Abstract
Purpose
Although the benefits of treatment with angiotensin-converting enzyme (ACE) inhibitors and beta-blockers are well known, no method has as yet been established to predict the efficacy of drug therapy. This study tested whether cardiac 123I-metaiodobenzylguanidine (MIBG) activity is of prognostic value and can predict the improvement in heart failure patients resulting from treatment with ACE inhibitors and/or beta-blockers.
Methods
Following quantification of the heart-to-mediastinum ratio (HMR) of MIBG activity, 88 patients with heart failure who were treated with ACE inhibitors and/or beta-blockers (treated group) and 79 patients with heart failure who were treated conventionally without the aforementioned agents, and who served as controls, were followed up for 43 months with a primary endpoint of cardiac death.
Results
The treated group had a significantly lower prevalence of cardiac death and a significantly lower mortality at 5 years compared with the control group (15% vs 37% and 21% vs 42%, p<0.05, respectively). Multivariate analysis revealed that significant predictors were HMR, age, nitrate use and ventricular tachycardia for the treated group, and HMR, nitrate use and NYHA class for the control group. The drug treatment significantly reduced mortality from 36% to 12% when HMR was 1.53 or more and from 53% to 37% when HMR was less than 1.53. The reduction in risk of mortality within 5 years in patients without a severe MIBG defect (67%) was twice that in patients with such a defect (32%) (p<0.05).
Conclusion
The reduction in mortality risk achieved by using ACE inhibitors and/or beta-blockers is associated with the severity of impairment of cardiac MIBG uptake. Cardiac MIBG activity can consequently be of long-term prognostic value in predicting the effectiveness of such treatment in patients with heart failure.
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References
Zipes DP. Sympathetic stimulation and arrhythmias. N Engl J Med 1991;325:656–7.
Kaye D, Lefkovits J, Jennings G, et al. Adverse consequence of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol 1995;26:1257–63.
Merlet P, Valette H, Dubois-Rande JL, et al. Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med 1992;33:471–7.
Nakata T, Miyamoto K, Doi A, et al. Cardiac death prediction and impaired cardiac sympathetic innervation assessed by metaiodobenzylguanidine in patients with failing and non-failing hearts. J Nucl Cardiol 1998;5:579–90.
Cohen-Solal A, Esanu Y, Logeart D, et al. Cardiac metaiodobenzylguanidine uptake in patients with moderate chronic heart failure: relationship with peak oxygen uptake and prognosis. J Am Coll Cardiol 1999;33:759–66.
Wakabayashi T, Nakata T, Hashimoto A, et al. Assessment of underlying etiology and cardiac sympathetic innervation to identify patients at high risk of cardiac death. J Nucl Med 2001;42:1757–67.
Pritchett AM, Redfield MM. Beta-blockers: new standard therapy for heart failure. Mayo Clin Proc 2002;77:839–45.
Hunt HA, Baker DW, Chin MH, et al. American College of Cardiology/American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Circulation 2001;104:2996–3007.
Pitt B, Poole-Wilson PA, Sega R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—losartan heart failure survival study ELITE II. Lancet 2000;355:1582–7.
Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker Valsartan in chronic heart failure. N Engl J Med 2001;345:1667–75.
Takeishi Y, Atsumi H, Fujiwara S, et al. ACE inhibition reduced cardiac iodine-123-MIBG release in heart failure. J Nucl Med 1997;38:1085–9.
Merlet P, Pouillart F, Dubois-Rande JL, et al. Sympathetic nerve alterations assessed with 123I-MIBG in the failing human heart. J Nucl Med 1999;40:224–31.
Sakata K, Shirotani M, Yoshida H, et al. Physiological fluctuation of the human left ventricle sympathetic nervous system assessed by iodine-123-MIBG. J Nucl Med 1998;39:1667–71.
Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986;314:1547–52.
Nakata T, Wakabayashi T, Kyuma M, et al. Prognostic implications of an initial loss of cardiac metaiodobenzylguanidine uptake and diabetes mellitus in patients with left ventricular dysfunction. J Card Fail 2003;9:113–21.
Inoue H, Zipes DP. Result of sympathetic denervation in the canine heart: supersensitivity that may be arrhythmogenic. Circulation 1987;75:877–87.
Barron HV, Lesh MD. Autonomic nervous system and sudden cardiac death. J Am Coll Cardiol 1996;27:1053–60.
Mitrani RD, Klein LS, Miles WM, et al. Regional cardiac sympathetic denervation in patients with ventricular tachycardia in the absence of coronary artery disease. J Am Coll Cardiol 1993;22:1344–53.
Nakata T, Nagao K, Tsuchihashi K, et al. Regional cardiac sympathetic nerve dysfunction and the diagnostic efficacy of metaiodobenzylguanidine tomography in stable coronary artery disease. Am J Cardiol 1996;78:292–7.
McGhie AI, Corbett JR, Akers MS, et al. Regional cardiac adrenergic function using I-123 metaiodobenzylguanidine tomographic imaging after myocardial infarction. Am J Cardiol 1991;67:236–42.
Tobes MC, Jaques S, Wieland DM, et al. Effect of uptake-1 inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine. J Nucl Med 1985;26:897–907.
Miyazaki T, Zipes DP. Presynaptic modulation of efferent sympathetic and vagal neurotransmission in canine heart by hypoxia, high K+, low pH, and adenosine. Possible relevance to ischemia-induced denervation. Circ Res 1990;66:289–301.
Rabinovitch MA, Rose CP, Schwab AJ, et al. A method of dynamic analysis of iodine-123-metaiodobenzylguanidine scintigrams in cardiac mechanical overload hypertrophy and failure. J Nucl Med 1993;34:589–600.
Eisenhofer G, Friberg P, Rundqvist B, et al. Cardiac sympathetic nerve function in congestive heart failure. Circulation 1996;93:1667–76.
Arora R, Ferrick KJ, Nakata T, et al. 123I-metaiodobenzylguanidine (MIBG) imaging and heart rate variability analysis to predict the need for implantable cardioverter defibrillator. J Nucl Cardiol 2003;10:121–31.
Nagahara D, Nakata T, Uno K, et al. Cardiac metaiodobenzylguanidine activity in combination with cardiac function or plasma brain natriuretic level can predict the need for an implantable cardioverter defibrillator. Circulation 2003;108(Suppl):IV-544 [Abstract].
Acknowledgements
The authors are grateful to the staff of the Cardiology and Nuclear Medicine Departments, Sapporo Medical University School of Medicine, Sapporo Jun-kanki Clinic, Hokkaido Cardiovascular Hospital, and Sapporo Social Insurance General Hospital, Sapporo, Japan for their cooperation in the multicentre clinical study.
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Nakata, T., Wakabayashi, T., Kyuma, M. et al. Cardiac metaiodobenzylguanidine activity can predict the long-term efficacy of angiotensin-converting enzyme inhibitors and/or beta-adrenoceptor blockers in patients with heart failure. Eur J Nucl Med Mol Imaging 32, 186–194 (2005). https://doi.org/10.1007/s00259-004-1624-8
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DOI: https://doi.org/10.1007/s00259-004-1624-8