Adjunctive Renal Sympathetic Denervation to Modify Hypertension as Upstream Therapy in the Treatment of Atrial Fibrillation (H-FIB) Study: Clinical Background and Study Design
HUMERA AHMED B.A.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorMARC A. MILLER M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorSRINIVAS R. DUKKIPATI M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorSAM CAMMACK M.P.H.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorJACOB S. KORUTH M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorSANDEEP GANGIREDDY M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorBETSY A. ELLSWORTH M.S.N.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorANDRE D'AVILA M.D., Ph.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorMICHAEL DOMANSKI M.D.
International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorANNETINE C. GELIJNS Ph.D.
International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorALAN MOSKOWITZ M.D.
International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorCorresponding Author
VIVEK Y. REDDY M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Address for correspondence: Vivek Y. Reddy, M.D., Helmsley Electrophysiology Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029. Fax: +646-537-9691; E-mail: [email protected]Search for more papers by this authorHUMERA AHMED B.A.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorMARC A. MILLER M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorSRINIVAS R. DUKKIPATI M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorSAM CAMMACK M.P.H.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorJACOB S. KORUTH M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorSANDEEP GANGIREDDY M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorBETSY A. ELLSWORTH M.S.N.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorANDRE D'AVILA M.D., Ph.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorMICHAEL DOMANSKI M.D.
International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorANNETINE C. GELIJNS Ph.D.
International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorALAN MOSKOWITZ M.D.
International Center for Health Outcomes and Innovation Research, Department of Health Evidence and Policy, Mount Sinai School of Medicine, New York, New York, USA
Search for more papers by this authorCorresponding Author
VIVEK Y. REDDY M.D.
Helmsley Electrophysiology Center, Mount Sinai School of Medicine, New York, New York, USA
Address for correspondence: Vivek Y. Reddy, M.D., Helmsley Electrophysiology Center, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1030, New York, NY 10029. Fax: +646-537-9691; E-mail: [email protected]Search for more papers by this authorBiosense Webster is the sponsor of this trial; it played no role in the collection or analysis of data.
Drs. D'Avila and Reddy have received consulting fees from Biosense Webster. Other authors: No disclosures.
Adjunctive Renal Sympathetic Denervation to Modify Hypertension
Background
Hypertension is the most important risk factor directly attributable to the high prevalence of atrial fibrillation (AF), and is one of the few modifiable risk factors for AF. Activation and overactivity of the sympathetic nervous system (SNS) have been implicated in the pathogenesis of both essential hypertension and AF. Catheter-based renal sympathetic denervation (RSDN) appears to be an effective adjunctive treatment for refractory hypertension, and may be beneficial in other conditions characterized by SNS overactivity, such as left ventricular hypertrophy and atrial arrhythmias.
Objective
The H-FIB study is a multicenter prospective, double-blind, randomized (1:1) controlled trial. The primary efficacy endpoint is antiarrhythmic drug-free freedom from AF recurrence through 12 months.
Methods
Patients with a history of significant hypertension who are receiving treatment with at least one antihypertensive agent who are planned for a first time ablation for symptomatic paroxysmal or persistent AF will be randomized to either AF ablation alone (control group) or AF ablation + RSDN (study group).
Conclusions
H-FIB is a multicenter, randomized trial that will test the hypothesis that adjunctive renal sympathetic denervation, at the time of AF ablation, will increase the freedom from recurrent AF.
References
- 1Vital signs: Awareness and treatment of uncontrolled hypertension among adults–United States, 2003–2010. MMWR Morb Mortal Wkly Rep 2012; 61: 703-709.
- 2Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ: Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association. Circulation 2011; 123: 933-944.
- 3Kannel WB, Wolf PA, Benjamin EJ, Levy D: Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: Population-based estimates. Am J Cardiol 1998; 82: 2N-9N.
- 4Benjamin EJ, Chen PS, Bild DE, Mascette AM, Albert CM, Alonso A, Calkins H, Connolly SJ, Curtis AB, Darbar D, Ellinor PT, Go AS, Goldschlager NF, Heckbert SR, Jalife J, Kerr CR, Levy D, Lloyd-Jones DM, Massie BM, Nattel S, Olgin JE, Packer DL, Po SS, Tsang TS, Van Wagoner DR, Waldo AL, Wyse DG: Prevention of atrial fibrillation: Report from a national heart, lung, and blood institute workshop. Circulation 2009; 119: 606-618.
- 5Healey JS, Connolly SJ: Atrial fibrillation: Hypertension as a causative agent, risk factor for complications, and potential therapeutic target. Am J Cardiol 2003; 91: 9G-14G.
- 6Savelieva I, Kakouros N, Kourliouros A, Camm AJ: Upstream therapies for management of atrial fibrillation: Review of clinical evidence and implications for European Society of Cardiology guidelines. Part I: Primary prevention. Europace 2011; 13: 308-328.
- 7Schotten U, Verheule S, Kirchhof P, Goette A: Pathophysiological mechanisms of atrial fibrillation: A translational appraisal. Physiol Rev 2011; 91: 265-325.
- 8Lau DH, Mackenzie L, Kelly DJ, Psaltis PJ, Brooks AG, Worthington M, Rajendram A, Kelly DR, Zhang Y, Kuklik P, Nelson AJ, Wong CX, Worthley SG, Rao M, Faull RJ, Edwards J, Saint DA, Sanders P: Hypertension and atrial fibrillation: Evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model. Heart Rhythm 2010; 7: 1282-1290.
- 9Dimmer C, Tavernier R, Gjorgov N, Van Nooten G, Clement DL, Jordaens L: Variations of autonomic tone preceding onset of atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 1998; 82: 22-25.
- 10Arimoto T, Tada H, Igarashi M, Sekiguchi Y, Sato A, Koyama T, Yamasaki H, Machino T, Kuroki K, Kuga K, Aonuma K: High washout rate of iodine-123-metaiodobenzylguanidine imaging predicts the outcome of catheter ablation of atrial fibrillation. J Cardiovasc Electrophysiol 2011; 22: 1297-1304.
- 11Shen MJ, Shinohara T, Park HW, Frick K, Ice DS, Choi EK, Han S, Maruyama M, Sharma R, Shen C, Fishbein MC, Chen LS, Lopshire JC, Zipes DP, Lin SF, Chen PS: Continuous low-level vagus nerve stimulation reduces stellate ganglion nerve activity and paroxysmal atrial tachyarrhythmias in ambulatory canines. Circulation 2011; 123: 2204-2212.
- 12Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M: Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): A randomised controlled trial. Lancet 2010; 376: 1903-1909.
- 13Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension 2011; 57: 911-917.
- 14Witkowski A, Prejbisz A, Florczak E, Kadziela J, Sliwinski P, Bielen P, Michalowska I, Kabat M, Warchol E, Januszewicz M, Narkiewicz K, Somers VK, Sobotka PA, Januszewicz A: Effects of renal sympathetic denervation on blood pressure, sleep apnea course, and glycemic control in patients with resistant hypertension and sleep apnea. Hypertension 2011; 58: 559-565.
- 15Brandt MC, Mahfoud F, Reda S, Schirmer SH, Erdmann E, Bohm M, Hoppe UC: Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension. J Am Coll Cardiol 2012; 59: 901-909.
- 16Pokushalov 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: 1163-1170.
- 17Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D: 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation. Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society. Heart Rhythm 2012; 9: 632-696.
- 18Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY, Kay GN, Lowe JE, Olsson SB, Prystowsky EN, Tamargo JL, Wann S, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Hunt SA, Nishimura R, Ornato JP, Page RL, Riegel B, Priori SG, Blanc JJ, Budaj A, Camm AJ, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Zamorano JL: ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation—executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006; 48: 854-906.
10.1016/j.jacc.2006.07.009 Google Scholar
- 19Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003; 42: 1206-1252.
- 20Singh SM, D'Avila A, Kim SJ, Houghtaling C, Dukkipati SR, Reddy VY: Intraprocedural use of ibutilide to organize and guide ablation of complex fractionated atrial electrograms: Preliminary assessment of a modified step-wise approach to ablation of persistent atrial fibrillation. J Cardiovasc Electrophysiol 2010; 21: 608-616.
- 21Ahmed H, Neuzil P, Skoda J, Petru J, Sediva L, Schejbalova M, Reddy VY: Renal sympathetic denervation using an irrigated radiofrequency ablation catheter for the management of drug-resistant hypertension. JACC Cardiovasc Interv 2012; 5: 758-765.
- 22Patterson E, Jackman WM, Beckman KJ, Lazzara R, Lockwood D, Scherlag BJ, Wu R, Po S: Spontaneous pulmonary vein firing in man: Relationship to tachycardia-pause early afterdepolarizations and triggered arrhythmia in canine pulmonary veins in vitro. J Cardiovasc Electrophysiol 2007; 18: 1067-1075.
- 23Tan AY, Zhou S, Jung BC, Ogawa M, Chen LS, Fishbein MC, Chen PS: Ectopic atrial arrhythmias arising from canine thoracic veins during in vivo stellate ganglia stimulation. Am J Physiol Heart Circ Physiol 2008; 295: H691-H698.
- 24Chen PS, Tan AY: Autonomic nerve activity and atrial fibrillation. Heart Rhythm 2007; 4: S61-S64.
- 25Jayachandran JV, Zipes DP, Weksler J, Olgin JE: Role of the Na(+)/H(+) exchanger in short-term atrial electrophysiological remodeling. Circulation 2000; 101: 1861-1866.
- 26Akutsu Y, Kaneko K, Kodama Y, Li HL, Suyama J, Shinozuka A, Gokan T, Hamazaki Y, Tanno K, Kobayashi Y: Iodine-123 mIBG imaging for predicting the development of atrial fibrillation. JACC Cardiovasc Imaging 2011; 4: 78-86.
- 27Okin PM, Wachtell K, Devereux RB, Harris KE, Jern S, Kjeldsen SE, Julius S, Lindholm LH, Nieminen MS, Edelman JM, Hille DA, Dahlof B: Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension. JAMA 2006; 296: 1242–1248.
- 28Wachtell K, Gerdts E, Aurigemma GP, Boman K, Dahlof B, Nieminen MS, Olsen MH, Okin PM, Palmieri V, Rokkedal JE, Devereux RB: In-treatment reduced left atrial diameter during antihypertensive treatment is associated with reduced new-onset atrial fibrillation in hypertensive patients with left ventricular hypertrophy: The LIFE Study. Blood Pressure 2010; 19: 169-175.
- 29Burns J, Sivananthan MU, Ball SG, Mackintosh AF, Mary DA, Greenwood JP: Relationship between central sympathetic drive and magnetic resonance imaging-determined left ventricular mass in essential hypertension. Circulation 2007; 115: 1999-2005.
- 30Schlaich MP, Kaye DM, Lambert E, Sommerville M, Socratous F, Esler MD: Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy. Circulation 2003; 108: 560-565.
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