DIAGNOSTIC METHODSCONGESTIVE HEART FAILURE

The relationship between left ventricular systolicfunction and congestive heart failure diagnosedby clinical criteria

PAUL R. MARANTZ, M.D., M.P.H., JONATHAN N. TOBIN, PH.D.,SYLVIA WASSERTHEIL-SMOLLER, PH.D., RICHARD M. STEINGART, M.D.,JOHN P. WEXLER, M.D., PH.D., NANCY BUDNER, M.P.H., LLOYD LENSE, M.D.,AND JOSEPH WACHSPRESS, M.D.

ABSTRACT There is no uniformly accepted clinical definition for congestive heart failure (CHF),although criteria have been published by various groups. There is also no reference standard for CHF,although left ventricular ejection fraction (LVEF) gives a quantitative assessment of systolic functionand is useful in predicting prognosis. To determine the relationship between LVEF and clinicallydiagnosed CHF, we compared resting LVEF determined by radionuclide ventriculography withdiagnosis of CHF by clinical criteria in 407 patients, based on clinical data collected by a cardiologyfellow. Of 153 patients with a low LVEF (s0.40), 30 (20%) met none of the criteria for CHF.Conversely, of 204 patients with normal LVEF (.0.50), 105 (51%) met at least one of the criteria.We conclude that different criteria for CHF will have varying utility depending on the population beingexamined, and that a combination of clinical features and an objective measure of cardiac performanceis needed to diagnose CHF.Circulation 77, No. 3, 607-612, 1988.

CONGESTIVE HEART FAILURE is among the mostfrequently encountered cardiac diagnoses. Prevalenceof congestive heart failure is estimated to be 1% in theUnited States,1 and Framingham data gives an inci-dence rate of about 2 per 1000 persons per year.2 Only50% of patients diagnosed as having congestive heartfailure survive for 5 years.' It also has major impact interms of morbidity and hospitalization; among elderlypatients, it is the most common medical indication forhospitalization.3

Epidemiologic studies in congestive heart failurehave been hampered by the lack of uniform diagnosticcriteria, relying instead on physician diagnosis of thedisease. The Framingham Study2 created clinical cri-teria for diagnosing congestive heart failure (table 1);however, these criteria have never been validatedagainst a reference standard. A study performed at

From the Department of Epidemiology and Social Medicine, Med-icine and Nuclear Medicine, Montefiore Medical Center and AlbertEinstein College of Medicine, Bronx, NY.

Supported in part by grant number HS 04854 from the National Centerfor Health Services Research, OASH. Dr. Marantz was supported byNRSA training grant 5T32-HL07379-09.

Address for correspondence: Paul Marantz, M.D., M.P.H., Depart-ment of Epidemiology and Social Medicine, Montefiore Medical Center,111 East 210th St., Bronx, NY 10467.

Received Sept. 28, 1987; revision accepted Dec. 10, 1987.

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Duke4 derived another set of clinical criteria for con-gestive heart failure by a multivariate analysis of clin-ical variables against left ventricular end-diastolic pres-sure greater than 15 mg Hg in patients referred forcardiac catheterization with anatomically confirmedcoronary artery disease. The criteria generated by thisstudy were the presence of either an S3 on examinationor cardiomegaly on the chest x-ray (cardiothoracic ratio> 0.48). A third group in Boston5 used clinical judg-ment to derive a set of diagnostic criteria (table 2), andthen validated these against a pulmonary capillarywedge pressure greater than 12 mm Hg in patientsundergoing nonemergency right heart catheterization.

To determine the relationship between the clinicaldiagnosis of congestive heart failure and objectivemeasurement of systolic cardiac function, we com-pared the diagnosis of congestive heart failure, asdetermined by applying three different rating scales,with resting left ventricular ejection fraction, as mea-sured by radionuclide wall motion studies. Althoughnot a reference standard for the diagnosis of congestiveheart failure per se, resting left ventricular ejectionfraction has clinical significance as the most importantpredictor of prognosis in patients with coronary heartdisease.6 It also can identify the subgroup of patients

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TABLE 1Framingham criteria for congestive heart failure

Major criteriaParoxysmal nocturnal dyspnea or orthopneaNeck-vein distentionRalesCardiomegalyAcute pulmonary edemaS3 gallopIncreased venous pressure >16 cm of waterCirculation time >25 secHepatojugular reflux

Minor criteriaAnkle edemaNight coughDyspnea on exertionHepatomegalyPleural effusionVital capacity decreased 1/3 from maximumTachycardia (rate of >120/min)

Major or minor criterionWeight loss >4.5 kg in 5 days in response to treatment

For establishing a definite diagnosis of congestive heart failure in thisstudy, two major or one major and two minor criteria had to be presentconcurrently.

with congestive heart failure who have normal systolicfunction, an important pathophysiologic mechanismthat may require a different therapeutic approach.7

Materials and methodsBetween July 1982 and June 1983, a study to evaluate the

efficacy of cardiovascular nuclear medicine studies (CVNMS)was conducted at the Albert Einstein College of Medicineaffiliated hospitals. The design of this study has been describedin detail previously.8 During this period, radionuclide evalu-ation was performed on 2321 patients who were not on car-diotoxic drugs. Physicians referring patients for CVNMS wererequired to complete a form before the test, specifying reasonfor the test, suspected heart disease, and predicted outcome.There were 1272 patients who underwent a standardized clin-ical assessment by a cardiology fellow immediately before thenuclear scan as part of the CVNMS efficacy study. Thesepatients were similar to those not examined by a study fellowwith regard to reason for referral for the CVNMS and CVNMSresults.

There were 596 patients referred for exercise study, and 676for resting radionuclide ventriculograms. We selected only thosepatients who were referred for resting wall motion study, sinccthese patients are more likely to represent a population withsuspected congestive heart failure than with suspected ischemia.Based on data from the standardized referral form, the referringphysician suspected congestive heart failure in 66% of subjectsreferred for resting study, but in only 6% of those referred forexercise study. Among the resting study subjects, there were 407for whom a complete history, physical data, and a chest x-raywere obtained, and in whom the wall motion study was tech-nically adequate.The Framingham and Duke scales are dichotomous with

respect to the presence or absence of congestive heart failure,while the Boston scale classifies patients as having definite,possible, or unlikely congestive heart failure. Some modifica-

tions of the grading criteria had to be made for this study.Specifically, although cardiomegaly was a factor in all threescales, Framingham did not specify how cardiomegaly would bedefined, the Duke scale required a cardiothoracic ratio on chestx-ray greater than 0.48, and the Boston scale required a ratiogreater than or equal to 0.50. For our analysis, we accepted a

radiologist's reading of cardiomegaly on the chest x-ray, sinceexplicit measures of cardiothoracic ratio were not in our database. The Boston scale gave different point counts to "'dyspneaon climbing," "dyspnea on walking on level," and "rest dysp-nea"; we equated these with dyspnea on "extreme exertion,-"minimal/moderate exertion," or "at rest," respectively, asrecorded during our clinical assessment. In adapting the Fra-mingham scale, we excluded criteria that were either not enteredin our data base (namely, night cough or weight loss) or that arenot routinely used in the clinical diagnosis of congestive heartfailure (venous pressure, circulation time, or vital capacity).

Once patients were classified, the groups were compared withrespect to ejection fraction, by mean ejection fraction and byproportion with ejection fraction of 0.40 or less, 0.41 to 0.49,and 0.50 or more. These levels were selected to separate equiv-ocal levels of ejection fraction from those that are more clearlynormal or abnormal. We also related the clinical classificationwith patient's medication history.

Ejection fractions are reported as the mean SEM. Statis-tical analysis was performed with computer software from Sta-tistical Analysis Systems (SAS), with the use of analysis ofvariance to compare group means for continuous data, and where

TABLE 2Boston criteria for congestive heart failure

PointCriterion valueA

Category I: HistoryRest dyspnea 4Orthopnea 4Paroxysmal nocturnal dyspnea 3

Dyspnea on walking on level 2Dyspnea on climbing l

Category II: Physical examinationHeart rate abnormality 1-2

(if 91- 110 beats/min, 1 point;if >110 beats/min. 2 points)

Jugular-venous pressure elevation 2-3(if >6 cm H20, 2 points; if >6 cm H20 plus

hepatomegaly or edema, 3 points)Lung crackles 1-2

(if basilar, 1 point; if more than basilar, 2 points)Wheezing 3Third heart sound 3

Category III: Chest radiographyAlveolar pulmonary edema 4Interstitial pulmonary edema 3Bilateral pleural effusions 3Cardiothoracic ratio >0.50 3

(posteroanterior projection)Upper zone flow redistribution

ANo more than 4 points were allowed from each of three categories,and hence the composite score, the sum of the subtotal from eachcategory, had a maximum possible of 12 points. The diagnosis of heartfailure was classified definite for a score of 8 to 12 points, possible for a

score of to 7 points, and unlikely for a score of 4 points or less.

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appropriate, the Scheffe test for multiple comparisons. Cate-gorical data were evaluated by the use of chi-square tests. Valuesof p < .05 were considered statistically significant. Interscaleagreement was measured by means of the kappa statistic, whichtakes observed agreement and corrects for agreement expectedby chance alone.9

ResultsOf our 407 patients, 91% were in-patients at the time

of CVNMS. The mean age was 64 years, with 34% age

70 or greater. Sixty-five percent of the study subjectswere men. The reason for the test, as given by thereferring physician, was to determine severity of dis-ease in 61%, to confirm the presence of disease in 25%,to confirm absence of disease in 6%, and in 8% tomonitor therapy.

Ejection fraction. For the total group, the mean leftventricular ejection fraction was 0.49, with a left ven-tricular ejection fraction less than 0.50 in 204 (50%).Patients classified as having congestive heart failure byany of the scoring systems had significantly lower meanleft ventricular ejection fractions when compared withthose classified as not having congestive heart failure.Mean left ventricular ejection fraction for patients withcongestive heart failure classified as present or absentaccording to the Framingham criteria was 0.450.018 vs 0.53 + 0.014 (p < .001), and according tothe Duke criteria 0.43 0.015 vs 0.58 + 0.016 (p <

.0001). The Boston scale classified patients as havingdefinite, possible, or unlikely congestive heart failure;mean left ventricular ejection fraction in these patientswas 0.41 ± 0.021 vs 0.51 + 0.020 vs 0.55 + 0.016,respectively (p < .0001). The Scheffe test shows thesignificant difference to lie between those classified as

having "definite congestive heart failure" and thosewith "possible or unlikely congestive heart failure."Therefore, in the following discussion we will refer tothe "definite" group as having congestive heart failure,

TABLE 3

and those classified as "possible or unlikely congestiveheart failure" as not having congestive heart failure.

To determine the relationship between clinical clas-sification of congestive heart failure and resting leftventricular ejection fraction, predetermined levels ofleft ventricular ejection fraction were used to classifypatients into three distinct groups: low left ventricularejection fraction (s0.40), borderline (0.41 to 0.49),and normal left ventricular ejection fraction (.0.50)(table 3). The data indicate significant associations on

all three scales, with patients classified as having con-

gestive heart failure more likely to have a low ejectionfraction. Sensitivity and specificity of clinical diag-nosis was calculated, setting left ventricular ejectionfraction of 0.40 or less as the reference standard forclinically or prognostically important left ventriculardysfunction (table 3).

Comparison of criteria. We compared patients' ratingsamong the various scales with results summarized infigure 1. We found that in patients with normal leftventricular ejection fraction (.0.50) over half hadcongestive heart failure diagnosed by at least one of thecriteria. Conversely, among subjects with low left ven-tricular ejection fraction (< 0.40), 20% met none of thecriteria for congestive heart failure.

Concordance among the three scales was measuredby calculation of the kappa statistic. The value of kappawas 0.38 comparing Duke with Boston, 0.52 compar-

ing Duke with Framingham, and 0.67 comparing Fra-mingham with Boston criteria. These values show an

interscale agreement that is fair, moderate, and sub-stantial, respectively.'0

Medication use. It was found that substantial propor-

tions of those subjects who did meet criteria for con-

gestive heart failure were on P-blocking drugs (12% to20%) (table 4). In addition, of those subject not meet-

Relationship between clinical classification and left ventricular ejection fraction

Study

Framingham Duke Boston

+ -+ -+_

n 191 216 228 179 132 275

LVEF category [%(n)]-'40 50 (96) 26 (57) 49 (112) 23 (41) 58 (76) 28 (77)41-49 10 (19) 14 (31) 14 (31) 11 (19) 8 (11) 14 (39)250 40 (76) 59 (128) 38 (85) 66 (119) 34 (45) 58 (159)

SensitivityA 0.63 0.73 0.50

SpecificityA 0.63 0.54 0.78

+ = CHF present by criteria; - = CHF absent by criteria.ACompared with LVEF c40%.

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ALL 3 CRITERIA

0 SOME BUT NOT ALL CRITERIA

PERCENTAGE OFPATIENTS

c_l 11 CHl IKI?- rwr_

50

40

30

E NO CRITERiA

r'ULrlLLIINkv (n 20 _0CRITERIA

<40 41-49 >50

LEFT VENTRICULAR EJECTION FRACTION (%)FIGURE 1. Interrelations among the congestive heart failure criteriaand resting left ventricular ejection fraction.

ing criteria for congestive heart failure, about a third(31% to 36%) were being treated with digoxin. Similarresults were found for patients without systolic dys-function on nuclear scan: of subjects with normal leftventricular ejection fraction (> 0.50), 34% were beingtreated with digoxin, compared with 55% of those withlow ejection fraction (<0.50).

DiscussionOur study indicates that although each of the three

clinical scales identified patients with significantlylower ejection fractions, the three scales have varyingsensitivities and specificities and could be expected tohave different utilities depending on the goals of diag-nosis (e.g., prognostication vs ruling out disease) andon the population being examined (e.g., high vs lowprevalence of disease).

Evaluating the clinical diagnosis of congestive heartfailure presents special problems due to the lack ofaccepted diagnostic criteria. 1l Indeed, none of the threesets of criteria used in the present study is in wide use.In addition, there is not technologic reference standardfor the diagnosis of heart failure. For example, pressuremeasurements (pulmonary capillary wedge pressure,left ventricular end-diastolic pressure) are not widelyapplicable. These measurements are extremely sensi-tive to therapeutic intervention, and may be normaldespite severe ventricular dysfunction.12 Echocardio-graphic measurements are not easily quantified

reproducibly,13 although the use of computer technol-ogies is improving this situation. Nuclear studies pro-vide a more quantifiable measure of cardiac function,but the resting left ventricular ejection fraction does notrelate linearly to exercise capacity. 14 Also, none of themeasurements has a well-accepted cutoff level for"normal." For example, clinical trials in congestiveheart failure use varying entry criteria of left ventricularejection fraction, ranging from 0.30 to 0.49." Ineffect, then, a study of clinical criteria for congestiveheart failure involves evaluating not only the criteriathemselves but also the reference standard used.

Despite its usefulness in predicting prognosis, themajor shortcoming of the left ventricular ejection frac-tion is its inability to identify diastolic dysfunction.The mechanism of diastolic dysfunction has beenreceiving increased attention, especially among theelderly. 15. 16 Given the high prevalence of elderly sub-jects in our study, it is possible that some of our subjectswith clinical congestive heart failure had abnormalitiesin diastolic function, which we did not measure. In aprevious study of patients with clinically diagnosedcongestive heart failure (confirmed by a modificationof the Boston criteria) referred for nuclear study, Souferet al.17 found that 42% had intact systolic function(defined as left ventricular ejection fraction .0.45).This estimate is similar to that of Dougherty et al.(36%) and to our own (34% to 40%) (table 3). Of 58such patients, 38% had diastolic dysfunction (definedas peak filling rate <2.5 end-diastolic volumes/sec),and an additional 24% had "probable diastolic dys-function" (peak filling rate 2.5 to 3.0 end-diastolicvolumes/sec). Objective measurement of diastolicfunction is not routinely obtained on radionuclideangiography, and even if available, would leave unex-plained between 38% and 62% of patients with clinicalcongestive heart failure and normal systolic function.This implies that clinical judgment provides informa-tion about congestive heart failure that cannot beobtained from a nuclear scan.

Conversely, in our study, 23% to 28% of subjects

TABLE 4Drug therapy and clinical classification of congestive heart failure

Study

Framingham Duke Boston

Treated with [%(n)] + - + - +

/3-Blocker 15 (29) 35 (76) 20 (45) 34 (60) 12 (16) 32 (89)Diuretic 80 (152) 45 (98) 75 (171) 44 (79) 87 (115) 49 (135)Digoxin 59 (112) 33 (71) 56 (128) 31 (55) 64 (84) 36 (99)

+ = CHF present by criteria: CHF absent by criteria.

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classified as not having congestive heart failure haddepressed left ventricular ejection fractions (<0.40).In fact, of all patients with clearly low left ventricularejection fractions, 20% were not diagnosed by any ofthe three sets of clinical criteria (figure 1). Since a leftventricular ejection fraction of 0.40 or less is generallyaccepted as abnormal, this indicates that an objectivemeasure of left ventricular ejection fraction gives moreinformation than can be obtained by clinical evaluationalone.

There are several limitations that must be consideredin interpreting these data. The first is the populationstudied, which was a referral population with a highprevalence of cardiac disease. History of hypertensionwas present in 53%, 37% had a confirmed history ofprior myocardial infarction, and 49% had typicalangina. Although our study population is subject to areferral filter bias, the noninvasive nature of the pro-cedure would make our sample more representative ofpatients with suspected congestive heart failure in clin-ical practice than were the catheterized populationspreviously studied.4 5

Another limitation was the need to categorizepatients according to congestive heart failure criteriathrough the retrospective application of a data base thatwas not designed to answer this question. The problemswere minor in categorizing subjects on the Duke andBoston criteria, involving simply substituting radiol-ogist's reading of cardiomegaly for a specific value ofcardiothoracic ratio, and applying slightly differentterminology in the assessment of dyspnea. This lim-itation was more serious with regard to the Framinghamcriteria, where entire major and minor criteria had tobe eliminated, such as circulation time and vital capac-ity. Inclusion of other criteria, however, could onlyserve to diagnose more subjects as having congestiveheart failure. This might increase sensitivity, but at theprobable expense of a loss of specificity from the valueswe derived of 0.63 and 0.63, respectively.

The effect of drug therapy in this population is dif-ficult to assess. Large proportions of the subjects weretaking medications such as digoxin (45%), diuretics(61%), and 13-blockers (26%) (table 4). The impact ofdrug therapy on left ventricular ejection fraction isunclear in previous reports. For instance, there are tworandomized double-blind placebo controlled crossoverstudies of digoxin that measured systolic left ventric-ular function. Fleg et al.18 found no clinical responseto digoxin, but did show a small but statistically sig-nificant rise in echocardiographically determinedvelocity of circumferential fiber shortening with digo-xin (0.90 circ/sec) compared with placebo (0.82

Vol. 77, No. 3, March 1988

circ/sec) (p < .05). Conversely, Lee et al.19 foundclinical benefit with digoxin use, but no change inresting radionuclide left ventricular ejection fractionwith digoxin (0.30) compared with placebo (0.29)(p = .49). In a study of digoxin use after myocardialinfarction there was a statistically significant but clin-ically insignificant rise in left ventricular ejection frac-tion with digoxin use (0.29 ± 0.09 vs 0.33 + 0.11,p < .03).20 A study of propranolol showed no effect onresting left ventricular ejection fraction in normal sub-jects or in patients with coronary artery disease.21

Our data indicate that many subjects without con-gestive heart failure by clinical criteria are being treatedwith digoxin. This finding is consistent with those ofCarlson et al.5 who devised the Boston criteria. How-ever, some of our subjects received digoxin for indi-cations other than congestive heart failure. For exam-ple, of 183 subjects taking digoxin, 27 had atrialfibrillation or flutter (15%), compared with seven of224 subjects not taking digoxin (3%). Significant leftventricular dysfunction frequently coexisted with thearrhythmia: 13 of the 27 subjects (48%) with atrialarrhythmias on digoxin had a left ventricular ejectionfraction of 0.40 or less. The use of digoxin for atrialarrhythmias would not account for the fact that only 84of 183 subjects taking digoxin in our study (46%) metthe Boston criteria for congestive heart failure.

There are no uniformly accepted criteria for thediagnosis of congestive heart failure, and there is no"gold standard" for the diagnosis. The inability ofresting left ventricular ejection fraction to serve thisfunction has been well demonstrated.7 14 We do notsuggest that our data can be used to validate clinicalcriteria with left ventricular ejection fraction as a goldstandard. Rather, they indicate that a combination ofclinical diagnosis and an objective measure of cardiacperformance is necessary to definitively diagnose con-gestive heart failure, since each provides informationnot available from the other.We thank Ms. Mindy Ginsberg for computer programming,

and Ms. Sheila Reyes for the preparation of the manuscript.

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5. Carlson KJ, Lee DC-S, Goroll AH, Leahy M, Johnson RA: Ananalysis of physicians' reasons for prescribing long-term digitalistherapy in outpatients. J Chron Dis 38: 733, 1985

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Lense and J WachspressP R Marantz, J N Tobin, S Wassertheil-Smoller, R M Steingart, J P Wexler, N Budner, L

diagnosed by clinical criteria.The relationship between left ventricular systolic function and congestive heart failure

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1988 American Heart Association, Inc. All rights reserved.

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