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Transcript
D958etukansi.kesken.fm Page 1 Tuesday, November 27, 2007 3:06 PM
inen
OULU 2008
UNIVERSITY OF OULU P.O. Box 7500 FI-90014 UNIVERSITY OF OULU FINLAND
A C TA
U N I V E R S I TAT I S
S E R I E S
A
B
C
D
E
F
G
E D I T O R S
SCIENTIAE RERUM NATURALIUM
Professor Mikko Siponen
HUMANIORA
TECHNICA
Professor Harri Mantila
Professor Juha Kostamovaara
MEDICA
O U L U E N S I S
D 958
ACTA
Jouni Heikkinen
OUTCOME AFTER
MITRAL VALVE SURGERY
FOR MITRAL VALVE
REGURGITATION
Professor Olli Vuolteenaho
SCIENTIAE RERUM SOCIALIUM
Senior Assistant Timo Latomaa
SCRIPTA ACADEMICA
Communications Officer Elna Stjerna
OECONOMICA
Senior Lecturer Seppo Eriksson
EDITOR IN CHIEF
Professor Olli Vuolteenaho
EDITORIAL SECRETARY
Publications Editor Kirsti Nurkkala
ISBN 978-951-42-8680-3 (Paperback)
ISBN 978-951-42-8681-0 (PDF)
ISSN 0355-3221 (Print)
ISSN 1796-2234 (Online)
U N I V E R S I T AT I S O U L U E N S I S
FACULTY OF MEDICINE,
DEPARTMENT OF SURGERY,
DEPARTMENT OF INTERNAL MEDICINE,
UNIVERSITY OF OULU
D
MEDICA
ACTA UNIVERSITATIS OULUENSIS
D Medica 958
JOUNI HEIKKINEN
OUTCOME AFTER MITRAL VALVE
SURGERY FOR MITRAL VALVE
REGURGITATION
Academic Dissertation to be presented, with the assent
of the Faculty of Medicine of the University of Oulu, for
public defence in Auditorium 1 of Oulu University
Hospital, on January 18th, 2008, at 12 noon
O U L U N Y L I O P I S TO, O U L U 2 0 0 8
Copyright © 2008
Acta Univ. Oul. D 958, 2008
Supervised by
Docent Martti Lepojärvi
Docent Fausto Biancari
Professor Tatu Juvonen
Reviewed by
Docent Jari Laurikka
Professor Keijo Peuhkurinen
ISBN 978-951-42-8680-3 (Paperback)
ISBN 978-951-42-8681-0 (PDF)
http://herkules.oulu.fi/isbn9789514286810/
ISSN 0355-3221 (Printed)
ISSN 1796-2234 (Online)
http://herkules.oulu.fi/issn03553221/
Cover design
Raimo Ahonen
OULU UNIVERSITY PRESS
OULU 2008
Heikkinen, Jouni, Outcome after mitral valve surgery for mitral valve regurgitation
Faculty of Medicine, Department of Surgery, Department of Internal Medicine, University of Oulu,
P.O.Box 5000, FI-90014 University of Oulu, Finland
Acta Univ. Oul. D 958, 2008
Oulu, Finland
Abstract
The repair of degenerative mitral valve regurgitation has been shown to be an effective procedure
with durable results. The techniques for mitral valve repair are not completely risk-free for late
failure, and the identification of factors associated with this increased risk is of clinical relevance as
it permits an appropriate selection of patients for whom mitral valve surgery should be offered and
by which technique. The European system for cardiac operative risk evaluation score (EuroSCORE)
has been used and demonstrated worldwide to be a valid tool for the prediction of immediate
postoperative outcome after coronary artery bypass surgery. There are only a few studies which
examine its value in heart valve surgery. Mitral valve repair has been shown to be associated with
significant improvement in terms of functional capacity, but the late quality of life in these patients
has not been adequately assessed, and there is no data on the quality of life of long-term survivors.
The study population consisted of two groups of patients operated on at our institution. The first
group included 164 patients who underwent isolated or combined mitral valve repair for mitral valve
regurgitation during the period 1993 to 2000, while the second group consisted of 207 patients who
underwent mitral valve repair (164 patients) or replacement (43 patients) for isolated mitral valve
regurgitation during the same time-period. The first study aimed to identify preoperative variables
which may have impact on the 30-day postoperative outcome. In the second study, the long-term
outcome after mitral valve repair was evaluated in order to identify the risk factors associated with
late failures. The third study analyzed quality of life after valve repair and compared it to that of an
age- and gender-adjusted Finnish general population. In the fourth study, the validity of EuroSCORE
was tested in predicting the immediate and late outcome of patients who had undergone mitral valve
repair or replacement for isolated valve regurgitation
Patient age, a history of prior cardiac surgery and NYHA functional class were independent
predictors of poor outcome. A residual regurgitation grade of more than one immediately after
primary repair and chronic pulmonary disease were independent predictors of mitral valve
reoperation. After valve repair, quality of life was similar to the age- and sex-adjusted general Finnish
population. Both additive and logistic EuroSCOREs were predictors of the immediate and late
outcomes of patients after surgery for mitral valve regurgitation.
Keywords: EuroSCORE, mitral valve regurgitation, mitral valve repair, mitral valve
replacement, quality of life, RAND-36 Health survey
To Katri, Kreeta and Saara
5
6
Acknowledgements
The present study was carried out in the Department of Surgery in co-operation
with the Department of Medicine, of the Oulu University Hospital, during the
years 2000–2007.
I am deeply grateful to my supervisor, Docent Martti Lepojärvi, M.D., Ph.D.,
Head of Cardiothoracic Surgery, for giving me the idea and possibility to study this
challenging aspect of cardiac surgery.
I also express my thanks to Professor Tatu Juvonen, M.D., Ph.D., Head of the
Department of Surgery. He provided me with valuable ideas, material, and
financial support to aid in performing the research.
I wish to express my deepest gratitude to my collegue Docent Fausto Biancari,
M.D., Ph.D., for helping me during this study. It was his knowledge of research
work, continuous support, never-failing optimism and guidance that made this
work possible.
I would like to thank Docent Kari Haukipuro, M.D., Ph.D., Head of Division
of Anesthesiology, Surgery and Neurosurgery, for giving me the opportunity to
practice my scientific and clinical work in my hometown clinic, and for aiding in
organizing the financing for this.
I wish to thank Docent Jari Satta, M.D., Ph.D. for his assistance with the study.
I am grateful to Professor Keijo Peuhkurinen M.D., Ph.D. and Docent Jari
Laurikka M.D., Ph.D. for reviewing the present manuscript.
I would like to thank Docent Paavo Uusimaa, M.D., Ph.D., Jukka Juvonen,
M.D., Ph.D., Docent Matti Niemelä, M.D., Ph.D., Kari Ylitalo, M.D., Ph.D., for
the echocardiography examinations.
I would like to express my gratitude to Virpi Honkala, M.D., the Head of the
Department of Surgery in the Raahe Central Hospital and Juhani Ottelin, M.D,
former Head of the Department of Surgery in the Western Ostrobothnia Central
Hospital (L-PKS), for introducing to the field of surgery and guiding me during
my first years.
I would also thank Professor Pentti Kärkölä, M.D., Ph.D., former Head of the
Division of Cardiothoracic and Vascular Surgery, for his expert guidance in the
field of cardiac surgery.
My thanks go to my roommates Jarmo Lahtinen, M.D., Martti Mosorin, M.D.
and Panu Taskinen, M.D., Ph.D. for their unfailing support in the clinical work. I
also thank all of my colleagues in the Division of Cardiothoracic and Vascular
surgery for their cooperation: Docent Risto Pokela, M.D., Ph.D., Kari Ylönen,
7
M.D., Esa Salmela, M.D., Docent Pekka Rainio, M.D., Ph.D., Docent Vesa Anttila
M.D. Ph.D., Docent Jussi Rimpiläinen, M.D., Ph.D., Pekka Romsi, M.D., Ph.D.,
and Arjaleena Ilo, M.D..
I am grateful to my brother-in-law Michael Spalding, M.D., Ph.D., for
revising the English language of this thesis.
I deeply thank my mother Aili Hannuniemi, his husband Aarne (”Ari”)
Hannuniemi and my sister Heli Spalding, M.D., Ph.D., for their love, support, and
encouragement throughout my life. I also thank my mother-in-law Liisa
Junnikkala and my father-in-law Juho (”Jussi”) Junnikkala for their trust and love.
Finally I express my loving thanks to my dear wife Katri, for her love and
support, and to my lovely little girls Kreeta and Saara, the true stars of my life. You
are the most precious thing in my life.
This work was supported financially by Oulu University Hospital and the
Finnish Foundation for Cardiovascular Research.
Oulu, October, 2007
8
Jouni Heikkinen
Abbreviations
ACE
Angiotensin converting enzyme
AF
Atrial fibrillation
AMI
Acute myocardial infarction
ASD
Atrial septal defect
BMI
Body mass index
BSA
Body surface area
CABG
Coronary artery bypass grafting
CI
Confidence interval
COPD
Chronic obstructive pulmonary disease
CPB
Cardiopulmonary bypass
LVEF
Left ventricular ejection fraction
EuroSCORE The European system for cardiac operative risk evaluation score
IMR
Ischemic mitral regurgitation
INR
International normalized ratio
IQR
Interquartile range
LV
Left ventricle
MOF
Multiorgan failure
MR
Mitral regurgitation
MRI
Magnetic resonance imaging
MV
Mitral valve
MVA
Mitral valve annuloplasty
MVR
Mitral valve repair
NYHA
New York Heart Association
OR
Odds ratio
PAP
Pulmonary artery pressure
PISA
Proximal isovelocity surface area
PTFE
polytetrafluoroethylene
ROC
Receiver operating characteristics
RR
Relative risk
SAM
Systolic anterior motion
SE
Standard error
TEE
Transesophageal echocardiography
TIA
Transient ischemic attack
TVP
Tricuspid valve plasty
9
10
List of original publications
This thesis is based on the following articles, which are referred to in the text by
their Roman numerals:
I
Heikkinen J, Biancari F, Satta J, Salmela E, Juvonen T & Lepojärvi M (2005)
Predictors of postoperative mortality after mitral valve repair: Analysis of a
series of 164 patients. Scand Cardiovasc J 39: 71–77.
II
Heikkinen J, Biancari F, Uusimaa P, Satta J, Juvonen J, Ylitalo K, Niemelä M,
Salmela E, Juvonen T & Lepojärvi M (2005) Long-term outcome after mitral
valve repair. Scand Cardiovasc J 39: 229–236.
III Heikkinen J, Biancari F, Satta J, Salmela S, Juvonen T & Lepojärvi M (2005)
Quality of life after mitral valve repair. J Heart Valve Dis 14: 722–726.
IV Heikkinen J, Biancari F, Satta J, Salmela E, Mosorin M, Juvonen T &
Lepojärvi M (2007) Predicting the immediate and late outcome after surgery
for mitral valve regurgitation with EuroSCORE. J Heart Valve Dis 16: 116–
121.
11
12
Contents
Abstract
Acknowledgements
Abbreviations
List of original publications
Contents
1 Introduction
15
2 Review of the literature
19
2.1 Surgical anatomy of the mitral valve ...................................................... 19
2.2 Mitral regurgitation ................................................................................. 23
2.2.1 Etiology......................................................................................... 23
2.2.2 Pathophysiology............................................................................ 26
2.2.3 Clinical manifestations.................................................................. 27
2.2.4 Diagnosis and assessment of mitral valve regurgitation............... 28
2.2.5 Treatment ...................................................................................... 31
2.2.6 Surgical procedures....................................................................... 34
2.2.7 Results of mitral valve surgery in mitral regurgitation ................. 38
3 Aims of the study
41
4 Materials and methods
43
4.1 Material ................................................................................................... 43
4.2 Methods................................................................................................... 48
4.3 Statistical analysis .................................................................................. 51
5 Results
53
5.1 Predictors of postoperative mortality after mitral valve repair ............... 53
5.1.1 Overall outcome............................................................................ 53
5.1.2 Immediate postoperative outcome after mitral valve repair
as a lone procedure........................................................................ 56
5.1.3 Immediate postoperative outcome after mitral valve repair
with concomitant procedures ........................................................ 56
5.2 Long-term outcome after mitral valve repair .......................................... 57
5.2.1 Long-term survival........................................................................ 57
5.2.2 Survival freedom from redo mitral valve surgery......................... 60
5.2.3 Survival freedom from stroke ....................................................... 62
5.2.4 Long-term outcome among patients with myxomatous
degenerative disease...................................................................... 62
5.2.5 Long-term echocardiographic findings......................................... 64
13
5.3 Quality of life after mitral valve repair ................................................... 66
5.4 Predicting the immediate and late outcome after surgery for
mitral valve regurgitation with EuroSCORE .......................................... 68
5.4.1 30-day postoperative outcome ...................................................... 68
5.4.2 Late outcome................................................................................. 71
6 Discussion
75
6.1 Predictors of postoperative mortality after mitral valve repair ............... 75
6.2 Long-term outcome of mitral valve repair .............................................. 76
6.3 Quality of life after mitral valve repair ................................................... 77
6.4 Predicting the immediate and late outcome after surgery for
mitral valve regurgitation using the EuroSCORE................................... 78
7 Conclusions
79
References
Original publications
14
1
Introduction
Mitral regurgitation (MR) is a common clinical condition in which there is an
abnormal flow of blood from the left ventricle back to the left atrium across an
incompetent mitral valve during ventricular systole. Mitral regurgitation was first
identified by Corvisart in 1808 (Selzer et al. 1972). Treatment of the disorder
consisted of diuretics and digitalis preparations for the next 150 years (Cooper &
Gersh 1998). The earliest attempts at reconstruction of the mitral valve were for
relief of mitral stenosis. Gibbon introduced the cardiopulmonary bypass in 1953
and this led to efforts to perform mitral valve repair for mitral insufficiency using
direct access through the left atrium. The first clinically successful mitral valve
prosthesis was implanted by Starr in 1960 (Starr & Edwards 1961). This was a
major step in the treatment of mitral regurgitation and calcified mitral stenosis.
The earliest techniques used for direct repair of mitral regurgitation involved
attempts to correct dilatation of the posterior mitral annulus by suture plication
(Kay et al. 1978). Modern mitral valve repair was initiated in the ‘70s by
Carpentier (Carpentier et al. 1971) and Duran (Duran et al. 1978). Indeed, the
single most important advance in valve repair was the description by Carpentier of
a systematic approach to the classification of abnormalities of the mitral valve
leaflets, annulus, and subvalvular apparatus of chordae and papillary muscles
(please, see paragraph 2.2.1 Etiology) (Carpentier 1983).
The true prevalence of chronic mitral regurgitation is still unknown. Mitral
regurgitation is the second most common heart valve disease in Europe and North
America after aortic valve stenosis (Cooper & Gersh 1998). In a review of all
patients seen at the Mayo Clinic from 1980 to 1989 with isolated mitral
regurgitation from flail mitral leaflet, the annual mortality rate was 6.3%, a rate
significantly higher than that for age-matched controls. Cardiovascular events
were the cause of death in 69% of cases, and the incidence of surgery or death was
90% at 10 years (Ling et al. 1996). A linear rate of 1–8% per year of sudden death
has recently been reported in patients with MR due to flail leaflets followed
conservatively (Grigoni et al. 1999, Lung et al. 2002). This figure ranges from 0 to
8% per year in patients with no or minimal symptoms (Grigoni et al. 1999, Lung et
al. 2002).
There are three different types of mitral operation currently used for the
correction of mitral regurgitation. These are mitral valve repair, mitral valve
replacement with preservation of part or all of the mitral apparatus, and mitral
valve replacement with removal of the mitral apparatus. Each procedure has its
15
advantages and disadvantages, and therefore the indications for each of them are
somewhat different. In most cases, mitral valve repair is the operation of choice
when the valve is suitable for repair and the appropriate surgical skill and expertise
are available (Bonow et al. 2006, Gillinov et al. 1998, Gillinov et al. 2001,
Gillinov et al. 2003a–b, Gillinov & Cosgrove 2003). Valve repair is currently a
feasible surgical option in 70% to 90% of cases of pure or predominant mitral
regurgitation at experienced centres and it should be possible in nearly all
instances of degenerative mitral valve disease (Barlow et al. 1996).
Repair of degenerative mitral valve regurgitation has been shown to be an
effective procedure with durable results. This has led to an increasing use of
techniques of repair over replacement (Nowicki et al. 2003, Savage et al. 2003).
Mitral valve repair for regurgitation is associated, however, with a significant
immediate postoperative mortality. In 1997, Muehrcke and Cosgrove (Muehrcke&
Cosgrove 1997) estimated a mortality of 3.4% by combining data from nine series
of mitral valve repair. A more recent series reported 30-day mortality rates which
vary from nil (Greelish et al. 2003) to 10% (Grossi et al. 2001), an observation
suggesting that, along with surgical expertise, patient selection and indication for
mitral valve repair may significantly influence the immediate outcome. Immediate
postoperative mortality rates seem to be significantly higher after mitral valve
replacement compared with mitral valve repair (Roques et al. 2003a, Thourani et
al. 2003, Gillinov et al. 2001, Edwards et al. 2001). In particular, early
postoperative mortality after mitral valve replacement may approach 15% (Roques
et al. 2003a, Gillinov et al. 2001, Edwards et al. 2001). A ten-year survival
freedom from fatal cardiac event after mitral valve repair has been reported to
range from 92% (Braunberger et al. 2001) to 94% (Yau et al. 2000) and 10-year
survival freedom from redo mitral valve surgery from 72% (Yau et al. 2000 ) to
about 90% (Braunberger et al. 2001, Gillinov et al. 1998, Mohty et al. 2001).
Gillinov et al ( Gillinov et al. 2003a) reported that unadjusted survival at 30 days
and 1, 5 and 10 years was 97%, 92%, 79% and 59% after mitral valve repair and
94%, 88%, 70%, and 37% after replacement. The survival benefit of repair
became evident after 2 years. Good results with mitral valve repair have also been
reported in patients with end-stage cardiomyopathy (Gummert et al. 2003, Szalay
et al. 2003, Bolling et al. 1998). Enriquez-Sarano et al. (1995) reported improved
LV function and survival in patients undergoing valve repair compared to valve
replacement with or without preservation of the subvalvular apparatus. In that
study 195 patients underwent valve repair and were compared with 214 patients
16
who underwent valve replacement. Operative mortality was 2.6% and 10.3 % and
ten-year survival was 68% and 52%, respectively.
Mitral valve repair has also been shown to be associated with a significant
improvement in terms of functional capacity (Goldsmith et al. 2001, Goldsmith et
al. 1998). Goldsmith and colleagues (Goldsmith et al. 2001) reported on the
improvement of quality of life, as assessed by the short form 36 questionnaire 3
months after mitral valve repair and replacement. Mitral valve repair was
associated with a significant increase in 7 out of 8 parameters, whereas
improvement was modest after mitral valve replacement. Mitral valve repair was
found to be an independent predictor of early better quality of life (Goldsmith et al
2001). The same authors also observed an improvement of quality of life in
patients aged 75 years or older who underwent mitral valve surgery (Goldsmith et
al. 1998). There is no data to date, however, on the quality of life long after mitral
valve repair.
The European system for cardiac operative risk evaluation score
(EuroSCORE) has been used and shown worldwide to be a valid tool for the
prediction of immediate postoperative outcome after adult cardiac surgery (Nashef
et al. 1999, Geissler et al. 2000, Nilsson et al. 2004). There is also some evidence
that this risk scoring method is a good predictor of late outcome after coronary
artery bypass surgery (Toumpoulis IK et al. 2004, De Maria et al. 2005, Biancari
et al. 2006) and after heart valve surgery (Toumpoulis IK et al. 2005, Kasimir et
al. 2004).
17
18
2
Review of the literature
2.1
Surgical anatomy of the mitral valve
The mitral valve is situated between the left atrium and left ventricle. The mitral
apparatus includes the leaflets, annulus, chordae tendinae, papillary muscles, and
left ventricle. It has two leaflets, the anterior (aortic) and posterior (mural) leaflet.
Both leaflets are attached directly to the mitral annulus and to the papillary
muscles by primary and secondary chordae. The chordae tendinae arise from the
papillary muscles and insert into the mural surface of the leaflets (Figure 1)
(Lawrie 1998).
Fig. 1. The relationships of the cardiac valves. Modified from Duran 1992.
The anterior mitral leaflet roughly resembles a truncated triangle and is much more
mobile than the posterior leaflet (Lawrie 1998). The anterior leaflet is in direct
continuity with the fibrous skeleton of the heart. It occupies 35–45% of the annular
circumference, but its leaflet area is almost identical to that of the posterior leaflet.
The posterior leaflet is rectangular and has three scallops: a middle, a
posteromedial and an anterolateral scallop (Gillinov & Cosgrove 2003). The two
leaflets are connected at the annulus by the posteromedial and anterolateral
commisures, which are usually distinctly developed (Fann et al. 2003). Motion of
the posterior leaflet is more restricted than that of the anterior leaflet (Gillinov &
19
Cosgrove 2003). The posterior mitral leaflet is attached to thinner chordae
tendinae than the anterior leaflet and its motion is restrained by chordae during
both systole and diastole (Fann et al. 2003). In normal valves, posterior movement
of the much more mobile anterior leaflet into apposition with the much less mobile
posterior leaflet is responsible for the bulk of the systolic closure of the mitral
orifice (Lawrie 1998). This is such as the posterior annulus is more flexible and it
is not attached to rigid surrounding structures (Gillinov & Cosgrove 2003).
The mitral annulus is a pliable junctional zone of fibrous and muscular tissue
joining the left atrium and ventricle which anchors the hinge portion of the anterior
and posterior mitral leaflets (Fann et al. 2003). The average area of the mitral
orifice as defined by the mitral annulus is 6.5 cm2 in women and 8 cm2 in men.
The effective orifice area through the level of the leaflets measured clinically is
about 30% less than the above mentioned values (Lawrie 1998.) The area of the
mitral orifice is reduced by 25–40 % during systole, mainly as a result of a
dynamic reduction of the size of the posterior annulus which decreases the
anteroposterior diameter of the valve orifice and increases the area of leaflet
coaptation (De Oliveira et al. 2006).
The mitral annulus is roughly elliptical (sometimes described as D- or kidneyshaped), with greater eccentricity in systole than in diastole, while in a threedimensional model the annulus is described as being “saddle-shaped” (Fann et al.
2003). During systole the height of the saddle is increased as the annular
dimensions decrease (Lawrie 1998). The mitral annulus moves upward into the
left atrium in diastole and toward the LV apex during systole. The annulus moves
little during late diastole. The annulus moves a greater distance (3 to 16 mm
toward the LV apex) during isovolumic contraction and ventricular ejection. The
orifice of the mitral valve changes shape, from elliptical during systole to circular
during late diastole. The annulus is flexible and decreases in diameter during each
systolic contraction by approximately 26%. This flexibility increases leaflet
coaptation during systole and maximizes the orifice area during diastole (Fann et
al. 2003).
The circumflex coronary artery courses laterally around the mitral annulus in
the posterior atrioventricular groove. The coronary sinus runs more medially in the
same groove. The aortic valve is situated between the anterior and posterior
fibrous trigones. The bundle of His is located near the posterior trigone. The artery
feeding the atrioventricular node, usually a branch of the right coronary artery,
runs a course parallel and is located close to the annulus of the anterior and
posterior fibrous trigones (Gillinov & Cosgrove 2003.)
20
Fig. 2. Surgical anatomy of the mitral valve. Note its important anatomic relationships
with the aortic valve, the circumflex coronary artery, and the coronary sinus. Modified
from Gillinow & Cosgrove 2003.
The chordae tendinae arise from the papillary muscles or the left ventricular wall
and are distributed to both leaflets. The papillary muscles typically consist of two
prominent structures: an anterolateral and posteromedial papillary muscle.
Papillary morphology may vary widely from this form. Flattened sheets of muscle
can give rise to the chordae, and in some cases the chordae appear to arise from the
wall of the ventricle itself (Lawrie 1998). The anterolateral papillary muscle
receives blood from the septal branches of the left anterior descending artery, and
from the branches of the circumflex artery. The posteromedial papillary muscle
receives its blood supply from either the left circumflex artery or from a distal
branch of the right coronary artery, depending on which is the dominant system. It
is more prone to ischemia and rupture caused by coronary artery occlusion than is
the anterior papillary muscle (De Oliveira et al. 2006). The chordae tendinae are
classically and functionally divided into three groups. First-order or primary
chordae originate near the papillary muscle tips and insert on the leading edge of
the leaflets. These chordae prevent valve edge prolapse during systole. The
second-order or secondary chordae originate in the same location and insert on the
21
ventricular surface of the leaflets at the junction of the rough and clear zones (Fann
et al. 2003). These chordae contribute to ventricular function. Secondary chordae
enable the ventricle to contract in an efficient cone-shaped fashion. In fact, when
the secondary chordae are excised, the left ventricle assumes a globular shape
(Gillinov & Cosgrove III 2003). The third-order, also termed the tertiary or basal
chordae, originate directly from the trabeculae carnae of the ventricular wall, and
attach to the posterior leaflet near the annulus (Fann et al. 2003). The chordae
insertions into the posterior leaflet are formed in three layers: marginal attached to
the edge, intermediate and mural. The chordae of the anterior leaflet insert
primarily into the free margin of the leaflet and there are fewer chordae attached to
other portions of the underside of the anterior leaflet (Lawrie 1998). The
contribution of the papillary muscles to left ventricle chamber volume is 5% to 8%
during diastole, and 15% to 30% during systole (Fann et al. 2003). The posterior
left ventricular wall and papillary muscles play an important role in leaflet
coaptation and valve competence (Gillinov & Cosgrove 2003). Papillary muscles
help to maintain the optimal position of the subjacent ventricular wall during
systole, which in turn preserves the conical shape of the ventricle during systole
(Lawrie 1998). Ventricular dilatation may affect the alignment and tension on the
papillary muscles and therefore valve competence (Gillinov & Cosgrove III 2003).
Fig. 3. Anatomy of the mitral valve. Modified from Duran 1992.
22
2.2
Mitral regurgitation
Mitral regurgitation (MR) is a common valvular disorder which can arise from
abnormalities of any part of the mitral valve apparatus. There is an abnormal flow
of blood from the left ventricle to the left atrium across an incompetent mitral
valve during ventricular systole (Cooper & Gersh 1998)
The widespread use of colour Doppler echocardiography, a sensitive
technique for detecting valvular regurgitation, has increased the recognition of this
condition in even healthy subjects. The true prevalence of chronic mitral
regurgitation is unknown. A trivial amount of mitral regurgitation is detectable
with sensitive Doppler techniques in up to 70% of normal adults. This is often
called physiologic mitral regurgitation. In a review of 3486 subjects in the Strong
Heart Study, the prevalence of moderate or severe mitral regurgitation was 0.2–
1.9% (Jones et al. 1999). In the Framingham study, a population-based cohort,
mitral regurgitation of mild severity or worse on colour Doppler echocardiography
was present in 19% of men and women (Singh et al. 1999). In the Coronary Artery
Risk Development in Young Adults study, which consists of 4352 healthy men and
women between 23 and 35 years of age, mitral regurgitation was noted as present
in 10.9% of the cohort. Of these cases, 93 % were mild in severity (Reid et
al.1994). The Cardiovascular Health Study assessed 5201 randomly selected
people aged 65 and older with echocardiography. The prevalence of MR was
30.1%, with 26.6% of the cases meeting the criteria for moderate-to-severe
regurgitation (Reid et al.1997.)
Mitral regurgitation burdens the left ventricle with an excessive volume load
which leads to a series of compensatory myocardial and circulatory adjustments.
These adjustments vary over the prolonged course of the disorder, so that the
changes that are operative in acute or subacute MR are eventually replaced by
other compensatory mechanisms. Finally, the myocardium fails, the ventricle
decompensates, and the patient exhibits signs of heart failure (Gaasch et al. 1985,
Carabello 1993, Gaasch et al 1993).
2.2.1 Etiology
Dysfunction of one or more components of the valvular-ventricular complex can
lead to mitral regurgitation during ventricular systole. Diastolic regurgitation
results from delayed ventricular contraction, but this phenomenon appears to have
few clinical implications (Fann et al. 2003).
23
In the past, rheumatic fever was the predominant cause of mitral regurgitation.
Nowadays, the most common etiology of systolic mitral regurgitation in patients
undergoing surgery is myxomatous degeneration, also termed flail leaflet, floppy
mitral valve or mitral valve prolapse (29–70% of cases) (Fann et al. 2003). Other
causes include ischemic mitral regurgitation (IMR), dilated cardiomyopathy (also
termed functional mitral regurgitation (FMR)), mitral annular calcification,
infective endocarditis, idiopathic chordal rupture, congenital anomalies,
endocardial fibrosis, collagen-vascular disorders and traumatic rupture (Fann et al.
2003). The use of appetite suppressants (phentermine, fenfluramine and
dexfenfluramine) for weight loss has also been associated with an increased
prevalence of cardiac valvular insufficiency (Khan et al. 1998).
Degenerative mitral valve disease is the most common form of valvular heart
disease and it is the most common indication for mitral valve surgery in North
America and Europe. The estimated prevalence is 4–5% of the general population.
Approximately 5% of the patients with mitral valve prolapse ultimately develop
mitral regurgitation requiring surgery (Gillinov & Cosgrove 2003). Some degree
of mitral valve prolapse is seen in echocardiography in 5% to 6% of the normal
female population. It can be familial and associated with hypertension (Procacci et
al. 1976). Although mitral valve prolapse appears to be more widespread in
women, severe mitral valve regurgitation due to mitral valve prolapse is more
common in men (Fann et al. 2003). The classic features of degenerative mitral
valve disease include leaflet prolapse (the posterior leaflet more commonly) and
annular dilatation (Gillinov & Cosgrove 2003). A prolapse is considered to be
present when the free edge of one or both leaflets overrides the plane of the valve
orifice (annulus) during systole (De Oliveira et al. 2006). Chordae may be
elongated, thinned, ruptured or thickened (Gillinov & Cosgrove 2003). The
prognosis for the mitral valve prolapse syndrome is benign. The age-adjusted
survival rate of both men and women with mitral valve prolapse syndrome is
similar to that of individuals without this common clinical entity (Bonow 2006).
Ischemic mitral regurgitation (IMR) is a complication of coronary heart
disease, particularly in the setting of a prior myocardial infarction. IMR caused by
previous myocardial infarction can be the result of a ruptured papillary muscle,
infarction of the papillary muscle without rupture, and functional regurgitation.
Ruptured papillary muscle is most frequently caused by infarction in the
circumflex and/ or right coronary artery distribution (Gillinov & Cosgrove 2003).
This is a life-threatening complication which accounts for 5% of deaths after acute
myocardial infarction. The complication usually occurs within two to seven days
24
after myocardial infarction (Gillinov et al. 2001, Miller 2001). Patients with
myocardial infarction, but not ruptured papillary muscles suffer leaflet prolapse,
while patients with isolated functional ischemic MR will have normal papillary
muscles, chordae and leaflets, but the leaflets fail to coapt. Failure of coaptation
can be caused by annular dilatation, leaflet tethering or both. Myocardial infarction
produces ventricular dilatation and dysfunction, and the resulting geometric
changes prevent leaflet coaptation (Gillinov & Cosgrove 2003).
In patients with functional mitral regurgitation the papillary muscles, chordae
and valve leaflets are normal. There are two major causes of this condition:
ischemia as discussed above, as well as any cause of dilated left ventricle. MR may
result from annular enlargement secondary to left ventricular dilatation or
papillary muscle displacement due to left ventricular remodelling (Trichon &
O`Connor 2002). Some degree of functional MR is almost always present in
patients with severe dilated cardiomyopathy, regardless of the etiology of
cardiomyopathy (Trichon & O`Connor 2002, Koelling et al. 2002, Strauss et al.
1987). Functional MR is also a common problem in patients with end-stage renal
disease on maintenance dialysis. Volume expansion is primarily responsible for the
cardiac enlargement (Cirit et al. 1998).
A decrease in the prevalence of rheumatic valve disease has been witnessed in
surgical practice in North America and Europe. Pathologic features of rheumatic
mitral valve disease produce varying degrees of regurgitation, stenosis or mixed
lesions. Acute rheumatic valvitis produces leaflet prolapse and mitral regurgitation
(Gillinov & Cosgrove III 2003).
Mitral annular calcification is a degenerative disease that is essentially limited
to the elderly. Most patients are older than 60 years of age, and women are affected
more often than men. Annular calcification causes mitral regurgitation by
displacing the mitral leaflets, by immobilizing the peripheral portion of the mitral
leaflets or by impairing the presystolic sphincteric action of the annulus (Fann et
al. 2003).
Native valve endocarditis is generally caused by streptococcal or
staphylococcal species. Pathologic findings include chordal rupture (70%),
vegetation (62%), leaflet perforation (53%) and abscess (7%) (Gillinov &
Cosgrove 2003).
Carpentier et al. classified mitral regurgitation into three pathoanatomic types
based on leaflet prolapse or excessive motion: normal leaflet motion (type I),
leaflet prolapse or excessive motion (type II) and restricted leaflet motion (type
25
III). Type III is further subdivided into two groups based on leaflet restriction
during diastole (type IIIa) or during systole (type IIIb) (Carpentier 1983).
Fig. 4. Carpentier`s segmental classification of the mitral valve and functional
classification of the types of leaflets and chordal motion associated with mitral
regurgitation. Modified from Carpentier 1983.
Type I MR is present when there is annular dilatation, as in cardiomyopathy, or
with leaflet perforation as in endocarditis. Type II MR is caused by elongation or
rupture of the chordae tendineae, as often occurs in degenerative disease, or of the
papillary muscles, as occurs in ischaemic disease. Type IIIa MR occurs when there
is commissural fusion and leaflet or chordal thickening, as seen in rheumatic
disease. In type IIIb MR there is chordal retraction (rheumatic) or papillary muscle
retraction (ischaemic) or displacement (ischaemic or functional cardiomyopathy)
(De Oliveira et al. 2006).
2.2.2 Pathophysiology
The pathophysiology of acute MR differs markedly from that of chronic MR. The
clinical impact of acute mitral incompetence is largely modulated by left atrium
compliance. Acute MR results in high left atrial pressure, which can rapidly lead to
pulmonary edema. In patients with chronic MR, compensatory changes increase
left atrial and pulmonary venous compliance over time so that symptoms of
pulmonary congestion may be negligible for several years. In mitral regurgitation,
impedance to LV emptying is decreased because the mitral orifice is in parallel
26
with the LV outflow tract. Regurgitation into the left atrium increases left atrial
pressure and reduces forward systemic flow. Left atrial pressure rises significantly
during ventricular systole, followed by an abrupt decline in early diastole (Fann et
al. 2003). The most significant change occurring during the evolution from acute
to chronic MR is the enlargement of the left ventricle. Despite LV chamber
enlargement, preload at the sarcomer level returns to a normal or near normal level
(Ross et al. 1971). Systolic unloading is gradually replaced by normal systolic wall
stresses as the end-systolic volume increases. LV contractility, loading conditions,
and ejection fraction remain within the normal range while a large end-diastolic
volume is responsible for an enhanced total stroke volume. An enlarged compliant
atrium contributes to a decline in pulmonary venous pressures. A very important
aspect of the pathophysiology of MR is the nature of the transition from a
compensated to a decompensated state. Such a change may occur as a
consequence of progressive increments in the regurgitant volume and/or chamber
size. This decompensated state is characterized by substantial and progressive
ventricular enlargement with increased LV diastolic pressures, increased systolic
wall stress, and a decline in the ejection fraction. The fall in left ventricular
ejection fraction is due to both a depressed contractile state and excessive
afterload. These changes in LV size and function are often accompanied by
progressive atrial enlargement, atrial arrhythmias, pulmonary hypertension, and,
eventually, signs and symptoms of congestive heart failure (Gaasch & Zile 1991).
2.2.3 Clinical manifestations
The nature and severity of symptoms associated with chronic MR are related to the
severity of regurgitation, its rate of progression, the pulmonary artery pressure and
associated cardiac disease. Patients with mild to moderate MR may remain
asymptomatic with little or no hemodynamic compromise for many years, as there
is little volume overload of the ventricle and cardiac hemodynamics and forward
cardiac output remain normal. Even in patients with severe MR, most remain
asymptomatic until the occurrence of left ventricular failure, pulmonary
hypertension or the onset of atrial fibrillation (Otto 2001).
The compensated phase of MR is variable and may last for many years, but the
prolonged burden of volume overload may eventually result in LV dysfunction.
Patients with chronic severe MR have a high likelihood of developing symptoms
or LV dysfunction over the course of six to ten years (Ling et al. 1996).
27
The most common symptoms are exertional dyspnea and fatigue due to the
combination of decreased forward cardiac output and an increase in left atrial
pressure due to backflow across the mitral valve. Another common clinical
presentation is paroxysmal, persistent or permanent atrial fibrillation. Patients with
more severe disease and left ventricular enlargement eventually progress to
symptomatic heart failure with pulmonary congestion and edema. Other symptoms
such as thromboembolism, hemoptysis and right-sided failure do occur, but are
less common than with mitral stenosis. There is a high risk for infective
endocarditis in patients with an abnormal mitral valve and moderate to severe
mitral regurgitation (Otto 2001).
2.2.4 Diagnosis and assessment of mitral valve regurgitation
Cardiac auscultation
Cardiac auscultation remains the most widely used method of screening for
valvular heart disease. A heart murmur may have no pathological significance or
may be an important clue to the presence of valvular, congenital, or other structural
abnormalities of the heart (Bonow et al. 2006).
The mitral regurgitation murmur is heard in the systolic phase, but its timing,
duration, quality, intensity, location, and radiation are variable and depend upon
the etiology and on which component of the mitral apparatus is diseased. In most
cases, the murmur is holosystolic, commencing immediately after S1 and
continuing up to and sometime beyond and obscuring A2, a result of the persistent
pressure gradient between the left ventricle and atrium (Otto 2001).
The murmur is heard best over the apex, radiating to the axilla, and when very
loud, it may often radiate to the back. It is most often blowing and high pitched in
quality. The loudness of the murmur does not necessarily correlate with the
severity of functional or ischemic MR. In IMR, severe regurgitation may be
present with a soft murmur. There is a better correlation between murmur grade
and regurgitant severity with primary mitral valve disease (Otto 2001). A loud
murmur associated with a thrill has a specificity of 91% for severe regurgitation,
but a sensitivity of only 24%. Conversely, severe regurgitation is rarely present
with a grade 1–2 murmur. There is, however, a wide range of regurgitant severity
with a grade 3 murmur (Desjardins et al. 1996).
Heart failure and the volume and geometry of the ventricle can affect the
timing, intensity, and quality of the mitral regurgitation murmur. In patients with
28
MR due to dilatation of the valvular annulus, the murmur often diminishes in
intensity or disappears as heart failure is treated and left ventricular function
improves (Otto 2001).
Chest radiograph
Chest x-rays often yield qualitative information on cardiac chamber size,
pulmonary blood flow, pulmonary and systemic venous pressure, and cardiac
calcification in patients with cardiac murmurs (Bonow et al. 2006). The most
common finding on the chest radiograph in patients with MR is cardiomegaly,
which is a result of an enlargement of the left ventricle and left atrium. Left
ventricular enlargement causes the cardiac silhouette to be displaced towards the
left chest wall and the chamber becomes globular. Enlargement of the left atrium
results in a straightening of the left heart border, with the appearance of a double
density and an elevation of the left main stem bronchus. The right ventricle is
usually normal in size, unless pulmonary hypertension is present. Similarly, the
lung fields are usually clear unless congestive heart failure is present. Calcification
of the mitral valve annulus may be seen (Otto 2001). Acute mitral regurgitation is
often not associated with an enlarged heart shadow and may produce only mild left
atrial enlargement. Interstitial edema is seen in patients with acute mitral
regurgitation or in those with progressive LV failure secondary to chronic mitral
regurgitation (Fann et al. 2003). When abnormal findings are present on chest Xray, an echocardiography should be performed (Bonow et al. 2006).
Echocardiography
Echocardiography with color flow and spectral Doppler evaluation is an important
non-invasive method for assessing the significance of cardiac murmurs.
Echocardiography is essential for establishing valve morphology and function,
chamber size, wall thickness, and ventricular function, as well as pulmonary and
hepatic vein flow. The initial transthoracic echocardiogram should disclose the
anatomic cause of the MR. Multiple parameters from the Doppler examination
should be used to diagnose severe MR, including the color flow jet width and area,
the intensity of the continuous-wave Doppler signal, the pulmonary venous flow
contour, the peak early mitral inflow velocity, and quantitative measures of the
effective orifice area and regurgitation volume (Bonow et al. 2006). Threedimensional echocardiography in patients with mitral regurgitation has been
29
shown to be fairly accurate in elucidating the dynamic mechanism of mitral
regurgitation leaks, but only offers qualitative information (Fann et al. 2003). The
handgrip test can also be used during echocardiography in order to evaluate any
increase of mitral valve regurgitation occurring during isometric exercise (Spain et
al. 1990).
Transthoracic imaging is diagnostic in most cases, but if image quality is
suboptimal, transesophageal imaging is recommended (Enriquez-Sarano et al.
1999). Transesophageal echocardiography (TEE) is always indicated to establish
the anatomic basis for severe MR in patients in whom surgery is recommended in
order to assess the feasibility of repair as well as to guide repair. TEE is not
indicated for routine follow-up or surveillance of asymptomatic patients with
native valve MR (Bonow et al. 2006).
Vena contracta is the point in a fluid stream where the diameter of the stream
is at its minimum as was first observed and defined by Evangelista Torricelli in the
seventeenth century. An echocardiographic measurement of the vena contracta has
been shown to provide a good estimate of the severity of the regurgitant orifice
area of the mitral valve (Hall et al. 1997).
An echocardiographic estimation of the proximal isovelocity surface area
(PISA) is also currently performed for assessement of the mitral valve regurgitant
orifice area (Utsunomiya et al. 1991).
Cardiac catheterization and angiography
Cardiac catheterization can provide important information as to the presence and
severity of valvular obstruction, valvular regurgitation, and intracardiac shunting.
Preoperative coronary angiography is recommended in all patients with MR over
40 years of age and in any patient with a history or clinical presentation suggesting
the presence of coronary artery disease (Gillinov & Cosgrove 2003). It is also
necessary when there is any discrepancy between clinical and non-invasive
findings. Hemodynamic measurements are indicated when pulmonary artery
pressure is out of proportion to the severity of MR as assessed by non-invasive
testing (Bonow et al. 2006). A left ventricular angiogram obtained during cardiac
catheterization may establish the presence and severity of MR. The diagnostic
finding is opacification of the left atrium during systole. The rapidity and density
of opacification of the left atrium provides a semi-quantitive index of regurgitant
severity. The angiogram can also provide a measurement of left atrial and
ventricular dimensions and left ventricular function (Otto 2001). By measuring
30
rest and exercise pulmonary artery pressures and cardiac outputs, left- and rightsided heart catheterization can occasionally be useful to identify patients with
primary myocardial disease who present with LV dilatation and relatively mild
degrees of mitral regurgitation (Fann et al. 2003).
Newer techniques
Magnetic resonance imaging (MRI) is a non-invasive modality which can be
employed to assess the cardiovascular system, including cardiac structure and
function (Hundley et al. 1995, Nayak et al. 2000, Kozerke et al. 2001). MRI and
newer advanced techniques, such as moving-slice velocity mapping, control
volume method, and real-time colour-flow MRI have been used to evaluate and
quantify the degree of mitral regurgitation. The presence of valvular regurgitation
can be determined, LV volumes and mitral regurgitant fraction estimated, and
information concerning mitral and coronary anatomy obtained (Fann et al. 2003).
2.2.5 Treatment
Medical treatment
In earlier years, the treatment for chronic mitral regurgitation consisted essentially
of the relief of symptoms of heart failure using diuretics and digitalis preparations
(Levine & Gaasch 1996). More recently, it has become clear that medical therapy
alone is not appropriate for the treatment of patients with mitral regurgitation with
symptoms of heart failure unless surgery is contraindicated. Therefore, attention is
at present focused on drugs which alter the hemodynamic abnormalities in patients
with minimal or no symptoms in an attempt to prevent the sequelae of chronic
volume overload (Cooper & Gersh 1998).
There is no generally accepted medical therapy for the treatment of
asymptomatic patients with chronic MR. No studies have been published which
would support the hypothesis that vasodilator therapy is beneficial in such
patients. In addition, the administration of vasodilators in patients with normal LV
function might limit the development of symptoms due to increasing LV
dysfunction, thereby masking symptoms indicating surgical treatment (Lung et al.
2002). Acute vasodilator therapy has a beneficial effect on patients with chronic
mitral regurgitation. Intravenous nitroprusside decreases left ventricular enddiastolic pressure and volume while increasing forward stroke volume and cardiac
31
index. Hydralazine has similar salutary effects. Data regarding the chronic effect
of vasodilators is less impressive. Chronic therapy provides the most benefit for
patients with the largest hearts, the poorest systolic function, and the most
disabling symptoms. When combined with digitalis and diuretics, for example,
hydralazine can produce substantial symptomatic and hemodynamic improvement
in patients who are in NYHA functional class II–IV (Greenberg et al. 1982).
Angiotensin converting enzyme (ACE) inhibitors may also be beneficial in this
setting (Schön et al. 1994). Chronic vasodilator therapy is only indicated in those
who are not surgical candidates. ACE inhibitors in combination with nitrates are a
reasonable choice in patients with coronary heart disease or idiopathic dilated
cardiomyopathy. Beta-blockers lower systolic pressure without reducing left
ventricular chamber size. Beta-blockers in combination with a diuretic can be used
in hypertensive patients. If LV systolic dysfunction is present, biventricular pacing
has been shown to reduce the severity of functional MR (Breithardt et al. 2003).
The risk of an embolic event is increased when atrial fibrillation or mitral
annular calcification is present. Long-term anticoagulation, with the INR
maintained at 2.0 to 3.0, is recommended in patients who have atrial fibrillation or
a history of systemic embolism and in patients with mitral annular calcification
complicated by systemic embolism not documented to be calcific in origin or by
atrial fibrillation (Salem et al. 2001). If atrial fibrillation occurs, the heart rate
should be controlled with digitalis, rate-lowering calcium channel blockers, betablockers or, rarely, amiodarone (Bonow et al. 2006).
Surgical treatment
The most important predictors of postoperative outcome after surgery for mitral
regurgitation are symptoms, age, atrial fibrillation, preoperative left ventricular
function and the reparability of the valve. Older age increases the operative risks
and negatively influences late outcome. It has been reported that the operative
mortality for patients in NYHA class I–II was 0% below the age of 75 years and 3–
6% over this age (Tribouilloy et al. 1999, Lung et al. 2002). Survival was also
reduced in patients older than 75 years, especially if mitral valve replacement was
necessary or if the patient had concomitant coronary artery disease (EnriquezSarano et al. 1995). Pre-operative atrial fibrillation is a predictor of an excess late
postoperative morbidity and mortality, while a duration of atrial fibrillation of over
one year and a left atrial diameter of more than 50 mm are predictors of permanent
postoperative atrial fibrillation. The most important predictors are left ventricular
32
ejection fraction and end-systolic diameter (Lung 2002.) A preoperative left
ventricular ejection fraction less than 50 % is associated with an excess late
mortality (Enriquez-Sarano et al. 1994a–b). The best results of surgery are
observed in patients with a preoperative left ventricular ejection fraction more than
60%, a finding which is independent of the type of surgery (Lung et al. 2002). A
preoperative left ventricle end-systolic diameter of more than 45 mm is closely
correlated with a poor postoperative prognosis (Enriquez-Sarano et al. 1994a),
while the progressive development of pulmonary hypertension is also a marker for
a poor prognosis (Bonow et al. 2006). The probability of a successful outcome for
valve repair is of crucial importance (Lung et al. 2002). In multiple studies
comparing patients who were managed with medical therapy alone to those who
had undergone surgery, the findings indicated that patients treated surgically have
had a lower mortality rate. In a cohort with flail mitral leaflet, patients with severe
MR treated surgically had 5-and 10-year survival rates no different than expected
for age-matched controls, and surgery independently and beneficially influenced
survival rate (Munoz et al. 1975, Braunwald 1997, Cooper & Gersh 1998).
Indications for corrective surgery
Patients with symptoms of severe (3–4/4) mitral regurgitation despite normal LV
systolic function (ejection fraction greater than 60 % and end-systolic dimension
less than 40 mm) require surgery. Surgery should be performed in patients with
mild symptoms and severe mitral regurgitation especially if it appears that mitral
valve repair can be performed. Mitral valve surgery should also be recommended
for symptomatic patients with evidence of LV dysfunction (an ejection fraction
equal to or less than 60% and an end-systolic diameter equal to or more than 40
mm) (Bonow et al. 2006).
Surgical treatment is also recommended for asymptomatic patients with severe
MR and with signs of left ventricular dysfunction (ejection fraction less than 60%
and/or left ventricular end-systolic diameter more than 40 mm). Surgery in this
group should be considered to prevent any further deterioration of left ventricular
function. Atrial fibrillation and pulmonary hypertension (a pulmonary systolic
pressure of more than 50 mmHg at rest or 60 mmHg on exercise) are also
indications for mitral valve surgery in these patients (Lung et al. 2002). Surgery
for asymptomatic patients with severe MR and normal LV function should be
considered if there is a greater than 90 % likelihood of successful valve repair in a
center experienced in this procedure (Bonow et al. 2006).
33
Preoperative atrial fibrillation is an independent predictor of reduced longterm survival after mitral valve surgery for chronic mitral regurgitation (EnriquezSarano et al. 1994). Predictors of the persistence of atrial fibrillation after
successful valve surgery are the presence of atrial fibrillation for more than one
year and a left atrial size more than 50 mm. Many clinicians consider the recent
onset of atrial fibrillation to be an indication in and of itself for surgery, if there is a
high likelihood of valve repair (Bonow et al. 2006). In patients presenting for
mitral valve operation with chronic atrial fibrillation, a concomitant Maze
procedure may prevent future thromboembolic events by restoring normal sinus
rhythm (Cox JL 2000).
In severe mitral regurgitation secondary to acute myocardial infarction,
hypotension and pulmonary edema often occur. Treatment is aimed at
hemodynamic stabilization. Revascularization of the coronary artery supplying an
ischemic papillary muscle may improve the degree of mitral valve regurgitation.
Such an improvement is unlikely on most cases, however, and severe MR requires
mitral valve repair with an annuloplasty ring or replacement (Bonow et al. 2006).
Surgical indications in cases with ischemic mitral regurgitation are
controversial. The indication for mitral valve operation in the patient who
undergoes CABG with mild to moderate MR is still unclear, but data does exist to
indicate a benefit of mitral valve repair in such patients. (Prifti et al. 2001). In
patients undergoing coronary artery bypass grafting, grade 3 to 4 MR should be
addressed (Gillinov & Cosgrove 2003). Mitral valve repair could be offered to
selected patients with ischemic cardiomyopathy and functional mitral
regurgitation. These patients should be offered surgery only if they have grade 3+
or 4 mitral regurgitation (Bolling et al. 1998, Chen et al. 1998, Bishay et al. 2000).
Surgical indication in cases of endocarditis is well established. This includes
heart failure unresponsive to medical therapy, multiple embolic events,
uncontrolled sepsis, and an extension of the infection into surrounding structures.
In addition, early operation is indicated for fungal and staphylococcal infections
(Gillinov & Cosgrove 2003).
2.2.6 Surgical procedures
Three different mitral operations are currently used for the correction of mitral
regurgitation: mitral valve repair, mitral valve replacement with preservation of
part or all the mitral apparatus, and mitral valve replacement with removal of the
mitral apparatus. In most cases, mitral valve repair is the operation of choice when
34
the valve is suitable for repair and the appropriate surgical skill and expertise are
available. This procedure preserves the patient`s native valve without a prosthesis
and therefore avoids the risk of chronic anticoagulation or prosthetic valve failure
late after surgery. Preservation of the mitral apparatus leads to better postoperative
LV function and survival than in cases in which the apparatus is disrupted (Bonow
et al. 2006).
The choice of procedure depends upon the cause of the mitral regurgitation,
the anatomy of the mitral valve, and the degree of left ventricle dysfunction. The
advantages of mitral valve repair over mitral valve replacement include improved
long-term survival, a better preservation of left ventricular function, and greater
freedom from endocarditis, thromboembolism and anticoagulant-related
hemorrhage (Gillinov & Cosgrove 2003). With the introduction of standardized
surgical techniques (Carpentier et al. 1971, Duran et al. 1978, David et al. 1993,
Gillinov et al. 1998), mitral valve repair has become reproducible and worldwide
performed. In experienced centres, valve repair is currently a feasible surgical
option in 70% to 90% of cases of pure or predominant mitral regurgitation and
should be feasible in nearly all instances of degenerative mitral valve disease
(Cooper & Gersh 1998, Barlow JB 1996).
For proper identification of the location of lesions in the leaflets, a segmental
classification has been created. The three scallops of the posterior leaflet are
designated as P1 (close to the anterolateral commisure), P2 (the middle scallop),
and P3 (close to the posteromedial commisure). The corresponding segments of
the anterior leaflet are called A1, A2 and A3 (Figure 4). The aim of mitral valve
repair is to obtain a valve that no longer leaks, and also to achieve anatomical
restoration of all components of the mitral apparatus. Mechanical stress on the
valve should be reduced to a minimum. Standard mitral valve repair is based on
two main groups of technical steps: to correct any abnormal motion of the leaflets
and chordal apparatus and to remodel and stabilise the annulus by implantation of
the supporting ring (De Oliveira et al. 2006).
Isolated prolapse of the posterior leaflet is the most frequent lesion leading to
mitral regurgitation and accounts for up to 60% of the cases in most surgical series
(De Oliveira et al. 2006). Prolapse of the posterior leaflet, whether the result of
ruptured chordae or elongated chordae, is treated by quadrangular resection of the
prolapsing segment, annular plication in the corresponding area, and a subsequent
suture of the free edges of the leaflets (Carpentier 1983). The sliding repair of the
posterior leaflet, an alternative for posterior annular plication, was devised by
Carpentier to prevent left ventricular outflow tract obstruction caused by systolic
35
anterior motion (SAM) of the anterior leaflet of the mitral valve (Carpentier 1988).
SAM only occurs in patients undergoing a quadrangular resection for degenerative
disease and, before the development of the sliding leaflet repair. SAM could
compromise the repair in 5% to 10% of cases (Gillinov & Cosgrove III 2003).
Quadrangular resection of the prolapsing segment may include up to 50% of the
length of the posterior leaflet if necessary (De Oliveira et al. 2006).
Fig. 5. Surgical technique used to repair a flail segment of the middle scallop of the
posterior leaflet. (a) Redundant area is isolated. (b) Flail or redundant areas are
excised. (c) Annuloplasty is performed with a pledgeted suture and the leaflets are
reapproximated using 5–0 suture. (d) Posterior annuloplasty device is inserted.
Modified from Duran 1992.
Prolapse of the anterior leaflet requires a different technique for repair (Gillinov &
Cosgrove 2003). This situation is usually the result of elongation or rupture of the
anterior leaflet chordae. Anterior leaflet resection is rarely indicated, because there
may not be enough tissue for reconstruction of the leaflet (De Oliveira et al. 2006).
Carpentier described two techniques effective for restoring normal motion in the
leaflet. The first is chordal or papillary muscle shortening and the second
technique is chordal transfer (Carpentier 1983). David was one of the pioneers
who used polytetrafluoroethylene (PTFE) sutures as neochordae (David 1989).
Annular enlargement is quite common in patients with degenerative disease. This
usually only occurs along the posterior annulus. Annuloplasty is performed to
36
correct annular dilatation, increase leaflet coaptation, reinforce suture lines, and
prevent further dilatation. Annuloplasty rings may be flexible or rigid, complete or
incomplete (Gillinov & Cosgrove III 2003).
In 1995, Alfieri et al. described the edge-to-edge repair which is also called
double orifice repair (Fucci et al. 1995). When employed to correct anterior leaflet
prolapse, a suture affixes the free edge of a segment of the normal posterior leaflet
to the free edge of a prolapsing portion of the anterior leaflet. The normal posterior
leaflet with its chordae serves to anchor the anterior leaflet, restricting its
excessive motion (Fucci et al. 1995, Alfieri et al. 2001). Satisfactory mid-term
results with this technique have been reported (Kuduvalli et al. 2006, Oc et al.
2005). This technique is currently also being performed percutaneously with
encouraging results (Feldman et al. 2006).
Patient with ischemic MR, CABG alone is usually insufficient and leaves
many suffering a significant residual MR. These patients would benefit from
concomitant mitral valve repair at the time of the CABG. Mitral annuloplasty
alone with a downsized annuloplasty ring is often effective for relieving MR
(Gillinov et al. 2001).
Functional MR is generally manageable with annuloplasty alone. Functional
MR may be corrected by placement of an annuloplasty ring which decreases the
annular circumference, shortens the intertrigonal distance, reduces the septallateral (anterior-posterior) annular diameter, and restores the geometry of the
annulus, thereby allowing the mitral valve leaflets to coapt (Prifti et al. 2001). The
precise choice of the type of annuloplasty (flexible vs. rigid, complete vs.
incomplete) is still controversial (Gillinov et al. 1998, Bolling et al. 1998).
Resection of the secondary chordae of the posterior leaflet may permit some
additional mobility of this structure and better coaptation. The issue of leaflet
tethering by malalignment of the papillary muscles, which results from
progressive left ventricle dilatation, can not yet be solved by surgery. New
solutions have been proposed, such as the Coapsys annuloplasty system (called
Myocor), in which artificial chords are implanted across the left ventricular cavity
and supported by synthetic buttons over the epicardium. A new annuloplasty ring,
geoForm, has been launched. It has a much narrower anteroposterior diameter and
a camel hump shape that suspends the postero-basal portion of the annulus and
ventricular wall (De Oliveira et al. 2006.) If leaflet tethering is extensive and
annuloplasty fails, mitral valve replacement and preservation of the subvalvular
apparatus is indicated (David & Ho 1986).
37
Eighty percent of infected mitral valves are amenable to repair. Radical
debridement is a cornerstone of the operative treatment of endocarditis. All
infected material must be removed. Leaflet perforations are repaired with
autologous patches, while abscess cavities are debrided and excluded with a
pericardial patch (Gillinov & Cosgrove III 2003).
2.2.7 Results of mitral valve surgery in mitral regurgitation
The outcome of patients who have undergone mitral valve repair is excellent. In a
review of 1072 patients who underwent primary isolated mitral valve repair for
mitral regurgitation due to degenerative disease in the Cleveland Clinic, the inhospital mortality was 0.3% (Gillinov et al. 1998). The long-term outcome was
addressed in another series of 242 patients followed for eight years after valve
repair, the survival rate being 91% (Flameng et al. 2003). Mitral valve
replacement, previously the only surgical option, is associated with an operative
mortality rate of 2% to 7%, as well as the long-term risks associated with a
prosthetic valve. No randomized trials have been published comparing these two
operations. A number of retrospective studies have demonstrated improved LV
function and survival in patients undergoing valve repair as compared to valve
replacement with or without preservation of the subvalvular apparatus. EnriquezSarano et al. performed a comparative analysis of patients undergoing mitral valve
repair (195 patients) or mitral valve replacement (214 patients) at the Mayo clinic
between 1980 and 1990 (Enriquez-Sarano et al 1995). Patients undergoing valve
repair were less symptomatic and had better LV function. Valve repair remained an
independent favourable predictor of operative mortality rate, late survival at 5 and
19 years, and postoperative ejection fraction. Survival was 100% of the expected
survival in the valve repair group at 10 years, whereas in the valve replacement
group it was only 83% of that expected (Enriquez-Sarano et al. 1995).
Thromboembolism is uncommon after mitral valve repair in contrast with
prosthetic mitral valve replacement. Warfarin is usually only used for three months
after mitral valve repair unless chronic atrial fibrillation is present, and
anticoagulant-related hemorrhage is therefore almost nonexistent. Furthermore,
repaired mitral valves suffer bacterial endocarditis much less frequently than
prosthetic valves (Lawrie 1998).
Braunberger et al. (Braunberger et al. 2001) reported very long-term results
(more than 20 years) of 162 patients who underwent mitral valve repair performed
by Carpentier`s group between 1970 and 1984. The valves were repaired using the
38
techniques of Carpentier. The 20-year Kaplan-Meier survival rate was 48%, which
is similar to the survival rate for a normal population with the same age structure.
During the 20 years of follow-up, 7 patients underwent reoperation. Valve
replacement was carried out in 5 patients, and repeat repair was carried out in 2
patients (Braunberger et al. 2001). Carpentier reported on a comparison of 100
mitral valve repairs with 100 porcine valves, 100 Starr valves and 100 Björk
valves. The clinical characteristics of the patients were similar. Hospital mortality
was 2% for repair and 12% to 13% for prosthesis. Survival at 7 years was 82%
after mitral valve repair and 56% to 61% after mitral valve replacement. Freedom
from thromboembolism was 96% after mitral valve repair, 94% after mitral valve
replacement with porcine valves, and 70% and 68% after mitral valve replacement
with mechanical valves. No fatal thromboembolism occurred in the mitral valve
repair group compared with a 20% to 28% fatal thromboembolism rate in the
prosthetic groups. The risk for reoperation at 7 years was 13% after mitral valve
repair, 8.5% after mitral valve replacement with a bioprosthesis, 8% after
replacement with a Starr prosthesis, and 18% after replacement with Björk valves
(Carpentier et al. 1983). Chauvaud et al. (2001) reported excellent long-term
results of reconstructive surgery in rheumatic mitral valve insufficiency. The
surgical techniques used were implantation of a prosthetic ring in 95%, shortening
of the chords and leaflet enlargement with autologous pericardium, and
commisurotomy. Hospital mortality rate was 2% and the mean follow-up was 12
years. Freedom from reoperation was 82±19% at 10 years and 55±25% at 20
years. The main cause (83%) of reoperation was progressive fibrosis of the mitral
valve.
Goldsmith and colleagues reported on improvement in the quality of life, as
assessed by a short form 36 questionnaire, 3 months after mitral valve repair and
replacement (Goldsmith et al. 2001). Mitral valve repair was associated with a
significant increase in 7 out of 8 parameters, whereas after mitral valve
replacement the improvement was modest. Mitral valve repair was found to be an
independent predictor of early better quality of life (Goldsmith et al. 2001). The
same authors also observed an improvement of quality of life in patients aged 75
years or older who underwent mitral valve surgery (Goldsmith et al. 1999).
Functional ischaemic mitral regurgitation is difficult to repair due to the
complex mechanism involved in the development of this condition. Surgical
treatment of functional ischemic mitral regurgitation is associated with poor longterm survival. Operative mortality ranges from 5 to 10%, and 5-year survival was
only about 50%, while 30% of the patients have significant recurrent mitral
39
regurgitation, as shown by McGee from Cleveland Clinic in a series of 585
patients (McGee et al. 2004). Bolling and others reported excellent freedom from
recurrent mitral regurgitation in patients with ischemic cardiomyopathy (Bolling et
al. 1998, Bishay et al. 2000). Calafiore reported a higher five year survival with
mitral valve repair (75%) than with mitral valve replacement (66%) (Calafiore et
al. 2004).
In patients operated on for endocarditis, hospital mortality is 0% to 7%
(Gillinov & Cosgrove 2003). When compared to replacement, repair of the
infected mitral valve results in greater freedom from recurrent infection and better
early and late survival (Muehrcke et al. 1997).
These results demonstrated the low operative risk associated with the
procedure and the durability of mitral valve repair in the long run, which makes
this operation the gold standard in surgical treatment of degenerative mitral valve
regurgitation The results in other types of pathology are less favourable, but
generally superior to those observed with valve replacement (De Oliveira et al.
2006). Patient selection, accurate evaluation of the cause or causes of mitral
regurgitation, and a well-executed operation using the appropriate repair technique
are all critical factors in the early and late success of mitral valve repair.
40
3
Aims of the study
The aims of the present study were:
1.
To identify those variables which were associated with an increased risk of
immediate postoperative mortality after mitral valve repair.
2.
To evaluate the long-term results and to identify the risk factors associated
with late adverse events after mitral valve repair.
3.
To compare the quality of life of patients who had undergone mitral valve
repair with that of an age- and gender-adjusted Finnish general population
using the RAND-36 Health Survey.
4.
To investigate the value of the European system for cardiac operative risk
evaluation score (EuroSCORE) for prediction of the immediate and late
outcome after mitral valve repair and replacement for mitral valve
regurgitation.
41
42
4
Materials and methods
4.1
Material
In studies I–III, one-hundred and sixty-four consecutive patients (mean age 60.7,
median 63.0, interquartile range 53.1–68.6) underwent mitral valve repair either
isolated or in combination with other procedures at our institution from January,
1993 to December, 2000. Any mitral valve repair performed as a lone procedure or
associated with any other cardiac procedure was included in these studies. Figure 6
depicts the number of mitral valve repairs done annually since 1993 and shows an
increase in the number of mitral valve repairs performed during the last years of
the series.
40
Overall no. of M VRs
No. of MVRs associated with other procedures
11.4%
35
10.3%
No. of M VRs/year
30
25
4.8%
10.5%
20
5.9%
15
0%
0%
0%
10
5
0
1993
1994
1995
1996
1997
1998
1999
2000
Fig. 6. Number of mitral valve repairs (MVRs) performed each year. Percentages
represent the 30-day mortality rate for each year. No significant association was
observed between the year of operation and postoperative mortality (p=0.64).
Data on pre-, intra- and postoperative variables were collected retrospectively
from patients’ records. Data on postoperative outcome after discharge from the
cardiac surgery ward were obtained by reviewing the hospital records inclusive of
data from all wards in our hospital. If the patient was discharged to another
hospital for medical treatment or rehabilitation, outcome data were retrieved from
43
discharge records of these institutions. Furthermore, patients were contacted by
mail and causes of late death obtained from a national registry.
In the second study, seventy-two long term survivors residing in the area close
to our Institution were evaluated using transthoracic echocardiography a median of
5.6 years (25 and 75 interquartile range, 3.8–7.5) after mitral valve repair. The
echocardiographic examination was carried out in our institution or in those
central hospitals where resources were available for long-term follow-up. Survival
outcome has been evaluated as secondary to all causes of death, cardiovascular
causes (cardiac causes and stroke) or cardiac causes (including immediate
postoperative deaths).
In the third study, the validated Finnish version of the RAND-36 Health
Survey questionnaire (Hays et al. 1993, Aalto et al. 1999) has been sent by surface
mail to all long-term survivors. Among 130 late survivors after mitral valve repair,
109 (83.8%) answered the RAND-36 Health Survey questionnaire and form the
basis for that study. The quality of life as assessed by the RAND-36 Health Survey
in these patients was compared to that of an age- and gender-adjusted Finnish
general population as previously assessed by Aalto and collaborators (Aalto et al.
1999).
Preoperative risk factors of studies I and II are summarized in Table 1,
respectively. Table 2 summarizes the clinical data of the patients included in study
III.
44
Table 1. Preoperative demographics (Study I and II).
Variables
No. (%)
Age
63.0 (53.1–68.6)
Females/males
42 (25.6) / 122 (74.4)
1.9 (1.8–2.0)
Body surface area (m2)
25.6 (23.0–28.0)
Body mass index (kg/m2)
Asthma / chronic obstructive pulmonary disease
12 (7.3)
Lower limb ischemia
7 (4.3)
Hypertension
26 (15.9)
Hyperlipidemia
14 (8.5)
Diabetes
16 (9.8)
Transient ischemic attack / stroke
()
Active endocarditis
0
Coronary artery disease
61 (37.2)
Previous myocardial infarction
21 (12.8)
Recent myocardial infarction
7 (4.3)
Unstable angina pectoris
4 (2.4)
Left main disease
11 (6.7)
NYHA functional class
I
4 (2.4)
II
69 (42.1)
III
59 (36.0)
IV
32 (19.5)
Atrial fibrillation
37 (22.6)
Mitral valve pathology
Annulus dilatation
4 (2.4)
Anterior leaflet disease
31 (18.9)
Posterior leaflet disease
88 (53.7)
Both anterior and posterior leaflet involved
11 (6.7)
Ruptured chordae
59 (36.0)
Ruptured papillary muscle
1 (0.6)
Calcified annulus
12 (7.3)
Etiology
Myxomatous degeneration
139 (84.8)
Rheumatic
3 (1.8)
Ischemic
6 (3.7)
Endocarditis
4 (2.4)
Penetrating trauma
2 (1.2)
No evident cause
10 (6.1)
Type
Mitral regurgitation
162 (98.8)
Mitral regurgitation and stenosis
2 (1.2)
Prior cardiac operation
11 (6.7)
Coronary artery bypass surgery
4 (2.4)
Atrial septal defect repair
4 (2.4)
Mitral valve repair
1 (0.6)
Aortic coartaction
1 (0.6)
Penthalogy of Fallot
1 (0.6)
Left ventricular ejection fraction (158 pts)
65 (57–71)
Left atrium diameter (mm) (137 pts)
50 (46–56)
Mitral valve regurgitation grade
II
11(6.7)
III
104(63.4)
IV
44(26.8)
Mean pulmonary artery pressure (mmHg) (147 pts)
26 (20–34)
2.33 (2.02–2.90)
Cardiac index (L/min/m2) (155 pts)
Continuous variables are reported as the median plus 25th and 75th interquartile range. NYHA:
New York Heart Association.
45
Table 2. Preoperative characteristics of mitral valve repair patients (Study III).
Variables
Mean age (years)
Gender ratio (F:M)
Mean body surface area (m2)
Mean body mass index (kg/m2)
Asthma / chronic obstructive pulmonary disease
Lower limb ischemia
Hypertension
Hyperlipidemia
Diabetes
Transient ischemic attack / stroke
Active endocarditis
Coronary artery disease
Previous myocardial infarction
Recent myocardial infarction
Unstable angina pectoris
Left main disease
NYHA functional class
I
II
III
IV
Atrial fibrillation
Mitral valve regurgitation grade
II
III
IV
Etiology
Myxomatous degeneration
Rheumatic
Ischemic
Endocarditis
Penetrating trauma
No evident cause
Prior cardiac operation
Atrial septal defect repair
Mean left ventricular ejection fraction (%)
NYHA: New York Heart Association.
No. (%)
60.4 (median 63.0, IQR 52.9–68.1)
28(25.7)/81 (74.3)
1.9 (median 1.9, IQR 1.8–2.0)
25.8 (median 25.4, IQR 22.8–27.7)
7 (6.4)
6 (5.5)
13 (11.9)
11 (10.1)
7 (6.4)
6 (5.5)
0 (0)
7 (6.4)
3 (2.8)
2 (1.8)
9 (8.3)
4 (3.7)
58 (53.2)
33 (30.3)
14 (12.8)
21 (19.3)
9 (8.3)
71 (65.1)
28 (25.7)
94 (86.2)
3 (2.8)
5 (4.6)
3 (2.8)
2 (1.8)
2 (1.8)
2 (1.8)
63 (median 65, IQR 57–70)
In study IV, two-hundred and seven patients underwent mitral valve repair or
replacement for mitral valve regurgitation at our institution from 1993 to 2000.
Data on 180 patients were available for the retrospective calculation of additive
and logistic EuroSCORE (Nashef et al. 1999, Roques et al. 2003b). Postoperative
outcome after discharge from the cardiac surgery ward was obtained by reviewing
the hospital records inclusive of data from all wards of our hospital. If the patient
was discharged to another hospital for medical treatment or rehabilitation,
outcome data was retrieved from discharge records of the latter institutions.
Preoperative risk factors in the overall series as well as in the mitral valve
replacement and mitral valve repair group are summarized in Table 3.
46
Table 3. Preoperative characteristics (Study IV)
Variables
Age (years)
Overall (%)
Mitral valve repair
(%)
Mitral valve
replacement (%)
p-value
63.3 (53.8–69.2)
63.1 (53.3–68.8)
65.2 (56.6–73.1)
0.22
Females
56 (31.1)
38 (27.0)
18 (46.2)
0.022
Asthma / COPD
14 (7.8)
10 (7.1)
4 (10.3)
0.51
Extracardiac arteriopathy
7 (3.9)
5 (3.5)
2 (5.1)
0.64
Neurological dysfunction
9 (5.0)
6 (4.3)
3 (7.7)
0.41
Prior cardiac operation
14 (7.8)
11 (7.8)
3 (7.7)
1.00
4 (2.2)
1 ((0.6)
4 (2.2)
3 (1.7)
1 (0.6)
4 (2.8)
0
4 (2.8)
1 (0.7)
1 (0.7)
1 (0.7)
0
1 (2.6)
0
2 (5.1)
0
0
–
–
–
–
–
–
Serum creatinine>200 µmol/L
3 (1.7)
1 (0.7)
2 (5.1)
0.12
Active endocarditis
3 (1.7)
0
3 (7.7)
0.010
Coronary artery bypass surgery
Aortic valve replacement
Atrial septal defect repair
Mitral valve repair
Aortic coartaction
Penthalogy of Fallot
Congestive heart failure
16 (8.9)
9 (6.4)
7 (17.9)
0.025
Critical pre-operative state
10 (5.6)
2 (1.4)
8 (20.5)
<0.0001
Diabetes
17 (9.4)
12 (8.5)
5 (12.8)
0.53
Coronary artery disease
68 (37.8)
52 (36.9)
16 (41.0)
0.64
28 (15.6)
14 (7.8)
9 (5.0)
17 (12.1)
4 (2.8)
4 (2.8)
11 (28.2)
10 (25.6)
5 (12.8)
0.014
<0.0001
0.024
1 (0.6)
13 (7.2)
106 (58.9)
53 (29.4)
0
8 (5.8)
92 (67.2)
37 (27.0)
1 (2.8)
5 (13.9)
14 (38.9)
16 (44.4)
–
–
–
–
<0.0001
Previous myocardial infarction
Myocardial infarction<3 months
Unstable angina pectoris
Regurgitation grade (173 patients)
1
2
3
4
0.005
NYHA functional class III–IV
112 (62.6)
77 (54.6)
35 (92.1)
Atrial fibrillation (174 patients)
39 (21.7)
32 (23.0)
7 (20.0)
0.018
Systolic pulmonary artery
pressure>60 mmHg
46 (25.6)
26 (18.4)
20 (51.3)
<0.0001
126 (70.0)
39 (21.7)
15 (8.3)
114 (80.9)
23 (16.3)
4 (2.8)
12 (30.8)
16 (41.0)
11 (28.2)
149 (82.8)
4 (2.2)
10 (5.6)
7 (3.9)
2 (1.1)
8 (4.4)
119 (84.4)
3 (2.1)
5 (3.5)
4 (2.8)
2 (1.4)
8 (5.7)
30 (76.9)
1 (2.6)
5 (12.8)
3 (7.7)
0
0
–
–
–
–
–
–
32 (17.8)
20 (14.2)
12 (30.8)
0.017
Type of operation
Elective operation
Urgent operation
Emergent operation
<0.0001
Etiology
Myxomatous degeneration
Rheumatic
Ischemic
Endocarditis
Trauma
No evident cause
Left ventricular ejection
fraction<50%
Additive EuroSCORE
Logistic EuroSCORE (%)
–
–
–
0.09
5 (3–7)
4 (3–6)
8 (5–11)
<0.0001
3.7 (2.1–7.6)
3.2 (1.9–5.8)
10.0 (4.0–26.8)
<0.0001
Continuous variables are reported as the median plus 25th and 75th interquartile range. P-value is for
difference between mitral valve repair and replacement groups. COPD: chronic obstructive pulmonary
disease. NYHA: New York Heart Association functional class.
47
4.2
Methods
A coronary angiography was routinely performed to assess the status of the
coronary arteries and, in patients previously having undergone coronary artery
bypass surgery, of the bypass grafts. The operation was performed through a
median sternotomy employing moderate systemic hypothermia and antegrade/
retrograde cold blood cardioplegia. A transesophageal echocardiographic
examination was carried out intraoperatively immediately before and after repair
in all patients. Transthoracic echocardiography was performed before discharge in
152 patients. Low molecular weight heparin was administered postoperatively
during the hospital stay and was followed by warfarin for three months, unless the
patients had a prosthetic valve or chronic atrial fibrillation which was an indication
for permanent anticoagulation treatment.
The operative details for studies I and II are summarized in Table 4, while
those for study III are summarized in table 5.
48
Table 4. Operative details (Study I and II).
Variables
No. (%)
Type of operation
Elective
131 (79.9)
Urgent
26 (15.9)
Emergent
7 (4.3)
Atrial incision
Superior
98 (59.8)
Transseptal
31 (18.9)
Lateral
28 (17.1)
Other
7 (4.2)
Findings at operation
Annulus dilatation
23 (14.0)
Anterior leaflet disease
28 (17.1)
Posterior leaflet disease
77 (47.0)
Both anterior and posterior leaflet involved
31 (18.9)
Ruptured chordae
87 (53.0)
Ruptured papillary muscle
5 (3.0)
Calcified valve
2 (1.2)
Annuloplasty
155 (94.5)
Ring annuloplasty
101 (65.1)
Other
54 (34.8)
Leaflet resection and reconstruction
118 (72.0)
Shortening of the chordae
12 (7.3)
Chordae reconstruction with PTFE thread
34 (20.7)
Associated procedures
84 (51.2)
Coronary artery bypass surgery
58 (35.4)
Tricuspid valve repair
20 (12.2)
Atrial septal defect closure
10 (6.1)
Maze
8 (4.9)
Aortic valve replacement
1 (0.6)
Aortic clamping time (min)
135 (113–177)
Cardiopulmonary bypass duration (min)
183 (154–233)
Length of operation (min)
275 (240–339)
Intraoperative bleeding (mL)
800 (500–1275)
PTFE: polytetrafluoroethylene
49
Table 5. Operative details (Study III).
Variables
No. (%)
Type of operation
Elective
Urgent
Emergent
93 (85.3)
12 (11.0)
4 (3.7)
Findings at operation
Annulus dilatation
Anterior leaflet disease
Posterior leaflet disease
Both anterior and posterior leaflet involved
Ruptured chordae
Ruptured papillary muscle
Calcified valve
12 (11.0)
15 (13.8)
55 (50.5)
25 (22.9)
61 (56.0)
2 (1.8)
0 (0)
Ring annuloplasty
62 (56.9)
Other annuloplasties
42 (38.5)
Leaflet resection and reconstruction
86 (78.9)
Shortening of the chordae
Chordae reconstruction with PTFE thread
8 (7.3)
25 (22.9)
Associated procedures
Coronary artery bypass surgery
Tricuspid valve repair
Atrial septal defect closure
Maze
Aortic valve replacement
32 (29.4)
6 (5.5)
4 (3.7)
5 (4.6)
1 (0.9)
Mean aortic clamping time (min)
142 (median 134, IQR 112–177)
Mean cardiopulmonary bypass duration (min)
189 (median 179, IQR 153–216)
Length of operation (min)
285 (median 270, IQR 240–310)
Intraoperative bleeding (mL)
957 (median 700, IQR 500–1025)
PTFE: polytetrafluoroethylene.
In study IV, a St Jude Medical mechanical prosthesis (median size: 29 mm. IQR
27–31 mm) was used in all patients undergoing mitral valve replacement. The
operative details for this study are summarized in Table 6.
50
Table 6. Operative details (Study IV).
Variables
Overall (%)
Mitral valve
repair (%)
Mitral valve
replacement
(%)
p-value
24 (13.3)
34 (18.9)
77 (42.8)
30 (16.7)
89 (49.4)
5 (2.8)
7 (48.9)
19 (13.5)
25 (17.7)
67 (47.5)
27 (19.1)
75 (53.2)
4 (2.8)
1 (0.7)
5 (12.8)
9 (23.1)
10 (25.6)
3 (7.7)
14 (35.9)
1 (2.6)
6 (15.4)
0.91
0.49
0.015
0.14
0.056
1.00
<0.0001
88 (48.9)
44 (24.4)
–
–
–
–
-
Findings at operation
Annulus dilatation
Anterior leaflet disease
Posterior leaflet disease
Both anterior and posterior leaflet involved
Ruptured chordae
Ruptured papillary muscle
Calcified valve
Annuloplasty
Ring annuloplasty
Other
101 (56.1)
–
–
-
Shortening of the chordae
Leaflet resection and reconstruction
12 (6.7)
–
–
-
Chordae reconstruction with PTFE thread
31 (17.2)
–
–
–
67 (37.2)
10 (5.6)
18 (10.0)
10 (5.6)
7 (3.9)
50 (35.5)
1 (0.7)
16 (11.3)
8 (5.7)
7 (5.0)
22 (56.4)
9 (23.1)
2 (5.1)
2 (5.1)
0
0.35
<0.0001
0.37
1.00
0.15
Aortic clamping time (min)
139 (114–182)
134 (113–
179)
156 (118–203)
0.090
Cardiopulmonary bypass duration (min)
189 (155–242)
183 (154–
234)
224 (170–260)
0.049
Length of operation (min)
285 (240–360)
275 (240–
349)
345 (265–380)
0.018
Associated procedures
Coronary artery bypass surgery
Aortic valve replacement
Tricuspid valve repair
Atrial septal defect closure
Maze
PTFE: polytetrafluoroethylene. P-value is for difference between mitral valve repair and replacement
groups.
4.3
Statistical analysis
Statistical analysis was performed using SPSS statistical software (SPSS v. 10.0.5
SPSS Inc., Chicago, IL, USA). Continuous variables were reported as the mean
and median with 25th and 75th interquartile range (IQR). In study I, the Chi-square
test and the Fisher`s exact test, with or without the Monte Carlo method, were used
for univariate analysis of categorical data. The Mann-Whitney test was used to
assess the distribution of continuous variables in different subgroups. The receiver
operating characteristics (ROC) curve was used for identification of the best cutoff value of age in predicting postoperative adverse outcome. Logistic regression
with the help of backward selection was used for multivariable analysis. In study
II, the Kaplan-Meier method and Cox regression was used to evaluate the impact
of variables on the long-term outcome. Only preoperative variables with p51
values<0.05 at univariate analysis were considered for inclusion in the regression
model in both studies. In study III, the Wilcoxon test was used to assess any
difference in terms of quality of life-related variables between the present patients
and an age- and gender-adjusted general Finnish population. The Kaplan-Meier
method was used to estimate survival. In study IV, a receiver operating
characteristics (ROC) curve was used to evaluate the impact of additive and
logistic EuroSCOREs on immediate postoperative mortality. The Kaplan-Meier
method was used to estimate the long-term outcome. The Kaplan-Meier method
and Cox regression were used to evaluate the impact of EuroSCOREs on longterm survival. Cox regression was used for multivariable analysis. In all studies, a
p-value less than 0.05 was considered to be statistically significant.
52
5
Results
5.1
Predictors of postoperative mortality after mitral valve repair
5.1.1 Overall outcome
Eleven (6.7%) out of 164 patients died during the immediate postoperative period,
a median of 14 days after surgery (range 1–29 days). Data on the main
preoperative variables and cause of death in these patients are reported in Table 7.
The overall postoperative complications encountered in this series are listed in
Table 8.
53
54
Female
11
67.7
51.3
73.0
77.2
79.4
65.7
69.5
82.6
63.3
74.2
65.2
Age
(years)
IV
III
III
IV
IV
IV
III
III
III
III
IV
NYHA
functional
class
60
68
–
60
72
30
65
73
67
65
32
2.12
1.87
2.77
2.59
1.37
1.89
1.57
1.77
1.99
2.02
–
3
4
3
4
3
3
4
3
3
4
3
sinus
FA
FA
Sinus
FA
Sinus
FA
Sinus
FA
Sinus
FA
Cardiac
LVEF (%) Cardiac index Preop. MV
regurgitation rythm
(L/min/m2)
grade
CABG
TVP
CABG
CABG
CABG
TVP
No
TVP
Associated
procedures
2
0
–
0
0
0
0
1
No
No
CABG
Cox-Maze
2
1
29
7
21
8
23
1
21
25
13
14
4
Postop. MV Postop.
regurgitatio day of
n grade
death
CABG, ASD CABG, TVP, –
ASD
No
No
CABG
MVA
No
No
No
CABG
Prior
cardiac
surgery
LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; MV: mitral valve, MVA: mitral valve annuloplasty; CABG: coronary
artery bypass grafting; ASD: repair of atrial septal defect, TVP: tricuspid valve plasty; AMI:acute myocardial infarction; MOF: multiorgan failure; –
: unknown.
Male
10
Male
6
Male
Male
9
Male
4
5
Female
Male
3
Male
Male
8
Male
1
2
7
Gender
Pts.
Table 7. Details of the patients who died immediately after the operation.
AMI
Sepsis,
pneumonia
MOF
AMI
Sepsis
AMI
MOF
AMI
Bleeding from
trachestomy
Cardiac
tamponade
AMI
Causes of
death
Table 8. Postoperative complications (Study I).
Type of postoperative complications
No. (%)
Postoperative bleeding requiring reoperation
22 (13.4)
Postpericardiotomy syndrome
20 (12.2)
Respiratory complications
19 (11.6)
Renal complications
6 (3.7)
Myocardial infarction
5 (3.0)
Stroke
5 (3.0)
Multiorgan failure
2 (1.2)
Transient ischemic attack
1 (0.6)
Wound complications
1 (0.6)
Mediastinitis
1 (0.6)
When patient age, NYHA functional class, unstable angina pectoris, cardiac
rhythm, baseline cardiac index, history of prior cardiac surgery and concomitant
procedures were included in the regression model (154 patients included in the
analysis), patient age (median age of deaths/survivors: 69.4/61.8 years; p=0.006,
for an increase of 10 units: OR 4.33, 95% CI 1.53–12.27), history of prior cardiac
surgery (mortality rates with and without risk factor: 36.4% vs. 4.6%, p=0.006, OR
118.56, 95% CI 4.03–3491.14) and NYHA functional class (mortality rates:
NYHA I: 0%, NYHA II: 0%, NYHA III: 10.2%, NYHA IV: 15.6%; p=0.011, OR
5.66, 95% CI 1.49–21.49) were shown to be significantly associated with an
increased risk of postoperative death. The ROC curve for the data showed that
patients’ age had an area under the curve of 0.762 (95% CI 0.622–0.901, p=0.004),
its best cut-off value being 65 years (mortality in higher vs. lower age category:
13.4% vs. 2.1%; p=0.008, sensitivity 81.8%, specificity 62.1%, accuracy 63.4%).
Age significantly correlated with baseline cardiac index (p<0.0001) and
preoperative serum level of creatinine (p=0.006). Atrial fibrillation was
significantly associated with older age (median, 65.9 vs. 60.8 years, p=0.024).
Figure 7 depicts the increased mortality risk of patients aged more than 65
years undergoing MVR with a history of prior cardiac surgery.
55
100%
(4/4 pts)
80
40
7.9%
(5/63 pts)
20
0%
(0/7 pts)
Po st op erat iv
60
e m or ta lit y
ra te (% )
1 00
0a c
≥6
5y
ea
i
rd
ca
u s t io n
o
i
e v ra
Pr op e
2.2%
(2/90 pts)
rs
<6
5y
ea
rs
d
ar
sc
ou on
i
e v ti
p r e ra
No op
ia c
Fig. 7. Increase of postoperative mortality after mitral valve repair by increasing age in
patients with or without a history of prior cardiac surgery (p< 0.0001).
5.1.2 Immediate postoperative outcome after mitral valve repair as a
lone procedure
Among patients who underwent mitral valve repair as lone procedure, only three
patients had a history of prior cardiac surgery. One patient (1.3%) died
postoperatively. He was a 74-year-old man who underwent elective operation and
died of cardiac tamponade 14 days after surgery (patient 2, table 7).
5.1.3 Immediate postoperative outcome after mitral valve repair with
concomitant procedures
Among 84 patients who underwent MVR associated with other procedures, 10
(11.9%) died postoperatively. The postoperative mortality was similar when the
analysis was restricted to those patients who had concomitant procedures other
than Maze (9 out of 77 patients, 11.7%).
Univariate analysis showed that a history of prior cardiac operation (p=0.006),
age (p=0.040), body mass index (p=0.017), NYHA functional class (p=0.024) and
56
mean pulmonary artery pressure (p=0.023) were associated with an increased risk
of postoperative death. When these factors were included in the regression model,
a history of prior cardiac operation (p=0.05, OR 115.50, 95% CI 1.01–13228.35),
age (p=0.027, for an increase of 10 units: OR 3.80, 95% CI 1.12–12.76) and
NYHA functional class (p=0.032, OR 5.89, 95% CI 1.17–29.80) were
significantly associated with an increased risk of postoperative death.
5.2
Long-term outcome after mitral valve repair
The median follow-up period was 4.9 years (IQR, 3.2–7.2). Among operative
survivors, 12 patients died of cardiac causes (7.9%), two of stroke (1.3%), one of
pneumonia (0.7%), three of cancer (2.0%), two of trauma (1.3%), one of
postoperative multiorgan failure (0.7%), one of gastrointestinal bleeding (0.7%),
and one of subdural haematoma (0.7%).
Nine patients (5.5%) underwent repeat cardiac surgery after mitral valve
repair, while eight patients (4.9%) underwent redo mitral valve surgery (6 patients
underwent mitral valve replacement and 2 underwent repeat mitral valve repair)
after a median of 2.0 years (IQR 1.3–4.7). Four of the nine patients underwent redo
mitral valve surgery within one year of surgery.
5.2.1 Long-term survival
The ten-year survival rate from any cause of death was 70.2% (Fig. 8), whereas
survival freedom from any fatal cardiovascular event was 73.2% (Fig. 9). Survival
freedom from any fatal cardiac event was 75.9% (Fig. 10).
57
Survival (%)
Pts. at risk
–
164
90.2
148
88.4
145
86.6
133
84.4
99
82.6
81
79.3
64
74.9
43
74.9
33
74.9
19
70.2
7
79.5
43
79.5
33
79.5
19
74.5
7
Fig. 8. Overall survival after mitral valve repair (SE<0.060).
Survival (%)
Pts. at risk
–
164
91.5
149
90.8
145
90.2
133
88.6
99
87.6
81
84.7
64
Fig. 9. Survival freedom from any fatal cardiovascular event after mitral valve repair
(SE<0.061).
58
Survival (%)
–
91.5
90.8
90.2
90.2
89.2
85.8
80.9
80.9
80.9
75.9
Pts. at risk
164
148
145
133
99
81
64
43
33
19
7
Fig. 10. Survival freedom from any fatal cardiac event after mitral valve repair
(SE<0.062).
When the patients who died immediately after mitral valve repair were excluded
from the survival analysis, the 10-year survival rate from any cause of death was
75.3% (SE 6.2%), survival freedom from any fatal cardiovascular event was
79.9% (SE 6.3%), and survival freedom from any fatal cardiac event was 81.3%
(S.E 6.3%).
Multivariable analysis showed that a history of previous cardiac surgery
(p=0.009, RR 8.44, 95% CI 1.72–41.46), age (p=0.030, RR 1.08, 95% CI 1.01–
1.16), and atrial fibrillation (p=0.043, RR 3.27, 95% CI 1.04–10.29) were
predictors of late cardiac death. At 10 years, survival freedom from fatal cardiac
event was 36.3% in patients with a history of previous cardiac surgery and 78.6%
in those who had not undergone any previous cardiac operation (p<0.0001). As
previous cardiac surgery had a major impact especially on the immediate
postoperative outcome, a subanalysis was done for prediction of late fatal cardiac
event excluding operative deaths.
Multivariable analysis showed that previous coronary artery bypass surgery
(p=0.001, RR 155.26, 95% CI 7.74–3114.66) and concomitant coronary artery
59
bypass surgery (p=0.023, RR 4.81, 95% CI 1.24–18.65) were predictors of late
cardiac death among operative survivors.
5.2.2 Survival freedom from redo mitral valve surgery
The ten-year survival freedom from redo mitral valve surgery was 93.8% (Fig. 11).
Survival (%)
–
97.4
97.4
97.4
95.6
94.4
93.2
93.2
93.2
93.2
93.2
Pts. at risk
164
145
143
131
95
79
63
42
32
17
6
Fig. 11. Survival freedom from redo mitral valve surgery (SE<0.024).
Table 9 summarizes the risk factors which the univariate analysis showed to be
significantly associated with poor survival freedom after redo mitral valve surgery.
Table 9. Preoperative risk factors predictive at univariate analysis of survival freedom
after redo mitral valve surgery.
Risk factors
p-value
RR (95% CI)
Chronic obstructive pulmonary disease/asthma
0.004
8.17 (1.95–34.24)
Calcified mitral valve
0.012
Immediate postoperative mitral valve regurgitation grade > 1 0.001
14.79 (1.80–121.33)
11.69 (2.60–52.56)
Multivariable analysis showed that residual mitral valve regurgitation grade>1 as
assessed during the immediate postoperative period (p=0.001, RR 21.64, 95% CI
3.60–130.20) and chronic obstructive pulmonary disease/asthma (p=0.013, RR
60
12.02, 95% CI 1.70–85.39) were predictors of late redo mitral valve surgery.
Similar results were obtained when the variable use of bronchodilators/steroids (9
patients, p=0.006, RR 15.77, 95% CI 2.22–111.96) was included in the regression
model instead of chronic obstructive pulmonary disease/asthma (12 patients).
Multivariable analysis was restricted to 143 patients due to a lack of definitive
immediate postoperative echocardiographic data in 12 patients, whereas 9 patients
were censored due to a short follow-up.
Ten-year survival freedom from redo mitral valve surgery was 95.7% in
patients with an immediate postoperative mitral valve regurgitation 1 and 60.6%
in those whose regurgitation grade was grade 2 (Fig. 12, p<0.0001).
Fig. 12. Survival freedom from redo mitral valve surgery in 13 patients with a residual
regurgitation grade 2 (--) (SE <19.7) versus 139 patients with a grade 0–1 (--) (SE <
0.021) as detected at echocardiography during the immediate postoperative period
(log-rank test: p<0.0001).
Ten-year survival freedom from redo mitral valve surgery was 66.8% in patients
with chronic obstructive pulmonary disease/asthma and 95.2% in those without it
(p=0.0006).
61
5.2.3 Survival freedom from stroke
During the follow-up period, nine patients experienced stroke, four patients once
and five patients twice. The ten-year survival freedom from stroke was 93.5%
(Fig. 13). The linearized rate for stroke was 9.7%/patient-year.
Survival (%)
–
98.6
96.7
95.2
93.5
93.5
93.5
93.5
93.5
93.5
93.5
Pts. at risk
164
146
141
128
96
78
62
41
31
18
7
Fig. 13. Survival freedom from stroke (SE<0.021).
5.2.4 Long-term outcome among patients with myxomatous
degenerative disease
The immediate postoperative mortality was 6.5% (9 out of 139 patients). Among
these patients with myxomatous degenerative mitral valve disease, the 10-year
survival rate from any cause of death was 73.9%, whereas survival freedom from
any fatal cardiovascular event was 83.7%. Survival freedom from any fatal cardiac
event was 79.9%. These patients tended to have a better 10-year overall survival
(73.9% vs. 53.9%, p=0.066) and a significantly better cardiovascular survival
(83.7% vs. 62.8%, p=0.008) and cardiac survival (79.9% vs. 57.7%, p=0.015) than
patients with other etiologies of mitral valve disease.
When patients who died immediately after mitral valve repair were excluded
from the survival analysis, the 10-year survival rate from any cause of death was
79.1%, survival freedom from any fatal cardiovascular event was 83.7%, and
survival freedom from any fatal cardiac event was 85.5%.
62
When operative deaths were excluded from the analysis, a number of risk
factors were shown to be associated with worse survival freedom from cardiac
death (Table 10). Multivariable analysis showed that a low preoperative cardiac
index was the only independent predictor of cardiac death (p=0.031, RR 0.10, 95%
CI 0.014–0.81). At 10 years, survival freedom from fatal cardiac event was 89.1%
in patients with a baseline cardiac index>2L/min/m2 and 73.7% in those with a
baseline cardiac index<2L/min/m2 (log-rank, p=0.002).
Table 10. Preoperative risk factors predictive at univariate analysis of survival freedom
from fatal cardiac event after mitral valve repair for myxomatous degenerative mitral
valve disease (operative deaths excluded).
Risk factors
p-value
RR (95% CI)
Age*
0.014
1.11 (1.02–1.22)
Age > 65 years
0.0013
15.05 (1.76–128.99)
Cerebrovascular disease
0.043
12.14 (1.08–137.03)
Any previous or recent myocardial infarction
0.007
10.50 (1.88–58.62)
Coronary artery disease
0.015
7.77 (1.49–40.53)
Annulus dilatation
0.009
7.33 (1.63–32.99)
Concomitant coronary artery bypass surgery*
0.014
7.93 (1.52–41.31)
Only annuloplasty done as mitral valve repair*
0.011
6.94 (1.54–31.16)
Baseline oxygen delivery
0.012
0.99 (0.98–0.99)
Baseline oxygen delivery < 350 ml/min/m2
0.021
6.04 (1.31–27.88)
Baseline cardiac index*
0.016
0.12 (0.02–0.67)
RR: relative risk, C.I.: confidence interval. Asterisks indicate the variable included in the multivariable
analysis.
Disease other than isolated to the anterior leafleft (p=0.036, RR 9.40, 95% CI
1.15–76.75), rupture of a papillary muscle (p=0.023, RR 11.44, 95% CI 1.40–
93.77), calcified mitral valve (p=0.019, RR 12.44, 95% CI 1.51–102.18), only
annuloplasty performed (p=0.020, RR 5.46, 95% CI 1.30–22.92), chronic
obstructive pulmonary disease/asthma (p=0.004, RR 8.29, 95% CI 1.98–34.72)
and residual mitral valve regurgitation grade>1 as assessed during the immediate
postoperative period (p=0.001, RR 11.68, 95% CI 2.60–52.53) were predictors at
univariate analysis of redo mitral valve surgery.
Multivariable analysis showed that residual mitral valve regurgitation of a
grade>1 as assessed during the immediate postoperative period (p=0.007, RR
15.87, 95% CI 2.16–116.67) and chronic obstructive pulmonary disease/asthma
63
(p=0.012, RR 14.75, 95% CI 1.80–121.09) were predictors of late redo mitral
valve surgery also among patients with myxomatous degenerative disease.
5.2.5 Long-term echocardiographic findings
After a median of 5.6 years (IQR, 3.8–7.5), no significant changes were detected
in terms of left ventricular ejection fraction (Fig. 14), whilst mitral valve
regurgitation grade (Fig. 15) along with New York Heart Association functional
class (Fig. 16) were significantly lower than baseline values in these long-term
survivors.
Wilcoxon's test p=0.73
90
Left ventricular ejection fraction (%)
80
70
60
50
40
30
20
Baseline
Last follow-up control
Median length of follow-up: 5.6 years (IQR, 3.8-7.5)
Fig. 14. Left ventricular ejection fraction before and a median of 5.6 years after mitral
valve repair in 71 patients who underwent echocardiographic examination.
64
4
Wilcoxon's test p<0.0001
Mitral valve regurgitation grade
3
2
1
0
Baseline
Last follow-up control
Median length of follow-up: 5.6 years (IQR, 3.8-7.5)
Fig. 15. Mitral valve regurgitation grade before and a median of 5.6 years after mitral
valve repair in 70 patients who underwent echocardiographic examination.
65
New York Heart Association class
4
Wilcoxon's test p<0.0001
3
2
1
Baseline
Last follow-up control
Median length of follow-up: 5.6 years (IQR, 3.8-7.5)
Fig. 16. New York Heart Association functional class before and a median of 5.6 years
after mitral valve repair in 72 patients who underwent echocardiographic examination.
The median left atrium diameter decreased from 50 mm (IQR, 46–57) to 44 mm
(IQR, 40–49) (64 patients available for analysis, p<0.0001).
5.3
Quality of life after mitral valve repair
The mean follow-up period was 5.1 years (median 4.9 years, IQR 3.2 to 7.2 years).
Eleven patients (6.7%) died during the immediate postoperative period. Amongst
operative survivors, 12 patients (7.9%) died later from cardiac causes, two of
stroke (1.3%), one of pneumonia (0.7%), three of cancer (2.0%), two of trauma
(1.3%), one of postoperative multiorgan failure (0.7%), one of gastrointestinal
bleeding (0.7%), and one of subdural hematoma (0.7%).
Nine patients (5.5%) underwent repeat cardiac surgery after mitral valve
repair, eight patients (4.9%) having undergone redo mitral valve surgery (six
patients underwent mitral valve replacement and two underwent repeat mitral
66
valve repair). Four patients underwent redo mitral valve surgery within the first
year after surgery.
At the 10-year follow-up, the overall survival rate in the study group was
70.2%, and it was 74.8% among the operative survivors. In the age- and genderadjusted general population, the expected 10-year survival is 93.9%.
Of 130 late survivors, 109 (83.8%) answered the questionnaire and form the
basis of the present study. The 21 non-responders were rather young at the time of
mitral valve repair (mean 53.4 years; median 55.8, IQR 44.5–64.2) and also had a
rather long survival after surgery (mean 7.5 years, median 7.8, IQR 5.8–9.7). Two
of these patients had previously undergone surgery for atrial septal defect and for
aortic coarctation, respectively. Six patients underwent concomitant coronary
artery bypass surgery. An echocardiographic examination had been performed in
all but three of these patients immediately after mitral valve repair. One patient
was shown to have a grade 2 residual mitral valve regurgitation, whilst the others
had from grade 0 to1 residual regurgitation.
Immediately after surgery, 56 patients (51.4%) had no signs of mitral valve
regurgitation at echocardiography, while 42 patients (38.5%) had grade 1 residual
regurgitation and six patients (5.5%) grade 2. Echocardiographic examinations
were not performed in five patients during their in-hospital stay.
Figure 17 depicts the median quality of life scores in the study group
compared with those of an age-and gender-adjusted general population. A
Wilcoxon test indicated significantly higher mental health (p=0.04) and pain
scores (p=0.015) and lower role functioning/physical score (p=0.008) in the study
group. The mean total score for the study group was 512 (median 532; IQR: 360 to
678), but was 522 (median 538; IQR: 468 to 549) in the age- and gender-adjusted
general population (p=0.72) (only 95 patients were included in the analysis due to
isolated missing scores).
Coronary artery disease, concomitant coronary artery bypass surgery and
immediate postoperative residual mitral valve regurgitation of a grade more than 1
were not associated with a significantly poorer quality of life.
67
Fig. 17. RAND-36 Health Survey variable scores of long-term survivors after mitral
valve repair (open bars) and of the age- and gender-adjusted general Finnish
population (filled bars). *: p<0.05.
5.4
Predicting the immediate and late outcome after surgery for
mitral valve regurgitation with EuroSCORE
5.4.1 30-day postoperative outcome
The thirty-day postoperative mortality rate was 10.0% overall (18 patients) –7.1%
(10 patients) in the mitral valve repair group and 20.5% (8 patients) in the mitral
valve replacement group (p=0.013), respectively. Both the additive and the logistic
EuroSCORE were significantly higher in the mitral valve replacement group
compared with the mitral valve repair group. The additive EuroSCORE
(p<0.0001, area under the ROC curve: 0.804, 95%CI 0.689–0.919, SE 0.059) as
well as the logistic EuroSCORE (p<0.0001, area under the ROC curve: 0.806,
68
95%CI 0.695–0.918, SE 0.057) were significantly associated with 30-day
postoperative death (Fig. 18). The thirty-day postoperative mortality rates are
shown in Figure 19 according to the different quintiles of the additive and the
logistic EuroSCORE.
1,0
Sensitivity
0,8
0,6
0,4
0,2
0,0
0,0
0,2
0,4
0,6
0,8
1,0
1 - Specificity
Fig. 18. Area under the receiver operating characteristics curve of the additive
EuroSCORE (__) and the logistic (--) EuroSCORE in predicting 30-day postoperative
death after surgery for mitral valve regurgitation.
69
30-day postoperative mortality (%)
40
30
25
20
15
10
5
0
35
30-day postoperative mortality (%)
p<0.0001
35
34 pts
44 pts
2
3-4
5-6
7-8
Additive EuroSCORE quintiles
45 pts
29 pts
28 pts
9-16
37 pts
36 pts
p<0.0001
30
25
20
15
10
5
0
36 pts
<1.85
35 pts
36 pts
1.85-3.07 3.08-4.99 5.00-9.23 9.24-60.6
Logistic EuroSCORE quintiles (%)
Fig. 19. Thirty-day postoperative mortality rates according to different quintiles of the
additive and the logistic EuroSCOREs. The number of patients per each quintile is
reported below each column
According to the ROC curve analysis, the best cutoff values for the additive and
the logistic EuroSCOREs were 6 and 4.0%, respectively. Patients with an additive
EuroSCORE of more than or equal to 6 had a 30-day postoperative mortality rate
of 20.0%, whereas it was 2.9% in patients with an additive EuroSCORE of less
than 6 (p<0.0001, sensitivity 83.3%, specificity 62.9%, accuracy 65.0%). Patients
70
with a logistic EuroSCORE of more than or equal to 4% had a 30-day
postoperative mortality rate of 18.8%, whereas it was 2.1% in patients with an
additive EuroSCORE of less than 4 (p<0.0001, sensitivity 88.8%, specificity
57.4%, accuracy 60.5%).
5.4.2 Late outcome
Among operative survivors, 25 patients died during a median follow-up period of
5.1 years (IQR, 3.5–7.3 years). The ten-year overall survival rate from any cause
of death was 74.7%. Patients who underwent mitral valve replacement had a
significantly poorer long-term survival than those who had undergone mitral valve
repair (p=0.01, Fig. 20). The additive EuroSCORE (median: 8 vs. 4, p<0.0001)
and the logistic EuroSCORE (median: 9.6 vs. 3.1, p<0.0001) were significantly
higher in the mitral valve replacement group compared with the mitral valve repair
group also among operative survivors. Both the additive EuroSCORE (p<0.0001)
and the logistic EuroSCORE (p=0.003) were predictors of late mortality of any
cause. These scores remained significant predictors of late outcome, even when
adjusted for type of surgery (mitral valve repair vs. replacement). Figures 21 and
22 shows the Kaplan-Meier estimates according to different quintiles of additive
and logistic EuroSCOREs among operative survivors. Survival was particularly
dismal in patients with an additive EuroSCORE of more than or equal to 6 (at 10
years, 54.4% vs. 86.6%, p<0.00001) or a logistic EuroSCORE of more than or
equal to 4% (at 10 years, 58.7% vs. 86.6%, p<0.00001).
71
Patients at risk
MV repair
MV replacement
131
31
127
25
85
20
54
9
28
6
6
2
Fig. 20. Overall long-term outcome of operative survivors after mitral valve repair
compared with mitral valve replacement.
Additive
EuroSCORE
2
5
3-4
8-16
6-7
Fig. 21. Kaplan-Meier estimate of overall long-term survival after surgery for mitral
valve regurgitation according to different additive EuroSCORE quintiles among
operative survivors (p<0.0001).
72
Logistic
EuroSCORE
1.5%
2.8-3.9%
1.6-2.7%
4.0-8.0%
8.1-55.3%
Fig. 22. Kaplan-Meier estimate of overall long-term survival after surgery for mitral
valve regurgitation according to different logistic EuroSCORE quintiles among
operative survivors (p<0.0001).
73
74
6
Discussion
6.1
Predictors of postoperative mortality after mitral valve repair
Mitral valve repair has been established as the method of choice in the treatment of
mitral valve regurgitation. Apart from the satisfactory long-term results, some
authors have reported markedly lower immediate postoperative mortality in
patients undergoing repair as compared with replacement (Gillinov et al. 2003,
Grossi et al. 2001, Reece et al. 2004, Yau et al. 2000, Muehrcke et al. 1997,
Roques et al. 2001). Such lower immediate mortality rates are, however, often
likely to be due to selection bias (Gillinov et al. 2003, Grossi et al. 2001, Yau et al.
2000) as was confirmed in study IV. We can therefore conclude that when
technically feasible, mitral valve repair is associated with a favourable operative
outcome. The present studies represent an attempt to identify those risk factors
associated with poor immediate outcome. The small size of this series and the
rather broad heterogeneity of this patient population made the analysis somewhat
complex, but the results are sound and reflect the current knowledge of risk factors
in heart valve surgery (Roques et al. 2001).
Repeat cardiac procedure is a well known risk factor in cardiac surgery. In our
experience this condition was invariably lethal in the mitral valve repair patients
older than 65 with a history of previous cardiac surgery. This observation calls for
possible contraindication to mitral valve repair in patients with both these risk
factors. Some recent studies (Bolotin et al. 2004, Burfeind et al. 2002, Byrne et al.
2001, Omnasch et al. 2002, Schroeyers et al. 2001), however, have shown that
patients undergoing mitral valve surgery in the setting of prior cardiac surgery can
benefit from avoiding a repeat median sternotomy. Right thoracotomy, videoassisted minithoracotomy or port-access surgery have been shown to be feasible in
this setting and operative mortality rates range from nil to 5.7%. These results are
remarkably better than our operative mortality after mitral valve repair in a prior
cardiac surgery setting (36.4%). This approach is not feasible, however, in patients
requiring concomitant procedures other than those involving the atrioventricular
valves. Among patients who died postoperatively, were older than 65 and had a
history of prior cardiac surgery, only one patient who in the present series
underwent mitral valve repair and tricuspid valve annuloplasty would have
potentially benefited from such minimally invasive approaches. Study I showed
that in about half of patients undergoing mitral valve repair, concomitant
procedures are required, the latter having been associated with a relevant increase
75
of mortality. In those patients not requiring any associated procedure, mortality is
very low. This condition was not shown, however, to be an independent predictor
of adverse outcome.
6.2
Long-term outcome of mitral valve repair
Study II confirmed that mitral valve repair for regurgitation is associated with a
favourable long-term outcome and a low risk of late reoperation, which is similar
to previously reported figures (Braunberger et al. 2001, Gillinov et al. 1998;
Mohty et al. 2001). A number of variables have been found to be associated with a
less satisfactory outcome, however, while a history of prior cardiac surgery was
the only independent predictor of cardiac death.
Residual regurgitation at intraoperative echocardiography has been identified
as an important factor associated with a significantly increased risk of reoperation
(Mohty et al. 2001). In the present study, a residual regurgitation larger than grade
1 was an independent predictor of late redo mitral valve surgery, and it can
therefore be considered an important measure of technical success beyond the
progressive nature of mitral valve disease.
This study showed a strong association between chronic obstructive
pulmonary disease/asthma and the risk of redo mitral valve surgery. Although this
may be coincidental, chronic obstructive pulmonary disease is frequently
associated with the development of degenerative vascular disease such as
aneurysms and pseudoaneuysms (Sakamaki et al. 2002; Ylönen et al. 2004). This
suggests that chronic obstructive pulmonary disease and degenerative mitral valve
disease may represent the results of an underlying connective tissue metabolic
disorder. This risk factor has not been considered in previous studies and deserves
further evaluation as it may be also a marker of accelerated progression of
degenerative mitral valve disease.
Long-term echocardiographic findings confirm the other clinical end-points,
but the lack of serial echocardiographic evaluation involving all of these patients
prevents any definitive conclusion as to whether mitral valve repair is effective
and durable in patients who died before any possible need for mitral valve
reoperation. In fact, it is possible that a few patients in this study deteriorated
before an adequate cardiologic evaluation was performed. A recent study by
Flameng and colleagues (Flameng et al. 2003) reminds us that continuous
echocardiographic follow-up may disclose much poorer results than that depicted
by late cardiac death or the need for repeat mitral valve surgery. These
76
observations suggest that, despite excellent clinical results, a number of patients
experience significant mitral valve incompetence after mitral valve surgery, but do
not undergo redo mitral valve surgery. In order to better identify the risk factors
associated with late failure after mitral valve repair, it would therefore be more
appropriate to evaluate actuarial estimates of echocardiographically verified
recurrent severe mitral valve regurgitation. This follow-up method is not feasible,
however, either in our hospital district or in many others due to a lack of resources.
6.3
Quality of life after mitral valve repair
The survey showed that long-term survivors of a major surgical procedure such as
mitral valve repair can experience a good quality of life which in, overall terms, is
similar to that of the general population. Thus, the well-demonstrated durability of
mitral valve repair is associated with improvement/preservation of the patient’s
physical and psychological conditions. This finding is of particular relevance as
this patient population is likely to be in rather poor general condition and to have a
variety of comorbidities. In fact, the long-term survival of these patients is much
lower than would be expected in an age- and gender-adjusted general population.
Nonetheless, it is possible that any small improvement in terms of physical and
psychological conditions following mitral valve repair is perceived by the patient
as a major, positive change in their quality of life. This is suggested by
significantly higher mental health and pain scores, despite a significantly lower
physical role limitation score among these patients. Indeed, there is evidence that
such a good quality of life is experienced by only some of the patients undergoing
mitral valve repair due to considerable immediate and late cardiac-related
mortality. Furthermore, the wide range of scores in the RAND-36 Health Survey
variables suggests that any beneficial effect of mitral valve repair on the patient’s
physical and psychological conditions is not shared equally by these patients.
The present results might have been biased by the retrospective nature of this
study and by the quite high number of non-responders.. Although the proportion of
non-responders was relatively high (16.1%), this group of patients was rather
young at the time of operation and survived long after surgery. Nonetheless, these
observations suggest that they are likely to be alive and in good condition.
77
6.4
Predicting the immediate and late outcome after surgery for
mitral valve regurgitation using the EuroSCORE
Study IV showed that The EuroSCORE can act as an important tool in predicting
both the immediate and late outcome after mitral valve surgery. This observation
confirms the validity of the EuroSCORE and previous observations as to its value
in predicting late outcome after isolated coronary artery bypass surgery as well as
adult heart valve surgery. To the best of our knowledge, however, this is the first
series dealing exclusively with patients who have undergone surgery for mitral
valve regurgitation. This finding has major relevance as this risk scoring method is
simple and, nowadays, used widely, thus making it an optimal tool for risk
stratification and a valid means for a comparison of results.
From the clinical point of view, it is worth noting that an additive EuroSCORE
of more than or equal to 9 was associated in our experience with a prohibitive
operative risk which, along with the observed poor late survival in operative
survivors within the subgroup of patients with an additive EuroSCORE of more
than or equal to 6, clearly distinguishes high-risk patients from low-risk patients.
This provides a good estimate of operative risk and life expectancy after mitral
valve surgery which can also be useful in the decision-making process.
Furthemore, according to the present findings, mitral valve replacement is
associated with rather poor immediate postoperative and late survival as compared
with mitral valve repair.
These considerations should be viewed along with the limitations of the small
size of the present series. However, these findings seem to indicate that, nowadays,
mitral valve replacement is only indicated in patients with mitral valve
regurgitation not amenable for repair and that their operative risk is significantly
higher than those in whom valve repair is technically feasible. Thus, in this study,
the EuroSCORE indicated that the results of mitral valve repair are not comparable
to those of mitral valve replacement, and further comparative analyses between
these two procedures may benefit from including this risk scoring method.
Finally, the present results indicate that prompt referral for mitral valve
surgery can be of utmost benefit for these patients as conservative management
may, in some case, dramatically increase the operative risk as well as shorten their
life-expectancy. This is especially true in the case of patients who underwent
mitral valve replacement in whom the prevalence of critical preoperative state and
raised pulmonary artery pressure along with grade 4 mitral valve regurgitation
were extremely high.
78
7
Conclusions
1.
Multivariable analysis identified that advanced age, NYHA functional classes
and history of prior cardiac surgery were independent predictors of 30-day
postoperative death. In patients older than 65 years and with prior cardiac
surgery, operative risk is very high.
2.
Mitral valve repair has an excellent clinical long-term outcome. An adequate
repair technique is advocated with every attempt to decrease the immediate
postoperative rate of residual regurgitation to less than 1, as this is the main
determinant of freedom from redo mitral valve surgery.
3.
The quality of life of long-term survivors after mitral valve repair, as assessed
by the RAND-36 Health Survey, is similar to that of an age- and genderadjusted general Finnish population.
4.
The EuroSCORE is an accurate and useful predictor of immediate
postoperative outcome and late survival of patients after surgery for mitral
valve regurgitation.
79
80
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Original publications
This thesis is based on the following articles, which are referred to in the text by
their Roman numerals:
I
Heikkinen J, Biancari F, Satta J, Salmela E, Juvonen T & Lepojärvi M (2005)
Predictors of postoperative mortality after mitral valve repair: Analysis of a
series of 164 patients. Scand Cardiovasc J 39: 71–77.
II
Heikkinen J, Biancari F, Uusimaa P, Satta J, Juvonen J, Ylitalo K, Niemelä M,
Salmela E, Juvonen T & Lepojärvi M (2005) Long-term outcome after mitral
valve repair. Scand Cardiovasc J 39: 229–236.
III Heikkinen J, Biancari F, Satta J, Salmela S, Juvonen T & Lepojärvi M (2005)
Quality of life after mitral valve repair. J Heart Valve Dis 14: 722–726.
IV Heikkinen J, Biancari F, Satta J, Salmela E, Mosorin M, Juvonen T &
Lepojärvi M (2007) Predicting the immediate and late outcome after surgery
for mitral valve regurgitation with EuroSCORE. J Heart Valve Dis 16: 116–
121.
Reprinted with permission from Taylor and Francis (I, II) and ICR publisher Ltd.
(III, IV).
Original publications are not included in the electronic version of the dissertation
89
90
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ACTA UNIVERSITATIS OULUENSIS
SERIES D MEDICA
945.
Tiainen, Johanna (2007) Bioresorbable plain and ciprofloxacin-releasing selfreinforced PLGA 80/20 implants' suitability for craniofacial surgery. Histological
and mechanical assessment
946.
Aaltonen, Vesa (2007) PKC and neurofibromin in the molecular pathology of
urinary bladder carcinoma. The effect of PKC inhibitors on carcinoma cell
junctions, movement and death
947.
Kuvaja, Paula (2007) The prognostic role of matrix metalloproteinases MMP-2
and -9 and their tissue inhibitors TIMP-1 and -2 in primary breast carcinoma
948.
Siira, Virva (2007) Vulnerability signs of mental disorders in adoptees with genetic
liability to schizophrenia and their controls measured with Minnesota Multiphasic
Personality Inventory
949.
Komulainen, Silja (2007) Effect of antihypertensive drugs on blood pressure
during exposure to cold. Experimental study in normotensive and hypertensive
subjects
950.
Anttonen, Vuokko (2007) Laser fluorescence in detecting and monitoring the
progression of occlusal dental caries lesions and for screening persons with
unfavourable dietary habits
951.
Torppa, Kaarina (2007) Managerialismi suomalaisen julkisen erikoissairaanhoidon
johtamisessa. Tutkimus yksityissektorin johtamisoppien soveltamisesta neljässä
yliopistollisessa sairaanhoitopiirissä ja arvio managerialismin soveltuvuudesta
julkisen erikoissairaanhoidon uudistamiseen
952.
Hokkanen, Eero (2007) Neurologian kehitysvaiheita Oulussa ja Pohjois-Suomessa
953.
Lahtinen, Jarmo (2007) Predictors of immediate outcome after coronary artery
bypass surgery
954.
Železnik, Danica (2007) Self-care of the home-dwelling elderly people living in
Slovenia
955.
Löfgren, Eeva (2007) Effects of epilepsy and antiepileptic medication on
reproductive function
956.
Jäälinoja, Juha (2007) The structure and function of normal and mutated collagen
IX
957.
Fonsén, Päivi (2007) Prolyl hydroxylases. Cloning and characterization of novel
human and plant prolyl 4-hydroxylases, and three human prolyl 3-hydroxylases
958.
Heikkinen, Jouni (2008) Outcome after mitral valve surgery for mitral valve
regurgitation
Book orders:
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inen
OULU 2008
UNIVERSITY OF OULU P.O. Box 7500 FI-90014 UNIVERSITY OF OULU FINLAND
A C TA
U N I V E R S I TAT I S
S E R I E S
A
B
C
D
E
F
G
E D I T O R S
SCIENTIAE RERUM NATURALIUM
Professor Mikko Siponen
HUMANIORA
TECHNICA
Professor Harri Mantila
Professor Juha Kostamovaara
MEDICA
O U L U E N S I S
D 958
ACTA
Jouni Heikkinen
OUTCOME AFTER
MITRAL VALVE SURGERY
FOR MITRAL VALVE
REGURGITATION
Professor Olli Vuolteenaho
SCIENTIAE RERUM SOCIALIUM
Senior Assistant Timo Latomaa
SCRIPTA ACADEMICA
Communications Officer Elna Stjerna
OECONOMICA
Senior Lecturer Seppo Eriksson
EDITOR IN CHIEF
Professor Olli Vuolteenaho
EDITORIAL SECRETARY
Publications Editor Kirsti Nurkkala
ISBN 978-951-42-8680-3 (Paperback)
ISBN 978-951-42-8681-0 (PDF)
ISSN 0355-3221 (Print)
ISSN 1796-2234 (Online)
U N I V E R S I T AT I S O U L U E N S I S
FACULTY OF MEDICINE,
DEPARTMENT OF SURGERY,
DEPARTMENT OF INTERNAL MEDICINE,
UNIVERSITY OF OULU
D
MEDICA