Diastolic effects of chronic digitalization in systolic heart failure.

BACKGROUND: The efficacy of short-term digitalization on exercise tolerance may, in part, reflect enhanced diastolic performance. However, cardiac glycosides can impair ventricular relaxation from cytosolic Ca++ overload. To detect any time-dependent adverse effect, we assessed the diastolic function after long-term use of digitalis in patients with mild to moderate systolic left ventricular failure. METHODS AND RESULTS: From a cohort of 80 patients who received long-term, randomized, double-blind treatment with digitalis versus placebo at the WJB Dorn Veterans Affairs Medical Center, 38 survivors were evaluated at the end of follow-up (mean 48.4 months) with evaluators blinded to treatment used. Each survivor underwent equilibrium scintigraphic and echocardiographic assessment of diastolic function. Peak and mean filling rates normalized with filling volume (FV), diastolic phase durations normalized with duration of diastole, and filling fractions were measured from the time-activity curve. The isovolumic relaxation period and ventricular dimensions were computed echocardiographically. By actual-treatment-received analysis, treated versus untreated patients manifested a trend toward longer isovolumic relaxation (80.76 ms vs 61.54 ms, P = .06) but a markedly lower peak rapid filling rate (6.39 FV/sec vs 10.56 FV/sec, P = .02) despite comparable loading conditions. In addition, treated patients exhibited a lower mean rate of rapid filling (2.75 FV/sec vs 3.78 FV/sec, P = .05) in the absence of a longer rapid filling duration. However, the end-diastolic ventricular dimension did not differ between the 2 groups. Similar results were obtained by intention-to-treat analysis. Importantly, the mortality rate from worsening heart failure in the inception cohort was lower in the digitalis group versus the placebo group (P = .05) with no difference in total cardiac or all-cause mortality. CONCLUSIONS: After long-term digitalization for systolic left ventricular failure, cross-sectional comparison with a control group from the same inception cohort shows a decrease in the rate and degree of ventricular relaxation. This effect did not interfere with the overall ventricular filling or with a favorable impact on outcome from worsening heart failure.

Influence of a randomized clinical trial on practice by participating investigators: lessons from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT). CAVEAT I and II Investigators.

OBJECTIVES: We sought to determine whether the results of the first Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) influenced subsequent practice patterns among the investigators. BACKGROUND: CAVEAT-I demonstrated that directional coronary atherectomy (DCA) resulted in higher rates of early complications at a higher cost and with no clinical benefit. We sought to determine whether these results influenced subsequent use of procedures among CAVEAT-I investigators. METHODS: We compared the results of a week-long registry of all coronary interventions performed at 35 CAVEAT-I sites in 1994 with those of a similar registry obtained in 1992 before the trial, the results of which were published in 1993. For control purposes, the use of procedures was studied at 24 additional sites to provide insight into practice at hospitals not participating in the trial. A total of 1,465 interventions were analyzed. RESULTS: Ninety-four percent of CAVEAT-I sites responded. Utilization rates differed between CAVEAT-I and CAVEAT-I follow-up (p < 0.001). Balloon angioplasty decreased from 83.8% to 68.5%, DCA increased slightly from 10.7% to 14.1%, and the use of other devices increased from 5.4% to 17.5%. Stand-alone balloon use was more prevalent at nonparticipating control sites than at sites that took part in CAVEAT-I (p < 0.001). CONCLUSIONS: Paradoxically, despite the negative findings of CAVEAT-I, there was a noteworthy trend toward an increase in the use of DCA and other devices at CAVEAT-I sites. Our findings suggest that among investigators in the trial, there may have been a lack of influence of trial data on clinical practice patterns 1 year after publication of the results. Ethics of protocol: Both CAVEAT I and II were approved by the Institutional Review Board at each study site.

Analysis and comparison of operator-specific outcomes in interventional cardiology. From a multicenter database of 4860 quality-controlled procedures.

BACKGROUND: Medical consumers are increasingly requesting methods to discriminate among the results of different providers. Standards for appropriate modeling, risk adjustment, and evaluation ("scorecarding") in this setting are not well developed, although such evaluation is being performed by the medical insurance industry and by several states in the United States. Our objectives were to develop and examine clinically meaningful methodology for assessing the operator-specific results for percutaneous coronary revascularization. METHODS AND RESULTS: From a multicenter database of patients treated since January 1, 1990, we used training and validation samples (n = 4860) to develop several models for risk adjustment and applied them to 38 providers performing 25 to 523 procedures in the database. Models were developed using multivariable logistic regression techniques for combinations of the end points of death, myocardial infarction, bypass surgery, and procedural success. Models were evaluated for predictive accuracy by using receiver operating characteristic (ROC) analysis, for the capacity to discriminate between superior and inferior provider outcomes, and for subjectivity and concordance. Major complications occurred in 3.6% of patients. The area under the ROC curve (with perfect discriminatory accuracy, area = 1.0; with no apparent accuracy, area = 0.5) in the validation sample, and frequency of identification of operators with outcomes outside the 95% CI for the outcome in question for the models were for death, 0.85 and 7.9%; for death, Q-wave infarction, and bypass surgery, 0.77 and 13.2%; for death, all infarction, and bypass surgery, 0.66 and 10.5%; and for procedural success, 0.76 and 23.7%. For the models as a group, identification of outliers was inversely related to provider volume (P = .05). Models evaluating non-Q-wave infarction or requiring measurement of percent diameter stenosis were identified as being most susceptible to provider manipulation. CONCLUSIONS: For percutaneous coronary revascularization, modeling to discriminate between provider outcomes is limited by the low incidence of major adverse events, subjectivity or susceptibility to manipulation of more frequently occurring adverse events, the generally modest predictive capacity of the models, and the low volume of individual provider treatments. Modeling will be most useful in the identification of providers with extremely poor outcomes and for discrimination between providers with very large procedural volume. Until improved understanding of the biological and mechanical correlates of major complications allows the development of more predictive models, interpretation of the results of scorecarding, particularly for low-volume providers, should be made with caution.

Outmigration for coronary bypass surgery in an era of public dissemination of clinical outcomes.

BACKGROUND: Since 1989, New York State has disseminated comparative information on outcomes of coronary bypass surgery to the public. It has been suggested that this program played a significant role in the 41% decrease in the risk-adjusted mortality rate between 1989 and 1992. We hypothesized that some high-risk patients had migrated out of state for surgery. METHODS AND RESULTS: We reviewed 9442 isolated coronary bypass operations performed from 1989 through 1993 to assess referral patterns of case-mix and outcome. Expected and risk-adjusted mortality rates were computed using logistic regression models derived from the Cleveland Clinic and New York State databases. A mortality comparison was performed using the 1980 to 1988 time period as a historical control. Patients from New York (n=482) had a higher frequency of prior open heart surgery (44.0%) than patients from Ohio (n=6046) (21.5%, P<.001), other states (n=1923) (37.4%, P=.008), and other countries (n=991) (17.3%, P<.001). They were also more likely to be in NYHA functional class III or IV (47.6% versus Ohio 42.7%, P=.037; other states, 41.2%, P=.011; other countries, 34.1%, P=.001). The expected mortality rate was thus higher than among other referral cohorts. The observed 5.2% mortality rate among these patients was significantly greater than the 2.9%, 3.1%, and 1.4% mortality rates observed for patients from Ohio (P=.004), other states (P=.028), and other countries (P<.001). These differences in outcome were not apparent between 1980 and 1988 among referrals from within the United States. CONCLUSIONS: Public dissemination of outcome data may have been associated with increased referral of high-risk patients from New York to an out-of-state regional medical center.

Peripheral vascular complications in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I).

OBJECTIVES: In-hospital peripheral vascular complications of balloon angioplasty were compared with those of directional atherectomy in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) to identify patients at risk and evaluate costs and outcomes. BACKGROUND: The incidence, costs and outcomes of peripheral vascular complications after coronary intervention have not been fully characterized as a function of randomly assigned therapy. METHODS: At 35 sites in the United States and Europe, 1,012 patients were randomized. Peripheral vascular complications were defined as the composite of pulse loss, pseudoaneurysm, hematoma > 4 cm in diameter or groin hemorrhage necessitating blood transfusion. Logistic models were derived to 1) predict these complications from baseline and procedural characteristics, 2) test the relevance of randomization assignment, and 3) assess their impact on hospital costs and long-term outcomes. RESULTS: Sixty-seven patients (6.6%) developed peripheral vascular complications, of whom 15 (22.4%) required a blood transfusion, 14 (20.9%) underwent vascular surgery, and 2 (3.0%) died. Both in-hospital deaths occurred in patients with peripheral vascular complications. There was no difference in composite peripheral vascular complication rates among patients randomized to angioplasty or atherectomy. Greater age, female gender, postprocedural heparin and intraaortic balloon counterpulsation were predictive of increased risk. In a representative 60% subset, mean hospital costs increased from $9,583 in patients without to $18,350 in those with peripheral vascular complications (p = 0.0001). The unadjusted mortality rate at 1 year was 7.5% for patients with peripheral vascular complications compared with 1.1% for all others (p = 0.0001). These complications identified patients at greater risk of death, myocardial infarction or repeat revascularization at 30 days and 1 year. The atherectomy group had a trend toward more frequent deaths and myocardial infarction. CONCLUSIONS: Directional atherectomy and balloon angioplasty had similar in-hospital peripheral vascular complication rates. Female gender, greater age, postprocedural heparin and intraaortic balloon counterpulsation were predictive of higher risk. The twofold increase in cost and sevenfold increase in long-term deaths highlight the need to prevent these periprocedural events and monitor patients closely.

In-hospital cost of percutaneous coronary revascularization. Critical determinants and implications.

BACKGROUND: Hospital charges associated with percutaneous transluminal coronary revascularization (PTCR) in the United States exceeded $6 billion in 1994 and are likely to be constrained in some manner in the near future. Despite this high cost to the public, little is known about the major determinants and sources of variability of PTCR. METHODS AND RESULTS: From a consecutive series of 1258 procedures with attempted PTCR at a single tertiary referral center, we analyzed 65 clinical, angiographic, physician, and outcome variables as potential correlates of total (hospital and physician) cost. Direct and indirect costs, both hospital and physician, were determined on the basis of resource utilization using "top-down" methodology and were available for 1237 procedures (1086 patients) (98.3%). Mean (+/- SD) patient age was 62 +/- 11 years, 76% were male, 3% had acute myocardial infarction, 71% had unstable angina, 58% had multivessel disease, left ventricular ejection fraction was 54 +/- 12%, 26% had use of at least one nonballoon revascularization device, and median length of stay was 4.4 days. Procedural success was obtained in 89%, and major complications (death, bypass surgery, or Q-wave myocardial infarction) occurred in 3.8%. The median cost was $9176, but it was asymmetrically distributed, and the interquartile and total ranges were wide ($7333 to $13,845 and $3422 to $193,474, respectively). Analyses of independent correlates of cost and loge(cost) were performed using multivariate linear regression in training and test populations. Modeling found 15 independent preprocedural correlates of loge(cost) (R2 = .37) and 23 overall correlates (R2 = .65), excluding length of stay per se. Additional of length of stay to the model increased the explanatory power of the model to R2 = .82. Preprocedural variables most predictive of loge(cost) included presentation with acute myocardial infarction, decision delay (> 48 hours between admission and diagnostic angiography and/or > 24 hours between angiography and intervention), weekend delay, use of intra-aortic balloon counterpulsation, intention to stent, creatinine > or = 2.0 mg%, and lesion complexity (modified American College of Cardiology/American Heart Association score) (all P < .001). In the model that included postprocedural variables as well, length of stay, noncardiac death, urgent bypass surgery, use of the Rotablator, Q-wave myocardial infarction, rise in creatinine > or = 1.0%, and blood product transfusion were all strong independent correlates of loge(cost) (P < .001). CONCLUSIONS: The range of total hospital costs associated with percutaneous intervention is extraordinarily wide. Baseline patient characteristics account for nearly half of the explained variance, but procedural complications and system delays account for much of the remainder. Quantification of the determinants of cost may promote more economically efficient care in the future.

Observational versus randomized medical device testing before and after market approval--the atherectomy-versus-angioplasty controversy.

Percutaneous transluminal coronary angioplasty was developed in the late 1970s as a nonsurgical alternative for revascularization of atherosclerotic coronary arteries. It gained widespread acceptance without a controlled trial. Introduced in 1986, directional coronary atherectomy was the first of other recently developed coronary devices that sought to improve on the results of angioplasty. It was approved in 1990 by the Food and Drug Administration (FDA) on the basis of observational data. Its use expanded rapidly, reaching over 35,000 procedures in 1992, accounting for more than 10% of all interventions. After premarket approval, two major randomized trials tested the hypothesis that atherectomy would be superior to angioplasty. Their results raised a cautionary flag and stood in contrast to projections made from prior observational data. It is concluded that randomized controlled trials validate claims of relative efficacy and safety of competing medical technologies, a lesson reflected in recent changes in policy at the FDA.

Cost of initial therapy in the Electrophysiological Study Versus ECG Monitoring trial (ESVEM).

BACKGROUND: Patients randomized to either serial electrophysiological testing (EPS) or serial Holter monitoring (HM) to guide antiarrhythmic therapy for life-threatening ventricular arrhythmias had equivalent rates of mortality and arrhythmia recurrence in the ESVEM study. This report analyzes the effects of EPS, HM, and clinical factors on the charges for initial evaluation and management of patients with life-threatening ventricular arrhythmias. METHODS AND RESULTS: Ten of 14 clinical centers participating in ESVEM provided bills from the initial hospitalization for randomized patients. Predictors of charges (1991 dollars) were analyzed by linear regression after logarithmic transformation. Initial hospital charge data were obtained for 286 patients randomized in ESVEM (88% of patients eligible for this substudy, 59% of all ESVEM patients). Patients with charge data were somewhat more likely to be older, to be female, and to have failed previous antiarrhythmic drug therapy at study entry and were less likely to have a drug predicted effective after randomization. Mean overall hospital charges were $35,986 (SD, $32,628) with a median of $24,532 (interquartile range, $16,126 to $43,593). Prerandomization patient characteristics generally had insignificant effects on charges, with the exception of presentation with resuscitated sudden death (28% increase in charges, P = .01) and heart failure (26% increase in charges, P = .02). Patients randomized to EPS had higher mean charges for evaluation ($42,002 versus $29,970, P = .0015) as well as more drug trials (3.0 versus 2.1, P = .0001) and a longer hospital stay (19.6 versus 13.9 days, P = .0007). In a multivariate regression model, failure to find an effective drug (P = .0001), the number of drug trials (P = .0001), and resuscitated sudden death as the presenting arrhythmia (P = .0001) were the only independent predictors of higher initial charges. CONCLUSIONS: (1) Initial hospital charges are significantly higher for EPS-guided than HM-guided therapy. (2) The higher charges for EPS-guided therapy were due to a greater number of drug trials and a lower probability of finding an effective drug. (3) Failure to find an effective drug, a larger number of drug trials, and a history of resuscitated sudden death independently predict higher charges.

Differential effects of antihypertensive agents in experimental and human atherosclerosis.

The association between hypertension and atherosclerosis is complex, incorporating endothelial dysfunction, abnormalities of insulin and lipid metabolism, altered vascular biology, and impaired arterial compliance. Results of experimental and human studies suggest that there is heterogeneity in the manifestations of disease and responses to therapy among different animal species, vascular territories, and individual patients. Antihypertensive therapy requires the careful selection of specific agents that reduce blood pressure and preferentially and positively modulate the synergistic interaction of the many facets of disease, with the goal of preventing or regressing atherosclerosis. Angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, and alpha-blockers appear to hold the greatest promise in this regard.

Adrenal insufficiency. A rare initial sign of metastatic colon carcinoma.

A 75-year-old woman evaluated for "drop attacks" 3 years after anterior resection for colo-rectal cancer developed hyponatremia associated with a morning cortisol of 5.7 micrograms/dl, a plasma adrenocorticotropic hormone level of 319 pg/ml, and an inadequate response to cosyntropin. Computed tomography scan demonstrated bilateral adrenal masses. Fine needle aspiration biopsy of the adrenals revealed adenocarcinoma, histologically similar to her previous colon carcinoma. Addison's disease secondary to isolated colon cancer metastases to the adrenals is rare. Our report represents the first antemortem histologically confirmed diagnosis of this entity. A review of the available literature is presented.