Advertisement

Renal iodine123-metaiodobenzylguanidine scintigraphy relates to muscle sympathetic nervous activity in heart failure with reduced ejection fraction

      Highlights

      • Cardiac and renal WR were higher in the HFrEF group than the controls.
      • The increase in WR of renal 123I-MIBG is accompanied by an increase in MSNA.
      • Cardiac MIBG images showed significant correlation with impaired hemodynamics, but not renal MIBG images.

      Abstract

      Background

      Renal denervation is effective for modulating augmented sympathetic nerve activity (SNA) in heart failure with reduced ejection fraction (HFrEF). We have demonstrated that renal iodine123-metaiodobenzylguanidine (123I-MIBG) scintigraphy is associated with muscle sympathetic nerve activity (MSNA) in patients with hypertension. However, it is unclear whether renal 123I-MIBG scintigraphy is useful for assessment of SNA in HFrEF.

      Methods

      The study population consisted of 24 HFrEF patients and 11 healthy subjects as controls. Patients with HFrEF underwent 123I-MIBG scintigraphy and hemodynamics using a Swan-Ganz catheter (SGC). HFrEF was defined as echocardiography with left ventricular ejection fraction (LVEF) < 50%. MSNA was measured from the peroneal nerve for direct evaluation of SNA. Renal 123I-MIBG scintigraphy was performed simultaneously with cardiac scintigraphy. The early and delayed kidney-to-mediastinum ratio (K/M), early and delayed heart-to-mediastinum ratio (H/M), and washout rate (WR) were calculated.

      Results

      LVEFs were 35% ± 11% in patients with HFrEF and 63% ± 10% in the controls (p < 0.01). The WR of cardiac 123I-MIBG showed no relation to MSNA, but was related to stroke volume (r = 0.45, p < 0.05). In contrast, the WR of renal 123I-MIBG scintigraphy (average of both sides) showed a strong correlation with MSNA (BI, r = 0.70, p < 0.01; BF, r = 0.66, p < 0.01); however, no significant correlations were detected between renal 123I-MIBG scintigraphy and SGC results.

      Conclusions

      The WR of renal 123I-MIBG scintigraphy may reflect MSNA. Further studies are needed to clarify the relationship between renal 123I-MIBG imaging and renal SNA.

      Keywords

      Abbreviations:

      SNA (sympathetic nerve activity), CCr (creatinine clearance), HFrEF (heart failure with reduced ejection fraction), 123I-MIBG (iodine123-metaiodobenzylguanidine), MSNA (muscle sympathetic nerve activity), NE (norepinephrine), BI (burst incidence), BF (burst frequency), K/M (kidney-to-mediastinum ratio), H/M (heart-to-mediastinum ratio), WR (washout rate), RDN (renal denervation), ROI (region of interest), SGC (Swan-Ganz catheter), CO (cardiac output), SV (stroke volume)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Azevedo E.R.
        • Kubo T.
        • Mak S.
        • Al-Hesayen A.
        • Schofield A.
        • Allan R.
        Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity.
        Circulation. 2001; 104: 2194-2199
        • Azizi M.
        • Schmieder R.E.
        • Mahfoud F.
        • Weber M.A.
        • Daemen J.
        • Davies J.
        • Basile J.
        • Kirtane A.J.
        • Wang Y.
        • Lobo M.D.
        • Saxena M.
        • Feyz L.
        • Rader F.
        • Lurz P.
        • Sayer J.
        • Sapoval M.
        • Levy T.
        • Sanghvi K.
        • Abraham J.
        • Sharp A.S.P.
        • Fisher N.D.L.
        • Bloch M.J.
        • Reeve-Stoffer H.
        • Coleman L.
        • Mullin C.
        • Mauri L.
        • RADIANCE-HTN Investigators
        Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO).
        Lancet. 2018; 391 (Epub 2018 May 23): 2335-2345https://doi.org/10.1016/S0140-6736(18)31082-1
        • Barajas L.
        • Wang P.
        • Powers K.
        • Nishio S.
        Identification of renal neuroeffector junctions by electron microscopy of reembedded light microscopic autoradiograms of semithin sections.
        J. Ultrastruct. Res. 1981; 77: 379-385
        • Barretto A.C.
        • Santos A.C.
        • Munhoz R.
        • Rondon M.U.
        • Franco F.G.
        • Trombetta I.C.
        • Roveda F.
        • de Matos L.N.
        • Braga A.M.
        • Middlekauff H.R.
        • Negrão C.E.
        Increased muscle sympathetic nerve activity predicts mortality in heart failure patients.
        Int. J. Cardiol. 2009; 135 (2008 Jun 26): 302-307https://doi.org/10.1016/j.ijcard.2008.03.056.Epub
        • Bhatt D.L.
        • Kandzari D.E.
        • O’Neill W.W.
        • D’Agostino R.
        • Flack J.M.
        • Katzen B.T.
        • Leon M.B.
        • Liu M.
        • Mauri L.
        • Negoita M.
        • Cohen S.A.
        • Oparil S.
        • Rocha-Singh K.
        • Townsend R.R.
        • Bakris G.L.
        • SYMPLICITY HTN-3 Investigators
        A controlled trial of renal denervation for resistant hypertension.
        N. Engl. J. Med. 2014; 370 (Epub 2014 Mar 29): 1393-1401https://doi.org/10.1056/NEJMoa1402670
        • Booth L.C.
        • Nishi E.E.
        • Yao S.T.
        • Ramchandra R.
        • Lambert G.W.
        • Schlaich M.P.
        • May C.N.
        Reinnervation following catheter-based radio-frequency renal denervation.
        Exp. Physiol. 2015; 100 (Epub 2015 Jan 22): 485-490https://doi.org/10.1113/expphysiol.2014.079871
        • Cohn J.N.
        • Levine T.B.
        • Olivari M.T.
        • Garberg V.
        • Lura D.
        • Francis G.S.
        • Simon A.B.
        • Rector T.
        Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure.
        N. Engl. J. Med. 1984; 311: 819-823
        • Despas F.
        • Detis N.
        • Dumonteil N.
        • Labrunee M.
        • Bellon B.
        • Franchitto N.
        • Galinier M.
        • Senard J.M.
        • Pathak A.
        Excessive sympathetic activation in heart failure with chronic renal failure: role of chemoreflex activation.
        J. Hypertens. 2009; 27: 1849-1854https://doi.org/10.1097/HJH.0b013e32832e8d0f
        • DiBona G.F.
        • Sawin L.L.
        Reflex regulation of renal nerve activity in cardiac failure.
        Am. J. Phys. 1994; 266: R27-R39
        • Ferguson D.W.
        • Berg W.J.
        • Sanders J.S.
        Clinical and hemodynamic correlates of sympathetic nerve activity in normal humans and patients with heart failure: evidence from direct microneurographic recordings.
        J. Am. Coll. Cardiol. 1990; 16: 1125-1134
        • Flotats A.
        • Carrió I.
        • Agostini D.
        • Le Guludec D.
        • Marcassa C.
        • Schaffers M.
        • Somsen G.A.
        • Unlu M.
        • Verberne H.J.
        Proposal for standardization of 123I-metaiodobenzylguanidine (MIBG) cardiac sympathetic imaging by the EANM Cardiovascular Committee and the European Council of Nuclear Cardiology.
        Eur. J. Nucl. Med. Mol. Imaging. 2010; 37: 1802-1812https://doi.org/10.1007/s00259-010-1491-4
        • Franchitto N.
        • Despas F.
        • Labrunee M.
        • Vaccaro A.
        • Lambert E.
        • Lambert G.
        • Galinier M.
        • Senard J.M.
        • Pathak A.
        Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity.
        Int. J. Cardiol. 2013; 168 (3. (Epub 2013 Feb 13)): 2352-2357https://doi.org/10.1016/j.ijcard.2013.01.023
        • Francis G.S.
        • Benedict C.
        • Johnstone D.E.
        • Kirlin P.C.
        • Nicklas J.
        • Liang C.S.
        • Kubo S.H.
        • Rudin-Toretsky E.
        • Yusuf S.
        Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).
        Circulation. 1990; 82: 1724-1729
        • Fukuta H.
        • Goto T.
        • Wakami K.
        • Ohte N.
        Effects of catheter-based renal denervation on heart failure with reduced ejection fraction: a systematic review and meta-analysis.
        Heart Fail. Rev. 2017; 22: 657-664https://doi.org/10.1007/s10741-017-9629-0
        • Glowniak J.V.
        • Turner F.E.
        • Gray L.L.
        • Palac R.T.
        • Lagunas-Solar M.C.
        • Woodward W.R.
        Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants.
        J. Nucl. Med. 1989; 30: 1182-1191
        • Grassi G.
        • Seravalle G.
        • Cattaneo B.M.
        • Lanfranchi A.
        • Vailati S.
        • Giannattasio C.
        • Del Bo A.
        • Sala C.
        • Bolla G.B.
        • Pozzi M.
        Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure.
        Circulation. 1995; 92: 3206-3211
        • Grassi G.
        • Cattaneo B.M.
        • Seravalle G.
        • Lanfranchi A.
        • Pozzi M.
        • Morganti A.
        • Carugo S.
        • Mancia G.
        Effects of chronic ACE inhibition on sympathetic nerve traffic and baroreflex control of circulation in heart failure.
        Circulation. 1997; 96: 1173-1179
        • Hasking G.J.
        • Esler M.D.
        • Jennings G.L.
        • Burton D.
        • Johns J.A.
        • Korner P.I.
        Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity.
        Circulation. 1986; 73: 615-621
        • Imamura Y.
        • Ando H.
        • Ashihara T.
        • Fukuyama T.
        Myocardial adrenergic nervous activity is intensified in patients with heart failure without left ventricular volume or pressure overload.
        J. Am. Coll. Cardiol. 1996; 28: 371-375
        • Kandzari D.E.
        • Böhm M.
        • Mahfoud F.
        • Townsend R.R.
        • Weber M.A.
        • Pocock S.
        • Tsioufis K.
        • Tousoulis D.
        • Choi J.W.
        • East C.
        • Brar S.
        • Cohen S.A.
        • Fahy M.
        • Pilcher G.
        • Kario K.
        SPYRAL HTN-ON MED trial investigators. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial.
        Lancet. 2018; 391 (2018 May 23): 2346-2355https://doi.org/10.1016/S0140-6736(18)30951-6. Epub
        • Lambert E.
        • Schlaich M.
        The role of renal sympathetic nerves in ischemia reperfusion injury.
        Auton. Neurosci. 2017; 204 (Epub 2017 Jan 17): 105-111https://doi.org/10.1016/j.autneu.2017.01.002
        • Matsuo S.
        • Nakajima K.
        Assessment of cardiac sympathetic nerve function using 123I-meta-iodobenzylguanidine scintigraphy: technical aspects and standardization.
        Ann Nucl Cardiol. 2015; 2015: 27-34
        • Millar P.J.
        • Murai H.
        • Floras J.S.
        Paradoxical muscle sympathetic reflex activation in human heart failure.
        Circulation. 2015; 131 (Epub 2014 Dec 2): 459-468https://doi.org/10.1161/CIRCULATIONAHA.114.010765
        • Murai H.
        • Takamura M.
        • Maruyama M.
        • Nakano M.
        • Ikeda T.
        • Kobayashi D.
        • Otowa K.
        • Ootsuji H.
        • Okajima M.
        • Furusho H.
        • Takata S.
        • Kaneko S.
        Altered firing pattern of single-unit muscle sympathetic nerve activity during handgrip exercise in chronic heart failure.
        J. Physiol. 2009; 587: 2613-2622
        • Murai H.
        • Takamura M.
        • Kaneko S.
        Advantage of recording single-unit muscle sympathetic nerve activity in heart failure.
        Front. Physiol. 2012; 3 (2012): 109https://doi.org/10.3389/fphys.2012.00109.eCollection
        • Ninomiya I.
        • Matsukawa K.
        • Nishiura N.
        Central and baroreflex control of sympathetic nerve activity to the heart and kidney in a daily life of the cat.
        Clin Exp Hypertens A. 1988; 10: 19-31
        • Ogita H.
        • Shimonagata T.
        • Fukunami M.
        • Kumagai K.
        • Yamada T.
        • Asano Y.
        • Hirata Asai M.
        • Kusuoka H.
        • Hori M.
        • Hoki N.
        Prognostic significance of cardiac (123)I metaiodobenzylguanidine imaging for mortality and morbidity in patients with chronic heart failure: a prospective study.
        Heart. 2001; 86: 656-660
        • Owan T.E.
        • Hodge D.O.
        • Herges R.M.
        • Jacobsen S.J.
        • Roger V.L.
        • Redfield M.M.
        Trends in prevalence and outcome of heart failure with preserved ejection fraction.
        N. Engl. J. Med. 2006; 355: 251-259
        • Rump L.C.
        • Bohmann C.
        • Schaible U.
        • Schultze-Seemann W.
        • Schollmeyer P.J.
        Beta-adrenergic, angiotensin II, and bradykinin receptors enhance neurotransmission in human kidney.
        Hypertension. 1995; 26: 445-451
        • Schofer J.
        • Spielmann R.
        • Schuchert A.
        • Weber K.
        • Schlter M.
        Iodine-123 meta-iodobenzylguanidine scintigraphy: a noninvasive method to demonstrate myocardial adrenergic nervous system disintegrity in patients with idiopathic dilated cardiomyopathy.
        J. Am. Coll. Cardiol. 1988; 12: 1252-1258
        • Sisson J.C.
        • Shapiro B.
        • Meyers L.
        • Mallette S.
        • Mangner T.J.
        • Wieland D.M.
        • Glowniak J.V.
        • Sherman P.
        • Beierwaltes W.H.
        Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man.
        J. Nucl. Med. 1987; 28: 1625-1636
        • Takamura M.
        • Murai H.
        • Okabe Y.
        • Okuyama Y.
        • Hamaoka T.
        • Mukai Y.
        • Tokuhisa H.
        • Inoue O.
        • Takashima S.I.
        • Kato T.
        • Matsuo S.
        • Usui S.
        • Furusho H.
        • Kaneko S.
        Significant correlation between renal 123I-metaiodobenzylguanidine scintigraphy and muscle sympathetic nerve activity in patients with primary hypertension.
        J. Nucl. Cardiol. 2017; 24 (Epub 2017 Jan 9): 363-371https://doi.org/10.1007/s12350-016-0760-4
        • Townsend R.R.
        • Mahfoud F.
        • Kandzari D.E.
        • Kario K.
        • Pocock S.
        • Weber M.A.
        • Ewen S.
        • Tsioufis K.
        • Tousoulis D.
        • Sharp A.S.P.
        • Watkinson A.F.
        • Schmieder R.E.
        • Schmid A.
        • Choi J.W.
        • East C.
        • Walton A.
        • Hopper I.
        • Cohen D.L.
        • Wilensky R.
        • Lee D.P.
        • Ma A.
        • Devireddy C.M.
        • Lea J.P.
        • Lurz P.C.
        • Fengler K.
        • Davies J.
        • Chapman N.
        • Cohen S.A.
        • DeBruin V.
        • Fahy M.
        • Jones D.E.
        • Rothman M.
        • Böhm M.
        SPYRAL HTN-OFF MED trial investigators. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.
        Lancet. 2017; 390 (Epub 2017 Aug 28): 2160-2170https://doi.org/10.1016/S0140-6736(17)32281-X
        • Triposkiadis F.
        • Karayannis G.
        • Giamouzis G.
        • Skoularigis J.
        • Louridas G.
        • Butler
        The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.
        J. Am. Coll. Cardiol. 2009; 54: 1747-1762https://doi.org/10.1016/j.jacc.2009.05.015
        • Wallin B.G.
        • Esler M.
        • Dorward P.
        • Eisenhofer G.
        • Ferrier C.
        • Westerman R.
        • Jennings G.
        Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans.
        J. Physiol. 1992; 453: 45-58
        • Yoh M.
        • Yuasa F.
        • Mimura J.
        • Yokoe H.
        • Kawamura A.
        • Sugiura T.
        • Iwasaka T.
        Resting muscle sympathetic nerve activity, cardiac metaiodobenzylguanidine uptake, and exercise tolerance in patients with left ventricular dysfunction.
        J. Nucl. Cardiol. 2009; 16 (Mar-Apr): 244-250