Predictors of death or bronchopulmonary dysplasia in preterm infants with respiratory failure.

OBJECTIVES: To identify the variables that predict death/physiologic bronchopulmonary dysplasia (BPD) in preterm infants with severe respiratory failure. STUDY DESIGN: The study was a secondary analysis of data from the NICHD Neonatal Research Network trial of inhaled nitric oxide (iNO) in preterm infants. Stepwise logistic regression models and Classification and Regression Tree (CART) models were developed for the outcome of death or physiologic BPD (O(2) at 36 weeks post-menstrual age). RESULT: Death and/or BPD was associated with lower birth weight, higher oxygen requirement, male gender, additional surfactant doses, higher oxygenation index and outborn status, but not the magnitude of response in PaO(2) to iNO. The positive predictive value of the CART model was 82% at 95% sensitivity. CONCLUSIONS: The major factors associated with death/BPD were an increased severity of respiratory failure, lower birth weight, male gender and outborn status, but not the magnitude of initial response to iNO.

Inhaled nitric oxide in infants >1500 g and <34 weeks gestation with severe respiratory failure.

OBJECTIVE: Inhaled nitric oxide (iNO) use in infants >1500 g, but <34 weeks gestation with severe respiratory failure will reduce the incidence of death and/or bronchopulmonary dysplasia (BPD). STUDY DESIGN: Infants born at <34 weeks gestation with a birth weight >1500 g with respiratory failure were randomly assigned to receive placebo or iNO. RESULTS: Twenty-nine infants were randomized. There were no differences in baseline characteristics, but the status at randomization showed a statistically significant difference in the use of high-frequency ventilation (P=0.03). After adjustment for oxygenation index entry strata, there was no difference in death and/or BPD (adjusted relative risk (RR) 0.80, 95% confidence interval (CI) 0.43 to 1.48; P=0.50), death (adjusted RR 1.26, 95% CI 0.47 to 3.41; P=0.65) or BPD (adjusted RR 0.40, 95% CI 0.47 to 3.41; P=0.21). CONCLUSIONS: Although sample size limits our ability to make definitive conclusions, this small pilot trial of iNO use in premature infants >1500 g and <34 weeks with severe respiratory failure suggests that iNO does not affect the rate of BPD and/or death.

When throughout the year is coronary death most likely to occur? A 12-year population-based analysis of more than 220 000 cases.

BACKGROUND: Previous studies have suggested that there is an increase in cardiac events in the morning. Fewer data relate cardiac events to months of the year and season. METHODS AND RESULTS: We analyzed all monthly death certificate data from Los Angeles County, California, for death caused by coronary artery disease from 1985 through 1996 (n=222 265). The mean number of deaths was highest in December at 1808 and January at 1925; the lowest rates were in June, July, August, and September at 1402, 1424, 1418, and 1371, respectively. December and January had significantly higher rates than would be expected from a uniform distribution of monthly deaths (P=0.00001). The percent of yearly coronary deaths was defined by the quadratic U-shaped equation [percent=13.1198-1.5238(month)+0. 0952(month(2)), where January=1, February=2, etc]. When monthly deaths were plotted by year, there was a decrease from 1985 through 1996. Monthly mortality correlated inversely with temperature. During the months with the highest frequency of death (December, January), however, there was an increase in deaths that peaked around the holiday season and then fell, which could not be explained solely on the basis of the daily temperature change. CONCLUSIONS: Even in the mild climate of Los Angeles County, there are seasonal variations in the development of coronary artery death, with approximately 33% more deaths occurring in December and January than in June through September. Although cooler temperatures may play a role, other factors such as overindulgence or the stress of the holidays might also contribute to excess deaths during these peak times.

Population-based analysis of the effect of the Northridge Earthquake on cardiac death in Los Angeles County, California.

OBJECTIVES: We sought to determine whether a natural disaster affected total cardiovascular mortality and coronary mortality in an entire population. BACKGROUND: The effect of the January 17, 1994 Northridge Earthquake (NEQ) on all deaths and causes of deaths within the entire population of Los Angeles County is unknown. The purposes of our study were to analyze all deaths in this entire population before, during and after the NEQ and to determine whether the NEQ temporally and spatially altered death due to cardiovascular disease. METHODS: We analyzed all death certificate data (n = 19,617) from Los Angeles County during January of 1992, 1993 (control periods) and 1994, using International Classification of Diseases, 9th Revision codes for ischemic heart disease (IHD) and atherosclerotic cardiovascular disease (ASCVD), as well as other causes of death. RESULTS: There was an average of 73 deaths per day due to IHD and ASCVD during January 1 to 16, 1994; this increased to 125 on the day of the NEQ, and then decreased to 57 deaths per day from January 18 to 31 (p < 0.00001, before NEQ vs. day of NEQ; after NEQ vs. day of NEQ; and before NEQ vs. after NEQ). The NEQ was associated with an increase in deaths due to myocardial infarction and trauma but not cardiomyopathy, hypertensive heart disease, valvular heart disease, cerebrovascular disease or noncardiovascular causes. Based on plots of daily deaths due to IHD and ASCVD, the decrease in deaths during the 14 days after the NEQ (-144) overcompensated for the increase on the day of the NEQ (+55). Geographic analysis revealed a redistribution of deaths due to IHD and ASCVD toward the epicenter on the day of the NEQ. CONCLUSIONS: When an entire population simultaneously experiences a major environmental stress, there is an increase in death due to coronary artery disease (but not other cardiac causes), followed by a decrease that overcompensates for the excess of death. The overcompensation may represent a residual population that is more resistant to stress or a possible preconditioning effect of the stress, or both. This study supports the concept that cardiovascular events within an entire population can be triggered by a shared stress.

Effects of gender and race on prognosis after myocardial infarction: adverse prognosis for women, particularly black women.

Controversy has arisen concerning whether gender influences the prognosis after myocardial infarction. Although some studies have shown there to be no difference between the sexes, most have indicated a worse prognosis for women, attributing this to differences in baseline characteristics. It has been further suggested that black women have a particularly poor prognosis after infarction. To determine the contribution of gender and race to the course of infarction, 816 patients with confirmed myocardial infarction who were enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) were analyzed. Of those patients, 226 were women and 590 were men, 142 were black and 674 were white. The cumulative mortality rate at 48 months was 36% for women versus 21% for men (p less than 0.001, mean follow-up 32 months). The cumulative mortality rate by race was 34% for blacks versus 24% for whites (p less than 0.005). Both women and blacks exhibited more baseline characteristics predictive of mortality than did their male or white counterparts. It was possible to account for the greater mortality rate of blacks by identifiable baseline variables; however, even after adjustment, the mortality rate for women remained significantly higher (p less than 0.002). The poorer prognosis for women was influenced by a particularly high mortality rate among black women (48%); the mortality rate for white women was 32%, for black men 23% and for white men 21%. The mortality for black women was significantly greater than that of the other subgroups. Thus, findings in the MILIS population indicate that the prognosis after myocardial infarction is worse for women, particularly black women.

Prognostic significance of location and type of myocardial infarction: independent adverse outcome associated with anterior location.

To determine the relative prognostic significance of location (anterior or inferior) and type (Q wave or non-Q wave) of infarction, the hospital course and follow-up outcome (mean duration 30.8 months) of 471 patients with a first infarction were analyzed. Analyses were performed grouping the patients according to infarct location (anterior, n = 253; inferior, n = 218), infarct type (Q wave, n = 323; non-Q wave, n = 148), and both location and type (inferior non-Q wave, n = 85; inferior Q wave, n = 133; anterior non-Q wave, n = 63; and anterior Q wave, n = 190). Patients with anterior infarction had a substantially worse in-hospital and follow-up clinical course compared with those with inferior infarction, evidenced by a larger infarct size (21.2 versus 14.9 g Eq/m2 creatine kinase, MB fraction [MB CK], p less than 0.001), lower admission left ventricular ejection fraction (38.1 versus 55.3%, p less than 0.001) and higher incidence of heart failure (40.7 versus 14.7%, p less than 0.001), serious ventricular ectopic activity (70.2 versus 58.9%, p less than 0.05), in-hospital death (11.9 versus 2.8%, p less than 0.001) and total cumulative cardiac mortality (27 versus 11%, p less than 0.001). Patients with Q wave infarction similarly experienced a worse in-hospital course compared with patients with non-Q wave infarction, evidenced by a larger infarct size (20.7 versus 12.7 MB CK g Eq/m2, p less than 0.001), lower admission left ventricular ejection fraction (43.7 versus 50.6%, p less than 0.001), and a higher incidence of heart failure (31.9 versus 21.6%, p less than 0.05) and in-hospital death (9.3 versus 4.1% p less than 0.05). However, there was no increased rate of reinfarction or mortality in hospital survivors with non-Q wave infarction compared with those with Q wave infarction, and total cardiac mortality was similar (16 versus 21%, p = NS). To evaluate the role of infarct location and type independent of infarct size, patients were grouped according to quartile of infarct size, and outcome was reanalyzed within each group. Patients with anterior infarction demonstrated a lower left ventricular ejection fraction on admission and after 10 days than did patients with inferior infarction, even after adjustment for infarct size, as well as a higher incidence of congestive heart failure and cumulative cardiac mortality.(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era.

OBJECTIVES: To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods. STUDY DESIGN AND PATIENTS: Comparative cohort study of very low birthweight (501-1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991-1994, n=1408; group II, 1995-1998, n=1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated. RESULTS: Mortality was higher for group I (63.1% v 56.7%; p=0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p=0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p=0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94). CONCLUSION: Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.

Overall and cause-specific mortality in a cohort of homo-/bisexual men, injecting drug users, and female partners of HIV-infected men. Pulmonary Complications of Human Immunodeficiency Virus Infection Study Group.

OBJECTIVE: To study the overall and cause-specific HIV-related mortality in a cohort of HIV-seropositive subjects according to transmission category, race/ethnicity, sex and severity of immunosuppression. DESIGN: A cohort of 1129 HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of HIV-infected men were enrolled at six centers in San Francisco, Los Angeles, Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November 1989. Subjects were evaluated every 6 months at least until 31 March 1994. METHODS: The analyses of overall mortality for the subgroups of interest were performed with Kaplan-Meier plots and Cox proportional hazards models. Cause-specific analyses were performed on the primary cause of death using rates per 100 person-years of exposure. RESULTS AND CONCLUSIONS: Baseline severity of immunosuppression is the strongest predictor of mortality. There were no statistically significant differences in overall HIV-related mortality among transmission categories, race/ethnicity groups or sexes. There were differences, however, in cause-specific mortality among the different risk groups.

Changes in the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one during pregnancy, labor, and delivery and the effect of dexamethasone treatment during the third trimester of pregnancy.

To study whether an alteration of placental steroid metabolism occurs during human pregnancy similar to that in the ewe, we measured the concentration of 17 alpha,20 alpha-dihydroxypregn-4-en-3-one (17,20 alpha-OHP) in peripheral plasma. As the pregnant ewe nears term, the utero-ovarian venous concentrations of 17,20 alpha-OHP increase, suggesting induction of placental 17 alpha-hydroxylase. The mean plasma concentration of 17,20 alpha-OHP measured by RIA in normal menstruating women was 1.1 +/- 0.12 (+/- SE) ng/ml. Similar values were found in plasma from ovariectomized women. In the first and second trimesters of pregnancy, the plasma values of 17,20 alpha-OHP were not significantly different from those in the nonpregnant women, while in the third trimester, the mean plasma concentration was significantly increased (mean +/- SE, 2.6 +/- 0.3 ng/ml). The plasma concentration of 17,20 alpha-OHP was studied in 15 women in late pregnancy, during labor, at delivery, and postpartum. The concentration increased during labor as delivery approached and reached a maximum at the time of delivery, ranging from 4.1-11.2 ng/ml, followed by a significant decrease within 1-4 h postpartum. The mean (+/- SE) 17,20 alpha-OHP concentrations in the venous and arterial cord blood were 8.7 +/- 1.6 and 5.8 +/- 2.0 ng/ml, respectively. To study the effect of increased circulating level of corticosteroids on the serum concentration of progestins, 74 women with premature labor with or without premature rupture of membranes were treated with either placebo or 4 im injections of dexamethasone phosphate (5 mg each) at 12-h intervals. Blood samples were drawn at 0, 14, 26, and 46 h, approximately 2 h after each dexamethasone dose. Plasma progesterone, 17 alpha-hydroxyprogesterone (17-OHP), and 17,20 alpha-OHP values at zero time were 140 +/- 15.8 (+/- SE; n = 21), 7.8 +/- 1.5 ng/ml (n = 16), and 2.3 +/- 0.3 ng/ml (n = 20), respectively. In patients treated with dexamethasone, the plasma progesterone values tended to increase at 14, 20, and 46 h, but 17-OHP and 17,20 alpha-OHP values decreased significantly compared to levels in placebo-treated patients. In conclusion, the concentration of plasma 17,20 alpha-OHP increased during the third trimester of pregnancy, and the increment continued through labor and delivery. During antenatal dexamethasone administration, progesterone in the maternal circulation tended to increase, while 17-OHP and 17,20 alpha-OHP decreased significantly. In the human, in contrast to the ewe, dexamethasone treatment in the third trimester does not appear to stimulate placental 17 alpha-hydroxylase activity.

Phenytoin and phenobarbital concentrations in saliva and plasma measured by radioimmunoassay.

Saliva and plasma levels of phenytoin (DPH) and phenobarbital (PB) in a series of epileptic patients were compared by means of a radioimmunoassat (RIA) that required only 10 mul of saliva or plasma. There was an excellent linear relation (r = 0.98) between the logarithms of the concentrations of DPH in the two fluids. The ratio saliva/plasma was remarkably constant at 0.10 and was unaffected by varying levels of PB. The ratio was close to the fraction of DPH reported unbound in plasma at 37 degrees. PB plasma and saliva levels were also closely related (r = 0.98 for logarithm of plasma and saliva levels). This relation was nonlinear [plasma ocncentration = 4.43 X (salivary concentration)0.86], but could be approximated by the ratio plasma/saliva = 3.4. The simplicity of sample collection and the sensitivity of the RIA procedure suggest that clinical monitoring of these anticonvulsant levels may be carried out by RIA on saliva samples.

A decreased incidence of necrotizing enterocolitis after prenatal glucocorticoid therapy.

In a large multicentered, collaborative randomized and blinded trial utilizing antenatal corticosteroids, the goals included determining the effectiveness of these agents in accelerating lung maturation, as well as monitoring any short-term or long-term adverse effects of this treatment on the parturient, fetus, and/or infant. More than 100 specific items, pertaining to diagnoses, complications, and outcomes were recorded for the 696 mothers enrolled in the study and their 745 infants. A significantly decreased incidence of necrotizing enterocolitis (P = .002) was found in the infants treated with steroids. The possibility of accelerated intestinal maturation induced by antenatal maternal steroid therapy exists. This treatment regimen is particularly attractive as adverse aspects of steroid therapy at the dosage utilized have not been demonstrated.

Factors leading to shorter survival after acute myocardial infarction in patients ages 65 to 75 years compared with younger patients.

Although the number of elderly patients with acute myocardial infarction (AMI) has steadily increased and these patients are known to have a higher early subsequent mortality than younger patients, the reasons for this adverse prognosis are poorly understood. We compared the clinical courses of 217 patients, ages 65 to 75 years, with 631 patients younger than 65 years of age enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). The older group had a higher prevalence of adverse baseline risk factors, including history of congestive heart failure (14 vs 7%, p less than 0.001), previous AMI (28 vs 22%, p less than 0.05), angina pectoris (42 vs 34%, p less than 0.05), systemic hypertension (64 vs 52%, p less than 0.01), diabetes mellitus (24 vs 17%, p less than 0.05) and female gender (37 vs 24%, p less than 0.001). Despite having a smaller infarct size index than younger patients (15 +/- 1 vs 18 +/- 1 CK-MB g-Eq/m2, p less than 0.002), the elderly patients had a lower admission left ventricular ejection fraction (43 +/- 1 vs 47 +/- 1%, p less than 0.01) and a higher frequency of clinical congestive heart failure (44 vs 28%, p less than 0.001) and in-hospital death (14 vs 7%, p less than 0.01). The 1-year mortality for elderly hospital survivors was also markedly greater (19 vs 5%, p less than 0.001) as was the 4-year mortality (35 vs 13%, p less than 0.001). Adjustment for 7 adverse baseline characteristics in the elderly could account for their increased in-hospital mortality. However, these and 12 additional in-hospital characteristics did not account for the increased 1- and 4-year mortalities of the elderly hospital survivors, which are presumably affected by variables not included in the present age-associated study.

Sudden death and its relation to QT-interval prolongation after acute myocardial infarction: two-year follow-up.

Risk of sudden death was assessed in 533 patients who survived 10 days after acute myocardial infarction (AMI) and were followed for up to 24 months (mean 18) in the Multicenter Investigation of the Limitation of Infarct Size. Analysis of clinical and laboratory variables measured before hospital discharge revealed that the QT interval, either corrected (QTc) or uncorrected for heart rate, did not contribute significantly to prediction of subsequent sudden death or total mortality. In this population, frequent ventricular premature complexes (more than 10 per hour) on ambulatory electrocardiographic monitoring and left ventricular (LV) dysfunction (radionuclide LV ejection fraction of 0.40 or less) identify patients at high risk of sudden death. In patients with these adverse clinical findings, the QTc was 0.468 +/- 0.044 second among those who died suddenly and 0.446 +/- 0.032 second in survivors, and was not statistically significant as an additional predictor of sudden death. Consideration of the use of type I antiarrhythmic agents, digoxin, presence of U waves and correction for intraventricular conduction delay did not alter these findings. Although QT-interval prolongation occurs in some patients after acute myocardial infarction, reduced LV ejection fraction and frequent ventricular premature complexes are the most important factors for predicting subsequent sudden death in this patient population.

Enzymatic estimation of myocardial infarct size when early creatine kinase values are not available.

Estimates of myocardial infarct (MI) size based on plasma creatine kinase (CK) are used widely for prognosis and in the assessment of therapy designed to salvage ischemic myocardium. However, if the initial plasma CK activity is elevated, MI size will be underestimated. To determine the impact of loss of early CK values on estimates of MI size and to develop a procedure to compensate for it, estimates of MI size based on complete and incomplete MB and total CK time-activity curves from 120 patients (experimental group) were compared. Estimates of MI size based on data inclusion intervals beginning at 24, 12, 8, and 4 hours before peak CK were 11, 14, 23, and 47% smaller than values based on complete CK curves, but the correlation was good between complete and incomplete estimates of MI size at any given interval, with r values ranging from 0.91 to 0.98. The derived correction factors were then prospectively applied to a new population (n = 25) with complete CK curves to compensate for purposely omitted early CK values. The corrected estimates of MI size were within 7% of those based on the complete CK curves. Similar results were obtained for transmural and nontransmural and anterior or inferior MI. Thus, if peak plasma CK is known, underestimation of MI size can be compensated for despite the unavailability of early CK values. Since greater than 90% of patients present before plasma CK has reached its peak (24 hours), MI size can be obtained in nearly all patients. Thus, being able to correct for unavailable early CK values makes MI size a more widely applicable endpoint for use in clinical trials and patient management.

Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients.

Over a 34.5-month period, all admissions to 5 university hospital coronary care units were screened for eligibility for the Multicenter Investigation of the Limitation of Infarct Size (MILIS), an ongoing study of the effects of hyaluronidase, propranolol and placebo on myocardial infarct (MI) size. Of 3,697 patients with greater than or equal to 30 minutes of discomfort that was thought to reflect myocardial ischemia who were assessed for the presence or absence of certain electrocardiographic abnormalities at the time of hospital admission, the electrocardiogram was considered predictive of acute MI if greater than or equal to 1 of the following abnormalities was present: new or presumably new Q waves (greater than or equal to 30 ms wide and 0.20 mV deep) in at least 2 of the 3 diaphragmatic leads (II, III, aVF), or in at least 2 of the 6 precordial leads (V1 to V6), or in I and aVL; new or presumably new ST-segment elevation or depression of greater than or equal to 0.10 mV in 1 of the same lead combinations; or complete left bundle branch block. In the screened population, the diagnostic sensitivity of the electrocardiographic criteria was 81%, whereas the overall infarct rate in the total population screened was 49%. The diagnostic specificity of these entry criteria was 69% and the predictive value 72%.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for sudden death after acute myocardial infarction: two-year follow-up.

The risk of sudden coronary death after myocardial infarction (MI) was assessed in 533 patients who survived 10 days after MI and were followed for up to 24 months (mean 18) in the Multicenter Investigation of the Limitation of Infarct Size. Analysis of multiple clinical and laboratory variables determined before hospital discharge revealed that frequent ventricular premature beats (VPBs) (greater than or equal to 10/hour) on ambulatory electrocardiographic monitoring and left ventricular (LV) dysfunction (radionuclide LV ejection fraction less than or equal to 0.40) were independently significant markers of risk for subsequent sudden death believed to be the result of a primary ventricular arrhythmia. The incidence of sudden death was 18% in patients with both LV dysfunction and frequent VPBs (11 times that of patients with neither of these findings). Seventy-nine percent of all sudden deaths occurred within 7 months after the index MI. In 280 survivors reclassified 6 months after MI with regard to the presence or absence of frequent VPBs and LV dysfunction, these risk factors could not be associated with sudden coronary death over a further follow-up period of up to 18 months; the overall incidence of sudden cardiac death was low (1.4%) after 6 months. Thus, the presence of frequent VPBs in association with LV dysfunction early after MI identifies patients at high risk for sudden death over the next 7 months.

Prognosis after cardiac arrest due to ventricular tachycardia or ventricular fibrillation associated with acute myocardial infarction (the MILIS Study). Multicenter Investigation of the Limitation of Infarct Size.

Previous studies have reached conflicting conclusions about whether cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF) in acute myocardial infarction (AMI) is of long-term prognostic significance. The mortality rate in 849 patients with confirmed AMI was analyzed. The mortality rate during the initial hospitalization was higher for patients in whom VT/VF occurred (27% vs 7%, p less than 0.001). The in-hospital mortality rate for patients with primary VT/VF, that is, VT/VF occurring in the absence of hypotension or heart failure, was similar to that of patients who did not have VT/VF (8% vs 7%, difference not significant), whereas the rate for patients with secondary VT/VF was significantly greater than that for patients with no VT/VF (51% vs 7%, p less than 0.001). The timing of occurrence of VT/VF also influenced mortality: Patients in whom VT/VF occurred more than 72 hours after admission had a higher in-hospital mortality rate than did patients in whom it occurred within 72 hours (57% vs 20%, p less than 0.05). All cases of primary VT/VF occurred within the first 72 hours of admission. The long-term mortality rate for hospital survivors was not significantly different for patients who had had VT/VF during acute infarction compared with those who had not (19% vs 21%) (mean follow-up 32 months). Thus, cardiac arrest due to ventricular tachyarrhythmia was associated with a higher in-hospital mortality rate but was not a prognostic factor among hospital survivors. Patients resuscitated from primary VT/VF, which characteristically occurs early after AMI, do not have an adverse prognosis.

Comparison of left ventricular function and infarct size in patients with and without persistently positive technetium-99m pyrophosphate myocardial scintigrams after myocardial infarction: analysis of 357 patients.

One hundred nine patients with persistently positive technetium-99m pyrophosphate (Tc-99m-PPi) myocardial scintigrams 6 months after acute myocardial infarction (MI) (Group A) and 185 patients without such persistently positive scintigrams (Group B) were compared with regard to enzymatically determined infarct size, early and late measurements of left ventricular (LV) function determined by radionuclide ventriculography, and preceding clinical course during the 6 months after MI. The CK-MB-determined infarct size index in Group A (17.4 +/- 10.6 g-Eq/m2) did not differ significantly from that in Group B (16.0 +/- 14.6 g-Eq/m2). Similarly, myocardial infarct areas in the 2 groups, determined by planimetry of acute Tc-99m-PPi scintigrams in those patients with well-localized 3+ or 4+ anterior pyrophosphate uptake, were not significantly different (35.7 +/- 13.4 vs 34.4 +/- 13.1 cm2, respectively). However, patients in Group A had significantly lower LV ejection fractions than those in Group B, both within 18 hours of the onset of MI (0.42 +/- 0.14 vs 0.49 +/- 0.14, p less than 0.01) and at 3 months after MI, both at rest (0.42 +/- 0.14 vs 0.51 +/- 0.14, p less than 0.01) and at maximal symptom-limited supine bicycle exercise (0.44 +/- 0.17 vs 0.51 +/- 0.17, p less than 0.01). Peak exercise levels achieved in the 2 groups were not significantly different. Furthermore, patients in Group A demonstrated a greater incidence of congestive heart failure during the initial hospital admission (41 vs 24%; p less than 0.01) and a greater requirement for digoxin (p less than 0.05) and furosemide (p less than 0.01) after discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective validation of a composite end point in thrombolytic trials of acute myocardial infarction (TIMI 4 and 5). Thrombosis In Myocardial Infarction.

Although the use of composite end points in clinical trials has increased in recent years, few data are available on the validity of such an approach. In the Thrombolysis In Myocardial Infarction (TIMI) 4 and 5 trials, we set out to validate prospectively the nonfatal components of the "unsatisfactory outcome" end point. This end point consisted of the in-hospital occurrence or observation of new-onset severe congestive heart failure/shock, left ventricular ejection fraction <40% (or <30% for patients with prior myocardial infarction), reinfarction, reocclusion by sestamibi perfusion imaging, TIMI flow grade <2 at 90 minutes or 18 to 36 hours, intracranial hemorrhage, major spontaneous hemorrhage, or anaphylaxis. Among 576 patients in TIMI 4 and 5 with 1-year follow-up, a nonfatal unsatisfactory outcome end point was reached in hospital in 45% of patients. Compared with patients without such an end point, patients with an end point had a relative risk of 1-year mortality of 2.5 (95% confidence interval 1.4 to 5.6, p = 0.001). For individual components, new-onset severe congestive heart failure/shock had a relative risk of 4.6 (p = 0.001), left ventricular ejection fraction <40% had a relative risk of 3.5 (p = 0.006), recurrent myocardial infarction had a relative risk of 2.2 (p = 0.047), and TIMI flow grade <2 at 90 minutes had a relative risk of 2.2 (p = 0.005). Our findings show that these nonfatal in-hospital end points and the composite end point are associated with an increased risk of 1-year mortality and as such are valid predictive survival markers for use in clinical trials.

Effect of mode of delivery on incidence of respiratory distress syndrome.

The effect of route of delivery on incidence of respiratory distress syndrome (RDS) has been controversial. While some investigators have reported no difference in RDS rates in infants born by cesarean section as compared to vaginal delivery, others have shown a significant increase in risk for RDS among infants born by cesarean section. Data from the 297 patients comprising the placebo group in the recently completed collaborative study of antenatal steroid therapy in the prevention of neonatal RDS, were analyzed to determine the effect of mode of delivery on RDS. The results indicate that infants born by cesarean section without labor have a higher risk for neonatal RDS than infants born vaginally or by cesarean section after a trial of labor.