title: Mechanism of decrease in mitral regurgitation after cardiac resynchronization therapy: optimization of the force-balance relationship.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). It has been proposed that the mechanism of MR reduction relates to geometric change or, alternatively, changes in left ventricular (LV) contractile function. Normal mitral valve (MV) function relies on a balance between tethering and closing forces on the MV leaflets. Functional MR results from a derangement of this force-balance relationship, and CRT may be an important modulator of MV function by its ability to enhance the force-balance relationship on the MV. We hypothesized that CRT improves the comprehensive force balance acting on the valve, including favorable changes in both geometry and LV contractile function.
  
  
  RESULTS
  We examined the effect of CRT on 34 patients with functional MR before and after CRT (209+/-81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio=velocity time integral/MR peak velocityxmitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253+/-111 versus 221+/-110 mL, P<0.001) and end-systolic volume (206+/-97 versus 167+/-91 mL, P<0.001) decreased and ejection fraction (19+/-6 versus 27+/-9%, P<0.001) increased. MR regurgitant volume decreased from 35+/-17 to 23+/-14 mL (P<0.001), MAA from 11.6+/-3.5 to 10.5+/-3.1 cm(2) (P<0.001), leaflet closing area from 15.4+/-5 to 13.7+/-3.8 cm(2) (P<0.001), and tenting volume from 5.7+/-2.6 to 4.6+/-2.2 mL (P<0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77+/-0.1 versus 0.84+/-0.1 before CRT versus after CRT, P=0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction.
  
  
  CONCLUSIONS
  Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures.
authors.affiliation: Division of Cardiology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Solis
authors.forename: David
authors.initials: D
authors.lastname: McCarty
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
authors.forename: Mark D
authors.initials: MD
authors.lastname: Handschumacher
authors.forename: Leticia
authors.initials: L
authors.lastname: Fernandez-Friera
authors.forename: Annabel
authors.initials: A
authors.lastname: Chen-Tournoux
authors.forename: Luis
authors.initials: L
authors.lastname: Mont
authors.forename: Barbara
authors.initials: B
authors.lastname: Vidal
authors.forename: Jagmeet P
authors.initials: JP
authors.lastname: Singh
authors.forename: Josep
authors.initials: J
authors.lastname: Brugada
authors.forename: Michael H
authors.initials: MH
authors.lastname: Picard
authors.forename: Marta
authors.initials: M
authors.lastname: Sitges
authors.forename: Judy
authors.initials: J
authors.lastname: Hung
mesh_terms: D000368:Aged; D002304:Cardiac Pacing, Artificial; D015150:Echocardiography, Doppler; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008297:Male; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D009200:Myocardial Contraction / Q000502:physiology; D018709:Statistics, Nonparametric; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy