Sympathetic Activity in Patients With Secondary Symptomatic Mitral Regurgitation or End-Stage Systolic Heart Failure

JACC Cardiovasc Interv. 2016 Oct 10;9(19):2050-2057. doi: 10.1016/j.jcin.2016.06.032. Epub 2016 Sep 14.

Abstract

Objectives: This study shows the impact of secondary mitral regurgitation (sMR) and transcatheter mitral valve repair (TMVR) with the MitraClip system on sympathetic nerve activity (SNA).

Background: An increase in SNA is associated with worse outcomes and limited survival in patients with chronic heart failure (CHF).

Methods: Twenty CHF-patients without relevant sMR and 30 CHF patients with symptomatic sMR were enrolled prospectively. All patients underwent standardized laboratory testing and microneurography. Sixteen patients from the sMR group underwent the MitraClip procedure; 10 patients after TMVR and 9 untreated sMR patients completed 6 months of follow-up.

Results: Comparing groups according to presence of sMR, we found no differences in left ventricular dimensions, and serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and noradrenaline; sMR was associated with increased MSNA (106 ± 60 burst/min vs. 74 ± 48 burst/min, d = 0.58), an impaired sympathetic baroreflex gain (10 ± 7 burst/mm Hg vs. 5 ± 5 burst/mm Hg, d = 0.61), and a higher heart rate (90 ± 27/beats/min vs. 78 ± 12/beats/min, d = 0.58). TMVR led to improved New York Heart Association functional class (d > 0.05), reduced levels of NT-proBNP (5,251 ± 3,760 pg/ml vs. 3,710 ± 2,464 pg/ml; d = 0.58) improvement in 6-minute walk test (204 ± 33 m vs. 288 ± 45 m, d = 0.64), but unchanged levels of noradrenaline. TMVR decreased MSNA burst-frequency (130 ± 78 bursts/min vs. 74 ± 21 bursts/min; d = 0.58) and baroreflex gain (7 ± 4 burst/mm Hg vs. 4 ± 1 burst/mm Hg; d = 0.61).

Conclusions: In patients with CHF, concomitant sMR is associated with increased sympathetic nerve activity, which was independent from measured levels of NT-proBNP, noradrenaline, and left ventricular dimensions. Reduction of sMR with the MitraClip procedure reduced SNA and improved baroreflex gain, in line with improvements of functional capacity.

Keywords: MitraClip; TMVR; mitral regurgitation; muscle sympathetic nerve activity; sympathetic nerve activity.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Baroreflex
  • Biomarkers / blood
  • Cardiac Catheterization / instrumentation
  • Case-Control Studies
  • Exercise Tolerance
  • Female
  • Heart Failure, Systolic / diagnosis
  • Heart Failure, Systolic / mortality
  • Heart Failure, Systolic / physiopathology*
  • Heart Rate
  • Humans
  • Male
  • Middle Aged
  • Mitral Valve / physiopathology*
  • Mitral Valve / surgery
  • Mitral Valve Insufficiency / diagnosis
  • Mitral Valve Insufficiency / mortality
  • Mitral Valve Insufficiency / physiopathology*
  • Mitral Valve Insufficiency / surgery
  • Natriuretic Peptide, Brain / blood
  • Neurologic Examination
  • Norepinephrine / blood
  • Peptide Fragments / blood
  • Prospective Studies
  • Recovery of Function
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology*
  • Time Factors
  • Treatment Outcome
  • Ventricular Function, Left
  • Walk Test

Substances

  • Biomarkers
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Norepinephrine