Patency Of Infarct-related Artery Research Articles

Clinical Significance of the Antibody against Oxidized Low-Density Lipoprotein in Acute Myocardial Infarction

To establish the clinical significance of the antibody against oxidized low-density lipoprotein (anti-Ox-LDL) titer in patients with acute myocardial infarction (AMI), we measured the anti-Ox-LDL titer in 39 patients with AMI and 25 controls. In all AMI patients, the anti-Ox-LDL titer on admission was higher (p < 0.05) than the value in the controls. One month after admission, the titer decreased significantly (p < 0.001) reaching control levels. In patients who underwent thrombolytic therapy, the anti-Ox-LDL titer on admission was identical in patients with occluded infarct-related arteries (IRA) and patients with patent IRA during emergency coronary angiography. In patients who did not undergo thrombolytic therapy, the anti-Ox-LDL titer on admission was higher in patients with occluded IRA than in patients with patent IRA. An increased anti-Ox-LDL titer may be a risk factor for the onset of AMI. Spontaneous recanalization of the IRA may be associated with increased anti-Ox-LDL titers, while thrombolysis-induced recanalization may be independent of it.

“Time Is Muscle” Only in Experienced Hands and High-Volume Centers

Acute myocardial infarction (MI) occurs in nearly 1.5 million patients and claims more than 450,000 lives each year in the United States. The past 3 decades have witnessed a dramatic reduction in the mortality rate of acute MI. The widespread use of thrombolytic therapy has revolutionized management of acute MI. However, the use of thrombolytic therapy is limited in that many patients have contraindications to its administration. In the recent Global Registry of Acute Coronary Events (GRACE) registry data of the 2501 patients who presented with ST segment elevation acute MI, 12.8% of patients had contraindications to thrombolytic treatment [1]. In addition, contemporary fibrinolytic and antithrombotic therapy is associated with a relatively low rate of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow and high rates of reocclusion. The most effective thrombolytic regimens achieve angiographic infarct related artery (IRA) patency in approximately only 50% of patients within 90 minutes. The GUSTO-I angiographic substudy strongly correlated 90-minute patency of the IRA with the mortality reduction achieved [2]. Regardless of the thrombolytic agent used, an occluded IRA (ie, TIMI grade 0 or 1 flow) at 90 minutes is associated with an 8.9% 30-day mortality rate and “normal” perfusion (TIMI grade 3 flow) is associated with a 4.0% mortality rate [3]. The incidence of complications with fibrinolytic therapy, especially intracranial hemorrhage, is not trivial. Thrombolysis is associated with an increase in the stroke rate of approximately 0.4% to 0.8%, and there is bleeding requiring transfusion in

Infarct-related artery patency can be assessed by quantification of myocardial blood flow velocity with contrast echocardiography

Infarct-related artery patency can be assessed by quantification of myocardial blood flow velocity with contrast echocardiography

Failed reperfusion after thrombolytic therapy: Recognition and management

Background: Failed reperfusion after thrombolysis occurs in as many as 30% of patients with acute myocardial infarction (MI). Furthermore, some patients have incomplete tissue perfusion despite reperfusion of the infarct-related artery. Close assessment of the efficacy of thrombolytic administration in people with evolving acute MI is necessary, particularly with regard to myocardial perfusion status, because some patients may benefit from incremental pharmacologic or invasive reperfusion strategies. Purpose and Method: This article reviews a number of strategies to assess infarct-related artery patency and myocardial tissue perfusion. These include coronary angiography, continuous ST-segment monitoring, serial electrocardiography, obtaining serial serum biochemical markers of myocardial necrosis, monitoring for reperfusion arrhythmias, and assessment of changes in chest pain intensity. Conclusion: The early detection of failed reperfusion is critical if incremental strategies to enhance myocardial salvage are to be considered. Continuous ST-segment monitoring is a relatively inexpensive, reliable, and accurate tool for assessing real-time myocardial perfusion. (Heart Lung® 2002;31:113-21.)

Inducible ventricular arrhythmias and patency of infarct-related artery in survivors of acute myocardial infarction.

Patency of infarct-related artery in patients who suffered an acute myocardial infarction (AMI) has been shown to be associated with improved survival. Ventricular tachyarrhythmias induced by programmed electrical stimulation may be predictive of arrhythmic events and sudden death. The study was undertaken to assess the possible effect of a patent infarct-related coronary artery on induced ventricular tachyarrhythmias during programmed ventricular stimulation in survivors of AMI. In this prospective study, programmed electrical stimulation was performed before hospital discharge (14 +/- 2 days) in 79 patients who survived an AMI. Patients were subdivided into two groups: Group I with patent infarct-related coronary artery (n = 64) and Group 2 with occluded infarct-related artery (n = 15) at coronary angiography performed at 14 +/- 2 days. These two groups were comparable in terms of mean left ventricular ejection fraction, location of infarct-related artery, number of diseased vessels, peak creatine kinase value, and infarct location. Ventricular arrhythmias were induced in 21 patients ( 32.6%) of Group I and 4 patients (26.6%) of Group 2. This difference was not statistically significant. This study suggests that ventricular arrhythmias induced by programmed ventricular stimulation in survivors of AMI did not differ whether the infarct-related artery was patent or occluded. Other factors may play a role in electrical instability as assessed by programmed ventricular stimulation.

The effect of thrombolytic therapy on left ventricular aneurysm formation in acute myocardial infarction: relationship to successful reperfusion and vessel patency.

Although there is increasing evidence for the beneficial effect of thrombolytic therapy on global left ventricular (LV) function in acute myocardial infarction (AMI), the data concerning the early effect of thrombolytic therapy on the incidence of left ventricular aneurysm (LVA) formation and its relationship to clinical and angiographic determinants are limited. The study aimed to determine the independent factors involved in the development of LVA and to evaluate whether thrombolytic therapy has any preventive effect on the development of LVA in AMI. In all, 350 consecutive patients suffering from a first attack of AMI were included. Of these, 205 who arrived within 12 h of onset of symptoms received thrombolytic therapy (thrombolytic group) and the remaining 145 patients served as control group. All patients received aspirin and maximal-dose anticoagulation with intravenous heparin therapy. Early successful reperfusion was assessed by enzymatic and electrocardiographic evidence, and late vessel patency was evaluated according to Thrombolysis in Myocardial Infarction (TIMI) classification. Patients with TIMI grade 2 or 3 flow were considered to have vessel patency. The overall incidence of LVA was 11.7% (41/350), and no statistical difference was found between the incidence of LVA between the two groups (11.7 vs. 11.7%, p>0.05). However, the patients receiving thrombolytic therapy and exhibiting a patent infarct-related artery (PIRA) (n = 125, 61%), had a significantly reduced incidence of LVA compared with those who did not (7.2 vs. 18.8%, p= 0.015). In univariate analysis, vessel patency, proximal left anterior descending artery (LAD) stenosis, total LAD occlusion, multivessel disease, and hypertension were found to be important factors in LVA formation after AMI. After adjustment for other clinical and angiographic variables, total LAD occlusion (odds ratio [OR] 3.62,95% confidence interval [CI] 2.45-8.42, p = 0.0014), absence of PIRA (OR 2.92, 95% CI 1.41-09, p = 0.0037) and proximal LAD stenosis (OR 2.11, 95% CI 1.05-4.71, p = 0.045) remained the independent determinants of LVA formation after AMI. Our data indicate that not all patients who received thrombolytic therapy, but only those with PIRA had evidently reduced the incidence of LVA. Patients with total LAD occlusion, with proximal LAD stenosis, and without PIRA were found to have increased risk for formation of LVA after AMI. These findings indicate that the presence of vessel patency has a preventive effect on LVA formation in AMI.

The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: Data from the National Registry of Myocardial Infarction 2

Background Cardiogenic shock complicating acute myocardial infarction (AMI) remains the leading cause of death in patients hospitalized with AMI. Although several studies have demonstrated the importance of establishing and maintaining a patent infarct-related artery, it remains unclear as to whether intra-aortic balloon counterpulsation (IABP) provides incremental benefit to reperfusion therapy. The purpose of this study was to determine whether IABP use is associated with lower in-hospital mortality rates in patients with AMI complicated by cardiogenic shock in a large AMI registry. Methods We evaluated patients participating in the National Registry of Myocardial Infarction 2 who had cardiogenic shock at initial examination or in whom cardiogenic shock developed during hospitalization (n = 23,180). Results The mean age of patients in the study was 72 years, 54% were men, and the majority were white. The overall mortality rate in all patients who had cardiogenic shock or in whom cardiogenic shock developed was 70%. IABP was used in 7268 (31%) patients. IABP use was associated with a significant reduction in mortality rates in patients who received thrombolytic therapy (67% vs 49%) but was not associated with any benefit in patients treated with primary angioplasty (45% vs 47%). In a multivariate model, the use of IABP in conjunction with thrombolytic therapy decreased the odds of death by 18% (odds ratio, 0.82; 95% confidence interval, 0.72 to 0.93). Conclusions Patients with AMI complicated by cardiogenic shock may have substantial benefit from IABP when used in combination with thrombolytic therapy. (Am Heart J 2001;141:933-9.)

Preinfarction angina prevents left ventricular remodeling in patients treated with thrombolysis for myocardial infarction.

It has been shown that preinfarction angina may have beneficial effects on infarct size and mortality. However, there are no studies that have serially assessed the impact of preinfarction angina on left ventricular (LV) function in a large series of patients. The study was undertaken to determine whether preinfarction angina (within 7 days before infarction) influences LV remodeling. In all, 119 consecutive patients with acute myocardial infarction were serially evaluated by 2-dimensional echocardiography (on Days 1, 2, 3, and 7; at 3 and 6 weeks; and at 3, 6, and 12 months following infarction). Left ventricular volumes were determined using Simpson's biplane formula and normalized for body surface area. Wall motion score index and sphericity index were calculated for each study. Coronary angiography was performed before discharge. Preinfarction angina was detected in 39 of 119 patients. Initial echocardiographic and clinical data as well as the incidence of patent infarct-related artery and collaterals were similar for patients with and without preinfarction angina. In the subset of thrombolysed patients, patients with preinfarction angina showed decrease of LV end-diastolic and end-systolic volumes during the follow-up period (p = 0.033 and p = 0.001, respectively), and improvement of wall motion score index (p < 0.001) and ejection fraction occurred (p = 0.001), without changing of LV shape (p > 0.05); in addition, patients with preinfarction angina had smaller LV volumes and higher ejection fraction than did those without angina, from 3 weeks onward. These favorable effects were not detected in patients not treated with thrombolysis. These data indicate that preinfarction angina has an inhibiting effect on long-term LV remodeling in patients who underwent thrombolysis for first acute myocardial infarction. It appears that preinfarction angina has no impact on infarct size and early postinfarction LV function.

Early patency of the infarct-related artery after myocardial infarction preserves diastolic filling

A patent infarct-related artery (IRA) following myocardial infarction has been associated with lower mortality, increased systolic function, decreased left ventricular remodeling, and electrical stability. The purpose of this study was to determine whether coronary artery patency early after myocardial infarction is associated with greater early diastolic filling than a closed artery. Radionuclide ventriculograms were performed at a central laboratory on 167 patients who received alteplase for an acute myocardial infarction and had infarct artery patency determined by cardiac catheterization. The peak early filling rate (PEFR) was assessed by 4 different methods: (1) PEFR (EDV/s)—normalized to the end-diastolic volume; (2) PEFR (SV/s)—normalized to the stroke volume; (3) PEFR (ml/s/m 2)—an absolute diastolic filling rate; and (4) PEFR (PER)—normalized to the peak ejection rate. Patients with a closed IRA (n = 16, Thrombolysis In Myocardial Infarction [TIMI] 0 or 1 flow) and patients with an open IRA (n = 151, TIMI 2 or 3 flow) had similar ages, ejection fractions, and cardiac volumes. However, among patients with an occluded IRA, the PEFR was decreased by 12% to 18% by the 4 measures of diastolic filling (3 of 4 methods, p <0.05). PEFR (EDV/s) was 1.69 ± 0.9 in the occluded group versus 2.06 ± 0.4 EDV/s in the open artery group (p = 0.005). By multivariate analysis, IRA patency was an independent predictor of the PEFR by all 4 methods. Early coronary artery patency after an acute myocardial infarction preserves diastolic filling. Improved diastolic function may in part explain part of the long-term benefits of a patent IRA after thrombolytic therapy when there is no documented improvement in the ejection fraction.

Corrected TIMI frame counts correlate with stenosis severity and infarct zone wall motion after thrombolytic therapy

Background The majority of patients with patent infarct-related arteries after thrombolytic therapy have slower than normal flow, which relates to myocardial perfusion. Methods To evaluate the relationships between blood levels of creatine kinase (CK) and the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC), infarct artery stenosis, and left ventricular function, we studied 397 patients with a first myocardial infarction who underwent angiography at 3 weeks. TIMI flow grades, the CTFC, infarct artery stenosis, and infarct zone wall motion (by contrast ventriculography using the centerline method) were assessed, and CK levels (in units per liter) were measured hourly for the first 4 hours after streptokinase (1.5 × 106 U over 30-60 minutes) and then every 4 hours over the next 20 hours, all blinded to treatment and outcome. Results Infarct artery stenosis and the CTFC, assessed as continuous variables, correlated in patients with patent infarct arteries (r = 0.33, P <.001). Also, there was a significant correlation between the CTFC and the sum of hypokinetic chords in the infarct zone (r = 0.15, P =.01). Patients with total occlusion or markedly slowed infarct artery flow (CTFC >100) had a higher fraction of chords with wall motion >2 SDs below normal (0.65 [0.41, 0.80] vs 0.37 [0.0, 0.67]) compared with patients with normal flow (CTFC ≤27) (P <.001). The rates of increase of median CK levels with respect to TIMI flow grades were 342 U/L/h for TIMI 3 versus 212 U/L/h for TIMI 2 versus 140 U/L/h for TIMI 0-1 (P <.0001). Conclusions Prolonged corrected TIMI frame counts correlate with stenosis severity in the infarct artery after infarction, infarct zone regional wall motion, and CK levels. (Am Heart J 2001;141:586-91.)

Abciximab and early adjunctive percutaneous coronary intervention are associated with improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 Trial

Background Percutaneous coronary intervention (PCI) improves clinical outcomes in selected patients with failed thrombolysis but has not been proven to benefit patients who achieve a patent infarct-related artery. Even after successful epicardial reperfusion, myocardial perfusion may be inadequate. We sought to evaluate whether a strategy that uses a reperfusion regimen containing abciximab and a reduced-dose thrombolytic agent (combination therapy), followed by early adjunctive PCI, would result in improved myocardial perfusion, as assessed by ST-segment resolution. Methods ST resolution from 90 to 180 minutes after therapy was calculated for all 410 patients from the TIMI 14 trial who had evaluable electrocardiograms at both time points and who were treated with alteplase or reteplase. Patients were grouped according to whether they were treated with combination therapy or full-dose thrombolytic agent alone and whether they underwent PCI between the 90- and 180-minute electrocardiographic measurements. Results Among 105 patients who underwent adjunctive PCI between 90 and 180 minutes, mean ST resolution from 90 to 180 minutes was significantly greater in those who had received combination therapy versus those who had received full-dose thrombolytic alone (54% vs 8%; P =.002). Among 241 patients with TIMI grade 3 flow in the infarct-related artery at 90 minutes, adjunctive PCI significantly improved mean ST resolution in patients who had been treated with combination therapy (57% [PCI] vs 24% [no PCI]; P =.006), but PCI did not have this effect in patients who had received thrombolytic therapy alone (1% [PCI] vs 10% [no PCI]; P =.70). In a multivariate model controlling for factors that would be expected to independently influence 90- to 180-minute ST resolution, abciximab treatment remained significantly associated with greater ST resolution (P =.008). Conclusions A strategy that uses a combination reperfusion regimen that includes abciximab, followed by early adjunctive PCI, is associated with greater ST-segment resolution, which may reflect enhanced tissue level and microvascular perfusion. Future studies should evaluate prospectively the clinical efficacy of this strategy. (Am Heart J 2001;141:592-8.)

Exploring the issues of appropriate dosing in the treatment of acute myocardial infarction: Potential benefits of bolus fibrinolytic agents

The Institute of Medicine report on the frequency and consequences of medical errors in clinical practice has stimulated physicians to evaluate current practice and means of improving medical care. In the treatment of patients with acute myocardial infarction, previous studies have found that dosing of fibrinolytic therapy is closely related to outcomes, with too low a dose associated with lower rates of infarct-related artery patency and higher doses associated with increased intracranial hemorrhage. Thus there is a narrow ″therapeutic window” for fibrinolytic-antithrombotic regimens, and the potential for adverse outcomes is high if incorrect doses are administered. The first demonstration of this concept came from the GUSTO-I trial, in which 13.5% of patients treated with streptokinase and 11.5% of patients treated with tissue plasminogen activator (t-PA) had a dosing regimen that deviated from the protocol, that is, an incorrect total dose or infusion length. In patients with protocol deviations, 24-hour and 30-day mortality rates were significantly higher compared with those of patients with per-protocol dosing: for t-PA, patients who received incorrect dosing had a 30-day mortality rate of 7.7% versus 5.5% for patients who received correct t-PA dosing (P < .001), with similar findings for streptokinase. More recent data from the InTIME-II trial have shown that the use of a bolus fibrinolytic agent significantly increases the percentage of patients who receive complete and optimally dosed fibrinolysis. Thus use of the simpler bolus fibrinolytic agents may reduce medication errors and thus may optimize clinical outcomes. (Am Heart J 2000;140:S154-60.)

Reducing medication errors: potential benefits of bolus thrombolytic agents.

A recent Institute of Medicine report highlighted the high incidence of medical errors in clinical practice, and the important fact that errors are associated with increased mortality. The administration of thrombolytic therapy for acute myocardial infarction is a particularly high-risk situation for emergency physicians. The combination of extreme time pressure with a narrow "therapeutic window" increases the potential for adverse outcomes due to dosing errors. Numerous trials have found that the dose of thrombolytic therapy is closely related to outcomes, with too low a dose associated with lower rates of infarct-related artery patency and higher doses associated with increased bleeding and intracranial hemorrhage. In the GUSTO-I trial, 13.5% of patients treated with streptokinase and 11.5% of patients treated with tissue plasminogen activator (t-PA) had a medication error (i.e., incorrect dose or infusion length). Most importantly, 30-day mortality was significantly higher in patients with medication errors: for t-PA dosing errors mortality was 7.7% vs 5.5% for patients who received the correct t-PA dose (p < 0.001), with similar findings for streptokinase. More recent data from the InTIME2 trial and other studies showed that use of a bolus thrombolytic agent reduced the rate of medication errors. Thus, use of the simpler bolus thrombolytic agents may reduce emergency department medication errors, and thus improve overall clinical outcome.

Relationship of infarct artery patency and left ventricular ejection fraction to health-related quality of life after myocardial infarction: the GUSTO-I Angiographic Study experience.

Post-myocardial infarction global ejection fraction and infarct-related artery patency might be expected to be associated with health-related quality-of-life (HRQOL) outcomes, but this association has not been previously shown. The GUSTO-I Angiographic Study cohort 2-year follow-up afforded an examination of such potential relationships. A total of 1848 patients (87.7% response rate) who were enrolled in the GUSTO-I Angiographic Study were contacted for a telephone interview regarding their current HRQOL (physical function, psychological well-being, perceived health status, and social function) 2 years after MI. In multivariable models, left ventricular ejection fraction (EF) was significantly related to physical (P:=0.021) and social (P:=0.014) function, psychological well-being (P:=0.042), and perceived health status (P:=0.024). Infarct-related artery patency was not directly related to any HRQOL outcome. A decreasing EF was predictive of poorer outcomes in each HRQOL dimension. Men consistently had better outcomes in all HRQOL dimension with the exception of perceived health status. Increasing age was predictive of poorer outcomes in all dimensions of HRQOL except for psychological well-being where the inverse occurred; younger patients experienced greater depression, anxiety and worry than their older counterparts. The presence of comorbidities increased the likelihood of worse outcomes in all dimensions. This is the first study to demonstrate a significant relationship between EF and long-term HRQOL outcomes. This advantage in left ventricular function preservation should be added to the mortality advantage when considering the impact of treatment strategies for myocardial infarction.

Early Prognostic Assessment and Treatment of Acute Myocardial Infarction in the Elderly.

The progressive aging of the population is associated with an increase in the proportion of very old patients (greater than 75 years) hospitalized with acute myocardial infarction. The lack of evidence regarding the efficacy of most therapeutic interventions for acute myocardial infarction in these patients is leading to a significant degree of uncertainty in the cardiology community with respect to their optimal management. When aggressive treatment (defined as a therapeutic strategy designed to obtain and maintain a patent infarct-related coronary artery at an early moment) of acute myocardial infarction is considered in very old patients, three main questions should be addressed: why should we treat? Whom should we treat? And how should we treat? To answer these questions, the authors reviewed the data available in the literature as well as new data from the PPRIMM75 (Pronóstico del PRimer Infarto de Miocardio en Mayores de 75 aÃ+/-os) Registry, a large, prospective database of patients aged 75 years or older, admitted to a single coronary care unit in Madrid, Spain, for their first acute myocardial infarction during the last decade. (c) 2000 by CVRR, Inc.

Heart-Type Fatty Acid Binding Protein as a marker of reperfusion after thrombolytic therapy

Accurate, rapid, and simple noninvasive measures of infarct-related artery (IRA) patency are needed to identify patients with failed coronary reperfusion for rescue percutaneous coronary intervention (PCI). Heart-type Fatty Acid Binding Protein (H-FABP) is a small, cytosolic protein found in high concentrations in the myocardium. We evaluated the efficacy of H-FABP as a marker for successful reperfusion after thrombolysis. Fifty-eight subjects from the TIMI 14 trial had H-FABP and myoglobin concentrations measured at baseline (immediately prior to thrombolysis) and 60, 90, and 180 min after thrombolysis. All patients underwent coronary angiography at 90 min. By 60 min after thrombolysis, median concentrations of H-FABP and myoglobin were significantly higher in patients with a patent IRA than in those with an occluded IRA ( P<0.01 for each). Similarly, the 60 and 90 min/baseline H-FABP and myoglobin ratios were significantly higher among patients with a patent IRA ( P<0.01 for each). There were no significant differences in marker concentrations or ratios between patients with TIMI grade 2 and TIMI grade 3 flow. The area under the ROC curve tended to be greater for the 60 and 90 min/baseline myoglobin ratios than for similar ratios of H-FABP (0.71 and 0.73 vs. 0.64 and 0.62; P=ns). In conclusion, successful reperfusion can be detected within the first 60 min after thrombolysis with either H-FABP or myoglobin. Despite a favorable kinetic profile, however, H-FABP does not appear to represent a significant advance over myoglobin in the noninvasive detection of reperfusion after thrombolysis.

Infarct related artery patency: relation to serial electropharmacological studies and outcome in patients with previous myocardial infarction and ventricular tachyarrhythmias.

Evidence suggests that infarct related artery (IRA) patency may improve survival after acute myocardial infarction, which is thought to be partially due to a lower incidence of malignant ventricular tachyarrhythmias. However, little is known about the effect of IRA patency on antiarrhythmic drug response and long-term outcome in patients with previous infarction who already experienced sustained ventricular tachyarrhythmias. A total of 152 patients with remote myocardial infarction and documented ventricular tachycardia (VT) or ventricular fibrillation (VF) underwent coronary angiography and programmed ventricular stimulation before and after oral administration of d,l-sotalol (240-640 mg/day). D,l-sotalol suppressed inducibility of VT/VF in 37 (25.2%) patients. The IRA was patent in 38.1% of all patients. There was no significant difference in the frequency of drug response between patients with patent or occluded IRAs (26.8% vs 24.2%, P = 0.87). In patients with a patent IRA, d,l-sotalol tended to be more effective in the absence of a left ventricular aneurysm, although this difference did not reach statistical significance (P = 0.38). Ejection fraction and collateral blood flow had no effect on drug response in the presence or absence of IRA patency. During follow-up (13.0 +/- 19.9 months) of 29 patients discharged on oral d,l-sotalol, 3 patients experienced symptomatic VT and 4 sudden death. Arrhythmia recurrence and death of all cause (n = 6) and cardiac death (n = 4) were independent of IRA patency status. IRA patency had no effect on short-term drug response to d,l-sotalol in patients with remote myocardial infarction and documented VT/VF. Long-term outcome of patients with sustained ventricular tachyarrhythmias is independent of IRA patency status. In contrast to a previous report, outcome of electropharmacological testing was not predicted by the patency of the IRA.

The open artery hypothesis: Potential mechanisms of action

The postinfarction period is one of intense dynamic activity because the cardiovascular system undergoes a number of adaptive responses attempting to maintain cardiac output. These homeostatic responses contribute to the processes involved in postinfarction ventricular remodeling and involve acute, chronic, systemic, and local reactions. Almost immediately, neurohormones are activated that alter hemodynamic load, and, later, stimulate myocyte hypertrophy, while locally, inflammatory processes clear necrotic debris, reorganize the extracellular matrix, and orchestrate scar formation. Where the initial cardiac insult is sufficiently large (eg, necrosis of more than 40% of left ventricular mass), remodeling responses are exaggerated and may become maladaptive, contributing to the poor long-term prognosis associated with myocardial infarction. Although several studies have shown clear benefits after neurohormonal modulation and/or manipulation of ventricular loading forces in the postinfarction setting, relatively few studies have investigated the potential merits of a patent infarct-related artery during postinfarction ventricular remodeling. In particular, the salutary effects of late revascularization of previously occluded vessels remains controversial. Thus, though this issue remains speculative, our present practice must be governed by circumstantial evidence and hypothetical arguments. This article discusses the potential mechanisms whereby late reperfusion of an infarcted myocardial region may benefit long-term prognosis. Copyright © 2000 by W.B. Saunders Company Progress in Cardiovascular Diseases, Vol. 42, No. 6 (May/June), 2000: pp 419-438

Thrombolysis medication errors: benefits of bolus thrombolytic agents

A recent report has highlighted the high incidence of medical errors in clinical practice and the important fact that errors are associated with increased mortality. This issue is now being examined closely in the field of thrombolytic therapy for acute myocardial infarction. Numerous trials have found that the dose of the thrombolytic agent is closely related to outcome, with too low a dose associated with lower rates of infarct-related artery patency and higher doses associated with increased bleeding and intracranial hemorrhage. Thus, the “therapeutic window” for thrombolytic therapy is small, and the potential for adverse outcome from dosing errors is high. In the Global Use of Strategies To Open occluded arteries (GUSTO)-I trial, 13.5% of patients treated with streptokinase and 11.5% of patients treated with tissue plasminogen activator (t-PA) were subjected to a medication error (e.g., incorrect dose or infusion length). Most importantly, 30-day mortality was significantly higher in patients with medication errors: For t-PA dosing errors, mortality was 7.7% versus 5.5% for patients who received the correct t-PA dose (p <0.001); findings were similar for streptokinase. More recent data from the Intravenous n-PA for Treatment of Infarcting Myocardium Early (InTIME)-II trial and other studies showed that use of a bolus thrombolytic agent reduced the rate of medication errors. Thus, use of the simpler bolus thrombolytic agents may improve overall clinical outcome.

Dispersion of ventricular repolarization is determined by the presence of myocardial viability in patients with old myocardial infarction. A dobutamine stress echocardiography study.

The study sought to investigate the relationship of myocardial viability detected by dobutamine stress echocardiography to changes of QT dispersion and to the presence of arrhythmias during dobutamine infusion in patients with old myocardial infarction. We also examined whether patency of the infarct-related artery is associated with the presence of myocardial viability and QT dispersion. QT dispersion and myocardial variability have been associated with the presence of arrhythmias during late post infarction but not during dobutamine stress. Restoration of anterograde coronary flow has beneficial effects on ventricular systolic function and repolarization, suggesting that the extent of viable myocardium may determine ventricular repolarization. Seventy five patients with previous myocardial infarction were studied in a low dose (up to 20 microg(-1) x kg(-1) x min(-1)) dobutamine stress echocardiography study. ECGs were obtained at rest and peak stress for measurement of QT intervals. The presence of ventricular arrhythmias (Lown grade >lb) during stress was noted. A reduction in the total wall motion score of the left ventricle at peak stress confirmed the presence of myocardial viability. Dobutamine infusion increased QT dispersion in all patients (P<0.01). Patients with myocardial viability had a lower resting QT dispersion (P<0.05) and a greater increase in QT dispersion% (P<0.01) than patients without. The combination of a resting QT dispersion <65 ms or an increase in QT dispersion >30% predicted viability with a sensitivity of 67%, a specificity of 96%, and an accuracy of 78%. A patent infarct-related artery, as well as ventricular arrhythmias, were more commonly observed in patients with evidence of viable myocardium (P<0.05). Patients with arrhythmias had a higher QT dispersion than patients without (P<0.05). The combination of a resting QT dispersion +/-65 ms or an increase in QT dispersion >30% predicts the presence of viable myocardium and thus, may represent a simple index for the assessment of viability in everyday clinical practice. Myocardial viability is related to a patent coronary artery and to a high incidence of arrhythmias accompanied by a greater increase in QT dispersion at peak dobutamine infusion.