Association of age and packed red blood cell transfusion to 1-year survival--an observational study of ICU patients.

OBJECTIVES: To compare the 1-year survival for different age strata of intensive care unit (ICU) patients after receipt of packed red blood cell (PRBC) transfusions. BACKGROUND: Despite guidelines documenting risks of PRBC transfusion and data showing that increasing age is associated with ICU mortality, little data exist on whether age alters the transfusion-related risk of decreased survival. METHODS: We retrospectively examined data on 2393 consecutive male ICU patients admitted to a tertiary-care hospital from 2003 to 2009 in age strata: 21-50, 51-60, 61-70, 71-80 and >80 years. We calculated Cox regression models to determine the modifying effect of age on the impact of PRBC transfusion on 1-year survival by using interaction terms between receipt of transfusion and age strata, controlling for type of admission and Charlson co-morbidity indices. We also examined the distribution of admission haematocrit and whether transfusion rates differed by age strata. RESULTS: All age strata experienced statistically similar risks of decreased 1-year survival after receipt of PRBC transfusions. However, patients age >80 were more likely than younger cohorts to have haematocrits of 25-30% at admission and were transfused at approximately twice the rate of each of the younger age strata. DISCUSSION: We found no significant interaction between receipt of red cell transfusion and age, as variables, and survival at 1 year as an outcome.

Effect of beta-blockade on mortality in patients with heart failure: a meta-analysis of randomized clinical trials.

OBJECTIVES: We sought to evaluate the current evidence for an effect of beta-blockade treatment on mortality in patients with congestive heart failure (CHF). BACKGROUND: Although numerous small studies have suggested a benefit with beta-blocker therapy in patients with heart failure, a clear survival benefit has not been demonstrated. A recent combined analysis of several studies with the alpha- and beta-adrenergic blocking agent carvedilol demonstrated a significant survival advantage; however, the total number of events was small. Furthermore, it is unclear if previous studies with other beta-blockers are consistent with this finding. METHODS: Randomized clinical trials of beta-blockade treatment in patients with CHF from January 1975 through February 1997 were identified using a MEDLINE search and a review of reports from scientific meetings. Studies were included if mortality was reported during 3 or more months of follow-up. RESULTS: We identified 35 reports, 17 of which met the inclusion criteria. These studies included 3,039 patients with follow-up ranging from 3 months to 2 years. Beta-blockade was associated with a trend toward mortality reduction in 13 studies. When all 17 reports were combined, beta-blockade significantly reduced all-cause mortality (random effect odds ratio [OR] 0.69, 95% confidence interval [CI] 0.54 to 0.88). A trend toward greater treatment effect was noted for nonsudden cardiac death (OR 0.58, 95% CI 0.40 to 0.83) compared with sudden cardiac death (OR 0.84, 95% CI 0.59 to 1.2). Similar reductions in mortality were observed for patients with ischemic (OR 0.69, 95% CI 0.49 to 0.98) and nonischemic cardiomyopathy (OR 0.69, 95% CI 0.47 to 0.99). The survival benefit was greater for trials of the drug carvedilol (OR 0.54, 95% CI 0.36 to 0.81) than for noncarvedilol drugs (OR 0.82, 95% CI 0.60 to 1.12); however, the difference did not reach statistical significance (p = 0.10). CONCLUSIONS: Pooled evidence suggests that beta-blockade reduces all-cause mortality in patients with CHF. Additional trials are required to determine whether carvedilol differs in its effect from other agents.

Transesophageal echocardiography predicts mortality in critically ill patients with unexplained hypotension.

OBJECTIVES: This study sought to determine the prognostic yield and utility of transesophageal echocardiography in critically ill patients with unexplained hypotension. BACKGROUND: Transesophageal echocardiography is increasingly utilized in the intensive care setting and is particularly suited for the evaluation of hypotension; however, the prognostic yield of transesophageal echocardiography in these patients is unknown. METHODS: We prospectively studied 61 adult patients in the intensive care unit with sustained (> 60 min) unexplained hypotension. Both transthoracic and transesophageal echocardiography were performed, and results were immediately disclosed to the primary physician, who reported any resulting changes in management. Patients were classified on the basis of transesophageal echocardiographic findings into one of three prognostic groups: 1) nonventricular (valvular, pericardial) cardiac limitation to cardiac output; 2) ventricular failure; and 3) noncardiac systemic disease (hypovolemia or low systemic vascular resistance, or both). Primary end points were death or discharge from the intensive care unit. RESULTS: A transesophageal echocardiographic diagnosis of nonventricular limitation to cardiac output was associated with improved survival to discharge from the intensive care unit (81%) versus a diagnosis of ventricular disease (41%) or hypovolemia/low systemic vascular resistance (44%, p = 0.03). Twenty-nine (64%) of 45 transthoracic echocardiographic studies were inadequate compared with 2 (3%) of 61 transesophageal echocardiographic studies (p < 0.001). Transesophageal echocardiography contributed new clinically significant diagnoses (not seen with transthoracic echocardiography) in 17 patients (28%), leading to operation in 12 (20%). CONCLUSIONS: Transesophageal echocardiography makes a clinically important contribution to the diagnosis and management of unexplained hypotension and predicts prognosis in the critical care setting.

The prognostic value of troponin in patients with non-ST elevation acute coronary syndromes: a meta-analysis.

OBJECTIVES: This study was designed to compare the prognostic value of an abnormal troponin level derived from studies of patients with non-ST elevation acute coronary syndromes (ACS). BACKGROUND: Risk stratification for patients with suspected ACS is important for determining need for hospitalization and intensity of treatment. METHODS: We identified clinical trials and cohort studies of consecutive patients with suspected ACS without ST-elevation from 1966 through 1999. We excluded studies limited to patients with acute myocardial infarction and studies not reporting mortality or troponin results. RESULTS: Seven clinical trials and 19 cohort studies reported data for 5,360 patients with a troponin T test and 6,603 with a troponin I test. Patients with positive troponin (I or T) had significantly higher mortality than those with a negative test (5.2% vs. 1.6%, odds ratio [OR] 3.1). Cohort studies demonstrated a greater difference in mortality between patients with a positive versus negative troponin I (8.4% vs. 0.7%, OR 8.5) than clinical trials (4.8% if positive, 2.1% if negative, OR 2.6, p = 0.01). Prognostic value of a positive troponin T was also slightly greater for cohort studies (11.6% mortality if positive, 1.7% if negative, OR 5.1) than for clinical trials (3.8% if positive, 1.3% if negative, OR 3.0, p = 0.2) CONCLUSIONS: In patients with non-ST elevation ACS, the short-term odds of death are increased three- to eightfold for patients with an abnormal troponin test. Data from clinical trials suggest a lower prognostic value for troponin than do data from cohort studies.

Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results.

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

Trends in treatment and outcomes for acute myocardial infarction: 1975-1995.

PURPOSE: To review the trends in treatment and survival for patients with acute myocardial infarction over the last 20 years. MATERIAL AND METHODS: Studies were identified through MEDLINE searches and review of study bibliographies. Additional data were obtained from the Health Care Financing Administration including data from Medicare claims files (part A). Thirty-day mortality rates were calculated using Medicare data and case fatality rates from the National Hospital Discharge Survey. Published meta-analyses were used to determine treatment effects. Published studies were included if they reported the use of therapies for acute myocardial infarction at a population level. Trends in the demographic characteristics of the patients as well as infarct characteristics, medication use, and revascularization were recorded. RESULTS: The use of acute treatments that are known to improve survival among patients with myocardial infarction has increased markedly during the last 20 years, leading to an estimated 9.6% reduction (from 27.0% to 17.4%) in 30-day mortality. After adjusting for potential interactions between therapies, the increase in use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and reperfusion can explain 71% of the decrease in the 30-day age- and sex-adjusted mortality rate from 1975 to 1995. The greatest effect of a given therapy was that of aspirin, which accounted for 34% of the decrease in 30-day mortality, followed by thrombolysis (17%), primary angioplasty (10%), beta-blockers (7%), and ACE inhibitors (3%). If other treatments (such as heparin or nonprimary angioplasty), whose effects on mortality are less certain, are included, up to 90% of the decrease in 30-day mortality can be explained by changes in treatment. CONCLUSIONS: The primary reason for the decrease in early mortality from myocardial infarction during the last 20 years appears to be increased use of effective treatments.

Medical therapy or coronary artery bypass graft surgery for chronic stable angina: an update using decision analysis.

PURPOSE: Randomized trials comparing medical and surgical therapies for the treatment of chronic stable angina were completed in the early 1980s. Therapies developed since then have decreased mortality and myocardial infarction rates from coronary artery disease. Using decision analysis and incorporating current recommendations for treatment, we simulated a trial comparing coronary artery bypass graft surgery and medical therapy. METHODS: A Markov decision analysis model was constructed to compare the 5-year and 10-year outcomes of a simulated trial of medical therapy versus bypass surgery for stable chronic angina. Baseline data were obtained from a meta-analysis of trials comparing the two treatments. Data on risk reduction from contemporary therapies were obtained from randomized trials and meta-analyses. RESULTS: All subgroups experienced modest gains in survival with current therapies. At 5 years, the survival rate was 90% in the medical group (an absolute gain of 6%) and 94% in the surgical group (an absolute gain of 4%). Similar results were obtained for patients with triple-vessel disease. Among patients with a low ejection fraction, the 5-year survival rate was 85% for medical patients and 92% for surgical patients. Sensitivity analyses did not substantially affect the conclusions. CONCLUSION: Advances in the treatment of chronic stable angina have improved the outcome both for patients treated initially with surgery and for those treated initially with medical therapy. The improvements were of similar magnitude in both groups, so the fundamental conclusions of the bypass trials are unchanged.

The clinical impact of echocardiography on antibiotic prophylaxis use in patients with suspected mitral valve prolapse.

PURPOSE: To determine the impact of echocardiography on the use of antibiotic prophylaxis in patients with suspected mitral valve prolapse (MVP). PATIENTS AND METHODS: We evaluated 147 consecutive patients who were referred for "rule out mitral valve prolapse" to a university hospital echocardiography laboratory. Chart review and phone contact were used to determine the demographic characteristics of the patients; past diagnosis of MVP, symptoms, and exam at referral; practice specialty of referring MD; echocardiographic findings; and change in prophylaxis usage as a result of the echocardiogram (ECHO). Prophylaxis was considered to be indicated if the echocardiogram demonstrated MVP with at least mild regurgitation or abnormal thickening of at least one mitral leaflet. RESULTS: Based on the ECHO a change in antibiotic prophylaxis was indicated in 20 of 147 (14%) patients including initiation of prophylaxis in 6, and discontinuation of prophylaxis in 14. However, only 4 of 20 patients (20%) actually changed their prophylaxis habits leading to an actual yield of 4 management changes per 131 ECHOs ordered (3%). This corresponded to 1 change in management per $36,250 in hospital and physician costs. Younger age, female gender, and presence of symptoms were associated with a benign ECHO. Indications for a change in management were not significantly different between physician specialities: 18% for generalists (internal medicine and family practice), 12% for cardiologists, and 7% for other specialists, P = 0.3. CONCLUSIONS: In patients referred for evaluation of MVP, echocardiography infrequently resulted in changes in antibiotic prophylaxis management and was associated with significant expense.

Echocardiography in patients with suspected endocarditis: a cost-effectiveness analysis.

PURPOSE: We sought to determine the appropriate use of echocardiography for patients with suspected endocarditis. PATIENTS AND METHODS: We constructed a decision tree and Markov model using published data to simulate the outcomes and costs of care for patients with suspected endocarditis. RESULTS: Transesophageal imaging was optimal for patients who had a prior probability of endocarditis that is observed commonly in clinical practice (4% to 60%). In our base-case analysis (a 45-year-old man with a prior probability of endocarditis of 20%), use of transesophageal imaging improved quality-adjusted life expectancy (QALYs) by 9 days and reduced costs by $18 per person compared with the use of transthoracic echocardiography. Sequential test strategies that reserved the use of transesophageal echocardiography for patients who had an inadequate transthoracic study provided similar QALYs compared with the use of transesophageal echocardiography alone, but cost $230 to $250 more. For patients with prior probabilities of endocarditis greater than 60%, the optimal strategy is to treat for endocarditis without reliance on echocardiography for diagnosis. Patients with a prior probability of less than 2% should receive treatment for bacteremia without imaging. Transthoracic imaging was optimal for only a narrow range of prior probabilities (2% or 3%) of endocarditis. CONCLUSION: The appropriate use of echocardiography depends on the prior probability of endocarditis. For patients whose prior probability of endocarditis is 4% to 60%, initial use of transesophageal echocardiography provides the greatest quality-adjusted survival at a cost that is within the range for commonly accepted health interventions.

Impact of the operating physician on costs of percutaneous transluminal coronary angioplasty.

The hospital charts and billing records of 250 consecutive admissions for percutaneous transluminal coronary angioplasty (PTCA) at a university hospital were reviewed. Clinical characteristics, performing physician, angiographic features of the dilated lesion, procedural outcome, length of stay, and total and departmental hospital costs were recorded for each patient. We identified several independent predictors of hospital cost, including the physician ($4,400 increase from highest- to lowest-cost physician, p=0.004), age ($790 increase per 10-year increase in age, p=0.002), urgency of the procedure ($4,100 increase for urgent vs elective, p < 0.001), and combined angiography and PTCA ($850 increase vs separate angiography, p=0.04). Independent predictors of catheterization laboratory cost included the physician ($1,280 increase from highest- to lowest-cost physician, p=0.03), American College of Cardiology/American Heart Association lesion type B2 or C ($320 increase, p=0.03), and combined angiography and PTCA ($430 increase, p=0.003). Expensive operators used more catheterization laboratory resources than inexpensive operators; however, there are no significant differences in success rate or need for emergent bypass surgery between physicians. PTCA cost is determined by both patient characteristics and the performing physician. The increase in cost due to the physician was not explained by patient variables, lesions characteristics, success rate, or complications.

Echocardiographic score as a predictor of in-hospital cost in patients undergoing percutaneous balloon mitral valvuloplasty.

Percutaneous balloon mitral valvuloplasty (PBMV) is an effective means of palliating mitral stenosis, but it sometimes leads to adverse clinical outcomes and exorbitant in-hospital costs. Because echocardiographic score is known to be predictive of clinical outcome in patients undergoing PBMV, we examined whether it could also be used to predict in-hospital cost. Preprocedure echocardiographic scores, baseline clinical characteristics, and total in-hospital costs were examined among 45 patients who underwent PBMV between January 1, 1992, and January 1, 1994. Patients ranged in age from 18 to 71 years and had preprocedure echocardiographic scores that ranged from 4 to 12. Following PBMV, mean mitral valve area increased from 1.1 +/- 0.3 to 2.4 +/- 0.6 cm2 (p = 0.0001), and mean pressure gradient decreased from 18.3 +/- 5.9 to 6.7 +/- 2.7 mm Hg (p = 0.0001). In-hospital cost for the 45 patients ranged from $3,591 to $70,975 (mean $9,417; median $5,311). Univariate and multiple linear regression analyses demonstrated that among the variables examined, echocardiographic score (p = 0.0007), age (p = 0.01), and preprocedure mitral valve gradient (p = 0.03) were associated with in-hospital cost. Regression modeling suggested that every increase in preprocedure echocardiographic score of one grade was associated with an increase in in-hospital cost of $2,663. Because echocardiographic score is predictive of both clinical outcome and in-hospital cost, we conclude that patients with elevated scores should be considered for alternative therapy.

Evaluation of mitral stenosis with velocity-encoded cine-magnetic resonance imaging.

Velocity-encoded cine-magnetic resonance imaging (VEC-MRI) is a new method for quantitation of blood flow with the potential to measure high-velocity jets across stenotic valves. The objective of this study was to evaluate the ability of VEC-MRI to measure transmitral velocity in patients with mitral stenosis. Sixteen patients with known mitral stenosis were studied. A 1.5 Tesla superconducting magnet was used to obtain velocity-encoded images in the left ventricular short-axis plane. Images were obtained throughout the cardiac cycle at 3 consecutive slices beginning proximal to the mitral coaptation point. To determine the optimal slice thickness for MRI imaging, both 10 mm and 5 mm thicknesses were used. Echocardiography including continuous-wave Doppler was performed on every patient within 2 hours of MRI imaging. Peak velocity was determined for both VEC-MRI and Doppler-echo images. Two observers independently measured the VEC-MRI mitral inflow velocities. Of the 16 patients, imaged data were incomplete in only 1 study, and all images were adequate for analysis. Strong correlations were found for measurements of mitral valve gradient for both 10 mm (peak r = 0.89, mean r = 0.84) and 5 mm (peak r = 0.82, mean r = 0.95) slice thicknesses. Measurements of peak velocity with VEC-MRI (10 mm) agreed well with Doppler: mean 1.46 m/s, mean of differences (Doppler MRI) 0.38 m/s, standard deviation of differences 0.2 m/s. These findings suggest that VEC-MRI can noninvasively determine the severity of mitral stenosis.

The diagnosis of pericardial effusion and cardiac tamponade by 12-lead ECG. A technology assessment.

OBJECTIVE: This study was designed to determine the diagnostic value of 12-lead ECG for pericardial effusion and cardiac tamponade. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENTS: Hospitalized patients with and without pericardial effusion and cardiac tamponade. MEASUREMENTS AND RESULTS: In a blinded manner, we reviewed 12-lead ECGs from 136 patients with echocardiographically diagnosed pericardial effusions (12 of whom had cardiac tamponade) and from 19 control subjects without effusions. We examined the diagnostic value of three ECG signs: low voltage, PR segment depression, and electrical alternans. We found that all three ECG signs were specific but not sensitive for pericardial effusion (specificity, 89 to 100%; sensitivity, 1 to 17%) and cardiac tamponade (specificity, 86 to 99%; sensitivity, 0 to 42%). None of the ECG signs were associated with pericardial effusions of all sizes, but low voltage was associated with large and moderate pericardial effusions (odds ratio = 2.5; 95% confidence interval [CI] = 0.9 to 6.5; p = 0.06) and with cardiac tamponade (odds ratio = 4.7; 95% CI = 1.1 to 21.0; p = 0.004). In contrast, PR segment depression was associated only with cardiac tamponade (odds ratio = 2.0; 95% CI = 1.0 to 4.0; p = 0.05), while electrical alternans was not associated with either pericardial effusion or cardiac tamponade. CONCLUSIONS: Low voltage and PR segment depression are ECG signs that are suggestive, but not diagnostic, of pericardial effusion and cardiac tamponade. Because these ECG findings cannot reliably identify these conditions, we conclude that 12-lead ECG is poorly diagnostic of pericardial effusion and cardiac tamponade.

In vitro calculation of flow by use of contrast ultrasonography.

Contrast echocardiography has been used for qualitative assessment of cardiac function, and its potential for quantitative assessment of blood flow is being explored. With the development of an ultrasound contrast agent capable of passage through the microcirculation, a mathematical model based on classic dye dilution theory, and a digital ultrasound acquisition system, absolute quantitation of myocardial perfusion may be feasible. This study validates the mathematical model in a simple in vitro tube system. Flow was delivered at variable rates through an in vitro tube system while a longitudinal section was imaged with a modified commercial ultrasound scanner. Albunex contrast agent was injected, and videointensity data were captured and analyzed off line. Time-intensity curves were generated, and flow was calculated by use of a mathematical model derived from classic dye dilution mathematics. For 39 different flow rates, ranging for 9.2 to 110 ml/seconds, a correlation coefficient of r = 0.928 (p < 0.001) with a slope of 0.97 was calculated. We conclude that (1) contrast ultrasonography is capable of quantitative determination of flow in an in vitro system, and (2) a mathematical model based on dye dilution theory can be used to calculate flow with accuracy and precision.

Does physician specialty affect the survival of elderly patients with myocardial infarction?

OBJECTIVE: To determine the effect of treatment by a cardiologist on mortality of elderly patients with acute myocardial infarction (AMI, heart attack), accounting for both measured confounding using risk-adjustment techniques and residual unmeasured confounding with instrumental variables (IV) methods. DATA SOURCES/STUDY SETTING: Medical chart data and longitudinal administrative hospital records and death records were obtained for 161,558 patients aged > or =65 admitted to a nonfederal acute care hospital with AMI from April 1994 to July 1995. Our principal measure of significant cardiologist treatment was whether a patient was admitted by a cardiologist. We use supplemental data to explore whether our analysis would differ substantially using alternative definitions of significant cardiologist treatment. STUDY DESIGN: This retrospective cohort study compared results using least squares (LS) multivariate regression with results from IV methods that accounted for additional unmeasured patient characteristics. Primary outcomes were 30-day and one-year mortality, and secondary outcomes included treatment with medications and revascularization procedures. DATA COLLECTION/EXTRACTION METHODS: Medical charts for the initial hospital stay of each AMI patient underwent a comprehensive abstraction, including dates of hospitalization, admitting physician, demographic characteristics, comorbid conditions, severity of clinical presentation, electrocardiographic and other diagnostic test results, contraindications to therapy, and treatments before and after AMI. PRINCIPAL FINDINGS: Patients admitted by cardiologists had fewer comorbid conditions and less severe AMIs. These patients had a 10 percent (95 percent CI: 9.5-10.8 percent) lower absolute mortality rate at one year. After multivariate adjustment with LS regression, the adjusted mortality difference was 2 percent (95 percent CI: 1.4-2.6 percent). Using IV methods to provide additional adjustment for unmeasured differences in risk, we found an even smaller, statistically insignificant association between physician specialty and one-year mortality, relative risk (RR) 0.96 (0.88-1.04). Patients admitted by a cardiologist were also significantly more likely to have a cardiologist consultation within the first day of admission and during the initial hospital stay, and also had a significantly larger share of their physician bills for inpatient treatment from cardiologists. IV analysis of treatments showed that patients treated by cardiologists were more likely to undergo revascularization procedures and to receive thrombolytic therapy, aspirin, and calcium channel-blockers, but less likely to receive beta-blockers. CONCLUSIONS: In a large population of elderly patients with AMI, we found significant treatment differences but no significant incremental mortality benefit associated with treatment by cardiologists.

Transesophageal echocardiography (TEE) in the critical care patient.

Critically ill patients often pose special diagnostic problems to the clinician, intensified by limited physical examination findings and difficulty in transportation to imaging suites. Mechanical ventilation and the limited ability to position the patient make transthoracic echocardiography difficult. Transesophageal echocardiographic (TEE) imaging, however, is well suited to the critical care patient and is frequently used to evaluate hemodynamic status, the presence of vegetations, a cardioembolic source, and an intracardiac cause of hypoxemia. Using proper precautions, TEE can be performed safely in unstable patients and frequently leads to important changes in management.

What a physician needs to know about cost-effectiveness.

The cost of medical care in the United States continues to spiral upward, partly as a result of new technological breakthroughs that promise improved length of life and quality of life for patients. But how good are these treatments in everyday practice? How do we make policies for adopting innovations that improve outcome but also increase costs? Cost-effectiveness studies are designed to answer these questions. They reveal important aspects of a particular medical decision and inform treatment choices by systematically analyzing the relationships between the costs and outcomes of alternative health care interventions. This article provides an introduction to the field of cost-effectiveness analysis and describes an approach to interpreting the rapidly proliferating cost-effectiveness literature.