Академический Документы
Профессиональный Документы
Культура Документы
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
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.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
1
ACCEPTED MANUSCRIPT
Hidehiro Kaneko, MD1, Michael Neuss, MD1, Jens Weissenborn, MD, and
PT
and Department of Cardiology, Medical School Brandenburg
RI
*Correspondence:
SC
Department of Cardiology, Heart Center Brandenburg,
U
Ladeburger Strae 17, 16321 Bernau, Germany
AN
Phone: +49 3338 694 610 Fax: +49 3338 694 644,
E-mail: c.butter@immanuel.de
M
Funding:
Funding
TE
This work was supported by the Japan Society for the Promotion of Science
(Hidehiro Kaneko).
C EP
AC
2
ACCEPTED MANUSCRIPT
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
(RVD) is an important predictor of patients with HF. We aimed to clarify the effect of
PT
RVD on outcomes of functional MR and LV dysfunction after MC implantation. We
RI
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
SC
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
U
patients with RVD. MR grades at baseline and discharge, and LVEF were not different
AN
between the groups. Six months after MC implantation, responders to the N-terminal
M
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
D
rates of patients with RVD were significantly lower than those without (36.2% vs. 69.6%,
TE
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
EP
Heart Failure
3
ACCEPTED MANUSCRIPT
Introduction
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
PT
established;4 therefore, mitral valve surgery is frequently hesitated in these
RI
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
SC
MC is considered an attractive therapeutic option for patients with high-risk
U
safety. Similar to LV dysfunction, right ventricular dysfunction (RVD) is closely
AN
associated with the prognosis of patients with HF.7-9 However, the association
effect of RVD on the outcomes of patients with functional MR treated with MC.
TE
Methods
EP
edge-to-edge mitral valve repair using MC at the Heart Center Brandenburg from
C
March 2009. All patients had a European System for Cardiac Operative Risk
AC
Evaluation > 20% or other severe comorbidities, suggesting that they had
team. All patients had symptomatic severe (functional) MR grade > 2+, despite
Milwaukee, WI, USA and Philips IE 33, Royal Philips Electronics, Amsterdam,
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
PT
severe diseases with a very unfavorable prognosis, and those whose morphology
RI
of the mitral valve was technically impossible or unlikely beyond the classic
EVEREST criteria. We screened 255 patients for this study, and we excluded
SC
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
U
LVEF data (n = 7), and lack of preprocedural tricuspid annular plane systolic
AN
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
M
protocols of this study. All patients were informed about the specific risks and
TE
alternative treatments, and they gave informed consent. The study was
We defined LV dysfunction as LVEF 40% and RVD as TAPSE < 15 mm. The
CA, USA) under general anesthesia with the use of fluoroscopic and
5
ACCEPTED MANUSCRIPT
chi-square test was used to compare data between groups, and the unpaired t-test
PT
analyze changes in the parameters (baseline and 6 months after MC
RI
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
SC
between patients with and without RVD. We conducted univariate and
U
mortality after MC therapy. In multivariable Cox regression analysis, the effect of
AN
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
M
performed statistical analyses by using SPSS, version 19.0 software (SPSS Inc.,
Results
patients (35%). Sex and the mean age were similar between patients with and
AC
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
6
ACCEPTED MANUSCRIPT
common in patients with RVD than in those without RVD (34% vs. 18%, p =
0.057).
baseline and hospital discharge were similar between patients with and without
RVD. Baseline LVEF was not different between patients with and without RVD.
PT
The incidence of a periprocedural complication was not different between
RI
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,
SC
arteriovenous fistula, and pneumothorax occurred among patients without RVD.
Six months after the procedure, MR grade (Figure 1A) and NYHA class
U
(Figure 1B) significantly improved in patients with and without RVD. NT-pro
AN
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
M
common in patients with RVD than in those without RVD (29% vs. 65%, p =
D
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
EP
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
C
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
Kaplan-Meier curves, univariate Cox regression analysis showed that RVD was
7
ACCEPTED MANUSCRIPT
associated with all-cause mortality (p = 0.010, hazard ratio [HR] 2.264, 95%
75 years, RVD was still associated with all-cause mortality (p = 0.042, HR 1.975,
Discussion
PT
RVD is a strong predictor of cardiovascular events in patients with HF.16-18
RI
Additionally, in patients with degenerative MR, RV function is associated with
SC
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
U
associated with the clinical outcomes of patients with moderate to severe
AN
functional MR.20 Furthermore, measuring TAPSE preoperatively may be useful
for predicting the clinical course of patients with MR undergoing mitral valve
M
surgery.21 However, the effect of RVD on the clinical outcomes of patients with
D
this is the first study to evaluate the effect of preprocedural RVD on the clinical
without RVD. Most study patients had severe HF such as an NYHA class III
C
and increased baseline NT-pro BNP levels. However, these parameters were also
AC
similar between the groups. Concordant with the results of a previous study,22 AF
parameters, baseline MR grade was not different between patients with and
RVD, and this improvement was sustained 6 months after the procedure. Despite
8
ACCEPTED MANUSCRIPT
patients with RVD. Interestingly, no response to NT-pro BNP was more common
among patients with RVD. Previous studies have demonstrated that natriuretic
established biomarker for patients with HF,23, 24 and we previously reported that
PT
a higher NT-pro BNP level at baseline was strongly associated with adverse
RI
clinical outcomes after MC.25 Therefore, the impaired HF improvement after MC
therapy may result in lower survival of patients with RVD. Furthermore, the
SC
improvement in LV function, including LV diameters and LVEF, seemed more
U
inconclusive, the impaired LV reverse remodeling may also contribute to the poor
AN
prognosis of patients with RVD.
Despite the poor prognosis of functional MR,3,26 there has been no reports
M
supporting the survival benefit of mitral valve surgery for functional MR.4,27
D
functional MR. Thus, the main target of this novel treatment is functional MR,
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
confounders may have affected the results. Further studies with larger patient
Conflict
onflict of Interest
Interest
PT
Christian Butter and Michael Neuss received lecture honoraria and travel grants
RI
from Abbott Laboratories, Abbott Park, Illinois, USA.
SC
Funding
This work was supported by the Japan Society for the Promotion of Science
(Hidehiro Kaneko).
U
AN
M
D
TE
C EP
AC
10
ACCEPTED MANUSCRIPT
2. Trichon BH, Felker GM, Shaw LK, Cabell CH, O'Connor CM. Relation of
PT
left ventricular systolic dysfunction and heart failure. Am J Cardiol
RI
2003;91:538-543.
SC
Oikawa Y, Yajima J, Koike A, Nagashima K, Kirigaya H, Sagara K, Tanabe H,
U
functional mitral regurgitation in Japanese patients with symptomatic heart
AN
failure. Heart Vessels 2014;29:801-807.
AM, Blackstone EH, Lytle BW. Impact of mitral valve annuloplasty combined
D
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
2013;62:317-328.
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
2010;121:252-258.
U
AN
10. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD,
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
12. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more
new prediction equation. Modification of Diet in Renal Disease Study Group. Ann
PT
Bettencourt P. Predictors of natriuretic peptide non-response in patients
RI
hospitalized with acute heart failure. Am J Cardiol 2015;115:69-74.
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
1983;2:217-224.
D
Additional predictive value of both left and right ventricular ejection fractions on
1997;18:276-280.
1998;32:948-954.
PT
Preoperative right ventricular function in patients with organic mitral
RI
regurgitation. Echocardiography 2010;27:282-285.
SC
Ordiene R, Nedzelskiene I. Determinants of reduced tricuspid annular plane
Butter C. Patient selection criteria and midterm clinical outcome for MitraClip
therapy in patients with severe mitral regurgitation and severe congestive heart
27. Wu AH, Aaronson KD, Bolling SF, Pagani FD, Welch K, Koelling TM.
PT
2005;45:381-387.
RI
28. Maisano F, Franzen O, Baldus S, Schafer U, Hausleiter J, Butter C, Ussia
SC
mitral valve interventions in the real world: early and 1-year results from the
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,
patients from the German TRAMI registry focusing on baseline renal function.
EuroIntervention 2016;12:508-514.
C EP
AC
15
ACCEPTED MANUSCRIPT
Figure Legends
Figure 1.
Serial changes of clinical parameters. MR grade (A), NYHA class (B), NT-pro
PT
Figure 2.
2.
RI
Kaplan-Meier curves for survival rate after MC implantation.
U SC
AN
M
D
TE
C EP
AC
1
ACCEPTED MANUSCRIPT
Right Ventricular
Variable
Dysfunction
PT
Absent Present
P-Value
RI
(n = 76) (n = 41)
SC
Age (years) 70 9 72 10 0.386
U
Age75 years AN 30% (23/76) 44% (18/41) 0.140
PT
Prior history of cardiac surgery 30% (23/76) 42% (17/41) 0.223
RI
Coronary artery bypass graft 18% (14/76) 29% (12/41)
SC
Vascular surgery 1.3% (1/76) 0% (0/41)
Implanted devices
D
Absent Present
PT
P-Value
(n = 76) (n = 41)
RI
MR grade at baseline 0.357
SC
MR4+ 67% (51/76) 58% (24/41)
U
MR grade at discharge AN 0.333
dimension (mm)
Left ventricular systolic
58 9 58 11 0.772
dimension (mm)
EP
MR = mitral regurgitation.
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.
U
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC