Ian B. A. Menown

Abciximab Facilitates the Rate and Extent of Thrombolysis Results of the Thrombolysis In Myocardial Infarction (TIMI) 14 Trial

BACKGROUND The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. METHODS AND RESULTS Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including abciximab received low-dose heparin (60-U/kg bolus; infusion of 7 U. kg-1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated alteplase alone was 57% compared with 32% for abciximab alone and 34% to 46% for doses of streptokinase between 500 000 U and 1.25 MU with abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P<0.02). The most promising regimen was 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1) heparin. TIMI 3 flow rates were significantly higher in the 50-mg alteplase plus abciximab group versus the alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major hemorrhage were 6% in patients receiving alteplase alone (n=235), 3% with abciximab alone (n=32), 10% with streptokinase plus abciximab (n=143), 7% with 50 mg of alteplase plus abciximab and low-dose heparin (n=103), and 1% with 50 mg of alteplase plus abciximab with very-low-dose heparin (n=70). CONCLUSIONS Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding.

Unfractionated and low-molecular-weight heparin as adjuncts to thrombolysis in aspirin-treated patients with ST-elevation acute myocardial infarction: a meta-analysis of the randomized trials.

Background— There is uncertainty about the role of intravenous unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in patients with ST-elevation myocardial infarction (STEMI) treated with aspirin and thrombolysis. Methods and Results— We performed a meta-analysis of the randomized trials to assess the effect of UFH and LMWH on reinfarction, death, stroke, and bleeding. Fourteen trials involving a total of 25 280 patients were included (1239 comparing intravenous UFH versus placebo or no heparin; 16 943 comparing LMWH versus placebo; and 7098 comparing LMWH versus intravenous UFH). Intravenous UFH during hospitalization did not reduce reinfarction (3.5% versus 3.3%; odds ratio [OR], 1.08; 95% CI, 0.58 to 1.99) or death (4.8% versus 4.6%; OR, 1.04; 95% CI, 0.62 to 1.78) and did not increase major bleeding (4.2% versus 3.4%; OR, 1.21; 95% CI, 0.67 to 2.18) but increased minor bleeding (19.6% versus 12.5%; OR, 1.72; 95% CI, 1.22 to 2.43). During hospitalization/at 7 days, LMWH compared with placebo reduced the risk of reinfarction by approximately one quarter (1.6% versus 2.2%; OR, 0.72; 95% CI, 0.58 to 0.90; number needed to treat [NNT]=167) and death by ≈10% (7.8% versus 8.7%; OR, 0.90; 95% CI, 0.80 to 0.99; NNT=111) but increased major bleeding (1.1% versus 0.4%; OR, 2.70; 95% CI, 1.83 to 3.99; number needed to harm [NNH]=143) and intracranial bleeding (0.3% versus 0.1%; OR, 2.18; 95% CI, 1.07 to 4.52; NNH=500). The reduction in death with LMWH remained evident at 30 days. LMWH compared with UFH during hospitalization/at 7 days reduced reinfarction by ≈45% (3.0% versus 5.2%; OR, 0.57; 95% CI, 0.45 to 0.73; NNT=45), did not reduce death (4.8% versus 5.3%; OR, 0.92; 95% CI, 0.74 to 1.13) or increase major bleeding (3.3% versus 2.5%; OR, 1.30; 95% CI, 0.98 to 1.72), but increased minor bleeding (22.8% vs 19.4%; OR, 1.26; 95% CI, 1.12 to 1.43). The reduction in reinfarction remained evident at 30 days. Conclusions— In aspirin-treated patients with STEMI who are treated with thrombolysis, intravenous UFH has not been shown to prevent reinfarction or death. LMWH given for 4 to 8 days compared with placebo reduces reinfarction by approximately one quarter and death by ≈10% and when directly compared with UFH reduces reinfarction by almost one half. These data suggest that LMWH should be the preferred antithrombin in this setting.

The Platinum Chromium Element Stent Platform: from Alloy, to Design, to Clinical Practice

Despite advances in polymer and drug technology, the underlying stent platform remains a key determinant of clinical outcome. A clear understanding of stent design and the differences between various stent platforms are of increasing importance for the interventional cardiologist. Reduction in stent strut thickness has been associated with improved stent deliverability, improved procedural outcome, and lower rates of subsequent restenosis. Newer-generation 316L-SS stent designs have enabled reduced strut thickness while retaining radial strength and minimizing recoil, but with significant loss of radiopacity, leading to reduced visibility. Cobalt chromium alloys have enabled a reduction in stent strut thickness to around 80–90 mm while retaining modest radiopacity, but due to higher elastic properties, have been associated with greater stent recoil. Development of a novel 33% platinum chromium alloy with high radial strength and high radiopacity has enabled design of a new, thin-strut, flexible, easily visualized, and highly trackable stent platform, the use of which is further illustrated in several clinical case descriptions.

Determinants of coronary blood flow after thrombolytic administration

OBJECTIVES This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 ± 17.2, n = 181) remained significantly slower than normal (21.0 ± 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.OBJECTIVES This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.

Early diagnosis of right ventricular or posterior infarction associated with inferior wall left ventricular acute myocardial infarction.

Right ventricular (RV) or posterior infarction associated with inferior wall left ventricular acute myocardial infarction (AMI) has important therapeutic and prognostic implications. However, RV and posterior chest leads in addition to the 12-lead electrocardiogram are required for accurate detection. Body surface mapping (BSM) has greater spatial sampling and may further improve inferior wall AMI classification. Consecutive patients with chest pain lasting <12 hours were assessed to identify those with AMI and > or =0.1 mV ST elevation in > or =2 contiguous inferior leads of the 12-lead electrocardiogram (bundle branch block or left ventricular hypertrophy excluded). A 12-lead electrocardiogram, RV leads (V(2)R, V(4)R), posterior chest leads (V(7), V(9)), and a BSM were recorded. From each BSM, the 12 electrodes overlying the RV region (regional RV map) and 10 electrodes overlying the posterior wall (regional posterior map) were assessed for ST elevation. Infarct size was estimated by serial cardiac enzymes. AMI occurred in 173 of 479 patients. Of the 62 patients with inferior wall AMI, ST elevation > or =0.1 mV occurred in 26 patients (42 in V(2)R or V(4)R compared with 36 patients (58%) in > or =1 electrode on the regional RV map (p = 0.0019). ST elevation > or =0.1 mV occurred in 1 patient (2%) in V(7) or V(9) compared with 17 patients (27%) in > or =1 electrode on the regional posterior map (p = 0.00003). ST elevation > or =0.05 mV occurred in 6 patients (10%) in V(7) or V(9) compared with 22 patients (36%) in > or =1 electrode on the regional posterior map (p = 0.00003). Patients with ST elevation on regional RV and/or posterior maps had a trend toward larger infarct size (mean peak creatine kinase 1,789+/-226 vs. 1,546+/-392 mmol/L; p = NS). Thus, BSM, when compared with RV or posterior chest leads, provides improved classification of patients with inferior wall AMI and RV or posterior wall involvement.

Comparison of the 80-lead body surface map to physician and to 12-lead electrocardiogram in detection of acute myocardial infarction☆

Diagnosis of non-ST-elevation acute myocardial infarction (AMI) by a 12-lead electrocardiogram has poor sensitivity and specificity and, therefore, relies on biochemical markers of myocardial necrosis, which can only be reliably detected within 14 to 16 hours from symptom onset. The body surface map (BSM) improves AMI detection but is limited by its interpretation by inexperienced medical staff. To facilitate interpretation, an automated BSM algorithm was developed and is evaluated in this study. One hundred three patients with ischemic-type chest pain were recruited for this study from December 2001 to April 2002. A 12-lead electrocardiogram (Marquette Mac 5K) and BSM (PRIME-ECG) were recorded at initial presentation, and cardiac troponin I and/or creatine kinase-MB levels measured at 12 hours after symptom onset. The admitting physicians 12-lead electrocardiographic (ECG) interpretation, 12-lead ECG algorithm (Marquette 12 SL V233) diagnosis, and BSM algorithm diagnosis were documented for each patient. AMI, defined by elevation of troponin I to >1 microg/L and/or creatine kinase-MB to >25U/L, occurred in 53 patients. The admitting physician diagnosed 24 patients with AMI (sensitivity 45%, specificity 94%), the 12-lead ECG algorithm diagnosed 17 patients with AMI (sensitivity 32%, specificity 98%), and the BSM algorithm diagnosed 34 patients with AMI (sensitivity 64%, specificity 94%). The BSM algorithm improved the diagnostic sensitivity by 2.0 (p <0.001) and 1.4 (p = 0.002) compared with the 12-lead ECG algorithm or the admitting physician, respectively. There was no significant difference in specificity. Thus, the BSM algorithm improves detection of AMI compared with the 12-lead ECG algorithm or physicians 12-lead ECG interpretation.

Body surface mapping improves early diagnosis of acute myocardial infarction in patients with chest pain and left bundle branch block

Objective: To test prospectively depolarisation and repolarisation body surface maps (BSMs) for mirror image reversal, which is less susceptible to artefact, in patients with acute ischaemic-type chest pain, and to compare these BSM criteria with previously published 12 lead ECG criteria Methods: An 80 lead portable BSM system was used to map patients presenting with acute ischaemic-type chest pain and a 12 lead ECG with left bundle branch block (LBBB). Acute myocardial infarction (AMI) was defined by serial cardiac enzymes. Each 12 lead ECG was assessed by the criteria of Sgarbossa et al and Hands et al for diagnosis of AMI. Depolarisation and repolarisation BSMs were assessed for loss of mirror image reversal of QRS with ST-T isointegral map patterns and a change in vector angle from QRS to ST-T outside 180±15°—findings typically seen in LBBB with AMI. Results: Of 56 patients with chest pain and LBBB, 18 had enzymatically confirmed AMI. Patients with loss of BSM image reversal were significantly more likely to have AMI (odds ratio 4.9, 95% confidence interval 1.5 to 16.4, p = 0.007). Loss of BSM image reversal was significantly more sensitive (67%) for AMI than either 12 lead ECG method (17%, 33%) albeit with some loss in specificity (BSM 71%, 12 lead ECG 87%, 97%). Patients with AMI compared with those without AMI had a greater mean change in vector angle outside the normal range (180±15°), particularly between QRS isointegral and ST60 isopotential (the potential 60 ms after the J point at each electrode site) BSMs (19° v 9°, p = 0.038). Loss of image reversal and QRS-ST60 vector change outside 180±15° had 61% sensitivity and 82% specificity for AMI (odds ratio 7.0, 95% confidence interval 2.0 to 24.4, p = 0.001). Conclusions: BSM compared with the 12 lead ECG improved the early diagnosis of AMI in the presence of LBBB.

Impact of pre-hospital care in patients with acute myocardial infarction compared with those first managed in-hospital

AIMS To compare prospectively the impact of pre-hospital care by a physician-staffed mobile coronary care unit with patients managed initially in-hospital, all with acute myocardial infarction. METHODS AND RESULTS This was a single centre registry of consecutive patients (n=750) admitted with acute myocardial infarction to the coronary care unit and cardiology wards of the Royal Victoria Hospital, Belfast between 1998 and 2001. For the 750 patients, in-hospital mortality was 11% and was significantly lower for those managed pre-hospital (8% vs 13%, P=0.04): patients who received fibrinolytic therapy (n=474), the in-hospital mortality was significantly lower in the pre-hospital group (7% vs 13%, P=0.02). Those managed pre-hospital had significant reduction in the median delay times (25th, 75th percentiles) from onset of symptoms to call for help 1.0 (0.5, 2.2) vs 2.0 (0.9, 6.0) h, P<0.001, from call for help to receiving fibrinolytic therapy 1.0 (0.8, 1.5) vs 1.8 (1.2, 2.5) h, P<0.001 resulting in a shorter pain-to-needle time for fibrinolytic therapy 2.3 (1.5, 3.8) vs 4.0 (2.6, 7.2) h, P<0.001. For all patients, older age, haemodynamic indicators on admission (hypotension, higher heart rate, heart failure) and managed by the in-hospital route were significant independent variables for an adverse in-hospital mortality. Although for patients aged >or=75 years no statistical significant reduction in mortality occurred for those managed pre-hospital (P=0.051), nevertheless patients in this age group first treated pre-hospital who received fibrinolytic therapy had a significantly lower mortality than those first treated in-hospital (21% vs 43%, P=0.02). CONCLUSIONS Consecutive patients with acute myocardial infarction seen and managed initially out-of-hospital by a physician-staffed mobile coronary care unit had significantly lower in-hospital mortality.

Prediction of recurrent events by D-dimer and inflammatory markers in patients with normal cardiac troponin I (PREDICT) study

BACKGROUND The independent predictive value of d-dimer and inflammatory markers for the risk of recurrent adverse events in patients with acute chest pain but normal levels of cardiac troponin I (cTnI) remains unclear. METHODS We studied 391 patients admitted to the hospital in 1 year with acute ischemic-type chest pain. Creatine kinase-myocardial band isoenzyme (CK-MB) mass and cTnI levels were measured in initial and 12-hour samples. Soluble intercellular adhesion molecule (sICAM)-1, vascular cell adhesion molecule (sVCAM)-1, sP-selectin, sE-selectin, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), fibrinogen, and d-dimer levels were measured in initial samples. A 1-year incidence of death, myocardial infarction (MI), revascularization, or readmission with chest pain was determined (with death/MI as the primary end point). RESULTS Patients with normal levels of CK-MB(mass) and cTnI (195/391[50%]) were at a lower risk than patients with elevated levels of CK-MB(mass) or cTnI, but still had an important incidence of events (77/195[39%]). Marker elevation was defined as >75th percentile (upper quartile). Elevated d-dimer levels (>580 ng/mL) was predictive of death/MI (odds ratio, 5.4; 95% CI, 1.5-20.2; P =.005). Elevated sP-selectin levels (>152 ng/mL; odds ratio, 3.2; 95% CI, 0.9-11.6; P =.06) trended to increased death/MI rates, with weaker trends for elevated levels of hsCRP (>7.1 mg/L), IL6 (>10.7 pg/mL), and ST depression. Other markers, other electrocardiogram changes, or classic risk factors were not predictive of death/MI. With a multivariate analysis, d-dimer and sP-selectin were found to be of independent significance for death/MI after adjustment for inflammatory, hemostatic, and electrocardiogram markers and d-dimer after adjustment for classic risk factors. CONCLUSION Normal cTnI levels after acute chest pain does not confer absence of future risk. Concurrent assessment of d-dimer and inflammatory markers may improve risk stratification.

Cardioprotective therapy and sodium-hydrogen exchange inhibition: current concepts and future goals*

Following acute myocardial infarction (MI), limitation of infarct size is central to long-term outcome [(1)][1]. Successful reperfusion results in smaller infarct size and a marked reduction in mortality [(1,2)][1]. However, following fibrinolytic therapy, ischemic myocardial injury continues during