Activation of polymorphonuclear leukocytes and increased plasma vasoconstrictors in vasospastic and nonvasospastic angina.

BACKGROUND: The cause of coronary vasoconstriction in patients with angina at rest, nonsignificant coronary stenosis, and endothelial dysfunction remains unknown. Our objective was to investigate the association between enhanced coronary vasoconstriction and increased circulating levels of vasoconstrictor agents. METHODS: Plasma levels of big endothelin-1, serotonin, and superoxide produced by polymorphonuclear leukocytes were measured in 38 patients with stable angina at rest without significant coronary artery stenosis-23 with nonvasospastic angina and 15 with vasospastic angina-and were compared with 10 patients with stable coronary disease and 20 age-matched controls. RESULTS: Patients with angina at rest showed higher big endothelin-1 (1.28 vs 0.72 fmol/mL, P < 0.001), serotonin (18.0 vs 9.1 ng/mL, P = 0.002), and superoxide produced by polymorphonuclear leukocytes (177 vs 67 nmol/10 × E8 × minutes, P = 0.001) than did controls. Serotonin and superoxide produced by polymorphonuclear leukocytes were also higher than in coronary disease patients (5.4 ng/mL, P = 0.001, and 97 nmol/10 x E8 x minutes, P = 0.005), and big endothelin-1 levels tended to be higher (0.99 fmol/mL, P = 0.073). Moreover, there were no significant differences in these 3 parameters between patients with vasospastic and nonvasospastic angina, and among the latter, between patients with a positive and those with a negative exercise stress test. CONCLUSION: Systemic plasma levels of agents with the potential to produce coronary vasoconstriction are increased in patients with stable vasospastic or nonvasospastic angina and, hence, may contribute to their angina, increased coronary tone, and impaired vasodilatory capacity. Furthermore, they may establish a mechanistic link between the 2 conditions.

Acute cardiac syndromes without significant coronary stenosis: differential features between myocardial infarction and apical-ballooning syndrome.

OBJECTIVE: Among patients with acute cardiac syndromes without coronary stenosis, the clinical, electrocardiographic, echocardiographic, and angiographic features of those with a first acute myocardial infarction (AMI) were compared with those with apical-ballooning syndrome (ABS). METHODS: Data of consecutive patients admitted with a first AMI (n=30) or ABS (n=45) were reviewed. RESULTS: Patients with ABS were older (72 vs. 56 years; P=0.001) and presented a higher frequency of female sex (91 vs. 43%; P=0.001), triggering emotional or physical stress (47 vs. 17%; P=0.003) and a lower rate of tobacco smoking (27 vs. 50%; P=0.051) than those with the first AMI. They also presented a greater number of leads (5.5 vs. 3.6; P=0.01) and more anterior or anterior+inferior involvement (96 vs. 40%; P<0.001), more depressed ejection fraction (45 vs. 57%; P=0.001), more proportion of akinesia or diskinesia (89 vs. 27%; P=0.001) that extended beyond the boundaries of a single-vessel territory, and a greater rate of left ventricular outflow obstruction (29 vs. 0%; P=0.001) and heart failure (38 vs. 10%; P=0.015). Frequency of nonsignificant coronary stenosis or smooth vessels, however, was similar in both groups. CONCLUSION: Patients with ABS were older and more frequently were women than those with first AMI without significant coronary stenosis and had larger hypocontractile areas. The preponderance of tobacco smoking, pain without triggers, and hypocontractility limited to one-vessel territory in the latter, however, may suggest a transient thrombotic/vasospastic event as their underlying mechanism as opposed to patients with ABS.

Prothrombotic profile in patients with vasospastic or non vasospastic angina and non significant coronary stenosis.

BACKGROUND: Patients with vasospastic (VA) or non vasospastic angina (NVA) without significant coronary stenosis have a reduced risk of infarction but is unclear whether or not this may be attributable to a lack of prothrombotic profile - similar to that present in patients with stable coronary artery disease (CAD). METHODS: Plasma levels of von Willebrand factor, total and free tissue factor pathway inhibitor, plasminogen activator inhibitor-1, and fibrinogen were analyzed in 15 patients with stable VA and 23 with NVA, all with vasoconstrictive response to acetylcholine although with different severity. Results were compared with those of 20 age-matched controls and 10 patients with CAD. RESULTS: Plasma levels of von Willebrand factor in patients with VA or NVA were higher than in controls (207 ± 62 and 203 ± 69% vs 121 ± 38%, p < 0.001) and tended to be lower than in CAD patients (264 ± 65, p = 0.145). They also presented higher total tissue factor pathway inhibitor (123 ± 18 and 111 ± 25 vs 88 ± 14, ng/ml p < 0.001) and plasminogen activator inhibitor-1 levels than controls (51 ± 30 and 52 ± 31% vs 19 ± 9 ng/ml, p < 0.001) and similar to CAD patients (134 ± 23 and 62 ± 31, respectively, ns). Moreover, free tissue factor pathway inhibitor plasma levels were lower than controls (18 ± 5 and 17 ± 5 vs 23 ± 8 ng/ml, p = 0.002) and similar to CAD patients (14 ± 5, ns). Despite this prothrombotic condition none of VA or NVA patients presented a myocardial infarction during a 9 year follow-up, an observation also reported in larger series. CONCLUSIONS: During a stable phase of their disease, patients with VA or NVA present a prothrombotic profile that might eventually contribute to occurrence of myocardial infarction. The rarity of these events, however, may suggests that ill defined factors would protect these patients from coronary plaque rupture/fissure.

Hospital outcome of moderate to severe pericardial effusion complicating ST-elevation acute myocardial infarction.

BACKGROUND: Hospital prognosis of moderate to severe pericardial effusion (MPE; ≥10 mm) in ST-elevation myocardial infarction is largely unknown. METHODS AND RESULTS: Data from 446 ST-elevation myocardial infarction patients, 228 with MPE-88 with cardiac tamponade (CT) and electromechanical dissociation (EMD), 44 with CT without EMD (w/oEMD), and 96 without initial CT-and 218 with small PE (5 to 9 mm), were compared. Patients with MPE without initial CT were also compared with 96 patients without PE. CT patients showed larger PE (P<0.001) than those without initial CT; 85% of those with CT+EMD and 86% with CTw/oEMD were treated with pericardiocentesis and 10% and 21% were treated with a surgical repair, respectively. Among MPE patients, 30-day mortality was 43% and was higher in those with CT+EMD (operated, 89%; and nonoperated, 85%) than in those with CTw/oEMD (22% and 11%, respectively; P<0.001) and those without initial CT (17%; P<0.001). It was also higher than in patients with small PE (10%; P<0.001) or those without PE (6%; P=0.001). Death was attributable to cardiac rupture in 83% of patients with CT+EMD, 7% with CTw/oEMD, and 8% with MPE without initial CT and occurred late (≥7 days) in 14%, 67%, and 100%, respectively. CONCLUSIONS: MPE carries an increased mortality that is highest in patients with CT+EMD. In those with CTw/oEMD, however, mortality is considerably low after pericardiocentesis, and subsequent management may be individualized because a conservative approach is often successful. Importantly, MPE patients without initial CT are not free from late rupture and deserve further investigation.

High incidence of TIMI flow 0 to I in patients with ST-elevation myocardial infarction without electrocardiographic lytic criteria.

BACKGROUND: Most patients with ST-elevation myocardial infarction fulfilling ST-segment elevation (STE) lytic criteria present an occluded culprit artery but the occlusion rate in those with minimal STE (minSTE) not fulfilling lytic criteria is unknown. METHODS: In 63 patients with minSTE (mean STE:1.2 +/- 0.6 mm) and 149 with lytic STE criteria (lyticSTE, 4.8 +/- 3.1 mm), an emergency coronary angiography was performed, serial creatine kinase-MB was determined, and ejection fraction was measured by 2-dimensional echocardiography. RESULTS: The 2 groups showed similar time from pain onset to electrocardiogram (minSTE 196 +/- 199 vs lyticSTE, 176 +/- 172 min, P = .444), and although time to catheterization was longer in patients with minSTE (426 +/- 314 vs 253 +/- 239 min, P < .001), the rate of TIMI flow 0 to I (88% vs 81%, P = .21) was similar and percutaneous coronary intervention was performed in >80% of patients from the 2 groups. Moreover, patients with minSTE had higher rate of collateral circulation (27% vs 13%, P = .013), lower rate of Q waves (44% vs 60%, P = .041), lower creatine kinase-MB (202 +/- 150 vs 335 +/- 280, microg/L, P < .001), higher ejection fraction (54% +/- 9% vs 49% +/- 12%, P = .004), and lower mortality (0% vs 7.4%, P = .036). CONCLUSIONS: ST-elevation myocardial infarction patients with minSTE present a high prevalence of TIMI flow 0 to I similar to those meeting lyticSTE suggesting an identical underlying mechanism and the potential to benefit from primary angioplasty.

Usefulness of electrocardiographic and echocardiographic left ventricular hypertrophy to predict adverse events in patients with a first non-ST-elevation acute myocardial infarction.

Left ventricular hypertrophy (LVH) portends a worse outcome after non-ST-elevation acute myocardial infarction (NSTEMI). However, its definition has varied and the incremental prognostic information provided by echocardiography has been unclear. Different electrocardiographic and echocardiographic criteria for LVH were compared for their ability to predict in-hospital complications in 451 consecutive patients with a first NSTEMI, 337 of whom had a reliable echocardiogram. Five to 8% had LVH using Sokolow-Lyon or Cornell (voltage or product) criteria on admission; 15%, using either electrocardiographic criteria; and 24%, using echocardiography. LVH predicted the occurrence of adverse events (death, reinfarction, or severe angina or heart failure), with the strongest association found for the Cornell product (50.0% vs 24.9% of patients meeting or not meeting this criterion had complications, respectively; p = 0.002). This association persisted after adjusting for baseline clinical predictors (odds ratio 2.52, 95% confidence interval 1.19 to 5.35), and considering echocardiographic LVH did not improve the prediction. LVH was more closely related to heart failure occurrence than to recurrent ischemic events. A progressive increase in the rate of complications was observed across quartiles of the components of all LVH criteria (17.1%, 23.7%, 31.7%, and 36.2% for Cornell product, respectively; p <0.001). In conclusion, LVH, especially an abnormal Cornell product, increased the risk of heart failure, but was weakly related to recurrent ischemia in patients with NSTEMI. Echocardiographic LVH did not appear to add prognostic information to the electrocardiogram. However, considering LVH criteria in a more quantitative manner may augment their ability to predict adverse events in this population.

Changes in hospital mortality rates in 425 patients with acute ST-elevation myocardial infarction and cardiac rupture over a 30-year period.

BACKGROUND: Possible changes in the incidence and outcome of cardiac rupture in patients with ST-elevation myocardial infarction over a long period of time have not been investigated. METHODS AND RESULTS: The incidence of cardiac rupture in ST-elevation myocardial infarction patients and its mortality rate were investigated during a 30-year period divided into 5 intervals (1977 to 1982, 1983 to 1988, 1989 to 1994, 1995 to 2000, and 2001 to 2006). Of a total of 6678 consecutive patients, 425 experienced a free wall rupture (280 with cardiac tamponade: 227 with electromechanical dissociation and 53 with hypotension) or a septal rupture (145). After the exclusion of referrals from other centers (n=44), the incidence of definite cardiac rupture (septal rupture, anatomic evidence of free wall rupture, or electromechanical dissociation) declined progressively (6.2% in 1977 to 1982 to 3.2% in 2001 to 2006; P<0.001) in parallel with a progressive use of reperfusion therapy (0% to 75.1%; P<0.001). In addition, among patients with cardiac rupture, there was a progressive fall in the rate of death (94% to 75%; P<0.001) despite a trend toward increasing age (66+/-8 to 75+/-8 years; P<0.054) in conjunction with better control of systolic blood pressure at 24 hours (130+/-24 versus 110+/-18 mm Hg; P<0.001); an increased use of reperfusion therapy (0% to 59%; P<0.001), beta-blockers (0% to 45%; P<0.001), angiotensin-converting enzyme inhibitors (0% to 38%; P<0.001), and aspirin (0% to 96%; P<0.001); and a lower use of heparin (99% to 67%; P<0.001). CONCLUSIONS: The decline in the incidence in cardiac rupture and its rate of death over the last 30 years appears to be associated with the increasing use of reperfusion strategies and adjunct medical therapy.

Extent of myocardial ischemia during coronary occlusion in single vessel disease. A comparison between patients with exercise-induced angina and patients with recurrent angina at rest.

Patients with exercise angina >2 months (n:13) showed significantly lower SigmaST elevation during 120 s balloon coronary occlusion than those with =<2 months (n:7), or those with angina at rest <=2 days (n:8) but similar to patients with angina at rest >2 days (n:7). These results underscore the importance of the kind and duration of angina in limiting the extent of ischemia during coronary occlusion.

Effect of clinical variables on the correlation between amount of ST elevation and myocardial scintigraphic perfusion defect during coronary occlusion.

PURPOSE: We investigated if the correlation between the amount of ST elevation (STE) and myocardial ischemia could be altered by variables such as hypertension or body mass index (BMI). METHODS: A 12-lead electrocardiogram and a technetium-99m tetrofosmin injection were performed during balloon coronary occlusion in 34 patients with single-vessel disease. RESULTS: The sum of STE correlated with scintigraphic extent of ischemia (r = 0.441; P = .009), but this correlation improved significantly in men and patients with BMI of 28 kg/m2 or less and was highest in nonhypertensive patients (r = 0.763; P < .001). In contrast, it was poor in women and patients with BMI greater than 28 kg/m2 or arterial hypertension, being lowest in the latter subset (r = 0.110; P = .664). Moreover, 8 (80%) of 10 patients with extensive hypoperfusion but with low SigmaSTE (< or =20 mm) were hypertensive. CONCLUSIONS: If confirmed by larger studies, electrocardiographic underestimation of transmural ischemia during coronary occlusion in patients with hypertension or increased BMI may lead to adjustments in STE criteria for reperfusion therapy.

Predischarge low-dose dobutamine test and prediction of left ventricular function at 1 year in patients with a first anterior myocardial infarction.

BACKGROUND: It is unclear whether spontaneous improvement in contractility following acute myocardial infarction (AMI) is related to severity of predischarge systolic dysfunction and can be predicted by isotopic ventriculography with a low-dose dobutamine test (DBT). HYPOTHESIS: Spontaneous improvement in contractility would be similar in patients with more preserved and those with depressed ventricular function, and a DBT test could predict it. METHODS: Left ventricular ejection fraction (LVEF), regional contractility score (RCS), and left ventricular end-diastolic volume index (EDVI) at predischarge, during DBT, and at 1 year were analyzed in 43 patients with a first anterior ST-elevation AMI. RESULTS: Changes produced by DBT in patients with LVEF < 40%, RCS > or = 3, or EDVI > or = 70 ml/m2 were smaller than in those observed at 1 year (LVEF: 30 +/- 5-35 +/- 7%, p < 0.001, vs. 39 +/- 10%, p = 0.005; RCS: 4.9 +/- 1.4-4.6 +/- 2.0, NS, vs. 3.4 +/- 2.0, p < 0.02; EDVI: 92 +/- 14-86 +/- 22, NS, vs. 78 +/- 23 ml/m2, p < 0.03). In contrast, in patients with EF > or = 40%, RCS < 3 or EDVI < 70 ml/m2, changes with DBT tended to be greater than those observed at 1 year (LVEF: 52 +/- 8-57 +/- 11%, p < 0.004 vs. 55 +/- 11%, p < 0.04); RCS: 1.1 +/- 0.9-0.8 +/- 0.8, NS, vs. 1.1 +/- 1.1, NS; and EDVI: 51 +/- 9-47 +/- 11, p < 0.005, vs. 54 +/- 13 ml/m2, NS). CONCLUSIONS: Among patients with a first anterior AMI, spontaneous improvement in contractility at 1 year was greatest in those with a more depressed ventricular function or a dilated ventricle, but its magnitude was underestimated by a predischarge DBT test.

Comparison of clinical and angiographic features and longterm follow-up events between patients with variant angina and patients with ST elevation myocardial infarction.

We investigated to what extent patients with variant angina and significant coronary stenosis (>or=70%) present a clinical and angiographic profile similar to patients with ST elevation myocardial infarction. Thus, the clinical and angiographic features as well as follow-up events of 200 patients were prospectively analyzed and were compared with those of 422 patients with a first ST elevation myocardial infarction survivors of the early phase (3 days) and those of 70 patients with variant angina and non significant stenosis. Age and incidence of smoking, systemic hypertension, diabetes and maximum ST elevation were similar in the 2 groups. Furthermore, among patients with significant coronary stenosis, stenosis severity and the proportion of eccentric lesions were also comparable. Incidence of recent-within 30 days prior to admission-angina at rest was higher in variant angina patients with significant stenosis (67% vs. 27%, p<0.001) than in those with myocardial infarction but long standing angina at rest (>30 days) was low and comparable in these 2 groups (15% vs. 11%, ns). Also, in a 5-year follow-up most patients from these 2 groups were free from angina at rest (86% vs. 84%) which in variant angina patients was largely attributable to a high revascularization rate (72%). Moreover, the rate of myocardial infarction/cardiac death (20% vs. 19%) was also similar. Patients with variant angina and non-significant stenosis, however, had longer antecedent angina, more frequent follow-up angina and a lower incidence of cardiac events than the other 2 groups. Thus, these findings suggest that patients with variant angina and significant coronary stenosis generally behave as an acute coronary syndrome-likely associated with an acutely complicated plaque-rather than as recurrent vasospastic angina, and should be managed accordingly.

Early negative T waves and viable myocardium in patients with a first ST-elevation acute coronary syndrome.

Deep negative T waves (NTW) are a frequent finding following acute ST-segment elevation coronary syndromes but its possible relation with the status of regional contractility remains unclear. We studied 52 patients with a first ST-elevation acute coronary syndrome with or without NTW in anterior leads (> or =3 mm in > or=3 leads) and assessed the ejection fraction and regional myocardial contractility by contrast left ventriculography at baseline and during a low-dose dobutamine test (10 microg/kg per minute). Ejection fraction and regional contractility tended to be more preserved in patients with NTW, but dobutamine increased regional contractility in the jeopardized area in most patients with or without NTW and the improvement was similar in those either with or without enzyme elevation. In conclusion, deep NTW after ST-elevation acute coronary syndromes tends to be associated with a more preserved myocardium but it is neither a sensitive nor a specific marker of viable myocardium.

Comparison of plasma serotonin levels in patients with variant angina pectoris versus healed myocardial infarction.

Patients with variant angina pectoris showed greater serotonin plasma levels than did control subjects and patients with healed myocardial infarction. The levels also tended to be greater in those with >1 episode/month than in those with fewer episodes. Moreover, patients with variant angina pectoris also had greater levels of nitrite and nitrate plasma levels than did control subjects or patients with healed myocardial infarction, partly, perhaps, as a compensatory mechanism.

Relevance of multivessel disease in the development of in-hospital refractory angina and myocardial infarction in patients with unstable angina.

We investigated the relationship between clinical, electrocardiographic and angiographic characteristics with development of refractory angina and acute myocardial infarction (AMI) in 976 consecutive patients with unstable angina (UA). AMI occurred in 63 (6%) and recurrent angina in 384 (39%), 201 of whom had >2 episodes (refractory, 21%). Patients with AMI were older (P<0.001) and had a higher rate of smoking (P<0.02), previous cerebrovascular accident (P<0.02), abnormal ST segment on admission (P<0.002), refractory angina (P<0.001) and multivessel disease (P<0.005) than those without AMI. Patients with refractory angina were older (P<0.001) and showed a higher incidence of abnormal ST segment on admission (P<0.001) and multivessel disease (P<0.001) than those without. A multivariate analysis, however, showed that refractory angina (P<0.0001), and multivessel disease (P<0.001) were the strongest predictors of AMI while age and multivessel disease were the strongest predictors of refractory angina (P<0.003). Thus, multivessel disease was the most frequent substrate of refractory angina and AMI in patients with UA. These findings may suggest that significant coronary stenosis in non-culprit arteries may facilitate recurrence of ischemia/AMI perhaps by reacting in concert with the culprit lesion and causing a further reduction of the ischemic threshold.

ST segment elevation at 72 hours in patients with a first anterior myocardial infarction best correlates with pre-discharge and 1-year regional contractility and ventricular dilatation.

AIMS: To analyse the relationship between the in-hospital course of ST segment elevation (STE) and negative T wave (NTW) with ejection fraction, regional contractility and left ventricular end-diastolic volume at pre-discharge and at 1 year in patients with a first anterior STE acute myocardial infarction (AMI). METHODS AND RESULTS: ECG changes were measured during hospitalization and at 1 year whereas ejection fraction, regional contractility score and end-diastolic volume index were measured by isotopic ventriculography at pre-discharge and at 1 year. At 72h but not earlier patients with SigmaSTE >0.6mV (group A, n: 35) had a lower ejection fraction (P<0.001), a higher regional contractility score (P<0.001) and a larger end-diastolic volume index (P<0.001) at discharge than those with <0.6mV (group B, n: 26). Negative T wave did not provide additional information. At 1 year, group A continued to show a more impaired ejection fraction and regional contractility than group B and a larger end-diastolic volume. CONCLUSION: Although reportedly changes in STE within the first hours correlate with coronary reperfusion our findings indicate that additional assessment of STE as early as at 72h correlates with wall motion, ejection fraction and ventricular dilatation at discharge and at 1 year.

Prognostic value of lead aVR in patients with a first non-ST-segment elevation acute myocardial infarction.

BACKGROUND: ST-segment elevation in lead aVR has been associated with severe coronary artery lesions in patients with acute coronary syndromes, but the prognostic significance of this finding is unknown. METHODS AND RESULTS: We analyzed the initial ECG in 775 consecutive patients admitted to our center with a first acute myocardial infarction without ST-segment elevation in leads other than aVR or V1. The rates of in-hospital death in patients without (n=525) and with 0.05 to 0.1 mV (n=116) or > or =0.1 mV (n=134) of ST-segment elevation in lead aVR were 1.3%, 8.6%, and 19.4%, respectively (P<0.001). After adjustment for the baseline clinical predictors and for ST-segment depression on admission, the odds ratios for death in the last 2 groups were, respectively, 4.2 (95% CI, 1.5 to 12.2) and 6.6 (95% CI, 2.5 to 17.6). The rates of recurrent ischemic events and heart failure during hospital stay also increased in a stepwise fashion among the groups, whereas creatine kinase-MB levels were similar. Among the 437 patients that were catheterized within 6 months, the prevalence of left main or 3-vessel coronary artery disease in the 3 groups was 22.0%, 42.6%, and 66.3%, respectively (P<0.001). CONCLUSIONS: Lead aVR contains important short-term prognostic information in patients with a first non-ST-segment elevation acute myocardial infarction. Because the poorer outcome predicted by ST-segment elevation in lead aVR seems to be related to a more severe coronary artery disease, an early invasive approach might be especially beneficial in patients presenting with this finding.

Nature and progression of pericardial effusion in patients with a first myocardial infarction: relationship to age and free wall rupture.

BACKGROUND: Left ventricular free wall rupture (FWR) usually develops within the first days of acute myocardial infarction (AMI) without warning, but it is uncertain whether a mild pericardial effusion might herald this complication. METHODS: A 2-dimensional echocardiogram (2DE) was performed in patients with first AMI with (1149) or without (324) ST-segment elevation within 2 days. A second 2DE was performed 2 to 4 days later in 300 patients, 100 with and 200 without an initial mild PE (3-9 mm), and in those with initial moderate-severe PE (> or =10 mm) (MSPE) or who developed hypotension or died. RESULTS: The first 2DE showed mild PE in 177 patients and MSPE in 51 patients, whereas a late (>2 days) MSPE occurred in 27 with a second routine 2DE, 15 (15%) with and 12 (6%) without initial mild PE (P =.01). Fourteen additional patients, 5 of 77 (6%) with and 9 of 1045 (1%) without initial PE, presented with hypotension and late MSPE (P <.002). Of 92 patients with MSPE, 90 had ST-segment elevation (98%), 60 had tamponade (65%), and 38 died of FWR or were operated on (41%). Results of pericardiocentesis performed in 64 patients were positive in 58, with hemopericardium in 57 (98%). Multivariant analysis showed mild PE on first 2DE and age of >60 years as the only independent predictors of late MSPE or late tamponade. CONCLUSIONS: Mild PE within the first 2 days in patients aged >60 years with a first ST-segment elevation AMI is associated with an increased risk of late MSPE. Moreover, in this setting MSPE is most frequently associated with hemopericardium, and two thirds of these patients may develop tamponade/FWR.