Titel
Barlow´s mitral valve disease: a comparison of neochordal (loops) and edge-to-edge (Alfieri)
minimally invasive repair techniques
Dissertation
zur Erlangung des akademischen Grades
Dr. med. / Dr. med. dent. /Dr. rer. med.
an der Medizinischen Fakultät
der Universität Leipzig
eingereicht von: Jaqueline Grace da Rocha e Silva
(akademischer Grad / Vorname / Name / Geburtsname)
Geburtsdatum / Geburtsort 06.11.1982 / Brasilien
angefertigt an / in: Universität Leipzig
(Hochschule / Einrichtung)
Betreuer: Prof. Dr. med. Sandra Eifert
Beschluss über die Verleihung des Doktorgrades vom: 15.12.2015
Inhaltverzeichnis
1
1. Titelblattes .................................................................................................1
2. Bibliographische Beschreibung..................................................................3
3. Einführung..................................................................................................4
4. Publikationsmanuskript.............................................................................11
5. Zusammenfassung...................................................................................26
6. References...............................................................................................29
7. Selbstäandigkeitserklärung......................................................................34
8. Lebenslauf................................................................................................35
9. Danksagung.............................................................................................38
Bibliographische Beschreibung
Name, Vorname
2
da Rocha e Silva, Jaqueline Grace
Titel der Arbeit
Barlow's mitral valve disease: a comparison of neochordal (Loop) and edge-to-edge
(Alfieri) minimally invasive repair techniques
Universität Leipzig, Dissertation
38 S.1, 43 Lit.2, 2 Abb., 6 Tab
Referat:
Minimally invasive MV repair can be performed with very good early and medium-term
outcomes in Barlow's patients. Edge-to-edge repair is associated with shorter myocardial
ischemic and operative times when compared with neochordae (Loop) implantation. Both
techniques are effective with regards to medium-term freedom from MR and reoperation,
although edge-to-edge repair results in mildly elevated transvalvular gradients. Longer term
follow up is required in order to determine if observed valvular performance remains stable
over time.
Einführung
Degenerative mitral valve (MV) disease is the most prevalent cause of mitral
regurgitation (MR) and the second most common valve-related indication for cardiac surgery
3
in developed countries. Degenerative MV disease encompasses a spectrum of lesions
ranging from fibroelastic deficiency to Barlow´s disease based on clinical patterns,
echocardiographic findings, and morphologic features. The pathological spectrum of
myxomatous degeneration is broad, and it ranges from mild changes in the central portion of
the posterior leaflet to generalized involvement of the entire MV apparatus resulting in
voluminous and thickened leaflets and chordae tendineae, and sometimes calcification of the
annulus and even of the myocardium and papillary muscles.
1,2
Myxomatous changes tend to
be more severe in the medial half than in the lateral half of the MV. Another type of
degenerative disease of the MV is the so called fibroelastic deficiency, first described by
3
Alain Carpentier, whereby the leaflets remain thin and transparent, and the chordae
tendineae become attenuate and may rupture, causing leaflet prolapse and MR. Dystrophic
calcification of the mitral annulus is also included in the group of degenerative diseases.
2
Degenerative disease represent 60-70% of major causes of surgical mitral regurgitation
in western countries.4
Several confusing terminologies (eg. myxomatous valve disease, mitral valve prolapse,
floppy valve, flail leaflet) have been used in the literature to describe degenerative mitral
valve disease. Trying to clarify this subject Alain Carpentier described the essential
differences between prolapse and billowing of mitral valve. He revolutionized mitral valve
disease understanding proposing the “functional approach”, where he urges surgeons to
change their focus from lesions and concentrate on the function of mitral valve apparatus.
The valve analysis determines whether leaflet motion is normal (Type I), excessive (Type II)
or restricted (Type III). Using this concept Barlow´s disease will be classified as Carpentier´s
Type II dysfunction. He also helped to elucidate the surgical characterization of what is now
known as Barlow´s disease.3
Barlow and colleagues were the first able to shown that the auscultatory features of an
apical late systolic murmur and non-ejection systolic click were originated of a mitral valve.
They were also responsible to recognize a specific syndrome correlating symptoms, clinical
signs and other features associated with this mitral valve anomaly.5,6
The syndrome was later corrected interpreted by Criley as result of a mitral valve
prolapse; term that was introduced by him in 1966 based on the cineangiographic
appearances of the valve 7. First in 1960 this mitral valve disorder was identified as
degenerative in etiology and macroscopic described.8 The appearance of 2-dimensional
echocardiography would some years later allow Barlow and Pocock to described the
4
billowing mitral leaflet syndrome and it would be posteriorly referred as Barlow´s disease.9
Barlow's disease is characterized by excess myxomatous leaflet tissue as result of
extensive myxoid degeneration with destruction of the normal three layer leaflet tissue
architecture.10 Barlow's patients also exhibit annular dilation, thickened leaflets, chordal
elongation, and leaflet billowing and prolapse that is multisegmental and often bileaflet in
distribution. Calcification of the annulus and subvalvular apparatus may also be present in
advanced cases.2,3
The extreme large areas of the mitral leaflets cause them during systole to work like
sails projecting horizontally inside left atria which is complicated by leaflet hypermobility
associated with the frequently finding of mitral annular disjunction in this patients. This will
lead to loss of leaflet apposition during systole and results in the classical late systolic mitral
regurgitation commonly seen in this disease. Furthermore loss of mitral annular reduction
during cardiac cycle leads to marked increase in systolic stress particularly at the chordae
tendinea what will probably enhance the pathologic findings of the disease. Besides mitral
papillary muscle traction due to excessive systolic loading on the chordae and loss of
diastolic locking (the progressive leaflet apposition caused by annular reduction) will
altogether favor the prolapse observed in Barlow´s MV.11,12
Barlow´s disease appears early in life, and patients typically have a long history of a
systolic murmur. Most patients who require surgery for MR are referred for surgery in their
fourth or fifth decades of life after development of symptoms or signs such as atrial fibrillation,
shortness of breath and fatigue, or echocardiographic documentation of ventricular or atrial
enlargement, or a decline in ventricular function, often accompanied by a varying degrees of
pulmonary hypertension.13
Echocardiography is a sensitive tool for preoperative diagnosis and differentiation of
degenerative MV disease. Barlow´s disease presented with a billowing valve with typically
thick leaflets and with marked excess tissue. The chordae are thickened and elongated, and
may be ruptured. Papillary muscles are also occasionally elongated. The annulus is dilated
and enlarged, often times greater then 36mm in the intercomissural distance and sometimes
calcified. Most Barlow’s valves present with the prolapse of multiple segments of the valve. Is
also frequently associated with disjunction of the mitral annulus fibrosus. The resultant atrial
displacement of the mitral leaflet attachment may lead to leaflet hypermobility and
subsequent excessive mucoid degeneration.In the other hand, fibroelastic disease is
associated with a fibrillin deficiency which often leads to a rupture of one or more thinned and
5
elongated chordae, usually involving the middle scallop of the posterior leaflet so called P2
prolapse. Valve analysis typically shows transparent leaflets with no excess tissue except the
prolapsing segment, and elongated, thin, frail, and often ruptured chordae. The annulus is
often dilated and may be calcified. Patients are normally older than in Barlow´s disease with
a relatively short history of mitral regurgitation and have a holosystolic murmur at
auscultation.14 Real time three-dimension echocardiography has brought additional
knowledge in identify and localize billowing and prolapse segments helping to differenciate
this valves and to identify underlying lesions that result in mitral valve dysfunction 15,16,17,
however a clear distinction between Barlow´s and fibroelastic deficiency is still not possible in
up to 20% of patients, how described from Carpentier´s group. They were the first to
recognize that even when surgical and histological findings are taken in consideration there
are valves that can´t be classified in one of this 2 groups. Etiologies unclassifiable into either
group include systemic connective tissue disorders, forms frustes of Barlow´s disease, senile
degeneration, dystrophic calcification and idiopathic degeneration. 10
MV repair has been well established as the gold standard for treatment of severe MR in
patients with degenerative MV disease.18,19 Besides obviating the need for anticoagulation
and decreasing the risk of endocarditis, MV repair allows preservation of left ventricular
function by maintaining the integrity of the subvalvular apparatus. As the procedure of choice,
surgical repair of MV prolapse requires a clear understanding of the relationship between the
etiology of DMVD, the anatomic and functional features related to the etiology, and,
importantly, the short- and long-term impact of any alterations on the MV anatomy.
13
The
success and planning of surgical correction rests on accurate MV anatomic assessment and
the detection of those lesions that may predict unsuccessful repair, such as extensive
bileaflet disease or anterior leaflet pathology.
20
The etilogy of degenerative mitral valve
disease will influence the complexity and number of repair techniques required to achieve a
sucessful mitral valve repair. In fibroelastic deficiency, there is most commonly a single lesion
resulting in a single segment prolapse, usually the P2 segment of the posterior leaflet. Since
this is the only abnormal segment sorrounded of normal tissue, repair in this valves will be
achieved with one technique that is generally straightfoward and with a high rate of sucess.
On the other hand, Barlow´s disease often presents several leasions coexisting in multiple
segments of the same valve. The surgical repair approach will need to adress all lesions
often requiring advanced repair techniques such as extensive leaflet resection, leaflet
detachment from the annulus, sliding-plasty to lower the height of remaining posterior leaflet
segments, multiple chordal transfers or multiple artificial chordae, and large annuloplasty
6
rings. Another issue of this valves is the risk of systolic anterior motion (SAM) after repair.
SAM is defined as displacement of the distal portion of the anterior leaflet of the mitral valve
toward the LVOT during systole. The primary lesion resulting in SAM after MV repair is a
mismatch between the mitral valve annular dimension and the amount of leaflet tissue
present. Different mechanisms have been described to result in SAM but the two most
importants are known as „drag effect“ and „venturi effect“ . As the left ventricle contracts and
ejects blood through the aorta it creates a drag on redundant anterior leaflet tissue, drawing
the tip of the anterior leaflet into the outflow. This creates a turbulent flow that will result in
venturi effect on the anterior leaflet and the consequent mitral regurgitation.Varghese et al.
propose an algorithm to manage SAM intraoperatively and postoperatively. They stress the
importance of a technically adequate repair ensuring a posterior leaflet heigh of less than
15mm and a posterior displaced closure line. Avoid an undersized annuloplasty ring is also
refereed as a key element to minimize the incidence of SAM. Considering that one of the
features of Barlow´s disease is the excess of tissue with extrem large areas of mitral valve
leaflets we understand the increased risk of SAM after mitral valve repair in this patients. 21
Yearly mortality rates with medical treatment in patients aged 50 years or older are
about 3% for moderate organic regurgitation and surgery is the only treatment proven to
improve symptoms and prevent heart failure in this patients. Furthermore in severe organic
mitral regurgitation valve repair improves outcome compared with valve replacement and
reduces mortality by about 70% 4. However, patients presenting with Barlow´s disease
represent the most severe form of myxomatous degeneration and the largest challenge for
cardiac surgeons, because of the extent of tissue involvement and frequent lack of normal
tissue to serve as a point of reference during the repair. Several different strategies are
therefore frequently required in order to achieve a satisfactory surgical result in these
patients.
Moreover Barlow´s disease is more commonly observed in young and otherwise
healthy patients, and can be completely asymtomaptic at the time of presentation. In our
series, 34% of patients were classified as NYHA I at the time of surgery. Similarly, Newcomb
et al. observed that one quarter of patients were asymptomatic in a large series of Barlow's
patients.22 With an increasing trend towards early MV surgery in asymptomatic patients with
severe MR, more consistent and reproducible approaches to achieving a succesful MV repair
procedure may be required, particularly in Barlow's patients.
7
Many surgical techniques have been described to enable MV repair in these
challenging patients.23,24 Most of the resectional techniques described for Barlow´s and
bileaflet MV repair are well established and carry very good long-term results. One of the
most traditional and well known of such techniques incorporates a complet resection of the
middle scallop of the posterior mitral leaflet (PML) followed by a sliding or a folding plasty
with the remaining lateral scallops. It might be supplemented furthermore with either a
triangular resection of the anterior leaflet (AML) especially in the cases with a long localized
AML or a correction of the AML prolapse with polytetrafluoroethylene (PTFE) chordae or
loops.18,25-26 Secondary MV lesions, such as leaflets clefts and minor comissural prolapses,
become apparent upon the water-sealing test. In such instances, the clefts are directly closed
with Prolene or Cardionyl 5-0 sutures and the residual comissural prolapse can be corrected
either by insertion of more artificial chords or by insertion of a vertical mattress stitch (also
known as „magical stitch“). When encountered, calcifications of the annulus should be
removed as proposed by Carpentier.27Although such resectional techniques are well
established, they can be technically challeging to perform through a minimal invasive
surgery(MIS) approach.
Perrier´s group first coined the term „respect rather tahn resect“ to describe an
alternative to traditional resection techniques28.The goal of this approach is to correct MV
prolapse without excision of leaflet tissue. This can be achieved for the PML with the use of
PTFE chordae or Loops, with adjustment of their lenght so that the PML remains nearly
vertical, posterior and parallel to the posterior wall of the left ventricle in the inflow region. The
correct length of the Gore-Tex loops is determined by measuring the distance from the tip of
the corresponding papillary muscle to the free margin of a nonprolapsing segment in the
targeted leaflet, or to the desired height of systolic leaflet motion in patients with diffuse
prolapse and no normal reference tissue. This transforms the PML into a smooth, regular
and vertical buttress against which the AML will come into apposition.The use of PTFE
neochordae has also been described for correction of AML prolapse, with the Loop technique
being particularly valuable for MIS surgery.The Loops to the AML are approximately 10mm
longer than those applied to the PML because of the increase AML mobility that is required to
achieve MV competence. One can envision the AML acting like a „door“ and the PML as
„doorframe“ for the „respect“ methods.
Another proposed approach to correct this challenging valve anomaly is the edge-toedge technique. This surgical repair proposed from the italian group headed by Alfieri was
first performed in 1991 to successfully treat a patient with anterior leaflet prolapse. Because
8
mid- term results suggested safety, effectiveness and durability this group adopted the
procedure as routine to treat mitral valve repair. The most common indications were anterior
mitral leaflet prolapse, bileaflet prolapse, and functional mitral regurgitation. 29 The edge-toedge technique also showed to be a rapid and effective option to correct suboptimal result of
„conventional“ MV repair.30 The surgical technique consists in a continuous suture of the free
edge of the leaflets at the site of the regurgitation and creates frequently a double orifice
valve. The main concern of this technique was the risk of creating stenosis. Many
experimental models addressed the hemodynamics and structural effects of this technique
suggesting that hemodynamics are not affected by the double orifice configurations, even in
case of asymmetric position of the double orifice suture.31,32 Also clinical studies showed that
the procedure does not impair valve diastolic function either at rest or under exercise and
preservation of physiological behaviour of the valve with normal response to exercise
echocardiography.33,34
Many different techniques habe been employed in order to treat Barlow´s mitral valve
disease. Lawrie et al. described sucessful repair through a nonresectional approach in 61
patients with Barlow´s disease. They described a surgical approach that does not involve
leaflet resection but through precise dynamic annular sizing, a predetermined zone of leaflet
apposition is achieved. They founded that with this technique leaflets are apposioned so that
their large area would be contained within the left ventricle. They didn´t have any
perioperative mortality and there was no systolic anterior motion with this technique.They
achieved more than 90% freedom from MR >= 3+ rate at 10 years and 90% freedom from
reoperation.35Newcomb et al. showed excellent early and long-term results by relocating the
posterior mitral annulus and correcting prolapse via neochordae with or without leaflet
resection in 183 Barlow's patients. They achieved a 10-year freedom from reoperation rate of
93% and freedom from moderate or more MR rate of 80%.22 Maisano et al. used the edge-toedge technique and accomplished very good medium-term outcomes in 82 patients with
Barlow's disease, with a freedom from reoperation rate of 86% at 5 years.(36) This group
also examined their very long-term results for edge-to-edge MV repair in 128 patients with
bileaflet prolapse.37 They found excellent results in these patients with a freedom from
moderate or more MR rate of 86% and a freedom from reoperation rate of 90% at 12 years
postoperatively. Castillo et al. described the use of differents techniques such as Loop
neochordae, chordal transfer and posterior leaflet flip in 188 patients with anterior and
bileaflet prolapse, including 110 Barlow´s patients. They reported a 7-year freedom from
moderate or more MR rate of 92% for bileaflet prolapse and 94% freedom from reoperation. 38
9
Despite the very good results from the above studies, the optimal MV repair technique
for Barlow's patients is still unknown. In addition, it is unknown whether the surgical approach
(i.e. full sternotomy versus mini-thoracotomy) affects outcomes achieved in such patients. In
order to address these issues, we compared outcomes for our two most commonly used MV
repair techniques -- i.e. Loop neochordae versus edge-to-edge repair -- in 112 consecutive
Barlow's patients undergoing minimal invasive MV surgery.
Publikationsmanuskript
10
Barlow's mitral valve disease: a comparison of neochordal (Loop) and edge-to-edge
(Alfieri) minimally invasive repair techniques
Rocha e Silva,J ; Spampinato,R; Misfeld,M; Seeburger,J ; Pfanmüller,B ; Eifert ,S. ;
Mohr,F.W. ; Borger,M.A.
Department of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany
and Division of Cardiac, Thoracic and Vascular Surgery, Columbia University Medical
Center, New York, USA
Presented at the 2014 Society of Thoracic Surgeons 51st Annual Meeting in San Diego,
California
Key words: mitral valve repair, Barlow’s disease, minimal invasive, outcomes
Word Count: 4.423
Address for correspondence:
Michael A. Borger, MD, PhD
Division of Cardiac, Thoracic, and Vascular Surgery
Columbia University Medical Center
177 Fort Washington Ave, Milstein 7GN-435
New York, NY 10032
Telephone: 212 305-4980
Fax: 212-305-2439
Email: mb3851@cumc.columbia.edu
11
Objectives: Barlow ́s mitral valve (MV) disease remains a surgical challenge. We compared shortand medium-term outcomes of neochordal ("Loop") vs edge-to-edge ("Alfieri") minimally invasive MV
repair in Barlow's patients.
Methods: From January 2009 to April 2014, 123 consecutive patients with Barlow ́s disease (defined
as bileaflet billowing and/or prolapse, excessive leaflet tissue and annular dilation with or without
calcification) underwent minimally invasive MV surgery for severe regurgitation (MR) at our institution.
Three patients (2.4%) underwent MV replacement during the study time period and were excluded
from subsequent analysis. The Loop MV repair technique was used in 68 patients (55.3%) and an
edge-to-edge repair in 44 patients (35.8%). Patients who underwent a combination of these two
techniques (n=8, 6.5%) were excluded. The median age was 48 years and 62.5% were male.
Concomitant procedures comprised of closure of a patent foramen ovale or atrial septal defect (n=
19), tricuspid valve repair (n= 5), and atrial fibrillation ablation (n= 15). Follow up was performed 24.7±
17 months postoperatively and was 98% complete.
Results: No deaths occurred perioperatively or during follow up. Aortic crossclamp (64.1 ± 17.6 vs
95.9 ± 29.5 min) and cardiopulmonary bypass times (110.0 ± 24.2 vs 146.4 ± 39.1min) were
significantly shorter (p < 0.001) in patients that received edge-to-edge repair. Although edge-to-edge
patients received a larger annuloplasty ring (38.6 ± 1.5 vs 35.8 ± 2.7 mm, p <0.001), the early
postoperative mean gradients were higher (3.3 ± 1.2 vs 2.6 ± 1.2 mmHg; p=0.007) and the mitral
orifice area tended to be smaller in this group (2.8 ± 0.7 vs 3.0 ± 0.7 cm2; p=0.06). The amount of
residual MR was similar between groups (0.3 ± 0.6 vs 0.6 ± 1.0 for edge-to-edge vs loops,
respectively ; p=0.08). More than mild MR requiring early MV reoperation was present in 3 Loop
patients (4.4%) and no edge-to-edge patients (p = 0.51). During follow up, 2 patients (1 in each
group) required MV replacement for severe MR. The 4-year freedom from MV reoperation was 92.8 ±
5.0% in the Alfieri group compared to 90.9 ± 4.6% in the Loop group (p = 0.94).
Conclusion: Minimally invasive MV repair can be accomplished with excellent early- and mediumterm outcomes in patients with Barlow’s disease. The edge-to-edge (Alfieri) repair can be performed
with reduced operative times when compared to the Loop technique, but results in mildly increased
transvalvular gradients and mildly decreased valve opening areas without any difference in residual
MR.
12
Introduction:
Degenerative mitral valve (MV) disease is the most prevalent cause of mitral regurgitation (MR) and
the second most common valve-related indication for cardiac surgery in developed countries.
Degenerative MV disease encompasses a spectrum of lesions ranging from fibroelastic deficiency to
Barlow´s disease based on clinical patterns, echocardiographic findings, and morphologic
features.(1,2) Barlow's disease is characterized by excess myxomatous leaflet tissue, bileaflet
prolapse or billowing, chordae elongation, and annular dilatation with or without calcification.
Extensive myxoid degeneration with destruction of the normal three-layer leaflet tissue architecture is
observed histologically in such patients.(3)
MV repair has been well established as the gold standard for treatment of severe MR in patients with
degenerative MV disease.(4,5) Barlow´s disease remains a surgical challenge, however, because of
the extent of tissue involvement and frequent lack of normal tissue to serve as a point of reference
during the repair. Several different strategies are therefore frequently required in order to achieve a
satisfactory surgical result in these patients. We have frequently performed MV repair using
neochordal formation with Gore-Tex (W.L. Gore, Flagstaff, AZ) loops (i.e. "Loop technique").(6,7) The
edge-to-edge (i.e. "Alfieri") technique has also been suggested as an effective method of performing
MV repair in patients with bileaflet prolapse.(8) We therefore compared short- and medium-term
outcomes of these two technique in Barlow's patients undergoing minimal invasive surgery (MIS) MV
repair.
Patients and Methods:
From January 2009 to April 2014, a total of 2050 consecutive patients underwent MIS MV surgery at
Leipzig Heart Center. Of this total, 123 (6.0%) were identified as having Barlow ́s disease. The
diagnosis of Barlow's was based on intraoperative transesophageal echocardiography (TEE)
examination and direct surgical inspection revealing excess leaflet tissue with bileaflet prolapse
and/or billowing, chordae elongation, and annular dilatation with or without calcification. So called
"formes fruste" of Barlow's disease and isolated bileaflets prolapse without excessive leaflet tissue
were not included in this study. Three Barlow's patients (2.4%) underwent MV replacement during the
study period and were excluded from further analysis.
From the remaining 120 patients, 112 underwent either the Loop technique or edge-to-edge (n=44)
MV repair. Patients who underwent other approaches or a combination of these two techniques (n=8,
6.5%) were also excluded. The mean patient age of the remaining patients was 48.3 ± 12.4 years,
and 70 (62.5%) were male. Preoperative patient demographics and echocardiographic MV
characteristics of both patient groups are shown in Tables 1 and 2.
13
MV Repair Technique
All patients underwent MV repair through a right lateral mini-thoracotomy using femoral cannulation
for cardiopulmonary bypass (CPB), as described in detail elsewhere.(9,10) An annuloplasty ring was
inserted in all patients. The annuloplasty ring was sized according to the size of anterior MV leaflet
and the intertrigonal distance. Loop patients underwent neochordae implantation using premeasured
Gore-Tex loops as previously described.(6,7) Concomitant leaflet resection was performed in some
Loop patients in whom the amount of prolapsing tissue was felt to be too large to correct with
neochordae alone. The correct length of the Gore-Tex loops was determined by measuring the
distance from the tip of the corresponding papillary muscle to the free margin of a nonprolapsing
segment in the targeted leaflet, or to the desired height of systolic leaflet motion in patients with
diffuse prolapse and no normal reference tissue.
In the Alfieri group, a generous edge-to-edge stitch that encompassed a large amount of leaflet tissue
was performed in order to reduce the height of both leaflets and lower the coaptation line point to
within the left ventricle. Two 4-0 polypropylene sutures were used to perform the edge-to-edge
repair. These sutures were placed in the area with the most diffusely diseased segments (usually the
middle of both leaflets), and the needles were inserted and removed through the atrial surface of the
leaflet. The insertion point for the anterior leaflet suture was approximately 1 cm from its free edge,
and the posterior suture was exteriorized approximately 1 cm from the posterior annulus. After
completion of the edge-to-edge repair, both valve orifices were probed with Hegar dilators (minimum
18 mm in diameter) in order to ensure an adequate MV opening area.
The decision as to whether to perform a Loop or edge-to-edge repair was at the surgeon's discretion.
However, we performed more Alfieri type repairs over the time period of the study as we gained
increasing confidence with this technique. In addition, some anatomical characteristics made patients
less amenable to edge-to-edge repair. For example, patients with assymetrical involvement of the
MV leaflets or flail segments (unless the flail was located at the planned area of edge-to-edge repair)
were more likely to be treated with the Loop technique.
Intraoperative TEE was performed in all patients to evaluate the presence of residual MR and to
quantify the MV gradient and valve opening area post-MV repair. Circumflex artery flow was also
assessed to rule out iatrogenic injury.(11) In addition, all patients underwent transthoracic
echocardiography prior to hospital discharge.
Follow-up
Clinical follow up was performed 2.4 ± 1.6 years postoperatively and was 98% complete. Patients
were contacted by mail and/or phone and requested to answer a questionnaire on an annual basis.
14
We also requested follow up echocardiography reports from referring or institutional cardiologists,
which were obtained in 96.4% of patients. The degree of MR was classified as grade 0 (absent or
trivial), 1+ (mild), 2+ (moderate), and 3+(severe) according to current guideliness (12,13). The mean
echocardiographic follow up time was 2.3 ±1.6 years.
Statistical Analysis
Statistical analysis was performed using SPSS 19 software (SPSS Inc, Chicago, IL). Continuous
variables are expressed as mean and standard deviation throughout the manuscript. Normally
distributed continuous variables were compared using the Student´s unpaired t test, while the MannWhitney U test or Wilcoxon´s signed-rank test were used for non-normally distributed independent or
related samples, respectively. Categorical variables, expressed as proportions, were compared using
the X2 test or the Fisher exact test as appropriate. New York Heart Association (NYHA) functional
class and grade of MR were treated as ordinal variables and compared with Wilcoxon´s signed-rank
or Mann-Whitney U test. Analysis of medium-term reoperation and survival rates were evaluated
using the Kaplan-Meier estimated model and tested for significance by the log-rank and Wilcoxon
tests. Results are reported using 95% confidence interval. P-value was considered statistically
significant if <0.05.
Results
Baseline patient profile and preoperative echocardiographic data of the 112 study patients are
summarized in Tables 1 and 2. There were no significant differences between the 2 groups in
baseline clinical characteristics. However, echocardiographic analysis showed a significantly larger
measured annulus and greater prevalence of flail leaflet in patients undergoing the Loop technique.
Intraoperative data are listed in Table 3. MV repair via the Loop technique was performed in 68
patients (60.7%) and with an edge-to-edge approach in 44 patients (39.3%). An annuloplasty ring was
inserted in all patients and consisted of a complete rigid ring in all but 2 (both of whom received a
flexible band). The implanted ring size was significantly larger in the edge-to-edge group than in the
Loop group (38.6 ± 1.5 mm versus 35.8 ± 2.7 mm, p<0.001).
Aortic crossclamp (64.1 ± 17.6 vs 95.9 ± 29.5 minutes), CPB (110.0 ± 24.2 vs 146.4 ± 39.1 minutes)
and total operative times (159.9 ± 31.3 vs 204.8 ± 32.0 minutes) were significantly shorter (all p <
0.001) in patients that received an Alfieri repair. There were no differences between groups regarding
concomitant surgical procedures such as atrial fibrillation ablation, tricuspid valve surgery, or closure
of an atrial septum defect or patent foramen ovale.
15
Perioperative complications are listed in Table 4 and included reoperation for bleeding in 6 patients
(5.4%) with no differences between groups (p = 0.6). Overall stroke rate was 1.6% with 2 strokes
occuring in the Loop group. There was no in-hospital mortality in either group. In the Loop group, 2
patients underwent a second CPB run and edge-to-edge rescue repair after intraoperative TEE show
residual grade 2+ MR.
Predischarge transthoracic echocardiography showed good results after MV repair in both groups
with no significant difference in mean grade of residual MR (0.3 ± 0.6 vs 0.6 ± 1.0 for Alfieri vs Loop,
respectively; p = 0.08). The early postoperative mean gradients were higher (3.3 ± 1.2 vs 2.6 ± 1.2
mmHg; p = 0.007) and the MV orifice area was smaller (2.8 ± 0.7 vs 3.0 ± 0.7 cm2; p=0.06) in the
edge-to-edge group (Table 5).
Systolic anterior motion (SAM) of the anterior leaflet was not observed in any patient after either
repair technique.
Mean clinical follow-up time was 2.3 ± 1.6 years: 2.7 ± 1.8 in the Loop group and 1.6 ± 1.2 years in
the edge-to-edge group (p < 0.001). Freedom from MR grade greater than mild, including those
patients who underwent MV reoperation, was 87.3 ± 5.7% in the Loop group and 92.8 ± 5.0% (p =
0.98) in the edge-to-edge group 4 years postoperatively (Fig.2).
Figure 1. Kaplan-Meier curves demonstrating freedom from mitral valve reoperation in patients
that underwent edge-to-edge and Loop repair techniques
Figure 2. Freedom from mitral regurgitation (more than mild) in edge-to-edge versus Loop
technique patients
16
Table 1. Preoperative characteristics of patients who underwent minimally
invasive mitral valve repair for Barlow´s disease
Loop
Alfieri
p Value
(n=68)
(n=44)
49.6±10.9
46.5±14.6
0.46
Age (years)
Male (%)
46 (67.6%)
24 (54.5%)
0.15
EuroSCORE
2.1±0.9
2.5±1.4
0.18
NYHA
I
II
III
IV
0.89
24(35.4%)
24(35.3%)
20 (29.3%)
0
14(31.8%)
20(45.5%)
10(22.6%)
0
9 (20.4%)
0.95
Atrial Fibrillation 23 (33.8%)
EuroSCORE = European System for cardiac Operative Risk Evaluation , NYHA = New
York Heart Association functional classification for congestive heart failure.
Table 2. Preoperative echocardiographic characteristics
Loop
(n=68)
Alfieri
(n=44)
p Value
LVEF (%)
63.7 ±7.5
62.9±4.7
0.51
Annulus diameter
(mm)
46.6 ± 4.6
44.7 ± 4.38
0.03
Flail leaflet n,%
37 (54.4%)
7 (15.9%)
<0.0001
MR grade
2.9 ± 0.29
2.9 ± 0.26
0.68
Central
regurgitation Jet
42 (61.7%)
33 (75.0%)
0.06
Calcification
7 (10.2%)
2 (4.5%)
0.47
LVEF = left ventricular ejection fraction, MR = mitral regurgitation.
17
Table 3. Intraoperative data
Total duration of surgery
(min)
CPB time (min)
Aortic crossclamp time (min)
Complete annuloplasty ring
Partial annuloplasty ring
Mean ring size (mm)
Concomitant procedures
Tricuspid valve repair
Cryoablation
ASD/PFO closure
Loop
(n=68)
204.8 ± 32.0
Alfieri
(n=44)
159.9 ± 31.3
p Value
146.4 ± 39.1
95.9 ± 29.5
66 (97.0%)
2 (3.0%)
35.8 ± 2.7
110.0 ± 24.2
64.1± 17.6
44 (100%)
0
38.6 ± 1.5
<0.0001
<0.0001
0.36
4 (5.8%)
11 (16.1%)
10 (14.7%)
1 (2.27%)
3 (6.8%)
9 (20.4%)
0.38
0.14
0.48
<0.0001
<0.0001
CPB = cardiopulmonary bypass, ASD/PFO = atrial septal defect/patent foramen ovale.
Table 4. Perioperative complications
Rethoracotomy for bleeding
Postoperative atrial
fibrillation
Respiratory failure
CVA
Sepsis
Hospital stay (days)
30-day mortality
Loop
(n=68)
3(4.4%)
5(7.3%)
Alfieri
(n=44)
3(6.8%)
3(6.8%)
P Value
1(1.4%)
2(2.9%)
1(1.4%)
9.9 ± 3.1
0
0
0
0
9.1± 3.0
0
0.32
0.15
0.32
0.19
---
0.6
0.87
CVA = cerebrovascular accident.
18
Table 5. Echocardiographic outcomes
Loop
Alfieri
(n=68)
(n=44)
MR grade
Predischarge
0.6±1.0
0.3±0.6
Long-term
0.1±0.3
0.1±0.3
LVEF (%)
Predischarge
53.6 ± 6.8
52.9 ± 6.3
Mitral orifice area(cm2)
Predischarge
3.0±0.7
2.8±0.7
Pmean,mmHg
Predischarge
2.6±1.2
3.3±1.2
MR = mitral regurgitation, LVEF = left ventricular ejection fraction
p Value
0.08
0.91
0.55
0.06
0.007
Table 6. Details of patients requiring mitral valve reoperation
Reoperations (n) Days after
Cause
Operative
surgery
technique
Early
Loop (3)
17
suture dehiscence at
posterior leaflet
MV Re-Repair
10
ring dehiscence
MV Re-Repair
14
residual prolapse
MV Re-Repair
Alfieri (1)
0
circumflex artery
stenosis
MV Re-Repair
Loop (1)
410
ring dehiscence
MV Replacement
Alfieri (1)
183
chordae rupture
with flail
MV Replacement
Late
19
Discussion
MV repair is the gold standard for treatment of patients with severe MR due to degenerative MV
disease.(12-15) However, patients presenting with Barlow´s disease represent the most severe form
of myxomatous degeneration and the largest challenge for cardiac surgeons. Several different
surgical strategies are frequently required in order to achieve a successful valve repair procedure in
such patients.
The hallmark of Barlow´s disease is excess leaflet tissue as the result of extensive myxoid
degeneration with destruction of the normal three layer leaflet tissue architecture.(3) Barlow's patients
also exhibit annular dilation, thickened leaflets, chordal elongation, and leaflet billowing and prolapse
that is multisegmental and often bileaflet in distribution. Calcification of the annulus and subvalvular
apparatus may also be present in advanced cases.(2)
Echocardiography is a sensitive tool for preoperative diagnosis and differentiation of degenerative MV
disease. However a clear distinction between Barlow´s and fibroelastic deficiency is still not possible
in up to 20% of patients.(3) In the present study, we classified patients as having Barlow´s disease
only if they had bileaflet involvement with diffuse myxomatous changes, while excluding patients with
form fruste variants. The diagnosis was made via intraoperative TEE and confirmed by surgical
inspection of the valve.
Barlow´s disease is more commonly observed in young and otherwise healthy patients, and can be
completely asymtomaptic at the time of presentation. In our series, 34% of patients were classified as
NYHA I at the time of surgery. Similarly, Newcomb et al. observed that one quarter of patients were
asymptomatic in a large series of Barlow's patients.(16) With an increasing trend towards early MV
surgery in asymptomatic patients with severe MR, more consistent and reproducible approaches to
achieving a succesful MV repair procedure may be required, particularly in Barlow's patients.
Many surgical techniques have been described to enable MV repair in these challenging patients.(1718) Lawrie et al. described sucessful repair through a nonresectional approach in 61 patients with
Barlow´s disease with more than 90% freedom from MR >= 3+ rate at 10 years and 90% freedom
from reoperation.(19) Newcomb et al. showed excellent early and long-term results by relocating the
posterior mitral annulus and correcting prolapse via neochordae with or without leaflet resection in
183 Barlow's patients. They achieved a 10-year freedom from reoperation rate of 93% and freedom
from moderate or more MR rate of 80%.(16) Maisano et al. used the edge-to-edge technique and
accomplished very good medium-term outcomes in 82 patients with Barlow's disease, with a freedom
from reoperation rate of 86% at 5 years.(8) This group also examined their very long-term results for
edge-to-edge MV repair in 128 patients with bileaflet prolapse.(20) They found excellent results in
these patients with a freedom from moderate or more MR rate of 86% and a freedom from
reoperation rate of 90% at 12 years postoperatively. Castillo et al. described the use of differents
techniques such as Loop neochordae, chordal transfer and posterior leaflet flip in 188 patients with
20
anterior and bileaflet prolapse, including 110 Barlow´s patients.(21) They reported a 7-year freedom
from moderate or more MR rate of 92% for bileaflet prolapse and 94% freedom from reoperation.(21)
Despite the very good results from the above studies, the optimal MV repair technique for Barlow's
patients is still unknown. In addition, it is unknown whether the surgical approach (i.e. full sternotomy
versus mini-thoracotomy) affects outcomes achieved in such patients. In order to address these
issues, we compared outcomes for our two most commonly used MV repair techniques -- i.e. Loop
neochordae versus edge-to-edge repair -- in 112 consecutive Barlow's patients undergoing minimal
invasive MV surgery.
We have previously described our results of using pre-made Gore-Tex loops in order to correct MV
prolapse through a right lateral mini-thoracotomy approach.(6,7,22). In the current study, 61% of
Barlow's patients were treated with this so-called Loop technique. The current and previous studies
from our group have demonstrated very good early- and medium-term outcomes for the Loop
technique, and we are therefore convinced that it is an effective approach to treat patients with
degenerative disease. However, the Loop technique can be particularly time-consuming in patients
with multisegment disease and may not be generalizable to centers that do not perform large volumes
of MV surgery. The publication of excellent long-term results from Alfieri's group inspired us to start
adopting their technique for patients with bileaflet prolapse. The edge-to-edge technique is a relatively
straightforward approach that can be performed with reduced myocardial ischemic times. Indeed, we
observed a statistically significant 33% reduction in aortic crossclamp times in the current study when
compared to the Loop technique.
It may seem counterintuitive that a pathology characterized by chordae elongation and excess leaflet
tissue can be successfully treated without leaflet resection or shortening of the distance between the
subvalvular apparatus and leaflets. However, our results reveal that a properly placed stitch that
encompasses a large amount of leaflet tissue is effective in shortening the height of both leaflets and
lowering the coaptation point to within the left ventricle. The amount of residual MR was very low in
these patients and not different from patients who underwent the Loop technique. In addition, our
observed medium-term freedom from MR and reoperation rates of 93% at 4 years compare
favourably to those observed in the literature.(23-25).
Although edge-to-edge patients displayed increased transvalvular gradients and decreased valve
opening areas when compared to the Loop group, the valvular hemodynamics remained well within
the non-stenotic range (i.e. mean gradient 3.3 mm Hg, mean orifice area 2.8 cm2). The satisfactory
hemodynamic performance for Alfieri repair in Barlow's disease is not surprising given the marked
annular dilation and large annuloplasty ring sizes that are used for such patients. Indeed, significantly
larger annuloplasty rings were inserted in patients undergoing the edge-to-edge repair technique in
our study. It is also important to note that we did not observe any cases of SAM with either repair
technique, a concern that is frequently mentioned when performing MV repair surgery for Barlow's
21
patients.
In addition to acceptable hemodynamics, we observed very good freedom from recurrent MR and
reoperation rates in Barlow's patients treated with an Alfieri repair. Longer term follow-up is required,
however, in order to determine if the valvular hemodynamics and recurrent MR rates remain stable
over time.
Study limitations
The current study is retrospective in nature and therefore subject to the inherent weakness of a
retrospective analysis. A relatively small number of patients is available for analysis at 5 years of
follow-up in the Alfieri group in comparison with the Loop group, which reflects our more recent
adoption of this technique. In contrast, Loop implantation has been used for over 15 years at our
hospital in order to treat Barlow´s and other degenerative disease. However, our increased number of
edge-to-edge repairs in the last years reveals how we have gained experience and confidence in this
approach over time.
Another limitation of our study is the fact that the repair technique was at the discretion of the
operating surgeon. As a result, edge-to-edge patients were found to have a more dilated annulus
while Loop patients were more likely to have flail segments. Whether such differences may have
favoured one group over the other is unkown.
Finally, late postoperative echocardiography was not obtained in all patients and was not
standardized, with the majority of echocardiographic reports coming from outside institutions. We
were therefore unable to directly analyze more quantitative aspects of MR.
Conclusions
Minimally invasive MV repair can be performed with very good early and medium-term outcomes in
Barlow's patients. Edge-to-edge repair is associated with shorter myocardial ischemic and operative
times when compared with neochordae (Loop) implantation. Both techniques are effective with
regards to medium-term freedom from MR and reoperation, although edge-to-edge repair results in
mildly elevated transvalvular gradients. Longer term follow up is required in order to determine if
observed valvular performance remains stable over time.
22
References
1- Carpentier A, Chavaude S, Fabiani JN, et al.Reconstructive surgery of mitral valve incompetence:
ten year appraisal. J Thorac Cardiovasc Surg 1980;79:338-48.
2- Adams DH, Rosenhek R, Falk V. Degenerative mitral valve regurgitation:best practice revolution.
Eur Heart J. 2010;31:1958-66.
3- Fornes P, Heudes D, Fuzellier JF, Tixier D, Bruneval P, Carpentier A. Correlation between clinical
and histologic patterns of degenerative mitral valve insufficiency: a histomorphometric study of 130
excised segments. Cardiovasc Pathol. 1999;8:81-92.
4- Braunberger E, Deloche A, Berrebi A, et al. Very long-term results (more than 20years) of valve
repair with Carpentier´s techniques in nonreumathic mitral valve insufficiency. Circulation
2001;104(12 Suppl 1):I8-I11.
5- David TE, Ivanov J, Armstrong S, Rakowski H. Late outcomes of mitral valve repair for floppy
valves: Implications for asymptomatic patients. J Thorac Cardiovasc Surg. 2003 ;125:1143-52.
6- Kuntze T, Borger MA, Falk V, et al. Early and mid-term results of mitral valve repair using
premeasured Gore-Tex loops (‘loop technique‘). Eur J Cardiothorac Surg. 2008;33:566-72.
7-von Oppell UO, Mohr FW. Chordal replacement for both minimally invasive and conventional mitral
valve surgery using premeasured Gore-Tex loops. Ann Thorac Surg. 2000;70:2166-8.
8- Maisano F,Schreuder JJ, Oppizzi M, Fiorani B, Fino C, Alfieri O. The double-orifice technique as a
standardized approach to treat mitral regurgitation due to severe myxomatous disease:surgical
technique. Eur J Cardiothorac Surg. 2000;17:201-5.
9- Mohr FW, Onnasch JF, Falk V, et al. The evolution of minimally invasive mitral valve surgery-- two
years experience. Eur J Cardiothorac Surg 1999;15:233-8.
10- Seeburger J,Borger MA, Doll N, et al. Comparison of outcomes of minimally invasive mitral valve
surgery for posterior, anterior and bileaflet prolapse. Eur J Cardiothorac Surg. 2009;36:532-8.
11- Ender J, Selbach M, Borger MA, et al. Echocardiographic identification of iatrogenic injury of the
circumflex artery during minimally invasive mitral valve repair. Ann Thorac Surg; 2010;89:1866-72.
12- Lancellotti P, Tribouilloy C, Hagendorff A, et al. Recommendations for the echocardiographic
23
assessment of native valvular regurgitation: an executive summary from the European Association of
Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2013;14:611-44.
13-Lancelotti P, Moura L, Pierard LA, et al. European Association of Echocardiography
recommendations for the assessment of valvular regurgitation.Part 2: mitral and tricuspid
regurgitation (native valve disease). Eur. J Echocardiogr. 2010;11:307-32.
14-Nishimura RA, Otto CM, Bonow RO, et al. 2014AHA/ACC Guideline for Management of Patients
with Valvular Heart Disease: Executive Summary: a Reporte of the american college of
cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol
2014;63:2438-88.
15-Filsoufi F, Carpentier A. Principles of reconstructive surgery in degenerative mitral valve disease.
Semin Thorac Cardiovasc Surg. 2007;19:103-10
16-Newcomb AE, David TE, Lad VS, Bobiarski J, Armstrong S, Maganti M. Mitral valve repair for
advanced myxomatous degeneration with posterior displacement of the mitral annulus. J Thorac
Cardiovasc Surg. 2008;136:1503-9
17-Borger MA, Mohr FW. Repair of bileaflet prolapse in Barlow syndrome. Semin Thorac Cardiovasc
Surg 2010:22;174-8
18-Adams DH, Anyanwu AC, Rahmanian PB. Large annuloplasty rings facilitate mitral valve repair in
Barlow´s disease. Ann Thorac Surg. 2006;82:2096-101
19-Lawrie GM, Earle EA, Earle NR. Nonresectional repair of the Barlow mitral valve: importance of
dynamic annular evaluation. Ann Thorac Surg. 2009;88:1191-6.
20- De Bonis M,Lapenna E, Lorusso R ,,et al. Very long-term results (up to 17 years) with doubleorifice mitral valve repair combined with ring annuloplasty for degenerative mitral regurgitation. J
Thorac Cardiovasc Surg 2012;144:1019-24.
21- Castillo JG, Anyanwu AC, El-Eshmawi A, Adams DH. All anterior and bileaflet mitral valve
prolapses are repairable in the modern era of reconstructive surgery. Eur J Cardiothoracic Surg
2014;45:139-45.
22-Seeburger J, Kuntze T, Mohr FW. Gore-Tex chordoplasty in degenerative mitral valve repair.
Semin Thorac Cardiovasc Surg 2007;19:111-5.
24
23-Flameng W, Meuris B, Herijgers P, Herregods MC. Durability of mitral valve repair in Barlow
disease versus fibroelastic deficiency. J Thorac Cardiovasc Surg 2008; 135(2):274-82.
24-Borger MA, Kaeding AF, Seeburger J,et al. Minimally invasive mitral valve repair in Barlow´s
disease: early and long-term results.J Thorac Cardiovasc Surg 2014;148:1379-85
25-David TE, Ivanov J, Armstrong S,Christie D, Rakowski H. A comparison of outcomes of mitral
valve repair for degenerative disease with posterior, anterior, and bileaflet prolapse. J Thorac
Cardiovasc Surg 2005;130:1242-9.
25
Zusammenfassung der Arbeit
Dissertation zur Erlangung des akademischen Grades
Dr. med.
Titel:
Barlow's mitral valve disease: a comparison of neochordal (Loop) and
edge-to-edge (Alfieri) minimally invasive repair techniques
eingereicht von:
Jaqueline Grace da Rocha e Silva
angefertigt am / in:
Klinik für Herzchirurgie, Herzzentrum Leipzig, Universität Leipzig
betreut von Prof. Dr. med. Sandra Eifert
Monat und Jahr (der Einreichung): März 2015
Zusammenfassung:
MV repair is the gold standard for treatment of patients with severe MR due to
degenerative MV disease.18,19 However, patients presenting with Barlow´s disease represent
the most severe form of myxomatous degeneration and the largest challenge for cardiac
surgeons. Several different surgical strategies are frequently required in order to achieve a
successful valve repair procedure in such patients.
The optimal MV repair technique for Barlow's patients is still unknown. In addition, it is
unknown whether the surgical approach (i.e. full sternotomy versus mini-thoracotomy) affects
outcomes achieved in such patients. In order to address these issues, we compared shortand medium-term outcomes for our two most commonly used MV repair techniques -- i.e.
Loop neochordae versus edge-to-edge repair in Barlow's patients undergoing minimal
invasive MV surgery.
26
From January 2009 to April 2014, 123 consecutive patients with Barlow ́s disease
(defined as bileaflet billowing and/or prolapse, excessive leaflet tissue and annular dilation
with or without calcification) underwent minimally invasive MV surgery for severe
regurgitation (MR) at our institution.
We have previously described our results of using pre-made Gore-Tex loops in order to
correct MV prolapse through a right lateral mini-thoracotomy approach.25,39,40 In the current
study, 61% of Barlow's patients were treated with this so-called Loop technique. The current
and previous studies from our group have demonstrated very good early- and medium-term
outcomes for the Loop technique, and we are therefore convinced that it is an effective
approach to treat patients with degenerative disease. However, the Loop technique can be
particularly time-consuming in patients with multisegment disease and may not be
generalizable to centers that do not perform large volumes of MV surgery. The publication of
excellent long-term results from Alfieri's group inspired us to start adopting their technique for
patients with bileaflet prolapse. The edge-to-edge technique is a relatively straightforward
approach that can be performed with reduced myocardial ischemic times. Indeed, we
observed a statistically significant 33% reduction in aortic crossclamp times in the current
study when compared to the Loop technique.
It may seem counterintuitive that a pathology characterized by chordae elongation and
excess leaflet tissue can be successfully treated without leaflet resection or shortening of the
distance between the subvalvular apparatus and leaflets. However, our results reveal that a
properly placed stitch that encompasses a large amount of leaflet tissue is effective in
shortening the height of both leaflets and lowering the coaptation point to within the left
ventricle. The amount of residual MR was very low in these patients and not different from
patients who underwent the Loop technique. In addition, our observed medium-term freedom
from MR and reoperation rates of 93% at 4 years compare favourably to those observed in
the literature.41-43
Although edge-to-edge patients displayed increased transvalvular gradients and
decreased valve opening areas when compared to the Loop group, the valvular
hemodynamics remained well within the non-stenotic range (i.e. mean gradient 3.3 mm Hg,
mean orifice area 2.8 cm2). The satisfactory hemodynamic performance for Alfieri repair in
Barlow's disease is not surprising given the marked annular dilation and large annuloplasty
ring sizes that are used for such patients. Indeed, significantly larger annuloplasty rings were
inserted in patients undergoing the edge-to-edge repair technique in our study. It is also
27
important to note that we did not observe any cases of SAM with either repair technique, a
concern that is frequently mentioned when performing MV repair surgery for Barlow's
patients.
In addition to acceptable hemodynamics, we observed very good freedom from
recurrent MR and reoperation rates in Barlow's patients treated with an Alfieri repair. Longer
term follow-up is required, however, in order to determine if the valvular hemodynamics and
recurrent MR rates remain stable over time.
Finally we observed that minimally invasive MV repair can be performed with very good
early and medium-term outcomes in Barlow's patients. Edge-to-edge repair is associated
with shorter myocardial ischemic and operative times when compared with neochordae
(Loop) implantation. Both techniques are effective with regards to medium-term freedom from
MR and reoperation, although edge-to-edge repair results in mildly elevated transvalvular
gradients. Longer term follow up is required in order to determine if observed valvular
performance remains stable over time.
28
References
1- Carpentier A, Chavaude S, Fabiani JN, et al.Reconstructive surgery of mitral valve
incompetence: ten year appraisal. J Thorac Cardiovasc Surg 1980;79:338-48.
2- Adams DH, Rosenhek R, Falk V. Degenerative mitral valve regurgitation:best practice
revolution. Eur Heart J. 2010;31:1958-66.
3-Carpentier, A. Cardiac valve surgery--the "French correction". J Thorac Cardiovasc Surg
1983;86: 323-337.
4-Enriquez-Sarano, M., et al. Mitral regurgitation. Lancet 2009;373: 1382-1394.
5- Barlow,J.B.: Conjoint clinic on the clinical significance of latte systolic murmurs and nonejection systolic clicks. J.chron. Dis. 18(1965),665
6- Barlow JB, Pocock WA, Marchand P,et al: The significance of late systolic murmurs. Am
Heart J 66:443-452, 1963
7- Criley JM, Lewis KB, Humpries JO, et al: Prolapse of the mitral valve:clinical and cineangiographic findings. Br Heart J 28:488-496,1966
8-Pomerance A:Balloning deformity (mucoid degeneration) of atrioventricular valves. Br
Heart J 31:343-351, 1969
9- Barlow JB, Pocock WA: Billowing,floppy,prolapsed or flail mitral valves? Am J Cardiol
55:501-502,1985
10- Fornes P, Heudes D, Fuzellier JF, Tixier D, Bruneval P, Carpentier A. Correlation
between clinical and histologic patterns of degenerative mitral valve insufficiency: a
histomorphometric study of 130 excised segments. Cardiovasc Pathol. 1999;8:81-92.
29
11- Kunzelman, K. S., et al. Annular dilatation increases stress in the mitral valve and delays
coaptation: a finite element computer model. Cardiovasc Surg 1997;5: 427-434.
12- Salgo, I. S., et al. Effect of annular shape on leaflet curvature in reducing mitral leaflet
stress. Circulation 2002;106: 711-717.
13- Filsoufi F, Carpentier A. Principles of reconstructive surgery in degenerative mitral valve
disease. Semin Thorac Cardiovasc Surg. 2007;19:103-10
14- Adams, D. H. and A. C. Anyanwu . The cardiologist's role in increasing the rate of mitral
valve repair in degenerative disease. Curr Opin Cardiol 2008;23: 105-110.
15- Sharma, R., et al. The evaluation of real-time 3-dimensional transthoracic
echocardiography for the preoperative functional assessment of patients with mitral valve
prolapse: a comparison with 2-dimensional transesophageal echocardiography. J Am Soc
Echocardiogr 2007;20: 934-940.
16- Patel, V., et al. . Usefulness of live/real time three-dimensional transthoracic
echocardiography in the identification of individual segment/scallop prolapse of the mitral
valve. Echocardiography 2006;23: 513-518.
17-Muller, S., et al. Comparison of three-dimensional imaging to transesophageal
echocardiography for preoperative evaluation in mitral valve prolapse. Am J Cardiol
2006;98:243-248.
18- Braunberger E, Deloche A, Berrebi A, et al. Very long-term results (more than 20years) of
valve repair with Carpentier´s techniques in nonreumathic mitral valve insufficiency.
Circulation 2001;104(12 Suppl 1):I8-I11.
19- David TE, Ivanov J, Armstrong S, Rakowski H. Late outcomes of mitral valve repair for
floppy valves: Implications for asymptomatic patients. J Thorac Cardiovasc Surg. 2003
;125:1143-52.
30
20- Omran, A. S., Woo A, David TE,Feindel CM,Rakowski H, Siu Sc. Intraoperative
transesophageal echocardiography accurately predicts mitral valve anatomy and suitability
for repair. J Am Soc Echocardiogr 2002;15: 950-957.
21.Varghese R, Anyanwu AC, Itagaki S, Milla F, Castillo J, Adams DH. Management of
systolic anterior motion after mitral valve repair: an algorithm. The Journal of thoracic and
cardiovascular surgery. 2012;143(4 Suppl):S2-7.
22- Newcomb AE, David TE, Lad VS, Bobiarski J, Armstrong S, Maganti M. Mitral valve
repair for advanced myxomatous degeneration with posterior displacement of the mitral
annulus. J Thorac Cardiovasc Surg. 2008;136:1503-9
23-Borger MA, Mohr FW. Repair of bileaflet prolapse in Barlow syndrome. Semin Thorac
Cardiovasc Surg 2010:22;174-8
24-Adams DH, Anyanwu AC, Rahmanian PB. Large annuloplasty rings facilitate mitral valve
repair in Barlow´s disease. Ann Thorac Surg. 2006;82:2096-101
25-von Oppell UO, Mohr FW. Chordal replacement for both minimally invasive and
conventional mitral valve surgery using premeasured Gore-Tex loops. Ann Thorac Surg.
2000;70:2166-8.
26- Falk V, Seeburger J, Czesla M, Borger MA, Willige J, Kuntze T, et al. How does the use
of polytetrafluoroethylene neochordae for posterior mitral valve prolapse (loop technique)
compare with leaflet resection? A prospective randomized trial. The Journal of thoracic and
cardiovascular surgery. 2008;136:1205; discussion -6
27- Carpentier AF, Pellerin M, Fuzellier JF, Relland JY. Extensive calcification of the mitral
valve anulus: pathology and surgical management. The Journal of thoracic and
cardiovascular surgery. 1996;111:718-29; discussion 29-30.
28- Perier P, Hohenberger W, Lakew F, Batz G, Urbanski P, Zacher M, et al. Toward a new
paradigm for the reconstruction of posterior leaflet prolapse: midterm results of the "respect
31
rather than resect" approach. The Annals of thoracic surgery. 2008;86:718-25; discussion 25.
29- Maisano F, La Canna G, Colombo A, Alfieri O. The evolution from surgery to
percutaneous mitral valve interventions: the role of the edge-to-edge technique. Journal of
the American College of Cardiology. 2011;58:2174-82.
30.De Bonis M, Lapenna E, Alfieri O. Edge-to-edge Alfieri technique for mitral valve repair:
which indications? Current opinion in cardiology. 2013;28:152-7.
31-Nielsen SL, Timek TA, Lai DT, et al. Edge-to-edge mitral repair: tension on the
approximating suture and leaflet deformation during acute ischemic mitral regurgitation in the
ovine heart. Circulation. 2001;104(12 Suppl 1):I29-35.
32-Votta E, Maisano F, Soncini M, Redaelli A, Montevecchi FM, Alfieri O. 3-D computational
analysis of the stress distribution on the leaflets after edge-to-edge repair of mitral
regurgitation. The Journal of heart valve disease. 2002;11:810-22.
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for mitral regurgitation: a clinical and exercise echocardiographic study. The Journal of heart
valve disease. 2008;17:476-84.
34-Agricola E, Maisano F, Oppizzi M, et al. Mitral valve reserve in double-orifice technique:
an exercise echocardiographic study. The Journal of heart valve disease. 2002;11:637-43.
35- Lawrie GM, Earle EA, Earle NR. Nonresectional repair of the Barlow mitral valve:
importance of dynamic annular evaluation. Ann Thorac Surg. 2009;88:1191-6.
36- Maisano F,Schreuder JJ, Oppizzi M, Fiorani B, Fino C, Alfieri O. The double-orifice
technique as a standardized approach to treat mitral regurgitation due to severe myxomatous
disease:surgical technique. Eur J Cardiothorac Surg. 2000;17:201-5.
37- De Bonis M,Lapenna E, Lorusso R,et al. Very long-term results (up to 17 years) with
double-orifice mitral valve repair combined with ring annuloplasty for degenerative mitral
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valve prolapses are repairable in the modern era of reconstructive surgery. Eur J
Cardiothoracic Surg 2014;45:139-45.
39- Kuntze T, Borger MA, Falk V, et al. Early and mid-term results of mitral valve repair using
premeasured Gore-Tex loops (‘loop technique‘). Eur J Cardiothorac Surg. 2008;33:566-72.
40- Seeburger J, Kuntze T, Mohr FW. Gore-Tex chordoplasty in degenerative mitral valve
repair. Semin Thorac Cardiovasc Surg 2007;19:111-5.
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Barlow disease versus fibroelastic deficiency. J Thorac Cardiovasc Surg 2008; 135(2):27482.
42-Borger MA, Kaeding AF, Seeburger J,et al. Minimally invasive mitral valve repair in
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Erklärung über die eigenständige Abfassung der Arbeit
Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig und ohne
unzulässige Hilfe oder Benutzung anderer als der angegebenen Hilfsmittel
angefertigt habe. Ich versichere, dass Dritte von mir weder unmittelbar noch
mittelbar geldwerte Leistungen für Arbeiten erhalten haben, die im
Zusammenhang mit dem Inhalt der vorgelegten Dissertation stehen, und dass
die vorgelegte Arbeit weder im Inland noch im Ausland in gleicher oder
ähnlicher Form einer anderen Prüfungsbehörde zum Zweck einer Promotion
oder eines anderen Prüfungsverfahrens vorgelegt wurde. Alles aus anderen
Quellen und von anderen Personen übernommene Material, das in der Arbeit
verwendet wurde oder auf das direkt Bezug genommen wird, wurde als solches
kenntlich gemacht. Insbesondere wurden alle Personen genannt, die direkt an
der Entstehung der vorliegenden Arbeit beteiligt waren.
................................ ....................................................
Datum
Unterschrift
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Curriculum vitae
Name
Adress
Phone
E-mail
Jaqueline Grace da Rocha e Silva
Trendelenburgstrasse 28, 04289 Leipzig
00491727796896
jaqgrace@yahoo.com.br
Place and date of Brasília, 6. november 1982 , brasilien nationality
birth
Present position Medical resident in cardiothoracic surgery in Herzzentrum Leipzig
- heart surgery department- Prof. Mohr
Education and Medical doctor of Medicine at Rio de Janeiro State University 2007
training -Residence training in general surgery at Servidores do Estado
Hospital (01.2008/01.2010)
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Courses Multidimensional imaging, 4D TTE and 4D TEE in Clinical Practice
with Prof. L. Badano, Prof J.Kasprzak and Prof. A. Hagendorff 10/2013
Wien
EACTA Echo 2014 Advanced and Certification Course for
Transesophageal Echocardiography Leipzig (17-20.05.2014)
Basic echocardiography course according to the german society of
ultrasound in medicine(DEGUM)- Chartté Berlin (12.2012)
Advanced+closing echocardiography courses according to the german
society of ultrasound in medicine(DEGUM) with Prof. A. Hagendorff
Leipzig (03/2013 - 03/2014)
Intensive Medicine course in Wendisch Rietz (03.2014)
Certification
Board Certification: ECFMG 2010 (USMLE Steps 1, 2CK, 2CS)
“Approbation als Ärtztin “ Germany 2013 (medical degree in Europe)
Practical skills Transthoracal and transesophageal echocardiography ( 2D+3D)
Basic and advanced life support
General surgery
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Languages
Portuguese- mother language
German- Proficient user in understanding (listening, reading),
speaking (spoken production, spoken interaction) and writing
English Proficient user in understanding (listening, reading), speaking
(spoken production, spoken interaction) and writing
Spanish- Basic user in understanding (listening, reading), speaking
(spoken production, spoken interaction) and writing
Publication
Poster
1-Etz CD, von Aspern K, da Rocha E Silva J, Girrbach FF, Leontyev S,
Luehr M, Misfeld M, Borger MA, Mohr FW. Impact of perfusion
strategy on outcome after repair for acute type a aortic dissection. Ann
Thorac Surg. 2014 Jan;97(1):78-85
1- da Rocha e Silva J, Meyer A.L., Eifert S., Garbade J., Mohr F.W. ,
Strüber M. Influence of Aortic Valve Opening in Patients With
Aortic Insufficiency After LVAD Implantation (ISHLT 2014)
2- R.A. Spampinato, M. Tasca, J.G. Rocha e Silva, E. Strodress, V.
Schloma, Y Dmitrieva, M. Dobrovie, M.A. Borger, F.W. Mohr.
Metabolic burden is associated with more pronounced
impairment of the longitudinal strain in patients with severe
aortic stenosis referred for valve surgery:2D speckel tracking
analysis.
(Euroecho 2014)
Lecture Imaging as a useful Tool for Mitral Operation: Echo is the
Surgeons Best Friend! (Winter-workshop Ismics 2014)
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Danksagung
I would like to express my gratitude to Prof. Dr. med. Friedrich Wilhelm Mohr,
director of Heart Center Leipzig, to have given me the opportunity to carry this project.
I also would like to thank Prof. Dr. med. Sandra Eifert for her outstanding
supervision and invaluable constructive criticismo during the project work.
My special recognition also to Prof. Dr. med. Michael Borger who has provided me
with immeasurable amount of support and guidance throughout this study.
To all cardiac surgeons from Heart Center Leipzig my sincerely gratitude for
sharing their knowledge and iluminating point of view concerning to this study.
I am especially grateful to my family for inspiring me to follow my dreams and to do
my best daily to make them a reality. Most of all I would like to thank my lord Jesus Christ
who guide my steps and gives me the strenght to enjoy the journey.
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