Accelerated plasminogen activator dose regimens for coronary thrombolysis. The TAMI-7 Study Group.

To determine the clinical profile and efficacy of accelerated recombinant tissue-type plasminogen activator (rt-PA) dose regimens, five different strategies of thrombolytic therapy in a total of 232 patients were systematically evaluated in the setting of acute myocardial infarction. The fifth strategy involved a combination of accelerated rt-PA and intravenous urokinase (regimen E). A weight-adjusted dose of 1.25 mg/kg body weight of tissue plasminogen activator over 90 min (regimen C) yielded the highest coronary patency rate (83%) at acute angiography. The associated in-hospital reocclusion rate for this regimen was low (4%). An exaggerated (60-min) dosage regimen yielded an inferior coronary patency rate (63%). Combination therapy (regimen E) was associated with a 72% patency rate and 3% reocclusion rate. Marginal improvement in global ejection fraction and regional wall function was demonstrated with all strategies by predischarge catheterization. Bleeding complications were most common at the periaccess site and were not different from those in previous experiences reported with conventional 3-h dosing regimens. Measurements of baseline, 30-min and 3-h levels of tissue plasminogen activator, fibrinogen and fibrin(ogen) degradation products were obtained. At 3 h, fibrinogen levels of less than 1 g/liter were demonstrated with combination therapy (regimen E) as well as with regimen C. Major clinical outcomes including death, reocclusion and reinfarction also showed a tendency to be less common with regimen C. Therefore, although accelerated dose regimens of rt-PA do not reliably yield acute coronary patency rates greater than 85%, an acute coronary patency rate of approximately 85% can be approached.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of impact of early catheterization and fibrin specificity on bleeding complications after thrombolytic therapy. The TAMI Study Group.

OBJECTIVES: The aim of this study was to assess the hemorrhagic risk associated with fibrin-specific thrombolytic therapy and invasive procedures with acute myocardial infarction. BACKGROUND: Successful coronary artery reperfusion has important prognostic implications. Because immediate coronary angiography is the only method proved to differentiate early fibrinolytic success from failure, its use may be important for selected patients. METHODS: Five hundred seventy-five patients were evaluated with six combined thrombolytic and catheterization strategies. Patients were randomized to intravenous urokinase alone, recombinant tissue-type plasminogen activator (rt-PA) alone, or both; simultaneously they were randomized to an immediate versus a deferred catheterization strategy. Hemorrhagic events were assessed. The correlation of hemorrhage with clinical and hemostatic variables was evaluated. Prespecified transfusion criteria were employed. RESULTS: No difference in baseline characteristics or in hemorrhagic complications was noted among the three thrombolytic regimens. Although mild (< 250 ml) bleeding was more common in the group with immediate catheterization, no clinically significant difference among catheterization groups was seen in moderate to life-threatening hemorrhagic events. Most bleeding occurred at vascular access sites, yet severe and life-threatening hemorrhage occurred in < 1% of patients. Baseline and nadir fibrinogen levels, change in baseline fibrinogen levels and peak fibrin and fibrinogen degradation products did not correlate with bleeding risk. A clinical predisposition for bleeding was observed in women as well as older (> or = 65 years) and lighter (< or = 70 kg) patients. With prespecified transfusion criteria, only a minimal increase in blood product usage was noted with immediate catheterization. CONCLUSIONS: Immediate cardiac catheterization can be accomplished without a clinically significant difference in bleeding risk. Fibrin specificity offers no clear advantage in reducing hemorrhagic risk. Bleeding risk correlates best with baseline patient characteristics. Finally, the amount of blood transfused can be reduced with lower transfusion criteria.

Administration of thrombolytic therapy in the community hospital: established principles and unresolved issues.

In patients with acute myocardial infarction presenting to community hospitals, thrombolytic therapy should be initiated as rapidly as possible under the supervision of a physician. Paramedic or nurse-initiated pre-hospital therapy is currently investigational. Each hospital must have a detailed evaluation and treatment protocol for acute myocardial infarction that specifies the timetable for patient evaluation, who should or should not receive thrombolytic therapy and the proper dose and mode of administration of the agent or agents to be used. Monitoring after the administration of thrombolytic therapy should focus on arrhythmias, hemodynamic problems, recurrent ischemia and bleeding. The role of early cardiac catheterization to detect patients who have unsuccessful thrombolysis or who require mechanical revascularization procedures is under active investigation. The design of the Thrombolysis and Angioplasty in Acute Myocardial Infarction (TAMI) 5 study, which addresses the role of acute interventional catheterization in the treatment of patients with acute myocardial infarction, is described.

Importance of time to reperfusion for 30-day and late survival and recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate the importance of time to reperfusion for outcomes after primary angioplasty for acute myocardial infarction. BACKGROUND: Survival benefit of thrombolytic therapy for acute myocardial infarction is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important for survival with primary angioplasty. METHODS: Consecutive patients (n=1,352) with acute myocardial infarction treated with primary angioplasty were followed for up to 13 years. Paired acute and follow-up ejection fraction data were obtained at cardiac catheterization in 606 patients. RESULTS: Reperfusion was achieved within 2 h in 164 patients (12%). Thirty-day mortality was lowest with early reperfusion (4.3% at <2 h vs. 9.2% at > or = 2 h, p=0.04) and was relatively independent of time to reperfusion after 2 h (9.0% at 2 to 4 h, 9.3% at 4 to 6 h, 9.5% at >6 h). Thirty-day-plus late cardiac mortality was also lowest with early reperfusion (9.1% at <2 h vs. 16.3% at > or = 2 h, p=0.02) and relatively independent at time to reperfusion after 2 h (16.4% at 2 to 4 h, 16.9% at 4 to 6 h, 15.6% at >6 h). Improvement in left ventricular ejection fraction was greatest in the early reperfusion group and relatively modest after 2 h (6.9% at <2 h vs. 3.1% at > or =2 h, p=0.007). CONCLUSIONS: Time to reperfusion, up to 2 h, is important for survival and recovery of left ventricular function. After 2 h, recovery of left ventricular function is modest and survival is relatively independent of time to reperfusion. These data suggest that factors other than myocardial salvage may be responsible for survival benefit in patients treated with primary angioplasty after 2 h.

Gonococcal endocarditis: a new look at an old disease.

Gonococcal endocarditis, like other gonococcal infections, occurs mainly in the young adult population. The onset of the disease tends to be subacute with an infrequent history of preceding infection or the discovery of a local source of infection. The presenting symptoms and signs fail to differentiate it from other types of endocarditis. Blood cultures are often negative for the first several days. Echocardiography has been useful in helping establish a diagnosis, and survival is favorable with medical and surgical therapy if the diagnosis is made early in the course of the disease. The disease can be quite aggressive, however, and lead to rapid clinical deterioration from valvular destruction and congestive heart failure. As with other forms of endocarditis, deterioration is an indication for aggressive management with early valve replacement.

Etiology of large pericardial effusions.

PURPOSE: To determine the effectiveness of the preoperative evaluation and overall diagnostic efficacy of subxiphoid pericardial biopsy with fluid drainage in patients with new, large pericardial effusions. DESIGN: A prospective interventional case series of consecutive patients admitted with new, large pericardial effusions. PATIENTS AND METHODS: Fifty-seven of 75 consecutive patients admitted to a university tertiary-care center and a university-affiliated Veterans Administration Medical Center with new, large pericardial effusions were studied over a 20-month period. Each patient was assessed by a comprehensive preoperative evaluation followed by subxiphoid pericardiotomy. The patients' tissue and fluid samples were studied pathologically and cultured for aerobic and anaerobic bacteria, fungi, mycobacteria, mycoplasmas, and viruses. RESULTS: A diagnosis was made in 53 (93%) patients. The principle diagnoses consisted of malignancy in 13 (23%) patients; viral infection in 8 (14%) patients; radiation-induced inflammation in 8 (14%) patients; collagen-vascular disease in 7 (12%) patients; and uremia in 7 (12%) patients. No diagnosis was made in four (7%) patients. A variety of unexpected organisms were cultured from either pericardial fluid or tissue: cytomegalovirus (three), Mycoplasma pneumoniae (two), herpes simplex virus (one), Mycobacterium avium-intracellulare (one), and Mycobacterium chelonei (one). The pericardial fluid yielded a diagnosis in 15 (26%) patients, 11 of whom had malignant effusions. The examination of pericardial tissue was useful in the diagnosis of 13 (23%) patients, 8 of whom had an infectious agent cultured. Of the 57 patients undergoing surgery, the combined diagnostic yield from both fluid and tissue was 19 patients (33%). CONCLUSIONS: A systematic preoperative evaluation in conjunction with fluid and tissue analysis following subxiphoid pericardiotomy yields a diagnosis in the majority of patients with large pericardial effusions. This approach may also result in the culturing of "unusual" infectious organisms from pericardial tissue and fluid.

Diagnosis and management (by subxiphoid pericardiotomy) of large pericardial effusions causing cardiac tamponade.

To determine the clinical features, course and outcome of patients with cardiac tamponade, 57 consecutive patients with new, large pericardial effusions were prospectively studied. Twenty-five patients (44%) developed cardiac tamponade with venous hypertension and a pulsus paradoxus greater than 10 mm Hg. Electrocardiography, radiographic studies and echocardiography did not differentiate patients with and without tamponade. All 57 patients underwent thorough diagnostic evaluation followed by subxiphoid pericardial biopsy and drainage. A diagnosis was obtained in 53 patients (93%). Collagen vascular disease was significantly more frequent in the 25 patients with than in the 32 without cardiac tamponade (24 vs 3%; p less than 0.05). The frequency of malignant and uremic effusions was equal in both groups, whereas radiation-induced effusions seldom produced tamponade. At 1-year follow-up, 3 patients (12%) with tamponade had recurrent effusions, and 1 needed reoperation. This was not significantly different from the 32 patients without tamponade. Twelve-month mortality was also similar in both groups (36 vs 44%). This prospective series disclosed several unexpected findings: (1) Cardiac tamponade occurred in almost 50% of patients with new large pericardial effusions; (2) both malignancy and collagen vascular disease occurred with equal frequency as etiologies, whereas radiation-induced tamponade was unusual; (3) thorough clinical evaluation resulted in few idiopathic etiologies; and (4) subxiphoid pericardiotomy was effective for both diagnosis and therapy of tamponade.

Prediction of early recurrent myocardial ischemia and coronary reocclusion after successful thrombolysis: a qualitative and quantitative angiographic study.

To determine the association of qualitative and quantitative measurements of the myocardial infarct-related coronary narrowing with subsequent recurrent ischemia/reocclusion after successful thrombolysis, 47 patients treated with high-dose (150 mg) tissue plasminogen activator over 6 to 8 hours were studied in the setting of acute myocardial infarction. No patient underwent emergent coronary angioplasty. All patients had Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow or higher at the baseline (90-minute) angiogram; 31 patients had a protocol 24-hour catheterization as well. Eighteen patients had recurrent ischemia/reocclusion whereas 29 had an uneventful hospital course. There was no significant difference in baseline clinical characteristics between the 2 groups. Twenty-five (86%) of those with an uneventful course had TIMI grade 3 flow at baseline angiogram compared with 56% of patients with recurrent events. No significant difference in angiographic morphologic characteristics was found between the 2 groups at baseline catheterization. At 24 hours, however, none of the patients who subsequently had recurrent events had a concentric narrowing, while 13 (58%) of them had a complex morphology. In contrast, quantitative parameters of minimal lumen diameter, percent area stenosis and percent diameter stenosis at baseline and 24 hours were not significantly different between those who did and did not have recurrent ischemia/reocclusion. These findings suggest that the degree and quality of coronary flow at baseline catheterization are more important determinants of sustained patency and event-free hospitalization than are quantitative dimensions or coronary morphology. In addition, narrowings that fail to become concentric within the first 24 hours are more likely to be associated with subsequent ischemia or reocclusion during the early periinfarct period.

Results of high dose intravenous urokinase for acute myocardial infarction.

To determine the outcome of patients after treatment with high-dose intravenous urokinase (3 million U) 102 patients were prospectively evaluated in the setting of acute myocardial infarction. The first 61 patients received intravenous urokinase as a continuous infusion and the last 41 patients were treated with an initial 1.5 million U intravenous bolus. Sixty-two percent of all patients had patent infarct-related arteries by the time of immediate angiography (median time 2.2 hours), which was performed in all patients. There was no significant difference in patency rates between patients treated with or without an initial intravenous bolus. Twenty-eight (28%) patients developed clinical evidence of recurrent ischemia (death, reocclusion, emergency angioplasty, urgent bypass surgery) during hospitalization, whereas only 7 (7%) developed angiographically documented reocclusion. Of 28 patients who failed to achieve successful reperfusion at the time of immediate catheterization, rescue angioplasty was technically successful in establishing reperfusion in all but 1 patient. No significant improvement in median global left ventricular function was seen between immediate (48%) and follow-up catheterization (48%). Significant bleeding complications were unusual except in 1 patient who experienced an intracranial hemorrhage. Eight (8%) patients died during hospitalization. Therefore, the use of high-dose intravenous urokinase in patients with acute myocardial infarction is associated with a 62% patency rate, a low incidence of reocclusion and bleeding complications and a high technical success rate with rescue angioplasty at the time of immediate catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized trial of vascular hemostasis techniques to reduce femoral vascular complications after coronary intervention.

This report details a prospectively randomized clinical trial comparing mechanical clamp compression to hand applied pressure for attaining vascular hemostasis after coronary intervention. Effectiveness was determined by comparing the incidence of femoral vascular complications resulting from each of the 2 techniques. Eligible participants included 778 consecutive patients scheduled for percutaneous coronary intervention over an 8-month period. An unselected cohort of the eligible patients (n = 592), determined by the availability of cross-trained clinicians, underwent follow-up serial physical examinations by blinded observers for the duration of their hospital stay. A second, similarly determined cohort (n = 390), underwent color-duplex ultrasonography within 24 hours of sheath removal. Baseline demographic and clinical characteristics, sheath removal parameters, and subsequent outcomes were collected prospectively. The primary end point was a composite of ultrasound-defined femoral vascular complications: femoral artery thrombosis, echogenic hematoma, pseudoaneurysm, or arteriovenous fistulae formation. Complications diagnosed by physical examination constituted the second fundamental end point and included: persistent oozing, ecchymosis, hematoma, bruit, and pulsatile mass. Compared to manual compression, mechanical clamp hemostasis reduced the primary adverse end point by 63% (p = 0.041). Physical examination detected ecchymosis, oozing, and hematomas at equally high frequencies in the two cohorts. Although 65% of the patients in both treatment groups encountered at least one of these cosmetic complications, the diagnoses made by physical examination did not correlate with ultrasound-defined pathology. Multivariable stepwise logistic regression analysis identified a relationship of advanced age and lower body weight to vascular complications. Utilization of a mechanical clamp rather than conventional hand pressure to attain vascular hemostasis significantly reduces ultrasound-defined femoral vascular pathology. Discrepancies between physical examination and ultrasound diagnoses challenge the utility of clinical assessment alone and establish ultrasound as the diagnostic modality of choice.

Usefulness of a pericardial friction rub after thrombolytic therapy during acute myocardial infarction in predicting amount of myocardial damage. The TAMI Study Group.

To evaluate the clinical incidence and outcomes of patients with pericarditis after thrombolytic therapy, 810 patients were prospectively studied during acute myocardial infarction (AMI). Pericarditis was defined as the presence of a pericardial friction rub during the hospital course. Only 5% of patients developed a rub during AMI, a low percent compared with that in the prethrombolytic era. A pericardial friction rub more often occurred in the setting of an anterior wall AMI. Patients with, compared to those without, a pericardial friction rub had lower ejection fractions (45 vs 51%, p = 0.002); worse regional left ventricular function (-3.2 vs 2.7, standard deviation per chord); higher in-hospital mortality (15 vs 6%, p = 0.056); a higher frequency of power failure (83 vs 57%); a higher frequency of anterior wall location of the AMI (53% of cases, p = 0.002); and a higher frequency of 3-vessel disease. Therefore, although the frequency of a pericardial friction rub was low (5%) compared with that in the prethrombolytic era, its occurrence denotes more extensive myocardial damage with a worse clinical outcome. Perhaps with successful reperfusion of the infarct-related vessel, transmural myocardial necrosis is prevented and with it the development of pericarditis. Cardiac tamponade did not occur clinically in any patient who developed a pericardial friction rub.

Subxiphoid pericardiotomy in the diagnosis and management of large pericardial effusions associated with malignancy.

To determine the safety, diagnostic value, and clinical outcome of patients with malignancy undergoing subxiphoid pericardiotomy for large pericardial effusions, we prospectively studied 25 consecutive patients with malignancy and new, large pericardial effusions diagnosed by echocardiography. Twenty-two of the 25 operations were done under local anesthesia, and no patient died at surgery. Pericardial fluid cytology revealed malignant cells in 11 patients (44 percent), while tumor was seen in only five (45 percent) of these 11 patients on pathologic examination. The remaining 14 patients showed no evidence of pericardial invasion with tumor. Evidence of intrathoracic disease by CT or MRI scanning, tamponade, a sanguineous pericardial fluid character, and an elevated serum and pericardial fluid lactate dehydrogenase level all were suggestive of malignant invasion of the pericardium. All 25 patients were followed at least 12 months postoperatively. Effusions recurred in three patients (12 percent), and one patient required reoperation. Overall mortality was 72 percent with a 91 percent (10 of 11) mortality for those with malignant effusions and a 57 percent (8 of 14) mortality for those with nonmalignant effusions. Diagnostically, subxiphoid pericardiotomy has little advantage over examination of pericardial fluid alone in this group of patients. Therapeutically, however, it is a low morbidity procedure which is safe and effective in treating patients with malignancy and large pericardial effusions.

Cytomegalovirus pericarditis: a case series and review of the literature.

Cytomegalovirus (CMV) commonly infects both normal and immunocompromised hosts. Although it usually produces an asymptomatic infection to mild illness, CMV has the potential to significantly injure many different organs. Reports of CMV causing pericardial disease, however, are limited and documentation of infection by growth of the virus from tissue or fluid is rare. As part of a prospective trial of subxiphoid pericardial biopsy in 57 adult patients with large pericardial effusions, three culture-proven cases and one serologically confirmed case of CMV pericardial disease were discovered. Subsequently, CMV was grown from the pericardium of an infant with congenital heart disease. A review of the documented cases of CMV pericarditis is provided along with a discussion of the pathogenesis and significance of this perhaps not so uncommon disease.

Effect of maternal weight on postterm delivery.

OBJECTIVE: Examine the effect of prepregnancy weight and maternal gestational weight gain on postterm delivery rates. STUDY DESIGN: This was a retrospective cohort study of term, singleton births (N=375 003). We performed multivariable analyses of the association between postterm pregnancy and both prepregnancy body mass index (BMI) and maternal weight gain. RESULT: Prolonged or postterm delivery (41 or 42 weeks) was increasingly common with increasing prepregnancy weight (P<0.001) and increasing maternal weight gain (P<0.001). Underweight women were 10% less likely to deliver postterm than normal weight women who gain within the recommendations (adjusted odds ratio 0.90 (95% confidence interval 0.83, 0.97)). Overweight women who gain within or above recommendations were also at increased risk of a 41-week delivery. Finally, obese women were at increased risk of a 41-week delivery with increasing risk with increasing weight (below, within and above recommendations adjusted odds ratios 1.19, 1.21, and 1.27, respectively). CONCLUSION: Elevated prepregnancy weight and maternal weight gain both increase the risk of a postterm delivery. Although most women do not receive preconceptional care, restricting weight gain to the within the recommended range can reduce the risk of postterm pregnancy in normal, overweight and obese women.

Comparison of inpatient charges between academic and nonacademic services in a children's hospital.

OBJECTIVE: To compare inpatient hospital charges generated within a children's hospital by academic and nonacademic pediatric services for common medical diagnoses. METHODS: Hospital admissions to a free-standing children's hospital between 9/1/90 and 8/30/94 were selected for patients who were hospitalized 1 to 14 days, with one of six selected diagnoses, and with discharge attending of record either a private pediatrician or an academic subspecialist. Discharge diagnoses, based on ICD-9 codes, included asthma (n = 1983), bronchiolitis (n = 692), gastroenteritis (n = 733), rule out sepsis (n = 1065), urinary tract infection (n = 516), and viral meningitis (n = 288). Charges associated with patient records were dichotomized as above or below the median charge for each diagnostic category. Each category was analyzed separately using a logistic regression model where the dichotomous-dependent variable was charges above the median charge for each diagnosis. Independent variables included physician type, payor status, patient residence, ICD-9 code as primary or secondary diagnosis, patient age, and presence of complicating conditions. RESULTS: By univariate comparison, academic physicians cared for a higher percentage of underinsured patients, and their care was more expensive. Complicated claims were associated with higher charges than uncomplicated claims for all diagnostic categories. Academic and nonacademic physicians were equally likely to generate above-median charges for five of the six diagnostic categories when controlling for confounding factors. A linear regression model in which charge was the dependent variable generated similar results. CONCLUSIONS: Within the same pediatric health care facility, no consistent difference was found between charges incurred on academic vs private inpatient services.

Experience with the use of tPA in the treatment of acute myocardial infarction.

Early experience with the use of tissue plasminogen activator (tPA) in acute myocardial infarction is reviewed, including comparisons with other thrombolytic agents, a summary of hemorrhagic complications associated with its use, and the rationale for adjunctive therapeutic strategies. The use of tPA has been associated with improvement in left ventricular function, a lower mortality, and a decrease in congestive heart failure signs and symptoms. A protocol for evaluation of patients with possible myocardial infarction for thrombolytic therapy is presented. Consideration must be given to other possible diagnoses, and the ECG must be evaluated carefully to ensure that appropriate criteria are met. Risk factors for hemorrhagic complications include recent trauma, surgery, gastrointestinal and genitourinary bleeding, stroke, and focal neurologic findings. Greater benefit of therapy is expected in patients with larger infarcts who have more marked ST segment changes or evidence of hemodynamic compromise, especially when they are treated early after the onset of symptoms (within the first several hours). Adjunctive measures that can be considered in the emergency department include prophylactic lidocaine, IV nitroglycerin, beta blockade, aspirin, volume replacement and monitoring for dysrhythmias, bleeding, and recurrent ischemia. A comprehensive understanding of these rapidly evolving concepts will assist the emergency physician in the evaluation and management of patients with acute myocardial infarction.

Optimal reporting of health care process measures: inferential statistics as help or hindrance?

In this paper we discuss the appropriate application of inferential statistics to practice profiles and other measures of care. To accomplish our objectives, we first describe the relative merits of measuring three well-recognized domains of medical quality: structure, process, and outcome. Next, we discuss inferential statistics as used in quality improvement. We then describe several common circumstances that arise in the measurement of medical care, giving attention to the application of inferential statistics to each situation. We end with a brief discussion of statistical techniques commonly used in the measurement of quality and challenges that arise with their use.