Stress Echocardiography in Octogenarians: Transesophageal Atrial Pacing is Accurate, Safe, and Well Tolerated

Stress Echocardiography in Octogenarians: Transesophageal Atrial Pacing is Accurate, Safe, and Well Tolerated Sergio L. Kobal, MD, Charles Pollick, MD, Shaul Atar, MD, Takashi Miyamoto, MD, Noune Aslanian, MD, Yoram Neuman, MD, Kirsten Tolstrup, MD, Tasneem Z. Naqvi, MD, Huai Luo, MD, Bruce Macrum, MD, and Robert J. Siegel, MD, FACC, Los Angeles, California

The feasibility and diagnostic accuracy of transesophageal pacing stress echocardiography for detection of inducible myocardial ischemia were evaluated in 161 patients 80 years of age or older (mean 84 ⴞ 3.9, range 80-97). The pacing time was 5.5 ⴞ 2.5 minutes with a total test time of 37 ⴞ 7 minutes. The mean achieved heart rate was 96 ⴞ 7% (83%-121%) of maximum predicted with an average rate pressure product of 21,560 ⴞ 5175 beats/min ⴛ mm Hg. There were minor adverse events in 8% of cases and no major complications occurred. Patient acceptance was

There are currently 9.2 million people older than 80 years in the United States and it is expected that this population will reach 18.6 million by 2030.1 The diagnosis of coronary artery disease (CAD) in the elderly can be challenging because of silent ischemia and atypical symptoms.2,3 Older patients are often unable to exercise,4 thus, dobutamine stress echocardiography (DSE) is commonly used to diagnose CAD.5-8 But DSE is problematic in elderly patients because of their diminished chronotropic response to catecholamine agents and incidence of hypotension and tachyarrhythmias.9-14 In the general population, transesophageal atrial pacing stress echocardiography (PASE) is rapid to perform, has rare complications, and has a similar accuracy as DSE for diagnosing CAD.15-24 However, the practicability, complication rate, and accuracy of PASE specific to the elderly are unknown. We report for the first time the feasibility and accuracy of PASE in a large cohort of patients 80 years of age or older.

From Cedars-Sinai Medical Center and Good Samaritan Hospital (C.P., B.M.). Reprint requests: Robert J. Siegel, MD, FACC, Cedars-Sinai Medical Center, Division of Cardiology, 8700 Beverly Blvd, Room 5635, Los Angeles, CA 90048 (E-mail: [email protected]). 0894-7317/$32.00 Copyright 2006 by the American Society of Echocardiography. doi:10.1016/j.echo.2006.03.009

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high. When compared with myocardial single photon emission computed tomography, pacing stress echocardiography had a sensitivity of 89% and a specificity of 93% for the detection of myocardial ischemia, and 91% agreement (␬ ⴝ 0.80, P < .001). We demonstrate that pacing stress echocardiography is safe and accurate for detection of myocardial ischemia and, thus, a reliable substitute to exercise and pharmacologic stress testing in octogenarians. (J Am Soc Echocardiogr 2006;19:1012-1016.)

METHODS We retrospectively studied 161 patients 80 years of age or older (mean 84 ⫾ 3.9, range 80-97) who were unable to perform exercise stress testing. In all, 114 (71%) patients had PASE to evaluate chest pain, 18 (11%) as a result of syncope or arrhythmia, 16 (10%) because of dyspnea, and 13 (8%) for surgical risk stratification in two medical centers. The institutional review boards of both medical centers approved the study protocol. The patient characteristics are listed in the Table. Patients were excluded from this study if they had contraindications to PASE such as esophageal stricture or varices, hiatal hernia, or atrial fibrillation. PASE Protocol Transesophageal atrial pacing was performed with a pacing system (Tapstress, Cardiocommand, Tampa, Fla). A 10F bipolar pacing catheter was introduced through the oropharynx to the esophagus by the physician in charge of the study. Before the insertion, local anesthesia was sprayed into the oropharynx (benzocaine 20%, Hurricane, Beutlich, Waukegan, Ill). To those patients who were anxious about swallowing the PASE catheter, intravenous sedation (midazolam) was offered. The proximal pacing electrode was covered with lubricating jelly (K-Y, JohnsonJohnson, Arlington, Tex). The catheter was slowly introduced into the esophagus up to the point that a stable atrial capture would be obtained. Pacing was started at a rate of 110/min (pulse width 10 milliseconds, output current 20 mA), and the pacing rate was increased within 30 seconds to a target heart rate (HR) calculated as equal

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Table Patient data (n ⫽ 161) Clinical characteristics

Age, y Women (n) Inpatients (n) Hypertension (n) Diabetes mellitus (n) Prior myocardial infarction (n) Prior coronary revascularization* (n) Paroxysmal atrial fibrillation (n) Suspected or documented VT (n) Beta-blocker treatment (n)

84 ⫾ 3.9 92 122 109 46 44 63 18 16 35

(range 80-97) (57%) (76%) (68%) (28%) (27%) (39%) (11%) (10%) (22%)

Rest echocardiography findings

LVEF, % Wall-motion index† LVH with dynamic outflow tract gradient‡

46 ⫾ 26 1.21 ⫾ 0.33 8%

LVEF, Left ventricular ejection fraction; LVH, left ventricular hypertrophy; VT, ventricular tachycardia. *Coronary artery bypass graft or percutaneous balloon angioplasty. †66% (106 of 161) of the patients had abnormal wall-motion contractility in at least 1/16 segments of the left ventricle. ‡Left dynamic outflow tract gradient was defined as ⱖ 30 mm Hg.

to 220- the patient’s age in years. To reduce patient uneasiness, pacing output was decreased to the minimum that allowed stable 1:1 atrial/ventricular pacing. Patients sustaining second-degree Wenckebach atrioventricular block during pacing were given intravenous atropine (0.4 mg to a maximum of 2 mg). Patient blood pressure (BP) was automatically measured every 2 minutes and HR was continuously monitored. A 12-lead electrocardiogram (ECG) was performed at baseline, peak HR, and recovery time. The study lasted until the 16 left ventricular (LV) segments were recorded in the 5 standard transthoracic echocardiographic views (parasternal long- and short-axis, and apical 4-, 3-, and 2-chamber). The other end points were severe angina, systolic BP greater than 240 mm Hg or a decrease greater than 40 mm Hg from the resting value, diastolic BP greater than 120 mm Hg, atrial and ventricular tachyarrhythmias, and new wall-motion abnormalities of at least two contiguous areas. Transthoracic echocardiography was performed with tissue harmonic imaging and recorded on super-VHS. A 16-segment model was used to evaluate LV wall motion that was graded as 1 ⫽ normal, 2 ⫽ hypokinetic, 3 ⫽ akinetic, and 4 ⫽ dyskinetic at baseline and peak pacing HR. Segments were considered ischemic if a new wallmotion abnormality or a worsening of pre-existing abnormalities of at least one grade were detected at the peak pacing HR.25 The duration, complications, and tolerability of PASE were used to evaluate its feasibility. Adverse events were categorized as minor (transient atrial arrhythmia, vomiting, or nausea) and major (ventricular tachycardia, worsening congestive heart failure, ECG changes of acute myocardial infarction, or esophageal perforation). Immediately after termination of pacing, the patients were asked to grade their level of discomfort and the tolerability

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of the test on a scale of 1 to 10 (1 ⫽ intolerable, 10 ⫽ not causing any discomfort). In 65 patients who were participating in an ongoing research study, PASE results were validated with adenosine or dobutamine myocardial single photon emission computed tomography (SPECT) within 24 hours after performing PASE using a protocol previously described by Berman et al.26 Myocardial perfusion assessed by SPECT used a LV segment model similar to that used by PASE by obtaining short- and long-axis myocardial tomograms. The segments that showed transient perfusion defect were considered as ischemic and those with a fixed perfusion defect as necrotic. A segment was defined as ischemic by PASE if there was the development of a new wall-motion abnormality or if worsening of pre-existing abnormalities of at least one grade was detected at the peak pacing HR. By using the LV segment model, we correlated PASE and myocardial SPECT for the presence or absence of inducible myocardial ischemia. Statistics The ␬ coefficient was used to assess agreement. Continuous measures are expressed as mean ⫾ 1 SD. Withinsubject mean changes on continuous measures were assessed using the paired t test. A P value less than .05 was considered significant.

RESULTS In 156 of 161 (97%) patients, PASE was completed in 35 ⫾ 7 minutes, with a pacing time of 5.5 ⫾ 2.5 minutes. Eight (5%) patients who were anxious received midazolam. In 3 patients PASE was discontinued prematurely because of failure to obtain stable atrial capture, and in two patients because of poor echocardiographic images. Achievement of the age-predicted target HR was the reason for PASE termination in 155 of 156 patients. The study was stopped prematurely in one patient because of the development of atrial fibrillation. The resting HR was 71 ⫾ 13 bpm and increased to 131 ⫾ 11 bpm at the peak pacing (P ⬍ .001). The mean achieved target HR was 96 ⫾ 7% (range 83%-121%) of the maximum age predicted heart rate. Intravenous atropine (maximum dose received 1.0 mg) was administered to 16 (10%) patients who developed atrioventricular block during pacing, to reach the target HR. Mean systolic BP at rest was 147 ⫾ 27 mm Hg and increased to 164 ⫾ 33 mm Hg (P ⫽ .012). Eleven (7%) patients had no change in the systolic BP, and 22 (14%) of them had an asymptomatic decline in the systolic BP during the pacing. The HR pressure product achieved was 21,560 ⫾ 5179 beats/min ⫻ mm Hg. Minor complications occurred in 13 (8%) patients; 11 patients developed gagging without vomiting during insertion of the esophageal pacing catheter and

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two patients developed transient atrial fibrillation resulting in termination of the study. No major complications (ventricular tachycardia, acute myocardial infarction, or worsening of congestive heart failure) were observed. The patients graded the test tolerability after the PASE procedure. Mean tolerability score was 8.9 ⫾ 1.1 (range 5-10). Echocardiographic criteria for myocardial ischemia were observed in 78 (50%) of the 156 patients who completed the PASE studies. Mean LV wallmotion index increased from 1.22 ⫾ 0.33 at rest to 1.44 ⫾ 0.46 (P ⫽ .024) at peak pacing. Concomitant ECG changes compatible with myocardial ischemia were observed in 35 (45%) of the PASE-positive cases; the ECG remained unchanged in 32 (41%) cases, and was nondiagnostic in the remaining 11 (14%). Typical angina or an angina equivalent was present in 12 (15%) PASE-positive cases and equivocal or nontypical symptoms were present in 9 (11%) of the other PASE-positive cases. The results of PASE were validated with myocardial SPECT in 65 (42%) patients. PASE had 89% (34/38) sensitivity and 93% (25/27) specificity for detection of myocardial ischemia. Agreement for detecting myocardial ischemia was high at 91% (59/65) (␬ ⫽ 0.80, P ⬍ .001). We studied the extent of the myocardial ischemia by analyzing the agreement between PASE and SPECT in the assessment of each one of the 16 LV myocardial segments. For the 1040 segments investigated in the 65 patients, there were 77% (802/1040) true-negative, 16% (168/1040) true-positive, 6% (59/1040) false-positive, and 1% (11/1040) false-negative segments. Exact correlation agreement was observed in 65% of the patients. Compared with SPECT, PASE overestimated the amount of inducible ischemia in 22% of the cases. In 13% of patients, PASE underestimated the extent of inducible ischemia.

DISCUSSION Our study demonstrates that PASE is a safe and accurate method to diagnose CAD in octogenarians unable to exercise. In fact, PASE has a high sensitivity (89%) and specificity (93%) for detecting inducible myocardial ischemia. Few patients in our population underwent coronary angiography. Nevertheless, two prior studies published by our group have compared the results of angiography and PASE. In one study (mean age 68 ⫾ 11 years), Atar et al21 showed that the sensitivity and specificity for PASE to identify myocardial ischemia was 93% and 100%, respectively. In another study by Atar et al23 (mean age 66 ⫾ 10 years), sensitivity for PASE according to lesion severity was 88% for 50% coronary artery stenoses and 95% for 75% coronary artery stenoses and specificity was 91% and 87%, respectively. The accuracy was

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89% and 92% for 50% and 75% stenoses, respectively. In addition, PASE is practical even in cases where DSE cannot be used as an alternative to exercise stress echocardiography. In our study patients had at least one contraindication (relative or absolute) to DSE. We considered absolute contraindication to DSE (9%) a systolic BP or diastolic BP more than 200 and 100 mm Hg, respectively (7 of 161 patients), history of intolerance to dobutamine (3 of 161 patients), documented malignant ventricular tachycardia (2 of 161 patients), and dynamic LV obstruction with peak gradient higher than 45 mm Hg (one patient). There are a number of clinical settings that, although not considered definite contraindications to DSE, must be thought as inconvenient when using beta-receptor agonists to stress the heart. Examples of nonoptimal settings for the use of DSE include patients treated with beta-blockers as a result of their blunted chronotropic response, patients who have known or suggested ventricular arrhythmias and history of paroxysmal atrial fibrillation, and patients with dynamic LV outflow tract gradient at rest who can develop hypotension during dobutamine infusion associated with increase in dynamic gradient. PASE is well tolerated and patient acceptance is high (8.9 on a scale of 10). This probably relates to the short duration of pacing (5.5 minutes) and few complications. Only 11 (7%) patients had gagging associated with insertion of the esophageal catheter, two patients developed transient atrial fibrillation that resolved spontaneously, and no patient had major complications. The rate of complications of PASE in our study of patients whose average age was 84 years (maximal age of 97 years) was similar to previously published studies where the population was significantly younger.15-24 The mean age of our patients (84 years) is older than any previously published stress echocardiographic study. Thus, it appears that the low incidence of adverse events in PASE does not increase with age. PASE lasted for 35 minutes. Physician presence in the stress room is needed only during the pacing period (5.5 minutes). Consequently, PASE is not time-consuming. Hypotension during exercise tests has been associated with the extent of myocardial ischemia and transient ventricular dysfunction, and is considered a marker of severity of CAD.27-29 PASE-induced hypotension can occur, unrelated to myocardial ischemia. The potential nonischemic mechanisms of PASE-induced hypotension are the shorter diastolic filling time and reduction in LV stroke volume with the increasing HR, LV cavity obliteration, and dynamic obstruction as the diastolic time decreases without an increment in the preload, and the use of intravenous midazolam for patient sedation and

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comfort. In our study, the incidence of hypotension (defined as any systolic BP value below the measured systolic BP at baseline) was similar in the ischemic and nonischemic groups (14% and 13%, respectively). In the ischemic group, LV wall-motion index at peak pacing (a marker of the burden of myocardial ischemia) was similar for those patients who developed hypotension (1.68 ⫾ 0.44) compared with those patients without hypotension (1.41 ⫾ 0.42), assuming that at least in our cohort of patients hypotension was not a marker of the amount of jeopardized myocardium. In the entire group of patients with hypotension, two of them received midazolam and LV dynamic obstruction was diagnosed in 3 other patients. The cause of hypotension was not identified in the rest of the patients. PASE was accurate for identifying myocardial ischemia. Although the increment of the systolic BP was modest, the rate pressure product (21,560 ⫾ 5179/ min/mm Hg) was satisfactory as the HR achieved during the peak pacing was high. The chronotropic response to catecholamines in the elderly is blunted,20 but PASE is not dependent on the responsiveness of the sympathetic nervous system. Consequently, the achievement of the target HR in our population (97%) was significantly higher than that obtained by DSE in prior studies of elderly patients.8,9,11-14 The accuracy of PASE to identify myocardial ischemia depends mainly on the quality of the ultrasound imaging to assess LV wall motion and thickening. In this study, we did not specifically evaluate whether different LV segments were problematic to evaluate by PASE. However, we have previously evaluated this issue in a study published by Atar et al.23 We found that 3% of the LV segments were classified by the PASE readers as being problematic for detecting segmental wall-motion abnormalities. Basal inferior wall, and mid and apical inferior wall were most frequently the segments that were difficult to assess. The use of contrast agents could potentially improve the detection of the endocardial borders of those difficult segments. In summary, this study found that PASE is a rapid, well-tolerated, and safe procedure that accurately identifies inducible myocardial ischemia. In octogenarians unable to exercise, PASE is not limited by conditions found in the elderly that represent contraindications to the performance of pharmacologic stress testing. REFERENCES 1. US Census Bureau. An aging world. International population report. Available from: URL:http://www.nia.nih.gov/research/ behavior/agingword2001. 2. Coodley EL. Clinical spectrum and diagnostic techniques of coronary heart disease in the elderly. J Am Geriatr Soc 1988; 36:447-56.

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3. Fleg JL. Angina pectoris in the elderly. Cardiol Clin 1991;9: 177-87. 4. Riley CP, Oberman A, Lampton TD, Hurst DC. Submaximal exercise testing in a random sample of an elderly population. Circulation 1970;62:43-52. 5. Sawada SG, Segar DS, Ryan T, Brown SE, Dohan AM, Williams R, et al. Echocardiographic detection of coronary artery disease during dobutamine infusion. Circulation 1991; 83:1605-14. 6. Salusti A, Fioretti P, McNeill A, Pozzoliand M, Roelandt J. Pharmacological stress echocardiography in the diagnosis of coronary artery disease and myocardial ischemia: a comparison between dobutamine and dipyridamole. Eur Heart J 1992;13: 1356-62. 7. Mathias W Jr, Arruda A, Santos FC, Arruda AL, Mattos E, Osorio A, et al. Safety of dobutamine-atropine stress echocardiography: a prospective experience of 4033 consecutive studies. J Am Soc Echocardiogr 1999;12:785-91. 8. Font VE, Lara WC, Bournigal DR. Stress echocardiography for predicting cardiac events in octogenarians: is myocardial perfusion scintigraphy necessary anymore? South Med J 1996; 89:1166-73. 9. Baudhuin T, Marwick T, Melin J, Wijns W, D’Hondt AM, Detry JM. Diagnosis of coronary artery disease in elderly patients: safety and efficacy of dobutamine echocardiography. Eur Heart J 1993;14:799-803. 10. Markovitz PA, Bach DS, Mathias W, Shayna V, Armstrong WF. Paradoxic hypotension during dobutamine stress echocardiography: clinical and diagnostic implications. J Am Coll Cardiol 1993;21:1080-6. 11. Poldermans D, Fioretti PM, Boersma E, Thomson IR, Cornel JH, Folkert J, et al. Dobutamine-atropine stress echocardiography in elderly patients unable to perform an exercise test. Arch Intern Med 1994;154:2681-6. 12. Anthopoulos LP, Bonou MS, Kardaras FG, Sioras EP, Kardara DN, Sideris AM, et al. Stress echocardiography in elderly patients with coronary artery disease: applicability, safety and prognostic value of dobutamine and adenosine echocardiography in elderly patients. J Am Coll Cardiol 1996;28:52-9. 13. Hiro J, Hiro T, Reid CL, Ebrahimi R, Matsuzaki M, Gardin JM. Safety and results of dobutamine stress echocardiography in women versus men and in patients older and younger than 75 years of age. Am J Cardiol 1997;80:1014-20. 14. Abreu JS, Diogenes TC, Farias AG, Morais JM, Paes JN Jr. Safety and feasibility of dobutamine-atropine stress echocardiography in octogenarian patients. Arq Bras Cardiol 2005; 83:198-204. 15. Gallagher JJ, Smith WM, Kerr CR, Kasell J, Cook L, Reiter M, et al. Esophageal pacing: a diagnostic and therapeutic tool. Circulation 1982;65:336-41. 16. Chapman PD, Doyle TP, Troup PJ, Gross CM, Wann LS. Stress echocardiography with transesophageal atrial pacing: preliminary report of a new method for detection of ischemic wall motion abnormalities. Circulation 1984;70:445-50. 17. Marangelli V, Iliceto S, Piccinni G, De Martino G, Sorgente L, Rizzon P. Detection of coronary artery disease by digital stress echocardiography: comparison of exercise, transesophageal atrial pacing and dipyridamole echocardiography. J Am Coll Cardiol 1994;24:117-24. 18. Schroder K, Voller H, Dingerkus H, Munzberg H, Dissmann R, Linderer T, et al. Comparison of the diagnostic potential of four echocardiographic stress test shortly after acute myocardial infarction: submaximal exercise, transesophageal atrial pacing,

Journal of the American Society of Echocardiography August 2006

1016 Kobal et al

19.

20.

21.

22.

23.

24.

dipyridamole, and dobutamine-atropine. Am J Cardiol 1996;77:909-14. Don Michael TA, Antonescu A, Bhambi B, Balasingam S. Accuracy and usefulness of atrial pacing in conjunction with transthoracic echocardiography in the detection of cardiac ischemia. Am J Cardiol 1996;77:187-90. Lee CY, Pellikka PA, McCully RB, Mahoney DW, Seward JB. Nonexercise stress transthoracic echocardiography: transesophageal atrial pacing versus dobutamine stress. J Am Coll Cardiol 1999;33:506-11. Atar S, Cercek B, Nagai T, Luo H, Lewin HC, Naqvi TZ, et al. Transthoracic stress echocardiography with transesophageal atrial pacing for bedside evaluation of inducible myocardial ischemia in patients with new-onset chest pain. Am J Cardiol 2000;86:12-6. Rainbird AJ, Pellikka PA, Stussy VL, Mahoney DM, Seward JB. A rapid stress-testing protocol for the detection of coronary artery disease: comparison of two-stage transesophageal atrial pacing stress echocardiography with dobutamine stress echocardiography. J Am Coll Cardiol 2000;36:1659-63. Atar S, Nagai T, Cercek B, Naqvi TZ, Luo H, Siegel RJ. Pacing stress echocardiography: an alternative to pharmacological stress testing. J Am Coll Cardiol 2000;36:1935-41. Anselmi M, Golia G, Rossi A, Zeni P, Gallo A, Marino P, et al. Feasibility and safety of transesophageal atrial pacing stress echo-

25.

26.

27.

28.

29.

cardiography in patients with known or suspected coronary artery disease. Am J Cardiol 2003;92:1384-8. Armstrong WF, Pellikka PA, Ryan T, Crouse L, Zoghbi WA. Stress echocardiography: recommendations for performance and interpretation of stress echocardiography; stress echocardiography task force of the nomenclature and standards committee of the American Society of Echocardiography. J Am Soc Echocardiogr 1998;11:97-104. Berman DS, Kiat H, Friedman JD, Wang FP, Train KV, Matzer L, et al. Separate acquisition rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion single-photon emission computed tomography: a clinical validation. J Am Coll Cardiol 1993;22:1455-64. Dubach P, Froelicher VF, Klein J, Oakes D, Grover-McKay M, Friis R. Exercise-induced hypotension in a male population: criteria, causes, and prognosis. Circulation 1988;78:1380-7. Iskandrian AS, Kegel JG, Lemlek J, Heo J, Cave V, Iskandrian B. Mechanism of exercise-induced hypotension in coronary artery disease. Am Heart J 1992;69:1517-20. Morris CK, Morrow K, Froelicher VF, Hideg A, Hunter D, Kawaguchi T, et al. Prediction of cardiovascular death by means of clinical and exercise test variables in patients selected for cardiac catheterization. Am Heart J 1993;125: 1717-26.