaemic threshold

Atrial pacing and ergonovine tests were performed in 18 consecutivepatients with unstable angina at rest and significant coronaryartery stenosis ( 90% in one vessel in 16 patients). 13 ofthem also had exertional angina. 14 patients presented at leastone positive response (1.0 mm ST-segment shift) to pacing, witha heart rate (144±11 vs 75±13 beats min^–1,P<0.001) and double product (195±26 vs 108±32x 10^–2 P<0.001) significantly higher than during anginaat rest. In the ten patients who presented nocturnal angina,the incidence of positive response to pacing and the pacingischaemic threshold, tested on three different days, were similarto those seen in the remaining patients. In contrast, the ergonovinetest was positive in all patients with nocturnal angina (100%),who required a low dose (0.28±0.2 mg), but it was positivein only four (50%) of those without nocturnal angina, who neededa higher dose (0.55±0.12 mg, P<0.005). Therefore, in patients with severe coronary stenosis and exertionalangina, spontaneous episodes, including nocturnal angina, arenot related to increases in heart rate. The increased coronaryvasoconstrictive sensitivity found in these patients, particularlythose with nocturnal angina, was not dependent on the statusof the coronary reserve, which strongly suggests that changesin coronary tone, focal or diffuse, are involved in the mechanismsof these ischaemic events.     

Ischaemic threshold and haemodynamic changes during angina at rest in patients with unstable angina

To examine whether increases in heart rate might be a commontrigger of angina at rest, changes in heart rate, blood pressureand rate-pressure product during pain were compared with theischaemic threshold (heart rate with ST segment shift >=1 mm), determined by atrial pacing, in 272 patients with unstableangina. During an average of 5.9±5.2 episodes of angina,heart rate was comparable to control values (77.0±14.5vs 75.2±11.5, beats. min^–1, ns) and significantlylower than the ischaemic threshold (147.9±22.9, P <0.00001).The rate-pressure product was also lower (955±183 vs2033±369, x 10, P <0.00001). Heart rate during restangina was lower than the ischaemic threshold even when we consideredonly patients with ST depression during pain (n: 71, 81.4±16.0 vs 132.8±21.4, P<0.00001), those with three-vesseldisease (n: 43, 79.9±15.9 vs 136.9±22.0, P <0.00001), or those with a low ischaemic threshold (= <130beats. min, n: 78, 77.0±14.9 vs 118.3±10.7, P<0.00001).In 154 patients in whom a second pacing test was performed theresponse was reproducible in 137 cases (89%). Thus, heart rate barely changes during angina at rest in patientswith unstable angina and is consistently much lower than theischaemic threshold. These findings support the concept thatincreases in heart rate are an unlikely trigger of ischaemiaat rest, even in patients with markedly reduced coronary reserve.     

Interventional cardiology: Differences in the morphology of unstable and stable coronary lesions and their impact on the mechanisms of angioplasty. An in vivo study with intravascular ultrasound

The aim of this study was to compare the morphology of stableand unstable coronary lesions using intravascular ultrasoundin patients undergoing coronary balloon angioplasty and to determinewhether lesion morphology had any influence on the mechanismof balloon angioplasty. Thirty three (15 stable and 18 unstable) patients undergoingsingle lesion percutaneous transluminal coronary angio plastywere studied with intravascular ultrasound before and afterintervention. All examinations, recorded on S-VHS video tape,were studied off-line and matched sites from the point of minimumlumen area after the procedure and the corresponding site priorto intervention were com pared. The morphology of lesions beforeintervention was noted and the mechanisms of angioplasty (vesselstretch, lesion remodelling and lesion tears) were determinedby comparing pre- and post-interventional morphology and dimensions. The only significant morphological difference between stableand unstable lesions was the presence of a demarcated innerlayer in unstable lesions, delimited by a fine circumferentialline. This pattern was noted in 77% (14/18) of unstable lesionsand in 7% (1/15) of stable lesions (P<0·0l). Unstablelesions tended to have more echolucent zones than stable lesions(72% (13/18) vs 46% (7/15), P=0·13) The mechanisms ofangioplasty were also found to differ. Whereas lesion remodelling(or ‘compression’) was seen in 77% (14/18) of unstablelesions, it occurred in only 13% (2/15) of stable lesions andmean lesion cross- sectional area reduction was greater in unstablelesions, –14·8±8·3% (2·1+1·3mm²) compared to stable lesions, –4sup1+8·4% (0·42+0·9mm P<0·0l. In contrast, vessel stretch was seen morefrequently in stable lesions (73%, 11/15) compared to unstablelesions (22%, 4/18) P<0·0l and the mean increase invessel cross-sectional area was +13·5±6·8(1·6±0·9 mm² in stable lesions comparedto +5·5±5·6% (0·8+0·9 mm²in unstable lesions, P<0·01. Lesion tear was presentto a similar degree in both groups of patients. In this observational study we found a set of echographic markersthat distinguished unstable lesions. The mechanisms of angioplastydiffered between stable and unstable angina, with greater lesionremodelling seen in unstable lesions and vessel stretch in stablelesions. Taken together, these findings suggest that the markerswe describe may be echographic indicators of mural thrombus.     

Thoracic epidural anaesthesia in patients with unstable angina pectoris

The effect of high thoracic epidural anaesthesia with intermittentepidural bolus injections of bupivacaine (2.5 or 5 mg ml^-1)was studied in 28 patients with unstable angina pectoris. Themajority of the patients had a history of previous acute myocardialinfarction(s) and/or angina pectoris and severe coronary arterydisease. All patients were treated wth nitroglycerin infusionfor gt;24 h and were included in the study if they had chestpain, not caused by acute myocardial infarction, at bed restor recurrent anginal pain at rest < 2 days after infarction.4.4 ± 0.3 ml of bupivacaine induced a blockade of theupper seven sympathetic segments ( Th_1-7) for 98 ± 9min.Heart rate decreased significantly from 70 ± 3 to 64± 3 beats min^-1 while blood pressure was unaffected bythoracic epidural anaesthesia. In 27 patients (96%) the anaesthesiainduced complete analgesia. Nitroglycerin infusion was discontinueddefinitely within 3 h in 26 patients (93%) and pain was thereaftercontrolled by means of thoracic epidural anaesthesia as thesole treatment in 23 patients (82%) and as the major treatmentin 25 patients (89%). Twenty-one patients (75%) were fully mobilizedand stabilized. Treatment with thoracic epidural anaesthesialasted for 6.0 ± 1.1 days. The number of daily epiduralinjections decreased significantly with time from 2.7 ±0.3the first day to 0.9 ± 0.3 the fourth day (P>0.01,n = 19). Two patients developed acute myocardial infarctionduring the anaesthesia treatment period, and one of these patientsdied. Exercise stress testing was performed on eight patients threeto five days after the start of thoracic epidural anaesthesia.At a comparable workload, ST-segment depression was significantly(P>0.05) less pronounced during anaesthesia ( – 0.6± 0.1 mm) compared with control ( – 1.3 ±0.2mm). The respective heart rate values were 95 ± 7and 107 ± 7 beats min ^-1 (P > 0.05), while systolicor diastolic blood pressure did not differ between the two conditions. We conclude that blockade of cardiac sympathetic afferents andefferents by means of thoracic epidural anaesthesia can effectivelytreat pain and stabilize patients with unstable angina pectorisrefractory to medical treatment. Furthermore, thoracic epiduralanaesthesia attenuates stress-induced myocardial ischaemia;thus, it may be an efficient supplementary treatment for thecontrol of pain and for stabilizing patients with unstable anginapectoris during diagnostic procedures and prior to coronarysurgery or angioplasty.     

Effect of magnesium sulphate in patients with unstable angina: A double blind, randomized, placebo-controlled study

AIM: Administration of intravenous magnesium sulphate has been shownto be protective during acute myocardial ischaemia and it maytherefore have beneficial effects in unstable angina. The purposeof this study was to assess the effects of a 24-h infusion ofmagnesium in patients with unstable angina. METHODS AND RESULTS: Patients who presented with unstable angina with electrocardiographicchanges were randomized to receive a 24-h intravenous infusionof magnesium or placebo within 12 h of admission. The primaryendpoint was myocardial ischaemia, as assessed by 48 h Holtermonitoring. Resting 12-lead ECGs, creatine kinase-MB releaseand urinary catecholamines were also assessed. Patients werefollowed for 1 month. Thirty-one patients received magnesiumsulphate and 31 placebo. Baseline characteristics and extentof coronary disease were similar in both groups. On 48 h Holtermonitoring, 14 patients (50%) had transient ST segment shiftsin the magnesium group vs 12 patients (46%) in the placebo group.However, there were fewer ischaemic episodes in the magnesiumgroup (51 vs 101, P<0·001) and there was a trend towardsan increase in the total duration of ischaemia in the placebogroup compared to the magnesium group in the second 24 h (2176min vs 719 min respectively, P=0·08). Regression of Twave changes on the 24 h ECG occurred more frequently in patientswho received magnesium compared to those treated with placebo(11 patients vs 0 patients respectively, P<0·005).Creatine kinase-MB release was significantly less at 6 and 24h in patients who received magnesium compared to those treatedwith placebo. Catecholamine excretion was lower in patientstreated with magnesium than in those treated with placebo (adrenaline:1·05±0·16 vs 1·61±0·32ng . mmol^–1 creatinine; noradrenaline: 9·99±1·82vs 18·48±2·41 ng.mmol^–1 creatininerespectively in the first 12 h sample, P<0·05). CONCLUSION: Intravenous magnesium reduces ischaemic ECG changes, creatinekinase-MB release and urinary catecholamine excretion in theacute phase of unstable angina. Thus, magnesium may be a beneficialadditional therapy for these patients. Further studies are requiredto confirm these findings.     

Plasma leukocyte elastase concentration in angiographically diagnosed coronary artery disease

OBJECTIVE: To evaluate the clinical usefulness of leukocyte elastase determinationin the diagnosis of coronary artery disease (CAD). BACKGROUND: Recent research has shown the important role of elastase, aproteolytic enzyme released by neutrophils, in the pathogenesisof CAD. METHODS: 141 patients underwent coronary angiography during investigationof chest pain and/or heart valve disease. Ninety-six had coronaryor absence of angina (stable or unstable), family history ofCAD, smoking, diabetes mellitus, hypertension, lesions and 45non-stenotic coronaries. The patients were characterized asregards presence leukocyte counts, and plasma lipid and elastaseconcentrations. Among CAD-group patients, those with simpleatheromatous plaques were distinguished from those with complexplaques. RESULTS: Elastase concentrations were greater in the CAD group than inthe non-CAD group (49.7 ± 2.8 µg. l^–1 asagainst 29.5 ± 2.2 µg. l^–1; P<0001), andgreater among complex-plaque CAD patients than among simple-plaqueCAD patients (65.2 ± 5.3 µg. l^–1 as against38.6 ± 1.9 µg. l^–1 P<0.001). Logisticregression analysis showed (a) that the risk of CAD varied withelastase concentration, angina status, age and sex, increasingby 11% for every 1 µg. l^–1 increase in elastaseconcentration; and (b) that among CAD patients the risk of complexplaques was greatest for those with unstable angina and highelastase concentration, increasing by 6% for every 1 µg.l^–1 increase in elastase concentration. CONCLUSIONS: Peripheral blood leukocyte elastase concentration is a sensitivediagnostic marker of CAD. High values suggest the presence ofcomplex atheromatous plaques.     

Recombinant hirudin as a periprocedural antithrombotic in coronary angioplasty for unstable angina pectoris

Percutaneous transluminal coronary angioplasty is often complicatedby thrombotic abrupt vessel closure in patients with unstableangina pectoris. The present multicentre trial was performedto determine the feasibility of two-dose regimens of recombinanthirudin (r-hirudin) compared to standard heparin in patientsundergoing coronary angioplasty for unstable angina, and toinvestigate the effects of the different treatment regimen onmarkers of coagulation activation. At five participating centres,61 patients were randomly enrolled in one of two sequentialgroups of r-hirudin (group 1: 0-3mg.kg^–1 i.v. bolus, 0·12mg. kg^–1 h^–1 i.v. infusion; 21 patients; group 2:0·5 mg. kg^–1 i.v. bolus, 0·24 mg. kg^–1h^–1 i.v. infusion; 19 patients) or in a heparin controlgroup (150 IU . kg^–1 i.v. bolus, 20 IU . kg^–1. h^–1i.v. infusion; 21 patients). Antithrombotic therapy was startedimmediately before coronary angioplasty and continued for 24h. This was followed by a low-dose anticoagulant infusion foranother 24 h (r-hirudin: 004 mg . kg^–1. h^–1; heparin:7 IU . kg^–1. h^–1). Activated partial thromboplastintime, r-hirudin plasma concentrations by both immunologicaland functional assay, thrombin-hirudin complex, thrombin-antithrombinIII complex, soluble fibrin, and prothrombin fragment 1+2 wereclosely monitored. The median partial thromboplastin time prolongationsat 24 h vs baseline were found to be 1·9-fold and 2·3-foldin r-hirudin group 1 and dose group 2, respectively, and 3·0-foldin the heparin group. There was a dose-dependent correlationbetween partial thromboplastin time and the r-hirudin plasmalevels (r=0·61). In five of 21 patients of dose group1, three of 19 patients of dose group 2, and 10/21 patientsof the heparin group, partial thromboplastin time values exceedingthe predefined target range prompted an interruption of theinfusion. One major bleeding complication occurred in dose group2. The functional assay for the estimation of r-hirudin plasmaconcentrations showed excellent correlations to the immunologicaltechnique (r=0·99). Differences between the thrombin-hirudincomplex levels could not be observed. Increased concentrationsof thrombin-antithrombin III complex, soluble fibrin, and prothrombinfragment 1+2 were seen 4–8 h after coronary angioplastyand after reduction of the high-dose therapy in dose group 1when compared with dose group 2 and the heparin group, respectively.Based on coagulation tests the present study showed the feasibilityof a periprocedural antithrombotic regimen with r-hirudin forpatients undergoing coronary angioplasty for unstable angina.In addition to the partial thromboplastin time the determinationof r-hirudin plasma levels by a chromogenic substrate assayconsiderably improves the monitoring of therapy. The lower doser-hirudin regimen seems to be suboptimal as periprocedural anticoagulationin coronary angioplasty patients as indicated by markers ofthrombin generation and thrombin activity.     

Dobutamine stress test to diagnose the presence and severity of coronary artery lesions in angina

To calculate the accuracy of dobutamine infusion as a stresstest to detect coronary lesions, 90 patients with angina andnine asymptonlatic subjects with nonsignificant coronary lesionswere submitted to a dobutamine test and coronary arteriography.Dobutamine was given in doses of 5, 10, 15 and 20µg kg^–1min^–1 every 5 min; a 12 lead ECG and blood pressure wasmonitored. Pressurexrate product increased from 8240±1667to 14898±3042. The test was negative (neither anginapain, nor ST seginent shift) in 31 patients, and positive in68. The ST segment was depressed in 33 cases and elevated in20. Significant (50%) coronary lesions were seen in 63 patientsand functional (coronary spasm or vasoconstriction) abnormalitiesin six. The sensitivity of the dobutamine test for the detectionof coronary lesions was 95%, specificity 78%, predictive valueof a positive test 88%, of a negative test 90% and diagnosticefficiency 89%. Strongly positive tests predictedsevere lesionsin 91% of the cases, and slightly positive tests ruled out severelesions in 84%. ST segment elevation was induced in 20 casesand corresponded to a severe coronary lesion. In conclusion,the dobutamine stress test is a simple and accurate method ofpredicting coronary artery disease in patients with angina,distinguishing between severe and mild lesions. It can be agood alternative to an exercise test.     

Relationship between ventilatory threshold and onset of ischaemia in ECG during stress testing

The study was carried out to determine the relationship betweenventilatory threshold and the onset of ischaemia, as shown onthe ECG (horizontal and/or descending ST depression of 0.05mV, on average). Twenty-seven male patients (aged 58 ±7 years) with angiographically documented coronary artery disease(CAD) were assessed by cardiopul-monary exercise testing withoutmedication. Oxygen uptake (VO₂), heart rate (HR), rate-pressure-product(RPP) and blood lactate were measured and/or calculated every30 s during exercise. In addition, 10 patients, comparable withthe above group, were examined to find out the acute effectsof isosorbide dinitrate (ISDN) at ventilatory threshold in relationto ischaemic threshold. The first cardiopulmonary exercise testwas carried out without medication, the second 1 h later with5 mg ISDN, taken sublingually 30 min before the test. RESULTS: (x SD): (1) The mean ventilatory threshold preceded the ischaemicthreshold in relation to exercise capacity (48 ±14 vs55±20 watts; P<0.05), VO₂. kg^–1 (10.0 ±2.2vs 12.0 ±2.9 ml. kg^–1. min; P<0.05), HR (93± 15 vs 100 ± 16. min ^–1; P<0.01), RPP(15095 ± 4424 vs 17166 ± 5245; P<0.01) andblood lactate (1.28 ± 0.53 vs 1.44 ±0.60 mmol.l^–1; P<0.05). (2) This relationship was observed moreoften in the subgroup of patients with angina during cardiopulmonaryexercise testing or with myocardial infarction or with three-vesseldisease than in patients without angina or infarction or withone- and two-vessel disease. (3) ISDN improved the ischaemicthreshold from 55 ±26 watts (without medication) to 81±32 watts (P<0.01) but not the ventilatory threshold(56 ±23 vs 59 ±21 watts, ns). CONCLUSION: The ventilatory threshold seems to precede the ischaemic thresholdbecause of impaired aerobic capacity of the leg muscles, causedby deconditioning on account of the disease. However, ischaemia-inducedleft ventricular dysfunction did not seem to have a direct influenceon ventilatory threshold as ISDN improved the ischaemic threshold,but not the ventilatory threshold.     

Enhanced red cell sodium-hydrogen exchange in microvascular angina

OBJECTIVES: Enhanced calcium content in arterial smooth muscle cells andaltered reactivity of coronary vessels to alkalinization havebeen reported in angina pectoris due to impaired motility ofcoronary arteries. An altered function of sodium-hydrogen exchange,a ubiquitous membrane transport system that links proton effluxto calcium drifts, may mediate these phenomena. DESIGN AND SUBJECTS: Twenty patients with microvascular angina (stable effort angina,reversible perfusion defects during effort thallium 201 heartscintigraphy, and angio-graphically normal coronary arteries)were compared to 20 patients with stable effort angina due tocoronary atherosclerosis and 20 healthy subjects. The sodium-hydrogenexchange was defined as the initial fraction of the amiloride-sensitiveproton efflux from red cells with inhibited anion exchanger(pHi 6·00–6·05) into an Na⁺-containing medium(pHo 8·00–8·05). 12-0-tetradecanoylphorbol-13-acetate(TPA, 600 nmol. 1^–1) and staurosporine (100 nmol. 1^–1)were used as phosphorylation modulators in vitro. RESULTS: The mean red blood cell Na⁺/H⁺ exchange was increased in patientswith microvascular angina (451±37 vs 142±17 and124±21 µmol H⁺. 1 cells^–1. min^–1, P<0·01).TPA and staurosporine abolished differences between the groups. CONCLUSION: Microvascular angina is associated with enhanced Na⁺/H⁺ exchangein erythrocytes, probably due to more extensive phosphorylationof the membrane antiporter sites.     

Platelet activation in angina at rest. Evidence by paired measurement of plasma beta-thromboglobulin and platelet factor 4

Indexes of in vivo platelet activation, beta-thromboglobulinand platelet factor 4 were measured in triplicate in plasmafrom venous blood of 69 patients with proven ischaemic heartdisease (IHD), discarding samples with a ratio of the plasmaconcentrations of the two proteins <2.6, in order to ruleout sampling artifacts. Compared with 60 control volunteers,differences were not significant [for beta-thromboglobulin controls(ng ml^–1, mean±SD) 27.8–8.6, ischaemic patients32.3±17.1; for platelet factor 4 controls 4.3±1.4,ischaemic patients 5.9±5.7]. However, when patients werestratified according to disease activity (Group I—;patientswithout spontaneous ischaemic episodes at rest during 4 daysof continuous electrocardiographic monitoring; Group II—patientswith <l ischaemic episode/day; Group III—patients with>l episode/day), these indexes were increased in ‘active’patients (for beta-thromboglobulin, in Group II—32.4±10.5ng ml^–1, P<0.05 vs. Group I; in Group III—42.6±14.6ng ml^–1, P<0.01 vs. Group I, P<0.05 vs. control.Platelet factor 4 was increased only in Group III—8.9±7.2ngml^–1, P<0.05 vs. control). Beta-thromboglobulin andplatelet factor 4 were 25.0±6.7 ng ml^–1 and 4.9±4.8ng ml^–1, respectively, in Group I (P=NS vs. control).A relationship with the number of spontaenous ischaemic episodesat rest was confirmed by linear regression analysis (in GroupIII patients for beta-thromboglobulin: r=0.76, P<0.01, andfor platelet factor 4 r=0.62, P<0.01). Levles were not elevatedin patients with pervious myocardial infarction without ischaemiaat rest and/or patients with stable angina, and were not influencedby the occurrence of a positive exercise stress test. Coronaryangiograms of ischaemic patients were analyzed to assess theextent and severity of atherosclerotic involvement; for bothextent and severity, involvement was similar in the three groups.These data support the hypothesis of the occurrence of plateletactivation in patients with spontaneous angina at rest, butnot in other subsets of IHD patients, and establish the possibilityof detecting in vivo platelet activation in IHD by means ofsuch circulating markers.     

Prognostic importance of early exercise testing in men with suspected unstable coronary artery disease

In 276 men with suspected unstable coronary artery disease i.e.recurring chest pain of new onset, increasing symptoms of anginalchest pain in formerly stable angina pectoris or suspected non-Q-waveinfarction, an exercise test was performed 2–7 days afteradmission. Coronary events i.e. cardiac death (N=4), Q-waveinfarction (N=11) and coronary artery bypass grafting (N=34),were registered during one year follow-up. The indication forbypass grafting was incapacitating angina pectoris despite medication,and suitable coronary anatomy. Stepwise multiple regressionanalysis showed that S–T segment depression and limitingchest pain were the most important prognostic parameters regardingcoronary events. In patients with S–T segment depression>0.1 mV or limiting chest pain (N=94) the occurrence of Q-wavemyocardial infarction or cardiac death was 10.6% (N=10) comparedto 2.8% (N=5) in patients without these criteria (N=182) (P<0.01).Coronary arterty bypass graft surgery was performed in 33% (N=31)of the group with S–T segment depression >0.1mV orlimiting chest pain but in only 1.7% (N=3) of the other patients(P<0.001). Thus, in patients with suspected unstable coronaryartery disease, whose symptoms and signs of ischaemia are stabilizedby medication, an exercise test can safely be performed aftera few days ambulation in the ward. The early exercise test providesimportant prognostic information regarding the risk for severecoronary events within the next year.     

Prognostic importance of early exercise testing in men with suspected unstable coronary artery disease

In 276 men with suspected unstable coronary artery disease i.e.recurring chest pain of new onset, increasing symptoms of anginalchest pain in formerly stable angina pectoris or suspected non-Q-waveinfarction, an exercise test was performed 2–7 days afteradmission. Coronary events i.e. cardiac death (N=4), Q-waveinfarction (N=11) and coronary artery bypass grafting (N=34),were registered during one year follow-up. The indication forbypass grafting was incapacitating angina pectoris despite medication,and suitable coronary anatomy. Stepwise multiple regressionanalysis showed that S–T segment depression and limitingchest pain were the most important prognostic parameters regardingcoronary events. In patients with S–T segment depression>0.1 mV or limiting chest pain (N=94) the occurrence of Q-wavemyocardial infarction or cardiac death was 10.6% (N=10) comparedto 2.8% (N=5) in patients without these criteria (N=182) (P<0.01).Coronary arterty bypass graft surgery was performed in 33% (N=31)of the group with S–T segment depression >0.1mV orlimiting chest pain but in only 1.7% (N=3) of the other patients(P<0.001). Thus, in patients with suspected unstable coronaryartery disease, whose symptoms and signs of ischaemia are stabilizedby medication, an exercise test can safely be performed aftera few days ambulation in the ward. The early exercise test providesimportant prognostic information regarding the risk for severecoronary events within the next year.     

Influence of nifedipine on coronary haemodynamics and myocardial metabolism in coronary artery disease

The effect of 30 mg sublingual nifedipine on cardiac metabolismand haemodynamics was studied during two identical periods ofpacing in 11 patients with chronic coronary artery disease.The pace time to angina pectoris improved after nifedipine in6 patients, deteriorated in 2 and was unchanged in 3. Nifedipinedecreased blood pressure (12%), rate pressure product (10%)and coronary vascular resistance (17%) during pacing. Aorto-coronarysinus (A-Cs) oxygen difference decreased at rest (9%) and postpacing(10%) after nifedipine, although an opposite tendency in coronarysinus blood flow resulted in unchanged myocardial oxygen uptakethroughout the study. Although mean myocardial lactate extractionafter nifedipine was unchanged during pacing in the whole groupof patients, it increased in 9 patients who showed a net lactaterelease at control pacing (from –50.9±33.5% to–35.9±30.2%, P>0.05). Nifedipine increased freefatty acid (FFA) extraction during pacing (from 1.5±12.9%to 17.4±13.1%, P<0.02) and uptake (from 1.8±8.5to 11.1±10.6 µmol min^–1, P<0.05). Nifedipineinfluenced only glucose exchange significantly (46% decreasedextraction) at 5 min postpacing. The A–Cs citrate gradientlessened 30–40% postpacing after nifedipine administration. Since the unloading effects of nifedipine did not alter myocardialoxygen uptake, the most important net haemodynamicfinding wasthe decrease in coronary vascular resistance. Although no significantantianginal effect of a fixed dose of nifedipine was found,the increased uptake of FFA may reflect improved myocardialoxidative metabolism after nifedipine     

Does exercise-induced myocardial ischaemia cause enhanced platelet activation and fibrin formation in patients with stable angina and severe coronary artery disease?

In this study, betathromboglobulin (BTG) and fibrinopeptideA (FPA) in peripheral venous blood were measured in 20 patientswith stable angina pectoris before and immediately after exercise-inducedmyocardial ischaemia; in 5 of the 20 patients stable anginawas associated with typical peripheral artery disease. A totalof 10 patients with angiographically documented peripheral arterydisease without angina and 10 normal volunteers were taken ascontrol groups. BTG and FPA in the 15 patients with stable anginabefore exercise were 41±14 ng ml^-1 and 2.3±09ng ml^-1 and were not statistically different from the valuesin normal controls; after exercise-induced myocardial ischaemiano significant increase occurred in these patients. Conversely,in the 5 patients with stable angina associated with peripheralartery disease BTG and FPA before exercise were 6l±10ng ml^-1 and 3.5±0.8 ng ml^-1 and increased to 114±14ng ml^-1 (P<0.001) and 4.l±0.5 ng ml^-1 (P<0.01):These results were similar to those found in the 10 patientswith isolated peripheral artery disease.We conclude that BTGand FPA in peripheral venous blood in patients with stable anginaare not elevated either at rest or after exercise-induced myocardialischaemia. Elevated values of BTG and FPA in patients with stableangina may reflect a major interaction between blood and atheroscleroticvessel wall, suggesting the presence of associated atheroscleroticlesions in peripheral artery disease.     

Prognostic significance of angina pectoris recurring soon after myocardial infarction

The prognostic significance of an early occurrence, or recurrence,of angina pectoris after myocardial infarction was studied in254 patients (221 male, 33 female; mean age 58±11 years).During the in-hospital rehabilitation program, 41 patients (16%)had anginal pain. The mean follow-up was 21 months (range 12–33months). Among the 254 patients, 21 died, five had recurrentmyocardial infarction, 13 had unstable angina, and 22 underwentaortocoronary bypass surgery. An early recurrence of anginapectoris was predictive of combined (medical+surgical) events(21 patients, P<0.05), medical events (11 patients, P<0.05)and surgical events (10 patients, P<0.001), but failed topredict individual death (six patients), recurrent myocardialinfarction (two patients) or unstable angina (three patients).Of the events that occurred in the 254 patients, 34% were predictedby the early recurrence of angina pectoris. Early post-infarctionangina was observed more frequently in older patients and patientswith previous history of angina pectoris. This represents animportant prognostic factor after myocardial infarction, whichdefines a high-risk group of patients requiring further investigationand appropriate therapeutic approaches.     

Mechanisms of angina pectoris in syndrome X assessed by myocardial perfusion dynamics and heart rate variability

The fundamental abnormality in syndrome X (angina pectoris,ischaemia-like stress ECG despite angiographically normal coronaryarteries) might be patchily distributed increased tone in pre-arteriolarcoronary vessels with compensatory release of adenosine. Theaim of this study was to confirm this hypothesis and to exploreits relationships with autonomic system functioning. Using parametric positron emission tomography, myocardial perfusionwas examined in 480 segments in 16 syndrome X patients and 16age- and sex-matched healthy volunteers. Autonomic functionwas explored by Holier monitoring of time domain parametersof heart rate variability. Compared to volunteers, both meanperfusion (123 ± 55 vs 87±16mg. min^–1. 100g^–1;P<0.01) and its coefficient of variation (17.0±3.2vs 13.6±2.2%; P<0.01) as a measure of perfusion heterogeneity,were higher in patients with syndrome X. In contrast to thefindings in the control subjects, patients showed an inverserelationship between perfusion heterogeneity (coefficient ofvariation of segmental perfusion) and autonomic tone (heartrate variability parameters). Since marked perfusion heterogeneity (inversely related to autonomictone) and higher overall perfusion were found, the study supportsthe data that in syndrome X hyperreactivity of small coronaryvessels with compensatory release of adenosine may be patchilydistributed.     

Monotherapy of stable angina with nicardipine hydrochloride: double-blind, placebo-controlled, randomized study

The effect of nicardipine hydrochloride, a calcium-channel blockingagent, was studied in 46 patients with stable angina in a double-blind,placebo-controlled, randomized, repeated cross-over protocol,using a 30 or 40 mg dose of nicardipine or placebo three timesa day. Mean resting heart rate and blood pressure did not changesignificantly with 30 mg nicardipine; heart rate increased from81 ±10 to 88 ±13 beats min^–1, systolic bloodpressure decreased from 129±18 to 119±16mmHg,and diastolic blood pressure from 81 ±12 to 74±11mmHg (P < 0·01 for all three variables) with a 40mg dose. Using a treadmill exercise protocol, mean exerciseduration increased from 5·4±1·8 to 6·0±1·8min (P<0·01) with 30 mg nicardipine, and from 5·8+1·7to 616+1·9 min (P<0101) with 40 mg. Time to onsetof angina increased from 4·6+1·9 to 5·2±1·7min(P<0·05) with 30 mg and from 5·1 ± 1·8to 5·7+1·8 min (P = NS) with 40 mg. Mean anginalfrequency and sublingual nitroglycerin consumption were lowduring the cross-over placebo period and did not change significantlyduring therapy with nicardipine. Non-cardiac side-effects weremild and required the withdrawal of only one patient from thestudy. However, during nicardipine therapy four patients hadunstable angina and two developed a non-Q wave myocardial infarction.Of these patients, five were receiving a ß-adrenergicblocker that was discontinued prior to the study. It is concludedthat nicardipine had only a mild positive effect on exerciseduration. As observed with other dihydropyridines, nicardipinehas the potential to precipitate important ischaemic eventsin patients with stable angina, particularly when started afterdiscontinuing a ß-adrenergic blocking agent.     

Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain

Aims An increase in platelet aggregability is associated withunstable angina and myocardial infarction. Platelet size andactivity correlate and mean platelet volume was found to beincreased before acute myocardial infarction. We measured themean platelet volume and platelet count in patients with stableangina, unstable angina and non-cardiac chest pain. Methods and results We studied 981 patients (734 men; 247 women)defined clinically as stable angina (n=688), unstable angina(n=108) and unstable angina requiring immediate angioplasty(n=52). After coronary angiography the patients were subdividedinto single (n=269), double (n=304) and triple-vessel disease(n=311) and the control group of non-cardiac chest pain (n=97).There was no significant difference in platelet count betweenthe control group and patients with 1, 2, or 3-vessel disease.However, the platelet size in patients with coronary arterydisease was significantly larger (single: 8·7±1·19fl;double: 8·7±1·12fl; triple-vessel disease:8·8±1·18fl) than the control group (8·2±0·95fl)(P<0·01). Patients with stable angina similarly hadno significant difference in platelet count compared to thecontrol group but did have a significantly increased mean plateletvolume (8·7±1·13;P<0·01). Incontrast, patients with unstable angina had a decreased plateletcount (245±56x10/l) compared to either stable angina(262±62x10/l;P<0·05) or the control group (261±58x10/l;P<0·05);furthermore, the mean platelet volume (9·4±1·23fl)was significantly greater than for stable angina (P<0·01).Patients with unstable angina requiring immediate PTCA had aneven lower platelet count (231±55x10/l) and higher meanplatelet volume (10·4±1·03fl) (P<0·01)than the rest of the population with unstable angina. Conclusions In stable angina the platelet count is unchangedcompared to patients with normal coronary arteries but the plateletsize is increased. However, in unstable angina there is a decreasein platelet count and an even larger increase in platelet size.We interpret this as meaning that unstable angina might be associatedor preceded by an increase in platelet destruction rate thatis not completely compensated for by an increase in plateletproduction rate. The large, more reactive platelets might becausally related to an ongoing coronary artery obstruction inunstable angina.