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Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce sudden cardiac death and all-cause mortality. They also may have direct antiarrhythmic properties. We retrospectively analyzed the data from the Multicenter UnSustained Tachycardia Trial (MUSTT), to determine the effects of ACE inhibitors on inducibility of sustained ventricular tachycardia and on sudden cardiac death and overall mortality in 2,087 patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. Results of electrophysiologic testing were compared by use of ACE inhibitors at baseline, and outcomes were compared between the 564 patients prescribed ACE inhibitors at discharge and the 1,523 patients who did not receive treatment. The inducibility of sustained ventricular tachycardia during electrophysiologic testing did not differ by baseline ACE inhibitor use (unadjusted p = 0.75). Patients discharged from hospital on ACE inhibitors had a lower ejection fraction, more extensive coronary artery disease, and fewer previous revascularizations at baseline. After adjustments for differences in baseline factors and initial hospitalization variables, there were no significant differences in total mortality (p = 0.47) or arrhythmic death or cardiac arrest (p = 0.51) with ACE inhibitor use at discharge over a median 43 months of follow-up.

Background: Patients with prior coronary bypass surgery with acute ST-segment elevation myocardial infarction (MI) pose an increasingly common clinical problem. We assessed the characteristics and outcomes of such patients undergoing thrombolysis for acute MI., Methods and Results: We compared the characteristics and outcomes of patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had prior bypass (n = 1784, 4% of the population) with those without prior coronary artery bypass grafting (CABG), all of whom were randomized to receive one of four thrombolytic strategies. Patients with prior bypass were older with significantly more prior MI and angina. Overall, 30-day mortality was significantly higher in patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these patients also had significantly more pulmonary edema, sustained hypotension, or cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated alteplase over the streptokinase monotherapies. In the 62% of patients with prior CABG who underwent coronary angiography, the infarct-related vessel was a native coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001)., Conclusions: The 30-day mortality in patients with prior CABG was significantly higher than that for patients without prior CABG. As in the overall trial, these patients derived an incremental survival benefit from treatment with accelerated alteplase, but mortality remained high (16.7%) at 1 year. These results are at least partially explained by the higher baseline risk of these patients and by the lower rate of patency of the infarct-related artery.

Background: A proportion of patients who present with suspected acute coronary syndrome (ACS) are found to have insignificant coronary artery disease (CAD) during coronary angiography, but these patients have not been well characterized., Methods and Results: Of the 5767 patients with non-ST-segment elevation ACS who were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin (Eptifibatide) Therapy (PURSUIT) trial and who underwent in-hospital angiography, 88% had significant CAD (any stenosis >50%), 6% had mild CAD (any stenosis >0% to

Background: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation., Methods and Results: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81)., Conclusions: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.

Background: When a patient survives thrombolysis for acute myocardial infarction, little information from large studies exists from which to estimate prognosis during follow-up visits., Methods and Results: Baseline, in-hospital, and later survival data were collected from 41 021 patients enrolled in Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries, a randomized trial of 4 thrombolytic-heparin regimens with standard aspirin and beta-blockade. Cox proportional hazards models were developed to predict 1-year survival in 30-day survivors (n=37 869) from baseline clinical and ECG factors and in-hospital factors; a combined model then was developed (C-index 0.800). The model was simplified into a nomogram to predict individual outcomes (C-index 0.754). Factors reflecting demographics (advanced age, lighter weight), larger infarctions (higher Killip class, lower blood pressure, faster heart rate, longer QRS duration), cardiac risk (smoking, hypertension, prior cerebrovascular disease), and arrhythmia were important predictors of death between 30 days and 1 year. Black race was associated with a substantial increase in risk after considering other factors. Revascularization was associated with reduced risk between 30 days and 1 year., Conclusions: When evaluating a patient who has survived acute infarction treated with thrombolysis, clinicians can estimate the likelihood of survival from factors easily measured during admission. Although many risk factors clearly relate to age, left ventricular dysfunction, or clinical instability, black race is an unexplained risk factor requiring further examination.

Objectives: To evaluate a quantitative model of restenosis in patients with vein graft disease undergoing percutaneous transluminal coronary angioplasty (PTCA) or directional coronary atherectomy (DCA)., Background: A quantitative relationship between acute gain and late loss has been developed to describe the late changes in lumen dimension after native vessel coronary intervention. This same relationship may also be seen after treatment of saphenous vein graft disease., Methods: Patients with native coronary artery stenoses (CAVEAT-I) or saphenous vein graft lesions (CAVEAT-II) were randomized to either DCA or PTCA, and data from these trials were analyzed retrospectively. Angiographic results of the target lesions were reviewed, and each lesion was assessed for vessel caliber and reference diameter, absolute minimal lumen diameter, percent diameter stenosis, percent stenosis of the cross-sectional area, acute gain and late loss. Linear regression models were used to determine late loss and to detect differences in angiographic outcomes., Results: Vein grafts had significantly larger reference vessel diameters than native coronary arteries; they also had significantly more acute gain and more late loss. Directional coronary atherectomy was associated with a larger acute gain in both studies. Patients undergoing DCA also experienced greater late loss although the effect was statistically significant only in the CAVEAT-I study. After adjusting for the acute gain, the treatment effect on late loss became nonsignificant in both studies., Conclusions: In patients undergoing DCA or PTCA of saphenous vein graft narrowings, the relationship between late loss and acute gain is also demonstrated, similar to the device-independent relationships seen in native coronary lesions. In CAVEAT-II, larger degrees of acute gain were also associated with higher degrees of late lumen loss.

Background: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists., Methods and Results: PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI., Conclusions: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively.

Background: Ventricular septal defect (VSD) complicating acute myocardial infarction has been studied primarily in small, prethrombolytic-era trials. Our goal was to determine clinical predictors and angiographic and clinical outcomes of this complication in the thrombolytic era., Methods and Results: We compared enrollment characteristics, angiographic patterns, and outcomes (30-day and 1-year mortality) of patients enrolled in the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial with and without a confirmed diagnosis of VSD. Univariable and multivariable analyses were used to assess relations between enrollment factors and the development of VSD. In all, 84 of the 41 021 patients (0.2%) developed VSD, a smaller percentage than reported in the prethrombolytic era. The median time from symptom onset to VSD diagnosis was 1 day. Enrollment factors most associated with this complication were advanced age, anterior infarction, female sex, and no previous smoking. The infarct artery was more often the left anterior descending and more likely to be totally occluded in patients who developed VSD. Mortality at 30 days was higher in patients with VSDs than in those without this complication (73.8% versus 6.8%, P<0.001). Patients with VSDs selected for surgical repair (n=34) had better outcomes than patients treated medically (n=35; 30-day mortality, 47% versus 94%)., Conclusions: Compared with historical control subjects, patients who undergo thrombolysis within 6 hours of infarction onset may have a reduced risk of later VSD. If patients develop this mechanical complication, however, it typically occurs sooner than described in the prethrombolytic era. Despite improvements in medical therapy and percutaneous and surgical techniques, mortality with this complication remains extremely high.

The connective tissue lamellae surrounding the n. occipitalis major are arranged in such a way that they form at least two compartments. An outer epineurial, and an inner endoneurial one. The outer compartment is a shifting and sliding layer, the inner one is probably filled with fluid which means that it is relatively incompressible. This fluid could be drawn off and supplied through the widely branched arterial and venous reticulum, the vasa nervorum. Measurements of the connective tissue space area (perineurium, subperineurial space, endoneurium with axon and glia) on the n. occipitalis major showed a high correlation between measured values. In addition, lammellar corpuscles of the Paccini type are regularly found in both compartments. These receptors measure the local pressure and shearing forces. The design of the suspension network along with the course of the muscles in the area of the regio occipitalis, the interdependence of the connective tissue compartments, the diffusion barrier of the perineurium, the mighty vasa nervorum and the occurrence of lamellar corpuscles, all point to a probable connection with the symptom complex of occipital neuralgia.

Background: Certain characteristics of unstable angina have been associated with worse clinical outcomes after percutaneous revascularization procedures., Methods and Results: We compared outcomes of patients with (n = 690) and those without (n = 320) unstable angina in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) by unstable angina subgroup: rest chest pain, postinfarction chest pain, chest pain with ischemic electrocardiographic changes, chest pain with recent acceleration, and no chest pain. Regression models were constructed to predict in-hospital and 6-month composite end point death, infarction, bypass surgery, percutaneous revascularization, and abrupt closure (in-hospital) or restenosis (6 months) for each subgroup. Only chest pain with electrocardiographic changes predicted the composite in-hospital outcome (24% vs 17% with no chest pain, P =.0374.) This subgroup also had a greater acute gain, more late loss, and more restenosis than patients in the other subgroups. Rest chest pain carried a higher incidence of the composite 6-month outcome (39.9% vs 29% with no chest pain, P =.0472). For all unstable angina categories, atherectomy was associated with worse overall outcomes than angioplasty., Conclusions: Patients with unstable angina have more complications of percutaneous revascularization than patients without unstable angina, but event rates vary by anginal subgroup. The clinical presentation may help to identify unstable angina patients at particularly high risk for adverse outcomes.

Objectives: The purpose of this study was to determine how risks associated with increasing age differed in patients treated with percutaneous transluminal coronary angioplasty versus thrombolysis., Background: Advancing age is a risk factor for adverse outcome in patients with acute myocardial infarction. Primary angioplasty has been thought to be particularly beneficial in higher risk patients including the elderly. There is, however, limited data on any differential incremental benefit of angioplasty compared with thrombolysis in candidates for either treatment., Methods: In the GUSTO-IIb angioplasty substudy, 1,138 patients were randomized to receive primary angioplasty or accelerated tissue-type plasminogen activator (t-PA). The effect of age on outcome was assessed as a discrete and continuous variable for each treatment group. Models using age as a linear factor as well as cubic spline transformations were used for the major end points of 30-day death or disabling stroke; death or reinfarction; and death, reinfarction or disabling stroke., Results: For each 10-year patient group, outcome was improved with angioplasty (n = 565) compared with t-PA (n = 573). Irrespective of treatment, however, risk increased with age. After adjusting for baseline characteristics, each increment of 10 years of age increased the risk of death or myocardial infarction by 1.32 (95% confidence interval 1.04 to 1.76, p = 0.022). For all adverse outcomes, this incremental effect of increasing age was constant., Conclusions: Advancing age is associated with worse outcomes, and the risks increase in proportion to age. Although primary angioplasty improves outcomes over thrombolysis, it does not appear to be more beneficial in older than in younger patient groups. The incremental adverse effect of age does not vary by treatment strategy.

Left atrial v-wave amplitude has been associated with the presence and severity of chronic mitral regurgitation (MR) but it has not been evaluated for the detection of acute MR. We evaluated the left atrial v-wave amplitude of 205 consecutive patients with mitral stenosis immediately before and after stepwise, incremental balloon mitral commissurotomy to determine predictors of large v waves at baseline and an increase in v-wave amplitude after balloon commissurotomy. The sensitivity and specificity of an increase in v-wave amplitude for detecting worsening and severe MR were determined. A large v wave was present in 44% of patients before balloon commissurotomy and was predicted by age, mean left atrial pressure, mean transmitral gradient, mean pulmonary artery pressure, and angiographic severity of MR. There was a strong inverse correlation between v-wave amplitude and calculated left atrial compliance (r = -0.92). An increase in v-wave amplitude after balloon commissurotomy was associated with an increasing probability of worsening or severe MR. This indicator had a sensitivity, specificity, and positive and negative predictive values of 35%, 91%, 64%, 75%, respectively, for detecting any increase in MR. For the detection of severe MR, the sensitivity was 79%, specificity 89%, positive predictive value 42%, and negative predictive value 98%. Thus, left atrial v-wave amplitude reflects left atrial compliance and severity of mitral stenosis before balloon commissurotomy. An increase in v-wave amplitude is an insensitive but very specific indicator of worsening or severe MR during stepwise, incremental balloon mitral commissurotomy.

To determine the time course of recovery of GH release from insulin-like growth factor I (IGF-I) suppression, 11 healthy adults (18-29 yr) received, in randomized order, 4-h i.v. infusions of recombinant human IGF-I (rhIGF-I; 3 microg/kg-h) or saline (control) from 25.5-29.5 h of a 47.5-h fast. Serum GH was maximally suppressed within 2 h and remained suppressed for 2 h after the rhIGF-I infusion; during this 4-h period, GH concentrations were approximately 25% of control day levels [median (interquartile range), 1.2 (0.4-4.0) vs. 4.8 (2.8-7.9) microg/L; P < 0.05]. A rebound increase in GH concentrations occurred 5-7 h after the end of rhIGF-I infusion [7.6 (4.6 -11.7) vs. 4.3 (2.5-6.0) microg/L; P < 0.05]. Thereafter, serum GH concentrations were similar on both days. Total IGF-I concentrations peaked at the end of the rhIGF-I infusion (432 +/- 43 vs. 263 +/- 44 microg/L; P < 0.0001) and remained elevated 18 h after the rhIGF-I infusion (360 +/- 36 vs. 202 +/- 23 microg/L; P = 0.001). Free IGF-I concentrations were approximately 140% above control day values at the end of the infusion (2.1 +/- 0.4 vs. 0.88 +/- 0.3 microg/L; P = 0.001), but declined to baseline within 2 h after the infusion. The close temporal association between the resolution of GH suppression and the fall of free IGF-I concentrations, and the lack of any association with total IGF-I concentrations suggest that unbound (free), not protein-bound, IGF-I is the major IGF-I component responsible for this suppression. The rebound increase in GH concentrations after the end of rhIGF-I infusion is consistent with cessation of an inhibitory effect of free IGF-I on GH release.

Increased T-wave amplitude is one of the earliest electrocardiographic (ECG) changes following coronary artery occlusion. Therefore, higher T waves in the presenting electrocardiogram should represent earlier time to treatment and thus be associated with lower mortality following thrombolytic therapy. However, T-wave amplitude has never been evaluated as a prognostic marker in this setting. We examined clinical outcomes in 3,317 patients with acute myocardial infarction (AMI) who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) Study. Patients were classified as either those with high T waves or those with low T waves. Higher T waves were defined as those >98th percentile of the upper limit of normal. T-wave amplitude was also evaluated as a continuous variable according to infarct location (maximum T-wave amplitude) and as the amount of excess T-wave amplitude above normal (excess T-wave amplitude). Patients with higher T waves had lower 30-day mortality than those without (5.2% vs 8.6%, p = 0.001) and were less likely to develop congestive heart failure (15% vs 24%, p <0.001) or cardiogenic shock (6.1% vs 8.6%, p = 0.023). Higher maximum T-wave amplitude and excess T-wave amplitude were predictive of lower 30-day mortality (chi-square = 67, p <0.001 and chi-square = 33, p <0.001, respectively). These differences remain significant after controlling for other prognostic baseline ECG variables. In addition, T-wave amplitude added prognostic significance after controlling for time to treatment. T-wave amplitude, an often-overlooked component of the electrocardiogram, can add significant prognostic information in initial evaluation of patients with AMI.

We compared cardiac troponins T (cTnT) and I (cTnI) collected within 3.5 h of ischemic symptoms for predicting clinical outcomes in 770 patients. cTnT (cutoff > 0.1 microgram/L) and cTnI (cutoff > 1.5 micrograms/L) were concordant (both positive or negative) in 90.4% of patients. Among discordant results, 66 were cTnT positive and cTnI negative vs 8 who showed the reverse (P < 0.001). Five cTnT-positive and cTnI-negative patients died within 30 days; none who were cTnT negative and cTnI positive died. cTnT showed a slightly greater association (chi 2 = 18.0, P < 0.001) with 30-day mortality than cTnI (chi 2 = 12.5, P = 0.002). The area of the ROC curve for predicting 30-day mortality was significantly larger (Z = 2.08; P = 0.0375) for cTnT, at 0.68 [95% confidence interval (CI) 0.60-0.75], compared with cTnI, at 0.64 (95% CI 0.56-0.72). When cTnI and the electrocardiogram (ECG) were put in a logistic multiple regression model, cTnT added significant information (chi 2 = 8.03, P = 0.045); however, cTnI did not add to a model containing cTnT and the ECG (chi 2 = 0.84, P = 0.657). cTnT provided more information than cTnI for predicting 30-day mortality early after presentation with acute coronary syndromes.

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

Background: Although the benefit of thrombolytic therapy in reducing mortality in acute myocardial infarction is well established, the types of bleeding and risk factors for bleeding are less well described in large trials., Methods and Results: We analyzed the baseline characteristics, outcomes, and incidence of bleeding by location, severity, and treatment assignment among 41,021 patients in the GUSTO-I trial of thrombolysis for acute myocardial infarction. Of the 40,903 patients for whom there were complete data, 1.2% suffered severe bleeding and 11.4% experienced moderate hemorrhage at a variety of sites. The most common sources of bleeding were procedure related. The thrombolytic regimen was strongly related to the incidence of bleeding; comparatively more bleeding was seen with the therapies of streptokinase plus intravenous heparin and the streptokinase and tissue plasminogen activator plus intravenous heparin combination. In multivariate analysis, the four most powerful independent predictors of hemorrhage were older age, lighter body weight, female sex, and African ancestry; they remained the most important predictors of bleeding when multivariate analysis was performed on patients who did not undergo invasive procedures. The presence of serious hemorrhage was associated with other undesirable outcomes (recurrent events, left ventricular dysfunction, arrhythmia, or stroke)., Conclusions: Important predictors of bleeding in this population are increased age, lighter weight, female sex, African ancestry, and experiencing invasive procedures. Other nonhemorrhagic adverse clinical outcomes were associated with moderate and severe bleeding, which was in turn associated with increased length of hospital stay and mortality at 30 days.

The Thrombolysis and Angioplasty in Acute Myocardial Infarction phase 5 (TAMI-5) trial randomized patients to 1 of 3 thrombolytic regimens (alteplase, urokinase, or both), then further randomized them to acute or deferred catheterization. The group of patients randomized to acute catheterization had improved infarct zone but not global left ventricular function on predischarge left ventriculography. To better explore the late effects of these strategies on global and regional left ventricular function, a subset of patients (n = 296) were prospectively evaluated at 6 weeks by multiple uptake gated acquisition (MUGA) radionuclide ventriculography scan. Of these patients, 219 had interpretable studies with paired predischarge and late left ventriculographic data for comparison. At 6 weeks, choice of thrombolytic regimen had no impact on either global or infarct-zone left ventricular function. Further, catheterization strategy (acute vs deferred) did not influence global or infarct-zone function at 6 weeks. In patients randomized to acute catheterization, those undergoing rescue angioplasty had worse infarct-zone wall motion at 6 weeks than patients with a patent infarct vessel not requiring rescue angioplasty (p = 0.002). The early benefit on regional left ventricular function of triage to acute catheterization after thrombolysis for acute myocardial infarction did not persist at 6 weeks, which is most likely attributable to a high incidence of reocclusion. The worse infarct-zone regional wall motion in patients undergoing rescue angioplasty in the acute-catheterization group likely reflects failed reperfusion and illustrates the difficulty in identifying and consequences of early thrombolytic failures.

We describe the development of a clinical data repository whose core consists of four years of inpatient administrative and billing data from the mainframe legacy systems of the University of Virginia Health System (UVAHS). To these data we have linked a cardiac surgery clinical database and our physician billing data (inpatient and outpatient). Other databases will be merged in the future. A relational database management system (Sybase) running on a dedicated IBM RS/6000 minicomputer was employed to assemble 2.5 Gigabytes of core data describing approximately 100,000 hospital admissions over the four year period. To enable convenient data queries, the system has been equipped with a custom-built WWW user interface, which generates Structured Query Language (SQL) automatically. We illustrate the rapid reporting capabilities of the resulting system with reference to patients undergoing coronary artery bypass graft surgery (CABG). We conclude that this information system: a) constitutes a convenient and low-cost method to increase data availability across the UVAHS; b) provides clinicians with a tool for surveillance of patient care and outcomes; c) forms the core of a comprehensive database from which clinical research may proceed; d) provides a flexible interface empowering a wide variety of clinical departments to share and enrich their own clinical data.

Objectives: We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction., Background: Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately quantified, partly because of small sample sizes and methodologic limitations in previous studies., Methods: We examined the clinical and angiographic outcomes of 16,521 patients with an acute inferior myocardial infarction who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) study. Patients were classified into those without precordial ST segment depression (n = 6,422 [38.9%]), those with ST segment depression in leads V1 to V3 only (n = 5,850 [35.4%]), those with ST segment depression in leads V4 to V6 only (n = 876 [5.3%]) and those with ST segment depression in both leads V1 to V3 and leads V4 to V6 (n = 3,373 [20.4%]) on initial electrocardiography. Outcome measures included postinfarction complications (second- or third-degree heart block, congestive heart failure or shock) and 30-day and 1-year mortality., Results: Patients with precordial ST segment depression had larger infarctions, more postinfarction complications and a higher mortality rate than those without precordial ST segment depression (4.7% vs. 3.2% at 30 days; 5.0% vs. 3.4% at 1 year; both p < 0.001), regardless of whether ST segment depression was noted in leads V1 to V6 or in leads V4 to V6. The magnitude of precordial ST segment depression (sum of leads V1 to V6) added significant independent prognostic information after adjustment for clinical risk factors; the risk of 30-day mortality increased by 36% for every 0.5 mV of precordial ST segment depression., Conclusions: Assessment of the magnitude of precordial ST segment depression is useful for acute risk stratification in patients with an inferior myocardial infarction.

Calcium channel antagonists possess a number of properties that may be beneficial after revascularization procedures. Therefore, we present an overview of the use of these drugs after percutaneous intervention in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT), and compare the results in CAVEAT with those in published randomized trials. Also reviewed are the use of calcium channel antagonists to control perioperative hypertension, reduce myocardial necrosis, and prevent arrhythmias during cardiopulmonary bypass.

Objectives: This study sought to determine the long-term outcome of adult patients undergoing percutaneous balloon aortic valvuloplasty., Background: Percutaneous balloon aortic valvuloplasty has been offered as an alternative to aortic valve replacement for selected patients with valvular aortic stenosis. Although balloon aortic valvuloplasty produces an immediate reduction in the transvalvular aortic gradient, a high incidence of restenosis frequently leads to recurrent symptoms. Therefore, it is unclear whether balloon aortic valvuloplasty impacts on the long-term outcome of these patients., Methods: Clinical, hemodynamic and echocardiographic data were collected at baseline in 165 patients undergoing balloon aortic valvuloplasty and examined for their ability to predict long-term outcome., Results: The median duration follow-up was 3.9 years (range 1 to 6). Ninety-nine percent follow-up was achieved. During this 6-year period, 152 patients (93%) died or underwent aortic valve replacement, and 99 (60%) died of cardiac-related causes. The probability of event-free survival (freedom from death, aortic valve replacement or repeat balloon aortic valvuloplasty) 1, 2 and 3 years after valvuloplasty was 40%, 19% and 6%, respectively. In contrast, the probability of survival 3 years after balloon aortic valvuloplasty in a subset of 42 patients who underwent subsequent aortic valve replacement was 84%. Survival after aortic valvuloplasty was poor regardless of the presenting symptom, but patients with New York Heart Association functional class IV congestive heart failure had events earliest. Univariable predictors of decreased event-free survival were younger age, advanced congestive heart failure symptoms, lower ejection fraction, elevated left ventricular end-diastolic pressure, presence of coronary artery disease and increased left ventricular internal diastolic diameter. Stepwise multivariable logistic regression analysis found that only younger age and a lower left ventricular ejection fraction contributed independent adverse prognostic information (chi-square 14.89, p = 0.0006)., Conclusions: Long-term event-free and actuarial survival after balloon aortic valvuloplasty is dismal and resembles the natural history of untreated aortic stenosis. Aortic valve replacement may be performed in selected subjects with good results. However, the prognosis for the remainder of patients who are not candidates for aortic valve replacement is particularly poor.

Objective: As part of a project to estimate physician requirements for the Department of Veterans Affairs, the Institute of Medicine (IOM) developed and tested empirically based models of physician staffing, by specialty, that could be applied to each VA facility., Data Source/study Setting: These analyses used selected data on all patient encounters and all facilities in VA's management information systems for FY 1989., Study Design: Production functions (PFs), with patient workload dependent on physicians, other providers, and nonpersonnel factors, were estimated for each of 14 patient care areas in a VA medical center. Inverse production functions (IPFs), with physician staffing levels dependent on workload and other factors, were estimated for each of 11 specialty groupings. These models provide complementary approaches to deriving VA physician requirements for patient care and medical education., Data Collection/extraction Methods: All data were assembled by VA and put in analyzable SAS data sets containing FY 1989 workload and staffing variables used in the PFs and IPFs. All statistical analyses reported here were conducted by the IOM., Principal Findings: Existing VA data can be used to develop statistically strong, clinically plausible, empirically based models for calculating physician requirements, by specialty. These models can (1) compare current physician staffing in a given setting with systemwide norms and (2) yield estimates of future staffing requirements conditional on future workload., Conclusions: Empirically based models can play an important role in determining VA physician staffing requirements. VA should test, evaluate, and revise these models on an ongoing basis.

Function of agonists and antagonists and the centering effect of the muscles on the connected joint result in constant changes of the site of load. Based on a model it is assumed that chondric cells organise in form of "functional units" within the single layers of the hyaline tectorial cartilage. In each case a small number of those units is subject to the rhythm of load and relief in a fixed period of time given. After 24-hour-culture of small pieces of cartilage in Ham's F-10 medium erected cilia are found on the predominantly ciliated chondrocytes with this indicating relief of pressure. In these cells massive glycogen synthesis and an active Golgi apparatus are present. In parallel, chondrones are found in which cellular contact functions via a cilium. Time-dependent glycogen occurs in these cells too. Cells having almost the same synthesis time course of the glycogen join up to form "functional units", which are particularly involved in the biomechanic cartilage behavior in the radiar cell zone.

We utilized low-dose intraembolic urokinase (UK) infusions in a canine model of experimental pulmonary embolism (PE) and compared the arteriographic extent of thrombolysis with three other treatment regimens. Group 1 animals (n = 16) received the intraembolic UK infused directly into the PE offering the mechanical effect of the infusion combined with pharmacologic thrombolysis. In the group 2 animals (n = 5), UK was delivered via a guide catheter placed proximal to the clot. Group 3 animals (n = 6) were treated with a direct intraembolic saline solution infusion. Group 4 (n = 7) received only intravenous heparin. The arteriographic extent of thrombolysis was graded 1+ to 3+. The extent of thrombolysis was 2.88+ in the group 1 animals and was significantly greater than in groups 2, 3, or 4 (p = 0.003, 0.0005, and 0.0001, respectively). Fibrinogen levels did not significantly decrease with intraembolic treatment (p = 0.07). Delivery of UK directly into emboli in an experimental canine PE model appears to elicit a combined mechanical and pharmacologic effect resulting in extensive thrombolysis.

Background: Percutaneous balloon aortic valvuloplasty is limited by a high risk of procedural morbidity, transient clinical benefit, and a high restenosis rate. The management of patients with symptomatic aortic valve restenosis after percutaneous balloon aortic valvuloplasty is unclear. We hypothesized that aortic valve replacement would produce superior midterm survival compared with repeat balloon aortic valvuloplasty or medication alone in patients with symptomatic aortic valve restenosis after prior balloon aortic valvuloplasty., Methods and Results: Baseline clinical, echocardiographic, and hemodynamic data were collected on 165 patients who underwent percutaneous balloon aortic valvuloplasty as treatment for symptomatic degenerative calcific aortic stenosis. In 144 of these patients (87%), aortic valve replacement was originally considered to carry excessive risk. The survival of three subgroups was calculated during a median follow-up period of 3.9 years (range, 1 to 6 years). Ninety-four patients (57%) had no further mechanical intervention (subgroup 1-BAV), 31 patients (19%) developed symptomatic aortic valve restenosis and underwent a repeat balloon aortic valvuloplasty (subgroup 2-BAV), and 40 patients (24%) subsequently underwent aortic valve replacement (subgroup BAV+AVR). Follow-up was 99% complete. Patients in subgroup BAV+AVR tended to be younger and have a lower prevalence of coronary artery disease or mitral regurgitation. Only 1 patient (2.5%) suffered a perioperative death during aortic valve replacement. The probability of survival 3 years from the date of the last mechanical intervention was 13% for subgroup 1-BAV, 20% for subgroup 2-BAV, and 75% for subgroup BAV+AVR. At the conclusion of follow-up, only 2 patients had symptoms of congestive heart failure or angina after aortic valve replacement., Conclusions: Aortic valve replacement may be performed with a low mortality rate, excellent palliation of symptoms, and prolongation of survival in selected high-risk patients with a history of previous balloon aortic valvuloplasty.

Despite the proven benefits of thrombolytic therapy in acute myocardial infarction, concern for its complications, especially in patients misdiagnosed with myocardial infarction, has led to hesitancy in its use. Historical, clinical and electrocardiographic criteria were developed for enrolling patients with suspected acute myocardial infarction into thrombolytic trials by noncardiovascular specialists. The incidence of misdiagnosis of myocardial infarction and the clinical outcomes when these criteria were used were evaluated for 1,387 consecutive patients given thrombolytic therapy. Twenty-five community hospitals and 7 interventional centers were the sites of enrollment. Most patients (63%) were enrolled from community hospitals. Criteria for thrombolytic therapy included: symptoms of acute myocardial infarction < 6 hours but > 20 minutes, and not relieved by nitroglycerin; and ST-segment elevation > or = 1 mm in 2 contiguous leads or ST-segment depression of posterior myocardial infarction. Exclusion criteria reflecting increased risk of bleeding were used. A final diagnosis of myocardial infarction was based on creatinine kinase-MB, electrocardiographic and ventriculographic evaluation. Acute myocardial infarction was misdiagnosed in 20 patients (1.4%; 95% confidence interval 0.8-2.0%). These patients were demographically similar to those with acute myocardial infarction. All misdiagnosed patients survived; no significant adverse events occurred. Thus, in several clinical settings, a simple algorithm with specific criteria was used for diagnosing acute myocardial infarction and administering thrombolytic therapy. The inclusion criteria used in this study led to a low rate of misdiagnosis.

Early angiography may not adequately subgroup patients with myocardial infarction if cyclic changes in coronary flow occur frequently. From a pilot experience using a new 12-lead ST-segment monitor, a continuously updated, self-referenced ST-recovery analysis method was developed to quantify both instantaneous recovery, as a noninvasive marker of patency, and cumulative ST recovery over time, as a marker of the speed, stability and duration of reperfusion. In 22 patients with acute infarction in whom 44 observations of unique angiographic patency were noted within 6 hours of presentation, serial patency assessments simultaneous with all angiographic observations predicted coronary occlusion with 90% sensitivity and 92% specificity. Of the 22 patients, 11 (50%) had multiple ST trend transitions suggesting cyclic changes in coronary flow before catheterization. Speed, stability and duration of ST-segment recovery were defined by the time to first 50% ST recovery, total number of ST-trend transitions and patent physiology index (percentage of monitoring period showing ST recovery), respectively. Subgrouped angiographically, the median (interquartile range) for cumulative ST parameters with patent (n = 8) versus occluded (n = 14) arteries were, respectively--time to 50% recovery, 1.57 (1.16, 1.70) versus 0.17 (-0.47, 0.32) hours; number of reelevation/recovery events, 1.5 (1, 3) versus 3 (1, 3); and patent physiology index, 52 (47, 59) versus 50 (5, 73). Thus, continuous ST-segment recovery analysis appears to predict simultaneous angiographic patency over serial assessments, whereas cumulative parameters appear to contain independent information, probably because of patency changes before or after angiography.

Objectives: The purpose of this study is to describe the outcome in cardiogenic shock treated with aggressive reperfusion therapy and to identify factors predictive of in-hospital and long-term mortality., Background: Cardiogenic shock is the most common cause of death in patients admitted to the coronary care unit. Although studies have reported lower mortality rates in shock treated with angioplasty, few studies have described a cohort of patients with shock who were not selected because they were most likely to benefit from reperfusion therapy., Methods: A consecutive series of 200 patients admitted with acute myocardial infarction complicated by cardiogenic shock were studied., Results: The in-hospital mortality rate was 53%. Variables with significant univariable association with in-hospital death included patency of the infarct-related artery, patient age, lowest cardiac index, highest arteriovenous oxygen difference and left main coronary artery disease. The most important independent predictors of in-hospital death were patency of the infarct-related artery, cardiac index and peak creatine kinase, MB fraction. The mortality rate in patients with patent infarct-related arteries was 33% versus 75% in those with closed arteries and 84% in those in whom arterial patency was unknown. Patients who survived to hospital discharge were followed up for a median of 2 years, with a mortality rate of 18% after 1 year. The best descriptors of the relation between these variables and postdischarge mortality included age, peak creatine kinase, ejection fraction and patency of the infarct-related artery., Conclusions: In a large consecutive series of patients with cardiogenic shock with complete follow-up, patency of the infarct-related artery was most strongly associated with in-hospital and long-term mortality. This finding supports an aggressive interventional strategy in patients with cardiogenic shock.

In this era of thrombolytic therapy, the standard 12-lead electrocardiogram (ECG) is easily available and noninvasive and could provide indicators of myocardial reperfusion and salvage. Previous reports have proposed that a decrease of total ST-segment elevation of > or = 20% from the pre- to the immediate posttreatment ECG is indicative of reperfusion, and that a > or = 20% decrease from the initial infarct size predicted by ST-segment deviation on the admission ECG to the final infarct size estimated by QRS score on the predischarge recording is indicative of myocardial salvage. This prospective study of 29 patients with myocardial infarction and angiographically documented reperfusion shows that the > or = 20% threshold for ST resolution achieved 79% sensitivity and 70% specificity in patients receiving intravenous therapy and 90% sensitivity in those receiving rescue intracoronary therapy. However, it should be noted that 21% of patients with successful intravenous therapy failed to achieve even this threshold of ST resolution. Regarding myocardial salvage, 63% of patients receiving intravenous and 90% of those receiving rescue intracoronary therapy achieved the threshold of > or = 20% decrease in infarct size.

Objective: To determine whether a gender bias exists in referral for coronary bypass graft surgery among patients with catheterization-documented coronary artery disease., Design: Historical cohort study (1969 to 1984)., Setting: A referral medical center., Patients: A total of 5795 patients with catheterization-documented coronary artery disease., Measurements: Surgical referral patterns of men and women grouped by risk for cardiac death and by treatment effectiveness. Time trends were evaluated for three periods: 1969 to 1974, 1975 to 1979, and 1980 to 1984., Results: Overall, when no adjustment was made for baseline risk for cardiac death, no statistical difference was found between men and women regarding referral for surgery (46% compared with 44%, respectively). When an adjustment was made for such risk, the male-to-female odds ratio for surgical referral was 1.28 (95% Cl, 1.05 to 1.58) among patients with a low risk for cardiac death. This effect was most evident in the 1980 to 1984 period (odds ratio, 1.73; Cl, 1.29 to 2.31). In the high-risk group, the odds ratio was 0.84 (Cl, 0.68 to 1.04), with little change occurring during the study. Men were more likely to be referred for surgery when surgery offered the least survival benefit relative to medical therapy (odds ratio, 1.29; Cl, 1.08 to 1.54). This effect was most pronounced in the 1980 to 1984 period (odds ratio, 1.63; Cl, 1.27 to 2.10)., Conclusions: Women are less likely than men to be referred for coronary bypass graft surgery among patients with a low risk for cardiac death, in whom surgery offers little or no survival benefit over medical treatment. Women are at least as likely as men to be referred for bypass surgery among more symptomatic and more severely diseased patients, in whom surgery offers the greatest survival benefits. These trends were most prominent in the recent years of the study. Based on surgical survival benefits, these referral patterns may represent more appropriate treatment referral for women than men.

Substantial time delays from symptom onset to diagnosis and treatment of patients with acute myocardial infarction have been demonstrated. To determine the relative importance of prehospital mode of patient transport and the relative impact of emergency medical system transport with or without a prehospital cellular electrocardiogram (ECG) on hospital time delays to initiation of thrombolytic therapy, four prospective parallel groups of patients with acute myocardial infarction were evaluated. The median hospital time delay to treatment median (twenty-fifth and seventy-fifth percentiles) was 64 minutes (46 and 87 minutes, respectively, for twenty-fifth and seventy-fifth percentiles) for patients transported by private automobile ("walk-in"); 55 minutes (45 and 68 minutes, respectively) for patients transported by local ambulance; 50 minutes (38 and 81 minutes, respectively) for patients transported by the emergency medical system without a prehospital ECG; and 30 minutes (27 and 35 minutes, respectively) for patients transported by the emergency medical system who had a 12-lead ECG transmitted from the field. Patients transported by the emergency medical system were randomized to receive cellular telephone transmission of a prehospital 12-lead ECG. Specialized emergency medical system transport alone did not facilitate in-hospital initiation of thrombolytic therapy in patients with acute myocardial infarction when compared with those brought by local ambulance or by private automobile. A significant reduction in hospital time delay to treatment was observed only in patients transported by the emergency medical system who had cellular transmission of a prehospital 12-lead ECG from the field.

The Duke Data Bank for Cardiovascular Diseases is an observational data bank capturing baseline, treatment, and follow-up information on patients referred for evaluation of suspected coronary artery disease. From 6829 patients referred between 1969 and 1990 for diagnostic angiography, baseline cholesterol levels were determined as part of the standard clinical procedure. Baseline total cholesterol values were found to be related to the presence of coronary disease in men and women, although in the elderly little evidence for a significant relationship was found. Formal tests for interactions revealed a significant interaction between age and cholesterol but not between gender and cholesterol. In subgroup analyses using the Cox proportional hazards model, no relationship was found between cholesterol and either cardiovascular death or total cardiac events (death or nonfatal myocardial infarction) in 2038 medically treated patients with 5 to 20 years of follow-up. In the subgroup of 1798 surgically treated patients, there was also no relationship between baseline cholesterol level and these end points. Finally, detailed lipid analysis was done at baseline and 6-month angiography in a second population of 759 patients undergoing percutaneous coronary angioplasty between 1986 and 1989. No substantial relationship between baseline or follow-up cholesterol, low-density or high-density lipoproteins, or triglyceride levels and restenosis was found.

The purpose of this investigation was to document the relative importance of three clinical and three radionuclide variables for prediction of cardiac death in a consecutive group of patients evaluated for coronary artery disease. During a 6 1/2-year period, beginning in January 1978, 2,042 consecutive patients underwent radionuclide angiocardiography, with a clinical diagnosis of coronary artery disease, at Duke University Medical Center. A subgroup of 318 patients who underwent surgical myocardial revascularization near the time of initial study were excluded from later analysis. Clinical follow-up information was complete in a group of 1,663 patients who did not undergo interventional therapy. The 141 cardiac deaths in these 1,663 patients were the study end point. Cox proportional hazards models analyzed the prognostic information contained in three clinical variables (pain type, age, and sex) and three radionuclide angiocardiogram variables (exercise ejection fraction, resting end-diastolic volume, and change in heart rate with exercise). One-variable models confirmed the prognostic importance of each of these six variables. A multivariable model in which all six variables were used showed clinical variables to contain only 5% and the radionuclide variables 95% of the prognostic information. The exercise ejection fraction was the single most important variable, which alone contained 85% of the total information in the model. Curves relating probability of no cardiac death to the exercise ejection fraction identified a value of 0.50 as an inflection point. Patients with exercise ejection fractions below 0.50 demonstrate a probability of cardiac death that increases as the ejection fraction decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Femoral artery injury after diagnostic and therapeutic cardiac catheterization is a frequently encountered clinical problem. This study reviews 150 femoral artery injuries that occurred in 16,350 patients over a 5-year period. A prospective computerized cardiac catheterization data bank was used to determine significant risk factors associated with the occurrence of vascular injury. Logistic regression analysis revealed that congestive heart failure, female gender, and percutaneous transluminal coronary angioplasty or valvuloplasty procedure were significantly associated with occurrence of vascular injury. Greater age, smaller body surface area, and smaller weight were also associated with injury. Recommendations for management include an aggressive approach to obstruction even if local vascular reconstruction is required. False aneurysms are studied by ultrasonography, and small ones may be observed expectantly. Larger aneurysms and aneurysms that persist beyond a few days are managed by use of general or regional anesthesia and by gaining proximal control of the iliac artery. Arteriovenous fistulas resulting from catheterization are rarely hemodynamically significant and often close spontaneously. Thus repair should be delayed.

Cardiac PET imaging using 13N-ammonia and 18FDG was performed on 17 normal volunteers in the glucose-loaded and fasted states. PET images (glucose-loaded and fasted) were subjected to qualitative visual analysis using the descriptors: image quality, FDG blood-pool activity, ammonia lung field activity, and clinical interpretability. Glucose-loaded studies had better image quality, diminished FDG blood-pool activity, and were more often clinically interpretable compared to fasted studies. Dietary state did not affect 13N-ammonia study parameters. Using a semi-quantitative region of interest method, 18FDG myocardial activity was homogeneous and significantly affected by dietary state (2.48 +/- 1.0 fold increase in myocardial-to-blood pool ratio in glucose-loaded versus fasted states). Serum glucose, insulin, and free-fatty acid concentrations responded physiologically to glucose loading and fasting but showed no correlation with myocardial 18FDG uptake. PET imaging using 13N-ammonia and 18FDG appears optimal in the glucose-loaded state.

Balloon aortic valvuloplasty (BAV) has been a therapeutic alternative treatment for severe symptomatic aortic stenosis. Previous studies have been unable to predict 1-year outcome because of limited acute and follow-up clinical, invasive and echocardiographic data. The purpose of this study was to predict long-term outcome based on comprehensive data obtained at the time of valvuloplasty and at 3 and 6 months after the procedure. Of 170 consecutive patients undergoing BAV, 108 (mean age 78 years) were at least 1 year from their procedure. Prospective clinical, micromanometer hemodynamic, digital ventriculographic and echocardiographic/Doppler data were collected at baseline and immediately after the procedure. Echocardiographic data were also obtained at 3 and 6 months. With use of Cox model analysis, major events (defined as cardiac death [n = 30], aortic valve replacement [n = 21] or repeat BAV [n = 13]) were predicted by advanced age, baseline heart failure class, and baseline echocardiographic-determined diastolic left ventricular diameter. Only baseline left ventricular ejection fraction proved to be a significant predictor of cardiac death (p = 0.002) in a multivariate model. Absolute values after BAV (stroke work, first derivative of left ventricular pressure, valve area, end-systolic volume, Fick cardiac output, transvalvular gradient) and acute changes measured by catheterization or echocardiography did not provide additional predictive information over that of post procedure ejection fraction. Similarly, echocardiographic valve area and transvalvular gradient at 3 months added no further prognostic data. With an ejection fraction greater than or equal to 45% (n = 63), cardiac survival at 1 year was 80%, irrespective of age, sex, congestive heart failure class or severity of coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available.

To evaluate the effectiveness and cost of low osmolarity, nonionic contrast agents for cardiac angiography, 443 patients were randomized to receive either iopamidol or diatrizoate. All adverse events that occurred within 24 h of the procedure were recorded prospectively by study personnel and classified according to previously determined criteria. Major events were defined as life threatening or requiring a procedure to treat, or both. Costs of the catheterization procedure, pharmacy, hospital laboratory and treatment of adverse events were determined on the basis of actual resource use. A total of 20 patients (8.5%) had major and 143 (61%) had minor adverse events with diatrizoate use; 10 patients (4.8%) had major and 53 (25%) had minor adverse events with iopamidol (p = 0.12 for major events; p less than 0.001 for total events). Most adverse events were treated fairly easily and inexpensively. The median overall cost was $186 higher for patients after iopamidol use compared with diatrizoate (p less than 0.0001), but all costs except the cost of the contrast agent were not significantly different between the two groups. Thus, patients who received iopamidol for cardiac angiography had a significantly lower rate of adverse events than those who received diatrizoate, but this difference was achieved at a considerably high overall cost.

The incidence of major complications associated with nonionic contrast media has not been defined in a large study. Accordingly, cardiovascular complications, especially thrombotic events, were prospectively evaluated in 8,517 consecutive patients undergoing diagnostic cardiac catheterization with either iopamidol (n = 6,293) or iohexol (n = 2,224). Thrombotic events were defined as coronary embolus, coronary occlusion, transient ischemic attack or stroke occurring at the time of catheterization. Thrombotic events occurred in 15 patients (0.18%). Coronary thrombus or embolus occurred in 7 patients, a thromboembolus from the ventricular catheter occurred in 1 patients and transient ischemic attack or stroke occurred in 7 patients. Six of 15 patients with thrombotic events were premedicated with heparin. Thrombotic events were unusual in that they tended to occur in clusters within short time intervals. On 1 occasion, a thrombus was observed in the catheter tip before embolization. Other cardiovascular complications were similarly low with an incidence of ventricular tachycardia/fibrillation of 0.1%, profound bradycardia of 0.2% and prolonged angina of 0.3%. There were 2 deaths unrelated to thrombotic events. Although the clinical thrombotic events associated with nonionic contrast have an unusual temporal clustering and may result in major complications, the overall incidence (0.18%) of these thrombotic complications with nonionic contrast agents is quite similar to that reported with ionic contrast media.

A total of seventy-four men divided into five groups performed a compensatory tracking task for 4 hr with group mean carboxyhemoglobin (COHb) levels of 0.9, 5.6, 6.1, 11.4 or 16.6%. In all but one group, COHb was formed in approximately 5 min by having the subject breathe a high concentration of carbon monoxide (CO) from a Douglas bag. An appropriate low level of CO in the exposure/test chamber maintained the elevated COHb for the 4-hr duration of the experiment. A slow COHb formation group, not exposed to CO during bag breathing, which was only exposed to low-level CO in the exposure/testing chamber, served as a positive control. Even though mean tracking error scores increased in a nearly monotone manner as a function of COHb, the effects were not statistically significant. Even at the highest dose, the increase in tracking error was small. The increased mean error score due to rapid formation was virtually the same as that due to slow formation.

A physiological maximal loading of the knee-joint of sheep is simulated by a 4-hour peak overloading of 24.5 N and a frequency of 42 impulses per minute. The reactions of articular cartilage, synovia and periarticular muscular tissue to the load were examined histologically, histochemically and biochemically. 20 hours after the loading we could observe a leucocytic influx into the joint and a metabolic hyperactivity in the examined tissue. The changes found during this acute phase are reversible as 180 days after peak overloading the parameters detected to be changed had returned to normal again.

We studied the influence of a 5-weeks training program, mainly with intense work-loads in form of explosive power, on the skeletal muscle system in 7 male sports students. Muscle biopsy specimens from m. vastus lateralis were analysed histochemically, biochemically and by means of electron microscopy. After the training of several weeks, a clear hypertrophy of FT-fibres (24%, p less than 0.05) and ST-fibres (20%, p less than 0.05) became evident. The fibre composition was not affected by the training program. The increase of mean cross-sectional areas of muscle fibres was not connected with any shifting of volume proportions of cellular compartments (volume density of mitochondria, myofibrils and sarcoplasm) at ultrastructural level. Only in the peripheric fibre region mitochondrial volume density increased from 5.9 +/- 2.5 to 8.3 +/- 1.2% in tendency. Contrary to endurance athletes and untrained subjects, power athletes show higher values of sarcoplasmic volume density in their muscle fibres. Results will be discussed in connection with specific demands of explosive powerful muscular performances.

The dynamic QRS amplitude changes that appear during 1-vessel percutaneous transluminal coronary angioplasty of the right and left circumflex coronary arteries were studied in 20 patients using continuous 3-lead electrocardiographic recordings representing leads aVF, V2 and V5. The balloon inflations that produced the greatest extent of ST-segment deviation were identified for each lead ("maximally ischemic periods"). QRS amplitude measurements were performed manually at both the PR and shifted J-ST baselines at 10-second intervals during these periods to determine that baseline from which the R and S waves most nearly maintained their control amplitudes. There was no significant baseline relation for either the R or the S waves in leads V2 and V5 during ischemia. However, the R-wave changes in lead aVF were significantly associated with the PR- versus the J-ST-segment baseline (p = 0.007); the S wave, when it occurred, had no tendency for either baseline. The electrocardiographic records were also examined visually for characteristics of left posterior (inferior) "periischemic block" likely to occur uniquely in patients with a dominant right or left circumflex occlusion. There were 2 patients with obstruction of the right circumflex artery who exhibited the characteristics of periischemic block during percutaneous transluminal coronary angioplasty, as evidenced by an increase in R-wave duration, amplitude or both in lead aVF.