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J Am Coll Cardiol, 2003; 41:765-770, doi:10.1016/S0735-1097(02)02937-6
© 2003 by the American College of Cardiology Foundation
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CLINICAL STUDY: HEART FAILURE

Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure

Ole A. Breithardt, MD*,*, Anil M. Sinha, MD*, Ehud Schwammenthal, MD, FESC{dagger}, Nadim Bidaoui, BSc*, Kai U. Markus, MD*, Andreas Franke, MD* and Christoph Stellbrink, MD, FESC*

* Department of Cardiology, University Hospital, Aachen, Germany
{dagger} Heart Institute, Sheba Medical Center, Tel Hashomer, Israel

Manuscript received August 13, 2002; revised manuscript received October 25, 2002, accepted November 11, 2002.

* Reprint requests and correspondence: Dr. Ole A. Breithardt, Department of Cardiology, University Hospital Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany.
olebreithardt{at}gmx.de

OBJECTIVES: We studied the acute effects of cardiac resynchronization therapy (CRT) on functional mitral regurgitation in heart failure (HF) patients with left bundle branch block (LBBB).

BACKGROUND: Both a decrease in left ventricular (LV) closing force and mitral valve tethering have been implicated as mechanisms for functional mitral regurgitation (FMR) in dilated hearts. We hypothesized that an increase in LV closing force achieved by CRT could act to reduce FMR.

METHODS: Twenty-four HF patients with LBBB and FMR were studied after implantation of a biventricular CRT system. Acute changes in FMR severity between intrinsic conduction (OFF) and CRT were quantified according to the proximal isovelocity surface area method by measuring the effective regurgitant orifice area (EROA). Results were compared with the changes in estimated maximal rate of left ventricular systolic pressure rise (LV+dP/dtmax) and transmitral pressure gradients (TMP), both measured by Doppler echocardiography.

RESULTS: Cardiac resynchronization therapy was associated with a significant reduction in FMR severity. Effective regurgitant orifice area decreased from 25 ± 19 mm2 (OFF) to 13 ± 8 mm2 (CRT). The change in EROA was directly related to the increase in LV+dP/dtmax (r = –0.83, p < 0.0001). Compared with OFF, TMP increased more rapidly during CRT, and a higher maximal TMP was observed (OFF 73 ± 24 mm Hg vs. CRT 85 ± 26 mm Hg, p < 0.01).

CONCLUSIONS: Functional mitral regurgitation is reduced by CRT in patients with HF and LBBB. This effect is directly related to the increased closing force (LV+dP/dtmax). The results support the hypothesis that an increase in TMP, mediated by a rise in LV+dP/dtmax due to more coordinated LV contraction, may facilitate effective mitral valve closure.

Abbreviations and Acronyms
  CAD
  coronary artery disease
  CRT
  cardiac resynchronization therapy
  CW
  continuous wave
  DCM
  dilated cardiomyopathy
  EF
  ejection fraction
  EROA
  effective regurgitant orifice area
  FMR
  functional mitral regurgitation
  LBBB
  left bundle branch block
  LV
  left ventricle/ventricular
  LV+dP/dtmax
  maximal rate of left ventricular systolic pressure rise
  MRVmax
  maximal velocity of the mitral regurgitant jet obtained by continuous wave Doppler
  MRVTI
  mitral regurgitant velocity time integral
  OFF
  intrinsic conduction, no pacing
  PISA
  proximal isovelocity surface area
  RegFlow
  regurgitant flow
  RegVol
  regurgitant volume
  TMP
  transmitral pressure gradient
  TMP100
  transmitral pressure gradient 100 ms after onset of the functional mitral regurgitation jet
  TMPmax
  maximal transmitral pressure gradient
  Valias
  aliasing velocity




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M. C. Porciani, R. Macioce, G. Demarchi, M. Chiostri, N. Musilli, F. Cappelli, A. Lilli, G. Ricciardi, and L. Padeletti
Effects of cardiac resynchronization therapy on the mechanisms underlying functional mitral regurgitation in congestive heart failure
Eur J Echocardiogr, January 1, 2006; 7(1): 31 - 39.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. J. Bax, T. Abraham, S. S. Barold, O. A. Breithardt, J. W.H. Fung, S. Garrigue, J. Gorcsan III, D. L. Hayes, D. A. Kass, J. Knuuti, et al.
Cardiac Resynchronization Therapy: Part 2--Issues During and After Device Implantation and Unresolved Questions
J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2168 - 2182.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. M. Aranda Jr, G. W. Woo, R. S. Schofield, E. M. Handberg, J. A. Hill, A. B. Curtis, S. F. Sears, J. S. Goff, D. F. Pauly, and J. B. Conti
Management of Heart Failure After Cardiac Resynchronization Therapy: Integrating Advanced Heart Failure Treatment With Optimal Device Function
J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2193 - 2198.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
S. Fukuda, R. Grimm, J.-M. Song, T. Kihara, M. Daimon, D. A. Agler, B. L. Wilkoff, A. Natale, J. D. Thomas, and T. Shiota
Electrical Conduction Disturbance Effects on Dynamic Changes of Functional Mitral Regurgitation
J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2270 - 2276.
[Abstract] [Full Text] [PDF]

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 Eur J EchocardiogrHome page
K. Dohi, M. Suffoletto, S. Murali, R. Bazaz, and J. Gorcsan
Benefit of cardiac resynchronization therapy to a patient with a narrow QRS complex and ventricular dyssynchrony identified by tissue synchronization imaging
Eur J Echocardiogr, December 1, 2005; 6(6): 455 - 460.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
G. Cioffi, L. Tarantini, S. De Feo, G. Pulignano, D. Del Sindaco, C. Stefenelli, A. Di Lenarda, and C. Opasich
Functional mitral regurgitation predicts 1-year mortality in elderly patients with systolic chronic heart failure
Eur J Heart Fail, December 1, 2005; 7(7): 1112 - 1117.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
R. A. Levine and E. Schwammenthal
Ischemic Mitral Regurgitation on the Threshold of a Solution: From Paradoxes to Unifying Concepts
Circulation, August 2, 2005; 112(5): 745 - 758.
[Full Text] [PDF]

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 HeartHome page
Y Abe, T Imai, K Ohue, R Otsuka, R Komatsu, M Otsuka, Y Sakanoue, T Naruko, A Itoh, M Yoshiyama, et al.
Relation between reduction in ischaemic mitral regurgitation and improvement in regional left ventricular contractility during low dose dobutamine stress echocardiography
Heart, August 1, 2005; 91(8): 1092 - 1093.
[Full Text] [PDF]

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 Eur Respir JHome page
J. Y. Gabor, D. A. Newman, V. Barnard-Roberts, V. Korley, I. Mangat, P. Dorian, and P. J. Hanly
Improvement in Cheyne-Stokes respiration following cardiac resynchronisation therapy
Eur. Respir. J., July 1, 2005; 26(1): 95 - 100.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
M. R. Mehra and B. P. Griffith
Is mitral regurgitation a viable treatment target in heart failure?: The plot just thickened
J. Am. Coll. Cardiol., February 1, 2005; 45(3): 388 - 390.
[Full Text] [PDF]

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 J Am Coll CardiolHome page
A. E. Weyman
The year in echocardiography
J. Am. Coll. Cardiol., February 1, 2005; 45(3): 448 - 455.
[Full Text] [PDF]

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 J Am Coll CardiolHome page
P. Bordachar, S. Lafitte, S. Reuter, P. Sanders, P. Jais, M. Haissaguerre, R. Roudaut, S. Garrigue, and J. Clementy
Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing
J. Am. Coll. Cardiol., December 7, 2004; 44(11): 2157 - 2165.
[Abstract] [Full Text] [PDF]

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 HeartHome page
R A Bleasdale and M P Frenneaux
Cardiac resynchronisation therapy: when the drugs don't work.
Heart, December 1, 2004; 90(suppl_6): vi2 - vi4.
[Full Text] [PDF]

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 HeartHome page
H J Nesser, O-A Breithardt, and B K Khandheria
Established and evolving indications for cardiac resynchronisation
Heart, December 1, 2004; 90(suppl_6): vi5 - vi9.
[Abstract] [Full Text] [PDF]

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 HeartHome page
R E Lane, A W C Chow, D Chin, and J Mayet
Selection and optimisation of biventricular pacing: the role of echocardiography
Heart, December 1, 2004; 90(suppl_6): vi10 - vi16.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. Janousek, V. Tomek, V. Chaloupecky, O. Reich, R. A. Gebauer, J. Kautzner, and B. Hucin
Cardiac resynchronization therapy: A novel adjunct to the treatment and prevention of systemic right ventricular failure
J. Am. Coll. Cardiol., November 2, 2004; 44(9): 1927 - 1931.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
H. Kanzaki, R. Bazaz, D. Schwartzman, K. Dohi, L. E. Sade, and J. Gorcsan III
A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy: Insights from mechanical activation strain mapping
J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1619 - 1625.
[Abstract] [Full Text] [PDF]

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 Eur Heart J SupplHome page
R. R Brandt, J. Sperzel, H. F Pitschner, and C. W Hamm
Echocardiographic assessment of mitral regurgitation in patients with heart failure
Eur. Heart J. Suppl., August 1, 2004; 6(suppl_D): D25 - D28.
[Abstract] [Full Text] [PDF]

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 Eur Heart J SupplHome page
C. Stellbrink, O.-A. Breithardt, A.-M. Sinha, and P. Hanrath
How to discriminate responders from non-responders to cardiac resynchronisation therapy
Eur. Heart J. Suppl., August 1, 2004; 6(suppl_D): D101 - D105.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
J. J. Bax, G. Ansalone, O. A. Breithardt, G. Derumeaux, C. Leclercq, M. J. Schalij, P. Sogaard, M. St. John Sutton, and P. Nihoyannopoulos
Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical use?: A critical appraisal
J. Am. Coll. Cardiol., July 7, 2004; 44(1): 1 - 9.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
A.-M. Sinha, E. C. Skobel, O.-A. Breithardt, C. Norra, K. U. Markus, C. Breuer, P. Hanrath, and C. Stellbrink
Cardiac resynchronization therapy improves central sleep apnea and Cheyne-Stokes respiration in patients with chronic heart failure
J. Am. Coll. Cardiol., July 7, 2004; 44(1): 68 - 71.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
M. R. Mehra and B. H. Greenberg
Cardiac resynchronization therapy: caveat medicus!
J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1145 - 1148.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
E. Puggioni, M. Brignole, M. Gammage, E. Soldati, M. G. Bongiorni, E. N. Simantirakis, P. Vardas, F. Gadler, L. Bergfeldt, C. Tomasi, et al.
Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation
J. Am. Coll. Cardiol., January 21, 2004; 43(2): 234 - 238.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
A. E. Weyman
The year in echocardiography
J. Am. Coll. Cardiol., January 7, 2004; 43(1): 140 - 148.
[Full Text] [PDF]


 
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