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Advanced experience allows robotic mitral valve repair in the presence of extensive mitral annular calcification
Journal Pre-proof Advanced Experience Allows Robotic Mitral Valve Repair in the Presence of Extensive Mitral Annular Calcification Didier F. Loulmet, MD, Neel K. Ranganath, MD, Siyamek Neragi-Miandoab, MD, Michael S. Koeckert, MD, Aubrey C. Galloway, MD, Eugene A. Grossi, MD PII:
S0022-5223(19)32405-5
DOI:
https://doi.org/10.1016/j.jtcvs.2019.10.099
Reference:
YMTC 15268
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 6 May 2019 Revised Date:
15 October 2019
Accepted Date: 17 October 2019
Please cite this article as: Loulmet DF, Ranganath NK, Neragi-Miandoab S, Koeckert MS, Galloway AC, Grossi EA, Advanced Experience Allows Robotic Mitral Valve Repair in the Presence of Extensive Mitral Annular Calcification, The Journal of Thoracic and Cardiovascular Surgery (2019), doi: https:// doi.org/10.1016/j.jtcvs.2019.10.099. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2019 Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery
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Advanced Experience Allows Robotic Mitral Valve Repair in the Presence of Extensive Mitral
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Annular Calcification
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Didier F Loulmet MD, Neel K Ranganath MD, Siyamek Neragi-Miandoab MD, Michael S Koeckert
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MD, Aubrey C Galloway MD, Eugene A Grossi MD
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NYU Langone Health, Department of Cardiothoracic Surgery
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Potential Conflict of Interest: Drs. Grossi and Galloway receive royalties from Medtronic and
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Edwards Lifesciences. Drs. Grossi and Loulmet receive proctoring fees from Intuitive Surgical; all
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other authors have no pertinent conflicts of interest to report for this manuscript. No external
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funding was obtained.
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Corresponding Author:
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Dr. Eugene A. Grossi, MD
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Department of Cardiothoracic Surgery, NYU Langone Health
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530 First Avenue, Suite 9V
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New York, NY 10016
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Phone: (212) 263-7452
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E-mail: [email protected]
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Presented as a podium presentation at the AATS 99th Annual Meeting in Toronto, Canada, May
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2019
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Word Count (excluding abstract and references): 3381/3500
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Central Picture (83/90 character limit):
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En-bloc resection of mitral annular calcification involving three leaflet segments.
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Central Message (197/200 character limit):
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Advanced robotic experience and a dedicated team approach allows for a high rate of
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successful mitral valve repair in the setting of extensive annular calcification and a pliable
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posterior leaflet.
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Perspective Statement (396/405 character limit):
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Mitral annular calcification is present in a significant portion of patients with degenerative
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mitral valve disease, remains a surgical challenge by complicating and limiting mitral valve
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repair, and entails increased patient risk. However, successful en-bloc resection and complex
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reconstruction can be consistently achieved with the robotic approach by utilizing a variety of
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repair techniques.
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3 40
Glossary of Abbreviations:
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MAC
Mitral annular calcification
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TERMVR
Totally endoscopic robotic mitral valve repair
43
PL
Posterior leaflet
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AL
Anterior leaflet
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LV
Left ventricle
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LA
Left atrium
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PM
Papillary muscle
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AV
Atrio-ventricular
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MV
Mitral valve
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MR
Mitral regurgitation
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MS
Mitral stenosis
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AS
Aortic stenosis
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TV
Tricuspid valve
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HOCM
Hypertrophic obstructive cardiomyopathy
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TTE
Transthoracic echocardiogram
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TEE
Transesophageal echocardiogram
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Abstract (Word Count: 254/250)
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Objective: Mitral annular calcification(MAC) is underdiagnosed in mitral regurgitation(MR)
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patients. After excision, it may require reconstruction of the atrio-ventricular(AV) groove, and
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decreases the probability of valve repair. We reviewed the safety and efficacy of totally
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endoscopic robotic mitral valve repair(TERMVR) in the presence of MAC, with an emphasis on
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pathology and repair techniques.
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Methods: Between May 2011 and August 2017, the same two-surgeon team attempted
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TERMVR in 64 MAC cases, accounting for 12.8% of our experience. MAC associated with a
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calcified posterior leaflet(PL) was not considered for TERMVR. When possible, MAC was excised
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en-bloc using electrocautery, PL separated from the MAC and spared, AV-groove reconstructed,
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PL reattached to the neo-annulus, and repair completed with annuloplasty.
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Results: Median age was 65 years with 21(32.8%) patients younger than 60, and 34(53.1%)
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were women. The etiology was Barlow’s disease in 54(84%). Repair was converted to
70
replacement in 2(3.1%) patients. Cryoablation was performed in 8(12.5%), hybrid PCI in
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5(7.8%), and tricuspid annuloplasty in 2(3.1%). Median aortic-occlusion was 122 minutes,
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excluding cases with concomitant tricuspid repair. Thirty-three (52%) patients were extubated
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in the operating room. Median length of stay was 4 days. Residual MR on discharge TTE was
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none-to-mild in all patients. None of the patients had a perioperative stroke or needed a
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pacemaker. Thirty-day mortality was 2(3.1%).
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Conclusion: MAC is present in a significant percentage of patients with MR, especially in
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Barlow’s disease, including younger patients. Utilizing a variety of repair techniques, TERMVR
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can be performed safely and effectively in most MAC cases with a non-calcified PL.
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Introduction
80
Posterior mitral annular calcification (MAC) is a degenerative process that involves the
81
region along the hinge of the posterior leaflet (PL) and may extend to leaflet body, papillary
82
muscles (PM), or the posterior walls of the left ventricle (LV) and left atrium (LA). While
83
posterior MAC may expand to the left and right trigones, involvement of the anterior aspect of
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the mitral valve (MV) annulus is rarely seen in the presence of a normal aortic valve (AV).
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Anterior MAC is a different pathological subset that usually results from the extension of calcific
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aortic valve stenosis (AS) to the subaortic curtain. Circumferential MAC may result from the
87
coexistence of both a submitral and a subaortic calcification process. MAC may also be
88
associated with hypertrophic obstructive cardiomyopathy (HOCM).
89
In the Pomerance study, the incidence of ‘marked’ annular calcification in autopsies of
90
patients over 50 years of age was almost 3%.1 Additionally, MAC was twice as common in
91
women and the incidence increased sharply with advanced age. In the Framingham study,
92
based on echocardiographic studies in the general population, the incidence of MAC in women
93
was again found to be twice that of men, and MAC was not observed in patients younger than
94
60 years.2 Furthermore, the incidence of MAC correlated strongly with the presence of
95
atherosclerosis risk factors. Since the publication of those two studies, MAC has been
96
considered a disease of elderly women.
97
The pathophysiology of MAC has not yet been elucidated, which precludes any
98
preventative measures or prophylactic treatment. Fortunately, MAC itself rarely causes MV
99
dysfunction.3 However, it may be associated with another MV pathology causing significant
100
stenosis (MS) or regurgitation (MR) requiring intervention. Two landmark studies have laid the
6 101
foundation of MV surgery in the presence of MAC, and both series advocate for complete MAC
102
excision. In Carpentier’s series of 68 patients, the atrio-ventricular (AV) groove was
103
reconstructed by sliding the LA towards the LV, or "sliding atrioplasty", and the MV was
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repaired in most instances4; this was accomplished with a 3% mortality. In David’s series of 54
105
patients, the AV-groove was repaired with a pericardial patch and the MV was most often
106
replaced.5 Of note, almost half of the patients in David’s series required a concomitant AV
107
replacement with the "commando" technique reflecting a more extensive pathological setting,
108
explaining the observed 9% mortality. We recently published an overview of our institution’s first 500 totally endoscopic robotic
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MV repairs (TERMVR) in patients with pure MR.6 None of the patients had MS, AS, or HOCM.
111
Significant MAC was identified in 64(12.8%) cases. The current study analyzes demographics,
112
pathology, and surgical techniques utilized in this subset of TERMVR patients with significant
113
MAC.
114 115
Materials and Methods
116 117
Patient Population
118
Between May 2011 and August 2017, 500 patients with MR underwent surgery with the intent
119
of performing a TERMVR. Patients were offered surgery in accordance with current American
120
College of Cardiology/American Heart Association (ACC/AHA) guidelines.7 Among these 500
121
patients, 64(12.8%) were found to have MAC and are the subject of this report. The data
7 122
collection was prospectively performed and approved for use in research by our Institutional
123
Review Board, with the need for individual patient consent waived.
124 125
Preoperative and intraoperative screening
126
All patients underwent: (i) preoperative transthoracic (TTE) echocardiography to assess MR
127
severity; (ii) cardiac catheterization or computed tomography angiography to identify coronary
128
artery disease (CAD) and MAC; (iii) computed tomography angiography of the
129
chest/abdomen/pelvis to evaluate for peripheral cannulation, retrograde perfusion, and
130
endoaortic clamping; (iv) intraoperative transesophageal echocardiogram (TEE) to assess MV
131
pathology, MAC extension, aortic and tricuspid valve (TV) regurgitation, tricuspid orifice
132
diameter, aortic atheromatous disease, and MV repair result; and (v) intraoperative screening
133
included stereoscopic inspection of the MV, after which the final decision to repair was made.6
134 135
Inclusion/exclusion criteria
136
Most categories of MV repair complexity were considered appropriate for TERMVR. No
137
systematic exclusion criteria were used empirically for patient selection, but there were a few
138
exceptions. In MAC patients, repair was considered only if the PL was pliable. If MAC was
139
associated with a totally calcified PL precluding a viable MV repair, patients were not
140
candidates for TERMVR.
141
As noted previously, 321 patients underwent TERMVR during the last 3 study years,
142
while isolated MV operations via sternotomy were performed in 26(7.5%) patients by either of
143
the team surgeons. Of these 26 patients, severe MAC with extensive posterior leaflet
8 144
calcification was present in 9 cases.6 During this time frame, 48% of the institution’s isolated
145
mitrals were performed by the robotic team.
146 147
Operative procedure
148
Our TERMVR technique has been described previously.6 All operations were performed by a
149
dedicated team including two experienced MV surgeons. Femoral perfusion, endoaortic balloon
150
clamping, and administration of antegrade del Nido cardioplegia was the preferred technique.
151
Surgery was performed with the da Vinci® Surgical System (Intuitive Surgical Inc., Sunnyvale, CA)
152
using five right chest ports. The right chest was insufflated with heated CO2 (2L/min) to prevent
153
camera fogging and decrease the risk of air embolization. On cardiopulmonary bypass (CPB),
154
MAC patients were typically cooled to 28°-30°C. The MV was exposed through Sondergaard’s
155
groove with dynamic retraction, and exposure was optimized by placing a 2.0 Ethibond (Ethicon
156
Inc., Somerville, NJ) stay suture to pull the LA wall towards the diaphragm (right below the
157
inferior vena cava). The left appendage was systematically closed to prevent its inversion into
158
the left atrium. Occasionally, to maximize exposure during MAC excision, a gauze roll was
159
introduced into the oblique sinus and placed behind the AV-groove.
160 161
MV repair techniques in the setting of MAC (Figure 1)
162
In most cases, MAC was excised en-bloc using robotic electrocautery. The cautery blade was
163
partially covered with a plastic sheath, exposing only the tip, to minimize contact with normal
164
tissue. While using electrocautery, CO2 flow was temporarily increased to 5 L/min to disperse
165
the smoke and prevent camera fogging. The dissection was initiated between the calcium bar
9 166
and the LA wall, eventually progressing towards the LV while staying as close as possible to the
167
calcification. Complete excision of MAC was considered paramount to allow for unhindered,
168
precise placement of repair sutures. Once the MAC was completely separated from the AV-
169
groove, the PL was detached from the MAC. Detachment of the PL usually required the division
170
of multiple dystrophic secondary chordae directly attached to the MAC. Careful suctioning was
171
intermittently performed with a long neuro-microsurgery tip suction tube when small calcium
172
fragments were identified. After complete separation from both the AV-groove and the PL, the
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MAC was extracted through the working port. The LA and LV were rinsed with cold saline using
174
a motorized suction irrigator (Stryker Corp., Kalamazoo, MI) to further remove calcium debris. A
175
dual blade retractor was used to elevate the detached PL against the LV septum, maximizing
176
exposure of the AV-groove.
177
In the absence of AV-groove disruption, simple conventional annuloplasty sutures (2.0
178
Ethibond) were placed through the MV annulus before reattaching the PL. If epicardial tissue
179
was visible through a limited AV-groove separation, reconstruction was performed with
180
compression mattress sutures on a pledget (2.0 Ethibond). When MAC extended onto the LV
181
and excision resulted in a large defect, the AV-groove was repaired with a bovine pericardial
182
patch, elliptically-fashioned with major and minor axes measured 1-cm larger than the resected
183
MAC dimensions. The lower edge of the patch was fixed to the LV wall with a series of
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horizontal mattress sutures on a pledget (2.0 Ethibond) and tied with CorKnot® titanium clips
185
(LSI Solutions, Victor, NY). The long axis, or diameter of the oval patch, was attached to the LA
186
wall with a series of horizontal mattress sutures (2.0 Ethibond); these sutures exiting through
187
the working port were left untied and later used to anchor the annuloplasty band. The upper
10 188
half of the patch was reserved to provide augmentation of the base of the PL or trimmed and
189
later used to reattach the PL (Figure 1).
190
If necessary, the PL was corrected for prolapse or restriction. In cases of excess tissue
191
(Barlow's disease), the prolapsed segment of the PL was resected and the remaining segments
192
were re-approximated with a running back-and-forth 5.0 PTFE suture. Next, the PL was re-
193
attached to the upper edge of the patch using Carpentier's running, interlocking suture
194
technique (4.0 PTFE). Alternatively, the PL could be re-attached to the patch first and corrected
195
for prolapse with a triangular excision-suture afterwards (Video). In cases without excess tissue
196
(fibroelastic deficiency), the upper half of the patch was made larger to compensate for the lack
197
of PL tissue, and a PL prolapse would be corrected with neochordae (pledgeted 4.0 PTFE) rather
198
than by resection of the prolapsed segment. Prosthetic annuloplasty was performed with a
199
semi-rigid annuloplasty band (CG Future™, Medtronic, Minneapolis, MN), secured using the
200
sutures placed previously from the attachment of the AV-groove patch to the LA wall, and the
201
sutures were terminated with CorKnot®.
202 203
Statistical analysis
204
Descriptive statistics for categorical variables are reported as frequency and percentages and
205
compared using the Fisher’s exact test (2 groups) or χ2 test (>2 groups). Continuous variables
206
were tested for normality of distribution and if normal, were reported as mean and standard
207
deviation. Non-normally distributed variables were reported as median [first and third
208
quartiles]. Parametrically distributed variables were compared with the student’s t-test and
209
non-parametrically distributed variables were compared using the Mann Whitney U test. A p-
11 210
value of 0.05 was predetermined to be significant. Statistical analysis was performed using SPSS
211
version 25 (IBM Corp., Armonk, NY).
212 213
Results
214 215
Preoperative demographics
216
The study population consisted of 34(53.1%) women with a median age of 68.5 years [ 59-74
217
and 30(46.9%) men with a median age of 61.5 years [52.5-72.5]. Twenty-one patients (32.8%)
218
were younger than 60 years. Body mass index was more than 30 kg/m2 in 8(12.5%) patients.
219
Fifty-two patients (81.3%) were in New York Heart Association class I or II. Mean LV ejection
220
fraction was 60%. None of the patients had undergone prior cardiac surgery.
221 222
Pathology
223
MV disease etiology and functional classification were defined for each patient (Table 1). The
224
most common etiology was Barlow’s disease, identified in 54(84.4%) patients, followed by
225
6(9.4%) cases of isolated MAC without an accompanying etiology. Fibroelastic deficiency was
226
identified in 2(3.1%) cases, functional secondary to high blood pressure in 1(1.6%), and healed
227
endocarditis in 1(1.6%). The incidence of MAC in our overall TERMVR patients was
228
64/500(12.8%). In patients with Barlow’s disease, it was 54/340(15.9%).
229
MAC was strictly limited to the mitral annulus in 25(39.1%) patients. Extension to the
230
PM through a large, aberrant muscle band was noted in 21(32.8%) patients, with extension to
231
the anterior PM in 15(23.4%) or to the posterior PM in 6(9.4%) (Figure 2). Extension to the LV
12 232
myocardium was noted in 19(29.7%) patients. Considering that patients with preoperative
233
evidence of PL calcification were generally excluded from repair, extension to the body of the
234
PL was rare as expected, only seen in 2(3.1%) cases.
235
Annular extension involved 1 segment in 35(54.6%) patients, 2 segments in 21(32.8%),
236
or 3 segments in 8(12.5%). Comparing women and men, 1 segment was involved in
237
19/34(55.9%) vs 16/30(53.3%), 2 segments in 9/34(26.5%) vs 12/30(40.0%), and 3 segments in
238
6/34(17.6%) vs 2/30(6.7%) (p=0.294). Between older patients (age≥70) and younger patients
239
(age<70), 1 segment was involved in 15/26(57.7%) vs 20/38(52.6%), 2 segments in 8(30.8%) vs
240
13(61.9%), and 3 segments in 3(11.5%) vs 5(13.2%) (p=0.923). P2 was the most frequently
241
calcified hinge segment as well as the most frequently prolapsed leaflet segment (Figure 3).
242 243
Surgical techniques
244
MAC was completely excised in 60(93.7%). The AV-groove was repaired with simple
245
annuloplasty sutures in 30(46.9%) cases, a bovine pericardial patch in 19(29.7%), and
246
compression mattress sutures on a pledget in 11(17.2%). The techniques used for MV repair are
247
presented in Table 2. An average of 5.5 MV repair techniques was used per MAC case as
248
opposed to 3.4 for non-MAC cases (p<0.001). Concomitant procedures included left appendage
249
closure in 62(96.9%) cases, PFO/ASD closure in 12(18.8%), cryoablation in 8(12.5%), hybrid PCI
250
in 5/64(7.8%), and TV repair in 2(3.1%). For isolated MV repair (without concomitant TV repair),
251
the overall median aortic occlusion and perfusion times were 122 and 161 min, respectively,
252
compared to 81 and 120 min in non-MAC patients (Table 3).
253
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Intraoperative outcomes
255
Successful MV repair was achieved in 62(96.9%) patients. Two (3.1%) patients (ages 76 and 81)
256
required intraoperative conversion sternotomy for MV replacement due to an extensively
257
calcified PL in both cases; another patient required conversion to sternotomy for MV repair
258
revision. These rates for conversion were low but higher than in the non-MAC patient cohort
259
(Table 3). There were no intraoperative deaths. No patients experienced myocardial ischemia
260
or required an intra-aortic balloon pump. One patient required iliac artery stenting for a
261
localized arterial dissection above the femoral cannulation site. Intraoperative TEE confirmed
262
that 62(96.9%) patients left the operating room with MR graded as none-to-mild. Extubation in
263
the operating room was achieved in 33(51.6%) patients.
264 265
Postoperative outcomes
266
One patient underwent thoracoscopic reoperation for hemothorax. One patient had a
267
laparotomy for a hepatic laceration followed by complete recovery. Three (4.7%) patients
268
underwent MV repair revision prior to hospital discharge; these were performed by TERMVR
269
(n=1) or sternotomy (n=2); this was higher for MAC patients than non MAC patients (Table 3).
270
Prolonged ventilation (>24 h) occurred in 6(9.4%) patients. There were no perioperative stroke,
271
surgical site infections, or need for a permanent pacemakers in this series. One patient (87 year
272
old, extensive MAC, patch reconstruction) died of unexplained cardiac arrest on postoperative
273
day 4. Pre-discharge TTE confirmed that all 64(100%) patients had MR graded as none-to-mild.
274
The median postoperative length of stay (LOS) was 4 days. One patient (81 year old, single
14 275
segment MAC, direct annuloplasty sutures, history of seizures, microvascular brain disease on
276
MRI) died after discharge on postoperative day 25 from brain hemorrhage while on warfarin.
277 278
Discussion
279
In a series of 500 consecutive MV regurgitation patients (which did not include patients with
280
MS, HOCM, or associated AS) who underwent TERMVR, the incidence of MAC was 12.8%.
281
Figure 4 (Graphical abstract) summarizes the pathology encountered and the clinical outcomes
282
of this cohort. MAC was most commonly associated with Barlow's disease (84.4%). Female
283
prevalence was 53.1% in MAC patients as opposed to only 33.9% in non-MAC patients.
284
However, MAC was not a pathology limited to elderly women as it was encountered in almost
285
an equal number of men (46.9%) and in a significant proportion of patients less than 60 years of
286
age (32.8%), including an 18-year-old woman. The presence of MAC made MV repair more
287
technically challenging, but a high repair rate was still achieved. MAC remains a marker for
288
added perioperative morbidity and mortality. While absolute rates were low, more reoperation
289
and conversion were encountered in the MAC cohort. Additionally,, 2 early mortalities and 2
290
conversions to valve replacement occurred in older patients. These exceptions may suggest
291
that above the age of 75 years and in the context of an extensive degenerative process, a
292
primary valve replacement strategy is preferable to a complex repair.8
293 294
Preoperative diagnosis
295
Due to its high x-ray attenuation, MAC was best detected preoperatively on cardiac
296
catheterization, which also allowed characterization of its relationship to the circumflex artery.
15 297
MAC was also consistently detected on CT angiogram. In our experience, TTE was not typically
298
useful in diagnosing MAC. However, TEE was highly effective in elucidating its extension,
299
particularly to the PL body, which determines the chances of a successful repair. Submitral
300
extension, particularly to the PMs, was usually well visualized on TEE.
301 302
Pathology
303
In this series of pure MR patients, MAC was most commonly associated with Barlow’s disease,
304
and less commonly associated with fibroelastic deficiency compared to other series.9 During
305
robotic surgery, the subvalvular apparatus could be observed in great detail with stereoscopic
306
magnification, and anatomic variations of the subvalulvar apparatus were frequently seen in
307
this series. One of the most characteristic and frequent anatomic variations was the presence
308
of a large, calcified band between the hinge of the PL and the PMs. It was most commonly
309
observed between the hinge of P1-P2 and the anterior PM thus making MAC extension towards
310
the lateral side (P1-P2) more common than to the medial side (P2-P3). This contrasted with the
311
observations reported in other series.4, 9 Similar muscle bands were sometimes seen anteriorly
312
between the hinge (or body) of the anterior leaflet and the PM. Contrasting with the posterior
313
muscle bands, the anterior bands were never calcified. The presence of an aberrant subvalvular
314
muscle band, calcified or non-calcified, can been explained by an incomplete delamination of
315
the trabecular ridge, which raises the question of a congenital etiology of calcific PM
316
extension.10 It supports the hypothesis that there is a subvalvular determinant of MV
317
degenerative disease. Of particular interest, an aberrant calcified muscle band could cause a
16 318
prolapse by attracting the PM towards the MV orifice. In two cases, dividing the band was
319
enough to correct a prolapse of the A1-P1 commissural region.
320 321
Surgical insights
322
Inserting the stereoscope into the 3rd intercostal space lateral to the midclavicular line provides
323
alignment with the LV long axis and allows excellent visualization of the MV and subvalvular
324
apparatus. Vigilant positioning of the endoballoon in the ascending aorta above the sinotubular
325
junction with adequate root decompression further exposes the anterior commissural region.
326
Placing a tacking stitch below the inferior vena cava to pull the LA wall towards the diaphragm
327
improves exposure of the posterior commissural region. A gauze roll placed behind the AV-
328
groove may be used to facilitate MAC excision. Electrocautery enables precise MAC dissection,
329
especially when the calcium bar extends into the LV myocardium and loses its encapsulated
330
sheath. Of note, electrocautery generates a copious amount of smoke, which must be
331
dispersed by temporarily increasing CO2 insufflation flow to prevent camera fogging. After MAC
332
excision, the detached PL can be elevated against the interventricular septum with the dual
333
blade retractor in order to maximize exposure on the AV-groove. Following debridement, the
334
edge of the LV myocardium can be left very fragile, which justifies suturing the pericardial patch
335
to the LV with mattress sutures on a pledget. Ventricular bites should not be transmural but
336
deep enough to provide adequate fixation. Overall, robotics provides excellent exposure into
337
the LV cavity and facilitates the placement of myocardial stitches. CorKnot® suture termination
338
allows for equal pressure on both strings and decreases the risk of a myocardial tear. More than
339
any other, this surgical sequence must be deconstructed and shared between the console and
17 340
patient-side surgeon, and an experienced two-surgeon model is highly recommended. In this
341
report, we described a modified AV-groove patch repair technique; the modification uses the
342
upper part of the patch to reattach and sometimes augment the PL. To maximize the likelihood
343
of successful repair, the upper part of the patch (above the annuloplasty stitches) should be
344
made larger if there is significant tissue loss at the base of the PL after MAC debridement.
345
Annuloplasty stitches should only be terminated after final hydrostatic testing of the valve. In
346
cases of a disappointing repair result, the annuloplasty band can be removed and the stitches
347
used for valve replacement.
348 349
"Resect rather than respect" and the robotic approach
350
The authors believe that complete MAC excision is preferable, because attempting to attach a
351
prosthetic device (annuloplasty or artificial valve) to a large bar of calcium can only provide
352
inconsistent results.3 Indeed, placing sutures around MAC increases the risk of a circumflex
353
artery injury, and tying sutures around MAC can cause a fracture with drainage of the liquefied
354
core into the LV. Moreover, the risk of prosthetic dehiscence is high in the setting of irregular
355
and rigid anatomy. With regards to the repair of the AV-groove after MAC excision, the use of a
356
patch technique minimizes tension on the suture lines, especially when anchoring the
357
annuloplasty device. Moreover, this technique allows the hinge of the PL to remain at its proper
358
anatomic level; by contrast, direct re-attachment of the LA to the LV may lower the posterior
359
MV orifice and cause pseudo-prolapse of the anterior leaflet. On the other hand, the "sliding
360
atrioplasty" technique may have an advantage in better preserving LV function, for pericardial
361
patches do not “contract". The high repair rate in this series was obtained with the utilization
18 362
of a combination of several different techniques, conforming to the “a technique for each
363
lesion” principle.11 This strategy allows for more versatility in the context of complex
364
pathologies and increases the likelihood of successful repair compared to the use of a
365
restricted, standardized set of techniques. With respect to the sternotomy versus robotics
366
debate, the authors’ experience has been that any MV repair technique traditionally performed
367
through a sternotomy can be performed with enhanced precision using robotics.
368 369
Limitations
370
This study is limited by its generalizability: this complex series of operations was conducted by a
371
very experienced surgical team. We would recommend that these procedures only be
372
undertaken by such team since as both sewing a patch to the debrided edge of the ventricular
373
myocardium and tying it with the proper tension requires extreme finesse and coordination by
374
both the console and bedside surgeons. It should be noted that our robotic MAC experience
375
was achieved after an initial learning curve. Additionally, the robotics approach for MAC is
376
limited to some extent by ‘fineness’ of the robotic instruments and their ability to cut dense
377
tissue encountered in this disease process.
378 379 380
Conclusion
381
In this series of patients with pure MV regurgitation, MAC was most often associated with
382
Barlow's disease, and was not seen exclusively in older patients. MAC increases the complexity
383
of MV repair, and requires extensive robotic experience. Successful en-bloc resection and
19 384
complex reconstruction, utilizing a variety of techniques, can be consistently achieved with a
385
TERMVR approach, offering a less invasive solution for these patients.
20 386
Figure Legends
387 388
Figure 1. Modified patch technique for atrio-ventricular groove reconstruction following
389
extensive mitral annular calcification (MAC) resection. A bovine pericardial patch is used
390
with interrupted suture fixation to the left ventricle, superior attachment to the left atrium,
391
and superior edge attachment to the base of the posterior mitral leaflet.
392
A: Attachment of the lower edge of the patch to the left ventricle with pledgeted mattress
393
sutures
394
B: Annuloplasty stitches placed through the long axis of the patch and the edge of the left
395
atrium
396
C: Attachment of the posterior leaflet to the upper edge of the patch with possible patch
397
augmentation of the base of the posterior leaflet
398
D: Placement of the annuloplasty band
21
399
22 400
Figure 2. Posterior mitral annular calcification extension to the anterior papillary muscle via
401
a calcified muscle band is seen intraoperatively in an 18-year-old woman. It is identified in
402
the left panel and resected from the trunk of the papillary muscle in the right panel.
403
404 405
23 406
Figure 3. Segmental distribution of annular calcification (blue) and leaflet prolapse (red) along
407
the mitral valve. This pictogram demonstrates the relative annular and leaflet pathologies
408
encountered in our patient series.
409 410
24 411
Figure 4. Graphical Abstract. Sixty-four patients with mitral annular calcification (MAC)
412
underwent robotic mitral valve surgery. A repair rate of 97% was achieved; 19 patients
413
required extensive atrio-ventricular (AV) groove patch repair.
414 415
416
25 417
Table 1. Etiologies and functional classifications of mitral valve pathology in the setting of
418
mitral annular calcification. Functional Classification Type II
Etiologies
n (%)
Type I
Type II (AL) Type II (PL)
Type IIIa
Type IIIb
(AL&PL) Barlow’s disease
54 (84.4)
0
0
37
17
0
0
6 (9.4)
2
0
3
1
0
0
2 (3.1)
0
0
2
0
0
0
Functional
1 (1.6)
0
0
0
0
0
1
Healed endocarditis
1 (1.6)
0
0
1
0
0
0
Total n (%)
64 (100)
2 (3.1)
0
43 (67.2)
18 (28.1)
0
1 (1.6)
419
MAC, mitral annular calcification
Isolated MAC Fibroelastic deficiency
420
26 421
Table 2. Repair techniques utilized over the 64 patients experience. Anterior leaflet repair
422 423 424
27
Posterior leaflet repair
115
PM repositioning
7
Quadrangular excision:
46
Artificial chord implant
4
Hemisliding plasty
31
Triangular excision-suture
4
Classic sliding plasty
16
Paracommissural sliding plasty
7
Triangular excision-suture
11
Other technique
5
Artificial chord implant
11
Annular techniques
154
Adjunctive techniques
59
Band annuloplasty
64
AL secondary chordae excision
36
MAC excision
60
P1-P2 or P2-P3 cleft stitch
11
AV-groove patch repair
19
Commissural stitch
10
AV-groove repair with compression stitches
11
Alfieri A2-P2 edge-to-edge
PM, papillary muscle; MAC, mitral annular calcification; AV, atrio-ventricular; AL, anterior leaflet
2
27 425
Table 3. Comparison of demographics and outcomes between MAC and non-MAC patients All patients
MAC patients
Non-MAC patients
(n=500)
(n=64)
(n=436)
Female sex
182 (36.4)
34 (53.1%)
148 (33.9%)
0.004
Women’s age, years*
65 [57-72]
68.5 [59-74]
65[57-71]
0.093
Men’s age, years*
61 [52-68]
61.5 [52.5-72.5]
61 [52-68]
0.179
Preoperative atrial fibrillation
139 (27.8)
13 (20.3%)
126 (28.9%)
0.179
NYHA class > 2
118 (23.6)
12 (18.8%)
106 (24.3%)
0.430
Obesity (BMI > 30)
82 (16.4)
8 (12.5%)
74 (17.0%)
0.470
Diabetes
29 (5.8)
2 (3.1%)
27 (6.2%)
0.564
Coronary artery disease
39 (7.8)
5 (7.8%)
34 (7.8%)
1.000
340 (68.0)
54 (84.4%)
286 (65.6%)
0.003
Aortic occlusion time (without TR), min**
86.5 [70-106]
122.5 [98.5-162]
81 [68-101]
<0.001
CPB time (without TR), min**
125 [106-152]
161 [133.5-205]
120 [103-143]
<0.001
Extubation in operating room
320 (64.0)
33 (51.6%)
287 (65.8%)
0.036
Barlow’s disease
p-value
28
Conversion to sternotomy
5 (1.0)
3 (4.7)
2 (0.4)
0.001
Return to OR Any Cause
13 (2.6)
5 (7.8)
8 (1.8)
0.005
Return to OR for Mitral Re-intervention
5 (1.0)
3 (4.7)
2 (0.4)
0.001
Postoperative length of stay**
4 [3-5]
4 [3-5]
4 [3-5]
0.053
MV repair rate
497 (99.4)
62 (96.9%)
435 (99.8%)
0.044
None-to-mild MR at discharge
489 (98.8)
64 (100%)
425 (98.6%)
1.000
30-day stroke
6 (1.2)
0
6 (1.4%)
0.562
30-day mortality
3 (0.6)
2 (3.1%)
1 (0.2%)
0.044
426
NYHA, New York Heart Association; TR, tricuspid repair; MV, mitral valve; MR, mitral regurgitation; CPB, cardiopulmonary bypass
427
*Presented as mean (range)
428
**Presented as median [first and third quartiles]
29 429
References
430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459
1.
460
2.
3. 4.
5. 6.
7.
8. 9.
10.
11.
Pomerance A. Pathological and clinical study of calcification of the mitral valve ring. J Clin Pathol. 1970;23:354-361. Savage DD, Garrison RJ, Castelli WP, et al. Prevalence of submitral (anular) calcium and its correlates in a general population-based sample (the Framingham Study). Am J Cardiol. 1983;51:1375-1378. Bedeir K, Kaneko T, Aranki S. Current and evolving strategies in the management of severe mitral annular calcification. J Thorac Cardiovasc Surg. 2019;157:555-566. Carpentier AF, Pellerin M, Fuzellier JF, Relland JY. Extensive calcification of the mitral valve anulus: pathology and surgical management. J Thorac Cardiovasc Surg. 1996;111:718-729; discussion 729-730. Feindel CM, Tufail Z, David TE, Ivanov J, Armstrong S. Mitral valve surgery in patients with extensive calcification of the mitral annulus. J Thorac Cardiovasc Surg. 2003;126:777-782. Loulmet DF, Ranganath NK, Neuburger PJ, Nampiaparampil RG, Galloway AC, Grossi EA. Can complex mitral valve repair be performed with robotics? An institution's experience utilizing a dedicated team approach in 500 patients. Eur J Cardiothorac Surg. 2019. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70:252-289. Uchimuro T, Fukui T, Shimizu A, Takanashi S. Mitral Valve Surgery in Patients With Severe Mitral Annular Calcification. Ann Thorac Surg. 2016;101:889-895. Fusini L, Ghulam Ali S, Tamborini G, et al. Prevalence of calcification of the mitral valve annulus in patients undergoing surgical repair of mitral valve prolapse. Am J Cardiol. 2014;113:18671873. Oosthoek PW, Wenink AC, Wisse LJ, Gittenberger-de Groot AC. Development of the papillary muscles of the mitral valve: morphogenetic background of parachute-like asymmetric mitral valves and other mitral valve anomalies. J Thorac Cardiovasc Surg. 1998;116:36-46. Filsoufi F, Carpentier A. Principles of reconstructive surgery in degenerative mitral valve disease. Semin Thorac Cardiovasc Surg. 2007;19:103-110.
S0022-5223(19)32405-5
DOI:
https://doi.org/10.1016/j.jtcvs.2019.10.099
Reference:
YMTC 15268
To appear in:
The Journal of Thoracic and Cardiovascular Surgery
Received Date: 6 May 2019 Revised Date:
15 October 2019
Accepted Date: 17 October 2019
Please cite this article as: Loulmet DF, Ranganath NK, Neragi-Miandoab S, Koeckert MS, Galloway AC, Grossi EA, Advanced Experience Allows Robotic Mitral Valve Repair in the Presence of Extensive Mitral Annular Calcification, The Journal of Thoracic and Cardiovascular Surgery (2019), doi: https:// doi.org/10.1016/j.jtcvs.2019.10.099. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Copyright © 2019 Published by Elsevier Inc. on behalf of The American Association for Thoracic Surgery
1 1
Advanced Experience Allows Robotic Mitral Valve Repair in the Presence of Extensive Mitral
2
Annular Calcification
3 4
Didier F Loulmet MD, Neel K Ranganath MD, Siyamek Neragi-Miandoab MD, Michael S Koeckert
5
MD, Aubrey C Galloway MD, Eugene A Grossi MD
6
NYU Langone Health, Department of Cardiothoracic Surgery
7 8
Potential Conflict of Interest: Drs. Grossi and Galloway receive royalties from Medtronic and
9
Edwards Lifesciences. Drs. Grossi and Loulmet receive proctoring fees from Intuitive Surgical; all
10
other authors have no pertinent conflicts of interest to report for this manuscript. No external
11
funding was obtained.
12
Corresponding Author:
13
Dr. Eugene A. Grossi, MD
14
Department of Cardiothoracic Surgery, NYU Langone Health
15
530 First Avenue, Suite 9V
16
New York, NY 10016
17
Phone: (212) 263-7452
18
E-mail: [email protected]
19 20
Presented as a podium presentation at the AATS 99th Annual Meeting in Toronto, Canada, May
21
2019
22
Word Count (excluding abstract and references): 3381/3500
23
2 24
Central Picture (83/90 character limit):
25
En-bloc resection of mitral annular calcification involving three leaflet segments.
26 27
Central Message (197/200 character limit):
28
Advanced robotic experience and a dedicated team approach allows for a high rate of
29
successful mitral valve repair in the setting of extensive annular calcification and a pliable
30
posterior leaflet.
31 32
Perspective Statement (396/405 character limit):
33
Mitral annular calcification is present in a significant portion of patients with degenerative
34
mitral valve disease, remains a surgical challenge by complicating and limiting mitral valve
35
repair, and entails increased patient risk. However, successful en-bloc resection and complex
36
reconstruction can be consistently achieved with the robotic approach by utilizing a variety of
37
repair techniques.
38 39
3 40
Glossary of Abbreviations:
41
MAC
Mitral annular calcification
42
TERMVR
Totally endoscopic robotic mitral valve repair
43
PL
Posterior leaflet
44
AL
Anterior leaflet
45
LV
Left ventricle
46
LA
Left atrium
47
PM
Papillary muscle
48
AV
Atrio-ventricular
49
MV
Mitral valve
50
MR
Mitral regurgitation
51
MS
Mitral stenosis
52
AS
Aortic stenosis
53
TV
Tricuspid valve
54
HOCM
Hypertrophic obstructive cardiomyopathy
55
TTE
Transthoracic echocardiogram
56
TEE
Transesophageal echocardiogram
4 57
Abstract (Word Count: 254/250)
58
Objective: Mitral annular calcification(MAC) is underdiagnosed in mitral regurgitation(MR)
59
patients. After excision, it may require reconstruction of the atrio-ventricular(AV) groove, and
60
decreases the probability of valve repair. We reviewed the safety and efficacy of totally
61
endoscopic robotic mitral valve repair(TERMVR) in the presence of MAC, with an emphasis on
62
pathology and repair techniques.
63
Methods: Between May 2011 and August 2017, the same two-surgeon team attempted
64
TERMVR in 64 MAC cases, accounting for 12.8% of our experience. MAC associated with a
65
calcified posterior leaflet(PL) was not considered for TERMVR. When possible, MAC was excised
66
en-bloc using electrocautery, PL separated from the MAC and spared, AV-groove reconstructed,
67
PL reattached to the neo-annulus, and repair completed with annuloplasty.
68
Results: Median age was 65 years with 21(32.8%) patients younger than 60, and 34(53.1%)
69
were women. The etiology was Barlow’s disease in 54(84%). Repair was converted to
70
replacement in 2(3.1%) patients. Cryoablation was performed in 8(12.5%), hybrid PCI in
71
5(7.8%), and tricuspid annuloplasty in 2(3.1%). Median aortic-occlusion was 122 minutes,
72
excluding cases with concomitant tricuspid repair. Thirty-three (52%) patients were extubated
73
in the operating room. Median length of stay was 4 days. Residual MR on discharge TTE was
74
none-to-mild in all patients. None of the patients had a perioperative stroke or needed a
75
pacemaker. Thirty-day mortality was 2(3.1%).
76
Conclusion: MAC is present in a significant percentage of patients with MR, especially in
77
Barlow’s disease, including younger patients. Utilizing a variety of repair techniques, TERMVR
78
can be performed safely and effectively in most MAC cases with a non-calcified PL.
5 79
Introduction
80
Posterior mitral annular calcification (MAC) is a degenerative process that involves the
81
region along the hinge of the posterior leaflet (PL) and may extend to leaflet body, papillary
82
muscles (PM), or the posterior walls of the left ventricle (LV) and left atrium (LA). While
83
posterior MAC may expand to the left and right trigones, involvement of the anterior aspect of
84
the mitral valve (MV) annulus is rarely seen in the presence of a normal aortic valve (AV).
85
Anterior MAC is a different pathological subset that usually results from the extension of calcific
86
aortic valve stenosis (AS) to the subaortic curtain. Circumferential MAC may result from the
87
coexistence of both a submitral and a subaortic calcification process. MAC may also be
88
associated with hypertrophic obstructive cardiomyopathy (HOCM).
89
In the Pomerance study, the incidence of ‘marked’ annular calcification in autopsies of
90
patients over 50 years of age was almost 3%.1 Additionally, MAC was twice as common in
91
women and the incidence increased sharply with advanced age. In the Framingham study,
92
based on echocardiographic studies in the general population, the incidence of MAC in women
93
was again found to be twice that of men, and MAC was not observed in patients younger than
94
60 years.2 Furthermore, the incidence of MAC correlated strongly with the presence of
95
atherosclerosis risk factors. Since the publication of those two studies, MAC has been
96
considered a disease of elderly women.
97
The pathophysiology of MAC has not yet been elucidated, which precludes any
98
preventative measures or prophylactic treatment. Fortunately, MAC itself rarely causes MV
99
dysfunction.3 However, it may be associated with another MV pathology causing significant
100
stenosis (MS) or regurgitation (MR) requiring intervention. Two landmark studies have laid the
6 101
foundation of MV surgery in the presence of MAC, and both series advocate for complete MAC
102
excision. In Carpentier’s series of 68 patients, the atrio-ventricular (AV) groove was
103
reconstructed by sliding the LA towards the LV, or "sliding atrioplasty", and the MV was
104
repaired in most instances4; this was accomplished with a 3% mortality. In David’s series of 54
105
patients, the AV-groove was repaired with a pericardial patch and the MV was most often
106
replaced.5 Of note, almost half of the patients in David’s series required a concomitant AV
107
replacement with the "commando" technique reflecting a more extensive pathological setting,
108
explaining the observed 9% mortality. We recently published an overview of our institution’s first 500 totally endoscopic robotic
109 110
MV repairs (TERMVR) in patients with pure MR.6 None of the patients had MS, AS, or HOCM.
111
Significant MAC was identified in 64(12.8%) cases. The current study analyzes demographics,
112
pathology, and surgical techniques utilized in this subset of TERMVR patients with significant
113
MAC.
114 115
Materials and Methods
116 117
Patient Population
118
Between May 2011 and August 2017, 500 patients with MR underwent surgery with the intent
119
of performing a TERMVR. Patients were offered surgery in accordance with current American
120
College of Cardiology/American Heart Association (ACC/AHA) guidelines.7 Among these 500
121
patients, 64(12.8%) were found to have MAC and are the subject of this report. The data
7 122
collection was prospectively performed and approved for use in research by our Institutional
123
Review Board, with the need for individual patient consent waived.
124 125
Preoperative and intraoperative screening
126
All patients underwent: (i) preoperative transthoracic (TTE) echocardiography to assess MR
127
severity; (ii) cardiac catheterization or computed tomography angiography to identify coronary
128
artery disease (CAD) and MAC; (iii) computed tomography angiography of the
129
chest/abdomen/pelvis to evaluate for peripheral cannulation, retrograde perfusion, and
130
endoaortic clamping; (iv) intraoperative transesophageal echocardiogram (TEE) to assess MV
131
pathology, MAC extension, aortic and tricuspid valve (TV) regurgitation, tricuspid orifice
132
diameter, aortic atheromatous disease, and MV repair result; and (v) intraoperative screening
133
included stereoscopic inspection of the MV, after which the final decision to repair was made.6
134 135
Inclusion/exclusion criteria
136
Most categories of MV repair complexity were considered appropriate for TERMVR. No
137
systematic exclusion criteria were used empirically for patient selection, but there were a few
138
exceptions. In MAC patients, repair was considered only if the PL was pliable. If MAC was
139
associated with a totally calcified PL precluding a viable MV repair, patients were not
140
candidates for TERMVR.
141
As noted previously, 321 patients underwent TERMVR during the last 3 study years,
142
while isolated MV operations via sternotomy were performed in 26(7.5%) patients by either of
143
the team surgeons. Of these 26 patients, severe MAC with extensive posterior leaflet
8 144
calcification was present in 9 cases.6 During this time frame, 48% of the institution’s isolated
145
mitrals were performed by the robotic team.
146 147
Operative procedure
148
Our TERMVR technique has been described previously.6 All operations were performed by a
149
dedicated team including two experienced MV surgeons. Femoral perfusion, endoaortic balloon
150
clamping, and administration of antegrade del Nido cardioplegia was the preferred technique.
151
Surgery was performed with the da Vinci® Surgical System (Intuitive Surgical Inc., Sunnyvale, CA)
152
using five right chest ports. The right chest was insufflated with heated CO2 (2L/min) to prevent
153
camera fogging and decrease the risk of air embolization. On cardiopulmonary bypass (CPB),
154
MAC patients were typically cooled to 28°-30°C. The MV was exposed through Sondergaard’s
155
groove with dynamic retraction, and exposure was optimized by placing a 2.0 Ethibond (Ethicon
156
Inc., Somerville, NJ) stay suture to pull the LA wall towards the diaphragm (right below the
157
inferior vena cava). The left appendage was systematically closed to prevent its inversion into
158
the left atrium. Occasionally, to maximize exposure during MAC excision, a gauze roll was
159
introduced into the oblique sinus and placed behind the AV-groove.
160 161
MV repair techniques in the setting of MAC (Figure 1)
162
In most cases, MAC was excised en-bloc using robotic electrocautery. The cautery blade was
163
partially covered with a plastic sheath, exposing only the tip, to minimize contact with normal
164
tissue. While using electrocautery, CO2 flow was temporarily increased to 5 L/min to disperse
165
the smoke and prevent camera fogging. The dissection was initiated between the calcium bar
9 166
and the LA wall, eventually progressing towards the LV while staying as close as possible to the
167
calcification. Complete excision of MAC was considered paramount to allow for unhindered,
168
precise placement of repair sutures. Once the MAC was completely separated from the AV-
169
groove, the PL was detached from the MAC. Detachment of the PL usually required the division
170
of multiple dystrophic secondary chordae directly attached to the MAC. Careful suctioning was
171
intermittently performed with a long neuro-microsurgery tip suction tube when small calcium
172
fragments were identified. After complete separation from both the AV-groove and the PL, the
173
MAC was extracted through the working port. The LA and LV were rinsed with cold saline using
174
a motorized suction irrigator (Stryker Corp., Kalamazoo, MI) to further remove calcium debris. A
175
dual blade retractor was used to elevate the detached PL against the LV septum, maximizing
176
exposure of the AV-groove.
177
In the absence of AV-groove disruption, simple conventional annuloplasty sutures (2.0
178
Ethibond) were placed through the MV annulus before reattaching the PL. If epicardial tissue
179
was visible through a limited AV-groove separation, reconstruction was performed with
180
compression mattress sutures on a pledget (2.0 Ethibond). When MAC extended onto the LV
181
and excision resulted in a large defect, the AV-groove was repaired with a bovine pericardial
182
patch, elliptically-fashioned with major and minor axes measured 1-cm larger than the resected
183
MAC dimensions. The lower edge of the patch was fixed to the LV wall with a series of
184
horizontal mattress sutures on a pledget (2.0 Ethibond) and tied with CorKnot® titanium clips
185
(LSI Solutions, Victor, NY). The long axis, or diameter of the oval patch, was attached to the LA
186
wall with a series of horizontal mattress sutures (2.0 Ethibond); these sutures exiting through
187
the working port were left untied and later used to anchor the annuloplasty band. The upper
10 188
half of the patch was reserved to provide augmentation of the base of the PL or trimmed and
189
later used to reattach the PL (Figure 1).
190
If necessary, the PL was corrected for prolapse or restriction. In cases of excess tissue
191
(Barlow's disease), the prolapsed segment of the PL was resected and the remaining segments
192
were re-approximated with a running back-and-forth 5.0 PTFE suture. Next, the PL was re-
193
attached to the upper edge of the patch using Carpentier's running, interlocking suture
194
technique (4.0 PTFE). Alternatively, the PL could be re-attached to the patch first and corrected
195
for prolapse with a triangular excision-suture afterwards (Video). In cases without excess tissue
196
(fibroelastic deficiency), the upper half of the patch was made larger to compensate for the lack
197
of PL tissue, and a PL prolapse would be corrected with neochordae (pledgeted 4.0 PTFE) rather
198
than by resection of the prolapsed segment. Prosthetic annuloplasty was performed with a
199
semi-rigid annuloplasty band (CG Future™, Medtronic, Minneapolis, MN), secured using the
200
sutures placed previously from the attachment of the AV-groove patch to the LA wall, and the
201
sutures were terminated with CorKnot®.
202 203
Statistical analysis
204
Descriptive statistics for categorical variables are reported as frequency and percentages and
205
compared using the Fisher’s exact test (2 groups) or χ2 test (>2 groups). Continuous variables
206
were tested for normality of distribution and if normal, were reported as mean and standard
207
deviation. Non-normally distributed variables were reported as median [first and third
208
quartiles]. Parametrically distributed variables were compared with the student’s t-test and
209
non-parametrically distributed variables were compared using the Mann Whitney U test. A p-
11 210
value of 0.05 was predetermined to be significant. Statistical analysis was performed using SPSS
211
version 25 (IBM Corp., Armonk, NY).
212 213
Results
214 215
Preoperative demographics
216
The study population consisted of 34(53.1%) women with a median age of 68.5 years [ 59-74
217
and 30(46.9%) men with a median age of 61.5 years [52.5-72.5]. Twenty-one patients (32.8%)
218
were younger than 60 years. Body mass index was more than 30 kg/m2 in 8(12.5%) patients.
219
Fifty-two patients (81.3%) were in New York Heart Association class I or II. Mean LV ejection
220
fraction was 60%. None of the patients had undergone prior cardiac surgery.
221 222
Pathology
223
MV disease etiology and functional classification were defined for each patient (Table 1). The
224
most common etiology was Barlow’s disease, identified in 54(84.4%) patients, followed by
225
6(9.4%) cases of isolated MAC without an accompanying etiology. Fibroelastic deficiency was
226
identified in 2(3.1%) cases, functional secondary to high blood pressure in 1(1.6%), and healed
227
endocarditis in 1(1.6%). The incidence of MAC in our overall TERMVR patients was
228
64/500(12.8%). In patients with Barlow’s disease, it was 54/340(15.9%).
229
MAC was strictly limited to the mitral annulus in 25(39.1%) patients. Extension to the
230
PM through a large, aberrant muscle band was noted in 21(32.8%) patients, with extension to
231
the anterior PM in 15(23.4%) or to the posterior PM in 6(9.4%) (Figure 2). Extension to the LV
12 232
myocardium was noted in 19(29.7%) patients. Considering that patients with preoperative
233
evidence of PL calcification were generally excluded from repair, extension to the body of the
234
PL was rare as expected, only seen in 2(3.1%) cases.
235
Annular extension involved 1 segment in 35(54.6%) patients, 2 segments in 21(32.8%),
236
or 3 segments in 8(12.5%). Comparing women and men, 1 segment was involved in
237
19/34(55.9%) vs 16/30(53.3%), 2 segments in 9/34(26.5%) vs 12/30(40.0%), and 3 segments in
238
6/34(17.6%) vs 2/30(6.7%) (p=0.294). Between older patients (age≥70) and younger patients
239
(age<70), 1 segment was involved in 15/26(57.7%) vs 20/38(52.6%), 2 segments in 8(30.8%) vs
240
13(61.9%), and 3 segments in 3(11.5%) vs 5(13.2%) (p=0.923). P2 was the most frequently
241
calcified hinge segment as well as the most frequently prolapsed leaflet segment (Figure 3).
242 243
Surgical techniques
244
MAC was completely excised in 60(93.7%). The AV-groove was repaired with simple
245
annuloplasty sutures in 30(46.9%) cases, a bovine pericardial patch in 19(29.7%), and
246
compression mattress sutures on a pledget in 11(17.2%). The techniques used for MV repair are
247
presented in Table 2. An average of 5.5 MV repair techniques was used per MAC case as
248
opposed to 3.4 for non-MAC cases (p<0.001). Concomitant procedures included left appendage
249
closure in 62(96.9%) cases, PFO/ASD closure in 12(18.8%), cryoablation in 8(12.5%), hybrid PCI
250
in 5/64(7.8%), and TV repair in 2(3.1%). For isolated MV repair (without concomitant TV repair),
251
the overall median aortic occlusion and perfusion times were 122 and 161 min, respectively,
252
compared to 81 and 120 min in non-MAC patients (Table 3).
253
13 254
Intraoperative outcomes
255
Successful MV repair was achieved in 62(96.9%) patients. Two (3.1%) patients (ages 76 and 81)
256
required intraoperative conversion sternotomy for MV replacement due to an extensively
257
calcified PL in both cases; another patient required conversion to sternotomy for MV repair
258
revision. These rates for conversion were low but higher than in the non-MAC patient cohort
259
(Table 3). There were no intraoperative deaths. No patients experienced myocardial ischemia
260
or required an intra-aortic balloon pump. One patient required iliac artery stenting for a
261
localized arterial dissection above the femoral cannulation site. Intraoperative TEE confirmed
262
that 62(96.9%) patients left the operating room with MR graded as none-to-mild. Extubation in
263
the operating room was achieved in 33(51.6%) patients.
264 265
Postoperative outcomes
266
One patient underwent thoracoscopic reoperation for hemothorax. One patient had a
267
laparotomy for a hepatic laceration followed by complete recovery. Three (4.7%) patients
268
underwent MV repair revision prior to hospital discharge; these were performed by TERMVR
269
(n=1) or sternotomy (n=2); this was higher for MAC patients than non MAC patients (Table 3).
270
Prolonged ventilation (>24 h) occurred in 6(9.4%) patients. There were no perioperative stroke,
271
surgical site infections, or need for a permanent pacemakers in this series. One patient (87 year
272
old, extensive MAC, patch reconstruction) died of unexplained cardiac arrest on postoperative
273
day 4. Pre-discharge TTE confirmed that all 64(100%) patients had MR graded as none-to-mild.
274
The median postoperative length of stay (LOS) was 4 days. One patient (81 year old, single
14 275
segment MAC, direct annuloplasty sutures, history of seizures, microvascular brain disease on
276
MRI) died after discharge on postoperative day 25 from brain hemorrhage while on warfarin.
277 278
Discussion
279
In a series of 500 consecutive MV regurgitation patients (which did not include patients with
280
MS, HOCM, or associated AS) who underwent TERMVR, the incidence of MAC was 12.8%.
281
Figure 4 (Graphical abstract) summarizes the pathology encountered and the clinical outcomes
282
of this cohort. MAC was most commonly associated with Barlow's disease (84.4%). Female
283
prevalence was 53.1% in MAC patients as opposed to only 33.9% in non-MAC patients.
284
However, MAC was not a pathology limited to elderly women as it was encountered in almost
285
an equal number of men (46.9%) and in a significant proportion of patients less than 60 years of
286
age (32.8%), including an 18-year-old woman. The presence of MAC made MV repair more
287
technically challenging, but a high repair rate was still achieved. MAC remains a marker for
288
added perioperative morbidity and mortality. While absolute rates were low, more reoperation
289
and conversion were encountered in the MAC cohort. Additionally,, 2 early mortalities and 2
290
conversions to valve replacement occurred in older patients. These exceptions may suggest
291
that above the age of 75 years and in the context of an extensive degenerative process, a
292
primary valve replacement strategy is preferable to a complex repair.8
293 294
Preoperative diagnosis
295
Due to its high x-ray attenuation, MAC was best detected preoperatively on cardiac
296
catheterization, which also allowed characterization of its relationship to the circumflex artery.
15 297
MAC was also consistently detected on CT angiogram. In our experience, TTE was not typically
298
useful in diagnosing MAC. However, TEE was highly effective in elucidating its extension,
299
particularly to the PL body, which determines the chances of a successful repair. Submitral
300
extension, particularly to the PMs, was usually well visualized on TEE.
301 302
Pathology
303
In this series of pure MR patients, MAC was most commonly associated with Barlow’s disease,
304
and less commonly associated with fibroelastic deficiency compared to other series.9 During
305
robotic surgery, the subvalvular apparatus could be observed in great detail with stereoscopic
306
magnification, and anatomic variations of the subvalulvar apparatus were frequently seen in
307
this series. One of the most characteristic and frequent anatomic variations was the presence
308
of a large, calcified band between the hinge of the PL and the PMs. It was most commonly
309
observed between the hinge of P1-P2 and the anterior PM thus making MAC extension towards
310
the lateral side (P1-P2) more common than to the medial side (P2-P3). This contrasted with the
311
observations reported in other series.4, 9 Similar muscle bands were sometimes seen anteriorly
312
between the hinge (or body) of the anterior leaflet and the PM. Contrasting with the posterior
313
muscle bands, the anterior bands were never calcified. The presence of an aberrant subvalvular
314
muscle band, calcified or non-calcified, can been explained by an incomplete delamination of
315
the trabecular ridge, which raises the question of a congenital etiology of calcific PM
316
extension.10 It supports the hypothesis that there is a subvalvular determinant of MV
317
degenerative disease. Of particular interest, an aberrant calcified muscle band could cause a
16 318
prolapse by attracting the PM towards the MV orifice. In two cases, dividing the band was
319
enough to correct a prolapse of the A1-P1 commissural region.
320 321
Surgical insights
322
Inserting the stereoscope into the 3rd intercostal space lateral to the midclavicular line provides
323
alignment with the LV long axis and allows excellent visualization of the MV and subvalvular
324
apparatus. Vigilant positioning of the endoballoon in the ascending aorta above the sinotubular
325
junction with adequate root decompression further exposes the anterior commissural region.
326
Placing a tacking stitch below the inferior vena cava to pull the LA wall towards the diaphragm
327
improves exposure of the posterior commissural region. A gauze roll placed behind the AV-
328
groove may be used to facilitate MAC excision. Electrocautery enables precise MAC dissection,
329
especially when the calcium bar extends into the LV myocardium and loses its encapsulated
330
sheath. Of note, electrocautery generates a copious amount of smoke, which must be
331
dispersed by temporarily increasing CO2 insufflation flow to prevent camera fogging. After MAC
332
excision, the detached PL can be elevated against the interventricular septum with the dual
333
blade retractor in order to maximize exposure on the AV-groove. Following debridement, the
334
edge of the LV myocardium can be left very fragile, which justifies suturing the pericardial patch
335
to the LV with mattress sutures on a pledget. Ventricular bites should not be transmural but
336
deep enough to provide adequate fixation. Overall, robotics provides excellent exposure into
337
the LV cavity and facilitates the placement of myocardial stitches. CorKnot® suture termination
338
allows for equal pressure on both strings and decreases the risk of a myocardial tear. More than
339
any other, this surgical sequence must be deconstructed and shared between the console and
17 340
patient-side surgeon, and an experienced two-surgeon model is highly recommended. In this
341
report, we described a modified AV-groove patch repair technique; the modification uses the
342
upper part of the patch to reattach and sometimes augment the PL. To maximize the likelihood
343
of successful repair, the upper part of the patch (above the annuloplasty stitches) should be
344
made larger if there is significant tissue loss at the base of the PL after MAC debridement.
345
Annuloplasty stitches should only be terminated after final hydrostatic testing of the valve. In
346
cases of a disappointing repair result, the annuloplasty band can be removed and the stitches
347
used for valve replacement.
348 349
"Resect rather than respect" and the robotic approach
350
The authors believe that complete MAC excision is preferable, because attempting to attach a
351
prosthetic device (annuloplasty or artificial valve) to a large bar of calcium can only provide
352
inconsistent results.3 Indeed, placing sutures around MAC increases the risk of a circumflex
353
artery injury, and tying sutures around MAC can cause a fracture with drainage of the liquefied
354
core into the LV. Moreover, the risk of prosthetic dehiscence is high in the setting of irregular
355
and rigid anatomy. With regards to the repair of the AV-groove after MAC excision, the use of a
356
patch technique minimizes tension on the suture lines, especially when anchoring the
357
annuloplasty device. Moreover, this technique allows the hinge of the PL to remain at its proper
358
anatomic level; by contrast, direct re-attachment of the LA to the LV may lower the posterior
359
MV orifice and cause pseudo-prolapse of the anterior leaflet. On the other hand, the "sliding
360
atrioplasty" technique may have an advantage in better preserving LV function, for pericardial
361
patches do not “contract". The high repair rate in this series was obtained with the utilization
18 362
of a combination of several different techniques, conforming to the “a technique for each
363
lesion” principle.11 This strategy allows for more versatility in the context of complex
364
pathologies and increases the likelihood of successful repair compared to the use of a
365
restricted, standardized set of techniques. With respect to the sternotomy versus robotics
366
debate, the authors’ experience has been that any MV repair technique traditionally performed
367
through a sternotomy can be performed with enhanced precision using robotics.
368 369
Limitations
370
This study is limited by its generalizability: this complex series of operations was conducted by a
371
very experienced surgical team. We would recommend that these procedures only be
372
undertaken by such team since as both sewing a patch to the debrided edge of the ventricular
373
myocardium and tying it with the proper tension requires extreme finesse and coordination by
374
both the console and bedside surgeons. It should be noted that our robotic MAC experience
375
was achieved after an initial learning curve. Additionally, the robotics approach for MAC is
376
limited to some extent by ‘fineness’ of the robotic instruments and their ability to cut dense
377
tissue encountered in this disease process.
378 379 380
Conclusion
381
In this series of patients with pure MV regurgitation, MAC was most often associated with
382
Barlow's disease, and was not seen exclusively in older patients. MAC increases the complexity
383
of MV repair, and requires extensive robotic experience. Successful en-bloc resection and
19 384
complex reconstruction, utilizing a variety of techniques, can be consistently achieved with a
385
TERMVR approach, offering a less invasive solution for these patients.
20 386
Figure Legends
387 388
Figure 1. Modified patch technique for atrio-ventricular groove reconstruction following
389
extensive mitral annular calcification (MAC) resection. A bovine pericardial patch is used
390
with interrupted suture fixation to the left ventricle, superior attachment to the left atrium,
391
and superior edge attachment to the base of the posterior mitral leaflet.
392
A: Attachment of the lower edge of the patch to the left ventricle with pledgeted mattress
393
sutures
394
B: Annuloplasty stitches placed through the long axis of the patch and the edge of the left
395
atrium
396
C: Attachment of the posterior leaflet to the upper edge of the patch with possible patch
397
augmentation of the base of the posterior leaflet
398
D: Placement of the annuloplasty band
21
399
22 400
Figure 2. Posterior mitral annular calcification extension to the anterior papillary muscle via
401
a calcified muscle band is seen intraoperatively in an 18-year-old woman. It is identified in
402
the left panel and resected from the trunk of the papillary muscle in the right panel.
403
404 405
23 406
Figure 3. Segmental distribution of annular calcification (blue) and leaflet prolapse (red) along
407
the mitral valve. This pictogram demonstrates the relative annular and leaflet pathologies
408
encountered in our patient series.
409 410
24 411
Figure 4. Graphical Abstract. Sixty-four patients with mitral annular calcification (MAC)
412
underwent robotic mitral valve surgery. A repair rate of 97% was achieved; 19 patients
413
required extensive atrio-ventricular (AV) groove patch repair.
414 415
416
25 417
Table 1. Etiologies and functional classifications of mitral valve pathology in the setting of
418
mitral annular calcification. Functional Classification Type II
Etiologies
n (%)
Type I
Type II (AL) Type II (PL)
Type IIIa
Type IIIb
(AL&PL) Barlow’s disease
54 (84.4)
0
0
37
17
0
0
6 (9.4)
2
0
3
1
0
0
2 (3.1)
0
0
2
0
0
0
Functional
1 (1.6)
0
0
0
0
0
1
Healed endocarditis
1 (1.6)
0
0
1
0
0
0
Total n (%)
64 (100)
2 (3.1)
0
43 (67.2)
18 (28.1)
0
1 (1.6)
419
MAC, mitral annular calcification
Isolated MAC Fibroelastic deficiency
420
26 421
Table 2. Repair techniques utilized over the 64 patients experience. Anterior leaflet repair
422 423 424
27
Posterior leaflet repair
115
PM repositioning
7
Quadrangular excision:
46
Artificial chord implant
4
Hemisliding plasty
31
Triangular excision-suture
4
Classic sliding plasty
16
Paracommissural sliding plasty
7
Triangular excision-suture
11
Other technique
5
Artificial chord implant
11
Annular techniques
154
Adjunctive techniques
59
Band annuloplasty
64
AL secondary chordae excision
36
MAC excision
60
P1-P2 or P2-P3 cleft stitch
11
AV-groove patch repair
19
Commissural stitch
10
AV-groove repair with compression stitches
11
Alfieri A2-P2 edge-to-edge
PM, papillary muscle; MAC, mitral annular calcification; AV, atrio-ventricular; AL, anterior leaflet
2
27 425
Table 3. Comparison of demographics and outcomes between MAC and non-MAC patients All patients
MAC patients
Non-MAC patients
(n=500)
(n=64)
(n=436)
Female sex
182 (36.4)
34 (53.1%)
148 (33.9%)
0.004
Women’s age, years*
65 [57-72]
68.5 [59-74]
65[57-71]
0.093
Men’s age, years*
61 [52-68]
61.5 [52.5-72.5]
61 [52-68]
0.179
Preoperative atrial fibrillation
139 (27.8)
13 (20.3%)
126 (28.9%)
0.179
NYHA class > 2
118 (23.6)
12 (18.8%)
106 (24.3%)
0.430
Obesity (BMI > 30)
82 (16.4)
8 (12.5%)
74 (17.0%)
0.470
Diabetes
29 (5.8)
2 (3.1%)
27 (6.2%)
0.564
Coronary artery disease
39 (7.8)
5 (7.8%)
34 (7.8%)
1.000
340 (68.0)
54 (84.4%)
286 (65.6%)
0.003
Aortic occlusion time (without TR), min**
86.5 [70-106]
122.5 [98.5-162]
81 [68-101]
<0.001
CPB time (without TR), min**
125 [106-152]
161 [133.5-205]
120 [103-143]
<0.001
Extubation in operating room
320 (64.0)
33 (51.6%)
287 (65.8%)
0.036
Barlow’s disease
p-value
28
Conversion to sternotomy
5 (1.0)
3 (4.7)
2 (0.4)
0.001
Return to OR Any Cause
13 (2.6)
5 (7.8)
8 (1.8)
0.005
Return to OR for Mitral Re-intervention
5 (1.0)
3 (4.7)
2 (0.4)
0.001
Postoperative length of stay**
4 [3-5]
4 [3-5]
4 [3-5]
0.053
MV repair rate
497 (99.4)
62 (96.9%)
435 (99.8%)
0.044
None-to-mild MR at discharge
489 (98.8)
64 (100%)
425 (98.6%)
1.000
30-day stroke
6 (1.2)
0
6 (1.4%)
0.562
30-day mortality
3 (0.6)
2 (3.1%)
1 (0.2%)
0.044
426
NYHA, New York Heart Association; TR, tricuspid repair; MV, mitral valve; MR, mitral regurgitation; CPB, cardiopulmonary bypass
427
*Presented as mean (range)
428
**Presented as median [first and third quartiles]
29 429
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