The aim of this study was to explore if estimates of renal function could explain variability of 123I-metaiodobenzylguanidine (123I-MIBG) assessed myocardial sympathetic activity. Furthermore estimates of renal function were compared to 123I-MIBG as predictors of cardiac death in chronic heart failure (CHF). Semi-quantitative parameters of 123I-MIBG myocardial uptake and washout were calculated using early heart/mediastinum ratio (H/M), late H/M and washout. Renal function was calculated as estimated Creatinine Clearance (e-CC) and as estimated Glomerular Filtration Rate (e-GFR). Thirty-nine patients with CHF (24 males; age: years; NYHA II/III/IV: 17/20/2; LVEF: ) were studied. Variability in any of the semi-quantitative 123I-MIBG myocardial parameters could not be explained by e-CC or e-GFR. During follow-up ( months) there were 6 cardiac deaths. Cox proportional hazard regression analysis showed that late H/M was the only independent predictor for cardiac death (Chi-square 3.2, regression coefficient: ？4.095; standard error: 2.063; hazard ratio: 0.17 [95% CI: 0.000–0.950]). Addition of estimates of renal function did not significantly change the Chi-square of the model. Semi-quantitative 123I-MIBG myocardial parameters are independent of estimates of renal function. In addition, cardiac sympathetic innervation assessed by 123I-MIBG scintigraphy seems to be superior to renal function in the prediction of cardiac death in CHF patients. 1. Introduction The myocardial sympathetic nervous system is activated in patients with chronic heart failure (CHF) and has been shown to be associated with increased mortality. Cardiac sympathetic innervation can be scintigraphically visualized by 123I-metaiodobenzylguanidine (123I-MIBG), a radiolabelled analog of noradrenalin and has been shown to be a powerful prognostic marker in patients with CHF [1, 2]. In addition to 123I-MIBG there are many other prognostic markers in patients with CHF. Estimates of renal function, for example, as measured by creatinine clearance and glomerular filtration rate (GFR), have been associated with mortality and morbidity in CHF [3–5]. Interestingly in patients with chronic renal failure myocardial washout of 123I-MIBG, as a measure of increased myocardial sympathetic activity, has been shown to be increased [6]. However, there is limited data on a direct comparison of the respective prognostic predictive value of sympathetic hyperactivity and renal dysfunction [7]. Major clinical trials aimed to assess the prognostic value of 123I-MIBG have often excluded patients with substantial
References
[1]
H. J. Verberne, L. M. Brewster, G. A. Somsen, and B. L. F. Van Eck-Smit, “Prognostic value of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: a systematic review,” European Heart Journal, vol. 29, no. 9, pp. 1147–1159, 2008.
[2]
A. F. Jacobson, R. Senior, M. D. Cerqueira et al., “Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) Study,” Journal of the American College of Cardiology, vol. 55, no. 20, pp. 2212–2221, 2010.
[3]
H. L. Hillege, D. Nitsch, M. A. Pfeffer et al., “Renal function as a predictor of outcome in a broad spectrum of patients with heart failure,” Circulation, vol. 113, no. 5, pp. 671–678, 2006.
[4]
S. Ljungman, J. Kjekshus, and K. Swedberg, “Renal function in severe congestive heart failure during treatment with Enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] trial),” American Journal of Cardiology, vol. 70, no. 4, pp. 479–487, 1992.
[5]
D. L. Dries, D. V. Exner, M. J. Domanski, B. Greenberg, and L. W. Stevenson, “The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction,” Journal of the American College of Cardiology, vol. 35, no. 3, pp. 681–689, 2000.
[6]
C. Kurata, Y. Wakabayashi, S. Shouda et al., “Enhanced cardiac clearance of iodine-123-MIBG in chronic renal failure,” Journal of Nuclear Medicine, vol. 36, no. 11, pp. 2037–2043, 1995.
[7]
T. Furuhashi and M. Moroi, “Importance of renal function on prognostic value of cardiac iodine-123 metaiodobenzylguanidine scintigraphy,” Annals of Nuclear Medicine, vol. 21, no. 1, pp. 57–63, 2007.
[8]
G. F. Dibona and U. C. Kopp, “Neural control of renal function,” Physiological Reviews, vol. 77, no. 1, pp. 75–197, 1997.
[9]
V. Kon, A. Yared, and I. Ichikawa, “Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion,” Journal of Clinical Investigation, vol. 76, no. 5, pp. 1913–1920, 1985.
[10]
G. M. Blake, V. J. Lewington, M. A. Zivanovic, and D. M. Ackery, “Glomerular filtration rate and the kinetics of 123I-metaiodobenzylguanidine,” European Journal of Nuclear Medicine, vol. 15, no. 9, pp. 618–623, 1989.
[11]
H. J. Verberne, D. O. Verschure, G. A. Somsen, B. L. F. Van Eck-Smit, and A. F. Jacobson, “Vascular time-activity variation in patients undergoing 123I-MIBG myocardial scintigraphy: implications for quantification of cardiac and mediastinal uptake,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 38, no. 6, pp. 1132–1138, 2011.
[12]
D. W. Cockcroft and M. H. Gault, “Prediction of creatinine clearance from serum creatinine,” Nephron, vol. 16, no. 1, pp. 31–41, 1976.
[13]
A. S. Levey, J. P. Bosch, J. B. Lewis, T. Greene, N. Rogers, and D. Roth, “A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation,” Annals of Internal Medicine, vol. 130, no. 6, pp. 461–470, 1999.
[14]
C. Tomson, S. Blades, R. Burden, et al., “Chronic Kidney Disease in Adults. In: UK Guidelines for Identification, Management and Referral,” 2009.
[15]
H. J. Verberne, C. Feenstra, W. M. De Jong, G. A. Somsen, B. L. F. Van Eck-Smit, and E. B. Sokole, “Influence of collimator choice and simulated clinical conditions on 123I-MIBG heart/mediastinum ratios: a phantom study,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 32, no. 9, pp. 1100–1107, 2005.
[16]
D. Agostini, I. Carrio, and H. J. Verberne, “How to use myocardial 123I-MIBG scintigraphy in chronic heart failure,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 36, no. 4, pp. 555–559, 2009.
[17]
R. C. Kline, D. P. Swanson, and D. M. Wieland, “Myocardial imaging in man with I-123 meta-iodobenzylguanidine,” Journal of Nuclear Medicine, vol. 22, no. 2, pp. 129–132, 1981.
[18]
H. J. Verberne, E. Busemann Sokole, A. F. van Moerkerken et al., “Clinical performance and radiation dosimetry of no-carrier-added vs carrier-added 123I-metaiodobenzylguanidine (MIBG) for the assessment of cardiac sympathetic nerve activity,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 4, pp. 798–807, 2008.
[19]
K. D. Aaronson, J. S. Schwartz, T. M. Chen, K. L. Wong, J. E. Goin, and D. M. Mancini, “Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation,” Circulation, vol. 95, no. 12, pp. 2660–2667, 1997.
[20]
J. M. Flack, J. D. Neaton, B. Daniels, and P. Esunge, “Ethnicity and renal disease: lessons from the multiple risk factor intervention trial and the treatment of mild hypertension study,” American Journal of Kidney Diseases, vol. 21, no. 4, pp. 31–40, 1993.
[21]
A. Al-Ahmad, W. M. Rand, G. Manjunath et al., “Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction,” Journal of the American College of Cardiology, vol. 38, no. 4, pp. 955–962, 2001.
[22]
N. G. Mahon, E. H. Blackstone, G. S. Francis, R. C. Starling, J. B. Young, and M. S. Lauer, “The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure,” Journal of the American College of Cardiology, vol. 40, no. 6, pp. 1106–1113, 2002.
[23]
M. T. Kearney, K. A. A. Fox, A. J. Lee et al., “Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure,” Journal of the American College of Cardiology, vol. 40, no. 10, pp. 1801–1808, 2002.
[24]
W. M. McClellan, W. D. Flanders, R. D. Langston, C. Jurkovitz, and R. Presley, “Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study,” Journal of the American Society of Nephrology, vol. 13, no. 7, pp. 1928–1936, 2002.
[25]
F. A. McAlister, J. Ezekowitz, M. Tonelli, and P. W. Armstrong, “Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study,” Circulation, vol. 109, no. 8, pp. 1004–1009, 2004.
[26]
D. Agostini, H. J. Verberne, W. Burchert et al., “I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 35, no. 3, pp. 535–546, 2008.
[27]
C. Opasich, L. Tavazzi, D. Lucci et al., “Comparison of one-year outcome in women versus men with chronic congestive heart failure,” American Journal of Cardiology, vol. 86, no. 3, pp. 353–357, 2000.
[28]
S. A. Hunt, W. T. Abraham, M. H. Chin et al., “ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the,” Circulation., vol. 112, no. 12, pp. e154–e235, 2005.
[29]
K. Dickstein, A. Cohen-Solal, G. Filippatos et al., “ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008,” European Heart Journal, vol. 29, no. 19, pp. 2388–2442, 2008.
