Advertisement
Canadian Journal of Cardiology

Renal Denervation for Drug-Resistant Hypertension: Suffering Its Original Sin, Seeking Redemption

  • John S. Floras
    Correspondence
    Corresponding author: Dr John S. Floras, Suite 1614, 600 University Ave, Toronto, Ontario M5G 1X5, Canada. Tel.: +1-416-586-8704; fax: +1-416-586-8702.
    Affiliations
    Peter Munk Cardiac Centre and University Health Network and Mount Sinai Hospital Division of Cardiology, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author
Published:February 21, 2014DOI:https://doi.org/10.1016/j.cjca.2014.02.008
      Before the January 9, 2014 announcement that the randomized sham-controlled SYMPLICITY HTN-3 trial had not achieved its primary efficacy end point, the evolution of percutaneous renal denervation, a descendent of years of experimentation by a core group of thoughtful mechanistic investigators, had been characterized by international migration, exponential growth, and rapid dominance of the resistant hypertension environment.
      • Krum H.
      • Schlaich M.
      • Whitbourn R.
      • et al.
      Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.
      • DiBona G.F.
      • Esler M.
      Translational medicine: the antihypertensive effect of renal denervation.
      • Schlaich M.P.
      • Schmieder R.E.
      • Bakris G.
      • et al.
      International expert consensus statement: percutaneous transluminal renal denervation for the treatment of resistant hypertension.
      • Froeschl M.
      • Hadziomerovic A.
      • Ruzicka M.
      Percutaneous renal sympathetic denervation: 2013 and beyond.
      Yet even without knowledge of this trial's full findings, which have yet to be published, this result could have been prophesied as an inevitable consequence of the ‘original sin' of selecting as this technology's target ‘drug-resistant hypertension,' a phenotype characterized by complexity, not simplicity.
      • Pedrosa R.P.
      • Drager L.F.
      • Gonzaga C.C.
      • et al.
      Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension.
      • Calhoun D.A.
      • Jones D.
      • Textor S.
      • et al.
      Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.
      • Clark D.
      • Ahmed M.I.
      • Calhoun D.A.
      Resistant hypertension and aldosterone: an update.
      Let us consider the rationale for this decision and its several key aftereffects.
      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 Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Krum H.
        • Schlaich M.
        • Whitbourn R.
        • et al.
        Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.
        Lancet. 2009; 373: 1275-1281
        • DiBona G.F.
        • Esler M.
        Translational medicine: the antihypertensive effect of renal denervation.
        Am J Physiol Regul Integr Comp Physiol. 2010; 298: R245-R253
        • Schlaich M.P.
        • Schmieder R.E.
        • Bakris G.
        • et al.
        International expert consensus statement: percutaneous transluminal renal denervation for the treatment of resistant hypertension.
        J Am Coll Cardiol. 2013; 62: 2031-2045
        • Froeschl M.
        • Hadziomerovic A.
        • Ruzicka M.
        Percutaneous renal sympathetic denervation: 2013 and beyond.
        Can J Cardiol. 2014; 30: 64-74
        • Pedrosa R.P.
        • Drager L.F.
        • Gonzaga C.C.
        • et al.
        Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension.
        Hypertension. 2011; 58: 811-817
        • Calhoun D.A.
        • Jones D.
        • Textor S.
        • et al.
        Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.
        Circulation. 2008; 11: e510-e526
        • Clark D.
        • Ahmed M.I.
        • Calhoun D.A.
        Resistant hypertension and aldosterone: an update.
        Can J Cardiol. 2012; 28: 318-325
        • Esler M.
        • Jennings G.
        • Korner P.
        • et al.
        Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover.
        Hypertension. 1988; 11: 3-20
        • Ramchandra R.
        • Hood S.G.
        • Denton D.A.
        • et al.
        Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure.
        Proc Natl Acad Sci U S A. 2009; 106: 924-928
        • Ng A.V.
        • Callister R.
        • Johnson D.G.
        • Seals D.R.
        Age and gender influence muscle sympathetic nerve activity at rest in healthy humans.
        Hypertension. 1993; 21: 498-503
        • Esler M.
        Sympathetic nervous activation in essential hypertension: commonly neglected as a therapeutic target, usually ignored as a drug side effect.
        Hypertension. 2010; 55: 1090-1091
        • Grassi G.
        • Seravalle G.
        • Dell'Oro R.
        • et al.
        Comparative effects of candesartan and hydrochlorothiazide on blood pressure, insulin sensitivity, and sympathetic drive in obese hypertensive individuals: results of the CROSS study.
        J Hypertens. 2003; 21: 1761-1769
        • Menon D.V.
        • Arbique D.
        • Wang Z.
        • et al.
        Differential effects of chlorthalidone versus spironolactone on muscle sympathetic nerve activity in hypertensive patients.
        J Clin Endocrinol Metab. 2009; 94: 1361-1366
        • Grassi G.
        • Seravalle G.
        • Turri C.
        • Bolla G.
        • Mancia G.
        Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension.
        Hypertension. 2003; 41: 558-562
        • Struck J.
        • Muck P.
        • Trubger D.
        • et al.
        Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects.
        J Hypertens. 2002; 20: 1143-1149
        • Schroeder C.
        • Heusser K.
        • Brinkmann J.
        • et al.
        Truly refractory hypertension.
        Hypertension. 2013; 62: 231-235
        • Floras J.S.
        • Jones J.V.
        • Johnston J.A.
        • et al.
        Arousal and the circadian rhythm of blood pressure.
        Clin Sci Mol Med Suppl. 1978; 4: 395s-397s
        • Hering D.
        • Lambert E.A.
        • Marusic P.
        • et al.
        Substantial reduction in single sympathetic nerve firing after renal denervation in patients with resistant hypertension.
        Hypertension. 2013; 61: 457-464
        • Brinkmann J.
        • Heusser K.
        • Schmidt B.M.
        • et al.
        Catheter-based renal nerve ablation and centrally generated sympathetic activity in difficult-to-control hypertensive patients: prospective case series.
        Hypertension. 2012; 60: 1485-1490
        • Hart E.C.
        • McBryde F.D.
        • Burchell A.E.
        • et al.
        Translational examination of changes in baroreflex function after renal denervation in hypertensive rats and humans.
        Hypertension. 2013; 62: 533-541
        • McGowan C.L.
        • Murai H.
        • Miller P.J.
        • et al.
        Simvastatin reduces sympathetic outflow and augments endothelium-independent dilation in non-hyperlipidaemic primary hypertension.
        Heart. 2013; 99: 240-246
        • Carter J.R.
        • Ray C.A.
        • Downs E.M.
        • Cooke W.H.
        Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects.
        J Appl Physiol. 2003; 94: 2212-2216
        • Savard S.
        • Frank M.
        • Bobrie G.
        • et al.
        Eligibility for renal denervation in patients with resistant hypertension: when enthusiasm meets reality in real-life patients.
        J Am Coll Cardiol. 2012; 60: 2422-2424
        • Pokushalov E.
        • Romanov A.
        • Corbucci G.
        • et al.
        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
        • US Burden of Disease Collaborators
        The state of US health 1990-2010: burden of diseases, injuries, and risk factors.
        JAMA. 2013; 310: 591-608
        • Khan N.A.
        • Herman R.J.
        • Quinn R.R.
        • et al.
        Renal denervation therapy for the treatment of resistant hypertension: a position statement by the Canadian Hypertension Education Program.
        Can J Cardiol. 2014; 30: 16-21