The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation

Klaus K. Witte; Janusz Lipiecki; Tomasz Siminiak; Ian T. Meredith; Christopher J. Malkin; Steven L. Goldberg; Matthew A. Stark; Ralph Stephan von Bardeleben; Paul C. Cremer; Wael A. Jaber; David S. Celermajer; David M. Kaye; Horst Sievert

doi:10.1016/j.jchf.2019.06.011

The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation

Klaus K. Witte^*, Janusz Lipiecki, Tomasz Siminiak, Ian T. Meredith, Christopher J. Malkin, Steven L. Goldberg, Matthew A. Stark, Ralph Stephan von Bardeleben, Paul C. Cremer, Wael A. Jaber, David S. Celermajer, David M. Kaye, Horst Sievert

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

131 Scopus citations

Abstract

Objectives: This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. Background: Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. Methods: In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. Results: Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: −11.7 to −2.5] vs. an increase of 3.3 ml/beat [95% CI: −6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: −18.5 to −2.4] vs. an increase of 6.5 ml [95% CI: −5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: −12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: −1.42 to 13.6]; p = 0.04). Conclusions: The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy.

Original language	English (US)
Pages (from-to)	945-955
Number of pages	11
Journal	JACC: Heart Failure
Volume	7
Issue number	11
DOIs	https://doi.org/10.1016/j.jchf.2019.06.011
State	Published - Nov 2019

Funding

The authors thank Meghan Schadow, MS, for editorial assistance; Teresa Yurik, MS, for statistical support; and Samir Kapadia, MD, and Martin Leon, MD for critical review of the manuscript. The authors also thank Rebeka McBride, MS, for study management and Annitta Flinn, L. Leonardo Rodrigues, MD, Zoran B. Popovic, MD, PhD, and the Imaging Core Lab, Cleveland Clinic Coordinating Center for Clinical Research, for core laboratory support and all the investigators and clinical staff for their outstanding contributions. The REDUCE-FMR trial was sponsored by Cardiac Dimensions. Dr. Witte has been recipient of a National Institute for Health Research (UK) Clinician Scientist Award; has received speaker fees and honoraria from Medtronic, Cardiac Dimensions, Novartis, Abbott, Bristol-Myers Squibb, Pfizer, and Bayer; and has received research grants from Medtronic. Dr. Lipiecki has been a proctor for Cardiac Dimensions. Dr. Siminiak has received proctoring fees from Cardiac Dimensions. Dr. Malkin has been a proctor for Medtronic and Boston Scientific. Dr. Goldberg holds stock options in and is a consultant for Cardiac Dimensions; and has received honoraria from Abbott. Dr. Stark is an employee of Cardiac Dimensions. Dr. Celermajer holds stock options in and serves on the Investment Committee of an investor in Cardiac Dimensions. Dr. von Bardeleben is a steering committee member and/or investigator for Abbott, Cardiac Dimensions, and Edwards; and has received honoraria from Abbott, Cardiac Dimensions, GE Healthcare, Edwards, Philips, and Siemens Healthineers. Dr. Kaye is a cofounder of and holds stock in Cardiac Dimensions. Dr. Sievert has received grants from Cardiac Dimensions; and has received grants, fees, and nonfinancial support from 4tech Cardio, Abbott, Ablative Solutions, Ancora Heart, Bavaria Medizin Technologie GmbH, Bioventrix, Boston Scientific, Carag, Celonova, Comed BV, Contego, CVRx, Dinova, Edwards, Endologix, Hemoteq, Hangzhou Nuomao Medtech, Lifetech, Maquet Getinge Group, Medtronic, Mitralign, Mokita, Occlutech, pfm Medical, Recor, Renal Guard, Rox Medical, Terumo, Vascular Dynamics, Vectorious Medtech, Venus, and Vivasure Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Keywords

functional mitral regurgitation
heart failure
percutaneous mitral annuloplasty
transcatheter mitral valve repair

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jchf.2019.06.011

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Witte, K. K., Lipiecki, J., Siminiak, T., Meredith, I. T., Malkin, C. J., Goldberg, S. L., Stark, M. A., von Bardeleben, R. S., Cremer, P. C., Jaber, W. A., Celermajer, D. S., Kaye, D. M., & Sievert, H. (2019). The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation. JACC: Heart Failure, 7(11), 945-955. https://doi.org/10.1016/j.jchf.2019.06.011

@article{310408bd6aea43f399c5753273a2d298,

title = "The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation",

abstract = "Objectives: This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. Background: Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. Methods: In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. Results: Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: −11.7 to −2.5] vs. an increase of 3.3 ml/beat [95% CI: −6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: −18.5 to −2.4] vs. an increase of 6.5 ml [95% CI: −5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: −12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: −1.42 to 13.6]; p = 0.04). Conclusions: The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy.",

keywords = "functional mitral regurgitation, heart failure, percutaneous mitral annuloplasty, transcatheter mitral valve repair",

author = "Witte, {Klaus K.} and Janusz Lipiecki and Tomasz Siminiak and Meredith, {Ian T.} and Malkin, {Christopher J.} and Goldberg, {Steven L.} and Stark, {Matthew A.} and {von Bardeleben}, {Ralph Stephan} and Cremer, {Paul C.} and Jaber, {Wael A.} and Celermajer, {David S.} and Kaye, {David M.} and Horst Sievert",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = nov,

doi = "10.1016/j.jchf.2019.06.011",

language = "English (US)",

volume = "7",

pages = "945--955",

journal = "JACC: Heart Failure",

issn = "2213-1779",

publisher = "Elsevier Inc.",

number = "11",

}

Witte, KK, Lipiecki, J, Siminiak, T, Meredith, IT, Malkin, CJ, Goldberg, SL, Stark, MA, von Bardeleben, RS, Cremer, PC, Jaber, WA, Celermajer, DS, Kaye, DM & Sievert, H 2019, 'The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation', JACC: Heart Failure, vol. 7, no. 11, pp. 945-955. https://doi.org/10.1016/j.jchf.2019.06.011

TY - JOUR

T1 - The REDUCE FMR Trial

T2 - A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation

AU - Witte, Klaus K.

AU - Lipiecki, Janusz

AU - Siminiak, Tomasz

AU - Meredith, Ian T.

AU - Malkin, Christopher J.

AU - Goldberg, Steven L.

AU - Stark, Matthew A.

AU - von Bardeleben, Ralph Stephan

AU - Cremer, Paul C.

AU - Jaber, Wael A.

AU - Celermajer, David S.

AU - Kaye, David M.

AU - Sievert, Horst

PY - 2019/11

Y1 - 2019/11

N2 - Objectives: This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. Background: Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. Methods: In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. Results: Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: −11.7 to −2.5] vs. an increase of 3.3 ml/beat [95% CI: −6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: −18.5 to −2.4] vs. an increase of 6.5 ml [95% CI: −5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: −12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: −1.42 to 13.6]; p = 0.04). Conclusions: The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy.

AB - Objectives: This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling. Background: Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis. Methods: In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis. Results: Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: −11.7 to −2.5] vs. an increase of 3.3 ml/beat [95% CI: −6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: −18.5 to −2.4] vs. an increase of 6.5 ml [95% CI: −5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: −12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: −1.42 to 13.6]; p = 0.04). Conclusions: The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy.

KW - functional mitral regurgitation

KW - heart failure

KW - percutaneous mitral annuloplasty

KW - transcatheter mitral valve repair

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DO - 10.1016/j.jchf.2019.06.011

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AN - SCOPUS:85073412419

SN - 2213-1779

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JO - JACC: Heart Failure

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IS - 11

ER -

The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation

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