• First-pass radionuclide cineangiography in diagnosis of coronary disease in patients older than 75 years: Evaluation of sensitivity

HOWARD L. SACHER, DO MICHAEL L. SACHER, DO STUART W. LANDAU, MD ROGER S. KERSTEN, DO FRANCES DOOLEY, RN, MSN ALLEN CHIEN, MS, CNMT KATHLEEN A. DIETRICH, DO AMY SACHER MANDY SACHER

The sensitivity of first-pass Radionuclide has proved to be a radionuclide cineangiography in the detection safe and sensitive noninvasive modality for the of was evaluated in diagnosis of coronary artery disease (CAD). 1,2 60 patients subdivided equally according to Never intended for use as a first-line screening age younger than or older than 75 years. The method, radionuclide angiocardiography is most mean age of group 1 (age;::: 75 years) was 80.2 useful in cases of intermediate disease probabil­ years ±5.3, and the mean age in group 2 (age ity. Currently, it is the beneficiary of technolog­ < 75 years) was 62.0 years ±6.4. Disease preva­ ic advances bestowed by a new generation of lence in group 1 was 87% versus 80% in group radioisotopes offering combination and 2. Group 1 had higher prevalence of hyper­ volumetric analyses. tension (67% vs 33%) and lower prevalence The sensitivity of in of typical angina pectoris (23% vs 55%). Over­ older patients remains to be defined, because vir­ all sensitivity of first-pass radionuclide cinean­ tually every clinical study has excluded subjects older giography in group 1 was 93% versus 97% in than 65 years. Reasons for this omission include group 2. Older patients had significantly the presumption of an abnormal ventricular exer­ lower maxi~al rates, workloads, and cise response in the "normal" geriatric patient and exercise durations, and age correlations were belief that interventional surgery would be inap­ significant for exercise heart rate, workload, propriate in this age group. The latter presumption and exercise duration. Failure to achieve an was recently rocked by a report that coronary adequate exercise endpoint had significant bypass surgery in patients older than 80 years is effect on testing sensitivity only in the younger associated with both a favorable postoperative subjects (98% vs 60%), indicating that sensi­ course and an excellent clinical prognosis.3 tivity of first-pass radionuclide cineangiog­ The question of the suitability of radionuclide raphy is age independent. angiography in patients older than 65 years focus­ (Key words: Radionuclide angiography, es on two factors: First, the prevalence of CAD angiocardiography, coronary artery disease, increases with age4; and, second, medical cost con­ exercise, left ventricular function, geriatdc straints place a special premium on the accurate patient) and economical evaluation of patients at risk for CAD. Further complicating this task is the increas­ ingly aged patient population. From the Departments oflnternal Medicine and Cardiology, Massapequa General Hospital, Seaford, NY. Therefore, a study was undertaken to evaluate Correspondence to Howard L. Sacher, DO, 510 Hicksville the comparative sensitivity of first-pass radionu­ Rd, Massapequa, NY 11758. clide cineangiography (FPRNA) in subjects aged 75

Original contribution • Sacher et al JAOA • Vol 95 • No 7 • July 1995 • 415 years and older. In the interests of objectivity, no working hypoth­ Table 1 esis was entertained. Sensitivity Values for First-Pass Radionuclide Angiography and the Influence of Endpoint Criteria

Subjects and methods Group 1 Group 2 Study population (age ;:.. 75 y) (age <75 y) A retrospective study was undertaken Variable (%) (%) P of records (1989 to 1992) of 100 patients who had undergone cardiac ­ • Sensitivity 93 97 NS* ization within 3 months after FPRNA. Subjects were selected consecutively • Coronary vessel involvement from the files alphabetically by last Single vessel 86 89 NS name and subdivided into groups 1 Double vessel 100 100 (aged 75 and older) and 2 (younger Triple vessel 86 97 NS than 75 years). Subjects were not pref­ erentially selected from a subgroup of • Wall motion abnormality patients completing the protocol. Resting 55 66 NS Excluded from the initial sample Exercise 80 82 NS were those with a history of cardiac 26 53 <.01 surgery or interventional therapy; sig­ • ST segment changes nificant ; con­ • Chest pain 33 30 NS genital heart disease; previous catheter­ ization; electrocardiographic evidence • Left ventricular ejection of left bundle branch block; history of fraction <45% 61 62 NS chronic (duration > 5 years) hyper­ tension or echocardiographic evidence • Percentage change in <6% 77 of left ventricular hypertrophy (or 80 NS both); or those with complications of • Sensitivity met CAD, such as left ventricular aneurysm. Any exercise endpoint 95 98 NS The final sample population comprised No exercise endpoint 86 60 <.05 60 individuals equally subdivided into the aforementioned age groups. *NS = Not significant. The initial clinical presentations were diverse, with the most patients evaluated to confirm clinical diagnosis of CAD, to esti­ resting measurement and electrocar­ mate disease severity, and to assess the need for inter­ diogram (ECG) were obtained. Acquisition of the rest­ ventional therapy. Most important, patients closely ing study involved bolus injection of 20 mCi of tech­ approximated those presenting to a tertiary care cen­ netium-99m diethylenetriaminepentaacetic acid, with ter with complaints suggestive of CAD. counts recorded at 25-msec intervals for a 30-second peri­ od by using a multi crystal . Exercise was then initiated at 200 kpm/min and increased by that Cardiac catheterizations were performed at three insti­ amount every 2 minutes. The ECG was monitored con­ tutions by physicians who were not involved in this tinuously, with tracings and blood pressures record­ study. Angiography included right and left ventricu­ ed every 2 minutes during exercise and into recovery. lography in accordance with previously described pro­ Exercise was continued until achievement of 85% max­ tocol. 5 Results were discussed in conference by at least imum pr~dicted heart rate, exercise for at least 5 min­ two experienced cardiologists, with interobserver dif- utes, development of chest pain suggestive of , ferences resolved by an independent arbiter. . identification of ischemic ST segment changes, or until In this study, a luminal narrowing of at least 50% severe fatigue or shortness of breath intervened. At vessel diameter involving at least one major coronary artery commencement of these points, a 25-mCi bolus was was considered to be significant CAD, with stenoses delivered, and exercise was continued until completion less than 50% regarded as insignificant. The coronary of data acquisition. Electrocardiograms were interpreted vasculature was regarded as normal if no disease or as positive, negative, or inconclusive. ("Inconclusive" insignificant disease was discovered. implies absence of ischemic ST segment changes in cases of failure to attain target heart rate.) First-pass technique and data analysis Typical angina pectoris was defined as pain or tight­ First-pass radionuclide cineangiography was performed ness in the chest, neck, or epigastrium that was con­ in our laboratory with the patient at rest and again sistently precipitated by exercise or stress and relieved after exercise, after obtainment of informed consent by rest or anti anginal medications(s) (or both). Atypical and in accordance with previously described protocol. 1 angina pectoris implied absence of at least one aspect of ~-Blocker therapy was discontinued at least 24 hours typical angina. Those individuals without chest pain, before testing. Subjects were seated in the erect posi­ or in whom chest pain was uncharacteristic, were cat­ tion on a bicycle ergometer (Fintron, Lumex), and a egorized in the nonanginal cohort.

416 • JAOA • Vol 95 • No 7 • July 1995 Ori . al contribution • Sacher et al ed as normal (2), hypoki­ Table 2 netic (1), akinetic (0), or Summary of the Testing Variables* dyskinetic (-1). Regional scores were summed for Group 1 Group 2 each study, and every Variable (age ;:,: 75 y) (age <75 y) P patient was assigned a resting and exercise wall • Heart rate, beats/min motion abnormality score, Resting 70.6 ± 6.0 72.9 ± 8.3 NSt with a total score of 8 Exercise 102.8 ± 22.2 128.9 ± 24.4 < .0001 implying an entirely nor­ mal study. • Left ventricular ejection fraction Resting 42.6 ± 6.9 40.7 ± 12.2 NS Statistical analysis Exercise 38.0 ± 8.8 39.2 ± 10.2 NS Data were analyzed by Percentage change -9.8 ± 15.7 -8.8 ± 10.2 NS using Student's t test for • Wall motion abnormality score paired data and the Z test. Resting 6.0 ± 1.6 6.0 ± 1.5 NS Correlation analysis Exercise 4.4 ± 2.0 4.6 ± 1.9 NS employed standard linear regression analysis. The • Percentage of maximum term "sensitivity" was predicted heart rate 78.8 ± 6.8 77.2 ±1l.4 NS defined according to World

3 Health Organization guide­ • Double product (10 ) 18.2 ± 2.6 19.0 ± 3.6 NS lines: true-positives divid­ • Workload, kpm 326.2 ± 98.5 396.9 ± 85.8 <.005 ed by true-positives and false-negatives. 7 • Exercise duration, min 4.5 ± 1.2 5.2 ± 1.4 < .05 Significance of data • Exercise wall motion was determined at the 95% abnormality, % 80 88 NS confidence level, as well as at the level of P<.05 • Exercise left ventricular (two-tailed), with all other work, g. m 86.4 ± 25.0 92.4 ± 35.2 NS differences regarded as insignificant. *Expressed as mean :!: SD. t NS = Not significant. Results The mean age for group All FPRNA data were processed by using software 1 was 80.2 years ±5.3, compared with 62.0 years of the Baird Atomic System (System Seventy-Seven) ±6.4 in group 2(P<.0000l). Women made up 57% after correction for background loss and detector nonuni­ of group 1 and 43% of group 2 (not significant). formity by the instrument. Consecutive data acquisi­ There were no significant intergroup differences in tion for 3 to 6 cardiac beats, producing a videomatic "representative" , was accomplished per a disease prevalence or vessel involvement. There previously described protocol.6 The left ventricular ejec­ were significant differences in clinical history for tion fraction (LVEF) was calculated from the back­ (67% vs 33%; P < .OI) and typical ground-corrected representative cycle as end-diastolic angina pectoris (23% vs 55%; P< .Ol). Significant counts minus end-systolic counts divided by end-dias­ differences in medications were noted for l3-block­ tolic counts. Values determined by use of this method ers (23% vs 55%; P<.05) and digitalis glycosides are highly reproducible and correlate closely with those (83% vs 50%; P< .05). obtained with contrast angiography, save for cases of Sensitivity of FPRNA was 93% in group 1, as significant valvular heart disease or intracardiac shunt­ ing (or both).2 opposed to 97% in group 2 (not significant). There Radionuclide results were viewed independently were no significant differences in testing sensi­ by three cardiologists, with an abnormal study imply­ tivity with regard to coronary vessel involvement. ing at least two of the following resting LVEFs: less Sensitivity values for the testing variables are than 45%; a stress LVEF less than 6% higher than rest­ outlined completely in Table 1. ing baseline; or development of an exercise-induced wall Older patients had significantly lower exer­ motion abnormality, defined as either a wall motion cise heart rates (P< .OOOl), exercise workloads abnormality not evident at rest or the intensification (P<.005), and exercise durations (P<.05), but most of a resting wall motion abnormality. Regional wall motion was assessed qualitatively by important, there were no significant differences using static and cinematic images of a representative car­ in the exercise LVEF, percentage change in LVEF, diac cycle, with a uniform decrease in wall motion not exercise double product, or percentage of maxi­ indicative of a regional abnormality. Images were sub­ mum predicted heart rate Table 2. divided into four regional zones and subjectively grad- Age correlations were significant for exercise

Original contribution • Sacher et al JAOA· Vol 95 • No 7· July 1995·417 heart rate (r = - .54; P <.005); workload (r = - .42; sive discussion of the topic transcends the scope P<.005 ), and exercise duration (r = - .36; P<.Ol), with of this article. Despite report ofthe former,15 there insignificant values for peak LVEF and percent­ exist no criteria in this study with which to accu­ age change in L VEF. rately estimate CAD severity. Nevertheless, pres­ ence of a lowered ischemic threshold in the elder­ Discussion ly may be surmised based on reports of age-related The primary challenge in the management of diastolic dysfunction,16 which could result in sig­ patients with suspected CAD is differentiation of nificantly impaired subendocardial perfusion. The a large group of relatively low-risk individuals physiologic basis for a lowered ischemic threshold from a smaller subgroup with high probability of has been asserted17,18 and may involve the follow­ a major future cardiac event. This differentiation ing: increased vascular impedance and elevation must be accomplished with an increasingly elder­ of myocardial oxygen consumption at any given ly patient population within the constraints of work level; decreased efficiency of myocardial oxy­ stringent medical cost-containment. Despite the gen utilization; impaired (35%) maximal coronary fact that more than 75% of all cardiac fatalities occur blood flow; and reduced ventricular compliance in patients older than 65 years,8 this cohort has producing elevated end-diastolic pressures and been systematically excluded from major diag­ myocardial oxygen consumption. nostic studies. Partly, this reflects well-recognized Our data suggest that aging is associated with age correlations for maximal heart rate and exer­ a higher incidence of "silent ischemia"; a conclusion cise duration,9.10 as well as presumption of a pre­ supported by both a lower incidence of typical angi­ requisite of the ability to perform a "reasonable" na in the elderly (P<.Ol) and lower sensitivity to level of exercise. ischemic electrocardiographic changes (P <.Ol). Strong age correlation for maximum heart Autopsy studies have revealed significant CAD in rate and exercise duration have fostered the pre­ approximately 50% of elderly cases, with almost half sumption that nuclear ventriculography is nec­ of these cases clinically undiagnosed. Although essarily less sensitive in the elderly. This con­ the prognostic significance of silent ischemia tention was supported by Port and colleagues,11 who remains controversial, one investigator19 report­ studied 77 apparently "healthy" older patients ed a 48% probability of a major cardiac event with­ and reported an age-related abnormal LVEF exer­ in a 5-year follow-up period. cise response. This study, however, was flawed by failure to exclude the possibility of occult CAD Comment through cardiac catheterization. Indeed, the high Limitations of this study are several, including the incidence of CAD in individuals older than 65 retrospective study design, which inherently intro­ years makes difficult the selection of subjects duces possibility of preselection bias. The other without significant disease. limitation, the fact that patients without signifi­ The importance of achievement of adequate cant CAD were not completely "normal," is less exercise endpoint criteria in patients younger relevant in a study that does not evaluate testing than 75 years has been noted previously.l2.14 Inap­ specificity. plicability of these criteria in those persons older To our knowledge, this study is the first to than 75 years is suggested by the insignificant examine the sensitivity of FPRNA in patients aged effect on testing sensitivity (Table 2 ). This occurs 75 and older. We emphasize the usual indications despite the fact that there are no significant inter­ and cautions for radionuclide angiography, and group differences in exercise double product, per­ we conclude that testing sensitivity is age inde­ centage of maximum predicted heart rate, or the pendent. Results of our study indicate a need for stroke work index, suggesting that comparable reevaluation of the exercise endpoint criteria in levels of myocardial stress result at lower absolute the elderly, and we predict expanded utilization work levels. of noninvasive nuclear techniques, perhaps as an Our study suggests that the sensitivity of eventual alternative to invasive modalities in the FPRNA is age independent. This is predicated on 21st century. the realization that elderly patients with CAD display a left ventricular exercise response com­ parable to that seen in younger patients. The References apparent inapplicability of traditional exercise 1. Bates BB, Rerych SK, J ones RH: Exercise techniques for endpoint criteria in the elderly may imply greater radionuclide angiography. J Nucl Tech 1978;6:199-204. 2. J ones RH, McEwan P, Newman GE, et al: Accuracy of diag­ disease severity or a lowered ischemic threshold (or nosis of coronary artery disease by radionuclide measurement both). of left ventricular function at rest and during exercise. Circu­ Estimation of CAD severity has proved frus­ lation 1981;64:586-60l. trating and highly imperfect, and a comprehen- 3. Tsai TP, Chaux A, Kass RM, et al: Aortocoronary bypass

418 • JAOA • Vol 95 • No 7 · July 1995 Original contribution • Sacher et al surgery in septugenarians and octogenarians. J Cardiovasc 11. Port S, Cobb FR, Coleman RE, et al: Effect of age on the Surg 1989;30:364-368. response of the left to exercise. N Engl J Med 4. Satler LF, Green CE, Wallace RB, et al: Coronary artery dis­ 1980;303: 1133-113l. ease in the elderly. Am J Cardiol1989;63 :245-247. 12. Jones RH, McEwan P, Newman GE, et al: Accuracy of diag­ 5. Borer JS, Kent KM, Bacharach ML, et al: Sensitivity, speci­ nosis of coronary artery disease by radionuclide measurement ficity, and predictive accuracy of radionuclide cineangiography ofleft ventricular fimction during exercise. Circulation 1981;64:586- during exercise in patients with coronary artery disease. Cir­ 600. culation 1979;60:572-580. 13. Campos CT, Chu HW, D'Agostino HJ Jr, et al: Comparison 6. Sandler H, Dodge HT: The use of single plane cineangiograms of rest and exercise radionuclide angiocardiography and exercise for the calculation of the left ventricular volume in man. Am treadmill testing for the diagnosis of anatomically extensive Heart J 1968;75:325-334. coronary artery disease. Circulation 1983;67:1204-1210. 7. Cohn K, Kamm B, Feteih N, et al: Use of treadmill score to 14. Sacher HL, Sacher ML, Landau SW, et al: First-pass radionu­ quantity ischemic response and predict extent of coronary dis­ clide cineangiography: A reevaluation of its sensitivity and lim­ ease. Circulation 1979;59:286-295. itations in the detection of significant coronary artery disease. 8. Kulick DL, Rahimtoola SH: Is noninvasive risk stratification Angiology 1992;43:470-476. sufficient, or should all patients undergo cardiac catheteriza­ 15. O'Rourke RA, Chatterjee K, Wei JY: Coronary artery dis­ tion and angiography after acute , in ease. JAm Coll Cardiol 1987;10:52A-56A. Cheitlin MD, Brest AN, Ceds): Dilemmas in Clinical Cardiology. 16. Pearson AC, Guidpati CV, Labovitz AJ: Effects of aging on Philadelphia, Pa, FA Davis Co, 1990, p 15. left ventricular structure and fimction. Am Heart J 1991;121:871- 9. Rodeheffer RJ, Gerstenblith G, Becker LC, et al: Exercise 875. is maintained with advancing age in healthy 17. Simon HB: The aging heart: Is dysfunction inevitable? Car­ human subjects: Cardiac dilatation and increased stroke vol­ diology 1987;16:46-49. ume compensate for a diminished heart rate. Circulation 18. Harris R: Geriatric Cardiology: Management of Elderly 1984;69:203-213. Patients. Philadelphia, Pa, JB Lippincott Co, 1990, p 22. 10. Hakki A-H, DePace NL, Iskandrian AS: Effect of age on left 19. Fleg JL: Prevalence and prognostic significance of exercise­ ventricular fimction during exercise in patients with coronary artery induced silent ischemia in apparently healthy subjects. Am J disease. JAm Coll Cardiol1983;2:645-651. Cardiol1992;69:14B-18B.

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