Europace Advance Access originally published online on May 21, 2008
Europace 2008 10(7):892; doi:10.1093/europace/eun133
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LETTERS TO THE EDITOR
Improvement in cardiac sympathetic nerve activity in responders to resynchronization therapy
Department of Cardiology
Virgen de la luz Hospital
Spain
Tel: +34 969219229
E-mail address: jgallegop{at}secardiologia.es
I am writing in connection with the article you published recently by Burri et al.1
in which cardiac sympathetic nerve activity is studied by 123-I-metaiodobenzylguanidine (MIBG) scintigraphy in patients undergoing cardiac resynchronization therapy (CRT). I feel obliged to make some observations that I believe are important.
123-I-metaiodobenzylguanidine is a radioiodinated analogue of guanetidin which has been widely accepted since Wieland's work2 as a tracker for sympathetic innervation. 123-I-metaiodobenzylguanidine is taken up and stored by the adrenergic nerves, using the same mechanism as for transporting noradrenalin in the membrane. Once inside the nerve cell, it accumulates as intraneuronal granules and is released when the nerve is stimulated. However, in MIBG cardiac scintigraphy, it is usual to establish an early heart/mediastinum (H/M) index (15 min) and a late one (180–240 min), because the MIBG also has a fast extravesicular uptake that has an effect on the early stages of the examination. The intravesicular uptake is more stable and remains constant at 3–6 h after injection. It is quantified by the late H/M index and is a more reliable indicator of sympathetic activity. In a sequential study, MIBG washout (W) can be calculated by the formula: %W = (Early H/M index–Late H/M index) x 100/Early H/M index. By this formula, the higher the late index (implying greater sympathetic neuron activity) the lesser the washout. To take an example, in one group of 10 healthy individuals, the H/M indices were high and the washout low (average 16.8 ± 14.9).3 While in patients presenting with advanced cardiac insufficiency and a drop in sympathetic activity, the H/M indices were low and the washout high; furthermore, higher values were a sign of a poor prognosis.4–6
123-I-metaiodobenzylguanidine scintigraphy has made it possible to verify that the sympathetic activity is reduced in cases of chronic insufficiency,4–6 and likewise in ‘Tako-tsubo’ syndrome.7 It has also been used as a marker of cardiac post-transplant reinnervation.3,8
In the article by Burri et al.,1 there is a false idea that leads to the authors' wrongly interpreting the results and drawing inappropriate conclusions. In the Material and Methods section, they say, ‘a decrease in washout reflects a reduction in sympathetic activity’, but we have explained why it is just the reverse. The reduced washout observed in responders to resynchronization therapy reflects an increase in sympathetic activity, and this agrees with the results of similar studies that Burri et al. actually cite, for example, the one by Erol-Yilmaz,9 where an increase in the late H/M index is reported along with a reduction in washout—two findings that suggest an improvement (increase) of sympathetic activity. Similar results are to be found in the study by Nishioka et al.10; there too washout decreases and H/M indexes increase in responders, and the combination likewise reflects an increase in sympathetic activity along with an improved degree of cardiac insufficiency.
To sum up, the study by Burri et al.1 shows that the data from CRT responders attest to an increase in cardiac sympathetic activity, the contrary of what the article concludes. It is an unfortunate example of how insufficient acquaintance with a methodology, or a bad application of it, can lead to misinterpreted results and false conclusions.
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[1] Burri H, Sunthorn H, Soasen A, Fleury E, Stettler C, Shah D, et al. Improvement in cardiac cardiac sympathetic nerve activity in responders to resynchronization therapy. Europace (2008) 10:374–8.
[2] Wieland DM, Bronwn LE, Rogers WL, Worthington KC, Wu JL, Clinthorne NH, et al. Myocardial imaging with a radiodinated norepinephrine storage analog. J Nucl Med (1981) 22:22–31.
[3] Gallego-Page JC, Segovia J, Alonso-Pulpón L, Alonso-Rodríguez M, Salas C, Ortíz-Berrocal J. Re-innervation after heart transplantation: a multidisciplinary study. J Heart Lung Transplant (2004) 23:674–82.[CrossRef][Web of Science][Medline]
[4] Kioka H, Yamada T, Mine T, Morita T, Tsukamoto Y, Tamaki S, et al. Prediction of sudden death in patients with mild-to-moderate chronic heart failure by using cardiac iodine-123 metaiodobenzylguanidine imaging. Heart (2007) 93:1213–8.
[5] Yamada T, Shimonagata T, Fukunami M, Kumagai K, Ogita H, Hirata A, et al. Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: a prospective study. J Am Coll Cardiol (2003) 41:231–8.
[6] Gerson MC, McGuire N, Wagoner LE. Sympathetic nervous system function as measured by I-123 metaiodobenzylguanidine predicts transplant-free survival in heart failure patients with idiopatic dilated cardiomyopathy. J Card Fail (2003) 9:384–91.[CrossRef][Web of Science][Medline]
[7] Gallego Page JC, Lafuente Gormaz C, Domínguez Rodríguez P, Cháfer Rudilla M, Fuentes Manso R, Aguilera Saldaña M. Transient ventricular dysfunction after emotional stress. Rev Esp Cardiol (2004) 57:1124–7.[CrossRef][Web of Science][Medline]
[8] Gallego Page JC, Segovia Cubero J, Alonso Pulpón LA, Alonso Rodríguez M, Salas C, Ortiz-Berrocal J. Angina pectoris in the heart transplant recipient: evidence of reinnervation. Rev Esp Cardiol (2001) 54:799–802.[Web of Science][Medline]
[9] Erol-Yilmaz A, Verberne HJ, Schrama TA, Hrudova J, De Winter RJ, Van Eck-Smit BL, et al. Cardiac resynchronization induces favorable neurohumoral changes. Pacing Clin Electrophysiol (2005) 28:304–10.[CrossRef][Medline]
[10] Nishioka SA, Martinelli Filho M, Brandão SC, Giorgi MC, Vieira ML, Costa R, et al. Cardiac sympathetic activity pre and post resynchronization therapy evaluated by 123I-MIBG myocardial scintigraphy. J Nucl Cardiol (2007) 14:852–9.[CrossRef][Web of Science][Medline]
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