Do race and gender influence the use of invasive procedures?

OBJECTIVE: To assess the influence of race and gender influence on the use of invasive procedures in patients with acute myocardial infarction (AMI) in community hospitals. DESIGN: Prospective, observational. SETTING: Five mid-Michigan community hospitals. PATIENTS: All patients (838) identified with AMI between January 1994 and April 1995 in 1 of these hospitals. MEASUREMENTS AND MAIN RESULTS: After adjusting for age, hospital of admission, insurance type, severity of AMI, and comorbidity, using white men as the reference group, the rate of being offered cardiac catheterization (CC) was 0.88 (95% confidence interval [95% CI], 0.60 to 1.29) for white women; 0.79 (95% CI, 0.41 to 1.50) for black men; and 1.14 (95% CI, 0.53 to 2.45)for black women. Among patients who underwent CC, after also adjusting for coronary artery anatomy, the rate of being offered angioplasty, using white men as the reference group, was 1.22 (95% CI, 0.75 to 1.98) for white women; 0.61 (5% CI, 0.29 to 1.28, P =.192) for black men; and 0.40 (95% CI, 0.14 to 1.13) for black women The adjusted rate of being offered bypass surgery was 0.47 (95% CI, 0.24 to 0.89) for white women; 0.36 (95% CI, 0.12 to 1.06) for black men; and 0.37 (95% CI, 0.11 to 1.28)for black women. CONCLUSIONS: Our study shows that white women are less likely than white men to be offered bypass surgery after AMI. Although black men and women with AMI are less likely than white men to be offered percutaneous transluminal coronary angioplasty or coronary artery bypass grafting in both unadjusted and adjusted analyses, these findings did not reach statistical significance. Our study is limited in power due to the small number of blacks in the sample.

The use of angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction in community hospitals. Michigan State University Inter-Institutional Collaborative Heart (MICH) Study Group.

BACKGROUND: Previous studies documenting underutilization of angiotensin-converting enzyme inhibitors (ACEIs) in acute myocardial infarction (AMI) have been limited to Medicare populations. HYPOTHESIS: This study examines ACEI prescription rates and predictors in a community sample of hospitalized patients with AMI. METHODS: The charts of 1163 community patients with AMI, prospectively identified at admission between January 1, 1994, and April 30, 1995, were reviewed. RESULTS: Only 64 of 158 (40%) patients considered ideal candidates for ACEI prescription were discharged with a prescription for an ACEI. In a multivariate logistic regression model, prior ACEI utilization [adjusted odds ration (OR) = 3.26; 95% confidence interval (CI) = 2.05-5.20], presence of congestive heart failure (OR = 2.33; CI = 1.50-3.61) and black race (OR = 2.20; CI = 1.34-3.64) were identified as positive predictors of ACEI prescription. Conversely, lack of left ventricular ejection fraction (LVEF) measurement (OR = 0.46; CI = 0.28-0.75), LVEF > 40 ( OR = 0.27; CI = 0.18-0.40), and acute renal failure (OR = 0.08; CI = 0.01-0.44) were negative predictors. Women were also less likely to be discharged with an ACEI prescription (OR = 0.71; CI = 0.48-1.05). Furthermore, women were significantly less likely to have LVEF measured prior to discharge than were males (77 vs. 85%, p = 0.001). CONCLUSION: This study underscores the need for improvement in the utilization of ACEI in eligible patients with AMI. It also identifies opportunities for improvement in prescription rates, especially in women.

Recurrent Merkel cell carcinoma of the upper extremity.

We report a case of recurrent Merkel cell carcinoma (MCC) of the upper extremity, treated aggressively with wide local excision, regional lymphadenectomy, and immediate reconstruction. Five years after surgery, there is no clinical or diagnostic evidence of locoregional recurrence or distant disease. The patient's upper extremity and hand remain fully functional, without evidence of median or ulnar nerve dysfunction. No donor site morbidity has been noted.

Mechanisms of triggered activity induction at the border zone of normal and abnormal cardiac tissue.

Ionic mechanisms that may be involved in inducing triggered activations at the border zone (BZTAs) of normal and abnormal Purkinje fiber segments were investigated. In a two-chamber bath, fibers were divided into a normal segment and segment treated with ethylenediaminetetraacetic acid to stimulate electrophysiologic alterations 24 hours after infarct. Interventions to normal segments included 1.8 mM lidocaine (n = 10), 3 x 10(-4) mM tetrodotoxin (n = 5), 10(-3) mM aconitine (n = 4), 3 mM cesium chloride (n = 7), 10(-2) mM verapamil (n = 4), and 6-8 mM (n = 7) of K+. Ethylenediaminetetraacetic acid (3.3 mM) prolonged action potentials and induced low diastolic potentials in the normal segment border zone. Tetrodotoxin, lidocaine, and high K+ levels suppressed BZTAs; cesium chloride and aconitine increased BZTAs; and verapamil did not reduce BZTAs. The finding that BZTAs were not abolished by verapamil suggests that abnormal automaticity is not a mechanism. Apparently, BZTAs depend on the Na+ inward current activated by depolarization of the membrane secondary to depolarization of adjacent cells.

Economic and angiographic factors in determining optimal catheter size in performing outpatient left-sided heart and coronary angiography.

A prospective randomized trial was performed in 300 patients to establish the optimal catheter size (5.2, 6, or 7Fr) in performing outpatient left heart and coronary arteriography. A secondary randomization was performed between an attending physician and cardiovascular fellow to determine if the experience level of the operator was an important factor when using smaller French-sized catheters. The primary end point of the trial was total resource utilization of the patient's hospitalization. Hospital cost was calculated with cost accounting methodology using a "bottom-up" approach, and physician "cost" was determined with the Resource-Based Relative Value Scale. Angiographic quality was graded with qualitative and quantitative methods. Procedures were faster and time to hemostasis shorter with smaller catheters. The more experienced operators performed faster procedures and used less fluoroscopy. In the cardiac catheterization laboratory, health-care personnel cost was higher with the 6Fr catheters and when the attending physician was the primary operator. Postprocedure care was slightly less expensive with the smaller catheters. Overall, there was no difference in total cost between the catheter sizes and primary operators. Angiographic quality was similar between the catheter sizes. Smaller catheters used in performing outpatient left-sided heart and coronary arteriography are not associated with cost savings but do not compromise angiographic quality.

Evaluating and improving the cost-effectiveness of the implantable cardioverter-defibrillator.

The implantable cardioverter defibrillator (ICD) is an expensive, widely used device for severe ventricular arrhythmias. Marginal cost-effectiveness analysis is a technique to examine the incremental cost of treatment strategy in relation to its effectiveness. In this study, we used this technique to analyze the cost-effectiveness of the ICD compared with that of electrophysiology (EP)-guided drug therapy and examined ways in which it may be improved. We analyzed Michigan Medicare discharge abstracts (1989 to 1992) and local physician visit, test, and ICD charges. Effectiveness was from 218 previously described patients with ICDs in whom the time of first event (first appropriate shock or death) was determined and presumed to represent "control" (EP-guided drug therapy) mortality. We assumed a 4-year life cycle for the ICD generator and 3.4% operative mortality and used a 5% discount to prevent value. Data were analyzed in a 1-month cycle Markov decision model over a 6-year horizon, and results were updated to 1993 dollars. ICD effectiveness was an increase in discounted mean life expectancy of 1.72 years. Cost-effectiveness was $31,100/year of life saved (YLS). Results were minimally or modestly sensitive to variations in preoperative mortality; resource use; consideration only of patients with ICDs who were receiving any antiarrhythmic drug or specifically amiodarone; and to a decrease in the percentage of first shocks that would equal death without the ICD until the assumed percentage decreased to < 38%. At ejection fraction of < 0.25 and > or = 0.25, cost-effectiveness was $44,000/YLS and $27,200/YLS, respectively, and without preimplant EP study was $18,100/ YLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Confidence intervals for cost-effectiveness ratios.

The problem of variability in computed cost-effectiveness ratios (CERs) is usually addressed by performing sensitivity analyses to determine the effects on these ratios of plausible ranges of values of input parameters. However, the sampling variation that exists in these estimated parameters can be utilized to obtain confidence intervals for cost-effectiveness ratios. As cost-effectiveness analysis becomes more widely used, new techniques need to be developed for establishing when a difference in strategies evaluated is meaningful. A first step is to establish the precision of the CER itself. The authors estimate the precision of a CER in the context of a statistical model in which the primary outcome is survival, with cost and effectiveness defined in terms of the underlying survival distribution (S). Effectiveness (alpha) is measured by life expectancy, restricted to a finite time horizon and discounted at a fixed rate r, alpha = integral of e-rtS(t)dt. Cumulative cost (beta) per patient is regarded as resource utilization and incurred randomly over time depending on the survival experience of the patient, beta = integral of e-rtS(t)dC(t), where C(t) is the total potential resources utilized up to time t. Average cost-effectiveness (ACE) of a single strategy is beta/alpha, and when comparing two strategies, the CER is delta beta/delta alpha, the ratio of the incremental cost to the difference in mean survival. Utilizing the sampling distribution of the Kaplan-Meier estimate of S yields standard errors and confidence intervals for ACE and CER. The technique is applied to survival data from 218 previously studied patients to assess 95% confidence intervals for the CER and ACE of the implantable cardioverter defibrillator as compared with electrophysiology-guided therapy.

Cost-effectiveness analysis in heart disease, Part III: Ischemia, congestive heart failure, and arrhythmias.

Cost-effectiveness analyses were reviewed in the following diagnostic and treatment categories: acute myocardial infarction (MI) and diagnostic strategies for coronary artery disease (CAD), coronary artery bypass graft (CABG) surgery, percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (CHF), and arrhythmias. In the case of acute MI, coronary care units, as presently used, are rather expensive but could be made much more efficient with more effective triage and resource utilization; reperfusion via thrombolysis is cost-effective, as are beta-blockers and angiotensin-converting enzyme (ACE) inhibitors post-MI in appropriate patients. Cost-effectiveness of CAD screening tests depends strongly on the prevalence of disease in the population studied. Cost-effectiveness of CABG surgery depends on targeting; eg, it is highly effective for such conditions as left-main and three-vessel disease but not for lesser disease. PTCA appears to be cost-effective in situations where there is clinical consensus for its use, eg, severe ischemia and one-vessel disease, but requires further analysis based on randomized data; coronary stents also appear to be cost-effective. In preliminary analysis, ACE inhibition for CHF dominates, ie, saves both money and lives. Cardiac transplant appears to be cost-effective but requires further study. For arrhythmias, implantable cardioverter defibrillators are cost-effective, especially the transvenous device, in life-threatening situations; radiofrequency ablation is also cost-effective in patients with Wolff-Parkinson-White syndrome apart from asymptomatic individuals; and pacemakers have not been analyzed except in the case of biofascicular block, where results were variable depending on the situation and preceding tests.

Cost-effectiveness analysis in heart disease, Part II: Preventive therapies.

Cost-effectiveness analysis of preventive therapies are reviewed in the following categories: lipid lowering, hypertension, smoking cessation, exercise, and anticoagulation. From review of 8 analyses, cost-effectiveness of primary prevention via cholesterol lowering drugs is generally expensive, whereas that of secondary prevention generally is favorable. However, targeting by age, coexisting risk factors, and gender strongly influence results that are also sensitive to drug costs. Treatment of hypertension (5 analyses) is cost-effective in virtually all patient populations and circumstances and for a wide variety of drugs. It is more so with coexisting risk. Issues relating to compliance and drug costs are important. Smoking cessation (4 analyses) is highly cost-effective and worthwhile. However, data on recidivism are incomplete, and cessation may be more difficult to achieve in the general population versus study patients. In one analysis, an exercise program was found to be cost-effective in prevention of coronary heart disease. Anticoagulants have been analyzed in various circumstances. Their cost-effectiveness is favorable for prosthetic valves, although sensitive to imprecision in monitoring. It is also favorable for mitral stenosis in the presence of atrial fibrillation but not normal sinus rhythm. Cost-effectiveness of heparinization for prosthetic valve patients undergoing surgery is rather variable and depends on type of surgery (major versus minor) and type of valve. Many topics in anticoagulant therapy remain to be explored from a cost-effectiveness point of view.

Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography.

To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined. The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids.

Role of junctional zone cells between Purkinje fibres and ventricular muscle in arrhythmogenesis.

OBJECTIVE: The aim was to examine under abnormal conditions the flow of currents across junctional (J-) cells found between Purkinje fibre cells and ventricular muscle cells, and determine whether these currents play a role in increasing the excitation rate of ventricular muscle. METHODS: Canine Purkinje fibre and papillary muscle preparations were mapped to locate the Purkinje fibre-ventricular muscle cell junction (PVJ). Using standard techniques, action potentials from Purkinje fibres, J-cells, and ventricular muscle cells and extracellular electrograms were simultaneously recorded at the PVJ. The tissue was then superfused with Tyrode solution plus 4.5-5.0 mmol of ethylenediamine tetra-acetate (EDTA). RESULTS: EDTA prolonged the action potential duration mainly in Purkinje fibres. Secondary plateaus were recorded at membrane potentials of -63.5(SD 7.6) mV (n = 16) in J-cells, and at membrane potentials of -74.9(4.3) mV (n = 9) in ventricular muscle cells. Triggered activations appeared on both secondary plateaus with the earliest site of activation at J-cells (n = 12), at ventricular muscle cells (n = 4), or in both (n = 6). Tetrodotoxin (3-9 x 10(-7) M) and verapamil (1 x 10(-6)-10(-5) M) suppressed triggered activations. CONCLUSION: The PVJ zone appears to be an important site for the generation of triggered activations. Interventions suggest that triggered activations originating in the J-cell depend on delayed repolarisations which trigger the activation of sodium and/or calcium channels.

Marked action potential prolongation as a source of injury current leading to border zone arrhythmogenesis.

The objective of this study was to delineate electrophysiologic phenomena in a border zone adjacent to a zone of marked action potential prolongation. By means of a standard microelectrode technique, we studied sheep Purkinje fibers placed in a partitioned chamber and superfused with Tyrode's solution. Ethylenediamine tetraacetic acid (EDTA) was added to one chamber. Recordings were made in the abnormal segment (ABN) superfused with EDTA and at two sites in the normal segment (NL)--at the border within 0.5 mm (NL-B) and 3 to 4 mm from the partition (NL-D). Exposure of ABN to EDTA caused marked prolongation of the action potential duration (APD) and triggered activations (TAs), which were found to have the earliest recorded activation at NL-B (n = 20), at ABN (n = 8), or at both sites (n = 12). NL-B recordings displayed prolonged low-amplitude secondary plateaus, which were termed "border zone early afterdepolarizations." These were coincident with the plateaus of the prolonged action potentials in ABN and appeared to be due to electrotonic transmission of current from ABN to NL-B. Border zone TAs arose from these low-amplitude plateaus and were either eliminated by the addition of lidocaine to NL consistent with their presumed NL site of origin or occurred after localized withdrawal of EDTA from one segment in fibers rendered quiescent at the plateau by generalized superfusion with EDTA. In conclusion, APD and membrane potential inhomogeneities lead to electrotonic transmission of injury current to border zones adjacent to zones of abnormal APD prolongation. This injury current leads to TAs originating at the border zone. These findings may be relevant to the role of injury current in clinical arrhythmias.

Manifestations of coronary atherosclerosis in young trauma victims--an autopsy study.

OBJECTIVES: The aim of this study was to look at the prevalence of coronary atherosclerosis, its severity and site of involvement in patients < 35 years old who died from noncardiac trauma. BACKGROUND: Autopsies performed on casualties of the Korean War revealed coronary artery involvement in 77.3% of the hearts studied, and data after the Vietnam War noted the presence of atherosclerosis in 45% of casualties with severe disease in 5%, suggesting a decline in the prevalence of coronary atherosclerosis in young men. METHODS: One hundred eleven victims of noncardiac trauma (86.4% white with a mean age of 26 +/- 6 years) underwent pathologic examination of their coronary arteries to estimate the presence and severity of coronary atherosclerosis grossly, microscopically and through computerized planimetry. Identified segments of the coronary arteries were sectioned at 3-mm intervals, stained with special stains and after microscopic examination transferred to videotape and digitized to allow estimation of the percent compromise in the lumen area by atherosclerotic plaque. RESULTS: Signs of coronary atherosclerosis were seen in 78.3% of the total study group, with > 50% narrowing in 20.7% and > 75% narrowing in 9%. No demographic or anatomic features separated the groups with less or more severe involvement of their coronary arteries. Proximal involvement was more common except in the right coronary artery, which was as frequently involved distally. CONCLUSIONS: The overall prevalence of coronary atherosclerosis in a young, predominantly male study group was comparable with that noted after the Korean War. Left main or significant two- and three-vessel involvement was noted in 20% of the group studied and emphasizes the need for aggressive risk factor modification in this group.

The influence of obesity on left ventricular filling and systolic function.

Little information on the possible influence of obesity on diastolic function is available. Thus we studied 24 asymptomatic obese volunteers (greater than 120% ideal body weight; mean 153 +/- 30%), aged 34 +/- 11 years. Each obese subject was matched for age, height, and sex, with a healthy normal-weight control subject. Isovolumic relaxation time (IVRT) and diastolic filling indexes were determined by pulsed Doppler echocardiography. The IVRT was significantly prolonged in the obese group (84 +/- 17 msec) as compared with the control group (57 +/- 13 msec; p less than 0.0002). Multiple regression analysis showed that percentage of ideal body weight was the most important predictor of peak early filling velocity (r = 0.59, p less than 0.005) and mean deceleration rate of early filling (r = 0.61, p less than 0.005) in the obese group. However, age as compared with percentage of ideal body weight was a more important determinant of the relative distribution of early and atrial filling, such as peak early-to-atrial filling velocity ratio (r = -0.75, p less than 0.0001). Ejection fraction, heart rate, and blood pressure did not differ between the obese and control groups. In conclusion, obesity is associated with preclinical abnormalities of IVRT, which may reflect impaired relaxation. The IVRT may be useful in the early detection of left ventricular dysfunction in obesity. Last, studies comparing Doppler indexes of diastolic filling among groups must control for potential differences in percentage of ideal body weight.

Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans.

A reasonably sensitive and specific noninvasive test for doxorubicin cardiotoxicity is needed. In addition, few data exist on the short- and long-term effects of doxorubicin on diastolic filling. To determine if pulsed Doppler indexes of diastolic filling could predict doxorubicin-induced systolic dysfunction, 26 patients (mean age 48 +/- 12 years) were prospectively studied before receiving chemotherapy (control) and 3 weeks after obtaining cumulative doses of doxorubicin. In nine patients developing doxorubicin-induced systolic dysfunction (that is, a decrease in ejection fraction by greater than or equal to 10 ejection fraction units to less than 55%), the isovolumetric relaxation time was prolonged (from 66 +/- 18 to 84 +/- 24 ms, p less than 0.05) after a cumulative doxorubicin dose of 100 to 120 mg/m2. This prolongation preceded a significant decrease in ejection fraction. Other Doppler indexes of filling were impaired after doxorubicin therapy but occurred simultaneously with the decrease in ejection fraction. A greater than 37% increase in isovolumetric relaxation time was 78% (7 of 9) sensitive and 88% (15 of 17) specific for predicting the ultimate development of doxorubicin-induced systolic dysfunction. In 15 patients studied 1 h after the first treatment, doxorubicin enhanced Doppler indexes of filling and shortened isovolumetric relaxation time. In 22 patients, indexes of filling remained impaired and isovolumetric relaxation time was prolonged 3 months after the last doxorubicin dose. In conclusion, doxorubicin-induced systolic dysfunction is reliably predicted by prolongation of Doppler-derived isovolumetric relaxation time. Early after administration, doxorubicin enhances filling and isovolumetric relaxation time. The adverse effects of doxorubicin on both variables persist at least 3 months after cessation of treatment.

Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model.

OBJECTIVE: Previous studies have attempted to characterise the genesis of triggered activity related to early afterdepolarisations. Little is known about their conduction behaviour. This study was designed to examine the origin and conduction behaviour of triggered activations to throw light on the pathogenesis of torsade de pointes. METHODS: Electrophysiological interactions related to triggered activations and early afterdepolarisations between papillary muscle and Purkinje fibres were studied in the guinea pig in a single chambered bath. EDTA (5 mM) in Tyrode's solution was used and microelectrodes were placed in both papillary muscle and Purkinje fibres. RESULTS: During early superfusion, marked prolongation of action potential duration and early afterdepolarisations occurred in Purkinje fibres but not in papillary muscle. In addition: (1) with prolongation of action potential duration and early afterdepolarisations in Purkinje fibres, triggered activations arose during phase 2 and were conducted to papillary muscle, where they induced activations; (2) the number of papillary muscle discharges increased with the increase in Purkinje fibre action potential duration in a linear correlation; (3) severing a segment of papillary muscle from Purkinje fibres eliminated these papillary muscle activations; (4) some triggered activations did not conduct to papillary muscle; these had smaller amplitude, slower rate of depolarisation (dV/dt), more positive activation voltage, and similar peak voltages compared to conducted triggered activations; (5) a low plateau resulting from electrotonic interaction was recorded at the Purkinje fibre-papillary muscle junction; this plateau may have facilitated conduction of triggered activations. CONCLUSIONS: In this preparation there was a disparity of effect on Purkinje fibre and papillary muscle. Prolongation of action potential duration and repetitive activations due to early afterdepolarisations originated in Purkinje fibres and were conducted to papillary muscle. Purkinje fibre-papillary muscle interactions are of interest in relation to torsade de pointes arrhythmias which are believed to arise from this mechanism.