Vascular endothelial growth factors in pulmonary edema: an update.

Pulmonary edema is a life-threatening complication of critical illness. Identification of the underlying mechanisms of pulmonary edema is a prerequisite for the development of adequate treatment. The initial description of fluid transportation across capillaries (Starling's law) while of critical importance, did not provide full insight into the underlying pathophysiology of vascular leakage. Pulmonary edema can be differentiated into two distinct categories based on the Starling theory; the high-permeability type is attributed to inflammatory changes occurring in conditions such as the adult respiratory distress syndrome (ARDS) and the cardiogenic type is characterized by an imbalance in the Starling hydrostatic forces and occurs in acute or decompensated heart failure. However, it has long been recognized that there is significant overlap between the various types of pulmonary edema, raising important questions regarding the role of novel mechanisms that may contribute to the development of interstitial and alveolar leakage. Recently, several studies on VEGF, an angiogenic growth factor which affects endothelial permeability, have identified this molecule as a potential regulator of vascular leakage and repair in pulmonary edema. We review here the underlying the mechanisms by which VEGF may do this and will discuss the still unanswered questions regarding vascular pharmacology in the setting of pulmonary edema.

Acute reperfusion therapy in ST-elevation myocardial infarction from 1994-2003.

BACKGROUND: Appropriate utilization of acute reperfusion therapy is not a national performance measure for ST-elevation myocardial infarction at this time, and the extent of its contemporary use among ideal patients is unknown. METHODS: From the National Registry of Myocardial Infarction, we identified 238,291 patients enrolled from June 1994 to May 2003 who were ideally suited for acute reperfusion therapy with fibrinolytic therapy or primary percutaneous coronary intervention. We determined rates of not receiving therapy across 3 time periods (June 1994-May 1997, June 1997-May 2000, June 2000-May 2003) and evaluated factors associated with underutilization. RESULTS: The proportion of ideal patients not receiving acute reperfusion therapy decreased by one half throughout the past decade (time period 1: 20.6%; time period 2: 11.4%; time period 3: 11.6%; P <.001). Utilization remained significantly lower in key subgroups in the most recent time period: those without chest pain (odds ratio [OR] 0.29; 95% confidence interval [CI], 0.27-0.32); those presenting 6 to 12 hours after symptom onset (OR 0.57; 95% CI, 0.52-0.61); those 75 years or older (OR 0.63 compared with patients <55 years old; 95% CI, 0.58-0.68); women (OR 0.88; 95% CI, 0.84-0.93); and non-whites (OR 0.90; 95% CI, 0.83-0.97). CONCLUSIONS: Utilization of acute reperfusion therapy in ideal patients has improved over the last decade, but more than 10% remain untreated. Measuring and improving its use in this cohort represents an important opportunity to improve care.

Sex and racial differences in the management of acute myocardial infarction, 1994 through 2002.

BACKGROUND: Although increased attention has been paid to sex and racial differences in the management of myocardial infarction, it is unknown whether these differences have narrowed over time. METHODS: With the use of data from the National Registry of Myocardial Infarction, we examined sex and racial differences in the treatment of patients who were deemed to be "ideal candidates" for particular treatments and in deaths among 598,911 patients hospitalized with myocardial infarction between 1994 and 2002. RESULTS: In the unadjusted analysis, sex and racial differences were observed for rates of reperfusion therapy (for white men, white women, black men, and black women: 86.5, 83.3, 80.4, and 77.8 percent, respectively; P<0.001), use of aspirin (84.4, 78.7, 83.7, and 78.4 percent, respectively; P<0.001), use of beta-blockers (66.6, 62.9, 67.8, and 64.5 percent; P<0.001), and coronary angiography (69.1, 55.9, 64.0, and 55.0 percent; P<0.001). After multivariable adjustment, racial and sex differences persisted for rates of reperfusion therapy (risk ratio for white women, black men, and black women: 0.97, 0.91, and 0.89, respectively, as compared with white men) and coronary angiography (relative risk, 0.91, 0.82, and 0.76) but were attenuated for the use of aspirin (risk ratio, 0.97, 0.98, and 0.94) and beta-blockers (risk ratio, 0.98, 1.00, and 0.96); all risks were unchanged over time. Adjusted in-hospital mortality was similar among white women (risk ratio, 1.05; 95 percent confidence interval, 1.03 to 1.07) and black men (risk ratio, 0.95; 95 percent confidence interval, 0.89 to 1.00), as compared with white men, but was higher among black women (risk ratio, 1.11; 95 percent confidence interval, 1.06 to 1.16) and was unchanged over time. CONCLUSIONS: Rates of reperfusion therapy, coronary angiography, and in-hospital death after myocardial infarction, but not the use of aspirin and beta-blockers, vary according to race and sex, with no evidence that the differences have narrowed in recent years.

Quality of care by classification of myocardial infarction: treatment patterns for ST-segment elevation vs non-ST-segment elevation myocardial infarction.

BACKGROUND: Practice guidelines for acute ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) recommend similar therapies and interventions, but differences in patterns of care between MI categories have not been well described in contemporary practice. METHODS: In-hospital treatments with similar recommendations from practice guidelines were compared with outcomes in 185 968 eligible patients (without listed contraindications) with STEMI (n = 53 417; 29%) vs NSTEMI (n = 132 551; 71%) from 1247 US hospitals participating in the National Registry of Myocardial Infarction 4 between July 1, 2000, and June 30, 2002. Hierarchical logistic regression modeling was used to determine adjusted differences in treatment patterns in MI categories. RESULTS: Unadjusted in-hospital mortality rates were high for NSTEMI (12.5%) and STEMI (14.3%), and the use of guideline-recommended medications and interventions was suboptimal in both categories of patients with MI. The adjusted likelihood of receiving early (within 24 hours of presentation) aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors was higher in patients with STEMI. Similar patterns of care were noted at hospital discharge: the adjusted likelihood of receiving aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, lipid-lowering agents, smoking cessation counseling, and cardiac rehabilitation referral was higher in patients with STEMI. CONCLUSIONS: Evidence-based medications and lifestyle modification interventions were used less frequently in patients with NSTEMI. Quality improvement interventions designed to narrow the gaps in care between NSTEMI and STEMI and to improve adherence to guidelines for both categories of patients with MI may reduce the high mortality rates associated with acute MI in contemporary practice.

Racial differences in reperfusion therapy use in patients hospitalized with myocardial infarction: a regional phenomenon.

BACKGROUND: Racial differences in reperfusion therapy use among patients hospitalized with myocardial infarction (MI) have been previously reported as national phenomenon. However, it is unclear whether racial differences in treatment vary by region. METHODS: Using data from the National Registry of Myocardial Infarction-2 and -3, a cohort of patients hospitalized with MI in the United States between 1994 and 2000, we sought to determine whether racial differences in reperfusion therapy use varied by geographic region in patients eligible for reperfusion therapy with no clinical contraindications to treatment (n = 204 230). RESULTS: Black patients had lower crude rates of reperfusion therapy than white patients (66.5% vs 69.9%, -3.3% racial difference, 99% CI -4.4% to -2.2%) overall. However, racial differences in reperfusion therapy use varied by geographic region. Reperfusion therapy rates were similar for black patients and white patients in the Northeast (67.9% black vs 65.3% white, +2.7% racial difference, 99% CI -0.5% to 5.8%) and statistically comparable for patients in the Midwest (68.3% black vs 69.0% white, -0.7% racial difference, 99% CI -2.9% to 1.5%) and West (70.7% black vs 72.6% white, -1.9% racial difference, 99% CI -5.1% to 1.2%). Racial differences in reperfusion therapy use were greatest for patients hospitalized in the South (64.5% black vs 71.7% white, -7.1% racial difference, 99% CI -8.7% to -5.6%). Racial differences were reduced, but geographic variations in racial differences persisted after multivariable adjustment. CONCLUSIONS: Lower rates of reperfusion therapy use among black patients with MI do not reflect a national pattern of racial differences in treatment, but a practice pattern predominantly attributable to the South.

The association between white blood cell count and acute myocardial infarction in-hospital mortality: findings from the National Registry of Myocardial Infarction.

OBJECTIVES: Although cross-sectional and prospective studies have shown that the white blood cell (WBC) count is associated with long-term mortality for patients with ischemic heart disease, the role of the WBC count as an independent predictor of short-term mortality in patients with acute myocardial infarction (AMI) has not been examined as extensively. The objective of this study was to determine whether the WBC count is associated with in-hospital mortality for patients with ischemic heart disease after controlling for potential confounders. METHODS: From July 31, 2000, to July 31, 2001, the National Registry of Myocardial Infarction 4 enrolled 186,727 AMI patients. A total of 115,273 patients were included in the analysis. RESULTS: WBC counts were subdivided into intervals of 1,000/mL, and in-hospital mortality rates were determined for each interval. The distribution revealed a J-shaped curve. Patients with WBC counts >5,000/mL were subdivided into quartiles, whereas patients with WBC counts <5,000/mL were assigned to a separate category labeled "subquartile" and were analyzed separately. A linear increase in in-hospital mortality by WBC count quartile was found. The unadjusted odds ratio (OR) for the fourth versus the first quartile showed strong associations with in-hospital mortality among the entire population and by gender: 4.09 (95% confidence interval [95% CI] = 3.83 to 4.73) for all patients, 4.31 (95% CI = 3.93 to 4.73) for men, and 3.65 (95% CI = 3.32 to 4.01) for women. Following adjustment for covariates, the magnitude of the ORs attenuated, but the ORs remained highly significant (OR, 2.71 [95% CI = 2.53 to 2.90] for all patients; OR, 2.87 [95% CI = 2.59 to 3.19] for men; OR, 2.61 [95% CI = 2.36 to 2.99] for women). Reperfused patients had consistently lower in-hospital mortality rates for all patients and by gender (p < 0.0001). CONCLUSIONS: The WBC count is an independent predictor of in-hospital AMI mortality and may be useful in assessing the prognosis of AMI in conjunction with other early risk-stratification factors. Whether elevated WBC count is a marker of the inflammatory process or is a direct risk factor for AMI remains unclear. Given the simplicity and availability of the WBC count, the authors conclude that the WBC count should be used in conjunction with other ancillary tests to assess the prognosis of a patient with AMI.

Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction.

BACKGROUND: Both epicardial and myocardial perfusion have been associated with clinical outcomes in the setting of ST elevation myocardial infarction (STEMI), and the performance of adjunctive/rescue percutaneous coronary intervention (PCI) may further improve clinical outcomes after fibrinolytic administration. METHODS: The goal was to develop a simple, broadly applicable angiographic metric that takes into account indices of epicardial and myocardial perfusion both before and after PCI to arrive at a single perfusion grade in patients undergoing cardiac catheterization after fibrinolysis. The angiographic perfusion score (APS) is the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG; 0-3) added to the TIMI myocardial perfusion grade (TMPG; 0-3) before and after PCI (total possible grade, 0-12). Failed perfusion was defined as an APS of 0 to 3, partial perfusion was defined as an APS of 4 to 9, and full perfusion was defined as an APS of 10 to 12. The APS was evaluated in patients from the Double-blind, Placebo-contolled, Multicenter Angiographic Trial of Rhumab CD18 in Acute Myocardial Infarction (LIMIT-AMI; n = 394) and Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis In Myocardial Infarction (ENTIRE-TIMI) 23 trials (n = 483), and infarct size (120-216 hours after AMI SPECT Technetium-99m Sestamibi data) was assessed in the LIMIT-AMI trial. RESULTS: The APS was associated with the incidence of death or myocardial infarction (failed, 16.7% [n = 18]; partial, 2.5% [n = 155]; full, 2.4% [n = 82]; P =.039 for trend) and larger SPECT infarct sizes (failed, median 39% [n = 10]; partial, 12% [n = 79]; and full, 8% [n = 35]; P =.002). No patient with full APS died, whereas the mortality rate was 11.1% in patients with a failed APS (P =.03). CONCLUSIONS: The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI. Partial or full angiographic perfusion scores are associated with a halving of infarct size, and no patients with full angiographic perfusion died.

The Risk Score Profile: a novel approach to characterising the risk of populations enrolled in clinical studies.

AIMS: Interpreting the results and practice implications of clinical studies requires accurate characterisation of the baseline risk of the population. We evaluated the Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI as a tool to describe and compare the risk profile of populations enrolled in three clinical trials (InTIME-II, ASSENT-2 and MAGIC) and the National Registry of Myocardial Infarction. METHODS AND RESULTS: The risk score was calculated for each patient (N=121,085) and the frequency distribution plotted for each population. The Risk Score Profiles were compared using the Kolmogorov-Smirnov test. The Risk Score Profile demonstrated a striking concordance between the baseline risk of patients in InTIME-II and ASSENT-2 (median scores in each= 3[1,4], P=0.11). In contrast, the distributions in MAGIC (designed to enroll high risk) and NRMI (registry) were shifted significantly toward higher risk (median scores=4[3,5] for MAGIC and 4[2,6] in NRMI, P < 0.0001 for each vs. InTIME-II). A graded relationship between the risk score and mortality was evident in each study (P<0.0001). CONCLUSIONS: The frequency distribution of the TIMI Risk Score, or similar tools for risk assessment, may be used to quantify and readily compare the risk profile of populations enrolled in clinical studies.

Relation of age and race with hospital death after acute myocardial infarction.

BACKGROUND: Prior studies have suggested that young blacks with acute myocardial infarction (AMI) may have higher hospital mortality rates than whites of similar age. However, the influence of age and race on short-term death has not been explored in detail. We examined the relation of age and race on short-term death in a large AMI population and ascertained the factors that may have contributed to differences in mortality rates. METHODS: We compared the crude and adjusted hospital mortality rates stratified by age among 40,903 blacks and 501,995 whites with AMI enrolled in the National Registry of Myocardial Infarction-2 in 1482 participating US hospitals from June 1994 through March 1998. RESULTS: Overall crude mortality was lower among blacks compared with whites (10.9% vs 12.0%, P <.0001). However, blacks had a significantly higher crude mortality rate compared with the whites in the age groups <65 years (<45 years, and 5-year age groups between 45 and 64 years). There was a statistically significant interaction between age and black race on hospital death (P value for interaction <.001). Each 5-year decrement in age from 85 years was associated with 7.2% higher odds of death in blacks compared with whites (95% CI, 5.7% to 7.6%). After adjusting for differences in the baseline, clinical presentation, early treatment, and hospital characteristics, 5-year decrements in age was still associated with increases in the odds for death in blacks compared with whites (5.4%; 95% CI, 3.6% to 7.2%). This interaction between age and black race was present in both sexes but was stronger among men. CONCLUSIONS: Blacks younger than 65 years had higher hospital mortality rates compared with whites hospitalized for AMI, and decreasing age was associated with progressively higher risk of hospital death for blacks. Differences in the clinical presentation, early treatment, and hospital characteristics could only partly explain this age-race interaction.

Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction.

We hypothesized that absolute and relative neutrophilia would be associated with adverse angiographic outcomes in the 394 patient Limitation of Myocardial Infarction Following Thrombolysis in Acute Myocardial Infarction (LIMIT) Acute Myocardial Infarction (AMI) trial of fibrinolysis in ST-elevation myocardial infarction. The mean neutrophil count was 7.9 x 10(9)/L, with a mean neutrophil percentage of 72%. Patients with time from symptom onset to fibrinolytic treatment more than the median (2.7 hours) had a higher neutrophil count and percentage of neutrophils than patients with shorter time to treatment. Patients with a closed infarct-related artery at 90 minutes (Thrombolysis In Myocardial Infarction [TIMI] grade 0/1 flow) had higher neutrophil counts (8.8 +/- 3.8 vs 7.6 +/- 3.0, p = 0.02) but no difference in the percentage of neutrophils than patients with an open artery. Higher neutrophil counts were also mildly correlated with longer corrected TIMI frame counts (CTFC) in the infarct-related artery (r = 0.14, p = 0.02). Patients with impaired myocardial perfusion by TIMI myocardial perfusion grade (TMPG) had a greater percentage of neutrophils (73.2 +/- 10.7% for TMPG 0/1 vs 69.9 +/- 12.6% for TMPG 2/3, p = 0.047) but no detectable difference in neutrophil counts (8.2 +/- 3.3 vs 7.7 +/- 2.9, p = 0.24). There were no significant associations between other indexes in the cell differential and angiographic or clinical outcomes. Higher neutrophil counts remained independently associated with both closed arteries and CTFC in multivariable models controlling for age, left anterior descending artery infarct location, time to treatment, and pulse and blood pressure on admission. A greater percentage of neutrophils remained independently associated with impaired microvascular perfusion in a similar multivariable model. In patients with ST-elevation myocardial infarction, absolute and relative neutrophilia were associated with impaired epicardial and microvascular perfusion.

Single lead ST-segment recovery: a simple, reliable measure of successful fibrinolysis after acute myocardial infarction.

BACKGROUND: Successful reperfusion after acute ST-elevation myocardial infarction improves prognosis. Among the different electrocardiographic markers of reperfusion, sum ST resolution is considered the hallmark of reperfusion, but is cumbersome to use. METHODS: To assess the usefulness of a single lead ST resolution at 90 minutes after fibrinolysis compared with the sum ST resolution in predicting Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, we used prospectively collected data from the Limitation of Myocardial Injury Following Thrombolysis in Acute Myocardial Infarction (LIMIT-AMI) study. All patients had electrocardiograms recorded at presentation and 90 minutes and a coronary angiogram 90 minutes after fibrinolysis. RESULTS: Infarction artery patency was assessed in 238 patients with 4 different ST resolution criteria: single lead ST resolution > or =50% and > or =70% and sum ST resolution > or =50% and > or =70%. The most sensitive criteria for TIMI grade 3 flow was single lead ST resolution > or =50% (sensitivity rate, 70%; specificity rate, 54%), whereas sum ST resolution > or =70% was most the specific criteria (sensitivity rate, 45%; specificity rate, 79%). The proportion of patients with TIMI grade 3 flow was similar in all 4 ST resolution groups (P =.84). Pre-discharge infarction size and ejection fraction were also similar. No single lead or sum lead measure of ST resolution was significantly associated with an increased risk of death, heart failure, or reinfarction. CONCLUSION: We propose that single lead ST-resolution > or =50% as an optimal electrocardiographic indicator for successful reperfusion 90 minutes after fibrinolysis. This simple electrocardiographic measure should be combined with bedside clinical and hemodynamic assessment to optimize decision making after fibrinolysis.

Is there evidence of implicit exclusion criteria for elderly subjects in randomized trials? Evidence from the GUSTO-1 study.

BACKGROUND: Some experts have raised concerns about the ability to generalize randomized trials, emphasizing that patients who participate in these studies are often not representative of those seen in clinical practice, particularly in the case of elderly patients. To determine the effect of implicit exclusion criteria on a trial study sample, we compared data from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial with data from a retrospective registry from selected hospitals, the National Registry of Myocardial Infarction (NRMI), and a nationally representative study of myocardial infarction care, the Cooperative Cardiovascular Project (CCP). METHODS: We compared GUSTO subjects aged 65 years and older who were enrolled in the United States with similarily aged patients in the 2 observational studies who met the trial's eligibility criteria. We examined baseline characteristics, clinical presentation, treatments, procedures, clinical events, and in-hospital mortality rates. RESULTS: We found modest, although significant, differences between patients in NRMI, CCP, and GUSTO in demographic and clinical characteristics, treatment, and outcome. For example, GUSTO patients were significantly younger (73.1 +/- 5.7 vs 74.7 +/- 6.8 for NRMI and 75.8 +/- 7.2 for CCP), less likely to have Killip class III/IV at presentation (3.1% vs 6.2% for NRMI and 32.7% for CCP), and more likely to receive aspirin (95.5% vs 86.3% for NRMI and 86.5% for CCP) and beta-blockers (71.9% vs 43.5% for NRMI and 52.7% for CCP). Overall, NRMI and CCP patients had a lower risk of 30-day mortality after adjustment for demographic, clinical, and hospital characteristics than patients in GUSTO (odds ratio, 0.79; 95% CI, 0.73-0.86 for NRMI; odds ratio, 0.65; 95% CI, 0.59-0.71 for CCP). CONCLUSIONS: Older patients enrolled in a randomized trial without an age restriction had many similarities compared with patients seen in clinical practice. The higher mortality rate of the GUSTO patients does not support the hypothesis that the trial enrolled a healthier cohort than is seen in practice.

Relation between hospital intra-aortic balloon counterpulsation volume and mortality in acute myocardial infarction complicated by cardiogenic shock.

BACKGROUND: Increasing evidence suggests an inverse relationship between outcome and the total number of invasive cardiac procedures performed at a given hospital. The purpose of the present study was to determine if a similar relationship exists between the number of intra-aortic balloon counterpulsation (IABP) procedures performed at a given hospital per year and the in-hospital mortality rate of patients with acute myocardial infarction complicated by cardiogenic shock. METHODS AND RESULTS: We analyzed data of 12 730 patients at 750 hospitals enrolled in the National Registry of Myocardial Infarction 2 from 1994 to 1998. The hospitals were divided into tertiles (low-, intermediate-, and high-IABP volume hospitals) according to the number of IABPs performed at the given hospital per year. The median number of IABPs performed per hospital per year was 3.4, 12.7, and 37.4 IABPs at low-, intermediate-, and high-volume hospitals, respectively. Of those patients who underwent IABP, there were only minor differences in baseline patient characteristics between the 3 groups. Crude mortality rate decreased with increasing IABP volume: 65.4%, lowest volume tertile; 54.1%, intermediate volume tertile; and 50.6%, highest volume tertile (P for trend <0.001). This mortality difference represented 150 fewer deaths per 1000 patients treated at the high IABP hospitals. In the multivariate analysis, high hospital IABP volume for patients with acute myocardial infarction was associated with lower mortality (OR=0.71, 95% CI=0.56 to 0.90), independent of baseline patient characteristics, hospital factors, treatment, and procedures such as PTCA. CONCLUSIONS: Among the myocardial infarction patients with cardiogenic shock who underwent IABP placement, mortality rate was significantly lower at high-IABP volume hospitals compared with low-IABP volume hospitals.

Early use of glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute myocardial infarction: observations from the National Registry of Myocardial Infarction 4.

OBJECTIVES: We sought to identify patient and hospital features associated with early glycoprotein (GP) IIb/IIIa inhibitor therapy for non-ST-elevation (NSTE) myocardial infarction (MI) and to relate this treatment to in-hospital outcomes. BACKGROUND: Glycoprotein IIb/IIIa inhibitors have improved outcomes in randomized trials of NSTE MI, leading national treatment guidelines to recommend their use. Their actual use, safety, and effectiveness have not been well characterized beyond trial populations. METHODS: We studied 60,770 patients with NSTE MI treated between July 2000 and July 2001 at 1,189 hospitals in a U.S. registry. Using logistic regression, we identified patient and hospital features associated with GP IIb/IIIa inhibition within 24 h after presentation. We also compared outcomes by early treatment versus no treatment after adjusting for patient and hospital characteristics and treatment propensity. RESULTS: Only 25% of eligible patients received early GP IIb/IIIa therapy. Elderly patients, women, minority patients, and those without private insurance received such therapy less often than their counterparts. Treated patients had lower unadjusted in-hospital mortality (3.3% vs. 9.6%, p < 0.0001) remaining significantly lower after adjustment for patient risk, treatment propensity, and hospital characteristics (adjusted odds ratio, 0.88; 95% confidence interval, 0.79 to 0.97). Hospitals that adopted early GP IIb/IIIa inhibition more rapidly also had lower adjusted mortality rates than those slower to adopt such therapy. CONCLUSIONS: Glycoprotein IIb/IIIa inhibitor therapy appears to be underused in early management of NSTE MI patients. Because this therapy is associated with better outcomes, it represents a target for quality improvement.

Time for contrast material to traverse the epicardial artery and the myocardium in ST-segment elevation acute myocardial infarction versus unstable angina pectoris/non-ST-elevation acute myocardial infarction.

Although the time for contrast material to fill the epicardial artery in the setting of acute coronary syndromes has been studied extensively, the time for contrast material to fill the myocardium has not been evaluated. We compared differences in myocardial contrast material transit among patients with unstable angina pectoris/non-ST-elevation acute myocardial infarction (UAP/NSTEAMI) with patients with ST-elevation acute myocardial infarction (STEAMI). The time it took for contrast material to first appear and to arrive at peak intensity in the myocardium was compared in 224 patients with STEAMI enrolled in the LIMIT-AMI study versus 430 patients with UAP/NSTEAMI enrolled in the TACTICS-TIMI 18 trial. In patients with STEAMI, there was a delay in both the time for contrast material to first enter the myocardium (5,619 +/- 1,789 vs 4,663 +/- 1,626 ms, p <0.0001) and the time from entrance to peak blush intensity (2,387 +/- 1,359 vs 1,959 +/- 1,244 ms, p = 0.003) compared with patients with UAP/NSTEAMI. STEAMI remained significantly associated with impaired entrance of contrast material into the myocardium (p <0.0001) in a multivariate model controlling for known correlates of impaired epicardial flow (presence of thrombus, percent diameter stenosis, left anterior descending artery location, and contrast material inflow in the epicardial artery [corrected TIMI frame count]). The time for contrast material to enter the myocardium is impaired to a greater degree in STEAMI compared with UAP/NSTEAMI, even after adjusting for other variables known to delay flow in the epicardial artery. These data provide insight into potential mechanistic differences between these 2 clinical syndromes.

Use of emergency medical services in acute myocardial infarction and subsequent quality of care: observations from the National Registry of Myocardial Infarction 2.

BACKGROUND: National practice guidelines strongly recommend activation of the 9-1-1 Emergency Medical Systems (EMS) by patients with symptoms consistent with an acute myocardial infarction (MI). We examined use of the EMS in the United States and ascertained the factors that may influence its use by patients with acute MI. METHODS AND RESULTS: From June 1994 to March 1998, the National Registry of Myocardial Infarction 2 enrolled 772 586 patients hospitalized with MI. We excluded those who transferred in, arrived at the hospital >6 hours from symptom onset, or who were in cardiogenic shock. We compared baseline characteristics and initial management for patients who arrived by ambulance versus self-transport. EMS was used in 53.4% of patients with MI, a proportion that did not vary significantly over the 4-year study period. Nonusers of the EMS were on average younger, male, and at relatively lower risk on presentation. In addition, payer status was significantly associated with EMS use. Use of EMS was independently associated with slightly wider use of acute reperfusion therapies and faster time intervals from door to fibrinolytic therapy (12.1 minutes faster, P<0.001) or to urgent PTCA (31.2 minutes faster, P<0.001). CONCLUSIONS: Only half of patients with MI were transported to the hospital by ambulance, and these patients had greater and significantly faster receipt of initial reperfusion therapies. Wider use of EMS by patients with suspected MI may offer considerable opportunity for improvement in public health.

Ambulatory electrocardiographic evidence of transmural dispersion of repolarization in patients with long-QT syndrome type 1 and 2.

BACKGROUND: Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and beta-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2. METHODS AND RESULTS: We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112+/-5 ms) than LQT1 (91+/-2 ms) or unaffected (86+/-3 ms) patients (P<0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs. CONCLUSIONS: TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP.