Accepted Manuscript

Prognostic Significance of Right Ventricular Dysfunction in Patients with Functional

Mitral Regurgitation Undergoing MitraClip

Hidehiro Kaneko, MD, Michael Neuss, MD, Jens Weissenborn, MD, Christian Butter,
MD
PII: S0002-9149(16)31445-X
DOI: 10.1016/j.amjcard.2016.08.054
Reference: AJC 22104

To appear in: The American Journal of Cardiology

Received Date: 17 May 2016

Revised Date: 11 August 2016
Accepted Date: 19 August 2016

Please cite this article as: Kaneko H, Neuss M, Weissenborn J, Butter C, Prognostic Significance of
Right Ventricular Dysfunction in Patients with Functional Mitral Regurgitation Undergoing MitraClip, The
American Journal of Cardiology (2016), doi: 10.1016/j.amjcard.2016.08.054.

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ACCEPTED MANUSCRIPT

Prognostic Significance of Right Ventricular Dysfunction in Patients with

Functional Mitral Regurgitation Undergoing MitraClip

Hidehiro Kaneko, MD1, Michael Neuss, MD1, Jens Weissenborn, MD, and

Christian Butter, MD*

Department of Cardiology, Heart Center Brandenburg

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and Department of Cardiology, Medical School Brandenburg

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*Correspondence:

Christian Butter, MD.

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Department of Cardiology, Heart Center Brandenburg,

Department of Cardiology, Medical School Brandenburg

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Ladeburger Strae 17, 16321 Bernau, Germany
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Phone: +49 3338 694 610 Fax: +49 3338 694 644,

E-mail: c.butter@immanuel.de
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1These authors contributed equally to this publication (share first authorship).

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Funding:
Funding
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This work was supported by the Japan Society for the Promotion of Science

(Hidehiro Kaneko).
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Abstract

Functional mitral regurgitation (MR) is common in patients with heart failure (HF) and

left ventricular (LV) dysfunction. MitraClip (MC) is a novel therapeutic option for

patients with high-risk MR. Similar to LV dysfunction, right ventricular dysfunction

(RVD) is an important predictor of patients with HF. We aimed to clarify the effect of

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RVD on outcomes of functional MR and LV dysfunction after MC implantation. We

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examined 117 patients with severe functional MR and reduced LV ejection fraction

(LVEF) (40%) treated with MC. RVD was defined as tricuspid annular plane systolic

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excursion <15 mm, and was observed in 41 patients (35%). Mean age and sex were

similar between patients with and without RVD. Atrial fibrillation was more common in

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patients with RVD. MR grades at baseline and discharge, and LVEF were not different
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between the groups. Six months after MC implantation, responders to the N-terminal
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pro-B type natriuretic peptide (NT-proBNP) were less common in patients with RVD

than those with out (29% vs. 65%, p=0.005). Kaplan-Meier curves showed that survival
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rates of patients with RVD were significantly lower than those without (36.2% vs. 69.6%,
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p=0.008). After adjusting for covariates, RVD was still associated with all-cause

mortality (hazard ratio 1.975, p=0.042). The present studys results suggest that RVD is
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associated with worse survival of functional MR and LV dysfunction in patients

undergoing MC in association with no response to NT-proBNP. The indication for MC

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should be carefully considered in functional MR patients with RVD.

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Keywords: MitraClip, Functional Mitral Regurgitation, Right Ventricular Function,

Heart Failure
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Introduction

Functional mitral regurgitation (MR) is commonly observed in patients with

left ventricular (LV) dysfunction and heart failure (HF).1-3 Mitral valve surgery is

a standard treatment for severe MR. However, the clinical benefit of mitral valve

surgery for patients with functional MR and LV dysfunction has not yet been

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established;4 therefore, mitral valve surgery is frequently hesitated in these

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patients. Percutaneous edge-to-edge mitral valve repair using MitraClip (MC) is

a novel therapeutic option for MR even in patients with a high surgical risk.5, 6

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MC is considered an attractive therapeutic option for patients with high-risk

functional MR with LV dysfunction and advanced HF because of its superior

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safety. Similar to LV dysfunction, right ventricular dysfunction (RVD) is closely
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associated with the prognosis of patients with HF.7-9 However, the association

between preprocedural RVD and the prognosis of patients with functional MR

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undergoing MC remains unclear. In the present study, we sought to clarify the

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effect of RVD on the outcomes of patients with functional MR treated with MC.
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Methods
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We enrolled consecutive patients with MR who underwent percutaneous

edge-to-edge mitral valve repair using MC at the Heart Center Brandenburg from
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March 2009. All patients had a European System for Cardiac Operative Risk
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Evaluation > 20% or other severe comorbidities, suggesting that they had

extremely high surgical risks, and they were evaluated by a multidisciplinary

team. All patients had symptomatic severe (functional) MR grade > 2+, despite

optimal medical treatment. Experienced investigators performed transthoracic

and transesophageal echocardiography by using commercially available

ultrasound diagnostic systems (Vivid 7 and Vivid E9, GE Medical Systems,

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Milwaukee, WI, USA and Philips IE 33, Royal Philips Electronics, Amsterdam,

The Netherlands). MR at baseline was graded according to the American Society

of Echocardiography guidelines.10 After the procedure, MR grade was assessed by

the technique reported by Foster et al.11 We did not consider MC therapy for

patiehts who had severe clinical comorbidities such as end-stage cancer or other

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severe diseases with a very unfavorable prognosis, and those whose morphology

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of the mitral valve was technically impossible or unlikely beyond the classic

EVEREST criteria. We screened 255 patients for this study, and we excluded

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those with unsuccessful clip deployment (n = 6), degenerative MR (n = 85) or an

unknown etiology (n = 2), LV ejection fraction (EF) (> 40%) (n = 37) or a lack of

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LVEF data (n = 7), and lack of preprocedural tricuspid annular plane systolic
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excursion (TAPSE) data (n = 1). Finally, we analyzed 117 patients in this study.

The median follow-up period was 707 590 days. No patient was referred for
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heart transplantation. The ethical committee of our institution approved the

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protocols of this study. All patients were informed about the specific risks and
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alternative treatments, and they gave informed consent. The study was

performed in accordance with the Declaration of Helsinki.

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We defined LV dysfunction as LVEF 40% and RVD as TAPSE < 15 mm. The

estimated glomerular filtration rate (eGFR) was calculated using the

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Modification of Diet in Renal Disease equation.12 Chronic kidney disease was

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defined as an eGFR < 60 mL/min/1.73m2. Responders to the N-terminal

pro-B-type natriuretic peptide (NT-pro BNP) were defined as patients whose

NP-pro BNP levels decreased by > 30% according to previous studies.13, 14

We performed the percutaneous edge-to-edge mitral valve repair procedure

by using a 24-French MC device (CDS01 or CDS02; Abbott Vascular, Santa Clara,

CA, USA) under general anesthesia with the use of fluoroscopic and
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transesophageal echocardiographic guidance, according to previous studies.5, 15

Categorical and consecutive data regarding patients background are

presented as numbers (%) and means standard deviations, respectively. The

chi-square test was used to compare data between groups, and the unpaired t-test

was used to compare consecutive variables. We performed the paired t-test to

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analyze changes in the parameters (baseline and 6 months after MC

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implantation). The long-term survival rate was estimated using Kaplan-Meier

curves, and the log-rank test was used to assess the significance of differences

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between patients with and without RVD. We conducted univariate and

multivariable Cox regression analyses to assess the effect of RVD on all-cause

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mortality after MC therapy. In multivariable Cox regression analysis, the effect of
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RVD was adjusted by age 75 years, New York Heart Association (NYHA) class

IV, NT-pro BNP level > 5,000 pg/mL, the presence of atrial fibrillation (AF), and a
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history of coronary artery bypass graft (CABG) (step-wise method). A probability

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value of < 0.05 was considered to indicate a statistically significant difference. We

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performed statistical analyses by using SPSS, version 19.0 software (SPSS Inc.,

Chicago, IL, USA).

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Results

Table 1 shows the study patients characteristics. RVD was observed in 41

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patients (35%). Sex and the mean age were similar between patients with and
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without RVD. More than 90% of the study patients had NYHA class III or IV, and

the preprocedural NYHA class was not different between the groups.

Approximately half of the study patients had NT-pro BNP level > 5,000 pg/mL at

baseline, and the preprocedural NT-pro BNP level was similar between patients

with and without RVD. AF was more frequently observed in patients with RVD

than without RVD (68% vs. 38%, p = 0.003). A history of CABG tended to be more
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common in patients with RVD than in those without RVD (34% vs. 18%, p =

0.057).

Table 2 summarizes the echocardiographic parameters. MR grades at

baseline and hospital discharge were similar between patients with and without

RVD. Baseline LVEF was not different between patients with and without RVD.

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The incidence of a periprocedural complication was not different between

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patients with and without RVD (2.4% [1/41] vs. 3.9% [3/76], p = 0.668). One

puncture site hematoma occurred among patients with RVD. One hematoma,

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arteriovenous fistula, and pneumothorax occurred among patients without RVD.

Six months after the procedure, MR grade (Figure 1A) and NYHA class

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(Figure 1B) significantly improved in patients with and without RVD. NT-pro
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BNP levels significantly decreased in patients without RVD, whereas it did not

change in those with RVD (Figure 1C). Responders to NT-pro BNP were less
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common in patients with RVD than in those without RVD (29% vs. 65%, p =
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0.005). LV diastolic dimensions significantly decreased 6 months after the MC

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procedures in patients with and without RVD (Figure 1D). LV systolic dimensions

also significantly decreased in patients without RVD, but this did not occur in
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those with RVD (Figure 1E). LVEF significantly increased 6 months after the

procedure in patients without RVD. In patients with RVD, LVEF also tended to
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increase 6 months after MC therapy (Figure 1F).

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The 30-day, 1-year, and total survival rates were 92.0%, 78.3%, and 69.6%,

respectively, in patients without RVD, and 87.6%, 69.0%, and 36.2%, respectively,

in those with RVD. Results of the Kaplan-Meier curves and log-rank test showed

that the survival rates of patients with RVD were significantly lower than those

of patients without RVD (p = 0.008) (Figure 2). Similar to findings of the

Kaplan-Meier curves, univariate Cox regression analysis showed that RVD was
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associated with all-cause mortality (p = 0.010, hazard ratio [HR] 2.264, 95%

confidence interval [CI] 1.2154.219). In multivariable analysis, as well as age

75 years, RVD was still associated with all-cause mortality (p = 0.042, HR 1.975,

95% CI 1.0263.805; Table 3).

Discussion

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RVD is a strong predictor of cardiovascular events in patients with HF.16-18

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Additionally, in patients with degenerative MR, RV function is associated with

mortality, regardless of LVEF.19 Among various parameters of RV function,

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TAPSE is more commonly used,7, 8 because this parameter is easily obtainable

and reproducible. Dini et al. reported that RV function assessed by TAPSE was

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associated with the clinical outcomes of patients with moderate to severe
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functional MR.20 Furthermore, measuring TAPSE preoperatively may be useful

for predicting the clinical course of patients with MR undergoing mitral valve
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surgery.21 However, the effect of RVD on the clinical outcomes of patients with
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functional MR and LV dysfunction undergoing MC remain unclear; therefore,

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this is the first study to evaluate the effect of preprocedural RVD on the clinical

outcomes of these patients.

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Baseline characteristics were almost similar between patients with and

without RVD. Most study patients had severe HF such as an NYHA class III
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and increased baseline NT-pro BNP levels. However, these parameters were also
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similar between the groups. Concordant with the results of a previous study,22 AF

was more common in patients with RVD. Regarding the echocardiographic

parameters, baseline MR grade was not different between patients with and

without RVD. LV diameters and LVEF at baseline were also similar.

After MC implantation, MR grade remarkably improved even in patients with

RVD, and this improvement was sustained 6 months after the procedure. Despite
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similar improvement in MR grade, the survival rates were significantly lower in

patients with RVD. Interestingly, no response to NT-pro BNP was more common

among patients with RVD. Previous studies have demonstrated that natriuretic

peptide nonresponders with HF had a worse prognosis.13, 14 NT-pro BNP is an

established biomarker for patients with HF,23, 24 and we previously reported that

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a higher NT-pro BNP level at baseline was strongly associated with adverse

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clinical outcomes after MC.25 Therefore, the impaired HF improvement after MC

therapy may result in lower survival of patients with RVD. Furthermore, the

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improvement in LV function, including LV diameters and LVEF, seemed more

remarkable in patients without RVD than in those with RVD. Although it is

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inconclusive, the impaired LV reverse remodeling may also contribute to the poor
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prognosis of patients with RVD.

Despite the poor prognosis of functional MR,3,26 there has been no reports
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supporting the survival benefit of mitral valve surgery for functional MR.4,27
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Therefore, we think MC implantation is advantageous for patients with

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functional MR. Thus, the main target of this novel treatment is functional MR,

not degenerative MR, in real-world clinical settings.28, 29 However, our studys

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results suggest that the clinical benefit of MC implantation in patients with

functional MR and RVD may be limited, so we may need to reconsider the

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indication for MC therapy in patients with RVD. In a further study, it will be

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important to clarify the functional benefit of MC therapy in patients with RVD.

We acknowledge several limitations of this study. As this study was conducted

at a single center, we cannot apply the results of this study to general populations.

The data sets were also not complete for all patients because of the nature of the

retrospective study. Additionally, follow-up echocardiography was not performed

in all patients. As with all observational studies, it is possible that unmeasured

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confounders may have affected the results. Further studies with larger patient

populations are required to confirm our results. TAPSE is a preload-dependent

parameter, and this was not considered in this study.

Conflict
onflict of Interest
Interest

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Christian Butter and Michael Neuss received lecture honoraria and travel grants

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from Abbott Laboratories, Abbott Park, Illinois, USA.

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Funding

This work was supported by the Japan Society for the Promotion of Science

(Hidehiro Kaneko).
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1. Grigioni F, Enriquez-Sarano M, Zehr KJ, Bailey KR, Tajik AJ. Ischemic

mitral regurgitation: long-term outcome and prognostic implications with

quantitative Doppler assessment. Circulation 2001;103:1759-1764.

2. Trichon BH, Felker GM, Shaw LK, Cabell CH, O'Connor CM. Relation of

frequency and severity of mitral regurgitation to survival among patients with

PT
left ventricular systolic dysfunction and heart failure. Am J Cardiol

RI
2003;91:538-543.

3. Kaneko H, Suzuki S, Uejima T, Kano H, Matsuno S, Otsuka T, Takai H,

SC
Oikawa Y, Yajima J, Koike A, Nagashima K, Kirigaya H, Sagara K, Tanabe H,

Sawada H, Aizawa T, Yamashita T. Prevalence and the long-term prognosis of

U
functional mitral regurgitation in Japanese patients with symptomatic heart
AN
failure. Heart Vessels 2014;29:801-807.

4. Mihaljevic T, Lam BK, Rajeswaran J, Takagaki M, Lauer MS, Gillinov

M

AM, Blackstone EH, Lytle BW. Impact of mitral valve annuloplasty combined
D

with revascularization in patients with functional ischemic mitral regurgitation.

TE

J Am Coll Cardiol 2007;49:2191-2201.

5. Feldman T, Foster E, Glower DD, Kar S, Rinaldi MJ, Fail PS, Smalling
EP

RW, Siegel R, Rose GA, Engeron E, Loghin C, Trento A, Skipper ER, Fudge T,

Letsou GV, Massaro JM, Mauri L. Percutaneous repair or surgery for mitral
C

regurgitation. N Engl J Med 2011;364:1395-1406.

AC

6. Mauri L, Foster E, Glower DD, Apruzzese P, Massaro JM, Herrmann HC,

Hermiller J, Gray W, Wang A, Pedersen WR, Bajwa T, Lasala J, Low R, Grayburn

P, Feldman T. 4-year results of a randomized controlled trial of percutaneous

repair versus surgery for mitral regurgitation. J Am Coll Cardiol

2013;62:317-328.

7. Ghio S, Recusani F, Klersy C, Sebastiani R, Laudisa ML, Campana C,

 11
ACCEPTED MANUSCRIPT

Gavazzi A, Tavazzi L. Prognostic usefulness of the tricuspid annular plane

systolic excursion in patients with congestive heart failure secondary to

idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol 2000;85:837-842.

8. Kjaergaard J, Akkan D, Iversen KK, Kober L, Torp-Pedersen C, Hassager

C. Right ventricular dysfunction as an independent predictor of short- and

PT
long-term mortality in patients with heart failure. Eur J Heart Fail

RI
2007;9:610-616.

9. Meyer P, Filippatos GS, Ahmed MI, Iskandrian AE, Bittner V, Perry GJ,

SC
White M, Aban IB, Mujib M, Dell'Italia LJ, Ahmed A. Effects of right ventricular

ejection fraction on outcomes in chronic systolic heart failure. Circulation

2010;121:252-258.
U
AN
10. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD,

Levine RA, Nihoyannopoulos P, Otto CM, Quinones MA, Rakowski H, Stewart

M

WJ, Waggoner A, Weissman NJ. Recommendations for evaluation of the severity

D

of native valvular regurgitation with two-dimensional and Doppler

TE

echocardiography. J Am Soc Echocardiogr 2003;16:777-802.

11. Foster E, Wasserman HS, Gray W, Homma S, Di Tullio MR, Rodriguez L,

EP

Stewart WJ, Whitlow P, Block P, Martin R, Merlino J, Herrmann HC, Wiegers SE,

Silvestry FE, Hamilton A, Zunamon A, Kraybill K, Gerber IL, Weeks SG, Zhang Y,
C

Feldman T. Quantitative assessment of severity of mitral regurgitation by serial

AC

echocardiography in a multicenter clinical trial of percutaneous mitral valve

repair. Am J Cardiol 2007;100:1577-1583.

12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more

accurate method to estimate glomerular filtration rate from serum creatinine: a

new prediction equation. Modification of Diet in Renal Disease Study Group. Ann

Intern Med 1999;130:461-470.

 12
ACCEPTED MANUSCRIPT

13. Karlstrom P, Alehagen U, Boman K, Dahlstrom U. Brain natriuretic

peptide-guided treatment does not improve morbidity and mortality in

extensively treated patients with chronic heart failure: responders to treatment

have a significantly better outcome. Eur J Heart Fail 2011;13:1096-1103.

14. Ribeiro A, Lourenco P, Silva S, Cunha F, Vilaca J, Gomes F, Araujo JP,

PT
Bettencourt P. Predictors of natriuretic peptide non-response in patients

RI
hospitalized with acute heart failure. Am J Cardiol 2015;115:69-74.

15. Seifert M, Schau T, Schoepp M, Arya A, Neuss M, Butter C. MitraClip in

SC
CRT non-responders with severe mitral regurgitation. Int J Cardiol

2014;177:79-85.

16.
U
Polak JF, Holman BL, Wynne J, Colucci WS. Right ventricular ejection
AN
fraction: an indicator of increased mortality in patients with congestive heart

failure associated with coronary artery disease. J Am Coll Cardiol

M

1983;2:217-224.
D

17. Juilliere Y, Barbier G, Feldmann L, Grentzinger A, Danchin N, Cherrier F.

TE

Additional predictive value of both left and right ventricular ejection fractions on

long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J

EP

1997;18:276-280.

18. de Groote P, Millaire A, Foucher-Hossein C, Nugue O, Marchandise X,

C

Ducloux G, Lablanche JM. Right ventricular ejection fraction is an independent

AC

predictor of survival in patients with moderate heart failure. J Am Coll Cardiol

1998;32:948-954.

19. Hochreiter C, Niles N, Devereux RB, Kligfield P, Borer JS. Mitral

regurgitation: relationship of noninvasive descriptors of right and left ventricular

performance to clinical and hemodynamic findings and to prognosis in medically

and surgically treated patients. Circulation 1986;73:900-912.

 13
ACCEPTED MANUSCRIPT

20. Dini FL, Conti U, Fontanive P, Andreini D, Banti S, Braccini L, De

Tommasi SM. Right ventricular dysfunction is a major predictor of outcome in

patients with moderate to severe mitral regurgitation and left ventricular

dysfunction. Am Heart J 2007;154:172-179.

21. Chrustowicz A, Gackowski A, El-Massri N, Sadowski J, Piwowarska W.

PT
Preoperative right ventricular function in patients with organic mitral

RI
regurgitation. Echocardiography 2010;27:282-285.

22. Ereminiene E, Vaskelyte JJ, Stoskute N, Kavoliuniene A, Bieseviciene M,

SC
Ordiene R, Nedzelskiene I. Determinants of reduced tricuspid annular plane

systolic excursion in patients with severe systolic left ventricular dysfunction.

Acta Cardiol 2012;67:657-663.

U
AN
23. Januzzi JL, van Kimmenade R, Lainchbury J, Bayes-Genis A,

Ordonez-Llanos J, Santalo-Bel M, Pinto YM, Richards M. NT-proBNP testing for

M

diagnosis and short-term prognosis in acute destabilized heart failure: an

D

international pooled analysis of 1256 patients: the International Collaborative of

TE

NT-proBNP Study. Eur Heart J 2006;27:330-337.

24. Moe GW, Howlett J, Januzzi JL, Zowall H. N-terminal pro-B-type

EP

natriuretic peptide testing improves the management of patients with suspected

acute heart failure: primary results of the Canadian prospective randomized

C

multicenter IMPROVE-CHF study. Circulation 2007;115:3103-3110.

AC

25. Neuss M, Schau T, Schoepp M, Seifert M, Holschermann F, Meyhofer J,

Butter C. Patient selection criteria and midterm clinical outcome for MitraClip

therapy in patients with severe mitral regurgitation and severe congestive heart

failure. Eur J Heart Fail 2013;15:786-795.

26. Kaneko H, Suzuki S, Uejima T, Kano H, Matsuno S, Takai H, Oikawa Y,

Yajima J, Aizawa T, Yamashita T. Functional mitral regurgitation and left

 14
ACCEPTED MANUSCRIPT

ventricular systolic dysfunction in the recent era of cardiovascular clinical

practice, an observational cohort study. Hypertens Res 2014;37:1082-1087.

27. Wu AH, Aaronson KD, Bolling SF, Pagani FD, Welch K, Koelling TM.

Impact of mitral valve annuloplasty on mortality risk in patients with mitral

regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol

PT
2005;45:381-387.

RI
28. Maisano F, Franzen O, Baldus S, Schafer U, Hausleiter J, Butter C, Ussia

GP, Sievert H, Richardt G, Widder JD, Moccetti T, Schillinger W. Percutaneous

SC
mitral valve interventions in the real world: early and 1-year results from the

ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of

U
the MitraClip therapy in Europe. J Am Coll Cardiol 2013;62:1052-1061.
AN
29. Schueler R, Nickenig G, May AE, Schillinger W, Bekeredjian R, Ouarrak T,

Schofer J, Hehrlein C, Sievert H, Boekstegers P, Lubos E, Hoffmann R, Baldus S,

M

Senges J, Hammerstingl C. Predictors for short-term outcomes of patients

D

undergoing transcatheter mitral valve interventions: analysis of 778 prospective

TE

patients from the German TRAMI registry focusing on baseline renal function.

EuroIntervention 2016;12:508-514.
C EP
AC
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Figure Legends

Figure 1.

Serial changes of clinical parameters. MR grade (A), NYHA class (B), NT-pro

BNP (C), LVDd (D), LVDs (E), and LVEF (F).

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Figure 2.
2.

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Kaplan-Meier curves for survival rate after MC implantation.

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Table 1. Characteristics of patients

Right Ventricular
Variable
Dysfunction

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Absent Present
P-Value

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(n = 76) (n = 41)

Male Gender 78% (59/76) 81% (33/41) 0.719

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Age (years) 70 9 72 10 0.386

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Age75 years AN 30% (23/76) 44% (18/41) 0.140

Logistic euro SCORE (%) 24 16 27 21 0.548

New York Heart Association 0.234

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Class II 1.3% (1/76) 7% (3/41)

Class III 62% (47/76) 59% (24/41)

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Class IV 37% (28/76) 34% (14/41)

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N-terminal pro-B type natriuretic 7,786 9,565

0.309
peptide (pg/mL) 7,979 10,115
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N-terminal pro-B type natriuretic

45% 47% 0.838
peptide > 5,000 pg/mL
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Hypertension 50% (38/76) 51% (21/41) 0.900

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Diabetes mellitus 41% (31/75) 39% (15/39) 0.767

Chronic kidney disease 71% (52/73) 71% (27/38) 0.984

Estimated glomerular filtration
49 25 47 22 0.661
rate (mL/min/1.73m2)
Chronic obstructive pulmonary
29% (22/76) 22% (9/41) 0.413
disease
Atrial fibrillation 38% (29/76) 68% (27/40) 0.003
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Prior history of myocardial

30% (23/76) 29% (12/41) 0.911
infarction
Prior history of percutaneous
49% (37/76) 46% (19/46) 0.809
coronary intervention
Prior history of coronary artery
18% (14/76) 34% (14/41) 0.057
bypass graft

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Prior history of cardiac surgery 30% (23/76) 42% (17/41) 0.223

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Coronary artery bypass graft 18% (14/76) 29% (12/41)

Valvular surgery 9.2% (7/76) 7.3% (3/41)

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Vascular surgery 1.3% (1/76) 0% (0/41)

Congenital heart disease 1.3% (1/76)) 0% (0/41)

Coronary artery bypass graft +
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0% (0/76)) 2.4% (1/41)
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valvular surgery
Coronary artery bypass graft +
0% (0/76) 2.4% (1/41)
Congenital heart disease
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Implanted devices
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Pacemaker 9.2% (7/76) 2.4% (1/41) 0.166

Implantable cardioverter
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59% (45/76) 59% (24/41) 0.944

defibrillator
Cardiac resynchronization therapy 34% (26/76) 32% (13/41) 0.784
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Data are expressed as mean standard deviation, or percentage (number).

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Table 2. Echocardiography findings

Variable Right Ventricular Dysfunction

Absent Present

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P-Value
(n = 76) (n = 41)

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MR grade at baseline 0.357

MR3+ 33% (25/76) 42% (17/41)

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MR4+ 67% (51/76) 58% (24/41)

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MR grade at discharge AN 0.333

MR1+ 43% (33/76) 34% (14/41)

MR2+ 53% (40/76) 54% (22/41)

M

MR3+ 2.6% (2/76) 9.8% (4/41)

MR4+ 1.3% (1/76) 2.4% (1/41)

D

Left ventricular diastolic

67 9 67 10 0.793
TE

dimension (mm)
Left ventricular systolic
58 9 58 11 0.772
dimension (mm)
EP

Left ventricular ejection fraction

26 7 23 8 0.106
(%)
C

Left atrial dimension (mm) 45 6 45 8 0.568

Tricuspid regurgitation
AC

24% (18/76) 17% (7/41) 0.405

Moderate
Tricuspid annular plane systolic
19 3 12 2 < 0.001
excursion (mm)

MR = mitral regurgitation.

Data are expressed as mean standard deviation, or percentage (number).

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Table 3. HRs of RV dysfunction for mortality

Univariate Analysis
P-Value HR 95% CI
RV dysfunction 0.010 2.264 1.215 4.219

PT
Multivariable Analysis
P-Value HR 95% CI

RI
RV dysfunction 0.042 1.975 1.026 3.805
Age 75 years 0.008 2.465 1.265 4.802

SC
RV = right ventricular
HR, hazard ratio; CI, confidence interval; RV, right ventricular.

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