Atrial fibrillation reduction by renal sympathetic denervation: 12 months' results of the AFFORD study

Lida Feyz, Dominic A Theuns, Rohit Bhagwandien, Mihai Strachinaru, Isabella Kardys, Nicolas M Van Mieghem, Joost Daemen, Lida Feyz, Dominic A Theuns, Rohit Bhagwandien, Mihai Strachinaru, Isabella Kardys, Nicolas M Van Mieghem, Joost Daemen

Abstract

Aim: The purpose of this pilot study was to assess whether renal sympathetic denervation (RDN) decreases atrial fibrillation (AF) burden in hypertensive patients with symptomatic AF at 6- and 12-month follow-up, as measured using an implantable cardiac monitor (ICM).

Methods and results: A total of 20 patients with symptomatic paroxysmal or persistent AF (EHRA ≥ II) and primary hypertension with a mean office systolic blood pressure (BP) of > 140 mmHg were enrolled. After enrolment, an ICM was implanted 3 months pre-RDN to monitor AF burden. Quality of life (QOL) was assessed using the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire. Mean age was 64 ± 7 years and 55% were females. AF burden in min/day decreased from a median (IQR) of 1.39 (0-11) pre-RDN to 0.67 (0-31.6) at 6 months (p = 0.64) and to 0.94 (0-6.0) at 12 months (pre-RDN vs. 12 months; p = 0.03). QOL improved significantly at both 6 months (+ 11 ± 15 points, p = 0.006) and 12 months (+ 10 ± 19, p = 0.04) as compared to pre-RDN. Office BP decreased significantly at 12-month follow-up (- 20 ± 19/- 7 ± 10 mmHg), p < 0.01) as compared to pre-RDN. Ambulatory BP decreased - 7 ± 16/- 3 ± 9 mmHg (p > 0.05) at 12-month follow-up as compared to pre-RDN.

Conclusion: This pilot study suggests that RDN might be able to decrease AF burden in min/day as measured using an ICM, with a positive effect on QOL. Large-scale randomized trials are needed to prove the definite value of RDN in hypertensive patients with atrial fibrillation.

Keywords: AF; Atrial fibrillation; Implantable cardiac monitor; Quality of life; RDN; Renal sympathetic denervation.

Conflict of interest statement

Joost Daemen received institutional research support from Abbott Vascular, Medtronic, Boston Scientific, Acist and Pie Medical as well as speaker and consultancy fees from Medtronic, Acist, Pythagoras. The other authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Screening process based on inclusion- and exclusion criteria. AF atrial fibrillation, antiHT antihypertensive medication, BMI body mass index, EHRA European Heart Rhythm Association, HT hypertension, PVI pulmonary vein isolation
Fig. 2
Fig. 2
Change in EHRA class at follow-up visits (6- and 12 months results). EHRA European Heart Rhythm Association, pre-RDN prior to renal sympathetic denervation, 6M 6 months, 12M 12 months
Fig. 3
Fig. 3
AFEQT questionnaire. pre-RDN prior to renal sympathetic denervation, 6M 6 months, 12M 12 months

References

    1. Haim M, Hoshen M, Reges O, Rabi Y, Balicer R, Leibowitz M. Prospective national study of the prevalence, incidence, management and outcome of a large contemporary cohort of patients with incident non-valvular atrial fibrillation. J Am Heart Assoc. 2015;4(1):e001486. doi: 10.1161/JAHA.114.001486.
    1. Jahangir A, Lee V, Friedman PA, Trusty JM, Hodge DO, Kopecky SL, Packer DL, Hammill SC, Shen WK, Gersh BJ. Long-term progression and outcomes with aging in patients with lone atrial fibrillation: a 30-year follow-up study. Circulation. 2007;115(24):3050–3056. doi: 10.1161/CIRCULATIONAHA.106.644484.
    1. Manolis AJ, Rosei EA, Coca A, Cifkova R, Erdine SE, Kjeldsen S, Lip GY, Narkiewicz K, Parati G, Redon J, Schmieder R, Tsioufis C, Mancia G. Hypertension and atrial fibrillation: diagnostic approach, prevention and treatment. Position paper of the Working Group ‘Hypertension Arrhythmias and Thrombosis’ of the European Society of Hypertension. J Hypertens. 2012;30(2):239–252. doi: 10.1097/HJH.0b013e32834f03bf.
    1. Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, Gillum RF, Kim YH, McAnulty JH, Jr, Zheng ZJ, Forouzanfar MH, Naghavi M, Mensah GA, Ezzati M, Murray CJ. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129(8):837–847. doi: 10.1161/CIRCULATIONAHA.113.005119.
    1. Corley SD, Epstein AE, DiMarco JP, Domanski MJ, Geller N, Greene HL, Josephson RA, Kellen JC, Klein RC, Krahn AD, Mickel M, Mitchell LB, Nelson JD, Rosenberg Y, Schron E, Shemanski L, Waldo AL, Wyse DG, Investigators A. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004;109(12):1509–1513. doi: 10.1161/01.CIR.0000121736.16643.11.
    1. Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, Shirokova N, Karaskov A, Mittal S, Steinberg JS. A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension. J Am Coll Cardiol. 2012;60(13):1163–1170. doi: 10.1016/j.jacc.2012.05.036.
    1. Mahfoud F, Schmieder RE, Azizi M, Pathak A, Sievert H, Tsioufis C, Zeller T, Bertog S, Blankestijn PJ, Bohm M, Burnier M, Chatellier G, Durand Zaleski I, Ewen S, Grassi G, Joner M, Kjeldsen SE, Lobo MD, Lotan C, Luscher TF, Parati G, Rossignol P, Ruilope L, Sharif F, van Leeuwen E, Volpe M, Windecker S, Witkowski A, Wijns W. Proceedings from the 2nd European Clinical Consensus Conference for device-based therapies for hypertension: state of the art and considerations for the future . Eur Heart J. 2017;38(44):3272–3281. doi: 10.1093/eurheartj/ehx215.
    1. Ouyang F, Tilz R, Chun J, Schmidt B, Wissner E, Zerm T, Neven K, Kokturk B, Konstantinidou M, Metzner A, Fuernkranz A, Kuck KH. Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation. 2010;122(23):2368–2377. doi: 10.1161/CIRCULATIONAHA.110.946806.
    1. Chen PS, Tan AY. Autonomic nerve activity and atrial fibrillation. Heart Rhythm. 2007;4(3 Suppl):S61–S64. doi: 10.1016/j.hrthm.2006.12.006.
    1. Tsai WC, Chan YH, Chinda K, Chen Z, Patel J, Shen C, Zhao Y, Jiang Z, Yuan Y, Ye M, Chen LS, Riley AA, Persohn SA, Territo PR, Everett TH, Lin SF, Vinters HV, Fishbein MC, Chen PS. Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs. Heart Rhythm. 2017;14(2):255–262. doi: 10.1016/j.hrthm.2016.10.003.
    1. Chen PS, Chen LS, Fishbein MC, Lin SF, Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res. 2014;114(9):1500–1515. doi: 10.1161/CIRCRESAHA.114.303772.
    1. Azizi M, Sapoval M, Gosse P, Monge M, Bobrie G, Delsart P, Midulla M, Mounier-Vehier C, Courand PY, Lantelme P, Denolle T, Dourmap-Collas C, Trillaud H, Pereira H, Plouin PF, Chatellier G, Renal Denervation for Hypertension. i Optimum and stepped care standardised antihypertensive treatment with or without renal denervation for resistant hypertension (DENERHTN): a multicentre, open-label, randomised controlled trial. Lancet. 2015;385(9981):1957–1965. doi: 10.1016/S0140-6736(14)61942-5.
    1. Spertus J, Dorian P, Bubien R, Lewis S, Godejohn D, Reynolds MR, Lakkireddy DR, Wimmer AP, Bhandari A, Burk C. Development and validation of the atrial fibrillation effect on quality-of-life (AFEQT) questionnaire in patients with atrial fibrillation. Circ Arrhythm Electrophysiol. 2011;4(1):15–15+. doi: 10.1161/CIRCEP.110.958033.
    1. Parati G, Stergiou G, O’Brien E, Asmar R, Beilin L, Bilo G, Clement D, de la Sierra A, de Leeuw P, Dolan E, Fagard R, Graves J, Head GA, Imai Y, Kario K, Lurbe E, Mallion JM, Mancia G, Mengden T, Myers M, Ogedegbe G, Ohkubo T, Omboni S, Palatini P, Redon J, Ruilope LM, Shennan A, Staessen JA, vanMontfrans G, Verdecchia P, Waeber B, Wang J, Zanchetti A, Zhang Y, European Society of Hypertension Working Group on Blood. Pressure M, Cardiovascular V. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014;32(7):1359–1366. doi: 10.1097/HJH.0000000000000221.
    1. Yu L, Huang B, Wang Z, Wang S, Wang M, Li X, Zhou L, Meng G, Yuan S, Zhou X, Jiang H. Impacts of renal sympathetic activation on atrial fibrillation: the potential role of the autonomic cross talk between kidney and heart. J Am Heart Assoc. 2017
    1. Gould PA, Yii M, McLean C, Finch S, Marshall T, Lambert GW, Kaye DM. Evidence for increased atrial sympathetic innervation in persistent human atrial fibrillation. Pacing Clin Electrophysiol. 2006;29(8):821–829. doi: 10.1111/j.1540-8159.2006.00447.x.
    1. Choi EK, Shen MJ, Han S, Kim D, Hwang S, Sayfo S, Piccirillo G, Frick K, Fishbein MC, Hwang C, Lin SF, Chen PS. Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs. Circulation. 2010;121(24):2615–2623. doi: 10.1161/CIRCULATIONAHA.109.919829.
    1. Hou Y, Hu J, Po SS, Wang H, Zhang L, Zhang F, Wang K, Zhou Q. Catheter-based renal sympathetic denervation significantly inhibits atrial fibrillation induced by electrical stimulation of the left stellate ganglion and rapid atrial pacing. PLoS One. 2013;8(11):e78218. doi: 10.1371/journal.pone.0078218.
    1. Linz D, Mahfoud F, Schotten U, Ukena C, Hohl M, Neuberger HR, Wirth K, Bohm M. Renal sympathetic denervation provides ventricular rate control but does not prevent atrial electrical remodeling during atrial fibrillation. Hypertension. 2013;61(1):225–231. doi: 10.1161/HYPERTENSIONAHA.111.00182.
    1. Huang B, Yu L, He B, Wang S, Lu Z, Liao K, Wang Z, Zhou X, He W, Jiang H. Sympathetic denervation of heart and kidney induces similar effects on ventricular electrophysiological properties. EuroIntervention. 2015;11(5):598–604. doi: 10.4244/EIJV11I5A119.
    1. Ukena C, Mahfoud F, Ewen S, Bollmann A, Hindricks G, Hoffmann BA, Linz D, Musat D, Pavlicek V, Scholz E, Thomas D, Willems S, Bohm M, Steinberg JS. Renal denervation for treatment of ventricular arrhythmias: data from an International Multicenter Registry. Clin Res Cardiol. 2016;105(10):873–879. doi: 10.1007/s00392-016-1012-y.
    1. Feyz L, Wijchers S, Daemen J. Renal denervation as a treatment strategy for vasospastic angina induced ventricular tachycardia. Neth Heart J. 2017;25(10):596–597. doi: 10.1007/s12471-017-1012-1.
    1. Jungen C, Scherschel K, Eickholt C, Kuklik P, Klatt N, Bork N, Salzbrunn T, Alken F, Angendohr S, Klene C, Mester J, Klocker N, Veldkamp MW, Schumacher U, Willems S, Nikolaev VO, Meyer C. Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias. Nat Commun. 2017;8:14155. doi: 10.1038/ncomms14155.
    1. Townsend RR, Mahfoud F, Kandzari DE, Kario K, Pocock S, Weber MA, Ewen S, Tsioufis K, Tousoulis D, Sharp ASP, Watkinson AF, Schmieder RE, Schmid A, Choi JW, East C, Walton A, Hopper I, Cohen DL, Wilensky R, Lee DP, Ma A, Devireddy CM, Lea JP, Lurz PC, Fengler K, Davies J, Chapman N, Cohen SA, DeBruin V, Fahy M, Jones DE, Rothman M, Bohm M, investigators* SH-OMt. 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
    1. Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, Tsioufis K, Tousoulis D, Choi JW, East C, Brar S, Cohen SA, Fahy M, Pilcher G, Kario K, Investigators SH-OMT. 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(10137):2346–2355. doi: 10.1016/S0140-6736(18)30951-6.
    1. Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Davies J, Basile J, Kirtane AJ, Wang Y, Lobo MD, Saxena M, Feyz L, Rader F, Lurz P, Sayer J, Sapoval M, Levy T, Sanghvi K, Abraham J, Sharp ASP, Fisher NDL, Bloch MJ, Reeve-Stoffer H, Coleman L, Mullin C, Mauri L, Investigators R-H. Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial. Lancet. 2018;391(10137):2335–2345. doi: 10.1016/S0140-6736(18)31082-1.
    1. Mahfoud F, Moon LB, Pipenhagen CA, Jensen JA, Pathak A, Papademetriou V, Ewen S, Linz D, Bohm M. Catheter-based radio-frequency renal nerve denervation lowers blood pressure in obese hypertensive swine model. J Hypertens. 2016;34(9):1854–1862. doi: 10.1097/HJH.0000000000001021.
    1. Henegar JR, Zhang Y, Hata C, Narciso I, Hall ME, Hall JE. Catheter-based radiofrequency renal denervation: location effects on renal norepinephrine. Am J Hypertens. 2015;28(7):909–914. doi: 10.1093/ajh/hpu258.
    1. Worthley SG, Tsioufis CP, Worthley MI, Sinhal A, Chew DP, Meredith IT, Malaiapan Y, Papademetriou V. Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: the EnligHTN I trial. Eur Heart J. 2013;34(28):2132–2140. doi: 10.1093/eurheartj/eht197.
    1. Romanov A, Pokushalov E, Ponomarev D, Strelnikov A, Shabanov V, Losik D, Karaskov A, Steinberg JS. Pulmonary vein isolation with concomitant renal artery denervation is associated with reduction in both arterial blood pressure and atrial fibrillation burden: data from implantable cardiac monitor. Cardiovasc Ther. 2017
    1. de Jong MR, Hoogerwaard AF, Adiyaman A, Smit JJJ, Ramdat Misier AR, Heeg JE, van Hasselt B, Van Gelder IC, Crijns H, Lozano IF, Toquero Ramos JE, Javier Alzueta F, Ibanez B, Rubio JM, Arribas F, Porres Aracama JM, Brugada J, Mont L, Elvan A. Treatment of atrial fibrillation in patients with enhanced sympathetic tone by pulmonary vein isolation or pulmonary vein isolation and renal artery denervation: clinical background and study design: the ASAF trial: ablation of sympathetic atrial fibrillation. Clin Res Cardiol. 2018
    1. Wang X, Huang C, Zhao Q, Huang H, Tang Y, Dai Z, Wang X, Guo Z, Xiao J. Effect of renal sympathetic denervation on the progression of paroxysmal atrial fibrillation in canines with long-term intermittent atrial pacing. Europace. 2015;17(4):647–654. doi: 10.1093/europace/euu212.
    1. Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, Tsioufis K, Tousoulis D, Choi JW, East C, Brar S, Cohen SA, Fahy M, Pilcher G, Kario K, Investigators SH-OMT. 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
    1. Ziegler PD, Koehler JL, Mehra R. Comparison of continuous versus intermittent monitoring of atrial arrhythmias. Heart Rhythm. 2006;3(12):1445–1452. doi: 10.1016/j.hrthm.2006.07.030.
    1. Cheung JW, Keating RJ, Stein KM, Markowitz SM, Iwai S, Shah BK, Lerman BB, Mittal S. Newly detected atrial fibrillation following dual chamber pacemaker implantation. J Cardiovasc Electrophysiol. 2006;17(12):1323–1328. doi: 10.1111/j.1540-8167.2006.00648.x.
    1. Padeletti L, Santini M, Boriani G, Botto G, Capucci A, Gulizia M, Ricci R, Spampinato A, Pieragnoli P, Warman E, Vimercati M, Grammatico A. Temporal variability of atrial tachyarrhythmia burden in bradycardia-tachycardia syndrome patients. Eur Heart J. 2005;26(2):165–172. doi: 10.1093/eurheartj/ehi059.
    1. Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005;293(21):2634–2640. doi: 10.1001/jama.293.21.2634.

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