Diagnostic Accuracy of Stress Thallium-201 Tomography in Patients With Left Ventricular Hypertrophy

1. Winkle RA, Mead H, Ruder MA, Gaudiani VA, Smith NA, Buch WS, Schmidt

P, Shipman T. Long-term outcome with the automatic implantable cardioverterdefibrillator. J Am Coll Cardiol 1989;13:1353–1361. 2. Powell AC, Fucjs T, Finkelstein DM, Garan J, Cannom DS, McGovern BA, Kelly E, Vlahakes GJ, Torchiana DF, Ruskin JN. Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-ofhospital cardiac arrest. Circulation 1993;88:1083–1092. 3. Newman D, Sauve MJ, Herre J, Langberg JL, Lee MA, Titus C, Franklin J, Scheinman MM, Griffin JC. Survival after implantation of the cardioverter defibrillator. Am J Cardiol 1992;69:899 –903. 4. Li H, Axtell K, Biehl M, Deshpande S, Dhala A, Blanck Z, Sra J, Jazayeri MR, Akhtar M. Sudden death in patients with implantable cardioverter-defibrillators. Am Heart J 1996;132:986 –988. 5. Tchou P, Axtell K, Anderson AJ, Keim S, Sra J, Troup P, Jazayeri M, Avitall B, Akhtar M. When is it safe not to replace an implantable cardioverterdefibrillator generator? PACE 1991;14:1875–1880.

6. The CABG Patch Trial Investigators and Coordinators. The coronary artery

bypass graft (CABG) patch trial. Prog Cardiovasc Dis 1993;36:97–114. 7. Buxton AE, Fisher JD, Josephson ME, and the MUSTT Investigators. Pre-

vention of sudden death in patients with coronary artery disease: The Multicenter Unsustained Tachycardia Trial. Prog Cardiovasc Dis 1993;36:215–226. 8. Soo K, Fogoros RN, Furman S, Connolly SJ, Kuck KH, Moss. Standardized reporting of ICD patient outcome: The report of a North American Society of Pacing and Electrophysiology policy conference, February 9 –10, 1993. PACE 1993;16:1358 –1362. 9. Morris PL, Dadger J, Chmielewski C, Berger E, Goldberg RJ. Psychiatric morbidity following the automatic implantable cardioverter defibrillator. Psychosomatics 1991;32:58 – 64. 10. Dougherty CM. Psychological reactions and family adjustment in shock versus no shock groups after implantation of internal cardioverter defibrillator. Heart Lung 1995;24:281–291.

Diagnostic Accuracy of Stress Thallium-201 Tomography in Patients With Left Ventricular Hypertrophy Periyanan Vaduganathan, MD, Zuo-Xiang He, MD, John J. Mahmarian, and Mario S. Verani, MD n increased incidence of ‘‘false positive’’ test results in patients with left ventricular (LV) hyA pertrophy has been reported during treadmill testing, exercise radionuclide angiography, and even during thallium scintigraphy.1– 4 Thus, our study was designed to evaluate the diagnostic accuracy of stress thallium-201 single-photon emission computed tomography (SPECT) in a large series of patients with LV hypertrophy documented by echocardiography. •••

Consecutive patients referred to our nuclear cardiology laboratory for thallium-201 stress SPECT between January 1989 and December 1994 were retrospectively selected. The inclusion criteria were: (1) presence of LV hypertrophy confirmed by 2-dimensional echocardiographic study; (2) stress thallium201 SPECT performed within 3 months of the echocardiographic study; and (3) coronary angiography performed within 1 month of the nuclear study. Patients with the following conditions were excluded: (1) previous myocardial infarction by history or electrocardiogram; (2) left bundle branch block; (3) previous coronary angioplasty or coronary bypass surgery; (4) LV ejection fraction ,50% and resting wall motion abnormalities by echocardiography; and (5) hypertrophic cardiomyopathy and asymmetric septal hypertrophy. Standard 2-dimensional echocardiography was performed and measurements were obtained in the parasternal long-axis view by experienced echocardiographers. A septal and LV posterior wall thickness .12 mm was considered diagnostic of LV hypertroFrom the Section of Cardiology, Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, Texas. Dr. Verani’s address is: Baylor College of Medicine, Nuclear Cardiology, The Methodist Hospital, 6550 Fannin, SM 677, Houston, Texas 77030. Manuscript received August 6, 1997; revised manuscript received and accepted January 2, 1998. ©1998 by Excerpta Medica, Inc. All rights reserved.

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phy. Standard criteria were used in the electrocardiographic diagnosis of LV hypertrophy.5 Exercise perfusion SPECT was performed in 117 patients using the standard Bruce protocol. Blood pressure, heart rate, and a 12-lead electrocardiogram were recorded at 1-minute intervals throughout the test. Pharmacologic stress SPECT was done in 83 patients. The stress agent was dipyridamole in 42, adenosine in 33, and dobutamine in 8 patients. Dipyridamole was administered intravenously at a dose of 142 mg/kg/min over 4 minutes and adenosine at a dose of 140 mg/kg/min for 6 minutes. Dobutamine was given at incremental doses from 5 to 40 mg/kg/min at 3-minute intervals. The vital signs and electrocardiograms were monitored in a similar fashion as during the exercise testing. Thallium-201 (3.0 mCi) was injected either at peak exercise, 4 minutes after dipyridamole administration, 3 minutes into the adenosine infusion, or 2 minutes before termination of dobutamine infusion. Imaging began 5 to 10 minutes after thallium injection and redistribution images were obtained 4 hours later. A standard tomographic gamma camera (ADAC ARC 3000-3300, Milipitas, California) was used and reconstruction and reorientation were done as previously reported from our laboratory.6 – 8 Tomographic images were interpreted by experienced nuclear cardiologists who were blind to the clinical findings and the results of coronary angiography. The images were quantified using computer-generated polar maps of the myocardial tracer activity and compared with stress-specific normal data banks previously generated in our laboratory.6,7 The vascular territories were assigned in a standard manner: anteroseptal, anterior, and anterolateral wall were assigned to the left anterior descending artery, and the posterolateral wall to the left circumflex artery and the inferior and posterior walls to the right coronary artery.6 – 8 A definite focal decrease in 0002-9149/98/$19.00 PII S0002-9149(98)00091-5

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TABLE I Comparison of SPECT and Coronary Angiography in the Total Cohort and in the Subgroup With LV Hypertrophy by ECG SPECT

Total (n 5 200) No CAD CAD LV hypertrophy by ECG (n 5 105) No CAD CAD

Normal

Abnormal

99 13

22 66

121 79

50 8

9 38

59 46

CAD 5 coronary artery disease; ECG 5 electrocardiography; LV 5 left ventricular; SPECT 5 single-photon emission computed tomography.

tracer distribution that measured $3% of the LV mass on the stress polar maps was considered abnormal. Isolated apical hypoperfusion was identified as abnormal only if $3% defect was shown on the polar maps. Selective coronary angiography was performed in multiple views because of a history suggestive of angina or abnormal perfusion imaging. Coronary stenoses were measured with calipers by an experienced angiographer. Significant coronary artery disease was defined as $50% luminal diameter stenosis. Results are reported as mean 6 SD. The patients’ mean age was 58 6 14 years and 61% were men. History of hypertension and diabetes mellitus were present in 73% and 13% of patients, respectively. Electrocardiographic evidence of LV hypertrophy was present in 105 patients (53%). In all of our patients the hypertrophy was concentric, with a mean septal wall thickness of 13.7 6 1.9 mm, whereas the mean posterior wall thickness was 13.4 6 1.8 mm. In all patients who underwent exercise testing, heart rate increased from 82 6 15 beats/min at baseline to 142 6 19 beats/min at peak exercise (p ,0.001). Systolic blood pressure increased from 137 6 18 mm Hg at baseline to 172 6 27 mm Hg (p ,0.001) at peak stress. Thirty-seven percent of patients had a submaximal exercise test. In patients who had adenosine stress, heart rate was 73 6 14 beats/min at baseline and increased to 92 6 16 beats/min (p ,0.001) at peak adenosine infusion, whereas systolic blood pressure did not change significantly. In patients who had dobutamine stress, heart rate increased from 69 6 11 beats/min at baseline to 113 6 17 beats/min (p ,0.001) at peak dobutamine infusion, whereas systolic blood pressure did not change significantly. Significant coronary artery disease was documented in 79 of the 200 patients (Table I). One-vessel disease was present in 39, 2-vessel disease in 24, and 3-vessel disease in 16 patients. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of thallium-201 SPECT for the diagnosis of coronary artery disease in the total group were 84% (66 of 79 patients), 82% (99 of 121 patients), 75% (66 of 88 patients), 88% (99 of 112 patients), and 83% (165 of 200 patients), respectively. The sensitivity was 74% in patients with 1-vessel disease, 92% in those with 2-vessel disease, and 94% 1206 THE AMERICAN JOURNAL OF CARDIOLOGYT

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in those with 3-vessel disease. The sensitivities and specificities for individual vascular territories were 71% and 96% for the left anterior descending artery, 65% and 87% for the left circumflex artery, and 74% and 97% for the right coronary artery, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of thallium201 SPECT in the 105 patients with electrocardiographic evidence of LV hypertrophy were 83% (38 of 46 patients), 85% (50 of 59 patients), 80% (50 of 58 patients), 86% (38 of 47 patients), and 84% (88 of 105 patients), respectively. In the 117 patients who had exercise thallium-201 SPECT, the sensitivity and specificity were 85% (39 of 46 patients) and 82% (59 of 71 patients), respectively. The sensitivity and specificity for the detection of individual diseased vessels were also good: 72% and 98% for the left anterior descending artery; 63% and 89% for the circumflex artery; and 77% and 98% for the right coronary artery. In the 83 patients who had pharmacologic stress, the sensitivity and specificity were both 82% (27 of 33 and 41 of 50 patients). The sensitivity and specificity for individual vascular territories were also good: 70% and 93% for the left anterior descending artery; 67% and 83% for the circumflex artery; and 70% and 97% for the right coronary artery. In the 117 patients with an exercise stress, 9 had noninterpretable electrocardiograms because of either exercise-induced left bundle branch block or a paced ventricular rhythm. In the remaining 108 patients with interpretable electrocardiograms, the sensitivity and specificity of the exercise electrocardiogram were 51% (19 of 39 patients) and 43% (30 of 69 patients), respectively. •••

This study is the largest series thus far reported in English publications assessing the value of thallium stress SPECT in patients with echocardiographically proven LV hypertrophy and who also underwent coronary angiography. The main finding in our study is that both exercise and pharmacologic thallium SPECT have good sensitivity and specificity for the diagnosis and location of coronary artery disease in patients with LV hypertrophy. The observed values were not, in fact, unlike those of unselected patient cohorts previously reported from our laboratory.6 – 8 The sensitivity and specificity of myocardial SPECT were equally high, irrespective of the stress modality used. Previous studies by Alshami et al9 and Ambrosi et al10 also showed high specificity despite the presence of LV hypertrophy. It has been suggested that myocardial perfusion defects may occur during stress scintigraphy in hypertensive patients without obstructive coronary artery disease.4,11 Some of these perfusion defects may be related to a decrease in myocardial perfusion secondary to microvascular disease.12,13 Houghton et al3 studied 172 patients with normal coronary angiography. They reported a 31% ‘‘false positive’’ rate with thallium scintigraphy in patients without hypertrophy and 59% in patients with LV hypertrophy. DePuey et al4 studied 100 renal hypertensive patients and reMAY 15, 1998

ported a decrease in thallium-201 lateral/septal count in 35 patients, mimicking an old lateral wall scar. However, only 12 of their patients had echocardiography and coronary angiography was not performed at all! In a smaller study of 16 patients with LV hypertrophy, Cecil et al14 reported lateral-septal count ratio to be similar in patients with or without LV hypertrophy. Other investigators have suggested that perfusion defects are not more common in hypertensive than in normotensive patients.9,10 The prevailing ‘‘myth’’ that more ‘‘false positive’’ thallium studies occur in hypertensive patients is thus based on a few studies, all substantially flawed, none of which investigated this issue in a systematic manner. Our study was specifically designed to answer this question. In conclusion, both exercise and pharmacologic thallium-201 SPECT have good sensitivity and specificity for diagnosing the presence and location of coronary artery disease in patients with LV hypertrophy. 1. Wasserman AG, Katz RJ, Varghese PJ, Leiboff RH, Bren GG, Schlesselman

S, Varma VM, Reba RC, Ross AM. Exercise radionuclide ventriculographic responses in hypertensive patients with chest pain. N Engl J Med 1984;311:1276 – 1280. 2. Schulman DS, Francis CK, Black HR, Wackers FJ. Thallium-201 stress imaging in hypertensive patients. Hypertension 1987;10:16 –21. 3. Houghton JL, Prisant LM, Carr AA, Flowers NC, Frank MJ. Racial differences in myocardial ischemia and coronary flow reserve in hypertension. J Am Coll Cardiol 1994;23:1123–1129.

4. DePuey EG, Guertler-Krawczynska E, Perkins JV, Robbins WL, Whelchel JD, Clements SD. Alterations in myocardial thallium-201 distribution in patients with chronic systemic hypertension undergoing single-photon emission computed tomography. Am J Cardiol 1988;62:234 –238. 5. Levy D, Labib SB, Anderson KM, Christiansen JC, Kannel WB, Castelli WP. Determinants of sensitivity and specificity of electrocardiographic criteria for left ventricular hypertrophy. Circulation 1990;81:815– 820. 6. Mahmarian JJ, Boyce TM, Goldberg RK, Cocanougher MK, Roberts R, Verani MS. Quantitative exercise thallium-201 single photon emission computed tomography for the enhanced diagnosis of ischemic heart disease. J Am Coll Cardiol 1990;15:318 –329. 7. Nishimura S, Mahmarian JJ, Boyce TM, Verani MS. Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease. J Am Coll Cardiol 1991;18:736 –745. 8. Hays JT, Mahmarian JJ, Cochran AJ, Verani MS. Dobutamine thallium-201 tomography for evaluating patients with suspected coronary artery disease unable to undergo exercise or vasodilator pharmacologic stress testing. J Am Coll Cardiol 1993;21:1583–1590. 9. Alshami AA, Jolly SR, Smith FL, Reeves WC, Movahed A. Exercise testing in patients with electrocardiographic evidence of left ventricular hypertrophy. Clin Nucl Med 1994;19:904 –909. 10. Ambrosi P, Habib G, Kreitman B, Metras D, Riberi A, Faugere G, Bernard P, Luccioni R. Thallium perfusion and myocardial hypertrophy in transplanted heart recipients with normal or near-normal coronary arteriograms. Eur Heart J 1994;15:1119 –1123. 11. Houghton JL, Frank MJ, Carr AA, von Dohlen TW, Prisant LM. Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease. J Am Coll Cardiol 1990;15:43–51. 12. Klepzig M, Eisenlohr H, Steindl J, Schmiebusch H, Strauer BE. Media hypertrophy in hypertensive coronary resistance vessels. J Cardiovasc Pharmacol 1987;10(suppl 6):S97–S102. 13. Brush JE Jr, Cannon RO III, Schenke WH, Bonow RO, Leon MB, Maron BJ, Esptein SE. Angina due to coronary microvascular disease in hypertensive patients without left ventricular hypertrophy. N Engl J Med 1988;319:1302–1307. 14. Cecil MP, Pilcher WC, Eisner RL, Chu TH, Merlino JD, Patterson RE. Absence of defects in SPECT thallium-201 myocardial images in patients with systemic hypertension and left ventricular hypertrophy. Am J Cardiol 1994;74: 43– 46.

Comparison of Plasma Neurohormones in Congestive Heart Failure Patients With Atrial Fibrillation Versus Patients With Sinus Rhythm Anton E. Tuinenburg, MD, Dirk J. Van Veldhuisen, MD, Frans Boomsma, MD, Maarten P. Van Den Berg, MD, Pieter J. De Kam, MSc, and Harry J.G.M. Crijns,

MD

large number of studies have shown that neurohumoral activation plays an important role in the A pathophysiology of congestive heart failure (CHF).

tion in a large group of patients with advanced CHF, comparing patients with AF and SR.

However, these studies have mainly focused on patients with sinus rhythm (SR) and not on patients with atrial fibrillation (AF), because patients with AF were either excluded from these studies or not separately analyzed. Yet AF is very common in patients with CHF (up to 40%), and there is reason to presume that AF has an additional effect on neurohumoral activation because AF, as such, has potentially important hemodynamic consequences in the setting of CHF.1 The present study investigates neurohumoral activa-

We studied 269 patients who participated in a neurohumoral substudy of the Prospective Randomized Ibopamine Mortality Evaluation-II (PRIME II) study, a survival study with ibopamine in moderate to severe CHF.2 Baseline data of the PRIME II study were used in this neurohumoral substudy, i.e., before any study medication was given. To eliminate effects on neurohormone values by differences in etiology of CHF, only patients with ischemic heart disease underlying CHF were included. CHF had to be characterized by symptoms at rest or a recent hospital admission for CHF, equivalent to functional class III to IV according to the New York Heart Association. Left ventricular dysfunction had to be proven by 1 of the following: (1) left ventricular ejection fraction ,0.35; (2) left ventricular internal end-diastolic diameter .60 mm; (3) left ventricular fractional shortening ,20%;

From the Department of Cardiology, Thoraxcenter, University Hospital Groningen, Groningen; and the Department of Internal Medicine I/COEUR, University Hospital Dijkzigt, Rotterdam, The Netherlands. Dr. Van Veldhuisen’s address is: Department of Cardiology, Thoraxcenter, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. Manuscript received July 9, 1997; revised manuscript received and accepted January 6, 1998. ©1998 by Excerpta Medica, Inc. All rights reserved.

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