Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Myocardial 123I-metaiodobenzylguanidine imaging in hypertension and left ventricular hypertrophy Riccardo Liga1, Alessia Gimelli2, Paolo Marzullo2,3, Giuseppe Ambrosio4, Matteo Cameli5, Elisabetta Cerbai6, Stefano Coiro4, Michele Emdin2, Rossella Marcucci7, Doralisa Morrone1, Alberto Palazzuoli8, Anna Sonia Petronio1, Ketty Savino4, Luigi Padeletti7, Roberto Pedrinelli1 on behalf of Società Italiana di Cardiologia, Sezione Regionale Tosco-Umbra 1 Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università di Pisa, Italy. 2 Fondazione Toscana G. Monasterio, Pisa, Italy. 3 Istituto di Fisiologia Clinica, CNR, Pisa, Italy. 4 Dipartimento di Medicina,Sezione di Cardiologia e Fisiopatologia Cardiovascolare, Università di Perugia, Italy. 5 Dipartimento di Biotecnologie Mediche, Cardiologia Universitaria, Università di Siena, Italy. 6 Dipartimento di Neuroscienze, Area del Farmaco e Salute del Bambino (NEUROFARBA), Università di Firenze, Italy. 7 Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Italy. 8 Dipartimento di Medicina Interna, Università di Siena, Italy. Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology BACKGROUND 1- Sympathetic nervous system plays a pivotal role in essential hypertension and in the development of left ventricular hypertrophy. 2- Moreover, cardiac sympathetic dys-regulation has been demonstrated as a con-causal factor in the genesis and progression of congestive heart failure and ischemic heart disease 3- However, the evaluation of cardiac sympathetic nervous system has never gained a wide clinical application, remaining mostly a research tool. 4- In this context, nuclear imaging techniques allow the direct evaluation of cardiac sympathetic nervous integrity 5- This review discusses the available evidence on cardiac 123Imetaiodobenzylguanidine scintigraphy in arterial hypertension and left ventricular hypertrophy and its diagnostic and prognostic potential in congestive heart failure and ischemic heart disease Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Summary- 1 1- Most of the clinically available techniques for the evaluation of autonomic function (i.e. baroreflex sensitivity and heart rate variability) do not allow to discriminate sympathetic from parasympathetic effects 2- MIBG imaging has become a standard tool for testing sympathetic cardiac innervation in man since its uptake depends on the integrity of the sympathetic pathway and correlates with myocardial NE content 3- However, MIBG planar scintigraphy precludes the precise identification of discrete areas of impaired cardiac innervation, a problem overcome by the topographical accuracy of single-photon emission computed-tomography (SPECT) 4- Initial reports have shown the advantages of SPECT MIBG, suggesting the additive clinical role of measures of regional cardiac sympathetic activity over traditional cardiac parameters 5- These features might be of particular relevance in the evaluation of patients with adverse cardiac remodeling, such as those with LV hypertrophy, a condition possibly associated with primitive alterations of cardiac sympathetic activity Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Summary- 2 Copyright American Society of Nuclear Cardiology

Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology Summary- 3 Images of hypertensive patients undergoing combined evaluation of cardiac perfusion and sympathetic innervation by 99mTc-Tetrofosmine (upper rows) / 123I-MIBG (lower rows) CZT scans. Despite similar degrees of LV hypertrophy the two patients present different patterns of regional cardiac sympathetic activity, suggesting a complex interaction between sympathetic dysfunction and adverse cardiac remodeling Copyright American Society of Nuclear Cardiology

CONCLUSIONS & FUTURE DIRECTIONS Journal of Nuclear Cardiology | Official Journal of the American Society of Nuclear Cardiology CONCLUSIONS & FUTURE DIRECTIONS 1- Cardiac sympathetic dysfunction plays a pivotal role in essential hypertension and LV hypertrophy although several pathophysiological aspects remain in need of further investigations 2- Similarly, although autonomic dys-regulation plays a key role in the pathogenesis of ischemic heart disease and heart failure, the assessment of cardiac sympathetic tone has never gained a wide clinical application 3- Several methods for SNS evaluation in man are available and, among them, MIBG imaging represents a most valuable tool for the assessment of cardiac sympathetic function. 4- In particular SPECT MIBG imaging may be of particular value for the demonstration of subtle alteration of cardiac sympathetic activity, a condition of possible clinical value in selected populations of patients. 5- However, further studies are needed to demonstrate the added value provided by MIBG imaging in the clinical and therapeutic management of cardiac patients. Copyright American Society of Nuclear Cardiology