Long-Term Prognosis in Women With NormalDobutamine Stress Echocardiography

Andres Mesa, MD, Maria Falcone, MD, Antonieta Hernandez, MD,Raymond F. Stainback, MD, and Susan Wilansky, MD

In patients with known or suspected coronary arterydisease, dobutamine stress echocardiography (DSE)

has proved accurate in assessing myocardial viabilityand predicting cardiac risk after myocardial infarctionor before major noncardiac surgery.1–5 Long-term fol-low-up of patients with normal cardiac angiogramshas shown that these patients have an excellent prog-nosis.6–8 Likewise, 1- to 10-year follow-up of patientswith normal myocardial perfusion studies, as assessedby exercise thallium testing, has revealed these pa-tients have an excellent cardiac prognosis, with a#1% likelihood of cardiac death or myocardial infarc-tion.9–11 Although the long-term prognosis for pa-tients with a normal dobutamine stress echocardio-graphic result is good,12,13 most studies of such pa-tients have focused on men. Fewer data existregarding the long-term prognosis for women. In thisstudy, we assess the long-term cardiac prognosis forwomen with a normal dobutamine stress echocardio-gram.

• • •We reviewed the cases of 120 women who under-

went DSE for evaluation of chest pain between Janu-ary 1993 and February 1997. All of the womenachieved$85% of the maximum predicted heart rateand had a normal test result. Twenty of the patientswere from abroad and were excluded from the studybecause they were unavailable for telephone follow-up. In the remaining 100 cases, all of the referringphysicians provided written consent for includingtheir patients in the study, which was approved by ourhospital’s institutional review board.

Each patient’s age, cardiac risk factors (Table I),and clinical history were obtained from previous med-ical records. Follow-up information was obtained bydirect telephone contact. Patients who had chest dis-comfort were considered to have typical angina if thediscomfort was substernal, precipitated by physicalexertion, and relieved by rest or nitroglycerin. Theywere considered to have atypical angina if the discom-fort was not substernal, not precipitated by exertion, ornot relieved by rest or nitroglycerin. If$2 of the latter3 characteristics were absent, the discomfort was con-sidered nonanginal.

DSE was performed with an integrated Hewlett-Packard Sonos 1500 or 2500 ultrasonograph (Hewlett-Packard, Andover, Massachusetts) and a FreelandPrism/Imaging System (Broomfield, Colorado). Aprogressively graded dobutamine infusion was given,

using the following protocol, in which each stagelasted approximately 3 minutes: 5, 10, 20, 30, 40, and50 mg/kg/min. If necessary, atropine was added (max-imum dose 1 mg). As described elsewhere,1 digitizedimages were acquired at baseline and during DSE at alow dose (10mg/kg/min), at the peak dose, and atrecovery. All studies were supervised and interpretedby an experienced echocardiographer. A normal resultwas characterized by augmented left ventricular sys-tolic function and the absence of a new regional wallmotion abnormality at peak stress. Data were re-viewed to verify the initial findings in the cases of allpatients who had a cardiac event.

Follow-up data were obtained by direct telephonecontact and a review of hospital records up to Sep-tember 1997. Risk factors were determined as previ-ously mentioned. Adverse events were categorized ascardiac death, congestive heart failure, myocardialinfarction, or need for revascularization (angioplastyor coronary artery bypass grafting).

Adverse cardiac events were analyzed by aKaplan-Meier survival curve.

From St. Luke’s Episcopal Hospital/Texas Heart Institute and BaylorCollege of Medicine, Houston, Texas. Dr. Wilansky’s address is:6624 Fannin, Suite 2480, Houston, Texas 77030. E-mail:hallgar@hgcardio.com. Manuscript received September 24, 1998;revised manuscript received and accepted November 30, 1998.

TABLE II Adverse Events After Normal Dobutamine StressEchocardiography

Cardiac events 4Congestive heart failure 2*Percutaneous transluminal coronary angioplasty 1Coronary artery bypass grafting 1

Noncardiac deaths 6Hepatic shock 2†

Cancer 2‡

Renal failure 1Trauma 1

*One patient had left ventricular systolic dysfunction, and the other had leftventricular diastolic dysfunction.

†One patient had cirrhosis, and the other had a failed liver transplant.‡One patient had breast cancer, and the other had lung cancer.

TABLE I Cardiac Risk Factors at Dobutamine StressEchocardiography

Risk Factor

No. ofPatients

(n 5 100)

Lack of estrogen replacement therapy 57Systemic hypertension (on medications) 54Family history of coronary artery disease 45Hypercholesterolemia (on medications) 28Coronary artery disease 22*Tobacco use 17Diabetes mellitus 12

*Eight patients underwent percutaneous transluminal coronary angioplasty,2 had coronary artery bypass grafting, and 1 had a myocardial infarction.

1127©1999 by Excerpta Medica, Inc. 0002-9149/99/$–see front matterAll rights reserved. PII S0002-9149(99)00027-2

Patients’ ages were 606 13 years. Sixty percent ofthe 100 women had atypical chest discomfort, and30% had typical discomfort. The remaining 10%, whohad either nonanginal discomfort or no chest discom-fort, underwent screening for coronary artery diseaseor organ transplantation. Table I shows the group’scardiac risk factors at the time of DSE. During thefollow-up period of 24.36 11 months (range 7 to 45),6 noncardiac deaths occurred (Table II). There wereno myocardial infarctions. Two women underwentcoronary revascularization procedures: 1 angioplasty(5 weeks after echocardiography) and 1 coronary ar-tery bypass (1 year after echocardiography). Twoother patients were hospitalized for congestive heartfailure: 1 with volume overload and a low ejectionfraction, and the other with isolated left ventriculardiastolic dysfunction. Forty-five months after echocar-diography, the rate of freedom from revascularizationwas 98% according to Kaplan-Meier analysis. Therisk of a cardiac event requiring revascularization wasonly 1% per patient-year.

• • •To our knowledge, we are the first to report the

2-year prognostic value of a normal dobutamine stressechocardigraphic result in women who have under-gone this test to rule out coronary artery disease. Ourdata suggest that these women have a low cardiacevent rate. Our findings are similar to those of severallong-term follow-up studies of cardiac and all-causemortality in patients with normal dobutamine stressechocardiographic results, normal exercise thalliummyocardial perfusion images, or normal or minimallyabnormal coronary angiograms (Table III), regardlessof sex. In some of these series, patients with eithernormal myocardial perfusion or#50% coronary lu-minal narrowing had an annual cardiac mortality of#0.5% per year and an all-cause mortality of#0.9%per year. Steinberg and associates12 demonstrated an

annual cardiac mortality of 0% per year and an all-cause mortality of 1.9% per year; in their VeteransAdministration study, all of the patients were men.Using DSE in 504 patients (including 295 women),Yeleti and coworkers13 showed that, in patients withnormal results, the risk of any cardiac event was0.28% and the risk of cardiac death or a myocardialinfarction was 0.16% per patient-year, regardless ofsex.

In our study, the cardiac mortality was 0% peryear, and the risk of a cardiac event requiring revas-cularization was 1% per patient-year. Interestingly,the all-cause mortality was 3% per patient-year. Thishigh mortality was probably due to a referral bias.According to the National Heart, Lung, and BloodInstitute, the leading causes of death for 45- to 64-year-old persons in 1995 were cancer, heart disease,and accidents, in that order; chronic liver disease wasin seventh place.14 The causes of death in our groupwere cancer (2 cases), end-stage liver disease (2 cas-es), trauma (1 case), and renal failure (1 case). Nopatient died of cardiac causes. Both patients withchronic liver disease underwent DSE as part of theirwork-up for a liver transplant.

Of the 2 patients who had a cardiac event requiringrevascularization, both had a history of coronary ar-tery disease at the time of DSE. One had undergone apercutaneous coronary intervention 2 years beforetesting. Five weeks after having DSE, this patient hadan episode of typical angina caused by recurrent dis-ease in a different coronary artery. She underwentpercutaneous transluminal coronary angioplasty of asubtotal dominant right coronary artery stenosis withgood collateral flow from the left coronary system.The previous percutaneous transluminal coronary an-gioplasty site had no significant lesion. The otherpatient had a myocardial infarction of the inferior wall3 years before DSE; at our evaluation, she had atyp-

TABLE III Long-Term Follow-Up of Patients With Normal Thallium or Dobutamine Echocardiographic Stress Tests or WithAngiographically Normal or Minimally Diseased Coronary Arteries

StudyNo. of Pts

by SexMean Age

(yr)

Length ofFollow-Up

[yr (% of pts)]

CardiacDeaths

[no. (%) of pts]All Deaths

[no. (%) of pts]Nonfatal MI

[no. (%) of pts]

Present study* 100 F0 M

60 2.0 (100) 0 (0) 6 (6.0) 0 (0)

Steinberg et al12* 0 F42 M

66 5.0 (100) 0 (0) 4 (9.5) 2 (4.8)

Yeleti et al13* 295 F209 M

57 4.2 (100) 11 (2.2) 119 (23.0) 23 (4.5)

Pamelia et al10† 140 F209 M

50 2.9 (99) 5 (1.4) 8 (2.3) 6 (1.7)

Steinberg et al11† 130 F179 M

55 10.3 (93) 3 (1.0) 18 (6.3) 14 (4.5)

Wackers et al9† 39 F56 M

50 1.8 (97) 0 (0) 0 (0) 2 (2.1)

Humphries et al6‡ 93 (N/A) 42 12.0 (97) 0 (0) 5 (5.4) 5 (5.4)Papanicolaou et al7‡ 1,088 F

889 M49 6.3 (96) 12 (0.6) 50 (2.6) 29 (1.5)

Proudfit et al8‡ 199 F322 M

50 10 (100) 14 (2.7) 48 (8.6) 20 (3.8)

*Dobutamine stress echocardiographic study; †exercise thallium echocardiography study; ‡angiographic study.MI 5 myocardial infarction; N/A 5 female/male ratio not available; pts 5 patients.

1128 THE AMERICAN JOURNAL OF CARDIOLOGYT VOL. 83 APRIL 1, 1999

ical chest pain. One year after echocardiography, sheunderwent coronary artery bypass grafting of the ob-tuse marginal and left anterior descending coronaryarteries.

In summary, women with a normal dobutaminestress echocardiographic result have an excellentlong-term cardiac prognosis, with a risk of cardiacmortality of 0% and risk of a cardiac event requir-ing revascularization of only 1% per patient-year.

Acknowledgment: We thank Vei-Vei Lee, MS, forhelp with the statistical analyses.

1. Cohen JL, Greene TO, Ottenweller JE, Binenbaum SZ, Wilchfort SD, Kim CS.Dobutamine digital echocardiography for detecting coronary artery disease.Am JCardiol 1991;67:1311–1318.2. Cohen JL, Ottenweller JE, George AK, Duvvuri S. Comparison of dobutamineand exercise echocardiography for detecting coronary artery disease.Am JCardiol 1993;72:1226–1231.3. Afridi I, Kleiman NS, Raizner AE, Zoghbi WA. Dobutamine echocardiogra-phy in myocardial hibernation. Optimal dose and accuracy in predicting recoveryof ventricular function after coronary angioplasty.Circulation 1995;91:663–670.4. Davila-Roman VG, Waggoner AD, Sicard GA, Geltman EM, Schechtman KB,Perez JE. Dobutamine stress echocardiography predicts surgical outcome inpatients with an aortic aneurysm and peripheral vascular disease.J Am CollCardiol 1993;21:957–963.

5. Poldermans D, Arnese M, Fioretti PM, Salustri A, Boersma E, Thomson IR,Roelandt JR, van Urk H. Improved cardiac risk stratification in major vascularsurgery with dobutamine-atropine stress echocardiography.J Am Coll Cardiol1995;26:648–653.6. Humphries JO, Kuller L, Ross RS, Friesinger GC, Page EE. Natural history ofischemic heart disease in relation to arteriographic findings: a twelve year studyof 224 patients.Circulation 1974;49:489–497.7. Papanicolaou MN, Califf RM, Hlatky MA, McKinnis RA, Harrel FE Jr, MarkDB, McCants B, Rosati RA, Lee KL, Pryor DB. Prognostic implications ofangiographically normal and insignificantly narrowed coronary arteries.Am JCardiol 1986;58:1181–1187.8. Proudfit WL, Bruschke AVG, Sones FM Jr. Clinical course of patients withnormal or slightly or moderately abnormal arteriograms: 10-year follow-up of521 patients.Circulation 1980;62:712–717.9. Wackers FJ, Russo DJ, Russo D, Clements JP. Prognostic significance ofnormal quantitative planar thallium-201 stress scintigraphy in patients with chestpain.J Am Coll Cardiol1985;6:27–30.10. Pamelia FX, Gibson RS, Watson DD, Craddock GB, Sirowatka J, Beller GA.Prognosis with chest pain and normal thallium-201 exercise scintigrams.Am JCardiol 1985;55:920–926.11. Steinberg EH, Koss JH, Lee M, Grunwald AM, Bodenheimer MM. Prog-nostic significance from 10-year follow-up of a qualitatively normal planarexercise thallium test in suspected coronary artery disease.Am J Cardiol1993;71:1270–1273.12. Steinberg EH, Madmon L, Patel CP, Sedlis SP, Kronzon I, Cohen JL.Long-term prognostic significance of dobutamine echocardiography in patientswith suspected coronary artery disease: results of a 5-year follow-up study.J AmColl Cardiol 1997;29:969–973.13. Yeleti R, Feinberg N, Segar DS, Feigenbaum H, Sawada SG. Long-termprognosis of patients with normal dobutamine stress echocardiogram studies(abstr).JASE1997;10:445.14. Anderson RN, Kochanek KD, Murphy SL. Report of final mortality statistics,1995.Monthly Vital Stat Rep1995;45(suppl 2):23–33.

Comparison of Quality of Life After Coronary and/orValvular Cardiac Surgery in Patients >75 Years of Age

With Younger PatientsJan A. Heijmeriks, MD, Salima Pourrier, MS, Pim Dassen, PhD, Kees Prenger, MD, and

Hein J.J. Wellens, MD

Contemporary studies have indicated that openheart surgery in elderly patients can be performed

with a low mortality rate.1–5 However, only limitedinformation is available about the quality of life afterdifferent types of open heart surgery in elderly pa-tients compared with younger patients. The effect ofcardiac surgery on quality of life was studied prospec-tively in 200 elderly patients aged$75 years and 400younger patients.

• • •From September 1993 to December 1996, we stud-

ied 200 patients$75 years (mean age 78, range 75 to91) who underwent open heart surgery. Each of thesepatients was matched with 2 patients,75 years old(mean age 65, range 35 to 74), who underwent sameprocedure and were the same sex (Table I). Sixty-sixpercent had coronary surgery; the remaining patientshad valvular surgery (18%), or combined coronaryand valvular surgery (16%). Fifty-four percent of thepatients were women. The median follow-up duration

of the surviving patients was 31 months (range 12 to52).

To evaluate quality of life, 2 tests were selected.These tests have a limited number of questions thatwere easy to respond to in a short time by the patientand covered various aspects, such as mood, socialfunctioning, and physical condition. The first test isthe Hospital Anxiety and Depression (HAD) scale(Snaith6 and Zigmund and Snaith,7 of which an offi-cial Dutch translation is available). This questionnairehas 14 multiple choice questions dealing with anxietyand depressive complaints, with a range from 0 to 21.A higher number represents a worse score for thatitem. The second test is the Nottingham Health Profile(NHP) (Hunt et al8 and Jenkinson et al,9 of which aDutch translation has been available since 1993). Thefirst part of this questionnaire has 6 main items, con-sisting of energy, pain, emotional reactions, sleep,social isolation, and physical mobility, with a total of38 questions that can be answered by filling out“yes”or “no.” The range for this scale is from 0 to 100.In this test also, a higher number represents a worsescore for that item. Part 2 of the NHP has 7 questionsabout daily activity limitations (work, housekeeping,social contacts in/outside home, sexual activity, hob-bies, and recreational activities). These items were put

From the Departments of Cardiology and Cardiothoracic Surgery,Academic Hospital, Maastricht, The Netherlands. Dr. Heijmeriks’ ad-dress is: Vivaldi 34, 2681 KN Monster, The Netherlands. E-mail:cardio@kabelfoon.nl. Manuscript received October 1, 1998; revisedmanuscript received and accepted November 24,1998.

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