Europace Advance Access originally published online on May 21, 2008
Europace 2008 10(7):892-893; doi:10.1093/europace/eun134
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LETTERS TO THE EDITOR
Improvement in cardiac sympathetic nerve activity in responders to resynchronization therapy: reply
University Hospital, Geneva
Switzerland
Tel: +41 22 372 72 01
Fax: +41 22 372 72 29
E-mail address: haran.burri{at}hcuge.ch
Department of Cardiology, Onze Lieve
Vrouwe Gasthuis, Amsterdam
The Netherlands
Department of Nuclear Medicine, Academic
Medical Center, University of Amsterdam
The Netherlands
We thank Dr Gallego Page for his comments, but nevertheless respectfully disagree with them. It is indeed important that the physiology and the kinetics of 123-I-metaiodobenzylguanidine (123I-MIBG) be properly understood, in order to avoid misinterpretation of results. We wish to briefly expand upon the use of 123I-MIBG in assessing cardiac sympathetic nerve function (which we felt were not relevant to our main article, but are now necessary). 123-I-metaiodobenzylguanidine is an analogue of norepinephrine that is internalized by presynaptic nerve endings of post-ganglionic neuronal cells by the vesicular uptake-1 system (the non-neuronal extravesicular uptake referred by Dr Gallego Page is negligible in humans1
). Anterior planar scintigraphic images are obtained 15 min (early) and 4 h (late) after 123I-MIBG injection, with regions of interest for measuring mean count density drawn over the heart (H) and the mediastinum (M), as previously described by our group.2 The commonly used indices are the H/M ratio (specific/non-specific activity) and myocardial washout. Myocardial 123I-MIBG washout is calculated as (H/Mearly–H/Mlate)/H/Mearly. The early H/M is believed to reflect the integrity of presynaptic nerve terminals and vesicular uptake-1 function.1 The late H/M reflects the neuronal function involving uptake as well as release by the nerve terminal storage vesicles. Therefore, a decrease in late H/M activity (leading to increased washout) is believed to result from the release of 123I-MIBG due to increased sympathetic nerve activity.1 This is consistent with the observed increase in 123I-MIBG washout in patients with evidence of increased sympathetic activity studied by heart rate variability.3 Conversely, β-blockers (that reduce sympathetic activity) have been shown to decrease 123I-MIBG washout.4 Increased washout has also been associated with worse prognosis in heart failure,5 which is consistent with the detrimental effects of sympathetic hyperactivity in these patients.
The statements made by Dr Gallego-Page are fundamentally wrong and in contradiction with widely accepted concepts. First, he wrongly states that a decrease in 123I-MIBG washout implies an increase in sympathetic activity. Secondly, he is misled in believing that increased sympathetic activity is beneficial in heart failure patients.
In conclusion, we maintain that our study, showing reduced washout of 123I-MIBG in responders to cardiac resynchronization therapy, reflects reduced (i.e. improved) cardiac sympathetic activity, which is perfectly in line with previous findings.6
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[1] Dae MW, De Marco T, Botvinick EH, O'Connell JW, Hattner RS, Huberty JP, et al. Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts—implications for clinical studies. J Nucl Med (1992) 33:1444–50.
[2] Somsen GA, Verberne HJ, Fleury E, Righetti A. Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals: implications for clinical studies. J Nucl Cardiol (2004) 11:126–33.[CrossRef][Web of Science][Medline]
[3] Somsen GA, Szabo BM, van Veldhuisen DJ, de Milliano PA, de Groot CA, Lie KI. Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure. Am Heart J (1997) 134:456–8.[CrossRef][Web of Science][Medline]
[4] Toyama T, Aihara Y, Iwasaki T, Hasegawa A, Suzuki T, Nagai R, et al. Cardiac sympathetic activity estimated by 123I-MIBG myocardial imaging in patients with dilated cardiomyopathy after {beta}-blocker or angiotensin-converting enzyme inhibitor therapy. J Nucl Med (1999) 40:217–23.
[5] Verberne HJ, Brewster LM, Somsen GA, van Eck-Smit BLF. Prognostic value of myocardial 123I-metaiodobenzylguanidine (MIBG) parameters in patients with heart failure: a systematic review. Eur Heart J (2008) doi: 10.1093/eurheartj/ehn113.
[6] Erol-Yilmaz A, Verbene HJ, Schrama TA, Hrudova J, De Winter RJ, Van Eck-Smit BLF, et al. Cardiac resynchronization induces favorable neurohumoral changes. Pacing Clin Electrophysiol (2005) 28:304–10.[CrossRef][Medline]
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