Usefulness of contrast echocardiography to improve the feasibility and accuracy of automated measurements of left ventricular volume and ejection fraction in patients with coronary artery disease

12. Stern R, Arntz HR. Prehospital thrombolysis in acute myocardial infarction.

Eur J Emerg Med 1998;5:471–479. 13. Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA, Giambartolomei A, Brodie BR, Madonna O, Eijgelshoven M, Lansky AJ, O’Neil WW, Morice MC. Coronary angioplasty with or without stent implantation for acute myocardial infarction. N Engl J Med 1999;341:1949 –1956. 14. Le May MR, Labinaz M, Davies RF, Marquis JF, Larame´ e LA, O’Brien ER, Williams WL, Beanlands RS, Nichol G, Higgison LA. Stenting versus Thrombolysis in Acute myocardial infarction Trial (STAT). J Am Coll Cardiol 2001; 37:985–991. 15. Scho¨ mig A, Kastrati A, Dirschinger J, Mehilli J, Schricke U, Pache J, Martinoff S, Neumann FJ, Schwaiger M. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. N Engl J Med 2000;343:385–391. 16. Bonnefoy E, Lapostolle F, Leizorovicz A, Steg G, McFadden EP, Dubien PY, Cattan S, Boullenger E, Machecourt J, Lacroute JM, et al, for the CAPTIM Study Group. Primary angioplasty versus prehospital thrombolysis in the acute myocardial infarction: a randomized study. Lancet 2002;360:825–829. 17. Kastrati A, Mehilli J, Dirchinger J, Schricke U, Neverve J, Pache J, Martinoff

S, Neumann FJ, Nekolla S, Blasini R, et al, for the Stent versus Thrombolysis for Occluded Arteries in Patients With Acute Myocardial Infarction (STOPAMI-2) Study Investigators. Myocardial salvage after coronary stenting plus abciximab versus fibrinolysis plus abciximab in patients with acute myocardial infarction: a randomised trial. Lancet 2002;359:920 –925. 18. Hochman JS, Sleeper LA, Webb JG, Sanborn TA, White HD, Talley JD, Buller CE, Jacobs AK, Slater JN, Col J, et al, for the SHOCK Investigators. Early revascularisation in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 1999;341:625–634. 19. Ryan TJ, Antman EM, Brooks NH, Califf RM, Hillis LD, Hiratzka LF, Rapaport E, Riegel B, Russel RO, Smith EE, et al. Update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1999;34:890 –911. 20. Van de Werf F, Ardissino D, Betriu A, Cokkinos DV, Falk E, Fox KAA, Julian D, Lengyel M, Neumann FJ, Ruzyllo W, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2003;24:28 –66.

Usefulness of Contrast Echocardiography to Improve the Feasibility and Accuracy of Automated Measurements of Left Ventricular Volume and Ejection Fraction in Patients With Coronary Artery Disease Shota Fukuda, MD, Takeshi Hozumi, MD, Hiroyuki Watanabe, MD, Takashi Muro, Koji Abo, RMS, Minoru Yoshiyama, MD, Kazuhide Takeuchi, MD, and Junichi Yoshikawa, MD ransthoracic echocardiography is the widely acceptable method for assessment of left ventricular T (LV) function in routine clinical practice. An automatic boundary detection (ABD) system was developed in expectation of providing beat-to-beat and realtime measurements of LV volume and ejection fraction (EF) automatically, using an automated border detection technique based on ultrasound backscatter.1–3 Even with harmonic imaging, however, the major limitations of this system are its low feasibility and tendency to underestimate absolute LV volume.3–5 Contrast echocardiography, combined with harmonic imaging and ultrasound contrast agents, has improved LV endocardial border delineation6,7 and the accuracy of manual tracing measurements of LV volume and EF.8 –10 This study evaluates the feasibility and accuracy of the ABD system in combination with contrast echocardiography for the measurements of LV volume and EF. •••

The study population consisted of 46 consecutive patients with coronary artery disease who were scheduled for transthoracic echocardiography to evaluate LV function. Patients without sinus rhythm were excluded from this study. For the measurements by conventional ABD From the Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, Osaka, Japan. Dr. Hozumi’s address is: Department of Internal Medicine and Cardiology, Osaka City University School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. E-mail: [email protected]. Manuscript received October 25, 2002; revised manuscript received and accepted March 19, 2003. ©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 July 1, 2003

MD,

method, the left ventricle was imaged in apical 4-chamber view using a Sonos 5500 (Philips Medical Systems, Andover, Massachusetts). The mean transmitted frequency was 2.0 MHz and the mean received frequency was 4.0 MHz. After the gain settings were optimized, the acoustic quantification system displayed a border following the detected cavity wall interface around the LV cavity.11 The values for LV measurements, such as end-diastolic volume, end-systolic volume, and EF, were averaged over 5 cardiac cycles. For contrast-enhanced ABD, we measured the same echocardiographic variables in the same manner during infusion of a contrast agent, Levovist (at a rate of 600 mg/min) (Shering AG, Berlin, Germany). We used the ultraharmonic imaging mode, in which the mean transmitting frequency was 1.3 MHz, and the mean receiving frequency was 3.6 MHz (Figure 1). Finally, the apical 4-chamber view was recorded during infusion of a contrast agent (Levovist at a rate of 600 mg/min), and digital loops were stored. LV volumes and EF were obtained by using the methods of disks after manual tracing the LV endocardial border.12 According to previous studies, “success” in both of the ABD methods was defined as detection of ⬎75% of the endocardial border.1,2 These 3 different kinds of measurements were performed separately by different investigators who did not know other patient data. Continuous values were expressed as mean ⫾ SD. Correlations were obtained using least-squares fit linear regression analysis. Differences were considered significant at p ⬍0.05. Differences were also com0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00471-5

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FIGURE 1. Contrast-enhanced apical 4-chamber view with ABD system.

pared with the mean values obtained by ABD and manual tracing by the Bland-Altman method.13 Interobserver variability was obtained by analysis of 23 random patients by 2 independent blinded observers. Intraobserver variability was performed by the analysis of the other 23 patients by the same observer at 2 different time points. The results were analyzed by the Bland-Altman method.13 Contrast enhancement increased the success rate of ABD measurements from 80% (37 of 46 patients) to 96% (44 of 46 patients) (p ⬍0.05). Two patients did not complete the conventional and contrast ABD studies. Another 7 patients were excluded from the conventional ABD alone test because their tests were incomplete. Correlations between LV volume measurements by conventional ABD and those by the manual tracing method were excellent (r ⫽ 0.83 for end-diastolic volume, r ⫽ 0.93 for end-systolic volume, and r ⫽ 0.89 for EF) (Figure 2). Correlations between LV measurements by contrast ABD and those by the manual tracing method were also excellent (r ⫽ 0.83 for end-diastolic volume, r ⫽ 0.96 for end-systolic volume, and r ⫽ 0.80 for EF) (Figure 2). For the measurement of EF in comparison with the manual tracing method, systemic bias and limits of agreement were small enough in conventional and contrast ABD (1.3% and 0.4%, ⫺3.8 to 6.4%, and ⫺7.0% to 7.8%, respectively) (Figure 3). For the LV volume measurements, however, systemic biases in conventional ABD (⫺10.3 ml for end-diastolic volume and ⫺3.5 ml for end-systolic volume) were not at a negligible level, whereas the measurements in contrast ABD were negligible (1.2 ml for end-diastolic volume and 0.7 ml for end-systolic volume). The limits of agreement between manual tracing and conventional ABD were greater than those between manual tracing and contrast ABD (conventional ABD vs contrast ABD, ⫺26.3 to 5.7 ml vs ⫺14.8 to 16.2 ml for end-diastolic volume and ⫺11.7 to 4.7 ml vs ⫺6.0 to 7.4 ml for end-systolic volume) (Figure 3). Observer variabilities were similar be72 THE AMERICAN JOURNAL OF CARDIOLOGY姞

VOL. 92

FIGURE 2. Regression plots showing correlation between manual tracing (x axis) and ABD measurement (y axis) without (circles) and with (triangles) contrast infusion for end-diastolic volume (A), end-systolic volume (B), and EF (C). Solid line, the regression lines between manual tracing and ABD measurements without (thin line) and with (thick line) contrast infusion. Dashed line, the identity line.

tween conventional and contrast ABD measurements for end-diastolic volume, end-systolic volume, and EF (Table 1). •••

The present study showed that contrast echocardiography, in combination with harmonic imaging and intravenous contrast injection, improves the feasibility and accuracy of the ABD system in the assessment of LV volume and EF. The ABD system, which is based on ultrasonic backscatter analysis, produces an on-line continuous display of the endocardial border, enabling rapid beat-to-beat measurements of LV cavity areas, volume, and EF. However, the ABD system has not been used widely enough for clinical purposes because of its low feasibility and tendency to underestimate LV volume.3–5 This study demonstrated the higher feasibility JULY 1, 2003

TABLE 1 Intra- and Interobserver Variabilities in Automatic Boundary Detection (ABD) Measurements End-diastolic Volume Intraobserver variability Conventional ABD Contrast ABD Interobserver variability Conventional ABD Contrast ABD

End-systolic Volume

EF

4% 4%

5% 7%

4% 4%

10% 5%

13% 9%

4% 3%

Data are presented mean percentages.

FIGURE 3. Scatterplot of the differences in end-diastolic volume (A), end-systolic volume (B), and EF (C) between manual tracing and ABD without (circles) contrast infusion, and between manual tracing and ABD with (triangles) contrast infusion, showing the mean difference and the limits of agreement as measured by manual tracing and ABD with contrast infusion (dashed lines).

(96%) of using the ABD system in nonselected patients, compared with previous studies (72% to 86%).1–3 This rate of success obtained in this study can be attributed to several factors. By using ultraharmonic imaging and selectively receiving third-harmonic signals, it is possible to detect ultrasound energy emanating specifically from the microbubbles. The increased signal-to-noise ratio afforded by thirdharmonic imaging resulted in a greater success rate of LV cavity opacification. Moreover, in comparison with a bolus injection, continuous infusion of microbubbles may contribute to providing the time and leisure to optimize the device settings and abolish basal segment attenuation.14 The ABD system, combined with contrast echocardiography, also successfully prevented the underestimation of LV volume, which is inherent in the con-

ventional ABD system, even in patients with poor endocardial definition. Intravenous echocardiographic contrast agents capable of producing LV cavity opacification can be useful in delineating the endocardial border6,7 and are able to ascertain the effect of this phenomenon on the calculation of LV volume and EF.8 –10 The mechanism for such improvement with contrast injection is directly related to ventricular anatomy. The LV endocardial border is obscured by true myocardial structures, trabeculations, irregularities, and papillary muscles, which, unlike artifacts and side lobes, are not eliminated by harmonic imaging without contrast infusion.15 In the present study, the accuracy for the assessment of LV volume by the ABD system was markedly improved with contrast infusion. The present study has several limitations. The study population was relatively small, and the results of this study should be confirmed in a much larger population. The LV volumes and EF were measured by a single plane-derived ABD algorithm in this study. Three-dimensional methods may have the potential to provide a more accurate measurement of LV volume, especially in patients with regional wall motion abnormalities. Contrast echocardiography improves the feasibility and accuracy of automated measurement of LV volume and EF with the ABD system. Contrast echocardiography improves the feasibility and accuracy of automated measurement of left ventricular volume and ejection fraction in patients with coronary artery disease. 1. Perez JE, Waggoner AD, Barzilai B, Melton HE Jr, Miller JG, Sobel BE.

On-line assessment of ventricular function by automatic boundary detection and ultrasonic backscatter imaging. J Am Coll Cardiol 1992;19:313–320. 2. Yvorchuk KJ, Davies RA, Chan KL. Measurement of left ventricular ejection fraction by acoustic quantification and comparison with radionuclide angiography. Am J Cardiol 1994;74:1052–1056. 3. Tsujita-Kuroda Y, Zhang G, Sumita Y, Hirooka K, Hanatani A, Nakatani S, Yasumura Y, Miyatake K, Yamagishi M. Validity and reproducibility of echocardiographic measurement of left ventricular ejection fraction by acoustic quantification with tissue harmonic imaging technique. J Am Soc Echocardiogr 2000;13:300 –305. 4. Zhang GC, Nakamura K, Tsukada T, Nakatani S, Uematsu M, Tanaka N, Masuda Y, Yasumura Y, Miyatake K, Yamagishi M. Impact of presence of abnormal wall motion on echocardiographic determination of left ventricular function with automated boundary detection technique: re-evaluation. Int J Card Imaging 1998;14:253–259. 5. Jiang L, Morrissey R, Handschumacher MD, Vazquez de Prada JA, He J,

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Picard MH, Weyman AE, Levine RA. Quantitative three-dimensional reconstruction of left ventricular volume with complete borders detected by acoustic quantification underestimates volume. Am Heart J 1996;131:553–559. 6. Lindner JR, Dent JM, Moos SP, Jayaweera AR, Kaul S. Enhancement of left ventricular cavity opacification by harmonic imaging after venous injection of albunex. Am J Cardiol 1997;79:1657–1662. 7. Kasprzak JD, Paelinck B, Ten Cate FJ, Vletter WB, de Jong N, Poldermans D, Elhendy A, Bouakaz A, Roelandt JR. Comparison of native and contrast-enhanced harmonic echocardiography for visualization of left ventricular endocardial border. Am J Cardiol 1999;83:211–217. 8. Thomson HL, Basmadjian AJ, Rainbird AJ, Razavi M, Avierinos JF, Pellikka PA, Bailey KR, Breen JF, Enriquez-Sarano M. Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements: a prospective, randomly assigned, blinded study. J Am Coll Cardiol 2001;38:867–875. 9. Lafitte S, Dos Santos P, Kerouani A, Robhan T, Roudaut R. Improved reliability for echocardiographic measurement of left ventricular volume using harmonic power imaging mode combined with contrast agent. Am J Cardiol 2000;85:1234 –1238. 10. Nahar T, Croft L, Shapiro R, Fruchtman S, Diamond J, Henzlova M, Machac J, Buckley S, Goldman ME. Comparison of four echocardiographic techniques

for measuring left ventricular ejection fraction. Am J Cardiol 2000;86:1358 – 1362. 11. Bednarz JE, Marcus RH, Lang RM. Technical guidelines for performing automated border detection studies. J Am Soc Echocardiogr 1995;8:293–305. 12. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2: 358 –367. 13. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–310. 14. Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Basis for detection of stenosis using venous administration of microbubbles during myocardial contrast echocardiography: bolus or continuous infusion? J Am Coll Cardiol 1998;32:252–260. 15. Schnittger I, Fitzgerald PJ, Daughters GT, Ingels NB, Kantrowitz NE, Schwarzkopf A, Mead CW, Popp RL. Limitations of comparing left ventricular volumes by two dimensional echocardiography, myocardial markers and cineangiography. Am J Cardiol 1982;50:512–519.

Value of Postoperative Blood Glucose in Predicting Complications and Length of Stay After Coronary Artery Bypass Grafting Lisa H. Fish,

MD,

Todd W. Weaver,

PhD,

Amy L. Moore,

oncern about frequent postoperative hyperglycemia in patients who undergo coronary artery byC pass grafting (CABG) has led to the initiation of a quality improvement protocol to evaluate outcomes in this patient population. Prior studies have addressed the issue of increased wound infections in patients with diabetes mellitus,1–3 but the prevalence of diabetes in this population and the effect of hyperglycemia on postoperative complications, including length of stay, readmission, or death, has not been evaluated. •••

A consecutive population of patients who underwent cardiovascular surgery between December 1998 and November 1999 was identified through a retrospective chart review. Exclusion criteria included valve surgeries and other non-CABG procedures. Auditing continued until 200 patients who underwent CABG were identified. A sample size of 200 patients was determined necessary to detect a twofold increased risk of complications in patients with previously diagnosed and suspected diabetes versus patients without diabetes using a 1-sided test with 80% power and a significance level of 0.05. The quality improvement protocol was reviewed and approved by the institutional review board of Methodist Hospital, Park Nicollet Health System. Study variables included age, gender, height, weight, body mass index, previous diagnosis of diaFrom the International Diabetes Center, and Hennepin County Medical Center, Minneapolis, Minnesota. Dr. Fish’s address is: 3800 Park Nicollet Blvd., Minneapolis, Minnesota 55416-2699. E-mail: [email protected]. This study was funded by an unrestricted educational research grant provided by Pfizer, Inc., New York, New York. Manuscript received December 11, 2002; revised manuscript received and accepted March 25, 2003.

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©2003 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 92 July 1, 2003

MS,

and Laraine G. Steel,

MS

betes, preoperative HbA1c (BioRad Variant, reference range 4.2% to 6.0%), intraoperative glucose ranges, immediate postoperative blood glucose, day 3 postoperative fasting blood glucose, dates of surgery and transfer out of intensive care, surgeon, number of vessels bypassed, length of time in surgery, and postoperative atrial fibrillation. Complications were defined as length of stay of ⬎9 days (upper decile), readmission within 60 days, or death. Patients meeting ⱖ1 of these criteria were considered to have a single complication. Of the 200 patients who underwent CABG in this cohort, 63 (31.5%) had previously diagnosed diabetes (11 with type 1 and 52 with type 2). An additional 43 patients (21.5%) were suspected to have diabetes as defined by a preoperative HbA1c ⬎6.0% (n ⫽ 36), or a 3-day fasting glucose level ⬎125 mg/dl (6.9 mm/L) when preoperative HbA1c was unavailable (n ⫽ 7). Descriptive characteristics of the study population, including demographics, anthropomorphic measures, as well as diabetes, surgical, and postoperative variables are listed in Table 1. With the exception of body mass index, preoperative HbA1c, and postoperative and day 3 fasting blood glucose levels, the patients with diabetes did not differ significantly from those without diabetes. Similarly, the suspected diabetes group only differed from the group without diabetes in glycemic-related variables, with anthropomorphic and diabetes mean values that were intermediary between the group with diagnosed diabetes and the group without diabetes. As Table 2 demonstrates, 42 of the 200 study subjects (21%) developed complications, with most of these patients (29 of 42, 69%) having diagnosed (n ⫽ 19) or suspected diabetes (n ⫽ 10). Patients with immediate postoperative glucose levels ⬍200 mg/dl 0002-9149/03/$–see front matter doi:10.1016/S0002-9149(03)00472-7