Background Patients with chest pain thought to be due to acutecoronary ischemia are typically taken by ambulance to the nearesthospital. The potential benefit of field triage directly toa hospital that treats a large number of patients with myocardialinfarction is unknown.
Methods We conducted a retrospective cohort study of the relationbetween the number of Medicare patients with myocardial infarctionthat each hospital in the study treated (hospital volume) andlong-term survival among 98,898 Medicare patients 65 years ofage or older. We used proportional-hazards methods to adjustfor clinical, demographic, and health-system–related variables,including the availability of invasive procedures, the specialtyof the attending physician, and the area of residence of thepatient (rural, urban, or metropolitan).
Results The patients in the quartile admitted to hospitals withthe lowest volume were 17 percent more likely to die within30 days after admission than patients in the quartile admittedto hospitals with the highest volume (hazard ratio, 1.17; 95percent confidence interval, 1.09 to 1.26; P<0.001), whichresulted in 2.3 more deaths per 100 patients. The crude mortalityrate at one year was 29.8 percent among the patients admittedto the lowest-volume hospitals, as compared with 27.0 percentamong those admitted to the highest-volume hospitals. Therewas a continuous inverse dose–response relation betweenhospital volume and the risk of death. In an analysis of subgroupsdefined according to age, history of cardiac disease, Killipclass of infarction, presence or absence of contraindicationsto thrombolytic therapy, and time from the onset of symptoms,survival at high-volume hospitals was consistently better thanat low-volume hospitals. The availability of technology forangioplasty and bypass surgery was not independently associatedwith overall mortality.
Conclusions Patients with acute myocardial infarction who areadmitted directly to hospitals that have more experience treatingmyocardial infarction, as reflected by their case volume, aremore likely to survive than are patients admitted to low-volumehospitals.
In most of the United States, patients with chest pain thoughtto be due to acute coronary ischemia are taken by ambulanceto the nearest hospital rather than to tertiary centers thattreat a large number (high volume) of patients with acute myocardialinfarction. The destination is determined by proximity alone,both for efficient operation of the emergency medical transportationsystem and because time is deemed paramount.
The importance of experience on the part of the hospital andphysician as a determinant of the patient's survival has beenincreasingly recognized for various specialties and procedures.1,2,3,4,5,6,7,8,9To determine whether hospital volume influences mortality amongpatients with acute myocardial infarction, we performed a retrospectivecohort study, using data from the Cooperative CardiovascularProject (CCP), which was conducted by the Health Care FinancingAdministration (HCFA). This cohort was uniquely suited for theanalysis of the effects of aspects of the health care deliverysystem: the nationwide sample comprised nearly 100 percent ofelderly patients with myocardial infarction who had fee-for-serviceinsurance coverage, and the study had extensive clinical data,blinded data abstraction, and reliable long-term follow-up.
Methods
The methods of the CCP are described fully elsewhere.10,11,12For each acute care hospital in the United States, HCFA identifiedall Medicare fee-for-service beneficiaries with the principal-discharge-diagnosiscode 410.xx (acute myocardial infarction), excluding codes 410.x2(subsequent care), of the International Classification of Diseases,9th Revision, Clinical Modification (ICD-9-CM), during a continuouseight-month sampling period that fell between February 1994and July 1995. Using photocopied medical-record charts, researchabstracters entered pertinent historical, clinical, and demographicvariables into an electronic data base.
Patients
By virtue of geography and the policy of the emergency medicalsystem, most patients with acute myocardial infarction are takento the nearest hospital. To reduce potential biases in selectionand referral of patients, we limited the analysis to patients65 years of age or older who were admitted from home with averified infarction that was present on admission. We excludedduplicate admissions, interhospital transfers, and admissionsfrom nursing and retirement homes. We also excluded patientswhose infarctions occurred after admission, those referred fromphysicians' offices and free-standing clinics, and patientswith coma on arrival or with preexisting dementia or terminalillness. We excluded patients from five states (Alabama, Connecticut,Iowa, Minnesota, and Wisconsin) because of intentional undersamplingrelated to other CCP research projects. We obtained demographicdata for the county of residence by linking the postal ZIP codesof the patients to governmental data bases.13,14,15,16 Dataon long-term survival, obtained from the enrollment data baseof the Social Security Administration, were assigned to theinitial admitting hospital regardless of subsequent transfer.
Myocardial infarction was deemed present if patients had a creatinekinase MB fraction greater than 0.05 or at least two of thefollowing three criteria: chest pain, a serum creatine kinaselevel at least two times the upper limit of normal, or diagnosticelectrocardiographic findings. We used dummy variables to codemissing values for categorical variables and for continuousvariables with a rate of missing values greater than 5 percent.The results were unchanged in several alternative analyses thatdid not include dummy variables.
Data on Hospitals and Physicians
Our unit of analysis was an individual patient from the CCP.For each patient, we constructed a variable for the total numberof CCP patients at the admitting hospital. We determined theavailability of invasive procedures at each hospital accordingto the capability for coronary angiography or revascularization(no angiography, angiography only, or angioplasty and bypasssurgery), assuming that hospitals billing for more than fourprocedures during the study had on-site capability. We obtainedinformation on the other characteristics of the hospitals fromthe data base of the American Hospital Association.17
We determined the specialty of the physician by matching theunique physician identification numbers of CCP attending physiciansto a HCFA data base of self-reported specialties. We limitedthe analysis of specialists to cardiologists, internists, familypractitioners, and general practitioners, who were the attendingphysicians for 82.3 percent of the patients in the study.
Statistical Analysis
Our multivariate model, adapted from models for the assessmentof 30-day mortality after myocardial infarction reported byNormand et al.18 and Lee et al.,19 included clinical, historical,and health-system–related variables. To the publishedmodels we added variables for hospital volume and availabilityof invasive procedures, specialty of the attending physician,presence or absence of electrocardiographic ST-segment elevation,presence or absence of contraindications to thrombolytic therapy,area of residence of the patient (rural, urban, or metropolitan),and geographic region (northeast, south, midwest, and west).Each clinical variable was significant at the level of P<0.001,with the exception of a third heart sound (S3) on admission(P=0.01). None of the independent variables were collinear (Spearmancorrelations, <0.5).
We divided the patient population into quartiles according tothe case volume of the hospitals to which they were admittedand used Kaplan–Meier curves to compare unadjusted survival.To determine whether there was a selection bias, we used logisticregression to calculate a predicted one-year mortality rate20for each quartile of hospital volume and for each physicianspecialty. We used data on covariates for each patient fromthe proportional-hazards model while neutralizing the effectsof hospital-related variables by standardizing them to the lowest-mortalitygroups. Thus, hospital volume was standardized to the medianof the highest-volume quartile, the specialty of cardiology,the availability of bypass surgery, the patient's residencein a major metropolitan county, and the northeastern geographicregion. We excluded the possibility that within-hospital clusteringmight affect the results, because the results of logistic regression,21the generalized estimating equation,22,23 and the Cox proportional-hazardssurvival analysis24 were virtually identical. Hospital volumewas scaled to the difference between the medians of the lowestand highest quartiles (5.5 Medicare patients with myocardialinfarction per week), approximating the maximal potential benefitof field triage for patients with myocardial infarction.
Results
Characteristics of the Patients
The original data set contained information on 234,769 admissions.We excluded admissions from the five undersampled states (4.2percent); admissions after the index admission (11.0 percent);patients admitted from places other than home (25.0 percent);patients who did not have a verified infarction on admission(10.0 percent); patients admitted to hospitals that were ableto provide emergency angioplasty without bypass surgery (2.7percent); and patients younger than 65 years (5.0 percent).
Overall, 98,898 patients met the criteria for the study. Dataon 3713 (3.8 percent) of these patients were excluded from themultivariate analysis because of missing information. The ratesof missing information for variables describing clinical characteristicswere less than 5 percent with the exception of the rates forserum albumin (27.0 percent) and chest radiographs (6.0 percent).Analyses that included the physician's specialty excluded 750patients (0.8 percent) for whom information on the specialtywas not available. The median follow-up period for survivorswas 910 days.
Demographic and clinical characteristics of the patients inthe study, by quartile, according to hospital volume, are shownin Table 1. Most differences were significant at the level ofP<0.001, but their magnitude and clinical significance weresmall, with predictable exceptions. A higher proportion of patientsat low-volume hospitals had rural ZIP codes, patients at high-volumehospitals tended to be city dwellers, and high-volume hospitalswere more likely to offer treatment by cardiologists as wellas coronary angiography and revascularization.
Table 1. Characteristics and Outcomes of the Study Patients, by Quartile, According to the Hospital's Volume of Patients with Acute Myocardial Infarction.
Survival
Unadjusted Kaplan–Meier survival curves for quartilesof hospital volume (Figure 1) showed an early survival advantageat high-volume hospitals. Thirty days after discharge, the unadjustedmortality rate was 16.7 percent at the lowest-volume centers,as compared with 14.4 percent at the highest-volume centers,with a progressive dose–response effect. The associationbetween higher mortality and admission to hospitals treatinga small number of patients with myocardial infarction (low volume)remained significant in a proportional-hazards analysis (Table 2):a decrease of 5.5 Medicare patients per week was associatedwith a hazard ratio for death at 30 days of 1.10 (95 percentconfidence interval, 1.05 to 1.16; P<0.001) and a long-termhazard ratio for death of 1.05 (95 percent confidence interval,1.02 to 1.08; P<0.001).
Table 2. Adjusted Hazard Ratios for Death Associated with Variables Pertaining to the Hospitals and Physicians.
In an otherwise identical model that treated hospital volumeas an ordinal variable according to quartile, the hazard ratiofor 30-day survival among patients in the lowest versus thehighest hospital-volume quartile was 1.17 (95 percent confidenceinterval, 1.09 to 1.26; P<0.001); for the second quartilethe ratio was 1.07 (95 percent confidence interval, 1.01 to1.13; P= 0.02); and for the third quartile the ratio was 1.05(95 percent confidence interval, 0.99 to 1.10; P=0.11). By comparison,the hazard ratio for 30-day survival was 1.09 for patients whohad had prior bypass surgery and 1.18 for patients with a historyof diabetes mellitus. The risk of death was disproportionatelyhigh at low-volume hospitals, but hospital volume as a continuousvariable remained significant when the analysis was limitedto the two highest-volume quartiles.
The association between hospital volume and mortality was notdue to imbalances among the quartiles in coexisting conditionsor the severity of the illness. The predicted 30-day and 1-yearmortality rates, which neutralize the effects of health-systemfactors (Table 1), were essentially identical in all quartilesof hospital volume. Subgroup analyses according to the demographicand clinical characteristics of the patients at presentation(Table 3) showed that survival at low-volume hospitals was consistentlyworse than at high-volume hospitals.
Table 3. Thirty-Day Mortality Rates and Adjusted Hazard Ratios for Death at 30 Days, According to Clinical Characteristics of Patients at Presentation.
Availability of Invasive Procedures, Physician Specialty, and Rural Residence
The availability of invasive procedures, after adjustment forhospital volume and the physician's specialty, was not associatedwith a significant survival advantage. For each type of hospitalinvasive procedure, there was a dose–response relationbetween hospital volume of patients with myocardial infarctionand long-term survival (Figure 2, top). When hospital volumewas treated as a continuous variable, the dose–responserelation for survival within 30 days after admission was highlysignificant at hospitals that did not offer angiography (hazardratio, 1.38 for a decrease of 5.5 patients with myocardial infarctionper week; 95 percent confidence interval, 1.16 to 1.63; P<0.001)and at hospitals that offered only angiography (hazard ratio,1.19; 95 percent confidence interval, 1.06 to 1.34; P<0.01).The hazard ratio for volume plateaued among hospitals that offeredbypass surgery and angioplasty, with borderline statisticalsignificance (hazard ratio, 1.07; 95 percent confidence interval,1.01 to 1.13; P=0.02). Figure 2 (top) confirms that no significantsurvival advantage can be attributed to hospital invasive proceduresalone, because there was a substantial overlap of hazard ratiosfor long-term mortality among hospitals with different technologicalcapability but equivalent volume, a finding confirmed by statisticalanalysis of interaction. After adjustment for volume, therewas no significant association between survival and the hospital'snumber of beds or teaching status.
Figure 2. Stratified Proportional-Hazards Ratios for Long-Term Mortality According to Potentially Confounding Factors Pertaining to the Health System.
The top panel shows the ratios according to the availability of invasive procedures; middle panel, according to the physician's specialty; and bottom panel, according to the residence of the patient (rural, urban, or metropolitan). In each panel, the study population is stratified according to the factor of interest and then divided into quartiles within each stratum according to hospital volume (the median number of patients per week). The proportional-hazards model uses the variables described for Table 2. The reference category (relative hazard, 1.00) for invasive procedures is the highest-volume quartile of patients at hospitals that provide angioplasty and bypass surgery; for physician's specialty, the highest-volume quartile of patients with cardiologists as attending physicians; and for county of residence, the highest-volume quartile of patients who reside in metropolitan areas that have a population greater than 1 million. The median follow-up period for survivors was 910 days.
Altogether, 30.0 percent of the patients had cardiologists asattending physicians, 37.0 percent had internists, and 15.3percent had family practitioners. The patients treated by cardiologistswere considerably healthier than the patients treated by otherspecialists, with a logistic predicted one-year mortality of23.0 percent, as compared with 26.9 percent for patients treatedby internists, a trend found previously.25 There was a smalllong-term survival advantage for patients of cardiologists,with a long-term hazard ratio for death of 0.97 (95 percentconfidence interval, 0.94 to 1.00; P=0.02). The specialty ofthe attending physician did not affect the association betweenhospital volume and survival, which had a dose–responserelation for patients of each type of specialist (Figure 2,middle). The benefit of having a cardiologist as an attendingphysician was essentially the same among hospitals that couldnot provide angiography, those that could provide only angiography,and those that could provide angioplasty and bypass surgery.During the eight-month sampling period, each cardiologist treateda median of six Medicare patients with myocardial infarction,as compared with a median of three for each internist, and amedian of two for each family practitioner and general practitioner.The number of patients treated by the attending physician wasnot significant in any of the analyses, which included the physician'sspecialty, excluded the specialty, or were restricted to a particularspecialty.
Living in a less populous region as opposed to a metropolitanarea was an independent risk factor for short- and long-termmortality (Figure 2, bottom). Hazard ratios for death at 30days were 1.11 for rural counties (95 percent confidence interval,1.06 to 1.17; P<0.001) and 1.06 for urban counties in metropolitanstatistical areas with a population of 1 million or less (95percent confidence interval, 1.02 to 1.11; P=0.005). Populationdensity did not affect the association between hospital volumeand survival, which had a dose–response relation withineach demographic subgroup.
Patterns of Hospital Practice
Only part of the survival advantage at high-volume hospitalswas explained by measurable differences in the quality of care.When we added to our basic model separate variables for eachpatient's receipt of aspirin and thrombolytic medications onadmission and beta-blockers and angiotensin-converting–enzymeinhibitors at discharge, the hazard ratio for death at 30 daysassociated with lower hospital volume at hospitals that didnot offer on-site angiography decreased from 1.38 to 1.23 (95percent confidence interval, 1.04 to 1.46; P=0.02). At hospitalsthat offered angiography only, the hazard ratio, 1.17, was essentiallyunchanged (95 percent confidence interval, 1.04 to 1.31; P=0.008).At hospitals that offered bypass surgery, the ratio decreasedfrom 1.07 to 1.02 (P=0.60). The diminution was due largely tothe use of aspirin and beta-blockers, a finding consistent withthe results of prior studies.11,26 The hazard ratio associatedwith lower hospital volume did not change when revascularizationwithin 30 days (including angioplasty or bypass surgery at anotherhospital) was added to the model, despite considerable variationin revascularization rates: 24 percent at hospitals withoutangiography, 29 percent at hospitals with angiography only,and 42 percent at hospitals with angioplasty and bypass surgery.
Discussion
We found that elderly patients with acute myocardial infarctionhave better outcomes when they are admitted directly to hospitalsthat treat a large number of patients with acute coronary syndromesthan when they are admitted to hospitals that treat a smallnumber of such patients. The crude difference in 30-day mortalitybetween patients in the lowest and highest quartiles of hospitalvolume was 2.3 deaths per 100 patients. There was a consistentdose–response relation between hospital volume and survival.There was virtually no change in the mortality differentialafter adjustment for clinical factors, the availability of invasiveprocedures, the physician's specialty, and the patient's countyof residence.
Although the hazard associated with low hospital volume is smallerfor patients with myocardial infarction than for patients undergoingsurgical procedures,1,3,4,5,6,7,8,9 the mortality attributableto hospital volume is considerable, because the population atrisk is large and because mortality from cardiac causes is highamong the elderly. For nearly half the Medicare patients withmyocardial infarction nationwide, the 30-day survival benefitat high-volume centers exceeds both a 1 percent absolute differencein mortality, the threshold generally applied to trials of thrombolyticdrugs,27 and the benefit found in landmark trials of medicaltherapy for acute myocardial infarction.28 Equally important,the survival advantage at high-volume hospitals applies to allpatients with acute myocardial infarction, not only to patientswho are eligible for a particular therapy; the CCP is a nationwidestudy of actual clinical practice rather than a study of efficacy.
In our study, the availability of invasive procedures did notconfer a significant survival benefit, a finding consistentwith the results of prior studies.29 The principal factor determiningoutcome in acute myocardial infarction thus may not be invasiveprocedures or the physician's specialty but the availabilityof an experienced health care team. For high-volume hospitals,distinctions between volume and the availability of invasiveprocedures are immaterial, because such hospitals typicallyoffer angioplasty and bypass surgery. But for health systemplanners, this finding, from data collected in 1994 and 1995,when primary angioplasty for acute myocardial infarction wasin its adolescence,30,31 raises questions about the benefitof the proliferation of technology at smaller hospitals.
Our study showed a small survival advantage for patients treatedby cardiologists: a long-term hazard ratio of 0.97 for death(P=0.02), as compared with the risk ratio of 0.79 for deathin the hospital reported by Nash et al.,32 the odds ratio of0.83 for death in the hospital reported by Casale et al.,33and the hazard ratio of 0.88 for death at one year reportedby Jollis et al.25 One reason for the varying estimates of theeffect of attending-physicians' specialties may be that thedata from Medicare Part A do not necessarily indicate the admittingphysician. About 14 percent of Medicare patients with myocardialinfarction reportedly have cardiologists as attending physiciansafter initially being admitted by noncardiologists34; such patientsmay have been considered at high risk and may thus have beenreferred to cardiologists. Another possible reason is selectionbias. When we applied our proportional-hazards model to theentire CCP data set, excluding only duplicate admissions andtransfers, and limited the model to variables used in the priorCCP analysis, the long-term hazard ratio for patients who hadcardiologists as attending physicians was 0.90. When we appliedour exclusion criteria and used the full model in Table 2, thehazard ratio changed to 0.97. Such confounding suggests thatany observational analysis of acute myocardial infarction accordingto the physician's specialty (including our own) may be inherentlylimited by selection bias, perhaps because a specializationin cardiology is often a prerequisite for performing initialtherapies such as thrombolysis and primary angioplasty.
We could not identify a predominant mechanism for the survivaladvantage at high-volume hospitals. The use of aspirin, thrombolyticagents, beta-blockers, angiotensin-converting–enzyme inhibitors,and revascularization accounted for about one third of the survivalbenefit. Because the experience of a health care team is multifactorial,the absence of a more specific mechanism is not surprising andis consistent with the effects of volume in other fields.1,2,3,4,5,6,7,8,9
From the standpoint of health policy, the existence of an effectof volume is as important as its mechanism, suggesting thatfield triage, with patients with myocardial infarction transporteddirectly to high-volume centers designated for the treatmentof cardiac disease, might improve survival after myocardialinfarction. The possibility of field triage arouses concernabout morbidity and mortality en route to hospitals and particularlyabout possible delays in thrombolysis for eligible patients.Published estimates of the effect of thrombolytic symptom-to-treatmentdelays range from 0.16 life saved per 100 patients treated perhour of earlier treatment35 to 3.3 lives per 100 patients treatedper hour within 1.6 hours after the onset of symptoms.36 Inany case, thrombolytic treatment is not the sole determinantof policy for the emergency medical system, because relativelyfew patients receive thrombolytic agents — only 19.3 percentof the CCP cohort. And even fewer patients present shortly afterthe onset of symptoms, when thrombolytic therapy has the greatestbenefit. In the Global Utilization of Streptokinase and TissuePlasminogen Activator for Occluded Coronary Arteries study,only one quarter of the patients presented within one hour afterthe onset of symptoms.37 As a practical matter, minor transportdelays might be clinically insignificant as compared with abenefit relating to hospital volume of more than 2 lives savedper 100 patients.
The actual effect of transport time on thrombolysis is an importantissue that needs to be resolved by the development and validationof criteria for triage, clinical trials, and regional adjudicationby policy makers for the emergency medical system. At high-volumehospitals, earlier administration of thrombolytic agents mightcompensate for short transport delays; in our CCP cohort, themedian interval between arrival at the hospital and the administrationof thrombolytic agents was five minutes shorter for the highest-volumequartile than for the lowest-volume quartile (P<0.001). Inaddition, hospitals are often clustered so closely that triagewould not involve appreciable transport delays, a common-senseobservation supported by analysis with the use of ZIP codesas a marker for hospital proximity. Twenty-two percent of theCCP patients in metropolitan areas and 36 percent of the patientsin urban areas were admitted to smaller hospitals (those treatingfewer than four CCP patients with myocardial infarction perweek) that had the same ZIP code as another hospital, and threequarters of such patients (74 percent and 78 percent, respectively)were treated at smaller hospitals within two ZIP-code integersof another hospital. In rural areas, field triage might be feasiblein conjunction with prehospital thrombolysis, a combinationthat has proved effective in randomized trials.38,39
The findings of any observational study must be interpretedcautiously. The possibility of confounding of hospital volumeby unmeasured variables cannot be ruled out. Our study doesnot include patients in managed-care plans or patients youngerthan 65 years. Systematic differences in ICD-9-CM coding ordocumentation could create bias. Technical advances in interventionalcardiology, such as intracoronary stents and glycoprotein IIB/IIIAreceptor antagonists, might benefit hospitals with high-technologyinterventions, regardless of their volume of patients.
In conclusion, we found that in the initial hospital care ofpatients with acute myocardial infarction, the more experiencethe hospital had, the better the patient's chance for survival.After comprehensive adjustment for coexisting clinical conditions,the patients in the quartile admitted to the lowest-volume hospitalswere 17 percent more likely to die within 30 days after admissionthan those in the highest-volume quartile (P<0.001), a differenceof 2.3 deaths per 100 patients. The capability of the hospitalsto perform coronary angiography, angioplasty, and bypass surgeryhad no significant effect on survival beyond that associatedwith increasing volume. In regions with acceptable transporttime, survival after acute myocardial infarction might be improvedby the use of field triage to transport patients directly tohigh-volume centers designated for the treatment of cardiacdisease.
Supported by grants from the Delmarva Foundation for MedicalCare, the Health Care Financing Administration, and the Harryand Jeanette Weinberg Foundation. Computational and statisticalassistance was provided by the General Clinical Research Center,through grants (RR00035 and RR00072) from the National Institutesof Health. The work of Dr. Powe was supported in part by a grant(K01 A600561) from the National Institute on Aging.
The analyses on which this study was based were performed undercontracts (500-96-P623 and 500-96-P624) with the Health CareFinancing Administration, Department of Health and Human Services.This article does not necessarily reflect the views or policiesof the Department of Health and Human Services, nor does mentionof trade names, commercial products, or organizations implyendorsement by the U.S. government.
We are indebted to the many people and organizations nationwidethat designed and conducted the Cooperative Cardiovascular Project.
Source Information
From the Departments of Medicine (D.R.T., J.C., N.R.P.), Epidemiology (J.C., N.R.P.), Biostatistics (J.C.), and Health Policy and Management (N.R.P.), the Program for Medical Technology and Practice Assessment (D.R.T.), and the Welch Center for Prevention, Epidemiology and Clinical Research (J.C., N.R.P.), Johns Hopkins University, Baltimore; Maryland HealthCare Associates, Clinton, Md. (W.J.O.); and the Delmarva Foundation for Medical Care, Easton, Md. (W.J.O.).
Address reprint requests to Dr. Thiemann at Carnegie 568, Johns Hopkins Hospital, Baltimore, MD 21287-6568.
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