Biomedical subjects

A M Ross

Publications and source records attributed to A M Ross.

At least 37 records · Page 2Linked to original sources

PubMed1999

New plasminogen activators: a clinical review.

Rapid restoration of patency of the infarct-related artery is the key to preserving myocardium and improving survival. This understanding has led to the application of genetic engineering to develop new plasminogen activators with specific clinical features. These novel activators may provide faster and more complete reperfusion in a greater number of patients, and do so with less risk of bleeding and intracranial hemorrhage. This article reviews the pharmacologic profiles and clinical performance of several novel plasminogen activators engineered from the human tissue plasminogen activator molecule or developed from animal and bacterial proteins.

Humans↗

PubMed1999

A randomized trial comparing primary angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: the PACT trial. PACT investigators. Plasminogen-activator Angioplasty Compatibility Trial.

OBJECTIVES: The study evaluated the efficacy and safety of a short-acting reduced-dose fibrinolytic regimen to promote early infarct-related artery (IRA) patency during the inherent delay experienced by infarct patients referred for angioplasty as the principal recanalization modality. BACKGROUND: Previous approaches using long-acting, full-dose thrombolytic infusions rarely showed benefit, but they did increase adverse event rates. METHODS: Following aspirin and heparin, 606 patients were randomized to a 50-mg bolus of recombinant tissue-type plasminogen activator (rt-PA) (alpha half-life 4.5 min) or to placebo followed by immediate angiography with angioplasty if needed. The end points included patency rates on catheterization laboratory (cath lab) arrival, technical results when PTCA (percutaneous transluminal coronary angioplasty) was performed, complication rates, and left ventricular (LV) function by treatment assignment and time to restored patency following angioplasty. RESULTS: Patency on cath lab arrival was 61% with rt-PA (28% Thrombolysis in Myocardial Infarction trial [TIMI]-2, 33% TIMI-3), and 34% with placebo (19% TIMI-2, 15% TIMI-3) (p = 0.001). Rescue and primary PTCA restored TIMI-3 in closed arteries equally (77%, 79%). No differences were observed in stroke or major bleeding. Left ventricular function was similar in both treatment groups, but convalescent ejection fraction (EF) was highest with a patent IRA (TIMI-3) on cath lab arrival (62.4%) or when produced by angioplasty within an hour of bolus (62.5%). However, in 88% of angioplasties, the delay exceeded 1 h: convalescent EF 57.3%. CONCLUSIONS: Tailored thrombolytic regimens compatible with subsequent interventions lead to more frequent early recanalization (before cath arrival), which facilitates greater LV function preservation with no augmentation of adverse events.

Aged↗

PubMed1998

Extended mortality benefit of early postinfarction reperfusion. GUSTO-I Angiographic Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial.

BACKGROUND: Reperfusion therapy for myocardial infarction, understood to reduce mortality by preserving left ventricular function, was initially expected to provide increasing benefits over time. Surprisingly, large controlled thrombolysis trials demonstrated maximum benefit at 4 to 6 weeks with no subsequent increased treatment advantage. Such studies, however, compared groups by assigned treatment, not physiological effectiveness. METHODS AND RESULTS: We calculated 2-year survival differences among 2431 myocardial infarction patients according to early infarct artery patency and outcome left ventricular ejection fraction using Kaplan-Meier curves. Hazard ratios for significant survival determinants were derived from Cox regression models. Two-year vital status (minimum, 688 days) was determined in 2375 patients (97.7%). A substantial mortality advantage for early complete reperfusion (Thrombolysis in Myocardial Infarction [TIMI] grade 3) and for preserved ejection fraction occurred beyond 30 days. The unadjusted hazard ratio for the TIMI 3 group compared with lesser grades at 30 days was 0.57 (95% confidence interval [CI], 0.35 to 0.94) and 30 days to > or = 688 days was 0.39 (95% CI, 0.22 to 0.69). Consequently, early TIMI 3 flow was associated with approximately a 3 patient per 100 mortality reduction the first month with an additional 5 lives per 100 from 30 days to 2 years. For ejection fraction >40% compared with < or = 40%, the unadjusted hazard ratio was 0.25 (95% CI, 0.16 to 0.37) at 30 days and 0.22 (95% CI, 0.15 to 0.33) after 30 days through 2 years (lives saved, approximately 9 and 11 per 100, respectively). CONCLUSIONS: Successful reperfusion and myocardial salvage produce significant mortality benefits that are amplified beyond the initial 30 days.

Female↗

PubMed1998

Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I Trial. GUSTO-I Hemostasis Substudy Group. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

OBJECTIVES: We sought to assess the effects of antithrombotic therapy after thrombolysis for acute myocardial infarction on markers of thrombin generation and activity and to determine the relation of these markers with clinical outcomes. BACKGROUND: Thrombin activation and generation often occur with thrombolysis for acute myocardial infarction. Antithrombotic regimens have been developed to reduce the resulting thrombotic complications. METHODS: We sampled plasma markers of thrombin generation and activity after thrombolysis in 292 patients. We assessed the relations of these markers with clinical outcomes at 30 days. RESULTS: Fibrinopeptide A (FPA), a marker of thrombin activity toward fibrinogen, was elevated at baseline (12.3 ng/ml) and increased to 18.4 ng/ml by 90 min after streptokinase and subcutaneous heparin treatment. With intravenous heparin, this increase was attenuated, but intravenous heparin did not prevent thrombin generation, as measured by prothrombin fragment 1.2 (F1.2). Heparin level, measured by anti-Xa activity, correlated with activated partial thromboplastin time (aPTT, r = 0.62 to 0.67). Thrombin activity, measured by FPA, was as closely related to aPTT as to the heparin level. Baseline levels of F1.2 were significantly related to the risk of death or reinfarction at 30 days (p = 0.008); values 12 h after enrollment also were related to 30-day mortality (p = 0.05). CONCLUSIONS: Although intravenous heparin partly suppresses the increased thrombin activity associated with thrombolysis, it does not inhibit thrombin generation. The aPTT was as good a measure of suppression of thrombin activity as the heparin level itself. Hematologic markers of thrombin generation were found to be related to the subsequent risk of thrombotic events.

Aged↗

PubMed1998

Non-Q-wave versus Q-wave myocardial infarction after thrombolytic therapy: angiographic and prognostic insights from the global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries-I angiographic substudy. GUSTO-I Angiographic Investigators.

BACKGROUND: Although the stratification of patients with myocardial infarction into ECG subsets based on the presence or absence of new Q waves has important clinical and prognostic utility, systematic evaluation of the impact of thrombolytic therapy on the subsequent development and prognosis of non-Q-wave infarction has been limited to date. METHODS AND RESULTS: We examined 12-lead ECG, coronary anatomy, left ventricular function, and mortality among 2046 patients with ST-segment elevation infarction from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries angiographic subset to gain further insight into the pathophysiology and prognosis of Q- versus non-Q-wave infarction in the thrombolytic era. Non-Q-wave infarction developed in 409 patients (20%) after thrombolytic therapy. Compared with Q-wave patients, non-Q-wave patients were more likely to present with lesser ST-segment elevation in a nonanterior location. The infarct-related artery in non-Q-wave patients was more likely to be nonanterior (67% versus 58%, P=.012) and distally located (33% versus 39%, P=.021). Early (90-minute, 77% versus 65%, P=.001) and complete (54% versus 44%, P<.001) infarct-related artery patency was greater among the non-Q-wave group. Non-Q-wave patients had better global (ejection fraction, 66% versus 57%; P<.0001) and regional left ventricular function (10 versus 24 abnormal chords, P=.0001). In-hospital, 30-day, 1-year, and 2-year (6.3% versus 10.1%, P=.02) mortality rates were lower among non-Q-wave patients. CONCLUSIONS: The excellent prognosis among the subgroup of patients who develop non-Q-wave infarction after thrombolysis is related to early, complete, and sustained infarct-related artery patency with resultant limitation of left ventricular infarction and dysfunction.

Aged↗

PubMed1998

Benefit of early sustained reperfusion in patients with prior myocardial infarction (the GUSTO-I trial). Global Utilization of Streptokinase and TPA for occluded arteries.

The primary objective of this study was to characterize a large cohort of patients receiving thrombolytic therapy for acute myocardial infarction with respect to the group with a prior event. Patients were randomly assigned to 1 of 4 thrombolytic strategies. Baseline characteristics, 30-day outcomes, and 1-year mortality were compared between patients with (n = 6,704) and without (n = 34,143) prior myocardial infarction. Patients with prior myocardial infarction presented to the hospital earlier than those having their first event, but institution of thrombolytic therapy was delayed. Mortality at 30 days (11.7% vs 5.9%, p = 0.001) and 1 year (17.3% vs 8.2%, p < 0.001) was greater among patients with prior infarction, and independent of other demographic variables. Accelerated alteplase was more effective than streptokinase or combination therapy (30-day mortality 10.4% vs 12.2%, p = 0.012; 1-year mortality 15.9% vs 17.8%, p = 0.041). Infarct vessel patency did not differ between those with and without prior myocardial infarction (67.3% vs 67% at 90 minutes, p = 0.92); however, recurrent ischemia was more common in patients with prior myocardial infarction. Patients with healed myocardial infarction should be educated to ensure early hospital admission if they develop symptoms suggestive of acute infarction, and upon hospital arrival should be promptly triaged to receive reperfusion therapy with accelerated alteplase.

Aged↗

PubMed1998

Rescue angioplasty after failed thrombolysis: technical and clinical outcomes in a large thrombolysis trial. GUSTO-1 Angiographic Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: We sought to assess the angiographic outcome, complication rates and clinical features of percutaneous transluminal coronary angioplasty (PTCA) after failed thrombolysis for acute myocardial infarction. BACKGROUND: "Rescue angioplasty" refers to mechanical reopening of an occluded infarct-related artery (IRA) after failed intravenous thrombolysis. Although the procedure is commonly performed, data describing its technical and clinical outcome are sparse. Early reports suggested that rescue PTCA is less often successful and produces more complications than primary PTCA. Other reports have described beneficial effects of successful rescue PTCA but adverse outcomes when PTCA is unsuccessful. METHODS: Using data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) angiographic substudy, we compared clinical and angiographic outcomes of 198 patients selected for a rescue PTCA attempt with those of 266 patients with failed thrombolysis but managed conservatively and, for reference, with those of 1,058 patients with successful thrombolysis. RESULTS: Patients offered rescue PTCA had more impaired left ventricular function than those in whom closed vessels were managed conservatively. Rescue successfully opened 88.4% of closed arteries, with 68% attaining Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. The interventions did not increase catheterization laboratory or postprocedural complication rates. Multivariate analysis identified severe heart failure to be a determinant of a failed rescue attempt. Successful rescue PTCA resulted in superior left ventricular function and 30-day mortality outcomes, comparable to outcomes in patients with closed IRAs managed conservatively, but less favorable than in patients in whom thrombolytic therapy was initially successful. The mortality rate after a failed rescue attempt was 30.4%; however, five of the seven patients who died after failed rescue PTCA were in cardiogenic shock before the procedure. CONCLUSIONS: Rescue PTCA tends to be selected for patients with clinical predictors of a poor outcome. It is effective in restoring patency. Patients who die after a failed rescue attempt are often already in extremis before the angioplasty attempt.

Aged↗

PubMed1998

Clinical predictors of early infarct-related artery patency following thrombolytic therapy: importance of body weight, smoking history, infarct-related artery and choice of thrombolytic regimen: the GUSTO-I experience. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

OBJECTIVES: The purpose of this study was to determine patient characteristics that are a priori predictors of early infarct related artery patency following thrombolytic therapy, and to provide a paradigm which may identify patients who would be most likely to achieve restoration of normal (TIMI 3) coronary flow in response to thrombolytic therapy. BACKGROUND: Restoration of infarct-related artery perfusion in acute myocardial infarction is necessary for preservation of ventricular function and mortality reduction. Clinical variables that are a priori predictors of early patency with currently available thrombolytic regimens have not been fully characterized. METHODS: The probability of early infarct-related artery patency (TIMI 3 flow) was determined by multivariable logistic regression. We determined a reduced (parsimonious) model for predicting early (90 min) infarct-related artery patency (TIMI grade 3) based on data from 1,030 patients in the GUSTO-I Angiographic study. RESULTS: Predictors of 90 min TIMI 3 flow are use of an accelerated t-PA regimen (vs. streptokinase containing regimens) (chi2=39.1; p < or = 0.0001), infarct related artery (RCA/Lcx vs. LAD) (chi2=12.7; p=0.0004), body weight (chi2=10.3; p=0.001) and history of smoking (chi2=7.4; p=0.007). Time from symptom onset to treatment was not significant (p=0.71). CONCLUSIONS: The efficacy of currently available thrombolytic regimens is chiefly dependent on choice of thrombolytic regimen, body weight, infarct-related coronary artery and smoking history. Clinical variables alone correctly predict a priori TIMI 3 flow in the infarct-related artery 64% of the time. Patients with body weights greater than 85 kg are at a significant disadvantage with regard to achieving successful thrombolysis compared to those with lesser body weights.

Aged↗

PubMed1997

End-systolic volume index at 90 to 180 minutes into reperfusion therapy for acute myocardial infarction is a strong predictor of early and late mortality. The Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I Angiographic Investigators.

BACKGROUND: Left ventricular remodeling is an important sequela of myocardial infarction (MI). Although remodeling occurs soon after MI, the effect of early left ventricular dilatation on outcome is not established and may be useful for early risk stratification. We assessed whether end-systolic volume index (ESVI) at 90 to 180 minutes into thrombolytic therapy for MI is associated with adverse outcomes. METHODS AND RESULTS: In the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-I study, 41021 patients with evolving MI received one of four thrombolytic regimens. At 90 or 180 minutes into reperfusion therapy, 1300 patients underwent left ventriculography. ESVI was measured and correlated with adverse outcomes: 30-day and 1-year mortality and in-hospital congestive heart failure, shock, and reinfarction. Clinical variables were also tested in a stepwise logistic regression analysis to determine predictors of left ventricular dilatation. ESVI was directly related to all adverse outcomes with univariate analysis. ESVI of > or = 40 mL/m2 was independently associated with mortality (adjusted odds ratio [95% confidence interval]: 30-day, 3.4 [2.0 to 5.9]; 1-year, 4:1 [2.6 to 6.2], both P < .001). Male sex, prior angina or MI, weight of < 70 kg, heart rate of > or = 80 bpm, systolic blood pressure of < 110 mm.Hg, and anterior infarction were independent predictors of an ESVI of > or = 40 mL/m2. CONCLUSIONS: Left ventricular ESVI early into reperfusion therapy for MI strongly predicts adverse outcomes, including early and late mortality. The study establishes the role of very early left ventricular dilatation on outcome in MI and may be useful in identifying high-risk patients who might benefit from aggressive treatment, including the early use of ACE inhibitors.

Aged↗

PubMed1997

Incidence and impact on outcome of streptokinase allergy in the GUSTO-I trial. Global Utilization of Streptokinase and t-PA in Occluded Coronary Arteries.

We evaluated allergic reactions in 20,201 patients randomized to the streptokinase arms of The Global Utilization of Streptokinase and t-PA (Tissue Plasminogen Activator) in Occluded Coronary Arteries (GUSTO-I) trial, and tested the hypothesis that patients with streptokinase allergy would exhibit higher mortality. After adjusting for baseline variables and time of death, we found comparable coronary patency, left ventricular function, mortality, and bleeding complications between patients with versus those without streptokinase allergy.

Anaphylaxis↗

PubMed1997

Prevalence of spinal disc disease among interventional cardiologists.

A suspected, but undocumented, excess of axial skeletal disease among interventional cardiologists (possibly a consequence of lead apron use) was investigated by comparing questionnaire responses from cardiologists, orthopedic surgeons, and rheumatologists (n = 714). Cardiologists reported more neck and back pain, more subsequent time lost from work, and a higher incidence of cervical disc herniations, as well as multiple level disc disease (all p <0.01): "interventionalist's disc disease" is a confirmed entity.

Adult↗

PubMed1997

Gender and acute myocardial infarction: is there a different response to thrombolysis?

OBJECTIVES: This study sought to 1) determine the effect of gender on early and late infarct-related artery patency and reocclusion after thrombolytic therapy for acute myocardial infarction; 2) examine the effect of gender on left ventricular function in response to injury/reperfusion; and 3) assess the independent contribution of gender to early (30-day) mortality after acute myocardial infarction. BACKGROUND: Women have a higher mortality rate than men after myocardial infarction. However, the effect of gender on infarct-related coronary artery patency and left ventricular response to injury/reperfusion have not been fully defined in the thrombolytic era. METHODS: Patency rates and global and regional left ventricular function were determined in patients at 90 min and 5 to 7 days after thrombolytic therapy for acute myocardial infarction. The effect of gender on infarct-related artery patency and left ventricular function was determined. Thirty-day mortality differences between women and men were compared. RESULTS: Women were significantly older and had more hypertension, diabetes, hypercholesterolemia, heart failure and shock. They were less likely to have had a previous myocardial infarction, history of smoking or previous bypass surgery. Ninety-minute patency rates (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) in women and men were 39% and 38%, respectively (p = 0.5). Reocclusion rates were 8.7% in women versus 5.1% in men (p = 0.14). Women had more recurrent ischemia than men (21.4% vs. 17.0%, respectively, p = 0.01). Ninety-minute ejection fraction and regional ventricular function were clinically similar in women and men with TIMI 2 or 3 flow (ejection fraction [mean +/- SD]: 63.4 +/- 6% vs. 59.4 +/- 0.7%, p = 0.02; number of chords: 21.4 +/- 0.9 vs. 21.0 +/- 1.9, p = 0.7; SD/chord: -2.4 +/- 08 vs. -2.4 +/- 0.2, p = 0.9, respectively). No clinically significant differences in left ventricular function were noted at 5- to 7-day follow-up. Women had a greater hyperkinetic response than men in the noninfarct zone (SD/chord: 2.4 +/- 0.2 vs. 1.7 +/- 0.1, p = 0.005). The 30-day mortality rate was 13.1% in women versus 4.8% in men (p < or = 0.0001). After adjustment for other clinical and angiographic variables, gender remained an independent determinant of 30-day mortality. CONCLUSIONS: Women do not differ significantly from men with regard to either early infarct-related artery patency rates or reocclusion after thrombolytic therapy or ventricular functional response to injury/reperfusion. Gender was an independent determinant of 30-day mortality after acute myocardial infarction.

Aged↗

PubMed1996

Evolution of early TIMI 2 flow after thrombolysis for acute myocardial infarction. GUSTO-1 Angiographic Investigators.

BACKGROUND: Patients with early Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolysis appear to have outcomes similar to thrombolytic failures. To evaluate the origin and evolution of early TIMI 2 flow, we examined early and late angiographic and ventriculographic data from the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-1) angiographic study. METHODS AND RESULTS: Of the 914 patients with both 90-minute and 5- to 7-day catheterizations, 278 patients had TIMI grade 2 flow at 90 minutes. At follow-up, 188 (67%) had improved to TIMI grade 3 flow. At 90 minutes, patients with TIMI grade 2 flow had greater infarct vessel narrowing and a significantly greater incidence of thrombus than patients with TIMI grade 3 flow. At the 5- to 7-day follow-up, patients whose flow had improved from TIMI grade 2 at 90 minutes to grade 3 flow at follow-up had larger-caliber vessels (minimum luminal diameter, 0.99 +/- 0.47 versus 0.84 +/- 0.48 mm; P = .03) and a lower incidence of visible thrombus (26% versus 38%, P = .04) than those with persistent TIMI grade 2 flow. These patients also had a higher mean ejection fraction (57.5 +/- 14.1% versus 52.8 +/- 12.9%, P = .02) and better infarct zone wall motion (-2.1 +/- 1.5 versus -2.6 +/- 1.3 SD per chord, P = .01) at the 5- to 7-day follow-up. Patients in whom flow improved from TIMI grade 2 at 90 minutes to TIMI grade 3 by 5 to 7 days had significantly better left ventricular function than patients with persistent TIMI grade 0, 1, or 2 flow and constituted a group whose left ventricular function was intermediate between those who had no reperfusion (TIMI grades 0 and 1) and those whose reperfusion was complete (TIMI grade 3). CONCLUSIONS: These data suggest that incomplete clot lysis plays a significant role in the pathogenesis of TIMI grade 2 flow. Furthermore, early TIMI grade 2 flow may be sufficient to provide prolonged myocyte viability, which will further recover if flow normalizes.

Aged↗

PubMed1996

Age and outcome with contemporary thrombolytic therapy. Results from the GUSTO-I trial. Global Utilization of Streptokinase and TPA for Occluded coronary arteries trial.

BACKGROUND: Elderly patients with acute myocardial infarction have much to gain from reperfusion with thrombolytic therapy but are also at increased risk of adverse events. We examined outcomes according to age of patients receiving thrombolysis in an international trial. METHODS AND RESULTS: Patients were randomized to streptokinase plus subcutaneous heparin, streptokinase plus intravenous heparin, accelerated tissue plasminogen activator (TPA) plus intravenous heparin, or streptokinase and TPA plus intravenous heparin. Clinical outcomes at 30 days (death, stroke, and nonfatal, disabling stroke) and 1-year mortality were summarized descriptively for patients aged < 65 (n = 24,708), 65 to 74 (n = 11,201), 75 to 85 (n = 4625), and > 85 years (n = 412) and assessed as continuous functions of age. Older patients had a higher-risk profile with regard to baseline clinical and angiographic characteristics. Mortality at 30 days increased markedly with age (3.0%, 9.5%, 19.6%, and 30.3% in the four groups, respectively), as did stroke, cardiogenic shock, bleeding, and reinfarction. Combined death or disabling stroke occurred less often with accelerated TPA in all but the oldest patients, who showed a weak trend toward a lower incidence with streptokinase plus subcutaneous heparin: odds ratio 1.13; 95% confidence interval 0.6, 2.1. Similarly, accelerated TPA treatment resulted in lower 1-year mortality in all but the oldest patients (47% TPA versus 40.3% streptokinase). CONCLUSIONS: Lower mortality and greater net clinical benefit were seen with accelerated TPA in patients aged < or = 85 years. Because data are limited for patients aged > 85 years, the relative superiority of a given thrombolytic regimen cannot be determined. The interactions of stroke and mortality with newer thrombolytic strategies must be examined explicitly in older patients.

Aged↗

PubMed1996

Heart rate variability assessment early after acute myocardial infarction. Pathophysiological and prognostic correlates. GUSTO ECG Substudy Investigators. Global Utilization of Streptokinase and TPA for Occluded Arteries.

BACKGROUND: Diminished heart rate variability is associated with less favorable prognosis after myocardial infarction. However, the prognostic value of early (first 48 hours) measurement and the influence of thrombolytic strategies, myocardial infarction location, left ventricular function, ST-segment shift, and infarct-related artery patency on heart rate variability have not been examined comprehensively. METHODS AND RESULTS: Heart rate variability and ST-segment analysis of 48-hour Holter tapes were performed with the use of a commercial system in 204 patients who were part of an ST-monitoring substudy of the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-I) trial. Both time-domain measures (SD of the average normal RR interval for all 5-minute segments of a 24-hour ECG recording [SDANN] and percent difference between adjacent normal RR intervals > 50 ms computed over the entire 24-hour ECG recording [pNN50]) and frequency-domain measures (low frequency [LF], high frequency [HF], and LF/HF ratio) were assessed on days 1 and 2 after acute myocardial infarction. Coronary angiography performed within the first 24 hours was also available in 75% of the patients. All heart rate variability measures decreased between day 1 and day 2 (P = .001) except the LF/HF ratio. There was no difference in heart rate variability among groups assigned to one of four different thrombolytic treatment strategies (streptokinase/subcutaneous heparin, streptokinase/intravenous heparin, accelerated tissue plasminogen activator, and combination streptokinase/tissue plasminogen activator). Heart rate variability measures were lower in anterior versus nonanterior infarcts (SDANN, 53 +/- 21 versus 63 +/- 24 ms; P < .005) and increased with TIMI grade 3 flow (LF, 5.3 +/- 1.0 versus 4.8 +/- 1.2 ms2; P < .01) and better ejection fraction (r = .2, P < .03). An inverse correlation between the duration of ST shift and frequency domain measures was observed (LF, r = -.2, P < .009; HF, r = -2, P < .03). Lower LF/HF ratio by 24 hours after myocardial infarction was seen in those who ultimately died at 30 days (1.0 +/- 0.2 versus 1.3 +/- 0.2, P < .001) or at 1 year (1.17 +/- 0.14 versus 1.26 +/- 0.19, P = .05). CONCLUSIONS: Changes in heart rate variability occurred early after thrombolysis and may be of prognostic value. Heart rate variability measures were improved in patients with better ejection fraction and greater angiographic patency. This suggests a possible mechanism for the enhanced survival observed with TIMI grade 3 flow in the GUSTO angiographic substudy. These data indicate that early heart rate variability assessment after myocardial infarction may be useful in noninvasive risk stratification.

Bradycardia↗

PubMed1996

Increased left ventricular dysfunction in elderly patients despite successful thrombolysis: the GUSTO-I angiographic experience.

OBJECTIVE: This study sought to determine whether the recovery of regional and global left ventricular function is reduced in elderly patients despite successful thrombolytic therapy for acute myocardial infarction. Comparisons were made between elderly (> or = 75 years old, n = 47) and adult (< 75 years old, n = 434) patients enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) angiographic trial who underwent catheterization at 90 min and 5 to 7 days after thrombolysis and who had an open infarct-related artery with Thrombolysis in Myocardial Infarction (TIMI) grade 2 to 3 flow at both times. BACKGROUND: The morbidity and mortality of acute myocardial infarction is increased in elderly patients, presumably because of multiple adverse coexistent baseline variables. However, functional recovery after thrombolysis has not been characterized in the elderly. METHODS: Ejection fraction, end-systolic volume index, infarct and noninfarct zone contractile function (SD/chord) and infarct extent (number of chords) were determined. RESULTS: At 90 min, elderly patients with an open infarct-related artery had decreased infarct zone contractile function (-2.8 +/- 0.2 vs. -2.3 +/- 0.1 SD/chord in adults, p < or = 0.05) and a greater extent of injury (26.0 +/- 2.6 vs. 20.7 +/- 0.8 chords in adults, p < or = 0.05). At 5- to 7-day follow-up ventriculography, ejection fraction was reduced, and end-systolic volume index was significantly increased in elderly patients compared with adults. The severity of regional wall motion dysfunction in the infarct zone was also greater in the elderly than in adults at 5- to 7-day follow-up (-2.6 +/- 0.2 vs. -1.9 +/- 0.1 SD/chord, respectively, p < or = 0.005). Non-infarct zone contractile function at 90-min ventriculography was similar in both groups. Despite a patent infarct-related artery at 90-min, the 30-day mortality rate in the elderly remained elevated (17.8%) compared with that of adults (4%) (p < or = 0.0001). Elderly patients were predominantly female and had a higher prevalence of hypertension, multivessel coronary disease, previous infarction, anterior infarctions and later time to treatment (between 3 and 6 h) than adults. However, age > or = 75 years remained an independent determinant by multivariable regression analysis of 1-week postinfarction end-systolic volume index, regional left ventricular dysfunction (p = 0.02 and p < or = 0.008, respectively) and 30-day mortality (p < or = 0.0001). CONCLUSIONS: Elderly patients had increased damage in the infarct zone and had persistently increased mortality despite sustained infarct-related artery patency after successful thrombolysis. Although the causes are probably multifactorial, a more rapid progression of ischemic injury or a blunted postreperfusion recovery appears to contribute to the poorer outcomes in elderly patients.

Adult↗

PubMed1996

Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience.

OBJECTIVES: This study sought to determine whether diabetes mellitus, in the setting of thrombolysis for acute myocardial infarction, affects 1) early infarct-related artery patency and reocclusion rates; and 2) global and regional ventricular function indexes. We also sought to assess whether angiographic or baseline clinical variables, or both, can account for the known excess mortality after myocardial infarction in the diabetic population. BACKGROUND: Mortality after acute myocardial infarction in patients with diabetes is approximately twice that of nondiabetic patients. It is uncertain whether this difference in mortality is due to a lower rate of successful thrombolysis, increased reocclusion after successful thrombolysis, greater ventricular injury or a more adverse angiographic or clinical profile in diabetic patients. METHODS: Patency rates and global and regional left ventricular function were determined in patients enrolled in the GUSTO-I Angiographic Trial. Thirty-day mortality differences between those with and without diabetes were compared. RESULTS: The diabetic cohort had a significantly higher proportion of female and elderly patients, and they were more often hypertensive, came to the hospital later and had more congestive heart failure and a higher number of previous myocardial infarctions and bypass surgery procedures. Ninety-minute patency (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) rates in patients with and without diabetes were 40.3% and 37.6%, respectively (p = 0.7). Reocclusion rates were 9.2% vs. 5.3% (p = 0.17). Ejection fraction at 90 min after thrombolysis was similar in diabetic and nondiabetic patients ([mean +/- SEM] 6.10 +/- 1.6% vs. 60.1 +/- 0.7%, p = 0.7), as was regional ventricular function (number of abnormal chords: 19.1 +/- 2.0 vs. 17.5 +/- 0.8, p = 0.3; SD/chord: -2.3 +/- 0.2 vs. -2.4 +/- 0.1, p = 0.6). Diabetic patients had less compensatory hyperkinesia in the noninfarct zone (SD/ chord: 1.3 +/- 0.2 vs. 1.7 +/- 0.1, p < or = 0.01). No significant difference in ventricular function was noted at 5- to 7-day follow-up. The 30-day mortality rate was 11.3% in diabetic versus 5.9% in nondiabetic patients (p < or = 0.0001). After adjustment for clinical and angiographic variables, diabetes remained an independent determinant of 30-day mortality (p = 0.02). CONCLUSIONS: Early (90-min) infarct-related artery patency as well as regional and global ventricular function do not differ between patients with and without diabetes after thrombolytic therapy, except for reduced compensatory hyperkinesia in the noninfarct zone among patients with diabetes. Diabetes remained an independent determinant of 30-day mortality after correction for clinical and angiographic variables.

Aged↗

PubMed1996

Non-invasive prediction of reperfusion and coronary artery patency by continuous ST segment monitoring in the GUSTO-I trial.

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 (> or = 400 microV), 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.

Arteries↗