Abstract
Background
Non-invasive approaches to investigate myocardial efficiency can help track the progression of heart failure (HF). This study evaluates the repeatability and reproducibility of 11C-acetate positron emission tomography (PET) imaging of oxidative metabolism.
Methods and results
Dynamic 11C-acetate PET scans were performed at baseline and followup (47 ± 22 days apart) in 20 patients with stable HF with reduced ejection fraction. Two observers blinded to patients’ clinical data used FlowQuant® to evaluate test–retest repeatability, as well as intra- and inter-observer reproducibility of 11C-acetate tracer uptake and clearance rates, for the measurement of myocardial oxygen consumption (MVO2), myocardial external efficiency (MEE), work metabolic index (WMI), and myocardial blood flow. Reproducibility and repeatability were evaluated using intra-class-correlation (ICC) and Bland–Altman coefficient-of-repeatability (CR). Test–retest correlations and repeatability were better for MEE and WMI compared to MVO2. All intra- and inter-observer correlations were excellent (ICC = 0.95-0.99) and the reproducibility values (CR = 3%-6%) were significantly lower than the test–retest repeatability values (22%-54%, P < 0.001). Repeatability was improved for all parameters using a newer PET–computed tomography (CT) scanner compared to older PET-only instrumentation.
Conclusion
11C-acetate PET measurements of WMI and MEE exhibited excellent test–retest repeatability and operator reproducibility. Newer PET–CT scanners may be preferred for longitudinal tracking of cardiac efficiency.
Spanish Abstract
Antecedentes
el abordaje no invasivo para investigar la eficiencia miocárdica puede ayudar en el seguimiento de la progresión de la insuficiencia cardíaca. Este estudio evalúa la repetibilidad y la reproducibilidad del estudio de metabolismo oxidativo con PET 11C-acetato.
Métodos y resultados
Se realizaron estudios de PET 11C-acetato dinámicos al inicio y durante el seguimiento (47 ± 22 días de diferencia) en 20 pacientes con insuficiencia cardíaca estable y fracción de eyección reducida. Dos observadores cegados a los datos clínicos de los pacientes utilizaron FlowQuant® para evaluar la repetibilidad de la prueba-reprueba, así como la reproducibilidad intra e interobservador de la captación de radiotrazador 11C-acetato y sus tasas de eliminación, la medición del consumo miocárdico de oxígeno (MVO2), la eficiencia externa miocardica (EEM), el índice trabajo-metabólico (ITM) y flujo sanguíneo miocárdico (FSM). La reproducibilidad y la repetibilidad se evaluaron mediante la correlación intraclase (ICC) y el coeficiente de repetibilidad (CR) de Bland-Altman. Las correlaciones Prueba-Reprueba y la repetibilidad fueron mejores para la EEM y el ITM en comparación con el MVO2. Todas las correlaciones intra e interobservador fueron excelentes (ICC = 0.95-0.99) y los valores de reproducibilidad (CR = 3-6%) fueron significativamente menores que los valores de repetibilidad prueba-reprueba (22-54%, p <0.001). La repetibilidad fue mejor para todos los parámetros utilizando un equipo PET-TC más nuevo en comparación con un equipo PET sin CT.
Conclusión
las mediciones del PET con 11C-acetato del ITM y EEM mostraron una excelente repetibilidad prueba-preprueba y reproducibilidad del operador. Los nuevos equipos PET-CT pueden ser elegidos para el seguimiento longitudinal de la eficiencia miocárdica.
Chinese Abstract
背景
采用非侵入式方法来研究心肌代谢效率可以帮助追踪心力衰竭的过程。本研究评估利用碳-11 醋酸盐为 PET 显影剂行氧化代谢成像的可重复性和可再现性。
方法和结果
纳入射血分数减低的 20 名稳定性心衰患者,对患者基线和 47±22 天随访都进行碳-11 醋酸盐 PET 扫描。为测量心肌耗氧量(MVO2), 心肌外效率(MEE), 工作代谢指标(WMI)和心肌血流量(MBF), 两名观察者按照双盲的方法利用 FlowQuant®对碳-11 醋酸盐的摄取率和清空率进行了重复性测试以及不同观察者之间的可再现性测试。采用组内相关系数(ICC)和 Bland Altman 可重复性系数(CR)分别对可再现性和可重复性进行评估。MEE 和 WMI 的两次试验系数和可重复性优于MVO2。所有观察者之间的相关系数都较好(ICC=0.95-0.99),可再现性系数的值(CR=3-6%)明显低于两次试验可重复性的值(22-54%, P<0.001)。相比于旧的只有 PET 的设备, 采用新型 PET-CT 扫描仪能够使所有参数的可再现性都有所提高。
结论
碳-11醋酸盐 PET 显像测量 WMI 和 MEE 有很好的可重复性和可再现性。新的 PET-CT 扫描仪可能更适合于心脏代谢效率的长期追踪。
French Abstract
Contexte
Les examens non invasifs de la fonction myocardique aident à suivre la progression de l’insuffisance cardiaque. Dans ce travail, nous avons évalué la répétabilité et la reproductibilité de l’étude du métabolisme oxydatif du myocarde par imagerie tomographique à positrons avec l’acétate marqué au carbone 11.
Méthodes et résultats
Une étude de base et un second examen TEP dynamique à l’ acétate marqué au carbone 11 ont été réalisés (47 ± 22 jours) chez 20 patients présentant une insuffisance cardiaque stable avec une fraction d’éjection réduite. Sans aucune connaissance des données cliniques et au moyen du programme FlowQuant®, deux observateurs ont évalué la répétabilité des TEPs de base et de leur suivi, la reproductibilité intra- et inter-observateur, l’absorption et la clearance du traceur, la mesure de la consommation d’oxygène du myocarde (MVO2), l’efficacité contractile du myocarde (MEE), l’index métabolique du travail myocardique (WMI) et le débit sanguin myocardique (MBF). La reproductibilité et la répétabilité ont été évaluées en utilisant la corrélation intra-classe (ICC) et le coefficient de répétabilité Altman (CR). Les corrélations entre les études de base et leur suivi et la répétabilité des données se sont avérées supérieures pour les paramètres MEE et WMI par rapport à MVO2. Toutes les corrélations intra- et inter-observateurs furent excellentes (ICC = 0,95-0,99). Les valeurs de reproductibilité (CR = 3-6%) furent significativement inférieures aux valeurs de répétabilité (22-54%, p <0.001). La répétabilité des paramètres mesurés s’est avérée supérieure avec un scanner TEP-TDM de nouvelle génération par rapport à l’utilisation de la TEP sans TDM
Conclusion
Les mesures réalisées dans cette étude TEP 11C-acétate montre une excellent répétabilité et reproductibilité des paramètres WMI et WMI entre les examens de base et leur suivi effectués par des opérateurs différents. Les nouveaux scanners TEP-TDM devraient être préférés pour le suivi longitudinal de la fonction cardiaque.
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Abbreviations
- LVEF:
-
Left ventricular ejection fraction (%)
- OSA:
-
Obstructive sleep apnea
- LVOT:
-
Left ventricle outflow tract
- MVO2 :
-
Myocardial oxygen consumption (mL O2·min−1·g−1 tissue)
- WMI:
-
Work metabolic index (mmHg·mL−1·m−2)
- MEE:
-
Myocardial external efficiency (unitless fraction)
- MBF:
-
Myocardial blood flow (mL blood·min−1·g−1 tissue)
- ICC:
-
Intra-class correlation coefficient
- ANOVA:
-
Analysis of variance
- SD:
-
Standard deviation
- CR:
-
Coefficient-of-repeatability (1.96 × SD)
- IQR:
-
Inter-quartile range
- NPC:
-
Non-parametric coefficient-of-repeatability (1.45 × IQR)
References
Gropler R. PET measurement of myocardial metabolism. In: cardiac PET and PET/CT imaging. New York: Springer; 2007.
Hall AB, Ziadi MC, Leech JA, Chen S-Y, Burwash IG, Renaud J, DeKemp RA, Haddad H, Mielniczuk LM, Yoshinaga K, Guo A, Chen L, Walter O, Garrard L, DaSilva JN, Floras JS, Beanlands RSB. Effects of short-term continuous positive airway pressure on myocardial sympathetic nerve function and energetics in patients with heart failure and obstructive sleep apnea: A randomized study. Circulation 2014;130:892-901.
Yoshinaga K, Burwash IG, Leech JA, Haddad H, Johnson CB, DeKemp RA, Garrard L, Chen L, Williams K, DaSilva JN, Beanlands RSB. The effects of continuous positive airway pressure on myocardial energetics in patients with heart failure and obstructive sleep apnea. J Am Coll Cardiol 2007;49:450-8.
Beanlands RS, Nahmias C, Gordon E, Coates G, DeKemp R, Firnau G, Fallen E. The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study. Circulation 2000;102:2070-5.
Ukkonen H, Beanlands RSB, Burwash IG, DeKemp RA, Nahmias C, Fallen E, Hill MRS, Tang ASL. Effect of cardiac resynchronization on myocardial efficiency and regional oxidative metabolism. Circulation 2003;107:28-31.
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015;28:1-39.
Burwash IG, Forbes AD, Sadahiro M, Verrier ED, Pearlman AS, Thomas R, Kraft C, Otto CM. Echocardiographic volume flow and stenosis severity measures with changing flow rate in aortic stenosis. Am J Physiol Circ Physiol 1993;265:H1734-43.
Klein R, Renaud JM, Ziadi MC, Thorn SL, Adler A, Beanlands RS. Intra- and inter-operator repeatability of myocardial blood flow and myocardial flow reserve measurements using rubidium-82 PET and a highly automated analysis program. J Nucl Cardiol 2010;17:600-16.
van den Hoff J, Burchert W, Börner A-R, Fricke H, Kühnel G, Meyer GJ, Otto D, Weckesser E, Wolpers H-G, Knapp WH. [1–11C] acetate as a quantitative perfusion tracer in myocardial PET. J Nucl Med 2001;42:1174-82.
Sun KT, Yeatman LA, Buxton DB, Chen K. Simultaneous measurement of myocardial oxygen consumption and blood flow using [1-carbon-11] acetate. J Nucl Med 1998;39:272.
Armbrecht JJ, Buxton DB, Schelbert HR. Validation of [1-11C] acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium. Circulation 1990;81:1594-605.
Beanlands RSB, Bach DS, Raylman R, Armstrong WF, Wilson V, Montieth M, Moore CK, Bates E, Schwaiger M. Acute effects of dobutamine on myocardial oxygen consumption and cardiac efficiency measured using carbon-11 acetate kinetics in patients with dilated cardiomyopathy. J Am Coll Cardiol 1993;22:1389-98.
Porenta G, Cherry S, Czernin J, Brunken R, Kuhle W, Hashimoto T, Schelbert HR. Noninvasive determination of myocardial blood flow, oxygen consumption and efficiency in normal humans by carbon-11 acetate positron emission tomography imaging. Eur J Nucl Med 1999;26:1465-574.
Timmer SAJ, Germans T, Götte MJW, Rüssel IK, Dijkmans PA, Lubberink M, Jurrien M, Folkert J, Lammertsma AA, Knaapen P. Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy. Eur J Nucl Med Mol Imaging 2010;37:779-88.
Hansson NH, Tolbod L, Harms J, Wiggers H, Kim WY, Hansen E, Zaremba T, Frøkiær J, Jakobsen S, Sørensen J. Evaluation of ECG-gated [11C] acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency. J Nucl Cardiol 2016;23:670-9.
Knaapen P, Germans T, Knuuti J, Paulus WJ, Dijkmans PA, Allaart CP, Lammertsma AA, Visser FC. Myocardial energetics and efficiency current status of the noninvasive approach. Circulation 2007;115:918-27.
Stolen KQ, Kemppainen J, Ukkonen H, Kalliokoski KK, Luotolahti M, Lehikoinen P, Hämäläinen H, Salo T, Airaksinen KEJ, Nuutila P. Exercise training improves biventricular oxidative metabolism and left ventricular efficiency in patients with dilated cardiomyopathy. J Am Coll Cardiol 2003;41:460-7.
Shrout PE, Fleiss JL. Intraclass correlations: Uses in assessing rater reliability. Psychol Bull 1979;86:420.
Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Int J Nurs Stud 2010;47:931-6.
Fleiss JL. Reliability of measurement. In: Design and analysis of clinical experiments. New York: Wiley; 2011.
Klein R, Ocneanu A, Renaud JM, Ziadi MC, Beanlands RSB. Consistent tracer administration profile improves test–retest repeatability of myocardial blood flow quantification with 82Rb dynamic PET imaging. J Nucl Cardiol 2016. https://doi.org/10.1007/s12350-016-0698-6.
Beanlands RS, Schwaiger M. Changes in myocardial oxygen consumption and efficiency with heart failure therapy measured by 11C acetate PET. Can J Cardiol 1995;11:293-300.
Ingwall JS, Weiss RG. Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 2004;95:135-45.
Katz AM. Cardiomyopathy of overload: A major determinant of prognosis in congestive heart failure. N Engl J Med 1990;322:100-10.
Nesterov S V, Turta O, Han C, Mäki M, Lisinen I, Tuunanen H, Knuuti J. C-11 acetate has excellent reproducibility for quantification of myocardial oxidative metabolism. Eur Hear J Cardiovasc Imaging. Oxford University Press; 2014;jeu289.
Mori Y, Manabe O, Naya M, Tomiyama Y, Yoshinaga K, Magota K, Oyama-Manabe N, Hirata K, Tsutsui H, Tamaki N. Improved spillover correction model to quantify myocardial blood flow by 11C-acetate PET: Comparison with 15O–H2O PET. Ann Nucl Med 2015;29:15-20.
Kitkungvan D, Johnson NP, Roby AE, Patel MB, Kirkeeide R, Gould KL. Routine clinical quantitative rest stress myocardial perfusion for managing coronary artery disease: Clinical relevance of test–retest variability. JACC Cardiovasc Imaging 2017;10:565-77.
Timmer SAJ, Lubberink M, Germans T, Götte MJW, Ten Berg JM, Ten Cate FJ, Van Rossum AC, Lammertsma AA, Knaapen P. Potential of [11C] acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy. J Nucl Cardiol 2010;17:264-75.
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JM Renaud (JMR) and R deKemp (RdK) receive royalties from FlowQuant® sales. JMR, RdK and RS Beanlands (RSB) are consultants for Jubilant DraxImage (JDI). RdK receives royalties from rubidium PET technology licenses. RSB is a consultant for Lantheus Medical Imaging (LMI), receives research grants from LMI and JDI; he is a Heart and Stroke Foundation of Ontario (HSFO) Career Investigator, Vered Chair of Cardiology and uOttawa Tier-1 Chair in Cardiovascular Imaging Research. L Mielniczuk is a HSFO mid-career clinician-scientist and uOttawa Tier-2 Chair in Heart Failure Research. The other authors (KY Wu, V Dinculescu, SY Chen and IG Burwash) have no conflict of interest with regards to the work. This study was funded by HSFO (T-6426, NA-7158) and Canadian Institutes of Health Research (CIF-99470) Grants.
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Wu, K.Y., Dinculescu, V., Renaud, J.M. et al. Repeatable and reproducible measurements of myocardial oxidative metabolism, blood flow and external efficiency using 11C-acetate PET. J. Nucl. Cardiol. 25, 1912–1925 (2018). https://doi.org/10.1007/s12350-018-1206-y
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DOI: https://doi.org/10.1007/s12350-018-1206-y