JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 67, NO. 5, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacc.2015.10.098
Effect of Recurrent Mitral Regurgitation Following Degenerative Mitral Valve Repair Long-Term Analysis of Competing Outcomes Rakesh M. Suri, MD, DPHIL,a Marie-Annick Clavel, DVM, PHD,b,c Hartzell V. Schaff, MD,a Hector I. Michelena, MD,b Marianne Huebner, PHD,d Rick A. Nishimura, MD,b Maurice Enriquez-Sarano, MDd
ABSTRACT BACKGROUND The risk for and consequences of recurrent mitral regurgitation (MR) following degenerative mitral valve repair are poorly understood. OBJECTIVES This study sought to examine recurrent MR risk along with reoperation and survival rates. METHODS We evaluated patients undergoing primary mitral repair for isolated degenerative MR over 1 decade. Median follow-up was 11.5 years (interquartile range: 9.2 to 13.6 years) and was 99% complete. Multivariate analysis of postrepair MR recurrence employed Cox proportional hazards and multistate modeling. RESULTS A total of 1,218 patients met the study criteria; the mean age was 64 13 years, mean ejection fraction was 63 9%, and 864 (71%) patients were men. Prolapse was posterior in 62%, bileaflet in 26%, and anterior in 12%. The 15-year incidence of recurrent MR (i.e., MR $2) was 13.3%, incidence of mitral reoperation was 6.9%, and overall mortality was 44.0%. Repair before 1996 independently predicted MR recurrence (hazard ratio: 1.52). Additional determinants were: age, mild intraoperative residual MR, anterior leaflet prolapse, bileaflet prolapse, perfusion time >90 min, and lack of annuloplasty. Recurrence of moderate or greater MR was associated with adverse left ventricular remodeling and increased likelihood of death (hazard ratio: 1.72). Among those undergoing repair after 1996, MR recurrence rate was 1.5 per 100 patient-years during the first year post-repair, decreasing markedly to 0.9 thereafter. CONCLUSIONS Our study demonstrated that recurrent MR following degenerative mitral valve repair is associated with adverse left ventricular remodeling and late death. The incidence of MR recurrence decreases markedly following the first year after intervention. A transparent discussion of recurrent MR risk has pressing relevance when referring patients with complex mitral valve prolapse. (J Am Coll Cardiol 2016;67:488–98) © 2016 by the American College of Cardiology Foundation.
E Listen to this manuscript’s
arly surgical correction of severe mitral regur-
Current consensus statements mandate “rescue”
gitation (MR) caused by prolapse due to flail
MR correction in the presence of left ventricular
leaflets improves long-term survival and
(LV) dysfunction or symptoms (8). In the absence
diminishes late heart failure risk (1,2), particularly
of these Class I triggers, early “restorative” surgery
when performed by valve repair specialists within
is
a center of excellence (3–5). Mitral valve (MV) repair
normal in the presence of atrial fibrillation (AF) or
is safe and preferred over replacement in correcting
pulmonary hypertension, or when performed at cen-
MR caused by degenerative valve disease (6,7).
ters where the procedural risk of mortality is 95% (9). Prior to taking
reversion to replacement in the current era (4),
ABBREVIATIONS
the step to generalize the recommendation for early
MR recurrence (not merely reoperation) rates
AND ACRONYMS
MR correction in the presence of Class IIa indica-
from multisurgeon practices must be better
tions, however, it is critically important to under-
understood to formulate guidelines applicable
stand
MV
to community cardiology practices world-
repair, along with the consequences and predictors
wide. Additionally, although mechanisms of
of this occurrence.
and therapeutic approaches to address recur-
recurrent
MR
rates
following
rent MR following prior repair have been
SEE PAGE 499
described (12,13), the effects on LV remodeling
Although prior series have demonstrated that
LV = left ventricular LVEF = left ventricular ejection fraction
MR = mitral regurgitation MV = mitral valve NYHA = New York Heart Association
and long-term life expectancy remain poorly
reoperation rate following degenerative MV repair is
defined. A final important limitation of prior work has
approximately 0.5% to 1% per year (7,10), assessing
been the inability to account for the attrition of pa-
durability on the basis of reintervention alone likely
tients during follow-up due to late death. The true
underestimates the long-term patient risk. While
incidence of recurrent MR and its determinants may
expert single surgeon series (3–5) have suggested that
therefore not be fully appreciated (13–15).
it is possible to repair degenerative mitral prolapse
We hypothesized that the use of multistate
with near 100% certainty (3,11) and infrequent
modeling to account for the competing risk of death
F I G U R E 1 Echocardiographic Follow-Up
Echo performed at Mayo Clinic Echo performed by treating physician Death 0.16% 0.08% 0.08%
Missing Echo End of Follow-up
100
1.23%
2.39%
11.65%
6.88%
2.72% 3.45%
2.46%
7.96%
17.24%
10.36% 4.13%
Percentage of Patients, (%)
80
43.92% 28.15%
29.64% 34.56%
60
39.48% 99.68%
40
4.76% 31.49% 56.51%
33.99% 48.21% 37.11%
20
24.38%
7.81% 9.52%
0 Mitral Valve Repair
30 Days
1 Year
5 Years
10 Years
15 Years
Follow-Up Time Although initially nearly all patients had an echocardiogram (echo) at Mayo Clinic following mitral valve repair, over time, patients more frequently underwent echocardiography at home institutions. The percentages of patients unavailable for an echocardiogram in a given period, had not yet returned, or had died all increased with time.
489
490
Suri et al.
JACC VOL. 67, NO. 5, 2016
Consequences of Recurrent Regurgitation Following Mitral Repair
FEBRUARY 9, 2016:488–98
METHODS
T A B L E 1 Baseline Pre-Operative Characteristics
Whole Cohort (n ¼ 1,218)
MR Recurrence (n ¼ 133)
No MR Recurrence (n ¼ 1,085)
p Value
Age, yrs
64 13
66 12
64 13
0.07
nesota. Eligible patients were those who underwent
Female
354 (29)
39 (29)
315 (29)
0.94
primary, isolated MV repair for pure MR (no stenosis),
Atrial fibrillation
308 (25)
37 (28)
271 (25)
0.48
and who had degenerative disease with surgically
Hypertension
421 (35)
60 (45)
361 (33)
0.008
59 (5)
12 (9)
47 (4)
0.03
verified MV prolapse as cause of regurgitation.
CAD
319 (26)
40 (30)
269 (26)
0.28
NYHA functional class III–IV
366 (30)
44 (33)
322 (30)
0.42
LVEDD, mm
59.9 7.4
60.2 8.0
59.8 7.3
0.69
repair; tricuspid valve replacement; previous mitral,
LVESD, mm
36.8 6.8
36.7 7.2
36.8 6.8
0.87
aortic, or tricuspid valve repair or replacement;
63 9
63 8
63 9
0.73
concomitant congenital (other than closure of patent
LV mass, g
265 68
272 65
264 68
0.40
foramen ovale), pericardial, or myocardial (particu-
Ruptured chordae
768 (64)
73 (55)
695 (65)
0.04
We studied consecutive patients who underwent degenerative MV repair between January 1, 1990, and December 31, 2000, at Mayo Clinic in Rochester, Min-
Clinical data
Diabetes
We excluded patients who had: mitral stenosis by hemodynamic assessment or surgical evaluation of the lesions; concomitant aortic valve replacement or
Echocardiographic data
LVEF, %
85%
1,052 (97)
Early post-operative Post-operative MI
Left atrial diameter was measured using parasternal
of alive patients for each time point between 0 to 4 (0.3)
0 (0)
4 (0.4)
0.34
17 (1.4)
0 (0)
17 (1.6)
0.05
138 (11)
22 (17)
116 (11)
0.06
27 (2)
8 (6)
19 (2)
0.007
10 years and 80% between 10 to 15 years (Figure 1). Echocardiographic
data
were
used
as
collected
without subsequent modification. FOLLOW-UP. Patients were followed by their per-
Values are n (%) or mean SD.
sonal physicians at a Mayo Clinic facility or at the
CABG ¼ coronary artery bypass grafting; IABP ¼ intra-aortic balloon pump; MI ¼ myocardial infarction; OR ¼ operating room; other abbreviations as in Table 1.
patient’s home institution. Information on follow-up events was obtained from medical examination or
JACC VOL. 67, NO. 5, 2016
Suri et al.
FEBRUARY 9, 2016:488–98
Consequences of Recurrent Regurgitation Following Mitral Repair
direct patient interview by the research team or use of repeated
follow-up
letters
and
questionnaires.
491
T A B L E 3 Echocardiographic LV Characteristics at Latest
Follow-Up
Follow-up echocardiographic reports from all sources Recurrent MR
No Recurrent MR
p Value
Interventricular septum thickness, mm
12.6 3.0
11.0 1.9
VOL. 67, NO. 5, 2016
ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
ISSN 0735-1097/$36.00
PUBLISHED BY ELSEVIER
http://dx.doi.org/10.1016/j.jacc.2015.10.098
Effect of Recurrent Mitral Regurgitation Following Degenerative Mitral Valve Repair Long-Term Analysis of Competing Outcomes Rakesh M. Suri, MD, DPHIL,a Marie-Annick Clavel, DVM, PHD,b,c Hartzell V. Schaff, MD,a Hector I. Michelena, MD,b Marianne Huebner, PHD,d Rick A. Nishimura, MD,b Maurice Enriquez-Sarano, MDd
ABSTRACT BACKGROUND The risk for and consequences of recurrent mitral regurgitation (MR) following degenerative mitral valve repair are poorly understood. OBJECTIVES This study sought to examine recurrent MR risk along with reoperation and survival rates. METHODS We evaluated patients undergoing primary mitral repair for isolated degenerative MR over 1 decade. Median follow-up was 11.5 years (interquartile range: 9.2 to 13.6 years) and was 99% complete. Multivariate analysis of postrepair MR recurrence employed Cox proportional hazards and multistate modeling. RESULTS A total of 1,218 patients met the study criteria; the mean age was 64 13 years, mean ejection fraction was 63 9%, and 864 (71%) patients were men. Prolapse was posterior in 62%, bileaflet in 26%, and anterior in 12%. The 15-year incidence of recurrent MR (i.e., MR $2) was 13.3%, incidence of mitral reoperation was 6.9%, and overall mortality was 44.0%. Repair before 1996 independently predicted MR recurrence (hazard ratio: 1.52). Additional determinants were: age, mild intraoperative residual MR, anterior leaflet prolapse, bileaflet prolapse, perfusion time >90 min, and lack of annuloplasty. Recurrence of moderate or greater MR was associated with adverse left ventricular remodeling and increased likelihood of death (hazard ratio: 1.72). Among those undergoing repair after 1996, MR recurrence rate was 1.5 per 100 patient-years during the first year post-repair, decreasing markedly to 0.9 thereafter. CONCLUSIONS Our study demonstrated that recurrent MR following degenerative mitral valve repair is associated with adverse left ventricular remodeling and late death. The incidence of MR recurrence decreases markedly following the first year after intervention. A transparent discussion of recurrent MR risk has pressing relevance when referring patients with complex mitral valve prolapse. (J Am Coll Cardiol 2016;67:488–98) © 2016 by the American College of Cardiology Foundation.
E Listen to this manuscript’s
arly surgical correction of severe mitral regur-
Current consensus statements mandate “rescue”
gitation (MR) caused by prolapse due to flail
MR correction in the presence of left ventricular
leaflets improves long-term survival and
(LV) dysfunction or symptoms (8). In the absence
diminishes late heart failure risk (1,2), particularly
of these Class I triggers, early “restorative” surgery
when performed by valve repair specialists within
is
a center of excellence (3–5). Mitral valve (MV) repair
normal in the presence of atrial fibrillation (AF) or
is safe and preferred over replacement in correcting
pulmonary hypertension, or when performed at cen-
MR caused by degenerative valve disease (6,7).
ters where the procedural risk of mortality is 95% (9). Prior to taking
reversion to replacement in the current era (4),
ABBREVIATIONS
the step to generalize the recommendation for early
MR recurrence (not merely reoperation) rates
AND ACRONYMS
MR correction in the presence of Class IIa indica-
from multisurgeon practices must be better
tions, however, it is critically important to under-
understood to formulate guidelines applicable
stand
MV
to community cardiology practices world-
repair, along with the consequences and predictors
wide. Additionally, although mechanisms of
of this occurrence.
and therapeutic approaches to address recur-
recurrent
MR
rates
following
rent MR following prior repair have been
SEE PAGE 499
described (12,13), the effects on LV remodeling
Although prior series have demonstrated that
LV = left ventricular LVEF = left ventricular ejection fraction
MR = mitral regurgitation MV = mitral valve NYHA = New York Heart Association
and long-term life expectancy remain poorly
reoperation rate following degenerative MV repair is
defined. A final important limitation of prior work has
approximately 0.5% to 1% per year (7,10), assessing
been the inability to account for the attrition of pa-
durability on the basis of reintervention alone likely
tients during follow-up due to late death. The true
underestimates the long-term patient risk. While
incidence of recurrent MR and its determinants may
expert single surgeon series (3–5) have suggested that
therefore not be fully appreciated (13–15).
it is possible to repair degenerative mitral prolapse
We hypothesized that the use of multistate
with near 100% certainty (3,11) and infrequent
modeling to account for the competing risk of death
F I G U R E 1 Echocardiographic Follow-Up
Echo performed at Mayo Clinic Echo performed by treating physician Death 0.16% 0.08% 0.08%
Missing Echo End of Follow-up
100
1.23%
2.39%
11.65%
6.88%
2.72% 3.45%
2.46%
7.96%
17.24%
10.36% 4.13%
Percentage of Patients, (%)
80
43.92% 28.15%
29.64% 34.56%
60
39.48% 99.68%
40
4.76% 31.49% 56.51%
33.99% 48.21% 37.11%
20
24.38%
7.81% 9.52%
0 Mitral Valve Repair
30 Days
1 Year
5 Years
10 Years
15 Years
Follow-Up Time Although initially nearly all patients had an echocardiogram (echo) at Mayo Clinic following mitral valve repair, over time, patients more frequently underwent echocardiography at home institutions. The percentages of patients unavailable for an echocardiogram in a given period, had not yet returned, or had died all increased with time.
489
490
Suri et al.
JACC VOL. 67, NO. 5, 2016
Consequences of Recurrent Regurgitation Following Mitral Repair
FEBRUARY 9, 2016:488–98
METHODS
T A B L E 1 Baseline Pre-Operative Characteristics
Whole Cohort (n ¼ 1,218)
MR Recurrence (n ¼ 133)
No MR Recurrence (n ¼ 1,085)
p Value
Age, yrs
64 13
66 12
64 13
0.07
nesota. Eligible patients were those who underwent
Female
354 (29)
39 (29)
315 (29)
0.94
primary, isolated MV repair for pure MR (no stenosis),
Atrial fibrillation
308 (25)
37 (28)
271 (25)
0.48
and who had degenerative disease with surgically
Hypertension
421 (35)
60 (45)
361 (33)
0.008
59 (5)
12 (9)
47 (4)
0.03
verified MV prolapse as cause of regurgitation.
CAD
319 (26)
40 (30)
269 (26)
0.28
NYHA functional class III–IV
366 (30)
44 (33)
322 (30)
0.42
LVEDD, mm
59.9 7.4
60.2 8.0
59.8 7.3
0.69
repair; tricuspid valve replacement; previous mitral,
LVESD, mm
36.8 6.8
36.7 7.2
36.8 6.8
0.87
aortic, or tricuspid valve repair or replacement;
63 9
63 8
63 9
0.73
concomitant congenital (other than closure of patent
LV mass, g
265 68
272 65
264 68
0.40
foramen ovale), pericardial, or myocardial (particu-
Ruptured chordae
768 (64)
73 (55)
695 (65)
0.04
We studied consecutive patients who underwent degenerative MV repair between January 1, 1990, and December 31, 2000, at Mayo Clinic in Rochester, Min-
Clinical data
Diabetes
We excluded patients who had: mitral stenosis by hemodynamic assessment or surgical evaluation of the lesions; concomitant aortic valve replacement or
Echocardiographic data
LVEF, %
85%
1,052 (97)
Early post-operative Post-operative MI
Left atrial diameter was measured using parasternal
of alive patients for each time point between 0 to 4 (0.3)
0 (0)
4 (0.4)
0.34
17 (1.4)
0 (0)
17 (1.6)
0.05
138 (11)
22 (17)
116 (11)
0.06
27 (2)
8 (6)
19 (2)
0.007
10 years and 80% between 10 to 15 years (Figure 1). Echocardiographic
data
were
used
as
collected
without subsequent modification. FOLLOW-UP. Patients were followed by their per-
Values are n (%) or mean SD.
sonal physicians at a Mayo Clinic facility or at the
CABG ¼ coronary artery bypass grafting; IABP ¼ intra-aortic balloon pump; MI ¼ myocardial infarction; OR ¼ operating room; other abbreviations as in Table 1.
patient’s home institution. Information on follow-up events was obtained from medical examination or
JACC VOL. 67, NO. 5, 2016
Suri et al.
FEBRUARY 9, 2016:488–98
Consequences of Recurrent Regurgitation Following Mitral Repair
direct patient interview by the research team or use of repeated
follow-up
letters
and
questionnaires.
491
T A B L E 3 Echocardiographic LV Characteristics at Latest
Follow-Up
Follow-up echocardiographic reports from all sources Recurrent MR
No Recurrent MR
p Value
Interventricular septum thickness, mm
12.6 3.0
11.0 1.9
