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Recurrent ischemia during continuous 12-lead ECG-ischemia monitoring in patients with acute coronary syndromes treated with eptifibatide: relation with death and myocardial infarction. PURSUIT ECG-Ischemia Monitoring Substudy Investigators. Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy
Abstract
Computer-assisted continuous monitoring of the ST-segment allows detection and quantification of recurrent ischemia in patients with acute coronary syndromes. In a substudy of the PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy) trial, this technique was used to evaluate the effects of the glycoprotein IIb/IIIa inhibitor eptifibatide on the incidence and severity of recurrent ischemia, and to investigate the relationship between recurrent ischemia and the occurrence of subsequent death or myocardial (re)infarction. A total of 258 patients with unstable angina or evolving myocardial infarction without ST elevation were monitored for 24 hours during infusion with either eptifibatide or placebo with a computer-assisted 12-lead ECG-ischemia monitoring device. Recurrent ischemic episodes were identified by an automated computer algorithm. Two hundred and sixteen patients (84%) had ECG recordings suitable for analysis. Ischemic episodes were detected in 35 (33%) of the 105 eptifibatide patients and in 32 (29%) of the 111 placebo patients (not significant). No difference in ischemic burden was apparent between both treatment groups. Patients who exhibited 2 or more episodes of recurrent ischemia more frequently died or suffered a myocardial infarction, both at 7 and 30 days, as well as through the 6-month follow-up. A greater ischemic burden was significantly related to adverse outcome during the 6-month follow-up period. Real-time computer-assisted continuous multilead ECG-ischemia monitoring may help to identify patients with unstable coronary syndromes at increased risk of adverse outcome and, thus, allow for better prognostic triage and more appropriate selection of therapeutic strategies. Integration of these systems in coronary care units and emergency wards should, therefore, be recommended.
... More recently, investigators 9,12-14 have used this technology to verify reperfusion via anticoagulant and thrombolytic therapies. Other researchers found that continuous ST-segment monitoring was beneficial in verifying the effectiveness of interventions such as percutaneous interventions, 15 platelet inhibitors, 6,7,16 and even intensive insulin therapy. 17 Detecting ischemia is of paramount importance because silent ischemia is common in hospitalized patients. ...
... [1][2][3] Continuous ST-segment monitoring is a reliable and accurate clinical diagnostic tool for detection of cardiac ischemia among hospitalized patients 4,5 and enables detection of patients at higher risk for adverse cardiac events. [6][7][8][9] caused by vasospasm rather than by occlusion). In summary, despite these consensus statements and practice guidelines, just over half of critical care units in the United States appear to be using continuous ST-segment monitoring. ...
... This benefit may have the widest recognition by cardiologists because of its breadth of supporting studies. 1,3,7,8,18,31 The next 2 benefits, early detection of reocclusion after percutaneous coronary interventions and after reperfusion via fibrinolytics, received higher agreement ratings by cardiologists whose practicing hospitals had continuous ST-segment practice standards. ...
Continuous ST-segment monitoring can be used to detect early and transient cardiac ischemia. The American Heart Association and American Association of Critical-Care Nurses recommend its use among specific patients, but such monitoring is routine practice in only about half of US hospitals.
To determine cardiologists' awareness and practice standards regarding continuous ST-segment monitoring and the physicians' perceptions of appropriate patient selection, benefits and barriers, and usefulness of this technology.
An electronic survey was sent to a random sample of 915 US cardiologists from a pool of 4985 certified cardiologists.
Of 200 responding cardiologists, 55% were unaware of the consensus guidelines. Of hospitals where respondents admitted patients, 49% had a standard of practice for using continuous ST-segment monitoring for cardiac patients. Most cardiologists agreed or strongly agreed that patients in the cardiovascular laboratory (87.5%) and intensive care unit (80.5%) should have such monitoring. Cardiologists routinely ordered ST monitoring for patients with acute coronary syndrome (67%) and after percutaneous coronary intervention (60%). The primary factor associated with higher perceptions for benefits, clinical usefulness, and past use of continuous ST-segment monitoring was whether or not hospitals in which cardiologists practiced had a standard of practice for using this monitoring. A secondary factor was awareness of published consensus guidelines for such monitoring.
Respondents (55%) were unaware of published monitoring guidelines. Hospital leaders could raise awareness by multidisciplinary review of evidence and possibly incorporating continuous ST-segment monitoring into hospitals' standards of practice.
... Continuous monitoring of ST segments in real time allows accurate prediction of prognosis of critically ill patients, including patients experiencing acute coronary syndrome (ACS). [5][6][7][8][9] Additionally, continuous ST-segment monitoring among cardiac patients has been useful for evaluating the effectiveness of interventions such as administration of thrombolytic agents [10][11][12] or platelet inhibitors [13][14][15] and percutaneous interventions, 8,16 as well as for detection of perioperative ischemia. 17,18 Fesmire 19 evaluated whether STsegment monitoring via serial ECGs colleagues: specifically for continuous ST-segment monitoring in 1999 20 and more comprehensive guidelines for cardiac monitoring in 2004. ...
What is the issue?People with chronic kidney disease (CKD) have an increased risk of heart disease that can block the blood supply to the heart or brain causing a heart attack or stroke. Drugs that prevent blood clots from forming (antiplatelet agents) can prevent deaths caused by clots in arteries in the general adult population. However, there may be fewer benefits for people who have CKD, because blood clots in arteries is a less common cause of death or reason to be admitted to hospital compared with heart failure or sudden death in these people. People with CKD also have an increased tendency for bleeding due to changes in how the blood clots. Antiplatelet agents may therefore be more hazardous when CKD is present. What did we do? This updated review evaluated the benefits and harms of antiplatelet agents to prevent cardiovascular disease and death, and the impact on dialysis vascular access (fistula or graft) function in people who have CKD. We identified 90 studies comparing antiplatelet agents with placebo or no treatment and 29 studies directly comparing one antiplatelet agent with another. What did we find?Antiplatelet agents probably prevent heart attacks, but do not clearly reduce death or stroke. Treatment with these agents may increase the risk of major and minor bleeding. Clotting of dialysis access was prevented with antiplatelet agents. Conclusions
The benefits of antiplatelet agents for people with CKD is probably limited to the prevention of a heart attack. The treatment does not appear to prevent stroke or death and probably incurs excess serious bleeding that may require hospital admission or transfusion.
Aims and objectivesTo confirm the accuracy of the EASI system compared to the standard 12-lead electrocardiogram, which is the gold standard, in monitoring the two major parameters used in the Coronary Care Units to detect myocardial ischaemia: ST-segment and J-point. Background
Continuous electrocardiograph monitoring is used in the Coronary Care Units to detect cardiac conduction abnormalities and to show the morphology of electrocardiographic waves and tracts. Its accuracy is essential for efficient nursing vigilance, particularly for monitoring the ST segment and the J-point, in which alterations may indicate the onset of myocardial ischaemia. DesignAn observational study was conducted. Methods
The enrolled patients (n=253) simultaneously underwent standard electrocardiogram (10 electrodes) and EASI electrocardiogram (five electrodes). Data were collected by the Coronary Care Units nurses. Tests to compare differences in means and medians between the two sets of measurements wereperformed, and the Bland-Altman plots were used to illustrate their agreement. ResultsAll 6072 electrocardiographic leads (3036 standard and 3036 EASI) were recorded and analysed. Between the two measurement methods, very small statistically significant differences were found in some leads which are not clinically relevant for both the ST-segment or the J-point. Conclusions
This study confirms that the accuracy of the EASI 12-leadelectrocardiogram, compared to the standard 12-leadelectrocardiogram, which is the gold standard, is acceptable for clinical practice to monitor the two major parameters used in the Coronary Care Units for detecting myocardial ischaemia: ST-segment and J-point. Relevance to clinical practiceThe EASI system ensures: (1) ease of use and comfort for patients admitted to Coronary Care Units because it only requires five electrodes; (2) increased efficacy of nursing vigilance in the early detection of changes in ST-segment and J- point measurements.
Patients with acute coronary syndromes (ACS) are at increased risk of death, and non-fatal MI. Rapid diagnosis and accurate risk stratification facilitates delivery of prompt and appropriate therapy, improving outcomes. Patients with symptoms of myocardial ischaemia, occurring in an accelerating pattern or at rest, but without ST-segment elevation or new LBBB on the electrocardiogram (ECG), should be considered to have unstable angina/non ST-segment elevation myocardial infarction (UA/NSTEMI) until proven otherwise. This is true even if the initial ECG and cardiac enzymes are normal. An ischaemic ECG or elevated cardiac enzymes confirms the diagnosis. Patients with definite UA/NSTEMI should be stratified as high, intermediate or low risk. Risk stratification guides both the pace of further investigation, and the selection of therapy. Risk stratification starts at the time of admission, and uses clinical, ECG and cardiac markers. High risk patients (recurrent pain, ST-segment shift, or positive cardiac markers) benefit from an invasive management strategy, and should proceed to early angiography. Patients initially considered at low or intermediate risk do not necessarily benefit from an early invasive management strategy, and their prognosis may be better with medical therapy. These patients should be repeatedly reassessed for changes in symptoms, ECG, and cardiac markers, and have non-invasive functional tests in order to identify the subset of patients who are at high risk of cardiac events.
Background, purpose
The efficacy of the transtelephonic ECG system (TTECG) in the management of ST segment elevation myocardial infarction (STEMI) was examined with regard to the ambulance service- and percutaneous coronary intervention (PCI)-related delay times, the prehospital medical therapy and the in-hospital mortality rate.
Methods
The study was conducted as a collaborative effort between the University of Debrecen and the Hungarian National Ambulance Service. Altogether 397 patients were recruited in the TTECG group, while 378 patients transported to the PCI centre without TTECG served as controls.
Results
More accurate prehospital medical therapy was achieved in the TTECG group. The PCI-related delay times were significantly shorter, while the in-hospital mortality rate was significantly lower in the TTECG group than among the controls.
Conclusions
The findings illustrate that TTECG is a valuable tool which may potentially improve the regional management of STEMI patients.
Background: Recurrent ischemia is frequent in patients with non-ST-elevation acute coronary syndromes (NST-ACS), and portends a worse prognosis. Continuous ST-segment monitoring (CSTM) reflects the dynamic nature of ischemia and allows the detection of silent episodes. The aim of this study is to investigate whether CSTM adds prognostic information to the risk scores (RS) currently used.
Methods: We studied 234 patients with NST-ACS in whom CSTM was performed in the first 24 hours after admission. An ST episode was defined as a transient ST-segment deviation in ≥1 lead of ≥ 0.1 mV, and persisting ≥1 minute. Three RS were calculated: Thrombolysis in Myocardial Infarction (TIMI; for NST-ACS), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Supression Using Integrilin (PURSUIT; death/MI model), and Global Registry of Acute Coronary Events (GRACE). The end point was defined as death or nonfatal myocardial infarction (MI), during 1-year follow-up.
Results: ST episodes were detected in 54 patients (23.1%) and associated with worse 1-year outcome: 25.9% end point rate versus 12.2% (Odds Ratio [OR]= 2.51; 95% Confidence Interval [CI], 1.18–5, 35; P = 0.026). All three RS predicted 1-year outcome, but the GRACE (c-statistic = 0.755; 95% CI, 0.695–0.809) was superior to both TIMI (c-statistic = 0.632; 95% CI, 0.567–0.694) and PURSUIT (c-statistic = 0.644; 95% CI: 0.579–0.706). A GRACE RS > 124 showed the highest accuracy for predicting end point. The presence of ST episodes added independent prognostic information the TIMI RS (hazard ratio [HR]= 2.23; 95% CI, 1.13–4.38) and to PURSUIT RS (HR = 2.03; 95% CI, 1.03–3.98), but not to the GRACE RS.
Conclusions: CSTM provides incremental prognostic information beyond the TIMI and PURSUIT RS, but not the GRACE risk score. Hence, the GRACE risk score should be the preferred stratification model in daily practice.
Ann Noninvasive Electrocardiol 2011;16(3):239–249
Recurrent ischaemia, detected by continuous ECG monitoring, in patients with unstable angina increases the risk of unfavourable outcome. Studies that evaluated this relationship have been limited by the small series of patients. By combining data from three studies, the present analysis aims to provide an accurate assessment of the impact of recurrent ischaemia detected by multilead ECG-ischaemia monitoring on the occurrence of death and myocardial infarction in patients with acute coronary syndromes.
Data were obtained from CAPTURE, PURSUIT and FROST, three trials evaluating glycoprotein IIb/IIIa blockers in patients with non-ST-elevation acute coronary syndromes. Patients were monitored for 24 h after enrollment with a computer-assisted 12-lead or a vectorcardiographic ECG-ischaemia monitoring device. In a retrospective blinded analysis, recurrent ischaemic episodes were identified by a computer algorithm. The number of ischaemic episodes was normalized to 24 h. Ischaemic episodes were detected in 271 (27%) of 995 patients. There was a direct proportional relationship between the number of ischaemic episodes per 24 h and the probability of cardiac events at 5 and 30 days. The 30-day composite of death and myocardial infarction occurred in 5.7% of patients without episodes and increased to 19.7% in patients with >/=5 episodes. After adjustment for baseline predictors of adverse outcome, the relative risk of death or myocardial infarction at 5 and 30 days increased by 25% for each additional ischaemic episode per 24 h.
This analysis emphasizes the need for integration of multilead ECG-ischaemia monitoring systems in coronary care units and emergency wards to improve early risk stratification in patients with acute coronary syndromes.
Patients with non-ST-segment elevation acute coronary syndromes constitute a heterogeneous group concerning prognosis. The 12-lead ECG at rest is recommended for early risk stratification but is unable to reflect the dynamic nature of myocardial ischemia and coronary thrombosis. This study investigated whether continuous ST-segment monitoring provides early prognostic information in such patients.
We prospectively studied 183 patients admitted due to chest pain at rest suggestive of an acute coronary syndrome. ST-segment monitoring was performed continuously for 24 hours from admission. Cardiac-specific troponin I levels were determined on admission and every 6 hours for the first 24 hours. The endpoint was defined as death or nonfatal myocardial infarction, whichever occurred first by 30 days follow-up.
ST episodes, defined as transient ST deviations of at least 0.1 mV, were detected in 50 patients (27.3%) and associated with worse 30-day outcome: 22.0% endpoint rate compared to 6.8% for patients without ST episodes (P = 0.003). In a multivariate analysis, the presence of ST episodes (hazard ratio, 3.07; 95% CI, 1.26 to 7.46; P = 0.014) and peak troponin I levels > 0.2 microg/L (hazard ratio, 2.65; 95% CI, 1.01 to 6.95; P = 0.048) were independent predictors of prognosis. The combination of ST-segment monitoring and peak troponin I identified patients at low (2.5%, n = 79), intermediate (14.5%, n = 76), and high (25.0%, n = 28) risk for the 30-day endpoint.
In patients with non-ST-segment elevation acute coronary syndromes, continuous ST-segment monitoring provides on-line early prognostic information, in addition to troponin I levels.
We investigated predictors of 90-day risk among patients surviving the early period after an acute coronary syndrome (ACS).
The study population included 15 904 stabilized ST-segment elevation or non-ST-segment elevation ACS patients randomized in SYMPHONY and 2nd SYMPHONY. We developed risk models for death, death or myocardial infarction (MI), and death, MI, or severe recurrent ischaemia (SRI) using Cox proportional-hazards techniques. Demographic, history, and pre-randomization clinical and medication variables were tested. Validation techniques included development of individual trial models, backward elimination and bootstrapping. Of 118 variables, 17 independently predicted mortality. The strongest associations included greater age (chi(2)=31.1), higher randomization heart rate (chi(2)=27.4), and heart failure (HF) variables (HF between qualifying event and randomization, chi(2)=21.8; history of HF, chi(2)=12.2). Higher creatinine clearance (chi(2)=17.7) and percutaneous coronary intervention between qualifying event and randomization (chi(2)=11.1) most strongly predicted lower risk. Similar characteristics entered the double and triple composite models, but HF variables and age less strongly predicted these end-points.
In patients stabilized after ACS, those at highest risk over the next 90 days can be identified. Typical clinical markers are better at identifying risk of death than non-fatal MI or SRI. Novel risk markers are needed for these outcomes.
ST-segment analyses from electrocardiograms during acute coronary syndromes (ACS) have repeatedly shown strong mechanistic links to coronary artery patency and myocardial reperfusion. In these patients, such analyses have also consistently been reported to have close correlations with outcome--correlations superior even to those reported for invasive coronary flow measurements and outcome. Continuous multilead ST-monitoring of patients with ACS provides accurate and noninvasive information on the dynamics of the myocardial reperfusion process over time. This information can be used for improved early diagnostic accuracy, evaluation of treatment efficacy, early risk-stratification, and can be supportive in clinical decision making regarding these patients. Continuous multilead ST-monitoring during ACS is no longer a cumbersome source of more nuisance than benefit, but can be an accurate and useful tool in multicenter clinical trials, as well as in clinical medicine.
Background:
In patients with refractory unstable angina, the platelet glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of cardiac events before and during coronary angioplasty. We investigated whether serum troponin T levels identify patients most likely to benefit from therapy with this drug.
Methods:
Among 1265 patients with unstable angina who were enrolled in the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) trial, serum samples drawn at the time of randomization to abciximab or placebo were available from 890 patients; we used these samples for the determination of troponin T and creatine kinase MB levels. Patients with postinfarction angina were not included.
Results:
Serum troponin T levels at the time of study entry were elevated (above 0.1 ng per milliliter) in 275 patients (30.9 percent). Among patients receiving placebo, the risk of death or nonfatal myocardial infarction was related to troponin T levels. The six-month cumulative event rate was 23.9 percent among patients with elevated troponin T levels, as compared with 7.5 percent among patients without elevated troponin T levels (P<0.001). Among patients treated with abciximab, the respective six-month event rates were 9.5 percent for patients with elevated troponin T levels and 9.4 percent for those without elevated levels. As compared with placebo, the relative risk of death or nonfatal myocardial infarction associated with treatment with abciximab in patients with elevated troponin T levels was 0.32 (95 percent confidence interval, 0.14 to 0.62; P=0.002). The lower event rates in patients receiving abciximab were attributable to a reduction in the rate of myocardial infarction (odds ratio, 0.23; 95 percent confidence interval, 0.12 to 0.49; P<0.001). In patients without elevated troponin T levels, there was no benefit of treatment with respect to the relative risk of death or myocardial infarction at six months (odds ratio, 1.26; 95 percent confidence interval, 0.74 to 2.31; P=0.47).
Conclusions:
The serum troponin T level, which is considered to be a surrogate marker for thrombus formation, identifies a high-risk subgroup of patients with refractory unstable angina suitable for coronary angioplasty who will particularly benefit from antiplatelet treatment with abciximab.
The prognosis of patients hospitalized with acute myocardial ischemia is quite variable. We examined the value of serum levels of cardiac troponin T, serum creatine kinase MB (CK-MB) levels, and electrocardiographic abnormalities for risk stratification in patients with acute myocardial ischemia.
We studied 855 patients within 12 hours of the onset of symptoms. Cardiac troponin T levels, CK-MB levels, and electrocardiograms were analyzed in a blinded fashion at the core laboratory. We used logistic regression to assess the usefulness of baseline levels of cardiac troponin T and CK-MB and the electrocardiographic category assigned at admission-ST-segment elevation, ST-segment depression, T-wave inversion, or the presence of confounding factors that impair the detection of ischemia (bundle-branch block and paced rhythms)-in predicting outcome.
On admission, 289 of 801 patients with base-line serum samples had elevated troponin T levels (> 0.1 ng per milliliter). Mortality within 30 days was significantly higher in these patients than in patients with lower levels of troponin T (11.8 percent vs. 3.9 percent, P < 0.001). The troponin T level was the variable most strongly related to 30-day mortality (chi-square = 21, P < 0.001), followed by the electrocardiographic category (chi-square = 14, P = 0.003) and the CK-MB level (chi-square = 11, P = 0.004). Troponin T levels remained significantly predictive of 30-day mortality in a model that contained the electrocardiographic categories and CK-MB levels (chi-square = 9.2, P = 0.027).
The cardiac troponin T level is a powerful, independent risk marker in patients who present with acute myocardial ischemia. It allows further stratification of risk when combined with standard measures such as electrocardiography and the CK-MB level.
It can now be appreciated that there are two quite different processes encompassed by the term 'plaque haemorrhage.' The fact that the media behind plaques becomes intensely vascularised and that these vessels enter the intima is beyond dispute. Bleeding from such vessels crossing the media causes a limited number of red cells to lie free within the lipid pool of many plaques. No fibrin or platelets are present, and the process is almost ubiquitous in large lipid rich plaques. The second process is the presence of large numbers of red cells, masses of platelets, and considerable amounts of fibrin within the plaque. If serial histological sections are used these elements can be traced to an entry into the lumen via a fissure, although this may be closed by a mass of thrombus. The two processes must be clearly separated and the term intraplaque thrombosis is more applicable to that associated with fissures from the lumen. It is plaque fissuring with related intraintimal thrombosis progressing to the formation of an intraluminal thrombus that is the important dynamic process unifying crescendo agina, acute myocardial infarction, and sudden ischaemic death. It is difficult to escape the conclusion that the failure of pathologists to think in terms of dynamic processes and to believe what was seen at necropsy was an immutable reflection of events in life that occurred days before has seriously hindered the understanding by clinicians of how atheroma produces acute clinical symptoms.
The recent international GUSTO trial of 41,021 patients with acute myocardial infarction demonstrated improved 90-min infarct related artery patency as well as reduced mortality in patients treated with an accelerated regimen of tissue plasminogen activator, compared to patients treated with streptokinase. A regimen combining tissue plasminogen activator and streptokinase yielded intermediate results. The present study investigated the effects of treatment on infarct size and enzyme release kinetics in a subgroup of these patients.
A total of 553 patients from 15 hospitals were enrolled in the study. Four thrombolytic strategies were compared: streptokinase with subcutaneous heparin, streptokinase with intravenous (i.v.) heparin, tissue plasminogen activator with i.v. heparin, and streptokinase plus tissue plasminogen activator with i.v. heparin. The activity of alpha-hydroxybutyrate dehydrogenase (HBDH) in plasma was centrally analysed and infarct size was defined as cumulative HBDH release per litre of plasma within 72 h of the first symptoms (Q(72)). Patency of the infarct-related vessel was determined by angiography in 159 patients, 90 min after treatment.
Infarct size was 3.72 g-eq.1(-1) in patients with adequate coronary perfusion (TIMI-3) at the 90 min angiogram and larger in patients with TIMI-2 (4.35 g-eq.1(-1) or TIMI 0-1 (5.07 g-eq.1(-1) flow (P = 0.024). In this subset of the GUSTO angiographic study, early coronary patency rates (TIMI 2 + 3) were similar in the two streptokinase groups (53 and 46%). Higher, but similar, patency rates were observed in the tissue plasminogen activator and combination therapy groups (87 and 90%). Median infarct size for the four treatment groups, expressed in gram-equivalents (g-eq) of myocardium, was 4.4, 4.5, 3.9 and 3.9 g-eq per litre of plasma (P = 0.04 for streptokinase vs tissue plasminogen activator). Six hours after the first symptoms, respectively 5.3, 6.6, 14.0 and 13.6% of total HBDH release was complete (P < 0.0001 for streptokinase vs tissue plasminogen activator).
Rapid and complete coronary reperfusion salvages myocardial tissue, resulting in limitation of infarct size and accelerated release of proteins from the myocardium. Treatment with tissue plasminogen activator, resulting in earlier reperfusion was more effective in reducing infarct size than the streptokinase regimens, which contributes to the differences in survival between treatment groups in the GUSTO trial.
In patients with acute coronary syndromes, it is desirable to identify a sensitive serum marker that is closely related to the degree of myocardial damage, provides prognostic information, and can be measured rapidly. We studied the prognostic value of cardiac troponin I levels in patients with unstable angina or non-Q-wave myocardial infarction.
In a multicenter study, blood specimens from 1404 symptomatic patients were analyzed for cardiac troponin I, a serum marker not detected in the blood of healthy persons. The relation between mortality at 42 days and the level of cardiac troponin I in the specimen obtained on enrollment was determined both before and after adjustment for baseline characteristics.
The mortality rate at 42 days was significantly higher in the 573 patients with cardiac troponin I levels of at least 0.4 ng per milliliter (21 deaths, or 3.7 percent) than in the 831 patients with cardiac troponin I levels below 0.4 ng per milliliter (8 deaths, or 1.0 percent; P < 0.001). There were statistically significant increases in mortality with increasing levels of cardiac troponin I (P < 0.001). Each increase of 1 ng per milliliter in the cardiac troponin I level was associated with a significant increase (P = 0.03) in the risk ratio for death after adjustment for the base-line characteristics that were independently predictive of mortality (ST-segment depression and age > or = 65 years).
In patients with acute coronary syndromes, cardiac troponin I levels provide useful prognostic information and permit the early identification of patients with an increased risk of death.
The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia.
We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the first > or = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately.
ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P < 0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P < 0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P < 0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively.
Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended.
Evaluation of patients with acute chest pain in emergency rooms is time-consuming and expensive, and it often results in uncertain diagnoses. We prospectively investigated the usefulness of bedside tests for the detection of cardiac troponin T and troponin I in the evaluation of patients with acute chest pain.
In 773 consecutive patients who had had acute chest pain for less than 12 hours without ST-segment elevation on their electrocardiograms, troponin T and troponin I status (positive or negative) was determined at least twice by sensitive, qualitative bedside tests based on the use of specific monoclonal antibodies. Testing was performed on arrival and four or more hours later so that one sample was taken at least six hours after the onset of pain. The troponin T results were made available to the treating physicians.
Troponin T tests were positive in 123 patients (16 percent), and troponin I tests were positive in 171 patients (22 percent). Among 47 patients with evolving myocardial infarction, troponin T tests were positive in 44 (94 percent) and troponin I tests were positive in all 47. Among 315 patients with unstable angina, troponin T tests were positive in 70 patients (22 percent), and troponin I tests were positive in 114 patients (36 percent). During 30 days of follow-up, there were 20 deaths and 14 nonfatal myocardial infarctions. Troponin T and troponin I proved to be strong, independent predictors of cardiac events. The event rates in patients with negative tests were only 1.1 percent for troponin T and 0.3 percent for troponin I.
Bedside tests for cardiac-specific troponins are highly sensitive for the early detection of myocardial-cell injury in acute coronary syndromes. Negative test results are associated with low risk and allow rapid and safe discharge of patients with an episode of acute chest pain from the emergency room.
Non-Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization).
We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non-Q-wave infarction. Death or nonfatal infarction made up the combined primary end point.
During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P= 0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01).
Most patients with non-Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective.
To assess the long-term prognostic significance of total ischemic time (silent plus painful ischemia) and silent ischemia in patients with unstable angina whose condition stabilized with medical treatment, 76 patients were studied. All patients underwent Holter ambulatory electrocardiographic (ECG) monitoring for ≥48 h beginning within the 1st 12 h of the hospital stay. Forty-three patients (Group A) had a total ischemic time ≥60 min, whereas 33 patients (Group B) had a total ischemic time <60 min. More than 78% of the ischemic episodes in patients in Group A and 62% of those in Group B were silent (p < 0.05); nine patients in Group A and six in Group B had only silent episodes. Patients in Group A frequently showed three-vessel disease (65% vs. 18%, p < 0.01), angiographic findings of subtotal occlusion of the coronary arteries (TIMI grade I) (76.7% vs. 42.4%, p < 0.01) and ischemic alterations in the rest ECG (51.2% vs. 30.3%, p < 0.05).
Silent myocardial ischemia as detected on Holter electrocardiographic (ECG) monitoring is present in >50% of patients with unstable angina despite intensive medical therapy. The presence and the extent of silent ischemia have been correlated with an increased risk of early (1 month) unfavorable outcome including myocardial infarction and need for coronary revascularization for persistent symptoms. Seventy patients with unstable angina who had undergone continuous ECG monitoring for silent ischemia were followed up for 2 years; 37 patients (Group I) had Holter ECG evidence of silent ischemia at bed rest in the coronary care unit during medical treatment with nitrates, beta-receptor blockers and calcium channel antagonists; the other 33 patients (Group II) had no ischemic ST segment changes (symptomatic or silent) on Holter monitoring.Over a 2 year follow-up period, myocardial infarction occurred in 10 patients in Group I (in 2 it was fatal) compared with one nonfatal infarction in Group II (p < 0.01 by Kaplan-Meier analysis); revascularization with either coronary bypass surgery or angioplasty for symptomatic ischemia was performed in 11 Group I and 5 Group II patients (p < 0.05). Multivariate Cox's hazard analysis demonstrated that the presence of silent ischemia was the best predictor of 2 year outcome. Therefore, persistent silent myocardial ischemia despite medical therapy in patients with unstable angina carries adverse prognostic implications that persist over a 2 year period.
IN the 19th century there were two major hypotheses to explain the pathogenesis of atherosclerosis: the "incrustation" hypothesis and the "lipid" hypothesis. The incrustation hypothesis of von Rokitansky,1 proposed in 1852 and modified by Duguid,2 suggested that intimal thickening resulted from fibrin deposition, with subsequent organization by fibroblasts and secondary lipid accumulation. The lipid hypothesis, proposed by Virchow3 in 1856, suggested that lipid in the arterial wall represented a transduction of blood lipid, which subsequently formed complexes with acid mucopolysaccharides; lipid accumulated in arterial walls because mechanisms of lipid deposition predominated over those of removal. The two hypotheses are now . . .
The significance of ST segment shift with respect to coronary anatomy and hospital outcome was evaluated in 135 patients with unstable angina. ST shift was evident in 44% of patients on admission electrocardiogram (ECG) and in 66% on Holter monitor ECG. During hospitalization, 7% of patients had myocardial infarction, 4% died and 34% had urgent coronary revascularization. By comparing patients with and without ST shift on admission ECG, an unfavorable outcome was found in 55% versus 25% (p less than 0.005), multivessel disease in 77% versus 63% (p less than 0.05) and left main coronary artery stenosis in 22% versus 7% (p less than 0.025). When patients with and without ST shift on Holter monitor ECG were compared, an unfavorable outcome was found in 48% versus 20% (p less than 0.005), multivessel disease in 76% versus 54% (p less than 0.01) and left main coronary stenosis in 18% versus 4% (p less than 0.05). The duration of ST shift was also greater in patients with 1) unfavorable outcome (129 +/- 136 versus 52 +/- 111 min, p less than 0.01); 2) multivessel disease (98 +/- 129 versus 36 +/- 90 min, p less than 0.01); and 3) left main stenosis (150 +/- 147 versus 67 +/- 114 min, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
We examined the prevalence and prognostic importance of silent myocardial ischemia detected by continuous electrocardiographic monitoring in 70 patients with unstable angina. All the patients received intensive medical treatment with nitrates, beta-blockers, and calcium-channel blockers. Continuous electrocardiographic recordings were made during the first two days in the coronary care unit to quantify the frequency and duration of asymptomatic ischemic episodes, defined as a transient ST-segment shift of 1 mm or more. Thirty-seven patients (Group 1) had at least one episode of silent ischemia, and the other 33 patients had no silent ischemia (Group 2). Over the subsequent month, myocardial infarction occurred in 6 patients in Group 1 and in only 1 in Group 2 (P less than 0.01); bypass surgery or angioplasty was required for recurrent symptomatic angina in 10 patients in Group 1 and only 3 in Group 2 (P = 0.02). Survival-curve analysis demonstrated that silent ischemia was associated with these outcomes (P less than 0.002), and multivariate analysis showed that silent ischemia was the best predictor of these outcomes among the 15 variables tested (P less than 0.002). Patients in Group 1 with 60 minutes or more of silent ischemia per 24 hours had a worse prognosis than those with under 60 minutes per 24 hours (P = 0.04). Silent ischemia occurred in more than 50 percent of our patients with unstable angina, despite intensive medical therapy, and it identified a subset who were at high risk for early unfavorable outcomes.
Silent myocardial ischemia is common in unstable angina, but its prognostic significance is unknown. Fifty-two (42 with subsequent angiography) of 81 patients prospectively evaluated for unstable angina had ambulatory electrocardiographic (Holter) recordings analyzed by compact analog technique after they had received medical treatment (3 of the 52 had unanalyzable recordings and were excluded). From 1,103 hours of recordings, 298 ischemic episodes were identified, only 9% associated with angina. By Ridit analysis a significant correlation was found between the cumulative duration of transient myocardial ischemia and the number of diseased coronary vessels and indexes of proximal stenosis. During a 3 to 6 month follow-up period, there was one death and one patient was lost to follow-up among 20 patients without transient ischemia; in the group of 11 patients with a cumulative duration of transient ischemia less than 60 minutes/24 h, 7 were alive and well, 2 required coronary bypass surgery, 1 had coronary angioplasty for recurrence of angina and 1 was lost to follow-up. In the group of 18 patients with ischemia duration greater than 60 minutes/24 h, only 1 developed a stable angina pattern; 12 required coronary surgery (n = 11) or angioplasty (n = 1) and 5 developed myocardial infarction (2 died, 2 needed surgery for postinfarction angina and 1 recovered). A favorable clinical outcome occurred in only 6% of patients in the group with ischemia duration greater than 60 minutes/24 h; this rate was significantly lower (p less than 0.001) than that (70%) for the group with ischemia duration less than 60 minutes/24 h or that (95%) for the group without ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
The issue of whether a traditional or scientifically based system for applying electrodes to the body for routine electrocardiography may be resolved by deriving the 12‐lead ECG from the Frank XYZ signals. The result, the ECGD, is sufficiently close to the ECG for serial comparisons to be. valid. Reducing data acquisition to the XYZ signals alone has several technical advantages. These have been realized with the introduction of a computer system employing the ECGD at a large general hospital.
Plotting the lead vectors of the ECG Don Aitofrs projection of the sphere brings out important relationships between the leads, one to another, and to the spatial directions of the QRS and T vectors. Reversing the polarity of aVR enhances the sequential relationship between the limb leads; this is taken advantage of in an educational display generated by the computer.
Reperfusion therapy has lowered mortality in patients suffering from acute myocardial infarction. Failure to reperfuse is associated with an increased short- and long-term mortality. In a prospective study we used dynamic vectorcardiography to monitor 96 patients with acute myocardial infarction treated with reperfusion therapy to non-invasively assess coronary patency. The results from continuous monitoring were compared to those obtained from angiography. By using trend-analysis of QRS vector difference and ST vector magnitude, we were able to correctly identify 58 of the 70 patients (83%) with a reperfused infarct-related artery, and 19 of the 26 patients (73%) with a persistently occluded artery demonstrated at an early angiogram (diagnostic accuracy 80%). In patients with high-grade collateral flow to the infarct-related area, the results of the vectorcardiographic monitoring and of angiography showed the largest disagreement, whereas the accuracy of vectorcardiographic monitoring was high: 88% among patients without collaterals. The present results suggest that QRS complex and ST segment vectorcardiographic monitoring is a useful tool for assessing early coronary artery patency, and that dynamic vectorcardiography may help in identifying candidates for emergency coronary angiography.
The Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial was designed to test whether thrombolytic strategies achieving more complete, early, sustained coronary artery patency would lead to further reductions in mortality in patients with acute myocardial infarction. An angiographic substudy within GUSTO-I provided a unique opportunity to examine the relation between mortality and degrees of patency among the regimens.
Four thrombolytic strategies were compared in 41,021 patients in GUSTO-I: streptokinase with subcutaneous or intravenous heparin, accelerated tissue plasminogen activator (TPA) with intravenous heparin, and combination streptokinase plus TPA with intravenous heparin. Accelerated TPA was associated with lower 30-day mortality (6.3%) than the other strategies (7.2%, 7.4%, and 7.0%, respectively). Among the 1210 patients in the angiographic substudy randomized to angiography 90 minutes after starting treatment, there was improved patency, particularly Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, with accelerated TPA over the other regimens (P < .0001). Coronary artery perfusion (TIMI grade 3) at 90 minutes was also a significant predictor of 30-day survival (P < .01). To determine whether differences in mortality among the four strategies matched differences in 90-minute patency, a model was developed for predicting mortality differences in the main trial from the angiographic substudy. The model assumed that any differences in treatment effects on 30-day mortality were mediated through differences in 90-minute patency for the four treatments. The predicted rates were then compared with observed mortality rates of the remaining patients in the main trial for each treatment group. The predicted and observed 30-day mortality rates of the four treatments were streptokinase with subcutaneous heparin, 7.46% versus 7.28%; streptokinase with intravenous heparin, 7.26% versus 7.39%; accelerated TPA, 6.31% versus 6.37%; and streptokinase plus TPA, 6.98% versus 6.96%. The correlation between predicted and observed results was .97, and the proportion of squared error explained (R2) was .92.
The close relation between the predicted and observed 30-day mortality rates supports the concept that an important mechanism for improved survival with thrombolytic therapy is achievement of early, complete perfusion. The close match provides a strong biological explanation for the mortality differences seen in GUSTO-I and a sound rationale for the additional survival advantage of the accelerated TPA regimen. Irrespective of which treatment is used, early and complete restoration of infarct artery perfusion represents an essential goal of myocardial reperfusion therapy.
This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.
Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown.
Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay.
One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01).
The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia.
The prevalence and clinical significance of transient myocardial ischemia was evaluated prospectively in 43 patients with a clinical diagnosis of unstable angina. Continuous 2-channel Holter electrocardiographic monitoring was begun < 24 hours after admission. In 3,558 hours of recordings (mean 83 +/- 20 hours/patient), there were 1,671 episodes of transient ischemia; > 90% were asymptomatic. All patients but 1 had at least 1 episode of transient ischemia. Twenty-two patients (group 1) had a total ischemic duration of > or = 30 minutes/day, whereas 21 patients (group 2) had a total ischemic duration of < 30 minutes/day. A predischarge symptom-limited exercise test was performed in 40 of these patients after medical stabilization and 39 patients underwent exercise thallium-201 imaging, an average of 3 days after the exercise test. During a follow-up period of 39.9 +/- 9 months (range 28 to 49), 4 patients developed myocardial infarction and 22 required revascularization because of medically refractory angina. There were significantly more patients with total cardiac events (myocardial infarction or a need for revascularization) in group 1 than in group 2 (p < 0.05). Among patients undergoing an exercise test and exercise thallium-201 imaging, a positive exercise electrocardiogram and the presence of a reversible thallium-201 perfusion defect were also significant predictors of subsequent cardiac events (p < 0.05 and p < 0.001, respectively). The results of the Holter recordings did not add significantly more prognostic information.(ABSTRACT TRUNCATED AT 250 WORDS)
If a practical, reliable, noninvasive marker of failed reperfusion was available in real time, the benefits of further therapy in this patient subgroup could be tested. We developed a method of 12-lead ST-segment recovery analysis using continuously updated reference points to provide such a marker.
In this study, our method was prospectively tested in 144 patients given thrombolytic therapy early in myocardial infarction. All patients had 12-lead continuous ST-segment monitoring and acute angiography, each analyzed in an independent, blinded core laboratory. ST-segment recovery and re-elevation were analyzed up to the moment of angiography, at which time patency was predicted. Predictions were correlated to angiographic infarct artery flow, with TIMI flow 0 to 1 as occluded and TIMI flow 2 to 3 as patent. Infarct artery occlusion was seen on first injection in 27% of patients. The positive predictive value of incomplete ST recovery or ST re-elevation by our method was 71%, negative predictive value 87%, with 90% specificity and 64% sensitivity for coronary occlusion. ST recovery analysis predicted patency in 94% of patients with TIMI 3 flow versus 81% of patients with TIMI 2 flow and predicted occlusion in 57% of patients with collateralized occlusion versus 72% of patients with non-collateralized occlusion. In a regression model including other noninvasive clinical descriptors, ST recovery alone contained the vast majority of predictive information about patency.
In a blinded, prospective, angiographically correlated study design, 12-lead continuous ST-segment recovery analysis shows promise as a practical noninvasive marker of failed reperfusion that may contribute substantially to currently available bedside assessment. Our data also suggest that patients with TIMI 2 flow or with collateralized occlusions may represent a physiological spectrum definable with ST-segment recovery analysis.
Early risk assessment is important in patients with unstable coronary artery disease, ie, unstable angina or non-Q-wave myocardial infarction. Some previous small studies have indicated that patients with unstable angina and elevation of troponin T (tn-T) have worse short-term and long-term prognoses. In this study, the prognostic value of tn-T was evaluated and compared with other early available risk indicators.
Nine hundred seventy-six patients participating in a randomized study of low-molecular-weight heparin in unstable coronary artery disease were followed for 5 months after the index episode. The risk of cardiac events increased with increasing maximal levels of tn-T obtained in the initial 24 hours. The lowest quintile (<0.06 microgram/L) constituted a low-risk group, the second quintile (0.06 to 0.18 microgram/L) an intermediate-risk group, and the three highest quintiles (> or =0.18 microgram/L) a high-risk group, with 4.3%, 10.5%, and 16.1% risk of either myocardial infarction or cardiac death, respectively. Troponin T level was identified together with age, hypertension, number of antianginal drugs, and ECG changes at rest as independent prognostic variables for myocardial infarction or cardiac death in a multivariate analysis. The prognostic value of tn-T was independent of the classification of index event into unstable angina or myocardial infarction.
Troponin T determination is an inexpensive and widely applicable method for early risk assessment in patients with unstable coronary artery disease. The maximum tn-T value obtained during the first 24 hours provides independent and important prognostic information.
Thrombus formation on a fissured or disrupted atherosclerotic plaque is the main pathogenetic mechanism for the acute coronary syndromes of myocardial infarction and unstable angina. Myocardial infarction results from an acute total occlusion of the artery, while unstable angina is secondary in most cases to mural thrombus formation. Thrombus formation has also been implicated in chronic atherosclerotic disease progression and in restenosis following coronary angioplasty. Therapeutic measures to treat thrombus rely on the ability of drugs to either prevent thrombus extension, dissolve its fibrin component, or prevent further platelet aggregation. Other measures rely on the ability of intracoronary techniques to open coronary arteries. The primary prevention of intracoronary thrombus formation is evolving. Measures to stabilize plaques or to reduce hypercoagulability are being tested or have been tested in recent trials.
In the GUSTO-I ECG ischaemia monitoring substudy, 1067 patients underwent continuous ST segment monitoring, using vector-derived 12-lead (406 patients), 12-lead (373 patients) and 3-lead Holter (288 patients) ECG recording systems. Simultaneous angiograms at 90 or 180 min following thrombolytic therapy were performed as a part of the prospective study in 302 patients.
Infarct vessel patency was established as TIMI perfusion grades 2 or 3 and occlusion as TIMI perfusion grades 0 or 1. Coronary artery patency was predicted from ST trends up to the time of angiography. Predictive values at 90 and 180 min after the start of thrombolysis were 70% and 82% for patency and 58% and 64% for occlusion, respectively. In retrospect, accuracy appeared greatest (79–100%) in patients with extensive ST segment elevation (≥400 μV), if both speed of ST recovery and extent of ST segment: elevation were taken into account. Although the three recording systems differed considerably in signal processing, no significant difference in accuracy was demonstrated among these systems.
We conclude that continuous ECG monitoring may help select high risk patients without apparent reperfusion who may benefit from additional reperfusion therapy. As ST recovery may occur early after the start of thrombolytics and accuracy of the test is related to peak ST levels, the use of on-line ECG monitoring devices on emergency wards and cardiac care units is recommended. (Eur Heart J 1996; 17: 689–698)
Although aspirin is beneficial in patients with unstable angina, it is a relatively weak inhibitor of platelet aggregation. The effect of Integrelin, which inhibits the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa, on the frequency and duration of Holter ischemia was evaluated in 227 patients with unstable angina.
Patients received intravenous heparin and standard ischemic therapy and were randomized to receive oral aspirin and placebo Integrelin; placebo aspirin and low-dose Integrelin. 45 micrograms/kg bolus followed by a 0.5 microgram.kg-1. min-1 continuous infusion; or placebo aspirin and high-dose Integrelin, 90 micrograms/kg bolus followed by a 1.0-microgram.kg-1, min-1 constant infusion. Study drug was continued for 24 to 72 hours, and Holter monitoring was performed. Patients randomized to high-dose Integrelin experienced 0.24 +/- 0.11 ischemic episodes (mean +/- SEM) on Holter lasting 8.41 +/- 5.29 minutes over 24 hours of study drug infusion. Patients randomized to aspirin experienced a greater number (1.0 +/- 0.33, P < .05) and longer duration (26.2 +/- 9.8 minutes, P = .01) of ischemic episodes than the high-dose Integrelin group. There was no evidence of rebound ischemia after withdrawal of study drug. In 46 patients, platelet aggregation was rapidly inhibited by Integrelin in a dose-dependent fashion. The number of clinical events was small, and there were no bleeding differences in the three treatment arms.
Intravenous Integrelin is well tolerated, is a potent reversible inhibitor of platelet aggregation, and added to full-dose heparin reduces the number and duration of Holter ischemic events in patients with unstable angina compared with aspirin.
The acute ischemic coronary syndromes of unstable angina and non-Q-wave myocardial infarction are most commonly caused by intracoronary thrombosis at the site of ruptured atherosclerotic plaque. The main goals of therapy are the relief of ischemia and prevention of life-threatening thrombotic events. Current antithrombotic management includes heparin and aspirin, but recent insights into the pathophysiology of these syndromes have revealed that more effective management may be achieved by direct inhibition of the final common pathway to platelet aggregation--the platelet glycoprotein (GP) IIb-IIIa receptor. Earlier studies of the reversible peptide inhibitor of the GP IIb-IIIa receptor, eptifibatide (INTEGRILIN), in patients with unstable angina have demonstrated its potential in reducing acute ischemic events. The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, the largest clinical trial of any GP IIb-IIIa receptor inhibitor to date, is a recently completed phase III evaluation of eptifibatide as primary management for patients with acute coronary syndromes presenting without persistent ST-segment elevation.
Thrombin has been suggested as one of the main pharmacologic targets in unstable coronary syndromes. Electrocardiographic signs of ischemia during continuous monitoring convey prognostic information in these patients. This study assessed the anti-ischemic and clinical effects of the novel low-molecular weight thrombin inhibitor inogatran in patients with unstable angina and non-Q-wave infarction without persistent ST-segment elevation on hospital admission. Within 24 hours of the last episode of chest pain, 324 patients were randomized to 72 hours of treatment with inogatran or heparin. Continuous ST-segment analysis with computerized vectorcardiography was used to monitor ischemia for 24 hours. The occurrence of cardiac events during the first 7 days were studied and compared with ischemic episodes during the initial 24 hours. The heparin-treated patients had less episodes of ischemia (ST vector magnitude [ST-VM]: 1 +/- 2.6 vs 2 +/- 4.5, p < 0.001 and ST change vector magnitude [STC-VM]: 3 +/- 4.7 vs 6 +/- 7.6, p < 0.001) than the patients receiving inogatran. This was paralleled by a lower incidence of the combined end point of death, nonfatal infarction, refractory or recurrent angina during the first 7 days for the heparin-treated patients (35%) compared with the inogatran-treated patients (50%) (p < 0.05). Patients who had episodes of ischemia in spite of anti-ischemic therapy were at increased risk of all events studied. Heparin is more effective than inogatran in suppressing myocardial ischemia and clinical events at short-term follow-up. Continuous ST-segment monitoring with vectorcardiography identifies nonresponders who are at an increased level of risk.
In the CAPTURE (c7E3 Fab Anti Platelet Therapy in Unstable REfractory angina) trial, 1265 patients with refractory unstable angina were treated with abciximab or placebo, in addition to standard treatment from 16 to 24 hours preceding coronary intervention through 1 hour after intervention. To investigate the incidence of recurrent ischemia and the ischemic burden, a subset of 332 patients (26%) underwent continuous vector-derived 12-lead ECG-ischemia monitoring. METHODS and
Patients were monitored from start of treatment through 6 hours after coronary intervention. Ischemic episodes were detected in 31 (18%) of the 169 abciximab and in 37 (23%) of the 163 placebo patients (NS). Only 9 (5%) of abciximab versus 22 (14%) of placebo patients had >/=2 ST episodes (P<0.01). In patients with ischemia, abciximab significantly reduced total ischemic burden (P<0.02), which was calculated alternatively as the total duration of ST episodes per patient, the area under the curve of the ST vector magnitude during episodes, or the sum of the areas under the curves of 12 leads during episodes. Twenty-one patients (6%) suffered a myocardial infarction (MI) (18) or died (3) within 5 days of treatment. The presence of asymptomatic and symptomatic ST episodes during the monitoring period preceding coronary intervention was associated with an increased relative risk of these events of 3.2 (95% CI 1.4, 7.4) and 4.1 (95% CI 1.4, 12.2), respectively.
Recurrent ischemia predicts MI or death within 5 days of follow-up. Treatment with abciximab is associated with a reduction of frequent ischemia and a reduction of total ischemic burden in patients with refractory unstable angina. As such, patients with ischemia derive particularly high benefit from abciximab.
Recurrent ischemia after an acute coronary syndrome portends an unfavorable outcome and has major resource-use implications. This issue has not been studied systematically among the spectrum of patients with acute coronary presentations, encompassing those with and without ST-segment elevation.
We assessed the 1-year prognosis of the 12 142 patients enrolled in the GUSTO-IIb trial by the presence (n=4125) or absence (n=8001) of ST-segment elevation. This latter group was further categorized into those with baseline myocardial infarction (n=3513) or unstable angina (n=4488). We also assessed the incidence of recurrent ischemia and its impact on outcomes. Recurrent ischemia was significantly rarer in those with ST-segment elevation (23%) than in those without (35%; P<0.001). Mortality at 30 days was greater among patients with ST-segment elevation (6.1% versus 3.8%; P<0.001) but less so at 6 months; by 1 year, mortality did not differ significantly (9.6% versus 8.8%). Patients with non-ST-segment-elevation infarction had higher rates of reinfarction at 6 months (9.8% versus 6.2%) and higher 6-month (8.8% versus 5.0%) and 1-year mortality rates (11.1% versus 7.0%) than such patients who had unstable angina.
Refractory ischemia was associated with an approximate doubling of mortality among patients with ST-segment elevation and a near tripling of risk among those without ST elevation. This study highlights not only the substantial increase in late mortality and reinfarction with non-ST-segment-elevation infarction but also the opportunities for better triage and application of therapeutic strategies for patients with recurrent ischemia.
Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive.
We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI.
There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.